scholarly journals External Validation of a Nomogram to Predict Survival and Benefit of Concurrent Chemoradiation for Stage II Nasopharyngeal Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4286
Author(s):  
Pui-Lam Yip ◽  
Shing-Fung Lee ◽  
Cheuk-Wai Horace Choi ◽  
Po-Chung Sunny Chan ◽  
Ka-Wai Alice Cheung ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
External Validation ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage Ii ◽  
Concurrent Chemoradiation ◽  
Clinical Parameters ◽  
Concordance Index

A nomogram was recently published by Sun et al. to predict overall survival (OS) and the additional benefit of concurrent chemoradiation (CCRT) vs. radiotherapy (RT) alone, in stage II NPC treated with conventional RT. We aimed to assess the predictors of OS and to externally validate the nomogram in the IMRT era. We analyzed stage II NPC patients treated with definitive RT alone or CCRT between 2001 and 2011 under the territory-wide Hong Kong NPC Study Group 1301 study. Clinical parameters were studied using the Cox proportional hazards model to estimate OS. The nomogram by Sun et al. was applied with 1000 times bootstrap resampling to calculate the concordance index, and we compared the nomogram predicted and observed 5-year OS. There were 482 patients included. The 5-year OS was 89.0%. In the multivariable analysis, an age > 45 years was the only significant predictor of OS (HR, 1.98; 95%CI, 1.15–3.44). Other clinical parameters were insignificant, including the use of CCRT (HR, 0.99; 95%CI, 0.62–1.58). The nomogram yielded a concordance index of 0.55 (95% CI, 0.49–0.62) which lacked clinically meaningful discriminative power. The nomogram proposed by Sun et al. should be interpreted with caution when applied to stage II NPC patients in the IMRT era. The benefit of CCRT remained controversial.

scholarly journals Is there a measurable association of epidural use at cystectomy and postoperative outcomes? A population-based study

2016 ◽  
Vol 10 (9-10) ◽  
pp. 321 ◽  
Author(s):  
R. Christopher Doiron ◽  
Melanie Jaeger ◽  
Christopher M. Booth ◽  
Xuejiao Wei ◽  
D. Robert Siemens
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Long Term Outcomes ◽  
Cancer Specific Survival ◽  
Factors Associated ◽  
Provider Volume

Introduction: Thoracic epidural analgesia (TEA) is commonly used to manage postoperative pain and facilitate early mobilization after major intra-abdominal surgery. Evidence also suggests that regional anesthesia/analgesia may be associated with improved survival after cancer surgery. Here, we describe factors associated with TEA at the time of radical cystectomy (RC) for bladder cancer and its association with both short- and long-term outcomes in routine clinical practice.Methods: All patients undergoing RC in the province of Ontario between 2004 and 2008 were identified using the Ontario Cancer Registry (OCR). Modified Poisson regression was used to describe factors associated with epidural use, while a Cox proportional hazards model describes associations between survival and TEA use.Results: Over the five-year study period, 1628 patients were identified as receiving RC, 54% (n=887) of whom received TEA. Greater anesthesiologist volume (lowest volume providers relative risk [RR] 0.85, 95% confidence interval [CI] 0.75‒0.96) and male sex (female sex RR 0.89, 95% CI 0.79‒0.99) were independently associated with greater use of TEA. TEA use was not associated with improved short-term outcomes. In multivariable analysis, TEA was not associated with cancer-specific survival (hazard ratio [HR] 1.02, 95% CI 0.87‒1.19; p=0.804) or overall survival (HR 0.91, 95% CI 0.80‒1.03; p=0.136).Conclusions: In routine clinical practice, 54% of RC patients received TEA and its use was associated with anesthesiologist provider volume. After controlling for patient, disease and provider variables, we were unable to demonstrate any effect on either short- or long-term outcomes at the time of RC.

Microsatellite instability (MSI) in stage II and III colon cancer treated with 5FU-LV or 5FU-LV and irinotecan (PETACC 3-EORTC 40993-SAKK 60/00 trial)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4001-4001 ◽  
Author(s):  
S. Tejpar ◽  
F. Bosman ◽  
M. Delorenzi ◽  
R. Fiocca ◽  
P. Yan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Multiple Testing ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Biological Effects ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage Ii ◽  
Stage Iii

4001 Background: Patients with high MSI (MSI H) tumors are increasingly being recognized as a prognostic and predictive subgroup in colon cancer (COC). We investigated the incidence of MSI-H in stage II (n=395) and stage III (n=859) COC, its association with histopathological variables and its prognostic and predictive impact. Methods: The study accrued 3278 patients with Stage II and Stage III COC to receive post-operative 5-FU -LV with or without irinotecan (IRI). Paraffin tissue blocks of 1327/1405 available patients were successfully analyzed for MSI status using the NCI extended panel of 10 markers. MSI-H was defined as instability in ≥3 markers. Relapse Free Survival (RFS) and Overall Survival (OS, median follow up 68 months) were assessed. Results: MSI H was present in 22% (85) of Stage II and 12% (103)of Stage III colon cancer . MSI H status was significantly associated with age <60, higher T stage, higher grade, lower N stage and right sided tumor location. The table presents univariate RFS and OS hazard rates (with 95% confidence intervals) for prognostic and predictive impact per stage and arm, estimated by a survival regression analysis using Cox proportional hazards model and of selected P values by Wald tests. Conclusions: Microsatellite instability is a strong prognostic factor for RFS and OS when considering Stage II and Stage III COC. Subgroup analysis suggests a stronger effect in Stage II than in Stage III, but is limited by sample size and multiple testing. Taken together with differences in incidence between the stages, this may suggest stage specific biological effects of MSI. In contrast to previous reports (a) in Stage II the prognostic effect of MSI remained significant even in pts treated with 5FU (w/o IRI),(b) There is no evidence for an effect of the addition of IRI. [Table: see text] [Table: see text]

Clinical features and outcomes of secondary somatic malignancy (SSM) arising from teratoma in late relapse germ cell tumor (GCT).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 518-518
Author(s):  
Nathan Colin Wong ◽  
Shawn Dason ◽  
Lucas W. Dean ◽  
Sumit Isharwal ◽  
Mark Donoghue ◽  
...  
Keyword(s):  
Median Time ◽  
Surgical Resection ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Late Relapse ◽  
Hazards Model ◽  
Kaplan Meier

518 Background: Late relapse (>2 years) GCT is associated with an increased rate of SSM. We report our experience with SSM in the setting of late relapse and determine predictors of overall survival (OS). Methods: From 1985 to 2018, 46 patients with GCT and SSM at late relapse were identified. Clinical and pathologic parameters were reviewed. The Kaplan-Meier method was used to estimate OS from time of relapse and a Cox proportional hazards model to assess predictors of OS. Results: Of 46 men (44 testicular primary, 2 mediastinal primary), median time to late relapse with SSM was 10.4 years (range, 2.3 - 38.1). Most (n=27, 59%) were symptomatic at presentation but 11 were detected by elevated tumor markers (AFP 8, HCG 2, both 1) and 8 by surveillance imaging. SSMs were adenocarcinoma (25), sarcoma (14), poorly differentiated neoplasm (3), Wilms (2), PNET (1) and glioma (1). Median time to relapse was longer for adenocarcinoma vs other histotypes of SSM (14.6 vs 4.1 years, p < 0.001). The initial site of relapse was the retroperitoneum (RP, 26), pelvis (7), lung (6), retrocrural space (3), mediastinum (2), neck (1) and duodenum (1). Only 10 of 26 men with late relapse in the RP had undergone prior RPLND (all at outside institutions; variable templates) with histology in 7/10 showing teratoma. The other 16 men had received chemotherapy only (8), orchiectomy only for stage I (3), RPLND aborted due to cardiac arrest (1), and unknown (4). All 46 late relapses were managed with surgical resection; 26 also received chemotherapy (16 SSM-directed, 10 GCT-directed). Overall, 12 patients died and the median OS was 14.2 years. On univariable analysis, symptomatic presentation (HR = 3.1), SSM at multiple sites (HR = 3.9), extra-RP disease (HR: 3.9), and incomplete/no resection of SSM (HR = 3.6) predicted mortality. On multivariable analysis, only extra-RP disease was independently associated with inferior OS (5-year OS, 82 vs 52%, p = 0.017). Conclusions: SSM is an important potential complication of late relapse GCT and seems to be associated with the lack of resection of retroperitoneal metastases. Early identification and complete surgical resection prior to SSM arising in extra-RP sites is critical to optimizing outcomes.

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.

Association of radiation therapy with overall survival in patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 528-528
Author(s):  
David Mitchell Marcus ◽  
Dana Nickleach ◽  
Bassel F. El-Rayes ◽  
Jerome Carl Landry
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Entire Cohort ◽  
The Impact

528 Background: The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiation followed by surgery, but many physicians question the benefit of multimodality therapy in patients with stage T3N0M0 disease. We aimed to determine the impact of radiation therapy (RT) on overall survival (OS) in this group of patients. Methods: We used the Surveillance, Epidemiology, and End Results database to identify patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum from 2004 to 2010. The Kaplan-Meier method was used to compare OS for patients receiving RT vs. no RT, along with for pre-op vs. post-op RT among patients that received RT. Multivariable analysis (MVA) using a Cox proportional hazards model was performed to assess the association of RT with OS after adjusting for patient age, gender, race, tumor grade, carcinoembryonic antigen, type of surgery, and circumferential margin status. The analysis was repeated separately on patients that underwent total colectomy (TC) vs. sphincter-sparing surgery. Results: The cohort included 8,679 patients, including 4,705 who received RT and 3,974 who did not. Median age was 66 years. Five year OS was 76.5% in patients who received RT, compared to 60.0% in patients who did not receive RT (p <0.001). Five year OS was 76.9% for patients receiving pre-op RT vs. 75.7% in patients receiving post-op RT (p = 0.247). In patients undergoing TC, five year OS was 74.7% for patients receiving RT, compared to 47.5% in patients not receiving RT (p <0.001). In patients undergoing sphincter-sparing surgery, five year OS was 77.7% in patients receiving RT, compared to 62.9% in patients not receiving RT (p <0.001). Use of RT was significantly associated with OS on MVA, both in the entire cohort (HR 0.70 [95% CI 0.60-0.81]; p<0.001) and in subsets of patients undergoing TC (HR 0.55 [95% CI 0.38-0.79]; p=0.001) and sphincter-sparing surgery (HR 0.70 [95% CI 0.59-0.84]; p<0.001). Conclusions: The use of RT is associated with superior OS in patients undergoing surgery for T3N0M0 adenocarcinoma of the rectum. This benefit is demonstrated in both the pre-op and post-op settings and applies to patients undergoing both TC and sphincter-sparing surgery.

Germline polymorphisms in genes maintaining replication fork to predict the efficacy of oxaliplatin and irinotecan in metastatic colorectal cancer (mCRC) patients enrolled in MAVERICC trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3139-3139
Author(s):  
Hiroyuki Arai ◽  
Yi Xiao ◽  
Jingyuan Wang ◽  
Francesca Battaglin ◽  
Natsuko Kawanishi ◽  
...  
Keyword(s):  
Predictive Value ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Dna Lesions ◽  
Cox Proportional Hazards Model ◽  
Replication Forks ◽  
Univariable Analysis ◽  
Snp Interaction

3139 Background: Protection of replication forks is critical for the survival of cancer cells. Chemotherapeutic drugs such as oxaliplatin and irinotecan can impede the progression of replication forks by inducing DNA lesions, which cause fork collapse and generate double-strand breaks. We hypothesized that functional genetic variants in genes involved in the maintenance of replication forks may predict the efficacy of cytotoxic drugs in mCRC patients. Methods: We analyzed genomic and clinical data from MAVERICC, a phase II trial which compared mFOLFOX6 and FOLFIRI in combination with bevacizumab in untreated mCRC patients. Genomic DNA extracted from blood samples was genotyped using an OncoArray (Illumina, Inc., San Diego, CA, USA). Candidate six missense single nucleotide polymorphisms (SNPs) ( SLFN11 rs9898983, SLFN11 rs12453150, RPA1 rs5030749, MCM3 rs2230240, TIMELESS rs2291739, and TIMELESS rs774047) were tested for association with progression-free survival (PFS) and overall survival (OS), using Cox proportional hazards model. To confirm the predictive value, the treatment-by-SNP interaction was tested. Results: A total of 324 patients were available for the SNP analyses (mFOLFOX6 plus bevacizumab arm [OHP arm]: n = 161; FOLFIRI plus bevacizumab arm [IRI arm]: n = 163). In the OHP arm, univariable analysis showed a significantly better PFS in patients with G/G genotype of TIMELESS rs2291739 compared to those with any A allele, and in patients with T/T genotype of TIMELESS rs774047 compared to those with any C allele. However, neither of these SNP’s associations were confirmed by multivariable analysis: TIMELESS rs2291739 (any A allele vs G/G, hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.31–1.17, p = 0.12) and TIMELESS rs774047 (any C allele vs T/T, HR = 0.74, 95% CI = 0.41–1.36, p = 0.33). In the IRI arm, univariable analysis showed a significantly worse OS in patients with G/G genotype of TIMELESS rs2291739 compared to those with any A allele, and in patients with T/T genotype of TIMELESS rs774047 compared to those with any C allele. Multivariable analysis confirmed the significant associations in these SNPs: TIMELESS rs2291739 (any A allele vs G/G, HR = 3.06, 95% CI = 1.49–6.25, p < 0.01) and TIMELESS rs774047 (any C allele vs T/T, HR = 2.95, 95% CI = 1.43–6.08, p < 0.01). Treatment-by-SNP interaction test confirmed the significant predictive value of both SNPs, both on PFS and OS. Conclusions: Germline polymorphisms in the TIMELESS gene involved in the protection of replication forks may predict efficacy of oxaliplatin and irinotecan in mCRC patients. Our novel findings warrant further validation studies.

Neutrophil/lymphocyte ratio (NLR) as a prognostic factor in biliary tract cancer (BTC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4130-4130
Author(s):  
Mairead Geraldine McNamara ◽  
Arnoud J. Templeton ◽  
Manjula Maganti ◽  
Thomas Walter ◽  
Anne M Horgan ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Inflammatory Marker ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cancer Center ◽  
Neutrophil Lymphocyte Ratio ◽  
Tract Cancer

4130 Background: BTCs include intrahepatic (IHC), hilar, distal bile duct (DBD), and gallbladder carcinoma (GBC). Risk factors include conditions associated with chronic inflammation. NLR, an inflammatory marker, is prognostic in several cancers but has not been reviewed in large BTC series, hilar or GBC. Methods: Baseline demographics and NLR at diagnosis were evaluated in 864 patients (pts) with BTC from 01/87 - 12/12 treated at Princess Margaret Cancer Center. Their prognostic significance for overall survival (OS) was determined using a Cox proportional hazards model. Results: High NLR ≥3.0 was associated with poor survival using univariable analysis as was stage/site of primary (P<0.05), age >65yrs, lymphocytes ≤1.6 (P<0.01), neutrophils ≥5.0, platelets ≥280, hemoglobin (Hb) < 110 g/L (P<0.001). Median OS in pts with NLR<3.0 was 21.6 mo, 12.0 mo with NLR ≥3.0 (P<0.001). NLR retained its significance as a prognostic marker on multivariable analysis (Table), along with GBC (P<0.05), age>65yrs, DBD primary (P<0.01), stage and Hb <110g/L (P<0.001). NLR was prognostic for OS on multivariable analysis for hilar: overall (Table) and advanced grp (n=102) (HR 1.68, 95%CI 1.07-2.64, P<0.05) and in advanced DBD (n=102) (HR 1.63, 95%CI 1.03-2.57,P<0.05). On subgrp analysis, NLR was prognostic for OS in advanced BTC (ABTC) (n=538) (P<0.01) but not in surgical grp. NLR did not predict RECIST response to first line palliative chemotherapy in ABTC. Conclusions: Baseline NLR is prognostic in BTC, specifically ABTC and hilar subgrp, suggesting the importance of systemic inflammation influencing outcome in pts with ABTC, thus providing a simple inexpensive prognostic biomarker while also possibly identifying pts that may benefit from antiinflammatory mediation. NLR was not predictive for response in BTC. [Table: see text]

The role of adjuvant therapy after R0 resection for patients with intrahepatic and perihilar cholangiocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 302-302
Author(s):  
Young Saing Kim ◽  
Inkeun Park ◽  
Sung Yong Oh ◽  
Se-Il Go ◽  
Jung Hun Kang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Adjuvant Therapy ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
R0 Resection ◽  
Node Positive

302 Background: There is still debated regarding the optimal treatment strategy in cholangiocarcinoma (CC) after curative resection. The aim of this study was to analyze the role of adjuvant therapy in R0-resected intrahepatic and perihilar CC. Methods: We retrospectively reviewed the medical records of patients who underwent R0 resection for intrahepatic and perihilar CC between January 2001 and December 2013 at six cancer centers. Adjuvant therapy consisted of chemotherapy (CT), chemoradiotherapy (CRT), or radiotherapy (RT). The outcomes of our study were recurrence-free survival (RFS) and overall survival (OS). Multivariable Cox proportional hazards model was used to identify prognostic factors for survival. Results: A total of 137 patients were included in the analysis; 58.4% of patients had intrahepatic CC and 25.5% had lymph node involvement. Seventy-three patients (53.3%) received adjuvant therapy (CT/CRT/RT: 48/13/12, respectively). A greater percentage of patients receiving adjuvant therapy had stage III-IVA (P = 0.010), high histologic grade (P = 0.035), and positive lymph nodes (P = 0.088). Multivariable analysis identified positive nodes (hazard ratio (HR), 3.60; P < 0.001), poor tumor differentiation (HR, 2.35, P = 0.048), and high baseline CA 19-9 level (HR, 1.97; P = 0.013) as predictors of decreased OS. The effect of adjuvant therapy varied according to the treatment modality. Adjuvant CRT was significantly associated with longer RFS (HR, 0.44; P = 0.036) but OS benefit was non-significant HR, 0.56; P = 0.245). In node-positive patients, CRT had a trend for longer OS (HR, 0.24; P = 0.097). In contrast, CT did not improve RFS (HR, 1.13; P = 0.617) or OS (HR, 1.70; P = 0.114). RT alone was associated shorter RFS (HR 3.08; P = 0.009) and OS (HR, 6.86, P < 0.001). Conclusions: Adjuvant CT and RT were not associated with a survival advantage in R0-resected intrahepatic and perihilar CC. CRT appears to be appropriate treatment after complete resection especially in lymph node-positive patients.

scholarly journals A novel 14-gene signature for overall survival in lung adenocarcinoma based on the Bayesian hierarchical Cox proportional hazards model

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Na Sun ◽  
Jiadong Chu ◽  
Wei Hu ◽  
Xuanli Chen ◽  
Nengjun Yi ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Model ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
External Validation ◽  
Gene Signature ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Bayesian Hierarchical ◽  
Hazards Model

AbstractThere have been few investigations of cancer prognosis models based on Bayesian hierarchical models. In this study, we used a novel Bayesian method to screen mRNAs and estimate the effects of mRNAs on the prognosis of patients with lung adenocarcinoma. Based on the identified mRNAs, we can build a prognostic model combining mRNAs and clinical features, allowing us to explore new molecules with the potential to predict the prognosis of lung adenocarcinoma. The mRNA data (n = 594) and clinical data (n = 470) for lung adenocarcinoma were obtained from the TCGA database. Gene set enrichment analysis (GSEA), univariate Cox proportional hazards regression, and the Bayesian hierarchical Cox proportional hazards model were used to explore the mRNAs related to the prognosis of lung adenocarcinoma. Multivariate Cox proportional hazard regression was used to identify independent markers. The prediction performance of the prognostic model was evaluated not only by the internal cross-validation but also by the external validation based on the GEO dataset (n = 437). With the Bayesian hierarchical Cox proportional hazards model, a 14-gene signature that included CPS1, CTPS2, DARS2, IGFBP3, MCM5, MCM7, NME4, NT5E, PLK1, POLR3G, PTTG1, SERPINB5, TXNRD1, and TYMS was established to predict overall survival in lung adenocarcinoma. Multivariate analysis demonstrated that the 14-gene signature (HR 3.960, 95% CI 2.710–5.786), T classification (T1, reference; T3, HR 1.925, 95% CI 1.104–3.355) and N classification (N0, reference; N1, HR 2.212, 95% CI 1.520–3.220; N2, HR 2.260, 95% CI 1.499–3.409) were independent predictors. The C-index of the model was 0.733 and 0.735, respectively, after performing cross-validation and external validation, a nomogram was provided for better prediction in clinical application. Bayesian hierarchical Cox proportional hazards models can be used to integrate high-dimensional omics information into a prediction model for lung adenocarcinoma to improve the prognostic prediction and discover potential targets. This approach may be a powerful predictive tool for clinicians treating malignant tumours.

Oral Uracil and Tegafur Plus Leucovorin Compared With Intravenous Fluorouracil and Leucovorin in Stage II and III Carcinoma of the Colon: Results From National Surgical Adjuvant Breast and Bowel Project Protocol C-06

2006 ◽  
Vol 24 (13) ◽  
pp. 2059-2064 ◽  
Author(s):  
Barry C. Lembersky ◽  
H. Samuel Wieand ◽  
Nicholas J. Petrelli ◽  
Michael J. O'Connell ◽  
Linda H. Colangelo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Disease Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage Ii ◽  
Carcinoma Of The Colon ◽  
Primary Surgery ◽  
Stage Ii Colon Cancer

Purpose The primary aim of this study was to compare the relative efficacy of oral uracil and tegafur (UFT) plus leucovorin (LV) with the efficacy of weekly intravenous fluorouracil (FU) plus LV in prolonging disease-free survival (DFS) and overall survival (OS) after primary surgery for colon carcinoma. Patients and Methods Between February 1997 and March 1999, 1,608 patients with stage II and III carcinoma of the colon were randomly assigned to receive either oral UFT+LV or intravenous FU+LV. Results Of the total patients, 47% had stage II colon cancer, and 53% had stage III colon cancer. Median follow-up time was 62.3 months. The estimated hazard ratio (HR) for OS of patients who received UFT+LV versus that of patients who received FU+LV was 1.014 (95% CI, 0.825 to 1.246). The estimated HR for DFS was 1.004 (95% CI, 0.847 to 1.190). Cox proportional hazards model analyses with regard to age (< 60 v ≥ 60 years), stage, or number of involved nodes (none v one to three v ≥ four nodes) revealed no interaction with OS or DFS. Toxicity was similar in the two groups. In the UFT+LV arm, 38.2% of patients experienced any grade 3 or 4 toxic event compared with 37.8% of patients in the FU+LV arm. Primary quality-of-life end points did not differ between the two regimens, although convenience of care analysis favored UFT+LV. Conclusion UFT+LV achieved similar DFS and OS when compared with an intravenous, weekly, bolus FU+LV regimen. The two regimens were equitoxic and generally well tolerated.

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