Systematic review and meta-analysis of lung cancer brain metastasis and primary tumor receptor expression discordance
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Published on: February 8, 2017
Raees Tonse1, Muni Rubens2, Haley Appel1
1Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Office 1R203, Miami, FL, 33176, USA.
Background:
Treatment paradigms for metastatic non-small cell lung cancer are increasingly based on biomarker-driven therapies, with the most common alteration being mutation in the epidermal growth factor receptor (EGFR). Change in expression of such biomarkers could have a profound impact on the choice and efficacy of a selected targeted therapeutic, and hence the objective of this study was to analyze discordance in EGFR status in patients with lung cancer brain metastasis (LCBM).
Methods:
Using PRISMA guidelines, a systematic review was performed of series in the Medline database of biopsied or resected LCBM published before May, 2020. Key words included "lung cancer" and "brain metastasis" combined with "epidermal growth factor receptor/EGFR," and "receptor conversion/discordance or concordance." Weighted random effects models were used to calculate pooled estimates.
Results:
We identified 501 patients from 19 full-text articles for inclusion in this study. All patients underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. On primary/LCBM comparison, the weighted pooled estimate for overall EGFR receptor discordance was 10% (95% CI 5-17%). The weighted effects model estimated a gain of an EGFR mutation in a brain metastases in patients with negative primary tumors was 7% (95% CI 4-12%). Alternatively, the weighted effects model estimate of loss of an EGFR mutation in patients with detected mutations in the primary tumor was also 7% (95% CI 4-10%). KRAS testing was also performed on both primary tumors and LCBM in a subset of 148 patients. The weighted effects estimate of KRAS-mutation discordance among LCBM compared to primary tumors was 13% (95% CI 5-27%). The weighted effects estimated of KRAS gain and loss in LCBM was 10% (95% CI 6-18%) and 8% (95% CI 4-15%), respectively. Meta-regression analysis did not find any association with any factors that could be associated with discordances.
Conclusions:
EGFR and KRAS mutation status discordance between primary tumor and LCBM occurs in approximately 10% and 13% of patients, respectively. Evaluation of LCBM receptor status is key to biomarker-driven targeted therapy for intracranial disease and awareness of subtype switching is critical for those patients treated with systemic therapy alone for intracranial disease.
Insights
Tumor biomarker status, such as epidermal growth factor receptor (EGFR) and KRAS mutations, can change between primary lung cancer and brain metastases. This discordance, occurring in about 10-13% of cases, impacts targeted therapy effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastatic non-small cell lung cancer (NSCLC) treatment increasingly relies on biomarker-driven therapies.
- Epidermal growth factor receptor (EGFR) mutations are common alterations in NSCLC.
- Discordance in biomarker status between primary tumors and metastases can affect therapeutic efficacy.
Purpose of the Study:
- To analyze the discordance in EGFR mutation status between primary lung tumors and lung cancer brain metastases (LCBM).
- To investigate the frequency of EGFR and KRAS mutation discordance in patients with LCBM.
Main Methods:
- Systematic review of studies on biopsied or resected LCBM published before May 2020, following PRISMA guidelines.
- Inclusion of studies comparing EGFR status in primary tumors and corresponding LCBM.
- Application of weighted random effects models to calculate pooled estimates of discordance.
Main Results:
- Analysis of 501 patients from 19 articles revealed an overall EGFR discordance of 10% between primary tumors and LCBM.
- EGFR mutation gain in LCBM from EGFR-negative primary tumors was 7%, and loss was 7% in LCBM from EGFR-mutated primary tumors.
- KRAS mutation discordance in LCBM was 13%, with gains and losses estimated at 10% and 8%, respectively; no factors were associated with discordance.
Conclusions:
- Significant discordance in EGFR (10%) and KRAS (13%) mutation status exists between primary lung tumors and LCBM.
- Assessing receptor status in LCBM is crucial for guiding targeted therapies for intracranial disease.
- Awareness of biomarker subtype switching is critical for patients treated with systemic therapy alone for brain metastases.
