scholarly journals Moving beyond the Cox proportional hazards model in survival data analysis: a cervical cancer study

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e033965
Author(s):  
Lixian Li ◽  
Zijing Yang ◽  
Yawen Hou ◽  
Zheng Chen
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Figo Stage ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Time Varying ◽  
Node Metastasis ◽  
Hazards Model

ObjectivesThis study explored the prognostic factors and developed a prediction model for Chinese-American (CA) cervical cancer (CC) patients. We compared two alternative models (the restricted mean survival time (RMST) model and the proportional baselines landmark supermodel (PBLS model, producing dynamic prediction)) versus the Cox proportional hazards model in the context of time-varying effects.Setting and data sourcesA total of 713 CA women with CC and available covariates (age at diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis and radiation) from the Surveillance, Epidemiology and End Results database were included.DesignWe applied the Cox proportional hazards model to analyse the all-cause mortality with the proportional hazards assumption. Additionally, we applied two alternative models to analyse covariates with time-varying effects. The performances of the models were compared using the C-index for discrimination and the shrinkage slope for calibration.ResultsOlder patients had a worse survival rate than younger patients. Advanced FIGO stage patients showed a relatively poor survival rate and low life expectancy. Lymph node metastasis was an unfavourable prognostic factor in our models. Age at diagnosis, FIGO stage and lymph node metastasis represented time-varying effects from the PBLS model. Additionally, radiation showed no impact on survival in any model. Dynamic prediction presented a better performance for 5-year dynamic death rates than did the Cox proportional hazards model.ConclusionsWith the time-varying effects, the RMST model was suggested to explore diagnosis factors, and the PBLS model was recommended to predict a patient’s w-year dynamic death rate.

scholarly journals Prognosis of Stage IIB early gastric cancer has a unique and dismal property putatively requiring post operative adjuvant chemothrapy

2017 ◽  
Author(s):  
Hideki Ushiku ◽  
Keishi Yamashita ◽  
Akira Ema ◽  
Natsuya Katada ◽  
Kei Hosoda ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factors ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cancer Prognosis ◽  
Node Metastasis ◽  
Dismal Prognosis

Abstract Background Pathological T1 (pT1) gastric cancer showed excellent prognosis, however lymph node metastasis sometimes reflects patients with dismal prognosis. In this study, we investigated prognosis of pT1 gastric cancer with lymph node metastasis to identify prognostic factors. Patients and Methods Among 1,442 gastric cancer patients between 2002 and 2010, 73 (5%) of pT1 with lymph node metastasis were identified. Univariate prognostic factors were applied to multivariate Cox proportional hazards model. Results (1) Among the 1,442 patients, pT1 was composed of 333 patients with pT1a and 423 patients with pT1b, which included 9 (2.7%) and 64 cases (15.1%) with lymph node metastasis, respectively. (2) Ten (13.7%) patients of the 73 patients with lymph node metastasis showed tumor relapse.　　Univariate negative prognostic factors were tumor size (p=0.03), intraoperative bleeding (p=0.03), and perioperative transfusion (POT)(p=0.001), as well as 14th JGCA Stage (p<0.0001), and multivariate analysis identified 14th JGCA Stage (p=0.0004) and POT (p=0.03) as independent prognostic factors. (3) pT1 gastric cancer representing pN3 (Stage IIB) was rare (n=4) and unique entity from a prognostic point of view, exhibiting dismal prognosis (0% at 5 years). We thereafter identified 17 such cases from 5,204 gastric cancer including the earliest cases. Prognosis of such 17 patients was very unique, in that recurrences occurred even 5 years after curative operation, and the frequent recurrent sites were bone. Conclusion pT1 gastric cancer prognosis is robustly affected by pN3 and POT, and Stage IIB disease showed unique prognosis requiring special attention even after 5 years of operation.

scholarly journals Survival on four-times-per-week compared with three times a week haemodialysis in high ultrafiltration patients: an observational study

2020 ◽  
Author(s):  
James Fotheringham ◽  
Nicholas Latimer ◽  
Marc Froissart ◽  
Florian Kronenberg ◽  
Peter Stenvinkel ◽  
...  
Keyword(s):  
Observational Study ◽  
Vascular Access ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Time Varying ◽  
Cardiovascular Comorbidities ◽  
Hazards Model ◽  
Access Complications

Abstract Background The harm caused by the long interdialytic interval in three-times-per-week haemodialysis regimens (3×WHD) may relate to fluid accumulation and associated high ultrafiltration rate (UFR). Four-times-per-week haemodialysis (4×WHD) may offer a solution, but its impact on mortality, hospitalization and vascular access complications is unknown. Methods From the AROii cohort of incident in-centre haemodialysis patients, 3×WHD patients with a UFR >10 mL/kg/h were identified. The hazard for the outcomes of mortality, hospitalization and vascular access complications in those who switched to 4×WHD compared with staying on 3×WHD was estimated using a marginal structural Cox proportional hazards model. Adjustment included baseline patient and treatment characteristics with inverse probability weighting used to adjust for time-varying UFR and cardiovascular comorbidities. Results From 10 637 European 3×WHD patients, 3842 (36%) exceeded a UFR >10 mL/kg/h. Of these, 288 (7.5%) started 4×WHD and at baseline were more comorbid. Event rates while receiving 4×WHD compared with 3×WHD were 12.6 compared with 10.8 per 100 patient years for mortality, 0.96 compared with 0.65 per year for hospitalization and 14.7 compared with 8.0 per 100 patient years for vascular access complications. Compared with 3×WHD, the unadjusted hazard ratio (HR) for mortality on 4×WHD was 1.05 [95% confidence interval (CI) 0.78–1.42]. Following adjustment for baseline demographics, time-varying treatment probability and censoring risks, this HR was 0.73 (95% CI 0.50–1.05; P = 0.095). Despite these adjustments on 4×WHD, the HR for hospitalization remained elevated and vascular access complications were similar to 3×WHD. Conclusions This observational study was not able to demonstrate a mortality benefit in patients switched to 4×WHD. To demonstrate the true benefits of 4×WHD requires a large, well-designed clinical trial. Our data may help in the design of such a study.

scholarly journals Significance of the dissection of common hepatic arterial lymph nodes in patients with oesophageal carcinoma: a multicentre retrospective study

BMJ Open ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. e050280
Author(s):  
Huang-He He ◽  
Zhexue Hao ◽  
Zhuoyi Li ◽  
Fei Cheng ◽  
Junhui Fu ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymph Node Dissection ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Node Dissection ◽  
Node Metastasis ◽  
Enhanced Ct ◽  
Coeliac Trunk

ObjectivesTo explore the significance of intraoperative common hepatic arterial lymph node dissection in patients with ooesophageal squamous carcinoma (ESCC) without coeliac trunk lymph node metastasis indicated by abdominal enhanced CT.MethodsPatients aged 18–75 years who underwent oesophagectomy in three medical centres from June 2012 to June 2015, for whom R0 resection was completed and lymph node metastasis in the abdominal trunk was not identified before the operation were retrospectively analysed. The effects of the application value of common hepatic arterial lymph node dissection on survival were evaluated in patients with ESCC without coeliac trunk lymph node metastasis indicated by preoperative CT. According to the eighth version ofAmerican Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging, we selected patients with a Pathological Tumor Node Metastasis (pTNM) stage ranging from IA to IVA for analysis.ResultsAmong the 816 qualified patients, 577 did not have coeliac trunk lymph node metastasis based on preoperative abdominal enhanced CT, and common hepatic arterial lymph node dissection was performed during the operation (observation group). Two hundred and thirty-nine preoperative CT examinations indicated no coeliac trunk lymph node metastasis, and common hepatic arterial lymph node dissection was not performed during the operation (control group). A multifactor Cox proportional hazards model showed no risk factors for overall survival (OS) (adjusted HR (HRadj)=0.91; p=0.404) or disease-free survival (DFS) (HRadj=0.86; p=0.179), regardless of whether common hepatic arterial lymph node dissection was performed. For patients with positive left gastric arterial lymph node metastasis, a multifactor Cox proportional hazards model indicated that common hepatic arterial lymph node dissection was a risk factor for OS (HRadj=0.63; p=0.035) and DFS (HRadj=0.58; p=0.026).ConclusionsFor patients with ESCC without celiac trunk metastasis indicated by abdominal enhanced CT, common hepatic arterial lymph node dissection conferred no survival benefits. However, for patients with left gastric arterial lymph node metastasis, common hepatic arterial lymph node dissection was beneficial.

scholarly journals P326 Reasons for and effectiveness of switching back to originator infliximab after a prior switch to CT-P13 biosimilar

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S316-S317
Author(s):  
S Mahmmod ◽  
J P D Schultheiss ◽  
A C I T L Tan ◽  
M W M D Lutgens ◽  
L P L Gilissen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Time Varying ◽  
Loss Of Response ◽  
Hazards Model ◽  
Initial Conversion

Abstract Background In current clinical practice, patients with inflammatory bowel disease (IBD) treated with originator infliximab (IFX) have been or are being switched to biosimilar infliximab (CT-P13) because of lower costs and seemingly similar effectiveness of biosimilars. Over a one-year follow-up, 7%-26% of the patients discontinue CT-P13 treatment. Common reasons for CT-P13 discontinuation are (subjective) loss of response or adverse events. As a result of these newly experienced symptoms, patients are occasionally switched back to treatment with originator IFX. However, not much is currently known regarding reverse switching to originator IFX. We aimed to assess the prevalence of and the specific reasons for reverse switching to originator infliximab within 52-weeks after an initial conversion from originator infliximab to CT-P13 in patients with IBD. Additionally, we evaluated whether reinitiating originator infliximab led to the desired favourable effect and sustained infliximab use. Methods In this retrospective, multicentre cohort study, data of IBD patients from eight hospitals in the Netherlands were collected. Adult patients with IBD were eligible for inclusion if they were switched from infliximab originator to CT-P13 and had a follow-up time of at least 52 weeks after initial conversion. Reasons for re-switching were categorised into adverse events or loss of response on the biosimilar. Drug survival was analysed with a time-varying Cox proportional hazards model. Results A total of 684 patients with IBD were switched (516 Crohn’s disease, 168 ulcerative colitis). Reverse switching was seen in 74 (10.8%) patients after a median of 140 days (IQR 86–231). Reverse switchers were more often females (70.3% vs. 49.7%, p < 0.001) and had shorter originator treatment (4.0 [IQR 2.6–6.5] vs. 5.2 [IQR 3.0–7.5] years, p = 0.037) than those who stayed on CT-P13. A total of 105 symptoms for switching were reported. IBD-like symptoms (25.7%) and dermatological symptoms (21.9%) were the most common. Four patients had objectified loss of response. All regained response after switching back. IBD-like symptoms and dermatological symptoms were reversible in 74.1% and 87%, respectively. Overall reversibility of symptoms was 73.3%. Cox proportional hazards model with CT-P13/originator infliximab as time-varying covariate, yielded no difference in survival risk (hazard ratio 1.23, 95% CI 0.65–2.33). Conclusion Switching back to originator infliximab seems effective in patients with IBD, who experience adverse effects or loss of response after switching from originator to CT-P13. Switching patients back to originator infliximab might, therefore, be justified in case patients experience new side effects or loss of response after switching to CT-P13.

scholarly journals Risk factors associated with major adverse cardiac and cerebrovascular events following percutaneous coronary intervention: a 10-year follow-up comparing random survival forest and Cox proportional-hazards model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Farhadian ◽  
Sahar Dehdar Karsidani ◽  
Azadeh Mozayanimonfared ◽  
Hossein Mahjub
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Coronary Intervention ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Cerebrovascular Events ◽  
Long Term Follow Up ◽  
Stent Length

Abstract Background Due to the limited number of studies with long term follow-up of patients undergoing Percutaneous Coronary Intervention (PCI), we investigated the occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) during 10 years of follow-up after coronary angioplasty using Random Survival Forest (RSF) and Cox proportional hazards models. Methods The current retrospective cohort study was performed on 220 patients (69 women and 151 men) undergoing coronary angioplasty from March 2009 to March 2012 in Farchshian Medical Center in Hamadan city, Iran. Survival time (month) as the response variable was considered from the date of angioplasty to the main endpoint or the end of the follow-up period (September 2019). To identify the factors influencing the occurrence of MACCE, the performance of Cox and RSF models were investigated in terms of C index, Integrated Brier Score (IBS) and prediction error criteria. Results Ninety-six patients (43.7%) experienced MACCE by the end of the follow-up period, and the median survival time was estimated to be 98 months. Survival decreased from 99% during the first year to 39% at 10 years' follow-up. By applying the Cox model, the predictors were identified as follows: age (HR = 1.03, 95% CI 1.01–1.05), diabetes (HR = 2.17, 95% CI 1.29–3.66), smoking (HR = 2.41, 95% CI 1.46–3.98), and stent length (HR = 1.74, 95% CI 1.11–2.75). The predictive performance was slightly better by the RSF model (IBS of 0.124 vs. 0.135, C index of 0.648 vs. 0.626 and out-of-bag error rate of 0.352 vs. 0.374 for RSF). In addition to age, diabetes, smoking, and stent length, RSF also included coronary artery disease (acute or chronic) and hyperlipidemia as the most important variables. Conclusion Machine-learning prediction models such as RSF showed better performance than the Cox proportional hazards model for the prediction of MACCE during long-term follow-up after PCI.

scholarly journals Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

2020 ◽  
Author(s):  
Yuko Yamaguchi ◽  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Stefania Bandinelli ◽  
Yusuke Osawa ◽  
...  
Keyword(s):  
Older Adults ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Differentiation Factor ◽  
Hazards Model ◽  
Increased Risk ◽  
The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P<.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

scholarly journals Dementia Adjudication Triggers Associated With Increased Mortality for Older Australians: Evidence From ASPREE

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 161-161
Author(s):  
Jane Banaszak-Holl ◽  
Xiaoping Lin ◽  
Jing Xie ◽  
Stephanie Ward ◽  
Henry Brodaty ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
The Elderly ◽  
Cox Proportional Hazards ◽  
Service Planning ◽  
Cox Proportional Hazards Model ◽  
Cognitive Test ◽  
Risk Of Death ◽  
Hazards Model ◽  
Using Data

Abstract Research Aims: This study seeks to understand whether those with dementia experience higher risk of death, using data from the ASPREE (ASPirin in Reducing Events in the Elderly) clinical trial study. Methods: ASPREE was a primary intervention trial of low-dose aspirin among healthy older people. The Australian cohort included 16,703 dementia-free participants aged 70 years and over at enrolment. Participants were triggered for dementia adjudication if cognitive test results were poorer than expected, self-reporting dementia diagnosis or memory problems, or dementia medications were detected. Incidental dementia was adjudicated by an international adjudication committee using the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) criteria and results of a neuropsychological battery and functional measures with medical record substantiation. Statistical analyses used a cox proportional hazards model. Results: As previously reported, 1052 participants (5.5%) died during a median of 4.7 years of follow-up and 964 participants had a dementia trigger, of whom, 575 (60%) were adjucated as having dementia. Preliminary analyses has shown that the mortality rate was higher among participants with a dementia trigger, regardless of dementia adjudication outcome, than those without (15% vs 5%, Χ2 = 205, p <.001). Conclusion: This study will provide important analyses of differences in the hazard ratio for mortality and causes of death among people with and without cognitive impairment and has important implications on service planning.

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