RESUMO

PURPOSE: A combination of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard for adjuvant therapy of resected early-stage colon cancer (CC). Oxaliplatin leads to lasting and disabling neurotoxicity. Reserving the regimen for patients who benefit from oxaliplatin would maximize efficacy and minimize unnecessary adverse side effects. METHODS: We trained a new machine learning model, referred to as the colon oxaliplatin signature (COLOXIS) model, for predicting response to oxaliplatin-containing regimens. We examined whether COLOXIS was predictive of oxaliplatin benefits in the CC adjuvant setting among 1,065 patients treated with 5-fluorouracil plus leucovorin (FULV; n = 421) or FULV + oxaliplatin (FOLFOX; n = 644) from NSABP C-07 and C-08 phase III trials. The COLOXIS model dichotomizes patients into COLOXIS+ (oxaliplatin responder) and COLOXIS- (nonresponder) groups. Eight-year recurrence-free survival was used to evaluate oxaliplatin benefits within each of the groups, and the predictive value of the COLOXIS model was assessed using the P value associated with the interaction term (int P) between the model prediction and the treatment effect. RESULTS: Among 1,065 patients, 526 were predicted as COLOXIS+ and 539 as COLOXIS-. The COLOXIS+ prediction was associated with prognosis for FULV-treated patients (hazard ratio [HR], 1.52 [95% CI, 1.07 to 2.15]; P = .017). The model was predictive of oxaliplatin benefits: COLOXIS+ patients benefited from oxaliplatin (HR, 0.65 [95% CI, 0.48 to 0.89]; P = .0065; int P = .03), but COLOXIS- patients did not (COLOXIS- HR, 1.08 [95% CI, 0.77 to 1.52]; P = .65). CONCLUSION: The COLOXIS model is predictive of oxaliplatin benefits in the CC adjuvant setting. The results provide evidence supporting a change in CC adjuvant therapy: reserve oxaliplatin only for COLOXIS+ patients, but further investigation is warranted.

Assuntos

Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo , Fluoruracila , Leucovorina , Aprendizado de Máquina , Oxaliplatina , Humanos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Compostos Organoplatínicos/uso terapêutico , Compostos Organoplatínicos/administração & dosagem , Quimioterapia Adjuvante , Adulto , Ensaios Clínicos Fase III como Assunto , Estadiamento de Neoplasias

RESUMO

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The primary joint efficacy analysis of the Anthracyclines in Early Breast Cancer (ABC) trials reported in 2017 failed to demonstrate nonanthracycline adjuvant therapy was noninferior to anthracycline-based regimens in high-risk, early breast cancer. Full analyses of the studies had proceeded when the prespecified futility boundary was crossed at a planned futility analysis for the ability to demonstrate noninferiority of a nonanthracycline regimen with continued follow-up. These results were presented with 3.3 years of median follow-up. This manuscript reports results of the final analyses of the study efficacy end points conducted with 6.9 years of median follow-up. Long-term analysis of invasive disease-free survival (IDFS), the primary end point of the ABC trials, remains consistent with the original results, as noninferiority of the nonanthracycline regimens could not be declared on the basis of the original criteria. The secondary end point of recurrence-free interval, which excluded deaths not due to breast cancer as events, favored anthracycline-based regimens, and tests for heterogeneity were significant for hormone receptor status (P = .02) favoring anthracycline regimens for the hormone receptor-negative cohorts. There was no difference in overall survival, and review of the type of IDFS events in the groups suggested reductions in cancer recurrences achieved with anthracycline regimens were offset by late leukemias and deaths unrelated to breast cancer.

Assuntos

Neoplasias da Mama , Taxoides , Humanos , Feminino , Taxoides/uso terapêutico , Seguimentos , Neoplasias da Mama/tratamento farmacológico , Antraciclinas , Hormônios , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico

RESUMO

PURPOSE: To investigate the level of burnout in the oncology community in the United States. PATIENTS AND METHODS: Seven thousand seven hundred fifteen oncology physicians were queried by e-mail or during attendance at oncologic meetings and asked to complete a 22-question survey concerning their feelings of personal burnout and their perceptions of physician burnout in the oncology community. The data were analyzed using standard statistical methods including a multivariate analyses using logistic regression with stepwise selection. RESULTS: One thousand seven hundred forty oncologists (22.6%) completed and returned the survey, with 92.6 % representing medical oncologists or hematologist-oncologists. Two thirds of the respondents were from community practice and one third from academia. Overall, 61.7% of the respondents reported feelings of burnout, with the top three signs being frustration (78%), emotional exhaustion (69%), and lack of satisfaction with their work (50%). The highest-ranked causes for their feelings of burnout included overwork, lack of time away from the office, and reimbursement concerns. The top remedies for burnout were felt to be fewer patients, more time away from the office, and increased attendance at medical meetings. The multivariate analyses demonstrated highly significant associations between burnout and hours spent on patient care, personal time off, and number of educational meetings attended. CONCLUSION: The rate of burnout in the oncology community of the United States exceeds 60%. This report suggests causes and potential solutions for the high rate of burnout. Such information may lead to an improved understanding of the needed steps to improve the quality of life for the oncology community with the ultimate goal of further improving patient care. Patients deserve optimal medical and emotional support that is best provided by caring and well-informed practitioners.