Outcomes In Rhabdomyosarcoma Research Articles

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.

Single-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma

Paediatric rhabdomyosarcoma (RMS) is a soft tissue malignancy of mesenchymal origin that is thought to arise as a consequence of derailed myogenic differentiation. Despite intensive treatment regimens, the prognosis for high-risk patients remains dismal. The cellular differentiation states underlying RMS and how these relate to patient outcomes remain largely elusive. Here, we use single-cell mRNA sequencing to generate a transcriptomic atlas of RMS. Analysis of the RMS tumour niche reveals evidence of an immunosuppressive microenvironment. We also identify a putative interaction between NECTIN3 and TIGIT, specific to the more aggressive fusion-positive (FP) RMS subtype, as a potential cause of tumour-induced T-cell dysfunction. In malignant RMS cells, we define transcriptional programs reflective of normal myogenic differentiation and show that these cellular differentiation states are predictive of patient outcomes in both FP RMS and the less aggressive fusion-negative subtype. Our study reveals the potential of therapies targeting the immune microenvironment of RMS and suggests that assessing tumour differentiation states may enable a more refined risk stratification.

Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium.

PURPOSERhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor, and beyond PAX-FOXO1 fusion status, no genomic markers are available for risk stratification. We present an international consortium study designed to determine the incidence of driver mutations and their association with clinical outcome.PATIENTS AND METHODSTumor samples collected from patients enrolled on Children's Oncology Group trials (1998-2017) and UK patients enrolled on malignant mesenchymal tumor and RMS2005 (1995-2016) trials were subjected to custom-capture sequencing. Mutations, indels, gene deletions, and amplifications were identified, and survival analysis was performed.RESULTSDNA from 641 patients was suitable for analyses. A median of one mutation was found per tumor. In FOXO1 fusion-negative cases, mutation of any RAS pathway member was found in > 50% of cases, and 21% had no putative driver mutation identified. BCOR (15%), NF1 (15%), and TP53 (13%) mutations were found at a higher incidence than previously reported and TP53 mutations were associated with worse outcomes in both fusion-negative and FOXO1 fusion-positive cases. Interestingly, mutations in RAS isoforms predominated in infants < 1 year (64% of cases). Mutation of MYOD1 was associated with histologic patterns beyond those previously described, older age, head and neck primary site, and a dismal survival. Finally, we provide a searchable companion database (ClinOmics), containing all genomic variants, and clinical annotation including survival data.CONCLUSIONThis is the largest genomic characterization of clinically annotated rhabdomyosarcoma tumors to date and provides prognostic genetic features that refine risk stratification and will be incorporated into prospective trials.

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.

Outcomes in rhabdomyosarcoma: Experience from a tertiary cancer centre in India

Outcomes in rhabdomyosarcoma: Experience from a tertiary cancer centre in India

Genomic Determinants of Clinical Outcomes in Rhabdomyosarcoma.

Increased availability of next-generation sequencing has allowed for the genomic characterization of a variety of pediatric tumors, although genomic determinants of response to treatment remain largely unknown. We sought to evaluate the genomic landscape and genomic determinants of clinical outcomes in rhabdomyosarcoma (RMS). Of 29,067 patients who underwent genomic profiling at our institution using a 468-gene oncopanel with complete records, 87 had RMS, of whom 22 were fusion positive. The 10 most common genetic alterations were associated with locoregional control (LC), disease-free survival (DFS), and overall survival (OS). Tumor mutational burden (TMB), defined as the total number of somatic nonsynonymous mutations normalized to the number of sequenced megabases, was also associated with clinical outcomes. Median age at diagnosis was 16.4 years and median follow-up, 2.1 years. Patients with fusion-negative RMS had more genomic alterations and a higher TMB than those with fusion-positive RMS (mean number of genomic alterations, 6.0 vs. 2.9; P = 0.007 and mean TMB, 2.6 vs. 1.0; P = 0.01). Genetic alterations in TP53 were associated with worse OS (P = 0.03). High TMB (defined as the top quartile ≥ 2.8) was associated with worse LC (P = 0.05), DFS (P = 0.04), and OS (P = 0.01), with significance retained on multivariable analysis after controlling for risk group, fusion status, and receipt of chemotherapy as per pediatric protocols. High TMB was associated with worse clinical outcomes in patients with RMS. With further validation, TMB and other genomic classifiers may be combined with traditional clinicopathologic risk factors to guide risk stratification and ultimately treatment decisions.

Genomic Predictors of Survival Outcomes in Pediatric Sarcomas

Increased availability of next generation sequencing has allowed for the genomic characterization of a variety of pediatric tumors, although genetic determinants of response to treatment remain largely unknown. We sought to evaluate the genomic landscape and genomic predictors of survival outcomes in rhabdomyosarcoma (RMS) and Ewing sarcoma (ES). Of 29,067 patients who underwent genomic profiling at our institution using a 468-gene oncopanel with complete records, 164 had either RMS (n=87, of whom 22 were fusion-positive) or ES (n=77) For the analysis, the 10 most common genetic alterations were associated with locoregional control (LC), progression-free survival (PFS), and overall survival (OS) for each individual tumor type. Tumor mutational burden (TMB), defined as the total number of somatic non-synonymous mutations normalized to the number of sequenced megabases, was also associated with disease outcomes. Median age at diagnosis was 15.7 years and 20.6 years for RMS and ES, respectively, and median follow up was 27.1 months. The median number of alterations found on genomic sequencing for RMS and ES were 4 (range, 0-25) and 2 (range, 0-21), respectively. Patients with fusion-positive RMS had less alterations on sequencing than patients with fusion-negative RMS (median 2 versus 5, p=0.007). The most common genetic alterations in RMS included TP53 (17%), NF1 (13%), CDKN2A (11%), NRAS (11%), MYOD1 (10%) MDM2 (9%), BCOR (9%) CDKN2B (9%), CDK4 (8%), and GLI1 (7%). The most common genetic alterations in ES included TP53 (12%), STAG2 (10%), ERG (9%), ERF (6%), CDKN2A (5%), CREBBP (5%), TERT (5%), BCOR (5%), FAT1 (4%), and CCND1 (4%). The 3-year LC, PFS, and OS for RMS were 52.4%, 27.5%, and 56.1%. The 3-year LC, PFS, and OS for ES were 84.7%, 61.6%, and 82.2%. Genetic alterations in TP53 were associated with significantly worse OS in RMS (p=0.03), while genetic alterations in CDKN2A were associated with worse OS in ES (p=0.002). Higher TMB (defined as >3) was significantly associated with worse LC (p=0.05), PFS (p=0.04), and OS (p=0.01) in RMS (with significance retained when separated by fusion status). Higher TMB was also associated with worse LC (p=0.02) and PFS (p=0.009) in ES, with a trend toward worse OS (p=0.16). Higher TMB predicted for worse local control and survival outcomes in both RMS and ES. Our preliminary results must be correlated with other well-known clinicopathologic risk factors with the ultimate goal of guiding risk stratification and treatment decisions.

Temporal trends among survivors of rhabdomyosarcoma: A report from the Childhood Cancer Survivor Study (CCSS).

11570 Background: Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols included treatment modifications, which may have ameliorated late health outcomes for rhabdomyosarcoma (RMS) survivors treated in more recent era. Methods: We evaluated chronic health conditions (CHCs) and late mortality ( &gt; 5 years from diagnosis) among survivors treated 1970-1990 (IRSG I-III) and 1991-1999 (IRSG IV), and associations with specific treatments to identify treatment-related factors for adverse outcomes. Associations between treatments and CHCs and mortality were evaluated using Fine and Gray’s proportional hazards method accounting for competing risks. Results: 856 survivors treated 1970-90 (median diagnosis age 5.4 years [0- 20]) and 306 treated 1991-99 (median diagnosis age 5.5 years [0-20]) were included. Significant exposure differences between eras included higher percentage (53% vs. 17%, p &lt; 0.01) receiving ≥ 20gm/m2 cumulative alkylators in 1991-99, but more receiving platinums (13% vs 5%, p &lt; 0.01) and abdomen/ pelvis radiation (29% vs. 23%, p = 0.04) in 1970-90. 20-year cumulative incidence for any (40% vs. 28%, p &lt; 0.01), ≥2 (16% vs. 7%, p &lt; 0.01), and endocrine (8% vs. 2.5%, p &lt; 0.01) grade 3-5 CHCs was higher in 1970-90 compared to 1991-99. The hazard ratio (HR) for any (HR 0.7, 95% Confidence Interval [CI] 0.55-0.9), ≥2 (HR 0.38, 95% CI 0.22-0.66) and endocrine (HR 0.25, 95% CI 0.09-0.67) grade 3-5 CHC was lower for 1991-99 survivors than 1970-90. The effect of era (1991-99 vs 1970-90, HR 0.73; 95% CI 0.59-0.91) on CHC was not attenuated when treatment variables were added to multivariable model. Exposures with increased risk of grade 3-5 CHC included platinums (hearing, HR 2, 95% CI 1.07-3.8), anthracycline ≥250mg/m2 (cardiovascular, HR 2.7, 95% CI 1.2-6) and abdomen/ pelvis radiation (second malignant neoplasms, HR 2.1, 95% CI 1.1-4, gastrointestinal, HR 7.4, 95% CI 3.5-16 and endocrine, HR 2.5, 95% CI 1.4-4.4). Gonadal dysfunction was the most common endocrine CHC. There was no difference in all cause or cause-specific mortality between the two cohorts. Conclusions: RMS survivors from the IRSG IV era are at reduced risk for late onset chronic health conditions compared to previous era.

Outcomes in rhabdomyosarcoma: Experience from a tertiary cancer center in India

Background: Rhabdomyosarcoma (RMS) is an embryonal tumor seen commonly in children. There is a paucity of literature on RMS from India. The present study was conducted to look at the disease characteristics and outcome of RMS patients treated at our center. Methods: This was a retrospective study that included patients with RMS of all age groups treated at our center between 2001 and 2016. Overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan–Meier method. Results: The study included 70 patients with a median age of 7 years (1–70 years) and 42/70 (60%) were male. The common sites of disease were parameningeal in 31 (44%) and extremity in 17 (24%) patients. Metastasis at presentation was seen in 22/70 (31%) patients. Embryonal (66%) followed by alveolar (9%) and pleomorphic (4%) were the common histologic subtype. The risk stratification showed good-risk in 13 (18%), intermediate-risk in 35 (50%), and high-risk in 22 (32%) patients. The median duration of follow-up was 70.4 months (Confidence interval: 26.1–114.8 months). The median EFS and OS in the study were 11 months and 21 months, respectively. The factors associated with better OS were male gender (P = 0.038), nonmetastatic disease (P = 0.028), good- and intermediate-risk subgroup (P = 0.002), complete surgical excision (P = 0.002), and radiotherapy (P = −0.002). Conclusion: Outcomes in RMS remain dismal with most patients presenting with advanced disease. Multimodality management with chemotherapy, surgery, and radiotherapy in patients with nonmetastatic disease improves outcome.

Outcomes in rhabdomyosarcoma: Indian perspective

Outcomes in rhabdomyosarcoma: Indian perspective

18F 2Fluoro-2deoxy-D-glucose positron emission tomography (FDG-PET) response to predict event-free survival (EFS) in intermediate risk (IR) or high risk (HR) rhabdomyosarcoma (RMS): A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group (COG).

10549Background: Change in tumor size by anatomic imaging is not a reliable predictor of outcome in RMS. We reviewed metabolic response by FDG-PET for patients with IR and HR RMS enrolled on two CO...

Predicting Outcome in Patients with Rhabdomyosarcoma: Role of [18F]Fluorodeoxyglucose Positron Emission Tomography

To evaluate whether [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) response of the primary tumor after induction chemotherapy predicts outcomes in rhabdomyosarcoma (RMS). After excluding those with initial tumor resection, 107 patients who underwent FDG-PET after induction chemotherapy at Memorial Sloan Kettering Cancer Center from 2002 to 2013 were reviewed. Local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated according to FDG-PET response and maximum standardized uptake value (SUV) at baseline (PET1/SUV1), after induction chemotherapy (PET2/SUV2), and after local therapy (PET3/SUV3). Receiver operator characteristic curves were used to determine the optimal cutoff for dichotomization of SUV1 and SUV2 values. The SUV1 (<9.5 vs ≥9.5) was predictive of PFS (P=.02) and OS (P=.02), but not LC. After 12 weeks (median) of induction chemotherapy, 45 patients had negative PET2 scans and 62 had positive scans: 3-year PFS was 72% versus 44%, respectively (P=.01). The SUV2 (<1.5 vs ≥1.5) was similarly predictive of PFS (P=.005) and was associated with LC (P=.02) and OS (P=.03). A positive PET3 scan was predictive of worse PFS (P=.0009), LC (P=.05), and OS (P=.03). [(18)F]fluorodeoxyglucose positron emission tomography is an early indicator of outcomes in patients with RMS. Future prospective trials may incorporate FDG-PET response data for risk-adapted therapy and early assessment of new treatment regimens.

Outcome of Rhabdomyosarcoma in First Year of Life: Children’s Cancer Hospital 57357 Egypt

Background. Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children. Fifty percent of RMS cases occur in the first 10 years of life and less commonly in infants younger than one-year old. These infants require adapted multimodality treatment approaches. Patients and Methods. We analyzed patients' characteristics, treatment modalities, and the outcome for RMS infants treated at Children's Cancer Hospital Egypt (CCHE) between July 2007 and December 2010 and compared them to patients above one year treated on the same protocol. Results. Out of the 126 RMS treated during this period, 18 were below the age of one year. The male: female ratio was 1.25 : 1. The median age at diagnosis was 0.7 ± 0.2 years. Most of the cases (27.8%) were presented in head and neck regions. The estimated 4-years failure-free survival and overall survival for infants were 49 ± 12% and 70 ± 12%, respectively. These failure-free survival rate and overall survival rate did not differ from those for older patients (P = 0.2). Conclusion. Infants with RMS are a unique group of RMS who needs special concerns in tailoring treatment in addition to concerns regarding toxicity and morbidity in infants.

Positron Emission Tomography (PET) Evaluation After Initial Chemotherapy and Radiation Therapy Predicts Local Control in Rhabdomyosarcoma

18-fluorodeoxyglucose positron emission tomography (PET) is already an integral part of staging in rhabdomyosarcoma. We investigated whether primary-site treatment response characterized by serial PET imaging at specific time points can be correlated with local control. We retrospectively examined 94 patients with rhabdomyosarcoma who received initial chemotherapy 15 weeks (median) before radiotherapy and underwent baseline, preradiation, and postradiation PET. Baseline PET standardized uptake values (SUVmax) and the presence or absence of abnormal uptake (termed PET-positive or PET-negative) both before and after radiation were examined for the primary site. Local relapse-free survival (LRFS) was calculated according to baseline SUVmax, PET-positive status, and PET-negative status by the Kaplan-Meier method, and comparisons were tested with the log-rank test. The median patient age was 11 years. With 3-year median follow-up, LRFS was improved among postradiation PET-negative vs PET-positive patients: 94% vs 75%, P=.02. By contrast, on baseline PET, LRFS was not significantly different for primary-site SUVmax≤7 vs >7 (median), although the findings suggested a trend toward improved LRFS: 96% for SUVmax≤7 vs 79% for SUVmax>7, P=.08. Preradiation PET also suggested a statistically insignificant trend toward improved LRFS for PET-negative (97%) vs PET-positive (81%) patients (P=.06). Negative postradiation PET predicted improved LRFS. Notably, 77% of patients with persistent postradiation uptake did not experience local failure, suggesting that these patients could be closely followed up rather than immediately referred for intervention. Negative baseline and preradiation PET findings suggested statistically insignificant trends toward improved LRFS. Additional study may further understanding of relationships between PET findings at these time points and outcome in rhabdomyosarcoma.

New Treatments for Rhabdomyosarcoma: The Importance of Target Practice

To address the poor outcomes in rhabdomyosarcoma, particularly the alveolar subtype, new therapies are needed. Potential cancer-specific alterations that may be molecular targets include gene fusions or copy number changes. Following the latter strategy, an attractive antigene approach was developed to inhibit MYCN oncogene expression in rhabdomyosarcoma.

The effect of age at diagnosis on outcome in rhabdomyosarcoma.

Survival for rhabdomyosarcoma appears to be more favorable in children and adolescents compared with adults. To determine the significance of age at diagnosis as a prognostic indicator in rhabdomyosarcoma, we performed a retrospective analysis of a combined pediatric and adult rhabdomyosarcoma data base. Pertinent prognostic variables, including age, TNM stage, histopathologic subtype, anatomic site, resectability, radiation to the primary site, and dose intensity of chemotherapy, were compared in a Cox proportional hazards model with mortality as the outcome variable. Age at diagnosis (P = 0.0001) and local tumor invasiveness (P < 0.0001), distant parenchymal metastases (P < 0.0001), regional lymph node involvement (P = 0.0027), and histopathologic subtype (P = 0.0446) contributed information to the proportional hazards model. Age at diagnosis is an independent predictor of outcome in patients with rhabdomyosarcoma along with tumor invasiveness, metastases, regional lymph node involvement, and histopathologic subtype.

Local and regional disease extent as a predictor of outcome in rhabdomyosarcoma

Local and regional disease extent as a predictor of outcome in rhabdomyosarcoma