Re-examining prophylactic cranial irradiation in small cell lung cancer: a systematic review and meta-analysis

Karolina Gaebe; Anders W Erickson; Alyssa Y Li; Andrew N Youssef; Bhagyashree Sharma; Kelvin K W Chan; Benjamin H Lok; Sunit Das

doi:10.1016/j.eclinm.2023.102396

Re-examining prophylactic cranial irradiation in small cell lung cancer: a systematic review and meta-analysis

EClinicalMedicine. 2024 Jan 3:67:102396. doi: 10.1016/j.eclinm.2023.102396. eCollection 2024 Jan.

Authors

Karolina Gaebe¹, Anders W Erickson², Alyssa Y Li¹, Andrew N Youssef², Bhagyashree Sharma¹, Kelvin K W Chan³, Benjamin H Lok^{1

4}, Sunit Das^{1

5}

Affiliations

¹ Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada.
² Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
³ Division of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
⁴ Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
⁵ Division of Neurosurgery, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario, Canada.

Abstract

Background: Patients with small cell lung cancer (SCLC) are at high risk for brain metastases. Prophylactic cranial irradiation (PCI) is recommended in this population to reduce the incidence of brain metastases and prolong survival. We aimed to assesses the efficacy of PCI in this population in the era of routine brain imaging. To our knowledge, this is the first systematic review and meta-analysis to examine the use among patients who were radiographically confirmed not to have brain metastases after completion of first-line therapy.

Methods: In this systematic review and meta-analysis, cohort studies and controlled trials reporting on the use of PCI for patients SCLC were identified in EMBASE, MEDLINE, CENTRAL, and grey literature sources. The literature search was conducted on November 12, 2023. Summary data were extracted. Random-effects meta-analyses pooled hazard ratios (HR) for the primary outcome of overall survival between PCI and no intervention groups. This study is registered with the Open Science Framework, DOI:10.17605/OSF.IO/BC359, and PROSPERO, CRD42021249466.

Findings: Of 4318 identified records, 223 were eligible for inclusion. 109 reported on overall survival in formats amenable to meta-analysis; PCI was associated with longer survival in all patients with SCLC (HR 0.59; 95% CI, 0.55-0.63; p < 0.001; n = 56,770 patients), patients with limited stage disease (HR 0.60; 95% CI, 0.55-0.65; p < 0.001; n = 78 studies; n = 27,137 patients), and patients with extensive stage disease (HR 0.59; 95% CI, 0.51-0.70; p < 0.001; n = 28 studies; n = 26,467 patients). Between-study heterogeneity was significant when pooled amongst all studies (I2 = 73.6%; 95% CI 68.4%-77.9%). Subgroup analysis did not reveal sources of heterogeneity. In a subgroup analysis on studies that used magnetic resonance imaging to exclude presence of brain metastases at restaging among all patients, overall survival did not differ significantly between patients who did or did not receive PCI (HR 0.74; 95% CI, 0.52-1.05; p = 0.08; n = 9 studies; n = 1384 patients).

Interpretation: Our findings suggested that administration of PCI is associated with a survival benefit, but not when considering studies that radiographically confirmed absence of brain metastases, suggesting that the survival benefit conferred by PCI might be therapeutic rather than prophylactic.

Funding: No funding.

Keywords: Brain metastases; PCI; Prophylactic cranial irradiation; SCLC; Small cell lung cancer.