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Cranial irradiation in patients with EGFR-mutant non-small cell lung cancer brain metastases.

ABSTRACT: The most effective treatment approach for brain metastases in patients with non-small cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations is a current subject of investigation. Cranial irradiation is the standard treatment for brain metastases, but tyrosine kinase inhibitors (TKIs) such as erlotinib have also activity against brain metastases in this subset of patients. The combination of TKI and radiotherapy is a promising one, but data is lacking to indicate whether this is superior to erlotinib or whole brain radiation therapy (WBRT) alone. Retrospective data suggest that WBRT achieves more durable intracranial control compared to erlotinib alone. Randomized, prospective studies will be necessary to determine whether TKI, cranial irradiation, or both is the optimal initial treatment for brain metastases in EGFR-mutant NSCLC.

SUBMITTER: Yang TJ

PROVIDER: S-EPMC4758984 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Cranial irradiation in patients with EGFR-mutant non-small cell lung cancer brain metastases.

Yang T Jonathan TJ Wu Abraham J AJ

Translational lung cancer research 20160201 1

The most effective treatment approach for brain metastases in patients with non-small cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations is a current subject of investigation. Cranial irradiation is the standard treatment for brain metastases, but tyrosine kinase inhibitors (TKIs) such as erlotinib have also activity against brain metastases in this subset of patients. The combination of TKI and radiotherapy is a promising one, but data is lacking to indica ...[more]

PMID: 26958508

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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:ObjectivesTo explore the rationale and value of consolidative cranial local therapy (CLT) in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastases (BMs).MethodsEGFR-mutant NSCLC patients with baseline BMs who received first-line EGFR-tyrosine kinase inhibitors (TKIs) at two academic centers from May 2015 to June 2020 were retrospectively enrolled. Patterns of tumor response and treatment failure were extensively analyzed in order to explore the rationale of CLT. Cranial lesions with number ⩽3 and largest tumor size ⩽3 cm at baseline and best response to EGFR-TKIs were defined as oligo-BMs and oligo-residual cranial disease (ORCD), respectively. To provide preliminary data supporting CLT, survival outcomes were compared in patients with ORCD, stratified by CLT status.ResultsOf the 216 patients enrolled, 57.1% had oligo-BMs and 24.5% received first-line osimertinib. At best response to the first-line EGFR-TKIs, intracranial complete response, partial response, and stable disease occurred in 18.5, 31.9, and 44.4% of the whole population, respectively. For patients without CLT (n = 193), ORCD was observed in 78.1% of the 105 patients with baseline oligo-BMs and 10.2% of the 88 patients with baseline multiple-BMs. With a median follow-up of 22.8 months, 107 patients had cranial first progressive disease (PD); more than 60% developed their first PD solely from the residual tumor sites at best response to EGFR-TKIs. Moreover, among patients with ORCD (n = 108), patients who received CLT (n = 17) achieved significantly longer progression-free survival (13.4 versus 8.5 months, p = 0.001) and overall survival (58.9 versus 28.8 months, p = 0.021) than those without CLT. Meanwhile, CLT remained as an independent prognostic factor associated with improved survival after Cox regression analyses.ConclusionsCranial progressive disease developed mostly at the residual cranial lesions in EGFR-mutant NSCLC patients with baseline BMs who received first-line EGFR-TKIs. Consolidative cranial local therapy targeting the oligo-residual cranial tumor lesions may provide survival benefit, which warrants future validation.

Dataset Information

Cranial irradiation in patients with EGFR-mutant non-small cell lung cancer brain metastases.

Publications

Cranial irradiation in patients with EGFR-mutant non-small cell lung cancer brain metastases.

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