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Hippocampal-sparing prophylactic cranial irradiation (PCI) can protect cognitive function in patients with small cell lung cancer (SCLC) without increasing the risk of intracranial relapse, according to research presented at the 2023 ASTRO Annual Meeting.
PCI with hippocampal avoidance prevented first failure in any cognitive domain, said study presenter Vinai Gondi, MD, of the Northwestern Medicine Proton Center in Warrenville, Illinois.
These findings come from the phase 2/3 NRG CC003 trial (ClinicalTrials.gov Identifier: NCT02635009). The trial included 393 SCLC patients who were stratified by tumor stage, age, and administration of memantine and were randomly assigned to receive PCI (25 Gy in 10 fractions) either as standard whole-brain PCI (n=196) or as hippocampal-sparing PCI (n=197).
Baseline characteristics were generally well balanced between the treatment arms, but the hippocampal-sparing PCI arm had higher baseline scores for the Controlled Oral Word Association (COWA) test.
The median follow-up was 14.9 months. The primary endpoints were intracranial relapse at 12 months and Hopkins Verbal Learning Test (HVLT-R) delayed recall failure at 6 months.
Hippocampal-sparing PCI was noninferior to standard PCI with regard to intracranial relapse (P <.0001). The 12-month intracranial relapse rate was 14.8% with standard PCI and 14.2% with hippocampal-sparing PCI (hazard ratio [HR], 0.93; 95% CI, 0.61-1.43; P =.75).
Similarly, there was no significant difference between the treatment arms with regard to HVLT-R delayed recall. The 6-month HVLT-R delayed recall failure rate was 30.0% with standard PCI and 26.0% with hippocampal-sparing PCI (P =.31).
On the other hand, hippocampal avoidance prevented first failure in any cognitive test, with a 23% relative reduction in risk (HR, 0.77; 95% CI, 0.61-0.98; P =.033).
Patients who received hippocampal-sparing PCI also had a greater decline in COWA scores over time (P =.042). Dr Gondi noted, however, that this may have been related to the higher baseline COWA scores in this arm. He also noted that isolated COWA failure made up 3.3% of first cognitive failure events, and verbal fluency is not mediated by the hippocampus.
There was no significant difference in overall survival between the treatment arms. The median overall survival was 24.1 months with standard PCI and 24.3 months with hippocampal-sparing PCI (HR, 0.83; 95% CI, 0.63-1.09; P =.189).
Similarly, there were no significant differences in treatment-related toxicities between the treatment arms. Grade 3 or higher treatment-related toxicity was observed in 11% of patients in the whole-brain PCI arm and 8.5% of those in the hippocampal-sparing PCI arm (P =.09). There were no fatal toxicities attributed to treatment.
In closing, Dr Gondi noted that, although the primary endpoint of HVLT-R delayed recall was not met, hippocampal-sparing PCI prevented first failure in any cognitive domain, which “has been used as a practice-changing primary endpoint in prior cognitive toxicity prevention trials.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Gondi V, Pugh S, Mehta MP, et al. Primary endpoint results of NRG CC003: Phase IIR/III trial of prophylactic cranial irradiation (PCI) with or without hippocampal avoidance (HA) for small cell lung cancer (SCLC). Presented at ASTRO 2023. September 30-October 4, 2023. Abstract LBA 04.
This article originally appeared on Cancer Therapy Advisor
