Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: a retrospective cohort study

Author(s): Ning Pu , MD, PhD ^a ^, ^b ^, ^c ^, , Wenchuan Wu , MD, PhD ^a ^, ^b ^, ^c , Siyao Liu , MD ^a ^, ^c , Yuqi Xie , MD ^a ^, ^b , Hanlin Yin , MD ^a ^, ^c , Qiangda Chen , MD ^a ^, ^c , Taochen He , MD ^a ^, ^c , Zhihang Xu , MD ^a ^, ^c , Wenquan Wang , MD, PhD ^a ^, ^b ^, ^c , Jun Yu , MD, PhD ^d , Liang Liu , MD, PhD ^a ^, ^b ^, ^c ^, , Wenhui Lou , MD, PhD ^a ^, ^b ^, ^c ^,

Publication date (Electronic): 6 July 2023

Journal: International Journal of Surgery (London, England)

Publisher: Lippincott Williams & Wilkins

Keywords: adjuvant chemotherapy, neoadjuvant chemotherapy, pancreatic ductal adenocarcinoma, prognosis

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Abstract

Background:

Patients with pancreatic ductal adenocarcinoma (PDAC) are increasingly receiving systemic neoadjuvant chemotherapy (NAC), particularly those with borderline resectable and locally advanced disease. However, the specific role of additional adjuvant chemotherapy (AC) in these patients is unknown. The objective of this study is to further assess the clinical benefit and impact of systemic AC in patients with resected PDAC after NAC.

Methods:

Data on PDAC patients with or without AC following systemic NAC and surgical resection were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2006 and 2019. A matched cohort was created using propensity score matching (PSM), and baseline characteristics were balanced to reduce bias. Overall survival (OS) and cancer-specific survival (CSS) were calculated using matching cohorts.

Results:

The study enrolled a total of 1589 patients, with 623 (39.2%) in the AC group and 966 (51.8%) in the non-AC group [mean age, 64.0 (9.9) years; 766 (48.2%) were females and 823 (51.8%) were males]. All patients received NAC, and among the crude population, 582 (36.6%) received neoadjuvant radiotherapy, while 168 (10.6%) received adjuvant radiotherapy. Following the 1:1 PSM, 597 patients from each group were evaluated further. The AC and non-AC groups had significantly different median OS (30.0 vs. 25.0 months, P=0.002) and CSS (33.0 vs. 27.0 months, P=0.004). After multivariate Cox regression analysis, systemic AC was independently associated with improved survival ( P=0.003, HR=0.782; 95% CI, 0.667–0.917 for OS; P=0.004, HR=0.784; 95% CI, 0.663–0.926 for CSS), and age, tumor grade, and AJCC N staging were also independent predictors of survival. Only patients younger than 65 years old and those with a pathological N1 category showed a significant association between systemic AC and improved survival in the subgroup analysis adjusted for these covariates.

Conclusion:

Systemic AC provides a significant survival benefit in patients with resected PDAC following NAC compared to non-AC patients. Our study discovered that younger patients, patients with aggressive tumors and potentially well response to NAC might benefit from AC to achieve prolonged survival after curative tumor resection.

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Most cited references 32

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Cancer statistics, 2023

Rebecca L Siegel, Kimberly D Miller, Nikita Sandeep Wagle … (2023)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries and mortality data collected by the National Center for Health Statistics. In 2023, 1,958,310 new cancer cases and 609,820 cancer deaths are projected to occur in the United States. Cancer incidence increased for prostate cancer by 3% annually from 2014 through 2019 after two decades of decline, translating to an additional 99,000 new cases; otherwise, however, incidence trends were more favorable in men compared to women. For example, lung cancer in women decreased at one half the pace of men (1.1% vs. 2.6% annually) from 2015 through 2019, and breast and uterine corpus cancers continued to increase, as did liver cancer and melanoma, both of which stabilized in men aged 50 years and older and declined in younger men. However, a 65% drop in cervical cancer incidence during 2012 through 2019 among women in their early 20s, the first cohort to receive the human papillomavirus vaccine, foreshadows steep reductions in the burden of human papillomavirus-associated cancers, the majority of which occur in women. Despite the pandemic, and in contrast with other leading causes of death, the cancer death rate continued to decline from 2019 to 2020 (by 1.5%), contributing to a 33% overall reduction since 1991 and an estimated 3.8 million deaths averted. This progress increasingly reflects advances in treatment, which are particularly evident in the rapid declines in mortality (approximately 2% annually during 2016 through 2020) for leukemia, melanoma, and kidney cancer, despite stable/increasing incidence, and accelerated declines for lung cancer. In summary, although cancer mortality rates continue to decline, future progress may be attenuated by rising incidence for breast, prostate, and uterine corpus cancers, which also happen to have the largest racial disparities in mortality.

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Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States.

Lola Rahib, Benjamin D Smith, Rhonda Aizenberg … (2014)

Cancer incidence and deaths in the United States were projected for the most common cancer types for the years 2020 and 2030 based on changing demographics and the average annual percentage changes in incidence and death rates. Breast, prostate, and lung cancers will remain the top cancer diagnoses throughout this time, but thyroid cancer will replace colorectal cancer as the fourth leading cancer diagnosis by 2030, and melanoma and uterine cancer will become the fifth and sixth most common cancers, respectively. Lung cancer is projected to remain the top cancer killer throughout this time period. However, pancreas and liver cancers are projected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related death by 2030, respectively. Advances in screening, prevention, and treatment can change cancer incidence and/or death rates, but it will require a concerted effort by the research and healthcare communities now to effect a substantial change for the future. ©2014 American Association for Cancer Research.

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FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.

Thierry Conroy, Françoise Desseigne, Marc Ychou … (2011)

Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer. We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival. The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001). As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.).

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Author and article information

Contributors

Ning Pu

Wenchuan Wu

Siyao Liu

Yuqi Xie

Hanlin Yin

Qiangda Chen

Taochen He

Zhihang Xu

Wenquan Wang

Jun Yu

Liang Liu

Wenhui Lou

Journal

Journal ID (nlm-ta): Int J Surg

Journal ID (iso-abbrev): Int J Surg

Journal ID (publisher-id): JS9

Title: International Journal of Surgery (London, England)

Publisher: Lippincott Williams & Wilkins (Hagerstown, MD )

ISSN (Print): 1743-9191

ISSN (Electronic): 1743-9159

Publication date Collection: October 2023

Publication date (Electronic): 6 July 2023

Volume: 109

Issue: 10

Pages: 3137-3146

Affiliations

[a ]Department of Pancreatic Surgery

[b ]Cancer Center

[c ]Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

[d ]Departments of Medicine and Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Author notes

[* ]Corresponding author. Address: Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, People’s Republic of China. Tel.: +86 1 391 743 1681. E-mail: npu15@ 123456fudan.edu.cn (N. Pu), and Tel.: +021 640 419 901 0554. E-mail: lou.wenhui@zs-hospital.sh.cn (W. Lou), and Tel.: +021 640 419 901 3589. E-mail: liu.liang@zs-hospital.sh.cn (L. Liu).

Article

Publisher ID: IJS-D-23-00866 Accession ID: 00029

DOI: 10.1097/JS9.0000000000000589

PMC ID: 10583928

PubMed ID: 37418574

SO-VID: 158db849-9c21-4049-b322-ed8d68084705

License:

This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/

History

Date received : 11 May 2023

Date accepted : 26 June 2023

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ScienceOpen disciplines: Surgery

Keywords: adjuvant chemotherapy,neoadjuvant chemotherapy,pancreatic ductal adenocarcinoma,prognosis

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ScienceOpen disciplines: Surgery

Keywords: adjuvant chemotherapy, neoadjuvant chemotherapy, pancreatic ductal adenocarcinoma, prognosis

Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: a retrospective cohort study

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Abstract

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Karger: Oncology

Most cited references 32

Cancer statistics, 2023

Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States.

FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.

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