Increased incidence of brain metastases in ERCC1-negative NSCLC patients treated with adjuvant cisplatin-based chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7581-7581
Author(s):  
B. Besse ◽  
C. Massard ◽  
V. Haddad ◽  
F. André ◽  
A. Dunant ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Brain Metastases ◽  
Small Cell ◽  
Clinical Parameters ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Increased Risk ◽  
Metastatic Sites ◽  
Nsclc Patients

7581 Background: We have recently demonstrated that ERCC1 is a predictor of the benefit of cisplatin-based adjuvant chemotherapy in resected non-small cell lung cancer (NSCLC). Non-squamous carcinomas have an increased risk of brain metastases (BM). Since brain is considered as a sanctuary site for chemotherapy, we hypothesised that there was an increased incidence of BM in ERCC1- negative non-squamous NSCLC patients treated with adjuvant cisplatin-based chemotherapy. Methods: Incidence of BM and histo- clinical parameters were analyzed in a population of 783 patients enrolled in the IALT trial. A subgroup analysis was performed in ERCC1 negative non-squamous NSCLC patients. Results: One hundred and one patients out of 783 (13%) developed BM alone or in association with other metastatic sites. In multivariate analysis, the clinical parameters associated with the occurrence of BM were nodal status (p=0.02), histological type (p=0.001) and pleural invasion (p=0.02). There is no effect of chemotherapy on BM (HR 1.38 [0.91–2.07], p=0.13). In patients with non-squamous histology (n=335) adjuvant chemotherapy was associated with an increased risk of BM (HR=2.10, [1.01–4.32], p=0.04) for ERCC1-negative tumours whereas there was no evidence of an effect on brain metastasis for ERCC1-positive tumours (HR=1.07 [0.38–2.99] p=0.90). These 2 effects are nevertheless not different (p for interaction=0.30) possibly by lack of power in this subsample. Conclusions: This study would suggest that cisplatin-based adjuvant chemotherapy is associated with an increased risk of BM in resected NSCLC patients with chemosensitive tumors. This data, if confirmed, could provide a rationale to evaluate prophylactic strategies in this subset of patients. No significant financial relationships to disclose.

Efficacy of immune checkpoint inhibitors in non-small cell lung cancer patients with different metastatic sites: A systematic review and meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21684-e21684
Author(s):  
Kaili Yang ◽  
Lin Zhao ◽  
Jiarui Li ◽  
Chunmei Bai
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Liver Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Metastatic Sites ◽  
Nsclc Patients

e21684 Background: Previous studies have demonstrated that bone, brain and liver metastases are poor prognosis factors of immune checkpoint inhibitors (ICIs) therapy in patients with non-small-cell lung cancer (NSCLC). This study aims to compare the efficacy of ICIs with conventional therapy in NSCLC patients with bone, brain or liver metastases. Methods: MEDLINE, Embase and CENTRAL were searched for prospective studies comparing ICIs with conventional therapy in NSCLC patients with bone, brain or liver metastases. Quality assessment was performed using the Newcastle-Ottawa Scale. The pooled hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) among included studies was analyzed using the random-effects model. Results: From 1,195 relevant articles, eight studies with high methodological quality consisting of 988 patients were included in the analysis. ICIs significantly improved OS for patients with brain metastases (HR = 0.57; 95%CI: 0.37-0.86; P = 0.007). Among patients with liver metastases, OS (HR = 0.72; 95%CI: 0.57-0.91; P = 0.006) and PFS (HR = 0.72; 95%CI: 0.49-0.87; P = 0.004) improvement was observed in the ICI treatment arm. No available study with bone metastases information was identified. Subgroup analysis revealed that PD-1 inhibitors could benefit patients on OS and PFS regardless of metastatic sites. Sensitivity analysis indicated good stability of this analysis. No obvious heterogeneity or publication bias was detected. Conclusions: ICIs could significantly improve OS in patients with brain metastases and both OS and PFS in patients with liver metastases. Although brain and liver metastases are generally regarded as poor prognostic factors for immunotherapy, this study still indicates ICIs are effective therapeutic options for NSCLC patients with these metastatic sites.

scholarly journals OTHR-15. PATIENTS WITH LIMITED STAGE SMALL CELL LUNG CANCER THAT RECUR WITH ISOLATED BRAIN METASTASES HAVE PROLONGED SURVIVAL

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i21-i21
Author(s):  
Bryan Bonder ◽  
Fatemeh Ardeshir Larijani ◽  
Afshin Dowlati ◽  
Lisa Rogers
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Limited Stage ◽  
Stage Disease ◽  
Extensive Stage ◽  
Metastatic Sites ◽  
The Brain

Abstract INTRODUCTION: Small cell lung cancer (SCLC) frequently metastasizes to the brain. In patients with limited-stage disease (disease confined to one radiation portal), the incidence of brain metastasis after 3 years is 50–60%. We reviewed patients with SCLC and hypothesized that isolated brain recurrence has a unique natural history. METHODS: 471 adult SCLC patients seen at University Hospitals Case Medical Center from 1998 to 2014 were screened. Patients were separated by those with isolated brain metastases and those with other patterns of metastasis. Demographic data including age, race, sex, smoking history and clinical data such as TNM classification, stage, treatment, and time to relapse and death were collected. Median overall survival (mOS) and progression free survival (mPFS) were compared using log-rank tests and Kaplan-Meier plots were constructed. In a separate cohort of metastatic SCLC we examined differences in next generation sequencing (NGS) of targeted exomes between primary and metastatic sites including the brain. RESULTS: 281 extensive-stage patients and 40 limited-stage patients were included. 12% (30/281) of the extensive-stage patients and 25% (10/40) of limited-stage patients had isolated brain metastases. Patients with limited-stage disease who developed isolated brain metastases had significantly improved mOS as compared to those who developed other sites of metastasis (OS = 38.7 months vs. 20.2 months, p=0.033). Furthermore, mPFS for limited-stage patients with isolated brain metastases was improved compared to other patterns of metastases (PFS = 17.9 months vs. 10.1 months, p = 0.03). NGS demonstrated that NOTCH1 mutations were infrequent in biopsies from all metastatic sites but were common in primary lung tumors. CONCLUSION: In our single center review, patients with limited-stage SCLC who recurred only in the brain had improved survival as compared to those who had other patterns of metastases. Our initial work demonstrates differences in oncogenic gene mutations between the metastatic and primary tumors.

scholarly journals Tumor Mutation Burden as a Biomarker in Resected Non–Small-Cell Lung Cancer

2018 ◽  
Vol 36 (30) ◽  
pp. 2995-3006 ◽  
Author(s):  
Siddhartha Devarakonda ◽  
Federico Rotolo ◽  
Ming-Sound Tsao ◽  
Irena Lanc ◽  
Elisabeth Brambilla ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Tumor Mutation Burden ◽  
Resected Nsclc ◽  
Mutation Burden ◽  
Disease Free

Purpose The survival benefit with adjuvant chemotherapy for patients with resected stage II-III non–small-cell lung cancer (NSCLC) is modest. Efforts to develop prognostic or predictive biomarkers in these patients have not yielded clinically useful tests. We report findings from the Lung Adjuvant Cisplatin Evaluation (LACE)-Bio-II study, in which we analyzed next-generation sequencing and long-term outcomes data from > 900 patients with early-stage NSCLC treated prospectively in adjuvant landmark clinical trials. We used a targeted gene panel to assess the prognostic and predictive effect of mutations in individual genes, DNA repair pathways, and tumor mutation burden (TMB). Methods A total of 908 unmatched, formalin-fixed, paraffin-embedded, resected lung cancer tumor specimens were sequenced using a targeted panel of 1,538 genes. Stringent filtering criteria were applied to exclude germline variants and artifacts related to formalin fixation. Disease-free survival, overall survival, and lung cancer—specific survival (LCSS) were assessed in Cox models stratified by trial and adjusted for treatment, age, sex, performance score, histology, type of surgery, and stage. Results Nonsynonymous mutations were identified in 1,515 genes in 908 tumor samples. High nonsynonymous TMB (> 8 mutations/Mb) was prognostic for favorable outcomes (ie, overall survival, disease-free survival, and LCSS) in patients with resected NSCLC. LCSS benefit with adjuvant chemotherapy was more pronounced in patients with low nonsynonymous TMBs (≤ 4 mutations/Mb). Presence of mutations in DNA repair pathways, tumor-infiltrating lymphocytes, TP53 alteration subtype, and intratumor heterogeneity was neither prognostic nor predictive. Statistically significant effect of mutations in individual genes was difficult to determine due to high false-discovery rates. Conclusion High nonsynonymous TMB was associated with a better prognosis in patients with resected NSCLC. In addition, the benefit of adjuvant chemotherapy on LCSS was more pronounced in patients with low nonsynonymous TMBs. Studies are warranted to confirm these findings.

scholarly journals Success of Crizotinib Combined with Whole-Brain Radiotherapy for Brain Metastases in a Patient with Anaplastic Lymphoma Kinase Rearrangement-Positive Non-Small-Cell Lung Cancer

2018 ◽  
Vol 11 (3) ◽  
pp. 777-783 ◽  
Author(s):  
Sachi Okawa ◽  
Takuo Shibayama ◽  
Atsushi Shimonishi ◽  
Jun Nishimura ◽  
Taichi Ozeki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Anaplastic Lymphoma Kinase ◽  
Whole Brain Radiotherapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma ◽  
Brain Radiotherapy ◽  
Nsclc Patients

Although crizotinib shows marked antitumor activity in anaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancer (NSCLC) patients, all treated patients ultimately develop resistance to this drug. Isolated central nervous system failure without progression at extracranial sites is a common progression pattern in ALK rearrangement-positive NSCLC patients treated with crizotinib. Here, we report the success of crizotinib combined with whole-brain radiotherapy in an ALK rearrangement-positive NSCLC patient who developed leptomeningeal carcinomatosis and progression of multiple brain metastases. Additionally, we focused on the mechanism involved by examining the plasma and cerebrospinal fluid concentrations of crizotinib in the present case.

Development of brain metastases in stage III/IV non-small cell lung cancer patients treated with or without erlotinib.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19011-e19011 ◽  
Author(s):  
Jing Liu ◽  
Li Kong ◽  
Xue Meng ◽  
Jinbo Yue ◽  
Xindong Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iii ◽  
Control Group ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
And Control

e19011 Background: Non-small cell lung cancer (NSCLC) has a risk of death from brain metastases (BM) that exceeds potential mortality from extracranial disease progression. Erlotinib has been proved to be effective for NSCLC patients. We hold a study to evaluate value of erlotinib in preventing BM in stage III/IV NSCLC patients. Methods: Pathologically confirmed NSCLC stage III/IV patients were included and divided into erlotinib group and control group according to whether erlotinib administration (at least one month) in 1- or 2-line therapy or not. Stage IV patients with BM were excluded. Patients with any EGFR-TKI treatment were excluded from control group. Times of erlotinib administration to BM and to death or last follow-up were recorded for erlotinib group. Times of corresponding 1- or 2-line chemotherapy to BM and to death or last follow-up were recorded for control group correspondingly. Time to BM, 1- and 2-year incidence of BM were end points. Results: 140 patients were included (68 in erlotinib group and 72 in control group) and all clinical characteristics between two groups were balanced. At a median follow-up of 20.0 months, the median time to BM for all patients was 28.0 months (95% CI, 23.795-32.205 months). 1- and 2-year incidence of BM were 17.8% (95% CI, 10.744-24.856%) and 38.8% (95% CI, 27.236-50.364%) respectively. The median time to BM were 42.0 months (95% CI, 15.567-68.433 months) and 19.0 months (95% CI, 11.305-26.695 months) (P=0.028) for erlotinib group and control group. Erilotinib group has a lower BM incidence than control group (1-year: 14.4%, 95% CI: 4.992%-23.808%, vs 21.1%, 95% CI: 10.712%-31.488%, P=0.384; 2-year: 26.2%, 95% CI: 18.712%-33.688%, vs 50.2%, 95% CI: 34.128%-66.272%, P=0.005). Multivariate analysis shows interval to BM were longer for erlotinib group (HR, 2.531; 95% CI, 1.272-5.051; P=0.008) and stage III disease (HR, 2.093; 95% CI, 1.035-4.231; P=0.040). Conclusions: Erlotinib administration improves time to BM and 2-year incidence of BM of stage III/IV NSCLC patients. Erlotinib administration and stage III disease predicts lower incidence of BM in all patients.

Risk factors associated with brain metastases in ECOG-ACRIN E1505, a phase III randomized trial of adjuvant chemotherapy with or without bevacizumab for patients with completely resected stage IB (>/= 4 cm) - IIIA non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8539-8539
Author(s):  
John M. Varlotto ◽  
Suzanne Eleanor Dahlberg ◽  
Heather A. Wakelee ◽  
Suresh S. Ramalingam ◽  
Joan H. Schiller
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Resected Stage

8539 Background: ECOG-ACRIN E1505 was a phase III randomized trial of adjuvant chemotherapy with or without bevacizumab for patients with completely-resected Stage IB (>4CM) – IIIA non-small cell lung cancer. Prior studies have shown that the risk of brain recurrence in patients after definitive surgical resection is approximately 10%; however, covariates associated with development of brain recurrence have varied across these studies. We sought to estimate the incidence of and risk factors for brain recurrence. Methods: Among the 1501 patients enrolled to ECOG-ACRIN E1505, 121 patients developed brain metastases as their first site of recurrence and are the subject of this investigation. All 1501 patients underwent a pneumonectomy (N = 192) or (bi)lobectomy and had an R0 resection. The cumulative incidence of brain recurrence was estimated after adjusting for recurrence at other sites and death as competing events. A multivariable regression model was fitted using the methodology of Fine and Gray to evaluate the effect of covariates on the subdistribution of brain recurrence. Results: With a median follow-up of 50.3 months, a total of 121 brain metastases had been reported as the first site of recurrence. The incidence of brain recurrence at 12 months post-randomization was 3.7% (95% CI: 2.8% – 4.7%), and it increased to 8.5% (95% CI: 7.0% - 10.0%) at 3 years, and to 9.9% (95% CI: 8.0% - 11.7%) at 6 years. Risk factors for brain metastases included pneumonectomy(HR=1.8; p=0.01), and nonsquamous histology(HR=2.04; p=0.003), but bevacizumab(HR=0.64; p=0.02) was associated with potentially protective effect. Conclusions: The cumulative incidence of brain recurrence increased over time to 9.9% at 6 years in this population of patients with surgically-resected non-small cell lung cancer. Treatment, tumor histology, and type of resection appear to be associated with the risk of brain recurrence. Clinical trial information: NCT00324805.

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