Nivolumab maintenance improves overall survival of patients with advanced melanoma who experience severe immune-related adverse events on nivolumab plus ipilimumab.

BACKGROUND: The combination of ipilimumab and nivolumab is a highly effective treatment for metastatic cutaneous melanoma. However, immune-related adverse events (irAEs) are common, often necessitating treatment interruption and the use of immunosuppressive agents. There is no data on the impact of resuming nivolumab on survival following recovery from the irAE and completion of immunosuppressive treatment. PATIENTS AND METHODS: In this retrospective analysis, we examined a cohort of patients treated with ipilimumab/nivolumab who developed irAEs requiring treatment interruption and immunosuppressive therapy. The differences in physician practice patterns at our institution allowed us to examine the survival effect of restarting single-agent nivolumab. A multivariate analysis of clinical factors associated with improved survival was performed. RESULTS: We identified 165 patients who were treated with ipilimumab/nivolumab and developed irAEs requiring treatment interruption and immunosuppressive therapy. Patients with the best overall response of progressive disease were excluded. Of the remaining 122 patients, 46 resumed single-agent nivolumab. When stratified by age and adjusted for sex, M-stage, lactate dehydrogenase (LDH), therapy duration, and irAE type, the effect of resumption of nivolumab on survival was highly significant (p=0.02). Patients who resumed nivolumab had a 68% reduction in the hazard of death compared with patients who had not yet or never resumed nivolumab (HR: 0.32, 95% CI: 0.12 to 0.84). Of the patients who resumed nivolumab, 12 (26%) patients had subsequent irAEs, with five patients having grade 3 irAEs. No grade 4 or 5 irAEs were noted. CONCLUSIONS: Resuming single-agent nivolumab following a treatment interruption for ipilimumab/nivolumab-associated irAE and completion of immunosuppressive therapy increased overall survival compared with discontinuing nivolumab permanently in patients with metastatic melanoma. Toxicity observed post-resumption of single-agent nivolumab was manageable with no severe irAEs observed.

Assessing healthcare provider knowledge of human trafficking.

BACKGROUND AND OBJECTIVES: Human trafficking is a significant problem in which healthcare workers are in a unique position to intervene. This study sought to determine the self-reported knowledge levels of healthcare providers most likely to come in direct contact with victims of human trafficking. METHODS: An anonymous survey assessing self-reported knowledge of human trafficking was developed and distributed online. Demographic information and questions pertaining to training and knowledge of trafficking in a healthcare setting were asked. The primary outcomes were descriptive statistics and secondary outcomes were comparisons among demographic groups. Qualitative methodology via content analysis was implemented on an open-ended question. RESULTS: The 6,603 respondents represented all regions of the country. Medical, nursing, and physician assistant students comprised 23% of the sample, while 40% were either physicians, fellows, or residents. Less than half the respondents (42%) have received formal training in human trafficking, while an overwhelming majority (93%) believe they would benefit by such training. Overall, respondents thought their level of knowledge of trafficking was average to below average (mean = 2.64 on a 5-point scale). There were significant differences in knowledge of trafficking by age group (p < .001), region (p < .001), and educational training level (p < .001). 949 respondents (14.4%) provided free-text comments that further described their opinions. CONCLUSION: Most respondents stated they have not received training but felt they would benefit from it. There were significant differences between demographic groups. Further innovation is needed to design a universally appropriate curriculum on human trafficking that is accessible to all healthcare providers as well as mandatory training programs for healthcare institutions.

Considerations on Conducting Research on Wellness in the Context of the Learning Environment.

The learning environment (LE) provides a context for many educational phenomena, of which wellness and burnout are particularly important. The LE can be thought of as consisting of a psychosocial dimension of personal, social, and organizational factors and a sociomaterial dimension that consists of spatial and technical factors. The interplay between elements of the LE and wellness of the participants is complex and only partially understood, requiring further research. Using this multidimensional model to describe and to plan to deliberately modify the learning environment can foster more rigorous and meaningful research evidence about the interaction of wellness and the LE. This article highlights four key considerations that scholars of wellness should consider when exploring the impact of the LE or designing interventions to modify the environment. These include 1) a thoughtful definition and theoretical conceptualization of the LE, 2) clarity about the study variables that are essential to the study question(s), 3) thoughtful and appropriate measurement of those variables, and 4) a study design that balances quality with feasibility. We provide a practical illustration of how these considerations can be applied in studies exploring the intersection of wellness and the LE.

Long-term Quality of Life in Survivors of Brain Metastases: A Roller Coaster of Perspective.

Longevity in cancer patients with brain metastases is increasingly being observed. This raises discussions about how best to maintain a good quality of life for these patients. Recent data suggest that post-treatment quality of life (QoL) can be maintained using new treatment options, but little data exist regarding the QoL in long-term survivors. This study of 19 patients surviving greater than two years from the initial treatment of brain metastases suggests that long-term QoL can be better than at the start of treatment and perhaps even better than normal, especially between three and five years post-treatment. This improved QoL seems mostly attributable to improved functional and social well-being and is possible as long as emotional and physical well-being are maintained within the normal range.

Management of small bowel adenocarcinoma.

Small bowel adenocarcinoma is a relatively rare malignancy. Only limited information is available on the incidence, prognosis, and role of chemotherapy in the treatment of this disease. We present a review of currently available clinical data to assist the practicing oncologist in the treatment of these patients. Approximately 5,300 new cases and 1,100 deaths from small bowel adenocarcinoma are reported annually in the United States. Increased incidence is seen in patients with Crohn's disease, hereditary nonpolyposis colorectal cancer, and familial adenomatouspolyposis. Factors associated with poor prognosis are age > 75 years, lack of surgical resection, advanced stage, and tumor arising in the duodenum. The median survival of patients with localized, locally advanced, and metastatic disease is 50.1, 22.2, and 8.6 months, respectively. Few data exist on the use of (neo)adjuvant or palliative chemo(radio)therapy in this setting. Fluorouracil (5-FU)based chemotherapy, as a single agent or in combination with others, has been used in most case series. Duodenal adenocarcinoma accounts for more than 50% of all cases of small bowel adenocarcinoma. Resectability is the key prognostic factor, along with age, performance status, tumor location, and presence of distant metastasis. Although the activity of 5-FU-based regimens has been documented, the assessment of clinical benefit is hindered by the lack of prospective, randomized data.