{
  "abstract": "Background Brain metastases are a life-limiting complication of advanced melanoma. With the advent of immune checkpoint inhibitors (ICI), survival outcomes for these patients have significantly improved. 1 2 However, the optimal sequencing of ICI relative to radiation (RT), and surgery remains unclear.3 4 This study aims to evaluate progression-free survival (PFS) and overall survival (OS) in patients with melanoma brain metastases (MBM) based on different treatment sequences involving ICI, RT, and surgery.Methods We conducted a retrospective cohort study of melanoma patients with brain metastases treated at Brown University Health between 2005 to 2024. Patients were categorized based on the sequencing of ICI before or after either RT only, surgery only, or both RT and surgery. Primary endpoints, OS and intracranial PFS, were analyzed using Kaplan-Meier survival curves, log-rank tests and cox proportional hazards models.Results Of 382 patients with metastatic melanoma, 76 were found to have brain metastasis. Sixteen patients had MBM at time of diagnosis. Regardless of the treatment order, patients that received all three treatment modalities ICI, RT and surgery (n=14) had improved PFS (HR=0.25, 95% CI: 0.118-0.531, p=.0003) and OS (HR= 0.212, 95% CI: 0.0748–0.600, p=.0035) compared to those receiving just one treatment modality. Receiving ICI before RT (n=19) or ICI after RT (n=18) did not have better OS (p=.68) compared to RT or ICI alone (n=17). Patients who first underwent surgical resection (n=15) had a lower risk of disease progression compared to those treated with ICI first (n=32) (HR=0.479, 95% CI 0.246-0.931, p=0.03), though this did not impact OS (HR=0.438, 95% CI: 0.190–1.01, p= 0.536). The use of ICI in combination with surgery significantly improved PFS (figure 1) and OS (figure 2) compared to surgery or ICI alone. ICI combined with surgery had a median OS of 90.60 months (95% CI: 58.28-N/A), and PFS of 35.46 months (95% CI: 7.33-83.54). Patients who underwent surgery as initial treatment modality surgery experienced a median PFS of 21.15 months (95% CI: 7.32-83.54) compared to 9.57 months (95% CI: 2.36-19.28) for patients initially treated with ICI.Conclusions Our findings suggest that combining multiple treatment modalities provides greater survival benefit than the specific sequence in which treatments are given. Combining ICI with surgery may improve survival in MBM patients. Upfront surgery was associated with longer progression-free survival but not overall survival compared to initial ICI therapy. Larger studies are needed to confirm these results and guide optimal treatment strategies.References Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, Khushalani NI, Lewis K, Lao CD, Postow MA, Atkins MB, Ernstoff MS, Reardon DA, Puzanov I, Kudchadkar RR, Thomas RP, Tarhini A, Pavlick AC, Jiang J, Avila A, … Margolin K. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. The New England Journal of Medicine 2018;379(8):722–730. https://doi.org/10.1056/NEJMoa1805453Amouzegar A, Tawbi H. Local and systemic management options for melanoma brain metastases. The Cancer Journal 2024;30(2):102-107. doi: 10.1097/PPO.0000000000000711Petrelli F, De Stefani A, Trevisan F, Parati C, Inno A, Merelli B, Ghidini M, Bruschieri L, Vitali E, Cabiddu M, Borgonovo K, Ghilardi M, Barni S, Ghidini A. (Combination of radiotherapy and immunotherapy for brain metastases: A systematic review and meta-analysis. Critical Reviews in Oncology/Hematology 2019;144:102830. https://doi.org/10.1016/j.critrevonc.2019.102830Alvarez-Breckenridge C, Giobbie-Hurder A, Gill CM, Bertalan M, Stocking J, Kaplan A, Nayyar N, Lawrence DP, Flaherty KT, Shih HA, Oh K, Batchelor TT, Cahill DP, Sullivan R, Brastianos PK. Upfront surgical resection of melanoma brain metastases provides a bridge toward immunotherapy-mediated systemic control. The Oncologist 2019;24(5):671–679. https://doi.org/10.1634/theoncologist.2018-0306Ethics Approval This retrospective study involving patient information was approved by the Lifespan- Rhode Island Hospital Institutional Review Board (IRB #00000482). The IRB determined that the research met criteria for a waiver of informed consent, as it involved no more than minimal risk to participants and could not be practicably conducted without the waiver. The IRB approved the study in accordance with institutional and federal guidelines.Abstract 680 Figure 1Progression-free survival of combined ICI and surgery vs. ICI or surgery aloneAbstract 680 Figure 2Overall survival of combined ICI and surgery vs. ICI or surgery alone",
  "authors": [
    {
      "affiliations": [
        "Brown University Health, Providence, RI, USA"
      ],
      "name": "Charmi Trivedi"
    },
    {
      "affiliations": [
        "Brown University Health, Providence, RI, USA"
      ],
      "name": "Kaavya Mandi"
    },
    {
      "affiliations": [
        "Warren Alpert Medical School of Brown University, Providence, RI, USA"
      ],
      "name": "Victoria Gill"
    },
    {
      "affiliations": [
        "Brown University Health, Providence, RI, USA"
      ],
      "name": "Bridget Harrop"
    },
    {
      "affiliations": [
        "Warren Alpert Medical School of Brown University, Providence, RI, USA"
      ],
      "name": "Justine Elshama"
    },
    {
      "affiliations": [
        "Warren Alpert Medical School of Brown University, Providence, RI, USA"
      ],
      "name": "Julia Contini"
    },
    {
      "affiliations": [
        "Brown University Health, Providence, RI, USA"
      ],
      "name": "Hetal Mistry"
    },
    {
      "affiliations": [
        "Brown University Health, Providence, RI, USA"
      ],
      "name": "Matthew J Hadfield"
    }
  ],
  "title": "680 Assessing outcomes in melanoma patients with brain metastases: a retrospective study of immunotherapy, radiation, and surgical treatment sequencing",
  "uid": "e7a00d80-8411-5dc1-978c-5f1a46747ae5"
}