TOTAL NEOADJUVANT THERAPY AND PATHOLOGIC TREATMENT RESPONSE: DOES CHEMORADIATION SEQUENCING AFFECT DOWNSTAGING IN PANCREATIC CANCER?
Andrew B. Crocker*1, Navya Vemula2, Anthony Villano1, Karen Ruth1, Sanjay S. Reddy1
1Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA; 2Lewis Katz School of Medicine at Temple University, Philadelphia, PA
Introduction:
Total neoadjuvant therapy (TNT) consisting of induction chemotherapy (CT) and consolidative chemoradiation therapy (CRT), while controversial, may offer higher rates of pathologic complete response (pCR) in pancreatic ductal adenocarcinoma (PDAC). Recent literature in rectal adenocarcinoma has demonstrated potentially greater pathologic responses CRT is delivered prior to CR, but sequencing of TNT remains understudied in PDAC. In this analysis, we examine how the sequence of TNT impacts pathologic responses and operative outcomes in patients with PDAC.
Methods:
In this single-institution retrospective review 67 patients with PDAC who received TNT (induction CT followed by CRT) (n= 51) or reverse TNT (induction CRT followed by consolidative CT) (n=16) prior to major pancreatic resection were reviewed between 2010-2020. Cohort characteristics were compared using Fisher's exact and Wilcoxon tests.
Results:
Among these patients median age of diagnosis was 67 IQR[60-73], 50.7% were female, 71.6% underwent pancreaticoduodenectomy, while 28.4% underwent distal or total pancreatectomy. There was no significant difference in these values, or AJCC stage of diagnosis between TNT groups. When looking at the rates of both pathologic downstaging, or complete pathologic response, there was no significant difference between conventional and reverse TNT groups (58.8% vs 68.8%, p=0.56, and 9.8% vs 6.3%, p=0.37, respectively). Despite this, patients in the reverse TNT group were significantly more likely to develop post operative pancreatic fistula than in conventional TNT (18.7% vs 2.0%, p=0.04). There was no significant difference in positive lymph node ratio between the two groups (p=0.61).
Conclusion:
While sequence of TNT did not significantly impact pathologic response, patients who received reverse TNT did have a significantly increased rate of pancreatic fistula formation. In the absence of improved pathologic response, higher operative complication rates may limit the viability of reverse TNT for PDAC. Though additional investigation is warranted.
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