Hematologic Toxicity of Single Posterior Pencil-Beam Scanning Versus IMRT Approaches for Esophageal Cancer

Abstract

Proton beam therapy has been shown to decrease heart and lung dose in esophageal cancers. Our group has previously published on the feasibility and safety of a single posterior field pencil-beam scanning (SPF-PBS) approach that has the advantage of maximally sparing heart and lung, but potentially at the cost of increased dose to the vertebral bodies (VBs). In this single-institution retrospective study, we assessed the hematologic toxicity and associated dosimetric factors with SPF-PBS as compared with IMRT. Twenty-one patients treated with SFP-PBS and seventeen patients treated with IMRT for locally advanced esophageal cancer between 2011-2017 were analyzed. All patients were treated concurrently with paclitaxel and platinum-based chemotherapy. Lymphocyte, neutrophil and total leukocyte values while under treatment were recorded and graded per the CTCAE v4.03 toxicity scale, and the neutrophil-to-lymphocyte ratio (NLR) was also computed. VBs were contoured 4 cm superior and inferior to the volume receiving at least 45 Gy (PTV45). The spleen was also contoured if present within the fields. Mean dose and volumes (cc) receiving at least 5, 10, 20, 30, 40 and 50 Gy were calculated (V5-V50) for both VB and spleen contours. A receiver-operator characteristic (ROC) analysis was performed for univariate correlation between incidence of grade ≥3 neutropenia, lymphopenia and dose-volume parameters. The mean VB dose was higher in the proton group than in the IMRT group (30.7Gy vs 24.5Gy, p < 0.00001). The rates of grade 3 or 4 toxicity in the proton group were 33.3% (leukopenia), 19.0% (neutropenia), and 80.0% (lymphopenia); grade 3-4 toxicity rates for the IMRT group were 47.1%, 17.6% and 93.3%, respectively. There was a significant correlation between neutropenia and VB mean dose in proton patients (AUC=0.85, p=0.031); in IMRT patients, neutropenia showed a significant correlation with D5-50 as well as V30-50. NLR values were significantly higher in the IMRT group (12.62 vs 4.69 with protons, p = 0.0038). No statistically significant correlations were seen between lymphopenia or neutropenia and splenic dose parameters. The SPF-PBS approach for esophageal cancer yields hematologic toxicity rates comparable with or superior to patients treated with IMRT at the same institution despite delivering higher mean VB doses. The use of SPF-PBS technique remains a safe method of approach for locally advanced esophageal patients that maximally spares heart and lung tissue without compromising hematologic toxicity.