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e20012 Background: PM 2.5, particulate matter with a diameter of 2.5 micrometers or less, is a major contributor to lung cancer and associated mortality. Epidemiological studies reveal a concerning trend, with each 10 micrograms per cubic meter increase in PM 2.5 associated with a 15% higher risk of lung cancer and a 13% increase in mortality rates, underscoring the significant burden it imposes on public health systems globally. We aimed to evaluate the odds of association between environmental exposure to PM 2.5 and the risk of lung cancer and associated mortality. Methods: We performed a systematic review and umbrella meta-analysis using studies containing quantitative data on PM 2.5 and lung cancer. We used PRISMA guidelines and the MOOSE protocol using PubMed and MeSH terms like PM 2.5, non-small cell cancer, lung cancer, pollutants, particulate matter 2.5, and environmental factors. We had excluded non-full-length articles, non-meta-analysis studies, and non-human studies. RavMan 5.4 was used, and generic inverse variance methods with mixed effect models were applied to identify a pooled risk ratio with a 95% confidence interval. Forest plots were obtained, and sensitivity analysis was performed based on funnel plots and I2 (heterogeneity) values. Results: Of the 245,529 articles evaluated for the quality of the data, 99 met the inclusion and exclusion criteria. Out of 99, we used six articles to derive the quantitative data. In umbrella meta-analysis, PM 2.5 exposure was associated with a 1.16 times higher risk (95%CI: 1.1-1.22, p<0.00001, I2=0%) of lung cancer and a 1.22 times higher risk of non-lung cancers (95%CI: 1.15-1.30, p<0.00001, I2=0%). PM 2.5 was associated with non-significant higher mortality (RR: 1.06, 95%CI: 0.99-1.13, p=0.09, I2=97%) with leave-on-out analysis (excluding Chen et al.) significant association between mortality and PM 2.5 (RR: 1.08, 95%CI: 1.06-1.10, p<0.00001, I2=0%). Conclusions: Our umbrella meta-analysis shows a significant risk of lung cancer and mortality from PM 2.5 exposure. Further investigation and increased consciousness are necessary to mitigate the risk of lung cancer associated with this pollutant.

PURPOSE Telisotuzumab vedotin (Teliso-V) is a c-Met–directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536 ) aimed to identify the optimal c-Met protein–overexpressing non–small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage I) and expand the selected group for efficacy evaluation (stage II). Stage II enrolled patients with nonsquamous epidermal growth factor receptor ( EGFR )-wildtype NSCLC. METHODS Eligible patients had locally advanced/metastatic c-Met protein–overexpressing NSCLC and ≤2 previous lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in nonsquamous EGFR -wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%–<50%]). Teliso-V was administered at 1.9 mg/kg once every 2 weeks. The primary end point was overall response rate (ORR) by independent central review. RESULTS In total, 172 patients with nonsquamous EGFR -wildtype NSCLC received Teliso-V in stages I and II. ORR was 28.6% (95% CI, 21.7 to 36.2; c-Met high, 34.6% [95% CI, 24.2 to 46.2]; c-Met intermediate, 22.9% [95% CI, 14.4 to 33.4]). The median duration of response was 8.3 months (95% CI, 5.6 to 11.3; c-Met high, 9.0 [95% CI, 4.2 to 13.0]; c-Met intermediate: 7.2 [95% CI, 5.3 to 11.5]). The median overall survival was 14.5 months (95% CI, 9.9 to 16.6; c-Met high, 14.6 [95% CI, 9.2 to 25.6]; c-Met intermediate, 14.2 [95% CI, 9.6 to 16.6]). The median progression-free survival was 5.7 months (95% CI, 4.6 to 6.9; c-Met high, 5.5 [95% CI, 4.1 to 8.3]; c-Met intermediate: 6.0 [95% CI, 4.5 to 8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 AE was peripheral sensory neuropathy (7%). CONCLUSION Teliso-V was associated with durable responses in c-Met protein–overexpressing nonsquamous EGFR -wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.

LBA3 Background: National guidelines recommend the early integration of palliative and oncology care for patients with advanced cancer, given robust evidence showing that this care model improves quality of life (QOL) and other important outcomes. However, most patients do not receive early palliative care (EPC) in the outpatient setting due to limited access and resources. To overcome these barriers, we conducted a large-scale comparative effectiveness trial of EPC delivered via secure video versus in person among patients with advanced non-small cell lung cancer (NSCLC) and their caregivers. Methods: Between 6/14/2018 and 5/4/2023, we enrolled 1250 patients with advanced NSCLC, diagnosed in the past 12 weeks, into a randomized trial of telehealth versus in-person EPC across 22 cancer centers in the US. Patients were randomly assigned to meet with a palliative care clinician every four weeks from enrollment through the course of disease either via video or in the outpatient clinic. Participants completed self-report measures at baseline and weeks 12 and 24. The primary aim was to evaluate the equivalence of the effect of telehealth versus in-person EPC on QOL at week 24, using regression modeling with an equivalence margin of ±4 points on the Functional Assessment of Cancer Therapy-Lung (FACT-L, range = 0-136). We also compared rates of caregiver participation in EPC visits and patient-reported depression and anxiety symptoms (Patient Health Questionnaire-9; Hospital Anxiety and Depression Scale), coping (Brief COPE), and perceptions of prognosis (Perceptions of Treatment and Prognosis Questionnaire) between groups. Study recruitment ceased for two months at the onset of the COVID-19 pandemic. Results: Participants (mean age = 65.5 years; 54.0% female; 82.1% White) had a mean of 4.75 and 4.92 palliative care encounters by week 24 in the telehealth and in-person groups, respectively. Due to the pandemic, the in-person group had 3.9% of visits occur via video. QOL scores at week 24 for patients assigned to the telehealth group were equivalent to those receiving in-person EPC (adjusted means: 99.67 versus 97.67, p < 0.043 for equivalence). The rate of caregiver participation in EPC visits was lower in the telehealth versus in-person group (36.6% versus 49.7%, p < 0.0001). Study groups did not differ in depression and anxiety symptoms, use of coping skills, or perceptions of the goal of treatment and curability of their cancer. Conclusions: The delivery of EPC via video versus in-person visits demonstrated equivalent effects on QOL in patients with advanced NSCLC. The two modalities also did not differ across a range of patient-reported outcomes, though caregivers attended more in-person versus video visits. The findings underscore the considerable potential for improving access to and broader dissemination of this evidence-based care model through telehealth delivery. Clinical trial information: NCT03375489 .

Abstract Aims Patients with pulmonary hypertension (PH) are grouped based upon clinical and haemodynamic characteristics. Groups 2 (G2, left heart disease [LHD]) and 3 (G3, lung disease or hypoxaemia) are most common. Many patients display overlapping characteristics of heart and lung disease (G2–3), but this group is not well-characterized. Methods and results Patients with PH enrolled in the prospective, NHLBI-sponsored PVDOMICS network underwent intensive clinical, biomarker, imaging, gas exchange and exercise phenotyping. Patients with pure G2, pure G3, or overlapping G2–3 PH were compared across multiple phenotypic domains. Of all patients with predominant G2 (n = 136), 66 (49%) were deemed to have secondary lung disease/hypoxaemia contributors (G2/3), and of all patients categorized as predominant G3 (n = 172), 41 (24%) were judged to have a component of secondary LHD (G3/2), such that 107 had G2–3 (combined G2/3 and G3/2). As compared with G3, patients with G2 and G2–3 were more obese and had greater prevalence of hypertension, atrial fibrillation, and coronary disease. Patients with G2 and G2–3 were more anaemic, with poorer kidney function, more cardiac dysfunction, and higher N-terminal pro-B-type natriuretic peptide than G3. Lung diffusion was more impaired in G3 and G2–3, but commonly abnormal even in G2. Exercise capacity was severely and similarly impaired across all groups, with no differences in 6-min walk distance or peak oxygen consumption, and pulmonary vasoreactivity to nitric oxide did not differ. In a multivariable Cox regression model, patients with G2 had lower risk of death or transplant compared with G3 (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30–0.86), and patients with G2–3 also displayed lower risk compared with G3 (HR 0.57, 95% CI 0.38–0.86). Conclusions Overlap is common in patients with a pulmonary or cardiac basis for PH. While lung structure/function is clearly more impaired in G3 and G2–3 than G2, pulmonary abnormalities are common in G2, even when clinically judged as isolated LHD. Further study is required to identify optimal systematic evaluations to guide therapeutic innovation for PH associated with combined heart and lung disease. Clinical Trial Registration: ClinicalTrials.gov NCT02980887.

1105 Background: Approximately 2-5% of breast cancers harbor HER2 mutations, often occurring in hormone receptor-positive (HR+) disease. There are currently no approved treatment options for patients (pts) with HER2-mutated metastatic breast cancer (HER2-mut MBC). Tucatinib (TUC) is a tyrosine kinase inhibitor highly selective for HER2 and is approved for previously treated HER2+ MBC with or without brain metastases in combination with trastuzumab (Tras) and capecitabine. Here, we report the efficacy and safety results of TUC combined with Tras in pts with previously treated HER2-mut MBC. Methods: SGNTUC-019 (NCT04579380) is an open-label phase 2 basket study evaluating efficacy, safety, and tolerability of TUC and Tras in pts with metastatic HER2-altered solid tumors. Pts in the HER2-mut MBC cohort must have HER2 mutations determined locally by tissue- or blood-based next-generation sequencing, not be HER2+ per local testing, been previously treated with ≥1 systemic therapy in the locally advanced, unresectable, or metastatic setting, and if HR+, have received a CDK4/6 inhibitor. Pts were treated in 21-day cycles with TUC (300 mg orally twice a day) and Tras (8 mg/kg IV followed by 6 mg/kg every 3 wks). Pts with HR+ disease also received fulvestrant (F; 500 mg IM once every 4 wks starting from cycle 1 day 1, and cycle 1 day 15). Disease status was determined based on RECIST v1.1 with assessments performed every 6 wks for 24 wks and every 12 wks thereafter. The primary endpoint is cORR per investigator assessment. Secondary endpoints include OS, DCR, DOR, PFS, and safety. Results: As of Nov 1, 2023, 31 pts were enrolled in the HER2-mut MBC cohort. The median duration of follow-up for OS was 15.0 months. Twenty-seven (87%) pts had HR+ disease and 18 (58%) had lobular histology. The pts received a median of 4 prior lines of systemic therapy in any setting. cORR was 41.9% (90% CI, 26.9-58.2) with 13 responses including 2 complete responses. Median DOR was 12.6 months (90% CI, 4.7, not estimable), DCR was 80.6% (n=25; 90% CI, 65.3-91.2), median PFS was 9.5 months (90% CI, 5.4-13.8), and median OS was 20.1 months (90% CI, 15.9 to not estimable). The most common treatment-emergent adverse events (TEAEs) reported were diarrhea (64.5%) and nausea (35.5%). The most common grade ≥3 TEAEs reported were diarrhea (13%), alanine aminotransferase increase (10%), and hypertension (10%). Two (6.5%) pts discontinued TUC due to TEAEs, but these pts continued Tras. No deaths were due to TEAEs. Additional biomarker analyses will be included in the presentation. Conclusions: The investigational combination of TUC and Tras, plus F in pts with HR+ disease, was well tolerated and had clinical activity in pts with previously treated HER2-mut MBC. The results support further evaluation of the combination of TUC and Tras as a potential treatment option for this pt population. Clinical trial information: NCT04579380 .

11167 Background: Successful outcomes of surgical treatment of cancer requires expertise and high-quality supportive services for surgical care. Previous studies have shown that case volume and availability of other in-house supportive services affect surgical outcomes. Latest studies have shown that this gap has now significantly reduced. Issues related to access, availability of funding for latest technologies and continuous medical education still exist and likely still impact the surgical outcomes. The objective of the study is to understand the impact of surgical center related factors on survival outcomes for cancer patients based on race and other demographic features. Methods: We conducted a retrospective analysis of patients diagnosed with Stage I-III Non-small cell lung cancer (NSCLC) between 2004 to 2020 using the National Cancer Database (NCDB). Patients were divided into 4 cohorts of NCDB assigned facility type (Community Cancer Program, Comprehensive Community Cancer Program, Academic/Research Program, Integrated Network Cancer Program). Racial and other demographic data was analyzed for each of the facility types. Differences in categorical variables were evaluated using a Chi-square test. Results: 298,393 adenocarcinoma and 129,144 squamous cell carcinoma patients underwent surgery for NSCLC between 2004-2020. 326,798 patients with clinical stages I-III were selected for the analysis. Most surgeries were performed at the academic/research programs and comprehensive community programs. Utilization of each facility type was uniform across all races. The 30-day mortality rate was lowest for the academic/research programs (Community Cancer Program 3.1%, Comprehensive Community Cancer Program 2.6%, Academic/Research Program 1.8%, Integrated Network Cancer Program 2.3%; p=0.000). 30-day mortality rate was higher for American Indian, Aleutian, or Eskimo racial subgroups amongst all age-groups at all the surgical facility types especially for Stage IIIB NSCLC (White: 6%, Black: 3.4%, American Indian, Aleutian, or Eskimo: 14.3%, p=0.006). For each race, the 30-day mortality rate was better at the academic/research programs. Females had lower 30-day mortality for all racial subgroups. Having private insurance was associated with the lowest 30-day mortality rate. This was noted for all races across all the facility types. Lower income status was associated with higher mortality rates across all facility types. This difference was statistically significant for white patients. Majority of patients had less than 10 days of length of stay at all the surgical facility types. Conclusions: Outcomes of NSCLC surgery are significantly better at academic/research programs where a higher number of procedures are performed and access to latest surgical technologies is available. Short-term mortality rates are higher for American Indian, Aleutian, or Eskimo racial subgroup.

Prostate cancer lung metastasis represents a clinical conundrum due to its implications for advanced disease progression and the complexities it introduces in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, this review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, this review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.

The evidence on indications, outcomes, and complications with the use of extracorporeal membrane oxygenation (ECMO) in the setting of interstitial lung disease (ILD) is limited in the existing literature. We performed a systematic review and meta-analysis for the use of ECMO in the setting of ILD to study the prognostic factors associated with in-hospital mortality. Eighteen unique studies with a total of 1,356 patients on ECMO for ILD were identified out of which 76.5% were on ECMO as a bridge to transplant (BTT) and the rest as a bridge to recovery (BTR). The overall in-hospital mortality was 45.76%, with 71.3% and 37.8% for BTR and BTT, respectively. Among the various prognostic factors, mortality was lower with younger age (mean difference = 3.15, 95% confidence interval [CI] = 0.82–5.49), use of awake veno-arterial (VA)-ECMO compared to veno-venous (VV)-ECMO (unadjusted odds ratio [OR] = 0.22, 95% CI = 0.13–0.37) in the overall cohort. In the setting of BTT, the use of VA-ECMO had a decreased hazard ratio (HR) compared to VV-ECMO (adjusted HR = 0.34, 95% CI = 0.15–0.81, p = 0.015). The findings of our meta-analysis are critical but are derived from retrospective studies with small sample sizes and thus are of low to very low-GRADE certainty.

Pulmonary alveolar proteinosis (PAP) is a rare syndrome in which phospholipoproteinaceous matter accumulates in the alveoli leading to compromised gas exchange. Whole-lung lavage is considered the gold standard for severe autoimmune PAP and offers favorable long-term outcomes. In this case report, we describe the perioperative management and procedural specifics of a patient undergoing WLL for PAP in which an anesthesiologist serves as the proceduralist and a separate anesthesiologist provides anesthesia care for the patient.

Neutrophil accumulation is a key feature of ARDS, but their contribution to the pathogenesis is still uncertain. We investigated the effect of reducing neutrophils in a clinically relevant mouse model of pneumococcal pneumonia treated with antibiotics. When appropriate antibiotics were administered, neutrophil reduction with Ly6G antibody markedly attenuated lung injury and improved oxygenation. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense.