scholarly journals The combination of fibrinogen concentrations and the platelet-to-lymphocyte ratio predicts survival in patients with advanced lung adenocarcinoma treated with EGFR-TKIs

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110040
Author(s):  
Qiong He ◽  
Yamin Li ◽  
Xihong Zhou ◽  
Wen Zhou ◽  
Chunfang Xia ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Characteristic Curve ◽  
Performance Status ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Egfr Mutant ◽  
Egfr Tkis

Objective This study aimed to identify a predictive marker of response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant advanced lung adenocarcinoma. Methods A cohort of 190 patients with EGFR-mutant advanced lung adenocarcinoma was analyzed. Receiver operating characteristic curve analysis was used to evaluate the optimal cutoffs for fibrinogen levels, the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR) for predicting progression-free survival (PFS). Univariate and multivariate survival analyses were performed to identify factors correlated with PFS and overall survival (OS). Results High NLR was associated with worse performance status. In univariate analysis, fibrinogen levels, NLR, and PLR were correlated with OS and PFS. In multivariate analysis, all three variables remained predictive of OS, whereas only fibrinogen levels and PLR were independent prognostic factors for PFS. Furthermore, the combination of fibrinogen levels and PLR (F-PLR score) could stratify patients into three groups with significantly different prognoses, and the score was independently predictive of survival. Conclusion The F-PLR score predicted the prognosis of patients with EGFR-mutant advanced lung adenocarcinoma who received EGFR-TKIs, and this score may serve as a convenient blood-based marker for identifying high-risk patients.

scholarly journals Prognostic Factors in Lung Adenocarcinoma with Bone Metastasis Treated with EGFR-TKIs

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 967
Author(s):  
Tzu-Hsuan Chiu ◽  
Chun-Yu Lin ◽  
Meng-Heng Hsieh ◽  
Shu-Min Lin ◽  
Yueh-Fu Fang
Keyword(s):  
Prognostic Factors ◽  
Bone Metastasis ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Progression Free Survival ◽  
Advanced Lung Cancer ◽  
First Line ◽  
Cancer Management ◽  
Egfr Tkis

Background and Objectives: Patients who have advanced lung cancer and bone metastasis (BM) often suffer from skeletal-related events (SREs) that lead to poor quality of life and poor prognosis. Our study aimed to investigate the prognostic factors in patients with BM from epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma. Materials and Methods: This retrospective study included 77 lung adenocarcinoma patients with synchronous BM. These patients had first-line EGFR tyrosine kinase inhibitors (EGFR-TKIs) between January 2017 and December 2019. Among them, 42 patients were treated with 120 mg of subcutaneous denosumab monthly. We investigated their baseline characteristics, cancer management, SREs, progression-free survival (PFS), and overall survival (OS). Results: The PFS in the patients treated with or without denosumab were 10.1 vs. 12.5 months (p = 0.971). The median OS was 26.9 vs. 29.5 months (p = 0.967) in no denosumab and denosumab groups, respectively. Univariate analyses showed benefit of afatinib in PFS and good performance status in OS. Conclusion: Those patients that took afatinib as first-line EGFR-TKIs had significantly longer PFS than those treated with other TKIs. Denosumab had no prognostic effect on PFS or OS.

scholarly journals Combining Carcinoembryonic Antigen and Platelet to Lymphocyte Ratio to Predict Brain Metastasis of Resected Lung Adenocarcinoma Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Wei Wang ◽  
Chao Bian ◽  
Di Xia ◽  
Jin-Xi He ◽  
Ping Hai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Brain Metastasis ◽  
Lung Adenocarcinoma ◽  
Carcinoembryonic Antigen ◽  
Roc Curve ◽  
Univariate Analysis ◽  
Significant Risk ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Increased Risk

We aimed to evaluate the role of pretreatment carcinoembryonic antigen (CEA) and platelet to lymphocyte ratio (PLR) in predicting brain metastasis after radical surgery for lung adenocarcinoma patients. The records of 103 patients with completely resected lung adenocarcinoma between 2013 and 2014 were reviewed. Clinicopathologic characteristics of these patients were assessed in the Cox proportional hazards regression model. Brain metastasis occurred in 12 patients (11.6%). On univariate analysis, N2 stage (P = 0.013), stage III (P = 0.016), increased CEA level (P = 0.006), and higher PLR value (P = 0.020) before treatment were associated with an increased risk of developing brain metastasis. In multivariate model analysis, CEA above 5.2 ng/mL (P = 0.014) and PLR ≥ 120 (P = 0.036) remained as the risk factors for brain metastasis. The combination of CEA and PLR was superior to CEA or PLR alone in predicting brain metastasis according to the receiver operating characteristic (ROC) curve analysis (area under ROC curve, AUC 0.872 versus 0.784 versus 0.704). Pretreatment CEA and PLR are independent and significant risk factors for occurrence of brain metastasis in resected lung adenocarcinoma patients. Combining these two factors may improve the predictability of brain metastasis.

scholarly journals Prognostic Value of BIM Deletion in EGFR-Mutant NSCLC Patients Treated with EGFR-TKIs: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Fangfang Lv ◽  
Liang Sun ◽  
Qiuping Yang ◽  
Zheng Pan ◽  
Yuhua Zhang
Keyword(s):  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Deletion Polymorphism ◽  
Asian Populations ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

Background. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable in EGFR-mutant non-small-cell lung cancer (NSCLC) patients. A germline 2903 bp deletion polymorphism of Bcl-2-like protein 11 (BIM) causes reduced expression of proapoptotic BH3-only BIM protein and blocks TKI-induced apoptosis of tumor cells. Yet the association between the deletion polymorphism and response to EGFR-TKI treatment remains inconsistent among clinical observations. Thus, we performed the present meta-analysis. Methods. Eligible studies were identified by searching PubMed, Embase, and ClinicalTrials.gov databases prior to March 31, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) and 95% CIs of objective response rate (ORR) and disease control rate (DCR) were calculated by using a random effects model. Sensitivity, metaregression, and publication bias analyses were also performed. Results. A total of 20 datasets (3003 EGFR-mutant NSCLC patients receiving EGFR-TKIs from 18 studies) were included. There were 475 (15.8%) patients having the 2903-bp intron deletion of BIM and 2528 (84.2%) wild-type patients. BIM deletion predicted significantly shorter PFS ( HR = 1.35 , 95% CI: 1.10-1.64, P = 0.003 ) and a tendency toward an unfavorable OS ( HR = 1.22 , 95% CI: 0.99-1.50, P = 0.068 ). Patients with deletion polymorphism had lower ORR ( OR = 0.60 , 95% CI: 0.42-0.85, P = 0.004 ) and DCR ( OR = 0.59 , 95% CI: 0.38-0.90, P = 0.014 ) compared with those without deletion. Conclusion. BIM deletion polymorphism may confer resistance to EGFR-TKIs and can be used as a biomarker to predict treatment response to EGFR-TKIs in EGFR-mutant NSCLC patients from Asian populations.

Local ablative therapy (LAT) for oligoprogressive, EGFR-mutant, non-small cell lung cancer (NSCLC) after treatment with osimertinib.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20545-e20545 ◽  
Author(s):  
Chul Kim ◽  
Nitin Roper ◽  
Chuong D. Hoang ◽  
Eva Szabo ◽  
Maureen Connolly ◽  
...  
Keyword(s):  
Disease Progression ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
T790m Mutation ◽  
Tki Treatment ◽  
Egfr Mutant ◽  
A Prospective Study ◽  
Egfr Tki ◽  
Egfr Tkis

e20545 Background: EGFR tyrosine kinase inhibitors (EGFR-TKIs) improve progression-free survival (PFS) in patients with EGFR-mutant NSCLC, but disease progression limits efficacy. Retrospective studies show a survival benefit to LAT in patients with oligoprogressive disease (progression at a limited number of anatomic sites). Methods: This is a prospective study of LAT in patients with oligoprogressive EGFR-mutant NSCLC. Patients with no prior EGFR-TKI therapy (cohort 1) or progression after 1st/2ndgeneration EGFR-TKIs with acquired T790M mutation (cohort 2) receive osimertinib. Upon progression, eligible patients with < = 5 progressing sites undergo LAT and resume osimertinib until disease progression. Patients previously treated with osimertinib qualifying for LAT upon disease progression are also eligible for treatment (cohort 3). Primary endpoint: evaluation of safety and efficacy of reinitiation of osimertinib after LAT (assessed by PFS). Additional goals are assessment of mechanisms of resistance to osimertinib by multi-omics analyses of tumor, blood, and saliva. Results: Between 04/2016 and 01/2017, 15 patients were enrolled (cohort 1: 9, cohort 2: 3, cohort 3: 3). Median age was 57 (range 36-71). Treatment was well tolerated. The most common adverse events (AEs) were rash, diarrhea, thrombocytopenia, and alanine transaminase elevation. Grade 3/4 AEs were observed in 4 (27%) patients. Among evaluable patients, objective response rates prior to LAT in cohorts 1 and 2 were 71% (5/7) and 100% (2/2), respectively, with 6.8 months median PFS (95% CI: 3.4 months-undefined) in cohort 1 and no progressions in cohort 2. To date, 5 patients (33%; cohort 1: 2; cohort 3: 3) had LAT. Two patients with 3 progressing sites underwent a combination of surgery and radiation. Three patients with 1 progressing site underwent surgery alone. Post-LAT PFS and results of molecular analyses will be presented. Conclusions: Patients with EGFR-mutant NSCLC and oligoprogression after EGFR-TKI therapy can be safely treated with LAT. In selected patients, this approach could potentially maximize duration of EGFR-TKI treatment and prevent premature switching to other systemic therapies. Clinical trial information: NCT02759835.

scholarly journals Efficacy of EGFR-TKI Plus Chemotherapy or Monotherapy as First-Line Treatment for Advanced EGFR-Mutant Lung Adenocarcinoma Patients With Co-Mutations

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhengyu Yang ◽  
Ya Chen ◽  
Yanan Wang ◽  
Shuyuan Wang ◽  
Minjuan Hu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
First Generation ◽  
Progression Free Survival ◽  
Poor Response ◽  
Time To Progression ◽  
Free Survival ◽  
Egfr Mutant ◽  
Egfr Tki ◽  
Generation Sequencing ◽  
Egfr Tkis

BackgroundCo-mutations was associated with poor response to EGFR-TKIs. First-generation EGFR-TKIs combined with chemotherapy was reported to be more effective than TKIs alone in advanced lung adenocarcinoma patients.ObjectiveThis retrospective study aimed to explore whether EGFR-mutant patients with co-mutations can benefit from EGFR-TKIs plus chemotherapy.Patients and MethodsWe retrospectively collected data of 137 EGFR-mutant patients with advanced lung adenocarcinoma who underwent next-generation sequencing in our hospital in 2018. Among them, 96 were treated with EGFR–TKIs alone and 41 received EGFR–TKIs plus chemotherapy. We analyzed the progression-free survival (PFS) of patients with co-mutations using different treatments.ResultsConcurrent TP53 mutations, especially exon 4 and 6, were associated with a markedly shorter time to progression on EGFR-TKI monotherapy (11.4 months vs. 16.6 months, P=0.003), while EGFR–TKIs plus chemotherapy would benefit those patients more (with TP53: 11.4 months vs. 19.1 months, P=0.001, HR=0.407; without TP53: 16.6 months vs. 18.9 months, P=0.379, HR=0.706). The incidence of T790M after resistance was equal in patients treated with different treatments (53% vs. 53%, P=0.985).ConclusionsIn our study, concurrent TP53 mutations were found to be risk factors for EGFR-TKI monotherapy, but TKI combined with chemotherapy could eliminate this heterogeneity.

scholarly journals Lung Adenocarcinoma Patient Harboring EGFR-KDD Achieve Durable Response to Afatinib: A Case Report and Literature Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Lingling Zhao ◽  
Zhen Wang ◽  
Haiwei Du ◽  
Songan Chen ◽  
Pingli Wang
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Case Reports ◽  
Rapid Development ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Kinase Domain ◽  
Durable Response ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Egfr Tkis

The rapid development of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations including but not limited to exon 19 deletions (19 del) and point mutation L858R in exon 21. However, the efficacy of EGFR-TKIs in patients with rare mutations, such as EGFR-kinase domain duplication (KDD), remains elusive. EGFR-KDD often results from in-frame tandem duplication of EGFR exons 18–25, causing subsequent constitutive activation of EGFR signaling. Several case reports have revealed the efficacies of EGFR-TKIs in advanced lung adenocarcinoma (LUAD) with EGFR-KDD but yielded variable antitumor responses. In the present study, we report a 61-year-old male patient diagnosed with T1N3M0 (stage IIIB) LUAD harboring EGFR-KDD involving exons 18–25. He was treated with afatinib and achieved partial response (PR) with progression-free survival (PFS) of 12 months and counting. Our work, confirming EGFR-KDD as an oncogenic driver and therapeutic target, provides clinical evidence to administer EGFR-TKIs in patients with advanced LUAD harboring EGFR-KDD.

scholarly journals Platelet-to-lymphocyte Ratio (PLR) as an Indicator of Survival in Rare Histopathological Subtypes of Renal Cell Carcinoma

2021 ◽  
Vol 8 (4) ◽  
pp. 283-288
Author(s):  
Emrah Eraslan ◽  
Mutlu Doğan
Keyword(s):  
Renal Cell ◽  
Inflammatory Markers ◽  
Kinase Inhibitors ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Platelet To Lymphocyte Ratio ◽  
Independent Predictive Factor ◽  
Lymphocyte Ratio ◽  
The Relationship

Objective: Inflammatory markers have prognostic significance for renal cell carcinomas (RCC) as in many types of cancer. The prognostic effect of inflammatory markers in the rare histological subtypes of RCC has not been adequately evaluated. In our study, we aimed to evaluate the relationship between basal inflammatory indices (neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte ratio [PLR], lymphocyte to monocyte ratio [LMR], and systemic immune-inflammation [SII]) and survival (progression-free survival [PFS] and overall survival [OS]). Material and Methods: Patients with metastatic non-clear cell RCC (nccRCC) or RCC with sarcomatoid differentiation (sRCC) were included in the study. The relationship between inflammatory indices, which was calculated before any systemic treatment and survival, were retrospectively assessed. Results: Thirty patients, predominantly males (n = 20, 66.7%), with a median age of 59.1 (IQR, 52.5-70.3) years, were included in the study. Median PFS achieved with first-line tyrosine kinase inhibitors for patients with a PLR level less or greater than the median value (238) was 12.6 (95% CI 1.4-23.9) months and 4.8 (95% CI, 2.3-7.3) months, respectively (p = 0.021). Median OS for patients with a PLR level less or greater than the median (238) was 16.7 (95% CI, 3.7-29.7) months and 8.6 (95% CI, 4.9-12.3) months (p = 0.008), respectively. In the Cox-regression model (including gender, age, presence of metastasis at diagnosis, NLR, PLR, LMR, SII) only PLR was the independent predictive factor for both PSF (HR = 0.131; 95% Cl 0.028-0.620, p = 0.010) and OS (HR = 0.199; 95% Cl 0.048-0.819, p = 0.025).

Afatinib (Afa) plus bevacizumab (Bev) combination after acquired resistance (AR) to EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC): Multicenter single arm phase II trial (ABC-study).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9034-9034 ◽  
Author(s):  
Akito Hata ◽  
Nobuyuki Katakami ◽  
Reiko Kaji ◽  
Toshihide Yokoyama ◽  
Toshihiko Kaneda ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Synergistic Effects ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Median Number ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Grade 3 ◽  
Egfr Mutant ◽  
Ecog Ps ◽  
Egfr Tkis

9034 Background: Irreversible EGFR-TKI monotherapies showed only moderate efficacy after AR to reversible EGFR-TKIs. Preclinical studies suggested that addition of Bev to EGFR-TKIs could overcome AR, and Bev demonstrated synergistic effects with Afa in TKI-resistant xenograft models. Methods: ECOG PS 0-2 patients (pts) with EGFR-mutant NSCLC after AR to EGFR-TKIs were enrolled at any lines. Rebiopsy was essential to confirm T790M status after AR. Afa was prescribed at 30 mg, and Bev administered at 15 mg/kg tri-weekly until progression. Results: Between October 2014 and September 2016, 33 eligible pts were enrolled. Median age was 66 (range, 48-86). Twenty-one (64%) pts were female, and 22 (67%) were never smoker. Mutation subtypes were 20 (61%) Del-19, 12 (36%) L858R, and 1 (3%) L861Q. T790M was detected in 14 (42%) pts. Median number of prior regimens was 4 (range, 1-10). First prior TKIs were 20 (61%) gefitinib, 10 (30%) erlotinib or 3 (9%) Afa. Six pts obtained partial response and 23 stable disease, resulting in response rate (RR) of 18.2% (95% confidence interval [CI], 7.0-35.5%) and disease control rated of 87.9% (95% CI, 71.8-96.6%). Median progression-free survival (PFS) and overall survival were 5.9 (95% CI, 3.5-8.8) months and not reached, respectively. Median RR and PFS of T790M+ vs. T790M- were 14.3% vs. 21.2% (p = 0.6189) and 6.2 vs. 5.2 months (p = 0.8619), respectively. Median RR and PFS of Del-19 vs. L858R were 20.0% vs. 8.3% (p = 0.3789) and 5.9 vs. 5.1 months (p = 0.8996), respectively. Afa dosage was reduced to 20 mg in 15 (45%) pts and increased to 40 mg in 2 (6%) pts. Median number of Bev administrations was 6 (range, 1-14). Bev was interrupted in 5 (15%) pts. Adverse events ≥grade 3: rash (3%); paronychia (24%); mucositis (6%); diarrhea (3%); liver dysfunction (3%); hypertension (39%); and proteinuria (15%) were observed. There were no treatment-related deaths, interstitial lung disease, nor Bev-associated severe bleedings. Conclusions: Afa + Bev demonstrated the efficacy and safety after AR to EGFR-TKIs. It could be a therapeutic salvage option for T790M- populations. Clinical trial information: UMIN000014710.

scholarly journals Pretreatment Platelet-to-Lymphocyte Ratio (PLR) is associated with prognosis in gastric cancer patients with immunotherapy

2021 ◽  
Author(s):  
Miaomiao Gou ◽  
Yong Zhang
Keyword(s):  
Gastric Cancer ◽  
Response Rate ◽  
Univariate Analysis ◽  
Objective Response ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Significant Difference

Abstract Background: previous studies had demonstrated that system inflammation indexes were associated with prognosis ability in various cancers. We aim to explore the prognostic value of platelet to lymphocyte ratio (PLR) in patients with advanced or metastatic gastric cancer (AGC or MGC) receiving immunotherapy. Method: patients with AGC and MGC who received anti-PD-1 treatment at the Chinese PLA General Hospital between January 2016 and August 2020 were reviewed. The study analyzed the association of PLR and overall survival (OS) or progression-free survival (PFS) and anti-tumor response rate with immunotherapy.Results: 137 patients were included in the final analysis. The area under the curve values of PLR for 6 months PFS was 0.68(P<0.05). The best cut-off value for PLR was 816.43. Patients in PLR <816.43 group had PFS of 7.9m compared to 4.3m in PLR>= 816.43 group (HR = 0.61`, 95% CI, 0.42-0.89, p < 0.001).OS in PLR <816.43 group was longer than PLR>= 816.43 group (11.1m vs 9.2m, HR = 0.62`, 95% CI, 0.42-0.93, p < 0.001). The objective response rate (ORR) and disease control rate (DCR) were 34.1% and 84.6% respectively in PLR <816.43 group while 30.4% and 80.4% in the>= 816.43 group. No significant difference was observed among two group in terms of ORR and DCR (p=0.669, p=0.536). Univariate analysis and multivariate analysis found that PLR was an independent prognosis biomarker for PFS and OS(p<0.05). Conclusions: Pre-treatment PLR was significantly associated with PFS and OS in patients with AGC and MGC who received immunotherapy. Clinicians might consider patients with elevated PLR as one factor for decisions on immunotherapy strategy.

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