Modeling of High-Grade Hematologic Toxicity in Anal Cancer Patients Treated With Intensity Modulated Proton Therapy (IMPT) and Volumetric Modulated Arc Therapy (VMAT)

Abstract

Intensity Modulated Radiation Therapy (IMRT) is increasingly used to spare organs at risk in definitive treatment of anal cancer, however, treatment continues to result in significant hematologic toxicity. In a cooperative trial assessing IMRT (RTOG 0529), the rate of grade 2+ and grade 3+ hematologic toxicity was 73% and 58% respectively. During IMRT planning, sparing of the bone marrow compartment is often sacrificed in favor of small bowel sparing or PTV coverage. The mean bone marrow dose can predict for grade 3+ hematologic toxicity. Intensity Modulated Proton Therapy (IMPT) may reduce acute toxicity by decreasing the integral bone marrow dose and dose to other organs at risk (OARs). CT datasets of 9 patients with anal cancer previously treated with IMRT, VMAT, or 3DCRT at our institution were used for comparison. Both VMAT and IMPT plans were created for each patient. The IMPT plans were created using a Multi-Field Optimized (MFO), split-target technique. Planning constraints for RTOG 0529 as well as bone marrow (mean <22 Gy, V10 <90%, and V40 <37%) were used for treatment planning. The dose to OARs including the bone marrow, bladder, small bowel, large bowel, femoral heads, and genitalia were compared with a paired t-test. IMPT provided similar PTV coverage as VMAT plans (99% vs 98%, P = 0.0381). The mean bone marrow dose with IMPT and VMAT plans was 17.42 Gy and 30.76 Gy respectively (P<0.0001). Based on the NTCP modeling for bone marrow toxicity IMPT should reduce the rate of grade III or higher hematologic events from 40% to <5%. IMPT also showed significant sparing of other organs at risk including the small and large bowel, femoral heads, and genitalia. Mean results of the OARs are included in Table 1 below.Abstract 2353; Table 1.IMPTVMATP-valueBone Marrow V10<90%48.97%92.56%<0.0001Bone Marrow V40<37%23.67%20.82%0.3460Bladder V40<35%38.9%52.35%0.1243Small Bowel V30<200cc176.64cc400cc0.0009Small Bowel V35<150cc151.12cc291.91cc0.0051Large Bowel V35<150cc70.37cc114.23cc0.0136Femoral Heads V40<35%2.80%21.94%0.0160Genitalia V20<50%2.55%63.68%0.0006Genitalia V30<35%1.24%41.67%0.0164 Open table in a new tab Dosimetric sparing of the bone marrow and other OARs using IMPT may reduce hematologic toxicity and improve acute tolerance of therapy. Reduction in acute toxicity should reduce treatment breaks, and in return potentially improve local control. Prospective studies assessing proton therapy for anal cancer are ongoing and in development to evaluate these potential improvements in acute toxicity.