Dr Shields on the Evolving Role of Prophylactic Cranial Irradiation in SCLC

"[PCI] is not without potential burden, [such as] acute and late toxicities, including cognitive effects. We want to be cautious and [make decisions with the goal of improving] patients' quality of life. [It is important to make] sure we have data from the modern era…"

Misty D. Shields, MD, PhD, a translational medical oncologist at Indiana University (IU) Health; an assistant professor of clinical medicine in the Department of Medicine in the Division of Hematology/Oncology at the IU School of Medicine; and an associate member of Experimental and Developmental Therapeutics at the IU Melvin and Bren Simon Comprehensive Cancer Center, discussed the historical and contemporary role of prophylactic cranial irradiation (PCI) in the management of extensive-stage small cell lung cancer (ES-SCLC).

PCI is preventive radiation to the brain aimed at improving survival and outcomes by targeting intracranial progression of metastases, Shields explained. Historically, PCI was considered beneficial for both limited-stage and extensive-stage disease. This historical recommendation was based on findings from the Saltzman and cooperative groups, Shieldsstated. However, this dogma was challenged in 2017 following data from an ex-United States phase 3 trial (UMIN000001755). This trial, led by Toshiaki Takahashi, MD, PhD, et al, demonstrated no benefit from PCI in extensive-stage disease, she reported. These results caused the practice to fall out of favor for ES-SCLC patients who achieved an excellent response to induction chemotherapy and radiation or chemoimmunotherapy, Shields explained.

While assessing the role of PCI, clinicians must be mindful of potential confounding variables, such as investigator choice selecting patients who might be fitter for therapy and thus achieve better outcomes independent of the disease or biology, Shields continued. Importantly, Shields stressed that PCI is "not without potential burden" and is associated with acute and late toxicities, including negative cognitive effects. Therefore, caution is essential, and treatment decisions must prioritize improving the patient’s quality of life, she emphasized.

The phase 3 MAVERICK study (NCT04155034), a cooperative group study, is currently investigating whether patients with limited- or extensive-stage disease benefit from PCI, Shields noted. Ultimately, there is a critical need for data from the modern era that compares the benefit of PCI against a strategy where all patients undergo baseline MRIs followed by routine MRIs every 3 months as a potential standard of care, Shieldsconcluded.