The algorithms that the authors developed achieved a cross-validated accuracy of 64% and an accuracy of 64% on an 1851-patient independent test set, compared with 9% accuracy when a random classifier was used.
This is the first large report of borderline resectable PA and includes objective definitions for this stage of disease. Our neoadjuvant approach allowed for identification of the marked subset of patients that was most likely to benefit from surgery, as evidenced by the favorable median survival in this group.
With recent advances in pancreatic imaging and surgical techniques, a distinct subset of pancreatic tumors is emerging that blurs the distinction between resectable and locally advanced disease: tumors of "borderline resectability." In our practice, patients with borderline-resectable pancreatic cancer include those whose tumors exhibit encasement of a short segment of the hepatic artery, without evidence of tumor extension to the celiac axis, that is amenable to resection and reconstruction; tumor abutment of the superior mesenteric artery involving <180 degrees of the circumference of the artery; or short-segment occlusion of the superior mesenteric vein, portal vein, or their confluence with a suitable option available for vascular reconstruction because the veins are normal above and below the area of tumor involvement. With currently available surgical techniques, patients with borderline-resectable pancreatic head cancer are at high risk for a margin-positive resection. Therefore, our approach to these patients is to use preoperative systemic therapy and local-regional chemoradiation to maximize the potential for an R0 resection and to avoid R2 resections. In our experience, patients with favorable responses to preoperative therapy (radiographical evidence of tumor regression and improvement in serum tumor marker levels) are the subset of patients who have the best chance for an R0 resection and a favorable long-term outcome.
Preoperative gemcitabine-based chemoradiation followed by restaging and evaluation for surgery separated the study population into two different subsets: patients likely to benefit from PD (n = 64) and those in whom surgery would be unlikely to provide clinical benefit (n = 22). Furthermore, the encouraging overall survival observed in this large trial supports the continued investigation of gemcitabine-based preoperative therapy in resectable pancreatic cancer.
Exosomes are a distinct source of tumor DNA that may be complementary to other liquid biopsy DNA sources. A higher percentage of patients with localized PDAC exhibited detectable KRAS mutations in exoDNA than previously reported for cfDNA. A substantial minority of healthy samples demonstrated mutant KRAS in circulation, dictating careful consideration and application of liquid biopsy findings, which may limit its utility as a broad cancer-screening method.
Introduction
Actual 5-year survival rates of 10–18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy.
Methods
We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were rereviewed. A multivariate model of factors associated with long-term survival was constructed.
Results
Patients underwent pancreaticoduodenectomy (n = 302; 92%), distal (n = 20; 6%), or total pancreatectomy (n = 7; 2%). A total of 108 patients (33%) underwent vascular reconstruction, 301 patients (91%) received neoadjuvant or adjuvant therapy, 157 specimens (48%) were node positive, and margins were microscopically positive in 52 patients (16%). Median overall survival and disease-specific survival was 23.9 and 26.5 months. Eighty-eight patients (27%) survived a minimum of 5 years and had a median overall survival of 11 years. Of these, 21 (24%) experienced recurrence, 7 (8%) after 5 years. Late recurrences occurred most frequently in the lungs, the latest at 6.7 years. Multivariate analysis identified disease-negative lymph nodes (P = .02) and no prior attempt at resection (P = 0.01) as associated with 5-year survival.
Conclusions
Our 27% actual 5-year survival rate for patients with resected PC is superior to that previously reported, and it is influenced by our emphasis on detailed staging and patient selection, a standardized operative approach, and routine use of multimodality therapy.
Preoperative Gem-Cis-XRT did not improve survival beyond that achieved with preoperative gemcitabine-based chemoradiation (Gem-XRT) alone. The longer preoperative interval required more durable biliary decompression (metal stents) but was not associated with local tumor progression. The gemcitabine-based chemoradiation platform is a reasonable foundation on which to build future phase II multimodality trials for stage I/II pancreatic cancer incorporating emerging systemic therapies.
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