Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Surgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach. METHODS: This multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤ 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m2). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. 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 the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. DISCUSSION: The multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. TRIAL REGISTRATION: Clinical Trials: NCT04927780. Registered June 16, 2021.

Gadoxetic acid-enhanced magnetic resonance imaging significantly influences the clinical course in patients with colorectal liver metastases.

BACKGROUND: Gadoxetic acid (Primovist™)-enhanced magnetic resonance imaging (P-MRI) scans have higher accuracy and increased detection of small colorectal liver metastases (CRLM) compared to CT scans or conventional MRI scans. But, P-MRI scans are still inconsistently acquired in the diagnostic work up of patients with CRLM. The aim of this study was to determine the influence of P-MRI scans on treatment plan proposition and subsequently the clinical course of the patient. METHODS: Eighty-three consecutive patients with potentially resectable CRLM based on a conventional CT scan underwent P-MRI scanning prior to treatment. Treatment plans proposed by the multidisciplinary team were compared before and after P-MRI scanning and related to the final treatment and diagnosis, the accuracy for the CT scan and P-MRI scan was calculated. RESULTS: P-MRI scans led to a change of treatment in 15 patients (18%) and alteration of extensiveness of local therapy in another 17 patients (20%). All changes were justified leading to an accuracy of 93% for treatment proposition based on P-MRI scan, compared to an accuracy of 75% for the CT scan. CONCLUSIONS: P-MRI scans provide additional information that can aid in proposing the most suitable treatment for patients with CRLM and might prevent short-term reintervention.

Staging laparoscopy with ultrasound and near-infrared fluorescence imaging to detect occult metastases of pancreatic and periampullary cancer.

INTRODUCTION: Up to 38% of pancreatic and periampullary cancer patients undergoing curative intended surgery turn out to have incurable disease. Therefore, staging laparoscopy (SL) prior to laparotomy is advised to spare patients the morbidity, inconvenience and expense of futile major surgery. The aim of this study was to assess the added value of SL with laparoscopic ultrasonography (LUS) and laparoscopic near-infrared fluorescence imaging (LFI). METHODS: All patients undergoing curative intended surgery of pancreatic or periampullary cancer were included prospectively in this single arm study. Patients received an intravenous infusion of 10 mg indocyanine green (ICG) one or two days prior to surgery to allow LFI. Suspect lesions were analyzed via biopsy or resection. Follow-up visits after surgery occurred every three months. RESULTS: A total of 25 patients were included. Suspect lesions were identified in 7 patients: liver metastases (n = 2; identified by inspection, LUS, and LFI), peritoneal metastases (n = 1; identified by inspection only), and benign lesions (n = 4; identified by inspection or LUS). Quality of LFI was good in 67% (10/15) of patients dosed one day and 89% (8/9) dosed two days prior to surgery. A futile laparotomy was averted in 3 patients (12%). Following SL the primary tumor was resected in 20 patients. Two patients (10%) developed metastases within 3 months after resection. CONCLUSIONS: Despite current preoperative imaging modalities metastases are still identified during surgery. This study shows limited added value of LUS during SL in patients with pancreatic or periampullary cancer. LFI was of added value due to its high negative predictive value in case of suspect hepatic lesions identified by inspection.