To evaluate the timing of mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B1) during melanocytic neoplasia, we carried out mutation analysis on microdissected melanoma and nevi samples. We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi. These data suggest that mutational activation of the RAS/RAF/MAPK pathway in nevi is a critical step in the initiation of melanocytic neoplasia but alone is insufficient for melanoma tumorigenesis.

Purpose Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity. Patients and Methods Patients age ≥ 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events. Results In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P < .001). Conclusion A risk stratification schema can establish the risk of chemotherapy toxicity in older adults. Geriatric assessment variables independently predicted the risk of toxicity.

Purpose Factors captured in a geriatric assessment can predict morbidity and mortality in older adults, but are not routinely measured in cancer clinical trials. This study evaluated the implementation of a geriatric assessment tool in the cooperative group setting. Patients and Methods Patients age ≥ 65 with cancer, who enrolled on cooperative group cancer trials, were eligible to enroll on Cancer and Leukemia Group B (CALGB) 360401. They completed a geriatric assessment tool before initiation of protocol therapy, consisting of valid and reliable geriatric assessment measures which are primarily self-administered and require minimal resources and time by healthcare providers. The assessment measures functional status, comorbidity, cognitive function, psychological state, social support, and nutritional status. The protocol specified criteria for incorporation of the tool in future cooperative group trials was based on the time to completion and percent of patients who could complete their portion without assistance. Patient satisfaction with the tool was captured. Results Of the 93 patients who enrolled in this study, five (5%) met criteria for cognitive impairment and three did not complete the cognitive screen, leaving 85 assessable patients (median age, 72 years). The median time to complete the geriatric assessment tool was 22 minutes, 87% of patients (n = 74) completed their portion without assistance, 92% (n = 78) were satisfied with the questionnaire length, 95% (n = 81) reported no difficult questions, and 96% (n = 82) reported no upsetting questions. One hundred percent of health care professionals completed their portion. Conclusion This brief, primarily self-administered geriatric assessment tool met the protocol specified criteria for inclusion in future cooperative group clinical trials.