Radiotherapy, lymphopenia and improving the outcome for glioblastoma: a narrative review

Background and Objective: Standard treatment for glioblastoma includes maximal safe resection followed by adjuvant radiation and concurrent temozolomide for 6 weeks, followed by 6 months of maintenance temozolomide; additionally, concurrent high doses of corticosteroids are required for many patients to reduce intracranial pressure and reduce inflammatory side effects. This combination of cytotoxic therapies (including radiotherapy, temozolomide, and corticosteroids) often results in severe treatment-related lymphopenia that can persist beyond the duration of therapy. Methods: Papers on treatment-related lymphopenia were retrieved to analyze the role of lymphocytes in tumor control, the role of radiotherapy in inducing lymphopenia, understand other contributing factors to lymphopenia and investigate strategies (including altered radiation approaches) that may reduce the impact of lymphopenia for patients with glioblastoma in the future. Key Content and Findings: Radiation, in particular, plays an important role in lymphopenia. Lymphocytes are considered the most radiosensitive cells in the human body, and ionizing radiation often results in apoptotic response and rapid death of lymphocytes within hours of exposure. As a result, radiotherapy can lead to systemic immunosuppression including lymphopenia which is permissive of tumor growth and is linked to impaired local control and reduced survival. For this reason, interactions between radiotherapy treatment and the immune response to tumor is the subject of active study. This study also explores promising lymphocyte-medicated immune therapies which have developed clinical use for many non-glioblastoma cancer types, with promising preclinical results in glioblastoma treatment. Conclusions: Limiting treatment-related lymphopenia is especially important in improving treatment outcomes for glioblastoma. Research on strategies to reduce the impact of lymphopenia may promote improved treatment outcomes for glioblastoma patients.