Intensity-Modulated Proton Therapy (IMPT) Reduces Dose to Pelvic Bone Marrow and Normal Pelvic Organs when Compared to Volumetric-Modulated Arc Therapy (VMAT) for patients with Anal Cancer

Abstract

Anal squamous cell carcinoma (SCCa) has high cure rates with concurrent chemoradiotherapy (CRT), but acute toxicity rates are high. Severe lymphopenia, resulting from low absolute lymphocyte count (ALC), has been correlated with worse overall survival in several cancer types. We hypothesized that decreased dose to the pelvic bone marrow (PBM) correlates with decreased ALC nadir. In this work, we compared doses to the PBM and other organs-at-risk for patients treated with IMPT and VMAT. We also evaluated ALC, white blood cell counts (WBC) and absolute neutrophil counts (ANC) values and correlated these values with PBM doses. We analyzed 16 consecutive stages I-III anal SCCa patients treated between 1/1/2017 and 1/1/2018 with cisplatin and 5-fluorouracil-based CRT using VMAT. WBC, ANC, and ALC values were obtained weekly during treatment. The nadirs were identified and compared with various dosimetric parameters for PBM using the Pearson correlation. Ten consecutive patients treated with either VMAT (N = 8) or IMPT (N = 2) had both VMAT and IMPT plans generated and 6 patients had only VMAT plans. IMPT plans were generated using two posterior oblique beams for posterior pelvic targets (hinge angle ranged between 40 and 70 degrees with respect to each other) and anterior beam for inguinal nodal targets. Field specific targets were created for each beam, and plan was robustly optimized with Isocenter-shift of 0.5 cm and 3.5% range uncertainty in combination (12 perturbations). Dosimetric parameters for the PBM, bowel bag, bladder and external genitalia were compared with the Wilcoxon signed-rank test. For the 16 patients, the WBC, ANC, and ALC nadirs (mean ± SD) were 3.2 ± 1.0 K/uL, 2.2 ± 1.3 K/uL and 0.32 ± 0.17 K/uL, respectively. Increased volume of PBM receiving 10 Gy or more (V10) significantly correlated with decreased ALC nadir (R2 = 0.25, p = 0.049). There were no significant differences between PBM parameters and WBC or ANC nadirs. For the 10 patients for whom VMAT and IMPT plans were generated, IMPT was associated with lower doses to the PBM, bladder and genitalia but a higher maximum dose to the bowel (Table). Decreased V10 of the PBM is associated with decreased ALC nadirs in patients undergoing CRT for anal SCCa. IMPT is able to spare unnecessary dose to the PBM as well as the bladder and genitalia compared with VMAT. Clinical studies are needed to see whether these dosimetric benefits yield meaningful reductions in acute or long-term hematologic or non-hematologic toxicity.Abstract SU_2_2013; Table 1IMPT; mean±SDVMAT; mean±SDWilcoxon P-valueMean Pelvic BM21±4 Gy(RBE)29±3 Gy.004Pelvic BM V10 (%)65±1393±5.004Pelvic BM V20 (%)51±1276±8.004Pelvic BM V30 (%)37±748±7.004Pelvic BM V40 (%)20±425±5.016Bowel Bag Dmax52±3 Gy(RBE)42±21.010Bowel Bag V45 (cm3)178±120176±131.193Bladder V40 (%)28±1542±18.002Genitalia V30 (%)10±827±15.008 Open table in a new tab