The European Organization for Research and Treatment for Cancer (EORTC) strategy for quality assurance in surgical clinical research: Assessment of the past and moving towards the future.

AIMS: Quality assurance (QA) in a surgical trial must be planned and implemented from study development to completion. Elements of quality must be consistently described in a protocols, case report forms (CRFs) and reported in publications. The purpose of this review was to evaluate the most common surgical parameters and how consistently they were described in EORTC study documents where surgery was included. This was the preliminary step in mapping out the challenges of developing a surgical QA strategy in EORTC. METHODS: A systematic review of EORTC surgical protocols from 1980 to 2013 was performed. Two independent reviewers selected and reviewed the protocols. Data extraction was done using a questionnaire developed by EORTC QA committee. The results were compared across the time period. RESULTS: The most common quality parameters described in protocols were surgical technique, definition of resectability, surgical margins and methods of assessing adverse events using the Common Terminology Criteria for Adverse Event (CTCAE). However, these were not consistently reported in publications. A general improvement in the method of protocol development was observed since year 2000 after standardization measures by EORTC. A new surgical chapter template has been proposed. CONCLUSION: There is a need to consistently define and report surgical parameters from protocol development to publication as a first step to QA. A standard surgical chapter in the EORTC protocol template can help address this need. A framework to consistently implement QA for future surgical trials is needed and the rationale for this is described in this review.

Early clinical trial concept for boron neutron capture therapy: a critical assessment of the EORTC trial 11001.

BNCT causes selective damage to tumor cells by neutron capture reactions releasing high LET-particles where (10)B-atoms are present. Neither the (10)B-compound nor thermal neutrons alone have any therapeutic effect. Therefore, the development of BNCT to a treatment modality needs strategies, which differ from the standard phase I-III clinical trials. An innovative trial design was developed including translational research and a phase I aspect. The trial investigates as surrogate endpoint BSH and BPA uptake in different tumor entities.

The role and impact of pathology review on stage and grade assessment of stages Ta and T1 bladder tumors: a combined analysis of 5 European Organization for Research and Treatment of Cancer Trials.

PURPOSE: Pathological interpretations are largely subject to interpathologist and intrapathologist variation. Differences in tumor stage and grade exist in local and review pathological findings in patients with stage Ta-T1 bladder tumors who are entered in randomized trials of adjuvant treatment after transurethral resection. Because they are diagnosed and treated based on local pathological results, it is important to determine the reliability of local pathological evaluations and the extent to which pathology review may change the treatment decision process. MATERIALS AND METHODS: We assessed local and review pathology results in 1,400 patients treated in 5 European Organization for Research and Treatment of Cancer randomized phase III trials comparing various adjuvant prophylactic treatment strategies for primary or recurrent stage Ta-T1 transitional cell bladder cancer. RESULTS: We noted large variations in T category and grade. Pathology review down staged T category to stage Ta in 53% of cases originally classified as stage T1. There was agreement in only 57% and 50% of stage Ta grade 1 and stage T1 grade 3 cases, of which 10% were reclassified as muscle invasive disease greater than stage T1. While T category and grade have prognostic importance, differences in the prognosis based on local and review pathological studies were slight. CONCLUSIONS: Pathology review is not mandatory in low and intermediate risk cases since it has little impact on the prognosis and treatment decision making. In high risk cases of stage T1 grade 3 disease stage or grade is often changed, so that review remains essential in this subgroup.

Validation of the methods of cosmetic assessment after breast-conserving therapy in the EORTC "boost versus no boost" trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. European Organization for Research and Treatment of Cancer.

PURPOSE: To evaluate both qualitative and quantitative scoring methods for the cosmetic result after breast-conserving therapy (BCT), and to compare the usefulness and reliability of these methods. METHODS AND MATERIALS: In EORTC trial 22881/10882, stage I and II breast cancer patients were treated with tumorectomy and axillary dissection. A total of 5318 patients were randomized between no boost and a boost of 16 Gy following whole-breast irradiation of 50 Gy. The cosmetic result was assessed for 731 patients in two ways. A panel scored the qualitative appearance of the breast using photographs taken after surgery and 3 years later. Digitizer measurements of the displacement of the nipple were also made using these photographs in order to calculate the breast retraction assessment (BRA). The cosmetic results after 3-year follow-up were used to analyze the correlation between the panel evaluation and digitizer measurements. RESULTS: For the panel evaluation the intraobserver agreement for the global cosmetic score as measured by the simple Kappa statistic was 0.42, considered moderate agreement. The multiple Kappa statistic for interobserver agreement for the global cosmetic score was 0.28, considered fair agreement. The specific cosmetic items scored by the panel were all significantly related to the global cosmetic score; breast size and shape influenced the global score most. For the digitizer measurements, the standard deviation from the average value of 30.0 mm was 2.3 mm (7.7%) for the intraobserver variability and 2.6 mm (8.7%) for the interobserver variability. The two methods were significantly, though moderately, correlated; some items scored by the panel were only correlated to the digitizer measurements if the tumor was not located in the inferior quadrant of the breast. CONCLUSIONS: The intra- and interobserver variability of the digitizer evaluation of cosmesis was smaller than that of the panel evaluation. However, there are some treatment sequelae, such as disturbing scars and skin changes, that can not be evaluated by BRA measurements. Therefore, the methods of cosmetic evaluation used in a study must be chosen in a way that balances reliability and comprehensiveness.