Management of non-small cell lung cancer with EGFR mutation: the role of radiotherapy in the era of tyrosine kinase inhibitor therapy—opportunities and challenges

Xia, Bing; Zhang, Shirong; Ma, Shenglin

doi:10.21037/jtd.2017.09.67

Cited by 10 publications

(4 citation statements)

References 51 publications

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“…Radiotherapy is an important treatment strategy for the locally advanced NSCLCs [ 16 ]. Previous studies showed that the radiotherapy dose scheme of 60–66 Gy is an ideal radical radiation dose scheme, which can increase the OS of patients without increasing the incidence of radiation pneumonia for the locally advanced NSCLCs [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of thoracic radiotherapy dose on the prognosis of advanced lung adenocarcinoma harboring EGFR mutations

Qin

Dong

et al. 2022

BMC Cancer

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Background The aim of this study was to investigate the effects of different thoracic radiotherapy doses on OS and incidence of radiation pneumonia which may provide some basis for optimizing the comprehensive treatment scheme of these patients with advanced EGFR mutant lung adenocarcinoma. Methods Data from 111 patients with EGFR-mutant lung adenocarcinoma who received thoracic radiotherapy were included in this retrospective study. Overall survival (OS) was the primary endpoints of the study. Kaplan–Meier method was used for the comparison of OS. The Cox proportional-hazard model was used for the multivariate and univariate analyses to determine the prognostic factors related to the disease. Results The mOS rates of the patients, who received radiotherapy dose scheme of less than 50 Gy, 50–60 Gy (including 50 Gy), and 60 Gy or more were 29.1 months, 34.4 months, and 51.0 months, respectively (log-rank P = 0.011). Although trend suggested a higher levels of pneumonia cases with increasing radiation doses, these lack statistical significance (χ2 = 1.331; P = 0.514). The multivariate analysis showed that the thoracic radiotherapy dose schemes were independently associated with the improved OS of patients (adjusted hazard ratio [HR], 0.606; 95% CI, 0.382 to 0.961; P = 0.033). Conclusions For the patients with advanced EGFR-mutant lung adenocarcinoma, the radical thoracic radiotherapy dose scheme (≥ 60 Gy) could significantly prolong the OS of patients during the whole course management.

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Section: Discussionmentioning

confidence: 99%

Effect of thoracic radiotherapy dose on the prognosis of advanced lung adenocarcinoma harboring EGFR mutations

Qin

Dong

et al. 2022

BMC Cancer

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“…In particular, a large number of mutated genotypes (e.g., exon 19 deletion, exon 21 missense substitution) of activated EGFR have been reported in lung cancer patients, and tumor tissues with increased mutations are known to be more invasive and metastatic than normal cells [13]. Conventional chemotherapy (e.g., radiation and chemotherapy) has been applied, but the prognosis of patients is usually poor [14]. Tyrosine kinase inhibitors (gefitinib and erlotinib), which are currently used as first-line treatments by targeting EGFR, also have the drawback of inducing secondary mutations and tend to be resistant to further treatment [15].…”

Section: Introductionmentioning

confidence: 99%

Specificity Assessment of CRISPR Genome Editing of Oncogenic EGFR Point Mutation with Single-Base Differences

Bae

Kim

et al. 2019

Molecules

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In CRISPR genome editing, CRISPR proteins form ribonucleoprotein complexes with guide RNAs to bind and cleave the target DNAs with complete sequence complementarity. CRISPR genome editing has a high potential for use in precision gene therapy for various diseases, including cancer and genetic disorders, which are caused by DNA mutations within the genome. However, several studies have shown that targeting the DNA via sequence complementarity is imperfect and subject to unintended genome editing of other genomic loci with similar sequences. These off-target problems pose critical safety issues in the therapeutic applications of CRISPR technology, with particular concerns in terms of the genome editing of pathogenic point mutations, where non-mutant alleles can become an off-target with only a one-base difference. In this study, we sought to assess a novel CRISPR genome editing technique that has been proposed to achieve a high specificity by positioning the mismatches within the protospacer adjacent motif (PAM) sequence. To this end, we compared the genome editing specificities of the PAM-based and conventional methods on an oncogenic single-base mutation in the endothelial growth factor receptor (EGFR). The results indicated that the PAM-based method provided a significantly increased genome editing specificity for pathogenic mutant alleles with single-base precision.

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“…With the evolution of sophisticated radiation technology, most clinicians integrate radiotherapy (RT) into the comprehensive treatment of patients under TKIs in order to maximize the therapeutic effects 12,13 . The life expectancy in EGFR-mutant patients has been significantly prolonged 14–16 . Because of an aging population and advances in the treatment of NSCLC, patients are living longer and are more likely to experience distant metastases.…”

Section: Introductionmentioning

confidence: 99%

Brain surgery in combination with tyrosine kinase inhibitor and whole brain radiotherapy for epidermal growth factor receptor-mutant non-small-cell lung cancer with brain metastases

Lee

Chen

Chuang

et al. 2019

Sci Rep

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The role of brain surgery (BS) on the survival of patients with non-small-cell lung cancer (NSCLC) and brain metastases (BM), particularly those with epidermal growth factor receptor (EGFR) mutations under tyrosine kinase inhibitors (TKIs) is yet to be defined. We aimed to investigate whether BS could improve the survival of patients in addition to the combination of TKIs and whole brain radiotherapy (WBRT). A cohort of 1394 NSCLC patients between 2011 and 2016 was retrospectively studied. One hundred patients with BM receiving TKI + RT were enrolled. Forty patients (40%) received TKI + BS + RT, and 60 patients (60%) received TKI + RT. Survival time was calculated from the date of BM diagnoses to the date of death or last follow-up. With a median follow-up of 25.6 months (95% CI, 18.6–35.7), the median survival after BM was 18.2 months (95% CI, 10.8 to 27.4) in the TKI + BS + RT group and 11.8 months (95% CI, 5.2 to18) in the TKI + RT group. Cox proportional hazards regression model for the patients with the largest BM over 1 cm showed that TKI + BS + RT group was associated with improved survival relative to TKI + RT group (HR, 0.49; 95% CI, 0.29 to 0.83; P = 0.008). BS adds significant survival benefits in addition to TKIs and WBRT, especially for patients with EGFR-mutant NSCLC and the largest BM over 1 cm.

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Management of non-small cell lung cancer with EGFR mutation: the role of radiotherapy in the era of tyrosine kinase inhibitor therapy—opportunities and challenges

Cited by 10 publications

References 51 publications

Effect of thoracic radiotherapy dose on the prognosis of advanced lung adenocarcinoma harboring EGFR mutations

Effect of thoracic radiotherapy dose on the prognosis of advanced lung adenocarcinoma harboring EGFR mutations

Specificity Assessment of CRISPR Genome Editing of Oncogenic EGFR Point Mutation with Single-Base Differences

Brain surgery in combination with tyrosine kinase inhibitor and whole brain radiotherapy for epidermal growth factor receptor-mutant non-small-cell lung cancer with brain metastases

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