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Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?

ABSTRACT: We investigated effects of genetic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS) on overall survival (OS) and local control after stereotactic radiosurgery for brain metastases in non-small cell lung cancer (NSCLC).A cohort of 89 out of 262 NSCLC patients (2003-2013) treated with gamma knife radiosurgery for brain metastases had genotyping available and were selected as our study population.Median follow-up was 12 months. Median OS rates for the EGFR, KRAS, echinoderm microtubule-associated protein-like 4 (EML4)-ALK mutated, and wild-type cohorts were 17, 7, 27, and 12 months, respectively (P = .019), and for targeted versus nontargeted therapy 21 and 11 months, respectively (P = .071). Targeted therapy was a strong predictor of increased OS on univariate (P = .037) and multivariate (P = .022) analysis. Gender, primary tumor controlled status, recursive partitioning analysis class, and graded prognostic assessment score were associated with OS (P < .05). On multivariate analysis, positive EGFR mutational status was a highly significant predictor for decreased survival (hazard ratio: 8.2; 95% CI: 2.0-33.7; P = .003). However, when we recategorized EGFR-mutant cases based on whether they received tyrosine kinase inhibitor, OS was no longer significantly shorter (hazard ratio: 1.5; P = .471). Median OS for patients with and without local failure was 17 and 12 months, respectively (P = .577). Local failure rates for EGFR, KRAS, EML4-ALK mutated, and wild-type cohorts by lesion were 8.7%, 5.4%, 4.3%, and 5.1%, respectively.This study suggests that EGFR tyrosine kinase mutation and ALK translocation results in improved survival to targeted therapies and that mutation status itself does not predict survival and local control in patients with brain metastases from NSCLC.

SUBMITTER: Wang TJ

PROVIDER: S-EPMC5762012 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?

Wang Tony J C TJ Saad Shumaila S Qureshi Yasir H YH Jani Ashish A Nanda Tavish T Yaeh Andrew M AM Rozenblat Tzlil T Sisti Michael B MB Bruce Jeffrey N JN McKhann Guy M GM Lesser Jeraldine J Halmos Balazs B Stoopler Mark B MB Lassman Andrew B AB Cheng Simon K SK Isaacson Steven R SR

Neuro-oncology 20150424 7

<h4>Background</h4>We investigated effects of genetic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma viral oncogene homolog (KRAS) on overall survival (OS) and local control after stereotactic radiosurgery for brain metastases in non-small cell lung cancer (NSCLC).<h4>Methods</h4>A cohort of 89 out of 262 NSCLC patients (2003-2013) treated with gamma knife radiosurgery for brain metastases had genotyping available and were select ...[more]

PMID: 25910841

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Project description:Purpose:This study aimed to report on our institutional experience in the use of stereotactic body radiation therapy (SBRT) for the treatment of adrenal gland metastases. Specifically, we examined the outcomes and toxicity from this treatment modality on adjacent organs at risk. Methods and Materials:Data were retrieved from patients with adrenal metastases who were treated with SBRT between 2008 and 2017. Patients with primary adrenal malignancies were excluded. Toxicities were graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Time-to-event rates were calculated from the date of SBRT delivery. Results:In total, 35 patients with adrenal metastases were identified. Four patients were treated for bilateral disease. The median dose was 40?Gy (range, 20-54?Gy) in 5 fractions (range, 1-6 fractions). The median follow-up time was 37 months (range, 14-451 months) from disease diagnosis and 7 months (range, 1-54 months) from the SBRT start date. With death treated as a competing risk event, the cumulative incidence of local failure was 7.6% at 1 year after SBRT and 19.2% at 3 years. The median overall survival (OS) time was 19 months (95% confidence interval, 8-54 months) and tumor size correlated with survival (P?=?.0006). Patients with metastases <2.9?cm had a median OS of 54 months compared with 11 months for those with adrenal metastases ?2.9?cm (P?=?.01). Incidence of grade 2 toxicity was 17% with no case of grade ?3 toxicity. SBRT did not impact renal function with a mean estimated decline in glomerular filtration rate of only 2.6?±?8?mL/min/1.73?m2 compared with baseline. Combined kidneys V5 and combined renal cortex V17.5 did not correlate with a change in estimated glomerular filtration rate (P?=?.7 and P?=?.9, respectively). Conclusions:SBRT offers excellent local control for the treatment of adrenal gland metastases with very low toxicity rates and no significant short-term impact on renal function.

Project description:To assess the role of radiomic features in distinguishing squamous and adenocarcinoma subtypes of nonsmall cell lung cancers (NSCLC) and predict EGFR mutations.Institution Review Board-approved study included chest CT scans of 93 consecutive patients (43 men, 50 women, mean age 60 ± 11 years) with biopsy-proven squamous and adenocarcinoma lung cancers greater than 1 cm. All cancers were evaluated for epidermal growth factor receptor (EGFR) mutation. The clinical parameters such as age, sex, and smoking history and standard morphology-based CT imaging features such as target lesion longest diameter (LD), longest perpendicular diameter (LPD), density, and presence of cavity were recorded. The radiomics data was obtained using commercial CT texture analysis (CTTA) software. The CTTA was performed on a single image of the dominant lung lesion. The predictive value of clinical history, standard imaging features, and radiomics was assessed with multivariable logistic regression and receiver operating characteristic (ROC) analyses.Between adenocarcinoma and squamous cell carcinomas, ROC analysis showed significant difference in 3/11 radiomic features (entropy, normalized SD, total) [AUC 0.686-0.744, P = .006 to <.0001], 1/3 clinical features (smoking) [AUC 0.732, P = .001], and 2/3 imaging features (LD and LPD) [AUC 0.646-0658, P = .020 to .032]. ROC analysis for probability variables showed higher values for radiomics (AUC 0.800, P < .0001) than clinical (AUC 0.676, P = .017) and standard imaging (AUC 0.708, P < .0001). Between EGFR mutant and wild-type adenocarcinoma, ROC analysis showed significant difference in 2/11 radiomic features (kurtosis, K2) [AUC 0.656-0.713, P = .03 to .003], 1/3 clinical features (smoking) [AUC 0.758, P < .0001]. The combined probability variable for radiomics, clinical and imaging features was higher (AUC 0.890, P < .0001) than independent probability variables.The radiomics evaluation adds incremental value to clinical history and standard imaging features in predicting histology and EGFR mutations.

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Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?

Publications

Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?

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