Translational Studies

Identify Immune Modulatory Changes of Stereotactic Ablative Radiotherapy (SAbR) of Renal Tumor Thrombus

A unique feature of renal cell carcinoma (RCC) is its ability to invade the venous system to form a tumor thrombus in the inferior vena cava (IVC-TT), which may extend as high as the right atrium. Nevertheless, at least 4-10% of patients are still diagnosed with advanced disease and IVC-TT. Surgery is the mainstay of treatment for these patients and the only one with curative potential. However, due to its high complexity, surgery harbors high risk of perioperative morbidity and mortality. Furthermore, despite extirpative surgery, these patients are at high risk of recurrence, emphasizing the need for additional methods to reduce recurrence rates. Contemporary reports indicate that RCC is sensitive to extremely hypofractionated radiation therapy, such as stereotactic body radiation therapy (SBRT). Initial reports, including those from our group, further indicate that SBRT may be effective for treating RCC IVC-TT in specific settings.

Based on our previous experience with SBRT for IVC-TT, we initiated a safety lead-in phase II study aimed to evaluate a multimodal treatment approach including neoadjuvant SBRT for IVC-TT followed by radical nephrectomy and thrombectomy. We have completed the safety lead-in portion of this trial to confirm the safety of this approach. Interestingly, we noticed complete abscopal response in one patient and a partial response in another, even in this small cohort size. The translational studies that correlate the benefit of RT with patient response include the analysis of radiated thrombus, primary tumor and patient blood for immune components and investigation of T-cell receptor repertoire in tumor and circulation. In addition, the involvement of an antitumor response from SAbR is also being analyzed by next generation sequencing.

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