scholarly journals Competitive Risk Analysis of Prognosis in Patients With Cecum Cancer: A Population-Based Study

2021 ◽  
Vol 28 ◽  
pp. 107327482198931
Author(s):  
Wentao Wu ◽  
Jin Yang ◽  
Daning Li ◽  
Qiao Huang ◽  
Fanfan Zhao ◽  
...  

Background: The presence of competing risks means that the results obtained using the classic Cox proportional-hazards model for the factors affecting the prognosis of patients diagnosed with cecum cancer (CC) may be biased. Objective: The purpose of this study was to establish a competitive risk model for patients diagnosed with CC to evaluate the relevant factors affecting the prognosis of patients, and to compare the results with the classical COX proportional risk model. Methods: We extracted data on patients diagnosed with CC registered between 2004 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. The univariate analysis utilized the cumulative incidence function and Gray’s test, while a multivariate analysis was performed using the Fine-Gray, cause-specific (CS), and Cox proportional-hazards models. Results: The 54463 eligible patients diagnosed with CC included 24387 who died: 12087 from CC and 12300 from other causes. The multivariate Fine-Gray analysis indicated that significant factors affecting the prognosis of patients diagnosed with CC include: age, race, AJCC stage, differentiation grade, tumor size, surgery, radiotherapy, chemotherapy and regional lymph nodes metastasis. Due to the presence of competitive risk events, COX model results could not provide accurate estimates of effects and false-negative results occurred. In addition, COX model misestimated the direction of association between regional lymph node metastasis and cumulative risk of death in patients diagnosed with CC. Competitive risk models tend to be more advantageous when analyzing clinical survival data with multiple endpoints. Conclusions: The present study can help clinicians to make better clinical decisions and provide patients diagnosed with CC with better support.

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S426-S426
Author(s):  
Christopher M Rubino ◽  
Lukas Stulik ◽  
Harald Rouha ◽  
Zehra Visram ◽  
Adriana Badarau ◽  
...  

Abstract Background ASN100 is a combination of two co-administered fully human monoclonal antibodies (mAbs), ASN-1 and ASN-2, that together neutralize the six cytotoxins critical to S. aureus pneumonia pathogenesis. ASN100 is in development for prevention of S. aureus pneumonia in mechanically ventilated patients. A pharmacometric approach to dose discrimination in humans was taken in order to bridge from dose-ranging, survival studies in rabbits to anticipated human exposures using a mPBPK model derived from data from rabbits (infected and noninfected) and noninfected humans [IDWeek 2017, Poster 1849]. Survival in rabbits was assumed to be indicative of a protective effect through ASN100 neutralization of S. aureus toxins. Methods Data from studies in rabbits (placebo through 20 mg/kg single doses of ASN100, four strains representing MRSA and MSSA isolates with different toxin profiles) were pooled with data from a PK and efficacy study in infected rabbits (placebo and 40 mg/kg ASN100) [IDWeek 2017, Poster 1844]. A Cox proportional hazards model was used to relate survival to both strain and mAb exposure. Monte Carlo simulation was then applied to generate ASN100 exposures for simulated patients given a range of ASN100 doses and infection with each strain (n = 500 per scenario) using a mPBPK model. Using the Cox model, the probability of full protection from toxins (i.e., predicted survival) was estimated for each simulated patient. Results Cox models showed that survival in rabbits is dependent on both strain and ASN100 exposure in lung epithelial lining fluid (ELF). At human doses simulated (360–10,000 mg of ASN100), full or substantial protection is expected for all four strains tested. For the most virulent strain tested in the rabbit pneumonia study (a PVL-negative MSSA, Figure 1), the clinical dose of 3,600 mg of ASN100 provides substantially higher predicted effect relative to lower doses, while doses above 3,600 mg are not predicted to provide significant additional protection. Conclusion A pharmacometric approach allowed for the translation of rabbit survival data to infected patients as well as discrimination of potential clinical doses. These results support the ASN100 dose of 3,600 mg currently being evaluated in a Phase 2 S. aureus pneumonia prevention trial. Disclosures C. M. Rubino, Arsanis, Inc.: Research Contractor, Research support. L. Stulik, Arsanis Biosciences GmbH: Employee, Salary. H. Rouha, 3Arsanis Biosciences GmbH: Employee, Salary. Z. Visram, Arsanis Biosciences GmbH: Employee, Salary. A. Badarau, Arsanis Biosciences GmbH: Employee, Salary. S. A. Van Wart, Arsanis, Inc.: Research Contractor, Research support. P. G. Ambrose, Arsanis, Inc.: Research Contractor, Research support. M. M. Goodwin, Arsanis, Inc.: Employee, Salary. E. Nagy, Arsanis Biosciences GmbH: Employee, Salary.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16051-e16051
Author(s):  
Aline Fusco Fares ◽  
Daniel Vilarim Araujo ◽  
Eliza Dalsasso Ricardo ◽  
Marcelo Corassa ◽  
Maria Nirvana Cruz Formiga ◽  
...  

e16051 Background: NLR is a marker of inflammation and when elevated is associated with poor outcome in many tumors, including RCC. Hereby we evaluate the association of NLR with the likelihood of curative intent MSX. Methods: We retrospectively studied 846 patients diagnosed with metastatic RCC between 2007 and 2016. 116 patients fulfilled inclusion criteria: previous nephrectomy, no sarcomatoid features and available tumor specimens from metastatic site. Regression tree for censored data method was used to find the best NLR cut-off value. NLR was examined baseline – prior to MSX or targeted therapy. Chi-square test was used to evaluate associations between variables. We estimated overall survival (OS) using Kaplan-Meier curves. Cox proportional hazards regression models were fitted to evaluate the prognostic significance of NLR in univariable and multivariable analysis. Results: The median OS for the whole cohort was 45 months (95% CI, 27.6 to 62.4 months), and the median follow-up was 78.2 months. The best cut-off NLR value was 4.07. Higher NLR was associated with shorter OS when compared to the lower NLR cohort (11.5 months vs 68.3 months HR = 0.26, 95% CI: 0.15 – 0.97, p ≤ 0.0001, respectively). Univariate analysis revealed that bone metastasis and poor IMDC criteria were associated with worse OS and that MSX and lower NLR were associated with better OS. On multivariate analysis MSX, lower NLR and favourable/intermediate group on IMDC criteria were associated with a decreased risk of death (HR = 0.41, 95% CI 0.19-0.85, p = 0.018 and HR = 0.45, 95% CI 0.22-0.90, p = 0.025, HR = 0.35, 95% CI 0.16-0.79, p = 0.012, respectively). We found a positive association of lower NLR and curative intent MSX (p = 0.002). Conclusions: NLR is a prognostic marker in metastatic RCC and a ratio ≤ 4,07 is associated with a higher likelihood of curative intent MSX.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8006-8006
Author(s):  
P. A. Soriano ◽  
S. K. Libutti ◽  
J. F. Pingpank ◽  
T. Beresenev ◽  
S. M. Steinberg ◽  
...  

8006 Background: In transit disease afflicts about 10% of MM patients and no single systemic or regional treatment has been widely accepted as most effective or appropriate. Previously, the impact of ILP on the natural history of MM patients has been difficult to gauge. We report long-term outcomes in MM patients undergoing hyperthermic ILP in an era of increasingly accurate staging, uniform operative and treatment conditions, and regular follow-up. Methods: Between 5/1992 to 2/2005, 90 patients (median age: 57 y [range: 24–84]; F: 49, M: 41) with Stage IIIA or IIIAB MM underwent a 90 min hyperthermic (mean calf T: 39.3° C) ILP (melphalan: 10–13 mg/L limb volume, TNF: 3–6 mg [n=44], or IFN: 200 μg [n=38]) using uniform operative technique including intra-operative leak monitoring. There was 1 operative mortality (1/91, 1.1%). Patients were prospectively followed for response, in-field progression free (PFS), and overall survival (OS). Parameters associated with in-field PFS and OS were analyzed by the Kaplan-Meier method with log rank tests, as well as by Cox proportional hazards models. Results: There were 61 complete responses (68%) and 23 partial responses (26%). At a median follow-up of 47 months, median in-field PFS was 12.4 months, and median OS was 47.4 months; 5 and 10-year actuarial OS were 43 and 34%, respectively. Female gender and low tumor burden (< 20 tumors) were associated with prolonged in-field PFS (M:F hazard ratio (HR): 2.07, CI:1.27–3.38; 21+ vs. ≤20 tumors HR: 2.29, CI: 1.21- 4.34; p<0.011 for both) in a Cox model, whereas TNF, IFN, perfusion pressure, and tumor stage were not. Female gender was associated with improved OS (p=0.027, M:F HR=1.82, 95% CI 1.07–3.09) and Stage IIIA marginally so, in univariate analysis, (p=0.065). Conclusions: ILP for MM patients is associated with noteworthy in-field PFS and prolonged OS. Neither use of TNF nor tumor stage were significantly associated with in-field PFS in Cox models, while female gender was associated with better outcomes. In appropriately selected patients using standardized technique, ILP has clinical benefit in this setting. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 589-589 ◽  
Author(s):  
Raffaella Palumbo ◽  
Antonio Bernardo ◽  
Alberto Riccardi ◽  
Federico Sottotetti ◽  
Cristina Teragni ◽  
...  

589 Background: Although the development of modern systemic therapies has clearly improved outcome of patients with MBC, the true impact of further CT on overall survival (OS) and QoL of these women is still debated. The aim of this study was to determine which benefit could be brought by successive CT lines in patients with HR-positive disease, aiming to identify factors affecting outcome and survival. Methods: This retrospective analysis included 980 women treated with CT for MBC at our Institution over a eight year period (July 2000-July 2008). With OS data updated in March 2010, the median follow-up was 146 months (range 48-198), OS and time to treatment failure (TTF) were calculated according to the Kaplan-Meyer method for each CT line. Cox proportional hazards model was used to identify factors that could influence TTF and OS. Results: Median OS evaluated from day 1 of each CT line decreased with the line number from 34.8 months for first line to 8.2 months for 7 or more lines). Median TTF ranged from 9.2 months to 7.8 and 6.4 months for the first, second and third line, respectively, with no significant decrease observed beyond the third line (median 5.2 months, range 4.8-6.2). No statistically significant difference was found between HR-positive and HR-negative patients in terms of OS and TTF by each CT line. In univariate analysis factors positively linked to a longer duration of TTF for each CT line were positive hormonal receptor status, more than 3 hormonotherapy lines, absence of liver metastasis, adjuvant CT exposure, response to CT for the metastatic disease; in the multivariate analysis the duration of TTF for each CT line was the only one factor with significant impact on survival benefit for subsequent treatments, in both HR-positive and negative populations (p<0.001). Conclusions: Our results support the benefit of multiple lines of CT in a significant subset of women treated for MBC, since each CT line may contribute to a longer OS. Of interest, such a benefit was also observed for patients with HR-positive disease, although the number of hormonotherpy lines received did not significantly influence the outcome.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4086-4086
Author(s):  
Carles Besses ◽  
Alberto Alvarez-Larrán ◽  
Montserrat Gómez ◽  
Anna Angona ◽  
Paula Amat ◽  
...  

Abstract Abstract 4086 Definition of resistance/intolerance to hydroxyurea (HU) in essential thrombocythemia (ET) has been proposed by the European LeukemiaNet (ELN) however its clinical utilility has not been validated yet. We have retrospectively evaluated such criteria in 166 ET patients treated with HU for a median of 4.5 years. Response to HU treatment was categorized using the ELN criteria. The ELN definitions of resistance/intolerance to HU required the fulfillment of at least one of the following criteria: platelet count greater than 600 × 109/L after 3 months of at least 2 g/day of HU (2.5 g/day in patients with a body weight over 80 kg); platelet count greater than 400 × 109/L and leukocytes less than 2.5 × 109/L or hemoglobin (Hb) less than 100 g/L at any dose of HU; presence of leg ulcers or other unacceptable mucocutaneous manifestations at any dose of HU; HU-related fever. Survival and time-to-event curves were estimated using the Kaplan-Meier method.Variab les attaining a significant level at the univariate analysis were included in a Cox proportional hazards model. Overall, 134 patients achieved a complete clinicohematologic response (CR) and 25 a partial response. Thirty-three patients met at least one of the ELN criteria defining resistance (n=15) or intolerance (n=21) to HU. Fifteen cases developed anemia with thrombocytosis. Other definitions of resistance were less useful. When compared with the others, resistant patients were more likely to display hyperproliferative features at ET diagnosis, such as higher levels of leukocytes (p= 0.05), platelets (p=0.004) and serum LDH (p=0.02). Eleven patients developed leg ulcers leading to a permanent discontinuation of the drug in 8 cases. No distinctive clinical profile could be ascribed to patients exhibiting leg ulcers, with the exception of a high prevalence of cardiovascular risk factors. Other unacceptable mucocutaneous manifestations occurred in 9 patients. Hematologic and mucocutaneous complications were unrelated, with only two patients presenting both types of toxicities. With a median follow-up from ET diagnosis of 7 years (range: 0.5–23), 38 patients (23%) had died, resulting in a survival probability of 65% at 10 years from HU start. The risk of death from any cause was increased by 6.2-fold (95%CI: 2.3–16.7, P<0.001) in patients who met any of the ELN criteria of resistance to HU. Anemia was in all instances the first finding qualifying for resistance to HU, with the median subsequent survival of patients with anemia being only 2.4 years (range, 0.01–4.9). A remarkable incidence of myelofibrosis was observed in patients fulfilling the ELN criteria for resistance, since this complication was recorded in 7 of 15 such cases (p>0.001). In conclusion, the best discriminating ELN criterion of resistance to HU is based on the detection of anemia. Moreover, such criterion is particularly useful since it also identifies a subset of ET patients with a poor prognosis. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7014-7014
Author(s):  
Gail J. Roboz ◽  
Andrew H. Wei ◽  
Farhad Ravandi ◽  
Christopher Pocock ◽  
Pau Montesinos ◽  
...  

7014 Background: Demographic and disease factors influence outcomes for patients (pts) with AML. In the phase 3 QUAZAR AML-001 trial, Oral-AZA significantly prolonged OS and RFS vs. placebo (PBO) for pts with AML in first remission after IC (Wei, NEJM, 2020). Univariate analyses showed OS and RFS benefits with Oral-AZA vs. PBO across pt subgroups defined by baseline (BL) characteristics. MV analyses were performed to identify BL characteristics independently predictive of OS/RFS in QUAZAR AML-001, and to assess Tx effects of Oral-AZA vs. PBO on survival when adjusted for BL factors. Methods: Pts were aged ≥55 yrs with AML in complete remission (CR) or CR with incomplete count recovery (CRi) after induction ± consolidation. Within 4 months of CR/CRi, pts were randomized 1:1 to receive Oral-AZA 300 mg or PBO for 14d/28d cycle. Cox proportional hazards models were used to estimate Tx effects of Oral-AZA vs. PBO on OS and RFS, adjusting for BL age, sex, ECOG PS score, cytogenetic risk at diagnosis (Dx), prior MDS, geographic region, CR/CRi after induction (per investigator) and at BL (per sponsor), MRD status, receipt of consolidation, number of consolidation cycles, platelet count, and ANC. In a stepwise procedure, randomized Tx and BL variables were selected incrementally into a Cox model if P ≤ 0.25. After each addition, the contribution of the covariate adjusted for other covariates in the model was evaluated and retained in the model if P ≤ 0.15. Results : Oral-AZA Tx remained a significant independent predictor of improved OS (HR 0.70) and RFS (HR 0.57) vs. PBO after controlling for BL characteristics (Table). MRD status, cytogenetic risk, and pt age were each also independently predictive of OS and RFS. Response after induction (CR vs. CRi) and BL ANC were predictive of OS but not RFS, whereas prior MDS, CR/CRi at BL, and number of consolidation cycles were only predictive of RFS. Conclusions: Tx with Oral-AZA reduced the risk of death by 30% and risk of relapse by 43% vs. PBO independent of BL characteristics. Cytogenetic risk at Dx, MRD status, and pt age also independently predicted survival outcomes. Clinical trial information: NCT01757535. [Table: see text]


2017 ◽  
Vol 01 (01) ◽  
pp. 1650003
Author(s):  
Lu Bai ◽  
Daniel Gillen

The Cox proportional hazards model is commonly used to examine the covariate-adjusted association between a predictor of interest and the risk of mortality for censored survival data. However, it assumes a parametric relationship between covariates and mortality risk though a linear predictor. Generalized additive models (GAMs) provide a flexible extension of the usual linear model and are capable of capturing nonlinear effects of predictors while retaining additivity between the predictor effects. In this paper, we provide a review of GAMs and incorporate bivariate additive modeling into the Cox model for censored survival data with applications to estimating geolocation effects on survival in spatial epidemiologic studies.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Luís Meira-Machado ◽  
Carmen Cadarso-Suárez ◽  
Francisco Gude ◽  
Artur Araújo

The Cox proportional hazards regression model has become the traditional choice for modeling survival data in medical studies. To introduce flexibility into the Cox model, several smoothing methods may be applied, and approaches based on splines are the most frequently considered in this context. To better understand the effects that each continuous covariate has on the outcome, results can be expressed in terms of splines-based hazard ratio (HR) curves, taking a specific covariate value as reference. Despite the potential advantages of using spline smoothing methods in survival analysis, there is currently no analytical method in theRsoftware to choose the optimal degrees of freedom in multivariable Cox models (with two or more nonlinear covariate effects). This paper describes anRpackage, calledsmoothHR, that allows the computation of pointwise estimates of the HRs—and their corresponding confidence limits—of continuous predictors introduced nonlinearly. In addition the package provides functions for choosing automatically the degrees of freedom in multivariable Cox models. The package is available from theRhomepage. We illustrate the use of the key functions of thesmoothHRpackage using data from a study on breast cancer and data on acute coronary syndrome, from Galicia, Spain.


2020 ◽  
pp. 004912412091492
Author(s):  
Grace Li ◽  
Mary Lesperance ◽  
Zheng Wu

The Cox proportional hazards model has been pervasively used in many social science areas to examine the effects of covariates on timing to an event. The standard Cox model is intended to study univariate survival data where there is a singular event of interest, which can only be experienced once. However, we may additionally wish to explore a number of other complexities that are prevalent in survival data. For example, an individual may experience events of the same type more than once or may experience multiple types of events. This study introduces innovations in recurrent (repeatable) event analysis, jointly modeling several endogenous survival processes. As an example and an application, we simultaneously model two types of recurrent events in the presence of a dependent terminal event. This model not only correctly handles different types of recurrent events but also explicitly estimates the direction and magnitude of relationships between recurrences and survival. This article concludes with an example of the model to examine how the timing of retirement is associated with the risks of multiple spells of employment and childbearing. The theoretical discussions and empirical analyses suggest that the multivariate joint models have much to offer to a wide variety of substantive research areas.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9068-9068
Author(s):  
E. D. Whitman ◽  
R. T. Bustami

9068 Background: Malignant melanoma (MM) and papillary thyroid cancer (PTC) may share genetic mutations. The expected mortality of a patient with both MM and PTC should be predominantly influenced by MM and unchanged by the PTC diagnosis, unless shared genetic abnormalities or other factors alter the phenotype of either or both diseases. We hypothesize patients with both MM and PTC have altered mortality risk compared to patients with either cancer alone. Methods: The study population included patients identified in the SEER 1973–2004 database who were diagnosed with MM or PTC as a primary tumor. The population was divided into four groups: (1) patients with MM only (MEL); (2) patients with PTC only (PAP); (3) patients who developed MM as a second primary after PTC (2MEL); and (4) patients diagnosed with PTC after MM (2PAP). Time between diagnosis and death or last follow up (December 2005) and other demographic data was obtained from SEER. Comparisons between the group death rates were made using the Chi-Square Test. A Cox proportional hazards regression model, adjusted for patient characteristics, predicted the risk of death and survival by group. Results: 9575 SEER patient records were included: 6622 in MEL, 2778 in PAP, 113 in 2MEL and 62 in 2PAP. Overall, 2095 patients (22%) died. There was a significant difference in mortality rates between the groups: MEL 27%, PAP 9%, 2MEL 21% and 2PAP 18%, p<0.001 by Chi-Square. Controlling for other variables in a multivariate Cox model, patients in the 2MEL group were significantly less likely to die than MEL patients (HR 0.52, 95% CI 0.35–0.79, p=0.002). 2PAP patients, the smallest sample, also had a reduced likelihood of death that did not reach statistical significance (HR=0.75, 95% CI 0.42–1.37, p=.35). PAP patients had the best survival (HR=0.43, 95% CI 0.36–0.50,p<0.001). Other factors (age, race, gender and radiation therapy, data not shown) also significantly affected mortality. Conclusions: This study suggests that MM patients also diagnosed with PTC are more likely to survive than patients with MM alone. Identification of the causative factor(s) for this survival benefit will require additional epidemiologic and genetic studies. No significant financial relationships to disclose.


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