The Influence of Radiation Therapy Dose Escalation on Overall Survival in Unresectable Pancreatic Adenocarcinoma

Abstract

.Purpose: Radiation therapy (RT) dose escalation in unresectable pancreatic adenocarcinoma (PAC) remains investigational. We examined the association between total RT dose and overall survival (OS) in patients with unresectable PAC.Methods and materials: National cancer data base (NCDB) data were obtained for patients who underwent definitive chemotherapy and RT (chemo-RT) for unresectable PAC. Univariate (UV) and multivariate (MV) survival analysis were performed along with Kaplan-Meier (KM) estimates for incremental RT dose levels.Results: A total of 977 analyzable patients met inclusion criteria. Median tumor size was 4.0 cm (0.3-40 cm) and median RT dose was 45 Gy. Median OS was 10 months (95% CI, 9-10 months). On MV analysis RT dose <30 Gy [HR, 2.38 (95% CI, 1.85-3.07); P<0.001] and RT dose ≥30 to <40 Gy [HR, 1.41 (95% CI, 1.04-1.91); P=0.026] were associated with lower OS when compared with dose ≥55 Gy. Patients receiving RT doses from 40 to <45, 45 to <50, 50 to <55, and ≥55 Gy did not differ in OS.Conclusions: Lack of benefit to OS with conventionally delivered RT above 40 Gy is shown. Optimal RT dose escalation methods in unresectable PAC remain an important subject for investigation in prospective clinical trials.Keywords: Radiation dose escalation pancreatic cancer; radiation dose escalation in pancreatic adenocarcinoma (PAC); unresectable pancreatic cancer; PAC and radiation therapy (RT); RT dose in unresectable pancreatic cancer; PAC and intensity modulated radiation therapy (IMRT); dose response pancreatic cancer Submitted Jan 18, 2014. Accepted for publication Feb 19, 2014Feb 19, . doi: 10.3978/j.issn.2078Feb 19, -6891.2014 View this article at: http://www.thejgo.org/article/view/2321/2900 78 Hall et al. Radiation therapy dose escalation and unresectable PAC© Pioneer Bioscience Publishing Company. All rights reserved.J Gastrointest Oncol 2014;5(2):77-85 www.thejgo.org conducted examining RT dose escalation (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). These trials have resulted in conflicting conclusions regarding the benefits of increasing RT dose. The goal of this series was to examine the effect of RT dose escalation in nonmetastatic, unresectable PAC through an analysis of the national cancer data base (NCDB). Patients and methodsOur patient population was obtained from the Pancreatic Participant Use Data File (PUF) from the NCDB, which is one of the world's largest clinical cancer registries (15). The NCDB is supported by the American College of Surgeons and the American Cancer Society (15) and includes more than 1,440 hospitals in the United States. Data available include patient demographics, pathologic characteristics, detailed staging, RT dose information, chemotherapy data, and overall survival (OS) data.Emory University was granted alpha-test user site status for the Pancreatic PUF, which includes all incident cases of PAC reported to the NCDB for the 5-year period of 1998-2002. PUF's are entirely de-identified data files available to selected investigators at Commission on Cancer (CoC) a...

Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma

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“…Escalated dose of radiation has been shown to be associated with prolonged survival in unresectable intrahepatic cholangiocarcinoma and unresectable pancreatic ductal adenocarcinoma. [18][19][20] Despite the acceptable toxicity of higher RT doses in our study, we found that selective escalated RT doses (up to 98 Gy BED) did not significantly benefit patients with unresectable EHCC with regard to increasing OS or FFLP. Unlike intrahepatic cholangiocarcinoma, EHCC is almost always close to bowel, limiting the maximal dose and the dose coverage given to the GTV.…”

EGLN Inhibition Reduces Gastrointestinal Radiation Toxicity and Improves Survival in a Murine Model of Locally Advanced Pancreatic Cancer

“…While single fractions of highdose radiation (such as 10-20Gyx1) are often preferred in preclinical studies due to ease of administration (31) these subtherapeutic doses often lead to treatment failure (16) and unacceptable toxicity in both preclinical experiments and (16,32) and in clinical trials (33). Fractionated (4,34) or stereotactic (35) A common concern with radioprotectors is that they may shield tumors from cytotoxic therapy. Our data clearly demonstrate that EGLN inhibition does not increase intratumoral HIF levels ( Fig 2B) nor does it impair treatment outcomes as evidenced by the improved survival in the groups that received FG-4592.…”

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