Treatment Design and Rationale for a Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for SCLC: PREMER Trial on Behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Radiation Oncology Group-Radiation Oncology Clinical Research Group

Abstract Background Prophylactic cranial irradiation (PCI) is part of the usual treatment in most patients with small-cell lung cancer (SCLC) and response after treatment of the primary tumor. Clinical evidence suggests that radiation dose received by the hippocampus during whole brain radiotherapy might play a role in radiation-induced neurocognitive decline. Patients and Methods This study is a multicenter phase III trial (NCT02397733) randomizing SCLC patients after informed consent, to receive standard PCI treatment or PCI with hippocampus avoidance (PCI-HA) by using intensity modulated radiation therapy or volumetric modulated arc therapy. The primary objective is assessment of hippocampus-dependent memory functioning and safety after PCI with or without hippocampus sparing by the Free and Cued Selective Reminding Test. Secondary objectives are assessment of other neurotoxicity/quality of life, radiological brain abnormalities on magnetic resonance images, and evaluation of the incidence and location of brain metastases after PCI-HA compared with standard PCI. The originally planned sample size (n = 150) has been calculated to detect a 50% difference in the 3-month delayed recall score between the 2 treatment arms, with a statistical power of 80% (β = 20%) and a significance level of 5% (α = 5%), with a maximum loss to follow-up of 10%. Conclusion This study is an important step in introducing a new therapeutic approach to patients with SCLC candidates for PCI.