ORIGINAL ARTICLE – PANCREATIC TUMORS
Analysis of Perioperative Chemotherapy in Resected Pancreatic
Cancer: Identifying the Number and Sequence of Chemotherapy
Cycles Needed to Optimize Survival
Irene Epelboym, MD
, Mazen S. Zenati, MD, PhD
, Ahmad Hamad, MD
, Jennifer Steve, BS
, Kenneth K. Lee,
, Nathan Bahary, MD, PhD
, Melissa E. Hogg, MD
, Herbert J. Zeh, MD
, and Amer H. Zureikat, MD
Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA;
Department of Surgery and
Epidemiology, University of Pittsburgh, Pittsburgh, PA;
Department of Medical Oncology, University of Pittsburgh
Medical Center, Pittsburgh, PA
Purpose. Receipt of 6 cycles of adjuvant chemotherapy
(AC) is standard of care in pancreatic cancer (PC).
Neoadjuvant chemotherapy (NAC) is increasingly utilized;
however, optimal number of cycles needed alone or in
combination with AC remains unknown. We sought to
determine the optimal number and sequence of periopera-
tive chemotherapy cycles in PC.
Methods. Single institutional review of all resected PCs
from 2008 to 2015. The impact of cumulative number of
chemotherapy cycles received (0, 1–5, and C6 cycles) and
their sequence (NAC, AC, or NAC ? AC) on overall
survival was evaluated Cox-proportional hazard modeling,
using 6 cycles of AC as reference.
Results. A total of 522 patients were analyzed. Based on
sample size distribution, four combinations were evaluated:
0 cycles = 12.1%, 1–5 cycles of combined
NAC ? AC = 29%, 6 cycles of AC = 25%, and C6
cycles of combined NAC ? AC = 34%, with corre-
sponding survival. 13.1, 18.5, 37, and 36.8 months. On
MVA (P \ 0.0001), tumor stage [hazard ratio (HR) 1.35],
LNR (HR 4.3), and R1 margins (HR 1.77) were associated
with increased hazard of death. Compared with 6 cycles
AC, receipt of 0 cycles [HR 3.57, conﬁdence interval (CI)
2.47–5.18] or 1–5 cycles in any combination (HR 2.37, CI
1.73–3.23) was associated with increased hazard of death,
whereas receipt of C6 cycles in any sequence was associ-
ated with optimal and comparable survival (HR 1.07, CI
Conclusions. Receipt of 6 or more perioperative cycles of
chemotherapy either as combined neoadjuvant and adju-
vant or adjuvant alone may be associated with optimal and
comparable survival in resected PC.
The multimodality management of pancreatic cancer
(PC) has evolved signiﬁcantly over the past three decades.
Early trials demonstrated a beneﬁt to gemcitabine or 5FU
monotherapy therapy over observation in the adjuvant
More recently, ESPAC 4 demonstrated that
combination adjuvant chemotherapy (AC) was superior to
Additionally, correlative data from ESPAC
3 suggests that completion of 6 cycles of adjuvant
chemotherapy is more important than time to adjuvant
therapy in optimizing survival.
Although these studies have established adjuvant
chemotherapy as the standard of care for resected PC,
actuarial 5-year survival for resected patients remains
Reasons for this poor prognosis include that
nearly 30% of patients do not receive intended adjuvant
therapy due to postoperative morbidity and prolonged
recovery after resection.
More recent national data
suggest this fraction to be as high as 50% even at high-
volume pancreatic centers.
Consequently, and due to
Oral presentation at the meeting of the Society of Surgical Oncology
(HPB session), Seattle, Washington, March 16, 2017.
Electronic supplementary material The online version of this
article (doi:10.1245/s10434-017-5975-3) contains supplementary
material, which is available to authorized users.
Ó Society of Surgical Oncology 2017
First Received: 11 April 2017;
Published Online: 5 July 2017
A. H. Zureikat, MD
Ann Surg Oncol (2017) 24:2744–2751