Real-world Cohort Research Articles

Global Leadership Initiative in Sarcopenia (GLIS)–defined sarcopenia increases the mortality of esophageal cancer patients after esophagectomy: A Chinese real-world cohort study

ObjectivesTo assess the impact of the definition of the Global Leadership Initiative in Sarcopenia (GLIS) on mortality in esophageal cancer (EC) patients, postesophagectomy, within a Chinese cohort and to validate the effectiveness of a new GLIS framework in oncology. MethodsWe performed an observational real-world cohort study in a single center at Daping Hospital of the Army Medical University in China, spanning from December 2014 to July 2022. We used the combined definition of muscle mass and muscle strength in a new GLIS framework for the diagnosis of sarcopenia. Potential covariates were identified through univariate and multivariate analyses. The association between GLIS-defined sarcopenia and mortality was estimated using Kaplan–Meier curves and Cox models. We also conducted stratified analyses to assess the stability of multivariable Cox models. ResultsA total of 520 EC patients were included in the study, with a median follow-up of 48.7 months. A total of 229 EC patients (44.0%) were identified with GLIS-defined sarcopenia. Patients with GLIS-defined sarcopenia had significantly worse overall survival in Kaplan–Meier curves (log-rank P = 0.015). Age; sex; tumor, node, metastasis stage; blood glucose; bleeding volume in operation; and operating time were introduced as covariates in a fully adjusted Cox model. Multivariable-adjusted Cox models revealed that GLIS-defined sarcopenia was an independent prognostic factor for EC patients postesophagectomy (hazard ratio, 1.87, 95% confidence interval, 1.28–2.74, P = 0.001). Stratified analyses confirmed the stability of the relationship between GLIS-defined sarcopenia and mortality in EC patients. ConclusionsGLIS-defined sarcopenia is prevalent among Chinese EC patients and is linked to increased mortality risk postesophagectomy. This finding offers compelling evidence and serves as a valuable reference for the establishment of an operational definition of GLIS sarcopenia.

Real world evidence on the effectiveness and safety of tofacitinib in ulcerative colitis in Lebanon

ObjectiveTo evaluate the effectiveness and safety of tofacitinib in patients with ulcerative colitis (UC) in clinical practice in Lebanon.DesignThis was a retrospective cross-sectional study. The data were collected from hospital records. Patients with moderate to severe UC treated with tofacitinib between 2018 and 2021 were included. Patients’ demographics, disease-specific characteristics, clinical assessment at three time points (8, 26, and 52 weeks), endoscopic evaluation at 24 weeks, and adverse events were collected.ResultsA total of 60 UC patients with a mean duration of disease of 7.9 ± 4.7 years were enrolled. 61.7% of patients had extensive disease, and 58.3% had received ≥ 1 biologic prior to tofacitinib. Clinical remission was reported in 25, 34, and 31 patients (41.7%, 56.7%, and 56.4%) at 8, 26, and 52 weeks respectively. Endoscopic remission (endoscopic Mayo score 0 or 1) was observed in 58.3% of patients at 52 weeks. About one-third of patients (31.7%) stopped tofacitinib at one year, primarily for lack of efficacy or loss of response, with no significant difference between biologics-naïve and experienced patients (24% vs. 37.1% respectively). No serious adverse events or deaths were reported. Adverse events were reported in 3 patients (5.0%) - one C. difficile infection, one case of reversible lymphopenia, and one case of facial acne. No serious adverse events or deaths were noted. On multivariate analysis, biologic-naïve status and reduction or normalization of CRP were associated with clinical remission (OR = 10.87, 95% CI = 1.57, 100, and OR = 78.47, 95% CI = 2.09, 2940.32 respectively), while reduction or normalization of CRP was associated with endoscopic remission at 1 year (OR = 19.03, 95% CI = 1.64, 221.09).ConclusionTofacitinib was effective in the treatment of moderately severe ulcerative colitis in this real-world cohort in Lebanon. Further, the predictors associated with clinical and endoscopic remissions were found to be biologic-naïve status and reduction in CRP. Observed AEs were consistent with the known safety profile. One of the major limitations of this study is the smaller sample size and the retrospective nature of the study.

Real-world pan-tumor comprehensive genomic profiling sample adequacy and success rates in tissue and liquid specimens.

Real-world success rate of liquid and tissue-based comprehensive genomic profiling (CGP) is unknown. We analyzed real-world pan-tumor cohorts that underwent CGP during clinical care via FoundationOne CDx (F1CDx) and FoundationOne Liquid CDx (F1LCDx) to determine tissue and liquid sample adequacy based on tumor type. Pan-tumor presequencing adequacy was high (>90%) by both tissue-based F1CDx (median: 92.3%; range: 88.2%-96.9%) and liquid-based F1LCDx (median: 94.8%; range: 86.6%-96.7%). Similarly, postsequencing analysis revealed that most tissue and liquid samples yielded successful sequencing results with a median sequencing success rate of 97.9% and 98.1% for F1CDx and F1LCDx, respectively. One exception is central nervous system (CNS) tumors, for which F1CDx had dramatically higher sample sufficiency (96.9%) and postsequencing success rate (97.0%) compared with F1LCDx (86.6% and 92.9%, respectively). The pan-tumor median sample-to-success rate was 90.4% (range: 84.8%-94.4%) for F1CDx. The equivalent rate for F1LCDx was slightly higher at 93.2% (range: 80.4%-95.7%). Conversely, when examining the prevalence of F1LCDx results with high tumor fraction (TF≥1%), the sample-to-high TF results rate was dramatically lower (median: 37.7%, range: 2.1% [CNS tumors]-46.0%). In conclusion, except in CNS tumors or when accounting for liquid TF, success rates of F1CDx and F1LCDx are equivalently high. These results may guide informed decision on when to pursue tissue vs liquid testing of patients with cancer.

Plasma exchange does not improve overall survival in patients with acute liver failure in a real world cohort

Background and AimsTherapeutic plasma exchange (PEX) has emerged as a potential treatment option for patients with acute liver failure (ALF). The effect of PEX on survival outcomes outside of clinical trials is not yet well established. In this study we aimed to evaluate the real-world use and outcomes of PEX for the treatment of ALF. MethodsThis multicentre retrospective cohort study included consecutive patients with ALF admitted to all 7 tertiary liver transplant centres in the United Kingdom (UK) between June 2013 and December 2021. Changes in clinical variables following PEX treatment was assessed and overall survival and transplant free survival (TFS) to hospital discharge of patients receiving PEX were compared to those receiving standard medical therapy (SMT). Propensity score matching was performed to control for intergroup covariates and selection bias. ResultsWe included 378 patients with ALF (median (IQR) age 36 (28-48), 64% (n=242) female) of which 120 received PEX. There was a significant improvement in most clinical variables following PEX, including median dose of noradrenaline (reduction from 0.35 μg/kg/min (0.19 - 0.70 μg/kg/min) to 0.16 μg/kg/min (0.08 - 0.49) (p = 0.001). There was no significant difference between PEX and SMT groups in overall survival (51.4 % v 62.6 % respectively, p = 0.12) or TFS (42.6 % v 53.1 %, p = 0.24). ConclusionPEX is now frequently used in the management of ALF patients in the UK. It is associated with significant improvement in haemodynamic parameters but there is no survival benefit. Impact and implicationsPEX is frequently used in the management of patients with ALF in the UK. This real-world study demonstrates significant improvement in haemodynamic status but has not confirmed the survival benefit seen in previous published literature. These results should help inform future use of PEX.

Analytical and clinical validation of a NGS panel in detecting targetable variants from ctDNA of metastatic NSCLC patients.

Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for noninvasive cancer diagnostics, particularly in the context of metastatic non-small-cell lung cancer (NSCLC). Detecting targetable variants through ctDNA analysis offers the potential to guide treatment decisions, especially in cases where tissue samples are insufficient or unavailable. In this study, we developed and validated a next-generation sequencing panel targeting 101 cancer-related genes (101-test) to detect somatic variants in ctDNA from a large cohort of Chinese patients with metastatic NSCLC. The performance of the 101-test was assessed by evaluating its limit of detection (LOD), accuracy, and precision in identifying molecular variants. Additionally, the concordance between ctDNA and tissue samples for detecting targetable variants was analyzed in 904 patients. The 101-test demonstrated a LOD of 0.38% for single-nucleotide variants (SNVs), 0.33% for insertions and deletions (InDels), and 0.33% for fusions. Sensitivity was 98.3% for SNVs, 100% for InDels, and 100% for fusions when compared to digital droplet PCR (ddPCR)/breakpoint PCR reference methods. The by-variant sensitivity for somatic variants was 97.5%, with a specificity of 99.9% between tumor-only and tumor-normal analyses. In a real-world cohort, the concordance between ctDNA and tissue samples for identifying targetable variants was 72.2% (457/633). Notably, the EGFR S768I variant, recently recommended by clinical guidelines, achieved an 80% concordance rate. Furthermore, 4.3% of patients (27/633) with targetable variants were identified exclusively through ctDNA testing. The ctDNA-based 101-test is a highly sensitive and specific tool for detecting targetable variants in metastatic NSCLC, particularly in cases with insufficient tissue samples. The findings support the use of ctDNA testing as a reliable and complementary method to traditional tissue-based molecular analysis, enhancing the precision of treatment strategies for NSCLC patients.

Reduced Effectiveness of Anti-IgE Treatment Among Adults with Severe Asthma with Older Age of Asthma Onset: Results from the CHRONICLE Study.

Younger age of asthma onset (AAO) has been associated with an allergic phenotype, whereas eosinophilic phenotypes have been associated with older AAO. In randomized trials, biologic efficacy among adults with severe asthma (SA) has varied by age at asthma onset. To determine whether these associations observed in trials apply to real-world outcomes, this study examined biologic effectiveness by AAO and biologic class in a large, real-world cohort. CHRONICLE is an ongoing, real-world study of US adults with subspecialist-treated SA receiving biologics, maintenance corticosteroids, or who are uncontrolled on high-dosage inhaled corticosteroids with additional controllers. Patients enrolled between February 2018 and February 2022 who initiated a biologic for SA and had complete data for analysis were included. A locally estimated scatterplot smoothing (LOESS) analysis was used to plot the relationship between percentage exacerbation rate reduction and AAO by biologic class. Of 578 patients with complete data, 198, 149, and 231 were diagnosed with asthma at age <18, 18-39, and ≥40 years, respectively. Across subgroups, patients were predominantly White (72-78%), female (67-73%), and commercially insured (54-71%). In the LOESS analysis, exacerbation rate reductions were similar for anti-IgE and anti-IL-5/5R and anti-IL-4R subgroups with younger AAO, but the exacerbation rate reduction diminished for patients with older AAO receiving anti-IgE therapy, particularly with asthma onset age ≥40 years. Clinicians should consider age of onset in biologic treatment decisions, given reduced effectiveness of omalizumab in patients with asthma onset at age ≥40 years. NCT03373045.

Comparative analysis of GLP-1 receptor agonists versus metformin on cancer outcomes in patients with polycystic ovarian syndrome: A real-world multi-center cohort study in the United States.

402 Background: To compare the effects of GLP-1 receptor agonists (GLP1RA) versus metformin on incident cancer outcomes in the female polycystic ovarian syndrome (PCOS) population. Methods: This retrospective cohort study utilized electronic health records from over 50 U.S. healthcare organizations (TriNetX). The baseline cohort comprised females aged ≥ 18 with ≥ two prescriptions for GLP1 RAor metformin following a diagnosis of PCOS, between May 1, 2005 (first GLP1 RA approval date), and December 31, 2021. All cancer types were identified using ICD-10 codes. The index date was the initiation of GLP1RA or metformin. We performed a 1:1 propensity score matched based on demographics, comorbidities, socioeconomic factors, healthcare utilization, and biomarkers (HbA1c, LDL, HDL, triglycerides, and cholesterol), insulin use and PCOS medications before index date. Analysis was performed with intention-to-treat approach. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the comparison groups were calculated by the Cox regression model. Patients were followed and censored upon meeting any of the following criteria: development of an outcome, the study end date of May 19, 2024, or loss to follow-up, whichever occurred first. Results: A total of 8,223 pairs of GLP1RA initiators and metformin initiators were included. Compared to metformin, GLP1RA was associated with a lower risk of incident colorectal cancer (HR 0.35, 95% CI 0.22-0.57) and breast cancer (HR 0.55, 95% CI 0.39-0.78). There were no significant differences in risk between the GLP1RA group and metformin group for endometrial (HR 0.82, 95% CI 0.49-1.37), cervical (HR 1.17, 95% CI 0.64-2.12), ovarian (HR 1.09, 95% CI 0.56-2.11), respiratory (HR 0.32, 95% CI 0.17-0.60), skin (HR 0.51, 95% CI 0.37-0.69), kidney cancer(HR 0.99, 95% CI 0.33-3.06), thyroid cancer (HR 1.37, 95% CI 0.88-2.13), other endocrine (HR 0.81, 95% CI 0.15- 0.44), leukemia and lymphoma (HR 1.03, 95% CI 0.91-1.16), brain (HR 0.97, 95% CI 0.24-3.96), pancreatic cancer(HR 0.50, 95% CI 0.16-1.55), esophageal cancer (HR 1.99, 95% CI 0.24-16.18), stomach cancer (HR 0.33, 95% CI 0.07-1.47), and intrahepatic cancer (HR 0.89, 95% CI 0.40-1.99). Conclusions: GLP-1 receptor agonists were associated with a lower risk of colorectal and breast cancer compared to metformin in females with PCOS, with no significant differences in risk for other cancer types.Further investigation is necessary to verify the underlying therapeutic mechanisms.

A review of serious adverse events linked with GLP-1 agonists in type 2 diabetes mellitus and obesity treatment.

Glucagon-like peptide-1 (GLP-1) agonists play a crucial role in treating type 2 diabetes mellitus and obesity by providing glycemic control and aiding weight management. Despite their widespread use, concerns about serious adverse events have prompted extensive research. This review aims to describe the current understanding of serious adverse events associated with GLP-1 agonists. A comprehensive search of PubMed, Google Scholar and Embase databases was performed starting from 2010. Studies reporting evidence of an association between GLP-1 agonists and serious adverse events from 22 articles (5 case reports, 5 randomized controlled trials (RCTs), 9 real-world data cohort analyses, 2 meta-analyses and 1 systematic review and meta-analysis) were included and categorized by the type of adverse event. While some studies reported risks, including anaphylaxis, cardiovascular, gastrointestinal, psychiatric and thyroid-related events, others found no significant associations. The evidence remains mixed, necessitating further research to fully understand the safety profile of GLP-1 agonists and inform clinical practice.

Docetaxel Versus Androgen-Receptor Signaling Inhibitors (ARSI) as Second-Line Therapy After Failure of First-Line Alternative ARSI for the Elderly ≥ 75 Years Old With Metastatic Castration-Resistant Prostate Cancer (mCRPC): A SPARTACUSS—Meet-URO 26 Real-World Study

BackgroundAndrogen receptor signalling inhibitors (ARSIs) abiraterone acetate (AA) enzalutamide (Enza), are currently the standard first-line (L1) treatments for metastatic castration-resistant prostate cancer (mCRPC), and docetaxel (D) is reserved as second-line (L2) after ARSI failure. Nonetheless, D use in men ≥ 75 years old is restricted owing to treatment toxicities and patient comorbidities, and a L2 alternative ARSI is frequently used. We aimed to evaluate real-life survival and toxicity outcomes of these elderly patients after failure of L1 ARSI treatment. Material and MethodsWe retrospectively evaluated efficacy and safety in a real-world international cohort of consecutive patients ≥ 75 years old when starting L1 ARSI for mCRPC according to the choice of L2 treatment (D versus alternative ARSI). ResultsOf the 122 identified patients, 57 (46.7%) had received L2 ARSI and 65 (53.3%) L2 D. No difference was found in the L1 overall survival (OS) for the ARSI and D groups (32.8 vs. 30.0 months, respectively; Hazard ratio [HR] = 1.22; 95% CI, 0.77-1.95; P = .40) or in the L2 OS (18.5 vs. 17.8 months, respectively; HR = 1.09; 95% CI, 0.69-1.74; P = .71). No difference was observed for rPFS from L2 (P = .12), although a trend was observed for a numerically improved rPFS on D. ConclusionWithin the limitations of a retrospective design and small population, our study suggests that D or ARSI after failure of L1 alternative ARSI are clinically comparable L2 options for elderly patients with mCRPC.

Real-World Clinical Outcomes With Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.

Sacituzumab govitecan (SG) is approved for the treatment of metastatic triple-negative breast cancer (mTNBC). We report the real-world clinical effectiveness and toxicity data of SG in patients with mTNBC. A multi-institution retrospective study of patients with mTNBC treated with SG from January 2021 to May 2023 was conducted. Demographic and clinicopathologic variables were collected. Univariate and multivariate Cox regression models were used for survival analysis. A total of 115 patients were included. The median age at SG initiation was 60 years (range, 31-85). All patients were female; 73 (63.5%) were White and 31 (27.0%) were Black. The median number of previous therapies in the metastatic setting was two (range, 0-8). Sixty-one (56.0%) patients had primary refractory disease. Median relative dose intensity was 92% (range, 33%-100%). Grade 3 or higher adverse events (AEs) were seen in 50.9% of patients, which included neutropenia (35.7%), anemia (27.0%), vomiting (16.5%), fatigue (8.7%), and diarrhea (7.0%). Dose reductions and treatment discontinuation due to AEs were required in 51.3% and 13.2%, respectively. The objective response rate (ORR) was 27.8%. Median overall survival was 9.6 months (95% CI, 7.8 to 12.9) and median progression-free survival (PFS) was 4.8 months (95% CI, 3.6 to 5.9). In patients with human epidermal growth factor receptor 2 (HER2)-low mTNBC who received trastuzumab deruxtecan (T-DXd) after SG, the ORR to T-DXd was 34.8% and median PFS was 7 months (95% CI, 4.6 to 10.1). In a real-world cohort of heavily pretreated patients with mTNBC, SG retains its clinical activity. In a subgroup with HER2-low disease, T-DXd continues to demonstrate promising clinical activity after SG, supporting the use of sequential antibody-drug conjugates in this population.

On-Treatment Clinical Remission of Severe Asthma With Real-World Longer-Term Biologic Use

BackgroundThere are limited real-world data describing the proportion of patients with severe asthma (SA) who achieve on-treatment clinical remission with long-term biologic treatment. ObjectiveTo examine the proportion and characteristics of adults with SA who achieved clinical remission with biologic therapy. MethodsCHRONICLE is an observational study of US subspecialist-treated adults with SA. Sites reported exacerbations and biologic use from 12 months prior to enrollment forward. Monthly Asthma Control Test (ACT) scores and 6-monthly specialist assessments of asthma control were collected. Patients enrolled from February 2018–February 2023 with biologic initiation during the study observation period and continued use for ≥12 months were evaluated. Incident on-treatment clinical remission was defined in a 12-month interval as the absence of exacerbations and systemic corticosteroid (SCS) use, ≥50% of ACT scores ≥20 in the latest 6 months, and specialist report of asthma control. ResultsAmong evaluable patients (N=611), median duration of biologic use was 39.6 months. In at least one 12-month interval during the study, 79.9% of patients had no exacerbations or SCS use, and 46.0% met the definition of clinical remission at any point. The point prevalence of clinical remission increased from 22.3% at 12–13 months of biologic use to 34.3% at 47–48 months of biologic use. ConclusionsIn a real-world cohort of patients with SA with longer-term biologic treatment, almost one-half achieved on-treatment clinical remission. With a year or more of biologic therapy, clinical remission is a feasible treatment goal in SA.

P3.13D.09 Prevalence and Prognostic Impact of SEZ6 Expression in a Real-World Cohort of Patients with Small-Cell Lung Cancer

P3.13D.09 Prevalence and Prognostic Impact of SEZ6 Expression in a Real-World Cohort of Patients with Small-Cell Lung Cancer

Real-World Outcomes of Pralsetinib in RET Fusion-Positive NSCLC

IntroductionPralsetinib is a RET inhibitor found to have antitumor activity in advanced, metastatic, RET fusion-positive NSCLC. ObjectiveTo assess real-world efficacy of pralsetinib and treatment sequences in patients with RET fusion-positive NSCLC. DesignRetrospective study of consecutive patients enrolled in the French expanded-access program for pralsetinib from December 1, 2019, to December 31, 2021. ParticipantsA total of 41 patients with advanced, refractory, RET fusion-positive NSCLC were included. Pralsetinib was administered at a daily dose of 400 mg based on safety and pharmacokinetic outcomes from previous phase 1/2 study. ResultsPralsetinib was administered as second line in 23 patients (56%) and as third line and beyond in 15 patients (37%). After a median follow-up of 26.3 months, pralsetinib was ongoing in 13 patients. Median real-world progression-free survival was 11.8 (95% confidence interval [CI]: 9.3–15.5) months. Objective response rate was 68% (95% CI: 50%–82%), and disease control rate was 89% (95% CI: 75%–97%). Subsequent line of systemic therapy was initiated in 11 patients. Median overall survival from pralsetinib initiation was 23.8 (95% CI: 16.5–not reached) months. ConclusionIn this extensive real-world cohort of patients with advanced or metastatic NSCLC harboring RET fusions, we highlight the antitumor efficacy of pralsetinib, particularly when administered in later treatment lines. We also observe the aggressive nature of disease progression, frequent utilization of chemotherapy and antiangiogenic agents as initial subsequent therapies, and limited insight into resistance mechanisms due to infrequent rebiopsy and genomic profiling at progression.

Real-World Outcomes of Patients With Malignant Pleural Mesothelioma Receiving a Combination of Ipilimumab and Nivolumab as First- or Later-Line Treatment

ObjectivesOn the basis of the positive results of CheckMate-743, first-line (1L) treatment of malignant pleural mesothelioma (MPM) with the combination of ipilimumab and nivolumab (ipi/nivo) has become a standard-of-care. Furthermore, patients who received 1L platinum/pemetrexed chemotherapy are often considered for second or further-line (2L+) ipi/nivo on the basis of MAPS2 results. Here we report on real-world survival and safety outcomes of ipi/nivo for patients with MPM in Switzerland. MethodsTwelve cancer centers contributed data to this retrospective cohort. Baseline characteristics including age, sex, histology, programmed death-ligand 1 expression, Eastern Cooperative Oncology Group performance status (ECOG PS), and previous/subsequent therapies were collected. The efficacy and safety outcomes were assessed by local investigators. ResultsOf the 109 patients with MPM treated with ipi/nivo between November 2017 and March 2023 (median follow-up of 16.6 months) 75% had epithelioid, 9% biphasic, and 16% sarcomatoid histology. The median age was 72 years; 91% were males, and 83% had an ECOG PS of 0 to 1. Ipilimumab in combination with nivolumab was given as 1L in 43% and as 2L+ treatment in 57% of patients. The objective response rate was 21% in 1L and 15% in 2L+. Median progression-free survival was 6.5 and 2.8 months, respectively. Median overall survival (OS) from the start of ipi/nivo was 12.6 months for 1L and 6.9 months for 2L+. No differences in OS were observed depending on age and programmed death-ligand 1 expression. Nevertheless, the median OS was significantly worse in patients with an ECOG PS of 2 or higher than those with an ECOG PS of 0 to 1 (2.4 versus 11.9 months, p < 0.001). Treatment-related adverse events (TRAEs) of any grade related to ipi/nivo treatment occurred in 65 patients (62%). The highest-grade TRAE was 1 to 2 in 58% of these patients and 3 or higher in 42% Treatment discontinuation due to a TRAE occurred in 22% of patients. ConclusionIn this real-world cohort of patients with MPM treated with ipi/nivo survival outcomes were inferior to those reported in the CheckMate-743 and MAPS2 trials, whereas safety outcomes were similar.

Intensive Uric Acid-Lowering Improved Outcomes in Type 2 Diabetes with CKD: A Multicenter, Retrospective, Real-World Cohort Study

Intensive Uric Acid-Lowering Improved Outcomes in Type 2 Diabetes with CKD: A Multicenter, Retrospective, Real-World Cohort Study

The association of diabetes mellitus and routinely collected patient-reported outcomes in patients with cancer. A real-world cohort study.

Current studies have indicated that diabetes mellitus (DM) is highly prevalent in patients with cancer, but there is little research on consequences on the well-being of patients during cancer treatment. This analysis evaluates the relationship between DM and patient-reported outcomes (PRO) in patients with cancer, using a large and well-characterized cohort. This study utilized the Total Cancer Care protocol at the University of Utah Huntsman Cancer Institute. For this analysis, we integrated data from electronic health records, the Huntsman Cancer Registry, and routinely collected PRO questionnaires. We assessed the association between DM in patients with cancer and PRO scores for anxiety, depression, fatigue, pain interference, and physical function using multiple linear regression and t-tests. The final cohort comprised 3512 patients with cancer, with a mean age of 57.8 years at cancer diagnosis. Of all patients, 49.1% (n = 1724) were female, with 82.0% (n = 2879) patients reporting PROs at least at one time point. Compared with patients who responded, nonresponders were more often female (p = 0.0035), less frequently non-Hispanic White (p = 0.0058), and had a higher BMI (p = 0.0759). Patients with cancer and diabetes had worse PRO scores for anxiety (p = 0.0003), depression (p < 0.0001), fatigue (p < 0.0001), pain interference (p < 0.0001), and physical function (p < 0.0001) compared to patients with cancer without diabetes. Significant associations between diabetes and PRO scores were observed for anxiety (β ± SE: 1.27 ± 0.48; p = 0.0076), depression (β ± SE: 1.46 ± 0.45; p = 0.0011), fatigue (β ± SE: 2.11 ± 0.52; p < 0.0001), pain interference (β ± SE: 1.42 ± 0.50; p = 0.0046), and physical function (β ± SE: -2.74 ± 0.48; p < 0.0001). The results of this study suggest that patients with cancer and diabetes may be at greater risk for anxiety, depression, fatigue, higher pain interference, and reduced physical function. Strengthening diabetes management is imperative to address the negative impact of diabetes on PROs. In particular, this may be true for patients with skin, breast, prostate, and kidney cancer.

Uptake of Risk-Reducing Surgeries in an International Real-World Cohort of Hispanic Women.

Women with pathogenic variants (PVs) in breast cancer (BC) and ovarian cancer (OC) associated genes are candidates for cancer risk-reducing strategies. Limited information is available regarding risk-reducing surgeries (RRS) among Hispanics. The aim of this study was to describe the uptake of RRS in an international real-world experience of Hispanic women referred for genetic cancer risk assessment (GCRA) and to identify factors affecting uptake. Between July 1997 and December 2019, Hispanic women, living in the United States or in Latin America, enrolled in the Clinical Cancer Genomics Community Research Network registry were prospectively included. Demographic characteristics and data regarding RRS were obtained from chart reviews and patient-reported follow-up questionnaires. Median follow-up was 41 months. Among 1,736 Hispanic women referred for GCRA, 27.2% women underwent risk-reducing mastectomy (RRM), 25.5% risk-reducing salpingo-oophorectomy (RRSO) and, 10.7% both surgeries. Among BRCA carriers, rates of RRM and RRSO were 47.6% and 56.7%, respectively. In the multivariate analyses, being a carrier of a BC susceptibility gene (odds ratio [OR], 3.44), personal history of BC (OR, 6.22), living in the US (OR, 3.90), age ≤50 years (OR, 1.68) and, family history of BC (OR, 1.56) were associated with a higher likelihood of undergoing RRM. Carrying an OC susceptibility gene (OR, 6.72) was associated with a higher likelihood of undergoing RRSO. The rate of RRS among Hispanic women is suboptimal. PV carriers, women with personal history of cancer, and those with a family history of cancer were more likely to have RRS, with less uptake outside the US. Understanding personal and systemic factors influencing uptake may enable interventions to increase risk appropriate uptake of RRS.

EP.08E.03 Clinical Characteristics and Outcomes in Resectable Stage III ALK-Positive Non-Small Cell Lung Cancer: A Multicenter Real-World Cohort Study

EP.08E.03 Clinical Characteristics and Outcomes in Resectable Stage III ALK-Positive Non-Small Cell Lung Cancer: A Multicenter Real-World Cohort Study

First-Line Chemo-Immunotherapy in SCLC: Outcomes of a Binational Real-World Study

IntroductionSCLC is characterized by aggressiveness and limited treatment options, especially in extensive-stage SCLC (ES-SCLC). Immunotherapy added to the platinum-etoposide combination has recently become standard in this setting. This retrospective study aims to evaluate the real-world effectiveness of chemo-immunotherapy in patients with ES-SCLC, focusing on subpopulations excluded from clinical trials. MethodsA retrospective binational multicenter study was conducted, involving consecutive patients with ES-SCLC from 10 British and 10 Swiss institutions. Patients received platinum-etoposide chemotherapy in combination with immunotherapy (atezolizumab or durvalumab). Patient, tumor, and treatment details were collected. Overall survival (OS), progression-free survival, overall response rate, and safety outcomes were analyzed. ResultsA total of 436 patients were included. One hundred forty-two patients (32.6%) in our cohort would not have been eligible for the pivotal registrational trials owing to an Eastern Cooperative Oncology Group performance status of 2 or higher, autoimmune disease, active brain metastases, and/or steroid use. Most patients received carboplatin (96.8%) and atezolizumab (97.9%). The median progression-free survival was 5.5 months and the median OS was 9.3 months. The two-year OS was 14%. Patients with liver or bone metastases or an Eastern Cooperative Oncology Group performance status of 2 or higher had worse survival outcomes. Treatment-related adverse events were reported in 222 patients (51%) whereas immune-related adverse events occurred in 95 patients (22%). Three out of five grade 5 immune-related adverse events were caused by pneumonitis. ConclusionsTo our knowledge, this is the largest real-world cohort of patients treated with chemo-immunotherapy for ES-SCLC. Although one-third of patients would not have been eligible for pivotal trials, the survival outcomes in our cohort are similar to those in registrational trials. In particular, the number of long-term survivors and the safety data are comparable, supporting the use of chemo-immunotherapy as first-line treatment for ES-SCLC in daily clinical practice.

Ocular neuropathic pain in a real-world patient cohort with dry eye disease: A save sight dry eye registry study

PurposeTo compare patient demographics, clinical signs, and questionnaire scores in dry eye disease (DED) patients with and without ocular neuropathic pain. MethodsA cross-sectional cohort study was performed using the Save Sight Dry Eye Registry (SSDER). Patients were divided into two groups based on a clinician diagnosis of ocular neuropathic pain and Tear Film and Ocular Surface Society Dry Eye Workshop II definitions. Patient demographics, Ocular Surface Disease Index (OSDI) and Ocular Comfort Index (OCI) scores, and DED signs were compared along with Patient Health Questionnaire-4 (PHQ-4) scores, average screen time and treatment compliance. Statistical analyses included descriptive statistics, Mann-Whitney U test, Chi-squared test of independence, and Fisher's exact test. P-values were Bonferroni corrected (p*). ResultsData from 298 patients with DED symptoms and signs (26 with ocular neuropathic pain) were analysed. There was no statistical difference in patient demographics (p*>0.0063). Patients with ocular neuropathic pain had worse final, domain, and pain-related question scores for the OSDI (p*<0.0031) and OCI (p*<0.0039) and had higher scores for anxiety and depression for the PHQ-4 (p*<0.0083). Patients with ocular neuropathic pain had a lower rate and severity of meibomian gland dysfunction (p*<0.0063). ConclusionReal-world data from the SSDER demonstrated patient demographics and clinical signs poorly differentiated patients with ocular neuropathic pain within a DED cohort. Patients with ocular neuropathic pain reported significantly worse OSDI and OCI scores, indicating greater symptom severity. While this highlighted symptom differences, further research is required to determine whether OSDI and OCI scores can assist in identifying ocular neuropathic pain in DED.