Emerging Treatment Paradigms in Radiation Oncology

摘要

Rapid advancements in radiotherapy and molecularly targeted therapies have resulted in the development of potential paradigm-shifting use of radiotherapy in the treatment of cancer. In this review, we discuss some of the most promising therapeutic approaches in the field of radiation oncology. These strategies include the use of highly targeted stereotactic radiotherapy and particle therapy as well as combining radiotherapy with agents that modulate the DNA damage response, augment the immune response, or protect normal tissues. The combination of radiotherapy and cytotoxic chemotherapy has become the standard of care for many locally advanced cancers, including those in the brain, head and neck, and lung, and in the gastrointestinal, gynecologic, and genitourinary tracts. Chemotherapy, when given concomitantly with radiotherapy, can enhance radiation efficacy, thus serving as a radio-sensitizer in many cases. Clinical trials have confirmed that concomitant chemoradiation (CRT) is superior to radiotherapy alone in several solid tumors, including head and neck, cervical, esophageal, and lung cancers (1-7). However, the addition of chemotherapy to radiotherapy has also resulted in a higher rate of acute and late toxicity, thereby limiting the use of this combination (8). Clearly, there is room to improve the efficacy of radiotherapy. Because the therapeutic index of radiotherapy is favorable if the response of the tumor is greater than the toxicity of the surrounding normal tissues, two different strategies can be used to maximize this therapeutic index. The most common approach is to deliver ablative radiotherapy with large fractions or to develop novel radiosensitizers by targeting the DNA damage response (DDR), cell-cycle checkpoints, signaling or metabolic pathways, the tumor microenvironment, and immune checkpoints.