The major histocompatibility complex class I (MHCI) is a large gene family, with over 30 members in mouse. Some MHCIs are well-known for their critical roles in the immune response. Studies in mice which lack stable cell-surface expression of many MHCI proteins suggest that one or more MHCIs also play unexpected, essential roles in the establishment, function, and modification of neuronal synapses in the central nervous system (CNS). However, there is little information about which genes mediate MHCI’s effects in neurons. In this study, RT-PCR was used to simultaneously assess transcription of many MHCI genes in regions of the central and peripheral nervous system where MHCI has a known or suspected role. In the hippocampus, a part of the CNS where MHCI regulates synapse density, synaptic transmission, and plasticity, we found that more than a dozen MHCI genes are transcribed. Single-cell RT-PCR revealed that individual hippocampal neurons can express more than one MHCI gene, and that the MHCI gene expression profile of CA1 pyramidal neurons differs significantly from that of CA3 pyramidal neurons or granule cells of the dentate gyrus. MHCI gene expression was also assessed at the neuromuscular junction (NMJ), a part of the peripheral nervous system (PNS) where MHCI plays a role in neuronal regeneration, and could potentially influence developmental synapse elimination. Four MHCI genes are expressed at the NMJ at an age when synapse elimination is occurring in three different muscles. Several MHCI mRNA splice variants were detected in hippocampus, but not at the NMJ. Together, these results establish the first profile of MHCI gene expression at the developing NMJ, and demonstrate that MHCI gene expression is under tight spatial and temporal regulation in the nervous system. They also identify more than a dozen MHCIs that could play important roles in synaptic transmission and plasticity in the central and peripheral nervous systems.

83 Background: Concurrent chemotherapy (CTX) with checkpoint inhibitors (CPI) has become a new standard of care for treatment naïve stage IV non-small cell lung cancer (NSCLC). Little is known about the timing and pattern of immune-related adverse events (irAEs) when CTX and CPI are combined. We sought to characterize irAEs and determine if combination CTX+CPI affects time to first irAE in comparison to patients (pts) receiving CPI alone. Methods: Advanced NSCLC patients who received at least one dose of a CPI at our institution between 2015 and 2018, either alone or with CTX, were identified. Retrospective review for occurrence of irAEs and clinical outcomes was performed. Proportional hazards models were used to assess time to first irAE for CPI vs CTX+CPI and overall survival (OS) for CPI alone. Results: 149 pts were identified. 112 pts received CPI alone and 37 received CTX+CPI. The proportion of pts with at least 1 irAE was higher in the combination therapy group than the monotherapy group (59% vs 34% of patients). Time to any grade first irAE was shorter with CTX+CPI vs CPI alone (6.0 m vs 36.7 m, HR 1.8, p = 0.0304). Among pts treated with CPI alone, OS was significantly longer with any irAE (38.0 m vs 11.4 m, HR 2.9, p = 0.0026). While there were more irAEs in the CTX+CPI cohort, the frequency of irAEs by organ system was similar to previous reports. Conclusions: For patients receiving CTX+CPI, there is an increased risk of irAEs and a significantly shorter time to first irAE occurrence compared to CPI alone. Among patients receiving CPI alone, the presence of irAE was associated with a 3-fold improvement in OS. Further analysis of OS for the CTX+CPI group is planned with additional follow-up. [Table: see text]

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Background: Lung cancer (LC) is the leading cause of cancer death in Asian Americans, the fastest growing racial/ethnic group in the US. Early palliative care (PC) is recommended for patients with stage IV LC. Research on PC and end of life care (EOLC) for Asian patients (AP) with stage IV LC in the US is limited. This retrospective study examines racial influences on PC and EOLC in patients with stage IV LC at an urban academic medical center serving a large proportion of AP. Methods: Patients newly diagnosed with stage IV LC from 01/01/2014 to 12/31/2019 were identified from Tufts Medical Center cancer registry. Baseline demographics, disease characteristics, treatment history, PC and hospice use, and EOLC were compared between AP and White patients (WP) by Mann-Whitney U test and Chi-square/Fisher's exact tests for continuous and categorical variables, respectively. Time to palliative care (TTPC) in AP and WP was compared via log-rank test. Results: Of 89 AP and 197 WP (similar median age: 71 and 68 years old, respectively), AP had significantly more male representation (71.9% vs 48.2%), never-smokers (36.0% vs 7.1%), non-small cell histology (85.4% vs 72.6%), linguistic diversity (non-English languages: 6 vs 2), and interpreter use (43.8% vs 0.5%), with less preference for English (12% vs 99%). No difference in brain metastasis at diagnosis was noted. PC use was similar in AP and WP (38.2% vs 37.6%); relatively more first encounters occurred inpatient vs outpatient in both groups. Median TTPC tended to be longer in AP (15.7 vs 12.4 months, p=0.120). PC evaluation occurred within 12 months after diagnosis in 27 (30.3%) AP and 63 (32.0%) WP. Of those seen by PC, only 7 (20.6%) AP and 16 (21.3%) WP had more than one PC encounter. Of 22 AP and 74 WP with confirmed death, relatively more AP patients died in hospital (68.2% vs 32.4%, p=0.004), more often in ICU (40.9% vs 24.3%); no differences were found in use of mechanical ventilation (18.2% vs 16.2%) or cardiopulmonary resuscitation (0% vs 1.4%) preceding death. Within 6 months of death, outpatient oncologists and AP patients had fewer code status (0% vs 24.3%, p=0.010) but similar rates of health care proxy (18.2% vs 32.4%, p=0.110) and hospice care (18.2% vs 28.4%, p=0.411) discussions. Hospice enrollment (29.2% vs 32.0%, p=0.722), median time from entering hospice to death (16.5 vs 12.5 days, p=0.795) and from last systemic treatment to death (39 vs 55.5 days, p=0.844) were similar in AP and WP. Conclusion: PC utilization was similarly sub-optimal in AP and WP with newly diagnosed stage IV LC in this study, though TTPC tended to be longer in AP. While hospice utilization was also similar in AP and WP, AP had a higher rate of in-hospital death and fewer code status discussions with their outpatient oncologists in the 6 months preceding death. Whether these findings reflect racial disparities, cultural preferences, or other factors influencing PC and EOLC for AP with advanced LC warrants further study. Citation Format: Xiao Hu, John W. Melson, Stacey Pan, Yana Salei, Yu Cao. Palliative and end of life care utilization in Asian and White patients with stage IV lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5528.

115 Background: Cancer is the leading cause of death in Asian Americans (AA), the fastest growing racial/ethnic group in the US. Lung cancer is a leading cancer diagnosis and cause of cancer death in AA. Yet data on the quality of lung cancer care in AA are limited. This retrospective study examines racial disparities in lung cancer care at an urban academic medical center serving a large proportion of Asian patients. Methods: Newly diagnosed patients with lung cancer from 01/01/2014 to 12/31/2019 were identified in the Tufts Medical Center cancer registry; clinical data were collected through 05/31/2022. Patient demographics, smoking status, utilization of screening low dose CT (LDCT), disease characteristics (diagnosis stage, histology, driver mutation presence), and treatment history were compared between Asian and White patients. The influence of race on presenting stage was evaluated via ordinal logistic regression. Time to treatment initiation (TTI) and overall survival (OS) in Asian and White patients were analyzed via log-rank tests. Multivariable Cox regression adjusting for baseline patient characteristics, tumor histology and stage was performed to evaluate the impact of race on OS. Results: Of 145 Asian and 476 White patients, the Asian cohort had significantly (p < 0.001) older age (72 vs 68 years), more male representation (74.5% vs 43.9%) and never-smokers (31.0% vs 9.7%). Of 45 Asian never-smokers, women comprised 75.6%. Of 216 patients eligible for lung cancer screening by the 2013 USPSTF criteria, the Asian cohort had relatively lower LDCT utilization (11.9% vs 21.3%, p = 0.198). Asians were 2.13 times (p = 0.003) more likely to be diagnosed with lung cancer at a later stage than White patients, adjusting for age, sex, income, smoking status, and histology. No difference was found in presence of CNS metastasis at diagnosis. Driver mutations were more often found in Asians (45.5% vs 29.4%). Of 206 patients with detected oncogenic mutations, EGFR alterations comprised 62.1% vs 15.0% in Asian and White cohorts, respectively. Asian patients had longer median TTI (1.13 vs 0.83 months, p = 0.005) and more often did not receive cancer directed therapy (12.6% vs 6.1%, p = 0.016). Of 536 patients who received cancer directed therapy, Asians more often received upfront targeted therapy (16.1% vs 2.2%, p < 0.001). No difference was seen in median OS between Asian and White (not reached vs 78.43 months, p = 0.410). Multivariable Cox regression suggested that Asians tended toward better OS (hazard ratio = 0.66, p = 0.091). Conclusions: This study done in Boston shows that Asian patients are diagnosed with lung cancer at more advanced stages and experience longer delays prior to treatment initiation, compared to White patients. Racial disparities persist in lung cancer care, particularly in detection/diagnosis and early management. Yet Asian patients, in aggregate, do not have inferior survival, warranting further research.