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Adaptive Dynamic Therapy and Survivorship for Operable Pancreatic Cancer
IMPORTANCE: Neoadjuvant therapy is increasingly used in localized pancreatic carcinoma, and survival is correlated with carbohydrate antigen 19-9 (CA19-9) levels and histopathologic response following neoadjuvant therapy. With several regimens now available, the choice of chemotherapy could be best...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Medical Association
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227002/ https://www.ncbi.nlm.nih.gov/pubmed/35737385 http://dx.doi.org/10.1001/jamanetworkopen.2022.18355 |
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author | AlMasri, Samer Zenati, Mazen Hammad, Abdulrahman Nassour, Ibrahim Liu, Hao Hogg, Melissa E. Zeh, Herbert J. Boone, Brian Bahary, Nathan Singhi, Aatur D. Lee, Kenneth K. Paniccia, Alessandro Zureikat, Amer H. |
author_facet | AlMasri, Samer Zenati, Mazen Hammad, Abdulrahman Nassour, Ibrahim Liu, Hao Hogg, Melissa E. Zeh, Herbert J. Boone, Brian Bahary, Nathan Singhi, Aatur D. Lee, Kenneth K. Paniccia, Alessandro Zureikat, Amer H. |
author_sort | AlMasri, Samer |
collection | PubMed |
description | IMPORTANCE: Neoadjuvant therapy is increasingly used in localized pancreatic carcinoma, and survival is correlated with carbohydrate antigen 19-9 (CA19-9) levels and histopathologic response following neoadjuvant therapy. With several regimens now available, the choice of chemotherapy could be best dictated by response to neoadjuvant therapy (as measured by CA19-9 levels and/or pathologic response), a strategy defined herein as adaptive dynamic therapy. OBJECTIVE: To evaluate the association of adaptive dynamic therapy with oncologic outcomes in patients with surgically resected pancreatic cancer. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients with localized pancreatic cancer who were treated with either gemcitabine/nab-paclitaxel or fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) preoperatively between 2010 and 2019 at a high-volume tertiary care academic center. Participants were identified from a prospectively maintained database and had a median follow-up of 49 months. Data were analyzed from October 17 to November 24, 2020. EXPOSURES: The adaptive dynamic therapy group included 219 patients who remained on or switched to an alternative regimen as dictated by CA19-9 response and for whom the adjuvant regimen was selected based on CA19-9 and/or pathologic response. The nonadaptive dynamic therapy group included 103 patients who had their chemotherapeutic regimen selected independent of CA19-9 and/or tumoral response. MAIN OUTCOMES AND MEASURES: Prognostic implications of dynamic perioperative therapy assessed through Kaplan-Meier analysis, Cox regression, and inverse probability weighted estimators. RESULTS: A total of 322 consecutive patients (mean [SD] age, 65.1 [9] years; 162 [50%] women) were identified. The adaptive dynamic therapy group, compared with the nonadaptive dynamic therapy group, had a more pronounced median (IQR) decrease in CA19-9 levels (−80% [−92% to −56%] vs −45% [−81% to −13%]; P < .001), higher incidence of complete or near-complete tumoral response (25 [12%] vs 2 [2%]; P = .007), and lower median (IQR) number of lymph node metastasis (1 [0 to 4] vs 2 [0 to 4]; P = .046). Overall survival was significantly improved in the dynamic group compared with the nondynamic group (38.7 months [95% CI, 34.0 to 46.7 months] vs 26.5 months [95% CI, 23.5 to 32.9 months]; P = .03), and on adjusted analysis, dynamic therapy was independently associated with improved survival (hazard ratio, 0.73; 95% CI, 0.53 to 0.99; P = .04). On inverse probability weighted analysis of 320 matched patients, the average treatment effect of dynamic therapy was to increase overall survival by 11.1 months (95% CI, 1.5 to 20.7 months; P = .02). CONCLUSIONS AND RELEVANCE: In this cohort study that sought to evaluate the role of adaptive dynamic therapy in localized pancreatic cancer, selecting a chemotherapeutic regimen based on response to preoperative therapy was associated with improved survival. These findings support an individualized and in vivo assessment of response to perioperative therapy in pancreatic cancer. |
format | Online Article Text |
id | pubmed-9227002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Medical Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-92270022022-07-08 Adaptive Dynamic Therapy and Survivorship for Operable Pancreatic Cancer AlMasri, Samer Zenati, Mazen Hammad, Abdulrahman Nassour, Ibrahim Liu, Hao Hogg, Melissa E. Zeh, Herbert J. Boone, Brian Bahary, Nathan Singhi, Aatur D. Lee, Kenneth K. Paniccia, Alessandro Zureikat, Amer H. JAMA Netw Open Original Investigation IMPORTANCE: Neoadjuvant therapy is increasingly used in localized pancreatic carcinoma, and survival is correlated with carbohydrate antigen 19-9 (CA19-9) levels and histopathologic response following neoadjuvant therapy. With several regimens now available, the choice of chemotherapy could be best dictated by response to neoadjuvant therapy (as measured by CA19-9 levels and/or pathologic response), a strategy defined herein as adaptive dynamic therapy. OBJECTIVE: To evaluate the association of adaptive dynamic therapy with oncologic outcomes in patients with surgically resected pancreatic cancer. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients with localized pancreatic cancer who were treated with either gemcitabine/nab-paclitaxel or fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) preoperatively between 2010 and 2019 at a high-volume tertiary care academic center. Participants were identified from a prospectively maintained database and had a median follow-up of 49 months. Data were analyzed from October 17 to November 24, 2020. EXPOSURES: The adaptive dynamic therapy group included 219 patients who remained on or switched to an alternative regimen as dictated by CA19-9 response and for whom the adjuvant regimen was selected based on CA19-9 and/or pathologic response. The nonadaptive dynamic therapy group included 103 patients who had their chemotherapeutic regimen selected independent of CA19-9 and/or tumoral response. MAIN OUTCOMES AND MEASURES: Prognostic implications of dynamic perioperative therapy assessed through Kaplan-Meier analysis, Cox regression, and inverse probability weighted estimators. RESULTS: A total of 322 consecutive patients (mean [SD] age, 65.1 [9] years; 162 [50%] women) were identified. The adaptive dynamic therapy group, compared with the nonadaptive dynamic therapy group, had a more pronounced median (IQR) decrease in CA19-9 levels (−80% [−92% to −56%] vs −45% [−81% to −13%]; P < .001), higher incidence of complete or near-complete tumoral response (25 [12%] vs 2 [2%]; P = .007), and lower median (IQR) number of lymph node metastasis (1 [0 to 4] vs 2 [0 to 4]; P = .046). Overall survival was significantly improved in the dynamic group compared with the nondynamic group (38.7 months [95% CI, 34.0 to 46.7 months] vs 26.5 months [95% CI, 23.5 to 32.9 months]; P = .03), and on adjusted analysis, dynamic therapy was independently associated with improved survival (hazard ratio, 0.73; 95% CI, 0.53 to 0.99; P = .04). On inverse probability weighted analysis of 320 matched patients, the average treatment effect of dynamic therapy was to increase overall survival by 11.1 months (95% CI, 1.5 to 20.7 months; P = .02). CONCLUSIONS AND RELEVANCE: In this cohort study that sought to evaluate the role of adaptive dynamic therapy in localized pancreatic cancer, selecting a chemotherapeutic regimen based on response to preoperative therapy was associated with improved survival. These findings support an individualized and in vivo assessment of response to perioperative therapy in pancreatic cancer. American Medical Association 2022-06-23 /pmc/articles/PMC9227002/ /pubmed/35737385 http://dx.doi.org/10.1001/jamanetworkopen.2022.18355 Text en Copyright 2022 AlMasri S et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License. |
spellingShingle | Original Investigation AlMasri, Samer Zenati, Mazen Hammad, Abdulrahman Nassour, Ibrahim Liu, Hao Hogg, Melissa E. Zeh, Herbert J. Boone, Brian Bahary, Nathan Singhi, Aatur D. Lee, Kenneth K. Paniccia, Alessandro Zureikat, Amer H. Adaptive Dynamic Therapy and Survivorship for Operable Pancreatic Cancer |
title | Adaptive Dynamic Therapy and Survivorship for Operable Pancreatic Cancer |
title_full | Adaptive Dynamic Therapy and Survivorship for Operable Pancreatic Cancer |
title_fullStr | Adaptive Dynamic Therapy and Survivorship for Operable Pancreatic Cancer |
title_full_unstemmed | Adaptive Dynamic Therapy and Survivorship for Operable Pancreatic Cancer |
title_short | Adaptive Dynamic Therapy and Survivorship for Operable Pancreatic Cancer |
title_sort | adaptive dynamic therapy and survivorship for operable pancreatic cancer |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227002/ https://www.ncbi.nlm.nih.gov/pubmed/35737385 http://dx.doi.org/10.1001/jamanetworkopen.2022.18355 |
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