Clinical Usefulness of Double Biomarkers 18F-Flurodeoxyglucose-Positron Emission Tomography and Carbohydrate Antigen 19-9 for Survival Prediction in Locally Advanced Pancreatic Cancer Patients Treated with Chemoradiation Therapy

Abstract

To investigate the clinical significance of 18F-Flurodeoxyglucose-positron emission tomography (FDG-PET) parameters and carbohydrate antigen 19-9 (CA 19-9) levels in stratifying prognostic groups in patients with locally advanced pancreatic cancer after concurrent chemoradiotherapy (CRT) From our institutional database, we selected 257 patients with locally advanced pancreatic cancer who underwent both pretreatment 18F-FDG PET and CA 19-9 test, and received concurrent CRT between January 2004 and December 2011. The maximum standardized uptake value (SUVmax) was calculated at regions of primary tumors from pre-CRT and post-CRT FDG-PETs. SUV parameters (pre- and post-CRT SUVmax), SUV decline rate (%), CA 19-9 levels (pre- and post-CRT CA 19-9), and CA 19-9 decline rate (%) were analyzed for comparing radiologic response and survival outcomes (progression-free survival (PFS), overall survival (OS)). Median OS and PFS were 14.6 months and 8.8 months from the date of first diagnosis, respectively, at a median follow-up time of 14.2 months (range, 2.3-133.8 months). Radiologic responses after CRT (complete or partial response) were firstly obtained in 17% of the patients (n=43). Of the 164 patients with recurrences after CRT, distant metastasis (DM) was the most common (n=141, 86%), followed by local recurrence (LR) (n=12, 7%), and LR+DM (n=11, 7%). Additional surgical resection, maintenance chemotherapy, post-CRT CA 19-9 <66, and CA 19-9 decline ratio ≥91.2% were independent predictors of favorable PFS (p=<0.001, <0.001, 0.001, and 0.003), and pre-CRT CA 19-9 <760, CA 19-9 decline ratio ≥91.2% were independent predictors of favorable OS (p=0.017, <0.001) in multivariate analysis. For the PET parameters, SUV decline ≥63% was the most significant prognostic factor (p=0.029 for PFS, 0.017 for OS). Patients with SUV decline ≥63% were included in the responder group more than in the non-responder group (12% vs. 2%, p=0.057). We also divided patients into 4 risk groups according to the number of positive favorable factors (SUV decline ratio ≥63%, pre-CRT CA 19-9 <760 (for OS groups) or post-CRT CA 19-9 <66 (for PFS groups), and CA 19-9 decline ratio ≥91.2%) (0: high-risk, 1: intermediate high-risk, 2: intermediate low-risk, 3: low risk). The low-risk group showed significantly favorable PFS than other groups (median 59.4 months, p=0.001, 0.014, and 0.005, respectively). The low-risk group also showed the most favorable OS than others (median 85.4 months, p=0.020, 0.043, and 0.109, respectively). In patients with locally advanced pancreatic cancer, the use of a combination of double biomarkers, SUVmax and CA 19-9, appears useful in predicting survival outcomes after CRT. In other words, three prognostic factors such as SUV decline ratio, pre or post-CRT CA 19-9, and CA 19-9 decline ratio seem to have substantial advantages over single-parameter by facilitating better treatment selection for locally advanced pancreatic tumors.