The utilization of immunotherapy with radiation therapy in lung cancer: a narrative review

Abstract

Despite decreasing smoking rates, lung cancer remains the leading cause of death from cancer in the United States. Radiation therapy has been established as an effective locoregional therapy for both early stage and locally advanced disease and is known to stimulate local immune response. Past treatment paradigms have established the role of combining cytotoxic chemotherapy regimens and radiation therapy to help address the local and systemic nature of lung cancer. However, these regimens have limitations in their tolerability due to toxicity. Additionally, cytotoxic chemotherapy has limited efficacy in preventing systemic spread of lung cancer. Newer systemic agents such as immune checkpoint inhibitors have shown improved survival in metastatic and locally advanced lung cancer and have the advantage of more limited toxicity profiles compared to cytotoxic chemotherapy. Furthermore, improved overall response rates and systemic tumor responses have been observed with the combination of radiation therapy and immunotherapy, leading to numerous active clinical trials evaluating the combination of immune checkpoint inhibition with radiotherapy. This comprehensive review discusses the current clinical data and ongoing studies evaluating the combination of radiation therapy and immunotherapy in both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).

Pneumonitis after Stereotactic Thoracic Radioimmunotherapy with Checkpoint Inhibitors: Exploration of the Dose–Volume–Effect Correlation

“…The majority of existing data in the literature investigated the incidence of pneumonitis after sequential or concurrent ICB treatment with RT and revealed increased all-grade lung injury with no increased high-grade toxicity [ 23 , 46 , 47 ] an thus is regarded to be safe. A multitude of studies analyzing SBRT and ICB therapy is currently ongoing and has been gathered in several reviews [ 7 , 25 , 48 ]. However, limited data suggest that the risk for pneumonitis and the resulting consequences with regard to treatment discontinuation might be underestimated [ 49 , 50 , 51 ] and the dose–volume relationships regarding the development of pneumonitis remain unclear.…”

Research Progress on the Microenvironment and Immunotherapy of Advanced Non-Small Cell Lung Cancer With Liver Metastases

“…In contrast, liver-directed radiotherapy increased hepatic T-cell infiltration, decreased hepatic myeloid numbers, and decreased the ratio of CD11b+F4/ 80+ myeloid/CD8+ T cells; in addition, combination therapy Enhanced therapeutic effect on Ki67+, gamma-interferon and granzyme B+ cd8 T cells. These studies demonstrate that liverdirected radiation therapy can simultaneously block the myeloid components of immunosuppression, stimulate liver T-cell immunity, reshape the immune microenvironment, and restore the antitumor effect of immunotherapy (54) Tumor irradiation can increase antigen expression and exposure, and has been found to increase T cell repertoires in preclinical models and patients (55). Radiation therapy can act as an immune adjuvant by inducing the formation of tumor micronuclei, generating cytoplasmic DNA, and causing lipid oxidation that stimulates immune responses (56).…”

“…Tumor irradiation can increase antigen expression and exposure, and has been found to increase T cell repertoires in preclinical models and patients ( 55 ). Radiation therapy can act as an immune adjuvant by inducing the formation of tumor micronuclei, generating cytoplasmic DNA, and causing lipid oxidation that stimulates immune responses ( 56 ).…”

Rationale for Combing Stereotactic Body Radiation Therapy with Immune Checkpoint Inhibitors in Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

“…Chemotherapy, which sensitizes the tumor within the irradiated volume to radiotherapy, has not been shown to lower the incidence of distant metastases following concurrent chemoradiation in locally advanced NSCLC [51][52][53]. Strategies to combine radiotherapy and ICIs in the treatment of lung cancer have been under intense investigation in recent years [54][55][56]. When combined with radiotherapy, ICIs have been shown to induce a significant and durable distant response in NSCLC patients.…”