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BackgroundRadiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease.MethodsIn this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3 cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3 cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY).DiscussionIf thermal ablation proves to be non-inferior in treating lesions ≤3 cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM.Trial registrationNCT03088150, January 11th 2017.

Purpose To (a) investigate the safety of percutaneous irreversible electroporation (IRE) for locally advanced pancreatic cancer and (b) evaluate the quality of life (QOL), pain perception, and efficacy in terms of time to local progression, event-free survival, and overall survival (OS). Materials and Methods The study was approved by the local review board (NL42888.029.13). All patients provided written informed consent for study participation, the ablation procedure, and data usage. Between January 2014 and June 2015, 25 patients with histologically proved locally advanced pancreatic cancer 5 cm or smaller (13 women, 12 men; median age, 61 years; age range, 41-78 years) were prospectively included to undergo percutaneous computed tomographic-guided IRE. Patients with a metallic biliary Wallstent, epilepsy, or ventricular arrhythmias were excluded. Kaplan-Meier estimates were used to investigate time to local progression, event-free survival, and OS. Safety was assessed on the basis of adverse events, which were graded according to the Common Terminology Criteria for Adverse Events. Pain perception and QOL were evaluated by using specific questionnaires. Results All patients underwent IRE. The median largest tumor diameter was 4.0 cm (range, 3.3-5.0 cm). After a median follow-up of 12 months (interquartile range: 7-16 months), median event-free survival after IRE was 8 months (95% confidence interval [CI]: 4 months, 12 months); the median time to local progression after IRE was 12 months (95% CI: 8 months, 16 months). The median OS was 11 months from IRE (95% CI: 9 months, 13 months) and 17 months from diagnosis (95% CI: 10 months, 24 months). There were 12 minor complications (grade I or II) and 11 major complications (nine grade III, two grade IV) in 10 patients. There were no deaths within 90 days after IRE. Conclusion Percutaneous IRE for locally advanced pancreatic cancer is generally well tolerated, although major adverse events can occur. Preliminary survival data are encouraging and support the setup of larger phase II and III clinical trials to assess the efficacy of IRE plus chemotherapy in the neoadjuvant and adjuvant or second-line setting compared with more widely adopted regimens such as chemotherapy and/or radiation therapy. RSNA, 2016 Online supplemental material is available for this article.

Background Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients. Methods This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up. Discussion The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer. Trial registration Primary registry and trial identifying number: EudraCT: 2017–002036-17. Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register – NL7094, NL61961.078.17, MEC-2018-004.