scholarly journals Subtype Classification of Lung Adenocarcinoma Predicts Benefit From Adjuvant Chemotherapy in Patients Undergoing Complete Resection

2015 ◽  
Vol 33 (30) ◽  
pp. 3439-3446 ◽  
Author(s):  
Ming-Sound Tsao ◽  
Sophie Marguet ◽  
Gwénaël Le Teuff ◽  
Sylvie Lantuejoul ◽  
Frances A. Shepherd ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Lung Adenocarcinoma ◽  
Predictive Value ◽  
International Association ◽  
Disease Free Survival ◽  
Pooled Analysis ◽  
European Respiratory Society ◽  
Cox Models ◽  
Significance Level ◽  
Histologic Pattern

Purpose The classification for invasive lung adenocarcinoma by the International Association for the Study of Lung Cancer, American Thoracic Society, European Respiratory Society, and WHO is based on the predominant histologic pattern—lepidic (LEP), papillary (PAP), acinar (ACN), micropapillary (MIP), or solid (SOL)—present in the tumor. This classification has not been tested in multi-institutional cohorts or clinical trials or tested for its predictive value regarding survival from adjuvant chemotherapy (ACT). Patients and Methods Of 1,766 patients in the IALT, JBR.10, CALGB 9633 (Alliance), and ANITA ACT trials included in the LACE-Bio study, 725 had adenocarcinoma. Histologies were reclassified according to the new classification and then collapsed into three groups (LEP, ACN/PAP, and MIP/SOL). Primary end point was overall survival (OS); secondary end points were disease-free survival (DFS) and specific DFS (SDFS). Hazard ratios (HRs) and 95% CIs were estimated through multivariable Cox models stratified by trial. Prognostic value was estimated in the observation arm and predictive value by a treatment effect interaction with histologic subgroups. Significance level was set at .01 for pooled analysis. Results A total of 575 patients were included in this analysis. OS was not prognostically different between histologic subgroups, but univariable DFS and SDFS were worse for MIP/SOL compared with LEP or ACN/PAP subgroup (P < .01); this remained marginally significant after adjustment. MIP/SOL patients (but not ACN/PAP) derived DFS and SDFS but not OS benefit from ACT (OS: HR, 0.71; 95% CI, 0.51 to 0.99; interaction P = .18; DFS: HR, 0.60; 95% CI, 0.44 to 0.82; interaction P = < .01; and SDFS: HR, 0.59; 95% CI, 0.42 to 0.81; interaction P = .01). Conclusion The new lung adenocarcinoma classification based on predominant histologic pattern was not predictive for ACT benefit for OS, but it seems predictive for disease-specific outcomes.

Predictive Value of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification of Lung Adenocarcinoma in Tumor Recurrence and Patient Survival

2014 ◽  
Vol 32 (22) ◽  
pp. 2357-2364 ◽  
Author(s):  
Jung-Jyh Hung ◽  
Yi-Chen Yeh ◽  
Wen-Juei Jeng ◽  
Kou-Juey Wu ◽  
Biing-Shiun Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Lung Adenocarcinoma ◽  
Classification System ◽  
Predictive Value ◽  
International Association ◽  
American Thoracic Society ◽  
European Respiratory Society ◽  
Pattern Of Recurrence

Purpose This study investigated the pattern of recurrence of lung adenocarcinoma and the predictive value of histologic classification in resected lung adenocarcinoma using the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification system. Patients and Methods Histologic classification of 573 patients undergoing resection for lung adenocarcinoma was determined according to the IASLC/ATS/ERS classification system, and the percentage of each histologic component (lepidic, acinar, papillary, micropapillary, and solid) was recorded. The pattern of recurrence of those components and their predictive value were investigated. Results The predominant histologic pattern was significantly associated with sex (P < .01), invasive tumor size (P < .01), T status (P < .01), N status (P < .01), TNM stage (P < .01), and visceral pleural invasion (P < .01). The percentage of recurrence was significantly higher in micropapillary- and solid-predominant adenocarcinomas (P < .01). Micropapillary- and solid-predominant adenocarcinomas had a significantly higher possibility of developing initial extrathoracic-only recurrence than other types (P < .01). The predominant pattern group (micropapillary or solid v lepidic, acinar, or papillary) was a significant prognostic factor in overall survival (OS; P < .01), probability of freedom from recurrence (P < .01), and disease-specific survival (P < .01) in multivariable analysis. For patients receiving adjuvant chemotherapy, solid-predominant adenocarcinoma was a significant predictor for poor OS (P = .04). Conclusion In lung adenocarcinoma, the IASLC/ATS/ERS classification system has significant prognostic and predictive value regarding death and recurrence. Solid-predominant adenocarcinoma was also a significant predictor in patients undergoing adjuvant chemotherapy. Prognostic and predictive information is important for stratifying patients for aggressive adjuvant chemoradiotherapy.

scholarly journals Khorana Score: Νew Predictor of Early Mortality in Patients With Lung Adenocarcinoma

2018 ◽  
Vol 24 (8) ◽  
pp. 1347-1351 ◽  
Author(s):  
Ioannis Vathiotis ◽  
Evangelos P. Dimakakos ◽  
Paraskevi Boura ◽  
Angeliki Ntineri ◽  
Andiani Charpidou ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Adjuvant Chemotherapy ◽  
Lung Adenocarcinoma ◽  
Treatment Period ◽  
Predictive Value ◽  
First Line ◽  
Thromboembolic Risk ◽  
Patients With Cancer ◽  
Risk Of Death ◽  
Significant Difference

Venous thromboembolism (VTE) is a typical complication in patients with lung cancer. Khorana score is an established tool for thromboembolic risk stratification of ambulatory patients with cancer undergoing outpatient chemotherapy. The aim of this study was to evaluate the predictive value of the Khorana score for VTE and death in patients with lung adenocarcinoma during first-line or adjuvant chemotherapy. Medical records of 130 patients with lung adenocarcinoma receiving first-line or adjuvant chemotherapy were retrospectively studied during the time period June 2013 to May 2015. Venous thromboembolism occurred in 13 (10.0%) patients. Thromboembolic events were significantly correlated with reduced survival during treatment period (hazard ratio [HR]: 3.24; 95% confidence interval [CI]: 1.11-9.49; P = .032). The VTE rates did not present statistically significant difference between different Khorana score groups ( P = .96). In univariate analysis, the risk of death during treatment period (median: 16 weeks) was 3.75 times higher in high-risk versus intermediate-risk patients (HR: 3.75, 95% CI: 1.36-10.36; P = .001) and had 2.25 times higher per point increase in the Khorana score (HR: 2.25, 95% CI: 1.36-3.73; P = .002); the above results were also reproduced in multivariate analysis. Khorana score represents a valuable tool for identifying patients with cancer in low thromboembolic risk but does not preserve its predictive value for higher risk individuals. Khorana score is an independent risk factor for death in patients with lung adenocarcinoma receiving first-line or adjuvant chemotherapy.

scholarly journals Prognostic implications of programmed death ligand 1 expression in resected lung adenocarcinoma: a systematic review and meta-analysis

2020 ◽  
Vol 58 (5) ◽  
pp. 888-898
Author(s):  
Donglai Chen ◽  
Yiming Mao ◽  
Qifeng Ding ◽  
Wei Wang ◽  
Feng Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Lung Adenocarcinoma ◽  
Messenger Rna ◽  
Disease Free Survival ◽  
Pooled Analysis ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
L1 Protein ◽  
Disease Free

Abstract OBJECTIVES Conflicting results have been reported about the prognostic value of programmed death ligand 1 (PD-L1) protein and gene expression in lung adenocarcinoma. METHODS We performed a comprehensive online search to explore the association between PD-L1 expression (protein and messenger RNA) and overall survival (OS) or disease-free survival. Outcomes also included pooled rates of high PD-L1 protein expression in different cell types, per threshold used and per antibody used. A pooled gene expression analysis was also performed on 3 transcriptomic data sets that were obtained from The Cancer Genome Atlas database and the Gene Expression Omnibus database. RESULTS A total of 6488 patients from 25 studies were included. The pooled results suggested that high PD-L1 expression was associated with shorter OS [hazard ratio (HR) 1.57; P &lt; 0.001] and disease-free survival (HR 1.341; P = 0.037) in the overall population. The overall pooled rate of high PD-L1 protein expression was 29% (95% confidence interval 23–34%) in tumour cells. In subgroup analysis, high PD-L1 protein expression in tumour cells predicted worse OS and disease-free survival. A pooled analysis of The Cancer Genome Atlas and Gene Expression Omnibus data sets revealed that higher levels of PD-L1 messenger RNA predicted poorer OS in the entire population. CONCLUSIONS This study is, to our knowledge, the largest pooled analysis on the subject to shed light on the high expression rate of PD-L1 and the prognostic value of high PD-L1 expression in resected lung adenocarcinomas. PD-L1 gene expression is a promising prognostic factor for patients with surgically resected lung adenocarcinoma. Standardization of staining should be underscored prior to routine implementation.

The Novel Histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification System of Lung Adenocarcinoma Is a Stage-Independent Predictor of Survival

2012 ◽  
Vol 30 (13) ◽  
pp. 1438-1446 ◽  
Author(s):  
Arne Warth ◽  
Thomas Muley ◽  
Michael Meister ◽  
Albrecht Stenzinger ◽  
Michael Thomas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
International Association ◽  
Disease Free Survival ◽  
American Thoracic Society ◽  
Adjuvant Chemoradiotherapy ◽  
Prognostic Impact ◽  
The Novel ◽  
European Respiratory Society ◽  
Tumor Stages ◽  
Survival Pattern

Purpose Our aim was to analyze and validate the prognostic impact of the novel International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) proposal for an architectural classification of invasive pulmonary adenocarcinomas (ADCs) across all tumor stages. Patients and Methods The architectural pattern of a large cohort of 500 patients with resected ADCs (stages I to IV) was retrospectively analyzed in 5% increments and classified according to their predominant architecture (lepidic, acinar, solid, papillary, or micropapillary), as proposed by the IASLC/ATS/ERS. Subsequently, histomorphologic data were correlated with clinical data, adjuvant therapy, and patient outcome. Results Overall survival differed significantly between lepidic (78.5 months), acinar (67.3 months), solid (58.1 months), papillary (48.9 months), and micropapillary (44.9 months) predominant ADCs (P = .007). When patterns were lumped into groups, this resulted in even more pronounced differences in survival (pattern group 1, 78.5 months; group 2, 67.3 months; group 3, 57.2 months; P = .001). Comparable differences were observed for overall, disease-specific, and disease-free survival. Pattern and pattern groups were stage- and therapy-independent prognosticators for all three survival parameters. Survival differences according to patterns were influenced by adjuvant chemoradiotherapy; in particular, solid-predominant tumors had an improved prognosis with adjuvant radiotherapy. The predominant pattern was tightly linked to the risk of developing nodal metastases (P < .001). Conclusion Besides all recent molecular progress, architectural grading of pulmonary ADCs according to the novel IASLC/ATS/ERS scheme is a rapid, straightforward, and efficient discriminator for patient prognosis and may support patient stratification for adjuvant chemoradiotherapy. It should be part of an integrated clinical, morphologic, and molecular subtyping to further improve ADC treatment.

scholarly journals Pooled Analysis of the Prognostic and Predictive Effects of TP53 Comutation Status Combined With KRAS or EGFR Mutation in Early-Stage Resected Non–Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy

2017 ◽  
Vol 35 (18) ◽  
pp. 2018-2027 ◽  
Author(s):  
Frances A. Shepherd ◽  
Benjamin Lacas ◽  
Gwénaël Le Teuff ◽  
Pierre Hainaut ◽  
Pasi A. Jänne ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Small Cell Lung Cancer ◽  
Disease Free Survival ◽  
Pooled Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Prognostic Effect ◽  
Disease Free

Purpose Our previous work evaluated individual prognostic and predictive roles of TP53, KRAS, and EGFR in non–small-cell lung cancer (NSCLC). In this analysis, we explore the prognostic and predictive roles of TP53/KRAS and TP53/EGFR comutations in randomized trials of adjuvant chemotherapy versus observation. Patients and Methods Mutation analyses (wild-type [WT] and mutant) for TP53, KRAS, and EGFR were determined in blinded fashion in multiple laboratories. Primary and secondary end points of pooled analysis were overall survival and disease-free survival. We evaluated the role of TP53/KRAS comutation in all patients and in the adenocarcinoma subgroup as well as the TP53/EGFR comutation in adenocarcinoma only through a multivariable Cox proportional hazards model stratified by trial. Results Of 3,533 patients with NSCLC, 1,181 (557 deaths) and 404 (170 deaths) were used for TP53/KRAS and TP53/EGFR analyses. For TP53/KRAS mutation status, no prognostic effect was observed ( P = .61), whereas a borderline predictive effect ( P = .04) was observed with a deleterious effect of chemotherapy with TP53/KRAS comutations versus WT/WT (hazard ratio, 2.49 [95% CI, 1.10 to 5.64]; P = .03). TP53/EGFR comutation in adenocarcinoma was neither prognostic ( P = .83), nor significantly predictive ( P = .86). Similar results were observed for both groups for disease-free survival. Conclusion We could identify no prognostic effect of the KRAS or EGFR driver and TP53 tumor suppressor comutation. Our observation of a potential negative predictive effect of TP53/KRAS comutation requires validation.

A pooled analysis of the effect of age on adjuvant cisplatin-based chemotherapy for completely resected non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7553-7553 ◽  
Author(s):  
M. Fruh ◽  
H. Tribodet ◽  
J. Pignon ◽  
T. Winton ◽  
T. Le Chevalier ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Elderly Patients ◽  
Performance Status ◽  
Age Groups ◽  
Young Patients ◽  
Disease Free Survival ◽  
The Elderly ◽  
Pooled Analysis ◽  
Severe Toxicity ◽  
Cox Models

7553 Background: Adjuvant cisplatin-based chemotherapy (CT) has been shown to increase survival in NSCLC, but uncertainty exists concerning its efficacy and toxicity in elderly patients (≥ 70). Methods: We performed a pooled analysis using individual patient data from 4,584 patients in the LACE database with resected stage IA-III NSCLC enrolled in 5 randomized trials, comparing postoperative CT to no CT (ALPI, ANITA, BLT, IALT and JBR10). Patient and treatment characteristics, CT toxicity and delivery, overall survival, disease-free survival (DFS) and cause-specific mortality were compared among 3 age groups: 3,269 (71%) young (<65), 901 (20%) mid-category (65–69) and 414 (9%) elderly (≥70). The analysis was performed on an intent-to-treat basis. Cox models stratified by trials and adjusted for age, associated drug, planned radiotherapy, total dose of cisplatin (<300, 300, >300), gender, stage, performance status, type of surgery and histology were used with a test for trend to study the effect of CT on survival according to age. Results: Baseline characteristics differed among the age groups, but this was due mainly to the different trial populations and designs. No difference in severe toxicity rate was observed among the age groups. Elderly patients received significantly smaller total doses of cisplatin than the other patients (Chi2-test: p<0.0001) and also the cisplatin doses received were more often lower than the planned one (Kruskal-Wallis test: p<0.0001). The Hazard ratio (HR) of death for the young patients was 0.82 (95% CI 0.73–0.92), 0.86 (95% CI 0.70–1.07) for the mid category and 1.01 (95% CI 0.78–1.32) for elderly patients (test for trend: p=0.17). The HR for DFS was 0.79 (95% CI 0.71–0.87) for the young, 0.76 (95% 0.62–0.93) for the mid category and 0.94 (95% CI 0.73–1.22) for the elderly patients (test for trend: p=0.35). More elderly patients died from non- lung cancer related causes (10% young, 16% mid category and 20% elderly; p<0.0001). Conclusions: The survival benefit from cisplatin-based adjuvant therapy for NSCLC patients was not significantly different according to age, but this may be due to lack of power. Supported by unrestricted grants from PHRC and LNCC No significant financial relationships to disclose.

Prognostic and predictive value of immunoscore signature in gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15594-e15594 ◽  
Author(s):  
Xiaolong Qi ◽  
Yuming Jiang ◽  
Qi Zhang ◽  
Yanfeng Hu ◽  
Tuanjie Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Predictive Value ◽  
Prognostic Value ◽  
Cox Regression ◽  
External Validation ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Predictive Tool

e15594 Background: TNM staging system is not adequate to define the prognosis of patients with gastric cancer (GC). This system is also unable to predict whether the GC patients are likely to benefit from adjuvant chemotherapy. We postulated that ImmunoScore of GC (ISGC) could markedly improve the prediction of postsurgical survival and adjuvant chemotherapeutic benefits. Methods: 125 GC patients were enrolled as a training cohort to detect the expression of 27 immune features using immunohistochemistry and then constructed a five-feature-based ISGC using the LASSO Cox regression model. Internal validation cohort (126 specimens) and two external validation cohorts (628 specimens) were utilized to validate the prognostic and predictive value of ISGC. Results: We established the ISGC classifier based on the five features: CD3invasive margin (IM), CD3center of tumor (CT), CD8IM, CD45ROCT, and CD66bIM. The ISGC classifier could distinguish GC patients with high-ISGC from those with low-ISGC with significant differences in 5-year disease-free survival (45.0% v.s. 4.4%, p < 0.001) and 5-year overall survival (48.8% v.s. 6.7%, p < 0.001). According to the multivariate analysis, the ISGC classifier was proved to be an independent prognostic factor. A combination of ISGC and TNM had better prognostic value than TNM stage alone. In a further analysis, stage II and III GC patients with high-ISGC exhibited a favorable response to adjuvant chemotherapy. To provide a quantitative method to predict stage II and III GC patients’ probability of 3- and 5-year overall survival, we constructed two nomograms that integrated the ISGC and clinicopathological risk factors. Calibration plots showed that the nomograms performed well compared with an ideal model. The predictive accuracy and clinical usefulness of the nomograms were also demonstrated. Conclusions: The ISGC classifier could effectively predict recurrence and survival of GC, and complemented the prognostic value to TNM system. Moreover, the classifier might be a useful predictive tool to identify candidates with stage II and III GC who would benefit from adjuvant chemotherapy. Therefore, the ISGC might facilitate the counseling and personalize the postoperative management of GC patients.

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