Presenting Author: Naamit Gerber, MD Affiliation: Memorial Sloan Kettering Cancer Center, New York, NY
Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. Greater than 50% of cases are diagnosed before the age of 10. For unknown reasons, adults with RMS have worse outcomes.
In children, RMS is classified by favorable or unfavorable site and by histology as most commonly embryonal or alveolar. Most alveolar cases are associated with a (2; 13) translocation which involves the FKHR, PAX3, and PAX7 genes.
This study reports clinical features and outcomes of a large cohort of adult patients with RMS at a single institution. The goals were to assess what extent the difference in survival between pediatric and adult RMS patients were due to the disease itself and to determine what extent it was influenced by discrepancies in the treatment of RMS.
Materials and Methods
The authors analyzed data from all patients who presented to Memorial Sloan-Kettering between 1990 and 2011 who were diagnosed with RMS at age 16 or older.
Variables analyzed included the following:
Age at diagnosis
Favorable was embryonal
Unfavorable was alveolar, pleomorphic, or NOS
Primary site distrubition
Favorable was genitourinary (non-bladder/prostate), head and neck (non-parameningeal), orbit
Unfavorable was bladder/prostate, parameningeal, extremity, or other
Children’s Oncology Group (COG) risk group
148 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 (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 yrs for non-metastatic patients were 36% locally and 46% distantly.
Histology and risk group were significant predictors of local failure (p<.05). Local failure rates did not differ for surgery vs. definitive radiation treatment. Among all patients, significant predictors of OS on univariate analysis were risk group, histology, site, and age ? 19 (all p<.05), though 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=.04), site (HR 2.25, p=.02), risk group (HR 2.36, p=.01), and RMS protocol treatment (HR .49, p=.03).
Five-yr OS was 54% for RMS protocol patients vs 39% for non-protocol patients.
On multivariate analysis, the only significant variable was protocol treatment (HR .44, 95% CI .22-.90, p=.02).
Adults with RMS have certain poor prognostic features (e.g. unfavorable site).
Patients treated on or per a prospective RMS protocol had improved overall survival.
High rates of leptomeningeal failure emphasizes the need for further CNS treatments.
This study is a very large, single institution retrospective study that attempts to identify prognostic features in adult RMS. They find certain poor prognostic features that are similar to pediatric poor prognostic features.
There is a paucity of data in the literature regarding adult RMS. Ogilvie et al. reported on the University of Pennsylvania experience (Ogilvie et al. Am J Clin Oncol. 2010 Apr;33(2):128-31). They found that when combined with surgery and radiation therapy, chemotherapy using doxorubicin, ifosfamide, and vincristine yielded 55% overall and 64% disease-free survival at 2 years.
The best outcomes for RMS occur when patients are treated on prospective protocols.
The current ARST 0531 study for intermediate-risk RMS patients starts radiation at week 4 for all patients and randomizes VAC vs. VAC/VI (VI concurrent with RT).
This study does not address what dose of radiation the patients received. One potential explanation for the poorer survival of adult RMS could be inadequate radiotherapy dosing, particularly for gross disease.
Proton beam therapy is one modality that potentially can be used to increase dose to tumor without increasing complication rates. Childs et a. (Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):635-42) recently reported on proton radiotherapy for patients with PM-RMS and they found tumor control and survival comparable to historical controls and rates of late effects from proton radiotherapy improved to historical photon controls.
In addition, the question remains as to whether elective nodal irradiation is required in adult RMS patients, and if this is dependent on histology.
Further analysis could include molecular analysis of adult rhabdomyosarcoma in comparison to the pediatric tumors. Specifically, it would be interesting to identify if these patients harbor the t(2;13).
Nov 23, 2014 - Adults with rhabdomyosarcoma, though rare, have significantly worse long-term survival than children with the disease, although many of the same factors predict survival in both cases, according to a study published online April 27 in the Journal of Clinical Oncology.