Radiation Delay in NSCLC May Aid Outcomes, But Raises Toxicity Risks

Deferring upfront CNS-directed radiation in EGFR-variant and ALK-positive NSCLC may improve outcomes but raises treatment-related toxicity risks: © stock.adobe.com

For patients with EGFR-variant and ALK-positive non-small cell lung cancer (NSCLC) with brain metastases, deferring up-front central nervous system-directed radiation therapy has been associated with improved outcomes, but with an increase in treatment-related toxicity, according to recent findings.

Dr. Luke R.G. Pike and colleagues published their findings in a recent article from JAMA Oncology. Pike is a radiation oncologist and director of brain radiation oncology at Memorial Sloan Kettering Cancer Center in New York City.

“In the era of [central nervous system]-active [tyrosine kinase inhibitors], the largest multicenter study to date of patients with EGFR-variant and ALK-positive NSCLC found that up-front [stereotactic radiosurgery] was associated with superior local control and time to [central nervous system] progression at the cost of increased treatment-related toxic effects in a minority of patients. Patients with higher-risk [brain metastases], including those with lesions that are large, symptomatic or located in eloquent areas, may benefit more from early [stereotactic radiosurgery],” Pike and his colleagues wrote in the article.

Pike and his colleagues came to their findings after reviewing three multi-institutional cohort studies from the United States and Japan between 2013 to 2022. These studies comprised 591 patients, 52% of whom were male and who had an age range of 35 to 92 years old. Investigators compared central nervous system-active tyrosine kinase inhibitors with or without radiotherapy.

Contemporary practice guidelines, Pike and his colleagues noted, support the deferral of up-front stereotactic radiosurgery for some patients with EGFR-variant and ALK-positive NSCLC who have limited, asymptomatic brain metastases.

Given a lack of clear survival benefit, Pike and his co-authors stated that, “based on clinical factors and patient preferences [specific points] appear reasonable in light of the available evidence.” These points include:

• Multidisciplinary evaluation and individualized decisions regarding therapeutic intensification, such as early stereotactic radiosurgery delivery as either up-front therapy or as consolidation after patients’ response to tyrosine kinase inhibitors.
• Deintensification, such as treatment with tyrosine kinase inhibitors alone, close brain MRI surveillance and early salvage therapy at central nervous system progression.

Looking forward, Pike and his colleagues stated that randomized clinical trials testing a strategy of using central nervous system-active tyrosine kinase inhibitors with or without stereotactic radiosurgery are warranted.

More About Brain Metastases and NSCLC

Brain metastases, as the reseach states, have been shown to be a common cause of morbidity and mortality among patients with EGFR-variant and ALK-positive NSCLC. Stereotactic radiosurgery is the current standard of care for limited brain metastases, and it has shown what Pike and his fellow researchers described as “excellent long-term lesion control rates”, although they note that late cerebral radionecrosis, or damage to brain tissue, can be a concern for long-lived and heavily treated patients.

Brain metastases, as explained by the American Lung Association on its website, can occur when cancer cells metastasize, or spread from the original cancer site in the lung, to the brain. Brain metastases may form one or multiple tumors in the brain, and as the metastatic brain tumors grow, they create pressure on parts of brain and they can change the function of surrounding brain tissue, which can cause a range of symptoms.

Reference:

“Management of EGFR-Variant and ALK-Positive Non–Small Cell Lung Cancer Brain Metastasis” by Dr. Luke R. G. Pike et al., JAMA Oncology.

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