Molecular and Clinical Premises for the Combination Therapy Consisting of Radiochemotherapy and Immunotherapy in Non-Small Cell Lung Cancer Patients

Abstract

Non-small cell lung cancer (NSCLC) is one of the most common malignancies around the world. Due to the advanced stage of the disease at the time of diagnosis, most patients require systemic treatment. Immunotherapy with immune checkpoints inhibitors is becoming the main treatment method for many cancers, including NSCLC. Numerous studies have shown greater efficacy of immunotherapy used monoclonal antibodies anti-PD-1 (pembrolizumab and nivolumab) or anti-PD-L1 (atezolizumab and durvalumab) compared to chemotherapy. Unfortunately, cancer cells can develop a number of mechanisms to escape from immune surveillance, including avoidance of cancer cells by the immune system (immune desert), production of immunosuppressive compounds (prostaglandins, IDO, TGF-beta), or direct immune checkpoints interactions. Therapy based on the use of radiochemotherapy with subsequent immunotherapy is becoming the main focus of research in the field of new NSCLC therapies. Radiation therapy stimulates the immune response multidirectionally, affects production of neoantigens and proinflammatory compounds, which transform non-immunogenic (“cold”) tumors into highly immunogenic (“hot”) tumors. As a result, the mechanisms of escape of cancer cells from immune surveillance break down and the effectiveness of immunotherapy increases significantly. The results of clinical trials in this area bring new hope and indicate greater effectiveness of such treatment in terms of prolongation of progression-free survival and overall survival.

Development and validation of a prediction model using molecular marker for long‐term survival in unresectable stage III non‐small cell lung cancer treated with chemoradiotherapy

“…8 Due to the prominent heterogeneity of locally advanced NSCLC (LANSCLC), survival of patients varied widely and whether all the patients were suitable for consolidated immunotherapy remained unclear. [9][10][11] Therefore, predicting survival and identifying patients at low or high risk of death after CRT were essential for individualized treatment and enhanced immunotherapy decisions. The American Joint Committee on Cancer (AJCC) TNM staging system was the gold standard for the survival risk classification, but was initially developed to evaluate operability rather than outcome after CRT.…”

Local consolidative therapy for synchronous oligometastatic non‐small cell lung cancer treated with first‐line pembrolizumab: A retrospective observational study

“…Recently, more and more studies have suggested that radiation therapy could stimulate an immune response, increase the production of neoantigens and transform nonimmunogenic tumors (cold tumors) into highlyimmunogenic tumors (hot tumors), known as the abscopal effect. 31,32 In addition, the abscopal effect may lead to a survival benefit of the combination of radiotherapy and immunotherapy. However, the mechanism of the abscopal effect remains unclear and needs further study.…”

Real-World Journey of Unresectable Stage III NSCLC Patients: Current Dilemmas for Disease Staging and Treatment

“…Theoretically, the combination of RT and ICI might lead to enhanced responses by increasing the exposure or altering the presentation of tumor-related antigens to immune system cells [ 4 ]. Although current research studies are still investigating the timing and duration of ICI treatments [ 14 , 37 ], all experts agreed that ICI should be started soon after RT completion.…”