Issue: May 25, 2021
Disclosures: Voss reports grants and/or research support from Bristol Myers Squibb, Genentech and Pfizer; scientific advising fees from Alexion Pharmaceuticals, Calithera Biosciences, Corvus Pharmaceuticals, Exelixis, Eisai, Natera, Novartis and Pfizer; consultant fees from Eisai and Takeda; and honoraria from Novartis. Healio could not confirm Jonasch’s relevant financial disclosures at the time of reporting. Please see the study for all other authors’ relevant financial disclosures.
April 29, 2021
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Occult brain metastases found in about 4% of patients with advanced kidney cancer

Issue: May 25, 2021
Disclosures: Voss reports grants and/or research support from Bristol Myers Squibb, Genentech and Pfizer; scientific advising fees from Alexion Pharmaceuticals, Calithera Biosciences, Corvus Pharmaceuticals, Exelixis, Eisai, Natera, Novartis and Pfizer; consultant fees from Eisai and Takeda; and honoraria from Novartis. Healio could not confirm Jonasch’s relevant financial disclosures at the time of reporting. Please see the study for all other authors’ relevant financial disclosures.
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About 4% of patients with advanced renal cell carcinoma had asymptomatic brain metastases, according to results of a retrospective multi-institutional cohort study published in Journal of the National Comprehensive Cancer Network.

As a result, researchers at Memorial Sloan Kettering Cancer Center and Gustave Roussy Institute concluded that baseline brain imaging should be considered for all patients with advanced kidney cancer, including those with favorable-risk features.

Seventy-two patients had incidental brain metastases without neurologic symptoms documented on chart reviews.
Data were derived from Voss MH, et al. J Natl Compr Canc Netw. 2021;doi:10.6004/jnccn.2020.7634.

“Brain imaging is routinely obtained for [patients with kidney cancer] with symptoms that suggest central nervous system metastases, but none of the patients with brain metastases included here were symptomatic,” Martin H. Voss, MD, clinical director of genitourinary medical oncology service at Memorial Sloan Kettering Cancer Center, said in a press release. “In current practice, chest abdomen and pelvis are routinely imaged from the time that the metastatic disease is first detected, yet many oncologists do not image the brain.”

Researchers evaluated data from 68 clinical trials conducted from 2001 to 2019 at Memorial Sloan Kettering and Gustave Roussy that included 1,689 patients with advanced renal cell carcinoma who had mandatory brain screening by CT or MRI at study entry.

Median follow-up for surviving patients was 14.1 months.

Seventy-two patients (4.3%; men, n = 54; median age at diagnosis, 56 years; range, 37-77) had incidental brain metastases without neurologic symptoms documented on chart reviews. Of these patients, 26% had favorable-risk disease, 61% and intermediate-risk disease and 13% had poor-risk disease, according to International Metastatic Database Consortium (IMDC) criteria.

Researchers also noted 38.5% of patients had multifocal CNS involvement, and the largest brain metastasis of 40% of patients was smaller than 1 cm in diameter. Fourteen percent of patients had two brain metastases and 24% had three or more lesions.

Radiographic assessment revealed 86% of patients with asymptomatic brain metastases also had metastatic disease in two or more additional organ systems, including the lung (n = 66), liver (n = 18) and bone (n = 18).

Ninety-three percent of patients underwent localized, brain-directed therapy.

Researchers reported median OS of 10.3 months (range, 7-17.9) and 1-year OS probability of 48% (95% CI, 37-62). One-year OS did not appear to differ significantly by IMDC risk score (favorable risk, 53%; intermediate risk, 52%; poor risk, 29%) nor by lesion number (solitary, 57%; multifocal, 33%) or size (1 cm, 49%; > 1 cm, 52%).

Researchers noted that selection bias toward fit patients could be a limitation of the study, as their patient population included only those considered for clinical trial participation. Additionally, Voss and colleagues called for additional studies, acknowledging their data could not provide insight into how frequently brain surveillance should be repeated.

Eric Jonasch, MD, professor of genitourinary medical oncology at The University of Texas MD Anderson Cancer Center and vice chair of the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology Panel for Kidney Cancer — who did not participate in the study — said the study demonstrated brain metastases occur “in a clinically significant percentage” of patients newly diagnosed with metastatic renal cell carcinoma.

“The findings in this study are important for two reasons,” Jonasch said in the press release. “First they show that the overall prognosis of patients with brain metastases is consistently worse than the broader population of patients with metastatic renal cell carcinoma. We need to develop a deeper scientific understanding of why this patient population has a worse outcome and we need to include them in future clinical trials.

“Second, they underscore the utility for MRI imaging of all patients with metastatic renal cell carcinoma both at initial diagnosis and at regular intervals to detect occult brain metastases, since specific treatment strategies are required for this patient population,” he added.