Annals of surgery · 2025
Carbohydrate Antigen 19-9 Delta Function for Survival Prediction in Borderline Pancreatic Cancer. A PANC-PALS Consortium International Multicenter Derivation and Validation Study.
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Garnier Jonathan, Marchetti Alessio, Campbell Brady, Andel Paul C M, Alfano Marie-Sophie, Hidalgo Salinas Camila, Traversari Eddy, Habib Joseph R, Lionetto Gabriella, Palen Anaïs, Ewald Jacques, Lafaro Kelly, Hewitt Daniel Brock, Burkhart Richard A, Paiella Salvatore, Sacks Greg D, Malleo Giuseppe, Wolfgang Christopher L, Salvia Roberto, He Jin, Turrini Olivier, Javed Ammar A
Аннотация
OBJECTIVE: To establish a novel method for evaluating carbohydrate antigen 19-9 (CA19-9) during neoadjuvant therapy (NAT) and assess its role in predicting overall (OS) and disease-free (DFS) survival in borderline resectable pancreatic adenocarcinoma (BR-PC).
SUMMARY BACKGROUND DATA: Static CA19-9 values or percentage changes often fail to capture therapeutic responses in patients with BR-PC undergoing NAT. Improved evaluation methods are essential for guiding the treatment.
METHODS: This was a retrospective multicenter study of patients who underwent BR-PC surgery. Two parameters were developed: slope coefficient (SC, change in CA19-9 divided by therapy duration) and mean δf (mδf, calculated as the sum of CA19-9 values over therapy intervals divided by the number of 15-day periods). The main objective was to correlate mδf with OS thresholds derived using a maximally selected log-rank statistic and validated in independent cohorts.
RESULTS: Overall, 991 patients (median age 65 [59-71] years; 49% male) were included. The thresholds for mδf were defined as 206 U.mL -1 . month -1 (negative SC) and 115 U.mL -1 . month -1 (positive SC). Patients with mδf below these thresholds had significantly better prognoses, with hazard ratios (HR) for OS (95% CI) of 0.6 (0.4-0.8; P <0.01) and 0.4 (0.2-0.9; P =0.04) for negative and positive SC, respectively. Both thresholds were validated for mOS, with 29 vs 22 months ( P =0.015) and 32 vs 16 months ( P =0.0034) for negative and positive SC, respectively. Similarly, the mDFS was 13 vs 10 months ( P =0.011) and 12 vs 7 months ( P =0.0018), respectively.
CONCLUSION: This CA19-9 evaluation approach accurately predicts survival outcomes, offering a valuable tool for optimizing treatment strategies. An mδf calculator is available at https://www.pancpals.com/tools .
SUMMARY BACKGROUND DATA: Static CA19-9 values or percentage changes often fail to capture therapeutic responses in patients with BR-PC undergoing NAT. Improved evaluation methods are essential for guiding the treatment.
METHODS: This was a retrospective multicenter study of patients who underwent BR-PC surgery. Two parameters were developed: slope coefficient (SC, change in CA19-9 divided by therapy duration) and mean δf (mδf, calculated as the sum of CA19-9 values over therapy intervals divided by the number of 15-day periods). The main objective was to correlate mδf with OS thresholds derived using a maximally selected log-rank statistic and validated in independent cohorts.
RESULTS: Overall, 991 patients (median age 65 [59-71] years; 49% male) were included. The thresholds for mδf were defined as 206 U.mL -1 . month -1 (negative SC) and 115 U.mL -1 . month -1 (positive SC). Patients with mδf below these thresholds had significantly better prognoses, with hazard ratios (HR) for OS (95% CI) of 0.6 (0.4-0.8; P <0.01) and 0.4 (0.2-0.9; P =0.04) for negative and positive SC, respectively. Both thresholds were validated for mOS, with 29 vs 22 months ( P =0.015) and 32 vs 16 months ( P =0.0034) for negative and positive SC, respectively. Similarly, the mDFS was 13 vs 10 months ( P =0.011) and 12 vs 7 months ( P =0.0018), respectively.
CONCLUSION: This CA19-9 evaluation approach accurately predicts survival outcomes, offering a valuable tool for optimizing treatment strategies. An mδf calculator is available at https://www.pancpals.com/tools .