Dosimetric Parameters Correlate With Node Negative Resection in Borderline and Initially Unresectable Pancreatic Adenocarcinoma Patients Treated With Stereotactic Body Radiation Therapy Followed by Surgical Resection

Definitive stereotactic body radiation therapy (SBRT) in borderline and locally advanced pancreatic adenocarcinoma is an emerging alternative to conventional external beam radiation therapy with concurrent chemotherapy. Here we aim to identify dosimetric parameters which correlate with improved pathologic outcome in a cohort of patients treated with definitive SBRT followed by surgical resection. We retrospectively identified 37 patients at our institution with histologically confirmed borderline-resectable or initially unresectable pancreatic adenocarcinoma who underwent neoadjuvant chemotherapy and SBRT followed by surgical resection. SBRT was prescribed to a median dose of 33 Gy (range: 25-33) in 5 fractions. Pathology was reviewed and pathologic complete response, resection margin status, and lymph node involvement were identified. Tumor volumes, anatomical volumes, and 3D dosimetry were restored and transferred to a platform which allows comprehensive inter-patient clinical and dosimetric correlations. Heat map analysis was performed to represent cumulative dose-volume histogram (DVH) data with respect to pathologic outcomes to identify trends. Binary logistic regression was used for analysis. This model was used to estimate absolute rates of toxicity for PTV coverage percentages. Median age at diagnosis was 60 years (range: 43-83). Median follow-up from surgery was 3.9 months (Range: 0.2-43.9). Of the 37 patients, 19 (51%) were borderline resectable and 18 (49%) were unresectable. Five patients (14%) achieved a pathologic complete response, while rates of margin-negative and node-negative resection were 86% and 73% respectively. Comparison of node-negative and node-positive resections through heat map analysis identified a separation in outcome based on increases in dose to 94-99% (D94-D99) of the planning tumor volume (PTV). Of these, increased D99 had the strongest association with improved pathologic nodal response (P=.037). As an example, based on this logistic regression model, a PTV D99 of 25 Gy is associated with a 30% risk of node-positive resection, while a PTV D99 of 33 Gy is associated with a 3.2% risk of a node-positive resection. Increased D94-99 correlates with node-negative resection in borderline and initially unresectable pancreatic adenocarcinoma patients treated with neoadjuvant SBRT. This analysis suggests that a minimum dose to high volumes of the PTV is a parameter for dosimetric evaluation and improved incidence of node-negative resection. Validation with increased numbers of patients should be pursued.