Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Nov 24, 2021; 12(11): 983-999
Published online Nov 24, 2021. doi: 10.5306/wjco.v12.i11.983
New challenges in the combination of radiotherapy and immunotherapy in non-small cell lung cancer
Javier Luna, Juan Zafra, Mª Carmen Areses Manrique, Aurora Rodríguez, Amalia Sotoca, Jose Luis Fírvida, Rodolfo Chicas-Sett, Xabier Mielgo, Juan Carlos Trujillo Reyes, Felipe Couñago
Javier Luna, Department of Radiation Oncology, Oncohealth Institute, Fundación Jiménez Díaz, Madrid 28040, Spain
Juan Zafra, Rodolfo Chicas-Sett, Department of Radiation Oncology, Dr. Negrín University Hospital of Gran Canaria, Las Palmas 35010, Spain
Mª Carmen Areses Manrique, Jose Luis Fírvida, Department of Medical Oncology, Ourense University Hospital, Ourense 32005, Spain
Aurora Rodríguez, Amalia Sotoca, Department of Radiation Oncology, Ruber International Hospital, Madrid 28034, Spain
Xabier Mielgo, Department of Medical Oncology, Hospital Universitario Fundación Alcorcón, Alcorcón 28922, Spain
Juan Carlos Trujillo Reyes, Department of Thoracic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona 08029, Spain
Felipe Couñago, Department of Radiation Oncology, Hospital Universitario QuirónSalud Madrid, Hospital La Luz, Universidad Europea de Madrid, Madrid 28223, Spain
Author contributions: Luna J, Zafra J, Areses Manrique MC, Rodríguez A, Sotoca A, Fírvida JL, Chicas-Sett R, Mielgo X, Reyes JCT, and Couñago F contributed equally to this work.
Conflict-of-interest statement: No conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Javier Luna, PhD, Staff Physician, Department of Radiation Oncology, Oncohealth Institute, Fundación Jiménez Díaz, Reyes Catolicos Avenue No. 2, Madrid 28040, Spain.
Received: March 28, 2021
Peer-review started: March 28, 2021
First decision: June 25, 2021
Revised: July 6, 2021
Accepted: October 12, 2021
Article in press: October 12, 2021
Published online: November 24, 2021

Immunotherapy has represented one of the main medical revolutions of recent decades, and is currently a consolidated treatment for different types of tumors at different stages and scenarios, and is present in a multitude of clinical trials. One of the diseases in which it is most developed is non-small cell lung cancer. The combination of radiotherapy and immunotherapy in cancer in general and lung cancer in particular currently represents one of the main focuses of basic and clinical research in oncology, due to the synergy of this interaction, which can improve tumor response, resulting in improved survival and disease control. In this review we present the biochemical and molecular basis of the interaction between radiotherapy and immunotherapy. We also present the current clinical status of this interaction in each of the stages and cases of non-small cell lung cancer, with the main results obtained in the different studies both in terms of tumor response and survival as well as toxicity. Finally, we mention the main studies underway and the challenges of this interaction in the coming years, including how these treatments should be combined to achieve the greatest efficacy with the fewest possible side effects (dose, type of radiotherapy and drugs, sequence of treatments).

Keywords: Lung cancer, Radiotherapy, Immunotherapy, Main trials

Core Tip: Immunotherapy has revolutionised cancer treatment. Its association with radiotherapy has synergistic effects studied at a preclinical and clinical level, especially in metastatic patients. Currently, clinical research in this field is very prolific, and no doubt, as with the PACIFIC trial in non-small cell lung cancer (NSCLC), we will see further changes in the standard of care in the coming years. This review highlights the most important published work in NSCLC in the field of radio-immunotherapy, listing the clinical trials currently existing in each stage of NSCLC.