Modeling individual and relative accuracy of screening tools in geriatric oncology.

BACKGROUND: Classification probabilities reflect to what degree a screening test represents the true disease state and include true positive (TPF) and false positive fractions (FPF). With two tests, one can compare TPF and FPF using relative probabilities which offer advantages in terms of interpretation and statistical modeling. Our objective was to highlight how individual and relative TPF and FPF can be easily estimated and compared within a regression modeling framework. This allows the modeling of tests' accuracy while adjusting for multiple covariates, and thus provides valuable information in addition to the crude TPF and FPF. We illustrate our purpose with the G8 and VES-13 screening tests aimed at identifying elderly cancer patients in need for a comprehensive geriatric assessment (CGA). METHODS: Prospective cohort with a paired design. TPF and FPF of each test, as well as relative TPF and FPF were modeled using log-linear models. RESULTS: G8 detected patients in need for CGA better than VES-13 at the expense of misclassifying a large number of normal patients. Both tests had better TPF with older age and poorer performance status (PS), and for all cancer subtypes compared with prostate cancer. Effect of age and PS on TPF was more pronounced with VES-13. Age affected FPF, but not differentially. CONCLUSIONS: Regression modeling helps provide a thorough assessment of the accuracy of diagnostic tests and should be used more frequently. In the context of screening, we encourage the use of G8 as failing to identify patients in need of a CGA might be more problematic than over-detection. Moreover, although we identified variables associated with the sensitivity of these tests, this association was less pronounced for the G8.

Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). METHODS: We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. RESULTS: Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. CONCLUSION: Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities.

Screening older cancer patients: first evaluation of the G-8 geriatric screening tool.

BACKGROUND: Development of a geriatric screening tool is necessary to identify elderly cancer patients who would benefit from comprehensive geriatric assessment (CGA). We develop and evaluate the G-8 screening tool against various reference tests. PATIENTS AND METHODS: Analyses were based on 364 cancer patients aged>70 years scheduled to receive first-line chemotherapy included in a multicenter prospective study. The G-8 consists of seven items from the Mini Nutritional Assessment (MNA) questionnaire and age. Our primary reference test is based on a set of seven CGA scales: Activities Daily Living (ADL), Instrumental ADL, MNA, Mini-Mental State Exam, Geriatric Depression Scale, Cumulative Illness Rating Scale-Geriatrics, and Timed Get Up and Go. We considered the presence of at least one questionnaire with an impaired score as an abnormal reference exam. Additional reference exams are also discussed. RESULTS: The prevalence of being at risk varied from 60% to 94% according to the various definitions of the reference test. When considering the primary reference test, a cut-off value of 14 for the G-8 tool provided a good sensitivity estimate (85%) without deteriorating the specificity excessively (65%). CONCLUSION: The G-8 shows good screening properties for identifying elderly cancer patients who could benefit from CGA.

Delayed colo-anal anastomosis is an alternative to prophylactic diverting stoma after total mesorectal excision for middle and low rectal carcinomas.

BACKGROUND: After total mesorectal excision (TME), a low colorectal or colo-anal anastomosis is usually performed. A prophylactic covering stoma is often used, especially for patients receiving neoadjuvant chemo-radiotherapy. However, morbidity is high, mainly due to anastomotic leakage. METHODS: From May 2000 to October 2008, patients with middle or low rectal cancer who underwent a trans-anal pull-through procedure after TME were prospectively recorded. No covering stoma was performed in these patients. However, they all underwent a delayed colo-anal anastomosis (DCA), which was performed 6 days following the TME, on average. Both the surgical technique and follow-up were standardised. Patients with T3, T4 and/or N+ cancers were given preoperative radiotherapy. A retrospective analysis was done to assess post-operative mortality, morbidity, and oncologic and functional results. RESULTS: One hundred consecutive patients with rectal tumours at a median distance of 5 cm from the anal verge underwent DCA after TME. The 5-year overall and disease-free survival rates were 81% and 66%, respectively. The post-operative mortality rate was 3% and the overall post-operative morbidity rate was 36%, with only 3 anastomotic leakages. After two years, 73% of the patients had good functional outcomes. CONCLUSION: The trans-anal pull-through procedure after TME, followed by DCA seems to be a safe and efficient sphincter-preserving procedure to treat patients with middle or low rectal cancer while avoiding a prophylactic, diverting stoma.