{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:35:08Z","timestamp":1785497708426,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2013macrophage 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\u2013Meier 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\u201358.7 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\u2013NR mos) and 2.8 mos (95% CI, 0.7\u20134.4 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\u2013NR mos) and 2.8 mos (95% CI, 0.7\u20134.4 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\u2013not reached [NR] mos) and those who received treatments in different regions (18.5 mos, 95% CI, 1.0\u2013NR 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\u201326.0 mos) compared to patients who received TVEC and RT in different regions (4.4 mos) (95% CI, 0.7\u2013NR 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.<\/jats:p>","DOI":"10.3390\/cancers16111951","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T06:54:09Z","timestamp":1716360849000},"page":"1951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Combined Regional Approach of Talimogene laherparepvec and Radiotherapy in the Treatment of Advanced Melanoma"],"prefix":"10.3390","volume":"16","author":[{"given":"Andrew","family":"Tam","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd., Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2668-3415","authenticated-orcid":false,"given":"Colton","family":"Ladbury","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd., Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Kassardjian","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd., Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badri","family":"Modi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd., Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"McGee","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd., Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laleh","family":"Melstrom","sequence":"additional","affiliation":[{"name":"Department of Surgery, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd., Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Margolin","sequence":"additional","affiliation":[{"name":"St. John\u2019s Cancer Institute, 2121 Santa Monica Blvd., Santa Monica, CA 90404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arya","family":"Amini","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd., Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1200\/JCO.2014.58.3377","article-title":"Talimogene Laherparepvec Improves Durable Response Rate in Patients with Advanced Melanoma","volume":"33","author":"Andtbacka","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s40425-019-0623-z","article-title":"Final Analyses of OPTiM: A Randomized Phase III Trial of Talimogene Laherparepvec versus Granulocyte-Macrophage Colony-Stimulating Factor in Unresectable Stage III\u2013IV Melanoma","volume":"7","author":"Andtbacka","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1158\/1078-0432.CCR-15-2667","article-title":"Molecular Pathways: Mechanism of Action for Talimogene Laherparepvec, a New Oncolytic Virus Immunotherapy","volume":"22","author":"Kohlhapp","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1200\/JCO.2017.73.7379","article-title":"Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination with Ipilimumab Versus Ipilimumab Alone in Patients with Advanced, Unresectable Melanoma","volume":"36","author":"Chesney","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1111\/bcp.14351","article-title":"Radiation Therapy and the Innate Immune Response: Clinical Implications for Immunotherapy Approaches","volume":"86","author":"Mustapha","year":"2020","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1093\/jnci\/djaa190","article-title":"Parallels Between the Antiviral State and the Irradiated State","volume":"113","author":"McGee","year":"2021","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1056\/NEJMoa1112824","article-title":"Immunologic Correlates of the Abscopal Effect in a Patient with Melanoma","volume":"366","author":"Postow","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1159\/000505487","article-title":"Systemic Antitumor Effects and Abscopal Responses in Melanoma Patients Receiving Radiation Therapy","volume":"98","author":"Reddy","year":"2020","journal-title":"Oncology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1200\/JCO.2023.41.16_suppl.2639","article-title":"A Phase II Randomized Trial of Talimogene Laherparepvec (T-VEC) Oncolytic Immunotherapy with or without Radiotherapy for Patients with Cutaneous Metastases from Solid Tumors","volume":"41","author":"Barker","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.ejca.2022.04.018","article-title":"European Consensus-Based Interdisciplinary Guideline for Melanoma. Part 2: Treatment\u2014Update 2022","volume":"170","author":"Garbe","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"367","DOI":"10.6004\/jnccn.2019.0018","article-title":"Cutaneous Melanoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology","volume":"17","author":"Coit","year":"2019","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.critrevonc.2017.12.020","article-title":"ECCO Essential Requirements for Quality Cancer Care: Melanoma","volume":"122","author":"Wouters","year":"2018","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1007\/s00262-008-0467-8","article-title":"Experimental Manipulations of Afferent Immune Responses Influence Efferent Immune Responses to Brain Tumors","volume":"57","author":"Thomas","year":"2008","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_14","unstructured":"(2024, February 07). Memorial Sloan Kettering Cancer Center A Phase II Randomized Trial of Intralesional Talimogene Laherparepvec (TALIMOGENE LAHERPAREPVEC) with or without Radiotherapy for Cutaneous Melanoma, Merkel Cell Carcinoma, or Other Solid Tumors, Available online: https:\/\/clinicaltrials.gov."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3857\/roj.2015.33.4.265","article-title":"Radiobiological Mechanisms of Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery","volume":"33","author":"Kim","year":"2015","journal-title":"Radiat. Oncol. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1038\/sj.cdd.4402148","article-title":"Cell Death Modalities: Classification and Pathophysiological Implications","volume":"14","author":"Galluzzi","year":"2007","journal-title":"Cell Death Differ."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/jnci\/djs629","article-title":"Combining Radiotherapy and Cancer Immunotherapy: A Paradigm Shift","volume":"105","author":"Formenti","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Jarosz-Biej, M., Smolarczyk, R., Cicho\u0144, T., and Ku\u0142ach, N. (2019). Tumor Microenvironment as A \u201cGame Changer\u201d in Cancer Radiotherapy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133212"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.ijrobp.2011.09.049","article-title":"Maximizing Tumor Immunity with Fractionated Radiation","volume":"83","author":"Schaue","year":"2012","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.ijrobp.2021.04.009","article-title":"Fractionated Radiation Severely Reduces the Number of CD8+ T Cells and Mature Antigen Presenting Cells within Lung Tumors","volume":"111","author":"Reijmen","year":"2021","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1158\/2326-6066.CIR-18-0793","article-title":"Phase II Trial of Ipilimumab with Stereotactic Radiation Therapy for Metastatic Disease: Outcomes, Toxicities, and Low-Dose Radiation\u2013Related Abscopal Responses","volume":"7","author":"Welsh","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_22","first-page":"25","article-title":"Role of Radiotherapy in Extracranial Metastatic Malignant Melanoma in the Modern Era","volume":"6","author":"Youland","year":"2017","journal-title":"Clin. Transl. Radiat. Oncol."},{"key":"ref_23","unstructured":"IMLYGIC (2024, January 18). FDA 2023, Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/cellular-gene-therapy-products\/imlygic."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1074477","DOI":"10.3389\/fimmu.2022.1074477","article-title":"Radiotherapy Induced Immunogenic Cell Death by Remodeling Tumor Immune Microenvironment","volume":"13","author":"Zhu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41590-019-0561-4","article-title":"Immunological Impact of Cell Death Signaling Driven by Radiation on the Tumor Microenvironment","volume":"21","author":"Vitale","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_26","first-page":"8466","article-title":"Radiotherapy Potentiates the Therapeutic Efficacy of Intratumoral Dendritic Cell Administration","volume":"63","author":"Li","year":"2003","journal-title":"Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/s41416-020-0942-3","article-title":"Radiation-Induced Bystander and Abscopal Effects: Important Lessons from Preclinical Models","volume":"123","author":"Daguenet","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.semcancer.2022.04.003","article-title":"Radiation Therapy-Induced Remodeling of the Tumor Immune Microenvironment","volume":"86","author":"Charpentier","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e003119","DOI":"10.1136\/jitc-2021-003119","article-title":"Intratumoral Talimogene Laherparepvec Injection with Concurrent Preoperative Radiation in Patients with Locally Advanced Soft-Tissue Sarcoma of the Trunk and Extremities: Phase IB\/II Trial","volume":"9","author":"Monga","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Young, K.H., Baird, J.R., Savage, T., Cottam, B., Friedman, D., Bambina, S., Messenheimer, D.J., Fox, B., Newell, P., and Bahjat, K.S. (2016). Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157164"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5458","DOI":"10.1158\/0008-5472.CAN-14-1258","article-title":"Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade","volume":"74","author":"Dovedi","year":"2014","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"612","DOI":"10.3389\/fonc.2018.00612","article-title":"Radiation, Immune Checkpoint Blockade and the Abscopal Effect: A Critical Review on Timing, Dose and Fractionation","volume":"8","author":"Buchwald","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/14737159.2024.2314574","article-title":"Emerging Prognostic Biomarkers in Advanced Cutaneous Melanoma: A Literature Update","volume":"24","author":"Roccuzzo","year":"2024","journal-title":"Expert Rev. Mol. Diagn."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/11\/1951\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:45:57Z","timestamp":1760107557000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/11\/1951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,21]]},"references-count":33,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["cancers16111951"],"URL":"https:\/\/doi.org\/10.3390\/cancers16111951","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,21]]}}}