Assessment of response to chemotherapy in pancreatic ductal adenocarcinoma: Comparison between diffusion-weighted MR quantitative parameters and RECIST.

PURPOSE: To prospectively assess chemotherapy-induced changes in pancreatic ductal adenocarcinoma (PDA) with diffusion-weighted (DW)-MR quantitative metrics, including apparent diffusion coefficient (ADC) and histogram-derived parameters, compared with RECIST 1.1. METHODS: 24 patients underwent DW-MR at baseline, week-2 and week-8 after chemotherapy initiation. Tumour diameter was assessed on T2-weighted images. Regions-of-interest (ROI) were drawn on ADC map for ROI-ADC. Volume segmentation (b = 1000 s/mm2 images) provided DW-volume and histogram-derived diffusion parameters (H-ADC, H-D and H-PF). All variables and their relative change were compared to baseline or between responders and non-responders. Discriminant analysis was performed. RESULTS: 15/24 patients were responders. RECIST 1.1 correctly characterized 6/15 responders at week-8. At week-2, in responders DW-volume decreased (P = .002); ROI-ADC mean H-D increased (P = .047; P = .048;). The 25th percentile H-D increased in responders and decreased in non-responders (P = .016; P = .048). At week-8 in responders DW-volume decreased and ROI-ADC mean, 25th, 50th, 75th percentiles of H-ADC and H-D increased (P < .05). No changes were observed in non-responders (P > .05). At week-2, 25th percentile of H-D and H-PF relative change correctly classified 20/24 patients (P = .003); at week-8, DW-volume relative change correctly classified 22/24 patients (P < .0001). CONCLUSIONS: ROI-ADC, DW-volume and histogram-derived diffusion parameters are more accurate to categorize responding and non-responding PDA patients treated with chemotherapy compared with RECIST 1.1.

Clinical Benefit and Health-Related Quality of Life Assessment in Patients Treated with Cisplatin/S-1 Versus Cisplatin/5-FU: Secondary End Point Results From the First-Line Advanced Gastric Cancer Study (FLAGS).

PURPOSE: Patient-reported outcomes (PRO) of health-related quality of life (HRQoL) and time to worsening of clinical benefit parameters were evaluated as secondary end points in the phase 3 first-line advanced gastric cancer study (FLAGS) trial of cisplatin/S-1 versus cisplatin/5-fluorouracil (5-FU) in patients with previously untreated advanced gastric cancer. METHODS: The primary PRO end point was the Trial Outcome Index of the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga). FACT-Ga was completed at the beginning of the first 4 cycles, cycle 6, and then every 3 cycles thereafter. The Chemotherapy Convenience and Satisfaction Questionnaire (CCSQ) was administered before the first 4 cycles; clinical benefit parameters (performance status, weight loss, and anorexia) were assessed at baseline, prior to study drug administration on day 1 of each cycle after cycle 1, and at the end of study treatment. RESULTS: Compliance to questionnaire fulfillment was more than 80 % through cycle 9. Significantly, fewer patients treated with cisplatin/S-1 reported worsened physical well-being (PWB) scores (45.1 versus 51.7 %, p = 0.044) and experienced significantly longer time to worsening in PWB scores, with a median of 4.5 months (95 % confidence interval (CI), 3.1-5.1) compared to 3.0 months (2.8-4.6) with cisplatin/5-FU (CF) (p = 0.01). Patients receiving cisplatin/S-1 also reported significantly higher best and worst score of PWB as well as CCSQ scores and a longer median time to worsening in clinical benefit parameters. CONCLUSIONS: Differences in secondary end points of PWB, CCSQ scores, and clinical benefit parameters favoring the cisplatin/S-1 arm provide further evidence for considering this combination a standard therapeutic option for first-line treatment of advanced gastric cancer.

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

BACKGROUND: Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. METHODS: Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). RESULTS: For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. CONCLUSION: The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.