Immune Checkpoints Inhibitors and SRS/SBRT Synergy in Metastatic Non-Small-Cell Lung Cancer and Melanoma: A Systematic Review

• Published in: International journal of molecular sciences Vol. 22; no. 21; p. 11621
• Main Authors: Rodríguez Plá, María, Dualde Beltrán, Diego, Ferrer Albiach, Eduardo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27-10-2021; MDPI
• Subjects: anti-CTLA4; anti-PD-L1; Antigens; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - radiotherapy; Clinical trials; Combined Modality Therapy - methods; Criteria; Histology; Humans; Immune checkpoint; immune checkpoint inhibitors; Immune Checkpoint Inhibitors - pharmacology; Immunotherapy; Immunotherapy - methods; Inhibitors; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - radiotherapy; Lymphocytes; Medical prognosis; Melanoma; Melanoma - drug therapy; Melanoma - radiotherapy; Metastases; Metastasis; Non-small cell lung carcinoma; Radiation therapy; Radiosurgery; Radiosurgery - methods; Review; stereotactic body radiation therapy; stereotactic radiosurgery; Synergistic effect; T cell receptors; Tumors; ICI-SRS; anti-CTLA4; anti-PD-L1; ICI-SBRT; radiation therapy; immune checkpoint inhibitors; stereotactic body radiation therapy; stereotactic radiosurgery
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222111621

Several immunotherapy (IT) agents are FDA approved for treatment of melanoma and non-small-cell lung cancer (NSCLC). The addition of stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT) to immunotherapy looks promising. A systematic review was conducted to evaluate the possible synergistic effects of immune checkpoints inhibitors (ICIs) and stereotactic radiation therapy in melanoma and NSCLC.
Pubmed databases from January 2010 to December 2020 were reviewed to identify English language studies reporting control of local and abscopal effect of the combination of ICI-SBRT/SRS in metastatic NSCLC and melanoma cancer. The inclusion criteria were followed according to PICO criteria.
Thirty-nine articles were included of the 2141 initial results. The reported rates for local control were 16.5-100% and 40-94% in brain and extracerebral metastases, respectively. Distant/abscopal response rates were 1-45% in extracerebral metastases. Abscopal effect could not be evaluated in brain metastases because it was not reported in studies. Treatments were well tolerated with few grade 4 toxicities and no grade 5.
The combined treatment of ICI-SBRT/SRS achieves high local control and non-negligible abscopal response in patients with extracerebral metastases, with its benefit in cerebral metastases being more controversial. Clinical trials are needed to better characterize the potential synergism.