Challenges in the Study of Adjuvant Chemoradiation After Pancreaticoduodenectomy

Excerpt

Inadequate preoperative staging, high rates of incomplete tumor resection, and early distant tumor dissemination make the study of adjuvant therapy in pancreatic adenocarcinoma particularly challenging. To understand the value of chemoradiation in an adjuvant study, one needs to confirm that patients accrued to the study have undergone a potentially curative resection. This is of critical importance because patients left with a positive surgical margin have a median survival of less than 12–14 months, a result that may be achieved by nonsurgical therapies.1 Surprisingly, even high-volume university-based hospitals report positive surgical margins as high as 50%.2,3 The frequency of positive surgical margins is probably much higher in lower-volume centers. Strict assessments of surgical margins with particular attention to the retroperitoneal margin (also known as the SMA margin or uncinate margin) have not been widely adopted, leading to underreporting of the true margin positive rate in some studies. Furthermore, the critical distinction between potentially curative (R1) resection and noncurative gross residual disease (R2 resection) cannot be made through pathologic examination alone. This was reflected in the Radiation Therapy Oncology Group (RTOG) 97-04 trial, where the surgical margin status for approximately 25% of enrolled patients was not reported in the operative note or pathology report, and R1 versus R2 resection status could not be retrospectively determined.4 A similar disparity was observed in the European Study Group for Pancreatic Cancer (ESPAC-1) and Charite Onkologie (CONKO-001) trials.5,6 Although the proportion of patients having a positive surgical margin was quite low, local failure rates as a component of failure were high, ranging from 35% to 62%. These local failure rates imply that a substantial proportion of patients receiving adjuvant therapy actually had incomplete, noncurative (R2) surgical resections and the “adjuvant” therapy they received after surgery actually served as treatment for incompletely resected locally advanced disease. …