Br J Haematol. 2024 Oct 15. doi: 10.1111/bjh.19795. Online ahead of print.
NO ABSTRACT
PMID:39406689 | DOI:10.1111/bjh.19795
32878 items (32878 unread) in 74 feeds
Br J Haematol. 2024 Oct 15. doi: 10.1111/bjh.19795. Online ahead of print.
NO ABSTRACT
PMID:39406689 | DOI:10.1111/bjh.19795
Head Neck Pathol. 2024 Oct 15;18(1):97. doi: 10.1007/s12105-024-01702-w.
ABSTRACT
Mast cell sarcoma (MCS) is an extremely rare and aggressive malignancy primarily affecting bones, with limited literature associating it with neuroendocrine marker expression. This report presents a rare case of MCS arising in the maxillary sinus and gingiva. A 74-year-old man presented with a progressively enlarging ulcer on the right-sided upper gingiva. Magnetic resonance imaging revealed a 3.4 cm tumor on the floor of the right maxillary sinus. The patient underwent an inferior maxillectomy and right-sided neck dissection. Microscopically, the tumor consisted of monotonous round cells with oval nuclei, vesicular chromatin, inconspicuous nucleoli, and brisk mitoses. A panel of immunohistochemical stains was initially applied to exclude common sinonasal undifferentiated neoplasms, such as sinonasal undifferentiated carcinoma, melanoma, rhabdomyosarcoma, Ewing sarcoma, and lymphoma. The tumor cells showed patchy staining for INSM1 and synaptophysin, but were negative for AE1/AE3, CAM5.2, p40, chromogranin, S100, HMB45, NKX2.2, desmin, CD45 (LCA), CD3, and CD20, with intact INI1 and BRG1 expression. No specific diagnosis could be rendered based on the staining results, leading to consideration of other rare malignancies. Additional staining revealed positivity for CD117, mast cell tryptase, CD13, CD33, CD43, and CD68, confirming the MCS diagnosis. Molecular testing for KIT mutation was negative. Subsequent bone marrow biopsy demonstrated infiltration of atypical mast cells, which led to a diagnosis of mast cell leukemia. Despite high-dose chemotherapy, the patient died three months after the initial diagnosis. The undifferentiated epithelioid morphology and unusual aberrant neuroendocrine marker expression posed significant diagnostic challenges. The major differential diagnoses were discussed in this report.
PMID:39404971 | DOI:10.1007/s12105-024-01702-w
Cancer Med. 2024 Oct;13(19):e70303. doi: 10.1002/cam4.70303.
ABSTRACT
BACKGROUND: The highly homologous T-box transcription factors TBX2 and TBX3 are critical for embryonic development, and their overexpression in postnatal tissues contributes to a wide range of malignancies, including melanoma and rhabdomyosarcoma. Importantly, when TBX2 and TBX3 are depleted in cancers where they are overexpressed, the malignant phenotype is inhibited, and they have therefore been regarded as druggable targets. However, the time and costs associated with de novo drug development are challenging and result in drugs that are costly, especially for patients in low- and middle-income countries. In the current study, we therefore combined a targeted and drug repurposing approach to identify drugs that are expected to be more efficacious and cost-effective with significantly reduced side effects.
METHODS: A high-throughput cell-based immunofluorescence screen was performed to identify drugs in the Pharmakon 1600 drug library that can negatively regulate TBX2 and/or TBX3 levels. "Hit" drugs were validated for their effect on TBX2/TBX3 levels and cytotoxicity in TBX2/TBX3-dependent melanoma and rhabdomyosarcoma cells. To this end, immunofluorescence, western blotting, quantitative real-time PCR, and MTT cell viability assays were performed.
RESULTS: Niclosamide, piroctone olamine, and pyrvinium pamoate, were identified as TBX2 and/or TBX3-targeting drugs, and they exhibited cytotoxicity in a TBX2/TBX3-dependent manner. Furthermore, these "Hit" drugs were shown to induce senescence and/or apoptosis.
CONCLUSIONS: Niclosamide, piroctone olamine, and pyrvinium pamoate are promising, cost-effective therapeutic agents for the treatment of TBX2/TBX3-dependent cancers.
PMID:39403898 | DOI:10.1002/cam4.70303
Int Cancer Conf J. 2024 Aug 10;13(4):476-480. doi: 10.1007/s13691-024-00712-3. eCollection 2024 Oct.
ABSTRACT
Space-making particle therapy, which consists of surgical placement of a spacer followed by particle therapy, has become a solution to the problem of normal organs being exposed to a high radiation dose. A bioabsorbable spacer is particularly suitable for this purpose, but is not widely used. Surgical placement of a spacer is performed mostly to protect the digestive tract, but can also be used to protect the kidneys. Therefore, we have been interested in the use of space-making particle therapy to preserve renal function. A 14 month-old boy with intermediate-risk retroperitoneal rhabdomyosarcoma underwent surgery with placement of a bioabsorbable spacer following neoadjuvant chemotherapy and then received proton beam therapy of 41.4 Gy (relative biological effectiveness) in 23 fractions. In the 41 months since PBT, he has survived without local recurrence or signs of renal impairment. This report describes the first-ever case of surgical placement of a bioabsorbable spacer with the aim of preserving renal function during proton beam therapy. Space-making particle therapy is an innovative solution for peritoneal tumors adjacent to the kidneys.
PMID:39398927 | PMC:PMC11465098 | DOI:10.1007/s13691-024-00712-3
Rev Esp Cardiol (Engl Ed). 2024 Oct 11:S1885-5857(24)00299-8. doi: 10.1016/j.rec.2024.09.007. Online ahead of print.
NO ABSTRACT
PMID:39396622 | DOI:10.1016/j.rec.2024.09.007
BMJ Open. 2024 Oct 11;14(10):e084477. doi: 10.1136/bmjopen-2024-084477.
ABSTRACT
BACKGROUND: Metronomic chemotherapy ('less is more, regularly') could be an alternative to the maximum tolerated dose ('the more, the better') in the chemotherapeutic cancer treatment of high-risk malignant solid extracranial tumours in children or young adults.
OBJECTIVE: To evaluate the efficacy of metronomic chemotherapy compared with placebo or stop treatment in paediatric patients with extracranial malignant solid tumours.
METHODS: We searched the databases MEDLINE and CENTRAL on 8 September 2023 and included randomised clinical trials (RCTs). Primary outcome was overall survival, and the main outcome measure was the HR.
RESULTS: We identified three RCTs with parallel assignment and intention-to-treat analyses of data from 775 people. The studies primarily reported on participants with rhabdomyosarcoma, neuroblastoma and osteosarcoma. The HR favoured the metronomic chemotherapy group (0.75 (95% CI 0.56 to 0.98)).
CONCLUSIONS: The evidence base is compatible with a favourable effect of metronomic chemotherapy on children and young adults with high-risk extracranial malignant solid tumours, especially other than bone tumours, when compared with placebo or stop treatment. Statistical heterogeneity is low while clinical heterogeneity is substantial. Thus, the results must be interpreted with caution and applicability of the results is limited. Future RCTs could provide more data on individual tumour entities and subsequently add information on tumour-specific responses.
PROSPERO REGISTRATION NUMBER: CRD42023457195.
PMID:39395824 | DOI:10.1136/bmjopen-2024-084477
J Surg Case Rep. 2024 Oct 10;2024(10):rjae634. doi: 10.1093/jscr/rjae634. eCollection 2024 Oct.
ABSTRACT
Giant cell carcinomas of the lung (GCCL) are aggressive tumors, with most patients having metastatic disease at presentation. However, giant cell carcinomas of the lungs are rare and account for 0.1%-0.4% of primary lung malignancies. Thus, the literature on the disease is limited. This case report presents an asymptomatic young patient with an incidental lung mass on a background of childhood abdominal rhabdomyosarcoma with lung metastasis. After undergoing surgical resection, the final tumor pathology was in keeping with primary giant cell carcinoma. The purpose of this case report is to contribute to the understanding of giant cell carcinomas of the lung.
PMID:39391204 | PMC:PMC11465411 | DOI:10.1093/jscr/rjae634
bioRxiv [Preprint]. 2024 Sep 26:2024.09.24.614809. doi: 10.1101/2024.09.24.614809.
ABSTRACT
Caspase activated DNase (CAD) induced DNA breaks promote cell differentiation and therapy-induced cancer cell resistance. CAD targeting activity is assumed to be unique to each condition, as differentiation and cancer genesis are divergent cell fates. Here, we made the surprising discovery that a subset of CAD-bound targets in differentiating muscle cells are the same genes involved in the genesis of cancer-causing translocations. In muscle cells, a prominent CAD-bound gene pair is Pax7 and Foxo1a, the mismatched reciprocal loci that give rise to alveolar rhabdomyosarcoma. We show that CAD-targeted breaks in the Pax7 gene are physiologic to reduce Pax7 expression, a prerequisite for muscle cell differentiation. A cohort of these CAD gene targets are also conserved in early differentiating T cells and include genes that spur leukemia/lymphoma translocations. Our results suggest the CAD targeting of translocation prone oncogenic genes is non-pathologic biology and aligns with initiation of cell fate transitions.
PMID:39386486 | PMC:PMC11463586 | DOI:10.1101/2024.09.24.614809
J Exp Clin Cancer Res. 2024 Oct 9;43(1):282. doi: 10.1186/s13046-024-03197-3.
ABSTRACT
BACKGROUND: Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma, with embryonal (ERMS) and alveolar (ARMS) representing the two most common histological subtypes. ARMS shows poor prognosis, being often metastatic at diagnosis. Thus, the discovery of novel biomarkers predictive of tumor aggressiveness represents one of the most important challenges to overcome and may help the development of tailored therapies. In the last years, miRNAs carried in extracellular vesicles (EVs), small vesicles of endocytic origin, have emerged as ideal candidate biomarkers due to their stability in plasma and their tissue specificity.
METHODS: EVs miRNAs were isolated from plasma of 21 patients affected by RMS and 13 healthy childrens (HC). We performed a miRNA profile using the Serum/Plasma Focus microRNA PCR panels (Qiagen), and RT-qPCR for validation analysis. Statistically significant (p < 0.05) miRNAs were obtained by ANOVA test.
RESULTS: We identified nine EVs miRNAs (miR-483-5p, miR-132-3p, miR-766-3p, miR-454-3p miR-197-3p, miR-335-3p, miR-17-5p, miR-486-5p and miR-484) highly upregulated in RMS patients compared to HCs. Interestingly, 4 miRNAs (miR-335-5p, miR-17-5p, miR-486-5p and miR-484) were significantly upregulated in ARMS samples compared to ERMS. In the validation analysis performed in a larger group of patients only three miRNAs (miR-483-5p, miR-335-5p and miR-484) were differentially significantly expressed in RMS patients compared to HC. Among these, mir-335-5p was significant also when compared ARMS to ERMS patients. MiR-335-5p was upregulated in RMS tumor tissues respect to normal tissues (p = 0.00202) and upregulated significantly between ARMS and ERMS (p = 0.04). Furthermore, the miRNA expression correlated with the Intergroup Rhabdomyosarcoma Study (IRS) grouping system, (p = 0.0234), and survival (OS, p = 0.044; PFS, p = 0.025). By performing in situ hybridization, we observed that miR-335-5p signal was exclusively in the cytoplasm of cancer cells.
CONCLUSION: We identified miR-335-5p as significantly upregulated in plasma derived EVs and tumor tissue of patients affected by ARMS. Its expression correlates to stage and survival in patients. Future studies are needed to validate miR-335-5p as prognostic biomarker and to deeply elucidate its biological role.
PMID:39385294 | PMC:PMC11463097 | DOI:10.1186/s13046-024-03197-3
Histopathology. 2024 Oct 9. doi: 10.1111/his.15341. Online ahead of print.
ABSTRACT
AIMS: CIC-rearranged sarcomas (CRS) are clinically aggressive undifferentiated round cell sarcomas (URCS), commonly driven by CIC::DUX4. Due to the repetitive nature of DUX4 and the variability of the fusion breakpoints, CIC::DUX4 fusion may be missed by molecular testing. Immunohistochemical (IHC) stains have been studied as surrogates for the CIC::DUX4 fusion. We aim to assess the performance of DUX4 IHC in the work-up of CRS and its expression in non-CRS round cell or epithelioid neoplasms.
METHODS AND RESULTS: Cases of molecularly confirmed CRS (n = 48) and non-CRS (n = 105) were included. CRS cases consisted of 35 females and 13 males, with ages ranging from less than 1 year to 67 years (median = 41 years). Among the molecularly confirmed non-CRS cases, C-terminal DUX4 expression was investigated in Ewing sarcomas (38 cases), alveolar rhabdomyosarcomas (18 cases), desmoplastic small round cell tumours (12 cases) and synovial sarcomas (n = five), as well as in non-mesenchymal neoplasms such as SMARCA4/SMARCB1-deficient tumours (n = five), carcinomas of unknown primary (n = three) and haematolymphoid neoplasms (four cases). DUX4 IHC was considered positive when strong nuclear expression was detected in more than 50% of neoplastic cells. When used as a surrogate for the diagnosis of CRS, the sensitivity and specificity of DUX4 IHC was 98 and 100%, respectively. Only one CRS case was negative for DUX4 IHC and harboured a CIC::FOXO4 fusion.
CONCLUSIONS: DUX4 IHC is a highly sensitive and specific surrogate marker for the presence of CIC::DUX4 fusion, demonstrating its utility in establishing a diagnosis of CRS.
PMID:39381843 | DOI:10.1111/his.15341
Pediatr Blood Cancer. 2024 Oct 8:e31385. doi: 10.1002/pbc.31385. Online ahead of print.
NO ABSTRACT
PMID:39380199 | DOI:10.1002/pbc.31385
Diagn Pathol. 2024 Oct 8;19(1):135. doi: 10.1186/s13000-024-01555-5.
ABSTRACT
BACKGROUND: Embryonal rhabdomyosarcoma (ERMS) is a highly aggressive form of soft-tissue sarcoma that predominantly affects children. Due to limited benefits and resistance to therapy, there is an unmet need to explore alternative therapeutic strategies.
CASE PRESENTATION: In this report, we present a rare case of pediatric ERMS located on the right side of the maxillary gingiva. A composite reference guide integrating clinical, radiographic, and histopathologic findings was used for a definitive diagnosis. Targeted next-generation sequencing of tumor biopsy was performed to identify genetic alterations. A 12-year-old female was admitted to the Pediatric Intensive Care Unit (PICU) and underwent a tracheotomy to relieve asphyxiation caused by a 5.5 cm diameter mass compressing the tongue root and pharyngeal cavity. Hematoxylin and eosin staining revealed a hybrid morphology characterized by clusters of round and spindle cells. Further immunohistochemistry assays indicated positive immunoreactivity for desmin, myogenin, and MyoD1. Various genetic alterations were identified, including mutations in GNAS, HRAS, LRP1B, amplification of MDM2 and IGF1R, and two novel IGF1R fusions. Negative PAX-FOXO1 fusion status supported the clinical diagnosis of ERMS. Initial treatment involved standard chemotherapy; however, the tumor persisted in its growth, reaching a maximum volume of 12 cm × 6 cm × 4 cm by the completion of treatment. Subsequent oral administration of anlotinib yielded a significant antitumor response, characterized by substantial tumor necrosis and size reduction. Following the ligation of the tumor pedicle and its removal, the patient developed a stabilized condition and was successfully discharged from PICU.
CONCLUSIONS: Our study highlights the importance of accurate diagnosis established on multifaceted assessment for the effective treatment of ERMS. We present compelling evidence supporting the clinical use of anlotinib as a promising treatment strategy for pediatric ERMS patients, especially for those resistant to conventional chemotherapy.
PMID:39379998 | PMC:PMC11460102 | DOI:10.1186/s13000-024-01555-5
Clin Transl Radiat Oncol. 2024 Sep 18;49:100862. doi: 10.1016/j.ctro.2024.100862. eCollection 2024 Nov.
ABSTRACT
BACKGROUND: Perianal rhabdomyosarcoma ((P)RMS) are rare and have a poor prognosis. Data in young children are limited and local therapy is not well defined. Combined brachytherapy and surgery is routinely being used for RMS at other sites in children as it provides good oncologic outcomes and allows for organ-sparing surgery. The objective of this study was to evaluate this combination treatment for local tumor control and organ-sparing surgery in young children with (P)RMS.
METHODS: A retrospective review of the medical records of all children who underwent surgery and brachytherapy for (P)RMS at our institution since 2009 was conducted.
RESULTS: Surgery for (P)RMS was performed in 6 patients at a median age of 19 months (range 8-50). Embryonal RMS was diagnosed in 4 patients and alveolar RMS in 2 patients, of which 1 patient had FOXO1 fusion-positive RMS. All patients underwent postoperative high-dose rate (HDR) brachytherapy. Organ-preserving surgery was achieved in 5 of 6 patients (83 %). In 1 patient, the entire sphincter was infiltrated, making organ-preserving resection impossible. 5 of 6 patients (83 %) exhibited an event-free and overall survival at a median follow-up of 26 months (range 8-107). One patient died due to locoregional recurrence. Complications were urethral leakage in 1 patient followed by urethral stenosis and delayed wound healing and vaginal stenosis in another patient. No patient reported fecal incontinence.
CONCLUSIONS: Combined treatment with surgery and HDR brachytherapy is feasible in very young children with (P)RMS and leads to a favorable oncologic outcome. Preliminary data show a good functional preservation.
PMID:39376617 | PMC:PMC11456901 | DOI:10.1016/j.ctro.2024.100862
Pediatr Blood Cancer. 2024 Oct 7:e31366. doi: 10.1002/pbc.31366. Online ahead of print.
ABSTRACT
BACKGROUND: Treatment options for advanced intra-abdominal pediatric rhabdomyosarcoma (RMS) with peritoneal sarcomatosis (PS) include cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). However, optimal dosages and combination regimens of drugs used for HIPEC are underexplored. We aimed to evaluate the efficacy of HIPEC with cisplatin, doxorubicin, and their combination in vivo.
METHODS: We established PS/RMS mouse model by intraperitoneally injecting RH30 cells into NOD/LtSz-scid IL2Rγ-null mice. Two weeks post xenotransplantation, mice underwent a single HIPEC procedure at 42°C for 60 minutes. Treatment groups received cisplatin (50, 100, and 150 mg/m2) and doxorubicin (30, 45, and 60 mg/m2), administered alone or combined. The control group underwent an intraperitoneal lavage with isotonic saline. Peritoneal cancer index (PCI) was used to quantify the extent of peritoneal tumor spread. Tissue samples were evaluated regarding proliferation (Ki-67) and apoptosis (caspase 3).
RESULTS: Mice treated with cisplatin at 100 mg/m2 (PCI of 3.875, p = .007) and 150 mg/m2 (PCI of 4.556, p = .026), and doxorubicin at 30 mg/m2 (PCI of 2.875, p < .001) and 45 mg/m2 (PCI of 4.143, p = .021) showed reduced PCI, with the combination of cisplatin 50 mg/m2 and doxorubicin 30 mg/m2 showing the most prominent effect (PCI of 3.333, p < .001) compared to the control group (PCI of 8.615). Histologically, there was no difference in Ki-67 or caspase 3 expression among the groups.
CONCLUSIONS: The cisplatin- and doxorubicin-based HIPEC significantly reduces peritoneal tumor dissemination in vivo. Further investigations are needed to explore the underlying molecular responses to optimize therapeutic strategies.
PMID:39375886 | DOI:10.1002/pbc.31366
Eur J Case Rep Intern Med. 2024 Sep 26;11(10):004820. doi: 10.12890/2024_004820. eCollection 2024.
ABSTRACT
BACKGROUND: Sarcomas of the breast are exceedingly rare, accounting for less than 1% of malignant breast tumors, with primary rhabdomyosarcomas being even rarer. Due to the scarcity of reported cases, the imaging characteristics of breast rhabdomyosarcoma are not well-defined, making diagnosis challenging, especially in adolescents.
CASE DESCRIPTION: We present the case of a 17-year-old female diagnosed with embryonal rhabdomyosarcoma following a comprehensive workup for right breast masses. Initial imaging showed no distant metastasis, and the patient underwent a right mastectomy followed by adjuvant chemoradiotherapy. A few months post-treatment, she developed recurrent nodules in the chest wall. Further investigation confirmed the recurrence of embryonal rhabdomyosarcoma.
CONCLUSIONS: This case underscores the importance of considering primary rhabdomyosarcoma as a differential diagnosis in adolescent breast lesions. Given its rare occurrence and potential imaging overlap with more common tumors like cystosarcoma phyllodes, awareness and careful evaluation are critical for accurate diagnosis and timely management.
LEARNING POINTS: Critical imaging insights: The report provides valuable imaging characteristics that can help differentiate rhabdomyosarcoma from more common breast tumors like fibroadenoma and cystosarcoma phyllodes, resulting in more accurate and timely diagnosis.
PMID:39372159 | PMC:PMC11451838 | DOI:10.12890/2024_004820
J Pediatr Surg. 2024 Sep 14:161928. doi: 10.1016/j.jpedsurg.2024.161928. Online ahead of print.
ABSTRACT
BACKGROUND/PURPOSE: Rhabdomyosarcoma risk stratification is traditionally determined by tumor histology and staging. Recent studies revealed the importance of molecular features in predicting prognosis. We investigated prognosis by age of onset and mutation incidence in rhabdomyosarcoma tumors.
METHODS: We retrospectively extracted clinical and genomic data from the Clinomics dataset (n = 641). Inclusion criteria was tumors with at least one gene mutation with >5% mutation incidence. Exclusion criteria were unknown risk stratification and age of onset. Statistical analysis was performed using ANOVA (p < 0.05) and Tukey's HSD to compare mutation incidence, EFS, and OS among age groups.
RESULTS: Among 641 patients with rhabdomyosarcoma, 8 of 39 screened genes had >5% mutation incidence: NRAS, BCOR, NF1, TP53, FGFR4, KRAS, HRAS, and CTNNB1. The final cohort consisted of 370 patients: 51 (Age: 0-2 Years), 140 (Age: 2-5 Years), 112 (Age: 5-12 Years) and 67 (Age: 12+). Later age of onset is associated with higher incidence of BCOR and HRAS mutations (p < 0.005, p < 0.001) and poorer EFS and OS (p < 0.05, p < 0.001). In patients with BCOR mutations, later age of onset is associated with poorer EFS and OS (p < 0.005, p < 0.001). NF1 mutations are equally distributed among age groups (p = 0.82), but later age of onset is associated with poorer EFS and OS (p < 0.005, p < 0.001).
CONCLUSION: In patients with at least one mutation in BCOR, NF1, TP53, KRAS, HRAS, or CTNNB1, later age of onset is associated with poorer prognosis. In patients with mutations only in tumor suppressor genes BCOR or NF1, later age of onset is associated with poorer prognosis.
TYPE OF STUDY: Retrospective Cohort Study.
LEVEL OF EVIDENCE: II.
PMID:39368853 | DOI:10.1016/j.jpedsurg.2024.161928
Adv Radiat Oncol. 2024 Jun 29;9(8):101561. doi: 10.1016/j.adro.2024.101561. eCollection 2024 Aug.
ABSTRACT
PURPOSE: To describe early tumor volume change in patients with rhabdomyosarcoma (RMS) and investigate its association with overall survival (OS) and local failure.
METHODS AND MATERIALS: This retrospective study included patients who received diagnoses of group III/IV RMS with available computed tomography and/or magnetic resonance imaging scans at 2 time points: (1) pretherapy and (2) early therapy (acquired during weeks 8-12 of chemotherapy). Relative volumetric change (RVC) was calculated as the percentage of (early therapy - pretherapy volume) / (pretherapy volume). Cox regression was used to identify variables associated with OS. The Fine-Gray model was used to estimate local failure.
RESULTS: Eligible patients (n = 55) had the following characteristics: median age at diagnosis, 9.6 years and median follow-up, 30.4 months. Most tumors were alveolar (61.8%), followed by embryonal (34.6%) and spindle cell/sclerosing (4%). The median RVC was -86.4% with larger decreases observed in alveolar versus nonalveolar RMS (-89.4% vs -69.8%, P = .043). For embryonal and spindle cell/sclerosing RMS, all of which were FOXO1 fusion negative, RVC was independently associated with OS (hazard ratio for every 50% reduction in RVC [HRRVC], 0.5; 95% CI, 0.26-0.96; P = .037) and local failure (HRRVC, 0.57; 95% CI, 0.33-0.99; P = .049). The predominant pattern of failure in embryonal and spindle cell/sclerosing RMS was local, and most were group III.
CONCLUSIONS: There was a greater reduction in tumor volume in alveolar versus nonalveolar RMS. Early tumor volume reduction was associated with OS and local failure in embryonal or spindle cell/sclerosing RMS, all of which were confirmed FOXO1 fusion negative and had higher incidence of local compared with distant failures.
PMID:39346695 | PMC:PMC11427727 | DOI:10.1016/j.adro.2024.101561
Pediatr Blood Cancer. 2024 Sep 29:e31344. doi: 10.1002/pbc.31344. Online ahead of print.
ABSTRACT
BACKGROUND: Osteosarcoma may arise as a secondary malignancy following rhabdomyosarcoma (RMS). We utilized the Cooperative Osteosarcoma Study Group (COSS) database to better understand this association.
PATIENTS AND METHODS: The COSS database (1980-05/2023) was searched for patients whose osteosarcoma was preceded by RMS. Eligible patients were analyzed for patient-, tumor-, and treatment-related variables as well as outcomes.
RESULTS: The search revealed 28 eligible osteosarcomas (27 high-grade central, one periosteal; male:female = 16:12; median age RMS 2.1 [range: 0.9-10.0] years, osteosarcoma 13.5 [7.2-29.0] years). Genetic tumor-predisposition syndromes were documented in 12 patients. One patient had had a distinct malignancy prior to RMS, two intermittently, seven following osteosarcoma. Local RMS treatment had included radiotherapy in 20/26 cases (two unknown). Secondary osteosarcoma sites were extremity 13, trunk seven, head and neck eight; 15 osteosarcomas were radiation-associated. There was only one case of primary osteosarcoma metastases. Osteosarcoma treatment included chemotherapy (27), surgery (26), or radiotherapy (2). A macroscopically complete remission of all osteosarcoma sites was achieved in 24 cases. Median follow-up was 5.8 (range: 0.5-18.4) years after osteosarcoma and 8.1 (1.0-15.4) years for 14 survivors. Actuarial 5-year overall and event-free survival were 66% (standard error 9%) and 45% (10%), respectively. Five of 14 deaths were caused by further malignancies.
CONCLUSION: This series offers a benchmark for patients who develop a secondary osteosarcoma after RMS. Affected patients are generally still in the pediatric age. The results obtained strongly argue for genetic predisposition testing in RMS and against therapeutic leniency in comparable situations.
PMID:39344062 | DOI:10.1002/pbc.31344
Asian Pac J Cancer Prev. 2024 Sep 1;25(9):3051-3057. doi: 10.31557/APJCP.2024.25.9.3051.
ABSTRACT
BACKGROUND: Prodigiosin is a naturally occurring compound produced by various bacteria, including Serratia marcescens. It is known for its diverse biological properties. The present study was conducted to extract and purify prodigiosin from Serratia marcescens and investigate its anticancer and immunomodulatory activities.
METHODS: S. presence was isolated from soil samples and characterized. Different solvents were used to extract prodigiosin from Serratia marcescens. The cytotoxic activity of prodigiosin was tested against human rhabdomyosarcoma (RD), rat embryo fibroblasts (REF), and human breast cancer MDA-MB-231 (MDA) epithelial cell lines. Albino mice were divided into six groups: Negative control (normal saline); positive control (injected with 100 µ l of Serratia marcesence); groups A-D were injected with 100 µ l of prodigiosin (1, 3, 6, and 9 µ g/mouse, respectively). After 14 days of treatment, whole blood samples were collected for immunomodulatory analysis.
RESULTS: The study found that the highest yield of prodigiosin (65-230 mg/l) was obtained with methanol as the extraction solvent. Prodigiosin had a cytotoxic effect on cancer cells, particularly against MDA epithelial cells. However, it did not have a cytotoxic effect on normal cells. Immunological analysis revealed significant differences (p ≤ 0.01) in absolute neutrophil counts between the positive control and prodigiosin-treated groups, with the highest value in group C and the lowest in group A. Immunological analysis showed significant differences in neutrophil counts, IL-4, and IL-10 levels between prodigiosin-treated groups and the control group.
CONCLUSION: Serratia marcescens prodigiosin showed cytotoxic effects on cancer cells and boosted IL-10 and IL-4 serum levels, acting as an immunomodulator.
PMID:39342582 | DOI:10.31557/APJCP.2024.25.9.3051
Childs Nerv Syst. 2024 Sep 28. doi: 10.1007/s00381-024-06583-6. Online ahead of print.
ABSTRACT
BACKGROUND: Rhabdomyosarcoma (RMS) is the most prevalent soft tissue sarcoma in children, with approximately 30% of head and neck RMS occurring in the orbit. The management of orbital RMS is complex, requiring a multidisciplinary approach and careful surgical planning. The objective of the present paper is to provide the neurosurgeon with an update on this challenging tumor.
CASE DESCRIPTION: A 12-year-old boy was admitted to our department after the onset of diplopia in his right eye, associated with quickly worsening ipsilateral eyelid edema and mild proptosis. MRI revealed an anterior superomedial, extraconal, and intraorbital expansive lesion. Complete tumor removal was performed through a trans-orbital approach. Histological diagnosis of embryonal RMS was done. The patient underwent radio-chemotherapy in accordance with the EpSSG RMS2005 subgroup C protocol. The patient is alive and disease-free.
DISCUSSION AND CONCLUSION: The intricacies of treating orbital tumors necessitate meticulous planning to safeguard vital structures while guaranteeing comprehensive oncological treatment. A multidisciplinary approach with a specific protocol depending on the location and characteristics of the tumor is required. The available treatment options include surgical intervention or combination therapies, such as chemotherapy and radiotherapy. The successful management of these diseases depends on the careful coordination and application of the available techniques.
PMID:39340563 | DOI:10.1007/s00381-024-06583-6
Biomolecules. 2024 Sep 20;14(9):1180. doi: 10.3390/biom14091180.
ABSTRACT
Rhabdomyosarcoma (RMS), the most common form of sarcoma typical of pediatric age, arises from the malignant transformation of the mesenchymal precursors that fail to differentiate into skeletal muscle cells. Here, we investigated whether the protein phospholipase C δ4 (PLCδ4), a member of the PLC family involved in proliferation and senescence mechanisms of mesenchymal stromal stem cells, may play a role in RMS. Our molecular and morpho-functional data reveal that PLCδ4 is highly expressed in the fusion-negative, p53-positive, SMARCB1 heterozygous mutated embryonal RMS (ERMS) cell line A204, while it is poorly expressed in the ERMS cell lines RD (fusion-negative, MYC amplification, N-RAS (Q61H), homozygous mutated p53) and Hs729 (homozygous mutated p53) and the alveolar rhabdosarcoma (ARMS) cell line SJCRH30 (RH30; fusion positive, heterozygous mutated RARA, polyheterozygous mutated p53). To characterize the role of PLCδ4, the RD cell line was stably transfected with wild-type PLCδ4 (RD/PLCδ4). Overexpressed PLCδ4 mainly localized to the nucleus in RD cells and contributed to the phosphorylation of PRAS40 (T246), Chk2(T68), WNK1(T60), and Akt 1/273 (S473), as revealed by proteome profiler array analysis. Overexpression of PLCδ4 in RD cells enhanced cyclin B1 expression and resulted in G2/M-phase cell cycle arrest. In contrast, siRNA-mediated knockdown of PLCδ4 in A204 cells resulted in reduced cyclin B1 expression. Our study identifies a novel role for nuclear PLCδ4 as a regulator of cyclin B1 via Akt-dependent phosphorylation. The modulation of PLCδ4 expression and its downstream targets could represent a crucial signaling pathway to block embryonal RMS cell proliferation.
PMID:39334946 | PMC:PMC11430102 | DOI:10.3390/biom14091180
J Fungi (Basel). 2024 Sep 14;10(9):654. doi: 10.3390/jof10090654.
ABSTRACT
We analyzed data on pediatric invasive fungal diseases of the central nervous system (CNS-IFDs) reported by five of a total of eight Pediatric Hematology-Oncology Departments in Greece for 16 years (2007-2022). A total of twelve patients (11 boys, median age: 9.5 years, range: 2-16) were reported suffering from CNS-IFDs. The underlying malignancy was acute lymphoblastic leukemia in 9/12 and acute myeloid leukemia, Ewing sarcoma, and rhabdomyosarcoma in one each. Eleven patients presented with CNS-related symptoms (i.e., seizures, headache, cerebral palsy, ataxia, hallucination, seizures, blurred vision, amaurosis). All patients had pathological MRI findings. Multifocal fungal disease was observed in 6/12 patients. Nine proven and three probable CNS-IFD cases were diagnosed. Causative pathogens in proven cases were Aspergillus spp. and Candida albicans (n = 2 each), Mucor spp., Rhizopus arrhizus, Absidia spp., Fusarium oxysporum and Cryptococcus neoformans (n = 1 each). Causative pathogens in probable cases were Aspergillus spp. (n = 2) and Candida spp. (n = 1). All patients received appropriate antifungal therapy (median duration: 69.5 days, range 19-364). Two patients underwent additional surgical treatment. Six patients were admitted to the Intensive Care Unit due to complications. Three patients (25%) died, two due to IFD and one due to an underlying disease. Early recognition and prompt intervention of CNS-IFDs may rescue the patients and improve overall survival.
PMID:39330414 | PMC:PMC11433548 | DOI:10.3390/jof10090654
Indian J Surg Oncol. 2024 Sep;15(Suppl 3):408-413. doi: 10.1007/s13193-024-01980-4. Epub 2024 Jun 11.
ABSTRACT
Invasive breast cancer, no special type, is the most frequent subtype of breast malignancy encountered as compared to secondary breast cancer. The most common tumors metastasizing to the breast include lymphoma and melanoma. Rhabdomyosarcoma (RMS) is a common soft-tissue neoplasm in the paediatric population, often seen in regions such as the head and neck, genitourinary system, trunk, and extremities. While metastatic RMS to the breast is uncommon, it tends to occur primarily in adolescent girls, with the alveolar variant being the most frequently encountered. In this case presentation, we describe the unique instance of a 17-year-old girl admitted to the hospital with quadriplegia which on initial clinical evaluation was diagnosed as disseminated tuberculosis involving the spine (Pott's spine), but on further cytologic and histopathologic assessment revealed the unexpected diagnosis of rhabdomyosarcoma. This case draws attention to the unusual occurrence of rhabdomyosarcoma metastasis to bilateral breasts, that to with an embryonal morphology, and underscores the challenge of identifying the primary site of this rare manifestation.
PMID:39328719 | PMC:PMC11422538 | DOI:10.1007/s13193-024-01980-4
Genes Chromosomes Cancer. 2024 Sep;63(9):e23274. doi: 10.1002/gcc.23274.
NO ABSTRACT
PMID:39324699 | DOI:10.1002/gcc.23274
Head Neck. 2024 Sep 25. doi: 10.1002/hed.27933. Online ahead of print.
ABSTRACT
PURPOSE: This study analyzed the demographics, clinicopathological, treatment, and survival characteristics of head and neck sarcomas (HNS) diagnosed in a tertiary reference center in Brazil.
MATERIALS AND METHODS: HNS cases were retrospectively retrieved from the Department of Pathological Anatomy of the School of Medical Sciences of the State University of Campinas. The medical records were examined to extract demographic, clinicopathological, and follow-up information. The Pearson chi-square test, Kaplan-Meier curve, and Cox proportional hazards regression model were employed to identify survival and potential prognostic factors.
RESULTS: A total of 47 patients were included in the study. The majority were men (61.7%) with a mean age of 38.9 years. The nasal cavity (34.0%) was the most common anatomical site. The lesions are usually presented as volume increases (78.7%). The most common histological subtypes were chondrosarcoma, osteosarcoma, and alveolar rhabdomyosarcoma. Surgical excision alone was the most common treatment modality. Local recurrence was observed in 10 cases, and metastases in 3 cases. During a mean follow-up period of 71.9 months, from diagnosis to the last follow-up, 31 patients (65.9%) were alive without the disease. A total of 10 patients (21.3%) died of the HNS for a mean follow-up period of 14.3 months. The time to presentation of more than 6 months (p = 0.0309) and the presence of metastases (p = 0.0315) were identified as prognostic factors for survival, while male sex was found to be an independent prognostic factor for recurrence.
CONCLUSION: In conclusion, the results of this study indicate that the occurrence of a shorter lesion time to presentation and the presence of metastases were associated with a reduction in survival rates in patients with HNS.
PMID:39323102 | DOI:10.1002/hed.27933
iScience. 2024 Aug 31;27(10):110862. doi: 10.1016/j.isci.2024.110862. eCollection 2024 Oct 18.
ABSTRACT
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood and adolescence. The availability of appropriate and well-characterized preclinical models for RMS is limited, posing a challenge for investigating the molecular mechanisms and evaluating new targeted compounds in preclinical settings. Here, we collected 51 RMS specimens (referred to as ZJUCH-RMS cohort) and established 9 patient-derived cells (PDCs) and validated the identity of these cells by the expression of RMS-specific markers. Whole-transcriptome analysis identified high-confidence mutations in ZJUCH-RMS cohort including RAS, TP53, ARID1A, MYOD1, and MYCN. Further studies showed that RMS PDCs retained the genetic alterations and the expression of RMS hallmark and dependency genes in matched primary tumors and acted as valuable tools to assess drug responses and pharmacogenomic interactions. Our study provides unique PDCs that are available for preclinical studies of RMS and further advances the feasibility of RMS PDCs as valuable tools for developing personalized treatments for patients.
PMID:39319271 | PMC:PMC11417342 | DOI:10.1016/j.isci.2024.110862
Health Sci Rep. 2024 Sep 23;7(9):e70084. doi: 10.1002/hsr2.70084. eCollection 2024 Sep.
ABSTRACT
BACKGROUND AND AIM: Globally, over 180,000 children develop cancers yearly, with about 80% residing in low- or middle-income countries where cancer-associated mortality is also high. In The Gambia, cumulative incidence rate of 27.6 childhood cancers/million population was reported between 2002 and 2011. The current study appraised newly-established pediatric oncological services in The Gambia.
METHODS: In this prospective registry study, children with cancer who presented at the pediatric units, Edward Francis Small Teaching Hospital, Banjul, between November 2022 and October 2023 were assessed. Data on sociodemographic variables, mode of admission and presentation, tumor type, diagnostic methods, and challenges such as laboratory support, treatment, use of blood/blood products; and eventual outcome were analyzed.
RESULTS: The median (interquartile range, IQR) age at presentation of the 44 children was 36.0 (22.3-117.0) months. Wilms tumor was the most common tumor 12 (27.3%); followed by leukemia 11 (25.0%); germ cell tumor 8 (18.2%); lymphoma 6 (13.6%); retinoblastoma 4 (9.1%); rhabdomyosarcoma 2 (4.5%) and one central nervous system tumor (2.3%). The median(IQR) duration of symptoms before presentation was 48 (21-90) days, presentation to diagnosis 7.5 (3-20.8) days, and first symptom to diagnosis 62.5 (32-126.8) days. Treatment refusal and abandonment rates were 20.5% and 13.6%, respectively. Families of 93.8% of children could not procure cytotoxic drugs due to nonavailability, high cost, or both. Adequate laboratory monitoring was only available in 6.8%, and none had platelet concentrate transfusion or radiotherapy. The nine (20.5%) who completed treatment are currently being followed up, 10(22.7%) are still receiving chemotherapy, while 2(4.5%) were referred. Eight (18.2%) died, predominantly from metastasis (75%) and severe drug toxicities (25%).
CONCLUSION: Late presentation and diagnosis, poverty, unavailability of drugs, suboptimal or lack of laboratory testing, blood product, adjuvant medications, and psychosocial supports contributed to high treatment refusal, abandonment, and mortality. These daunting challenges can be ameliorated with regular community sensitization, frequent cancer auditing, and strong political will.
PMID:39319248 | PMC:PMC11420287 | DOI:10.1002/hsr2.70084
Ear Nose Throat J. 2024 Sep;103(2_suppl):22S-25S. doi: 10.1177/01455613241281550. Epub 2024 Sep 24.
ABSTRACT
Awake tracheostomy is rare in the pediatric population. We describe the case of a 10-year-old male who underwent awake tracheostomy due to airway obstruction from an oropharyngeal rhabdomyosarcoma. Given the varying medical understanding and communication skills in children, advanced planning and interdisciplinary collaboration are essential to keep the patient calm and safe during awake tracheostomy.
PMID:39315816 | DOI:10.1177/01455613241281550
Ann Surg Oncol. 2024 Sep 23. doi: 10.1245/s10434-024-16258-w. Online ahead of print.
ABSTRACT
BACKGROUND: This study aimed to examine clinicopathologic characteristics, treatment patterns, and survival rates in a contemporary population-based cohort of adult prostate sarcoma patients.
METHODS: In the Surveillance, Epidemiology, and End Results database (2004-2020), adult patients with prostate sarcoma were identified. Descriptive statistics, Kaplan-Meier analyses, smoothed cumulative incidence plots, and Cox regression models were used.
RESULTS: Of 125 patients, 45 (36%) harbored leiomyosarcoma, 17 (14%) had rhabdomyosarcoma, 15 (12%) had stromal sarcoma, 17 (14%) had sarcoma not otherwise specified (NOS), and 31 (25%) had other sarcoma subtypes. Metastatic stage was most common in the rhabdomyosarcoma patients (44%) and least common in the leiomyosarcoma (21%) and stromal sarcoma (20%) patients. Most of the rhabdomyosarcoma patients received the combination of systemic and radiation therapy with (24%) or without radical surgery (35%), whereas most of the leiomyosarcoma and stromal sarcoma patients underwent radical surgery with (22 and 13%) or without (22 and 47%) radiation. In the overall population, the median overall survival was 27 months. The 5-years overall versus cancer-specific versus other-cause mortality rates were respectively 71 versus 58 versus 13%. In the multivariable Cox regression models, the highest overall mortality was exhibited by the patients with metastatic disease (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.55-5.31; p < 0.001) or unknown disease stage (HR 2.94; 95% CI 2.20-7.21; p = 0.019). Conversely, of all the histologic subtypes, only stromal sarcoma distinguished itself by lower overall mortality (HR 0.41; 95% CI 0.18-0.96; p = 0.039).
CONCLUSIONS: Four major histologic subtypes were identified. Among most adult sarcoma patients, treatment patterns vary according to histology, from multimodal therapy to radical prostatectomy alone. These treatment differences reflect equally important heterogeneity in survival patterns.
PMID:39313727 | DOI:10.1245/s10434-024-16258-w
Radiol Case Rep. 2024 Sep 12;19(12):5794-5797. doi: 10.1016/j.radcr.2024.08.096. eCollection 2024 Dec.
ABSTRACT
Botryoid rhabdomyosarcoma is a rare and aggressive malignancy that primarily affects the female genital tract in children. It arises from embryonal rhabdomyoblasts. The vagina is the most common site, but it can also occur, although rarely, in the cervix or uterine fundus. We report the case of a 2-year-old girl who presented with a rapidly growing mass in the vulvar region. A pelvic MRI revealed a grape-like mass occupying the vaginal lumen, suggestive of botryoid rhabdomyosarcoma. Biopsy of the mass confirmed the diagnosis.
PMID:39308616 | PMC:PMC11416461 | DOI:10.1016/j.radcr.2024.08.096
Int J Radiat Oncol Biol Phys. 2024 Sep 20:S0360-3016(24)03405-9. doi: 10.1016/j.ijrobp.2024.09.037. Online ahead of print.
ABSTRACT
INTRODUCTION: Rhabdomyosarcoma (RMS) is the most common soft tissue cancer in children. Around 15% of RMS involve the bladder and/or prostate (BP). Overall survival is around 85%. After chemotherapy, patients receive local treatment based on surgery and/or radiotherapy. In recent decades, image guidance and pulsed dose-rate (PDR) brachytherapy have made it possible to personalize treatment, reduce radiation-related toxicity, while maintaining a good tumor control. We report one of the largest series of image-guided brachytherapy for pediatric RMS BP.
MATERIAL AND METHODS: The clinical and dosimetric parameters of children treated with brachytherapy for BP RMS between July 2014 and September 2020 were retrospectively reviewed. Patients were treated with a multimodal conservative approach, combining partial conservative surgery (preservation of the bladder neck and urethra), followed by an interstitial brachytherapy procedure. Iridium-192 PDR treatment was administered on the basis of CT and MRI planning. Toxicities were reported according to version 4.0 of the Common Terminology Criteria for Adverse Events.
RESULTS: A total of 75 patients were identified, with a median age of 29 months (range 2-84) at diagnosis. The median brachytherapy dose was 60.06 Gy (143 pulses, 0.42 Gy/pulse). With a median follow-up of 44.1 months (range 0.7-90), the 5-year OS and PFS rates were 97.3% and 92% respectively. Median D50% for the bladder and D1cc for the rectum were 38.6 Gy and 49 Gy respectively. The 5-year probability of survival without severe late urinary toxicity (grade 3 or higher) was estimated at 78.8% (CI95%: 68.1-91.1). A total of 9.3% of children experienced grade 2 or 3 late rectal toxicity.
CONCLUSIONS: Image-guided PDR brachytherapy offers a personalized treatment for pediatric BP RMS, with a favorable therapeutic index. No prognostic factors for urinary toxicity have been identified. Multicenter studies with larger numbers of patients are needed to clarify these data.
PMID:39307320 | DOI:10.1016/j.ijrobp.2024.09.037
Gene Ther. 2024 Sep 21. doi: 10.1038/s41434-024-00488-4. Online ahead of print.
ABSTRACT
Gallbladder cancer (GBC) is highly aggressive and has poor prognosis, with most patients only diagnosed at an advanced stage. Furthermore, treatment options are limited, and their effect is unsatisfactory. Bromodomain-containing protein (BRD) is an epigenetic regulator that plays a carcinogenic role in several tumors, including squamous cell lung cancer, acute myeloid leukemia, synovial sarcoma, and malignant rhabdomyosarcoma. However, the expression, biological function, and molecular mechanisms of action of BRD9 in GBC are still unknown. Kaplan-Meier analysis, qRT-PCR, and analysis of clinical features were used to assess the clinical significance of BRD9 in GBC. Cell Counting Kit-8 and colony formation assays were performed to determine the effects of BRD9 on cell growth. The functional role of BRD9 in GBC was explored using qRT-PCR, western blotting, siRNA, and CHIP-qPCR. mRNA sequencing was performed to explore the underlying mechanisms of BRD9, and a nude mouse model of GBC was established to explore the anti-tumor effects of the BRD9 inhibitor I-BRD9 in vivo. BRD9 expression was elevated in GBC tissues compared with adjacent non-tumor tissues, and high BRD9 expression was associated with poor prognosis in patients with GBC. BRD9 knockdown by siRNA significantly decreased cell growth. Targeting BRD9 with I-BRD9 inhibited the proliferation of GBC cells without significant toxic effects. Additionally, I-BRD9 treatment suppressed CST1 expression in GBC cell lines, thereby inhibiting the PI3K-AKT pathway. The transcription factor FOXP1 was found to interact with BRD9 to regulate CST1 expression. Collectively, these results suggest that BRD9 may be a promising biomarker and therapeutic target for GBC.
PMID:39306629 | DOI:10.1038/s41434-024-00488-4
J Surg Res. 2024 Sep 19;303:117-124. doi: 10.1016/j.jss.2024.08.018. Online ahead of print.
ABSTRACT
INTRODUCTION: Advanced retroperitoneal sarcoma (RPS) can include unresectable locoregional disease, systemic or multifocal intra-abdominal metastasis, or abdominal sarcomatosis, all of which are associated with high morbidity and may be addressed through palliative therapy. Current trends in the use of palliative therapy and factors associated with its use in patients with advanced RPS remain largely unexplored. The objectives of this study are to (1) describe the temporal trend in the use of palliative therapy and (2) identify factors associated with its use in patients with advanced RPS in the United States from 2004 to 2020.
METHODS: This study is a retrospective cohort study using the National Cancer Database. We identified adult patients who were diagnosed with advanced RPS (American Joint Committee on Cancer stages III and IV) from 2004 to 2020. We performed a trend analysis to describe the use of palliative therapy over time, followed by univariable and multivariable logistic regression analyses to identify predictors of palliative therapy use in this patient population.
RESULTS: A total of 6149 patients with advanced RPS were identified, of which only 383 used palliative therapy, including surgery (n = 28), radiation therapy (n = 87), systemic therapy (n = 115), pain management (n = 61), combination therapy (n = 55), or other palliative therapy (n = 37). The proportion of patients using palliative therapy increased significantly from 2.6% in 2004 to 6.5% in 2020 (Ptrend < 0.001). On multivariable logistic regression, age (odds ratio [OR] 1.03, 95 confidence interval [CI] 1.01-1.04), year of diagnosis (OR 1.05, 95 CI 1.02-1.08), lack of insurance (OR 2.18, 95 CI 1.17-4.04), community cancer program status (OR 1.83, 95 CI 1.05-3.19), stage IV disease (OR 5.19, 95 CI 4.49-7.79), and rhabdomyosarcoma (OR 2.75, 95 CI 1.32-5.72) histology were found to be predictors of palliative therapy use.
CONCLUSIONS: This study sheds light on the evolving landscape of palliative therapy use for patients with advanced RPS in the United States from 2004 to 2020. The observed gradual increase in the use of palliative therapy underscores the growing recognition of its importance in managing the unique challenges associated with this complex disease. Despite this positive trend, the persistently low overall rates highlight the need for further efforts to enhance awareness and accessibility of palliative therapy for this patient population.
PMID:39303648 | DOI:10.1016/j.jss.2024.08.018
Genes Chromosomes Cancer. 2024 Sep;63(9):e23259. doi: 10.1002/gcc.23259.
ABSTRACT
The identification of gene fusions in rare sarcoma subtypes can have diagnostic, prognostic, and therapeutic impacts for advanced cancer patients. Here, we present a case of a 31-year-old male with a lytic lesion of the left mandible initially diagnosed as an osteosarcoma but found to have a TFCP2 fusion and ALK alteration, redefining the diagnosis and providing rationale for a novel treatment strategy. Histologically, the tumor displayed hypercellular, spindled to epithelioid neoplasm and nuclear pleomorphism, while immunohistochemistry showed diffuse SATB2 and focal desmin staining. Whole genome and transcriptome analysis revealed a FUS::TFCP2 fusion, the defining alteration of a rare molecularly characterized subtype of soft tissue sarcoma termed intraosseous rhabdomyosarcoma. An internal ALK deletion and extremely high ALK RNA expression were also identified, suggesting potential benefit of an ALK inhibitor. This patient displayed a rapid and dramatic clinical and radiographic response to an ALK inhibitor, alectinib. Unfortunately, the response was short-lived, likely due to the advanced stage and aggressiveness of the disease. This report describes genome and transcriptome characterization of an intraosseous rhabdomyosarcoma, few of which exist in the literature, as well as providing evidence that inhibition of ALK may be a rational treatment strategy for patients with this exceedingly rare soft tissue sarcoma subtype characterized by TFCP2 fusions and ALK activation.
PMID:39302072 | DOI:10.1002/gcc.23259
J Vet Diagn Invest. 2024 Sep 20:10406387241281914. doi: 10.1177/10406387241281914. Online ahead of print.
ABSTRACT
An 8-y-old National Show Horse mare was presented for evaluation of pneumonia and laminitis. Harsh bronchovesicular sounds were auscultated throughout both lung fields, and the mare had signs of moderately painful laminitis. Thoracic ultrasonography revealed lung consolidation throughout the dorsal aspect of both lungs, and radiography revealed an extensive diffuse-to-patchy bronchointerstitial lung pattern. The mare's clinical condition rapidly deteriorated, and euthanasia was elected. On postmortem examination, the lungs, omentum, spleen, liver, adrenal glands, kidneys, and femur contained 0.5-2.5-cm, firm, tan nodules. Histologically, the lungs, spleen, liver, kidneys, adrenal glands, omentum, left eye, and femur were infiltrated by bundles and nests of pleomorphic polygonal-to-spindloid cells intermixed with frequent multinucleate cells. Lymphatic vessels in the affected tissues were frequently distended with tumor emboli. Neoplastic cells were diffusely positive for vimentin, desmin, sarcomeric actin, myoblastic differentiation protein 1, and myogenin, supportive of the diagnosis of rhabdomyosarcoma (RMS), which is a rare neoplasm in horses. Cross-striations were not evident with H&E or phosphotungstic acid-hematoxylin stains. Markedly pleomorphic neoplastic cells, multinucleate cells, and lack of cross-striations suggested the subclassification of pleomorphic RMS.
PMID:39301962 | DOI:10.1177/10406387241281914
Front Microbiol. 2024 Sep 5;15:1430052. doi: 10.3389/fmicb.2024.1430052. eCollection 2024.
ABSTRACT
Previous studies demonstrated that EV71-infected cells secrete extracellular vesicles (EVs), facilitating the transfer of viral components to recipient cells and thereby promoting virus spread. Considering lipid signaling plays a crucial role in EVs-mediated cell-to-cell communication, we compared the lipid profile of EVs secreted from uninfected and EV71-infected cells (EVs-Mock and EVs-EV71) using the human rhabdomyosarcoma (RD) cell model. These two groups of EVs were purified by using size exclusion chromatography (SEC), respectively, and evaluated by transmission electron microscopy (TEM), nanoparticle tracking technology (NTA), and Western blotting (WB). In-depth lipidomic analysis of EVs identified 1705 lipid molecules belonging to 43 lipid classes. The data showed a significant increase in the lipid content of EVs after EV71 infection. Meanwhile, we deeply analyzed the changes in lipids and screened for lipid molecules with significant differences compared EVs-EV71 with EVs-Mock EVs. Altogether, we report the alterations in the lipid profile of EVs derived from RD-cells after EV71 infection, which may affect the function of the EVs in the recipient cells.
PMID:39301189 | PMC:PMC11411429 | DOI:10.3389/fmicb.2024.1430052
JCO Precis Oncol. 2024 Sep;8:e2400418. doi: 10.1200/PO-24-00418.
ABSTRACT
PURPOSE: The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice trial assigned patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II treatment arms of molecularly targeted therapies on the basis of genetic alterations detected in their tumor. Patients with tumors that harbored prespecified genomic alterations in the cyclinD-CDK4/6-INK4a-Rb pathway with intact Rb expression were assigned and treated with the cdk4/6 inhibitor palbociclib.
METHODS: Patients received palbociclib orally once daily for 21 days of 28-day cycles until disease progression, intolerable toxicity, or up to 2 years. The primary end point was objective response rate; secondary end points included safety/tolerability and progression-free survival.
RESULTS: Twenty-three patients (median age, 15 years; range, 8-21) were enrolled; 20 received protocol therapy and were evaluable for toxicity and response. Of the evaluable patients, the most common diagnoses were osteosarcoma (n = 9) and rhabdomyosarcoma (n = 6). A single actionable gene amplification was found in 19 tumors (CDK4, n = 11, CDK6, n = 2, CCND3, n = 6), with one tumor harboring two amplifications (CDK4 and CCND2). Hematologic toxicities were the most common treatment-related events. No objective responses were seen. Two patients with tumors harboring CDK4 amplifications (neuroblastoma and sarcoma) had best response of stable disease for six and three cycles. Six-month progression was 10% (95% CI, 1.7 to 27.2).
CONCLUSION: The CDK4/6 inhibitor palbociclib at 75 mg/m2 orally daily was tolerable in this heavily pretreated cohort. No objective responses were observed in this histology-agnostic biomarker-selected population with treatment-refractory solid tumors, demonstrating that pathway alteration alone is insufficient in pediatric cancers to generate a response to palbociclib monotherapy.
PMID:39298716 | DOI:10.1200/PO-24-00418
Diagn Cytopathol. 2024 Sep 19. doi: 10.1002/dc.25404. Online ahead of print.
ABSTRACT
INTRODUCTION: The cytology features of neoplastic paratesticular lesions are mostly documented as case reports. Thus, we conducted a case report-based literature review to identify the characteristics of paratesticular neoplasms and tried to determine the significance of FNAC in these tumors.
METHODS AND MATERIALS: The studies were searched using PubMed and Scopus. The quality assessment was done using the JBI critical appraisal checklist for case reports. The articles that received an overall rating of "Include" underwent data extraction. The data were extracted from the articles and analyzed.
RESULTS: We included 34 case reports from 33 published articles. The mean age of patients was 44.74 (13-85) years, and the most common clinical manifestation was scrotal swelling (70.59%, 24/34). Lesions were commonly observed on the right side (65.63%, 21/32), and the most common tumor site was epididymis (35.29%, 12/34). A total of 38.24% (13/34) cases were nonmalignant, and 61.76% (21/34) were malignant on the cytological diagnosis. The adenomatoid tumor (53.85, 7/13) was the most common nonmalignant tumor. Other entities were schwannoma, benign spindle cell neoplasm with atypia, nerve sheath tumor, lipoma, undifferentiated pleomorphic sarcoma, rhabdomyosarcoma, epithelioid sarcoma, liposarcoma, malignant rhabdoid tumor, pigmented neuroectodermal tumor of infancy and mesothelioma. Considering the malignant and nonmalignant groups, the sensitivity, specificity, and diagnostic accuracy of cytology were 95.00%, 84.62%, and 90.91%, respectively.
CONCLUSION: Cytopathologists should be familiar with the cytological features of various malignant and nonmalignant paratesticular tumors to prevent unnecessarily invasive surgical management. The current systematic review emphasizes usefulness of FNAC in the preoperative cytological identification of paratesticular tumors.
PMID:39295546 | DOI:10.1002/dc.25404
Transl Oncol. 2024 Sep 17;50:102124. doi: 10.1016/j.tranon.2024.102124. Online ahead of print.
ABSTRACT
We report a case of alveolar rhabdomyosarcoma of the infratemporal region in a female child. An 8year old female was diagnosed with alveolar rhabdomyosarcoma 10 years ago. A computed tomography (CT) scan showed large mass in the right pterygopalatine fossa extending into the buccal, masticator and parapharyngeal spaces with involvement of the pterygoid and masseter muscles. Several multidisciplinary discussions were held concerning the case to determine the best treatment strategy. Child received neoadjuvant chemotherapy followed by radiotherapy. Six months post radiotherapy, CT scan reported a residual lesion for which multiple biopsies showed no residual tumor. Patient is doing well 10 years after treatment with no evidence of recurrence, Notably, this was the first case discussed at the inception of the pediatric multidisciplinary tumor board.
PMID:39293230 | PMC:PMC11424970 | DOI:10.1016/j.tranon.2024.102124
Int J Surg Case Rep. 2024 Oct;123:110296. doi: 10.1016/j.ijscr.2024.110296. Epub 2024 Sep 17.
ABSTRACT
INTRODUCTION AND IMPORTANCE: Rhabdomyosarcoma [RMS] is a malignant soft-tissue neoplasm characterized by skeletal muscle differentiation. It accounts for 7 % of childhood malignancies and is, by a wide margin, the most common sarcoma of childhood (Pappo, 1996). Approximately 20 % of cases of childhood rhabdomyosarcoma occur in the genitourinary tract (vagina, urinary bladder, prostate, paratestis, and uterus), and they are most commonly observed in the head and neck region.
CASE PRESENTATION: We reviewed the case of a 42-year-old male who presented with a 2-week history of blood in the urine, which was painless, started on gradual onset, and progressively increased, involving the whole stream of urine. The blood clots were amorphous in shape but had no history of passed tissue shreds, childhood schistosomiasis, cigarette smoking, or working in chemical industries. On physical examination, the patient was anxious and conscious, with normal vital signs. The abdomen revealed distended abdomen shifting dullness, a palpable urinary bladder with suprapubic distension, and a tenderness on palpation, which disappeared upon catheterization 3-way 24F, with normal male genitalia and right lower limb edema. Other systems were essentially normal. On image KUB USS revealed a bladder mass, Cystoscopy showed a broad base bleeding tumor located at dome to the left lateral, fungating, with some necrotic tissue. TURBT was done into completion and histology revealed an embryonal rhabdomyosarcoma of urinary bladder, a botryoid subtype. After TURBT, the patient received adjuvant chemotherapy, the MAID protocol and underwent a 6-cycle cycle. The cycle was repeated every 21 days, and his height was 171.5 c, and his weight was 89 kg. Serial of check cystoscopy for one year revealed no recurrency of tumor. He repeated check CT scan, which showed a radiological improvement compared to the initial image.
CLINICAL DISCUSSION: Rhabdomyosarcoma in adults is a rare type of urinary bladder carcinoma that is quite aggressive and is usually reported to be a pediatric malignant urinary bladder tumor. The modality of treatment is not universal because of its rarity. We used a combination of TURB and chemotherapy and performed strict follow-up, with no tumor recurrence occurring at least after one year of follow-up. These patients show significant improvement from the first presentation, both clinically and radiologically.
CONCLUSION: The lack of a universal standard treatment approach for adult rhabdomyosarcoma indicates the need for more data on adult rhabdomyosarcoma, with a detailed description of its histological subtype.
PMID:39293226 | PMC:PMC11424959 | DOI:10.1016/j.ijscr.2024.110296
Int J Surg Pathol. 2024 Sep 17:10668969241268396. doi: 10.1177/10668969241268396. Online ahead of print.
ABSTRACT
Sarcomas of thyroid glands represent a distinctive subset of rare and perplexing anomaly that present a challenges in the field of thyroid pathology. Thyroid sarcomas, primary or secondary, are exceptionally rare with only a handful of case reports documented so far. The challenges lie in the fact that certain primary thyroid malignancies of epithelial origin may exhibit spindle cell morphology, making them difficult to differentiate from thyroid sarcomas. Despite the morphological similarities, discerning between these entities is crucial due to their distinct treatment and management implications. This report documents a series of unusual types of sarcoma in the thyroid gland. The aim is to explore the peculiarities of these lesions, the diagnostic challenges faced as well to study the potential implications for both clinicians and patients.
PMID:39289927 | DOI:10.1177/10668969241268396
Clin Cancer Res. 2024 Sep 17. doi: 10.1158/1078-0432.CCR-24-1928. Online ahead of print.
ABSTRACT
PURPOSE: To determine the cancer risk and spectrum in patients with multi-lineage mosaic RASopathies with pathogenic variants (PV) in HRAS or KRAS.
METHODS: We conducted a systematic literature review to identify multi-lineage mosaic RASopathy cases with a PV in HRAS or KRAS to create a retrospective cohort. We calculated cumulative incidence, cancer-free survival and hazard rates (HR) for cancer and standardized incidence rates (SIR).
RESULTS: This study identified 69 patients. Seventeen percent had cancer, including rhabdomyosarcoma located in the urogenital region (n=7), skin cancer (n=3), Wilms tumor (n=1), and bladder cancer (n=1). Cumulative cancer incidence by age 20 was 20% (95% CI, 4 to 37%). The annual cancer HR peaked at 14% within the first two years of life. The highest SIR was found for rhabdomyosarcoma (SIR = 800, 95% CI, 300 to 1648).
CONCLUSIONS: This is the first investigation of cancer risk in KRAS or HRAS PV-positive mosaic RASopathies to date. The high incidence and SIR values found highlight the need for rigorous rhabdomyosarcoma surveillance in young children and skin cancer surveillance in adults with this high-risk condition.
PMID:39287844 | DOI:10.1158/1078-0432.CCR-24-1928
J Virol. 2024 Sep 17:e0112924. doi: 10.1128/jvi.01129-24. Online ahead of print.
ABSTRACT
Because host kinases are key regulators of multiple signaling pathways in response to viral infections, we previously screened a kinase inhibitor library using rhabdomyosarcoma cells and human intestinal organoids in parallel to identify potent inhibitors against EV-A71 infection. We found that Rho-associated coiled-coil-containing protein kinase (Rock) inhibitor efficiently suppressed the EV-A71 replication and further revealed Rock1 as a novel EV-A71 host factor. In this study, subsequent analysis found that a variety of vascular endothelial growth factor receptor (VEGFR) inhibitors also had potent antiviral effects. Among the hits, Pazopanib, with a selectivity index as high as 254, which was even higher than that of Pirodavir, a potent broad-spectrum picornavirus inhibitor targeting viral capsid protein VP1, was selected for further analysis. We demonstrated that Pazopanib not only efficiently suppressed the replication of EV-A71 in a dose-dependent manner, but also exhibited broad-spectrum anti-enterovirus activity. Mechanistically, Pazopanib probably induces alterations in host cells, thereby impeding viral genome replication and transcription. Notably, VEGFR2 knockdown and overexpression suppressed and facilitated EV-A71 replication, respectively, indicating that VEGFR2 is a novel host dependency factor for EV-A71 replication. Transcriptome analysis further proved that VEGFR2 potentially plays a crucial role in combating EV-A71 infection through the TSAd-Src-PI3K-Akt pathway. These findings expand the range of potential antiviral candidates of anti-enterovirus therapeutics and suggest that VEGFR2 may be a key host factor involved in EV-A71 replication, making it a potential target for the development of anti-enterovirus therapeutics.
IMPORTANCE: As the first clinical case was identified in the United States, EV-A71, a significant neurotropic enterovirus, has been a common cause of hand, foot, and mouth disease (HFMD) in infants and young children. Developing an effective antiviral agent for EV-A71 and other human enteroviruses is crucial, as these viral pathogens consistently cause outbreaks in humans. In this study, we demonstrated that multiple inhibitors against VEGFRs effectively reduced EV-A71 replication, with Pazopanib emerging as the top candidate. Furthermore, Pazopanib also attenuated the replication of other enteroviruses, including CVA10, CVB1, EV-D70, and HRV-A, displaying broad-spectrum anti-enterovirus activity. Given that Pazopanib targets various VEGFRs, we narrowed the focus to VEGFR2 using knockdown and overexpression experiments. Transcriptomic analysis suggests that Pazopanib's potential downstream targets involve the TSAd-Src-PI3K-Akt pathway. Our work may contribute to identifying targets for antiviral inhibitors and advancing treatments for human enterovirus infections.
PMID:39287389 | DOI:10.1128/jvi.01129-24
Pediatr Blood Cancer. 2024 Sep 17:e31323. doi: 10.1002/pbc.31323. Online ahead of print.
NO ABSTRACT
PMID:39285754 | DOI:10.1002/pbc.31323
medRxiv [Preprint]. 2024 Sep 5:2024.09.04.24313032. doi: 10.1101/2024.09.04.24313032.
ABSTRACT
PURPOSE: Molecular markers, such as FOXO1 fusion genes and TP53 and MYOD1 mutations, increasingly influence risk-stratified treatment selection for pediatric rhabdomyosarcoma (RMS). This study aims to integrate molecular and clinical data to produce individualized prognosis predictions that can further improve treatment selection.
PATIENTS AND METHODS: Clinical variables and somatic mutation data for 20 genes from 641 RMS patients in the United Kingdom and the United States were used to develop three Cox proportional hazard models for predicting event-free survival (EFS). The 'Baseline Clinical' (BC) model included treatment location, age, fusion status, and risk group. The 'Gene Enhanced 2' (GE2) model added TP53 and MYOD1 mutations to the BC predictors. The 'Gene Enhanced 6' (GE6) model further included NF1, MET, CDKN2A, and MYCN mutations, selected through LASSO regression. Model performance was assessed using likelihood ratio (LR) tests and optimism-adjusted, bootstrapped validation and calibration metrics.
RESULTS: The GE6 model demonstrated superior predictive performance, offering 39% more predictive information than the BC model (LR p<0.001) and 15% more than the GE2 model (LR p<0.001). The GE6 model achieved the highest discrimination with a C-index of 0.7087, a Nagalkerke R2 of 0.205, and appropriate calibration. Mutations in TP53, MYOD1, CDKN2A, MET, and MYCN were associated with higher hazards, while NF1 mutation correlated with lower hazard. Individual prognosis predictions varied between models in ways that may suggest different treatments for the same patient. For example, the 5-year EFS for a 10-year-old patient with high-risk, fusion-negative, NF1-positive disease was 50.0% (95% confidence interval: 39-64%) from BC but 76% (64-90%) from GE6.
CONCLUSION: Incorporating molecular markers into RMS prognosis models improves prognosis predictions. Individualized prognosis predictions may suggest alternative treatment regimens compared to traditional risk-classification schemas. Improved clinical variables and external validation are required prior to implementing these models into clinical practice.
PMID:39281734 | PMC:PMC11398450 | DOI:10.1101/2024.09.04.24313032
Pak J Med Sci. 2024 Sep;40(8):1625-1631. doi: 10.12669/pjms.40.8.9843.
ABSTRACT
OBJECTIVE: To determine the relative frequency of orbital lesions based on the site of origin and histopathology at a Tertiary care hospital (Mayo Hospital, Lahore Pakistan) from 1996 till 2022 (27 years).
METHODS: This descriptive case series included 2651 patients of all age groups presenting with orbital lesions who initially got enrolled at Institute of Ophthalmology Mayo Hospital, Lahore from 1996 till 2022. Of these, 583 patients left against medical advice. So, clinical data of 2068 patients were completely analyzed. Lesions were managed medically and/ or surgically. Final clinical diagnosis, with the help of histopathology, was used to classify the lesions.
RESULTS: There were 1258 (60.9%) adults and 810 (39.1%) children, 1358 (65.66%) were neoplastic while 710 (34.33%) non-neoplastic lesions. Amongst the neoplastic lesions, 405 (29.8 %) were benign and 953 (70.2%) malignant. Primary orbital lesions were 1676 (81.04%), Secondary orbital lesions were 300 (14.51%), Endocrine/ hematopoietic reticulo-endothelial system lesions were 84 (4.06%) and Metastatic lesions from distant organs were 08 (0.39%).
CONCLUSION: Retinoblastoma, rhabdomyosarcoma, optic nerve gliomata were common in children. Pleomorphic adenoma & adenocystic carcinoma of lacrimal gland, cavernous hemangioma, optic nerve meningioma, neurofibroma, schwannoma, squamous cell carcinoma of eyelid, carcinoma of maxillary antrum and lymphomas were more common in adults.
PMID:39281227 | PMC:PMC11395349 | DOI:10.12669/pjms.40.8.9843
Clin Case Rep. 2024 Sep 12;12(9):e9437. doi: 10.1002/ccr3.9437. eCollection 2024 Sep.
ABSTRACT
Perianal alveolar rhabdomyosarcoma is a rare sarcoma that requires a high index of suspicion along with tissue biopsy for accurate diagnosis. Successful treatment, even in the setting of recurrence, requires a multidisciplinary approach.
PMID:39281027 | PMC:PMC11393001 | DOI:10.1002/ccr3.9437
Front Radiol. 2024 Aug 30;4:1445701. doi: 10.3389/fradi.2024.1445701. eCollection 2024.
ABSTRACT
Sinonasal tumors are often malignant and comprise approximately 3% of all head and neck malignancies. Half of these tumors arise in the nasal cavity, and other common locations of origin include the ethmoid and maxillary sinuses. Some unique clinical features are anosmia and altered phonation but the most common general features include headache, epistaxis, and diplopia. CT and MRI may be used to assess tumor location, invasion of adjacent tissue, presence of metastasis, internal tumor heterogeneity, and contrast enhancement. Local invasion of the tumor beyond the sinonasal tract can impact adjacent structures such as the cranial nerves, skull base, branches of the internal carotid artery, and orbit leading to neurologic signs, facial pain, and diplopia. Imaging is used in the diagnosis, staging, and treatment planning of sinonasal tumors. This collection of benign and malignant sinonasal tumors will include some rare and unique cases with an emphasis on imaging features demonstrating a wide variety of pathologies.
PMID:39280982 | PMC:PMC11392720 | DOI:10.3389/fradi.2024.1445701
Cancers (Basel). 2024 Sep 9;16(17):3110. doi: 10.3390/cancers16173110.
ABSTRACT
Rhabdomyosarcoma (RMS) of the biliary tract is a rare tumor in children, constituting 0.5-0.8% of all pediatric RMS. Still, it is the most common malignancy in this location in children. Due to its rarity and location, it may cause diagnostic and treatment difficulties. Above all, there are no therapeutic guidelines specific for this tumor location. The aim of the study was to present an analysis of our experience with the treatment of children with biliary tract rhabdomyosarcoma (RMS) and discuss clinical recommendations for this specific location published in the literature. A retrospective analysis of medical records of eight children with biliary tree RMS treated in one center between 1996-2022 was performed. Records of eight children, five boys and three girls aged 2 yrs 6 mo to 16 yrs 9 mo (median-6 yrs) were analyzed. All patients presented with jaundice as the first symptom. In two patients, initial diagnosis of a tumor was established. For the remaining six, the primary diagnoses were as follows: choledochal cyst-one, malformation of the biliary ducts-one, choledocholithiasis-one, cholangitis-three. In four patients, the extrahepatic bile ducts were involved; in four patients, both the intrahepatic and extrahepatic bile ducts were involved. Embryonal RMS was diagnosed in seven patients (three botryoides type). Alveolar RMS was found in one patient. Biopsy (three surgical, four during endoscopic retrograde cholangiopancreatography (ERCP)) was performed in seven patients. One child underwent primary partial tumor resection (R2). Seven patients received neoadjuvant chemotherapy, followed by delayed resection in five, including liver transplantation in one (five were R0). Two patients did not undergo surgery. Radiotherapy was administered in four patients (two in first-line treatment, two at relapse/progression). Six patients (75%) are alive with no evidence of disease, with follow-up ranging from 1.2 yrs to 27 yrs (median 11 yrs. and 4 mo.). Two patients died from disease, 2 y 9 mo and 3 y 7 mo from diagnosis. Children presenting with obstructive jaundice should be evaluated for biliary tract RMS. The treatment strategy should include biopsy and preoperative chemotherapy, followed by tumor resection and radiotherapy for residual disease and in case of relapse.
PMID:39272968 | PMC:PMC11394218 | DOI:10.3390/cancers16173110
Front Oncol. 2024 Aug 19;14:1399442. doi: 10.3389/fonc.2024.1399442. eCollection 2024.
ABSTRACT
INTRODUCTION: Alternative lengthening of telomeres (ALT) occurs in sarcomas and ALT cancers share common mechanisms of therapy resistance or sensitivity. Telomeric DNA C-circles are self-primed circular telomeric repeats detected with a PCR assay that provide a sensitive and specific biomarker exclusive to ALT cancers. We have previously shown that 23% of high-risk neuroblastomas are of the ALT phenotype. Here, we investigate the frequency of ALT in Ewing's family sarcoma (EFS), rhabdomyosarcoma (RMS), and osteosarcoma (OS) by analyzing DNA from fresh frozen primary tumor samples utilizing the real-time PCR C-circle Assay (CCA).
METHODS: We reviewed prior publications on ALT detection in pediatric sarcomas. DNA was extracted from fresh frozen primary tumors, fluorometrically quantified, C-circles were selectively enriched by isothermal rolling cycle amplification and detected by real-time PCR.
RESULTS: The sample cohort consisted of DNA from 95 EFS, 191 RMS, and 87 OS primary tumors. One EFS and 4 RMS samples were inevaluable. Using C-circle positive (CC+) cutoffs previously defined for high-risk neuroblastoma, we observed 0 of 94 EFS, 5 of 187 RMS, and 62 of 87 OS CC+ tumors.
CONCLUSIONS: Utilizing the ALT-specific CCA we observed ALT in 0% of EFS, 2.7% of RMS, and 71% of OS. These data are comparable to prior studies in EFS and OS using less specific ALT markers. The CCA can provide a robust and sensitive means of identifying ALT in sarcomas and has potential as a companion diagnostic for ALT targeted therapeutics.
PMID:39224814 | PMC:PMC11366626 | DOI:10.3389/fonc.2024.1399442
Histopathology. 2024 Sep 2. doi: 10.1111/his.15309. Online ahead of print.
ABSTRACT
AIMS: Melanomas are recognised for their remarkable morphological plasticity. Some tumours may lose conventional features and/or acquire non-melanocytic characteristics, referred to as undifferentiated, dedifferentiated and transdifferentiated melanoma. Despite this phenotypical variability, melanomas typically maintain their cancer driver aberrations, affecting genes such as BRAF, NRAS and NF1. Currently, little is known about whether the DNA methylation profile follows the loss or change of differentiation or is retained despite extensive morphological transformation.
METHODS AND RESULTS: In this study we analysed 11 melanoma cases, comprising six males and five females, with a median age of 67 years, including five undifferentiated, four trans-differentiated and two de-differentiated melanomas. Undifferentiated and trans-differentiated tumours either arose in a patient with known melanoma and/or presented in the groin/axilla with molecular alterations consistent with melanoma. Cases with heterologous differentiation resembled chondrosarcoma, osteosarcoma, angiosarcoma and rhabdomyosarcoma both morphologically and immunohistochemically, while undifferentiated tumours resembled undifferentiated pleomorphic sarcoma. Methylome profiling was performed, and unsupervised clustering analysis revealed nine cases (five undifferentiated, three trans-differentiated and one de-differentiated) to cluster closely together with conventional melanomas from a reference set. Two cases clustered separately with a distinct group of conventional melanomas exhibiting H3K27me3 loss.
CONCLUSIONS: Despite loss of differentiation and phenotypical plasticity, methylation patterns seem to be retained in undifferentiated, de-differentiated and trans-differentiated melanomas and represent useful diagnostic tools to enhance diagnostic precision in these diagnostically challenging cases.
PMID:39223066 | DOI:10.1111/his.15309
Int J Radiat Oncol Biol Phys. 2024 Aug 31:S0360-3016(24)03318-2. doi: 10.1016/j.ijrobp.2024.08.039. Online ahead of print.
ABSTRACT
PURPOSE: Radiation oncologists utilize radiation variably for children with metastatic rhabdomyosarcoma (RMS). Data from the XXXX study was retrospectively analyzed to validate the prior observation that the use of radiation is associated with improved outcomes, and guide future recommendations on radiation use in this patient group.
METHODS AND MATERIALS: The radiation delivered to 216 patients aged 0-21 years with metastatic RMS was retrospectively reviewed and classified as radical (all sites of disease irradiated within the protocol parameters), partial (some sites irradiated within the protocol parameters) and none (no radiation or delivered outside the protocol parameters). Landmark analysis excluded those with an event prior to day 221. Overall survival (OS) and progression free survival (PFS) were modelled using the Kaplan-Meier method to investigate the impact of radiation. The joint effect of treatment and known prognostic factors was examined using the Cox regression model.
RESULTS: Overall 56 patients received radical, 104 partial and 56 no radiation per protocol. Due to non-randomised data, the groups were heterogeneous, particularly fewer sites of metatatic disease and less with bone metatases in those receiving radical radiation. 3-year PFS was 62.0% (95%CI 47.9-73.4) v 39.5% (29.8-49.1) v 30.1% (18.7-42.3)(p=0.002) for radical v partial v no radiotherapy respectively; 3-year OS was 70.1 % (55.8-80.6) v 53.1% (42.6-62.5) v 52.3% (38.3-64.5)(p=0.019) respectively. Multivariable analysis confirmed incremental improvement in OS with additional radiation with hazard ratio (HR) 1 v 1.8 v 2.4 (p=0.022) for radical v partial v no per protocol radiation.
CONCLUSIONS: Radiation to all sites of disease seems to improve outcomes for children with metastatic RMS and should be considered when feasible. If not feasible, radiation is still recommended to the primary site and involved regional lymphadenopathy. Randomized clinical trials are required to confirm these findings, given the heterogeneity between the groups and potential confounding factors in this analysis.
PMID:39222824 | DOI:10.1016/j.ijrobp.2024.08.039
BMJ Case Rep. 2024 Aug 31;17(8):e254128. doi: 10.1136/bcr-2022-254128.
ABSTRACT
A man in his 70s presented with a left inguinoscrotal mass. Testicular tumour markers showed markedly elevated human chorionic gonadotropin (hCG). The 24.5 cm mass was resected, and histology confirmed a rare diagnosis of paratesticular dedifferentiated liposarcoma (DDLPS) with rhabdomyosarcomatous differentiation. The patient expired with distant metastasis 11 months after presenting to his general practitioner.HCG-producing soft tissue sarcomas (STS) are commonly reported as high-grade, poorly differentiated and with a poor prognosis. The role of hCG in tumour angiogenesis may influence these features.Paratesticular STS treatment guidelines have been influenced by the management of retroperitoneal STS, which are relatively more common. Studies of genitourinary STS demonstrate that positive surgical margins pose the greatest risk to local recurrence and metastasis-free survival.This case demonstrates the rapid growth of DDLPS-producing hCG, the propensity to metastasise, and poor prognosis, requiring further research into the benefit of adjuvant radiotherapy for DDLPS.
PMID:39216884 | DOI:10.1136/bcr-2022-254128
JACS Au. 2024 Aug 2;4(8):3248-3257. doi: 10.1021/jacsau.4c00546. eCollection 2024 Aug 26.
ABSTRACT
Hypoxia, characterized by nonphysiological levels of oxygen tension, is a key phenomenon common to the majority of malignant tumors with poor prognosis. Many efforts have been made to develop hypoxia imaging for diagnosis, staging, and monitoring of diseases, as well as for evaluating therapies. PET Imaging using 18F-fluoronitroimidazoles (i.e., [18F]FMISO as a lead radiotracer) has demonstrated potential for clinical investigations, but the poor contrast and prolonged acquisition times (>2.5 h) strongly limit its accuracy and routine developments. Here, we report an original [18F]fluoronitroimidazole bearing a sulfo group ([18F]FLUSONIM) that displays highly hydrophilic properties and rapid clearance, providing high-performance hypoxia specific PET imaging. We describe the synthesis and radiosynthesis of [18F]FLUSONIM, its in vivo preclinical evaluation by PET imaging in healthy rats and a rhabdomyosarcoma rat model, as well as its radiometabolization and histological studies. [18F]FLUSONIM was prepared in a single step by high yielding radiofluorination of a sultone precursor, highlighting the advantages of this new radiolabeling approach not yet explored for radiopharmaceutical development. PET imaging experiments were conducted by systematically comparing [18F]FLUSONIM to [18F]FMISO as a reference. The overall results unequivocally demonstrate that the developed radiopharmaceutical meets the criteria of an ideal candidate for hypoxia PET imaging-rapid and efficient radiosynthesis, total stability, exclusive urinary elimination, high specificity for hypoxic regions, unprecedented tumor/background ratios, short acquisition delays (<60 min), and promising potential for further preclinical and clinical applications.
PMID:39211595 | PMC:PMC11350728 | DOI:10.1021/jacsau.4c00546
bioRxiv [Preprint]. 2024 Aug 3:2024.07.31.606039. doi: 10.1101/2024.07.31.606039.
ABSTRACT
Alveolar rhabdomyosarcoma (ARMS) patients harboring PAX3-FOXO1 and PAX7-FOXO1 fusion proteins exhibit a greater incidence of tumor relapse, metastasis, and poor survival outcome, thereby underscoring the urgent need to develop effective therapies to treat this subtype of childhood cancer. To uncover mechanisms that contribute to tumor initiation, we developed a novel muscle progenitor model and used epigenomic approaches to unravel genome re-wiring events mediated by PAX3/7 fusion proteins. Importantly, these regulatory mechanisms are conserved across established ARMS cell lines, primary tumors, and orthotopic-patient derived xenografts. Among the key targets of PAX3- and PAX7-fusion proteins, we identified a cohort of oncogenes, FGF receptors, and genes essential for mitochondrial metabolism and protein translation, which we successfully targeted in preclinical trials. Our data suggest an explanation for the relative paucity of recurring mutations in this tumor, provide a compelling list of actionable targets, and suggest promising new strategies to treat this tumor.
PMID:39211084 | PMC:PMC11360909 | DOI:10.1101/2024.07.31.606039
Am J Surg Pathol. 2024 Aug 30. doi: 10.1097/PAS.0000000000002300. Online ahead of print.
ABSTRACT
Embryonal rhabdomyosarcoma (ERMS) is the most common subtype of RMS, occurring in soft tissue and visceral sites of young children, and is associated with favorable outcomes. A subset occurs in mucosal-lined luminal structures, displaying a unique grape-like growth termed as "botryoid-type." To further delineate the differences between conventional (cERMS) and botryoid-type (bERMS) RMS, we performed a comparative histologic review and comprehensive molecular profiling of 48 cases (25 bERMS and 23 cERMS). All tumors were subjected to a hybridization capture-based targeted matched tumor-normal DNA NGS assay. The mean age was 17 and 7 years for bERMS and cERMS, respectively. Most bERMS were female with a predilection for the gynecologic tract (75%), while cERMS had a slight male predominance and were preferentially located in abdominopelvic and paratesticular sites (30%, each). All bERMS exhibited an exophytic, bulbous architecture accompanied by a subepithelial "cambium layer." Distinctive germline alterations were detected, with DICER1 (18%) and FH (6%) mutations only in bERMS, and rare TP53, VHL, and APC mutations in cERMS. Similarly, contrasting somatic genomic landscapes were observed, with frequent DICER1 (52%, P**<0.0001) and TP53 (36%, P*<0.05) alterations exclusively in bERMS. Cartilaginous differentiation was only observed in DICER1-mutated bERMS. All patients had longitudinal follow-up. bERMS patients with somatic/germline DICER1 mutations showed significantly improved recurrence-free survival compared with that of DICER1-wild type patients (P*<0.05). Moreover, bERMS showed improved disease-specific survival compared with that of cERMS, with 8% versus 30% (P*<0.05) dead of disease, respectively. In summary, we compare the molecular underpinnings of the largest cohort of bERMS and cERMS with targeted DNA sequencing and long-term follow-up data. Our findings reveal divergent genomic topographies between the 2 groups, with bERMS showing unique germline and somatic abnormalities, including enrichment in DICER1 and TP53 alterations, and a trend towards improved survival.
PMID:39210566 | DOI:10.1097/PAS.0000000000002300
J Clin Pathol. 2024 Aug 28:jcp-2024-209640. doi: 10.1136/jcp-2024-209640. Online ahead of print.
NO ABSTRACT
PMID:39209443 | DOI:10.1136/jcp-2024-209640
Urology. 2024 Aug 27:S0090-4295(24)00722-2. doi: 10.1016/j.urology.2024.08.041. Online ahead of print.
NO ABSTRACT
PMID:39208941 | DOI:10.1016/j.urology.2024.08.041
Urology. 2024 Aug 27:S0090-4295(24)00742-8. doi: 10.1016/j.urology.2024.08.053. Online ahead of print.
NO ABSTRACT
PMID:39208939 | DOI:10.1016/j.urology.2024.08.053
J Stomatol Oral Maxillofac Surg. 2024 Aug 25:102024. doi: 10.1016/j.jormas.2024.102024. Online ahead of print.
ABSTRACT
INTRODUCTION: The aim of this study was to evaluate the systemic sequelae, as well as the dental and craniofacial development, of patients with rhabdomyosarcoma in relation to the treatment received and clinical-pathological variables.
MATERIALS AND METHODS: A retrospective cross-sectional study was performed. All individuals diagnosed with RMS between 1990 and 2022 were considered eligible. Cases who survived the primary tumor were included. Data were collected from medical records, and patients were called for clinical and radiographic examinations.
RESULTS: Thirty-eight patients were assessed, with a mean disease-free survival of 216.68 months (±84.99). The primary location of the tumor was mainly the head and neck region (57.9 %). All patients received chemotherapy, and 30 (78.9 %) also underwent radiotherapy. The most frequently observed sequela was sensory impairment, which was significantly associated with tumors in the head and neck (p < 0.05), as well as with the use of radiotherapy (p = 0.034). Root formation failure was observed in 60 % of cases, microdontia in 50 %, and delayed tooth eruption in 40 %. A convex profile was predominant (80 %), along with maxillary (50 %) and mandibular (80 %) retrusion and a skeletal class II diagnosis (60 %).
CONCLUSIONS: Late systemic, dental, and craniofacial developmental sequelae are observed in pediatric rhabdomyosarcoma survivors, especially in patients who underwent radiotherapy in the head and neck region. Younger individuals at the time of treatment are at greater risk of late sequelae.
PMID:39191300 | DOI:10.1016/j.jormas.2024.102024
Ann Ital Chir. 2024;95(4):481-496. doi: 10.62713/aic.3316.
ABSTRACT
AIM: Congenital tumors of the tongue are rare in pediatric patients but encompass a diverse range of entities. Each tumor type exhibits distinct clinical behaviors, necessitating a precise approach to differentiating the tumor types and a tailored, tumor-specific treatment regimen. Advanced imaging techniques, such as diffusion-weighted imaging and perfusion studies, play a vital role in differentiating benign and malignant tongue tumors. This review summarizes current knowledge regarding the presentation, imaging features, and treatment of congenital tongue tumors.
METHODS: A literature review was conducted by searching studies on congenital tongue tumors in databases such as PubMed, Embase, Web of Science, and Scopus. Relevant data, such as clinical features, radiologic characteristics, treatment modalities, and outcomes for different tumor types, were extracted from the selected articles.
RESULTS: Our literature review reveals the various entities of congenital tongue tumors, which can be categorized in terms of hereditary pattern, phenotype, and rarity. Congenital tongue tumors include a range of vascular malformations, such as hemangiomas, lymphatic malformations, arteriovenous malformations, and venous malformations. Another entity is represented by cystic lesions, including dermoid cysts, epidermoid cysts, ranulas, and mucous retention cysts. Rare malignant neoplasms include teratomas and rhabdomyosarcomas. These tumor types vary in terms of swelling, respiratory distress, or impaired oral function, depending on size and location. The detection of these tumors can be carried out using imaging modalities, such as ultrasound, magnetic resonance imaging, and computed tomography, which are utilized to facilitate diagnosis and differentiation. At present, surgical excision remains the cornerstone of treatment, while other modalities may be adopted, depending on tumor type and extent. The prognosis of congenital tongue tumors can be affected by tumor's site, size, involvement of vital structures, and malignancy.
CONCLUSIONS: Given their diversity and complexity, congenital tongue tumors, albeit uncommon, require specialized clinical treatments tailored to each tumor type's characteristics. Understanding the variable presentations and imaging features enables accurate diagnosis, while customized treatment strategies are key to optimizing outcomes and minimizing morbidity in pediatric tongue tumors. This review summarizes current knowledge aimed at enhancing differential diagnosis and management of these diverse entities.
PMID:39186358 | DOI:10.62713/aic.3316
Oncol Lett. 2024 Aug 8;28(4):487. doi: 10.3892/ol.2024.14620. eCollection 2024 Oct.
ABSTRACT
Perianal embryonal rhabdomyosarcoma (ERMS) is a rare disease with a poor prognosis. There are few reported cases of this disease, and specific clinical manifestations are lacking; therefore, making an early diagnosis before surgery is challenging. In November 2014, a 30-year-old man was admitted to Xiaoshan Affiliated Hospital of Wenzhou Medical University due to severe left perianal pain. Ultrasonography revealed a multilocular perianal abscess, and an emergency perianal abscess incision and drainage were performed. However, pathology combined with immunohistochemistry confirmed an ERMS. The patient did not receive postoperative radiotherapy or chemotherapy and died of multiple metastases and multiple organ failure 6 months later. Perianal ERMS is highly malignant and rare, and can easily be misdiagnosed as a perianal abscess. Clinicians must enhance their knowledge and improve preoperative diagnostic tests to prevent misdiagnoses.
PMID:39185492 | PMC:PMC11342414 | DOI:10.3892/ol.2024.14620
Cancer Gene Ther. 2024 Aug 25. doi: 10.1038/s41417-024-00823-2. Online ahead of print.
ABSTRACT
Metastatic rhabdomyosarcoma is associated with poor survival and unsatisfactory treatment outcomes. Therefore, new immunotherapeutic methods are urgently required. Fibroblast growth factor receptor 4 (FGFR4), a new therapeutic target for rhabdomyosarcoma, plays a crucial role in its onset and development. This study aimed to generate FGFR4 single-chain variable fragment-based chimeric antigen receptor (CAR) T cells without causing evident toxicity and incorporating an inducible caspase-9 (iCasp9) suicide gene system to enhance their safety. FGFR4 antigen expression was evaluated in normal murine tissues, normal human tissues, and specimens from patients with rhabdomyosarcoma. Combined with a 4-1BB co-stimulatory domain, a CD3ζ signaling domain, and an iCasp9 suicide gene, CAR-T cells with an FGFR4-specific single-chain variable fragment were developed. The specific cytotoxic effects, T-cell proliferation, cytokine secretion, apoptosis induction by chemical dimerization (AP20187), and toxicity of FGFR4 CAR-T cells were investigated in vitro and in vivo. FGFR4 CAR-T cells generated a variety of immune-promoting cytokines, including tumor necrosis factor α, interleukin 2, and interferon γ, and displayed effective cytotoxic activity against FGFR4-overexpressing rhabdomyosarcoma cells in vitro. FGFR4 CAR-T cells were relatively effective against FGFR4-overexpressing rhabdomyosarcoma, with tumor regression and poor survival in a subcutaneous xenograft model. The iCasp9 gene was incorporated into FGFR4 CAR-T cells and it was demonstrated that effective and reliable suicide gene activity depends on the administration of AP20187. By making use of the cross-reaction of FGFR4 CAR-T cells with murine FGFR4 in a syngeneic tumor model, this study found that FGFR4 CAR-T cells could regulate the growth of tumors without evident toxicity. Our study demonstrates that FGFR4 is a prospective target for CAR-T cell therapy in rhabdomyosarcoma without serious on-target off-tumor toxicity. FGFR4 CAR-T cells with the iCasp9 suicide gene system as a safety switch to limit toxicity may broaden the clinical applications of cellular therapy.
PMID:39183354 | DOI:10.1038/s41417-024-00823-2
Mol Metab. 2024 Aug 23;88:102016. doi: 10.1016/j.molmet.2024.102016. Online ahead of print.
ABSTRACT
OBJECTIVE: A prominent, safe and efficient therapy for patients with chronic myeloid leukemia (CML) is inhibiting oncogenic protein BCR::ABL1 in a targeted manner with imatinib, a tyrosine kinase inhibitor. A substantial part of patients treated with imatinib report skeletomuscular adverse events affecting their quality of life. OCTN2 membrane transporter is involved in imatinib transportation into the cells. At the same time, the crucial physiological role of OCTN2 is cellular uptake of carnitine which is an essential co-factor for the mitochondrial β-oxidation pathway. This work investigates the impact of imatinib treatment on carnitine intake and energy metabolism of muscle cells.
METHODS: HTB-153 (human rhabdomyosarcoma) cell line and KCL-22 (CML cell line) were used to study the impact of imatinib treatment on intracellular levels of carnitine and vice versa. The energy metabolism changes in cells treated by imatinib were quantified and compared to changes in cells exposed to highly specific OCTN2 inhibitor vinorelbine. Mouse models were used to test whether in vitro observations are also achieved in vivo in thigh muscle tissue. The analytes of interest were quantified using a Prominence HPLC system coupled with a tandem mass spectrometer.
RESULTS: This work showed that through the carnitine-specific transporter OCTN2, imatinib and carnitine intake competed unequally and intracellular carnitine concentrations were significantly reduced. In contrast, carnitine preincubation did not influence imatinib cell intake or interfere with leukemia cell targeting. Blocking the intracellular supply of carnitine with imatinib significantly reduced the production of most Krebs cycle metabolites and ATP. However, subsequent carnitine supplementation rescued mitochondrial energy production. Due to specific inhibition of OCTN2 activity, the influx of carnitine was blocked and mitochondrial energy metabolism was impaired in muscle cells in vitro and in thigh muscle tissue in a mouse model.
CONCLUSIONS: This preclinical experimental study revealed detrimental effect of imatinib on carnitine-mediated energy metabolism of muscle cells providing a possible molecular background of the frequently occurred side effects during imatinib therapy such as fatigue, muscle pain and cramps.
PMID:39182842 | DOI:10.1016/j.molmet.2024.102016
Int J Clin Oncol. 2024 Aug 23. doi: 10.1007/s10147-024-02608-x. Online ahead of print.
ABSTRACT
BACKGROUND: Failure-free survival (FFS) rates of low-risk patients with rhabdomyosarcoma improved in Intergroup Rhabdomyosarcoma Study IV after the escalation of cyclophosphamide total dose to 26.4 g/m2. However, this dose may increase the risk of adverse events, including infertility, in some patients. The JRS-I LRA0401 and LRB0402 protocols aimed to reduce the cyclophosphamide dose to 9.6 g/m2 and 17.6 g/m2, respectively, without decreasing the FFS rates.
METHODS: Subgroup-A patients received eight cycles (24 weeks) of vincristine, actinomycin D, and 1.2 g/m2/cycle cyclophosphamide. Subgroup-B patients received eight cycles (24 weeks) of vincristine, actinomycin D, and 2.2 g/m2/cycle cyclophosphamide, followed by six cycles (24 weeks) of vincristine and actinomycin D. Group II/III patients in both subgroups received radiotherapy.
RESULTS: In subgroup A (n = 12), the 3-year FFS rate was 83% (95% confidence interval [CI], 48-96), and the 3-year overall survival (OS) rate was 100%. Only one isolated local recurrence was observed (8.3%). There were no unexpected grade-4 toxicities and no deaths. In subgroup B (n = 16), the 3-year FFS and OS rates were 88% (95% CI, 59-97) and 94% (95% CI, 63-99), respectively. There were no unexpected grade 4 toxicities and no deaths.
CONCLUSIONS: Shorter duration therapy using vincristine, actinomycin D, and lower dose cyclophosphamide with or without radiotherapy for patients with low-risk subgroup A rhabdomyosarcoma (JRS-I LRA0401 protocol) and moderate reduction of cyclophosphamide dose for patients with low-risk subgroup B rhabdomyosarcoma (JRS-I LRB0402 protocol) did not compromise FFS.
PMID:39177879 | DOI:10.1007/s10147-024-02608-x
World J Nucl Med. 2024 Jun 20;23(3):212-216. doi: 10.1055/s-0044-1787537. eCollection 2024 Sep.
ABSTRACT
Chimeric antigen receptor T-cell (CAR-T) treatment has been widely used in the treatment of hematological malignancies, and its application has been gradually expanded to the research and treatment of solid tumors. However, unconventional types of response may occur after CAR-T treatment, such as hyperprogression, resulting in terrible outcomes. Here, we report the case of a 13-year-old adolescent boy with relapsed and refractory rhabdomyosarcoma who developed early hyperprogression 3 weeks after CAR-T treatment (target: B7H3 and CD171), which was detected by fluorine-18 fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT). The patient eventually underwent amputation. Attention should be paid to the possibility of early hyperprogression after CAR-T treatment, and 18 F-FDG PET/CT has an absolute advantage in early evaluating treatment response to immunotherapy.
PMID:39170844 | PMC:PMC11335383 | DOI:10.1055/s-0044-1787537
Front Pediatr. 2024 Aug 7;12:1436446. doi: 10.3389/fped.2024.1436446. eCollection 2024.
ABSTRACT
Pediatric rhabdomyosarcoma of the biliary tract (BRMS) is extremely rare. Here, we present a case of a 2-year-old child who was initially misdiagnosed with choledocholithiasis upon admission. The diagnosis was later confirmed as BRMS through endoscopic retrograde cholangiopancreatography (ERCP). The patient was cured through surgery followed by chemotherapy. Due to the lack of specific early symptoms and the challenges in imaging differentiation, particularly in pediatric patients, clinical awareness of this condition needs to be heightened. Our findings indicate that ERCP is currently the optimal diagnostic tool for this disease, and a combination of surgery and chemotherapy can yield better therapeutic outcomes.
PMID:39170603 | PMC:PMC11335511 | DOI:10.3389/fped.2024.1436446
Sci Rep. 2024 Aug 21;14(1):19456. doi: 10.1038/s41598-024-70541-0.
ABSTRACT
Approximately 80% of pediatric tumors occur in low- and middle-income countries (LMIC), where diagnostic tools essential for treatment decisions are often unavailable or incomplete. Development of cost-effective molecular diagnostics will help bridge the cancer diagnostic gap and ultimately improve pediatric cancer outcomes in LMIC settings. We investigated the feasibility of using nanopore whole transcriptome sequencing on formalin-fixed paraffin embedded (FFPE)-derived RNA and a composite machine learning model for pediatric solid tumor diagnosis. Transcriptome cDNA sequencing was performed on a heterogenous set of 221 FFPE and 32 fresh frozen pediatric solid tumor and lymphoma specimens on Oxford Nanopore Technologies' sequencing platforms. A composite machine learning model was then used to classify transcriptional profiles into clinically actionable tumor types and subtypes. In total, 95.6% and 89.7% of pediatric solid tumors and lymphoma specimens were correctly classified, respectively. 71.5% of pediatric solid tumors had prediction probabilities > 0.8 and were classified with 100% accuracy. Similarly, for lymphomas, 72.4% of samples that had prediction probabilities > 0.6 were classified with 97.6% accuracy. Additionally, FOXO1 fusion status was predicted accurately for 97.4% of rhabdomyosarcomas and MYCN amplification was predicted with 88% accuracy in neuroblastoma. Whole transcriptome sequencing from FFPE-derived pediatric solid tumor and lymphoma samples has the potential to provide clinical classification of both tissue lineage and core genomic classification. Further expansion, refinement, and validation of this approach is necessary to explore whether this technology could be part of the solution of addressing the diagnostic limitations in LMIC.
PMID:39169157 | PMC:PMC11339337 | DOI:10.1038/s41598-024-70541-0
Pediatr Surg Int. 2024 Aug 19;40(1):234. doi: 10.1007/s00383-024-05810-0.
ABSTRACT
PURPOSE: This study aimed to investigate the impact of nephrostomies on the outcome of total renal function (TRF) and split renal function (SRF) in patients with malignant pelvic tumors associated with upper urinary tract obstruction (UUTO).
METHODS: Patients with pelvic tumors suffering severe unilateral hydronephrosis treated at our hospital from 2000 to 2022 were included. Data for nephrostomy placement, short- and long-term renal function, and radiological and nuclear imaging studies were collected. The TRF and SRF of patients who underwent nephrostomy were compared to those who did not.
RESULTS: Seven patients were included (rhabdomyosarcoma: 5, ovarian germ cell tumor: 1, malignant rhabdoid tumor: 1). Nephrostomies were placed in four, which were successfully managed without severe infections. Estimated glomerular filtration rate (eGFR) was significantly improved at the end of treatment in patients with nephrostomy. In contrast, eGFR in patients who did not undergo nephrostomy was not improved. Nuclear imaging studies (renograms or renal scintigrams) revealed impaired SRF of the affected kidney compared to the contralateral kidney, even in patients whose eGFR was within normal levels. Notably, SRF showed a trend to improve over time in one patient treated with nephrostomy.
CONCLUSION: Nephrostomy for UUTO caused by pelvic tumors may improve renal outcome.
PMID:39158590 | PMC:PMC11333509 | DOI:10.1007/s00383-024-05810-0
Open Life Sci. 2024 Aug 16;19(1):20220908. doi: 10.1515/biol-2022-0908. eCollection 2024.
ABSTRACT
Recent scientific investigations have revealed the intricate mechanisms underlying bone formation, emphasizing the essential role of long non-coding RNAs (lncRNAs) as critical regulators. This process, essential for skeletal strength and functionality, involves the transformation of mesenchymal stem cells into osteoblasts and subsequent deposition of bone matrix. lncRNAs, including HOX transcript antisense RNA (HOTAIR), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), differentiation antagonizing non-coding RNA (DANCR), and maternally expressed gene 3 (MEG3), have emerged as prominent players in this regulatory network. HOTAIR modulates osteoblast differentiation by interacting with chromatin-modifying enzymes, while MALAT1 regulates osteogenic differentiation through microRNA interactions. DANCR collaborates with Runx2 to fine-tune osteoblast differentiation, and MEG3 orchestrates multiple signaling pathways crucial for bone formation. Moreover, other lncRNAs such as H19, lncRNA for enhancing osteogenesis 3, rhabdomyosarcoma 2-associated transcript, urothelial cancer associated 1, taurine up-regulated gene 1, and nuclear enriched abundant transcript 1 contribute to the complex regulatory network governing osteoblast activities. Understanding the precise roles of these lncRNAs offers promising avenues for developing innovative therapeutic strategies targeting bone-related disorders like osteoporosis. Overall, this review summarizes the pivotal role of lncRNAs in bone formation, highlighting their potential as targets for future research endeavors aimed at advancing therapeutic interventions in bone diseases.
PMID:39156986 | PMC:PMC11330173 | DOI:10.1515/biol-2022-0908
BMC Oral Health. 2024 Aug 17;24(1):961. doi: 10.1186/s12903-024-04709-5.
ABSTRACT
BACKGROUND: Parameningeal rhabdomyosarcoma (PM-RMS) is a rare and aggressive soft tissue malignancy that primarily occurs in the head and neck region. The standard treatment approach for RMS involves a multimodal therapy regimen, which includes surgery, chemotherapy, and radiotherapy. However, the routine use of radiotherapy and chemotherapy in young patients with RMS in the head and neck region can lead to adverse effects on dental development and thereby, pose a challenge in planning dental intervention.
CASE PRESENTATION: This case report outlines the dental and facial developmental consequences in a 13-year-old child, who received chemo-radiotherapeutic intervention at the age of 7 years for the management of PM-RMS. Following treatment, the child exhibited significant dental complications, including arrested root growth and restricted mouth opening.
CONCLUSIONS: This case highlights the necessity for interdisciplinary collaboration between oncologists, dentists, and other healthcare professionals to mitigate the adverse effects on dental health and overall quality of life in patients undergoing chemo-radiotherapy for rhabdomyosarcoma.
PMID:39154167 | PMC:PMC11330129 | DOI:10.1186/s12903-024-04709-5
J Indian Assoc Pediatr Surg. 2024 Jul-Aug;29(4):384-386. doi: 10.4103/jiaps.jiaps_16_24. Epub 2024 Jul 6.
ABSTRACT
The latissimus dorsi muscle flap is a robust option for reconstructing defects over the back, but the use of this flap in infants is not widely documented. We did this flap to cover a defect that was created after wide local excision of a rhabdomyosarcoma on the back of a 2-month-old infant. Reconstructive surgery was completed successfully, and postoperative recovery was uneventful.
PMID:39149427 | PMC:PMC11324074 | DOI:10.4103/jiaps.jiaps_16_24
Mod Pathol. 2024 Aug 13:100594. doi: 10.1016/j.modpat.2024.100594. Online ahead of print.
ABSTRACT
Alveolar rhabdomyosarcoma (ARMS) with FOXO1 gene rearrangements is an aggressive pediatric rhabdomyosarcoma subtype that is prognostically distinct from embryonal rhabdomyosarcoma and fusion-negative ARMS. Herein, we report two cases of ARMS with PAX3::MAML3 fusions. The tumors arose in an infant and an adolescent as stage IV metastatic disease (by Children's Oncology Group staging system). Histologically, both cases were small round blue cell tumors arranged in vague nests and solid sheets that were diffusely positive for desmin and myogenin. By methylation profiling and unsupervised clustering analysis, the tumors clustered with ARMS with classic FOXO1 rearrangements and ARMS with variant PAX3::NCOA1/INO80D fusions, but not with biphenotypic sinonasal sarcoma (BSNS) with PAX3::MAML3/NCOA2/FOXO1/YAP1 fusions, nor with other small round blue cell tumors, including embryonal rhabdomyosarcoma. The differentially methylated genes between ARMS and BSNS were highly enriched in genes involved in myogenesis, and 21% of these genes overlap with target genes of the PAX3::FOXO1 fusion transcription factor. On follow-up after initiation of vincristine/actinomycin/cyclophosphamide chemotherapy, the tumors showed partial and complete clinical response, consistent with typical upfront chemotherapy responsiveness of ARMS with the classic FOXO1 rearrangement. We conclude that PAX3::MAML3 is a novel variant fusion of ARMS, which displays a methylation signature distinct from BSNS despite sharing similar PAX3 fusions. These findings highlight the utility of methylation profiling in classifying ARMS with non-canonical fusions.
PMID:39147032 | DOI:10.1016/j.modpat.2024.100594
BMC Cancer. 2024 Aug 15;24(1):1013. doi: 10.1186/s12885-024-12766-w.
ABSTRACT
BACKGROUND: The chemotherapy regimens recommended for both rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) patients are myelosuppressive and can reduce the absolute neutrophil count (ANC) and subsequently increase the risk of febrile neutropenia (FN). However, only a few studies have focused on the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) drugs in pediatric and adolescent patients with RMS and ES. Our objective was to investigate the efficacy and safety of mecapegfilgrastim, a biosimilar of pegfilgrastim, in prophylaxis of FN for pediatric and adolescent patients with RMS or ES.
METHODS: In this single-arm, single-center, prospective study, pediatric and adolescent patients with RMS or ES were enrolled to receive either VAC (vincristine, cyclophosphamide, dactinomycin) regimen or VDC (vincristine, cyclophosphamide, doxorubicin) regimen in a 3-week cycle, followed by treatment with mecapegfilgrastim (100 μg/kg, maximum 6 mg) given at 24 h after completing chemotherapy. The primary endpoint was the incidence rate of FN. Secondary endpoints included the incidence rate of grade 4 neutropenia, duration of ANC ≤ 0.5 × 109/L, incidence rate of chemotherapy delay or reduction, use of antibiotics, and safety profile.
RESULTS: In total, 2 of the 30 (6.7%, 95% CI: 0.82-22.07) patients experienced FN after the first cycle of chemotherapy. Eight (26.7%, 95% CI: 12.28-45.89) patients experienced grade 4 neutropenia after receiving prophylactic mecapegfilgrastim. Eight patients experienced ANC ≤ 0.5 × 109/L with a median duration of 4.5 days; among them, 6 patients reached the lowest point of their ANC level on day 7, and 5 of them recovered by day 10. No dose reductions, delays, or discontinuation of chemotherapy was reported. Twenty-one (70.0%) patients received antibiotics during the treatment period. No patient experienced FN in the 0-5 years and the 13-18 years groups, and 2 patients experienced FN in the 6-12 years group. Two patients, 6 patients, and no patient experienced grade 4 neutropenia in the 0-5 years, 6-12 years, and 13-18 years groups, respectively.
CONCLUSION: Mecapegfilgrastim showed acceptable efficacy and safety profile in pediatric and adolescent patients with RMS or ES. Further randomized studies with large sample size are warranted.
TRIAL REGISTRATION: This clinical trial was registered at Chictr.org.cn (No.ChiCTR1900022249). Registered on March 31, 2019.
PMID:39148050 | PMC:PMC11325604 | DOI:10.1186/s12885-024-12766-w
Sci Rep. 2024 Aug 15;14(1):18936. doi: 10.1038/s41598-024-66545-5.
ABSTRACT
Rhabdomyosarcoma (RMS) is the most common childhood soft tissue sarcoma. For the alveolar subtype (ARMS), the presence of the PAX3::FOXO1 fusion gene and/or metastases are strong predictors of poor outcome. Metastatic PAX3::FOXO1+ ARMS often responds to chemotherapies initially, only to subsequently relapse and become resistant with most patients failing to survive beyond 8 years post-diagnosis. No curative intent phase II or phase III clinical trial has been available for patients in the past 10 years (ARST0921). Thus, metastatic ARMS represents a significantly unmet clinical need. Chemotherapy resistance in ARMS has previously been attributed to PAX3::FOXO1-mediated cell cycle checkpoint adaptation, which is mediated by an HDAC3-SMARCA4-miR-27a-PAX3::FOXO1 circuit that can be disrupted by HDAC3 inhibition. In this study, we investigated the therapeutic efficacy of combining the epigenetic regulator entinostat, a Class I Histone Deacetylase (HDAC1-3) inhibitor, with RMS-specific chemotherapies in patient derived xenograft (PDX) models of RMS. We identified single agent, additive or synergistic relationships between relapse-specific chemotherapies and clinically relevant drug exposures of entinostat in three PAX3::FOXO1+ ARMS mouse models. This preclinical data provides further rationale for clinical investigation of entinostat, already known to be well tolerated in a pediatric phase I clinical trial (ADVL1513).
PMID:39147820 | PMC:PMC11327338 | DOI:10.1038/s41598-024-66545-5
Eur J Pediatr. 2024 Aug 15. doi: 10.1007/s00431-024-05731-z. Online ahead of print.
ABSTRACT
Pancreatic masses are extremely rare in pediatric patients, with limited data available. This lack of data makes the diagnosis and management of these tumors in children extremely challenging. Therefore, we aimed to describe the presentations, clinical course, and outcomes of children with pancreatic tumors at our center. A retrospective analysis was performed of all pediatric patients diagnosed with pancreatic masses between 2003 and 2022 in an academic freestanding children's hospital. Data including demographics, clinical presentation, workup, management, and subsequent morbidity and mortality were collected and aggregated. Furthermore, we reviewed cases of pancreatic tumor resections in the National Surgical Quality Improvement Program - Pediatric (NSQIP-P) database to identify common adverse outcomes and measures for quality improvement. In total, 17 patients were identified at our institution. Diagnoses included solid pseudopapillary (n = 9), gastrinoma (n = 1), rhabdomyosarcoma (n = 2), pancreatoblastoma (n = 2), and insulinoma (n = 1). Two patients did not have a histopathologic diagnosis and were excluded from subsequent analysis. Overall, 12 patients underwent surgical intervention, with the most common procedures being pancreaticoduodenectomy and distal pancreatectomy, and all 12 were known to be alive at last contact. There were 3 deaths, all due to complications related to metastatic disease. Furthermore, 30-day postoperative outcomes in the NSQIP-P dataset for pancreatic surgeries in pediatric patients are excellent, with negligible morbidity and no mortalities after the index surgery.
CONCLUSIONS: Children with pancreatic tumors amenable to surgical resection appear to have adequate long-term survival. Short-term outcomes at diagnosis are excellent and mainly appear to be influenced by the presence of metastatic disease at initial presentation.
WHAT IS KNOWN: • Pancreatic masses are a rare entity in children with limited data on their presentation, management and surgical outcomes. • Solid Pseudopapillary tumors are one of the most common pancreatic tumors in children with a fair prognosis after surgical intervention.
WHAT IS NEW: • Surgical management of pediatric patients with pancreatic tumors is safe and effective in patients who do not have aggressive tumor types or metastatic disease. • Our case series provides a notable cohort of these pancreatic tumors with insight into the presentation, management and outcomes of five of these tumor types.
PMID:39145888 | DOI:10.1007/s00431-024-05731-z
Transl Pediatr. 2024 Jul 31;13(7):1086-1096. doi: 10.21037/tp-24-41. Epub 2024 Jul 29.
ABSTRACT
BACKGROUND: Parameningeal rhabdomyosarcoma (PM-RMS) accounts for about 20% of all rhabdomyosarcoma (RMS) cases. At present, most research on PM-RMS has been conducted in Europe and the United States of America, and research in China has been very limited. This study sought to analyze the clinical outcomes and prognostic factors of PM-RMS in children and adolescents from two consecutive protocols at Beijing Children's Hospital (BCH).
METHODS: A total of 80 patients aged up to 18 years with previously untreated PM-RMS who had received treatment under two consecutive protocols [i.e., either the BCH-RMS-2006 protocol or the Chinese Children Cancer Group (CCCG)-RMS-2016 protocol] were included in the statistical analysis. The Kaplan-Meier method was used for the survival analysis, and Cox regression was used for the univariate and multivariate analyses.
RESULTS: Of the 80 patients enrolled in the study, 69 (86.2%) had meningeal invasion (MI). Of these 69 MI patients, 18 (22.5%) had cranial nerve palsy (CNP), 64 (80.0%) had cranial base bone erosion (CBBE), 25 (31.3%) had intracranial extension (ICE), and 2 (2.5%) had positive cerebrospinal fluid (CSF) tumor cells. The median follow-up time was 20.5 months (range, 5-100 months). The 5-year overall survival (OS) and progression-free survival (PFS) rates for the entire cohort were 51.7% and 45.6%, respectively. The 5-year OS rates of the patients who received the BCH-RMS-2006 protocol (18/80, 22.5%) and the CCCG-RMS-2016 protocol (62/80, 77.5%) were 33.3% and 57.0%, respectively (P<0.05), while the PFS rates of these patients were 22.2% and 53.6%, respectively (P<0.05). In relation to the PM-RMS patients with MI, the 5-year OS rates were 21.4% and 52.7%, and the 5-year PFS rates were 14.3% and 51.1% for the patients who received the old and new regimens, respectively (P<0.05). The extent of surgical resection had no significant effect on survival. The multivariate analysis showed that the coexistence of CBBE and ICE, no radiotherapy, a poor response to induction chemotherapy, and the BCH-RMS-2006 protocol were risk factors affecting PFS and OS.
CONCLUSIONS: Of the patients examined in this study, those with PM-RMS with CBBE accompanied by ICE had the worst prognosis. The patients with MI benefited from intensive chemotherapy combined with radiation therapy, but the effect of surgery was very limited.
PMID:39144439 | PMC:PMC11320008 | DOI:10.21037/tp-24-41
J Pediatr Hematol Oncol. 2024 Aug 12. doi: 10.1097/MPH.0000000000002930. Online ahead of print.
ABSTRACT
RMS is a malignant tumor of soft tissues affecting primarily children and adolescents. Around 6% to 23% RMS patients present bone marrow infiltration but leukemia-like involvement is very rare; in these patients cytomorphology on bone marrow smears can lead to misdiagnosis. Differential diagnosis with alveolar RMS should be kept in mind in every pediatric patient presenting with a marked bone marrow involvement in the absence of typical lymphoproliferative findings.
PMID:39141773 | DOI:10.1097/MPH.0000000000002930
Clin Case Rep. 2024 Aug 12;12(8):e9260. doi: 10.1002/ccr3.9260. eCollection 2024 Aug.
ABSTRACT
Early diagnosis and aggressive treatment of testicular rhabdomyosarcomas including surgery and chemotherapy significantly reduce local recurrence and improve survival rates in young adults with metastases. Adjuvant chemotherapy is highly recommended to enhances prognosis and survival outcomes.
PMID:39139618 | PMC:PMC11319223 | DOI:10.1002/ccr3.9260
Urol Case Rep. 2024 Jul 22;56:102811. doi: 10.1016/j.eucr.2024.102811. eCollection 2024 Sep.
ABSTRACT
Embryonal rhabdomyosarcoma of the prostate in adults is rare and often diagnosed at an advanced stage, with metastases. We report the case of a 23-year-old young adult presenting with low back pain and dysuria, whose imaging revealed a voluminous metastatic prostate mass. Biopsy confirmed embryonal rhabdomyosarcoma. Treatment was initiated with chemotherapy, resulting in significant regression of the tumour mass and metastases after 3 courses. Pediatric advances suggest improved survival with a multimodal approach, but its efficacy in adults requires further investigation.
PMID:39139383 | PMC:PMC11321368 | DOI:10.1016/j.eucr.2024.102811
Front Oncol. 2024 Jul 30;14:1396368. doi: 10.3389/fonc.2024.1396368. eCollection 2024.
ABSTRACT
BACKGROUND: Rhabdomyosarcoma of the bladder is an infrequent neoplastic condition characterized by a pronounced malignant situation with challenges in treatment due to the lack of standardized guidelines and large-scale of clinical studies. The patient in this case is tested TP53 mutation that may provide new diagnostic and therapeutic options.
CASE PRESENTATION: Here, we reported a 34-year-old male who received bladder tumor resection, and diagnosed as bladder rhabdomyosarcoma with TP53 mutation after the pathology test. This patient underwent 6 rounds of chemotherapy. However, the pelvic tumor recurred 11 months after the first surgery. So, the patient accepted the pelvic tumor resection. Only 3 months after the surgical intervention, the patient underwent abdominal massive metastasis and ultimately succumbed to the illness six months following the second surgery. The course of the illness was 22 months.
CONCLUSION: Bladder rhabdomyosarcoma is a disease with an extremely poor prognosis. Genetic testing holds significant value in the diagnosis and treatment. Perhaps targeted therapy against TP53 is potential valuable for such rare diseases.
PMID:39139286 | PMC:PMC11319136 | DOI:10.3389/fonc.2024.1396368
Pediatr Blood Cancer. 2024 Aug 13:e31257. doi: 10.1002/pbc.31257. Online ahead of print.
ABSTRACT
Non-rhabdomyosarcoma soft tissue sarcoma (STS) comprises most STS in pediatric patients. It is a diverse set of over 30 histologic subtypes. Treatment is based on risk group determined by tumor size, grade, and the presence of metastases. Surgical resection is a cornerstone of therapy, as tumors are often resistant to chemotherapy or radiation. While patients with isolated tumors less than 5 cm may undergo upfront resection, strong consideration should be given to neoadjuvant chemoradiotherapy to ensure negative margins at surgical resection and optimal outcomes. Sentinel lymph node biopsy is strongly recommended for clear cell and epithelioid sarcomas. The most common metastatic site is the lung, and metastases should be resected at the end of therapy, when feasible. Unfortunately, many high-risk patients progress on therapy, and alternative strategies including earlier metastatic control require investigation.
PMID:39138613 | DOI:10.1002/pbc.31257
Indian J Otolaryngol Head Neck Surg. 2024 Aug;76(4):3652-3655. doi: 10.1007/s12070-024-04665-0. Epub 2024 Apr 6.
ABSTRACT
Rhabdomyosarcoma (RMS) is commonly reported in children and very rarely in adults. Laryngeal RMS is a rare but extremely aggressive malignancy with a high mortality rate. Surgery followed by postoperative radiotherapy is the preferred treatment. The use of chemotherapy is debatable. This report highlights a case of rare pleomorphic rhabdomyosarcoma of glottis in a 67-year-old male who presented with hoarseness and a description of its management.
PMID:39130312 | PMC:PMC11306833 | DOI:10.1007/s12070-024-04665-0
Indian J Otolaryngol Head Neck Surg. 2024 Aug;76(4):3676-3678. doi: 10.1007/s12070-024-04684-x. Epub 2024 Apr 12.
ABSTRACT
Malignancies in paediatric age group are the second leading cause of death, next only to accidents. The variety of malignancies involving the head and neck region in paediatric age group is bewildering. Rhabdomyosarcoma of thyroid gland is one such entity very rarely seen. We present the case of an adolescent who presented with a neck mass and suffered rapid deterioration. Establishment of final diagnosis was possible only because of a skilfully performed pathological examination which revealed a thyroid gland rhabdomyosarcoma. An alveolar variety of rhabdomyosarcoma presenting in the thyroid gland is extremely rare. To the best of our knowledge, only two cases of the aforementioned are documented as yet. Through this report, we aim at highlighting the possibility of such an occurrence and vigilance on part of the treating surgeon so that timely intervention can be instituted.
PMID:39130284 | PMC:PMC11306890 | DOI:10.1007/s12070-024-04684-x
Pediatr Blood Cancer. 2024 Aug 11:e31256. doi: 10.1002/pbc.31256. Online ahead of print.
ABSTRACT
In the era of big data, young patients may be overwhelmed by artificial intelligence-based tools, like chatbots. Five clinical experts were asked to evaluate the performance of the most currently used chatbots in providing information on a rare cancer affecting young people, like rhabdomyosarcoma. Generally speaking, despite their high performance in giving general information about the disease, these chatbots were considered by the experts to be inadequate in providing suggestions on cancer treatments and specialized centers, and also lacking in "sensitivity." Efforts are planned by the pediatric oncology community to improve the quality of data used to train these tools.
PMID:39129151 | DOI:10.1002/pbc.31256
Hum Pathol. 2024 Aug 8;152:105636. doi: 10.1016/j.humpath.2024.105636. Online ahead of print.
ABSTRACT
Tumors with pathogenic DICER1 mutation are rare and encompass sporadic or hereditary benign, intermediate and malignant tumors. DICER1-associated sarcomas are heterogeneous; however, the prototypical ones in the GYN-tract include embryonal rhabdomyosarcoma, adenosarcoma and moderately to poorly differentiated Sertoli-Leydig tumor. In this report, we present three unique uterine sarcomas with DICER1 mutation and remarkable diffuse round/spindle cell morphology. The tumors occurred in cervix (n = 1), and uterine corpus (n = 2). The patient ages were 30, 37 and 59 years with tumor size of 8.8, 10 and 8.6 cm, respectively. Morphologically all three tumors were characterized by distinct spindle/round cell morphology and various amounts of neuroectodermal differentiation (yolk sac-like tubules, blastomatous areas and rosette formation). Other morphologic features of DICER1-sarcoma reported in the literature including cambium layer, focal or diffuse anaplasia, solid and cystic architecture, and chondroid/osteoid areas were absent. All three sarcomas were positive for SALL4 and had variable neuroendocrine marker expression. Whole genome methylation analysis was performed on one of the uterine sarcomas, which clustered the tumor with embryonal tumor with multilayered rosettes. Follow up information was available on all three cases. Two patients were alive with no evidence of disease 13 and 14 months post operation, while one patient had imaging evidence of local recurrence 4 months post operation. In summary, we describe three unique DICER1-sarcomas and expand the phenotypic spectrum of this emerging entity, particularly with GYN-tract origin.
PMID:39127354 | DOI:10.1016/j.humpath.2024.105636
Cell Death Discov. 2024 Aug 6;10(1):351. doi: 10.1038/s41420-024-02115-y.
ABSTRACT
Radiotherapy (RT) plays a critical role in the management of rhabdomyosarcoma (RMS), the prevalent soft tissue sarcoma in childhood. The high risk PAX3-FOXO1 fusion-positive subtype (FP-RMS) is often resistant to RT. We have recently demonstrated that inhibition of class-I histone deacetylases (HDACs) radiosensitizes FP-RMS both in vitro and in vivo. However, HDAC inhibitors exhibited limited success on solid tumors in human clinical trials, at least in part due to the presence of off-target effects. Hence, identifying specific HDAC isoforms that can be targeted to radiosensitize FP-RMS is imperative. We, here, found that only HDAC3 silencing, among all class-I HDACs screened by siRNA, radiosensitizes FP-RMS cells by inhibiting colony formation. Thus, we dissected the effects of HDAC3 depletion using CRISPR/Cas9-dependent HDAC3 knock-out (KO) in FP-RMS cells, which resulted in Endoplasmatic Reticulum Stress activation, ERK inactivation, PARP1- and caspase-dependent apoptosis and reduced stemness when combined with irradiation compared to single treatments. HDAC3 loss-of-function increased DNA damage in irradiated cells augmenting H2AX phosphorylation and DNA double-strand breaks (DSBs) and counteracting irradiation-dependent activation of ATM and DNA-Pkcs as well as Rad51 protein induction. Moreover, HDAC3 depletion hampers FP-RMS tumor growth in vivo and maximally inhibits the growth of irradiated tumors compared to single approaches. We, then, developed a new HDAC3 inhibitor, MC4448, which showed specific cell anti-tumor effects and mirrors the radiosensitizing effects of HDAC3 depletion in vitro synergizing with ERKs inhibition. Overall, our findings dissect the pro-survival role of HDAC3 in FP-RMS and suggest HDAC3 genetic or pharmacologic inhibition as a new promising strategy to overcome radioresistance in this tumor.
PMID:39107280 | PMC:PMC11303816 | DOI:10.1038/s41420-024-02115-y
Rare Tumors. 2024 Aug 4;16:20363613241271669. doi: 10.1177/20363613241271669. eCollection 2024.
ABSTRACT
Background: Rhabdomyosarcomas are the most common soft tissue sarcoma in children, and pediatric alveolar rhabdomyosarcoma (ARMS) prognosis has improved based on cooperative studies. However, in adults, ARMS is significantly rarer, has poorer outcomes, and currently lacks optimal treatment strategies. Objective: This study aimed to evaluate the clinical outcome of an adult ARMS population with different front-line systemic chemotherapies and determine if any chemotherapy regimen is associated with improved survival. Materials and methods: This is a retrospective study of histologically confirmed fusion-positive ARMS patients over 18 years of age, who were treated at MD Anderson Cancer Center (MDACC) from 2004 to 2021 and received systemic chemotherapy. Descriptive clinical statistics were performed, including staging, front-line chemotherapy, multimodal therapy usage, response rates, and survival analyses. Results: 49 ARMS patients who received upfront chemotherapy were identified. Locoregional treatments included radiotherapy (RT) alone (29%, n = 14), surgery alone (10%, n = 5), or both (45%, n = 22). Median overall survival (OS) for the entire cohort was 3.6 years, and the overall response rate to systemic therapy was 89%. No chemotherapy regimen showed OS benefit, specifically analyzing the pediatric-based vincristine, actinomycin-D, cyclophosphamide (VAC) or adult-based vincristine, doxorubicin, ifosfamide (VDI) regimens, even when controlled for other clinical risk factors. Conclusion: In this single-center contemporary series, adult ARMS patient outcomes remain poor. There was no statistically significant OS difference in patients who did or did not receive adult or pediatric based ARMS regimens, although a high overall response rate to chemotherapy was seen across the entire cohort. Based on these observations, further randomized prospective studies are necessary to delineate which frontline chemotherapy regimen is most beneficial in this rare adult cancer.
PMID:39105190 | PMC:PMC11299201 | DOI:10.1177/20363613241271669
Cureus. 2024 Jul 5;16(7):e63915. doi: 10.7759/cureus.63915. eCollection 2024 Jul.
ABSTRACT
Malignant phyllodes tumors (MPTs) represent the most pernicious type of intralobular stromal proliferation known as a "fibroepithelial lesion" (FEL). They comprise a small fraction of breast malignancies and can present as either a pure MPT or sometimes include a heterologous component (liposarcoma, chondrosarcoma, osteosarcoma, or rhabdomyosarcoma). Of the fraction of MPTs that include heterologous components, very little about those with chondroblastic osteosarcomatous differentiation has been described in the literature. As such, a characteristic staining profile has yet to be established, even though morphological analysis is the cornerstone of diagnosis. The few reported cases have described a poor prognosis. Therefore, we present a case of MPT with chondroblastic osteosarcomatous differentiation to contribute to the dearth of literature examining this entity.
PMID:39105035 | PMC:PMC11298328 | DOI:10.7759/cureus.63915
NPJ Precis Oncol. 2024 Aug 3;8(1):172. doi: 10.1038/s41698-024-00657-z.
ABSTRACT
Liquid biopsies are emerging as an alternative source for pediatric cancer biomarkers with potential applications during all stages of patient care, from diagnosis to long-term follow-up. While developments within this field are reported, these mainly focus on dedicated items such as a specific liquid biopsy matrix, analyte, and/or single tumor type. To the best of our knowledge, a comprehensive overview is lacking. Here, we review the current state of liquid biopsy research for the most common non-central nervous system pediatric solid tumors. These include neuroblastoma, renal tumors, germ cell tumors, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and other soft tissue sarcomas, and liver tumors. Within this selection, we discuss the most important or recent studies involving liquid biopsy-based biomarkers, anticipated clinical applications, and the current challenges for success. Furthermore, we provide an overview of liquid biopsy-based biomarker publication output for each tumor type based on a comprehensive literature search between 1989 and 2023. Per study identified, we list the relevant liquid biopsy-based biomarkers, matrices (e.g., peripheral blood, bone marrow, or cerebrospinal fluid), analytes (e.g., circulating cell-free and tumor DNA, microRNAs, and circulating tumor cells), methods (e.g., digital droplet PCR and next-generation sequencing), the involved pediatric patient cohort, and proposed applications. As such, we identified 344 unique publications. Taken together, while the liquid biopsy field in pediatric oncology is still behind adult oncology, potentially relevant publications have increased over the last decade. Importantly, steps towards clinical implementation are rapidly gaining ground, notably through validation of liquid biopsy-based biomarkers in pediatric clinical trials.
PMID:39097671 | PMC:PMC11297996 | DOI:10.1038/s41698-024-00657-z
Cancer Epidemiol Biomarkers Prev. 2024 Jul 31. doi: 10.1158/1055-9965.EPI-24-0510. Online ahead of print.
ABSTRACT
BACKGROUND: We examined association between late stage diagnosis and individual- and community-level characteristics among pediatric Hodgkin lymphoma (HL) and rhabdomyosarcoma (RMS) patients.
METHODS: We obtained Children's Oncology Group (COG) data from 1999-2021 including summary stage (local (L), regional (R), distant (D)), tumor subtype, demographics, and ZIP code at diagnosis. We linked ZIP codes to county-level redlining scores (C,D=greatest redlining), Child Opportunity Index (COI), and measures of segregation (racial dissimilarity indices (DI)). Logistic regressions calculated odds ratios for late stage diagnosis, and by race within tumor subtype.
RESULTS: 5,933 HL and 2,800 RMS patients were included. Late stage diagnosis of HL was correlated with Black race (ORDistant(D) vs regional/local(R&L)=1.38 [1.13-1.68]), being uninsured (ORD vs R&L=1.38 [1.09-1.75]), and subtype (Nodular sclerosis vs Other HL: ORD vs R&L=1.64 [1.34-2.01], Untyped: ORD vs R&L=1.30 [1.04-1.63]). Late stage rhabdomyosarcoma was correlated with bilingual households (ORDistant/regional(D&R) vs local(L)=2.66 [1.03-6.91]) and tumor type (Alveolar vs Embryonal ORD vs R&L=6.16 [5.00-7.58]. Community-level factors associated with late stage HL were greater Black (OR80-100%=1.83; 95% CI=1.11-3.02) and Hispanic (OR60-79%=1.30; 95%CI=1.05-1.60) DI. Late stage diagnosis for RMS was associated with more redlined census tracts within counties (OR=1.54; 95% CI =1.02-2.35) and low/very low COI (OR=1.21; 95% CI=1.02-1.45).
CONCLUSION: Novel markers of community deprivation, such as redlining and racial segregation, likely affect cancer outcomes for children with HL and RMS in this first disparities study using COG registries.
IMPACT: The interplay of multilevel risk factors provides important consideration for efforts to improve early detection of pediatric cancer diagnosis.
PMID:39083086 | DOI:10.1158/1055-9965.EPI-24-0510
Ann R Coll Surg Engl. 2024 Jul 31. doi: 10.1308/rcsann.2024.0065. Online ahead of print.
ABSTRACT
Rhabdomyosarcoma (RMS) is a form of soft tissue sarcoma that can arise from muscle or fibrous tissue almost anywhere in the body. The two major subtypes of RMS are alveolar and embryonal, whereas the two rarer subtypes are pleomorphic, which typically occurs in adults, and the spindle cell/sclerosing variant, typically seen in children. RMS usually involves the extremities, the head and neck or the genitourinary system. Although it can arise from anywhere in the body, other sites of involvement are rare and usually present only at an advanced stage owing to a mass effect on surrounding tissues and organs. We present a rare case of a child who presented with the signs and symptoms of an acute abdomen, but intraoperatively was found to have a bleeding necrotic mass arising from the anterior abdominal wall. This was histologically confirmed to be a RMS of the embryonal type.
PMID:39081180 | DOI:10.1308/rcsann.2024.0065
bioRxiv [Preprint]. 2024 Jul 16:2024.07.12.603270. doi: 10.1101/2024.07.12.603270.
ABSTRACT
Fusion-positive rhabdomyosarcoma is an aggressive pediatric cancer molecularly characterized by arrested myogenesis. The defining genetic driver, PAX3::FOXO1, functions as a chimeric gain-of-function transcription factor. An incomplete understanding of PAX3::FOXO1's in vivo epigenetic mechanisms has hindered therapeutic development. Here, we establish a PAX3::FOXO1 zebrafish injection model and semi-automated ChIP-seq normalization strategy to evaluate how PAX3::FOXO1 initially interfaces with chromatin in a developmental context. We investigated PAX3::FOXO1's recognition of chromatin and subsequent transcriptional consequences. We find that PAX3::FOXO1 interacts with inaccessible chromatin through partial/homeobox motif recognition consistent with pioneering activity. However, PAX3::FOXO1-genome binding through a composite paired-box/homeobox motif alters chromatin accessibility and redistributes H3K27ac to activate neural transcriptional programs. We uncover neural signatures that are highly representative of clinical rhabdomyosarcoma gene expression programs that are enriched following chemotherapy. Overall, we identify partial/homeobox motif recognition as a new mode for PAX3::FOXO1 pioneer function and identify neural signatures as a potentially critical PAX3::FOXO1 tumor initiation event.
PMID:39071299 | PMC:PMC11275748 | DOI:10.1101/2024.07.12.603270
Asian Pac J Cancer Prev. 2024 Jul 1;25(7):2445-2455. doi: 10.31557/APJCP.2024.25.7.2445.
ABSTRACT
OBJECTIVES: Rhabdomyosarcoma (RMS) accounts for 50% of soft tissue sarcomas and 7% of pediatric malignancies. Cyclophosphamide (CPA) is the cornerstone of therapy and is a prodrug that is activated by the highly polymorphic drug-metabolizing enzyme CYP3A5. We aim to examine the possible CYP3A5 polymorphism association with CPA efficacy, survival outcomes, and toxicity in Egyptian pediatric RMS patients.
METHODS: The three non-functional SNPs, CYP3A5*3 rs776746 (C_26201809_30), CYP3A5*6 rs10264272 (C_30203950_10), and CYP3A5*7 rs41303343 (C_32287188_10) were genotyped by real-time PCR. We conducted a cohort retrospective study of 150 pediatric RMS patients treated with CPA-based first-line treatment to analyze the association between these genotypes and CPA efficacy/toxicities in RMS patients.
KEY FINDINGS: The frequency of having normal, intermediate, and poor metabolizers was 4.7%, 34%, and 61.3%, respectively. There was an association between these different phenotypes, genotypes, and CPA efficacy/toxicity. Hemorrhagic cystitis and pancytopenia were present in all patients, while nephrotoxicity incidence was 87.3%. There was a notable difference in the occurrence of hemorrhagic cystitis among CYP3A5 intermediate metabolizers *1/*3, *1/*6, and poor metabolizers *3/*3, *3/*6 with a significance level of p<0.05. Neither CYP3A5*7 polymorphism nor *6/*6 genotype was identified in our study.
CONCLUSION: Our results demonstrate that CYP3A5*3 (rs776746) and CYP3A5*6 (rs10264272) have a great association with CPA efficacy and toxicity in RMS patients.
PMID:39068579 | DOI:10.31557/APJCP.2024.25.7.2445
Medicina (Kaunas). 2024 Jul 19;60(7):1172. doi: 10.3390/medicina60071172.
ABSTRACT
Actinomycosis is a rare infectious disease characterized by slowly progressive, chronic suppurative lesions, often mistaken for malignancies due to its ability to mimic them. It is caused by Actinomyces bacteria, which are part of the normal flora of the human oropharynx, gastrointestinal, and urogenital tracts. This case report describes a 51-year-old male with a history of mandibular rhabdomyosarcoma presenting with severe shoulder and hip pain, dysphagia, and headaches, initially suspected to be a cancer recurrence. However, after further investigation, including a PET-CT and tonsillectomy, the diagnosis of actinomycosis was confirmed through histopathological examination. The case highlights the diagnostic challenges of actinomycosis, especially in patients with complex clinical histories, emphasizing the importance of considering it as a differential diagnosis in similar presentations. The patient was treated with long-term antibiotic therapy, predominantly beta-lactams, demonstrating the necessity of a comprehensive diagnostic approach and the implications of a delayed diagnosis. This case underscores the critical need for high clinical suspicion and awareness among healthcare professionals regarding the potential for actinomycosis to mimic more common diseases, ensuring timely and accurate treatment.
PMID:39064601 | PMC:PMC11278731 | DOI:10.3390/medicina60071172
Nat Commun. 2024 Jul 26;15(1):6307. doi: 10.1038/s41467-024-50527-2.
ABSTRACT
Rhabdomyosarcoma (RMS) is a pediatric tumor that resembles undifferentiated muscle cells; yet the extent to which cell state heterogeneity is shared with human development has not been described. Using single-cell/nucleus RNA sequencing from patient tumors, patient-derived xenografts, primary in vitro cultures, and cell lines, we identify four dominant muscle-lineage cell states: progenitor, proliferative, differentiated, and ground cells. We stratify these RMS cells/nuclei along the continuum of human muscle development and show that they share expression patterns with fetal/embryonal myogenic precursors rather than postnatal satellite cells. Fusion-negative RMS (FN-RMS) have a discrete stem cell hierarchy that recapitulates fetal muscle development and contain therapy-resistant FN-RMS progenitors that share transcriptomic similarity with bipotent skeletal mesenchymal cells. Fusion-positive RMS have tumor-acquired cells states, including a neuronal cell state, that are not found in myogenic development. This work identifies previously underappreciated cell state heterogeneity including unique treatment-resistant and tumor-acquired cell states that differ across RMS subtypes.
PMID:39060228 | PMC:PMC11282092 | DOI:10.1038/s41467-024-50527-2
Cancer. 2024 Jul 26. doi: 10.1002/cncr.35497. Online ahead of print.
ABSTRACT
BACKGROUND: The authors report the prospective evaluation of reduced dose alkylator chemotherapy combined with radiotherapy for European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) standard risk nonalveolar rhabdomyosarcoma (NA-RMS).
PATIENTS AND METHODS: Localized node negative Intergroup Rhabdomyosarcoma Study (IRS) II/III NA-RMS at favorable sites (subgroup C), <25 years old, received five cycles of ifosfamide, vincristine, and dactinomycin (IVA) chemotherapy (30 g/m2 ifosfamide) and four cycles of vincristine and dactinomycin (if receiving radiotherapy), or nine cycles of IVA (54 g/m2 ifosfamide) ± radiotherapy. Delayed primary tumor excision was considered for IRS III tumors. The primary end points were event-free survival (EFS) and overall survival (OS).
RESULTS: From October 2005 to December 2016, 359 evaluable patients were recruited: orbit, 164 (45.7%); head and neck nonparameningeal, 77 (21.4%); and genitourinary non-bladder/prostate, 118 (32.9%). EFS and OS were 77.4% (95% confidence interval [CI], 72.5-81.6) and 93.5% (95% CI, 90.1-95.8), respectively. Lower dose alkylator chemotherapy and radiotherapy achieved 5-year OS of 93.7% but the difference with higher dose alkylator chemotherapy +/- radiotherapy was not significant (p = 0.8003). Adjuvant radiotherapy improved EFS with 5-year estimates of 84.7% versus 65.2% for nonirradiated (p < .0001), but not OS (p = .9298). Omitting radiotherapy for orbital tumors reduced OS (5-year was 87.1% vs. 97.3% for irradiated, p = .0257). Following R0 resection (n = 60), radiotherapy did not significantly improve EFS or OS.
CONCLUSIONS: Radiotherapy for local tumor control allows for reduction of cumulative dose of alkylators in EpSSG standard risk subgroup C RMS patients. The omission of radiotherapy did not affect OS in all patients except those with orbital RMS and was associated with inferior EFS.
PMID:39058728 | DOI:10.1002/cncr.35497
Asian J Surg. 2024 Jul 24:S1015-9584(24)01465-9. doi: 10.1016/j.asjsur.2024.07.095. Online ahead of print.
NO ABSTRACT
PMID:39054120 | DOI:10.1016/j.asjsur.2024.07.095
Front Cell Dev Biol. 2024 Jul 10;12:1378548. doi: 10.3389/fcell.2024.1378548. eCollection 2024.
ABSTRACT
Skeletal muscle is one of the tissues with the highest ability to regenerate, a finely controlled process which is critically depending on muscle stem cells. Muscle stem cell functionality depends on intrinsic signaling pathways and interaction with their immediate niche. Upon injury quiescent muscle stem cells get activated, proliferate and fuse to form new myofibers, a process involving the interaction of multiple cell types in regenerating skeletal muscle. Receptors in muscle stem cells receive the respective signals through direct cell-cell interaction, signaling via secreted factors or cell-matrix interactions thereby regulating responses of muscle stem cells to external stimuli. Here, we discuss how muscle stem cells interact with their immediate niche focusing on how this controls their quiescence, activation and self-renewal and how these processes are altered in age and disease.
PMID:39050890 | PMC:PMC11266305 | DOI:10.3389/fcell.2024.1378548