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.

Proteomic assessment of markers for malignancy in the mucus of intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas evolve from dysplasia to invasive adenocarcinoma. The aims of this study were to look for candidate protein profiles in IPMN mucus according to histological grade, using a differential proteomic technique, and to highlight protein peaks associated with malignant transformation. METHODS: Forty-three mucus samples obtained from surgically resected IPMN and categorized as benign (low/moderate dysplasia) or malignant (severe dysplasia/invasive adenocarcinoma) in 21 and 22 patients, respectively. A surface-enhanced laser desorption ionization time-of-flight mass spectrometry was used to determine candidate protein expression profiles. Protein peaks that significantly differed between benign/malignant IPMN (area under curve > 0.88; P < 10; high intensity) were identified using adapted software. RESULTS: Among 952 protein peaks, 31 were differentially expressed in benign/malignant IPMN (P < 0.001). Among them, 5 candidate proteins of interest (mass-to-charge ratio [m/z]: 5217, 6326, 6719, 10,453, and 10,849 d) were selected by their high diagnostic accuracy and ability to distinguish between malignant and benign tumors. No correlation was found between peak profiles and duct involvement. CONCLUSIONS: Carcinogenic process in IPMN is associated with changes in mucus proteome with characteristic peaks that could be potential candidate biomarkers of malignancy. ABBREVIATIONS: IPMN - intraductal papillary mucinous neoplasm, EPC - extrapancreatic cancer, MRI - magnetic resonance imaging, ERCP - endoscopic retrograde cholangiopancreatography.