Development and validation of a pediatric disease risk index for allogeneic hematopoietic cell transplantation.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7503-7503
Author(s):  
Muna Qayed ◽  
Carrie L Kitko ◽  
Kwang Woo Ahn ◽  
Mariam H Johnson ◽  
Kirk R. Schultz ◽  
...  
Keyword(s):  
High Risk ◽  
Hematopoietic Cell Transplantation ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Disease Risk ◽  
Risk Index ◽  
Risk Groups ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model

7503 Background: Characteristics such as disease, disease status and cytogenetic abnormalities impact relapse and survival after transplantation for acute myeloid (AML) and acute lymphoblastic (ALL) leukemia. In adults, these attributes were used to derive the disease risk index for survival. Thus, the current analysis sought to develop and validate a pediatric disease risk index (p-DRI). Methods: Eligible were patients aged <18 years with AML (n=1135) and ALL (n=1228) transplanted between 2008 and 2017 in the United States. Separate analyses were performed for AML and ALL. Patients were randomly assigned (1:1) to a training and validation cohort. Cox proportional hazards model with stepwise selection was used to select significant variables (2-sided p<0.05). The primary outcome was leukemia-free survival (LFS; relapse or death were events). Based on the magnitude of log(HR), a weighted score was assigned to each characteristic that met the level of significance and risk groups were created. Results: Four risk groups were identified for AML and three risk groups for ALL (Table). The 5-year probabilities of LFS for AML were 81% (68-91), 56% (51-61), 44% (39-49) and 21% (15-28) for good, intermediate, high and very high-risk groups, respectively. The 5-year probabilities of LFS for ALL were 68% (63-72), 50% (45-54) and 15% (3-34) for good, intermediate, high risk groups, respectively. Conclusions: This validated p-DRI successfully stratified children with AML and ALL for prognostication undergoing allogeneic transplantation. [Table: see text]

scholarly journals A novel nomogram to predict the overall survival in esthesinoeroblastoma

2020 ◽  
Author(s):  
Lijie Jiang ◽  
Tengjiao Lin ◽  
Yu Zhang ◽  
Wenxiang Gao ◽  
Jie Deng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Validation Cohort ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cancer Center ◽  
P Value ◽  
Training Cohort

Abstract Background Increasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established. Methods This study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were identified. The Pearson’s chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p- value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram. Results The c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups. Conclusions The nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.

scholarly journals Incidence and Survival Changes in Patients with Esophageal Adenocarcinoma during 1984–2013

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Zhang Haiyu ◽  
Pei Xiaofeng ◽  
Mo Xiangqiong ◽  
Qiu Junlan ◽  
Zheng Xiaobin ◽  
...  
Keyword(s):  
United States ◽  
Risk Factors ◽  
Esophageal Adenocarcinoma ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Potential Risk Factors

Purpose. The morbidity of esophageal adenocarcinoma (EAC) has significantly increased in Western countries. We aimed to identify trends in incidence and survival in patients with EAC in the recent 30 years and then analyzed potential risk factors, including race, sex, age, and socioeconomic status (SES). Methods. All data were collected from the Surveillance, Epidemiology, and End Results or SEER database. Kaplan–Meier analysis and the Cox proportional hazards model were conducted to compare the differences in survival between variables, including sex, race, age, and SES, as well as to evaluate the association of these factors with prognosis. Results. A total of 16,474 patients with EAC were identified from 1984 to 2013 in the United States. Overall incidence increased every 10 years from 1.8 to 3.1 to 3.9 per 100. Overall survival gradually improved (p<0.0001), which was evident in male patients ((hazard ratio (HR) = 1.111; 95% confidence interval (CI) (1.07, 1.15)); however, the 5-year survival rate remained low (20.1%). The Cox proportional hazards model identified old age, black ethnicity, and medium/high poverty as risk factors for EAC (HR = 1.018; 95% CI (1.017, 1.019; HR = 1.240, 95% CI (1.151,1.336), HR = 1.000, 95% CI (1.000, 1.000); respectively). Conclusions. The incidence of EAC in the United States increased over time. Survival advantage was observed in white patients and patients in the low-poverty group. Sex was an independent prognostic factor for EAC, but this finding has to be confirmed by further research.

Long-Term Survivors of Gastric Cancer: A California Population-Based Study

2012 ◽  
Vol 30 (28) ◽  
pp. 3507-3515 ◽  
Author(s):  
Pamela L. Kunz ◽  
Matthew Gubens ◽  
George A. Fisher ◽  
James M. Ford ◽  
Daphne Y. Lichtensztajn ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Gastroesophageal Junction ◽  
The United States ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Intestinal Histology ◽  
Hospital Size

Purpose In the United States, gastric cancer is rapidly fatal with a 25% 5-year survival. Of the few patients who survive, little is known about their demographic, clinical, and tumor characteristics. Patients and Methods Data regarding all cases of gastric and gastroesophageal junction (GEJ) adenocarcinoma diagnosed in California between 1988 and 2005 were obtained from the California Cancer Registry, a member of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. A Cox proportional hazards model was constructed to understand the independent relationships of patient demographic, disease, and treatment factors with survival. Results We identified 47,647 patients diagnosed with gastric or GEJ cancer. Of those, only 9,325 (20%) survived at least 3 years. Variables associated with longer survival were localized stage (hazard ratio [HR], 0.20), surgery with diagnosis in 2002 or later (HR, 0.34), surgery with diagnosis in 2001 or before (0.37), regional stage (HR, 0.53), chemotherapy (HR, 0.56), intestinal histology (HR, 0.74), well- or moderately differentiated tumors (HR, 0.76), radiation (HR, 0.80), Asian/Pacific Islander race (HR, 0.81), treatment at an academic hospital (HR, 0.85), fundus/body/antrum location (HR, 0.90), highest socioeconomic status quintile (HR, 0.91), female sex (HR, 0.92), Hispanic race (HR, 0.92), and hospital size more than 150 beds (HR, 0.94). Kaplan-Meier curves showed longer median disease-specific survival (DSS) in patients with tumors originating in the fundus/body/antrum compared with esophagus/cardia (13.4 v 10.8 months). Intestinal histology had significantly longer median DSS (28.9 months) compared with other (11.0 months) or diffuse (10.1 months) histology. Conclusion Patients who survive gastric and GEJ cancer more than 3 years after diagnosis have demographic and pathologic characteristics distinct from those who do not survive.

scholarly journals Survival Analysis of COVID-19 on Democracy with Cox Proportional Hazards Model

2020 ◽  
Author(s):  
Yue Zhao ◽  
Deepika Dilip
Keyword(s):  
United States ◽  
Survival Analysis ◽  
South Korea ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Effective Measure ◽  
Hazards Model

Abstract Background: The outbreak of Coronavirus disease 2019 (COVID-19) has struck us in many ways and we observed that China and South Korea found an effective measure to contain the virus. Conversely, the United States and the European countries are struggling to fight the virus. China is not considered a democracy and South Korea is less democratic than the United States. Therefore, we want to explore the association between the deaths of COVID-19 and democracy. Methods: We collected COVID-19 deaths data for each country from the Johns Hopkins University website and democracy indices of 2018 from the Economist Intelligence Unit website in May 2020. Then we conducted a survival analysis, regarding each country as a subject, with the Cox Proportional Hazards Model, adjusting for other selected variables. Result: The result showed that the association between democracy and deaths of COVID-19 was significant (P=0.04), adjusting for other covariates. Conclusion: In conclusion, less democratic governments performed better in containing the virus and controlling the number of deaths.

scholarly journals Use of the Living Kidney Donor Profile Index in the Canadian Kidney Transplant Recipient Population: A Validation Study

2020 ◽  
Vol 7 ◽  
pp. 205435812090697
Author(s):  
Mohamed Shantier ◽  
Yanhong Li ◽  
Monika Ashwin ◽  
Olsegun Famure ◽  
Sunita K. Singh
Keyword(s):  
Validation Study ◽  
Graft Failure ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
External Validation ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Living Kidney Donor ◽  
Hazards Model

Background: The Living Kidney Donor Profile Index (LKDPI) was derived in a cohort of kidney transplant recipients (KTR) from the United States to predict the risk of total graft failure. There are important differences in patient demographics, listing practices, access to transplantation, delivery of care, and posttransplant mortality in Canada as compared with the United States, and the generalizability of the LKDPI in the Canadian context is unknown. Objective: The purpose of this study was to externally validate the LKDPI in a large contemporary cohort of Canadian KTR. Design: Retrospective cohort validation study. Setting: Toronto General Hospital, University Health Network, Toronto, Ontario, Canada Patients: A total of 645 adult (≥18 years old) living donor KTR between January 1, 2006 and December 31, 2016 with follow-up until December 31, 2017 were included in the study. Measurements: The predictive performance of the LKDPI was evaluated. The outcome of interest was total graft failure, defined as the need for chronic dialysis, retransplantation, or death with graft function. Methods: The Cox proportional hazards model was used to examine the relation between the LKDPI and total graft failure. The Cox proportional hazards model was also used for external validation and performance assessment of the model. Discrimination and calibration were used to assess model performance. Discrimination was assessed using Harrell’s C statistic and calibration was assessed graphically, comparing observed versus predicted probabilities of total graft failure. Results: A total of 645 living donor KTR were included in the study. The median LKDPI score was 13 (interquartile range [IQR] = 1.1, 29.9). Higher LKDPI scores were associated with an increased risk of total graft failure (hazard ratio = 1.01; 95% confidence interval [CI] = 1.0-1.02; P = .02). Discrimination was poor (C statistic = 0.55; 95% CI = 0.48-0.61). Calibration was as good at 1-year posttransplant but suboptimal at 3- and 5-years posttransplant. Limitations: Limitations include a relatively small sample size, predicted probabilities for assessment of calibration only available for scores of 0 to 100, and some missing data handled by imputation. Conclusions: In this external validation study, the predictive ability of the LKDPI was modest in a cohort of Canadian KTR. Validation of prediction models is an important step to assess performance in external populations. Potential recalibration of the LKDPI may be useful prior to clinical use in external cohorts.

Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC): Outcomes in the combined IMDC intermediate/poor risk and sarcomatoid subgroups of the phase 3 KEYNOTE-426 study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4500-4500 ◽  
Author(s):  
Brian I. Rini ◽  
Elizabeth R. Plimack ◽  
Viktor Stus ◽  
Rustem Gafanov ◽  
Robert Hawkins ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Risk Group ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
First Line ◽  
Poor Risk ◽  
First Line Therapy ◽  
Line Therapy

4500 Background: In KEYNOTE-426, pembro + axi significantly improved OS (HR 0.53, P < .0001), PFS (HR 0.69, P = .0001), and ORR (59.3% vs 35.7%, P < .0001) vs sunitinib and had manageable toxicity as first-line therapy for mRCC (NCT02853331). The pembro + axi benefit was observed across all IMDC risk groups and regardless of PD-L1 expression. We present data for the combined intermediate/poor risk group and for patients (pts) with sarcomatoid features. Methods: 861 eligible pts with clear-cell mRCC, no prior systemic therapy for mRCC, and KPS ≥70 were randomized 1:1 to pembro 200 mg IV Q3W for a maximum of 35 cycles plus axi 5 mg orally BID (N = 432) or sunitinib 50 mg orally QD (4-wk on/2-wk off) (N = 429). Primary endpoints were OS and PFS (RECIST v1.1 by blinded, independent central review [BICR]). ORR (RECIST v1.1 by BICR) was the key secondary endpoint. The intermediate/poor risk group was prespecified; the sarcomatoid group was exploratory. HRs and their 95% CIs were calculated with a Cox proportional hazards model. None of the analyses were multiplicity-controlled. Results: 592 (68.8%) of all randomized pts were of IMDC intermediate/poor risk — 294 in the pembro + axi arm, 298 in the sunitinib arm. Pembro + axi improved OS (HR 0.52, 95% CI 0.37-0.74; 12-mo rate 87.3% vs 71.3%), PFS (HR 0.67, 95% CI 0.53-0.85; median 12.6 vs 8.2 mo), and ORR (55.8% [95% CI 49.9-61.5] vs 29.5% [24.4-35.1]) in pts with intermediate/poor risk; CR rates were 4.8% (95% CI 2.6-7.9) vs 0.7% (0.1-2.4). Of the 578 pts with known status, 105 (18.2%) had sarcomatoid features — 51 in the pembro + axi arm, 54 in the sunitinib arm. Pembro + axi improved OS (HR 0.58, 95% CI 0.21-1.59; 12-mo rate 83.4% vs 79.5%), PFS (HR 0.54, 95% CI 0.29-1.00; median not reached vs 8.4 mo), and ORR (58.8% [95% CI 44.2-72.4] vs 31.5% [19.5-45.6]) in pts with sarcomatoid features; CR rates were 11.8% (95% CI 4.4-23.9) vs 0% (0.0-6.6). Conclusions: Pembro + axi provides benefit in the combined population of pts with IMDC intermediate or poor risk and in pts whose tumors had sarcomatoid features. The observed benefits were consistent with those seen in the total population. Clinical trial information: NCT02853331.

Tandem high-dose chemotherapy and autologous hematopoietic stem cell transplantation (SCT) compared to single SCT for relapsed/refractory germ cell tumors (GCT).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 572-572
Author(s):  
Deepak Kilari ◽  
Parameswaran Hari ◽  
Muna Qayed ◽  
Raphael Fraser ◽  
Omar Davila ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
High Dose ◽  
Hematopoietic Stem

572 Background: Single-center observational studies have established the use of single or tandem SCT to salvage relapsed GCT but randomized trials are lacking. We analyzed outcomes and prognostic factors in 2,395 male SCT recipients for relapsed GCT between 1990 and 2015. Methods: Recipients of single or tandem SCT reported to the Center for International Blood and Marrow Transplant Research were identified. Outcomes were compared by SCT year: 1990-94 (N = 288), 1995-99 (N = 351), 2000-04 (N = 376), 2005-09 (N = 509) and 2010-15 (N = 871). A recent subset (n = 267, 2000-2015) with detailed disease- and transplant-related data was further analyzed with a multivariate (MVA) Cox proportional hazards model. Results: Median age at SCT was 31 (11-76) years and 49% received SCT within 12 months of diagnosis consistent with early relapse/primary refractory GCT. 26% had primary extragonadal GCT; 1,167 (49%) had intent to tandem transplant (TT). The median follow up was 51 (3-313) months. Day 100 non-relapse mortality was statistically similar at 8% in 1990-94 (vs. 4% in 2010-15) but 3-year progression-free survival (PFS) improved from 24 (18-31)% in 1990-94 to 47 (43-50)% in 2010-15 (p < 0.0001) and 3-year survival (OS) from 35 (29-40)% to 54 (50-57)% in 2010-15 (p < 0.0001). Compared with single SCT, TT recipients were younger 31 (16-62) vs 34 (13-76), with lower Hematopoietic Cell Transplantation-Comorbidity Index, more likely to undergo SCT after 1 line of chemotherapy (28% vs 9%), and within 1 year of diagnosis (51% vs 38%). TT was preferred over single SCT over time (48% of SCT were TT in 2000-04 vs. 81% in 2010-15). In MVA, non-seminoma histology, residual tumor at SCT, receipt of > 1 line of pre-SCT chemotherapy and single SCT (vs. TT), were associated with worse PFS and OS. Year of SCT was not significant when adjusted for these covariates. Conclusions: In this large longitudinal cohort, improvements in PFS and OS were observed in recent years. SCT earlier in disease course and tandem SCT were associated with superior outcomes. These data involving a large cohort reported from 225 centers confirm specialized centers’ date in a real-world setting.

Molecular determinants of outcome for metastatic castration-sensitive prostate cancer (mCSPC) with addition of apalutamide (APA) or placebo (PBO) to androgen deprivation therapy (ADT) in TITAN.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5535-5535 ◽  
Author(s):  
Felix Y Feng ◽  
Shibu Thomas ◽  
Clemente Aguilar-Bonavides ◽  
Michael Gormley ◽  
Neeraj Agarwal ◽  
...  
Keyword(s):  
High Risk ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Molecular Subtypes ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
P Value ◽  
Average Risk ◽  
Luminal A

5535 Background: In TITAN, addition of APA to ADT improved radiographic progression-free survival (rPFS) and overall survival (OS) versus PBO plus ADT in patients (pts) with mCSPC. In this post hoc analysis, we performed transcriptome-wide profiling of tumor samples and assessed association of molecular subtypes with rPFS. Methods: The DECIPHER platform (Decipher Biosciences, Inc.) was used to assess gene expression in archival primary prostate tumors from TITAN. Samples were classified into high versus low to average risk of metastases (DECIPHER genomic classifier [GC] > 0.6 and ≤ 0.6, respectively), basal and luminal A/B (PAM50 classifier), and androgen receptor activity (AR-A) signature high and low. Associations between subtypes with rPFS were assessed with Cox proportional hazards model. Results: The biomarker population included 222 pts (APA, 110; PBO, 112). Benefit in rPFS from APA in the biomarker population (HR [95% CI]; p value; 0.49 [0.31-0.78]; 0.002) resembled that in the overall study population (0.49 [0.40-0.61]; < 0.0001). The majority of TITAN pts had GC high scores (n = 166, 75%). GC high risk subtype in the PBO group had poorer prognosis for rPFS than GC low to average risk subtype (median rPFS 18.2 mos for GC high vs not reached [NR] for GC low to average, 0.28 [0.11-0.69]; 0.006), but there was no difference in prognosis between high and low to average GC risk subtypes in the APA group (GC high NR vs GC low to average NR; 0.81 [0.35-1.89]; 0.625). Pts were further stratified based on basal/luminal and AR-A signatures. Basal (n = 112, 50%) and AR-A low (n = 96, 43%) subtypes, known to be nonresponsive to ADT, both showed significant benefit from APA vs PBO (0.30 [0.16-0.57]; < 0.001 and 0.25 [0.12-0.52]; < 0.001, respectively). The majority of AR-A low subtype (74%, 71/96) overlapped with basal subtype. Further conclusions for risk of rPFS in GC low, luminal, and AR-A high subtypes and OS across all subtypes will be assessed as more events occur. Conclusions: In TITAN, addition of APA to ADT improved rPFS for all subtypes of pts with mCSPC. APA overcame the poor prognosis of GC high risk subtype and prolonged rPFS in ADT-resistant AR-A low and basal molecular subtypes, suggesting APA is beneficial especially for the highest risk molecular subtypes. Clinical trial information: NCT02489318 .

scholarly journals Adjuvant Fuzheng Huayu Capsule Reduces the Incidence of Hepatocellular Carcinoma in Patients with Hepatitis B-Caused Cirrhosis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ke Shi ◽  
Yao Liu ◽  
Xiaojing Wang ◽  
Yuxin Li ◽  
Qun Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B ◽  
Lower Risk ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Antiviral Treatment ◽  
Risk Index ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Control Group

Aim. Fuzhenghuayu (FZHY) capsule can inhibit the progression of cirrhosis. This study explored whether FZHY can reduce the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B-caused cirrhosis (HBC) undergoing antiviral therapy. Methods. A retrospective review of 842 patients with HBC between 2011 and 2015 was performed, including 270 treated with FZHY combined with nucleos (t) ide analogues (NAs) and 572 with NAs alone. The incidence of HCC was compared between the FZHY (n = 259) and control (n = 259) groups using 1 : 1 propensity score (PS) matching. The incidence of HCC in patients with HBC with different Child-Turcotte-Pugh (CTP) classifications and Toronto HCC risk index (THRI) scores was analyzed using Kaplan–Meier curves. Results. The 5-year cumulative incidence of HCC before and after PS matching was 151 (17.9%) and 86 (16.6%), respectively. In PS-matched samples, the multivariate Cox proportional-hazards model indicated that the FZHY group demonstrated a significantly lower risk for HCC than the control group (adjusted hazard ratio [aHR] = 0.32, 95% CI 0.19–0.53 P < 0.001 ). The risk of HCC diminished with increased duration of FZHY use. The stratified analysis revealed that the FZHY group, regardless of CTP classification, benefited significantly from FZHY therapy. Patients in the medium- and high-THRI risk groups were the dominant population for FZHY. Conclusions. FZHY combined with NAs was associated with a significantly lower risk of HCC than NAs alone in patients with HBC, which supports the integration of FZHY with antiviral treatment into clinical practice.

scholarly journals Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lisa M. Hess ◽  
Yimei Han ◽  
Yajun Emily Zhu ◽  
Naleen Raj Bhandari ◽  
Anthony Sireci
Keyword(s):  
Proportional Hazards ◽  
Tumor Response ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Exact Test ◽  
Metastatic Nsclc ◽  
Baseline Covariates

Abstract Background Contradictory and limited data are available about the presentation and outcomes of patients with RET-fusion positive metastatic NSCLC as compared to patients without RET fusions. This observational study utilizing a linked electronic health records (EHR) database to genomics testing results was designed to compare characteristics, tumor response, progression-free (PFS) and overall survival (OS) outcomes by RET fusion status among patients with metastatic NSCLC treated with standard therapies. Methods Adult patients with metastatic NSCLC with linked EHR and genomics data were eligible who received systemic anti-cancer therapy on or after January 1, 2011. Adjusted, using all available baseline covariates, and unadjusted analyses were conducted to compare tumor response, PFS and OS between patients with RET-fusion positive and RET-fusion negative disease as detected by next-generation sequencing. Tumor response outcomes were analysed using Fisher’s exact test, and time-to-event analyses were conducted using Cox proportional hazards model. Results There were 5807 eligible patients identified (RET+ cohort, N = 46; RET- cohort, N = 5761). Patients with RET fusions were younger, more likely to have non-squamous disease and be non-smokers and had better performance status (all p < 0.01). In unadjusted analyses, there were no significant differences in tumor response (p = 0.17) or PFS (p = 0.06) but OS was significantly different by RET status (hazard ratio, HR = 1.91, 95% CI:1.22–3.0, p = 0.005). There were no statistically significant differences by RET fusion status in adjusted analyses of either PFS or OS (PFS HR = 1.24, 95% CI:0.86–1.78, p = 0.25; OS HR = 1.52, 95% CI: 0.95–2.43, p = 0.08). Conclusions Patients with RET fusions have different baseline characteristics that contribute to favorable OS in unadjusted analysis. However, after adjusting for baseline covariates, there were no significant differences in either OS or PFS by RET status among patients treated with standard therapy prior to the availability of selective RET inhibitors.

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