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Prophylactic cranial irradiation in non-small cell lung cancer: evidence and future development.

ABSTRACT: In non-small cell lung cancer (NSCLC) brain metastases (BM) will affect up to 50% of patients during whole disease period. BM themselves impact heavily not only on patient's prognosis but also are a source of symptoms aggravating quality of life. Standard (pemetrexed), and non-standard chemotherapy (temozolomide) in patients with NSCLC failed to prevent them from BM. In terms of systemic treatment there are promising results showed when durvalumab (PACIFIC study), osimertinib (FLAURA trial) or alectinib (JALEX study) was used. However, those substances are effective only in small cohort with ALK or EGFR alterations. Prophylactic cranial irradiation (PCI) as a non-specific treatment has proven to be a powerful tool in preventing BM without affecting overall survival in neither way. That has been proved in nearly all earlier and all recent studies-NVALT11/DLCRG-02, RTOG 0214 update, Li et al. The positive effect of BM incidence reduction may draw fear form PCI usage due to potential cognitive toxicity the PCI may cause. Results of recent trials show that after PCI only mild cognitive disorders (MCD) may arise. Promising results in terms of reducing MCD are shown when memantine is used or/and hippocampal avoidance techniques are implemented. HA in PCI seem to be cost effective but calculations were made on small-cell lung cancer cohorts. Still even recent studies did not clarify finally which patients could benefit from PCI or other forms of preventing BM. It seems that new trials should focus on younger, fit and non-squamous histology patients and use the tests for mild cognitive disorders (MoCA, BHA) rather than screening tests for dementia (MMSE, HVLT, ADL). The main obstacle in performing new trials on PCI in NSCLC cohorts may be, however, patients' accrual, as a difficulty which occurred during latest trials.

SUBMITTER: Chalubinska-Fendler J

PROVIDER: S-EPMC8182492 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

Project description:BackgroundPatients 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.MethodsIn 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.FindingsOf 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).InterpretationOur 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.FundingNo funding.

Project description:Background:We systematically reviewed the literature for trials addressing the efficacy of prophylactic cranial irradiation (PCI) in patients with non-small-cell lung cancer (NSCLC) treated with a curative intent. Methods:Randomized controlled trials (RCT) comparing PCI to no PCI in patients with NSCLC treated with a curative intent were eligible for inclusion. We searched EMBASE, MEDLINE, PubMed, and CENTRAL between 1946 and July 2016. We also received continual search alerts from PubMed through September 2017. Search terms included "non-small-cell lung carcinoma," "cranial irradiation," and "randomized controlled trials." We conducted meta-analyses using random-effects models for relative measures of treatment effect for the incidence of brain metastasis, overall survival (OS), and disease-free survival (DFS). We used Parmar's methodology to derive hazard ratios (HR) when not explicitly stated in RCTs. We narratively synthesized data for the impact of PCI on quality of life (QoL) and neurocognitive function (NCF). We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. Results:Out of 3,548 citations captured by the search strategy, we retained 8 papers and 1 abstract, reporting on 6 eligible trials. Patients who received PCI had a significant reduction in the risk of developing brain metastases as compared with patients who did not [relative risk (RR)?=?0.37; 95% confidence interval (CI): 0.26-0.52; moderate quality evidence]. However, there was no OS benefit (HR?=?1.08, 95% CI: 0.90-1.31; moderate quality evidence). Sensitivity analysis excluding older studies did not show substantively different findings. DFS was reported in the two most recent trials that included only stage III patients. There was significant improvement in DFS with PCI (HR?=?0.67; 95% CI: 0.46-0.98; high quality evidence). Two studies that reported on QoL reported no statistically significant differences. There was no significant difference in NCF decline in the only study that reported on this outcome, except in immediate and delayed recall, as assessed by the Hopkins Verbal Learning Test. Conclusion:There is moderate quality evidence that the use of PCI in patients with NSCLC decreases the risk of brain metastases, but does not provide an OS benefit. However, data limited to stage III patients suggests that PCI improves DFS, with no effect on QoL.

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Prophylactic cranial irradiation in non-small cell lung cancer: evidence and future development.

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