To the editor, Dr. Takatori and colleagues deserve praise for meticulously studying the extent and severity of upper gastrointestinal (GI) complications in 91 inoperable pancreatic cancer patients treated on a prospective clinical trial with proton-based radiotherapy and concomitant gemcitabine chemotherapy (GPT) (1). The significant complications observed in this series (49.4% rate of gastric/duodenal ulceration), however, starkly contrast the Inhibitors,research,lifescience,medical favorable toxicity profile we observed in our series of pancreatic cancer patients treated with proton therapy and concomitant capecitabine chemotherapy (2). In our series, we observed no grade 3 IWR-1 toxicities in patients

receiving proton doses ranging from 50.40 to 59.40 Cobalt Gray Equivalent (CGE) at 1.8 CGE per daily fraction with daily oral capecitabine Inhibitors,research,lifescience,medical (1,000 mg twice daily). The median weight loss during treatment was only 1.3 kg (1.75% of body weight). Additionally, when radiotherapy plans avoided the use of anterior or left lateral

fields—reducing small bowel and gastric exposure—grade 2 GI toxicity was eliminated and median weight loss was only 0.5 kg. Possible explanations for the disparity of outcomes between these two series might include: (I) aggressive radiotherapy doses [67.5 Gray equivalent (GyE)] and high dose per fraction (2.7 GyE) delivered in the GPT series; (II) concomitant delivery of full-dose gemcitabine Inhibitors,research,lifescience,medical (800 mg/m2 on days 1, 8, and 15), well-recognized as a potent radiosensitizing agent; and (III) radiotherapy fields expanded to include regional lymph nodes in addition to the primary tumor. Although details of the radiotherapy Inhibitors,research,lifescience,medical plans were not included in the GPT publication, it is possible that some of the toxicity might have been mitigated if anterior and left lateral fields had Inhibitors,research,lifescience,medical been avoided or the dose delivered through such fields was minimized. While the current study is well-designed and well-reported, it would be wrong to conclude that proton therapy for patients with pancreatic cancer is associated with a high rate of gastrointestinal toxicity. Indeed, we have every reason to believe,

based on its superior dosimetry (3), that proton therapy offers significant improvements in the therapeutic index compared to X-ray-based therapies such as intensity-modulated PAK6 radiotherapy. Our clinical experience helps confirm the hypothesis, based on this dosimetry, that proton therapy reduces GI toxicity and may allow for treatment intensification—although perhaps not to the same degree as the intensification offered on the GPT protocol. We appreciate you taking the time to consider our letter and look forward to hearing from you in the future. Acknowledgements Disclosure: The authors declare no conflict of interest.
While pancreatic cancer remains an almost uniformly fatal diagnosis, data suggest that advances in treatment have resulted in modest gains in overall survival for local (1,2) and metastatic (2,3) disease.