Neoadjuvant therapies provide numerous theoretical and practical advantages over postoperative treatment: Table 2 Neoadjuvant trials for borderline resectable pancreatic cancers Malignant cells are more likely to oxygenate preoperatively, allowing radiation to be more effective through the production of radicals causing DNA damage; Preoperative treatment may reduce the likelihood Inhibitors,research,lifescience,medical of tumor spillage, dissemination, or implantation at the time of surgery; Since the irradiated bowel is likely to be resected at the time of pancreaticoduodenectomy, patients treated with preoperative radiotherapy may experience less long-term nutritional problems compared to patients irradiated postoperatively;

With neoadjuvant therapy, there is no delay between systemic therapy and surgery, as opposed to adjuvant therapy where the delay is caused by postoperative recovery, possibly reducing the control of distant metastases; Neoadjuvant therapies may effectively downstage marginally resectable tumors and render Inhibitors,research,lifescience,medical them resectable. These theoretical advantages are promising, but, to date, there are no randomized

trials that directly compare neoadjuvant and Inhibitors,research,lifescience,medical adjuvant therapies. In a phase 1 clinical trial, Hong et al. demonstrated the feasibility of hypoSCH 900776 order fractionated neoadjuvant proton therapy with concomitant capecitabine for patients with resectable adenocarcinoma of the pancreatic head (11). Fifteen patients received doses ranging from 30 GyE in 10 fractions over 2 weeks to 25 GyE in 5 fractions over 1 week. Chemotherapy consisted of capecitabine at 825 mg/m2 twice daily. No dose-limiting toxicities were observed. Evaluation

of 30-day postoperative mortality and morbidity showed no deaths or anastomotic leaks. Limited elective nodal irradiation was offered. Inhibitors,research,lifescience,medical Of Inhibitors,research,lifescience,medical note, 10 of 11 patients undergoing surgery had positive lymph nodes in the operative specimen. Nichols et al. reported negligible weight loss and gastrointestinal toxicity in a group of 20 patients treated with conventionally fractionated protons and concomitant capecitabine (1,000 mg orally twice-daily) (12). Patients had marginally resectable (N=5), resected (N=5), or unresectable (N=10) disease and received planning target volume (PTV) proton doses about ranging from 50.40 to 59.40 CGE. No elective nodal irradiation was offered to the patients with measurable gross disease. The median PTV volume was 406 cm3 (range, 244 to 1,811 cm3). For the 17 patients treated with a 2-field plan (posterior oblique and right lateral oblique) which minimized gastric and small bowel exposure, the median weight loss was only 1.1l bs (range, gain of 10.4 lbs to loss of 14.1 lbs) over the course of treatment. No patient experienced grade 2 or greater GI toxicity. Conclusions Protons allow for substantial gastric and small bowel sparing compared with X-rays in the setting of neoadjuvant radiotherapy for pancreatic cancer.