RMS13: A phase II trial using risk adapted focal proton beam radiation and/or surgery with the addition of maintenance chemotherapy in intermediate risk rhabdomyosarcoma.

person Jessica Gartrell St. Jude Children's Research Hospital, Memphis, TN info_outline Jessica Gartrell, Alberto S. Pappo, Yimei Li, Tushar Patni, Daniel J. Indelicato, Sara Michele Federico, Elizabeth Stewart, Christopher L Tinkle, Sara Helmig, John Thomas Lucas, Michael W. Bishop, Mary B McCarville, Karen H. Albritton, Matthew J. Krasin

Authors person Jessica Gartrell St. Jude Children's Research Hospital, Memphis, TN info_outline Jessica Gartrell, Alberto S. Pappo, Yimei Li, Tushar Patni, Daniel J. Indelicato, Sara Michele Federico, Elizabeth Stewart, Christopher L Tinkle, Sara Helmig, John Thomas Lucas, Michael W. Bishop, Mary B McCarville, Karen H. Albritton, Matthew J. Krasin Organizations St. Jude Children's Research Hospital, Memphis, TN, St. Jude Children's Research Hosptial, Memphis, TN, Department of Radiation Oncology, University of Florida College of Medicine Jacksonville, Jacksonville, FL, Cook Children's Medical Center, Fort Worth, TX Abstract Disclosures Research Funding No funding sources reported Background: European trials have demonstrated improved outcomes in SIOP high-risk/COG intermediate risk (IR) rhabdomyosarcoma (RMS) when 6 months of maintenance therapy (MTC) was added to ifosfamide, vincristine (VCR), dactinomycin (DAC) +/-doxorubicin chemotherapy. The effectiveness of MTC integrated with VCR, DAC and cyclophosphamide (CYC), standard North American chemotherapy, remains unclear. Methods: RMS13 is a phase II multicenter trial evaluating the safety and efficacy of risk adapted proton radiation therapy (RT) and the addition of MTC in patients with IR RMS (embryonal stage 1, Group III non-orbit, and stage 3 Group I, II were not eligible for MTC). Patients received 12 cycles of VCR (1.5mg/m2 weekly), DAC (0.045mg/kg q3weeks), and CYC (1200mg/m2 q3weeks) (VAC) followed by MTC with 4 cycles of oral CYC (50mg/m2 daily), bevacizumab (15mg/kg) q3wks, and sorafenib (90mg/m2 bid) (CBvSor). RT was prescribed based on local tumor status at the time of RT (Table 1). Five-year disease-free survival (DFS) using the Kaplan-Meier method and the cumulative incidence (CI) of primary site local failure (LF) was described. Results: 46 patients were enrolled (Table 1). One patient refused further therapy and was removed from the analysis. 5-year DFS for the entire cohort was 67.5% with a median follow up of 54 mo. The trial was halted since < 75% of enrolled patients received all prescribed CBvSor MTC. Of the 35 who were eligible for MTC, 24 initiated MTC and 18 completed protocol-directed MTC. Three pts received vinorelbine/CYC MTC after enrollment was stopped. Reasons for not completing CBvSor MTC included: progression prior (6), toxicity (5), refusal (3). The 5-year DFS for the 24 patients that started cycle 3 was 70.3%. When limited to patients classified as high-risk in RMS2005 trial, the 5-year DFS was 81.4%. No patients experienced LF after margin negative surgery. The CI of LF was: 0% following 36GyRBE RT for microscopic residual disease, 8% for patients with unresected tumors < 5cm receiving standard dose RT (50.4GyRBE), and 10% for patients with unresected tumors > = 5cm receiving dose escalated RT (59.4GyRBE). 5/6 patients with alveolar N1 disease recurred. Conclusions: Local control with risk adapted dose-escalated RT was excellent in IR patients. Those with nodal involvement fared poorly. While 4-cycles of MTC with CBvSor was not feasible, those who underwent at least 3 cycles experienced enhanced DFS outcomes, aligning with the positive results seen in other trials incorporating MTC. Clinical trial information: NCT01871766. N (%) Age (yrs, median) 4.9 (0.3-21.5) Age Group (yrs) < 1 1-10 > 10 - 5 (11) 30 (67) 10 (22) Histology Alveolar (Fusion +) Embryonal Other - 9 (20) 34 (76) 2 (4) IRS Stage 1 2 3 - 9 (20) 9 (20) 27 (60) Group II III - 3 (7) 42 (93) Primary Site Bladder/Prostate Extremity Parameningeal Other - 7 (16) 7 (16) 16 (35) 15 (33) RT Dose (GyRBE) 0 36 50.4 59.4 - 7 (17) 12 (29) 12 (29) 10 (25)