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Simple Summary: Talimogene laherparepvec (TVEC), a modified virus, is a local injected therapy that has been demonstrated to be an effective treatment in patients with advanced melanoma. Recent reports have suggested that radiation treatment (RT) may activate the immune system when combined with TVEC to further improve both local and systemic responses. However, studies on the combined effect of TVEC and RT remain limited. Here, we reviewed twenty melanoma patients who had received TVEC and RT (fourteen patients to the same region and six patients to different regions of the body) and found a benefit in progression-free survival (PFS) and time to distance metastasis (DM) with a combined regional approach of TVEC and RT. These results suggest that the regional approach of using these two treatment modalities may confer a therapeutic benefit. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Based on recent clinical trials, radiation is a standard treatment option for limited metastatic sites in metastatic breast cancer, with the potential to improve survival. This is typically given in the form of high-dose radiation called stereotactic body radiotherapy (SBRT). However, SBRT is a newer technology that is not on option for all patients and does not have long-term follow-up. Prior to the widespread implementation of SBRT, we performed a clinical trial utilizing high-dose chemotherapy and standard radiation for metastases in patients with limited metastatic breast cancer. In this research, we analyzed the long-term outcomes of these patients. We found that, despite not using SBRT, radiation provided promising long-term disease control and survival. Therefore, conventional radiation might still be considered if SBRT in not an option for a patient, and our results also help suggest what long-term outcomes of SBRT treatment might look like. Background: Patients with oligometastatic breast cancer (oMBC) may benefit from aggressive local therapy. We sought to assess the effects of consolidative radiation therapy (RT) on outcomes in oMBC patients treated on a prospective phase II trial of high-dose chemotherapy (HDCT). Methods: Between 2005 and 2009, 12 patients with oMBC (≤3 metastatic sites) cancer were treated on protocol. Patients were to receive tandem HDCT supported by hematopoietic cell rescue (HCR). All radiographically identifiable oligometastatic sites received targeted radiation. Results: HDCT was initiated at a median of 6.7 (3.5–12.7) months after diagnosis of oMBC. Hormone receptors (HR) were positive in 91.6% of patients, and HER2 was overexpressed in 25% of patients. Median radiation dose (EQD2) was 41.2 (37.9–48.7) Gy. Median follow-up was 13.1 (6.8–15.1) years for living patients. Ten-year PFS and OS were 33% (95%CI, 10–59%) and 55% (95%CI, 22–79%), respectively. Durable local control of treated lesions was 87.5%. At the last follow up, two patients remained progression free and two more were without evidence of disease following additional salvage treatment. Conclusions: Although modern systemic therapies have obviated the use of HDC, aggressive local therapy warrants further evaluation and fractionated radiotherapy is a viable alternative if SBRT is not available. [ABSTRACT FROM AUTHOR]