Diversity of brain metastases screening and management in non-small cell lung cancer in Europe: Results of the European Organisation for Research and Treatment of Cancer Lung Cancer Group survey

Lévy, Antonin; Faivre-Finn, Corinne; Hasan, Baktiar; Maio, Eléonora De; Berghoff, Anna Sophie; Girard, Nicolas; Greillier, L.; Lantuéjoul, Sylvie; O’Brien, Mary; Reck, Martin; Dingemans, Anne Marie C.; Novello, Silvia; Berghmans, Thierry; Besse, Benjamin; Hendriks, Lizza

doi:10.1016/j.ejca.2018.01.067

Cited by 75 publications

(59 citation statements)

References 42 publications

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“…Recent real world data collected by EORTC Lung Cancer Group showed that NSCLC patients with driver mutations generally received more intensive local treatments . Further, a recent large‐scale retrospective study of EGFR ‐mutant NSCLC patients with BMs reported that survival time was improved by the combination of upfront SRS and EGFR‐TKI compared to that by upfront WBRT and EGFR‐TKI or TKI monotherapy (46 months vs. 30 months vs. 25 months, P < 0.001) .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of EGFR‐TKIs with or without upfront brain radiotherapy for EGFR‐mutant NSCLC patients with central nervous system metastases

et al. 2019

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BackgroundAlthough the clinical efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in EGFR‐mutant non‐small cell lung cancer (NSCLC) patients has been demonstrated, their efficacy in EGFR‐mutant NSCLCs with central nervous system (CNS) metastases and the role of radiotherapy remain unclear. This study aimed to determine if it is preferable to add upfront cranial radiotherapy to EGFR‐TKIs in patients with EGFR‐mutant NSCLC with newly diagnosed brain metastases.MethodsWe retrospectively analyzed the data of EGFR‐mutant NSCLC patients with CNS metastases who received EGFR‐TKIs as a first‐line therapy.ResultsA total of 104 patients were enrolled and 39 patients received upfront brain radiotherapy, while 65 patients received first and second generation EGFR‐TKIs first. The median time to treatment failure (TTF) was 7.8 months (95% confidence interval [CI]: 6.3–9.4). The median survival time (MST) was 24.0 months (95% CI: 20.1–30.1). The overall response rate of the CNS was 37%. The median CNS progression‐free survival (PFS) was 13.2 months (95% CI: 10.0–16.2). Brain radiotherapy prior to EGFR‐TKI prolonged TTF (11.2 vs. 6.8 months, P = 0.038) and tended to prolong CNS‐PFS (15.6 vs. 11.1 months, P = 0.096) but was not significantly associated with overall survival (MST 26.1 vs. 24.0 months, P = 0.525). Univariate and multivariate analyses indicated that poor performance status and the presence of extracranial metastases were poor prognostic factors related to overall survival.ConclusionEGFR‐TKI showed a favorable effect for EGFR‐mutant NSCLC patients with CNS metastases. Prolonged TTF and CNS‐PFS were observed with upfront brain radiotherapy.

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Section: Discussionmentioning

confidence: 99%

Efficacy of EGFR‐TKIs with or without upfront brain radiotherapy for EGFR‐mutant NSCLC patients with central nervous system metastases

et al. 2019

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“…An important factor which impoverishes patient prognosis is the presence of brain metastases (BM), a relatively frequent metastatic site for lung tumors. Baseline BM are present in 10% of non‐small cell lung cancer (NSCLC) patients, and this number is expected to increase with the standardization of brain imaging in asymptomatic patients, particularly in those with specific molecular alterations, such as EGFR mutations ( EGFR m) or ALK rearrangements ( ALK r), but also in those with elevated CEA . Additionally, the risk of presenting BM increases throughout the course of the disease, and overall 40% of NSCLC patients will eventually present BM, although this proportion increases to 80% in particular subgroups .…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5] Additionally, the risk of presenting BM increases throughout the course of the disease, and overall 40% of NSCLC patients will eventually present BM, although this proportion increases to 80% in particular subgroups. 4 BM usually leads to treatment failure and impaired quality of life despite treatment 4 ; moreover, the prognosis of BM is poor, with a median survival of two months when treated with systemic corticosteroids alone. Whole brain irradiation (WBI) and stereotactic radiosurgery (SRS) have been the mainstay treatment for BM in NSCLC patients irrespective of histology with objective response rates (ORR) of 60%-70% for intracranial lesions and a median survival of eight months.…”

Section: Introductionmentioning

confidence: 99%

Response rate of patients with baseline brain metastases from recently diagnosed non‐small cell lung cancer receiving radiotherapy according to EGFR, ALK and KRAS mutation status

et al. 2020

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Background Previous studies have identified that patients with EGFR mutations tend to have better responses to targeted therapy, as well as chemotherapy; however, the effect of genetic alterations in terms of radiotherapy (RT)‐related outcomes has not been fully assessed. We studied the impact of common non‐small cell lung cancer (NSCLC) genetic alterations (EGFR, ALK and KRAS) in relation to objective response rate (ORR) to RT in patients with brain metastases. Methods From 2009–2015, 153 patients with an available genotyping status were treated with whole‐brain irradiation (WBI) before receiving systemic therapy. Primary outcome was ORR; secondary outcomes included intracranial progression‐free survival (IPFS) and overall survival (OS). Results Overall, ORR was 47.1%. ORR to RT varied significantly according to molecular status: EGFR (64.5%) ALK (54.5%) KRAS (20%) and WT (35.4%) (P = 0.001). EGFR mutation was the only independently associated factor for response to WBI (RR 3.52 [95% CI 1.6–7.7]; P = 0.002). Median IPFS was 10.8 months [95% CI 8.2–13.5] overall; however, IPFS also varied significantly according to molecular status: EGFR (18.2 months), ALK (18.4 months), KRAS (6.0 months) and WT (8.7 months) (P < 0.0001). OS for EGFR, ALK, KRAS and WT patients was 36.6, 32.2, 15.5 and 22.4 months, respectively (P = 0.014). Intracranial‐ORR (HR 0.4 [95% CI 0.2–0.6], P < 0.001) and mutation status (HR 0.7 [95% CI 0.6–0.9], P < 0.042) were independently associated with a higher OS. Conclusions RT response varies as per tumor molecular status. The presence of EGFR mutations favors the organ‐specific response to RT, and is associated with longer OS in patients with NSCLC and BM. Key points This study addressed for the first time the difference in radiotherapy‐related outcomes in patients with different genotypes of non‐small cell lung cancer (NSCLC) before they received systemic therapy. Results show that response to radiotherapy varies as per tumor molecular status, particularly EGFR‐mutated tumors, have a favorable response to radiotherapy, contrary to KRAS‐mutated tumors.

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“…Surveys of lung cancer clinicians have found that 49% of UK clinicians and 85% of EORTC clinicians would routinely screen brains of neurologically asymptomatic patients . The use of screening differed by stage.…”

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confidence: 99%

“…Surveys of lung cancer clinicians have found that 49% of UK clinicians and 85% of EORTC clinicians would routinely screen brains of neurologically asymptomatic patients. 2,3 The use of screening differed by stage. In the EORTC study, screening by stage was 39% for Stage I and II, 63% for Stage III and 43% for Stage IV NSCLC patients 3 compared to 34% Stage I, 41% Stage II, 50% Stage III and 40% Stage IV reported by Diaz et al 1 The figures are similar except for a higher proportion of EORTC clinicians stating that they would screen Stage III patients.…”

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confidence: 99%

Should we screen for brain metastases in non‐small cell lung cancer?

Vinod

2018

J Med Imag Rad Onc

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Diversity of brain metastases screening and management in non-small cell lung cancer in Europe: Results of the European Organisation for Research and Treatment of Cancer Lung Cancer Group survey

Abstract: BM management is highly variable in Europe: screening is not uniform, prognostic classifications are not often used and MUT+ NSCLC patients generally receive more intensive local treatment. Prospective assessment of BM management in MUT+ NSCLC patients is required.

Cited by 75 publications

References 42 publications

Efficacy of EGFR‐TKIs with or without upfront brain radiotherapy for EGFR‐mutant NSCLC patients with central nervous system metastases

Efficacy of EGFR‐TKIs with or without upfront brain radiotherapy for EGFR‐mutant NSCLC patients with central nervous system metastases

Response rate of patients with baseline brain metastases from recently diagnosed non‐small cell lung cancer receiving radiotherapy according to EGFR, ALK and KRAS mutation status

Should we screen for brain metastases in non‐small cell lung cancer?

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