Background The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. Methods We used a new bioinformatics approach to search for biomarkers of colon epithelial differentiation across gene-expression arrays and then ranked candidate genes according to the availability of clinical-grade diagnostic assays. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. Results The transcription factor CDX2 ranked first in our screening test. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P = 0.002). In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein–negative colon cancers than among the 276 (87.9%) with CDX2 protein–positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P = 0.003). In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. Among patients with stage II cancer, the difference in 5-year disease-free survival was significant both in the discovery data set (49% among 15 patients with CDX2-negative tumors vs. 87% among 191 patients with CDX2-positive tumors, P = 0.003) and in the validation data set (51% among 15 patients with CDX2-negative tumors vs. 80% among 106 patients with CDX2-positive tumors, P = 0.004). In a pooled database of all patient cohorts, the rate of 5-year disease-free survival was higher among 23 patients with stage II CDX2-negative tumors who were treated with adjuvant chemotherapy than among 25 who were not treated with adjuvant chemotherapy (91% vs. 56%, P = 0.006). Conclusions Lack of CDX2 expression identified a subgroup of patients with high-risk stage II colon cancer who appeared to benefit from adjuvant chemotherapy. (Funded by the National Comprehensive Cancer Network, the National Institutes of Health, and others.)

IMPORTANCE Earlier clinician-patient conversations about patients' values, goals, and preferences in serious illness (ie, serious illness conversations) are associated with better outcomes but occur inconsistently in cancer care. OBJECTIVE To evaluate the efficacy of a communication quality-improvement intervention in improving the occurrence, timing, quality, and accessibility of documented serious illness conversations between oncology clinicians and patients with advanced cancer. DESIGN, SETTING, PARTICIPANTS This cluster randomized clinical trial in outpatient oncology was conducted at the Dana-Farber Cancer Institute and included physicians, advanced-practice clinicians, and patients with cancer who were at high risk of death. MAIN OUTCOMES AND MEASURES The primary outcomes (goal-concordant care and peacefulness at the end of life) are published elsewhere. Secondary outcomes are reported herein, including (1) documentation of at least 1 serious illness conversation before death, (2) timing of the initial conversation before death, (3) quality of conversations, and (4) their accessibility in the electronic medical record (EMR). RESULTS We enrolled 91 clinicians (48 intervention, 43 control) and 278 patients (134 intervention, 144 control). Of enrolled patients, 58% died during the study (n=161); mean age was 62.3 years (95% CI, 58.9-65.6 years); 55% were women (n=88). These patients were cared for by 76 of the 91 enrolled clinicians (37 intervention, 39 control); years in practice, 11.5 (95% CI, 9.2-13.8); 57% female (n=43). Medical record review after patients' death demonstrated that a significantly higher proportion of intervention patients had a documented discussion compared with controls (96% vs 79%, P = .005) and intervention conversations occurred a median of 2.4 months earlier (median, 143 days vs 71 days, P < .001). Conversation documentation for intervention patients was significantly more comprehensive and patient centered, with a greater focus on values or goals (89% vs 44%, P < .001), prognosis or illness understanding (91% vs 48%, P < .001), and life-sustaining treatment preferences (63% vs 32%, P = .004). Documentation about end-of-life care planning did not differ between arms (80% intervention vs 68% control, P = .08). Significantly more intervention patients had documentation that was accessible in the EMR (61% vs 11%, P < .001). CONCLUSIONS AND RELEVANCE This communication quality-improvement intervention resulted in more, earlier, better, and more accessible serious illness conversations documented in the EMR. To our knowledge, this is the first such study to demonstrate improvement in all 4 of these outcomes.

*Deep tendon, plantar, Babinski reflexes if tele-examiner present Limitations of the telemedicine neurologic examination Comprehensive eye examination Cannot assess corneal reflex May be difficult to assess visual fields Neuromuscular examination Reflex testing may not be possible Difficult to fully assess peripheral strength and grade subtle strength differences between sides of the body Limited assessment of tone and rigidity May be hard to detect subtle signs of Parkinson's disease: in particular rigidity and retropulsion pull testing 44 Vestibular examination Cannot perform HINTs exam (Head Impulse, Nystagmus, Test-of-skew) for vestibular syndrome Cerebellar examination Cannot perform Dix-Hallpike test for cerebellar infarction FDA, Food and Drug Administration. *Elements of the examination that may be more difficult to perform.