IntroductionEarly guidelines for minimally important differences (MIDs) for the EORTC QLQ-C30 proposed ≥10 points change as clinically meaningful for all scales. Increasing evidence that MIDs can... Show moreIntroductionEarly guidelines for minimally important differences (MIDs) for the EORTC QLQ-C30 proposed ≥10 points change as clinically meaningful for all scales. Increasing evidence that MIDs can vary by scale, direction of change, cancer type and estimation method has raised doubt about a single global standard. This paper identifies MID patterns for interpreting group-level change in EORTC QLQ-C30 scores across nine cancer types.MethodsData were obtained from 21 published EORTC Phase III trials that enroled 13,015 patients across nine cancer types (brain, colorectal, advanced breast, head/neck, lung, mesothelioma, melanoma, ovarian, and prostate). Anchor-based MIDs for within-group change and between-group differences in change over time were obtained via mean change method and linear regression, respectively. Separate MIDs were estimated for improvements and deteriorations. Distribution-based estimates were derived and compared with anchor-based MIDs.ResultsAnchor-based MIDs mostly ranged from 5 to 10 points. Differences in MIDs for improvement vs deterioration, for both within-group and between-group, were mostly within a 2-points range. Larger differences between within-group and between-group MIDs were observed for several scales in ovarian, lung and head/neck cancer. Most anchor-based MIDs ranged between 0.3 SD and 0.5 SD distribution-based estimates.ConclusionsOur results reinforce recent claims that no single MID can be applied to all EORTC QLQ-C30 scales and disease settings. MIDs varied by scale, improvement/deterioration, within/between comparisons and by cancer type. Researchers applying commonly used rules of thumb must be aware of the risk of dismissing changes that are clinically meaningful or underpowering analyses when smaller MIDs apply. Show less
Tumor visualization with near-infrared fluorescence (NIRF) imaging might aid exploration and resection of pancreatic cancer by visualizing the tumor in real time. Conjugation of the near-infrared... Show moreTumor visualization with near-infrared fluorescence (NIRF) imaging might aid exploration and resection of pancreatic cancer by visualizing the tumor in real time. Conjugation of the near-infrared fluorophore IRDye800CW to the monoclonal antibody bevacizumab enables targeting of vascular endothelial growth factor A. The aim of this study was to determine whether intraoperative tumor-specific imaging of pancreatic cancer with the fluorescent tracer bevacizumab-800CW is feasible and safe. Methods: In this multicenter dose-escalation phase I trial, patients in whom pancreatic ductal adenocarcinoma (PDAC) was suspected were administered bevacizumab-800CW (4.5, 10, or 25 mg) 3 d before surgery. Safety monitoring encompassed allergic or anaphylactic reactions and serious adverse events attributed to bevacizumab-800CW. Intraoperative NIRF imaging was performed immediately after laparotomy, just before and after resection of the specimen. Postoperatively, fluorescence signals on the axial slices and formalin-fixed paraffin-embedded tissue blocks from the resected specimens were correlated with histology. Subsequently, tumor-to-background ratios (TBR) were calculated. Results: Ten patients with clinically suspected PDAC were enrolled in the study. Four of the resected specimens were confirmed PDACs; other malignancies were distal cholangiocarcinoma, ampullary carcinoma, and neuroendocrine tumors. No serious adverse events were related to bevacizumab-800CW. In vivo tumor visualization with NIRF imaging differed per tumor type and was nonconclusive. Ex vivo TBRs were 1.3, 1.5, and 2.5 for the 4.5-, 10-, and 25-mg groups, respectively. Conclusion: NIRF-guided surgery in patients with suspected PDAC using bevacizumab-IRDye800CW is feasible and safe. However, suboptimal TBRs were obtained because no clear distinction between pancreatic cancer from normal or inflamed pancreatic tissue was achieved. Therefore, a more tumor-specific tracer than bevacizumab-IRDye800CWfor PDAC is preferred. Show less
Coens, C.; Pe, M.; Dueck, A.C.; Sloan, J.; Basch, E.; Calvert, M.; ... ; Setting Int Stand Analyzing Patien 2020
Patient-reported outcomes (PROs), such as symptoms, function, and other health-related quality-of-life aspects, are increasingly evaluated in cancer randomised controlled trials (RCTs) to provide... Show morePatient-reported outcomes (PROs), such as symptoms, function, and other health-related quality-of-life aspects, are increasingly evaluated in cancer randomised controlled trials (RCTs) to provide information about treatment risks, benefits, and tolerability. However, expert opinion and critical review of the literature showed no consensus on optimal methods of PRO analysis in cancer RCTs, hindering interpretation of results. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium was formed to establish PRO analysis recommendations. Four issues were prioritised: developing a taxonomy of research objectives that can be matched with appropriate statistical methods, identifying appropriate statistical methods for PRO analysis, standardising statistical terminology related to missing data, and determining appropriate ways to manage missing data. This Policy Review presents recommendations for PRO analysis developed through critical literature reviews and a structured collaborative process with diverse international stakeholders, which provides a foundation for endorsement; ongoing developments of these recommendations are also discussed. Show less
Bottomley, A.; Reijneveld, J.C.; Koller, M.; Flechtner, H.; Tomaszewski, K.A.; Greimel, E.; ... ; 5th EORTC Quality Life Canc 2019
