Role of Adjuvant Multimodality Therapy after Curative-Intent Resection of Ampullary Carcinoma

Brett L. Ecker, Charles M. Vollmer, Stephen W. Behrman, Valentina Allegrini, John Aversa, Chad G. Ball, Courtney E. Barrows, Adam C. Berger, Martha N. Cagigas, John D. Christein, Elijah Dixon, William E. Fisher, Mollie Freedman-Weiss, Francisco Guzman-Pruneda, Robert H. Hollis, Michael House, Tara S. Kent, Stacy J. Kowalsky, Giuseppe Malleo, Ronald R. Salem & 6 others Roberto Salvia, Carl R. Schmidt, Thomas F. Seykora, Richard Zheng, Amer H. Zureikat, Paxton V. Dickson

Research output: Contribution to journalArticle

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Abstract

Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined. Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype. Design, Setting, and Participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates. Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy. Main Outcomes and Measures: Overall survival. Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P =.05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P =.24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P =.01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P =.53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P =.41). Conclusions and Relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined..

Original languageEnglish (US)
JournalJAMA Surgery
DOIs
StatePublished - Jan 1 2019

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gemcitabine
Carcinoma
Survival
Adenocarcinoma
Fluorouracil
Therapeutics
Propensity Score
Kaplan-Meier Estimate
Adjuvant Chemotherapy
Patient Selection
Neoplasms
Cohort Studies
Radiotherapy
Retrospective Studies
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Surgery

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Ecker, B. L., Vollmer, C. M., Behrman, S. W., Allegrini, V., Aversa, J., Ball, C. G., ... Dickson, P. V. (2019). Role of Adjuvant Multimodality Therapy after Curative-Intent Resection of Ampullary Carcinoma. JAMA Surgery. https://doi.org/10.1001/jamasurg.2019.1170

Role of Adjuvant Multimodality Therapy after Curative-Intent Resection of Ampullary Carcinoma. / Ecker, Brett L.; Vollmer, Charles M.; Behrman, Stephen W.; Allegrini, Valentina; Aversa, John; Ball, Chad G.; Barrows, Courtney E.; Berger, Adam C.; Cagigas, Martha N.; Christein, John D.; Dixon, Elijah; Fisher, William E.; Freedman-Weiss, Mollie; Guzman-Pruneda, Francisco; Hollis, Robert H.; House, Michael; Kent, Tara S.; Kowalsky, Stacy J.; Malleo, Giuseppe; Salem, Ronald R.; Salvia, Roberto; Schmidt, Carl R.; Seykora, Thomas F.; Zheng, Richard; Zureikat, Amer H.; Dickson, Paxton V.

In: JAMA Surgery, 01.01.2019.

Research output: Contribution to journalArticle

Ecker, BL, Vollmer, CM, Behrman, SW, Allegrini, V, Aversa, J, Ball, CG, Barrows, CE, Berger, AC, Cagigas, MN, Christein, JD, Dixon, E, Fisher, WE, Freedman-Weiss, M, Guzman-Pruneda, F, Hollis, RH, House, M, Kent, TS, Kowalsky, SJ, Malleo, G, Salem, RR, Salvia, R, Schmidt, CR, Seykora, TF, Zheng, R, Zureikat, AH & Dickson, PV 2019, 'Role of Adjuvant Multimodality Therapy after Curative-Intent Resection of Ampullary Carcinoma', JAMA Surgery. https://doi.org/10.1001/jamasurg.2019.1170
Ecker, Brett L. ; Vollmer, Charles M. ; Behrman, Stephen W. ; Allegrini, Valentina ; Aversa, John ; Ball, Chad G. ; Barrows, Courtney E. ; Berger, Adam C. ; Cagigas, Martha N. ; Christein, John D. ; Dixon, Elijah ; Fisher, William E. ; Freedman-Weiss, Mollie ; Guzman-Pruneda, Francisco ; Hollis, Robert H. ; House, Michael ; Kent, Tara S. ; Kowalsky, Stacy J. ; Malleo, Giuseppe ; Salem, Ronald R. ; Salvia, Roberto ; Schmidt, Carl R. ; Seykora, Thomas F. ; Zheng, Richard ; Zureikat, Amer H. ; Dickson, Paxton V. / Role of Adjuvant Multimodality Therapy after Curative-Intent Resection of Ampullary Carcinoma. In: JAMA Surgery. 2019.
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title = "Role of Adjuvant Multimodality Therapy after Curative-Intent Resection of Ampullary Carcinoma",
abstract = "Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined. Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype. Design, Setting, and Participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates. Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy. Main Outcomes and Measures: Overall survival. Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P =.05). Histologic subtype was not associated with AT administration (intestinal, 52.9{\%} [101 of 191]; and pancreatobiliary, 59.5{\%} [78 of 131]; P =.24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0{\%} [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9{\%} [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0{\%} [17 of 34]; gemcitabine, 44.1{\%} [15 of 34]; P =.01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95{\%} CI, 0.67-2.16; P =.53; pancreatobiliary: hazard ratio, 1.35; 95{\%} CI, 0.66-2.76; P =.41). Conclusions and Relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined..",
author = "Ecker, {Brett L.} and Vollmer, {Charles M.} and Behrman, {Stephen W.} and Valentina Allegrini and John Aversa and Ball, {Chad G.} and Barrows, {Courtney E.} and Berger, {Adam C.} and Cagigas, {Martha N.} and Christein, {John D.} and Elijah Dixon and Fisher, {William E.} and Mollie Freedman-Weiss and Francisco Guzman-Pruneda and Hollis, {Robert H.} and Michael House and Kent, {Tara S.} and Kowalsky, {Stacy J.} and Giuseppe Malleo and Salem, {Ronald R.} and Roberto Salvia and Schmidt, {Carl R.} and Seykora, {Thomas F.} and Richard Zheng and Zureikat, {Amer H.} and Dickson, {Paxton V.}",
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TY - JOUR

T1 - Role of Adjuvant Multimodality Therapy after Curative-Intent Resection of Ampullary Carcinoma

AU - Ecker, Brett L.

AU - Vollmer, Charles M.

AU - Behrman, Stephen W.

AU - Allegrini, Valentina

AU - Aversa, John

AU - Ball, Chad G.

AU - Barrows, Courtney E.

AU - Berger, Adam C.

AU - Cagigas, Martha N.

AU - Christein, John D.

AU - Dixon, Elijah

AU - Fisher, William E.

AU - Freedman-Weiss, Mollie

AU - Guzman-Pruneda, Francisco

AU - Hollis, Robert H.

AU - House, Michael

AU - Kent, Tara S.

AU - Kowalsky, Stacy J.

AU - Malleo, Giuseppe

AU - Salem, Ronald R.

AU - Salvia, Roberto

AU - Schmidt, Carl R.

AU - Seykora, Thomas F.

AU - Zheng, Richard

AU - Zureikat, Amer H.

AU - Dickson, Paxton V.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined. Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype. Design, Setting, and Participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates. Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy. Main Outcomes and Measures: Overall survival. Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P =.05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P =.24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P =.01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P =.53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P =.41). Conclusions and Relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined..

AB - Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined. Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype. Design, Setting, and Participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates. Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy. Main Outcomes and Measures: Overall survival. Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P =.05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P =.24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P =.01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P =.53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P =.41). Conclusions and Relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined..

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