OL Oncology Letters 1792-1074 1792-1082 D.A. Spandidos 10.3892/ol.2025.14870 OL-29-3-14870 Articles Efficacy evaluation of prophylactic cranial irradiation for limited stage small‑cell lung cancer in the magnetic resonance imaging era: A meta‑analysis ShaoLihua 1 DongYumei 1 JiangMeiqiao 2 SongHaixia 1 QiYuexiao 1 GuoLiyun 1 TianJinhui 3 WeiShihong 1 2 Department of Radiotherapy, Sun Yat-sen University Cancer Center Gansu Hospital, Lanzhou, Gansu 730050, P.R. China School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730030, P.R. China School of Public Health, Lanzhou University, Lanzhou, Gansu 730030, P.R. China Correspondence to: Professor Shihong Wei, Department of Radiotherapy, Sun Yat-sen University Cancer Center Gansu Hospital, 2 Xiaoxihu Street, Lanzhou, Gansu 730050, P.R. China, E-mail: shaolh_ganzhong@sysucc.org.cn 03 2025 07 01 2025 29 3 123 16092024 04122024 Copyright: © 2025 Shao et al. 2025 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

The role of prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC) remains controversial in the era of magnetic resonance imaging (MRI). The present study aimed to evaluate the effectiveness of PCI in the treatment of LS-SCLC in the era of MRI. The PubMed, EMBASE and Cochrane Library databases were searched from the time of database creation until May 24, 2023, to identify clinical studies that evaluated the effectiveness of PCI in patients with LS-SCLC in the MRI era. The references of the obtained studies were also reviewed to identify clinical studies that were not discovered in the initial search. All studies were screened in accordance with the inclusion criteria, and the data were extracted and subjected to meta-analysis using STATA17.0. In total, 21 studies were included in the analysis. Notably, 10 studies only used brain MRI at baseline to confirm the absence of brain metastases (BMs; pre-chemoradiotherapy MRI group), 7 studies used brain MRI prior to PCI to confirm the absence of BMs (pre-PCI MRI group) and 4 studies used active surveillance in the form of brain MRI following PCI (MRI surveillance group). The results of the meta-analysis demonstrated that for all included patients, PCI was associated with a significant improvement in overall survival time [OS; hazard ratio (HR), 0.61; confidence interval (CI), 0.53–0.70] and progression-free survival (HR, 0.69; CI, 0.61–0.79), as well as a significant decrease in the rate of BM (HR, 0.59; CI, 0.50–0.70). Subgroup analyses revealed that PCI remained effective in improving OS and reducing the rate of BM in patients with LS-SCLC who did not have BMs confirmed via brain MRI performed at baseline or prior to PCI. However, in the MRI surveillance group, PCI failed to significantly improve the OS (HR, 0.65; CI, 0.41–1.05), despite significantly reducing the BM rate (HR, 0.6; CI, 0.45–0.8) of LS-SCLC. Collectively, the results of the present study demonstrated that PCI remained effective in improving OS and reducing the rate of BM in patients with LS-SCLC who had the absence of BM confirmed via brain MRI at baseline or prior to PCI. Additionally, in patients with LS-SCLC who had undergone active surveillance using brain MRI following PCI, the incidence of BM was reduced, while the OS was not significantly improved. However, additional randomized controlled clinical studies are required to verify these findings.

 limited-stage small-cell lung cancer prophylactic cranial irradiation magnetic resonance imaging brain metastasis meta-analysis Gansu Provincial Health Industry Scientific Research Project GSWSKY2021-057 Lanzhou Science and Technology Program 2022-5-101 Lanzhou Talent Innovation and Entrepreneurship Project 2021-RC-130 The present study was supported by grants from the Gansu Provincial Health Industry Scientific Research Project (grant no. GSWSKY2021-057), the Lanzhou Science and Technology Program (grant no. 2022-5-101) and the Lanzhou Talent Innovation and Entrepreneurship Project (grant no. 2021-RC-130). Introduction

Small-cell lung cancer (SCLC) accounts for 13–15% of all lung cancer cases and approximately one-third of cases are limited-stage (LS)-SCLC (1). LS-SCLC has a poor prognosis due to rapid growth and early distant and loco-regional dissemination. The median survival time of LS-SCLC is reported to be 16–20 months with a 5-year survival rate of 10–20% (2). Brain metastasis (BM) is a common complication of SCLC, occurring either at diagnosis or throughout the course of the disease (3). Additionally, >10% of patients with SCLC have BM at initial diagnosis and the cumulative incidence of BM at 2 years is >50% (4). Furthermore, ~65% of patients have detectable BM on autopsy (5). The survival advantage of prophylactic cranial irradiation (PCI) was first demonstrated in the 1990s and a 5.4% increase in the rate of survival was acquired at 3 years among patients with SCLC in complete remission (6). The National Comprehensive Cancer Network guidelines recommend PCI as the standard treatment for patients with LS-SCLC who have achieved remission after first-line chemoradiation therapy (7). However, these guidelines are primarily based on the results of a meta-analysis of multiple clinical studies conducted in the pre-magnetic resonance imaging (MRI) era (6,8). During this phase, the enrollment criteria were based on the absence of symptoms of BM or the use of computed tomography (CT) imaging to confirm the absence of BM, rather than MRI examination. In addition, the results of a previous study revealed that the detection rate of BM was 10% in the CT era and 24% in the MRI era (9), indicating that MRI may be more sensitive than contrast-enhanced CT for the detection of BMs. Thus, MRI may be more beneficial as an assessment tool for BM. Numerous previous retrospective studies conducted in the MRI era have re-evaluated the efficacy of PCI in patients with LS-SCLC (10–30). Some of these studies (10,15,18,20,26) suggest that PCI fails to significantly prolong the overall survival (OS) time of patients with LS-SCLC in modern pretreatment MRI staging. However, other studies (21–25,27–30) suggest that PCI does significantly prolong the OS time of patients with LS-SCLC in the era of MRI. As such, the results of these studies remain controversial. Therefore, the present study aimed to evaluate the efficacy of PCI in patients with LS-SCLC in the era of MRI, to provide a reference for the clinical management of LS-SCLC.

 Materials and methods <sec> <title>Literature search strategy

The PubMed (https://pubmed.ncbi.nlm.nih.gov/), EMBASE (https://www.cochranelibrary.com/) and Cochrane Library (https://www.embase.com/) databases were searched for clinical studies assessing the effectiveness of PCI in patients with LS-SCLC during the MRI era, from the time of database creation until May 24, 2023. The references of the obtained studies were also examined for the identification of pertinent clinical studies that were not discovered during the initial search. Search terms included ‘small-cell lung carcinoma’, ‘small-cell lung cancer’, ‘prophylactic brain irradiation’, ‘prophylactic cranial irradiation’, ‘PCI’ and ‘whole-brain radiotherapy’. A combination of subject terms and key words were used in the search.

 Inclusion and exclusion criteria

Literature were included in the present study according to the following criteria: i) Studies involving patients with LS-SCLC; ii) studies involving patients without BM, as confirmed using brain MRI at baseline or prior to PCI; iii) clinical trials evaluating the effectiveness of PCI in the treatment of LS-SCLC compared with non-PCI; and iv) clinical trials reporting outcomes, such as overall survival (OS) and the rate of BM. The following literature were excluded from the present meta-analysis: i) Abstracts; ii) case reports; iii) reviews; iv) study plans; v) studies that reported outcomes yet withheld raw data; and vi) studies that were not available in English.

 Literature screening and data extraction

In total, two researchers independently evaluated the literature and extracted data from the included studies. When a consensus on inclusion could not be reached, discussions were held within the research group. Primary information that were extracted from the literature was as follows: i) General information, including author names, year of publication, type of study, number of patients, patient sex, patient age and patient history of smoking; ii) clinical information, including tumor stage, initial treatment, percentage of complete response (CR) and partial response (PR) and PCI dose; and iii) outcome indices, including OS, progression-free survival (PFS), BM rate and BM-free survival (BMFS). The Newcastle-Ottawa scale (NOS) was used to assess the quality of each study (31), and those scored with seven stars or more were considered to be high-quality studies.

 Statistical analysis

Statistical analysis was performed using STATA 17.0 software (StataCorp LP). The included studies that provided OS-related hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed during the meta-analysis. For studies that only provided Kaplan-Meier survival curves, the associated HR and 95% CI were calculated using Engauge Digitizer v12.2.1 software (http://markummitchell.github.io/engauge-digitizer/) and methods as previously described (32). χ2 test and the I2 index were used to investigate heterogeneity. The Cochrane Guidance Manual for Systematic Evaluation (33) states that the significance level of heterogeneity should be set at P=0.1 for the χ2 test and I2 should be set at 50%. However, according to the recommendations provided by the Cochrane Handbook for Systematic Reviews of Interventions (33), the choice between a fixed-effect and a random-effects meta-analysis model should not be made on the basis of a statistical test for heterogeneity. Additionally, heterogeneity is always expected when examining the intervention effects among multiple studies from different research groups and geographical locations. Therefore, all data for the present meta-analysis were combined using the random-effects model. Publication bias was evaluated using a funnel plot.

 Results <sec> <title>Literature screening and baseline characteristics

A total of 21 retrospective clinical studies assessing the therapeutic efficacy of PCI in patients with LS-SCLC during the MRI era were included in the present study. The screening process is outlined in Fig. 1 and the baseline characteristics of the included studies are displayed in Table I. All patients with LS-SCLC included in the 21 retrospective studies underwent baseline or pre-PCI brain MRI to exclude the presence of BM. In total, 10 of the studies only used brain MRI at baseline to confirm the absence of BM, 7 studies used brain MRI prior to PCI and at baseline to confirm the absence of BM and only 4 studies used brain MRI as active surveillance following PCI. In 1 study, the initial treatment regimen consisted of surgery plus chemotherapy, 2 studies used surgery plus chemotherapy and the remaining 18 studies used chemoradiotherapy. In 10 of the included studies, the PCI dose was 25 Gy/10 fractions (F), compared with 30 Gy/15 F in 2 studies, and between 25 and 40 Gy in 5 studies. Notably, the PCI dose was not reported in the remaining 4 studies. The quality of all included trials was evaluated using the NOS (8) and all were rated as high quality. The results of the quality assessment are displayed in Table SI.

 Overall outcomes

The results of the present study revealed that the 1-, 2-, 3- and 5-year OS rates of patients in the PCI groups were 89, 67, 50 and 40%, respectively (Fig. S1), while in the non-PCI group the OS rates were 85, 48, 35 and 32% (Fig. S2). In addition, the combined HR was 0.61 (CI, 0.53–0.70; P<0.001; Fig. 2). Only 8 of the included studies performed propensity-matched analysis, and the combined results demonstrated that PCI significantly improved the OS of patients with LS-SCLC (HR, 0.73; CI, 0.62–0.88; P=0.001; Fig. 3). The 1-, 2-, 3- and 5-year BM rates in the PCI groups were 6, 18, 20 and 25%, respectively (Fig. S1), while in the non-PCI group the BM rates were 29, 38, 27 and 41% (Fig. S2). Notably, PCI significantly reduced the incidence of BM in patients with LS-SCLC (HR, 0.55; CI, 0.46–0.67; P<0.001; Fig. 2). The combined results also demonstrated that the PFS (HR, 0.69; CI, 0.61–0.79; P<0.001) and BMFS (HR, 0.39; CI, 0.24–0.62; P<0.001) in the PCI group were significantly improved compared with the non-PCI group (Fig. 2).

 Results of the pre-chemoradiotherapy (CRT) MRI group

In total, 10 studies included patients who had undergone brain MRI at baseline, which excluded the presence of BM. The combined results of these studies revealed that the 1-, 2-, 3- and 5-year OS rates of patients in the PCI groups were 84, 61, 50 and 36%, respectively (Fig. S3), while in the non-PCI group the OS rates were 82, 42, 33 and 27% (Fig. S4). In addition, the combined HR was 0.58 (CI, 0.50–0.68; P<0.001; Fig. 4). Notably, the propensity-matched analysis of 1 study revealed a significant increase in OS in patients in the PCI group (HR, 0.64; CI, 0.43–0.95; P=0.027; Fig. 3). The combined results revealed that the PCI group exhibited a significantly lower BM rate than the non-PCI group, with 1-, 2-, 3- and 5-year BM rates of 8, 14, 23 and 24%, respectively (Fig. S3), while in the non-PCI group the BM rates were 23, 27, 27 and 40% (Fig. S4). In addition, the combined HR was 0.54 (CI, 0.41–0.72; P<0.001; Fig. 4). Moreover, the PFS (HR, 0.61; CI, 0.48–0.79; P<0.001) and BMFS (HR, 0.39; CI, 0.18–0.84; P=0.016) rates observed in the PCI group were significantly improved, compared with the non-PCI group (Fig. 4).

 Results of the pre-PCI MRI group

The pooled analysis included 7 trials that comprised of patients without BM, verified using brain MRI prior to PCI. The results revealed that the 1-, 2-, 3- and 5-year OS rates of patients in the PCI groups were 89, 78, 57 and 54%, respectively (Fig. S5), while in the non-PCI group the OS rates were 83, 58, 60 and 42% (Fig. S6). In addition, the combined HR was 0.63 (CI, 0.49–0.81; P<0.001; Fig. 5). Propensity-matched analysis was carried out in 4 of the 7 studies that used brain MRI prior to PCI to confirm the absence of BMs, and the combined results also revealed that the OS was significantly higher in the PCI group (HR, 0.77; CI, 0.60–0.99; P=0.039; Fig. 3). The 1-, 2-, 3- and 5-year BM rates of patients in the PCI groups were 4, 26, 16 and 18%, respectively (Fig. S5), while in the non-PCI group the BM rates were 31, 40, 21 and 39% (Fig. S6). The combined HR was 0.43 (CI, 0.24–0.78; P=0.005; Fig. 5), indicating a significant decrease in BM rate in the PCI group. However, the combined results revealed that the PFS (HR, 0.62; CI, 0.38–1.02; P=0.059) and BMFS (HR, 0.47; CI, 0.19–1.17; P=0.105) in the PCI group were not significantly different from those in the non-PCI group (Fig. 5).

 Results of the MRI surveillance group

The results of the 4 studies that used brain MRI for active surveillance following PCI revealed that the 1-, 2-, 3- and 5-year OS rates of patients in the PCI groups were 91, 74, 49 and 32%, respectively (Fig. S7), while in the non-PCI group the OS rates were 87, 61, 33 and 27% (Fig. S8). Notably, the combined HR was 0.65 (CI, 0.41–1.05; P=0.078; Fig. 6). Propensity-matched analysis was performed in 3 of the 4 studies that used brain MRI for active surveillance following PCI, and the pooled findings did not reveal a statistically significant difference in OS between the two groups (HR, 0.70; CI, 0.48–1.03; P=0.068; Fig. 3). The 1-, 2-, 3- and 5-year BM rates of patients in the PCI groups were 6, 26, 22 and 34%, respectively (Fig. S7), while in the non-PCI group the BM rates were 31, 57, 31 and 40% (Fig. S8). The combined HR was 0.6 (CI, 0.45–0.80; P=0.001; Fig. 6), indicating that the rate of BM in the PCI group was significantly decreased. The combined results also demonstrated that the PCI group exhibited significantly higher rates of PFS (HR, 0.76; CI, 0.64–0.90; P=0.001) and BMFS (HR, 0.24; CI, 0.13–0.43; P<0.001) than the non-PCI group (Fig. 6).

To investigate the heterogeneity of the OS analysis in the MRI surveillance group, a subgroup analysis was performed (Fig. 7). The variables used to analyze the heterogeneity of OS were the male/female ratio, median age (<70 vs. ≥70 years), proportion of stages (I–II/III) and fraction of CR/PR. The results of the subgroup analysis revealed that there was no significant difference in OS between the PCI and non-PCI groups in any of the subgroups.

 Failure patterns

In total, 5 studies examined the failure patterns of LS-SCLC following treatment and demonstrated that the main cause of failure was extracranial failure. Notably, overall recurrence, extracranial progression alone, extracranial progression combined with intracranial progression, intracranial progression alone and overall intracranial progression rates in the PCI groups were 59, 51, 6, 6 and 21%, respectively (Fig. 8), while in the non-PCI groups the rates were 66, 43, 9, 14 and 33% (Fig. 9).

 Bias and sensitivity analyses

The results of the funnel plot analysis revealed that there was no indication of significant publication bias (Fig. 10). Sensitivity analyses were performed to determine the effect of each study on the overall meta-analysis estimate, through calculating the pooled HRs and omitting one study at a time. The pooled results did not significantly differ when single studies were removed, suggesting that the results of the meta-analysis were stable (Fig. 11).

 Discussion

The results of a previous meta-analysis revealed that PCI significantly decreased the incidence of BM by 25.3% (33.3 vs. 58.6%; P<0.001) and increased the 3-year OS rate by 5.4% (20.7 vs. 15.3%; P=0.01) in patients with LS-SCLC who achieved CR after chemoradiotherapy (6). PCI is the standard treatment recommendation for patients with LS-SCLC who achieve CR or PR with first-line chemoradiotherapy (7). The results of a previous study revealed a notable difference in the detection rates of BMs originating from SCLC between the CT and MRI eras (9). Notably, the observed rates of BM were 10 and 24%, respectively, indicating that MRI may be more effective for BM detection. However, the majority of the studies included in the previous meta-analysis utilized CT rather than MRI to assess the presence of BM in LS-SCLC. In a single-center study, 40 patients with LS-SCLC who achieved CR after chemoradiotherapy underwent cranial MRI prior to PCI (34). The results demonstrated that BM was detected in 13/40 patients (32.5%; 95% CI, 18–47%) and 11 cases exhibited asymptomatic BM. These results suggested that patients who did not undergo cranial MRI may have developed occult BM before or during treatment; thus, patients who underwent PCI in the pre-MRI era may have received treatment, rather than prevention. Thus, these results may have overstated the benefits of PCI. Based on the results of the aforementioned studies, numerous retrospective clinical studies have re-evaluated the effectiveness of PCI in patients with LS-SCLC during the MRI era (10–30). The results of the present meta-analysis indicated that PCI significantly decreased the incidence of BM (P<0.001) and prolonged the OS time (P<0.001) in patients with LS-SCLC who had the absence of BM confirmed via brain MRI at baseline or prior to PCI. In addition, the results of the present meta-analysis revealed that studies using propensity score matching also revealed that PCI significantly prolonged OS time (P=0.039), which was consistent with the findings of previous meta-analyses (35,36). Thus, in the era of MRI, PCI is required for patients with LS-SCLC who have undergone brain MRI at baseline or prior to PCI, to exclude the presence of BM.

The results of a previous prospective study revealed that PCI did not significantly increase the OS time of patients with extensive-stage SCLC compared with active surveillance using brain MRI. Notably, the median OS time in the PCI and non-PCI groups was 11.6 and 13.7 months, respectively (HR, 1.27; 95% CI, 0.96–1.68; P=0.094) (37). Previous retrospective clinical studies have also investigated whether active surveillance using brain MRI is superior to PCI in patients with LS-SCLC (10,14,18,19). The results of the present meta-analysis revealed that PCI was able to significantly reduce the incidence of BM in patients with LS-SCLC compared with active surveillance using brain MRIs (P=0.001); however, the observed benefit in OS was not significant (P=0.078). The studies included in the present meta-analysis were retrospective clinical studies. Thus, there may have been differences in the baseline characteristics of the included patients. In addition, propensity score matching analysis was carried out in 3 of the studies to reduce the impact of potential confounding, through reaching an equilibrium between the baseline characteristics of the two patient groups. The combined results of the studies that used propensity score matching also demonstrated that PCI did not significantly prolong OS in patients with LS-SCLC, compared with active surveillance using brain MRIs (P=0.068). Notably, brain MRI follow-up may be for the early detection of BM, leading to timely treatment with salvage radiation therapy and improved patient survival. The results of the present meta-analysis also revealed that the 1-, 2-, 3- and 5-year BM rates were higher in the MRI surveillance group than in the pre-CRT and pre-PCI groups, indicating that active surveillance using brain MRI may be used for the early detection of asymptomatic BM. Moreover, studies included in the present meta-analysis demonstrated that salvage cerebrospinal radiotherapy was administered to 69.4–91.5% of patients in the MRI surveillance group, compared with 23.1–58.5% of patients in the PCI cohort. These results indicated that the percentage of patients in the PCI group who received salvage radiotherapy following BM was lower; however, the effectiveness of systemic therapy for BM was suboptimal. This may have contributed to the poor prognosis of these patients. In addition, the results of previous studies demonstrated that patients with PR and stage III disease were at a higher risk of developing BM and may have been more likely to benefit from PCI (14,19). However, the results of the subgroup analysis in the present study revealed that PCI did not significantly improve the OS of patients with PR and stage III LS-SCLC, compared with active surveillance using brain MRI. Thus, even in patients at high risk of BM, brain MRI active surveillance and early effective salvage therapy may be not inferior to PCI in patients with LS-SCLC. Ongoing large-scale randomized clinical trials are focused on the effects of active surveillance using brain MRI and early effective salvage therapy in patients with LS-SCLC [NCT04790253 (38), PRIMALung (39) and SWOG1827 (40)].

The results of the present meta-analysis revealed that extracranial metastasis was the primary mode of recurrence following initial treatment for LS-SCLC. In addition, the results of a previous study revealed that intrathoracic recurrence alone was the most common mode of recurrence following treatment for LS-SCLC (28%), which was markedly higher than the incidence of BM (9%) (41). Although PCI may decrease the incidence of BM, the risk of extracranial metastasis remains high, which may impact the therapeutic efficacy of PCI. Thus, improved extracranial disease control may improve the observed benefits of PCI in patients with LS-SCLC. Following the introduction of immunotherapy, the ADRIATIC study (42) assessed the effectiveness of immunoconsolidation following immunotherapy combined with chemoradiotherapy for the treatment of LS-SCLC. The results demonstrated that treatment was well-tolerated and that the PFS (16.6 vs. 9.2 months; HR, 0.76; CI, 0.61–0.95; P=0.0161) and OS (55.9 vs. 33.4 months; HR, 0.73; CI, 0.57–0.93; P=0.0104) times of patients were improved. A trial including 40 patients with LS-SCLC demonstrated that immunotherapy combined with chemoradiotherapy was advantageous for patients with LS-SCLC, with median OS and median PFS times of 39.5 (CI, 8.0–71.0) and 19.7 (CI, 8.8–30.5) months, respectively (43). Notably, immunotherapy significantly increased the rate of systemic disease control in patients with LS-SCLC, which may have enhanced the therapeutic benefits of PCI. Therefore, in the era of immunotherapy, reassessing the curative value of PCI for patients with LS-SCLC is crucial.

Notably, the present study exhibits several limitations. The included studies were retrospective clinical studies, which may lead to selection bias and selective reporting. However, prospective studies focusing on the effects of PCI on LS-SCLC in the MRI era are ongoing and the results are yet to be reported. In addition, the included studies did not record or analyze neurotoxicity or cognitive function following PCI. Thus, post-PCI neurotoxicity response was not investigated in the present study. Moreover, the present study did not determine the impact of salvage therapy following BM on patient survival, as only a small number of the included studies described the use of salvage therapy following BM. In some cases, HR values were estimated based on Kaplan-Meier survival curves, as numerous included studies did not provide HR values. These factors may have limited the results of the present meta-analysis.

In conclusion, the results of the present meta-analysis revealed that PCI was effective in improving OS and reducing BM in patients with LS-SCLC, when the absence of BM had been confirmed using brain MRI at baseline or prior to PCI. In patients with LS-SCLC who underwent active surveillance using brain MRI following PCI, PCI reduced the rate of BM. However, PCI did not significantly improve OS. Notably, studies included in the present meta-analysis were retrospective; thus, additional randomized controlled clinical trials are required to verify the results.

 Supplementary Material Supporting Data Supporting Data Acknowledgements

Not applicable.

 Availability of data and materials

The data generated in the present study may be requested from the corresponding author.

 Authors' contributions

LS was involved in the conceptualization and design the work and wrote the manuscript. YD, MJ, HS, LG and YQ were responsible for acquiring, analyzing and interpreting the data. HS and LG confirm the authenticity of all the raw data. JT and SW interpreted the data and designed the study, and all of the authors carefully reviewed the manuscript. All authors have read and approved the final version of the manuscript.

 Ethics approval and consent to participate

Not applicable.

 Patient consent for publication

Not applicable.

 Competing interests

The authors declare that they have no competing interests.

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PéchouxCFaivre-FinnCProphylactic cranial irradiation for patients with SCLC-A new perspective in the immunotherapy eraJ Thorac Oncol15S1556-0864-02446-82024 LevyABerghmansTKollerMFournierBMauerMAndratschkeNFaivre-FinnCPRIMALung (EORTC-1901): PRophylactic cerebral irradiation (PCI) or active brain MAgnetic resonance imaging (MRI) surveillance in small-cell lung cancer (SCLC) patientsLung Cancer198107993202410.1016/j.lungcan.2024.10799339541773 S1827 (MAVERICK) Testing whether the use of brain scans alone instead of brain scans plus preventive brain radiation affects lifespan in patients with small cell lung cancerhttps://clinicaltrials.gov/study/NCT04155034 EllisPMSwaminathAPondGRPatterns of relapse in small cell lung cancer: Competing risks of thoracic versus CNS relapseCurr Oncol2827782788202110.3390/curroncol2804024334287307 DavidRSYingCByoungCCLaktionovKKFangJChenYZenkeYLeeKHWangQNavarroAADRIATIC: Durvalumab (D) as consolidation treatment (tx) for patients (pts) with limited-stage small-cell lung cancer (LS-SCLC)ASCOLBA52024 WelshJWHeymachJVGuoCMenonHKleinKCushmanTRVermaVHessKRShroffGTangCPhase 1/2 Trial of Pembrolizumab and Concurrent Chemoradiation Therapy for Limited-Stage SCLCJ Thorac Oncol1519191927202010.1016/j.jtho.2020.08.02232916308

Flow chart of the literature screening.

Forest plots for OS, PFS, BM and BMFS in all patients who did or did not receive prophylactic cranial irradiation. OS, overall survival; PFS, progression-free survival; BM, brain metastasis; BMFS, BM-free survival; HR, hazard ratio; CI, confidence interval.

Forest plot of the OS of patients in the studies that used propensity matching analysis. OS, overall survival; HR, hazard ratio; CI, confidence interval; CRT, chemoradiotherapy; PCI, prophylactic cranial irradiation; MRI, magnetic resonance imaging.

Forest plot for OS, PFS, BM and BMFS in the pre- chemoradiotherapy magnetic resonance imaging group of patients who did or did not receive prophylactic cranial irradiation. OS, overall survival; PFS, progression-free survival; BM, brain metastasis; BMFS, BM-free survival; HR, hazard ratio; CI, confidence interval.

Forest plot for OS, PFS, BM and BMFS in the pre-PCI magnetic resonance imaging group of patients who did or did not receive PCI. OS, overall survival; PFS, progression-free survival; BM, brain metastasis; BMFS, BM-free survival; HR, hazard ratio; CI, confidence interval; PCI, prophylactic cranial irradiation.

Forest plot for OS, PFS, BM and BMFS in the magnetic resonance imaging surveillance group of patients who did or did not receive prophylactic cranial irradiation. OS, overall survival; PFS, progression-free survival; BM, brain metastasis; BMFS, BM-free survival; HR, hazard ratio; CI, confidence interval.

Forest plots for subgroup analysis of overall survival in the magnetic resonance imaging surveillance group of patients who did or did not receive prophylactic cranial irradiation. HR, hazard ratio; CI, confidence interval; CR, complete response; PR, partial response.

Forest plot of failure patterns in the prophylactic cranial irradiation group. ES, effect size; CI, confidence interval.

Forest plot of failure patterns in the non-prophylactic cranial irradiation group. ES, effect size; CI, confidence interval.

Funnel plot for overall survival. hr, hazard ratio; s.e., standard error.

Sensitivity analysis of PCI vs. non-PCI for overall survival in limited-stage small-cell lung cancer. CI, confidence interval; PCI, prophylactic cranial irradiation.

Baseline characteristics of the included studies.

First author, year Group Time frame of the study Patients, n Median age (range), years Male/female I–II/III CCRT/SCRT EP/others CR/PR PCI dose, Gy/F Brain MRI time points (Refs.)
Chen et al, 2022 PCI 2009.6–2019.6 324 58.0 (51–64) 232/92 62/162 115/209 315/9 91/233 25-30/10 Baseline, before PCI, (10)
Non-PCI 324 59.0 (51–65) 229/95 54/270 132/192 305/15 99/225 MRI surveillance
Eze et al, 2017 PCI 1998-2012 71 - 36/35 - 34/37 68/3 - 30/15 Baseline, before PCI (11)
Non-PCI 113 - 75/38 - 35/78 96/17 -
Inoue et al, 2021 PCI 1998-2018 43 - 38/5 32/10 43/0 - 34/9 24-30/10-15 Baseline, before PCI (12)
Non-PCI 85 - 71/14 46/39 71/14 - 41/44
Zhu et al, 2014 PCI 2003.1–2009.12 67 55.0 (34–82) 49/18 27/40 - - - 25/10 Baseline, before PCI (13)
Non-PCI 126 55.0 (7–74) 101/25 65/61 - - -
Li et al, 2021 PCI 2013.7–2017.6 77 - 58/19 - 47/30 - - 25/10 Baseline, before PCI, (14)
Non-PCI 113 - 74/39 - 43/70 - - MRI surveillance
Mamesaya et al, 2018 PCI 2002.9–2015.8 60 64.0 (34–82) 43/17 8/52 58/2 - 23/37 25/10 Baseline, before PCI (15)
Non-PCI 20 72.5 (56–83) 11/9 6/14 11/9 - 4/16
Ozawa et al, 2015 PCI 2006.1–2013.6 28 - - - - - - NR Before PCI (16)
Non-PCI 57 - - - - - -
Pan et al, 2023 PCI 2006.1–2017.12 57 57.0 44/19 6/77 69/15 77/6 38/45 25/10 Baseline, before PCI (17)
Non-PCI 61 61.0 28/5 2/31 14/19 29/4 15/18
Qi et al, 2022 PCI 2012.1–2018.1 75 - 53/22 23/52 35/40 - 16/59 - Baseline, before PCI, (18)
Non-PCI 75 - 59/16 25/50 29/46 - 8/67 MRI surveillance
Ghanta et al, 2021 PCI 2009-2020 243 65.2 (60–71) 91/152 58/185 221/13 - 69/174 25-36/10-18 Before PCI, (19)
Non-PCI 106 68.9 (61–74) 42/64 29/77 89/11 - 32/74 MRI surveillance
Pezzi et al, 2020 PCI 1992-2012 205 62.2 (27–85) 110/95 - - 67/14 70/23 25-30/10-15 Baseline, before PCI (20)
Non-PCI 92 68.6 (40–86) 52/40 - - 34/8 36/28
Farooqi et al, 2017 PCI 1985-2012 364 61.0 (34–85) 187/177 - 301/63 - - 25/10 Baseline (21)
Non-PCI 294 64.0 (27–95) 155/139 - 230/64 - -
Sas-Korczyńska et al, 2017 PCI 2002-2015 167 59.0 (32–79) 103/64 - 100/67 - - 30/15 Baseline (22)
Non-PCI 104 63.5 (35–79) 71/33 - 22/82 - -
Chen et al, 2018 PCI 2003.1–2015.12 19 (44–73) 15/4 10/9 - - - 25/10 Baseline (23)
Non-PCI 33 (38–74) 27/6 17/16 - - -
Kim et al, 2019 PCI 1994.11–2010.6 139 60.0 (34–75) 123/16 34/105 - - - - Baseline (24)
Non-PCI 95 62.0 (40–77) 81/14 20/75 - - -
Lee et al, 2023 PCI 2004.1–2017.12 211 65.0 (39–79) 175/36 41/170 191/20 - 32/158 25/10 Baseline (25)
Non-PCI 60 70.0 (44–93) 51/9 15/45 32/28 - 4/41
Farris et al, 2019 PCI 2007-2018 39 62.0 (38–80) 20/19 12/27 - - 12/27 25/10 Baseline (26)
Non-PCI 53 66.0 (41–91) 28/25 18/34 - - 17/36
Yin et al, 2018 PCI 2010.1–2015.12 160 - - - - - 30-40/10-20 Baseline (27)
Non-PCI 109 - - - - -
Held et al, 2022 PCI 2012.1–2019.12 28 62.2 (47–71) 12/16 - - 28/0 - 25/10 Baseline (28)
Non-PCI 21 65.5 (57–71) 11/10 - - 21/0 -
Lim et al, 2022 PCI - 26 60.0 (43–76) 22/4 - - 25/1 - 25-37.5/10-25 Baseline (29)
Non-PCI 81 69.0 (44–82) 69/12 - - 68/3 -
Jeong et al, 2020 PCI 2005.8–2014.3 56 - - - - - 25/10 Baseline (30)
Non-PCI 45 - - - - -

PCI, prophylactic cranial irradiation; CCRT, concurrent chemoradiothrapy; SCRT, sequential chemoradiotherapy; EP, etoposide and cisplatin; MRI, magnetic resonance imaging; CR, complete response; PR, partial response; F, fractions.