Proton Therapy for Craniospinal Radiochemotherapy Reduces Myelotoxicity and Improves Chemotherapy Completion in Adult Medulloblastoma

Abstract

Combined radiochemotherapy for adult medulloblastoma (aMB) improves survival versus radiation alone but can be toxic. NOA-07—a phase II trial of photon craniospinal irradiation plus chemotherapy (chemo-CSI) for aMB—demonstrated high rates of myelotoxicity with just 70% of patients completing ≥4 cycles of adjuvant chemotherapy (primary endpoint). Proton therapy for chemo-CSI spares vertebral body marrow relative to photon chemo-CSI, which may reduce treatment-related myelotoxicity and improve rates of chemotherapy completion. This analysis tracks myelotoxicity and chemotherapy completion in aMB patients treated with proton chemo-CSI, comparing them to published NOA-07 results. Patients age ≥15 were included if they received vertebral-body-sparing proton chemo-CSI for newly-diagnosed aMB and were planned to receive concomitant weekly vincristine with radiotherapy followed by ≥4 cycles of adjuvant chemotherapy. The craniospinal axis was treated to 23.4 or 36 CGE with a boost to 54-55.8 CGE. Myelotoxicity and chemotherapy completion evaluated using NOA-07 criteria. Correlations with toxicities assessed using chi-square tests with Yates’ continuity correction. Progression-free and overall survival were estimated via the Kaplan-Meier method. Twenty-seven consecutive patients treated at a single institution met the above criteria. Median follow-up was 2.3 years. Median age was 27 (range: 16-58), 48% were female, 52% average-risk, and 52% received 36 CGE CSI. 2-year PFS and OS were 90% and 100%, respectively. Ninety-six percent completed ≥4 cycles of concomitant vincristine versus 93% in NOA-07. In the adjuvant phase, 89% and 80% completed ≥4 and ≥6 cycles of chemotherapy, respectively, versus 70% and 63% in NOA-07. Of 25 patients with available adjuvant-phase hematologic data: 96% received cisplatin, 80% vincristine, 60% CCNU, and 68% cyclophosphamide. Adjuvant-phase myelotoxicity rates were similar to NOA-07 overall, but lower in a subgroup not receiving cyclophosphamide (an agent not included in the NOA-07 regimen). Adjuvant cyclophosphamide was significantly associated with grade≥3 anemia (p<0.05), leukopenia (p<0.01) and neutropenia (p<0.01). Myelotoxicity rates listed in table below. There was no significant association between CSI dose and myelotoxicity.Abstract 1057; Table 1Grade 3/4 ToxicityConcomitant PhaseAdjuvant PhaseNOA-07Proton Chemo-CSINOA-07Proton Chemo-CSIProton Chemo-CSI w/o cyclophosphamideLeukopenia36.7%16.0%66.7%68.0%25.0%Thrombocytopenia3.3%8.0%36.7%44.0%25.0%Anemia13.3%12.0%20.0%48.0%12.5% Open table in a new tab Proton chemo-CSI for aMB increases rates of adjuvant chemotherapy completion, reduces rates of concomitant-phase leukopenia and, excluding patients receiving cyclophosphamide, lowers rates of adjuvant-phase myelotoxicity compared to photon chemo-CSI control.