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Background: Bone metastases and skeletal-related events (SREs) are a frequent cause of morbidity in patients with metastatic non–small cell lung cancer (mNSCLC). Data are limited on bone metastases and SREs in patients with mNSCLC treated using immune checkpoint inhibitors (ICIs), and on the efficacy of bone-modifying agents (BMAs) in this setting. Here we report the incidence, impact on survival, risk factors for bone metastases and SREs, and impact of BMAs in patients with mNSCLC treated with ICIs in a multi-institutional cohort. Patients and Methods: We conducted a retrospective study of patients with mNSCLC treated with ICIs at 2 tertiary care centers from 2014 through 2017. Overall survival (OS) was compared between patients with and without baseline bone metastases using a log-rank test. A Cox regression model was used to evaluate the association between OS and the presence of bone metastases at ICI initiation, controlling for other confounding factors. Results: We identified a cohort of 330 patients who had received ICIs for metastatic disease. Median patient age was 63 years, most patients were treated in the second line or beyond (n=259; 78%), and nivolumab was the most common ICI (n=211; 64%). Median OS was 10 months (95% CI, 8.4–12.0). In our cohort, 124 patients (38%) had baseline bone metastases, and 43 (13%) developed SREs during or after ICI treatment. Patients with bone metastases had a higher hazard of death after controlling for performance status, histology, line of therapy, and disease burden (hazard ratio, 1.57; 95% CI, 1.19–2.08; P=.001). Use of BMAs was not associated with OS or a decreased risk of SREs. Conclusions: Presence of bone metastases at baseline was associated with a worse prognosis for patients with mNSCLC treated with ICI after controlling for multiple clinical characteristics. Use of BMAs was not associated with reduced SREs or a difference in survival.

Key Points Question Is the American Joint Committee on Cancer (AJCC) eighth edition staging of metastatic cutaneous melanoma prognostic in the era of immune checkpoint inhibition? Findings In this cohort study of 357 patients with metastatic cutaneous melanoma treated with immune checkpoint inhibitors, the AJCC eighth edition M staging showed limited prognostic stratification; however, the overall survival rates among patients with liver metastases and those with elevated serum lactate dehydrogenase (LDH) levels were much worse than among patients with metastatic involvement of other organs and those with serum LDH levels in the reference range. The importance of these factors was confirmed in a multi-institutional external validation cohort. Meaning These findings suggest that other biomarkers that are associated with overall survival, such as liver metastases and LDH level, should be considered for emphasis in future staging systems.

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OBJECTIVE Cervical nerve 5 palsy can occur following surgery for cervical spine pathology. The prognosis of C5 palsy is generally favorable, and most patients recover useful function. However, some patients do not recover useful strength. Nerve transfers are a potential effective treatment of postoperative severe C5 palsy. This study aimed to further delineate the natural history of recovery from postoperative C5 palsy, determine whether lack of recovery at specific time points predicts poor recovery prognosis, and thereby determine a reasonable time point for referral to a complex peripheral nerve specialist. METHODS The authors conducted a retrospective review of 72 patients who underwent surgery for cervical spondylosis and stenosis complicated by C5 palsy. Medical Research Council (MRC) motor strength grades were recorded preoperatively; immediately postoperatively; at discharge; and at 2 weeks, 3 months, 6 months, and 12 months postoperatively. Univariate and multivariate logistic regression models were used to identify demographic and clinical risk factors associated with recovery of useful strength after severe C5 palsy. RESULTS The mean patient age was 62.5 years, and 36.1% of patients were female. Thirty patients (41.7%) experienced severe C5 palsy with less than antigravity strength (MRC grade 2 or less) at discharge. Twenty-one (70%) of these patients recovered useful strength (MRC grade 3 or greater) at 12 months postoperatively, and 9 patients (30%) did not recover useful strength at 12 months. Of those patients with persistent severe C5 palsy at 3 months postoperatively, 50% recovered useful strength at 12 months. Of those patients with persistent severe C5 palsy at 6 months postoperatively, 25% recovered useful strength at 12 months. No patient with MRC grade 0 or 1 strength at 6 months postoperatively recovered useful strength. A history of diabetes was associated with the occurrence of severe C5 palsy. On multivariate analysis, female sex was associated with recovery of useful strength. CONCLUSIONS Most patients with severe C5 palsy recover useful strength in their C5 myotome within 12 months of onset. However, at 3 months postoperatively, patients with persistent severe C5 palsy had only a 50% chance of recovering useful strength by 12 months. Lack of recovery of useful strength at 3 months postoperatively is a reasonable time point for referral to a complex peripheral nerve center to establish care and to determine candidacy for nerve transfer surgery if severe C5 palsy persists.

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