WBRT for brain metastases from non-small cell lung cancer: for whom and when?—Contemporary point of view

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Abstract

The incidence of brain metastases (BM) is estimated between 20% and 40% of patients with solid cancer. The most common cause of this failure is lung cancer, and in locally advanced non-small cell lung cancer (NSCLC) BM represent a common site of relapse in 30–55% cases. The basic criteria of therapeutic decision-making are based on the significant prognostic factors which are components of prognostic scores. The standard approach to treatment of BM from NSCLC include whole brain radiotherapy (WBRT) which is used as adjuvant modality after local therapy (surgery or stereotactic radiosurgery) or as primary treatment and it remains the primary modality of treatment for patients with multiple metastases. WBRT is also used in combination with systemic therapy. The aim of presented review of literature is trying to answer which patients with BM from NSCLC should receive WBRT and when it could be omitted. There were presented the aspects of application of WBRT in relation to (I) choice between WBRT or the best supportive care and (II) employment of WBRT in combination with local treatment modalities [surgical resection or stereotactic radio-surgery (SRS)] and/or with systemic therapy. According to data from literature we concluded that the most important factor that needs to be considered when assessing the suitability of a patient for WBRT is the patient’s prognosis based on the Lung-molGPA score. WBRT should be applied in treatment of multiple BM from lung cancer in patients with favourable prognosis and in in patients with presence of EML4-ALK translocation before therapy with crizotinib. Whereas WBRT could be omitted in patients with poor prognosis and after primary SRS.

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Cancer Statistics, 2017.

Rebecca L Siegel, Kimberly D Miller, Ahmedin Jemal (2017)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2017, 1,688,780 new cancer cases and 600,920 cancer deaths are projected to occur in the United States. For all sites combined, the cancer incidence rate is 20% higher in men than in women, while the cancer death rate is 40% higher. However, sex disparities vary by cancer type. For example, thyroid cancer incidence rates are 3-fold higher in women than in men (21 vs 7 per 100,000 population), despite equivalent death rates (0.5 per 100,000 population), largely reflecting sex differences in the "epidemic of diagnosis." Over the past decade of available data, the overall cancer incidence rate (2004-2013) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2005-2014) declined by about 1.5% annually in both men and women. From 1991 to 2014, the overall cancer death rate dropped 25%, translating to approximately 2,143,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the cancer death rate was 15% higher in blacks than in whites in 2014, increasing access to care as a result of the Patient Protection and Affordable Care Act may expedite the narrowing racial gap; from 2010 to 2015, the proportion of blacks who were uninsured halved, from 21% to 11%, as it did for Hispanics (31% to 16%). Gains in coverage for traditionally underserved Americans will facilitate the broader application of existing cancer control knowledge across every segment of the population. CA Cancer J Clin 2017;67:7-30. © 2017 American Cancer Society.

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Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial.

Rafael Rosell, Enric Carcereny, Radj Gervais … (2012)

Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC. We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (> 18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥ 6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m(2) on day 1 plus docetaxel (75 mg/m(2) on day 1) or gemcitabine (1250 mg/m(2) on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m(2) or AUC 5 with gemcitabine 1000 mg/m(2)) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥ 1 dose). This study is registered with ClinicalTrials.gov, number NCT00446225. Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5-5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25-0·54; p < 0·0001). Main grade 3 or 4 toxicities were rash (11 [13%] of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 [22%]), anaemia (one [1%] vs three [4%]), and increased amino-transferase concentrations (two [2%] vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes. Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Temática de Investigacion Cooperativa en Cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

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Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System.

Jill Barnholtz-Sloan, Andrew Sloan, Faith G. Davis … (2004)

Population-based estimates of the incidence of brain metastases are not generally available. The purpose of this study was to calculate population-based incidence proportions (IPs) of brain metastases from single primary lung, melanoma, breast, renal, or colorectal cancer. Patients diagnosed with single primary lung, melanoma, breast, renal, or colorectal cancer (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System (MDCSS) were used for analysis. IP of brain metastases by primary site and variable of interest (race, sex, age at diagnosis of primary cancer, and Surveillance, Epidemiology, and End Results [SEER] stage of primary cancer) was calculated with 95% CIs. Total IP percentage (IP%) of brain metastases was 9.6% for all primary sites combined, and highest for lung (19.9%), followed by melanoma (6.9%), renal (6.5%), breast (5.1%), and colorectal (1.8%) cancers. Racial differences were seen with African Americans demonstrating higher IP% of brain metastases compared with other racial groups for most primary sites. IP% was significantly higher for female patients with lung cancer, and significantly higher for male patients with melanoma. The highest IP% of brain metastases occurred at different ages at diagnoses: age 40 to 49 years for primary lung cancer; age 50 to 59 years for primary melanoma, renal, or colorectal cancers; and age 20 to 39 for primary breast cancer. IP% significantly increased as SEER stage of primary cancer advanced for all primary sites. Total IP% of brain metastases was lower than previously reported, and it varied by primary site, race, sex, age at diagnosis of primary cancer, and SEER stage of primary cancer.

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Author and article information

Journal

Journal ID (nlm-ta): J Thorac Dis

Journal ID (iso-abbrev): J Thorac Dis

Journal ID (publisher-id): JTD

Title: Journal of Thoracic Disease

Publisher: AME Publishing Company

ISSN (Print): 2072-1439

ISSN (Electronic): 2077-6624

Publication date (Print and electronic): May 2021

Publication date (Print): May 2021

Volume: 13

Issue: 5

Pages: 3246-3257

Affiliations

[1 ]deptInstitute of Medical Sciences , Medical College of Rzeszow University , Rzeszow, Poland;

[2 ]deptDepartment of Radiotherapy , Military Institute of Medicine , Warsaw, Poland;

[3 ]deptDepartment of Oncology, Collegium Medicum , University of Warmia and Mazury , Olsztyn, Poland

Author notes

Contributions: (I) Conception and design: B Sas-Korczynska; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: None; (V) Data analysis and interpretation: None; (VI) Manuscript writing: Both authors; (VII) Final approval of manuscript: Both authors.

Correspondence to: Beata Sas-Korczynska. Institute of Medical Sciences, Medical College of Rzeszow University, Rzeszow, Poland. Email: b.sas.korczynska@ 123456gmail.com .

Article

Publisher ID: jtd-13-05-3246

DOI: 10.21037/jtd-2019-rbmlc-06

PMC ID: 8182552

PubMed ID: 34164217

SO-VID: c24db96e-ffb4-41ce-99b2-830ea799dc3e

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Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

WBRT for brain metastases from non-small cell lung cancer: for whom and when?—Contemporary point of view

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Most cited references 91

Cancer Statistics, 2017.

Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial.

Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System.

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