Clinical Pearls & Morning Reports
Traditional radiation treatments deliver a consistent intensity of radiation across the treatment field. The development of dynamic multileaf collimators — small movable metal leaves that shape the radiation field and alter the intensity of radiation delivered to portions of the field and that are used in combination with conformal radiotherapy — has exponentially increased the potential complexity of treatment plans. Read the latest Review Article.
Q. What recent advance minimizes the potential for unnecessary radiation from respiratory motion to normal tissues that surround a tumor?
A. Although patients can be immobilized reproducibly for daily treatment, tumors are often situated in organs that move with normal bodily functions: breathing, peristalsis, swallowing, filling, and emptying. A variety of approaches have been used to account for tumor motion. For example, patients can be asked to hold their breath during inhalation or exhalation for the planning scan and treatment. A recent advance is four-dimensional computed tomography, which can be used to acquire treatment-planning images at multiple phases of the ventilatory cycle. This method provides an understanding of tumor motion during the ventilatory cycle, allowing the margin of normal tissue to be expanded in each direction only as much as needed to encompass the tumor during ventilation.
Q. What are some of the recent developments in the delivery of radiotherapy?
A. The delivery of modulated radiation beams, a technique known as intensity-modulated radiation therapy (IMRT), has resulted in the capacity to shape the high-dose region to match complex target volumes while maximally sparing surrounding normal tissues in a way that would not be possible with conventional radiation treatment methods. Additional refinements, such as volumetric-modulated arc therapy (VMAT), in which modulated treatments are delivered as the radiation treatment machine rotates in an arc around the patient, have both improved conformality (the ability to sculpt, or conform, the dose closely to the target) and reduced treatment times.
A: Traditionally, radiation treatments have been fractionated, or broken into multiple doses, to leverage differences in radiation response between tumor and normal tissue, such as reoxygenation of tumor, repair, redistribution of tumor cells into sensitive phases of the cell cycle, and repopulation between doses. In recent years, there has been substantial interest in regimens involving a relatively large dose per fraction and highly conformal techniques. With these regimens, ablative doses are delivered over a period of 1 to 2 weeks, in contrast to the previous standard of using protracted fractionation, with daily treatments lasting for many weeks. These highly conformal techniques, known as stereotactic body radiation therapy (SBRT) (also called stereotactic ablative radiotherapy [SABR]) have been used for both curative and palliative treatment and have demonstrated efficacy in randomized trials for some tumors. SBRT requires careful and reproducible immobilization of the patient, with organ motion accounted for and minimized and with a clear understanding of the extent of the tumor.
A: The impressive successes of immunotherapy in the treatment of metastatic cancer have led to tremendous excitement at the prospect of combining immunotherapy and radiotherapy. Preclinical studies have suggested that localized irradiation has immunomodulatory effects that may enhance tumor recognition. Compelling evidence of the efficacy of radiotherapy as a complement to immunotherapy has been observed with vaccines. More recently, it was observed that delivery of radiation in combination with antibodies against cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) resulted in regression of unirradiated tumors (known as an abscopal response), providing proof of concept that this approach can be successfully translated into use in patients. A number of immunosuppressive effects of localized irradiation have been described that may counteract the immunogenic effects, especially when conventionally fractionated radiation or larger treatment volumes that can result in lymphopenia are used. Radiation can alter the balance of regulatory T cells and local immunomodulatory cytokines, such as transforming growth factor β (TGF-β). These changes may suppress antitumor immunity. In addition, radiation may alter the number and phenotype of infiltrating macrophages, which may also serve as an immunosuppressive factor. Thus, radiation alone may not be capable of stimulating a coordinated and effective immune response.