Impact and optimal timing of local therapy addition in borderline resectable or locally advanced pancreatic cancer after FOLFIRINOX chemotherapy

Kangpyo Kim; Hee Chul Park; Jeong Il Yu; Joon Oh Park; Jung Yong Hong; Kyu Taek Lee; Kwang Hyuck Lee; Jong Kyun Lee; Joo Kyung Park; Jin Seok Heo; Sang Hyun Shin; Ji Hye Min; Kyunga Kim; In Woong Han

doi:10.1016/j.ctro.2024.100732

Impact and optimal timing of local therapy addition in borderline resectable or locally advanced pancreatic cancer after FOLFIRINOX chemotherapy

Clin Transl Radiat Oncol. 2024 Jan 24:45:100732. doi: 10.1016/j.ctro.2024.100732. eCollection 2024 Mar.

Authors

Kangpyo Kim¹, Hee Chul Park¹, Jeong Il Yu¹, Joon Oh Park², Jung Yong Hong², Kyu Taek Lee³, Kwang Hyuck Lee³, Jong Kyun Lee³, Joo Kyung Park³, Jin Seok Heo⁴, Sang Hyun Shin⁴, Ji Hye Min⁵, Kyunga Kim^{6

7

8}, In Woong Han⁴

Affiliations

¹ Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, 06351 Seoul, South Korea.
² Divisions of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
³ Divisions of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁴ Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, 06351 Seoul, South Korea.
⁵ Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁶ Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, South Korea.
⁷ Department of Digital Health, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea.
⁸ Department of Data Convergence & Future Medicine, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Abstract

Background: To evaluate the efficacy and optimal timing of local treatment in patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX.

Method: Between 2015 and 2020, 258 patients with pancreatic ductal adenocarcinoma (PDAC) were analysed. Treatment outcomes were compared between systemic treatment group (ST) and multimodality treatment groups (MT) using Kaplan-Meier curves and log-rank test. The MT were stratified as follows: FOLFIRINOX + radiation therapy (RT) (MT1), FOLFIRINOX + surgical resection (MT2), and FOLFIRINOX + RT + surgical resection (MT3).

Results: With median follow-up period of 18 months, the 2-year overall survival (OS) for the ST was 22.0%, and it was significantly worse than MT (MT1, 46.3%; MT2, 65.7% and MT3; 90.2%; P < .001). The 2-year locoregional progression free survival (LRPFS) and overall PFS in ST were 10.7% and 7.0%, which were also significantly lower than those of MT (2-year LRPFS: MT1, 31.8%; MT2, 45.3%; MT3, 81.0%; 2-year overall PFS: MT1, 23.3%; MT2, 35.0%; MT3, 66.3%; P < .001). In time-varying multivariate Cox proportional hazard model, local treatment contributed to better treatment outcomes, with adjusted hazard ratios of 0.568 (95% confidence interval [CI], 0.398-0.811), 0.490 (95% CI, 0.331-0.726), and 0.656 (95% CI, 0.458-0.940) for OS, LRPFS, and overall PFS, respectively. The time window of 11-17 months after FOLFIRINOX appeared to demonstrate the maximal efficacy of local treatments in OS.

Conclusions: Adding local treatment in BR/LAPC patients treated with upfront FOLFIRINOX seemed to contribute in improved treatment outcomes, and it showed maximal efficacy in OS when applied 11-17 months after the initiation of FOLFIRINOX. We suggest that administration of sufficient period of upfront FOLFIRINOX may intensify the efficacy of local treatments, and well controlled prospective trials are expected.

Keywords: FOLFIRINOX; Multimodal treatments; Neoadjuvant treatment; Pancreatic ductal adenocarcinoma; Timing of local treatments.