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A New Treatment for Brain Metastases from Small-Cell Lung Cancer

Chad Rusthoven, MD, is studying the effects of stereotactic radiosurgery on small cell lung cancer that spreads to the brain.

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Written by Greg Glasgow on April 8, 2021

A new phase 3 randomized clinical trial overseen by CU Cancer Center member Chad Rusthoven, MD, and Vinai Gondi, MD, from Northwestern University, is testing whether a new treatment approach could result in improved outcomes for patients with small cell lung cancer (SCLC) that has spread to the brain. 

Funded by the National Cancer Institute and carried out at clinics around the country — including the CU Cancer Center — the clinical trial (NRG-CC009) will compare the effects of two different types of radiation treatment on brain metastases related to SCLC, one called hippocampal-avoidance whole brain radiation therapy (WBRT) and the other called stereotactic radiosurgery (SRS).

“Historically, brain metastases related to SCLC have been treated with WBRT,” Rusthoven explains. “WBRT treats the brain metastases you can see, as well any microscopic disease that may not be visible yet. WBRT is a well-established treatment strategy for controlling brain metastases, but it can also have side effects related to cognitive function and quality of life for some patients.”

Interest in SRS

The new treatment strategy for SCLC brain metastases that Rusthoven and Gondi are studying in this trial is SRS, a more focused type of radiation that aims to treat the individual brain metastases with as little dose to the surrounding normal brain structures as possible. SRS is most often delivered as a one-time treatment, as opposed to a common 10-treatment cycle for WBRT. In previous clinical trials that have not included SCLC patients, SRS alone has been associated with similar survival outcomes and fewer side effects related to cognitive function and quality of life when compared to treatment strategies incorporating WBRT.

“There have been a number of randomized phase 3 trials comparing SRS to treatment strategies involving WBRT for brain metastases in other settings excluding SCLC patients,” Rusthoven says. “These trials have tended to show similar overall survival and better tolerability with SRS alone. Ours will be the first randomized phase 3 trial to compare a strategy of SRS alone to WBRT specifically in patients with SCLC.”

Patients with SCLC have been excluded from previous clinical trials evaluating SRS alone because SCLC is known to have a higher propensity for spread to the brain than other tumors and sometimes SCLC brain metastases can present diffusely with multiple areas of involvement. Through this new clinical trial, Rusthoven and Gondi hope to demonstrate that SRS is associated with superior cognitive preservation compared to WBRT and that SRS is a safe and effective treatment strategy for controlling brain metastases from SCLC.

The potential for a new standard of care

In the trial, which will aim to enroll 200 patients nationwide and will take an estimated four years to complete, eligible patients with one to 10 brain metastases from SCLC will be randomized to receive SRS or WBRT. If SRS is associated with superior cognitive preservation and encouraging survival and disease control outcomes, Rusthoven and Gondi expect that SRS would become an acceptable standard of care option for the upfront management of SCLC brain metastases.

“Although SRS is now considered a preferred treatment strategy for limited numbers of brain metastases in other settings, brain metastases from SCLC represent a unique circumstance where WBRT is considered the standard of care due, in part, to the lack of clinical trials studying SRS for SCLC patients,” Rusthoven says. “This is an exciting trial because it will allow us to evaluate whether SRS can offer better outcomes for appropriately selected SCLC patients. SRS alone may be great option for some SCLC patients, and it’s important to carefully evaluate this question in a randomized trial.”