Pretreatment Factors Associated with Second Malignancies Occuring After Frontline Fludarabine, Cyclophosphamide, and Rituximab (FCR) in Patients with Chronic Lymphocytic Leukemia (CLL).

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.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1001-1001
Author(s):  
Dennis J. Slamon ◽  
Patrick Neven ◽  
Stephen K. L. Chia ◽  
Guy Heinrich Maria Jerusalem ◽  
Michelino De Laurentiis ◽  
...  

1001 Background: The Phase III MONALEESA-3 trial (NCT02422615) previously demonstrated a statistically significant improvement in OS with RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), plus FUL compared with placebo (PBO) plus FUL as first-line (1L) or second-line (2L) treatment in postmenopausal pts with HR+/HER2− ABC (median, not reached vs 40.0 mo; hazard ratio [HR], 0.72; 95% CI, 0.57-0.92, P =.00455). This analysis was final per the protocol; following the unblinding of the study, pts still on study treatment in the PBO arm were allowed to cross over to the RIB arm. We report an exploratory analysis of OS after an additional median 16.9 mo of follow-up, allowing for further characterization of long-term survival benefits of RIB. Methods: Postmenopausal pts with HR+/HER2− ABC were randomized 2:1 to receive RIB + FUL or PBO + FUL in 1L and 2L settings. Updated OS was evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods. Additional postprogression endpoints such as progression-free survival 2 (PFS2), time to chemotherapy (CT), and CT-free survival were also evaluated and summarized. Results: At the data cutoff (Oct 30, 2020), the median follow-up was 56.3 mo (min, 52.7 mo) and 68 (14.0%) and 21 (8.7%) patients were still on treatment in the RIB vs PBO arms, respectively. With this extended follow-up, RIB + FUL continued to demonstrate an OS benefit vs PBO + FUL (median, 53.7 vs 41.5 mo; HR, 0.73; 95% CI, 0.59-0.90). RIB + FUL had prolonged OS vs PBO + FUL in the 1L (median, not reached vs 51.8 mo; HR, 0.64; 95% CI, 0.46-0.88) and 2L subgroups (median, 39.7 vs 33.7 mo; HR, 0.78; 95% CI, 0.59-1.04). Subgroup analyses also showed a consistent OS benefit compared with the intent-to-treat (ITT) population for most subgroups. PFS2, time to CT, and CT-free survival for the ITT population favored RIB + FUL (Table). Among pts who discontinued study treatment, 81.9% and 86.4% received a next-line subsequent antineoplastic therapy, while 14.0% and 30.0% received a CDK4/6i as any subsequent line in the RIB vs PBO arms, respectively. No new safety signals were observed. Conclusions: The previously demonstrated robust and clinically meaningful OS benefit with RIB + FUL compared with PBO + FUL was maintained after almost 5 years of follow-up in postmenopausal pts with HR+/HER2− ABC. The OS benefit of RIB was observed in the 1L and 2L subgroups, which further supports the use of RIB in these populations. The results also demonstrated a significant delay in the use of subsequent CT with RIB vs PBO. Clinical trial information: NCT02422615 .[Table: see text]


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<.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.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Fujino ◽  
H Ogawa ◽  
S Ikeda ◽  
K Doi ◽  
Y Hamatani ◽  
...  

Abstract Background Atrial fibrillation (AF) commonly progresses from paroxysmal type to sustained type in the natural course of the disease, and we previously demonstrated that the progression of AF was associated with increased risk of clinical adverse events. There are some patients, though less frequently, who regress from sustained to paroxysmal AF, but the clinical impact of the regression of AF remains unknown. Purpose We sought to investigate whether regression from sustained to paroxysmal AF is associated with better clinical outcomes. Methods Using the dataset of the Fushimi AF Registry, patients who were diagnosed as sustained (persistent or permanent) AF at baseline were studied. Conversion of sustained AF to paroxysmal AF during follow-up was defined as regression of AF. Major adverse cardiac events (MACE) were defined as the composite of cardiac death, stroke, and hospitalization for heart failure (HF). Event rates were compared between the patients with and without regression of AF. In patients with sustained AF at baseline, predictors of MACE were identified using Cox proportional hazards model. Results Among 2,253 patients who were diagnosed as sustained AF at baseline, regression of AF was observed in 9.0% (202/2,253, 2.0 per 100 patient-years) during a median follow-up of 4.0 years. Of these, 24.3% (49/202, 4.6 per 100 patient-years) of the patients finally recurred to sustained AF during follow-up. The proportion of asymptomatic patients was lower in patients with regression of AF than those without (with vs without regression; 49.0% vs 69.5%, p<0.01). The percentage of beta-blocker use at baseline was similar between the two groups (37.2% vs 33.8%, p=0.34). The prevalence of patients who underwent catheter ablation or electrical cardioversion during follow-up was higher in patients with regression of AF (catheter ablation: 15.8% vs 5.5%; p<0.01, cardioversion: 4.0% vs 1.4%; p<0.01, respectively). The rate of MACE was significantly lower in patients with regression of AF as compared with patients who maintained sustained AF (3.7 vs 6.2 per 100 patient-years, log-rank p<0.01). Figure shows the Kaplan-Meier curves for MACE, cardiac death, hospitalization for heart failure, and stroke. In patients with sustained AF at baseline, multivariable Cox proportional hazards model demonstrated that regression of AF was an independent predictor of lower MACE (adjusted hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.28 to 0.88, p=0.02), stroke (HR: 0.51, 95% CI: 0.30 to 0.88, p=0.02), and hospitalization for HF (HR: 0.50, 95% CI: 0.29 to 0.85, p=0.01). Conclusion Regression from sustained to paroxysmal AF was associated with a lower incidence of adverse cardiac events. Funding Acknowledgement Type of funding source: None


2019 ◽  
Vol 104 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Sung Uk Baek ◽  
Ahnul Ha ◽  
Dai Woo Kim ◽  
Jin Wook Jeoung ◽  
Ki Ho Park ◽  
...  

Background/AimsTo investigate the risk factors for disease progression of normal-tension glaucoma (NTG) with pretreatment intraocular pressure (IOP) in the low-teens.MethodsOne-hundred and two (102) eyes of 102 patients with NTG with pretreatment IOP≤12 mm Hg who had been followed up for more than 60 months were retrospectively enrolled. Patients were divided into progressor and non-progressor groups according to visual field (VF) progression as correlated with change of optic disc or retinal nerve fibre layer defect. Baseline demographic and clinical characteristics including diurnal IOP and 24 hours blood pressure (BP) were compared between the two groups. The Cox proportional hazards model was used to identify the risk factors for disease progression.ResultsThirty-six patients (35.3%) were classified as progressors and 66 (64.7%) as non-progressors. Between the two groups, no significant differences were found in the follow-up periods (8.7±3.4 vs 7.7±3.2 years; p=0.138), baseline VF mean deviation (−4.50±5.65 vs −3.56±4.30 dB; p=0.348) or pretreatment IOP (11.34±1.21 vs 11.17±1.06 mm Hg; p=0.121). The multivariate Cox proportional hazards model indicated that greater diurnal IOP at baseline (HR=1.609; p=0.004), greater fluctuation of diastolic BP (DBP; HR=1.058; p=0.002) and presence of optic disc haemorrhage during follow-up (DH; HR=3.664; p=0.001) were risk factors for glaucoma progression.ConclusionIn the low-teens NTG eyes, 35.3% showed glaucoma progression during the average 8.7 years of follow-up. Fluctuation of DBP and diurnal IOP as well as DH were significantly associated with greater probability of disease progression.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8014-8014
Author(s):  
Arjun Lakshman ◽  
Muhamad Alhaj Moustafa ◽  
S.Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Morie A. Gertz ◽  
...  

8014 Background: t(11;14) is a standard risk cytogenetic marker in MM. Methods: We reviewed 366 patients with MM who had t(11;14) by FISH and 732 age and period-matched controls without t(11;14), seen at our institution from 2004 to 2014 and outcomes were analyzed using time to first progression or death (PFS1) and overall survival (OS). Results: For the t(11;14) group at diagnosis, the median age was 63.7 yr (range, 22.1-95.4) with 64.5% of patients being male. Eighty nine (24.3%) patients were above 70 yr of age at diagnosis. 33.8%, 40.3% and 25.9% patients belonged to ISS 1, II and III stages respectively. 13% patients had elevated LDH. Monosomy 17 or del 17p were identified in 10.6% patients. The median follow up period was 56.9 months (m) (95% CI: 54.6-62.2) and 209 (57.1%) patients were alive at last follow-up. Among patients receiving proteasome inhibitor (PI)-based, immunomodulator (IMiD)-based, PI+IMiD based or other agent based induction therapy, 71.2%, 70.3%, 90.4% and 37.5% patients respectively attained ≥PR as best response to induction (p < 0.01). During their course, 223 (60.9%) patients underwent stem cell transplant. Median PFS1 and OS were 23.1 (CI: 20.8-27.9) and 78.6 (CI: 66.7-105.9) m respectively. Among the controls, high risk cytogenetics (HRC) was present in 142 (19.4%), and the median OS was 83.8 m (CI: 70.8-97.0) being comparable to t(11;14) group (p = 0.8). For all 1098 patients, using a Cox-proportional hazards model with age > 70 years, induction therapy (novel agent-based vs others), cytogenetics [HRC vs t(11;14) without HRC vs no HRC or t(11;14)], and ISS stage III vs II/I as predictors, age > 70 years [HR-2.2 (CI: 1.8-2.8) and p < 0.01], ISS III vs ISS II/I [HR-1.4 (CI: 1.1-1.8) and p < 0.01] and HRC [HR of 2.1 (CI: 1.6-2.8) vs no HRC or t(11;14) (p < 0.01) and 1.9 (CI = 1.4-2.6) for t(11;14) without HRC (p < 0.01)were associated with reduced OS. The risk for reduced OS did not differ between t(11;14) without HRC, and those without t(11;14) or HRC [HR-1.1 (CI: 0.9-1.4), p = 0.4]. Conclusions: Our study characterizes the outcomes of a large cohort of MM patients with t(11;14) at diagnosis. Advanced age, HRC and advanced stage at diagnosis were associated with worse OS in our cohort. t(11;14) MM without HRC does not differ in outcome compared to non-t(11;14) MM without HRC.


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.


2016 ◽  
Author(s):  
Michael S. Lauer

AbstractTo inform the retirement of NIH-owned chimpanzees, we analyzed the outcomes of 764 NIH-owned chimpanzees that were located at various points in time in at least one of 4 specific locations. All chimpanzees considered were alive and at least 10 years of age on January 1, 2005; transfers to a federal sanctuary began a few months later. During a median follow-up of just over 7 years, there were 314 deaths. In a Cox proportional hazards model that accounted for age, sex, and location (which was treated as a time-dependent covariate), age and sex were strong predictors of mortality, but location was only marginally predictive. Among 273 chimpanzees who were transferred to the federal sanctuary, we found no material increased risk in mortality in the first 30 days after arrival. During a median follow-up at the sanctuary of 3.5 years, age was strongly predictive of mortality, but other variables – sex, season of arrival, and ambient temperature on the day of arrival – were not predictive. We confirmed our regression findings using random survival forests. In summary, in a large cohort of captive chimpanzees, we find no evidence of materially important associations of location of residence or recent transfer with premature mortality.


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.


2005 ◽  
Vol 32 (3) ◽  
pp. 302-328 ◽  
Author(s):  
Mike Stoolmiller ◽  
Elaine A. Blechman

How well does substance use predict adolescent recidivism? When the Cox proportional hazards model was applied to officially recorded first rearrest of 505 juvenile offenders, a best-fitting complex multivariate model indicated that: (a) parent reports that youths “often” use substances more than doubles first rearrest risk, (b) averaged youth and parent substance use reports predict recidivism better than a single source, (c) parent or youth denial of youth substance use predicts recidivism, (d) age at first arrest does not predict recidivism, (e) non-White/non-Asians have a 79% higher recidivism risk than peers, (f) parent-reported delinquency predicts recidivism with declining accuracy, and (g) substance use robustly predicts recidivism despite prior reported delinquency, gender, ethnicity, age, follow-up time, or data source. Findings are related to host-provocation theory.


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