scholarly journals Significance of targeted therapy and genetic alterations in EGFR, ALK, or KRAS on survival in patients with non-small cell lung cancer treated with radiotherapy for brain metastases

2014 ◽  
Vol 17 (2) ◽  
pp. 296-302 ◽  
Author(s):  
K. S. Mak ◽  
J. F. Gainor ◽  
A. Niemierko ◽  
K. S. Oh ◽  
H. Willers ◽  
...  
Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3668
Author(s):  
Anna Cho ◽  
Helena Untersteiner ◽  
Dorian Hirschmann ◽  
Abdallah Shaltout ◽  
Philipp Göbl ◽  
...  

The combination of Gamma Knife radiosurgery (GKRS) and systemic immunotherapy (IT) or targeted therapy (TT) is a novel treatment method for brain metastases (BMs) in non-small cell lung cancer (NSCLC). To elucidate the safety and efficacy of concomitant IT or TT on the outcome after GKRS, 496 NSCLC patients with BMs, who were treated with GKRS were retrospectively reviewed. The median time between the initial lung cancer diagnosis and the diagnosis of brain metastases was one month. The survival after the initial BM diagnosis was significantly longer than the survival predicted by prognostic BM scores. After the first Gamma Knife radiosurgery treatment (GKRS1), the estimated median survival was 9.9 months (95% CI = 8.3–11.4). Patients with concurrent IT or TT presented with a significantly longer survival after GKRS1 than patients without IT or TT (p < 0.001). These significant differences in the survival were also apparent among the four treatment groups and remained significant after adjustment for Karnofsky performance status scale (KPS), recursive partitioning analysis (RPA) class, sex, and multiple BMs. About half of all our patients (46%) developed new distant BMs after GKRS1. Of note, no statistically significant differences in the occurrence of radiation reaction, radiation necrosis, or intralesional hemorrhage in association with IT or TT at or after GKRS1 were observed. In NSCLC-BM patients, the concomitant use of GKRS and IT or TT showed an increase in overall survival without increased complications related to GKRS. Therefore, the combined treatment with GKRS and IT or TT seems to be a safe and powerful treatment option and emphasizes the role of radiosurgery in modern BM treatment.


2020 ◽  
Vol 25 (4) ◽  
pp. 127-135
Author(s):  
Mark B. Bychkov ◽  
A. E. Kuzminov

The article present a review and experience from a a single institution on the morphology, diagnostics, and treatment (chemotherapy, radiation, targeted therapy, and immunotherapy)) of small cell lung cancer (SCLC). The characteristic molecular, genetic, histological, and immunohistochemical features of NSCLC and SCLC are compared. An important issue of SCLC histogenesis is highlighted, taking into account its neuroendocrine characteristics. Paraneoplastic syndromes associated with SCLC and other clinical features of SCLC are discussed. The algorithm of examination of a patient with histologically or cytologically confirmed SCLC, staging schemes, and main prognostic factors are presented. The following aspects of chemoradiotherapy of localized SCLC are considered: features of early, late, simultaneous, and sequential therapy, and the need for whole brain radiotherapy in patients with localized and extensive SCLC. The article discusses the treatment algorithm for extensive disease SCLC, taking into account the recent success of chemoimmunotherapy in the first-line treatment of SCLC. As is known, the combinations of atezolizumab, etoposide, carboplatin and durvalumab, etoposide, cisplatin, or carboplatin showed a real benefit compared to chemotherapy alone. Although the second line treatment has not changed, it is now possible to prescribe a third line therapy because of the proven effectiveness of immunotherapy. Targeted therapy, although not shown to be effective in SCLC, is discussed in terms of the key features of genetic alterations as a possible target for therapy. An important issue in the treatment of patients with superior vena cava syndrome is considered separately. The tasks of future prospective research in SCLC are described.


FEBS Open Bio ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 1544-1552 ◽  
Author(s):  
Li Liao ◽  
Xiaoyu Ji ◽  
Mengxi Ge ◽  
Qiong Zhan ◽  
Ruofan Huang ◽  
...  

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Yuya Fujita ◽  
Manabu Kinoshita ◽  
Tomohiko Ozaki ◽  
Koji Takano ◽  
Kei Kunimasa ◽  
...  

Abstract Background Molecular and genetic alterations of non-small-cell lung cancer (NSCLC) now play a vital role in patient care of this neoplasm. The authors focused on the impact of epidermal growth factor receptor mutation (EGFR-mt) status on the survival of patients after brain metastases (BMs) from NSCLC. The purpose of the study was to understand the most desirable management of BMs from NSCLC. Methods This was a retrospective observational study analyzing 647 patients with NSCLC, including 266 patients with BMs, diagnosed at our institute between January 2008 and December 2015. EGFR mutation status, overall survival (OS) following diagnosis, OS following BMs, duration from diagnosis to BMs, and other factors related to OS and survival after BMs were measured. Results Among 647 patients, 252 (38.8%) had EGFR mutations. The rate and frequency of developing BMs were higher in EGFR-mt patients compared with EGFR wildtype (EGFR-wt) patients. EGFR-mt patients showed longer median OS (22 vs 11 months, P &lt; .001) and a higher frequency of BMs. Univariate and multivariate analyses revealed that good performance status, presence of EGFR-mt, single BM, and receiving local therapies were significantly associated with favorable prognosis following BM diagnosis. Single metastasis, compared with multiple metastases, exhibited a positive impact on patient survival after BMs in EGFR-mt patients, but not in EGFR-wt NSCLC patients. Conclusions Single BM with EGFR-mt performed better than other groups. Furthermore, effective local therapies were recommended to achieve better outcomes.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20730-e20730
Author(s):  
Jia-Tao Cheng ◽  
Jinji Yang ◽  
Yilong Wu

e20730 Background: MET second-site mutations were previously reported in a few cases of MET-amplified or exon 14-mutant advanced non-small-cell lung cancer (NSCLC) treated with MET inhibitors. However, both the frequency of MET second-site mutations and clinical outcome of patients with such genetic alterations have not been investigated, particularly in EGFR-mutant, MET-amplified advanced NSCLC treated with combinatorial targeted therapy. Methods: Retrospectively, from November 2016 to January 2019, 22 patients with EGFR-mutant, MET-amplified advanced NSCLC had sufficient tumor samples after resistance to a combinatorial therapy with both EGFR and MET inhibitors. All tissue samples were detected using Next-generation sequencing (NGS). The progression-free survival (PFS) was calculated the start of subsequent treatment to progressive disease or death from any cause. The overall survival (OS) was calculated from the start of subsequent treatment to death from any cause. Last follow-up was on January 31, 2019. Results: Five kinds of MET second-site mutations were found in 7 patients: D1246N D1228N, D1228H, D1231Y and Y1230H. The frequency of MET second-site mutations was 31.8% (7/22). The median PFS and OS were 3.7 (95%CI: 1.13-6.3) months and 6.9 (95%CI: 0.2-13.7) months respectively. The ORR of EGFR TKIs plus cabozantinib for suchsecond-site mutaant patients was 50% (2/4). However, the ORR of other treatments was 0% (0/3), Two of them received single agent cabozantinib, and PFS was 0.7 and 1.7 months respectively. One had a PFS of 2.5 months with pemetrexed/carboplatin plus bevacizumab. Conclusions: MET second-site mutation might be one of the commonly-seen molecular mechanisms of acquired resistance to combinatorial targeted therapy in EGFR-mutant, MET-amplified advanced NSCLC. Patients with such mutations could respond to cabozantinib plus EGFR TKI. Further more investigations are warranted to improve the efficacy.


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