A novel 2-2 5-5 model for stratifying liver metastasis burden in patients with pancreatic cancer.

711 Background: In metastatic pancreatic cancer (MPC), hepatic metastasis is uniformly counted as just ‘one organ metastasis’ regardless of its metastatic tumor burden. This study aims to develop a novel stratification system for liver metastasis based on tumor burden, and to evaluate its prognostic significance in MPC patients. Methods: Patients with MPC treated at Seoul National University Bundang Hospital from 2011 to 2021 were included as the training cohort. Patients with liver-only metastasis were selected for analysis. Liver metastasis burden was categorized by the number and maximum diameter of metastases as measured from diagnostic CT images. Optimal cutoffs for metastasis number and size were determined using Cox proportional hazards regression, adjusted for chemotherapy regimen. An independent cohort from Seoul St. Mary’s Hospital and Hallym University Sacred Heart Hospital served as the validation group. The ‘H category classification’ suggested by the Japanese Society for Cancer of the Colon and Rectum (JSCCR) was also referenced. Results: A total of 1,257 patients were included, with 1,084 in the training cohort and 173 in the validation cohort. In the training cohort, data from 311 patients with liver-only metastasis were analyzed to derive the Two-two five-five (‘2-2 5-5’) criteria, classifying metastasis into Oligo-metastasis (≤2 metastases and ≤2 cm), Meso-metastasis (non-oligo and non-mega), and Mega-metastasis (≥5 metastases or ≥5 cm). Median overall survival (OS) significantly differed between the groups: Oligo (11.4 months), Meso (9.2 months, HR 1.66, 95% CI 1.14–2.43), Mega (5.6 months, HR 2.63, 95% CI 1.94–3.58) in the training cohort; Oligo (5.8 months) vs Mega (1.81 months, HR 1.94, 95% CI 1.16–3.22) in the validation cohort. Conclusions: This 2-2 5-5 model effectively stratifies MPC patients with hepatic metastasis into three prognostic groups, demonstrating significant survival differences in both training and validation cohorts. This could rationalize the independent therapeutic strategies by extent of hepatic metastasis. Demographic characteristics of patients classified according to “two-two five-five” criteria. Oligo-metastasis(n = 88) Meso-metastasis(n = 59) Mega-metastasis(n = 164) Total(n = 311) P-value* Age, median (range) 66.0 (33.2-91.0) 67.1(37.2-86.9) 68.7 (40.1-94.6) 67.9 (33.2-94.6) 0.587 Male, n (%) 43 (48) 36 (61) 91 (55) 170 (54) 0.330 Tumor location(Head), n(%) 47 (53) 27 (45) 60 (36) 134 (43) <0.05 Number of liver metastasis, median (range) 1 (1-2) 3 (1-4) 12 (2-14) 5 (1-14) <0.05 Maximal size of liver metastasis, cm (IQR)Average size of liver metastasis, cm (IQR) 10.6 (8.1-13.1)10.3 (8.0-12.1) 15.9 (10.1-24.2)13.5 (7.8-19.1) 21.6 (16.8-33.7)13.2 (10.5-19.2) 17.2 (10.9-25.2)11.9 (9.2-17.1) <0.05<0.05 CA19-9 (U/mL) 462 (103-1,334) 560 (89-1,480) 1,170 (100-9,500) 745 (100-3,700) <0.05