T. Board1, E. O’Halloran1, M. Hill1, A. Zaladonis1, M. Hotz1, L. Rhodes1, J. Farma1, I. Astsaturov4, E. Cukierman2, J. Meyer3, S. Reddy1 1Fox Chase Cancer Center,Department Of Surgical Oncology,Philadelphia, PA, USA 2Fox Chase Cancer Center,Department Of Pathology,Philadelphia, PA, USA 3Fox Chase Cancer Center,Department Of Radiation Oncology,Philadelphia, PA, USA 4Fox Chase Cancer Center,Department Of Medical Oncology,Philadelphia, PA, USA
Introduction: Total neoadjuvant therapy (TNT) in pancreas cancer, defined as administration of systemic chemotherapy followed by chemoradiotherapy prior to resection, is frequently used in the treatment of pancreas cancer at high volume centers. Resection 4-10 weeks after the completion of radiation therapy is currently recommended in eligible patients, but there is no data to suggest an optimal surgical window in which one would see a high treatment effect without compromising surgical dissection. We aimed to identify an optimal time interval between completion of TNT and resection.
Methods: We conducted a retrospective review of all patients who received TNT prior to pancreatic resection at our NCI designated cancer center between 2006 and 2017. Demographics and clinical characteristics, treatment regimens, surgical pathology reports, and outcomes were collected. Patients were divided into 5 subgroups based on the number of weeks elapsed between the completion of radiation therapy and operative intervention. Multivariate logistic regression models were used to analyze the relationship between time to surgery and outcome variables, while Cox proportional hazards models were used for survival analyses.
Results: Forty-four patients met inclusion criteria, 61.4% of whom were male, with a median age of 65.5 years (38-82). The cohort included 14 clinical stage I (31.1%), 22 stage II (48.9%), and 8 stage III patients (18.2%). Gemcitabine-based neoadjuvant chemotherapy was used in 19 patients (42.2%), FOLFIRINOX in 22 patients (50%), and FOLFOX in 3 patients (6.8%). Most patients received 5 weeks of radiation with a chemosensitizing agent, while 4 patients (9.1%) received short course radiation. The average time between completion of TNT to surgery was 8.3 weeks (range: 2.1-24.1): 5 (11.4%) had surgery in less than four weeks, 8 (18.2%) in four to less than six weeks, 8 (18.2%) in six to less than eight weeks, 13 (29.6%) in eight to less than 10 weeks, and 10 (22.7%) in ten or more weeks. Time to surgery did not impact margin positivity or the degree of fibrosis seen on final pathology. After controlling for clinical stage and type of neoadjuvant therapy received, overall survival (OS) was significantly better in patients who had surgery in 6-8 weeks after TNT compared to the other groups (HR 0.05, p=0.017), with a mean OS of 45.7 months in this group compared to 36.4 months in the rest of the cohort. Disease free survival, recurrence rate, and local recurrence rate did not differ between the groups.
Conclusion: These findings demonstrate that while overall survival was better in patients in the 6-8 week group after controlling for staging and type of therapy, the interval between completion of TNT and surgery did not significantly impact outcomes such as DFS, margin positivity, fibrosis, or recurrence. Further investigation is needed to determine an optimal window in which to operate to create guidelines as TNT becomes a more prevalent treatment strategy.