Assessment of the reliability of MSI status and dMMR proteins deficiency screening on endoscopic biopsy material in esophagus and gastric adenocarcinoma.

BACKGROUND: Microsatellite instability (MSI) is a negative predictive factor for neoadjuvant chemotherapy in resectable oesogastric adenocarcinoma and a crucial determinant for immunotherapy. We aimed to evaluate reliability of dMMR/MSI status screening performed on preoperative endoscopic biopsies. METHODS: Paired pathological samples from biopsies and surgical specimen of oesogastric adenocarcinoma were retrospectively collected between 2009 and 2019. We compared dMMR status obtained by immunohistochemistry (IHC) and MSI status by PCR. dMMR/MSI status on surgical specimen was considered as reference. RESULTS: PCR and IHC were conclusive on biopsies respectively for 53 (96.4%) and 47 (85.5%) of the 55 patients enrolled. IHC was not contributive for 1 surgical specimen. A third reading of IHC was carried out for 3 biopsies. MSI status was observed in 7 (12.5%) surgical specimens. When analyses were contributive, sensitivity and specificity of biopsies for dMMR/MSI were respectively 85% and 98% for PCR vs. 86% and 98% for IHC. Concordance rate between biopsies and surgical specimen was 96.2% for PCR and 97.8% for IHC. CONCLUSIONS: Endoscopic biopsies are a suitable source of tissue for dMMR/MSI status determination in oesogastric adenocarcinoma which should be routinely performed at diagnosis to better adapt neoadjuvant treatment. MINIABSTRACT: By comparison of dMMR phenotype obtained by immunohistochemistry and MSI status by PCR between match-paired samples of oesogastric cancer's endoscopic biopsies and surgical specimen, we observed that biopsies are a suitable source of tissue for dMMR/MSI status determination.

A Two-Step Frailty Assessment Strategy in Older Patients With Solid Tumors: A Decision Curve Analysis.

PURPOSE: The intended clinical value of frailty screening is to identify unfit patients needing geriatric assessment (GA) and to prevent unnecessary GA in fit patients. These hypotheses rely on the sensitivity and specificity of screening tests, but they have not been verified. METHODS: We performed a cross-sectional analysis of outpatients age ≥ 70 years with prostate, breast, colorectal, or lung cancer included in the ELCAPA cohort study (ClinicalTrials.gov identifier: NCT02884375) between February 2007 and December 2019. The diagnostic accuracy of the G8 Geriatric Screening Tool (G8) and modified G8 scores for identifying unfit patients was determined on the basis of GA results. We used decision curve analysis to calculate the benefit of frailty screening for detecting unfit patients and avoiding unnecessary GA in fit patients across different threshold probabilities. RESULTS: We included 1,648 patients (median age, 81 years), and 1,428 (87%) were unfit. The sensitivity and specificity were, respectively, 85% (95% CI, 84 to 87) and 59% (95% CI, 57 to 61) for G8, and 86% (95% CI, 84 to 87) and 60% (95% CI, 58 to 63) for the modified G8 score. For decision curve analysis, the net benefit (NB) for identifying unfit patients were 0.72 for G8, 0.72 for the modified G8, and 0.82 for GA at a threshold probability of 0.25. At a threshold probability of 0.33, the NBs were 0.71, 0.72, and 0.80, respectively. At a threshold probability of 0.5, the NBs were 0.68, 0.69, and 0.73, respectively. No screening tool reduced unnecessary GA in fit patients at predefined threshold probabilities. CONCLUSION: Although frailty screening tests showed good diagnostic accuracy, screening showed no clinical benefits over the GA-for-all strategy. NB approaches, in addition to diagnostic accuracy, are necessary to assess the clinical value of tests.

Prognostic value of health-related quality of life in patients with metastatic pancreatic adenocarcinoma: a random forest methodology.

PURPOSE: Eastern Cooperative Oncology Group Performance Status (ECOG-PS) is currently an important parameter in the choice of treatment strategy for metastatic pancreatic adenocarcinoma (mPA) patients. However, previous research has shown that patients' self-reported health-related quality of life (HRQOL) scales provided additional prognostic information in homogeneous groups of patients with respect to ECOG-PS. The aim of this study was to identify HRQOL scales with independent prognostic value in mPA and to propose prognostic groups for these patients. METHODS: We analysed data from 98 chemotherapy-naive patients with histologically proven mPA recruited from 2007 to 2011 in the FIRGEM phase II study which aimed to compare the effectiveness of two chemotherapy regimen. HRQOL data were assessed with the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. A random survival forest methodology was used to impute missing data and to identify major prognostic factors for overall survival. RESULTS: Baseline HRQOL assessment was completed by 60 % of patients (59/98). Twelve prognostic variables were identified. The three most important prognostic variables were fatigue, appetite loss, and role functioning, followed by three laboratory variables. The model's discriminative power assessed by Harrell's C statistic was 0.65. Fatigue score explained almost all the survival variability. CONCLUSION: HRQOL scores have prognostic value for mPA patients with good ECOG-PS. Moreover, the patient's fatigue, appetite loss, and self-perception of daily activities were more reliable prognostic indicators than clinical and laboratory variables. These HRQOL scores, especially the fatigue symptom, should be urgently included for prognostic assessment of mPA patients (with good ECOG-PS).

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.

A mini geriatric assessment helps treatment decision in elderly patients with digestive cancer. A pilot study.

UNLABELLED: Comprehensive geriatric assessment (CGA) is advocate to improved care of elderly with cancer but is not available in every hospital within a short delay. Therefore, a tool allowing gastroenterologist to detect rapidly specific abnormalities in elderly is needed. PATIENTS AND METHODS: the aim of our pilot study was to evaluate feasibility of a mini geriatric assessment (MGA) to adapt the anticancer treatments. MGA was done by a gastroenterologist and was taken into account during the cancer multidisciplinary team meeting for making decision. Then, CGA was realised and suggested adaptation of care. RESULTS: 21 patients over 75 years treated for different digestive cancers were enrolled. The treatments recommended by the cancer multidisciplinary team meeting after the GMA were: standard treatments in 9 (41%); modified in 10 (47%) and best supportive care in 2 (12%) patients. CGA led to an adaptation of the non-oncological treatment in 15 (72%) and of the social care in 8 (38%) patients, but never modified the oncological strategy. CONCLUSIONS: MGA could help gastroenterologists for adaptation of anticancer treatment. The characteristics of the patients that should subsequently have a geriatric follow-up remain to be defined.