Imaging & Biomarker Correlates on Outcomes in a Phase II Trial of Neoadjuvant Gemcitabine/Nab-Paclitaxel and Hypofractionated Image-Guided Radiotherapy (HIGRT) in Potentially Resectable Pancreas Cancer

Abstract

Pancreas cancer is a leading cause of cancer-related death with high rates of local and distant failures. Despite ongoing research, the optimal management of potentially resectable pancreas cancer remains unknown. We evaluated associations of changes in tumor size and blood biomarkers on outcomes in a phase II trial of neoadjuvant gemcitabine/nab-paclitaxel and HIGRT in patients with potentially resectable pancreas cancer. Patients with newly diagnosed potentially resectable pancreas cancer were prospectively enrolled on this study. Patients received 2 cycles of neoadjuvant gemcitabine/nab-paclitaxel followed by HIGRT (5 Gy x 5). Patients were restaged following chemotherapy and after HIGRT. Patients were considered for surgery 3-6 weeks post-HIGRT. Potential associations between changes in tumor size, tumor markers (CEA, CA 19-9), and outcomes (R0 resection, PFS, OS) were assessed using t-tests, proportional hazards regression, and the log rank test. Log transformation was used in analyses of CEA and CA 19-9. 40 patients (9 resectable, 31 borderline resectable) were enrolled from 2015-2018. Median age was 67 (range 38-81). Median follow-up was 24 months. 35 patients completed neoadjuvant treatment and 24 underwent resection. Most patients who did not undergo surgery had developed metastases (n=13). Median baseline tumor dimensions were 2.7 cm (greater) and 2.3 cm (smaller). 34 patients’ (85%) baseline CA 19-9 was >40 U/mL (median 150). Tumor size in the greater dimension was correlated with higher CA 19-9 (r=0.38; p=0.02). At restaging, tumor size was increased, stable, and decreased in 3, 17, and 19 patients, respectively, following chemotherapy, and in 5, 23, and 7 patients following HIGRT. CA 19-9 was increased in 5 and decreased/stable in 33 patients following chemotherapy, and increased in 5 and decreased/stable in 29 patients following HIGRT. Change in tumor size was associated with a significant difference in OS (median 7.6, 24.4, and 24.3 mo for increased, stable, decreased; p=0.006) and a trend towards a difference in PFS (median 4.8, 13.0, and 11.0 mo for increased, stable, decreased; p=0.11). Size following HIGRT was not associated with differences in OS or PFS. CEA was highly variable and associations with OS and PFS could not be accurately determined. Decrease in CA 19-9 was associated with improved PFS following chemotherapy (HR 0.53, 95% CI 0.39-0.83) and HIGRT (HR 0.39, 95% CI 0.25-0.62) and improved OS following chemotherapy (HR 0.41, 95% CI 0.24-0.71) and HIGRT (HR 0.24, 95% CI 0.12-0.50). In this phase II trial, changes in tumor size and CA 19-9 were associated with survival outcomes and may assist in adapting neoadjuvant therapy in potentially resectable pancreas cancer to optimize and personalize patient care.