Abstract
Background: Although surgical resection is the only potentially curative treatment for pancreatic cancer (PC), long-term outcomes of this treatment remain poor. The aim of this study is to describe the feasibility of a neoadjuvant treatment with induction polychemotherapy (IPCT) followed by chemoradiation (CRT) in resectable PC, and to develop a machine-learning algorithm to predict risk of relapse. Methods: Forty patients with resectable PC treated in our institution with IPCT (based on mFOLFOXIRI, GEMOX or GEMOXEL) followed by CRT (50 Gy and concurrent Capecitabine) were retrospectively analyzed. Additionally, clinical, pathological and analytical data were collected in order to perform a 2-year relapse-risk predictive population model using machine-learning techniques. Results: A R0 resection was achieved in 90% of the patients. After a median follow-up of 33.5 months, median progression-free survival (PFS) was 18 months and median overall survival (OS) was 39 months. The 3 and 5-year actuarial PFS were 43.8% and 32.3%, respectively. The 3 and 5-year actuarial OS were 51.5% and 34.8%, respectively. Forty-percent of grade 3-4 IPCT toxicity, and 29.7% of grade 3 CRT toxicity were reported. Considering the use of granulocyte colony-stimulating factors, the number of resected lymph nodes, the presence of perineural invasion and the surgical margin status, a logistic regression algorithm predicted the individual 2-year relapse-risk with an accuracy of 0.71 (95% confidence interval [CI] 0.56–0.84, p = 0.005). The model-predicted outcome matched 64% of the observed outcomes in an external dataset. Conclusion: An intensified multimodal neoadjuvant approach (IPCT + CRT) in resectable PC is feasible, with an encouraging long-term outcome. Machine-learning algorithms might be a useful tool to predict individual risk of relapse. A small sample size and therapy heterogeneity remain as potential limitations.
Highlights
Pancreatic cancer (PC) is expected to be the second cause of cancer deaths in Western countries by 2030. [1,2] Surgical resection remains the only potentially curative treatment, but only 10–20%of cases are resectable at diagnosis
All patients diagnosed of potentially curable pancreatic cancer (PC) from September 2005 to November 2016 were evaluated by a multidisciplinary team composed of hepatobiliary surgeons, endoscopists, interventional radiologists, medical and radiation oncologists
Initial workup included: clinical examination, laboratory tests including a serum CA-19.9 level, endoscopic ultrasound (EUS) with guided fine needle aspiration biopsy (FNA) of the pancreatic lesion and a CT-scan to define the extent of the disease
Summary
Pancreatic cancer (PC) is expected to be the second cause of cancer deaths in Western countries by 2030. [1,2] Surgical resection remains the only potentially curative treatment, but only 10–20%of cases are resectable at diagnosis. The high rate of disease relapse, coupled with a low compliance (only 51% of patients outside the context of a clinical trial receive adjuvant therapy [12]) remain major drawbacks of an adjuvant strategy This has led some authors to uphold the use of preoperative treatment, with potential advantages such as an increased R0 resection rate, better compliance, a reduction in the risk of intraoperative tumor spillage and avoidance of unnecessary surgery, with its related morbidity and mortality, in patients with unfavorable tumor biology. Preliminary data with this approach, either preoperative chemotherapy or chemoradiation, seem promising.
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