Comparison of whole brain radiation therapy for synchronous brain metastases with irradiation protecting the hippocampus versus whole brain radiotherapy for sequential brain metastases to boost irradiation in the treatment of brain metastases from SCLC: study protocol for a randomized controlled trial.

Background: This study is in regard to the comparison of whole brain radiation therapy for synchronous brain metastases with irradiation protecting the hippocampus versus whole brain radiotherapy for sequential brain metastases to boost irradiation in the treatment of brain metastases from small cell lung cancer (SCLC). Therapeutically, they have notably varying dose distributions. Based on theoretical and model studies, it has long been speculated that these modes may result in different prognostic outcomes. We aim to assess the efficacy of tomotherapy in the treatment of SCLC brain metastases while protecting the key functional area, the hippocampus, and minimizing any neurocognitive impairments incurred by radiation.

Methods: This is a randomized, controlled, prospective study including 102 SCLC patients with brain metastases randomized (1:1) to the experimental (whole brain radiation therapy for synchronous brain metastases with irradiation to protect the hippocampus) or control (whole brain radiotherapy for sequential brain metastases to boost irradiation) group. The sample size is calculated through a single-sided test; 102 participants will be required for the main results to have statistical and clinical significance. We aim to provide clinical trial data support for better prognostic treatment options in patients with SCLC and brain metastases. The clinical trial data include both the primary and secondary outcomes; the primary outcome is the intracranial progression-free survival time after the new technology application. The secondary study outcomes include the assessment of neurological function, the quality of life, and the overall survival rate. Follow-up consultations will be conducted every 2 months. After the final patient completes follow-up, the Statistical Product and Service Solutions software will be used for scientific and rigorous data analysis. Version 1.0 of the protocol was implemented on January 1, 2021; the recruitment process for this clinical trial commenced on April 1, 2021, and will end on March 31, 2024.

Discussion: The study will provide high-quality clinical evidence to support the efficacy and safety of whole brain radiation therapy for synchronous brain metastases with dose irradiation protecting the hippocampus versus whole brain radiotherapy for sequential brain metastases with push volume irradiation for the treatment of patients who have lung cancer as well as brain metastases. This has not been previously reported.

Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (ChiCTR1900027539; November 17, 2019) (URL: https://www.chictr.org.cn/hvshowproject.aspx?id=20515 ).