1. Holt, Chuck

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Recognizing the negative impacts that the side effects of systemic drug therapy were having on their patients, medical oncologists at The University of Texas MD Anderson Cancer Center in Houston decided a few years ago to try treating patients with stereotactic body radiation therapy (SBRT) and no systemic therapy.

Renal Cell Carcinoma... - Click to enlarge in new windowRenal Cell Carcinoma. Renal Cell Carcinoma

"We were seeing a number of patients looking to take a break from their side effects from systemic therapy," said Chad Tang, MD, Assistant Professor of Radiation Oncology at MD Anderson.


Tang was principal investigator of a single-arm clinical trial of SBRT as a monotherapy for oligometastatic renal cell carcinoma (RCC) at MD Anderson. Results from the Phase II study were recently published in The Lancet Oncology (2021; https// He is interested in shifting the treatment paradigm to relieve toxicities from select patients with metastatic RCC. To do this, he is exploring SBRT as a means to facilitate systemic therapy breaks or to prolong time until systemic therapy initiation.

Chad Tang, MD. Chad ... - Click to enlarge in new windowChad Tang, MD. Chad Tang, MD

"We began talking to patients about just using radiation therapy. They loved it as it offered them a potential break from drug therapies," Tang noted.


As hoped, the patients with RCC responded well to the novel serial radiation therapy strategy of the MD Anderson team. So well, in fact, that some patients went years without needing chemotherapy or another systemic therapy agent, Tang told Oncology Times.


"That was what led us to do the Phase II trial, to formally test this in patients with low-volume disease, and to see if we can buy them some time on the front end with sequential radiation strategy, and hold the systemic therapy," he said. "Although patients will have varying response, many have done really well."


The co-first author of the study was Pavlos Msaouel, MD, PhD, Assistant Professor of Genitourinary Medical Oncology, while Nizar Tannir, MD, Professor of Genitourinary Medical Oncology, both at MD Anderson, served as senior author.


A Measure of Monotherapy

SBRT allows physicians guided by medical imaging technologies including CT and MRI to target metastatic lesions with a series of highly concentrated doses of radiation repeatedly and without damaging the surrounding tissue. Because of the biology of RCC cells, higher treatment doses, as delivered by SBRT, may be more effective in controlling this disease.


A total of 30 patients were enrolled in the feasibility study of SBRT as monotherapy for oligometastatic RCC at MD Anderson, which also sought to estimate progression-free survival (PFS) during the reporting period between July 2018 and September 2020.


The clinical trial included 24 men and six women with a median age of 65, all of whom had clear cell histology, a nephrectomy, and had completed at least one round of radiotherapy with fewer than 7 days of unplanned breaks.


The patients were treated with SBRT or hypofractionated definitive radiation directed at all of their lesions and no systemic therapy. Each patient completed at least one round of radiation without requiring dose reduction or discontinuation due to toxicities. At a median follow-up of 17.5 months (IQR 13*2-24*6), the median PFS was 22.7 months (95% CI 10*4-not reached; 1-year PFS, 64 percent [95% CI 48-85]). Six patients had an adverse event of Grade 2 or less, two patients had a Grade 3 adverse event with pain and muscle weakness, and one patient had hyperglycemia, which is a Grade 4 adverse event.


Biopsies done 3 months after receiving SBRT, meanwhile, showed the elimination of viable tumor cells in six patients (43%), or if tumor cells were present, significant reduction in their proliferation, from 15 percent to 6 percent. Ultimately, 23 patients (77%) were still off any type of systemic drug therapy at the end of the reported study period.


"Radiation therapy is definitely an option for the management of some metastatic renal cell carcinoma," Tang said, when asked about the key takeaways from the study. "By using this strategy, you can buy some high-quality time for your patients upfront."


The favorable patient outcomes and minimal toxicity observed in the Phase II study are potentially practice-changing, he added. "The drug therapy will always be there, and as far as we are aware, they will be just as effective as they are now, or in a couple of years if we need to use them after we have tried this strategy. We tell patients to think of it as if we are putting the drug therapy in your back pocket for now."


The MD Anderson researchers plan to continue studying the serial radiation strategy in patients with slightly higher burdens of disease and analyze biomarkers from treated patients to improve patient selection for the treatment.


Challenging the Dogma

While Tang acknowledged that the clinical trial of SBRT for oligometastatic RCC at MD Anderson was small, and there was a selection bias, the protocol is being expanded to include patients who would have been excluded from the clinical trial based on previous criteria, specifically those patients with multiple (>5) small pulmonary nodules or lymph nodes. In fact, if anything surprises Tang about the results of the study and his experience treating patients with RCC, he said it is how slowly the cancers can be seen to grow in images over time.


"When I first started treating patients, I would get nervous about small, 2-5 millimeter specks. And you see 2.5 millimeter specks a lot, and the radiologist would comment that they could not rule out metastatic disease," Tang recalled. "Later on, as we began expanding the trial, I realized that these little nodules could be safely monitored and treated at a later date."


Importantly, the expanded clinical trial will also allow the MD Anderson researchers to collect more tissue and blood samples from patients with oligometastatic RCC, Tang noted, "because this entire endeavor really has been about the translation of correlatives."


But as far as the clinical implications of the findings from the study, Tang emphasized, "For me, the most exciting thing is that we are challenging the dogma that when you have a systemic disease you have to treat it with a systemic therapy."


Chuck Holt is a contributing writer.


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