Survival of Adult Rhabdomyosarcoma Patients Treated on Multimodality Protocols

Abstract

Purpose/Objective(s)Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes. We report clinical features and outcomes of a large cohort of adult patients with RMS at a single institution.Materials/MethodsWe analyzed data from all patients who presented between 1990 and 2011 who were diagnosed with RMS at age 16 or older.ResultsOne hundred forty-eight patients met study criteria. Ten were excluded for lack of adequate data. Median follow-up was 43 months for surviving patients. Median age was 27 years (range 16 - 85 years). Tumor histology was: embryonal 50%, alveolar 33%, pleomorphic 12%, spindle cell 4%, and not specified 2%. The tumor site was unfavorable in 67% of patients. When stratified by COG risk group, 33 patients (24%) were low risk, 61 (44%) intermediate risk, and 44 (32%) high risk. Most patients received multimodality treatment: 91% had chemotherapy; 65% had radiation therapy; 6% had surgery alone. Overall, 46% were treated on or per a prospective RMS protocol originally developed for pediatric patients. The most common chemotherapy regimens contained vincristine and cyclophosphamide with either doxorubicin (58%) or dactinomycin (26%). Median radiation dose was 50.4 Gy. Five-year overall survival (OS) was 45% for non-metastatic patients and 26% for metastatic patients. Failure rates at 5 years for non-metastatic patients were 36% locally and 46% distantly. Histology and risk group were significant predictors of local failure (p < 0.05). Local failure rates did not differ for surgery versus definitive radiation treatment. Among all patients, significant predictors of OS on univariate analysis were risk group, histology, site, and age ≤19 (all p < 0.05), although histology lost significance on multivariate analysis. Among patients with non-metastatic disease (n = 94), significant univariate predictors of OS were histology (HR = 1.82, p = 0.04), site (HR = 2.25, p = 0.02), risk group (HR = 2.36, p = 0.01), and RMS protocol treatment (HR = .49, p = 0.03). Five-yr OS was 54% for RMS protocol patients versus 39% for non-protocol patients. On multivariate analysis, the only significant variable was protocol treatment (HR = 0.44, 95% CI 0.22-0.90, p = 0.02). Leptomeningeal failure occurred in 17% of patients with parameningeal tumors. Four patients (13%) with extremity RMS, all with alveolar histology, also developed leptomeningeal disease. Two patients (1%) developed secondary AML.ConclusionsSurvival in non-metastatic adult patients was significantly improved for those treated on RMS protocols, most of which are now open to adults. The prognostic factors in adults, as in children, include tumor site and COG risk group. The high rate of distant failure, including CNS failure, emphasizes the need for novel systemic and CNS-directed therapies. Purpose/Objective(s)Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes. We report clinical features and outcomes of a large cohort of adult patients with RMS at a single institution. Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes. We report clinical features and outcomes of a large cohort of adult patients with RMS at a single institution. Materials/MethodsWe analyzed data from all patients who presented between 1990 and 2011 who were diagnosed with RMS at age 16 or older. We analyzed data from all patients who presented between 1990 and 2011 who were diagnosed with RMS at age 16 or older. ResultsOne hundred forty-eight patients met study criteria. Ten were excluded for lack of adequate data. Median follow-up was 43 months for surviving patients. Median age was 27 years (range 16 - 85 years). Tumor histology was: embryonal 50%, alveolar 33%, pleomorphic 12%, spindle cell 4%, and not specified 2%. The tumor site was unfavorable in 67% of patients. When stratified by COG risk group, 33 patients (24%) were low risk, 61 (44%) intermediate risk, and 44 (32%) high risk. Most patients received multimodality treatment: 91% had chemotherapy; 65% had radiation therapy; 6% had surgery alone. Overall, 46% were treated on or per a prospective RMS protocol originally developed for pediatric patients. The most common chemotherapy regimens contained vincristine and cyclophosphamide with either doxorubicin (58%) or dactinomycin (26%). Median radiation dose was 50.4 Gy. Five-year overall survival (OS) was 45% for non-metastatic patients and 26% for metastatic patients. Failure rates at 5 years for non-metastatic patients were 36% locally and 46% distantly. Histology and risk group were significant predictors of local failure (p < 0.05). Local failure rates did not differ for surgery versus definitive radiation treatment. Among all patients, significant predictors of OS on univariate analysis were risk group, histology, site, and age ≤19 (all p < 0.05), although histology lost significance on multivariate analysis. Among patients with non-metastatic disease (n = 94), significant univariate predictors of OS were histology (HR = 1.82, p = 0.04), site (HR = 2.25, p = 0.02), risk group (HR = 2.36, p = 0.01), and RMS protocol treatment (HR = .49, p = 0.03). Five-yr OS was 54% for RMS protocol patients versus 39% for non-protocol patients. On multivariate analysis, the only significant variable was protocol treatment (HR = 0.44, 95% CI 0.22-0.90, p = 0.02). Leptomeningeal failure occurred in 17% of patients with parameningeal tumors. Four patients (13%) with extremity RMS, all with alveolar histology, also developed leptomeningeal disease. Two patients (1%) developed secondary AML. One hundred forty-eight patients met study criteria. Ten were excluded for lack of adequate data. Median follow-up was 43 months for surviving patients. Median age was 27 years (range 16 - 85 years). Tumor histology was: embryonal 50%, alveolar 33%, pleomorphic 12%, spindle cell 4%, and not specified 2%. The tumor site was unfavorable in 67% of patients. When stratified by COG risk group, 33 patients (24%) were low risk, 61 (44%) intermediate risk, and 44 (32%) high risk. Most patients received multimodality treatment: 91% had chemotherapy; 65% had radiation therapy; 6% had surgery alone. Overall, 46% were treated on or per a prospective RMS protocol originally developed for pediatric patients. The most common chemotherapy regimens contained vincristine and cyclophosphamide with either doxorubicin (58%) or dactinomycin (26%). Median radiation dose was 50.4 Gy. Five-year overall survival (OS) was 45% for non-metastatic patients and 26% for metastatic patients. Failure rates at 5 years for non-metastatic patients were 36% locally and 46% distantly. Histology and risk group were significant predictors of local failure (p < 0.05). Local failure rates did not differ for surgery versus definitive radiation treatment. Among all patients, significant predictors of OS on univariate analysis were risk group, histology, site, and age ≤19 (all p < 0.05), although histology lost significance on multivariate analysis. Among patients with non-metastatic disease (n = 94), significant univariate predictors of OS were histology (HR = 1.82, p = 0.04), site (HR = 2.25, p = 0.02), risk group (HR = 2.36, p = 0.01), and RMS protocol treatment (HR = .49, p = 0.03). Five-yr OS was 54% for RMS protocol patients versus 39% for non-protocol patients. On multivariate analysis, the only significant variable was protocol treatment (HR = 0.44, 95% CI 0.22-0.90, p = 0.02). Leptomeningeal failure occurred in 17% of patients with parameningeal tumors. Four patients (13%) with extremity RMS, all with alveolar histology, also developed leptomeningeal disease. Two patients (1%) developed secondary AML. ConclusionsSurvival in non-metastatic adult patients was significantly improved for those treated on RMS protocols, most of which are now open to adults. The prognostic factors in adults, as in children, include tumor site and COG risk group. The high rate of distant failure, including CNS failure, emphasizes the need for novel systemic and CNS-directed therapies. Survival in non-metastatic adult patients was significantly improved for those treated on RMS protocols, most of which are now open to adults. The prognostic factors in adults, as in children, include tumor site and COG risk group. The high rate of distant failure, including CNS failure, emphasizes the need for novel systemic and CNS-directed therapies.