Hypofractionated Conformal Radiotherapy with Concurrent Full-Dose Gemcitabine Versus Standard Fractionation Radiotherapy with Concurrent Fluorouracil for Unresectable Pancreatic Cancer: a Multi-Institution Experience.
OBJECTIVE
The purpose of this study was to compare oncologic outcomes and toxicity profile of hypofractionated conformal radiotherapy (RT) with concurrent full-dose gemcitabine versus standard fractionation RT with concurrent 5-fluorouracil (5-FU) in the treatment of unresectable non-metastatic pancreatic cancer.


METHODS
Patients with unresectable non-metastatic adenocarcinoma of the pancreas treated at three institutions were included. All patients were treated with chemoradiotherapy (CRT) consisting of either hypofractionated RT to the gross disease concurrent with a full-dose gemcitabine-based regimen versus standard fractionation RT to the tumor and elective nodes concurrent with 5-FU. End points included rates of gastrointestinal (GI) toxicities, overall survival (OS), and distant metastasis free survival (DMFS).


RESULTS
From January 1999 to December 2009, 170 patients were identified (118 RT/gemcitabine, 52 RT/5-FU). There were no differences in demographic or clinical factors. Acute GI toxicities (grades <3 versus ≥3) were 82.2 and 17.8 %, respectively, for patients treated with RT/gemcitabine and 78.9 and 21.2 % for those treated with RT/5-FU (p = 0.67). Late GI toxicities (grades <3 versus ≥3) were 88.1 and 11.9 %, respectively, for RT/gemcitabine and 80.8 and 19.2 % for RT/5-FU (p = 0.23). OS for RT/gemcitabine and RT/5-FU were 52 versus 36 % at 1 year and 14 versus 6 % at 2 years favoring the RT/gemcitabine group (p = 0.02). DMFS at 1 and 2 years for RT/gemcitabine were 41 and 11 % versus 24 and 4 % for RT/5-FU (p = 0.02).


CONCLUSIONS
RT/gemcitabine was equivalent in toxicity to RT/5-FU but was associated with superior OS and DMFS. When RT is used in the treatment of unresectable pancreatic cancer, hypofractionated conformal RT with concurrent full-dose gemcitabine may be the preferred approach.
Department of Radiation Oncology, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
Sunpreet
S
Rakhra
Department of Radiation Oncology, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
Jonathan B
JB
Strauss
Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, USA.
John
J
Robertson
Department of Radiation Oncology, Maine Medical Center, Portland, ME, USA.
Cornelius J
CJ
McGinn
Department of Radiation Oncology, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
Thomas
T
Kim
Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI, USA.|Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Jiayi
J
Huang
Department of Radiation Oncology, Maine Medical Center, Portland, ME, USA.
Andrew
A
Blake
Northwestern University Cancer Biostatistics Core, Chicago, IL, USA.
Irene
I
Helenowski
Department of Radiation Oncology, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
John P
JP
Hayes
Division of Hematology/Oncology, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
Mary
M
Mulcahy
Department of Radiation Oncology, Cardinal Bernardin Cancer Center, Stritch School of Medicine, Loyola University Chicago, 2160 S 1st Ave Maguire Center, Rm 2932, Maywood, IL, 60153, USA. wmsmall@lumc.edu.
William
W
Small
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods; D012189:Retrospective Studies; D016019:Survival Analysis; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine
GEM/RT versus 5-FU/RT; Locally advanced pancreatic cancer