Talimogene laherparepvec (TVEC) is a genetically modified oncolytic herpes simplex virus (HSV-1) that is used for the intralesional treatment of advanced or metastatic melanoma. Given that TVEC produces the granulocyte–macrophage colony-stimulating factor (GM-CSF), recent reports have suggested that radiation treatment (RT) given in conjunction with TVEC may provide synergistic immune activation at the site, and possibly systemically. However, studies on combining RT with TVEC remain limited. We conducted a retrospective review of melanoma patients from a single cancer center who received TVEC and RT in the same region of the body and compared them to patients who received TVEC with RT at another site (other than the site of TVEC injection). Between January 2015 and September 2022, we identified twenty patients who were treated with TVEC and RT; fourteen patients received TVEC and RT in the same region, and six had treatments in separate regions. Regions were determined at the time of analysis and were based on anatomic sites (such as arm, leg, torso, etc.). Kaplan–Meier analysis of progression-free survival (PFS), analyses of time to distant metastasis (DM), overall survival (OS), and locoregional control (LRC), and the corresponding log-rank test were performed. With a median follow-up of 10.5 months [mos] (range 1.0–58.7 mos), we found an improvement in PFS with TVEC and RT in the same region compared to different regions, which were 6.4 mos (95% CI, 2.4–NR mos) and 2.8 mos (95% CI, 0.7–4.4 mos), respectively;p= 0.005. There was also a significant improvement in DM when TVEC and RT were used in the same region compared to different regions: 13.8 mos (95% CI, 4.6–NR mos) and 2.8 mos (95% CI, 0.7–4.4 mos), respectively (p= 0.001). However, we found no difference in overall survival (OS) between patients who had TVEC and RT in the same region (19.0 mos, 95% confidence interval [CI], 4.1–not reached [NR] mos) and those who received treatments in different regions (18.5 mos, 95% CI, 1.0–NR mos);p= 0.366. There was no statistically significant improvement in locoregional control (LRC) in patients who had TVEC and RT in the same region was 26.0 mos (95% CI, 6.4–26.0 mos) compared to patients who received TVEC and RT in different regions (4.4 mos) (95% CI, 0.7–NR mos) (p= 0.115). No grade 3 or higher toxicities were documented in either group. Overall, there were improvements in PFS and DM when TVEC and RT were delivered to the same region of the body compared to when they were used in different regions. However, we did not find a significant difference in locoregional recurrence or OS. Future studies are needed to assess the sequence and timing of combining RT and TVEC to potentially enhance the immune response both locally and distantly.
Talimogene laherparepvec（TVEC）是一种经过基因改造的溶瘤性单纯疱疹病毒（HSV-1），用于晚期或转移性黑色素瘤的病灶内治疗。鉴于TVEC能够产生粒细胞-巨噬细胞集落刺激因子（GM-CSF），近期有报道指出，联合使用放射治疗（RT）与TVEC可能在局部甚至全身产生协同免疫激活效应。然而，关于RT与TVEC联合应用的研究仍较为有限。本研究对来自单一癌症中心的黑色素瘤患者进行了回顾性分析，这些患者均接受了TVEC与RT治疗，其中一组在同一身体区域接受治疗，另一组则在TVEC注射部位以外的其他区域接受RT治疗。在2015年1月至2022年9月期间，我们共确定了20例接受TVEC与RT治疗的患者；其中14例患者在同一区域接受了TVEC与RT治疗，6例患者在不同区域接受了治疗。区域划分基于解剖部位（如手臂、腿部、躯干等）并在分析时确定。研究进行了无进展生存期（PFS）的Kaplan-Meier分析、远处转移时间（DM）、总生存期（OS）及局部区域控制（LRC）的分析，并进行了相应的对数秩检验。中位随访时间为10.5个月（范围1.0–58.7个月），我们发现，与在不同区域接受治疗相比，同一区域接受TVEC与RT治疗的患者PFS有所改善，分别为6.4个月（95% CI，2.4–NR个月）和2.8个月（95% CI，0.7–4.4个月）；p=0.005。同时，同一区域接受TVEC与RT治疗的患者DM时间也显著改善：分别为13.8个月（95% CI，4.6–NR个月）和2.8个月（95% CI，0.7–4.4个月）（p=0.001）。然而，我们发现同一区域接受治疗的患者（19.0个月，95% CI，4.1–未达到[NR]个月）与不同区域接受治疗的患者（18.5个月，95% CI，1.0–NR个月）在总生存期（OS）方面无显著差异；p=0.366。在局部区域控制（LRC）方面，同一区域接受治疗的患者（26.0个月，95% CI，6.4–26.0个月）与不同区域接受治疗的患者（4.4个月，95% CI，0.7–NR个月）相比，未观察到统计学上的显著改善（p=0.115）。两组均未记录到3级或更高级别的毒性反应。总体而言，与在不同区域应用相比，TVEC与RT在同一身体区域应用时，PFS和DM时间均有所改善。然而，在局部区域复发或OS方面，我们未发现显著差异。未来需要进一步研究评估RT与TVEC联合应用的顺序和时机，以潜在地增强局部及远处的免疫反应。
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