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Does Sparing the Hippocampus During Prophylactic Cranial Irradiation for SCLC Help to Preserve Cognitive Function?


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In the Spanish phase III PREMER trial reported in the Journal of Clinical Oncology, Rodríguez de Dios et al found that hippocampal avoidance during prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC) was associated with better preservation of cognitive function vs PCI alone and did not increase the risk of brain metastasis.

Study Details

In the trial, 150 patients enrolled through October 2019 at 13 institutions were randomly assigned to receive standard PCI at 25 Gy in 10 fractions (n = 75) or hippocampal avoidance PCI (n = 75). A total of 13 patients were found to be ineligible, leaving 68 and 69 evaluable patients in the PCI and hippocampal avoidance PCI groups, respectively. Overall survival was assessed in the total trial population. The primary outcome measure was delayed free recall on the Free and Cued Selective Reminding Test (FCSRT) at 3 months after PCI; a decrease of 3 or more points from baseline was considered a decline.

Key Findings

Proportions of patients with decline in delayed free recall from baseline to 3 months were 5.8% in the hippocampal avoidance PCI group vs 23.5% in the PCI group (odds ratio [OR] = 5.0, 95% confidence interval [CI] = 1.57–15.86, P = .003).

Among all FCSRT scales, significantly lower proportions of patients in the hippocampal avoidance PCI vs PCI group had declines in:

  • Total recall (8.7% vs 20.6%, P = .049) at 3 months
  • Delayed free recall (11.1% vs 33.3%, P  = .005) at 6 months
  • Total recall (20.3% vs 38.9%, P = .035) at 6 months
  • Total free recall (14.8% vs 31.5%, P = .040) at 6 months
  • Total recall (14.2% vs 47.6%, P = .019) at 24 months.

The cumulative incidence of brain metastases at 2 years was 22.8% in the hippocampal avoidance PCI group vs 17.7% in the PCI group (P = .430). Among those with metastases, multiple lesions were found in 70.5% vs 84.6% of patients. In the hippocampal avoidance PCI group, one patient developed an isolated metastasis in the hippocampal dentate gyrus. No patient developed a single metastasis in the hippocampal avoidance zone; 2 of the 12 patients with multiple metastases had a lesion in the hippocampal avoidance zone.

At end of survival follow-up at 60 months, death had occurred in 60.0% of those in the hippocampal avoidance PCI group vs 65.3% of the PCI group. Median overall survival was 23.4 months vs 24.9 months (P = .556).

Assessment with the EORTC QLQ-C30 Questionnaire (QLQ-C30) and brain cancer module (BN20) showed no significant differences between groups in changes over time on any quality-of-life scales.

The investigators concluded, “Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, overall survival, and quality of life compared with standard PCI.”

Núria Rodríguez de Dios, MD, PhD, of the Department of Radiation Oncology, Hospital del Mar, Barcelona, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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