Zeng Haiyan, Zheng Danyang, Witlox Willem J A, Levy Antonin, Traverso Alberto, Kong Feng-Ming Spring, Houben Ruud, De Ruysscher Dirk K M, Hendriks Lizza E L
Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht University Medical Center+, Maastricht, Netherlands.
Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Front Oncol. 2022 Jun 10;12:889161. doi: 10.3389/fonc.2022.889161. eCollection 2022.
The use of prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC) patients is controversial. Risk factors for brain metastasis (BM) development are largely lacking, hampering personalized treatment strategies. This study aimed to identify the possible risk factors for BM in SCLC.We systematically searched the Pubmed database (1 January 1995 to 18 January 2021) according to the PRISMA guidelines. Eligibility criteria: studies reporting detailed BM data with an adequate sample size (randomized clinical trials [RCTs]: N ≥50; non-RCTs: N ≥100) in patients with SCLC. We summarized the reported risk factors and performed meta-analysis to estimate the pooled hazard ratios (HR) if enough qualified data (i.e., two or more studies; the same study type; the same analysis method; and HRs retrievable) were available. In total, 61/536 records were eligible (18 RCTs and 39 non-RCTs comprising 13,188 patients), in which 57 factors were reported. Ten factors qualified BM data for meta-analysis: Limited stage disease (LD) (HR = 0.34, 95% CI: 0.17-0.67; P = 0.002) and older age (≥65) (HR = 0.70, 95% CI: 0.54-0.92; P = 0.01) were associated with less BM; A higher T stage (≥T3) (HR = 1.72, 95% CI: 1.16-2.56; P = 0.007) was a significant risk factor for BM. Male sex (HR = 1.24, 95% CI: 0.99-1.54; P = 0.06) tended to be a risk factor, and better PS (0-1) (HR = 0.66, 95% CI: 0.42-1.02; P = 0.06) tended to have less BM. Smoking, thoracic radiotherapy dose were not significant (P >0.05). PCI significantly decreased BM (P <0.001), but did not improve OS in ED-SCLC (P = 0.81). A higher PCI dose did not improve OS (P = 0.11). The impact on BM was conflicting between Cox regression data (HR = 0.59, 95% CI: 0.26-1.31; P = 0.20) and competing risk regression data (HR = 0.74, 95% CI: 0.55-0.99; P = 0.04). Compared to M0-M1a, M1b was a risk factor for OS (P = 0.01) in ED-SCLC, but not for BM (P = 0.19). As regular brain imaging is rarely performed, high-quality data is lacking. Other factors such as N-stage and blood biomarkers had no qualified data to perform meta-analysis. In conclusion, younger age, higher T stage, and ED are risk factors for BM, suggesting that PCI should be especially discussed in such cases. Individual patient data (IPD) meta-analysis and well-designed RCTs are needed to better identify more risk factors and further confirm our findings. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228391, identifier CRD42021228391.
小细胞肺癌（SCLC）患者预防性颅脑照射（PCI）的应用存在争议。脑转移（BM）发生的危险因素大多未知，这阻碍了个性化治疗策略的制定。本研究旨在确定SCLC患者发生BM的可能危险因素。我们根据PRISMA指南系统检索了Pubmed数据库（1995年1月1日至2021年1月18日）。纳入标准：报告详细BM数据且样本量充足的研究（随机临床试验[RCTs]：N≥50；非RCTs：N≥100）的SCLC患者。我们总结了报告的危险因素，并进行荟萃分析以估计合并风险比（HR），前提是有足够的合格数据（即两项或更多研究；相同的研究类型；相同的分析方法；且可检索到HR）。总共61/536条记录符合条件（18项RCT和39项非RCT，共13,188例患者），其中报告了57个因素。十个因素符合荟萃分析的BM数据标准：局限期疾病（LD）（HR = 0.34，95%CI：0.17 - 0.67；P = 0.002）和老年（≥65岁）（HR = 0.70，95%CI：0.54 - 0.92；P = 0.01）与较少的BM相关；较高的T分期（≥T3）（HR = 1.72，95%CI：1.16 - 2.56；P = 0.007）是BM的显著危险因素。男性（HR = 1.24，95%CI：0.99 - 1.54；P = 0.06）倾向于为危险因素，较好的体能状态（PS）（0 - 1）（HR = 0.66，95%CI：0.42 - 1.02；P = 0.06）倾向于有较少的BM。吸烟、胸部放疗剂量无统计学意义（P>0.05）。PCI显著降低了BM（P<0.001），但未改善广泛期小细胞肺癌（ED - SCLC）的总生存期（OS）（P = 0.81）。较高的PCI剂量未改善OS（P = 0.11）。Cox回归数据（HR = 0.59，95%CI：0.26 - 1.31；P = 0.20）和竞争风险回归数据（HR = 0.74，95%CI：0.55 - 0.99；P = 0.04）对BM的影响存在冲突。与M0 - M1a相比，M1b是ED - SCLC患者OS的危险因素（P = 0.01），但不是BM的危险因素（P = 0.19）。由于很少进行常规脑成像，缺乏高质量数据。其他因素如N分期和血液生物标志物没有合格数据进行荟萃分析。总之，年轻、较高的T分期和ED是BM的危险因素，表明在这些情况下应特别讨论PCI。需要个体患者数据（IPD）荟萃分析和精心设计的RCT来更好地识别更多危险因素并进一步证实我们的发现。https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228391，标识符CRD42021228391。
