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Multicenter Study
. 2025 May 1;281(5):852-860.
doi: 10.1097/SLA.0000000000006650. Epub 2025 Jan 31.

Validation of the PANAMA Score for Survival and Benefit of Adjuvant Therapy in Patients With Resected Pancreatic Cancer after Neoadjuvant FOLFIRINOX

Ingmar F Rompen  1   2   3 , Thomas F Stoop  2   3 , Stijn van Roessel  2   3 , Eran van Veldhuisen  2   3 , Quisette P Janssen  4 , Adnan Alseidi  5 , Alberto Balduzzi  6 , Gianpaolo Balzano  7 , Frederik Berrevoet  8 , Morgan Bonds  9 , Olivier R Busch  2 , Giovanni Butturini  10 , Ammar A Javed  2   3 , Marco Del Chiaro  11 , Kevin C Conlon  12 , Massimo Falconi  13 , Isabella Frigerio  10   14 , Giuseppe K Fusai  15 , Johan Gagnière  16 , Oonagh Griffin  17 , Thilo Hackert  18 , Ernesto Sparrelid  19 , Asif Halimi  19   20 , Knut J Labori  21 , Giuseppe Malleo  6 , Marco V Marino  22 , Michael B Mortensen  23 , Andrej Nikov  24 , Mickaël Lesurtel  25 , Tobias Keck  26 , Jörg Kleeff  27 , Rupaly Pandé  28 , Per Pfeiffer  29 , Daniel Pietrasz  30 , Keith J Roberts  28 , Antonio Sa Cunha  30 , Roberto Salvia  6 , Oliver Strobel  31 , Timo Tarvainen  32 , Hanneke W M van Laarhoven  3   33 , Bas Groot Koerkamp  4 , Martin Loos  1 , Christoph W Michalski  1 , Marc G Besselink  2   3 , Thomas Hank  1
Affiliations
Multicenter Study

Validation of the PANAMA Score for Survival and Benefit of Adjuvant Therapy in Patients With Resected Pancreatic Cancer after Neoadjuvant FOLFIRINOX

Ingmar F Rompen et al. Ann Surg. .

Abstract

Objective: To validate the prognostic value of the PAncreatic NeoAdjuvant MAssachusetts (PANAMA) score and to determine its predictive ability for survival benefit derived from adjuvant treatment in patients after resection of pancreatic ductal adenocarcinoma (PDAC) following neoadjuvant FOLFIRINOX.

Background: The PANAMA score was developed to guide prognostication in patients after neoadjuvant therapy and resection for PDAC. As this score focuses on the risk for residual disease after resection, it might also be able to select patients who benefit from adjuvant after neoadjuvant therapy.

Methods: This retrospective international multicenter study is endorsed by the European-African Hepato-Pancreato-Biliary Association. Patients with PDAC who underwent resection after neoadjuvant FOLFIRINOX were included. Mantel-Cox regression with interaction analysis was performed to assess the impact of adjuvant chemotherapy.

Results: Overall, 383 patients after resection of PDAC following neoadjuvant FOLFIRINOX were included of whom 187 (49%), 137 (36%), and 59 (15%) had a low-risk, intermediate-risk, and high-risk PANAMA-score, respectively. Discrimination in median overall survival (OS) was observed stratified by risk groups (48.5, 27.6, and 22.3 months, log-rank Plow-intermediate = 0.004, log-rank Pintermediate-high = 0.027). Adjuvant therapy was not associated with an OS difference in the low-risk group [hazard ratio (HR): 1.50, 95% CI: 0.92-2.50], whereas improved OS was observed in the intermediate (HR: 0.58, 95% CI: 0.34-0.97) and high-risk groups (HR: 0.47, 95% CI: 0.24-0.94; P interaction = 0.008).

Conclusions: The PANAMA 3-tier risk groups (low-risk, intermediate-risk, and high-risk, available through pancreascalculator.com) correspond with differential survival in patients with resected PDAC following neoadjuvant FOLFIRINOX. The risk groups also differentiate between survival benefits associated with adjuvant treatment, with only the intermediate- and high-risk groups associated with improved OS.

Keywords: FOLFIRINOX; adjuvant chemotherapy; neoadjuvant treatment; pancreatic neoplasm; prognostic score.

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Conflict of interest statement

M.D.C. has been awarded an industry grant (Haemonics, Inc.) to conduct a multicenter study to evaluate the prognostic implications of TEG in pancreatic caner. He is a co-principal investigator of a Boston Scientific sponsored international multicenter study on the use of intraoperative pancreatoscopy of patients with IPMN. I.F.R. received funding from the Swiss National Science Foundation. The remaining authors report no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Kaplan-Meier curves for OS (A) and time to recurrence (B) stratified by PANAMA risk groups. Survival curves stratified by PANAMA risk groups showed differences in OS and time to recurrence. Censored patients are indicated by crosses. P values for group comparisons are calculated by log-rank test.
FIGURE 2
FIGURE 2
Comparisons PANAMA and AJCC-TNM AUC over time. AUC (y-axis) in percentage are shown over time (years, x-axis) after 1:1000 bootstrapping. Comparisons were not significant with P values of 0.746, 0.957, 0.576, 0.221, and 0.387 for 1, 2, 3, 4, and 5-year survival, respectively.
FIGURE 3
FIGURE 3
Kaplan-Meier curve for OS stratified by PANAMA risk groups and receipt of adjuvant treatment. No receipt of adjuvant therapy is indicated by dotted lines, whereas continuous lines indicate subroups that received adjuvant treatment. Median OS for low-risk [no adjuvant: nr (95% CI: 58.9–nr) vs adjuvant 43.6 months (95% CI: 31.1–57.7), log-rank P = 0.152], intermediate risk [no adjuvant: 23.6 months (95% CI: 12.8–nr) vs adjuvant 36.5 months (95% CI: 26.4–nr), log-rank P = 0.008], and high-risk [no adjuvant: 12.5 months (95% CI: 10.8–nr) vs adjuvant 26.3 months (95% CI: 16.5–42.6), log-rank P = 0.038]. C-index: 0.62.
FIGURE 4
FIGURE 4
Treatment benefits derived from adjuvant chemotherapy. Subgroup analyses show different OS benefits associated with the receipt of adjuvant treatment. P interaction for differing treatment effects between subgroups: PANAMA score risk groups (P = 0.008), resection margin status (P = 0.030), pathologic tumor size (P = 0.013), lymph-node status (P = 0.003), and CA19-9 (P = 0.274).
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Comment in

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