Proton Therapy and Concomitant Capecitabine for Non-Metastatic Unresectable Pancreatic Adenocarcinoma

Abstract

Purpose: To review early outcomes for patients enrolled on our institution's protocol (PC01) for patients with unresectable pancreatic cancer, and to test whether the serious adverse event rate could be reduced from 15% (expected) to ,5%. Patients and Methods: Twelve patients were enrolled, but only 11 patients are reported in this analysis. Pathology on all patients was reviewed at University of Florida Health Medical Center in Jacksonville to confirm the diagnosis of pancreatic adenocarcinoma. Unresectability was defined by radiographic evidence of encasement of the celiac axis and/or superior mesenteric artery or by occlusion of the superior mesenteric vein, portal vein, or both confluences. Patients received proton therapy to a planning target volume dose of 59.4 Gy (relative biological effective) at 1.8 Gy (relative biological effective) per fraction over 7 weeks with concomitant oral capecitabine (1000 mg orally twice-daily, 5 days/week on radiation treatment days only). Only gross disease was targeted. Results: Median follow-up for all patients was 14 months (range, 5 to 25 months). Median follow-up for surviving patients was 23 months (range, 8 to 25 months). Median age was 68 years (range, 51 to 86 years). One-and 2-year overall survival, progression-free survival, distant metastasis-free survival, and freedom from local progression rates were 61% and 31% (median, 18.4 months), 55% and 14%, 68% and 27%, and 86% and 69%, respectively. No patient experienced a grade 3 or greater toxicity during treatment or follow-up. Grade 2 toxicity was limited to a single patient experiencing grade 2 fatigue. Median weight loss over the course of treatment was 1.7 kg (range, loss of 5.7 to gain of 4.9 kg). Four patients had an adequate radiographic response to radiation therapy to justify surgical exploration. Conclusion: Proton therapy with concomitant capecitabine as delivered on the PC01 protocol was well-tolerated with no grade 2 or greater gastrointestinal toxicities. The

Clinical Limitations of Photon, Proton and Carbon Ion Therapy for Pancreatic Cancer

“…A gap which may possibly be exploited by particle therapy and the further development of systemic therapies such as HAPs. Table 3 demonstrates an improved 2-year OS and MST ranging from 31-50.8% and 18.4-25.6 months [45,50]. The enhanced biological damage of PT radiation dose delivery compared to XRT (i.e., dose reporting) across the studies varies in terms of: RBE, cobalt Gray equivalents (CGE refers to absorbed dose × 1.1 (RBE) to express the biologic effective proton dose), Gray equivalents (GyE refers to proton physical dose (in Gray) × 1.1 (RBE)).…”

“…Kim To date, while PT clinical results have had a positive impact on MST and OS for pancreatic cancer treatment, no chemoradiation combination has resulted in a statistically significant increase in survival. Investigations into concomitant capecitabine by Sachsman et al [50] and Nichols, et al's [59] reported no acute grade 3 GI toxicities and minimal acute grade 2 GI toxicities (9% and 13.6%, respectively). All 3 patients who received grade 2 acute GI toxicities in Nichols, et al [59] prospective PT trial received anterior and lateral beams.…”

Current and emerging radiotherapy strategies for pancreatic adenocarcinoma: stereotactic, intensity modulated and particle radiotherapy

“…In another prospective study of 11 patients by Sachsman et al . (28) using a conventional fractionated regimen (59.4 Gy in 33 fractions) demonstrated a 2-year freedom from local progression rate of 69% and 2-year OS rate of 31%. No significant late effects were reported.…”

Management of Borderline Resectable Pancreatic Cancer

“…The University of Florida treated PDAC and ampullary cancers patients neoadjuvantly using doses 59.4 Gy (relative biological effectiveness) in 33 fractions, combined with capecitabine, with a similarly low incidence of gastrointestinal toxicity (89). In a separate phase II trial, the same investigators treated 11 unresectable PDAC patients (90). They reported a median OS of 18.4 months, with 1-and 2-year OS rates of 61% and 31%, respectively.…”