"Radiological and Surgical Implications of Neoadjuvant Treatment With FOLFIRINOX for Locally Advanced and Borderline Resectable Pancreatic Cancer."

To the Editor: We congratulate the authors for giving us an insight into the radiological and surgical implications of neoadjuvant chemotherapy in borderline respectable/unresectable pancreatic cancer. Historically, pancreatic tumors were classified as resectable, locally advanced unresectable and metastatic. But with advances in pancreatic imaging, a new subset of tumors evolved which blurs the distinction between locally advanced and resectable tumors, and these are being classified as borderline resectable. The management of this subset of patients is confusing as to whether these patients should undergo upfront surgery or they should be subjected to neoadjuvant therapy. The authors have argued that imaging no longer predicts unresectability after neoadjuvant therapy, for which they deserve our compliments. We would like to discuss some issues with regards to the article. The authors subjected borderline respectable/locally advanced disease to FOLFIRINOX regimen. We would want to know if the authors performed preoperative biopsy or staging laparoscopy for all these patients before neoadjuvant therapy as presently there is evidence to recommend the same. We are also interested in knowing the mean time between initiation of FOLFIRINOX and surgery. The authors observed 3 patients to have metastatic disease and 4 to have locally advanced unresectable disease. The authors have excluded these patients from analysis, which portrays progression of the disease despite FOLFIRINOX. Table 2 shows 0% progression post-FOLFIRINOX, which is flawed as these 7 patients have been excluded. Overall survival would also be affected if these patients are to be included. When comparing overall survival, we would also want to know the adjuvant treatment received by non-neoadjuvant group. Still it is a significant result as the upfront surgery group was less advanced to start with. The authors have performed only 5 venous resections in 40 patients who were locally advanced or borderline resectable to start with. We are interested to know whether these patients, when retrospectively analyzed, were borderline resectable or locally advanced preneoadjuvant therapy and did they show any response to neoadjuvant therapy on CT scan. The authors have performed intraoperative radiotherapy in 12 of 40 patients. We believe this will add to the OR time and the author should have accounted this separately. Finally, the 0% pancreatic fistula rate after FOLFIRINOX is an outstanding result, which makes us curious to know how the authors defined pancreatic fistula. Their fistula rate in patients without neoadjuvant was 22%, which is closer to our 15% achieved with Blumgart’s technique. Is there some fibrosis in the pancreatic remnant? Was this evident on pathology specimens? In an era when there is evidence to show that patients can safely undergo pancreatectomy with vein resection with no increase in morbidity, surgeons have argued that patients with borderline resectability be offered surgery upfront. Results here suggest that these patients are better served with neoadjuvant regime. The Alliance trial is analyzing the modified FOLFIRINOX regime for these patients and their results will be awaited.