Proton beam therapy and concurrent chemotherapy for esophageal cancer

Abstract

Purpose: Proton beam therapy (PBT) is a promising modality for the management of thoracic malignancies. We report our preliminary experience of treating esophageal cancer patients with concurrent chemotherapy (CChT) and PBT (CChT/PBT) at MD Anderson Cancer Center.

Methods and materials: This is an analysis of 62 esophageal cancer patients enrolled on a prospective study evaluating normal tissue toxicity from CChT/PBT from 2006 to 2010. Patients were treated with passive scattering PBT with two- or three-field beam arrangement using 180 to 250 MV protons. We used the Kaplan-Meier method to assess time-to-event outcomes and compared the distributions between groups using the log-rank test.

Results: The median follow-up time was 20.1 months for survivors. The median age was 68 years (range, 38-86). Most patients were males (82%) who had adenocarcinomas (76%) and Stage II-III disease (84%). The median radiation dose was 50.4 Gy (RBE [relative biologic equivalence]) (range, 36-57.6). The most common grade 2 to 3 acute toxicities from CChT/PBT were esophagitis (46.8%), fatigue (43.6%), nausea (33.9%), anorexia (30.1%), and radiation dermatitis (16.1%). There were two cases of grade 2 and 3 radiation pneumonitis and two cases of grade 5 toxicities. A total of 29 patients (46.8%) received preoperative CChT/PBT, with one postoperative death. The pathologic complete response (pCR) rate for the surgical cohort was 28%, and the pCR and near CR rates (0%-1% residual cells) were 50%. While there were significantly fewer local-regional recurrences in the preoperative group (3/29) than in the definitive CChT/PBT group (16/33) (log-rank test, p = 0.005), there were no differences in distant metastatic (DM)-free interval or overall survival (OS) between the two groups.

Conclusions: This is the first report of patients treated with PBT/CChT for esophageal cancer. Our data suggest that this modality is associated with a few severe toxicities, but the pathologic response and clinical outcomes are encouraging. Prospective comparison with more traditional approach is warranted.

Figure 1. PBT treatment plans for two patients

A-C) Two field AP/PA plan for this patient with a mid-to-distal esophageal cancer. D) DVH analysis of the plan for this patient shows a MLD=12.5 Gy, Heart V40=37%, cord maximum 27 Gy, Liver V30=12%. E-G) Three field RPO, LPO, left lateral posterior oblique PBT plan for this patient with GEJ tumor adenocarcinoma. H) DVH analysis of the plan. MLD=3.8 Gy, Heart V40=8%, cord maximum 37.1 Gy, Liver V30=7%.

Figure 2. Dose Volume Histogram (DVH) analysis of the accessible patients treated with CChT/PBT

A-B) Summary DVH curves of the total lung and heart depending on whether the tumors were in the distal or mid-esophageal regions. C) Tabular summary of the mean and maximal doses to normal and target structures for the entire cohort (average) or for the primary sites of disease (distal, middle (mid), proximal (prox) esophagus).

Figure 3

Survival and disease specific outcomes in the preoperative (n=29) and definitively treated (n=33) patients.