Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer.

BACKGROUND: The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood. METHODS: We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use. RESULTS: Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, -4.1 to 6.2 [noninferiority margin, -8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not. CONCLUSIONS: A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival. (Supported by the Australian National Health and Medical Research Council and others; DYNAMIC Australian New Zealand Clinical Trials Registry number, ACTRN12615000381583.).

Utility of selection methods for specialist medical training: A BEME (best evidence medical education) systematic review: BEME guide no. 45.

BACKGROUND: Selection into specialty training is a high-stakes and resource-intensive process. While substantial literature exists on selection into medical schools, and there are individual studies in postgraduate settings, there seems to be paucity of evidence concerning selection systems and the utility of selection tools in postgraduate training environments. AIM: To explore, analyze and synthesize the evidence related to selection into postgraduate medical specialty training. METHOD: Core bibliographic databases including PubMed; Ovid Medline; Embase, CINAHL; ERIC and PsycINFO were searched, and a total of 2640 abstracts were retrieved. After removing duplicates and screening against the inclusion criteria, 202 full papers were coded, of which 116 were included. RESULTS: Gaps in underlying selection frameworks were illuminated. Frameworks defined by locally derived selection criteria, and heavily weighed on academic parameters seem to be giving way to the evidencing of competency-based selection approaches in some settings. Regarding selection tools, we found favorable psychometric evidence for multiple mini-interviews, situational judgment tests and clinical problem-solving tests, although the bulk of evidence was mostly limited to the United Kingdom. The evidence around the robustness of curriculum vitae, letters of recommendation and personal statements was equivocal. The findings on the predictors of past performance were limited to academic criteria with paucity of long-term evaluations. The evidence around nonacademic criteria was inadequate to make an informed judgment. CONCLUSIONS: While much has been gained in understanding the utility of individual selection methods, though the evidence around many of them is equivocal, the underlying theoretical and conceptual frameworks for designing holistic and equitable selection systems are yet to be developed.