Stereotactic Ablative Radiation for RCC: Novel Paradigms Emerge as the Myth of Radioresistance Fades Are we at an inflection point for the use of radiotherapy in renal cell carcinoma? Perhaps. Definitive, high-dose-per-fraction stereotactic radiation is having a sharp impact as an option for a growing population of patients. A review of the emerging data calls for guidelines for its use as an alternative to invasive approaches. A new consensus is emerging for the treatment of a broad spectrum of renal cell tumors at multiple stages, including primary renal cell carcinoma (RCC), locally advanced RCC, central nervous system (CNS) RCC metastases, and extra cranial oligo-metastases. It is part of a significant evolution in thinking emphasizing the use of stereotactic ablative radiotherapy (SAbR) to deliver high ablative doses of radiation focally to the tumor to achieve local control in cases previously thought to be a radioresistant histology. SAbR is an emerging treatment that delivers a very high and ablative dose of radiation very precisely to any site within the body. SAbR has been implemented successfully in the definitive management of several cancers including primary lung and prostate,1-4 and is currently under investigation in many other sites including breast, pancreas and liver.5-9 SAbR has also been successfully implemented for the local control of metastatic lesions in multiple sites.5,10-12 Several lines of evidence have converged in recent years to largely debunk the long-held belief that radiotherapy is not well suited to the paradigm of treatment in kidney cancer. First, for early stage RCC (T1a) as the standard of care has shifted away from radical nephrectomy and toward more nephron-sparing approaches, the goals of treatment have also pivoted toward less invasive ablative 72 Kidney Cancer Journal treatments such as radiofrequency ablation or cryoablation. However, these modalities are also invasive, have attendant risks and limited to treatment on selective tumor locations within the kidney.1 RCC has traditionally been considered a radioresistant tumor.13 This conclusion was based entirely on a single study that examined the radiosensitivity of multiple human cancer cell lines in vitro14 and examined one human RCC cell line, which happened to be the most radioresistant among all tested cell lines when conventional low dose per fraction radiation was used. Since then, multiple in vitro and in vivo studies have demonstrated that RCC is indeed radiosensitive, particularly at higher doses per fraction such as are used for SAbR.15,16 Clinical experience mimics this conclusion with SABR showing efficacy ranges of 90-100% and 82-95% for RCC CNS and extra-CNS metastases respectively.17-23 Nomenclature is not always the same in the literature. Different terminology is often used to refer to SAbR. In some cases, it has been referred to as “stereotactic radiosurgery” or stereotactic body radiotherapy (SBRT). The significant advantage of SAbR is its ability to deliver highdose radiotherapy to the tumor while minimizing dose to adjacent normal tissues.24 In their review of SAbR with respect to local control and toxicity outcomes, Siva et al25 delineate the reasons for the technique’s effectiveness. The very large hypofractionated doses used in SAbR can be given safely because: 1) The treated volumes are small with tight margins (Figure 1) and 2) The technique employs a large number of beams (8 or more) which individually contribute small dose along their path but together result in a much larger dose where they intersect and are summed at the locus of the cancer (Figure 2). The utilization of volumetric modulated arc (VMAT) therapy, where the gantry delivering radiation rotates continuously around the tumor to deliver radiation and Raquibul Hannan, MD, PhD Associate Professor of Radiation Oncology UT Southwestern Medical Center Dallas, Texas Keywords: Stereotactic ablative radiation, renal cell carcinoma, SBRT, primary RCC, metastatic, CNS metastases, oligometastases, spine. Corresponding Author: Raquibul Hannan, MD, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390. Email: Raquibul.Hannan@UTSouthwestern.edu
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