Adjuvant Therapy in Pancreas Cancer: Does It Influence Patterns of Recurrence?

Alexander A. Parikh, Amelia Maiga, David Bentrem, Malcolm H. Squires, David A. Kooby, Shishir K. Maithel, Sharon M. Weber, Clifford S. Cho, Matthew Katz, Robert C. Martin, Charles R. Scoggins, Jeff Sutton, Syed A. Ahmad, Daniel E. Abbott, Jacquelyn Carr, Hong Jin Kim, Danny Yakoub, Kamran Idrees, Nipun Merchant

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Abstract

Background: Level 1 data demonstrate that adjuvant chemotherapy (ACT) improves survival after surgical resection of pancreatic ductal adenocarcinoma (PDAC), (adjuvant gemcitabine, CONKO-001 study; adjuvant 5-FU, ESPAC3 study). The role of adjuvant chemoradiation therapy (ACRT) remains controversial. What is less clear is whether adjuvant therapy influences patterns of recurrence. The purpose of this study was to perform the first multicenter study analyzing patterns of recurrence after adjuvant therapy for PDAC. Study Design: Patients undergoing resection for PDAC from 8 medical centers over a 10-year period were analyzed. Demographics, tumor characteristics, operative treatment, type of adjuvant therapy, recurrence pattern, and survival were reviewed. Using Cox-proportional hazards multivariate (MV) regression, the impact of ACT and ACRT on overall survival (OS), local recurrence (LR), and distant recurrence (DR) was investigated. Results: There were 1,130 patients who were divided into those having surgery alone (n = 392), ACT (n = 291), or ACRT (n = 447). Median follow-up was 18 months. Compared with patients undergoing surgery alone, ACT, but not ACRT, demonstrated a significant OS advantage on MV analysis. Patients receiving ACT had significantly fewer recurrences (LR and DR); those receiving ACRT had significantly less LR but not DR. On subset MV analysis, ACT and ACRT resulted in less LR in patients with lymph node (LN) positive and margin negative disease. No improvements in LR, DR, or OS were seen in margin positive patients with either ACT or ACRT. Conclusions: This is the first analysis demonstrating differences in recurrence patterns in PDAC patients based on type of adjuvant therapy. Adjuvant chemotherapy provided an OS advantage likely related to its effect on reducing both LR and DR. Adjuvant chemoradiation therapy appears to decrease LR, but not DR, and therefore has less impact on OS. Future investigations and treatment protocols should consider additional ACT rather than ACRT in the treatment of PDAC.

Original languageEnglish (US)
JournalJournal of the American College of Surgeons
DOIs
StateAccepted/In press - Dec 14 2015

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Pancreatic Neoplasms
Recurrence
Adjuvant Chemotherapy
Therapeutics
Survival
Adenocarcinoma
gemcitabine
Multivariate Analysis
Clinical Protocols
Fluorouracil
Multicenter Studies

ASJC Scopus subject areas

  • Surgery

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Adjuvant Therapy in Pancreas Cancer : Does It Influence Patterns of Recurrence? / Parikh, Alexander A.; Maiga, Amelia; Bentrem, David; Squires, Malcolm H.; Kooby, David A.; Maithel, Shishir K.; Weber, Sharon M.; Cho, Clifford S.; Katz, Matthew; Martin, Robert C.; Scoggins, Charles R.; Sutton, Jeff; Ahmad, Syed A.; Abbott, Daniel E.; Carr, Jacquelyn; Kim, Hong Jin; Yakoub, Danny; Idrees, Kamran; Merchant, Nipun.

In: Journal of the American College of Surgeons, 14.12.2015.

Research output: Contribution to journalArticle

Parikh, AA, Maiga, A, Bentrem, D, Squires, MH, Kooby, DA, Maithel, SK, Weber, SM, Cho, CS, Katz, M, Martin, RC, Scoggins, CR, Sutton, J, Ahmad, SA, Abbott, DE, Carr, J, Kim, HJ, Yakoub, D, Idrees, K & Merchant, N 2015, 'Adjuvant Therapy in Pancreas Cancer: Does It Influence Patterns of Recurrence?', Journal of the American College of Surgeons. https://doi.org/10.1016/j.jamcollsurg.2015.12.031
Parikh, Alexander A. ; Maiga, Amelia ; Bentrem, David ; Squires, Malcolm H. ; Kooby, David A. ; Maithel, Shishir K. ; Weber, Sharon M. ; Cho, Clifford S. ; Katz, Matthew ; Martin, Robert C. ; Scoggins, Charles R. ; Sutton, Jeff ; Ahmad, Syed A. ; Abbott, Daniel E. ; Carr, Jacquelyn ; Kim, Hong Jin ; Yakoub, Danny ; Idrees, Kamran ; Merchant, Nipun. / Adjuvant Therapy in Pancreas Cancer : Does It Influence Patterns of Recurrence?. In: Journal of the American College of Surgeons. 2015.
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title = "Adjuvant Therapy in Pancreas Cancer: Does It Influence Patterns of Recurrence?",
abstract = "Background: Level 1 data demonstrate that adjuvant chemotherapy (ACT) improves survival after surgical resection of pancreatic ductal adenocarcinoma (PDAC), (adjuvant gemcitabine, CONKO-001 study; adjuvant 5-FU, ESPAC3 study). The role of adjuvant chemoradiation therapy (ACRT) remains controversial. What is less clear is whether adjuvant therapy influences patterns of recurrence. The purpose of this study was to perform the first multicenter study analyzing patterns of recurrence after adjuvant therapy for PDAC. Study Design: Patients undergoing resection for PDAC from 8 medical centers over a 10-year period were analyzed. Demographics, tumor characteristics, operative treatment, type of adjuvant therapy, recurrence pattern, and survival were reviewed. Using Cox-proportional hazards multivariate (MV) regression, the impact of ACT and ACRT on overall survival (OS), local recurrence (LR), and distant recurrence (DR) was investigated. Results: There were 1,130 patients who were divided into those having surgery alone (n = 392), ACT (n = 291), or ACRT (n = 447). Median follow-up was 18 months. Compared with patients undergoing surgery alone, ACT, but not ACRT, demonstrated a significant OS advantage on MV analysis. Patients receiving ACT had significantly fewer recurrences (LR and DR); those receiving ACRT had significantly less LR but not DR. On subset MV analysis, ACT and ACRT resulted in less LR in patients with lymph node (LN) positive and margin negative disease. No improvements in LR, DR, or OS were seen in margin positive patients with either ACT or ACRT. Conclusions: This is the first analysis demonstrating differences in recurrence patterns in PDAC patients based on type of adjuvant therapy. Adjuvant chemotherapy provided an OS advantage likely related to its effect on reducing both LR and DR. Adjuvant chemoradiation therapy appears to decrease LR, but not DR, and therefore has less impact on OS. Future investigations and treatment protocols should consider additional ACT rather than ACRT in the treatment of PDAC.",
author = "Parikh, {Alexander A.} and Amelia Maiga and David Bentrem and Squires, {Malcolm H.} and Kooby, {David A.} and Maithel, {Shishir K.} and Weber, {Sharon M.} and Cho, {Clifford S.} and Matthew Katz and Martin, {Robert C.} and Scoggins, {Charles R.} and Jeff Sutton and Ahmad, {Syed A.} and Abbott, {Daniel E.} and Jacquelyn Carr and Kim, {Hong Jin} and Danny Yakoub and Kamran Idrees and Nipun Merchant",
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T1 - Adjuvant Therapy in Pancreas Cancer

T2 - Does It Influence Patterns of Recurrence?

AU - Parikh, Alexander A.

AU - Maiga, Amelia

AU - Bentrem, David

AU - Squires, Malcolm H.

AU - Kooby, David A.

AU - Maithel, Shishir K.

AU - Weber, Sharon M.

AU - Cho, Clifford S.

AU - Katz, Matthew

AU - Martin, Robert C.

AU - Scoggins, Charles R.

AU - Sutton, Jeff

AU - Ahmad, Syed A.

AU - Abbott, Daniel E.

AU - Carr, Jacquelyn

AU - Kim, Hong Jin

AU - Yakoub, Danny

AU - Idrees, Kamran

AU - Merchant, Nipun

PY - 2015/12/14

Y1 - 2015/12/14

N2 - Background: Level 1 data demonstrate that adjuvant chemotherapy (ACT) improves survival after surgical resection of pancreatic ductal adenocarcinoma (PDAC), (adjuvant gemcitabine, CONKO-001 study; adjuvant 5-FU, ESPAC3 study). The role of adjuvant chemoradiation therapy (ACRT) remains controversial. What is less clear is whether adjuvant therapy influences patterns of recurrence. The purpose of this study was to perform the first multicenter study analyzing patterns of recurrence after adjuvant therapy for PDAC. Study Design: Patients undergoing resection for PDAC from 8 medical centers over a 10-year period were analyzed. Demographics, tumor characteristics, operative treatment, type of adjuvant therapy, recurrence pattern, and survival were reviewed. Using Cox-proportional hazards multivariate (MV) regression, the impact of ACT and ACRT on overall survival (OS), local recurrence (LR), and distant recurrence (DR) was investigated. Results: There were 1,130 patients who were divided into those having surgery alone (n = 392), ACT (n = 291), or ACRT (n = 447). Median follow-up was 18 months. Compared with patients undergoing surgery alone, ACT, but not ACRT, demonstrated a significant OS advantage on MV analysis. Patients receiving ACT had significantly fewer recurrences (LR and DR); those receiving ACRT had significantly less LR but not DR. On subset MV analysis, ACT and ACRT resulted in less LR in patients with lymph node (LN) positive and margin negative disease. No improvements in LR, DR, or OS were seen in margin positive patients with either ACT or ACRT. Conclusions: This is the first analysis demonstrating differences in recurrence patterns in PDAC patients based on type of adjuvant therapy. Adjuvant chemotherapy provided an OS advantage likely related to its effect on reducing both LR and DR. Adjuvant chemoradiation therapy appears to decrease LR, but not DR, and therefore has less impact on OS. Future investigations and treatment protocols should consider additional ACT rather than ACRT in the treatment of PDAC.

AB - Background: Level 1 data demonstrate that adjuvant chemotherapy (ACT) improves survival after surgical resection of pancreatic ductal adenocarcinoma (PDAC), (adjuvant gemcitabine, CONKO-001 study; adjuvant 5-FU, ESPAC3 study). The role of adjuvant chemoradiation therapy (ACRT) remains controversial. What is less clear is whether adjuvant therapy influences patterns of recurrence. The purpose of this study was to perform the first multicenter study analyzing patterns of recurrence after adjuvant therapy for PDAC. Study Design: Patients undergoing resection for PDAC from 8 medical centers over a 10-year period were analyzed. Demographics, tumor characteristics, operative treatment, type of adjuvant therapy, recurrence pattern, and survival were reviewed. Using Cox-proportional hazards multivariate (MV) regression, the impact of ACT and ACRT on overall survival (OS), local recurrence (LR), and distant recurrence (DR) was investigated. Results: There were 1,130 patients who were divided into those having surgery alone (n = 392), ACT (n = 291), or ACRT (n = 447). Median follow-up was 18 months. Compared with patients undergoing surgery alone, ACT, but not ACRT, demonstrated a significant OS advantage on MV analysis. Patients receiving ACT had significantly fewer recurrences (LR and DR); those receiving ACRT had significantly less LR but not DR. On subset MV analysis, ACT and ACRT resulted in less LR in patients with lymph node (LN) positive and margin negative disease. No improvements in LR, DR, or OS were seen in margin positive patients with either ACT or ACRT. Conclusions: This is the first analysis demonstrating differences in recurrence patterns in PDAC patients based on type of adjuvant therapy. Adjuvant chemotherapy provided an OS advantage likely related to its effect on reducing both LR and DR. Adjuvant chemoradiation therapy appears to decrease LR, but not DR, and therefore has less impact on OS. Future investigations and treatment protocols should consider additional ACT rather than ACRT in the treatment of PDAC.

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