A joint model of tumor size dynamics and survival with new lesions in EGFR mutation-positive non-small cell lung cancer patients with treatment of gefitinib or carboplatin and paclitaxel.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20697-e20697
Author(s):  
James Dunyak ◽  
Hong Yan ◽  
Nidal Al-Huniti
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Size ◽  
Egfr Mutation ◽  
Joint Model ◽  
Small Cell ◽  
Small Cell Lung ◽  
Predictive Values ◽  
Nsclc Patients

e20697 Background: Tumor dynamics have been serving as significant predictors in diagnosis, staging, prognosis and treatment of patients with non-small cell lung cancer (NSCLC). The purpose of this study is to propose a joint model that links the longitudinal tumor burden to progression free survival (PFS) with the appearance of new lesion in a population of NSCLC patients with gefitinib treatment or Carboplatin/Paclitaxel. Methods: The model was extended to the estimation of new lesion based on a previously developed tumor size and survival joint model. The derivative of the tumor loads and the probability of new lesions served as biomarkers in the survival submodel. Parameters were estimated from the posterior distribution in a Bayesian framework and numerical study was realized with R and STAN. A total of 434 NSCLC patients with EGFR mutation positive treated with gefitinib or chemotherapy (carboplatin+paclitaxel) from IPASS (‘NCT00322452’) were used to construct the model. Predictions were performed on the IFUM study (‘NCT01203917’) with 102 EGFR mutation positive NSCLC patients. Results: The model performed well in PFS prediction in both within-sample and out-of-sample estimations. Further improvement of model specifications is necessary since the tumor load developing rate and appearance of new-lesion negatively impacted survival predictions. About 90% accuracy was realized by the joint model when recapitulating the outcomes from the response evaluation criteria in solid tumors (RECIST). The appearance of new lesion contributed less than tumor size in accommodating drug effect when comparing progression-specific hazards. Conclusions: This Bayesian joint model well recapitulated the outcomes from the RECIST with sequentially updated tumor size that linked to survival predictions. New insights of relative predictive values were provided by the joint model regarding the components of RESICT.

Anti-PD-1 antibody monotherapy or anti-PD-1 antibody combination with chemotherapy treated non-small cell lung cancer (NSCLC) patients with EGFR mutation: A retrospective analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21691-e21691
Author(s):  
Shaorong Yu ◽  
Ran Hu ◽  
Meiqi Shi
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Objective Response ◽  
Small Cell ◽  
Combined Chemotherapy ◽  
Small Cell Lung ◽  
Egfr Mutant ◽  
Nsclc Patients

e21691 Background: Anti-PD-1/PD-L1 antibody has been approved as first- or second-line therapy in non-small cell lung cancer (NSCLC) patients and modified the management of patients with locally advanced or metastatic NSCLC. However, anti-PD-1 treatment shows less effective in patients with EGFR mutation than in those without driver gene mutation. To determine the activity of anti-PD-1 antibody in EGFR mutant NSCLC, we retrospectively evaluated response patterns among EGFR mutant NSCLC patients. Methods: We identified 58 patients with EGFR mutation who were treated with anti-PD-1 monotherapy or anti-PD-1 antibody combined with chemotherapy from March 2018 to December 2019. All of patients have received more than one treatment regimen including EGFR-TKI treatment. Objective response rates (ORR) were assessed using RECIST v1.1. Results: A total of 58 patients including 53 cases of lung adenocarcinoma, 4 cases of squamous cell carcinoma and 1 case of adenosquamous carcinoma were analyzed. Among them 26 patients received nivolumab treatment, 9 patients with pembrolizumab treatment, 9 patients with sintilimab treatment, 8 patients with JS001 treatment and 6 patients with camrelizumab treatment. Seven patients received anti-PD-1 monotherapy and the other 51 patients received anti-PD-1 combined chemotherapy. The main chemotherapeutic drugs contain docetaxel, pemetrexed, paclitaxel and paclitaxel-albumin. ORR was observed in 6 out of 58 (10%) patients. The disease control rate was 50% (29/58). The median PFS was 2.82 months. All six patients who achieved PR were received anti-PD-1 combined chemotherapy. Four patients died during treatment with anti-PD-1 therapy and we can’t confirm if these were due to cancer progress or immune related tumor hyperprogression. The adverse events were immune related pneumonia (two cases with grade 2 and one case with grade 3) and immune related hepatitis (one case with grade 2). Conclusions: Anti-PD-1 antibody combined chemotherapy seems showed moderate effect on NSCLC patients with EGFR mutation who have received anti-EGFR therapy.

scholarly journals Comprehensive Statistical Exploration of Prognostic (Bio-)Markers for Responses to Immune Checkpoint Inhibitor in Patients with Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 75
Author(s):  
Stefanie Hiltbrunner ◽  
Meta-Lina Spohn ◽  
Ramona Wechsler ◽  
Dilara Akhoundova ◽  
Lorenz Bankel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Patient Group ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Tumor Size ◽  
Small Cell ◽  
Size Reduction ◽  
Small Cell Lung ◽  
Nsclc Patients

Metastatic non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) may suffer from heavy side effects and not all patients benefit from the treatment. We conducted a comprehensive statistical analysis to identify promising (bio-)markers for treatment response. We analyzed retrospective data from NSCLC patients treated with ICIs in first- or further-line therapy settings at the University Hospital Zurich. We investigated 16 possible prognostic markers with respect to overall survival, tumor size reduction, and the development of an immune-related adverse event (irAE) and assessed the robustness of our results. For the further-line patient group, the most significant result was that increased basophil counts were associated with increased odds of tumor size reduction within three months and with the development of an irAE. For the first-line patient group, the most significant results were that increased lymphocyte counts, the histology of adenocarcinoma, and the intake of non-steroidal anti-rheumatic drugs (NSAR) were associated with decreased hazards of dying. Our study yielded new hypotheses for predictive (bio-)markers for response to ICIs in NSCLC patients. The possibly beneficial role of high basophil counts is a particularly interesting finding. Our results should be tested on independent data in a prospective fashion.

Assessment of EGFR mutations in patients diagnosed of squamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18106-e18106
Author(s):  
Francisco Lobo ◽  
Manuel Domine ◽  
Federico Rojo ◽  
Yann Izarzugaza ◽  
Ana Leon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Exon 20 ◽  
Nsclc Patients

e18106 Background: Mutations in the Epidermal Growth Factor Receptor (EGFR) predict a better outcome to EGFR tyrosine kinase inhibitors than platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Previous studies with Caucasian patients have shown a prevalence of EGFR mutation of 10-15%. The aim of this study is to analyze the prevalence of EGFR mutations in squamous-cell NSCLC patients from an area of influence of 500,000 habitants. Methods: Prospective mutation testing in NSCLC patients included in our institution since October 2010 to January 2012 was performed on DNA obtained from available tumor tissue and cytologic samples, using ARMS-scorpion TheraScreen EGFR 29 Mutation Test Kit (Qiagen). Results: From 218 consecutive NSCLC diagnoses, 18 (8.25%) patients showed EGFR mutations: 6 (33.3%) exon 19 deletion, 9 (50%) exon 21 mutations (7 L858R and 2 L861Q) and 3 (16.6%) cases exon 20 insertion. In the EGFR mutated population, 16 (88.88%) patients were diagnosed as adenocarcinoma and 2 (11.11%) as squamous cell carcinoma. The characteristics of these squamous cell cancer patients were: 2 male; 1 non-smoker, 1 former-smoker; 1 stage IV and 1 stage IB at diagnosis; one case exon 20 insertion and one exon 21 mutation (L858R). Conclusions: The EGFR mutation rate in squamous-cell NSCLC patients in our referral area is superior (11.17%) than previously reported, reinforcing the importance of including EGFR mutation testing in squamous-cell NSCLC population for selecting optimal therapy for these patients.

Biologic markers guiding the treatment of non-small cell lung cancer: RRM-1, class III ß tubulin, and ERCC-1.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19127-e19127
Author(s):  
Esat Namal ◽  
Mustafa Bozkurt ◽  
Akin Ozturk ◽  
Kezban Nur Planci ◽  
Nuray Bassullu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Patient Population ◽  
Small Cell ◽  
Small Cell Lung ◽  
Old Patients ◽  
Predictive Values ◽  
Nsclc Patients ◽  
Β Tubulin

e19127 Background: Lung cancer is the most common cause of cancer deaths in the world. Despite the developments in diagnosis and treatment, the high mortality rate in metastatic non small cell lung cancer (NSCLC) is still an important problem. Recent non-targeted standard therapy for NSCLC is the dual therapy regimens which involve platins. Our former knowledge whether these therapies can be effective or not would save the patient from the redundant toxicity and provide us to use more effective drugs formerly. Understanding the biology of NSCLC can allow choosing the effective and appropriate therapy in terms of life quality, survival rate and relapses. There are ongoing studies upon prognostic and predictive values of ERCC1, RRM1 and β tubulin in NSCLC patients. In this study we aimed to investigate the role of β tubulin, ERCC1 and RRM1 expressions as predictive biomarkers. Methods: 47 patients who are on follow up by Bilim University, Medical Oncology Department, were taken to the study. ß tubulin, ERCC1 and RRM1 over expressions were investigated in the biopsy materials of these patients by Pathology Department. Retrospectively, it was evaluated whether there is correlation between these biological markers and patients’ survial rates and responses to antineoplastic therapies. Results: In the literature, there are some studies which show that β tubulin score is a predictive marker for the good response to taxan therapy. On the other hand, it was shown that taxans enhance the platin sensitivity decreasing the β tubulin expressions. Our study was also correlated with these studies in the literature. Furthermore, there was relationship between the β tubulin score and age. 15 patients (%32) were 65 or under 65 and these were accepted as ‘young patient population’; 32 patients were over 65 and were accepted as ‘old patient population’. Most of the patients whose β tubulin score was high (n=29), were young (n=19); and most of the patients whose β tubulin score was low (n=18) were old patients (n=12) (p=0.032). Conclusions: Detecting the levels of β tubulin, ERCC1 and RRM1 before treatment in NSCLC patients, can be predictive to organize the treatment. Unquestionably, it must be supported by the studies involve more patients.

Longitudinal tumor size and NLR as predictive factors of individual survival compared to their baseline values in patients with non-small cell lung cancer treated with durvalumab.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20047-e20047
Author(s):  
Kirill Zhudenkov ◽  
Sergey Gavrilov ◽  
Kirill Peskov ◽  
Gabriel Helmlinger ◽  
Sergey Aksenov
Keyword(s):  
Lung Cancer ◽  
Longitudinal Data ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Size ◽  
Predictive Performance ◽  
Small Cell ◽  
Small Cell Lung ◽  
Prognostic Accuracy ◽  
Nsclc Patients

e20047 Background: Our ability to accurately predict survival of patients with non-small cell lung cancer (NSCLC) while on treatment is limited. Prognostic markers such as stage and tumor size are well established, while neutrophil-to-lymphocytes ratio (NLR) and other hemogram measurements have recently been studied. Gain in prognostic accuracy of these markers when measured longitudinally has not been established. Methods: There were 679 NSCLC patients (Stage 3 or 4, ECOG PS 0 or 1) from clinical studies of durvalumab 10 mg/kg every two weeks (NCT02087423 and NCT01693562). We developed three models of overall survival (OS) all with ECOG as covariate: a Cox proportional hazards model with baseline tumor sum-of-longest-diameters (SLD) and NLR as covariates (COX); a joint model of OS and longitudinal SLD and baseline NLR (JM SLD); and a joint model of OS and longitudinal SLD and NLR (JM SLD&NLR). We compared prognostic accuracy of these markers measured longitudinally vs. at baseline, using predicted probability of OS at 12 months after start of durvalumab as a prognostic score. We evaluated predictive performance of the models using area under the receiver-operating characteristic curve (ROC AUC) describing trade-off between true and false positives (i.e., survival past 12 months). The AUCs were calculated for patients in the dataset using longitudinal data up to different cut-offs. Results: The AUC for all patients starting durvalumab using baseline ECOG, SLD and NLR was 0.73, while it decreased to 0.64 for patients surviving to 6 months, compared to 0.50 for noninformative models. The AUC using longitudinal information for SLD and NLR was larger the more longitudinal data was used for prediction and was 0.81 using 6 months’ worth of data. Conclusions: Using longitudinal information for SLD and NLR increased individual predictive performance of these markers compared to only baseline information in NSCLC patients. [Table: see text]

scholarly journals A Significant Statistical Advancement on the Predictive Values of ERCC1 Polymorphisms for Clinical Outcomes of Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer: An Updated Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Yali Han ◽  
Jie Liu ◽  
Meili Sun ◽  
Zongpu Zhang ◽  
Chuanyong Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Predictive Values ◽  
Platinum Based Chemotherapy ◽  
Nsclc Patients

Background. There is no definitive conclusion so far on the predictive values of ERCC1 polymorphisms for clinical outcomes of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). We updated this meta-analysis with an expectation to obtain some statistical advancement on this issue.Methods. Relevant studies were identified by searching MEDLINE, EMBASE databases from inception to April 2015. Primary outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). All analyses were performed using the Review Manager version 5.3 and the Stata version 12.0.Results. A total of 33 studies including 5373 patients were identified. ERCC1 C118T and C8092A could predict both ORR and OS for platinum-based chemotherapy in Asian NSCLC patients (CT + TT versus CC, ORR: OR = 0.80, 95% CI = 0.67–0.94; OS: HR = 1.24, 95% CI = 1.01–1.53) (CA + AA versus CC, ORR: OR = 0.76, 95% CI = 0.60–0.96; OS: HR = 1.37, 95% CI = 1.06–1.75).Conclusions. Current evidence strongly indicated the prospect of ERCC1 C118T and C8092A as predictive biomarkers for platinum-based chemotherapy in Asian NSCLC patients. However, the results should be interpreted with caution and large prospective studies are still required to further investigate these findings.

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