Defining a High-Risk Subgroup of Pathological T2N0 Gastric Cancer by Prognostic Risk Stratification for Adjuvant Therapy

2011 ◽  
Vol 15 (12) ◽  
pp. 2153-2158 ◽  
Author(s):  
Chunyan Du ◽  
Ye Zhou ◽  
Kai Huang ◽  
Guangfa Zhao ◽  
Hong Fu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Risk Stratification

The potential of a CLIA-certified prognostic/predictive molecular test to address the rising costs of non-small cell lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21671-e21671
Author(s):  
Michael J Mann ◽  
David Jablons ◽  
Ken O'Day ◽  
Wayne Su ◽  
Padma Sundar
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Risk Stratification ◽  
Small Cell ◽  
Stage I ◽  
Molecular Test ◽  
Small Cell Lung ◽  
Prospective Data ◽  
Risk Patients

e21671 Background: Treating recurrences of non-small cell lung cancer (NSCLC) is increasingly expensive but still rarely curative. Disease free survival (DFS) among resected stage I-IIA patients remains only 50-70%. Guidelines advocate adjuvant therapy in “high-risk” patients in this population to reduce these costly and deadly recurrences, but recognize that conventional criteria have not been validated to stratify risk or predict benefit. A CLIA-certified, commercially available 14-gene expression risk profile (DetermaRx) has been extensively validated among stage I-IIA non-squamous NSCLC patients; prospective data now suggest that the test predicts improved DFS with adjuvant therapy. We therefore studied the potential economic impact of this molecular test on early stage NSCLC. Methods: Model variables included: relative increase in DFS with adjuvant treatment of molecular intermediate- and high-risk patients (25.5%; range 12.3-41.3%); cost of adjuvant ($8,760; $8,144-$9,376) or late-stage ($284,500; $224,900-345,200) treatment; and compliance with recommendations for adjuvant therapy (75%; 60-90%). Ranges were based on: historical trials and recent prospective data, published cost literature, and published survey data, respectively. Parameters were varied in a multifactorial, one-way sensitivity analysis to assess the impact of parameter uncertainty. Results: Reduction of recurrences with implementation of the 14-gene assay resulted in an average cost savings of $11,608/patient (potential systems savings of ~$450 million), even when including the cost of molecular risk stratification ($4000/patient) and of cisplatin-based adjuvant chemotherapy for molecular high- and intermediate-risk patients. Lower bound assumptions for relative improvement, cost of care, and compliance yielded persistent savings of $3,699, $8,091 and $8,486, respectively. Conclusions: Utilization of this predictive molecular risk stratification assay in the management of stage I-IIA non-squamous NSCLC has the potential to significantly reduce lung cancer costs in an era of targeted therapy and immunotherapy, while at the same time improving DFS and saving lives.

scholarly journals A SEER population analysis of stage IB resected gastric cancer: Who can benefit from adjuvant therapy?

2019 ◽  
Vol 5 (suppl) ◽  
pp. 122-122
Author(s):  
Yue Wang
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Clinical Decision Making ◽  
Family Income ◽  
Population Analysis ◽  
Low Risk ◽  
High Risk Patients ◽  
Stage Ib ◽  
Risk Patients

122 Background: The benefit of adjuvant therapy (AT) remains controversial in stage IB gastric cancer (GC). This study aimed to offer a reference for the rational indications of AT. Methods: We retrospectively included 1935 stage IB GC patients who experienced curative surgery from the SEER database between 2004 and 2015. These patients were allocated into two groups: Group AT and Group surgery alone (Group SA). Risk factors associated with AT were examined using univariate/multivariate analyses. A nomogram to project overall survival (OS) of AT was established and internally validated. Results: Five variables, which were significantly related with OS of AT, were incorporated in the nomogram. These variables were sex, age, examined lymph nodes, tumor site, and family income. The C-index of the model was 0.636 and the calibration curve showed that the anticipated values were in accordance with the actual values. The decision curve demonstrated that the optimal clinical impact was achieved when the threshold possibility was 0-47%. Then the entire cohort was separated into low-risk (≤107 points) as well as high-risk ( > 107 points) groups based on the projected 5-year OS. Group SA revealed a significantly poorer OS than Group AT for high-risk patients (P < 0.001); on the other hand, there was a comparable OS for low-risk patients (P = 0.067). Conclusions: We have developed an effective, intuitional and applied prognostic tool based on nomogram to clinical decision-making. For stage IB GC after surgical resection, AT was only recommended for high-risk patients. However, AT may be dispensable for low-risk patients.

Residual pathologic stage at radical cystectomy and risk stratification of patients with pT2N0 bladder cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5076-5076
Author(s):  
H. Isbarn ◽  
G. Sonpavde ◽  
S. F. Shariat ◽  
G. S. Palapattu ◽  
A. I. Sagalowsky ◽  
...  
Keyword(s):  
High Risk ◽  
Urinary Bladder ◽  
Adjuvant Therapy ◽  
Risk Stratification ◽  
Radical Cystectomy ◽  
Cox Regression ◽  
Transitional Cell ◽  
Invasive Disease ◽  
Cancer Specific Survival ◽  
Muscle Invasive

5076 Background: We hypothesized that in patients with pT2N0 transitional cell carcinoma (TCC) of the urinary bladder, residual muscle-invasive disease at radical cystectomy (RC) may confer poorer outcomes than residual non-muscle invasive disease due to larger tumor volume and/or biologically more aggressive disease. Patients with high-risk pT2N0 disease may be candidates for trials of adjuvant therapy. Methods: Patients from the BCRC database with pT2N0 stage (N = 208) at TUR (transurethral resection) whose tumors were organ-confined at RC (≤pT2N0) were analyzed. T1N0 patients (N=33) with pT2 disease at RC were also examined in order to include all pT2 patients. None of the patients had received perioperative chemotherapy. The effect of residual pT-stage at RC on outcomes was evaluated in Kaplan-Meier, as well as in univariable and multivariable Cox-regression models. Covariates consisted of age, gender, grade, lymphovascular invasion, concomitant carcinoma-in-situ (CIS), number of lymph nodes removed, and the year of surgery. Results: Among baseline T2N0 patients, residual pT-stage at RC was pT0 in 24 (11.5%), pTa in 9 (4.3%), pCIS in 22 (10.6%), pT1 in 35 (16.8%), and pT2 in 118 patients (56.7%). The median follow-up was 50.1 months. The 5-year recurrence-free survivals of patients with residual pT0/pTa/pCis, pT1 and pT2 were 100%, 85% and 75%, respectively. The 5-year cancer-specific survival rates for the same patient cohorts were 100%, 93%, and 81%, respectively. In multivariable analyses, the effect of residual stage <pT2 at RC achieved independent predictor status for recurrence (adjusted HR 0.20; p = 0.002), as well as for cancer-specific survival (adjusted HR: 0.24; p = 0.02). Initial T1 patients who were pT2 at RC did not have statistically different outcomes compared to initial T2 followed by pT2 at RC. Conclusions: Patients with pT2N0 TCC of the urinary bladder with residual non-muscle invasive disease at RC have significantly better long-term outcomes compared to residual muscle-invasive disease. With further validation, these data may facilitate the risk-stratification of patients with pT2N0 disease and enable the selection of high-risk patients for trials of adjuvant therapy. No significant financial relationships to disclose.

scholarly journals A Risk Signature with Immune and Inflammatory Cells Infiltration in Gastric Cancer Predicts Survival and Efficiency of Chemotherapy

2020 ◽  
Author(s):  
Sen Li ◽  
Wenpeng Wang ◽  
Pengfei Ma ◽  
Junli Zhang ◽  
Yanghui Cao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
T Lymphocytes ◽  
Risk Stratification ◽  
Validation Cohort ◽  
Risk Group ◽  
Inflammatory Cells ◽  
High Risk Group ◽  
Training Cohort

Abstract Background In order to accurately predict outcomes of gastric cancer (GC), we developed a risk signature with tumor infiltration immune and inflammatory cells for prognosis.Methods A risk signature model in combination with CD66b + neutrophils, CD3 + T, CD8 + T lymphocytes, and FOXP3 + regulatory T cells was developed in a training cohort of 327 GC patients undergoing surgical resection between 2011 and 2012, and validated in a validation cohort of 285 patients from 2012 to 2013.Results High CD66b expression predicted poor disease-special survival (DSS) as well as inversely correlated with CD8 (P < 0.05) and FOXP3 expression (P < 0.05) in the training cohort, comparable disease-free survival (DFS) findings were observed in the validation cohort.Furthermore, a risk stratification was developed from integration of CD66b + neutrophils and T immune cells. In both DFS and DSS, the high-risk group all demonstrated worse prognosis than low-risk group in both the training cohort and the validation cohort (all P < 0.05). In addition, the high-risk group was associated with post-operative relapses. Furthermore, this risk signature model increase the predictive accuracy and efficiency for post-operative relapses. At last, the high-risk group identified a subgroup of GC patients who tend to not benefit from adjuvant chemotherapy.Conclusions Incorporation of neutrophils into T lymphocytes could provide more accurate prognostic information in GC, and this risk stratification predicted survival benefit from post-operative adjuvant chemotherapy in GC.

scholarly journals Development and Verification of an Immune-Based Gene Signature for Risk Stratification and Immunotherapeutic Efficacy Assessment in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-41
Author(s):  
Feng Qiu ◽  
Yumei Zhu ◽  
Yafeng Shi ◽  
Jingjing Ji ◽  
Yingchao Jin
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Score ◽  
Immune Cells ◽  
Gene Signature ◽  
Risk Scores ◽  
Training Set ◽  
Chemotherapy Drugs ◽  
Efficacy Assessment

Objective. Due to the molecular heterogeneity of gastric cancer, only minor patients respond to immunotherapeutic schemes. This study is aimed at developing an immune-based gene signature for risk stratification and immunotherapeutic efficacy assessment in gastric cancer. Methods. An immune-based gene signature was developed in gastric cancer by LASSO method in the training set. The predictive performance was validated in the external datasets. KEGG pathways related to risk scores were assessed by GSEA. Based on multivariate Cox regression analysis, a nomogram was established. Sensitivity to chemotherapy drugs was evaluated between high- and low-risk samples. The relationships of risk scores with infiltration levels of immune cells, stromal scores, immune scores, immune cell subgroups, and overall response to anti-PD-L1 therapy were determined. Results. Our results showed that high risk scores were indicative of undesirable survival outcomes both in the training set ( p < 0.0001 ) and the validation set ( p = 0.002 ). Moreover, this signature could independently predict patients’ survival (HR: 2.656 (1.919-3.676) and p < 0.001 ). Subgroup analysis confirmed the sensitivity of this signature in predicting prognosis (all p < 0.05 ). Cancer-related pathways were primarily enriched in high-risk samples, such as MAPK and TGF-β pathways ( p < 0.05 ). By incorporating stage and the risk score, we established a nomogram for predicting one-, three-, and five-year survival probability. Patients with high-risk scores were more sensitive to chemotherapy drugs ( p < 0.05 ). There was heterogeneity in immune cells between high- and low-risk samples ( p < 0.05 ). Samples with progressive disease exhibited the highest risk score, and those with complete response had the lowest risk score ( p < 0.05 ). Conclusion. This immune-based gene signature might be representative of a promising prognostic classifier for predicting risk stratification and immunotherapeutic efficacy in gastric cancer, assisting personalized therapy and follow-up plan.

scholarly journals Risk assessment in precapillary pulmonary hypertension: a comparative analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Thomas Sonnweber ◽  
Eva-Maria Schneider ◽  
Manfred Nairz ◽  
Igor Theurl ◽  
Günter Weiss ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Pulmonary Hypertension ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Prediction ◽  
Mortality Risk ◽  
Assessment Tool ◽  
Risk Models ◽  
Non Invasive

Abstract Background Risk stratification is essential to assess mortality risk and guide treatment in patients with precapillary pulmonary hypertension (PH). We herein compared the accuracy of different currently used PH risk stratification tools and evaluated the significance of particular risk parameters. Methods We conducted a retrospective longitudinal observational cohort study evaluating seven different risk assessment approaches according to the current PH guidelines. A comprehensive assessment including multi-parametric risk stratification was performed at baseline and 4 yearly follow-up time-points. Multi-step Cox hazard analysis was used to analyse and refine risk prediction. Results Various available risk models effectively predicted mortality in patients with precapillary pulmonary hypertension. Right-heart catheter parameters were not essential for risk prediction. Contrary, non-invasive follow-up re-evaluations significantly improved the accuracy of risk estimations. A lack of accuracy of various risk models was found in the intermediate- and high-risk classes. For these patients, an additional evaluation step including assessment of age and right atrium area improved risk prediction significantly. Discussion Currently used abbreviated versions of the ESC/ERS risk assessment tool, as well as the REVEAL 2.0 and REVEAL Lite 2 based risk stratification, lack accuracy to predict mortality in intermediate- and high-risk precapillary pulmonary hypertension patients. An expanded non-invasive evaluation improves mortality risk prediction in these individuals.

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