Grynberg Shirly, Stoff Ronen, Asher Nethanel, Shapira-Frommer Ronnie, Schachter Jacob, Haisraely Ory, Lawrence Yaacov, Ben-Betzalel Guy
Ella Lemelbaum Institute of Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel.
Department Radiation Oncology, Sheba Medical Center, Ramat Gan, Israel.
Ther Adv Med Oncol. 2022 Oct 31;14:17588359221131521. doi: 10.1177/17588359221131521. eCollection 2022.
Uveal melanoma (UM) is a subtype of melanoma arising from the ocular region. Despite various local therapies available, a significant portion of patients develop distant metastases, primarily to the liver. While cutaneous melanoma is very sensitive to immunotherapy, UM is known to be less responsive and patients were excluded from pivotal clinical trials. To date, there is no standard first line therapy for metastatic UM and clinical trial participation is encouraged. While UM is considered a radio-resistant tumor, there is a role for radiotherapy (RT) as palliative treatment and possibly for immune sensitization. This a retrospective analysis aimed at addressing the role of combination checkpoint inhibitors (ICI) with RT as a synergistic treatment in metastatic UM patient. We hypothesized that concurrent RT would improve the clinical response to immunotherapy.
Retrospective chart review of patients with metastatic UM treated with ICI at Ella Lemelbaum Institute between 2015 and 2021. Patients' electronic medical records were analyzed for baseline characteristics, response rate and survival data. Patients were grouped according to receipt of concomitant RT. Study was approved by local IRB and statistical analyses done using Stata V.17.
Thirty-nine patients were treated with immunotherapy. Fifty percent were treated with anti-programmed cell death (PD)-1 and 50% with anti-PD1- anti CTLA4 combination therapy. Nine patients were treated concomitantly with immunotherapy and external beam RT or with stereotactic body RT (group A) and 29 patients were treated with immunotherapy alone (group B). Overall response rate was significantly higher in group A (44% 10%, = 0.004). Median progression-free survival was longer for patients in group A (22 months 3 m, Hazard Ratio (HR) = 0.37, = 0.036). Median overall survival was also longer for group A (26 months 7.5 m, HR = 0.34, = 0.03). Toxicity was comparable between the groups.
RT may improve response to immunotherapy with ICI in metastatic UM patients and may confer an advantage in survival. Further prospective, larger studies are warranted.
葡萄膜黑色素瘤（UM）是一种起源于眼部区域的黑色素瘤亚型。尽管有多种局部治疗方法，但仍有相当一部分患者会发生远处转移，主要转移至肝脏。虽然皮肤黑色素瘤对免疫疗法非常敏感，但已知UM对免疫疗法的反应较差，患者被排除在关键临床试验之外。迄今为止，转移性UM尚无标准的一线治疗方法，鼓励患者参与临床试验。虽然UM被认为是一种放射抗拒性肿瘤，但放射治疗（RT）在姑息治疗中以及可能在免疫致敏方面具有一定作用。这是一项回顾性分析，旨在探讨联合检查点抑制剂（ICI）与RT作为转移性UM患者的协同治疗方法的作用。我们假设同步RT会改善对免疫疗法的临床反应。
对2015年至2021年期间在埃拉·莱梅尔鲍姆研究所接受ICI治疗的转移性UM患者进行回顾性病历审查。分析患者的电子病历以获取基线特征、缓解率和生存数据。根据是否接受同步RT对患者进行分组。该研究获得当地机构审查委员会的批准，并使用Stata V.17进行统计分析。
39例患者接受了免疫治疗。50%的患者接受抗程序性细胞死亡（PD）-1治疗，50%的患者接受抗PD1-抗细胞毒性T淋巴细胞相关抗原4（CTLA4）联合治疗。9例患者同时接受免疫治疗和外照射RT或立体定向体部RT（A组），29例患者仅接受免疫治疗（B组）。A组的总体缓解率显著更高（44%±10%，P = 0.004）。A组患者的无进展生存期中位数更长（22个月±3个月，风险比（HR）= 0.37，P = 0.036）。A组的总生存期中位数也更长（26个月±7.5个月，HR = 0.34，P = 0.03）。两组之间的毒性相当。
RT可能会改善转移性UM患者对ICI免疫疗法的反应，并可能在生存方面具有优势。有必要进行进一步的前瞻性、更大规模的研究。
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