The Path to Individualized Adjuvant Chemotherapy for All Four Types of Non-Pancreatic Periampullary Cancers: An International Multi-Method Cohort Study

Background and Study Aim

Although duodenal adenocarcinoma (DAC), intestinal type ampullary adenocarcinoma (AMPIT), pancreatobiliary type ampullary adenocarcinoma (AMPPB), and distal cholangiocarcinoma (DCCA) exhibit differing tumor behavior and characteristics, the impact of adjuvant chemotherapy (ACT) on these cancers and the optimal chemotherapy regimen have yet to be fully evaluated. Therefore, this study aims to assess the impact of individualized adjuvant chemotherapy on DAC, AMPIT, AMPPB, and DCCA.

The author team includes dozens of experts from 36 treatment centers. The paper was published in the 2024 edition of the British Journal of Cancer. The study retrospectively collected data from patients in 36 tertiary centers from 2010 to 2021.

Study Methods

Study Design

This study is an international multicenter retrospective cohort study, implemented with the assistance of the International Study Group on Non-Pancreatic Periampullary Cancer (ISGACA). Patient data was collected and analyzed according to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines and checklist.

Patient Selection

Inclusion criteria included patients with pathologically confirmed non-pancreatic periampullary cancer (AMPIT, AMPPB, DCCA, and DAC) who underwent curative resection (open or minimally invasive pancreaticoduodenectomy). Exclusion criteria included patients undergoing palliative surgery, post-operative pathology diagnoses unrelated to non-pancreatic periampullary adenocarcinoma, margin-positive (R2) patients, patients who received neoadjuvant chemotherapy, and patients lacking adjuvant chemotherapy information.

Data Collection and Definitions

Collected statistical data included age, gender, body mass index (BMI), American Society of Anesthesiologists (ASA) score, and adjuvant chemotherapy regimens used. Tumor types were classified according to the World Health Organization (WHO) guidelines.

Interventions and Outcomes

Firstly, propensity score matching (PSM) was used to compare patients who received or did not receive adjuvant chemotherapy. The primary outcome was overall survival (OS), and the secondary outcome was disease-free survival (DFS). Patients with each cancer type were divided into three different adjuvant chemotherapy regimen groups, and the OS and DFS of these groups were compared.

Study Results

Patient Characteristics

The total number of patients included in the study was 2866, comprising 330 DAC patients, 765 AMPIT patients, 819 AMPPB patients, and 952 DCCA patients. Among them, 1329 patients received ACT, and 1537 patients did not receive ACT. PSM resulted in more balanced baseline characteristics.

DAC

After propensity score matching, 91 DAC patients did not receive ACT, and 91 patients received ACT. Results showed no significant difference in OS (p=0.113) and DFS (p=0.357) between the two groups. No significant differences in OS (p>0.240) and DFS (p>0.314) were found among the different adjuvant chemotherapy regimen groups.

AMPIT

Among the 765 AMPIT patients, 194 received ACT, and 191 did not receive ACT. Results showed no significant differences in OS (p=0.445) and DFS (p=0.347) between the two groups. No significant differences in OS (p>0.226) and DFS (p>0.299) were found among the different ACT regimen groups.

AMPPB

Among the 819 AMPPB patients, 277 received ACT, and 271 did not receive ACT. Results showed a significant improvement in OS (p=0.004) in the ACT group but no significant difference in DFS (p=0.766). Differences in OS and DFS among the different ACT regimen groups did not reach statistical significance, indicating the need for further research.

DCCA

Among the 952 DCCA patients, 362 received ACT, and 355 did not receive ACT. The study found significant improvement in OS (p<0.001) and DFS (p=0.007) in the ACT group. Among the different ACT regimens, capecitabine monotherapy showed the best effect (p=0.004, p=0.001, and p=0.014).

Discussion

Overall, this study suggests that AMPPB and DCCA patients may benefit from ACT, particularly with capecitabine monotherapy showing the best survival benefit for DCCA patients. However, ACT did not significantly improve survival for DAC and AMPIT patients.

Although this study boasts significant international multicenter data, it still has limitations, such as slight variations in tumor classification and treatment standards across different centers and the reliance on local protocols for adjuvant chemotherapy regimens.

Conclusion

This study highlights the potential benefits of ACT for AMPPB and DCCA patients, particularly the significant OS and DFS benefits of capecitabine monotherapy for DCCA patients. The findings support further prospective studies on individualized adjuvant therapy for all four types of non-pancreatic periampullary cancers to identify the optimal treatment strategies.

Value and Significance

This large-scale international multicenter study not only provides new insights into individualized adjuvant chemotherapy for non-pancreatic periampullary cancers but also lays the groundwork for future clinical trials aiming to further optimize and standardize the treatment of these tumors, thereby improving patient prognosis.