Soft Tissue Sarcoma In Children Research Articles

DCX and CRABP2 are candidate genes for differential diagnosis between pre-chemotherapy embryonic and alveolar rhabdomyosarcoma in pediatric patients.

ABSTRACTImportanceRhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. More than 90% of cases are classified as embryonic RMS (ERMS) or alveolar RMS (ARMS). ERMS has a worse prognosis than ARMS. Early differential diagnosis is of paramount importance for optimization of treatment.ObjectiveTo identify genes that are differentially expressed between ARMS and ERMS, which can be used for accurate rhabdomyosarcoma classification.MethodsThree Gene Expression Omnibus datasets composed of ARMS and ERMS samples were screened and 35 differentially expressed genes (DEGs) were identified. Receiver operating characteristic curve analysis and area under the curve analysis was performed for these 35 DEGs and seven candidate genes with the best differential expression scores between ARMS and ERMS were determined. The expression of these seven candidate genes was validated by immunohistochemical analysis of pre‐chemotherapy ARMS and ERMS specimens.ResultsThe levels of DCX and CRABP2 were confirmed to be remarkably different between paraffin‐embedded ARMS and ERMS tissues, while EGFR abundance was only marginally different between these two RMS subtypes.InterpretationDCX and CRABP2 are potential biomarkers for distinguishing ARMS from ERMS in pre‐chemotherapy pediatric patients.

Clinical Characteristics and Treatment Outcome of Paediatric Rhabdomyosarcoma; A Retrospective Review.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. This paper aimed to assess the stage, site and treatment outcome among RMS patients. A retrospective chart review was completed from January 2011 to December 2017 of patients that presented to the Department of Paediatric Oncology, Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan, for the management of RMS. Data collection included clinical characteristics, staging, grouping, risk stratification, treatment plan, radiotherapy doses and treatment outcome. Among 24 subjects, there were a total of 13 (54.2%) males and 11 (45.8%) females. The median age at the time of diagnosis was 2.5 years (range: 0.75-17 years). The majority of the subjects (91.7%) were <10 years of age. The median follow-up time was 0.6 years. According to the Children's Oncology Group Classification, 4 (16.7%) subjects were classified as low risk, 14 (58.3%) subjects were rated as intermediate risk and 6 (0.25%) subjects were stratified as high risk. The most common primary tumour site was genitourinary (62.5%) and abdomen/retroperitoneal (20.8%) regions. At the time of analysis, nine (37.5%) subjects had died because of the disease, 12 (50%) were alive with no evidence of disease and one subject had a recurrence of disease and was alive. One subject had abandoned the therapy and another was lost to follow-up. Patients with RMS presented at the late stages of the disease and it most frequently affected genitourinary and abdomen or retroperitoneal areas. Overall, RMS was found to have a poor outcome to therapy.

Pediatric Rhabdomyosarcoma: Epidemiology and Genetic Susceptibility.

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children, yet little is known about its etiology. Studies that examine either environmental exposures or germline genetic predisposition in RMS have begun to identify factors that contribute to this malignancy. Here, we summarize epidemiological reports of RMS incidence in terms of several factors, including age at diagnosis, biological sex, and geographic location. We then describe findings from association studies, which explore the role of parental exposures, birth and perinatal characteristics, and childhood exposures in RMS. Further, we discuss RMS predisposition syndromes and large-scale sequencing studies that have further identified RMS-associated genes. Finally, we propose future directions of study, which aim to advance our understanding of the origin of RMS and can provide knowledge for novel RMS therapies.

Rhabdomyosarcoma in the first year of life. Experience of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood, but is very rare in infants. RMS diagnosed during the first year of life is reported to have poor outcome. The aim of the study was to analyze the results of therapy of RMS in the first year of life treated in federal center in Russian Federation. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. All prospectively registered patients with RMS in infants treated during the period 02.2012–05.2018 (75 month) were included. Diagnosis was confirmed by histology. All patients were examined and stratified according to the GPOH Cooperative Weichteilsarkom Study (CWS) Group guidance 2009. 13 prospectively registered patients with RMS in infants treated during the period were included. Median age at initial diagnosis was 6.7 (range 0.23–11.9) months. The tumor was detected prenatally at 32 and 33 weeks of gestation in 2 (15%) patients. The age of these patients was ≤ 1 month in 2 of 13 patients. Tumor size was ≤ 5 cm in 8 (61,5%) of 13 patients. Median volume tumor was 24 (range 0.001–150) ml. The primary site was head and neck (n = 4; 31.5%), pelvis (n = 3; 23%), extremities (n = 3; 23%), genitourinary system (n = 2; 15%), other (n = 1; 7.5%). IRS stage distribution was stage III in 12 (92.5%) patients, stage IV – 1 (7.5%). Regional nodal metastasis (N1) occurred in 1 (7.5%) patient with tumor of the head and neck nonparameningeal. Distant metastasis occurred in 1 (7.5%) patient and the site of spread was subcutaneous fat (blueberry muffin syndrome), pleura, roots of both lungs, pancreas, bone marrow. Histology of these infants was RMA (n = 6; 46%), RME (n = 6; 46%) and spindle-cell RMS (n = 1; 7.5%). The FOXO1-fusion positive status was found in 4/6 patients RMA by fluorescence in situ hybridization (FISH). 11/13 (85%) patients were categorized as high risk, 1/13 (7.5%) as very high risk, 1/13 (7.5%) – treatment for stage IV patients with metastatic disease. All patients (n = 13; 100%) received chemotherapy according to CWS guidance 2009 protocol. All patients were administered at a reduced dose according to body weight. The distribution of treatment regimens was as follows: 11/13 (85%) – IVA, 1/13 (7.5%) – IVADO, 1/13 (7.5%) – CEVAIE. 3/13 patients aged less than 1 month was administered chemotherapy according to VAC. Initial surgery included biopsy in 8/13, surgery – 5/13 (R2 – resection). Local control was provided in 11/13 (85%) patients: only surgery in 7/13 (54%) patients, only radiotherapy in 1/13 (7.5%), radiotherapy and surgery 1/13 (7.5%), only brachytherapy 1/13 (7.5%), brachytherapy and surgery in 1/13 (7.5%). 2/13 patients were not local control: one patient with favorable site (vagina) and one patient with stage IV that showed complete response after chemotherapy in both cases. Radiotherapy including brachytherapy was administered of the all patients at the over 1 year. Radiotherapy was used in 2 of 13 patients (dose range 50.4 Gy and 51.2 Gy), brachytherapy – 36 Gy. At the start of the radiotherapy the age was 21.1 and 13.37 months, brachytherapy – 12,4 and 14,5 months. Second-look surgery was performed in 9/13 (69%) patients: R0 (n = 7), R1 (n = 1), R2 (n = 1). 2/9 patients were performed mutilating surgery: orbital exenteration and cystectomy. Induction therapy was completed in 12 (92.5%) of 13 patients. Median follow-up time was 42.7 (range 3.7–90) months. 8 patients were alive, 5 died. 8/13 patients whom alive were observation: 6/8 patients no relapse/progressive, 2/8 patients – remission after local relapse and progression. 3-year overall survival was 68,4% (95% confidence interval 42,6–94,1. 3-year event-free survival was 46,2% (95% confidence interval 19,1–73,3). Patients aged less than 1 year are particularly problematic. The relatively low event-free survival rate in this age group is associated with the impossibility of carrying out the entire volume of multimodal therapy and required a tailored therapeutic approach.

Complexity index in sarcoma and genomic grade index gene signatures in rhabdomyosarcoma of pediatric and adult ages.

Rhabdomyosarcoma (RMS), the most frequent soft-tissue sarcoma in childhood, shows extensive heterogeneity in histology, site and age of onset, clinical course, and prognosis. Adolescents and young adults (AYA) with RMS form a subgroup of patients whose survival lacks behind that of children while diagnosed with histologically similar tumors. A 67-gene prognostic signature related to chromosome integrity, mitotic control, and genome complexity in sarcomas (CINSARC) is considered a powerful tool for identifying tumors with a highly metastatic potential. With this study, we investigated the prognostic value of CINSARC signature on a cohort of 48 pediatric (PEDs) and AYAs-RMS. CINSARC resulted not significantly correlated with age, suggesting other determinants to be responsible for that difference in survival. It remained a significant prognostic variable in both the groups of PEDs and AYAs. Also, genomic grade index signature was tested on the same cohort and showed very similar results with CINSARC. Our study showed that CINSARC correlated with outcome in RMS patients and may be potentially considered a tool to predict outcome, and so stratify RMS patients.

Identification of pannexin 1-regulated genes, interactome, and pathways in rhabdomyosarcoma and its tumor inhibitory interaction with AHNAK

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, is an aggressive cancer with a poor prognosis. Despite current management, the 5-year survival rate for patients with metastatic RMS is ∼30%; underscoring the need to develop better treatment strategies. We have recently reported that pannexin 1 (PANX1) levels are downregulated in RMS and that restoring its expression inhibits RMS progression. Here, we have surveyed and characterized the molecular changes induced by PANX1 re-expression in RMS. We cataloged transcriptomic changes in this context by RNA sequencing. At the protein level, we unveiled PANX1 interactors using BioID, complemented by co-immunoprecipitation coupled to high-performance liquid chromatography/electrospray ionization tandem mass spectrometry performed in PANX1-enriched fractions. Using these data, we generated searchable public databases for the PANX1 interactome and changes to the RMS transcriptome occurring when PANX1 expression is restored. STRING network analyses revealed a PANX1 interactome involving plasma membrane and cytoskeleton-associated proteins including the previously undescribed interactor AHNAK. Indeed, AHNAK knockdown abrogated the PANX1-mediated reduction in RMS cell viability and migration. Using these unbiased approaches, we bring insight to the mechanisms by which PANX1 inhibits RMS progression, identifying the cell migration protein AHNAK as a key modifier of PANX1-mediated changes in RMS malignant properties.

Embryonal rhabdomyosarcoma completely resected at diagnosis: The European paediatric Soft tissue sarcoma Study Group RMS2005 experience

BackgroundRhabdomyosarcoma (RMS) is the most common form of soft tissue sarcoma in children. We report the results of the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 study, which prospectively evaluated the reduction of chemotherapy in patients with embryonal RMS (ERMS) after initial surgery. MethodsBetween October 2005 and December 2016, all patients with localised ERMS with an initial microscopically complete resection (IRS group I) with lymph node-negative (N0) were prospectively enrolled in the low-risk (n = 70, subgroup A; age < 10 years and tumour size ≤ 5 cm) or standard-risk group (n = 108, subgroup B; age ≥ 10 years or tumour size > 5 cm. Subgroup A received 8 courses of vincristine and dactinomycin (VA) for 22 weeks; subgroup B received 4 courses of VA with ifosfamide (IVA) and 5 courses of VA for 25 weeks. ResultsThe 5-year event-free survival (EFS) and overall survival (OS) were 90.8% (95% confidence interval [CI]: 85.0–94.4) and 95.7% (95% CI: 90.5–98.1), respectively (n = 178). The EFS and OS were 95.5% (95% CI: 86.8–98.5) and 100% (subgroupA), and 87.8% (95% CI: 79.3–93.0) and 93.0% (95% CI: 84.8–96.8)(subgroup B), respectively. Bearman stage 2 veno-occlusive disease (VOD) occurred in 4 very young patients. ConclusionVA treatment for 8 courses was effective and well tolerated by the subgroup of patients with low-risk ERMS (group A). Four courses of IVA and 5 courses of VA instead of 9 courses of IVA also has very good results. Careful monitoring for liver toxicity is important in very young patients.European union drug regulating authorities clinical trials EUDRACT No. 2005-000217-35.

The Value of Early Tumor Size Response to Chemotherapy in Pediatric Rhabdomyosarcoma.

Simple SummaryRhabdomyosarcoma is the most common soft tissue sarcoma in childhood. At diagnosis, tumor and patient characteristics determine the prognosis and subsequent treatment stratification. There are currently no early biomarkers that identify good or poor responders to chemotherapy regimens, survival being the only valid endpoint. Early tumor size response, which is assessed by imaging, could be such a marker. We performed a systematic assessment of literature to November 2020. Six studies were included describing 2010 patients; quality assessment showed methodological limitations. We conclude that there is evidence that early progressive disease is associated with poorer survival compared to patients with non-progressive disease, being either stable disease, partial, or complete response. However, for the vast majority of patients with non-progressive disease, we found no evidence that the degree of response is prognostic for survival. Therefore, the value of early tumor size response as a prognostic marker, and its translation into treatment modifications on an individual patient or trial level should be reconsidered.Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood. Results of clinical trials, with three-year event-free and overall survival as primary outcomes, often take 7 to 10 years. Identification of an early surrogate biomarker, predictive for survival, is therefore crucial. We conducted a systematic review to define the prognostic value of early tumor size response in children with IRSG group III rhabdomyosarcoma. The search included MEDLINE/EMBASE from inception to 18 November 2020. In total, six studies were included, describing 2010 patients, and assessed by the Quality in Prognosis Studies (QUIPS) instrument. Four studies found no prognostic value for tumor size response, whereas two studies reported a prognostic effect. In these two studies, the survival rate of patients with progressive disease was not separately analyzed from patients with stable disease, potentially explaining the difference in study outcome. In conclusion, our findings support that early progression of disease is associated with poorer survival, justifying adaptation of therapy. However, in patients with non-progressive disease, there is no evidence that the degree of response is a prognostic marker for survival. Because the vast majority of patients do not have progressive disease, early tumor size response should be reconsidered for assessment of treatment efficacy. Therefore, at present, early surrogate biomarkers for survival are still lacking.

Rhabdomyosarcoma: From Obscurity to Clarity in Diagnosis … But With Ongoing Challenges in Management: The Farber-Landing Lecture of 2020.

Rhabdomyosarcoma, the most common soft tissue sarcoma in childhood, has challenged and intrigued soft tissue pathologists ever since the original descriptions. Once based on the identification of rhabdomyoblastic cells with elongate eosinophilic cytoplasm, the diagnosis has evolved to include tumors composed only of primitive mesenchymal cells but now relies heavily on immunohistochemical stains for desmin, myogenin, and MyoD. Rhabdomyosarcomas show a variety of histological patterns, giving rise to classifications that have included embryonal, alveolar, botryoid, pleomorphic, spindle cell, and sclerosing subtypes. These have been linked to prognosis and treatment assignment in the past, but that concept has been superseded by the identification of PAX3-FOXO1 or PAX7-FOXO1 fusions. Fusion testing results are more predictive of outcome and have become standard practice in clinical management. However, high risk tumors with alveolar histology or metastatic disease continue to resist oncologic treatment.

Rabdomiossarcoma intraósseo femoral: relato de caso e revisão da literatura

INTRODUCTION: Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood. However, primary bone rhabdomyosarcoma is a rare entity with some few cases reported. CASE REPORT: We present a case of a 19-year-old female patient referred from another service with three months history of a bone tumor on the femur. The first anatomopathological study was consistent with high-grade osteogenic sarcoma. After revision exams and analysis of surgically resected tumor, the primary osseous rhabdomyosarcoma was confirmed. The patient had undergone tumor resection and reconstruction with mega prosthesis. After surgery, she received chemotherapy following rhabdomyosarcoma protocol. CONCLUSION: Primary osseous rhabdomyosarcoma is a rare but important differential diagnosis to be thought on atypical presentation of primary bone sarcomas.

Rhabdomyosarcoma—Updated Histologic and Molecular Classification for 2021

Abstract Rhabdomyosarcomas are the most common soft tissue sarcoma in children and adolescents, but some specific histologic subtypes occur in adult patients. They involve various soft tissue or visceral sites, and most follow an aggressive clinical course. Currently, rhabdomyosarcomas are classified into 4 distinct clinical and morphological subtypes: embryonal, alveolar, spindle cell/sclerosing, and pleomorphic. This article reviews the clinical, histopathologic, and updated genetic features of these rhabdomyosarcoma subtypes.

Embryonal Rhabdomyosarcoma of Middle Ear and Temporal Bone: A Rare Case Report

Introduction: Rhabdomyosarcoma accounts for up to 60% of childhood soft tissue sarcoma, occurring mostly in the head and neck region but rarely in the ear and temporal areas. Case Report: A 4-year-old boy came to our hospital due to a purulent discharge, bleeding from his left ear. Also seen mass in the left ear along with facial weakness and diplopia. After histopathologic evaluation, it was diagnosed as embryonal rhabdomyosarcoma. Conclusion: Rhabdomyosarcoma should be kept in mind as a differential diagnosis in all children presenting with otitis media with mastoiditis. Biopsy should be considered who are not responding to medications and those worsening condition.

Radiation diagnostics of peripheral primitive&#x0D; neuroectodermal tumors (PNET)&#x0D; in children at the Scientific Center&#x0D; of Pediatrics and Pediatric Surgery&#x0D; (Almaty, Kazakhstan)

Relevance: Peripheral primitive neuroectodermal tumor (primitive neuroectodermal tumor – PNET) belongs to the group&#x0D; of malignant tumors that develop from migrating embryonic neural crest cells. PNET includes several nosological forms: Askin’s&#x0D; tumor, esthesioneuroblastoma, the very peripheral primitive neuroectodermal tumor, and Ewing’s sarcoma. PNET accounts for&#x0D; 3–9% of all soft tissue tumors and 19% of all soft tissue sarcomas in children. In Europe and the US, PNETs account for 3.4 cases&#x0D; per year per 1 million children below 15 years; in Kazakhstan – 0.6-1.2 cases per 1 million child population. Rapid tumor growth,&#x0D; malignancy, and early metastasis to other organs and systems predetermine the PNET’s specific role in oncology.&#x0D; The purpose of the study was to improve the quality and availability of early sarcoma diagnostics in children at medical&#x0D; institutions of the general medical network.&#x0D; Results: 35 cases of peripheral PNET in children were analyzed. The age of the patients was 1.5 to 17 years, the average age –&#x0D; 9.3 years. Boys were 1.3 times more than girls. One patient (3.6%) had extra-skeletal tumor localization. Children with stage IIB&#x0D; prevailed – 46.4% of cases (13 children).&#x0D; Radiographical differentiation between Ewing’s sarcoma and primary chronic or “healed” (antibiotic) acute hematogenous&#x0D; osteomyelitis in the initial phase of the process is almost impossible before the extraosseous soft tissue component is formed.&#x0D; The bone damage process is more often localized in the bone diaphysis and subsequently spreads to its metaphyses.&#x0D; Conclusion: PNET is more likely to come from the chest wall, so it is advisable to start the X-ray examination from the chest.&#x0D; In terms of radiation semiotics, PNET is similar to Ewing’s sarcoma and Askin’s tumor; therefore, an additional immunohistochemical study of the tumor tissue is required. An important indirect diagnostic criterion in Ewing’s sarcoma is the predominance of the soft tissue component over the bone manifestations. Extended CT and MRI studies with contrast enhancement&#x0D; (chest, abdominal cavity, pelvis, and the primary lesion area) and skeletal scintigraphy are required to clarify the extent of&#x0D; changes, stage the tumor accurately, and assess the tumor dynamics after treatment. The above conclusions generally confirm&#x0D; the available literature data.

Embryonal rhabdomyosarcoma with distant spinal cord metastasis: case and MR-imaging

Embryonal rhabdomyosarcoma (eRMS) is one of the most common soft tissue sarcomas in children, accounting for 4.5% of all childhood tumors. Half of the eRMS occuring in the head and neck are parameningeal. About 40% of patients with eRMS can develop distant metastases. In patients with intracranial tumors, metastatic spread can occur along the central nervous system (CNS) meninges. The literature describes only 4 clinical cases of eRMS with distant metastases in the spinal cord and along the meninges. Only in two out of these four cases, CSF cytology was positive (meaning that tumor cells were detected in cerebrospinal fluid). Magnetic resonance imaging (MRI) of the central nervous system with contrast enhancement can be used to detect distant metastases in the CNS and meninges. We present a clinical case of a 4-year old girl with parameningeal eRMS. MRI of the CNS performed as part of a diagnostic check-up revealed nodal metastatic foci along the meninges of the spinal cord. In accordance with the treatment protocol, the patient was diagnosed with stage 4 disease and received intensive polychemotherapy resulting in the disappearance of the nodal lesions in the spinal cord and a good prognosis. The parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.

Circulating miR-26a as Potential Prognostic Biomarkers in Pediatric Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) arises from myogenic precursors that fail to complete muscle differentiation and represents the most frequent soft tissue sarcoma in children. Two major histological subtypes are recognized: alveolar RMS, characterized by a more aggressive behavior and a greater proneness to metastasis, and embryonal RMS which accounts for the 80% of cases and carries a better prognosis. Despite the survival of patients with localized tumors has progressively improved, RMS remains a challenging disease especially for metastatic patients and in case of progressive or recurrent disease after front-line therapy. MicroRNAs, a class of small non-coding RNA, have emerged as crucial players in cancer development and progression, and their detection in plasma (circulating miRNAs) represents a promising minimally invasive approach that deserve to be exploited in clinical practice. We evaluated the utility of circulating miRNAs as diagnostic and prognostic biomarkers in children with RMS profiling miRNAs from plasma of a small cohort of RMS patients and healthy donors (HD) using a qPCR Cancer Panel. An assessment of hemolysis status of plasma using miR-451/miR-23a ratio was performed as pre-analytical analysis. Statistical analysis revealed that miRNAs expression pattern clearly distinguished RMS patients from HD (p < 0.05). Interestingly, plasma levels of muscle-specific miR-206 were found to be significantly increased in RMS patients compared to HD, whereas levels of three potential tumor-suppressor miRNAs, miR-26a and miR-30b/30c, were found lower. Reduced levels of circulating miR-26a and miR-30b/c were further measured in an independent larger cohort of patients (validation set) by digital droplet PCR. In particular, we evidenced that miR-26a absolute plasma levels were associated with fusion status and adverse outcome (p < 0.05). Taken together, these findings demonstrate the potential of circulating miRNA as diagnostic and prognostic biomarker in children affected by this malignancy and enforced the key role of miR-26a in pediatric rhabdomyosarcoma.

The prognostic significance of anaplasia in childhood rhabdomyosarcoma: A report from the Children's Oncology Group.

Established prognostic indicators in rhabdomyosarcoma (RMS), the most common childhood soft tissue sarcoma, include several clinicopathologic features. Among pathologic features, anaplasia has been suggested as a potential prognostic indicator, but the clinical significance of anaplasia remains unclear. Patients enrolled on one of five recent Children's Oncology Group clinical trials for RMS (D9602, n=357; D9802, n=80; D9803, n=462; ARST0331, n=335; and ARST0531, n=414) with prospective central pathology review were included in this study. Clinicopathologic variables including demographic information, risk group, histologic subtype, and anaplasia were recorded along with overall survival (OS) and failure-free survival (FFS) with failure defined by recurrence, progression, or death. The log-rank test was used to compare OS and FFS. Anaplasia was more common in embryonal RMS (27% of all embryonal RMS) than other subtypes of RMS (11% for alveolar RMS, 7% for botryoid RMS, 11% for spindle cell RMS). On multivariate analyses, anaplasia was not an independent prognostic factor in RMS (OS:hazard ratio (HR)=1.12, p=0.43; FFS:HR=1.07, p=0.56) across all subtypes or within embryonal RMS only (OS:HR=1.41, p=0.078; FFS:HR=1.25, p=0.16). Among tumors with TP53 mutations, 69% had anaplasia, while only 24% of tumors with anaplasia had a tumoral TP53 mutation. Anaplasia is not an independent indicator of adverse outcomes in RMS. Emerging information on the prognostic significance of TP53 mutations raises the possibility that anaplasia may be a surrogate marker of TP53 mutations in some cases. Tumoral TP53 mutation status may be investigated as a prognostic indicator in future studies.

FAK Signaling in Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of children and adolescents. The fusion-positive (FP)-RMS variant expressing chimeric oncoproteins such as PAX3-FOXO1 and PAX7-FOXO1 is at high risk. The fusion negative subgroup, FN-RMS, has a good prognosis when non-metastatic. Despite a multimodal therapeutic approach, FP-RMS and metastatic FN-RMS often show a dismal prognosis with 5-year survival of less than 30%. Therefore, novel targets need to be discovered to develop therapies that halt tumor progression, reducing long-term side effects in young patients. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that regulates focal contacts at the cellular edges. It plays a role in cell motility, survival, and proliferation in response to integrin and growth factor receptors’ activation. FAK is often dysregulated in cancer, being upregulated and/or overactivated in several adult and pediatric tumor types. In RMS, both in vitro and preclinical studies point to a role of FAK in tumor cell motility/invasion and proliferation, which is inhibited by FAK inhibitors. In this review, we summarize the data on FAK expression and modulation in RMS. Moreover, we give an overview of the approaches to inhibit FAK in both preclinical and clinical cancer settings.

Adult parameningial alveolar rhabdomyosarcoma: Case report and literature review

Alveolar rhabdomyosarcoma (ARMS) represents the most common childhood soft tissue sarcoma, but they are rarely seen among adults. Most of the protocols for adults are adapted from pediatric protocols. Here we report a case of a 53-year-old woman diagnosed with a nasal alveolar rhabdomyosarcoma, stage IV at diagnosis, treated by chemotherapy (a regimen inspired from the pediatric protocole pEpSSG RMS 2005) which led to partial response followed by chemo-radiotherapy. We performed a systematic review of adult head and neck ARMS and found 29 cases. Primary chemotherapy with different protocols (VAC, VAI or VIE) should be done followed by surgery and/or external beam radiotherapy (preferably with IMRT). EBRT seems beneficial to every ARMS with a dose around 50Gy in a conventional fractionation, eventually completed with a boost on residual tumor. The target volume must be defined on pre-chemotherapy imaging. Brachytherapy and proton therapy are under evaluation.

Pseudolaric acid B induces apoptosis in human rhabdomyosarcoma RD cells.

Pseudolaric acid B (PAB) is a diterpene-type acid isolated from the root and trunk bark of Pseudolarix kaempferi Gordon of the Pinaceae family that has been demonstrated to induce apoptosis in various cell lines and autophagy in certain cell lines including murine fibrosarcoma L929, human thyroid squamous cell carcinoma SW579 and human lung fibroblast MRC5 cells. However, in human rhabdomyosarcoma RD cells, which are derived from the most common soft tissue sarcoma in children and represent a high-grade neoplasm of a skeletal myoblast type, it is not clear whether PAB induces apoptosis or autophagy. The identification of the exact mechanism of PAB is important for studying its antitumor effects and its potential application in the treatment of human rhabdomyosarcoma. To confirm the inhibitory ability of PAB on RD cells, the inhibitory ratio of PAB was analyzed, and the results of MTT assay demonstrated that PAB inhibited RD cell proliferation. Meanwhile aggregation of the microtubule fibers was found in PAB-treated RD cells compared with that in control-treated cells, which was consistent with previous studies. In addition, PAB inhibited RD cell migration, induced apoptosis and cell cycle arrest at the G2/M phase. These results suggested that the mechanism of PAB-mediated growth inhibition in RD was similar to that reported in the human breast cancer cell line MCF-7 and the neuroglioma cell line A172; however, it was different from that reported in the L929, MRC5 and SW579 cell lines. Additional experiments demonstrated that PAB regulated the activation of caspase-8 and caspase-9 to induce apoptosis and caused an upregulation of phosphorylated H2A histone family member X and cyclin B1 expression in order to induce cell cycle arrest. Therefore, PAB may be considered a potential treatment agent for human rhabdomyosarcoma.

Stratégie diagnostique des sarcomes des tissus mous de l’enfant et adolescent

Soft tissue sarcomas in children are rare tumor, representing around 6 to 7% of children cancer. They spread mostly sporadically (90%) and therefore are rarely associated to an underlying constitutional genetic disease (10%). About half of those sarcomas are rhabdomyosarcomas and the others are a very heterogenous histologic group with various bio-pathologies and prognosis. Clinical presentation is mainly a soft tissue lump often difficult to distinguish from more frequent benign causes (malformative, infectious, benign, or pseudotumor). Inappropriate initial diagnosis work-up has a strong impact on soft tissue sarcomas' prognosis. Adapted complementary investigations (first ultrasound and MRI) are important to compile arguments for a malign origin and to indicate a biopsy. However, predictive value of imaging exams still remains imperfect, and histological analysis by percutaneous image-guided biopsy and sometimes by surgical biopsy is often necessary. Authors realize an update on optimal diagnostic pathway including molecular tests in presence of a soft tissue mass in a child.