The performance status gap in immunotherapy for frail patients with advanced non-small cell lung cancer.

PURPOSE: In advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI) monotherapy is often preferred over intensive ICI treatment for frail patients and those with poor performance status (PS). Among those with poor PS, the additional effect of frailty on treatment selection and mortality is unknown. METHODS: Patients in the veterans affairs national precision oncology program from 1/2019-12/2021 who received first-line ICI for advanced NSCLC were followed until death or study end 6/2022. Association of an electronic frailty index with treatment selection was examined using logistic regression stratified by PS. We also examined overall survival (OS) on intensive treatment using Cox regression stratified by PS. Intensive treatment was defined as concurrent use of platinum-doublet chemotherapy and/or dual checkpoint blockade and non-intensive as ICI monotherapy. RESULTS: Of 1547 patients receiving any ICI, 66.2% were frail, 33.8% had poor PS (≥ 2), and 25.8% were both. Frail patients received less intensive treatment than non-frail patients in both PS subgroups (Good PS: odds ratio [OR] 0.67, 95% confidence interval [CI] 0.51 - 0.88; Poor PS: OR 0.69, 95% CI 0.44 - 1.10). Among 731 patients receiving intensive treatment, frailty was associated with lower OS for those with good PS (hazard ratio [HR] 1.53, 95% CI 1.2 - 1.96), but no association was observed with poor PS (HR 1.03, 95% CI 0.67 - 1.58). CONCLUSION: Frail patients with both good and poor PS received less intensive treatment. However, frailty has a limited effect on survival among those with poor PS. These findings suggest that PS, not frailty, drives survival on intensive treatment.

Teleoncology in the Veterans Health Administration: Models of Care and the Veteran Experience.

The Veterans Health Administration (VHA) has pioneered teleoncology to address access challenges faced by Veterans requiring cancer care. This ASCO Educational Book highlights the development of teleoncology programs within the VHA: the local VA Pittsburgh Healthcare System (VAPHS) Virtual Cancer Care Center, the National TeleOncology Program (NTO), and the regional Clinical Resource Hub (CRH) Oncology Program. These initiatives provide oncology care using a hub-and-spoke model, which centralizes expertise at hub sites and reaches Veterans at distant spoke sites through synchronous and asynchronous care. The deployment of these teleoncology programs has resulted in significant benefits, such as decreased travel for Veterans, high levels of patient satisfaction, and improved access to specialized treatments. Despite these advancements, disparities in teleoncology utilization and access to clinical trials persist. This educational manuscript highlights the successes and challenges of tele-oncology within the VHA, underscoring the critical role of telehealth in overcoming access barriers.

Randomized Trial of a Volunteer-Led Symptom Assessment Intervention on Documentation, Patient-Reported Outcomes, and Health Care Use Among Veterans With Lung Cancer.

PURPOSE: Identification and documentation of Veterans' symptoms are crucial for optimal lung cancer care delivery. The objective of this study was to determine whether a volunteer-led proactive telephone symptom assessment intervention could improve comprehensive symptom documentation. METHODS: Veterans with lung cancer were randomly assigned to usual care (control group) or usual care with proactive symptom assessment in which a peer volunteer made weekly phone calls to assess patient symptoms under nurse practitioner supervision. The primary outcome was oncologist documentation of symptoms in the electronic health record at all clinical visits within 6 months after enrollment. Secondary outcomes included patient satisfaction with decision, patient activation, health-related quality of life (HRQOL), and symptom burden, measured at baseline, and 3, 6, and 9 months after enrollment, and acute care use within 9 months after enrollment. RESULTS: Among 60 Veterans randomly assigned, median (range) age was 70.2 (50-86) years; 57 (95.0%) were male. More intervention participants had oncologist documentation of symptoms than control group participants (24 [77.4%] v seven [24.1%], respectively; odds ratio, 16.46 [95% CI, 4.58 to 59.16]). Intervention group participants had greater improvements over time in HRQOL (expected mean difference, 25.3 [95% CI, 15.00 to 35.70]) and patient activation (expected mean difference, 13.6 [95% CI, 3.79 to 23.39]), lower symptom burden (expected mean difference, -6.39 [95% CI, -15.21 to -2.46]), lower rates of emergency room visits (incidence rate ratio, 0.48 [95% CI, 0.30 to 0.75]), and hospitalizations (incidence rate ratio, 0.47 [95% CI, 0.28 to 0.77]) than control group participants. CONCLUSION: This symptom assessment intervention is an effective strategy for Veterans with lung cancer.

UCHL1 is a potential molecular indicator and therapeutic target for neuroendocrine carcinomas.

Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis and limited therapeutic options. We report that ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme, is elevated in tissues and plasma from patients with neuroendocrine carcinomas. Loss of UCHL1 decreases tumor growth and inhibits metastasis of these malignancies. UCHL1 maintains neuroendocrine differentiation and promotes cancer progression by regulating nucleoporin, POM121, and p53. UCHL1 binds, deubiquitinates, and stabilizes POM121 to regulate POM121-associated nuclear transport of E2F1 and c-MYC. Treatment with the UCHL1 inhibitor LDN-57444 slows tumor growth and metastasis across neuroendocrine carcinomas. The combination of UCHL1 inhibitors with cisplatin, the standard of care used for neuroendocrine carcinomas, significantly delays tumor growth in pre-clinical settings. Our study reveals mechanisms of UCHL1 function in regulating the progression of neuroendocrine carcinomas and identifies UCHL1 as a therapeutic target and potential molecular indicator for diagnosing and monitoring treatment responses in these malignancies.