Hematologic Toxicity Comparison of Intensity-Modulated Proton Therapy and Intensity-Modulated Radiation Therapy in Anal Cancer Patients

Abstract

<h3>Purpose/Objective(s)</h3> IMPT has been shown to decrease the pelvic bone marrow (PBM) dose compared to IMRT in anal cancer dosimetric studies, however it is unknown whether IMPT reduces hematologic toxicity. By converting discrete adverse event (AEs) data into a continuous variable (0-5), the Toxicity Index (TI) is a novel method of accounting for all AEs within a class and multiple events with the same grade (Rogatko et al. Clin Cancer Res 2004). We hypothesize that the hematologic TI (Hem TI) is a feasible method for evaluating all AEs within the hematologic class during chemoradiation for anal cancer and that IMPT results in a decrease in Hem TI compared to IMRT. <h3>Materials/Methods</h3> Patients enrolled on a prospective feasibility trial assessing the use of IMPT for anal cancer were compared to contemporaneous patients treated with IMRT. All patients received concurrent chemotherapy (83% 5-Fluorouracil/Mitomycin C). Radiation dose was prescribed according to RTOG 0529 in both groups. All hematologic events (CTCAE version 5.0 anemia, lymphopenia, thrombocytopenia, neutropenia, and leukopenia) during treatment were used to calculate the Hem TI for each patient. PBM was defined as all bone from L5/S1 interspace through the ischial tuberosity including the bilateral femoral heads. Demographics, PBM dosimetric parameters, and the Hem TI were compared between groups using the Wilcoxon rank-sum test and Fisher's exact test. A multivariable, probabilistic index model (PIM) was used to evaluate predictors of Hem TI in the setting of demographic and treatment (IMPT vs IMRT) variables. <h3>Results</h3> Forty-eight patients treated with definitive chemoradiation for anal cancer between 2015 and 2021 at a single institution were included in this analysis (IMRT = 34, IMPT = 14). Table 1 displays demographic, hematologic toxicity and PBM dose comparisons between the IMRT and IMPT groups. The Hem TI was not decreased in patients receiving IMPT despite reduction in all PBM metrics. Based on the PIM model, the probability that a randomly selected patient in the IMPT group has a higher Hem TI compared to a similar patient in the IMRT group is 82% (<i>P</i> < 0.05). <h3>Conclusion</h3> Hem TI is a feasible method for reporting the totality of hematologic events in anal cancer treatment. IMPT patients had lower PBM dose metrics but this was not associated with lower hematologic toxicity when compared to IMRT. Preferential treatment of the active bone marrow-rich lumbosacral space with standard PA fields used during IMPT will be evaluated further as a potential explanation of these findings.