Optimizing Radiotherapy with Immunotherapeutic Approaches.
Several factors must be considered to successfully integrate immunotherapy with radiation into clinical practice. One such factor is that concepts arising from preclinical work must be tested in combination with radiation in preclinical models to better understand how combination therapy will work in patients; examples include checkpoint inhibitors, tumor growth factor-beta (TGF-β) inhibitors, and natural killer (NK) cell therapy. Also, many radiation fields and fractionation schedules typically used in radiation therapy had been standardized before the introduction of advanced techniques for radiation planning and delivery that account for changes in tumor size, location, and motion during treatment, as well as uncertainties introduced by variations in patient setup between treatment fractions. As a result, radiation therapy may involve the use of large treatment volumes, often encompassing nodal regions that may not be irradiated with more conformal techniques. Traditional forms of radiation in particular pose challenges for combination trials with immunotherapy. This chapter explores these issues in more detail and provides insights as to how radiation therapy can be optimized to combine with immunotherapy.
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jonathan E
JE
Schoenhals
Department of Radiation Oncology, University of Arizona, Tucson, AZ, USA.
Tijana
T
Skrepnik
Department of Radiation Oncology, Koc University, Istanbul, Turkey.|Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Anderson Central (Y2.5316), 1515 Holcombe Blvd., Unit 0097, Houston, TX, 77030, USA.
Ugur
U
Selek
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Maria A
MA
Cortez
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China.
Ailin
A
Li
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Anderson Central (Y2.5316), 1515 Holcombe Blvd., Unit 0097, Houston, TX, 77030, USA. jwelsh@mdanderson.org.
James W
JW
Welsh
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011829:Radiation Dosage; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D059016:Tumor Microenvironment
D000970:Antineoplastic Agents; D007155:Immunologic Factors
CD8+ T-cell; CTLA4; Clinical trial; Immunotherapy; PD1; Radiation; SABR; SBRT; TGF-β