Study Demonstrates Feasibility and Tolerability of 45 Gy Novel Radiotherapy in CNS Cancers

Rupesh Kotecha, MD

Research shows that the use of pulse reduced dose rate intensity-modulated radiotherapy is feasible in patients with central nervous system (CNS) malignancies who have exhausted other options.¹

During the American Society for Radiation Oncology (ASTRO) Annual Meeting, results from 18 patients with CNS malignancies treated with 45 Gy of pulse reduced dose rate intensity-modulated radiation were presented in a poster. The results came from clinical information of patients treated between April 2017 and September 2021 as well as a systematic review of published literature.

At a median follow-up of 6.2 months, the median progression-free survival with the novel radiation modality was 6.3 months (95% Cl, 0.9-11.6 months), and the median overall survival was 8.6 months (95% Cl, 4.9-12.3 months). Grade 2 or higher toxicities were observed in 66.7% of patients. Only 2 patients experienced grade 3 toxicity, which included fatigue and hearing impairment. No grade 4 or higher toxicities occurred.

In an interview with Targeted Oncology™, Rupesh Kotecha, MD, chief of Radiosurgery and director of Central Nervous System Metastasis with Baptist Health Miami Cancer Institute, discussed research around the use of pulse reduced dose rate intensity-modulated radiotherapy in patients with CNS malignancies

TARGETED ONCOLOGY: Can you discuss the current standard of care for recurrent primary CNS malignancies?

Kotecha: The interesting thing is that there isn't a standard of care for patients with recurrent primary brain tumors. There are several salvage options that can be used for patients. F For example, different systemic therapy agents, tumor treating fields, and then re-irradiation is 1 of the approaches that is also considered in very select patients. Obviously, our first option for anybody with a recurrent primary brain tumor is to consider enrollment on a clinical trial that is available to them.

Prior to your systemic review, what was known about the use of pulse reduced dose rate intensity-modulated radiotherapy in this patient population?

Pulse reduced dose rate intensity-modulated radiotherapyis a very specific radiation approach which has been used primarily in the central nervous system space for recurrent primary brain tumors. It's also been explored in a couple of circumstances outside of the brain itself. This research was previously limited to very few institutions who had experience with using this technique, and who see this patient volume.

Typically, patients with recurrent primary brain tumors would travel to specific Centers of Excellence or those who have clinical trials. Then, sometimes those centers may not have clinical trials that the patient will be eligible for. But then we have a larger experience or volume of patients with that need. This was developed at a number of institutions as one of those reirradiation approaches to try and control the disease, after somebody has progressed on multiple lines of systemic therapy. We know from a previous series that there were some aspects of disease control that looked very favorable for about 6 months or longer, and in some series, the disease control was even shorter.

The purpose of our study is to incorporate the prior radiation therapy plans and then add the new array of radiation plans together to come up with those constraintsand safety threat thresholds that could be used in the future andwhen patients are undergoing radiation. The second goal was to pull the analyses from these different institutions so that we would know what the composite outcomes are instead of just know what institution A, B, or C present.

Can you discuss the results of the analysis?

Our study looked at 18 patients with recurrent primary CNS tumors that were treated at our institution over a 4-year period, and the median dose of radiation therapy in our series was 45 Gy. But then that cumulative dose of radiation when we incorporate the prioritization that those patients have had is over 100 Gy in this series, it's a very high dose of radiation. Even with that our toxicity rates are very modest in this patient population.

We saw that the median progression-free survival or was 6.3 months. Now going back to that systematic review of the literature that we performed, we also looked at the outcomes across the 5 studies that have been published in the literature to date on this same topic. It was a limited series, but at least in pooled analyses. The median progression-free survival across the literature across these studies was 5.7 months. Overall, our results are basically in line with those that have been published. This gives us some idea of what are our baseline statistics or safety thresholds that we can determine as we think about newer techniques to build upon this.

What are the key takeaways from this research and how can these data inform future studies?

The first key takeaway is that pulse reduced dose rate intensity-modulated radiotherapyis a technique that can be utilized in clinical practice now. Out of the institutions that have been using it, for example, those 5 that have published outcomes, this should be available across the country at other institutions. In our experience, it was relatively safe and is a feasible treatment for patients who have recurrent tumors. This technique can provide disease control for a number of months.

The second takeaway is that this provides us with baseline estimates of what are the toxicity rates at certain thresholds of dose to the key organs at risk in the brain.Using these, we can now build and develop newer techniques to help reduce the toxicity more and potentially improve our control rates further. This is where our research is going.

_REFERENCES:

_{Kutuk T, McAllister N, Hall MD, et al. Pulsed reduced dose rate (PRDR) intensity modulated radiotherapy for recurrent primary central nervous system malignancies: dosimetric and clinical results. Presented at ASTRO 2022 Annual Meeting; October 23-26, 2022; San Antonio, TX.}