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Prophylactic cranial irradiation for extensive-stage small cell lung cancer: Analysis based on active brain MRI surveillance

ABSTRACT: Highlights • The value of PCI remains controversial in ES-SCLC.• Under the active brain MRI surveillance, PCI improve the PFS and BSS for ES-SCLC.• PCI reduce the incidence of BM for ES-SCLC. Background and purpose The value of prophylactic cranial irradiation (PCI) for extensive-stage small-cell lung cancer (ES-SCLC) has recently been challenged. This study was conducted to evaluate the role of PCI for ES-SCLC under active brain magnetic resonance imaging (MRI) surveillance. Materials and methods Patients with ES-SCLC who showed any responses after first-line chemotherapy and no initial brain metastasis (BM) were retrospectively included. Active brain MRI surveillance was performed for all patients. Progression-free survival (PFS) and overall survival (OS) were compared between PCI and non-PCI patients. The time-related hazard of BM was evaluated in non-PCI patients. Results One hundred and eighteen consecutive patients were included in the study. The median follow-up time was 26.5 months (3–72 months). The median PFS and OS were better in the PCI cohort than in the non-PCI group. Multivariate analyses revealed first-line chemotherapy cycles (> 4 vs. ? 4 cycles, HR: 0.29; 95% CI: 0.15–0.55, P < 0.01) and PCI (Yes vs. No, HR: 0.54; 95% CI: 0.29–0.99, P = 0.04) were independent prognostic factors for disease progression. In the non-PCI group, 47.4% (46/97) of the patients developed BM and the hazard of BM increased continuously in three-quarters of the first year since diagnosis. Conclusion Under active brain MRI surveillance, PCI could be beneficial for patients with ES-SCLC who show good responses after first-line chemotherapy.

SUBMITTER: Yu J

PROVIDER: S-EPMC7508717 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe recommendation of PCI for limited-stage small cell lung cancer (LS-SCLC) is primarily based on evidence from the pre-magnetic resonance imaging (MRI) era. However, as MRI accuracy improves and stereotactic radiosurgery advances, the role of PCI for LS-SCLC has become uncertain. This study aims to compare the contemporary survival outcomes of patients with LS-SCLC treated with PCI versus active surveillance.MethodsWe conducted a retrospective cohort study in which 1068 patients with LS-SCLC who achieved a good response to first-line chemoradiotherapy were consecutively enrolled from 5 tertiary medical centres between June 2009 and June 2019. Of these patients, 440 received PCI, while 628 received surveillance without PCI. Propensity score matching with a 1:1 ratio was performed to balance the baseline characteristics of the two cohorts. The endpoints were overall survival (OS) and the incidence of brain metastasis (BM).ResultsIn total, 648 patients were matched. The baseline characteristics were generally well balanced. At a median follow-up of 64.5 months (range 2-190), patients who underwent PCI had a significantly lower risk for BM than those who underwent surveillance. The 3-year cumulative incidence rate of BM was 28.2% (95% CI 22.5-33.8%) in the PCI cohort and 38.5% (32.6-44.5%) in the surveillance cohort (Gray's p = 0.002). However, the lower incidence of BM in the PCI cohort did not translate into a significant extension of OS. The median OS was 35.8 months (95% CI 27.6-44.0 months) in the PCI cohort versus 32 months (26.4-37.6 months) in the surveillance cohort (HR 0.90, 95% CI 0.74-1.10, p = 0.29). Multivariable analysis showed that disease stage, chemoradiotherapy sequence, and response to chemoradiotherapy were independent prognostic factors for BM or OS.ConclusionsOverall, PCI reduces the risk for BM but does not substantially prolong OS compared with active surveillance. A phase 3, prospective clinical trial (NCT04829708) we initiated is currently underway, which is expected to corroborate our results.

Project description:BackgroundNon-small cell lung cancer (NSCLC) patients frequently develop brain metastases (BM), even though the initial imaging with brain CT or MRI was negative. Stage III patients have the highest risk to develop BM, with an incidence of approximately 30%. BM can lead to neurocognitive disorders, loss of quality of life (QoL), and they are the most important factors influencing patient's overall survival (OS). Although a radical local treatment of BM may be possible with primary radiosurgery or after resection, the prognosis often remains poor. Preventing the development of BM through prophylactic cranial irradiation (PCI) may improve the outcome of these patients.MethodsData from published randomized trials comparing PCI with non-PCI were sought using electronic database (PubMed) searching, hand searching, and by contacting experts. Trials were included if they considered a randomized comparison of PCI and non-PCI, enrolled NSCLC patients, excluded patients with recurrent or metastatic disease, and reported results on BM occurrence. Each randomized controlled trial (RCT) was assessed for methodological quality using the Cochrane collaboration's tool for the assessment of risk of bias. Study estimates were pooled using a fixed effects sample-weighted meta-analysis approach to calculate an overall estimate and 95% confidence interval (CI). Results on PCI-related toxicity, QoL, and OS were only reported descriptively.ResultsSeven RCTs were included in the meta-analysis. In total, 1,462 patients were analyzed, including 717 patients who received PCI and 745 patients who did not. The risk of developing BM was significantly decreased through PCI (13% reduction, RR 0.33; 95% CI 0.22-0.45). PCI-related toxicity and QoL data were limited. Acute toxicity mostly included fatigue, skin-related toxicity, and nausea or vomiting. Late toxicities such as headache, dyspnea, lethargy, and low grade cognitive impairments were also reported in some of the included RCTs. Results on OS were inconclusive.ConclusionThe risk of developing BM was reduced in patients who received PCI compared to patients who did not. To implement PCI as the standard treatment for patients with NSCLC, the impact of PCI-related toxicity on QoL should be further investigated, as well as long-term OS. A future individual patient data meta-analysis could produce definitive answers to this clinical question.

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Prophylactic cranial irradiation for extensive-stage small cell lung cancer: Analysis based on active brain MRI surveillance

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