5061 - Impact of early prophylactic cranial irradiation with hippocampal avoidance on neurocognitive function in patients with limited disease small-cell lung cancer. A multicenter phase II trial (SAKK 15/12)

Background

In limited disease small-cell lung cancer (LD SCLC) prophylactic cranial irradiation (PCI) is the standard of care following chemotherapy (CHT) and thoracic radiotherapy (tRT) in patients with a good clinical response. It is unknown if PCI concomitant with CHT and tRT has an impact on neurocognitive function (NCF) and clinical outcome.

Methods

In a phase II trial, patients with LD SCLC received hippocampal avoidance (HA)-PCI concomitant to the 2nd cycle of CHT (cisplatin or carboplatin and etoposide) and tRT. All patients underwent objective NCF testing before starting HA-PCI (baseline), at 6 weeks, and at 6 and 12 months after HA-PCI. NCF tests included the Hopkins Verbal Learning Test Revised (HVLT-R) for verbal learning and memory, the Controlled Oral Word Association (COWAT) for verbal fluency, and Trail Making Tests A and B (TMT A&B) for visual search, scanning, speed of processing and executive function. The primary endpoint was NCF decline at 6 months after HA-PCI, defined as a decrease of one standard error of measurement in any of the tests. We assumed a rate of ≤ 30% of patients with no NCF decline as unpromising and a rate of ≥ 50% as promising. Secondary endpoints included overall survival (OS) and quality of life.

Results

Among the 44 patients enrolled in the trial, 37 had evaluable NCF assessment at 6 months after HA-PCI (2 had no CHT, 2 had no BL TMT B assessment, 1 died and 2 have pending NCF results). At the time of analysis, 13 patients (35%; 90% CI: 22-50%) showed no NCF decline. The median follow-up was 12 months with a 1-year OS rate of 84% (95% CI: 65-93%). Four patients died due to SCLC, 1 due to respiratory failure, 1 due to hemorrhage, and 1 for unknown reason. The most common acute adverse events grade ≥3 were anemia (21%), febrile neutropenia (19%) and fatigue (14%).

Conclusions

The rate of patients with no NCF decline 6 months after HA-PCI in LD SCLC does not seem to be better, but rather similar to that observed in patients receiving sequential PCI. Early HA-PCI appears feasible. OS was promising in this selected population. Updated and additional results will be presented.

Clinical trial identification

Legal entity responsible for the study

SAKK (Swiss Group for Clinical Cancer Research).

Funding

Schweizerische Stiftung für Klinische Krebsforschung (SSKK); Hirslanden Klinik Zuerich; Krebsliga Zuerich Schweizerische Stiftung für Klinische Krebsforschung (SSKK).

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.