Background: TROP2 (TACSTD2) expression is associated with decreased overall survival (OS) in some solid tumors, and the TROP2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan has been approved in breast and urothelial carcinomas. We aimed to explore the multi-omic landscape associated with TACSTD2 gene expression in various solid tumors to identify patients most likely to benefit from this approach. Methods: Breast (N = 11 246), colorectal (N = 15 425), hepatocellular (N = 433), pancreatic (N = 5488), and urothelial (N = 4125) tumors were stratified into quartiles by TACSTD2 gene expression, analyzed by next-generation DNA sequencing, whole transcriptome sequencing, and immunohistochemistry at Caris Life Sciences (Phoenix, AZ). Survival data were obtained from insurance claims, and Kaplan-Meier estimates were calculated for molecularly defined cohorts. Results: Several pathogenic mutations were associated with TACSTD2-high tumors, including TP53 in breast, colorectal (CRC), pancreatic, and hepatocellular cancers; KRAS in pancreatic and CRC cancers; ARID1A and FGFR3 in urothelial cancer; and CTNNB1 in hepatocellular cancer. TACSTD2-low breast tumors were enriched for copy number amplifications in CCND1 and FGF/R family member genes. TACSTD2 high was generally associated with more immune cell infiltration and greater T-cell inflammation scores. Patients with TACSTD2-high breast, CRC, and pancreatic cancers demonstrated a significantly shorter OS than TACSTD2-low tumors. This was restricted to CRC with microsatellite stable tumors and patients with pancreatic cancer with KRAS-mutant tumors. Patients with breast cancer with TACSTD2-high tumors also experienced significantly worse OS following immune checkpoint inhibitors. Conclusions: TACSTD2 expression is associated with key driver alterations and a more active immune microenvironment, suggesting possible combinatorial strategies with TROP2-targeting ADCs plus immunotherapy in various solid tumors.

Malignant pleural mesothelioma (MPM) represents a relatively rare histologic tumor type both in the US and globally. It accounts for less than 0.17% (approximately 3000 total) of all US tumor diagnoses as of 2018, and this proportion is expected to continue decreasing given greater awareness of causality linked to asbestos exposure.¹ Guidelines suggest that multimodality therapy, including surgery, chemotherapy, and possible radiation therapy, can lead to the best possible outcomes for this rare tumor type.² Unfortunately, outcomes of localized MPM remain poor despite multimodality therapy.

Background: Despite the increasing adoption of stereotactic body radiotherapy (SBRT) as a recommended alternative for early-stage non–small cell lung cancer (NSCLC), population-based research on racial/ethnic disparities in curative-intent treatment accounting for SBRT remains limited. This study investigated trends and disparities in receiving curative-intent surgery and/or SBRT in a diverse, retrospective cohort. Methods: Early-stage NSCLC cases (2005–2017) from the Florida cancer registry were linked to individual-level statewide discharge data containing comorbidities and specific treatment information. Joinpoint regression assessed trends in treatment receipt. Multivariable logistic regression examined associations between race/ethnicity and treatment type. Results: Among 64,999 patients with early-stage NSCLC, 71.6% received curative-intent treatment (surgery and/or SBRT): 73.1%, 72.4%, and 60.3% among Hispanic, White, and Black patients, respectively (P < 0.01). SBRT use increased steeply from 2005 to 2007 and then by 7.9% annually from 2007 to 2017 (P < 0.01); curative-intent surgery remained stable from 2005 to 2014 before declining by 6.2% annually during 2014–2017 (P = 0.04). The Black-White disparity in receipt of curative-intent treatment was significant [ORadj, 0.65; 95% confidence interval (CI), 0.60–0.71]. Patients with Charlson comorbidity index (CCI)≥3 had 36% (ORadj, 0.64; 95% CI, 0.60–0.69) lower odds of receiving curative-intent surgery and no significant difference for SBRT (ORadj, 1.06; 95% CI, 0.93–1.20) compared with CCI = 0. Conclusions: Racial disparities in receiving curative-intent treatment for early-stage NSCLC persist despite the availability of SBRT, suggesting the full potential of curative-intent treatment for early-stage NSCLC remains unachieved. Impact: Addressing disparities in early-stage NSCLC requires addressing differential treatment patterns and enhancing accessibility to treatments like underutilized SBRT, particularly for high-comorbidity populations such as Black patients.

Background: Despite United States Preventive Services Task Force (USPSTF) recommendations, low uptake of lung cancer screening (LCS) highlights the need for measures to promote adoption. This scoping review aims to outline the global landscape of mobile low-dose computed tomography (LDCT) platforms, summarizing research and evaluating efficacy in screening at-risk populations. Methods: We comprehensively searched Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Embase, Scopus, and Web of Science for articles published between 2017 and 2023. Selected studies focused on mobile LCS programs using LDCT, providing details on program location, design, sample size, age, targeted population, lung cancer detection rate, and outcomes. Only studies meeting these criteria were considered. Results: The search found 12 studies meeting inclusion criteria, documenting ten mobile LDCT platforms across several countries. These studies primarily evaluated platform effectiveness in screening populations at risk, particularly targeting individuals who have ever smoked, high-risk individuals, and underserved populations. Two studies compared outcomes between mobile and hospital-based screening, while 10 other studies reported outcomes from mobile LDCT platforms. In US studies, most participants in mobile LCS programs came from rural areas, were uninsured or under-insured, and included a notable number of racial/ethnic minorities. The frequency of lung cancer diagnoses ranged from 0.33% to 3%, with the majority (80%) of detected at stages I and II. Conclusions: The mobile LDCT platforms emerge as a powerful solution to enhance access to LCS, especially for marginalized populations. By improving screening rates and enabling early detection, these platforms hold promise in narrowing healthcare disparities. Mobile LDCT presents a crucial opportunity to save lives and promote equity in healthcare access.

Tipifarnib is the only targeted therapy breakthrough for HRAS-mutant (HRASmt) recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The molecular profiles of HRASmt cancers are difficult to explore given the low frequency of HRASmt. This study aims to understand the molecular co-alterations, immune profiles, and clinical outcomes of 524 HRASmt solid tumors including urothelial carcinoma (UC), breast cancer (BC), non-small-cell lung cancer (NSCLC), melanoma, and HNSCC. HRASmt was most common in UC (3.0%), followed by HNSCC (2.82%), melanoma (1.05%), BC (0.45%), and NSCLC (0.44%). HRASmt was absent in Her2+ BC regardless of hormone receptor status. HRASmt was more frequently associated with squamous compared to non-squamous NSCLC (60% vs. 40% in HRASwt, p = 0.002). The tumor microenvironment (TME) of HRASmt demonstrated increased M1 macrophages in triple-negative BC (TNBC), HNSCC, squamous NSCLC, and UC; increased M2 macrophages in TNBC; and increased CD8+ T-cells in HNSCC (all p < 0.05). Finally, HRASmt was associated with shorter overall survival in HNSCC (HR: 1.564, CI: 1.16–2.11, p = 0.003) but not in the other cancer types examined. In conclusion, this study provides new insights into the unique molecular profiles of HRASmt tumors that may help to identify new targets and guide future clinical trial design.

PURPOSE: In the United States, there are disparities in access to care for patients with non–small cell lung cancer (NSCLC) on the basis of socioeconomic and racial/ethnic factors. This study investigates the association between race/ethnicity and the utilization of immune checkpoint inhibitor (ICI) therapy among older patients with advanced NSCLC (aNSCLC). METHODS: This retrospective study used data from the SEER-Medicare–linked database. The cohort included patients (age 66 years or older) diagnosed with aNSCLC (stage III/IV) between March 2015 and December 2017, and they were followed through December 2019. Race/ethnicity was categorized as non-Hispanic (NH)-White, NH-Black, Hispanic, and Other. ICI therapy utilization was determined by identifying any usage of ICI agents (nivolumab, pembrolizumab, atezolizumab, durvalumab, ipilimumab, and cemiplimab-rwlc) from the Medicare database. Multivariable logistic regression models assessed the association between race/ethnicity and ICI therapy utilization (yes, no). Effect measure modification analyses were conducted by sex, socioeconomic status, and comorbidity. RESULTS: The final sample included 26,836 patients; 76.2% were NH-White, 10.1% NH-Black, 5.7% Hispanic, and 8.0% Other. The overall ICI therapy utilization proportion was 17.8%, varying across ethnicities: NH-Black 14.1%, Hispanic 16.3%, NH-White 18.4%, and Other 18.5%. In comparison with NH-White patients, NH-Black patients were 15% less likely to receive ICI therapy (adjusted odds ratio, 0.85 [95% CI, 0.75 to 0.96]). Furthermore, the association between race/ethnicity and utilization of ICI therapy was modified by comorbidity status, sex, and socioeconomic status. CONCLUSION: NH-Black patients with aNSCLC were less likely to receive ICI therapy than their NH-White counterparts. Our findings indicate the racial/ethnic disparities in ICI therapy utilization and call for further interventions to optimize access to care.