{
  "abstract": "Background Immune checkpoint inhibitors (ICIs) have revolutionized therapy for metastatic melanoma, substantially improving survival outcomes. 1 2 However, as ICI-treated patients live longer, non-cancer causes of death, especially cardiovascular disease (CVD), have become more clinically relevant. ICIs are associated with immune-related cardiovascular toxicities such as myocarditis and arrhythmias,3 4 yet their population-level impact on CVD mortality in melanoma survivors remains unclear. This study investigates trends in melanoma-specific and CVD mortality across treatment eras to guide future survivorship models.5 Methods We conducted a retrospective cohort analysis using SEER 18 (2005–2017), identifying patients diagnosed with AJCC stage IV cutaneous melanoma. Treatment periods were categorized into pre-ICI (2005–2010) and ICI (2015–2017) eras, excluding transitional years. Cause-specific mortality was assessed using cumulative incidence functions (CIFs), accounting for competing risks. A multivariable logistic regression model evaluated predictors of 5-year CVD death, adjusted for age, sex, race, and treatment modalities. Subgroup analyses included stratification by demographic features.Results Among 6,868 patients (median age 70 years, 63% male), 5-year melanoma-specific death declined from 69.8% in the pre-ICI era to 48.4% during the ICI era. Simultaneously, 5-year CVD mortality increased from 2.9% to 4.2% (p=0.02). The largest absolute increase in CVD mortality was seen among patients ≥70 years, males, and non-Hispanic Whites. In adjusted analyses, surgical treatment was an independent predictor of CVD death (OR 1.69, 95% CI 1.21–2.36), while chemotherapy, sex, and era were not significant ( figure 1, table 1).Conclusions While ICIs have substantially improved melanoma-specific survival, a corresponding rise in cardiovascular mortality among survivors highlights the evolving nature of long-term risk. 6 7 These findings signal the emergence of CVD as a competing cause of death in durable responders, underscoring the need for a paradigm shift in post-treatment care. Integrating cardio-oncology frameworks into survivorship pathways will be essential for risk-adapted monitoring, early detection of subclinical toxicity, and timely cardioprotective intervention. Surveillance and longitudinal collaboration between oncology and cardiology may ultimately enhance both quality of life and overall survival in this growing patient population.8 References Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–2532. https://doi.org/10.1056/NEJMoa1503093Schadendorf D, Hodi FS, Robert C, et al. Pooled analysis of long-term survival data from phase II and III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol. 2015;33(17):1889–1894. https://doi.org/10.1200/JCO.2014.56.2736Mahmood SS, Fradley MG, Cohen JV, et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol. 2018;71(16):1755–1764. https://doi.org/10.1016/j.jacc.2018.02.037Lyon AR, Yousaf N, Battisti NML, et al. Immune checkpoint inhibitors and cardiovascular toxicity. Lancet Oncol. 2018;19(9):e447-e458. https://doi.org/10.1016/S1470-2045(18)30443-4Zaorsky NG, Churilla TM, Egleston BL, et al. Causes of death among cancer patients. Ann Oncol. 2017;28(2):400–407. https://doi.org/10.1093/annonc/mdw604Barac A, Gilchrist SC, Barr RD, et al. Quality-of-care measures for cardio-oncology: An IC-OS and ACC Cardio-Oncology Leadership Council perspective. JACC CardioOncol. 2025;7(3):191–202. https://doi.org/10.1016/j.jaccao.2024.11.003Waliany S, Dent S, Patel S, et al. Cardiovascular considerations during cancer therapy: gaps in evidence and JACC: CardioOncology expert panel recommendations. JACC CardioOncol. 2024;6(6):815–834. https://doi.org/10.1016/j.jaccao.2024.06.005Okwuosa TM, Armenian SH, Bhatia S, et al. Cardiovascular toxicity in patients treated for childhood cancer: A scientific statement from the American Heart Association. Circulation 2025;151(15):e926-e943. https://doi.org/10.1161/CIR.0000000000001308Abstract 726 Table 1Cumulative incidence function (CIF) estimates for melanoma-specific and cardiovascular (CVD) death in patients with stage IV melanoma, stratified by treatment era (pre-ICI vs. ICI) and follow-up time (1, 3, and 5 years)Abstract 726 Figure 1Forest plot of adjusted odds ratios for 5-year cardiovascular death. Adjusted odds ratios for 5-year cardiovascular death by demographic and clinical variables. Higher age and surgery were associated with increased risk; ORs shown with 95% confidence intervals",
  "authors": [
    {
      "affiliations": [
        "Pakistan Institute of Medical Sciences, Islamabad, Punjab, Pakistan"
      ],
      "name": "Manzer Ali"
    },
    {
      "affiliations": [
        "Internal Medicine Residency Program, Mercyhealth GME Consortium, Rockford, IL, USA"
      ],
      "name": "Saad Rashid"
    },
    {
      "affiliations": [
        "Oncology Program, Moffitt Cancer Center, Tampa, FL, USA"
      ],
      "name": "Mohammed Al-Jumayli"
    },
    {
      "affiliations": [
        "Rutgers-Trinitas Regional Medical Center, Elizabeth, NJ, USA"
      ],
      "name": "Hanzala Jahangir"
    },
    {
      "affiliations": [
        "Pakistan Institute of Medical Sciences, Islamabad, Punjab, Pakistan",
        "Internal Medicine Residency Program, Mercyhealth GME Consortium, Rockford, IL, USA",
        "Oncology Program, Moffitt Cancer Center, Tampa, FL, USA",
        "Rutgers-Trinitas Regional Medical Center, Elizabeth, NJ, USA",
        "Mercy Catholic Medical Center, Darby, PA, USA",
        "The New York Medical College Graduate Medical Education Program at St. Mary’s General Hospital and Saint Clare’s Health, Denville, NJ, USA",
        "Memorial HealthCare System, Hollywood, FL, USA",
        "Cleveland Clinic Akron General, Akron, OH, USA",
        "Mercyhealth GME Consortium, Rockford, IL, USA",
        "Mercy St. Vincent Internal Medicine Residency Program, Toledo, OH, USA"
      ],
      "name": "Aftab Ahmed"
    },
    {
      "affiliations": [
        "Mercy Catholic Medical Center, Darby, PA, USA"
      ],
      "name": "Resident Physician"
    },
    {
      "affiliations": [
        "The New York Medical College Graduate Medical Education Program at St. Mary’s General Hospital and Saint Clare’s Health, Denville, NJ, USA"
      ],
      "name": "Bolivia Fernandes"
    },
    {
      "affiliations": [
        "Memorial HealthCare System, Hollywood, FL, USA"
      ],
      "name": "Hareem Saleem"
    },
    {
      "affiliations": [
        "Cleveland Clinic Akron General, Akron, OH, USA"
      ],
      "name": "Kirti Arora"
    },
    {
      "affiliations": [
        "Mercyhealth GME Consortium, Rockford, IL, USA"
      ],
      "name": "Zayd Parekh"
    },
    {
      "affiliations": [
        "Mercyhealth GME Consortium, Rockford, IL, USA"
      ],
      "name": "Taqi Khaja"
    },
    {
      "affiliations": [
        "Mercy St. Vincent Internal Medicine Residency Program, Toledo, OH, USA"
      ],
      "name": "Sanam Farooq"
    }
  ],
  "title": "726 From cancer to cardiovascular disease: a SEER based competing-risk analysis of cause-specific mortality in stage IV melanoma before and after ICI adoption",
  "uid": "06944bb8-af6e-5118-bf88-9ad04d1399a0"
}