scholarly journals Causes of death and effect of non-cancer-specific death on rates of overall survival in adult classic Hodgkin lymphoma: a populated-based competing risk analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jie Gao ◽  
Yingying Chen ◽  
Pengqiang Wu ◽  
Fujue Wang ◽  
Huan Tao ◽  
...  

Abstract Background The improved prognosis of classic Hodgkin lymphoma (cHL) has been accompanied by elevated risks of non–cancer-specific death (non-CSD). The aim of this study was to verify the occurrence of non-CSD and its effect on rates of overall survival among adult patients with cHL. Methods To ensure sufficient follow-up time, we analyzed retrospective data from patients aged ≥20 years with cHL that was diagnosed between 1983 and 2005 in the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was applied to analyze the non-CSD occurrence in relation to all factors. Using Fine-Gray’s method, we calculated the cumulative incidences of CSD and non-CSD. Stacked cumulative incidence plots and ratio of non-CSD to all causes of death were applied to evaluate the effect of non-CSD on rates of overall survival. Finally, we analyzed long-term mortality through Cox proportional hazard regression analysis and competing risk regression analysis to emphasize a more appropriate model of survival for patients with cHL. Results Among the 18,518 patients included, there were 3768 cases of CSD (20.3%) and 3217 of non-CSD (17.4%). Older age, earlier period, male sex, unmarried status, mixed cellularity (MC) and lymphocyte-depletion (LD) histological subtype, and patients received radiotherapy (RT) only were associated with more non-CSD according to binary logistic analysis. The cumulative incidence of non-CSD exceeded CSD after approximately 280 months follow-up. The most common causes of non-CSDs were cardiovascular disease, subsequent primary neoplasms, infectious diseases, accidents, and suicide. In a Cox proportional hazards model, patients who were black, unmarried, at an advanced stage or underwent chemotherapy (CT) alone were at greater risk of mortality than were white patients, who were married, at an early stage, and underwent combined modality; these populations were also found to be at greater risk for CSD in a competing risk model, but the risk of non-CSD did not differ significantly according to race and marital status, patients with early-stage disease and who underwent RT only were found to be at higher risk of non-CSD instead. Conclusions Lymphoma was the cause of death in most patients who died, but non-CSD was not unusual. Patients with cHL should be monitored closely for signs of cardiovascular disease and malignant tumors. Rates of overall survival of patients were diminished by non-CSD, and a competing risk model was more suitable for establishing the prognosis than was the Cox proportional hazards model.

2019 ◽  
Vol 15 (35) ◽  
pp. 4083-4093
Author(s):  
Jingjing Wu ◽  
Da Man ◽  
Kaicen Wang ◽  
Lanjuan Li

Aim: The occurrence of nonappendiceal cancer-specific death (non-ACSD) and its impact on overall survival are unclear. Methods: Patients were extracted from the Surveillance, Epidemiology, and End Results. Results: Nearly 33.2 and 24.0% patients suffered ACSD and non-ACSD. In a Cox proportional-hazards model, unmarried patients were at greater risk of mortality than were married patients. In a competing risk model, unmarried patients were at greater risk of non-ACSD than were married patients, but the risk of ACSD did not differ significantly according to marriage status. Conclusion: The overall survival of patients with appendiceal cancer was reduced by non-ACSD. A competing risk model was more predictive of the prognosis than was a Cox proportional hazards model.


2020 ◽  
Author(s):  
Shilong Wu ◽  
Mengyang Liu ◽  
Weixue Cui ◽  
Guilin Peng ◽  
Jianxing He

Abstract Background Thymoma is an uncommon intrathoracic malignant tumor and has a long natural history. It is uncertain whether the survival of thymoma patient is affected by prior cancer history. Finding out the impact of a prior cancer history on thymoma survival has important implications for both decision making and research. Method The Surveillance, Epidemiology, and End Results (SEER) database was queried for thymoma patients diagnosed between 1975 and 2015. Kaplan-Meier methods and Cox proportional hazards model were used to analyze overall survival across a variety of stages, age, and treatment methods with a prior cancer history or not. Results A total of 3604 patients with thymoma were identified including 507 (14.1%) with a prior cancer history. The 10-year survival rate of patients with a prior cancer history (53.8%) was worse than those without a prior cancer history (40.32%, 95%CI 35.24-45.33, P < 0.0001). However, adjusted analyses showed that the impact of a prior cancer history was heterogenous across age and treatment methods. In subset analyses, prior cancer history was associated with worse survival among patients who were treated with chemoradiotherapy (HR: 2.80, 95% CI: 1.51-5.20, P = 0.001) and age ≤ 65 years (HR: 1.33, 95%CI: 1.02-1.73, P = 0.036). Conclusions Prior cancer history provides an inferior overall survival for patients with thymoma. But it does not worsen the survival in some subgroups and these thymoma patients should not be excluded from clinical trials.


2017 ◽  
Vol 63 (6) ◽  
pp. 915-919
Author(s):  
Edvard Zhavrid ◽  
Pavel Demeshko ◽  
Nataliya Artemova ◽  
V. Sinayko

The outcomes of multimodality treatment of 227 glioblastoma (grade IV) patients were evaluated in relation to the postoperative chemoradiotherapy (ChRT) regimen. No statistically significant differences were found in groups with conventional ChRT (temozolomide 75 mg/m2 per os 1 hour before the radiation treatment during the whole course of radiotherapy, n=111) and modified ChRT (temozolomide 75 mg/m2 per os 5 days a week 1 hour before the radiation treatment in the first and last two weeks of radiotherapy, n=116), the median overall survival being 16 months and 16 months respectively (P=0,889). The Cox proportional hazards model demonstrated that the postoperative ChRT regimen was not a prognostic factor affecting patient survival.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3448-3448
Author(s):  
Nicolas Batty ◽  
Xavier C. Badoux ◽  
Michael Keating ◽  
E. Lin ◽  
Susan Lerner ◽  
...  

Abstract Abstract 3448 Poster Board III-336 Introduction Patients (pts) with CLL have more than twice the risk of developing second malignancies [1]. Frontline therapy with FCR was the strongest independent determinant of survival when compared to FC in patients with CLL in retrospective analysis [2]. This study aims to identify pretreatment factors that may be associated with the development of 2nd malignancies in patients with CLL treated with FCR as initial therapy. Methods Our analysis includes pts with CLL treated between July 1999 and November 2003, on a Phase II trial of FCR as initial therapy. Patients who had developed a 2nd malignancy prior to initiation of therapy were excluded. Patients were divided in 2 groups according to whether they developed a 2nd malignancy during the follow up period. Time to 2nd malignancy was defined as the time from treatment to the first occurrence of 2nd malignancy. Chromosomal abnormalities were detected by metaphase karyotype of bone marrow leukemia cells. Patient characteristics, response to FCR, and overall survival were compared between the two groups using: Wilcoxon rank for continuous variables or Chi-square tests for categorical variables; Kaplan-Meier method was used to generate survival curves and log-rank test was used to assess differences in survival between subgroups. Responses were assessed by 1996 NCI-WG criteria after completion of treatment. Univariate and multivariate Cox proportional hazards model were fitted to assess the association between pts' characteristics and the second malignancy-free survival. Results Among 300 pts with CLL treated with frontline FCR, 46 had a 2nd cancer diagnosed prior to FCR were therefore excluded from this analysis, resulting in a total of 254 pts (85%). With a median follow-up of 76 months, 58 pts (23%) have developed a 2nd malignancy. These included hematological malignancies n=20, non-melanoma skin cancer n=18, solid tumors n=15 and 5 patients have more than 1 type of malignancy. Pts who developed a 2nd malignancy had significantly higher pretreatment percent of lymphocyte in the bone marrow (p=0.04), were less likely to have enlarged spleen size (p=0.024), and were more likely to have deletion of or abnormal chromosome 17 (p=0.008). The overall survival or the responses to treatment were not different between the 2 groups of pts. In the Cox proportional hazards model, abnormalities of chromosome 17 and 13 were statistically significantly associated with shorter time to 2nd malignancy: HR, 9.79 (95% CI, 2.84 - 33.82), p=0.0003 and HR, 4.019 (95% CI, 1.41 - 11.42), p=0.009, respectively. Conclusion Chromosome 17 and 13 abnormalities identified by standard metaphase karyotype analysis were more common in patients with CLL who develop 2nd malignancy after FCR therapy. The response rates and overall survival were not different between patients with CLL with or without 2nd malignancy after frontline therapy with FCR. Univariate Cox proportional hazards model in estimating the associations between covariates and 2nd malignancy free survival. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1560-1560 ◽  
Author(s):  
Ryan C. Johnson ◽  
Peter L. Greenberg ◽  
Dita Gratzinger

Abstract Introduction We have previously shown that CD271+ MSC density is increased in MDS; that MDS MSCs overexpress a key chemokine, CXCL12; and that CD271+ MSCs are in direct contact with CD34+ progenitors (Lab Invest. 92:1330), suggesting an active role for CD271+ MSCs in MDS biology. Amid increasing evidence of a role for MSCs in the hematopoietic stem cell niche and in myeloid neoplasia, we present a retrospective study of CD271+ MSC density in diagnostic bone marrow core biopsies of cytopenic patients with and without MDS. Methods Tissue microarrays (TMAs) were constructed using duplicate 1mm cores of the bone marrow core biopsy. Immunohistochemistry with anti-CD271 was visualized in red against hematoxylin counterstain. A CD271 density scoring schema (CD271Score) was developed: 1, scattered; 2, loose or partial network; 3, prominent uniform network involving >75% of core. Automated quantitation of CD271 density as % hematoxylin+ marrow (CD271Quant) was performed on 40x photomicrographs using CellProfiler 2.0 (www.cellprofiler.org). Results The patient population (Table 1) was divided into diagnostic categories of benign (B9, n=61), low grade MDS (LGMDS, <5% marrow blasts, n=40), and high grade MDS (HGMDS, ≥5% marrow blasts and/or therapy-related, n=24). CD271 density varied with diagnostic category (Figure 1, X2 = 10.6, p = 0.0051 for CD271Score; X2= 8.0, p = 0.018 for CD271Quant). High CD271 density was overrepresented in the HGMDS group; in two-way comparisons, B9 and LGMDS differ from HGMDS but not each other (B9 vs HGMDS, X2 = 10.1, p = 0.0015 for CD271Score and X2 = 7.7 p = 0.0056 for CD271Quant; LGMDS vs HGMDS X2 = 2.5, p = 0.11 for CD271Score and X2 = 5.4, p = 0.021 for CD271Quant). Among patients with MDS, CD271 density also correlated with poorer risk as assessed by IPSS-R (Spearman's rho = 0.32, p = 0.019 for CD271Score; Spearman's rho = 0.28 p = 0.037 for CD271Quant). CD271Score was reproducible (intraobserver kappa value 0.72, p < 0.0001) and correlated with CD271Quant (Spearman's rho = 0.68, p < 0.0001). Regarding the impact on overall survival (OS), univariate Cox regression confirmed the expected predictive value of IPSS-R (p<0.001); red blood cell transfusion within 3 months prior to diagnosis (p<0.001); and therapy-related MDS subtype (trend, p = 0.11). Kaplan Meyer plots revealed shorter OS in the high CD271Score category (Figure 2) and in the upper quartile of CD271Quant. On univariate Cox analysis, normalized CD271Quant (p = 0.037) but not CD271Score was statistically significant. Much of the effect on OS appeared to be in the upper quartile of CD271 density (HR 3.0, p = 0.023 for highest versus lowest quartile of CD271Quant). In the multivariate Cox proportional hazards model, normalized CD271Quant remained statistically significant (p=0.027) together with IPSS-R (p<0.001) and transfusion requirement (p=0.001). Median follow-up of MDS patients OS was 21.4 months (range, 1 day to 115 months) with 34 deaths among 64 patients. Conclusions In the intact bone marrow core biopsy, a dense CD271+ MSC network, as assessed by two separate techniques (morphologic scoring by a pathologist or quantitation through automated image analysis), is associated with higher-risk diagnostic categories of MDS (refractory anemia with excess blasts, therapy-associated MDS) and with poor IPSS-R risk scores. Quantitative CD271+ MSC density is also associated with poorer OS, both on univariate analysis and in a Cox proportional hazards model including IPSS-R, transfusion, and therapy-related disease. Increased CD271+ MSC density may reflect an abnormal positive feedback loop between the myeloid clone and its dysfunctional mesenchymal niche. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 15s2 ◽  
pp. CIN.S39364 ◽  
Author(s):  
Wei Xu ◽  
Jiahua Che ◽  
Qin Kong

In some cancer clinical studies, researchers have interests to explore the risk factors associated with competing risk outcomes such as recurrence-free survival. We develop a novel recursive partitioning framework on competing risk data for both prognostic and predictive model constructions. We define specific splitting rules, pruning algorithm, and final tree selection algorithm for the competing risk tree models. This methodology is quite flexible that it can corporate both semiparametric method using Cox proportional hazards model and parametric competing risk model. Both prognostic and predictive tree models are developed to adjust for potential confounding factors. Extensive simulations show that our methods have well-controlled type I error and robust power performance. Finally, we apply both Cox proportional hazards model and flexible parametric model for prognostic tree development on a retrospective clinical study on oropharyngeal cancer patients.


2020 ◽  
Author(s):  
Shilong Wu ◽  
Mengyang Liu ◽  
Weixue Cui ◽  
Guilin Peng ◽  
Jianxing He

Abstract Background: Thymoma is an uncommon intrathoracic malignant tumor and has a long natural history. It is uncertain whether the survival of thymoma patient is affected by prior cancer history. Finding out the impact of a prior cancer history on thymoma survival has important implications for both decision making and research.Method: The Surveillance, Epidemiology, and End Results (SEER) database was queried for thymoma patients diagnosed between 1975 and 2015. Kaplan-Meier methods and Cox proportional hazards model were used to analyze overall survival across a variety of stages, age, and treatment methods with a prior cancer history or not.Results: A total of 3604 patients with thymoma were identified including 507 (14.1%) with a prior cancer history. The 10-year survival rate of patients with a prior cancer history (53.8%) was worse than those without a prior cancer history (40.32%, 95%CI 35.24-45.33, P < 0.0001). However,adjusted analyses showed that the impact of a prior cancer history was heterogenous across age and treatment methods. In subset analyses, prior cancer history was associated with worse survival among patients who were treated with chemoradiotherapy (HR: 2.80, 95% CI: 1.51-5.20, P = 0.001) and age ≤ 65 years (HR: 1.33, 95%CI: 1.02-1.73, P = 0.036).Conclusions: Prior cancer history provides an inferior overall survival for patients with thymoma. But it does not worsen the survival in some subgroups and these thymoma patients should not be excluded from clinical trials.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi116-vi116
Author(s):  
Sebastian Otto-Meyer ◽  
Rian DeFaccio ◽  
Corey Dussold ◽  
Erik Ladomersky ◽  
Rimas Lukas ◽  
...  

Abstract Glioblastoma (GBM) is the most common and aggressive form of primary brain tumor in adults. We recently investigated the hypothesis that treating GBM patients with psychosocial modifiers would be associated with improved overall survival (OS). Our study retrospectively analyzed 497 patients with GBM treated at Northwestern Medicine with or without selective serotonin reuptake inhibitors (SSRI) between the years 2000 and 2018. Information from the Northwestern Medicine Enterprise Data Warehouse was analyzed for baseline covariates including sex, age at diagnosis, type of surgery, and Charlson Comorbidity Index Score. Approximately one-third of analyzed patients were prescribed SSRIs, with highly variable treatment times. Several statistical methods were used to perform adjusted analyses including: (i) an extended Cox Proportional Hazards Model with SSRI as a time-dependent variable; (ii) a Cox Model using inverse probability weights; and (iii) a Cox Proportional Hazards model with landmark analyses. The hazard ratios (95% CIs) for each statistical model analyzing the association between SSRI treatment and OS were (i) 1.26 (0.97–1.63), (ii) 1.06 (0.8–1.4), and (iii) ranged from 1.01 (0.74–1.38) to 1.26 (0.75–2.09). Our analysis found no significant association between the time of SSRI treatment and GBM patient OS. Future work will study additional considerations for psychosocial modifier treatment and their potential effect(s) on GBM patient OS including: (i) confounders due to the extent of cancer treatment; (ii) comorbidities not associated with tumor burden; (iii) absolute leukocyte counts; and (iv) length of treatment time required for enhancing immune-mediated anti-GBM mechanisms.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Farhadian ◽  
Sahar Dehdar Karsidani ◽  
Azadeh Mozayanimonfared ◽  
Hossein Mahjub

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.


Author(s):  
Yuko Yamaguchi ◽  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Stefania Bandinelli ◽  
Yusuke Osawa ◽  
...  

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&lt;.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.


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