Intergroup Rhabdomyosarcoma Study Research Articles

Late Events Occurring After 5Years in Pediatric Rhabdomyosarcoma: A Report From the Children's Oncology Group.

Rhabdomyosarcoma is the most common pediatric soft tissue sarcoma, and 5-year overall survival exceeds 70%. With more long-term survivors, it is critical to understand the frequency of late events, including recurrence, second malignant neoplasm, and death, occurring 5years after diagnosis, and the variables associated with these events. We report late events in patients enrolled on Intergroup Rhabdomyosarcoma Study Group and Children's Oncology Group trials from 1997 to 2013 including D9602, D9803, D9802, ARST0331, ARST0431, ARST0531, and ARST08P1. A late event occurred in 2.9% of 5-year event-free survivors supporting guidelines to limit surveillance for these events to 5years from diagnosis.

Primary orbital and adnexal rhabdomyosarcoma: a study of 54 Asian Indian patients

ABSTRACT Purpose To describe the clinical presentation, management, and outcomes of orbital and adnexal rhabdomyosarcoma (RMS) in an Asian-Indian cohort and analyze the factors predictive of outcomes. Methods Retrospective interventional case series of 54 patients of histopathology-proven RMS Results The mean age of presentation with RMS was 10 years (median, 7 years; range, <1–54 years). The most common tumor location was the superonasal quadrant (n = 21, 39%). Extensions beyond the orbit into the sinuses, temporal fossa, and brain were seen in 15 (28%), 3 (6%), and 8 (15%), respectively. First-line treatment modalities included a combination of surgical debulking, chemotherapy, and external beam radiotherapy in 20 (37%) patients; chemotherapy and radiation in 20 (37%); complete surgical excision and chemotherapy in 3 (6%); orbital exenteration, chemotherapy, and external beam radiotherapy in 1 (2%); chemotherapy alone in 1 (2%) patient, and 9 (17%) patients were lost to follow up. By Intergroup Rhabdomyosarcoma Study Group (IRSG) grouping, tumors belonged to groups I (n = 2,4%), II (n = 13, 29%), and III (n = 30, 67%). Kaplan-Meier survival estimates for tumor recurrence, lymph node metastasis, systemic metastasis, and death (n = 45) were 84%, 82%, 95%, and 95% at 1 year, 69%, 76%, 81%, and 77% at 5 years, 69%, 76%, 81%, and 77% at 10 years, respectively. On multivariate regression, age >18 years was found to have a significantly increased risk of locoregional LN metastasis (p = 0.005). Conclusion Despite aggressive treatment modalities, the 5–year disease-specific survival rate was 77% in Asian-Indian cohort. Age > 18 years at presentation was associated with a poorer prognosis.

Plasma-derived extracellular vesicles miR-335–5p as potential diagnostic biomarkers for fusion-positive rhabdomyosarcoma

BackgroundRhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma, with embryonal (ERMS) and alveolar (ARMS) representing the two most common histological subtypes. ARMS shows poor prognosis, being often metastatic at diagnosis. Thus, the discovery of novel biomarkers predictive of tumor aggressiveness represents one of the most important challenges to overcome and may help the development of tailored therapies. In the last years, miRNAs carried in extracellular vesicles (EVs), small vesicles of endocytic origin, have emerged as ideal candidate biomarkers due to their stability in plasma and their tissue specificity.MethodsEVs miRNAs were isolated from plasma of 21 patients affected by RMS and 13 healthy childrens (HC). We performed a miRNA profile using the Serum/Plasma Focus microRNA PCR panels (Qiagen), and RT-qPCR for validation analysis. Statistically significant (p < 0.05) miRNAs were obtained by ANOVA test.ResultsWe identified nine EVs miRNAs (miR-483-5p, miR-132-3p, miR-766-3p, miR-454-3p miR-197-3p, miR-335-3p, miR-17-5p, miR-486-5p and miR-484) highly upregulated in RMS patients compared to HCs. Interestingly, 4 miRNAs (miR-335-5p, miR-17-5p, miR-486-5p and miR-484) were significantly upregulated in ARMS samples compared to ERMS. In the validation analysis performed in a larger group of patients only three miRNAs (miR-483-5p, miR-335-5p and miR-484) were differentially significantly expressed in RMS patients compared to HC. Among these, mir-335-5p was significant also when compared ARMS to ERMS patients. MiR-335-5p was upregulated in RMS tumor tissues respect to normal tissues (p = 0.00202) and upregulated significantly between ARMS and ERMS (p = 0.04). Furthermore, the miRNA expression correlated with the Intergroup Rhabdomyosarcoma Study (IRS) grouping system, (p = 0.0234), and survival (OS, p = 0.044; PFS, p = 0.025). By performing in situ hybridization, we observed that miR-335-5p signal was exclusively in the cytoplasm of cancer cells.ConclusionWe identified miR-335-5p as significantly upregulated in plasma derived EVs and tumor tissue of patients affected by ARMS. Its expression correlates to stage and survival in patients. Future studies are needed to validate miR-335-5p as prognostic biomarker and to deeply elucidate its biological role.

Results of the JRS-I LRA0401 and LRB0402 Japan Rhabdomyosarcoma Study Group trials for low-risk embryonal rhabdomyosarcoma.

Failure-free survival (FFS) rates of low-risk patients with rhabdomyosarcoma improved in Intergroup Rhabdomyosarcoma Study IV after the escalation of cyclophosphamide total dose to 26.4g/m2. However, this dose may increase the risk of adverse events, including infertility, in some patients. The JRS-I LRA0401 and LRB0402 protocols aimed to reduce the cyclophosphamide dose to 9.6g/m2 and 17.6g/m2, respectively, without decreasing the FFS rates. Subgroup-A patients received eight cycles (24weeks) of vincristine, actinomycin D, and 1.2g/m2/cycle cyclophosphamide. Subgroup-B patients received eight cycles (24weeks) of vincristine, actinomycin D, and 2.2g/m2/cycle cyclophosphamide, followed by six cycles (24weeks) of vincristine and actinomycin D. Group II/III patients in both subgroups received radiotherapy. In subgroup A (n = 12), the 3-year FFS rate was 83% (95% confidence interval [CI], 48-96), and the 3-year overall survival (OS) rate was 100%. Only one isolated local recurrence was observed (8.3%). There were no unexpected grade-4 toxicities and no deaths. In subgroup B (n = 16), the 3-year FFS and OS rates were 88% (95% CI, 59-97) and 94% (95% CI, 63-99), respectively. There were no unexpected grade 4 toxicities and no deaths. Shorter duration therapy using vincristine, actinomycin D, and lower dose cyclophosphamide with or without radiotherapy for patients with low-risk subgroup A rhabdomyosarcoma (JRS-I LRA0401 protocol) and moderate reduction of cyclophosphamide dose for patients with low-risk subgroup B rhabdomyosarcoma (JRS-I LRB0402 protocol) did not compromise FFS.

Localized incompletely resected standard risk rhabdomyosarcoma in children and adolescents: Results from the European Paediatric Soft Tissue Sarcoma Study Group RMS 2005 trial.

The authors report the prospective evaluation of reduced dose alkylator chemotherapy combined with radiotherapy for European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) standard risk nonalveolar rhabdomyosarcoma (NA-RMS). Localized node negative Intergroup Rhabdomyosarcoma Study (IRS) II/III NA-RMS at favorable sites (subgroup C), <25 years old, received five cycles of ifosfamide, vincristine, and dactinomycin (IVA) chemotherapy (30 g/m2 ifosfamide) and four cycles of vincristine and dactinomycin (if receiving radiotherapy), or nine cycles of IVA (54 g/m2 ifosfamide) ± radiotherapy. Delayed primary tumor excision was considered for IRS III tumors. The primary end points were event-free survival (EFS) and overall survival (OS). From October 2005 to December 2016, 359 evaluable patients were recruited: orbit, 164 (45.7%); head and neck nonparameningeal, 77 (21.4%); and genitourinary non-bladder/prostate, 118 (32.9%). EFS and OS were 77.4% (95% confidence interval [CI], 72.5-81.6) and 93.5% (95% CI, 90.1-95.8), respectively. Lower dose alkylator chemotherapy and radiotherapy achieved 5-year OS of 93.7% but the difference with higher dose alkylator chemotherapy +/- radiotherapy was not significant (p=0.8003). Adjuvant radiotherapy improved EFS with 5-year estimates of 84.7% versus 65.2% for nonirradiated (p<.0001), but not OS (p=.9298). Omitting radiotherapy for orbital tumors reduced OS (5-year was 87.1% vs. 97.3% for irradiated, p=.0257). Following R0 resection (n=60), radiotherapy did not significantly improve EFS or OS. Radiotherapy for local tumor control allows for reduction of cumulative dose of alkylators in EpSSG standard risk subgroup C RMS patients. The omission of radiotherapy did not affect OS in all patients except those with orbital RMS and was associated with inferior EFS.

Roadmap for the next generation of Children's Oncology Group rhabdomyosarcoma trials.

Clinical trials conducted by the Intergroup Rhabdomyosarcoma (RMS) Study Group and the Children's Oncology Group have been pivotal to establishing current standards for diagnosis and therapy for RMS. Recent advancements in understanding the biology and clinical behavior of RMS have led to more nuanced approaches to diagnosis, risk stratification, and treatment. The complexities introduced by these advancements, coupled with the rarity of RMS, pose challenges to conducting large-scale phase 3 clinical trials to evaluate new treatment strategies for RMS. Given these challenges, systematic planning of future clinical trials in RMS is paramount to address pertinent questions regarding the therapeutic efficacy of drugs, biomarkers of response, treatment-related toxicity, and patient quality of life. Herein, the authors outline the proposed strategic approach of the Children's Oncology Group Soft Tissue Sarcoma Committee to the next generation of RMS clinical trials, focusing on five themes: improved novel agent identification and preclinical to clinical translation, more efficient trial development and implementation, expanded opportunities for knowledge generation during trials, therapeutic toxicity reduction and quality of life, and patient engagement.

Reappraisal of prognostic factors used in the European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 study for localized rhabdomyosarcoma to optimize risk stratification and generate a prognostic nomogram.

The objective of this study was to investigate the role of clinical factors together with FOXO1 fusion status in patients with nonmetastatic rhabdomyosarcoma (RMS) to develop a predictive model for event-free survival and provide a rationale for risk stratification in future trials. The authors used data from patients enrolled in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 study (EpSSG RMS 2005; EudraCT number 2005-000217-35). The following baseline variables were considered for the multivariable model: age at diagnosis, sex, histology, primary tumor site, Intergroup Rhabdomyosarcoma Studies group, tumor size, nodal status, and FOXO1 fusion status. Main effects and significant second-order interactions of candidate predictors were included in a multiple Cox proportional hazards regression model. A nomogram was generated for predicting 5-year event-free survival (EFS) probabilities. The EFS and overall survival rates at 5years were 70.9% (95% confidence interval, 68.6%-73.1%) and 81.0% (95% confidence interval, 78.9%-82.8%), respectively. The multivariable model retained five prognostic factors, including ageat diagnosis interacting with tumor size, tumor primary site, Intergroup Rhabdomyosarcoma Studies clinical group, and FOXO1 fusion status. Based on each patient's total score in the nomogram, patients were stratified into four groups. The 5-year EFS rates were 94.1%, 78.4%, 65.2%, and 52.1% in the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively, and the corresponding 5-year overall survival rates were 97.2%, 91.5%, 74.3%, and 60.8%, respectively. The results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG.

Retrospective study of 70 cases with the head and neck non-parameningeal rhabdomyosarcoma

Objective: To analyze the treatment outcomes and prognoses of children with head and neck non-parameningeal rhabdomyosarcoma (HNnPM RMS). Methods: A retrospective analysis was performed on the clinical data of children with HNnPM RMS admitted to Beijing Children's Hospital from September 2012 to September 2022. The clinical features, comprehensive treatment modes and prognoses of the patients were analyzed. The overall survival rate (OS) and event free survival rate (EFS) were calculated using the Kaplan-Meier method, and univariate analysis was performed using the Log-rank test. Results: A total of 70 children were included in this study, 38 males and 32 females, with a median age of 47 months (2-210 months). Pathological subtypes including the embryonal in 27 cases, the alveolar in 36 cases and the spindle cell and sclerosing in 7 cases. Thirty children (83.3%) with alveolar type were positive for FOXO1 gene fusion. All 70 children underwent chemotherapy, including 38 with neoadjuvant chemotherapy and 32 with adjuvant chemotherapy. Sixty of 70 children underwent surgery, of whom, 10 underwent two or more surgeries. There were 63 children underwent radiotherapy, including 54 with intensity-modulated radiation therapy, 4 with particle implantation and 5 with proton therapy. The median follow-up was 45 (5-113) months, the 5-year OS was 73.2%, and the 5-year EFS was 57.7%. Univariate analysis showed lymph node metastasis (χ2=5.022, P=0.025), distant metastasis (χ2=8.258, P=0.004), and high Intergroup Rhabdomyosarcoma Study (IRS) group (χ2=9.859, P=0.029) as risk factors for poor prognosis. Before June 2016, the 5-year OS based on BCH-RMS-2006 scheme was 63.6%, and after 2016, the 5-year OS based on CCCG-RMS-2016 scheme was 79.6%. Conclusion: Multidisciplinary combined standardized treatment can offer good treatment outcome and prognosis for children with HNnPM RMS. Local control is a key to the efficacy of comprehensive treatment.

Clinicopathologic characteristics, treatment, prognosis and pregnancy outcomes in rhabdomyosarcoma of the uterine cervix: a case series.

In this retrospective observational study, cases from our institution were included and the published literature reviewed to investigate the diagnosis and prognosis of cervical rhabdomyosarcoma, a rare group of tumours. The clinicopathological data of 12 patients with cervical rhabdomyosarcoma (RMS) treated at the West China Second University Hospital of Sichuan University from January 2006 to May 2023 were collected, and their clinicopathological characteristics, diagnoses, treatments, prognoses and pregnancy outcomes were retrospectively analysed. (1) Clinical characteristics: The ages of the 12 RMS patients ranged from 15 to 50 years, with a median age of 17 years. Five of the patients were adults, and seven were adolescents. The initial symptoms were vaginal bleeding in 5 patients, vaginal tissue prolapse in 6 patients, and abdominal pain and urinary frequency in 1 patient. Two patients were considered to have "cervical polyps" and underwent polypectomy at the other hospitals, but the cervical mass recurred soon thereafter. (2) Pathological features: The maximum tumour diameter ranged from 3 to 25 cm. The twelve cases of cervical RMS consisted of embryonal rhabdomyosarcoma (ERMS) in 7 adolescents, ERMS in 3 adults, and pleomorphic rhabdomyosarcoma (PRMS) in 2 adults. Immunohistochemical results showed the expression of one or more characteristic markers of RMS. We reclassified tumour stage according to the Intergroup Rhabdomyosarcoma Study (IRS) clinical group and tumour node metastasis (TNM) classification. (3) Treatment: Eight patients underwent radical surgery (66.7%, 8/12), including all 5 of the included adults and 3 of the adolescents, 2 of whom were treated 10 years ago. Conservative surgical resection was performed on four patients (33.3%, 4/12), all of whom were adolescents. Postoperative chemotherapy was given to all patients except one, but one patient who underwent radical surgery discontinued chemotherapy on her own without receiving a full course. Two of the ERMS patients underwent preoperative chemotherapy, and the lesions were significantly reduced. (4) Prognosis: One of the 12 patients with cervical RMS was lost to follow-up. Of the remaining 11 patients, 10 (including seven adolescents and three adults) survived tumour free (90.9%, 10/11), and 1 adult patient with existing pulmonary multiple metastases (IRS stage IV, T2N0M1) at the initial diagnosis survived 9 months with progression-free disease (9.1%, 1/11). The median survival time was 91 months (5 to 213 months). Among 4 patients receiving fertility-sparing management, 1 conceived and delivered successfully (25%). The treatment of cervical RMS must take the patient's age and reproductive intent into account. The overall prognosis for cervical RMS in children and adolescents is good, and conservative surgical resection combined with chemotherapy is recommended to preserve fertility. The pregnancy outcome is also worth anticipating. For patients who have completed childbirth, radical surgery is preferred. Approaches to accurately assessing the patient's condition, grasping the indications and scope of surgery, and developing chemoradiotherapy regimens deserve further exploration.

Quantitative diffusion-weighted MRI response assessment in rhabdomyosarcoma: an international retrospective study on behalf of the European paediatric Soft tissue sarcoma Study Group Imaging Committee

ObjectiveTo investigate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) as a predictive imaging marker after neoadjuvant chemotherapy in patients with rhabdomyosarcoma.Material and methodsWe performed a multicenter retrospective study including pediatric, adolescent and young adult patients with rhabdomyosarcoma, Intergroup Rhabdomyosarcoma Study group III/IV, treated according to the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 or MTS2008 studies. DW-MRI was performed according to institutional protocols. We performed two-dimensional single-slice tumor delineation. Areas of necrosis or hemorrhage were delineated to be excluded in the primary analysis. Mean, median and 5th and 95th apparent diffusion coefficient (ADC) were extracted.ResultsOf 134 included patients, 82 had measurable tumor at diagnosis and response and DW-MRI scans of adequate quality and were included in the analysis. Technical heterogeneity in scan acquisition protocols and scanners was observed. Mean ADC at diagnosis was 1.1 (95% confidence interval [CI]: 1.1–1.2) (all ADC expressed in * 10−3 mm2/s), versus 1.6 (1.5–1.6) at response assessment. The 5th percentile ADC was 0.8 (0.7–0.9) at diagnosis and 1.1 (1.0–1.2) at response. Absolute change in mean ADC after neoadjuvant chemotherapy was 0.4 (0.3–0.5). Exploratory analyses for association between ADC and clinical parameters showed a significant difference in mean ADC at diagnosis for alveolar versus embryonal histology. Landmark analysis at nine weeks after the date of diagnosis showed no significant association (hazard ratio 1.3 [0.6–3.2]) between the mean ADC change and event-free survival.ConclusionA significant change in the 5th percentile and the mean ADC after chemotherapy was observed. Strong heterogeneity was identified in DW-MRI acquisition protocols between centers and in individual patients.Graphical

Clinical features and outcomes of infantile soft-tissue sarcoma: A multicenter retrospective study in Beijing.

Soft-tissue sarcomas during infancy are rare and understudied. With no data on this specific condition, we performed a retrospective study of infant-onset sarcomas based on a multi-institutional cohort in Beijing, China, collected over the past decade. We reviewed infantile soft-tissue sarcomas' clinical characteristics, treatments, and outcomes. The patients with soft-tissue sarcoma diagnosed from 0 to 12 months in four primary children's hospitals in Beijing from January 2010 to December 2019 were evaluated. Fifty-one patients were enrolled, including 31 males and 20 females. The median age at the diagnosis was five months (range, 0-12), and seven (13.7%) patients were diagnosed in the first month of their life. Histologically, twenty-five patients were diagnosed with rhabdomyosarcoma (RMS), six were diagnosed with extraosseous Ewing sarcoma (EES), and twenty were diagnosed with nonrhabdomyosarcoma soft-tissue sarcoma (NRSTS). The treatment principles and details of RMS focused on reference to the Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols. For EES and NRSTS, chemotherapy was prescribed according to children's oncology group protocols. The five-year EFS/OS rates of RMS were 26.4% ± 19.5%/56.2 ± 17.8%, the five-year EFS/OS rate of EES was 50% ± 20.4%, and the five-year EFS/OS of NRSTS was 85.2% ± 9.8%/100%. Infant-onset soft-tissue sarcoma is heterogeneous. The primary location of the abdominal or pelvic cavity of RMS and EWS was at a later stage and had a poorer prognosis. Multimodal therapy resulted in successful disease control for the majority of patients. Standardization of treatment protocols will facilitate care for such challenging conditions.

Rhabdomyosarcoma in Uterine Cervix: A 30-Year-Old Tunisian Woman Case Report

Introduction: Rhabdomyosarcoma (RMS) is a rare and aggressive mesenchymal tumor arising from skeletal muscle cells. Although it is predominantly seen in children, it can also affect adults. RMS typically presents as a rapidly growing mass in the head and neck region, genitourinary tract, or extremities. Among these sites, cervical RMS is exceedingly rare and has only been reported in a handful of cases. Case Presentation: In this report, we present a case of cervical RMS in a 30-year-old woman diagnosed and treated at the Salah Azaiez Institute. We describe the clinical presentation, imaging findings, histopathological characteristics, and treatment modalities used in this patient's management. Additionally, we review the existing literature on cervical RMS to highlight the rarity of this entity and the challenges in its diagnosis and management. A 30-year-old woman with no pathological history suddenly presented with a cervical polyp with no other symptoms. On gynecological examination, a polypoid mass measuring 3 cm developed in the lower lip of the cervix. A surgery consisting of the cervical polyp removal was performed, showing at macroscopy several polypoid fragments measuring up to 1.5 cm, microscopically non-characterizable. Gynecologists opted for conization. Definitive histology concluded with an embryonic RMS with spindle cells (desmin+, myogenin+) of the uterine cervix with microscopically involved margins, resulting in the amputation of the whole cervix. The pelvic MRI showed no residual mass. The PET-CT did not find any hypermetabolic site. The tumor was classified as IA IRSG (Intergroup Rhabdomyosarcoma Study Group) favorable group (T1a according to the TNM classification), corresponding to the low risk of recurrence subgroup. Multidisciplinary reunion decided to treat with adjuvant chemotherapy based on 4 cycles of Doxorubicin and Ifosfamide and did not retain the indication of postoperative radiation therapy. Conclusions: Given the rarity of RMS in adults and the absence of standardized protocols for managing these tumors, a multidisciplinary decision is essential, and case reports remain highly relevant.

Genitourinary embryonal rhabdomyosarcoma clinicopathologic determinants of clinical outcomes: Analysis of a pooled database.

e23536 Background: Embryonal rhabdomyosarcoma (ERS) refers to malignant soft tissue tumors with phenotypical, histological features of primitive skeletal muscle. ERS commonly involves the head and neck region and genitourinary system. Genitourinary embryonal rhabdomyosarcoma (GUERS) is considered an entity similar to other ERS based on Intergroup Rhabdomyosarcoma Study Group (IRSG) with non-prostate GUERS considered low risk. This study seeks to define other high-risk subtypes in this population. Methods: To study the demographic and molecular characteristics, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 137 cases of GUERS. Kaplan-Meier survival curves, Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results: 137 patients with confirmed GUERS were identified: median age was 16 and F:M ratio of 1.6. Female reproductive organs (49%), renal and urinary tract (24%), male reproductive organs (23%), and abdomino-pelvis (4%) were involved. Lymph node involvement and metastasis occurred in 11% and 13%, respectively. Staging consisted of stage I (65%), stage II (15%), stage III (8%), and stage IV (12%). Rhabdomyosarcoma clinical groups were mostly IA (41%), IIIA (31%) and IV (13%). Risk groups consisted of low (71%), intermediate (17%), and high (13%). Median OS and DFS were 96 and 42 months, respectively. The primary site of involvement impacted OS, with urinary tract organ involvement having the best median OS, compared to female reproductive organs, male reproductive organs, and abdomino-pelvis involvement (p = 0.01). While primary pelvic disease (p = 0.03), prostate (p = 0.008), and lymph node involvement (p = 0.001) were associated with worse OS, cervix/vaginal involvement tended to have better OS (p = 0.06). Constitutional symptoms (p = 0.0007), obstruction (p = 0.047) and metastases (p = 0.02) were associated with worse OS. Clinical staging system (p = 0.0008), risk groupings (p = 0.06) correlated with OS, but not clinical groupings (p = 0.26). GUERS with vimentin+, CD99- and SMA+ had worse survival (only the latter was statistically significant). Compared to no treatment, RT, CT+/-RT, S+CT+RT were superior with mOS of 2, 6, NR, 96 months, respectively (p &lt; 0.0001). Achieving CR had superior OS (p &lt; 0.0001). OS was not impacted by age, sex, or extent of surgery. Conclusions: Genitourinary embryonal rhabdomyosarcoma is a distinct clinical entity with outcomes worse than other forms of ERS defined by the Clinical Groups of IRSG. Prostate, primary pelvic and obstructive symptoms have worse OS compared to bladder and cervical involvement and we propose their inclusion in the current Clinical Group. This study presents updated clinicopathologic data from a pooled cohort of patients with GUERS.

Head and neck embryonal rhabdomyosarcoma clinical outcomes determinates: A pooled database analysis.

e23537 Background: Embryonal rhabdomyosarcoma (ERS) is a soft tissue sarcoma of skeletal muscle with mesenchymal precursor cells that involve the genitourinary system or head and neck. Currently, head and neck embryonal rhabdomyosarcoma (HNERS) is considered a similar entity to other ERS subtypes by the Intergroup Rhabdomyosarcoma Study Group (IRSG), with only parameningeal disease being considered as high risk. We seek to identify other higher risk phenotypes in this population. Methods: To study the demographic, molecular and IHC characteristics, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 101 cases of HNERS. Kaplan-Meier survival curves, Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: 101 patients with confirmed HNERS were identified: median age of 6.5 years, male predominance with M:F ratio of 1.7. While R0 was achieved in 44%, surgical R1 and R2 were feasible in 13% and 44% of the cases. HNERS involved the following anatomic sites: Parameningeal (49%), Skull (40%), Maxilla (39%), Nasopharynx (34%), Ears (25%), Oropharynx (17%), Nervous system (16%), Larynx (14%), Mandible (12%), Internal Jugular (7%), Orbit and Carotids (6% each), Tongue (3%), and thyroid (2%). Lymph nodes, and bone marrow were involved in 11% and 2%, respectively. Metastases occurred in 4%. The stage distribution consisted of stage I (41%), stage II (34%), stage III (19%), and stage IV (6%). Clinical groups comprised: IA(23%), IB(4%), IIA(8%), IIB(3%), IIIA(45%), IIIB(12%), and IVA(4%). Risk groups consisted of low (53%), intermediate (41%), and high (6%). The cohort’s median DFS was 240 months whereas the median OS was not reached. OS was negatively affected by parameningeal (p = 0.01), nasopharyngeal (p = 0.02), ear (p = 0.02), nerve (p = 0.0001), bone (p = 0.002), and LN (p = 0.0004) involvement. The presence of metastases was associated with worse OS (p = 0.0001). The IRSG staging system (p &lt; 0.0001), the risk groupings (p = 0.0001), and the clinical groupings (p = 0.06) correlated with OS, though the latter did not reach statistical significance. Compared to no treatment, localized therapies such as surgery and radiation therapy, and combination chemotherapy had statistically significant improvement in OS (p = 0.027). Achieving CR was associated with superior OS (p &lt; 0.0001). OS wasn't impacted by age, sex, extent of surgery, IHC, BM involvement or other head and neck anatomic site involvement. Conclusions: Embryonal Rhabdomyosarcoma of the Head and Neck is a distinct clinical subtype of ERS not fully defined by IRSG clinical groups when compared to other types of embryonal rhabdomyosarcoma. Parameningeal, nasopharyngeal, ear involvement had poor OS and should be considered as a clinical grouping. This study presents updated data from a pooled cohort of patients with HNERS.

Outcome of patients with undifferentiated embryonal sarcoma of the liver treated according to European soft tissue sarcoma protocols.

To assess the outcomes of pediatric patients with undifferentiated embryonal sarcoma of the liver (UESL) and treatment including at least surgery and systemic chemotherapy. This study included patients aged up to 21years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three European trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT), and chemotherapy. Out of 65 patients with a median age at diagnosis of 8.7years (0.6-20.8), 15 had T2 tumors, and one had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, nine IRS II, 38 IRS III, and four IRS IV. Twenty-eight upfront surgeries resulted in five operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (p=.0119) and three infiltrated margins (p=.0238). All patients received chemotherapy, including anthracyclines in 47. RT was administered in 15 patients. With a median follow-up of 78.6months, 5-year overall and event-free survivals (EFS) were 90.1% (95% confidence interval [CI]: 79.2-95.5) and 89.1% (95% CI: 78.4-94.6), respectively. Two out four local relapses had previous infiltrated margins and two out of three patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (p=.1607), T2 stage (p=.3870), use of RT (p=.8731), and anthracycline-based chemotherapy (p=.1181) were not correlated with EFS. Multimodal therapy improved the outcome of UESL. Neoadjuvant chemotherapy for pediatric patients increases the probability of complete surgical resection. The role of anthracyclines and RT for localized disease remains unclear.

Parameningeal or non-parameningeal head and neck rhabdomyosarcoma: a study based on propensity score matching and survival analysis

Objective: To compare the prognoses between parameningeal and non-parameningeal head and neck rhabdomyosarcoma based on propensity score matching and to explore the prognostic factors of overall survival in patients with head and neck rhabdomyosarcoma. Methods: The medical records of 64 patients with pathologically diagnosed as head and neck rhabdomyosarcoma from January 2016 to May 2020 in Peking Union Medical College Hospital were retrospectively retrieved, including 31 males and 33 females, with an average age of (8.0±8.9) years. Kaplan-Meier method was used to draw and compare survival curves in subgroup analysis according to different histopathological characteristics. Patients were divided into non-parameningeal (27 cases) and parameningeal (37 cases) group based on the location of primary lesion. Patients were further selected using 1∶1 propensity score matching method. The basic clinical data and overall survival were compared before and after matching. Prognostic factors were anlysed using Cox's proportional hazards regression model. Results: In 64 patients with head and neck rhabdomyosarcoma, lower risk stratification, and lower TNM stage indicated higher overall survival (all P<0.05). Before matching, patients in parameningeal group presented with higher T stage and IRS (Intergroup Rhabdomyosarcoma Study) staging (all P<0.05). There were no significant differences in basic clinical data and 1-, 2-, and 3-year overall survival rates between two groups after matching(P>0.05). Tumor size smaller than 5 cm, embryonal histology, negative FOXO1 fusion gene, lower risk stratification, and lower TNM stage were associated with higher overall survival (all P<0.05). Among these, tumor size and histology were independent prognostic factors (HR=2.36, 95%CI:1.07-5.20, P=0.033; HR=5.54, 95%CI: 1.18-25.95, P=0.030). Conclusions: There is no significant difference in overall survival between patients with parameningeal and non-parameningeal rhabdomyosarcomas. Tumor size smaller than 5 cm and embryonal histology are two independent prognostic factors.

Therapy and prognostic significance of regional lymph node involvement in embryonal rhabdomyosarcoma: a report from the European paediatric Soft tissue sarcoma Study Group

PurposeRegional lymph node disease (N1) is a component of the risk-based treatment stratification in rhabdomyosarcoma (RMS). The purpose of this study was to determine the contribution of nodal disease to the prognosis of patients with non-metastatic embryonal RMS (ERMS) and analyse their outcome by treatment received. Patients and methodsBetween 2005 and 2016, 1294 children with ERMS were enrolled in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 protocol, 143 patients with N1. Treatment comprised 9 cycles of ifosfamide, vincristine and dactinomycin. Some patients also received doxorubicin and/or maintenance if enrolled in the randomised studies. Local treatment was planned after 4 cycles of chemotherapy and included surgery to remove macroscopic residual tumour and/or radiotherapy (primary tumour and involved nodes). ResultsN1 patients were older and presented with tumours of unfavourable size, invasiveness, site and resectability. Unlike alveolar RMS, nodal involvement was more frequent in the head and neck area and rare in extremity sites. The 5-year event-free and overall survival were 75.5% and 86.3% for patients with N0, and 65.2% and 70.7% for patients with N1, respectively. The nodal involvement and the result of surgery at diagnosis (Intergroup Rhabdomyosarcoma Study group) were independent prognostic factors on multivariate analysis. Considering only patients with N1 ERMS, we were not able to identify any treatment variables which correlated with the outcome. ConclusionIn the case of nodal involvement, patients with ERMS present different characteristics and a better outcome than alveolar RMS. Regional nodal involvement is an independent prognostic factor in ERMS, therefore it is appropriate to include this population in the high-risk category.

A Web-Based Prognostic Model for Pediatric Genitourinary Rhabdomyosarcoma: Analysis of Population-Based Cohort With External Validation.

BackgroundWe conduct an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) database, intending to identify prognostic factors of pediatric genitourinary rhabdomyosarcoma (PGU–RMS). Prognostic nomogram and web-based calculator were developed for potential clinical use.MethodsData of PGU–RMS patients were extracted from the SEER database as training and internal validation cohort, patients diagnosed as PGU–RMS from 2001 to 2015 in Beijing Children's Hospital were collected as an external validation cohort. We used log-rank tests to seek risk factors on the overall survival (OS) in the overall SEER cohort, tumor site subgroups, radiation subgroups, and metastasis subgroups. The univariable and multivariate Cox regression analyses were applied to establish the prognosis model.ResultsA total of 372 PGU-RMS patients in SEER and 84 patients from our center were included. 1-, 3-, and 5-year OS of the overall SEER cohort were 95.8, 82.1, and 78.8%. Subgroup analysis indicated that tumors located in the prostate/bladder were associated with a worse prognosis than the paratesticular, female genital system, and other sites (P < 0.001). Tumors of the T1/T2 stage, without regional lymph node, involvement or metastasis, can benefit from radiotherapy (P < 0.05). For patients without metastasis, younger age, T1/T2 stage, and undergoing radiation were associated with better prognosis (P < 0.05). The prognosis nomogram was well-calibrated, the concordance index (C-index) for the OS prediction was 0.823, 0.803, and 0.768 in training, internal and external validation cohort, the area under the receiver operating characteristic curve for 3-, and 5-year OS were 0.84, 0.84 in the training cohort, 0.90, 0.84 in internal validation cohort and 0.75, 0.80 in the external validation cohort. Decision curve analysis showed good clinical utility. The predictive performance of the nomogram was higher than the Intergroup Rhabdomyosarcoma Study Group (IRSG) pretreatment stage system based on the comparison of overtime C-index, net reclassification index, and integrated discriminatory index (P < 0.001).ConclusionA comprehensive analysis of OS for PGU–RMS patients was conducted based on population cohort. The established prognosis nomogram has been fully validated and evaluated, exhibits better performance than the IRSG pretreatment stage system. Furthermore, a web-based risk calculator was developed to optimize clinical decisions.

Treatment of Pediatric Inflammatory Myofibroblastic Tumor: The Experience from China Children's Medical Center.

Background: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor with intermediate malignancy that tends to affect children primarily. To date, no standardized therapies exist for the treatment of IMT. This study aimed to share experience from China Children’s Medical Center for the explorative treatment of IMT. Methods: Patients with newly diagnosed IMT between January 2013 and December 2018 were included. Patients were grouped according to surgical margins and Intergroup Rhabdomyosarcoma Study Group (IRSG) staging. The clinical characteristic, therapeutic schedules, treatment response and clinical outcome were described. Results: Six patients were enrolled in this study, including two boys and four girls, with a median age of 57 months (range 10–148 months). Among them, five patients were anaplastic lymphoma kinase positive. Four patients achieved complete remission and two patients attained partial remission after treatment with this protocol. All patients were alive after a median follow-up of 4 years (range 3–7 years). The most common treatment-related adverse reaction was myelosuppression. Conclusion: In this study, we demonstrated that IMT has a good prognosis and the treatment selected according to risk stratification was effective and feasible.

Five-Year Follow-up After Multimodal Treatment Incorporating HDR Brachytherapy for Bladder Prostate Rhabdomyosarcoma in Children

Five-Year Follow-up After Multimodal Treatment Incorporating HDR Brachytherapy for Bladder Prostate Rhabdomyosarcoma in Children