Integration of Stereotactic Body Radiation Therapy With Tyrosine Kinase Inhibitors in Stage IV Oncogene‐Driven Lung Cancer

BackgroundStereotactic body radiation therapy (SBRT) and tyrosine kinase inhibitors (TKIs) are effective treatments for metastatic renal cell carcinoma, but data on combining these two modalities are scarce. We aimed to investigate the survival outcomes of SBRT plus TKIs.MethodsData of patients treated with TKIs from December 2007 to June 2019 were collected. Patients received SBRT plus TKIs (TKI + SBRT group) or TKIs alone (TKI alone group). Local control (LC), time to change of systemic therapy (TTS), and overall survival (OS) were assessed.ResultsA total of 190 patients were included, and 85 patients received TKI + SBRT. The 2-year LC rate was 92.8%. The median OS in the TKI + SBRT group was significantly longer than that of the TKI alone group (63.2 vs 29.8 months; P < 0.001). In multivariate analysis, IMDC intermediate (HR 1.96; 95% CI 1.10–3.48; P = 0.022) and poor risk (HR 2.43; 95% CI 1.25–4.75; P = 0.009), oligometastasis (HR 0.41; 95% CI 0.26–0.65; P < 0.001), and the addition of SBRT (HR 0.48; 95% CI 0.31–0.75; P = 0.001) were prognostic factors for OS. Patients with oligometastasis (P = 0.009) and those with IMDC favorable (P = 0.044) or intermediate (P = 0.002) risk had significantly longer OS with TKI + SBRT. The median TTS were 21.5, 6.4, and 9.0 months in patients receiving SBRT before first-line TKI failure, SBRT after first-line TKI failure, and first-line TKI alone (P < 0.001). Five patients (5.9%) experienced SBRT-related grade 3 toxicities.ConclusionsCombining SBRT with TKIs is tolerable and associated with longer OS in selected patients, such as those with oligometastasis and favorable or intermediate risk.

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Faculty Opinions recommendation of Stereotactic body radiation therapy (SBRT) for early-stage lung cancer in the elderly.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734120948.793574022 ◽

2020 ◽

Author(s):

Lorenzo Livi ◽

Isacco Desideri

Keyword(s):

Lung Cancer ◽

Radiation Therapy ◽

Stereotactic Body Radiation Therapy ◽

Early Stage ◽

The Elderly ◽

Early Stage Lung Cancer ◽

Stereotactic Body Radiation ◽

Stage Lung Cancer

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Stereotactic Body Radiation Therapy: Lung Cancer

10.2217/9781909450189 ◽

2013 ◽

Author(s):

Simon Lo ◽

Bin S Teh ◽

Nina A Mayr ◽

Mitchell Machtay

Keyword(s):

Lung Cancer ◽

Radiation Therapy ◽

Stereotactic Body Radiation Therapy ◽

Stereotactic Body Radiation

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Efficacy of tyrosine kinase inhibitors against lung cancer with EGFR exon 18 deletion: Case report and pooled analysis

Cancer Treatment and Research Communications ◽

10.1016/j.ctarc.2021.100407 ◽

2021 ◽

pp. 100407

Author(s):

Rafael Rubiera-Pebe ◽

James K. Hicks ◽

Tawee Tanvetyanon

Keyword(s):

Lung Cancer ◽

Case Report ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Pooled Analysis

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Drug Tolerance to EGFR Tyrosine Kinase Inhibitors in Lung Cancers with EGFR Mutations

Cells ◽

10.3390/cells10071590 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1590

Author(s):

Kenichi Suda ◽

Tetsuya Mitsudomi

Keyword(s):

Lung Cancer ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Molecular Mechanisms ◽

Kinase Inhibitors ◽

Drug Tolerance ◽

Lung Cancers ◽

Egfr Tyrosine Kinase ◽

Egfr Tyrosine Kinase Inhibitors ◽

Egfr Mutated

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) serve as the standard of care for the first-line treatment of patients with lung cancers with EGFR-activating mutations. However, the acquisition of resistance to EGFR TKIs is almost inevitable, with extremely rare exceptions, and drug-tolerant cells (DTCs) that demonstrate reversible drug insensitivity and that survive the early phase of TKI exposure are hypothesized to be an important source of cancer cells that eventually acquire irreversible resistance. Numerous studies on the molecular mechanisms of drug tolerance of EGFR-mutated lung cancers employ lung cancer cell lines as models. Here, we reviewed these studies to generally describe the features, potential origins, and candidate molecular mechanisms of DTCs. The rapid development of an optimal treatment for EGFR-mutated lung cancer will require a better understanding of the underlying molecular mechanisms of the drug insensitivity of DTCs.

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