PRospective rEgistry OF Advanced Stage cancER (PREFER) Patients to Assess Prevalence of Actionable Biomarkers and Driver Mutations to Address Disparities in Precision Medicine

Posted: January 25th, 2023, 3:00pm GMT

Conditions: Lung Cancer; Ovarian Cancer; Uterine Cancer; Colorectal Cancer; Stomach Cancer; Esophageal Cancer; Pancreatic Cancer; Melanoma; Breast Cancer; Head and Neck Cancer; Soft Tissue Sarcoma; Rhabdomyosarcoma; Prostate Cancer
Intervention: Diagnostic Test: OmniSeq Test
Sponsor: Labcorp Drug Development Inc
Recruiting
$Permalink for 'Disulfiram With Copper Gluconate and Liposomal Doxorubicin in Treatment-Refractory Sarcomas'$
Disulfiram With Copper Gluconate and Liposomal Doxorubicin in Treatment-Refractory Sarcomas

Posted: January 27th, 2022, 3:00pm GMT

Condition: Relapsed Sarcomas
Interventions: Drug: Disulfiram; Drug: Copper Gluconate; Drug: Liposomal Doxorubicin (Doxil)
Sponsor: Case Comprehensive Cancer Center
Recruiting
B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

Posted: May 21st, 2021, 2:00pm GMT

Conditions: Pediatric Solid Tumor; Osteosarcoma; Rhabdomyosarcoma; Neuroblastoma; Ewing Sarcoma; Wilms Tumor; Adrenocortical Cancer; Desmoplastic Small Round Cell Tumor; Germ Cell Cancer; Rhabdoid Tumor; Clear Cell Sarcoma; Hepatoblastoma; Melanoma; Carcinoma; Malignant Peripheral Nerve Sheath Tumors; Soft Tissue Sarcoma
Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: MESNA; Drug: B7-H3 CAR T cells
Sponsor: St. Jude Children's Research Hospital
Recruiting
$Permalink for 'B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults'$
B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

Posted: July 23rd, 2020, 2:00pm GMT

Conditions: Pediatric Solid Tumor; Germ Cell Tumor; Retinoblastoma; Hepatoblastoma; Wilms Tumor; Rhabdoid Tumor; Carcinoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Synovial Sarcoma; Clear Cell Sarcoma; Malignant Peripheral Nerve Sheath Tumors; Desmoplastic Small Round Cell Tumor; Soft Tissue Sarcoma; Neuroblastoma; Melanoma
Interventions: Biological: second generation 4-1BBζ B7H3-EGFRt-DHFR; Biological: second generation 4-1BBζ B7H3-EGFRt-DHFR(selected) and a second generation 4-1BBζ CD19-Her2tG
Sponsor: Seattle Children's Hospital
Recruiting
$Permalink for 'EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults'$
EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults

Posted: August 7th, 2018, 2:00pm GMT

Conditions: Pediatric Solid Tumor; Germ Cell Tumor; Retinoblastoma; Hepatoblastoma; Wilms Tumor; Rhabdoid Tumor; Carcinoma; Osteosarcoma; Ewing Sarcoma; Rhabdomyosarcoma; Synovial Sarcoma; Clear Cell Sarcoma; Malignant Peripheral Nerve Sheath Tumors; Desmoplastic Small Round Cell Tumor; Soft Tissue Sarcoma; Neuroblastoma
Interventions: Biological: second generation 4-1BBζ EGFR806-EGFRt; Biological: second generation 4-1BBζ EGFR806-EGFRt and a second generation 4 1BBζ CD19-Her2tG
Sponsor: Seattle Children's Hospital
Recruiting
$Permalink for 'Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors'$
Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors

Posted: December 31st, 2015, 3:00pm GMT

Conditions: Diffuse Intrinsic Pontine Glioma; Brain Tumor, Recurrent; Solid Tumor, Recurrent; Neuroblastoma, Recurrent, Refractory; Ewing Sarcoma, Recurrent, Refractory; Rhabdomyosarcoma, Recurrent, Refractory; Osteosarcoma, Recurrent, Refractory; Rhabdoid Tumor, Recurrent, Refractory
Intervention: Drug: Abemaciclib
Sponsor: Emory University
Recruiting

PubMed - Rhabdomyosarcoma

Zebrafish her3 knockout impacts developmental and cancer-related gene signatures

Fetched: January 26th, 2023, 5:02am GMT by Matthew R Kent

Dev Biol. 2023 Jan 23;496:1-14. doi: 10.1016/j.ydbio.2023.01.003. Online ahead of print.

ABSTRACT

HES3 is a basic helix-loop-helix transcription factor that regulates neural stem cell renewal during development. HES3 overexpression is predictive of reduced overall survival in patients with fusion-positive rhabdomyosarcoma, a pediatric cancer that resembles immature and undifferentiated skeletal muscle. However, the mechanisms of HES3 cooperation in fusion-positive rhabdomyosarcoma are unclear and are likely related to her3/HES3's role in neurogenesis. To investigate HES3's function during development, we generated a zebrafish CRISPR/Cas9 null mutation of her3, the zebrafish ortholog of HES3. Loss of her3 is not embryonic lethal and adults exhibit expected Mendelian ratios. Embryonic her3 zebrafish mutants exhibit dysregulated neurog1 expression, a her3 target gene, and the mutant her3 fails to bind the neurog1 promoter sequence. Further, her3 mutants are significantly smaller than wildtype and a subset present with lens defects as adults. Transcriptomic analysis of her3 mutant embryos indicates that genes involved in organ development, such as pctp and grinab, are significantly downregulated. Further, differentially expressed genes in her3 null mutant embryos are enriched for Hox and Sox10 motifs. Several cancer-related gene pathways are impacted, including the inhibition of matrix metalloproteinases. Altogether, this new model is a powerful system to study her3/HES3-mediated neural development and its misappropriation in cancer contexts.

PMID:36696714 | DOI:10.1016/j.ydbio.2023.01.003
Redundant Signaling as the Predominant mechanism for Resistance to Antibodies Targeting IGF-1R in Cells Derived from Childhood Sarcoma

Fetched: January 26th, 2023, 5:02am GMT by Terry J Shackleford

Mol Cancer Ther. 2023 Jan 24:MCT-20-0625. doi: 10.1158/1535-7163.MCT-20-0625. Online ahead of print.

ABSTRACT

Antibodies targeting IGF-1R induce objective responses in only 5-15% of children with sarcoma. Understanding mechanisms of resistance may identify combination therapies that optimize efficacy of IGF-1R-targeted antibodies. Sensitivity to the IGF1R-targeting antibody TZ-1 was determined in rhabdomyosarcoma (RMS) and Ewing sarcoma (EWS) cell lines. Acquired resistance to TZ-1 was developed and characterized in sensitive Rh41 cells. BRD4 inhibitor, JQ1 was evaluated as an agent to prevent acquired TZ-1 resistance in Rh41 cells. The phosphorylation status of RTKs was assessed. Sensitivity to TZ-1 in vivo was determined in Rh41 parental and TZ-1-resistant xenografts. Of 20 sarcoma cell lines, only Rh41 was sensitive to TZ-1. Cells intrinsically resistant to TZ-1 expressed multiple (>10) activated RTKs or a relatively less complex set of activated RTKs (~5). TZ-1 decreased the phosphorylation of IGF-1R, but had little effect on other pRTKs in all resistant lines. TZ-1 rapidly induced activation of RTKs in Rh41 that was partially abrogated by knockdown of SOX18 and JQ1. Rh41/TZ-1 cells selected for acquired resistance to TZ-1 constitutively expressed multiple activated RTKs. TZ-1 treatment caused complete regressions in Rh41 xenografts, and was significantly less effective against the Rh41/TZ-1 xenograft. Intrinsic resistance is a consequence of redundant signaling in pediatric sarcoma cell lines. Acquired resistance in Rh41 cells, is associated with rapid induction of multiple RTKs indicating a dynamic response to IGF-1R blockade and rapid development of resistance. The TZ-1 antibody had greater antitumor activity against Rh41 xenografts compared to other IGF-1R-targeted antibodies tested against this model.

PMID:36696581 | DOI:10.1158/1535-7163.MCT-20-0625
Massive nasopharyngeal rhabdomyosarcoma in an adult patient: a rare case report

Fetched: January 26th, 2023, 5:02am GMT by Christopher Seifen

Oxf Med Case Reports. 2023 Jan 18;2023(1):omac148. doi: 10.1093/omcr/omac148. eCollection 2023 Jan.

ABSTRACT

Rhabdomyosarcoma (RMS) is a highly invasive malignant soft tissue sarcoma that rarely affects adults. The head and neck region accounts for most adult RMSs. Here, we report a case of a 24-year-old Caucasian woman who was diagnosed with persistent hoarseness and a painless left-sided neck mass. Physical examination and image studies showed a massive tumor of the nasopharynx, extending from the left-sided skull base to supraglottic structures. Histopathologic evaluation revealed the diagnosis of a poorly differentiated RMS. Due to the primary tumor size and involvement of crucial structures, extensive surgical excision was not amenable. Thus, the patient was treated with radiotherapy and chemotherapy. Although very rare, nasopharyngeal RMSs should be considered in the differential diagnosis of neck masses in adult patients. This case report illustrates the difficulty in the diagnosis and treatment of rare head and neck malignancies and encourages its reporting.

PMID:36694602 | PMC:PMC9853934 | DOI:10.1093/omcr/omac148
Comment on: Diagnosis and treatment interval are not associated with survival in rhabdomyosarcoma: A cancer in young people in Canada study

Fetched: January 26th, 2023, 5:02am GMT by Sabahat Hafeez

Pediatr Blood Cancer. 2023 Jan 24:e30209. doi: 10.1002/pbc.30209. Online ahead of print.

NO ABSTRACT

PMID:36694408 | DOI:10.1002/pbc.30209
GLI1 Immunohistochemistry Distinguishes Mesenchymal Neoplasms With GLI1 Alterations from Morphologic Mimics

Fetched: January 25th, 2023, 5:02am GMT by Paige H Parrack

Am J Surg Pathol. 2023 Jan 23. doi: 10.1097/PAS.0000000000002018. Online ahead of print.

ABSTRACT

Glioma-associated oncogene 1 (GLI1) alterations have been described in pericytoma with t(7;12), gastroblastoma, plexiform fibromyxoma, and an emerging class of GLI1-rearranged or amplified mesenchymal neoplasms including "nested glomoid neoplasm". The immunophenotype of these tumor types is nonspecific, making some cases difficult to diagnose without sequencing. The utility of GLI1 immunohistochemistry (IHC) in distinguishing nested glomoid neoplasms and pericytomas with t(7;12) from morphologic mimics is unknown. To investigate the diagnostic value of GLI1 IHC, we determined its sensitivity and specificity in a "test cohort" of 23 mesenchymal neoplasms characterized by GLI1 alterations, including 12 nested glomoid neoplasms (7 GLI1-rearranged, 4 GLI1 amplified, and 1 unknown GLI1 status), 9 pericytomas with t(7;12), 1 gastroblastoma, and 1 malignant epithelioid neoplasm with PTCH1::GLI1 fusion. GLI1 IHC was 91.3% sensitive in this cohort; all tumors except 2 pericytomas with t(7;12) expressed GLI1. GLI1 was also expressed in 1 of 8 (12%) plexiform fibromyxomas. Nineteen of 22 GLI1-positive tumors showed nuclear and cytoplasmic staining, while 3 showed nuclear staining only. GLI1 IHC was 98.0% specific; among morphologic mimics [40 well-differentiated neuroendocrine tumors, 10 atypical lung carcinoids, 20 paragangliomas, 20 glomus tumors, 20 solitary fibrous tumors, 10 Ewing sarcomas, 10 alveolar rhabdomyosarcomas (ARMS), 10 BCOR-altered sarcomas, 10 myoepitheliomas, 9 myopericytomas, 9 epithelioid schwannomas, 9 ossifying fibromyxoid tumors, 10 biphasic synovial sarcomas, 10 PEComas, 31 gastrointestinal stromal tumors, 10 inflammatory fibroid polyps, 11 pseudoendocrine sarcomas], 5 of 249 tumors expressed GLI1 (2 well-differentiated neuroendocrine tumors, 1 ARMS, 1 Ewing sarcoma, 1 BCOR-altered sarcoma). GLI1 IHC was also performed on a separate cohort of 13 molecularly characterized mesenchymal neoplasms in which GLI1 copy number gain was identified as a putatively secondary event by DNA sequencing (5 dedifferentiated liposarcoma [DDLPS], 2 adenosarcomas, 2 unclassified uterine sarcomas, 1 leiomyosarcoma, 1 ARMS, 1 intimal sarcoma, 1 osteosarcoma); 2 DDLPS, 1 ARMS, and 1 unclassified uterine sarcoma expressed GLI1. Lastly, because pleomorphic sarcomas sometimes show GLI1 amplification or copy number gain, GLI1 IHC was performed on a separate "pleomorphic sarcoma" cohort: GLI1 was expressed in 1 of 27 DDLPS, 1 of 9 leiomyosarcomas, and 2 of 10 pleomorphic liposarcomas, and it was negative in 23 well-differentiated liposarcomas and 9 unclassified pleomorphic sarcomas. Overall, GLI1 IHC was 91.3% sensitive and 98.0% specific for mesenchymal tumor types with driver GLI1 alterations among morphologic mimics. GLI1 expression was less frequent in other tumor types with GLI1 copy number gain. Given its specificity, in the appropriate morphologic context, GLI1 IHC may be a useful diagnostic adjunct for mesenchymal neoplasms with GLI1 alterations.

PMID:36693363 | DOI:10.1097/PAS.0000000000002018
Case report: Clinical features and prognosis of two Infants with rhabdomyosarcoma of the tongue

Fetched: January 24th, 2023, 5:02am GMT by Peiyi Yang

Front Oncol. 2023 Jan 4;12:934882. doi: 10.3389/fonc.2022.934882. eCollection 2022.

ABSTRACT

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue tumor in children, and its most common pathological types include embryonal RMS and alveolar RMS. In contrast, spindle cell RMS (SRMS) is a rare type. Moreover, the tongue is a rare primary site of RMS, and infancy is a rare age at onset.

CASE PRESENTATION: Two infants were diagnosed with lingual RMS at 3 and 5 months after birth, respectively, and were admitted to Beijing Children's Hospital. The pathological type in both cases was SRMS. Both were classified as low-risk and were treated with surgery and chemotherapy. Case 1 was in complete remission at the latest follow-up, and Case 2 had a relapse 10 months after stopping chemotherapy, achieving complete remission after the multimodal treatment of chemotherapy, surgery, and radiotherapy. The venous blood gene test of the two infants did not indicate a pathogenic mutation or a possible pathogenic mutation related to RMS. In Case 1, variants of the CDK4 and BRCA1 genes, both with unknown significance and a possible relation to RMS, were detected. In Case 2, three gene variants of unknown significance that were possibly associated with RMS-TRIP13, APC, and RAD54L-were identified.

CONCLUSION: Lingual RMS in infants is rare. Its clinical manifestations lack specificity, and early recognition is complex. The success and timing of local treatment are important prognostic factors. Genetic testing may be helpful for the early detection of tumor susceptibility and the estimation of prognosis.

PMID:36686750 | PMC:PMC9846346 | DOI:10.3389/fonc.2022.934882
Institutional experience of using active breathing control for paediatric and teenage patients receiving thoraco-abdominal radiotherapy

Fetched: January 24th, 2023, 5:02am GMT by Jessica Gough

Clin Transl Radiat Oncol. 2023 Jan 2;39:100575. doi: 10.1016/j.ctro.2022.100575. eCollection 2023 Mar.

ABSTRACT

INTRODUCTION: Active Breathing Control (ABC) is a motion management strategy that facilitates reproducible breath-hold for thoracic radiotherapy (RT), which may reduce radiation dose to organs at risk (OARs). Reduction of radiation-induced toxicity is of high importance in younger patients. However, there is little published literature on the feasibility of ABC in this group. The purpose of this study was to report our experience of using ABC for paediatric and teenage patients.

METHODS: Patients ≤18 years referred for thoracic RT using ABC at our centre from 2013-2021 were identified. Electronic records were retrospectively reviewed to obtain information on diagnosis, RT dose and technique, OAR dosimetry, tolerability of ABC, post-treatment imaging and early toxicity rates.

RESULTS: 12 patients completed RT and were able to comply with ABC during planning and for the duration of RT. Median age was 15.5 years (10-18 years). Diagnoses were: Hodgkin lymphoma (n = 5), mediastinal B-cell lymphoma (n = 1), Ewing sarcoma (n = 5) and rhabdomyosarcoma (n = 1). For mediastinal RT cases (n = 6), median dose delivered was 30.6Gy(19.8-40Gy), median mean heart dose was 11.4Gy(4.8-19.4Gy), median mean lung dose was 9.9Gy(5.7-14.5Gy) and mean lung V20 was 10.9%. For ipsilateral RT cases, (n = 6), median hemithorax and total doses to primary tumour were 18Gy(15-20Gy) and 52.2Gy(36-60Gy) respectively. Median mean heart dose was 19.5Gy(10.6-33.2Gy) and median mean lung dose was 17.7Gy(16.3-30.5Gy). Mean bilateral lung V20 was 39.6%. Median mean contralateral lung dose was 5.2Gy(3.5-11.6Gy) and mean contralateral lung V20 was 1.5%. At a median follow-up of 36 months, only 1 patient had symptomatic radiation pneumonitis having received further thoracic RT following relapse.

CONCLUSIONS: ABC is feasible and well tolerated in younger patients receiving RT. Children as young as 10 years are able to comply. Use of ABC results in OAR dosimetry which is comparable to similar data in adults and can facilitate RT for extensive thoracic sarcoma.

PMID:36686562 | PMC:PMC9850023 | DOI:10.1016/j.ctro.2022.100575
Developments in the Surgical Approach to Staging and Resection of Rhabdomyosarcoma

Fetched: January 22nd, 2023, 5:02am GMT by Sheila Terwisscha van Scheltinga

Cancers (Basel). 2023 Jan 10;15(2):449. doi: 10.3390/cancers15020449.

ABSTRACT

Although survival after rhabdosarcoma treatment has improved over the years, one third of patients still develop locoregional relapse. This review aims to highlight developments pertaining to staging and local treatment of specific RMS tumor sites, including head and neck, chest/trunk, bladder-prostate, female genito-urinary, perianal, and extremity sites.

PMID:36672397 | PMC:PMC9857078 | DOI:10.3390/cancers15020449
Patient Reported Outcomes and Measures in Children with Rhabdomyosarcoma

Fetched: January 22nd, 2023, 5:02am GMT by Marloes van Gorp

Cancers (Basel). 2023 Jan 9;15(2):420. doi: 10.3390/cancers15020420.

ABSTRACT

In addition to optimising survival of children with rhabdomyosarcoma (RMS), more attention is now focused on improving their quality of life (QOL) and reducing symptoms during treatment, palliative care or into long-term survivorship. QOL and ongoing symptoms related to the disease and its treatment are outcomes that should ideally be patient-reported (patient-reported outcomes, PROs) and can be assessed using patient-reported outcome measures (PROMS). This commentary aims to encourage PRO and PROM use in RMS by informing professionals in the field of available PROMs for utilisation in paediatric RMS and provide considerations for future use in research and clinical practice. Despite the importance of using PROMs in research and practice, PROMs have been reported scarcely in paediatric RMS literature so far. Available literature suggests lower QOL of children with RMS compared to general populations and occurrence of disease-specific symptoms, but a lack of an RMS-specific PROM. Ongoing developments in the field include the development of PROMs targeted at children with RMS specifically and expansion of PROM evaluation within clinical trials.

PMID:36672371 | PMC:PMC9856469 | DOI:10.3390/cancers15020420
VGLL2-NCOA2 leverages developmental programs for pediatric sarcomagenesis

Fetched: January 20th, 2023, 5:03am GMT by Sarah Watson

Cell Rep. 2023 Jan 18;42(1):112013. doi: 10.1016/j.celrep.2023.112013. Online ahead of print.

ABSTRACT

Clinical sequencing efforts are rapidly identifying sarcoma gene fusions that lack functional validation. An example is the fusion of transcriptional coactivators, VGLL2-NCOA2, found in infantile rhabdomyosarcoma. To delineate VGLL2-NCOA2 tumorigenic mechanisms and identify therapeutic vulnerabilities, we implement a cross-species comparative oncology approach with zebrafish, mouse allograft, and patient samples. We find that VGLL2-NCOA2 is sufficient to generate mesenchymal tumors that display features of immature skeletal muscle and recapitulate the human disease. A subset of VGLL2-NCOA2 zebrafish tumors transcriptionally cluster with embryonic somitogenesis and identify VGLL2-NCOA2 developmental programs, including a RAS family GTPase, ARF6. In VGLL2-NCOA2 zebrafish, mouse, and patient tumors, ARF6 is highly expressed. ARF6 knockout suppresses VGLL2-NCOA2 oncogenic activity in cell culture, and, more broadly, ARF6 is overexpressed in adult and pediatric sarcomas. Our data indicate that VGLL2-NCOA2 is an oncogene that leverages developmental programs for tumorigenesis and that reactivation or persistence of ARF6 could represent a therapeutic opportunity.

PMID:36656711 | DOI:10.1016/j.celrep.2023.112013
Correlation NKX2.2 IHC and EWSR1 break-apart FISH in the diagnosis of Ewing sarcoma: Can combined NKX2.2 and CD99 immunoexpression obviate or minimize the need of FISH testing? First assessment study from Indian tertiary cancer care center

Fetched: January 20th, 2023, 5:03am GMT by Sunil Pasricha

Indian J Pathol Microbiol. 2023 Jan-Mar;66(1):58-62. doi: 10.4103/ijpm.ijpm_535_21.

ABSTRACT

CONTEXT: Ewing sarcoma (ES) are malignant small round cell tumors (MSRCT) characterized by rearrangements of EWSR1 gene. Although gold standard for diagnosis is detection of specific fusion genes by molecular testing, these ancillary tests are costly and only available in limited number of settings. There is a persuasive evidence for reliability of NKX2.2 immunohistochemistry (IHC) as a surrogate marker for EWSR1 gene rearrangement in ES.

AIMS: The aim of this study is to correlate the NKX2.2 immuno-expression with genetically confirmed ES cases and also to assess the reliability and accuracy of NKX2.2 along with combined positivity of NXX2.2 and CD99 in diagnosing ES and differentiating it from other relevant histological mimics.

SETTINGS AND DESIGN: The present study is a retrospective study conducted over a period of 6-year duration in a tertiary cancer care center.

METHODS AND MATERIAL: We evaluated NKX2.2 immunoexpression in 35 genetically confirmed cases of ES and also in pertaining differential entities (n = 58) of ES including rhabdomyosarcoma (n = 20), lymphoblastic lymphoma (n = 14), Wilms tumor (n = 10), poorly differentiated synovial sarcoma (n = 4), small-cell osteosarcoma (n = 4), neuroblastoma (n = 5), and mesenchymal chondrosarcoma (n = 1). CD99 was performed in the category of MSRCTs showing NKX2.2 positivity to evaluate combined specificity for the diagnosis of ES.

RESULTS: Of the 35 genetically confirmed cases of ES, 29 cases (83%) showed NKX2.2-positive expression (83% sensitivity). Compared to ES, NKX2.2 was positive in only 05% cases (3/58 cases) of non-ES MSRCT. Only two of five cases of neuroblastomas and one case of mesenchymal chondrosarcoma showed NKX2.2 positivity. CD99 positivity was seen in 100% of ES and in the single case of mesenchymal chondrosarcoma. All five cases (100%) of neuroblastoma were negative for CD99.

CONCLUSIONS: The presented study, which is the first from an Indian oncology center, showed NKX2.2 IHC is quite reliable in diagnosis of ES in the right clinicopathological context. With remarkable sensitivity and specificity of NKX2.2 IHC for diagnosis of ES, we propose that combined positivity of CD99 and NKX2.2 IHC can obviate or minimize the need of EWSR1 gene rearrangement molecular testing for diagnosis of ES.

PMID:36656211 | DOI:10.4103/ijpm.ijpm_535_21
Cell-Free DNA as a Diagnostic and Prognostic Biomarker in Pediatric Rhabdomyosarcoma

Fetched: January 19th, 2023, 5:02am GMT by Nathalie S M Lak

JCO Precis Oncol. 2023 Jan;7:e2200113. doi: 10.1200/PO.22.00113.

ABSTRACT

PURPOSE: Total cell-free DNA (cfDNA) and tumor-derived cfDNA (ctDNA) can be used to study tumor-derived genetic aberrations. We analyzed the diagnostic and prognostic potential of cfDNA and ctDNA, obtained from pediatric patients with rhabdomyosarcoma.

METHODS: cfDNA was isolated from diagnostic plasma samples from 57 patients enrolled in the EpSSG RMS2005 study. To study the diagnostic potential, shallow whole genome sequencing (shWGS) and cell-free reduced representation bisulphite sequencing (cfRRBS) were performed in a subset of samples and all samples were tested using droplet digital polymerase chain reaction to detect methylated RASSF1A (RASSF1A-M). Correlation with outcome was studied by combining cfDNA RASSF1A-M detection with analysis of our rhabdomyosarcoma-specific RNA panel in paired cellular blood and bone marrow fractions and survival analysis in 56 patients.

RESULTS: At diagnosis, ctDNA was detected in 16 of 30 and 24 of 26 patients using shallow whole genome sequencing and cfRRBS, respectively. Furthermore, 21 of 25 samples were correctly classified as embryonal by cfRRBS. RASSF1A-M was detected in 21 of 57 patients. The presence of RASSF1A-M was significantly correlated with poor outcome (the 5-year event-free survival [EFS] rate was 46.2% for 21 RASSF1A-M‒positive patients, compared with 84.9% for 36 RASSF1A-M‒negative patients [P < .001]). RASSF1A-M positivity had the highest prognostic effect among patients with metastatic disease. Patients both negative for RASSF1A-M and the rhabdomyosarcoma-specific RNA panel (28 of 56 patients) had excellent outcome (5-year EFS 92.9%), while double-positive patients (11/56) had poor outcome (5-year EFS 13.6%, P < .001).

CONCLUSION: Analyzing ctDNA at diagnosis using various techniques is feasible in pediatric rhabdomyosarcoma and has potential for clinical use. Measuring RASSF1A-M in plasma at initial diagnosis correlated significantly with outcome, particularly when combined with paired analysis of blood and bone marrow using a rhabdomyosarcoma-specific RNA panel.

PMID:36652664 | DOI:10.1200/PO.22.00113
Orbital Rhabdomyosarcoma

Fetched: January 18th, 2023, 5:02am GMT by Erich J Berg

N Engl J Med. 2023 Jan 19;388(3):e4. doi: 10.1056/NEJMicm2207328. Epub 2023 Jan 14.

NO ABSTRACT

PMID:36648076 | DOI:10.1056/NEJMicm2207328
Non-inferior efficacy of non-surgical treatment to surgical treatment in patients with nonmetastatic head and neck rhabdomyosarcoma: a SEER-based study

Fetched: January 15th, 2023, 5:01am GMT by Wenjing Liang

Clin Transl Oncol. 2023 Jan 14. doi: 10.1007/s12094-023-03076-x. Online ahead of print.

ABSTRACT

PURPOSE: Head and neck rhabdomyosarcoma (HNRMS) is a rare but aggressive malignant neoplasm. Given the young patient age and critical anatomy of the head and neck, performing surgery on the primary tumor still remains debatable. This study aimed to evaluate the impact of the non-surgery-based treatment versus surgery-based treatment on patients with nonmetastatic HNRMS.

METHODS: Patients diagnosed with nonmetastatic HNRMS between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled in our study. Inverse probability treatment weighting (IPTW) method was employed to balance confounding factors between surgery and non-surgery groups. Kaplan-Meier methods and COX regression analyses were used to analyze survival outcomes of overall survival (OS) and cancer-specific survival (CSS). Prognostic nomogram was established to predict survival.

RESULTS: A total of 260 eligible patients were extracted from the SEER database. Kaplan-Meier survival curves revealed that there was no significant difference in OS and CSS between the surgery and non-surgery groups both before and after IPTW (p > 0.05). Cox regression analyses and IPTW-adjusted Cox regression analyses for both OS and CSS showed similar survival between the two groups. Prognostic factors were explored and a nomogram for patients in the surgery group was constructed. Risk stratification based on the nomogram indicated that patients in surgery-high-risk group did not benefit from primary surgery. While those in surgery-low-risk group had an equal survival outcome to those in non-surgery group.

CONCLUSIONS: Our study revealed that compared to patients receiving surgery, those not receiving surgery had similar survival outcomes for nonmetastatic HNRMS. Our established nomogram may serve as a practical tool for individual prognostic evaluations.

PMID:36640207 | DOI:10.1007/s12094-023-03076-x
Rhabdomyosarcoma as the first presentation in Neurofibromatosis Type 1: case series and review of the literature

Fetched: January 11th, 2023, 5:02am GMT by Alison M R Castle

Pediatr Hematol Oncol. 2023 Jan 10:1-10. doi: 10.1080/08880018.2022.2153951. Online ahead of print.

ABSTRACT

Neurofibromatosis Type 1 (NF1) is a neurocutaneous syndrome characterized by multiple café-au-lait macules, neurofibromas, and predisposition to malignancies, including rhabdomyosarcomas (RMS). Somatic NF1 mutations occur in RMS and other cancers, and ∼1% of patients with RMS have NF1. We describe three patients who presented prior to one year of age with RMS and were subsequently diagnosed with NF1. Compared to sporadic RMS, patients with this cancer predisposition syndrome are diagnosed younger, genitourinary sites are more common, and tumors are almost exclusively the embryonal subtype. Genomic sequencing of the tumor was initiated in one patient, and we identified a second sequence variant in NF1. The identification of molecular drivers in tumors is changing the nature of pediatric oncology by informing therapeutics targeted to specific molecular pathways and selecting patients who are likely to harbor germline variants in cancer predisposition genes who would benefit from a Medical Genetics assessment.

PMID:36625737 | DOI:10.1080/08880018.2022.2153951
Botryoid embryonal rhabdomyosarcoma of the cervix: A case report

Fetched: January 10th, 2023, 5:02am GMT by Alejandro Delfos Hermoza

Int J Surg Case Rep. 2023 Jan;102:107858. doi: 10.1016/j.ijscr.2022.107858. Epub 2022 Dec 31.

ABSTRACT

INTRODUCTION AND IMPORTANCE: Rhabdomyosarcoma (RMS) is a malignant tumor that arises from embryonal skeletal muscle cells. It's responsible for 3 % of cancer cases among children aged from 0 to 14 and 1 % among adolescents and young adults aged from 15 to 19. Embryonal RMS (ERMS) is the most prevalent subtype of rhabdomyosarcoma in the female genital tract. Botryoid sarcomas are a polypoid variant of ERMS. Our objective is to describe the clinical, pathological features and the treatment of a patient diagnosed with RMS botryoid of the cervix.

CASE PRESENTATION: We report a case of a 19-year-old female patient diagnosed with botryoid RMS of the cervix. The histopathological evaluation of the cervix showed a polypoid tumor lined by squamous epithelium exhibiting a large hypocellular edematous area. It was classified as group II and stage 1, according to the IRSG multicenter studies. Cervical polypectomy was performed as an oncological surgical treatment and adjuvant chemotherapy consisting of Vincristine 1.5 mg/m2/day and Actinomycin D 0.045 mg/kg/day (VA) for 45 weeks. After 6 months of follow up, she had no evidence of recurrence.

CLINICAL DISCUSSION: Cervical ERMS is a rare tumor, especially in adolescence. It's usually presents as a cervical polyp or multiple polyps. Multimodal approaches have remarkably improved the prognosis and decreased the need for radical surgery with its associated morbidity.

CONCLUSION: There are a variety of treatment strategies for a rare disease such as cervical botryoid RMS. This case was approached through fertility-conserving surgery, followed by adjuvant chemotherapy and oncological clinical follow up.

PMID:36621217 | PMC:PMC9850064 | DOI:10.1016/j.ijscr.2022.107858
Orbital Dirofilariasis Masquerading As Orbital Rhabdomyosarcoma

Fetched: January 10th, 2023, 5:02am GMT by Farzad Pakdel

J Ophthalmic Vis Res. 2022 Nov 29;17(4):587-591. doi: 10.18502/jovr.v17i4.12340. eCollection 2022 Oct-Dec.

ABSTRACT

PURPOSE: To report a 12-year-old patient with a rapid growing orbital mass and imaging findings suggestive of rhabdomyosarcoma that was found to be dirofilariasis after mass resection.

CASE REPORT: We describe a 12-year-old patient with a rapid growing orbital mass involving medial part of orbit and medial rectus muscle and imaging findings suggestive of rhabdomyosarcoma. Histopathologic examination showed the mass to be composed of granulomatous inflammation and the thread-like object to be Dirofilaria repens. The patient was well post-operation without morbidity. In this paper, we describe distinct clinical features and imaging findings of this interesting case.

CONCLUSION: Deep orbital lesions due to dirofilariasis, as in our case, is extremely rare. It is important to add dirofilariasis to the differential diagnosis of orbital mass lesions. Attention to the imaging clues, as provided in this report, can be helpful.

PMID:36620711 | PMC:PMC9806317 | DOI:10.18502/jovr.v17i4.12340
Platinum-Based Regimens Are Active in Advanced Pediatric-Type Rhabdomyosarcoma in Adults and Depending on HMGB1 Expression

Fetched: January 9th, 2023, 5:02am GMT by Nadia Hindi

Int J Mol Sci. 2023 Jan 3;24(1):856. doi: 10.3390/ijms24010856.

ABSTRACT

Rhabdomyosarcoma (RMS) in adults is a rare and aggressive disease, which lacks standard therapies for relapsed or advanced disease. This retrospective study aimed to describe the activity of BOMP-EPI (bleomycin, vincristine, methotrexate and cisplatin alternating with etoposide, cisplatin and ifosfamide), an alternative platinum-based regimen, in adult patients with relapsed/metastatic RMS. In the study, 10 patients with RMS with a median age at diagnosis of 20.8 years and a female/male distribution of 6/4 received a mean of 2.5 cycles of BOMP-EPI. The best RECIST response was a complete response in 1/10 (10%) patients, a partial response in 5/10 (50%), stable disease in 3/10 (30%) and progression in 1/10 (10%). With a median follow-up in the alive patients from the start of therapy of 30.5 months (15.7-258), all patients progressed with a median progression-free survival of 8.47 months (95% CI 8.1-8.8), and 7/10 patients died with a median overall survival of 24.7 months (95% CI 13.7-35.6). BOMP-EPI was an active chemotherapy regimen in adults with pediatric-type metastatic RMS, with outcomes in terms of survival that seem superior to what was expected for this poor-prognosis population. Low HMGB1 expression level was identified as a predictive factor of better response to this treatment.

PMID:36614297 | PMC:PMC9821763 | DOI:10.3390/ijms24010856
Integrative Multi-OMICs Identifies Therapeutic Response Biomarkers and Confirms Fidelity of Clinically Annotated, Serially Passaged Patient-Derived Xenografts Established from Primary and Metastatic Pediatric and AYA Solid Tumors

Fetched: January 9th, 2023, 5:02am GMT by Pankita H Pandya

Cancers (Basel). 2022 Dec 30;15(1):259. doi: 10.3390/cancers15010259.

ABSTRACT

Establishment of clinically annotated, molecularly characterized, patient-derived xenografts (PDXs) from treatment-naïve and pretreated patients provides a platform to test precision genomics-guided therapies. An integrated multi-OMICS pipeline was developed to identify cancer-associated pathways and evaluate stability of molecular signatures in a panel of pediatric and AYA PDXs following serial passaging in mice. Original solid tumor samples and their corresponding PDXs were evaluated by whole-genome sequencing, RNA-seq, immunoblotting, pathway enrichment analyses, and the drug-gene interaction database to identify as well as cross-validate actionable targets in patients with sarcomas or Wilms tumors. While some divergence between original tumor and the respective PDX was evident, majority of alterations were not functionally impactful, and oncogenic pathway activation was maintained following serial passaging. CDK4/6 and BETs were prioritized as biomarkers of therapeutic response in osteosarcoma PDXs with pertinent molecular signatures. Inhibition of CDK4/6 or BETs decreased osteosarcoma PDX growth (two-way ANOVA, p < 0.05) confirming mechanistic involvement in growth. Linking patient treatment history with molecular and efficacy data in PDX will provide a strong rationale for targeted therapy and improve our understanding of which therapy is most beneficial in patients at diagnosis and in those already exposed to therapy.

PMID:36612255 | PMC:PMC9818438 | DOI:10.3390/cancers15010259
Using Evidence-Based Medicine to Support Clinical Decision-Making in RMS

Fetched: January 9th, 2023, 5:02am GMT by Robert S Phillips

Cancers (Basel). 2022 Dec 22;15(1):66. doi: 10.3390/cancers15010066.

ABSTRACT

The foundations of evidence-based practice are the triad of patient values and preferences, healthcare professional experience, and best available evidence, used together to inform clinical decision-making. Within the field of rhabdomyosarcoma, collaborative groups such as the European Paediatric Soft Tissue Sarcoma Group (EpSSG) have worked to develop evidence to support this process. We have explored many of the key research developments within this review, including patient and public involvement, decision-making research, research into areas other than drug development, core outcome sets, reporting and dissemination of research, evidence synthesis, guideline development and clinical decision rules, research of research methodologies, and supporting research in RMS.

PMID:36612064 | PMC:PMC9817945 | DOI:10.3390/cancers15010066
Alveolar Rhabdomyosarcoma with CD 56 Positivity: A Mimic of Extranodal NK/T Cell Lymphoma

Fetched: January 7th, 2023, 5:02am GMT by Uma Kumar

J Cytol. 2022 Oct-Dec;39(4):190-192. doi: 10.4103/joc.joc_211_21. Epub 2022 Oct 29.

NO ABSTRACT

PMID:36605875 | PMC:PMC9809421 | DOI:10.4103/joc.joc_211_21
Low Bcl-2 is a robust biomarker of sensitivity to nab-paclitaxel in Ewing sarcoma

Fetched: January 6th, 2023, 5:02am GMT by Guillem Pascual-Pasto

Biochem Pharmacol. 2023 Feb;208:115408. doi: 10.1016/j.bcp.2022.115408. Epub 2023 Jan 2.

ABSTRACT

Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) shows potent preclinical anticancer activity in pediatric solid tumors such as Ewing sarcoma, rhabdomyosarcoma and neuroblastoma, but responses in clinical trials have been modest. In this work, we aimed to discover a rational biomarker-based approach to select the right candidate patients for this treatment. We assessed the efficacy of nab-paclitaxel in 27 patient-derived xenografts (PDX), including 14 Ewing sarcomas, five rhabdomyosarcomas and several other pediatric solid tumors. Response rate (partial or complete response) was remarkable in rhabdomyosarcomas (four of five) and Ewing sarcomas (four of 14). We addressed several predictive factors of response to nab-paclitaxel such as the expression of the secreted protein acidic and rich in cysteine (SPARC), chromosomal stability of cancer cells and expression of antiapoptotic members of the B-cell lymphoma-2 (Bcl-2) family of proteins such as Bcl-2, Bcl-xL, Bcl-W and Mcl-1. Protein (immunoblotting) and gene expression of SPARC correlated positively, while immunoblotting and immunohistochemistry expression of Bcl-2 correlated negatively with the efficacy of nab-paclitaxel in Ewing sarcoma PDX. The negative correlation of Bcl-2 immunoblotting signal and activity was especially robust (r = 0.8352; P = 0.0007; Pearson correlation). Consequently, we evaluated pharmacological strategies to inhibit Bcl-2 during nab-paclitaxel treatment. We observed that the Bcl-2 inhibitor venetoclax improved the activity of nab-paclitaxel in highly resistant Bcl-2-expressing Ewing sarcoma PDX. Overall, our results suggest that low Bcl-2 expression could be used to select patients with Ewing sarcoma sensitive to nab-paclitaxel, and Bcl-2 inhibitors could improve the activity of this drug in Bcl-2-expressing Ewing sarcoma.

PMID:36603685 | DOI:10.1016/j.bcp.2022.115408
Invasive spindle-cell rhabdomyosarcoma with osteolysis in a dog: case report and literature review

Fetched: January 6th, 2023, 5:02am GMT by Junchao Shi

J Vet Diagn Invest. 2023 Jan 4:10406387221147319. doi: 10.1177/10406387221147319. Online ahead of print.

ABSTRACT

Rhabdomyosarcoma (RMS), a malignant mesenchymal neoplasm derived from skeletal muscle, is relatively rare in both human and veterinary medicine. Here we report an unusual case of invasive spindle-cell RMS (SCRMS) with bone infiltration and pathologic fracture in a 3.5-y-old intact female Bulldog. Radiographically, a large, predominantly osteolytic mass in the tibia and fibula of the left hindlimb had features typical of a malignant primary bone tumor. Clinically, osteosarcoma was suspected, and the leg was amputated. Histologically, the mass was composed of loosely interwoven spindle-cell fascicles; tumor cells were fusiform with cigar-shaped nuclei and abundant eosinophilic cytoplasm. The neoplastic cells were strongly immunopositive for vimentin, muscle-specific actin, desmin, myogenin, and myoD1. Invasive SCRMS with osteolysis was diagnosed based on the histologic examination and immunohistochemical (IHC) stains. The dog was alive without any evidence of local recurrence or distant metastasis 18 mo post-surgery. RMS should be included in the differential diagnosis when osteolysis occurs; IHC staining confirmation is of great value for definitive diagnosis and treatment planning.

PMID:36600502 | DOI:10.1177/10406387221147319
Any Concern About Delays in the Diagnosis of Childhood Cancers During the COVID-19 Pandemic?

Fetched: January 5th, 2023, 5:02am GMT by Begüm Şirin Koç

Turk Arch Pediatr. 2023 Jan;58(1):75-79. doi: 10.5152/TurkArchPediatr.2022.22224.

ABSTRACT

OBJECTIVE: The lockdown precautions during the COVID-19 pandemic led to concerns about the delayed diagnosis of malignancies. This study aimed to compare the duration of complaints at home and the presence of metastasis at diagnosis during the pre-pandemic and pandemic period in children with cancer.

MATERIALS AND METHODS: All children diagnosed with cancer and followed up in our clinic between 2017 and 2022 were included. Patients with a diagnosis of acute/chronic leukemia were excluded. Age, gender, cancer type, duration of complaints, and presence of metastasis at diagnosis of the children were recorded. The duration of complaints and presence of metastasis at diagnosis were compared statistically before and after March 11, 2020, the start point of the COVID-19 pandemic in our country.

RESULTS: A total of 161 patients diagnosed with cancer were analyzed retrospectively; 61% of patients were males and 39% were females. These patients were diagnosed with brain tumors (23.6%), lymphomas (23%), neuroblastoma (13.7%), rhabdomyosarcomas (10.6%), Ewing's sarcoma (4.3%), osteosarcoma (3.7%), Wilm's tumor (3.7%), and germ cell tumors (3.1%). The duration of complaint was longer during the pandemic than before the pandemic (median: 45 days vs. 30 days) (P < .05). The presence of metastases at diagnosis was 45.3% in the prepandemic period, while it was 40% during the pandemic with no statistical difference (P > .5).

CONCLUSION: We concluded that the duration of complaint before diagnosis was longer during the pandemic, while this delay did not affect the metastasis rate at diagnosis in children with cancer. The high rates of distant metastases in newly diagnosed patients both before and during the pandemic suggest that more studies are needed to diagnose these patients earlier.

PMID:36598215 | DOI:10.5152/TurkArchPediatr.2022.22224
Diagnosis and management of intraparenchymal rhabdomyosarcoma

Fetched: January 5th, 2023, 5:02am GMT by Melissa Lannon

Br J Neurosurg. 2023 Jan 4:1-8. doi: 10.1080/02688697.2022.2163980. Online ahead of print.

ABSTRACT

BACKGROUND: Intracranial rhabdomyosarcomas represent a rare condition, posing a diagnostic challenge to physicians. Brain intraparenchymal rhabdomyosarcomas are exceptionally rare with poorly understood pathogenesis.

METHODS: Here we report the first adult case of intraparenchymal rhabdomyosarcoma (RMS) with brainstem and cranial nerve involvement. We conducted a literature search using Embase, MEDLINE, and PubMed for published cases of patients with rhabdomyosarcoma of the brain. The keywords used were 'rhabdomyosarcoma' combined with 'intraparenchymal', 'parenchymal', 'cerebral' or 'brain' for title/abstract. Included cases were adult patients (>18 years of age).

RESULTS: A 59-year-old man presents with multiple cranial nerve palsies. MRI revealed a solitary pontine lesion that was not responsive to steroids. No systemic lesions were identified with an extensive imaging workup. A wide range of serum and cerebrospinal fluid tests were non-diagnostic during a ten-month workup until, ultimately, the patient died as a result of aspiration pneumonia. At autopsy, pathological examination on whole-brain autopsy revealed RMS, centred in the left side of pons with extension to the left side of the midbrain and the right side of pons with multiple cranial nerve involvement. There are only 20 adult cases of primary intraparenchymal RMS reported in the literature. Our present case is the first reported adult RMS in this location, with novel molecular information, providing some insight into the pathogenesis of this rare diagnosis.

CONCLUSIONS: Intraparenchymal rhabdomyosarcoma without evidence of systemic primary disease is extremely rare, resulting in delayed diagnosis in some cases, particularly those not amenable to biopsy. The diagnostic challenge posed by this complementary case highlights the importance of maintaining a differential of neoplasm in the face of non-diagnostic investigations to the contrary.

PMID:36597892 | DOI:10.1080/02688697.2022.2163980
An uncommon perineal embryonal rhabdomyosarcoma in adult: A case report

Fetched: January 4th, 2023, 5:03am GMT by Sifeng Qu

Medicine (Baltimore). 2022 Dec 30;101(52):e32529. doi: 10.1097/MD.0000000000032529.

ABSTRACT

RATIONALE: Embryonal rhabdomyosarcoma (ERMS) is a major subtype of rhabdomyosarcoma, mainly affect children. There is seldom report for perineal ERMS in adults, since its rare location and the age.

PATIENT CONCERNS: A 20-year old male adult was admitted due to the perineal mass.

DIAGNOSES: Diagnosis by histopathological examination of the biopsy sample was ERMS. Magnetic resonance imaging showed the tumor was found in the perineal region, with metastasis to pelvic cavity, right testis, lymph nodes and bone.

INTERVENTIONS: The patient received Isophosphamide and Epirubicin for 4 cycles, followed by Irinotecan and Vindesine Sulfate for 2 cycles, then cisplatin, Dacarbazine and Apatinib for 3 cycles.

OUTCOME: The patient showed no response to chemotherapy.

LESSONS: Perineal ERMS in adults is very rare. There is still no standard therapy for adult ERMS. Personalized therapy might be promising treatment for each individual.

PMID:36596039 | PMC:PMC9803527 | DOI:10.1097/MD.0000000000032529
Primary vaginal sarcoma in a single center

Fetched: January 3rd, 2023, 5:02am GMT by Hua Yuan

Gynecol Oncol Rep. 2022 Dec 13;44:101122. doi: 10.1016/j.gore.2022.101122. eCollection 2022 Dec.

ABSTRACT

OBJECTIVES: To investigate the clinical characteristics and prognosis of primary vaginal sarcoma.

METHODS: A retrospective analysis of patients with primary vaginal sarcoma treated at our center from 2000 to 2020 was conducted.

RESULTS: Fifteen patients were identified, among which 9 (60.0 %) patients had leiomyosarcoma, 2 (13.3 %) patients had Ewing's sarcoma, 2 (13.3 %) patients had rhabdomyosarcoma, 1 (6.7 %) patient had undifferentiated sarcoma, and 1 (6.7 %) patient had malignant peripheral schwannoma. Nine patients presented with vaginal mass that was the most common primary symptoms. Eleven patients received their primary surgery, and 7 of them received postoperative adjuvant chemotherapy or radiation therapy. The remaining 4 patients received initial chemotherapy and/or radiotherapy because of advanced stage. The distribution by stage was as follows: stage I in 10 patients, stage II in 1 patient, stage III in 2 patients and stage IV in 2 patients. The median follow-up was 43.7 months (10.1-137.5 months). Thirteen patients (86.7 %) had disease extent during follow-up, and among them, 11 patients (11/13, 84.6 %) developed local relapse or adjacent organ metastases, 1 patient (1/13, 7.7 %) developed liver metastases, and the remaining 1 patient (1/13, 7.7 %) developed lung metastases and local relapse during follow-up. Ten (10/13, 76.9 %) patients relapsed within 2 years after diagnosis. Eight patients (8/11, 72.7 %) with local recurrence or adjacent organ metastases received a secondary surgery treatment, and only 2 of them relapsed again. Two-year overall survival (OS) and 5-year OS were 80.0 % and 66.7 %, respectively. Patients with leiomyosarcoma had a tendency toward a better 5-year OS than those with other sarcomas (74.1 % vs 66.7 %, P = 0.307).

CONCLUSIONS: Primary vaginal sarcomas are aggressive neoplasms with different presenting characteristics. Surgery is the main treatment for primary vaginal sarcoma and for local relapse vaginal sarcoma.

PMID:36589507 | PMC:PMC9797610 | DOI:10.1016/j.gore.2022.101122
A National Referral Service for Paediatric Brachytherapy: An Evolving Practice and Outcomes Over 13 Years

Fetched: January 2nd, 2023, 5:02am GMT by M N Gaze

Clin Oncol (R Coll Radiol). 2022 Dec 30:S0936-6555(22)00609-4. doi: 10.1016/j.clon.2022.12.008. Online ahead of print.

ABSTRACT

AIMS: Most children requiring radiotherapy receive external beam treatment and few have tumours suitable for brachytherapy. No paediatric radiotherapy centre will treat enough patients from its own normal catchment population for expertise in brachytherapy to be developed and sustained. Following discussion and agreement in the national paediatric radiotherapy group, a service for paediatric brachytherapy in the UK has been developed. We report the process that has evolved over more than 10 years, with survival and functional outcome results.

MATERIALS AND METHODS: Since 2009, potential patients have been referred to the central paediatric oncology multidisciplinary team meeting, where imaging, pathology and treatment options are discussed. Since 2013, the National Soft Tissue Sarcoma Advisory Panel has also reviewed most patients, with the principal aim of advising on the most suitable primary tumour management for complex patients. Clinical assessment and examination under anaesthetic with biopsies may be undertaken to confirm the appropriateness of brachytherapy, either alone or following conservative surgery. Fractionated high dose rate brachytherapy was delivered to a computed tomography planned volume after implantation of catheters under ultrasound imaging guidance. Since 2019, follow-up has been in a dedicated multidisciplinary clinic.

RESULTS: From 2009 to 2021 inclusive, 35 patients (16 female, 19 male, aged 8 months to 17 years 6 months) have been treated. Histology was soft-tissue sarcoma in 33 patients and carcinoma in two. The treated site was pelvic in 31 patients and head and neck in four. With a median follow-up of 5 years, the local control and overall survival rates are 100%. Complications have been few, and functional outcome is good.

CONCLUSION: Brachytherapy is effective for selected paediatric patients, resulting in excellent tumour control and good functional results. It is feasible to deliver paediatric brachytherapy at a single centre within a national referral service.

PMID:36588012 | DOI:10.1016/j.clon.2022.12.008
Histopathological Review of Childhood and Adolescent Cancers in Northern Ghana

Fetched: December 30th, 2022, 5:03am GMT by E M Der

West Afr J Med. 2022 Dec 29;39(12):1229-1237.

ABSTRACT

BACKGROUND: Published data on childhood and adolescent cancers in northern Ghana is scanty. The aim of this retrospective histopathological study was to identify and describe the relative proportions of childhood and adolescent cancers and the associated clinico-pathological features at the Tamale Teaching Hospital.

MATERIALS AND METHODS: The cancers were classified according to the International Classification for Cancer in Children. Data was collected on the demographics and the clinico-pathological characteristics of the various types of cancers, from 1st January 2012 to 31st December, 2021, a 10-year period. The data was analysed using SPSS software (Version 26, Chicago).

RESULTS: A total of 196 childhood and adolescent cancers were reviewed, with a mean age of 9.5± 5.5 years. Approximately, 51.5% were female, with a younger mean age (years) of 8.4±5.3, compared to 10.6±5.6 for males. Majority (74.0%), were within the 0-14 years age group, (P<0.0001). All the patients presented with swellings and mostly after 6 months of disease onset. The common cancers for the study population were: soft tissue sarcoma (24.2%), primary bone cancer (21.1%), retinoblastoma (17.5%), lymphoma (13.3%), and germ cell tumours (6.7%). For females these were: soft tissue sarcoma (21.0%), retinoblastoma (20.0%), primary bone cancer (19.0%), nephroblastoma (13.0%), and ovarian tumours (12.0%). For males, these were: soft tissue sarcoma (27.7%), bone cancer (23.4%), lymphoma (19.1%), retinoblastoma (14.9%) and head and neck cancer (6.4%). The common soft tissue cancers were: rhabdomyosarcoma (46.8%), and spindle cell sarcoma (NOS) (17.0%). Osteosarcoma (70.7%), and Ewing's sarcoma 6 (14.6%) were the common primary bone cancers. Many (46.4%) of the retinoblastomas were of a high pathological TNM stage III. The optic nerve was involved in 70.6%, with 26.5% margin involvements.

CONCLUSION: Childhood and adolescent cancers were common in pediatric age group with late stage at presentation. The common histological subtypes were: soft tissue sarcoma, primary bone cancer and retinoblastoma. There is the need for detection, diagnosis, and prompt oncology care.

PMID:36580654
Harnessing immunotherapy to enhance the systemic anti-tumor effects of thermosensitive liposomes

Fetched: December 29th, 2022, 5:02am GMT by Maximilian Regenold

Drug Deliv Transl Res. 2022 Dec 28. doi: 10.1007/s13346-022-01272-w. Online ahead of print.

ABSTRACT

Chemotherapy plays an important role in debulking tumors in advance of surgery and/or radiotherapy, tackling residual disease, and treating metastatic disease. In recent years many promising advanced drug delivery strategies have emerged that offer more targeted delivery approaches to chemotherapy treatment. For example, thermosensitive liposome-mediated drug delivery in combination with localized mild hyperthermia can increase local drug concentrations resulting in a reduction in systemic toxicity and an improvement in local disease control. However, the majority of solid tumor-associated deaths are due to metastatic spread. A therapeutic approach focused on a localized target area harbors the risk of overlooking and undertreating potential metastatic spread. Previous studies reported systemic, albeit limited, anti-tumor effects following treatment with thermosensitive liposomal chemotherapy and localized mild hyperthermia. This work explores the systemic treatment capabilities of a thermosensitive liposome formulation of the vinca alkaloid vinorelbine in combination with mild hyperthermia in an immunocompetent murine model of rhabdomyosarcoma. This treatment approach was found to be highly effective at heated, primary tumor sites. However, it demonstrated limited anti-tumor effects in secondary, distant tumors. As a result, the addition of immune checkpoint inhibition therapy was pursued to further enhance the systemic anti-tumor effect of this treatment approach. Once combined with immune checkpoint inhibition therapy, a significant improvement in systemic treatment capability was achieved. We believe this is one of the first studies to demonstrate that a triple combination of thermosensitive liposomes, localized mild hyperthermia, and immune checkpoint inhibition therapy can enhance the systemic treatment capabilities of thermosensitive liposomes.

PMID:36577832 | DOI:10.1007/s13346-022-01272-w
Histone variant H3.3 promotes metastasis in alveolar rhabdomyosarcoma

Fetched: December 28th, 2022, 5:02am GMT by Nandini Karthik

J Pathol. 2022 Dec 27. doi: 10.1002/path.6048. Online ahead of print.

ABSTRACT

The relatively quiet mutational landscape of rhabdomyosarcoma (RMS) suggests that epigenetic deregulation could be central to oncogenesis and tumour aggressiveness. Histone variants have long been recognised as important epigenetic regulators of gene expression. However, the role of histone variants in RMS has not been studied hitherto. In this study, we show that histone variant H3.3 is overexpressed in alveolar RMS (ARMS), an aggressive subtype of RMS. Functionally, knockdown of H3F3A, which encodes for H3.3, significantly impairs the ability of ARMS cells to undertake migration and invasion and reduces Rho activation. In addition, a striking reduction in metastatic tumour burden and improved survival is apparent in vivo. Using RNA-sequencing and ChIP-sequencing analyses, we identified melanoma cell adhesion molecule (MCAM/CD146) as a direct downstream target of H3.3. Loss of H3.3 resulted in a reduction in the presence of active marks and an increase in the occupancy of H1 at the MCAM promoter. Cell migration and invasion were rescued in H3F3A-depleted cells through MCAM overexpression. Moreover, we identified G9a, a lysine methyltransferase encoded by EHMT2, as an upstream regulator of H3F3A. Therefore, this study identifies a novel H3.3 dependent axis involved in ARMS metastasis. These findings establish the potential of MCAM as a therapeutic target for high-risk ARMS patients. © 2022 The Pathological Society of Great Britain and Ireland.

PMID:36573560 | DOI:10.1002/path.6048
Transcription regulators and ultra-rare and other rare translocation-related sarcomas treated with trabectedin: A proof of principle from a post-hoc analysis

Fetched: December 27th, 2022, 5:02am GMT by Emanuela Palmerini

Front Oncol. 2022 Dec 8;12:1042479. doi: 10.3389/fonc.2022.1042479. eCollection 2022.

ABSTRACT

BACKGROUND: Among sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases and altogether account for ~20% of all soft tissue sarcomas (STS) and bone sarcomas. The Italian Sarcoma Group has recently performed a non-interventional, retrospective TrObs study with data from 512 anthracycline-pretreated patients with advanced multiple STS histologies and treated with trabectedin (Palmerini, Cancers 2021; ClinicalTrials.gov Identifier: NCT02793050).

METHODS: A post-hoc analysis of case series to evaluate the efficacy and safety of trabectedin on patients with ultra-rare and other rare translocation-related sarcomas included in TrObs study was performed. Main outcomes comprised investigator-assessed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety.

RESULTS: Thirty-six patients (18 women) with ultra-rare and other rare sarcoma and a median age of 53.0 years (range: 22-81) were included. Most patients had solitary fibrous tumor (SFT; n=11) followed by epithelioid sarcoma (n=5), malignant peripheral nerve sheath tumor (MPNST; n=4), extraskeletal myxoid chondrosarcoma (EMC; n=3), desmoplastic small round cell tumor (DSRCT; n=3), and alveolar soft part sarcoma (ASPS), rhabdomyosarcoma and clear cell sarcoma (n=2 each). Thirty-five patients had metastatic disease and 23 patients received trabectedin as a second-line treatment. Among 35 patients evaluable for response, two patients with SFT and ASPS had a partial response and one patient with DSRCT obtained a complete response, reaching an ORR of 8.6% (95% CI: 2.8-23.4%). Among patients with an ORR, 6-months PFS was 100% in patients with ASPS, 45.7% in patients with SFT and 33.3% in those with DSRCT. Two patients with epithelioid sarcoma and myoepithelioma had disease stabilization lasting >24 months. Nine patients had at least one grade 3/4 adverse event, mostly being bone marrow toxicity (n=6).

CONCLUSIONS: Trabectedin has some anti-tumor activity in some ultra-rare and other rare sarcomas, particularly translocation-related sarcomas, with the well-known manageable safety profile.

PMID:36568164 | PMC:PMC9780071 | DOI:10.3389/fonc.2022.1042479
Lymph node metastases in paediatric and young adult patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): Findings from Children's Oncology Group (COG) study ARST0332

Fetched: December 26th, 2022, 5:02am GMT by Elysia Alvarez

Eur J Cancer. 2023 Feb;180:89-98. doi: 10.1016/j.ejca.2022.11.014. Epub 2022 Nov 25.

ABSTRACT

PURPOSE: The aim of this paper is to better define the clinical features and outcomes of young patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) with regional and distant lymph node (LN) metastases treated in a standardised fashion, we analysed LN involvement in COG study ARST0332, which evaluated a risk-based treatment strategy for young patients with all stages of NRSTS.

PATIENTS AND METHODS: Patients <30 years old with newly diagnosed NRSTS and LN metastases enrolled on ARST0332 were studied. Regional LN sampling was required for those with epithelioid sarcoma, clear cell sarcoma or clinically/radiographically enlarged LNs. Tumour features and extent of pre-enrolment resection determined treatment, including chemotherapy, radiotherapy, and delayed surgery. Recommendations for LN metastases included LN dissection at the time of primary tumour resection and dose-adapted radiotherapy based on extent of LN resection.

RESULTS: Twenty of 529 eligible and evaluable ARST0332 patients with NRSTS had LN metastases; epithelioid sarcoma had the highest incidence (18%, 5 of 28). Pre-treatment imaging identified LN enlargement in 19 of 20 patients; 1 had no pre-treatment LN imaging. At 6.9 years median follow-up for surviving patients, 5-year overall survival was 85.7% (95% CI: 33.4%, 97.9%) for seven patients with isolated LN metastases and 15.4% (95% CI: 2.5%, 38.8%) for 13 patients with additional extranodal metastases. LN recurrence occurred in only one patient without LNs sampled at initial diagnosis.

CONCLUSION: LN metastases occur in about 4% of paediatric/young adult NRSTS, are limited to a few histologic subtypes, and are rare in patients who did not have clinical or imaging evidence of lymphadenopathy, suggesting that biopsies of non-enlarged LNs are not necessary to identify occult involvement. Patients with isolated LN metastases have high 5-year overall survival (∼85%) and should be treated with curative intent.

GOV REGISTRY NO: NCT00346164.

PMID:36566574 | DOI:10.1016/j.ejca.2022.11.014
Nucleolar Stress Response via Ribosomal Protein L11 Regulates Topoisomerase Inhibitor Sensitivity of P53-Intact Cancers

Fetched: December 24th, 2022, 5:02am GMT by Yuka Ishihara

Int J Mol Sci. 2022 Dec 15;23(24):15986. doi: 10.3390/ijms232415986.

ABSTRACT

Nucleolar stress response is caused by perturbations in ribosome biogenesis, induced by the inhibition of ribosomal RNA processing and synthesis, as well as ribosome assembly. This response induces p53 stabilization and activation via ribosomal protein L11 (RPL11), suppressing tumor progression. However, anticancer agents that kill cells via this mechanism, and their relationship with the therapeutic efficiency of these agents, remain largely unknown. Here, we sought to investigate whether topoisomerase inhibitors can induce nucleolar stress response as they reportedly block ribosomal RNA transcription. Using rhabdomyosarcoma and rhabdoid tumor cell lines that are sensitive to the nucleolar stress response, we evaluated whether nucleolar stress response is associated with sensitivity to topoisomerase inhibitors ellipticine, doxorubicin, etoposide, topotecan, and anthracyclines. Cell proliferation assay indicated that small interfering RNA-mediated RPL11 depletion resulted in decreased sensitivity to topoisomerase inhibitors. Furthermore, the expression of p53 and its downstream target proteins via western blotting showed the suppression of p53 pathway activation upon RPL11 knockdown. These results suggest that the sensitivity of cancer cells to topoisomerase inhibitors is regulated by RPL11-mediated nucleolar stress responses. Thus, RPL11 expression may contribute to the prediction of the therapeutic efficacy of topoisomerase inhibitors and increase their therapeutic effect of topoisomerase inhibitors.

PMID:36555627 | PMC:PMC9784028 | DOI:10.3390/ijms232415986
Twenty-Year Retrospective Study of Post-Enucleation Chemotherapy in High-Risk Patients with Unilateral Retinoblastoma

Fetched: December 24th, 2022, 5:02am GMT by Yoon Sunwoo

Children (Basel). 2022 Dec 16;9(12):1983. doi: 10.3390/children9121983.

ABSTRACT

Primary enucleation is a life-saving treatment for advanced intraocular retinoblastoma, particularly in patients with poor visual potential and functional contralateral eyes. This single-center study presents the treatment outcomes of patients with unilateral retinoblastoma who received primary enucleation and adjuvant chemotherapy with cyclophosphamide, vincristine, doxorubicin, and intrathecal methotrexate (CVDM) between 2000 and 2020. Twenty patients were enrolled in the study. The median age at diagnosis was 26 months (range, 1-45). Eighteen patients (90%) were in group E and two (10%) were in group D, according to the intraocular classification of retinoblastoma guidelines. Excluding one patient with an inadequate specimen, 19 patients (95%) had optic nerve involvement (ONI) at least up to the lamina cribrosa. Eight patients (40%) had choroidal invasion in addition to ONI. Two patients (10%) were surgical resection margin positive. The overall and event-free survival rates were 100% and 95%, respectively, for a median follow-up duration of 102.24 months (range 24.2-202.9). There were no relapses or deaths due to any cause, but one patient developed secondary rhabdomyosarcoma 99.6 months after chemotherapy. Treatment was well tolerated, with minimal hematotoxicity and hepatotoxicity. CVDM as a post-enucleation chemotherapy for advanced intraocular retinoblastoma has excellent outcomes with tolerable toxicity. However, in line with updated treatment trends, further risk stratification and lowering the treatment intensity should be considered. Continued long-term follow-up is required to further determine late effects.

PMID:36553426 | PMC:PMC9776909 | DOI:10.3390/children9121983
Shedding a Light on the Challenges of Adolescents and Young Adults with Rhabdomyosarcoma

Fetched: December 24th, 2022, 5:02am GMT by Andrea Ferrari

Cancers (Basel). 2022 Dec 9;14(24):6060. doi: 10.3390/cancers14246060.

ABSTRACT

Rhabdomyosarcoma (RMS) is a typical tumour of childhood but can occur at any age. Several studies have reported that adolescent and young adult (AYA) patients with RMS have poorer survival than do younger patients. This review discusses the specific challenges in AYA patients with pediatric-type RMS, exploring possible underlying factors which may influence different outcomes. Reasons for AYA survival gap are likely multifactorial, and might be related to differences in tumor biology and intrinsic aggressiveness, or differences in clinical management (that could include patient referral patterns, time to diagnosis, enrolment into clinical trials, the adequacy and intensity of treatment), as well as patient factors (including physiology and comorbidity that may influence treatment tolerability, drug pharmacokinetics and efficacy). However, improved survival has been reported in the most recent studies for AYA patients treated on pediatric RMS protocols. Different strategies may help to further improve outcome, such as supporting trans-age academic societies and national/international collaborations; developing specific clinical trials without upper age limit; defining integrated and comprehensive approach to AYA patients, including the genomic aspects; establishing multidisciplinary tumor boards with involvement of both pediatric and adult oncologists to discuss all pediatric-type RMS patients; developing dedicated projects with specific treatment recommendations and registry/database.

PMID:36551545 | PMC:PMC9775932 | DOI:10.3390/cancers14246060
Surgical resection of a massive residual retroperitoneal mass after chemotherapy for a paratesticular rhabdomyosarcoma: a case report

Fetched: December 23rd, 2022, 5:02am GMT by Takoua Chalouati

J Med Case Rep. 2022 Dec 23;16(1):476. doi: 10.1186/s13256-022-03707-x.

ABSTRACT

INTRODUCTION: Paratesticular rhabdomyosarcoma is a rare and aggressive mesenchymal tumor, accounting for only 7% of all rhabdomyosarcomas. It is mainly encountered in children and adolescents. The standard treatment consists of radical orchidectomy with negative surgical margins. However, chemotherapy is recommended to control retroperitoneal micrometastasis. The place of surgery for progressive retroperitoneal lymph node metastases remains controversial. We present a case of paratesticular rhabdomyosarcoma with progressive retroperitoneal lymph node metastases treated with surgery.

CASE REPORT: We report a case of a 17-year-old North African male with no particular medical history who presented with a left scrotal mass that had been evolving for several months. Beta-human chorionic gonadotropin, alpha-fetoprotein, and lactate dehydrogenase were normal. Scrotal ultrasonography revealed the presence of a 6 cm heterogeneous hypoechogenic tissular mass with cystic areas adherent to the left scrotal wall, which was thickened in some places and vascularized by color Doppler. It exerted a mass effect on the homolateral testicle, which was of average volume. The thoracic-abdominal-pelvic computed tomography scan showed the presence of suspicious paraaortic lymph nodes. The most voluminous one measured 16 × 23 mm². A left orchidectomy was performed. The final pathology report revealed an 8 cm paratesticular rhabdomyosarcoma of the embryonic type that displaced the testicle without invading it. Without going beyond it, it infiltrated the epididymis, the rete testis, and the albuginea. The surgical margin at the level of the spermatic cord was free. The patient had adjuvant chemotherapy (ifosfamide, vincristine, and dactinomycin). The patient had a challenging paraaortic lymph node dissection since the mass enlaced the left ureter and renal vessels. On histological examination, the paraaortic lymph nodes were metastatic.

CONCLUSION: Rhabdomyosarcoma is an aggressive malignancy with high metastatic potential. Therefore, only an accurate diagnosis and early treatment can ensure better survival. Surgery in expert hands seems to be a good option for progressive retroperitoneal nodes. However, further studies are needed to determine the place of surgery in this setting.

PMID:36550579 | PMC:PMC9783374 | DOI:10.1186/s13256-022-03707-x
ADAR1p110 promotes Enterovirus D68 replication through its deaminase domain and inhibition of PKR pathway

Fetched: December 23rd, 2022, 5:02am GMT by Kehan Zhang

Virol J. 2022 Dec 22;19(1):222. doi: 10.1186/s12985-022-01952-6.

ABSTRACT

BACKGROUND: Severe respiratory and neurological diseases caused by human enterovirus D68 (EV-D68) pose a serious threat to public health, and there are currently no effective drugs and vaccines. Adenosine deaminase acting on RNA1 (ADAR1) has diverse biological functions in various viral infections, but its role in EV-D68 infections remains undetermined.

METHODS: Rhabdomyosarcoma (RD) and human embryonic kidney 293 T (293 T) cells, and HeLa cells were used to evaluate the expression level of ADAR1 upon EV-D68 (Fermon strain) and human parainfluenza virus type 3 (HPIV3; NIH47885) infection, respectively. Knockdown through silencing RNA (siRNA) and overexpression of either ADAR1p110 or ADAR1p150 in cells were used to determine the function of the two proteins after viral infection. ADAR1p110 double-stranded RNA binding domains (dsRBDs) deletion mutation was generated using a seamless clone kit. The expression of ADAR1, EV-D68 VP1, and HPIV3 hemagglutinin-neuraminidase (HN) proteins was identified using western blotting. The median tissue culture infectious dose (TCID50) was applied to detect viral titers. The transcription level of EV-D68 mRNA was analyzed using reverse transcription-quantitative PCR (RT-qPCR) and the viral 5'-untranslated region (5'-UTR)-mediated translation was analyzed using a dual luciferase reporter system.

CONCLUSION: We found that the transcription and expression of ADAR1 was inhibited upon EV-D68 infection. RNA interference of endogenous ADAR1 decreased VP1 protein expression and viral titers, while overexpression of ADAR1p110, but not ADAR1p150, facilitated viral replication. Immunofluorescence assays showed that ADAR1p110 migrated from the nucleus to the cytoplasm after EV-D68 infection. Further, ADAR1p110 lost its pro-viral ability after mutations of the active sites in the deaminase domain, and 5'-UTR sequencing of the viral genome revealed that ADAR1p110 likely plays a role in EV-D68 RNA editing. In addition, after ADAR1 knockdown, the levels of both phosphorylated double-stranded RNA dependent protein kinase (p-PKR) and phosphorylated eukaryotic initiation factor 2α (p-eIF2α) increased. Attenuated translation activity of the viral genome 5'-UTR was also observed in the dual-luciferase reporter assay. Lastly, the deletion of ADAR1p110 dsRBDs increased the level of p-PKR, which correlated with a decreased VP1 expression, indicating that the promotion of EV-D68 replication by ADAR1p110 is also related to the inhibition of PKR activation by its dsRBDs. Our study illustrates that ADAR1p110 is a novel pro-viral factor of EV-D68 replication and provides a theoretical basis for EV-D68 antiviral research.

PMID:36550502 | PMC:PMC9773460 | DOI:10.1186/s12985-022-01952-6
Gingival rhabdomyosarcoma mimicking a non-neoplastic proliferative lesion: A diagnostic challenge

Fetched: December 23rd, 2022, 5:02am GMT by Israel Leal Cavalcante

Oral Oncol. 2023 Feb;137:106281. doi: 10.1016/j.oraloncology.2022.106281. Epub 2022 Dec 20.

ABSTRACT

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma that develops from skeletal striated muscle cells. RMSs are exceedingly rare in the oral cavity, particularly in the gingiva. Herein, we reported the clinicopathological and immunohistochemical features of a rare case of RMS in a 30-year-old female presenting clinically as a painful polypoid nodule on the mandibular gingiva. Microscopically, the tumor showed atypical spindle cells with elongated nuclei and eosinophilic cytoplasm arranged in a fascicular pattern. In focal areas, the tumor cells exhibited rhabdomyoblastic differentiation. Immunohistochemistry showed strong positivity for desmin, myogenin (scattered cells), and MyoD1. The patient underwent surgical resection followed by postoperative complementary radio- and chemotherapy. However, the patient had a local recurrence seven months after the initial treatment. She was submitted to a total mandibulectomy associated with adjuvant radiotherapy. However, she died two months after reoperation due to complications secondary to radiation therapy. Because of the rarity in the oral cavity and non-specific signs and symptoms, the clinical diagnosis of RMS is difficult and often overlooked. Therefore, careful histopathological and immunohistochemistry analysis of these tumors is essential to correct diagnosis. Early surgical excision with tumor-free margins and prolonged follow-up are strongly recommended.

PMID:36549241 | DOI:10.1016/j.oraloncology.2022.106281
Particle beam radiation therapy for head and neck rhabdomyosarcoma in adults

Fetched: December 23rd, 2022, 5:02am GMT by Jing Yang

Ann Transl Med. 2022 Nov;10(22):1191. doi: 10.21037/atm-20-8238.

ABSTRACT

BACKGROUND: Rhabdomyosarcoma (RMS) is rare in adults, with a significantly worse prognosis than its pediatric counterpart. Radiotherapy (RT) plays a significant role in treating head and neck RMS (HNRMS), but the outcomes of conventional RT are limited by the complex anatomy and unfavorable pathology subtypes of the adult H&N RMS. Here, we aim to report the effectiveness and safety of carbon-ion beam RT (CIRT), either alone or in combination with proton radiotherapy (PRT) in the management of adult HNRMS.

METHODS: Fifteen adult patients with HNRMS were enrolled on a prospective registry protocol between 06/2015 and 12/2019. Eight patients presented with parameningeal tumors, and eight had unfavorable pathology subtypes [alveolar =7, not otherwise specified (NOS) =1]. Eleven patients had gross tumors before the start of RT (volume range, 46.1-137.6 cm³). Two patients failed the earlier RT. All except for one patient received multi-drug chemotherapy. The median absolute dose of particle beam RT was 70.0 Gy [relative biological effectiveness (RBE)].

RESULTS: With a median follow-up of 21 months, local or distant recurrence occurred in three and four patients, respectively, and two added patients had both local and distant failure. One patient died of distant metastasis (DM), and another died of an unrelated condition. The 1- and 2-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates were 87.5% and 70.0%, 92.3% and 67.1%, 72.2% and 54.2%, and 65.0% and 24.4%, respectively, for the entire cohort. Both patients who failed earlier RT and received salvage CIRT developed DM but were alive at last follow-up. No acute toxicity of ≥ grade 3 or late toxicity of ≥ grade 2 was observed.

CONCLUSIONS: CIRT, either used alone or in combination with PRT, is not only feasible and safe but also useful in local disease control for HNRMS. DM is the most important cause of treatment failure; thus, more effective systemic treatment is needed to improve the prognosis of HNRMS further.

PMID:36544680 | PMC:PMC9761167 | DOI:10.21037/atm-20-8238
Bone and soft tissue tumors: clinicoradiologic-pathologic molecular-genetic correlation of novel fusion spindled, targetable-ovoid, giant-cell-rich, and round cell sarcomas

Fetched: December 22nd, 2022, 5:02am GMT by J C Fanburg-Smith

Skeletal Radiol. 2023 Mar;52(3):517-540. doi: 10.1007/s00256-022-04244-w. Epub 2022 Dec 21.

ABSTRACT

BACKGROUND: New entities in the classification of bone and soft tissue tumors have been identified by use of advanced molecular-genetic techniques, including next-generation sequencing. Clinicoradiologic and pathologic correlation supports diagnostic classification.

METHODS: Tumors from four morphologically grouped areas are selected to enhance diagnosis and awareness among the multidisciplinary team. These include select round cell tumors, spindle cell tumors, targetable tyrosine kinase/RAS::MAPK pathway-ovoid (epithelioid to spindled) tumors, and giant-cell-rich tumors of bone and soft tissue.

RESULTS: Round cell tumors of bone and soft tissue include prototypical Ewing sarcoma, newer sarcomas with BCOR genetic alteration and CIC-rearranged, as well as updates on FUS/EWSR1::NFATc2, an EWSR1 non-ETS tumor that is solid with additional amplified hybridization signal pattern of EWSR1. This FUS/EWSR1::NFATc2 fusion has now been observed in seemingly benign to low-grade intraosseous vascular-rich and simple (unicameral) bone cyst tumors. Select spindle cell tumors of bone and soft tissue include rhabdomyosarcoma with FUS/EWSR1::TFCP2, an intraosseous high-grade spindle cell tumor without matrix. Targetable tyrosine-kinase or RAS::MAPK pathway-tumors of bone and soft tissue include NTRK, ALK, BRAF, RAF1, RET, FGFR1, ABL1, EGFR, PDGFB, and MET with variable ovoid myopericytic to spindled pleomorphic features and reproducible clinicopathologic and radiologic clues to their diagnosis. Giant-cell-rich tumors of bone, joint, and soft tissue are now respectively characterized by H3F3A mutation, CSF1 rearrangement (targetable), and HMGA2::NCOR2 fusion.

CONCLUSION: This article is an update for radiologists, oncologists, surgeons, and pathologists to recognize these novel ovoid, spindled, giant-cell-rich, and round cell tumors, for optimal diagnostic classification and multidisciplinary team patient care.

PMID:36542130 | DOI:10.1007/s00256-022-04244-w
Analyzing spatial distribution between 18F-fluorodeoxyglucose and 18F-boronophenylalanine positron emission tomography to investigate selection indicators for boron neutron capture therapy

Fetched: December 20th, 2022, 5:02am GMT by Tetsu Nakaichi

EJNMMI Phys. 2022 Dec 19;9(1):89. doi: 10.1186/s40658-022-00514-7.

ABSTRACT

BACKGROUND: ¹⁸F-FDG PET is often utilized to determine BNCT selection due to the limited availability of ¹⁸F-BPA PET, which is performed by synthesizing ¹⁸F into the boron drug used for BNCT, although the uptake mechanisms between those are different. Additionally, only a few non-spatial point parameters, such as maximum SUV (SUVmax), have reported a correlation between those in previous studies. This study aimed to investigate the spatial accumulation pattern between those PET images in tumors, which would be expected to either show higher uptake on ¹⁸F-BPA PET or be utilized in clinical, to verify whether ¹⁸F-FDG PET could be used as a selection indicator for BNCT.

METHODS: A total of 27 patients with 30 lesions (11 squamous cell carcinoma, 9 melanoma, and 10 rhabdomyosarcoma) who received ¹⁸F-FDG and ¹⁸F-BPA PET within 2 weeks were enrolled in this study. The ratio of metabolic tumor volumes (MTVs) to GTV, histogram indices (skewness/kurtosis), and the correlation of total lesion activity (TLA) and non-spatial point parameters (SUVmax, SUVpeak, SUVmin, maximum tumor-to-normal tissue ratio (Tmax/N), and Tmin/N) were evaluated. After local rigid registration between those images, distances of locations at SUVmax and the center of mass with MTVs on each image and similarity indices were also assessed along its coordinate.

RESULTS: In addition to SUVmax, SUVpeak, and Tmax/N, significant correlations were found in TLA. The mean distance in SUVmax was [Formula: see text] and significantly longer than that in the center of mass with MTVs. The ratio of MTVs to GTV, skewness, and kurtosis were not significantly different. However, the similarities of MTVs were considerably low. The similarity indices of Dice similarity coefficient, Jaccard coefficient, and mean distance to agreement for MTV40 were [Formula: see text], [Formula: see text], and [Formula: see text] cm, respectively. Furthermore, it was worse in MTV50. In addition, spatial accumulation patterns varied in cancer types.

CONCLUSIONS: Spatial accumulation patterns in tumors showed low similarity between ¹⁸F-FDG and ¹⁸F-BPA PET, although the various non-spatial point parameters were correlated. In addition, the spatial accumulation patterns were considerably different in cancer types. Therefore, the selection for BNCT using ¹⁸F-FDG PET should be compared carefully with using ¹⁸F-FBPA PET.

PMID:36536190 | PMC:PMC9763526 | DOI:10.1186/s40658-022-00514-7
The botanical drug PBI-05204, a supercritical CO2 extract of Nerium oleander, sensitizes alveolar and embryonal rhabdomyosarcoma to radiotherapy in vitro and in vivo

Fetched: December 20th, 2022, 5:02am GMT by Sara Vaccaro

Front Pharmacol. 2022 Dec 1;13:1071176. doi: 10.3389/fphar.2022.1071176. eCollection 2022.

ABSTRACT

Treatment of rhabdomyosarcoma (RMS), the most common a soft tissue sarcoma in childhood, provides intensive multimodal therapy, with radiotherapy (RT) playing a critical role for local tumor control. However, since RMS efficiently activates mechanisms of resistance to therapies, despite improvements, the prognosis remains still largely unsatisfactory, mainly in RMS expressing chimeric oncoproteins PAX3/PAX7-FOXO1, and fusion-positive (FP)-RMS. Cardiac glycosides (CGs), plant-derived steroid-like compounds with a selective inhibitory activity of the Na⁺/K⁺-ATPase pump (NKA), have shown antitumor and radio-sensitizing properties. Herein, the therapeutic properties of PBI-05204, an extract from Nerium oleander containing the CG oleandrin already studied in phase I and II clinical trials for cancer patients, were investigated, in vitro and in vivo, against FN- and FP-RMS cancer models. PBI-05204 induced growth arrest in a concentration dependent manner, with FP-RMS being more sensitive than FN-RMS, by differently regulating cell cycle regulators and commonly upregulating cell cycle inhibitors p21^Waf1/Cip1 and p27^Cip1/Kip1. Furthermore, PBI-05204 concomitantly induced cell death on both RMS types and senescence in FN-RMS. Notably, PBI-05204 counteracted in vitro migration and invasion abilities and suppressed the formation of spheroids enriched in CD133⁺ cancer stem cells (CSCs). PBI-05204 sensitized both cell types to RT by improving the ability of RT to induce G2 growth arrest and counteracting the RT-induced activation of both Non-Homologous End-Joining and homologous recombination DSBs repair pathways. Finally, the antitumor and radio-sensitizing proprieties of PBI-05204 were confirmed in vivo. Notably, both in vitro and in vivo evidence confirmed the higher sensitivity to PBI-05204 of FP-RMS. Thus, PBI-05204 represents a valid radio-sensitizing agent for the treatment of RMS, including the intrinsically radio-resistant FP-RMS.

PMID:36532747 | PMC:PMC9751381 | DOI:10.3389/fphar.2022.1071176
Anaplastic Rhabdomyosarcoma of Upper Lip in a 3-Year-Old Girl

Fetched: December 20th, 2022, 5:02am GMT by Arti Khatri

J Indian Assoc Pediatr Surg. 2022 Sep-Oct;27(5):644-647. doi: 10.4103/jiaps.jiaps_242_21. Epub 2022 Sep 9.

ABSTRACT

Rhabdomyosarcoma is an aggressive malignant striated muscle neoplasm commonly seen in children involving orbit, paranasal sinuses, cheek, tongue, and rarely upper lip. The anaplastic subtype is further rare and associated with poor prognosis. Herein, we report a 3-year-old female with this uncommon variant at an uncommon site.

PMID:36530822 | PMC:PMC9757796 | DOI:10.4103/jiaps.jiaps_242_21
Current clinical perspective of urological oncology in the adolescent and young adult generation

Fetched: December 18th, 2022, 5:02am GMT by Ryohei Takahashi

Int J Clin Oncol. 2023 Jan;28(1):28-40. doi: 10.1007/s10147-022-02251-4. Epub 2022 Dec 17.

ABSTRACT

Among adolescents and young adults, hematological tumors are the most common malignancies in younger patients; however, solid tumors also increase with advancing age. The pathogenesis of some of these tumors differs from that of tumors which develop in children, or middle-aged and older adults, and special care should be taken in their treatment and management. A treatment plan that takes into consideration future fertility is necessary for testicular tumors, and an educational campaign to encourage early detection is also essential. The treatment of adolescents with advanced testicular tumors should resemble therapeutic approaches for young adults and not a pediatric regimen. Adrenal tumors often develop as part of familiar hereditary syndrome. Therefore, taking the personal and family history is very important, and genetic counseling should be also recommended. In renal tumors, the incidence of translocation renal cell carcinomas is higher. Complete resection is the only promising method for long-term prognosis because of no established treatment for translocation renal cell carcinomas with distant metastasis. Bladder tumors are often detected by symptoms of gross hematuria and are found at a relatively early stage. Along with renal tumors, oncological evaluation including cystoscopy is also considered essential for gross hematuria. Wilms tumors and rhabdomyosarcomas could be managed in accordance with pediatric protocols to improve the treatment outcomes. The dedicated cancer survivorship care for adolescents and young adults could be also indispensable to conquer cancer and maintain a better quality of life.

PMID:36527578 | DOI:10.1007/s10147-022-02251-4
National assessment of lymph node status indicators & predictors in pediatric head and neck rhabdomyosarcomas in the US

Fetched: December 18th, 2022, 5:02am GMT by David J Fei-Zhang

Int J Pediatr Otorhinolaryngol. 2023 Jan;164:111419. doi: 10.1016/j.ijporl.2022.111419. Epub 2022 Dec 12.

ABSTRACT

OBJECTIVES: Assessing the prognostic utility of lymph node status in pediatric rhabdomyosarcoma (RMS) patients and identifying demographic and clinical predictors of positive lymph node status among pediatric rhabdomyosarcoma patients.

STUDY DESIGN: Retrospective cohort study of head and neck RMS in patients with and without positive lymph node metastasis.

METHODS: National Cancer Database (NCDB) was queried for patients of young (0-11 years) and adolescent (12-21 years) ages with head and neck RMS and confirmed positive or negative lymph node metastasis status. Descriptive analyses, Kaplan-Meier survival analyses, and multivariate logistic regressions were performed on extracted demographic and clinical characteristics.

RESULTS: Among 272 head and neck RMS patients, 146 (54%) were found to have positive lymph node metastasis. Alveolar RMS (n = 147, 54%) followed by embryonal RMS (n = 74, 27%) were the most represented histology types. Positive lymph node metastasis conferred significantly decreased survivability (p < 0.001) with a median survival period of 36.42 months compared to negative lymph node metastasis with a period of 53.47 months. Older age showed markedly increased odds (OR-2.02; 95%CI 1.22-3.38) of having lymph node metastasis when controlling for sex, race, insurance status, and Charlson-Comorbidity score. Alveolar histologies showed markedly increased odds of having lymph node metastasis (OR-3.21; 95%CI 1.96-5.31); embryonal histologies showed markedly decreased odds of having lymph node metastasis (OR-0.32; 95%CI 0.18-0.56) CONCLUSIONS: This study highlights the significant prognostic value of lymph node status among pediatric head and neck rhabdomyosarcoma patients while showcasing crucial demographic and pathological predictors of lymph node metastasis in said patients. Use of lymph node status in pediatric head and neck rhabdomyosarcoma will present future steps towards improving its clinical course.

PMID:36525697 | DOI:10.1016/j.ijporl.2022.111419
Single-cell analyses reveal the therapeutic effects of ATHENA and its mechanism in a rhabdomyosarcoma patient

Fetched: December 17th, 2022, 5:01am GMT by Yujun Liu

Front Oncol. 2022 Nov 29;12:1039145. doi: 10.3389/fonc.2022.1039145. eCollection 2022.

ABSTRACT

BACKGROUND: Whole-cell tumor vaccines tend to suffer from low immunogenicity. Our previous study showed that irradiated lung cancer cell vaccines in mouse models enhance antitumor efficacy by eliciting an intensive T cells response and improving immunogenicity. Based on these findings, we developed an improved whole-cell tumor vaccine, Autologous Tumor Holo antigEn immuNe Activation (ATHENA).

METHODS: In this study, we report the successful treatment of a 6-year-old male diagnosed with meningeal rhabdomyosarcoma with pulmonary and liver metastases using ATHENA. After 6 cycles of therapy, PET/CT showed the therapeutic efficacy of ATHENA. We profiled the immune response by single-cell RNA sequencing (scRNA-seq). Flow cytometry analysis was implemented to validate the status transitions of CD8⁺ T cells.

RESULTS: In CD8⁺ T cells, the exhausted status was weakened after treatment. The exhausted CD4⁺ T cells shifted towards the central memory phenotype after the treatment. Breg cells were converted to Plasma or Follicular B cells. Survival analysis for pan-cancer and transcription factor analysis indicated that such T cell and B cell transitions represent the recovery of antitumoral adaptive immune response. We validated that the proportion of CD279⁺CD8⁺ T cells were reduced and the expression of CD44 molecule was upregulated by flow cytometry assay.

CONCLUSION: Such studies not only show that ATHENA therapy may be a promising alternative treatment for tumor patients but provide a novel idea to analyses the mechanisms of rare cases or personalized cancer treatment.

PMID:36523982 | PMC:PMC9745782 | DOI:10.3389/fonc.2022.1039145
Metastatic rhabdomyosarcoma with exclusive distant lymph node involvement: A European Pediatric Soft tissue sarcoma Study Group (EpSSG) report

Fetched: December 16th, 2022, 5:02am GMT by Federico Mercolini

Pediatr Blood Cancer. 2023 Mar;70(3):e30143. doi: 10.1002/pbc.30143. Epub 2022 Dec 15.

ABSTRACT

BACKGROUND: The prognosis of patients with metastatic rhabdomyosarcoma (RMS) is not uniformly poor. Tumors with nodal involvement beyond the first lymph node station are currently considered to have distant metastases. The aim of this study is to evaluate the characteristics and outcome of RMS patients with distal nodal involvement as the only site of metastasis.

METHODS: This study included all patients with a diagnosis of RMS and distant nodal involvement as the only metastatic site, enrolled in the European Pediatric Soft tissue sarcoma Study Group (EpSSG) protocols. Treatment comprised chemotherapy, surgery, and/or radiotherapy. The main outcome measures were event-free survival (EFS) and overall survival (OS).

RESULTS: A total of 22 patients (median age 7.1 years, range 1.4-16.7) fit the inclusion criteria. The extremities were the most common primary tumor site (59%). Twenty-one patients had regional and distant nodal involvement, 12 were PAX3/7-FOXO1 positive. Twenty patients had radiotherapy including 16 to the nodal metastatic area. After a median follow-up of 53.9 months (range 22.8-110.5), 15 patients remain in complete remission, seven had progressive disease or relapse, and six of them died. The 3-year EFS and OS were 67.1% (95% confidence interval [CI]: 42.9-82.9) and 71.9% (95% CI: 47.7-86.3), respectively. Patients with fusion-negative tumors had better outcomes than those with fusion-positive tumors (3-year EFS 100% vs. 46.6%; p = .04).

CONCLUSION: In our experience, patients with RMS and distant lymph node involvement as the only site of metastasis present an outcome superior than other metastatic patients and comparable to patients with locoregional nodal involvement. In particular, excellent outcomes were seen in the limited number of patients with fusion-negative tumors.

PMID:36519598 | DOI:10.1002/pbc.30143
Report of a Primary Testicular Embryonal Rhabdomyosarcoma

Fetched: December 16th, 2022, 5:02am GMT by Claudia I Bernaschina-Rivera

P R Health Sci J. 2022 Dec;41(4):250-253.

ABSTRACT

Primary testicular rhabdomyosarcoma is a rare pediatric genitourinary tumor with few cases reported in the literature. The clinical presentation is identical to that of other common testicular neoplasms. Diagnosis entails careful microscopic examination and immunohistochemical analysis to rule out other primary testicular malignancies. Treatment consists of radical orchiectomy and adjuvant chemotherapy with possible retroperitoneal lymph node dissection. This multimodal approach is required to improve survival outcomes and reduce disease recurrence. We present the case of a primary testicular embryonal rhabdomyosarcoma in a 19-year-old male who presented with a rapidly, enlarging, painless testicular mass. He was treated with radical orchiectomy and adjuvant chemotherapy. Once found with metastatic disease, he then received salvage chemotherapy and radiotherapy without success.

PMID:36516214

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Fetched: January 26th, 2023, 5:02am GMT by Matthew R Kent

Fetched: January 26th, 2023, 5:02am GMT by Terry J Shackleford

Fetched: January 26th, 2023, 5:02am GMT by Christopher Seifen

Fetched: January 26th, 2023, 5:02am GMT by Sabahat Hafeez

Fetched: January 25th, 2023, 5:02am GMT by Paige H Parrack

Fetched: January 24th, 2023, 5:02am GMT by Peiyi Yang

Fetched: January 24th, 2023, 5:02am GMT by Jessica Gough

Fetched: January 22nd, 2023, 5:02am GMT by Sheila Terwisscha van Scheltinga

Fetched: January 22nd, 2023, 5:02am GMT by Marloes van Gorp

Fetched: January 20th, 2023, 5:03am GMT by Sarah Watson

Fetched: January 20th, 2023, 5:03am GMT by Sunil Pasricha

Fetched: January 19th, 2023, 5:02am GMT by Nathalie S M Lak

Fetched: January 18th, 2023, 5:02am GMT by Erich J Berg

Fetched: January 15th, 2023, 5:01am GMT by Wenjing Liang

Fetched: January 11th, 2023, 5:02am GMT by Alison M R Castle

Fetched: January 10th, 2023, 5:02am GMT by Alejandro Delfos Hermoza

Fetched: January 10th, 2023, 5:02am GMT by Farzad Pakdel

Fetched: January 9th, 2023, 5:02am GMT by Nadia Hindi

Fetched: January 9th, 2023, 5:02am GMT by Pankita H Pandya

Fetched: January 9th, 2023, 5:02am GMT by Robert S Phillips

Fetched: January 7th, 2023, 5:02am GMT by Uma Kumar

Fetched: January 6th, 2023, 5:02am GMT by Guillem Pascual-Pasto

Fetched: January 6th, 2023, 5:02am GMT by Junchao Shi

Fetched: January 5th, 2023, 5:02am GMT by Begüm Şirin Koç

Fetched: January 5th, 2023, 5:02am GMT by Melissa Lannon