Explore the vast range of titles available.

BackgroundImmune checkpoint inhibitors (ICIs) have improved survival and are increasingly used for non-small cell lung cancer. However, use may be limited by immune-related adverse events such as checkpoint-inhibitor pneumonitis (CIP). Literature estimates for CIP incidence are inconsistent. Real-world adherence to guidelines, clinical course, and healthcare utilization in the treatment of CIP has not been described in large cohorts.MethodsA combined claims and electronic health record database (TriNetX) was used to identify 13,113 patients with lung cancer treated with programmed cell death receptor/ligand 1 (PD-1/PD-L1) inhibitors, and a propensity score-matched control cohort treated with chemotherapy or targeted therapies. The attributable risk of CIP was calculated in the first 12 months after therapy by comparing the incidence of diagnosis codes for pneumonitis/pneumonia between cohorts. Cases of CIP, identified by the most specific code for drug-induced respiratory conditions, were further analyzed for medication usage, rates of diagnostic bronchoscopy, ICI discontinuation rates, and usage of hospital services compared with patients receiving PD-1/PD-L1 inhibitors who did not develop CIP.ResultsThe attributable risk of pneumonitis to PD-1/PD-L1 inhibitors was 2.49% (95% CI, 1.50% to 3.47%). Median time to onset in the CIP subcohort was 3.9 months (IQR, 2.1–7.3 months). Steroid and antibiotic use increased dramatically after a pneumonitis diagnosis, and 70.2% of patients permanently discontinued ICI therapy. Compared with controls, patients with CIP had more than a threefold increased risk of needing critical care (relative risk 3.59, 95% CI, 2.31 to 5.57) and an increased risk of mortality (HR 2.34, 95% CI, 1.47 to 3.71).ConclusionsIn a large claims-based analysis, PD-1/PD-L1 inhibitors increase the risk of pneumonitis in patients with lung cancer by 2.49%. Cases of CIP are associated with high healthcare utilization, discontinuation of ICIs, and mortality.

BackgroundImmune-related adverse events (irAEs) are a serious side effect of immune checkpoint inhibitor (ICI) therapy for patients with advanced cancer. Currently, predisposing risk factors are undefined but understanding which patients are at increased risk for irAEs severe enough to require hospitalization would be beneficial to tailor treatment selection and monitoring.MethodsWe performed a retrospective review of patients with cancer treated with ICIs using unidentifiable claims data from an Aetna nationwide US health insurance database from January 3, 2011 to December 31, 2019, including patients with an identified primary cancer and at least one administration of an ICI. Regression analyses were performed. Main outcomes were incidence of and factors associated with irAE requiring hospitalization in ICI therapy.ResultsThere were 68.8 million patients identified in the national database, and 14 378 patients with cancer identified with at least 1 administration of ICI in the study period. Patients were followed over 19 117 patient years and 504 (3.5%) developed an irAE requiring hospitalization. The incidence of irAEs requiring hospitalization per patient ICI treatment year was 2.6%, rising from 0% (0/71) in 2011 to 3.7% (93/2486) in 2016. Combination immunotherapy (OR: 2.44, p<0.001) was associated with increased odds of developing irAEs requiring hospitalization, whereas older patients (OR 0.98 per additional year, p<0.001) and those with non-lung cancer were associated with decreased odds of irAEs requiring hospitalization (melanoma OR: 0.70, p=0.01, renal cell carcinoma OR: 0.71, p=0.03, other cancers OR: 0.50, p<0.001). Sex, region, zip-code-imputed income, and zip-code unemployment were not associated with incidence of irAE requiring hospitalization. Prednisone (72%) and methylprednisolone (25%) were the most common immunosuppressive treatments identified in irAE hospitalizations.ConclusionsWe found that 3.5% of patients initiating ICI therapy experienced irAEs requiring hospitalization and immunosuppression. The odds of irAEs requiring hospitalization were higher with younger age, treatment with combination ICI therapy (cytotoxic T lymphocyte-associated 4 and programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1)), and lower for other cancers compared with patients on PD-1 or PD-L1 inhibitors with lung cancer. This evidence from the first nationwide study of irAEs requiring hospitalization in the USA identified the real-world epidemiology, risk factors, and treatment patterns of these irAEs which may guide treatment and management decisions.

Background/Objectives: Demand for dermatologic services exceeds specialist capacity, with average wait times of 26–50 days in the United States. Current triage methods rely on subjective judgment or disease-specific indices that do not generalize across diagnoses or translate to operational decisions. We developed and validated the Dermatologic Complexity Score (DCS), a standardized instrument to guide case prioritization across dermatology care settings and evaluate DCS as a workload-reduction filter, enabling safe delegation of approximately half of routine teledermatology cases (DCS ≤ 40) away from specialist review. Methods: We conducted a prospective validation study of the DCS using 100 consecutive teledermatology cases spanning 30 common conditions. The DCS decomposes complexity into five domains (Diagnostic, Treatment, Risk, Patient Complexity, Monitoring) summed to a 0–100 total with prespecified bands: ≤40 (low) (41–70), (moderate) (71–89), (high), ≥90 (extreme). Five board-certified dermatologists and an automated module independently scored all cases. Two primary care physicians completed all ≤40 cases to assess feasibility. Primary outcomes were interrater reliability using ICC (2,1) and agreement with automation. Secondary outcomes included time-to-decision, referral rates, and primary care feasibility. Results: Mean patient age was 46.2 years; 47% of cases scored ≤40, 33% scored 41–70, 18% scored 71–89, and 2% scored ≥90. Interrater reliability was excellent (ICC (1,2)) = 0.979; 95% CI 0.974–0.983), with near-perfect agreement between automated and mean dermatologist scores (r = 0.998). Time-to-decision increased monotonically across DCS bands from 2.11 min (≤40) to 5 (90) min (≥90) (p = 1.36 × 10−14). Referral rates were 0% for ≤40, 3% for 41–70, 27.8% for 71–89, and 100% for ≥90 cases. DCS strongly predicted referral decisions (AUC = 0.919). Primary care physicians successfully managed all ≤40 cases but required 6–8 additional minutes per case compared to dermatologists. Conclusions: The DCS demonstrates excellent reliability and strong construct validity, mapping systematically to clinically relevant outcomes, including decision time and referral patterns. The instrument enables standardized, reproducible triage decisions that can optimize resource allocation across teledermatology, clinic, procedural, and inpatient settings. Implementation could improve access to dermatologic care by supporting appropriate delegation of low-complexity cases to primary care while ensuring timely specialist evaluation for high-complexity conditions.

Direct-to-consumer (DTC) telehealth platforms have enhanced healthcare accessibility and convenience, particularly for Individuals in remote areas or those with mobility limitations. These platforms offer virtual medical consultations and prescription services, improving access to treatment for conditions such as hair loss, anxiety, depression, and sexual dysfunction. However, concerns regarding limited physician oversight, lack of transparency in provider qualifications, privacy risks, and potential financial and legal vulnerabilities highlight the need for stricter regulations. Addressing these issues is crucial to ensure patient protection and trust as the use of DTC telehealth services continues to grow.

BackgroundIt is unclear whether treatment with immune checkpoint inhibitors (ICIs) is a risk factor for contracting COVID-19. We investigated whether patients prescribed ICIs were more or less likely to contract COVID-19 than matched controls in a collaboration between a large academic healthcare system and the Massachusetts Department of Health.MethodsWe performed a retrospective study of 1,577 cancer patients prescribed ICI and 26,241 matched controls. We included all patients infused with an ICI in the Mass General Brigham (MGB) network between 7/1/19 and 2/29/20 and generated an exact match of control patients from the MGB database on age, sex, and Charlson comorbidity index. For both groups, we cross referenced COVID-19 infection data through June 19, 2020 from the Massachusetts Department of Public Health using date of birth, last name, and first four letters of the first name. We calculated odds ratios (OR) for COVID-19 diagnosis using a multivariate logistic regression adjusting for age, sex, race, CCI, zip code income, and local infection rate.ResultsTwenty-one patients (1.3%) prescribed ICIs and 527 controls (2.0%) were identified as COVID positive in the Massachusetts department of health database. When controlling for local infection rate, age, sex, race, CCI, and zip code income, there were no significant differences in COVID infection between ICI recipients and matched controls (OR: 0.7, 95% CI: 0.45 – 1.09, p=0.1; table 1).Abstract 826 Table 1Multivariable logistic regression for patients treated with ICI with Odds Ratios for defining ‘event’ to be COVID-19 positivityConclusionsIn our experience, patients who were prescribed ICI were not more likely to contract COVID-19 than matched controls, which may assist in decision-making around continuation of therapy during the pandemic. More research needs to be conducted to determine potential behavioral and testing factors that may affect COVID-19 diagnosis.

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized cancer therapy over the last decade. Despite the efficacy of ICIs, immune-related adverse events (irAEs) occur in over a third of treated patients and can cause lasting morbidity and mortality.1–3 Cutaneous irAEs (cirAEs) are the most frequently reported toxicities, occurring in 20–40% of treated patients. Though recent reports have investigated the prognostic significance of irAEs on cancer outcomes, little is known about the specific impact of cirAEs and their subtypes on cancer survival.4 In this landmark analysis, we present the first population-level study examining the influence of cirAE development following ICI therapy on the mortality of cancer patients.Methods7,008 patients who developed cirAEs after treatment with anti-programmed cell death receptor/ligand 1 (PD-1/PD-L1) therapy for malignant neoplasms of digestive organs, bronchus or lung, melanoma of skin, and urinary tract were identified through the TriNetX Diamond network along with 7,008 matched controls (table 1). The malignant neoplasms and cutaneous diagnoses for this study were identified from published literature and expert opinion.5 6 Looking at cutaneous eruptions within 6 months of the first instance of ICI administration, a 6-month landmark analysis using a Cox proportional hazards model was performed to determine the impact of cirAE on overall survival.ResultsPresence of any cirAE (HR=0.695, p<0.0001), nonspecific rashes (HR=0.704 , p<0.0001), pruritus (HR=0.695, p<0.0001), drug eruption (HR=0.755, p=0.0013), and xerosis (HR=0.626, p=0.0013) were significantly protective of mortality using a Benjamini-Hochberg (BH) correction for multiple comparisons (table 2). Psoriasis (HR=0.703, p=0.0451) and lichen planus/lichenoid dermatitis (HR=0.511, p=0.0274) were nominally significant. Notably, though not reaching statistical significance, eczematous dermatitis (HR=0.0.612), vitiligo (HR=0.534), bullous pemphigoid (HR=0.524), and Grover's disease (HR=0.468) were associated with strong protective clinical effects. To explore the impact of landmark time on mortality, a sensitivity analysis was performed for cirAE onset within 3 months (HR=0.759, p<0.0001) and 9 months (HR=0.84, p<0.0001) of ICI initiation. A separate sensitivity analysis expanded to include all cancer types treated with ICI yielded similar results, with additional statistical significance reached for ICI-induced psoriasis (table 3).ConclusionsThis is the first population-level study and largest analysis to date of the impact of cirAEs on mortality among patients with advanced cancer. With the exception of mucositis and hyperhidrosis, there was a strong clinically protective effect of cirAEs across all individual morphologies investigated. Our results demonstrate that cirAE development after ICI initiation is an important positive prognostic indicator of response to ICI therapy and patient survival.Abstract 814 Table 1Propensity score-matched baseline characteristics for patients treated with PD-1 or PL-L1 therapyAbstract 814 Table 2Association between cutaneous eruptions and surviv‡Cutaneous diagnoses were identified based on published literature and expert opinion.*Benjamini-Hochberg p-value of significance = 0.0013.Abstract 814 Table 3Association between cutaneous eruptions and surviva‡Cutaneous diagnoses were identified based on published literature and expert opinion.*Benjamini-Hochberg p-value of significance = 0.0025.ReferencesPuzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer 2017;5(1):1–28. doi:10.1186/s40425-017-0300-z.Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. J Clin Oncol 2018;36(17):1714–1768. doi:10.1200/JCO.2017.77.6385.Phillips GS, Wu J, Hellmann MD, et al. Treatment outcomes of immune-related cutaneous adverse events. J Clin Oncol 2019;37(30):2746–2758. doi:10.1200/JCO.18.02141.Petrelli F, Grizzi G, Ghidini M, et al. Immune-related adverse events and survival in solid tumors treated with immune checkpoint inhibitors: a systematic review and meta-analysis. J Immunother. 2020;43(1):1–7. doi:10.1097/CJI.0000000000000300.Wongvibulsin S, Pahalyants V, Kalinich M, et al. Epidemiology and risk factors for the development of cutaneous toxicities in patients treated with immune checkpoint inhibitors: A United States population-level analysis. J Am Acad Dermatol. Published online 2021:1–10. doi:10.1016/j.jaad.2021.03.094.Kalinich M, Murphy W, Wongvibulsin S, Pahalyants V, et al. Prediction of severe immune-related adverse events requiring hospital admission in patients on immune checkpoint inhibitors: study of a population level insurance claims database from the USA. J Immunother Cancer. 2021;9(3):e001935. doi: 10.1136/jitc-2020-001935. PMID: 33789879; PMCID: PMC8016099.Ethics ApprovalStudy utilized de-identified data from a multi-institutional registry and is exempt from IRB approval.

BackgroundImmune checkpoint inhibitors (ICI) generate T-cell mediated anti-tumor responses that are effective across numerous malignancies, but their use is frequently complicated by immune-related adverse events (irAEs). irAEs may lead to treatment delays, need for immunosuppression, morbidity, and even mortality.1–3Checkpoint inhibitor pneumonitis (CIP) is the most common cause of fatality related to anti-programmed cell death receptor/ligand 1 (PD-1/PD-L1) agents, and can be difficult to diagnose.3 We aimed to characterize the real-world incidence and management of CIP, as well as its impact on clinical course and healthcare utilization, in a large cohort of ICI patients using a multi-institutional database.MethodsPropensity score-matched cohorts of 14,461 lung cancer patients who did or did not receive PD-1/PD-L1 inhibitors between 2014 to 2021 were identified from TriNetX Dataworks, a database of health records and claims data from over 40 institutions. Incidence of pneumonia/pneumonitis was estimated using billing codes. A subgroup of 158 patients was selected by the most specific code group and confirmed to have features consistent with suspected CIP, permitting analysis of management practices and outcomes. To describe differences in healthcare utilization and survival, a second propensity score-matched cohort was generated for the subgroup.ResultsThe attributable risk of pneumonitis to PD-1/PD-L1 inhibitors in lung cancer at 1 year after ICI initiation was 6.88% (95% CI 6.01–7.75%). Median time to onset of drug-induced pneumonitis in the subgroup was 4.4 months (IQR 2.1–7.8 months). Of 158 patients, 21 (13.3%) underwent bronchoscopy within 30 days after diagnosis. Prednisone (130/158, 82.3%), methylprednisolone (80/158, 50.6%), and antibiotics (135/158, 85.4%) were frequently prescribed. ICI was discontinued in 69.5% of patients within 90 days of drug-induced pneumonitis. Within the first year of PD-1/PD-L1 therapy, patients with pneumonitis had more hospitalizations (83.5% vs 49.4%, RR 1.69, p<0.0001) and ICU requirements than controls (28.5% vs 8.9%, RR 3.21, p<0.0001). Landmark analysis at 6 months demonstrated that CIP associated with reduced overall survival, with a mortality HR of 1.43 (95% CI 1.03–1.97, p=0.03).ConclusionsTo our knowledge, this is the largest study of CIP to date. Importantly, the study found that the incidence of PD-1/PD-L1-induced pneumonitis, 6.88%, is higher than clinical trial estimates (2–5%), but lower than reported in uncontrolled real-world studies (17–19%).4–8 CIP had significant negative impacts on therapy continuation, healthcare utilization, and overall survival in lung cancer. This work demonstrates proof of concept that studies of irAE incidences and patient outcomes are feasible using large claims and electronic health record databases.ReferencesBrahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. Journal of Clinical Oncology 2018;36(17):1714–1768. doi:10.1200/JCO.2017.77.6385.Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. Journal for ImmunoTherapy of Cancer 2017;5(1):95. doi:10.1186/s40425-017-0300-z.Wang DY, Salem JE, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncology 2018;4(12):1721–1728. doi:10.1001/jamaoncol.2018.3923.Nishino M, Giobbie-Hurder A, Hatabu H, Ramaiya NH, Hodi FS. Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer a systematic review and meta-analysis. JAMA Oncology 2016;2(12):1607–1616. doi:10.1001/jamaoncol.2016.2453.Naidoo J, Wang X, Woo KM, et al. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. Journal of Clinical Oncology 2017;35(7):709–717. doi:10.1200/JCO.2016.68.2005.Delaunay M, Cadranel J, Lusque A, et al. Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients. European Respiratory Journal 2017;50(2). doi:10.1183/13993003.00050-2017.Suresh K, Voong KR, Shankar B, et al. Pneumonitis in non–small cell lung cancer patients receiving immune checkpoint immunotherapy: incidence and risk factors. Journal of Thoracic Oncology 2018;13(12):1930–1939. doi:10.1016/j.jtho.2018.08.2035.Cathcart-Rake EJ, Sangaralingham LR, Henk HJ, Shah ND, Riaz I bin, Mansfield AS. A population-based study of immunotherapy-related toxicities in lung cancer. Clinical Lung Cancer 2020;21(5):421–427.e2. doi:10.1016/j.cllc.2020.04.003Ethics ApprovalAs described on TriNetX's website (https://trinetx.com/trinetx-publication-guidelines/), all data available on the network is de-identified and in-line with HIPAA Privacy Rule standards.

BackgroundImmune-related adverse events (irAEs) are serious side effects of immune checkpoint inhibitors (ICIs) for patients with advanced cancer. Understanding the epidemiology and risk factors for severe irAEs would be beneficial for patients and clinicians.MethodsWe performed a retrospective review of cancer patients treated with ICIs using un-identifiable claims data from a nationwide US health insurance plan from January 3rd, 2011 to December 31st, 2019. Patients with an identified primary cancer and at least one administration of an ICI were included in the study. We defined severe irAE as any inpatient hospitalization with new immunosuppression within 2 years after initiation of ICI. The main outcomes were incidence of severe irAE in ICI therapy and factors associated with severe irAE occurrence. Multivariable logistic regression, including Charlson comorbidity index, age, gender, primary cancer, region, and zip code average income and unemployment, was used to model risk factors for severe irAE (table 1).ResultsThere were 14,378 patients followed over 19,177 patient-years identified with a primary cancer and at least 1 administration of ICI. 504 (3.5%) patients developed a severe irAE. The incidence of severe irAEs per patient ICI treatment year was 2.6%, rising from 0% (0/71) in 2011 to 3.7% (93/2486) in 2016 (figure 1). Combination immunotherapy (OR: 2.44, p < 0.001) and younger age (OR: 0.77, p < 0.001) were associated with increased odds of developing severe irAEs, whereas patients with non-lung cancer were associated with decreased odds of irAEs (melanoma OR: 0.70, p = 0.01, renal cell carcinoma OR: 0.71, p = 0.03, other cancers OR: 0.50, p < 0.001; figure 1). Sex, region, zip code income, and zip-code imputed unemployment were not associated with severe irAE incidence. Prednisone (72%) and methylprednisone (25%) were the most common immunosuppressive treatments identified in irAE hospitalizations.Abstract 854 Table 1Multivariate Regression Results for Incidence of Severe irAEAbstract 854 Figure 1irAE hospitalizations vs. Total HospitalizationsConclusionsWe found that 3.5% of patients initiating ICI therapy experienced severe irAEs requiring hospitalization and immunosuppression. The odds of severe irAEs were higher with younger age, treatment with combination ICI therapy (CTLA-4 and PD-1 or PD-L1), and lower for other cancers compared with patients on PD-1 or PD-L1 inhibitors with lung cancer. This evidence from the first nationwide study of severe irAEs in the US identified the real-world epidemiology, risk factors, and treatment patterns of severe irAEs in the US which may guide treatment selection and decisions for patients and clinicians.

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a high rate of mortality. While still relatively rare, the incidence of MCC has been rapidly rising in the US and around the world. Since 2017, two immunotherapeutic drugs, avelumab and pembrolizumab, have been FDA-approved for the treatment of metastatic MCC and have revolutionized outcomes for MCC. However, real-world outcomes can differ from clinical trial data, and the adoption of novel therapeutics can be gradual. We aimed to characterize the treatment practices and outcomes of patients with metastatic MCC across the US. A retrospective cohort study of adult cases of MCC in the National Cancer Database diagnosed from 2004 to 2019 was performed. Multivariable logistic regressions to determine the association of a variety of patient, tumor, and system factors with likelihood of receipt of systemic therapies were performed. Univariate Kaplan–Meier and multivariable Cox survival regressions were performed. We identified 1017 cases of metastatic MCC. From 2017 to 2019, 54.2% of patients received immunotherapy. This increased from 45.1% in 2017 to 63.0% in 2019. High-volume centers were significantly more likely to use immunotherapy (odds ratio 3.235, p = 0.002). On univariate analysis, patients receiving systemic immunotherapy had significantly improved overall survival (p < 0.001). One-, 3-, and 5-year survival was 47.2% (standard error [SE] 1.8%), 21.8% (SE 1.5%), and 16.5% (SE 1.4%), respectively, for patients who did not receive immunotherapy versus 62.7% (SE 3.5%), 34.4% (SE 3.9%), and 23.6% (SE 4.4%), respectively, for those who did (Fig. 1). In our multivariable survival regression, receipt of immunotherapy was associated with an approximately 35% reduction in hazard of death (hazard ratio 0.665, p  < 0.001; 95% CI 0.548–0.808). Our results demonstrate that the real-world survival advantage of immunotherapy for metastatic MCC is similar to clinical trial data. However, many patients with metastatic disease did not receive this guideline-recommended therapy in our most recent study year, and use of immunotherapy is higher at high-volume centers. This suggests that regionalization of care to high-volume centers or dissemination of their practices, may ultimately improve patient survival.

Large language models (LLMs) are routinely used by physicians and patients for medical advice, yet their clinical safety profiles remain poorly characterized. We present NOHARM (Numerous Options Harm Assessment for Risk in Medicine), a benchmark using 100 real primary care-to-specialist consultation cases to measure frequency and severity of harm from LLM-generated medical recommendations. NOHARM covers 10 specialties, with 12,747 expert annotations for 4,249 clinical management options. Across 31 LLMs, potential for severe harm from LLM recommendations occurs in up to 22.2% (95% CI 21.6-22.8%) of cases, with harm of omission accounting for 76.6% (95% CI 76.4-76.8%) of errors. Safety performance is only moderately correlated (r = 0.61-0.64) with existing AI and medical knowledge benchmarks. The best models outperform generalist physicians on safety (mean difference 9.7%, 95% CI 7.0-12.5%), and a diverse multi-agent approach improves safety compared to solo models (mean difference 8.0%, 95% CI 4.0-12.1%). Therefore, despite strong performance on existing evaluations, widely used AI models can produce severely harmful medical advice at nontrivial rates, underscoring clinical safety as a distinct performance dimension necessitating explicit measurement.