A retrospective, quantitative assessment of disease burden in patients with leptomeningeal metastases from non-small-cell lung cancer

Abstract Background Improvements in detection and molecular characterization of leptomeningeal metastasis from lung cancer (LC-LM) coupled with cerebrospinal fluid (CSF)-penetrating targeted therapies have altered disease management. A barrier to formal study of these therapies in LM is quantification of disease burden. Also, outcomes of patients with targetable mutations in LC-LM are not well defined. This study employs molecular and radiographic measures of LM disease burden and correlates these with outcome. Methods We reviewed charts of 171 patients with LC-LM treated at Memorial Sloan Kettering. A subset had MRI and CSF studies available. Radiographic involvement (n = 76) was scored by number of gadolinium-enhancing sites in 8 locations. CSF studies included cytopathology, circulating tumor cell (CTC) quantification (n = 16), and cell-free DNA (cfDNA) analysis (n = 21). Clinical outcomes were compared with Kaplan–Meier log-rank test and Cox proportional hazards methodologies. Results Median overall survival was 4.2 months (95% CI: 3.6–4.9); 84 patients (49%) harbored targetable mutations. Among bevacizumab-naïve patients with MRI and CSF cytology at time of LC-LM diagnosis, extent of radiographic involvement correlated with risk of death (hazard ratio [HR]: 1.16; 95% CI: 1.02–1.33; P = 0.03), as did CSF CTC (HR: 3.39, 95% CI: 1.01–11.37; P = 0.048) and CSF cfDNA concentration (HR: 2.58; 95% CI: 0.94–7.05; P = 0.06). Those without a targetable mutation were almost 50% more likely to die (HR: 1.49; 95% CI: 1.06–2.11; P = 0.02). Conclusions Extent of radiographic involvement and quantification of CSF CTC and cfDNA show promise as prognostic indicators. These findings support molecular characterization and staging for clinical management, prognostication, and clinical trial stratification of LC-LM.

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A Proposal of a Personalized Surveillance Strategy for Gastric Cancer: A Retrospective Analysis of 9191 Patients

Gastroenterology Research and Practice ◽

10.1155/2019/3248727 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Si-wei Pan ◽

Peng-liang Wang ◽

Han-wei Huang ◽

Lei Luo ◽

Xin Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Rank Test ◽

Surveillance Strategy ◽

Risk Of Death ◽

Kaplan Meier ◽

Advanced Stages ◽

Personalized Cancer

Background. In gastric cancer, various surveillance strategies are suggested in international guidelines. The current study is intended to evaluate the current strategies and provide more personalized proposals for personalized cancer medicine. Materials and Methods. In the aggregate, 9191 patients with gastric cancer after gastrectomy from 1998 to 2009 were selected from the Surveillance, Epidemiology, and End Results database. Disease-specific survival was analyzed by Kaplan-Meier method and the log-rank test. Cox proportional hazards regression analyses were used to confirm the independent prognostic factors. As well, hazard ratio (HR) curves were used to compare the risk of death over time. Conditional survival (CS) was applied to dynamically assess the prognosis after each follow-up. Results. Comparisons from HR curves on different stages showed that earlier stages had distinctly lower HR than advanced stages. The curve of stage IIA was flat and more likely the same as that of stage I while that of stage IIB is like that of stage III with an obvious peak. After estimating CS at intervals of three months, six months, and 12 months in different periods, stages I and IIA had high levels of CS all along, while there were visible differences among CS levels of stages IIB and III. Conclusions. The frequency of follow-up for early stages, like stages I and IIA, could be every six months or longer in the first three years and annually thereafter. And those with unfavorable conditions, such as stages IIB and III, could be followed up much more frequently and sufficiently than usual.

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Survival after cancer diagnosis among patients with higher income and education in Israel, a country with highly appreciated health service.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1598 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1598-1598

Author(s):

Yakir Rottenberg ◽

Aviad Zick ◽

Tamar Peretz

Keyword(s):

Lung Cancer ◽

Cancer Diagnosis ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Lower Socioeconomic Status ◽

Cancer Data ◽

Risk Of Death ◽

Lower Socioeconomic ◽

Treatment Disparities ◽

After Cancer

1598 Background: In recent years, the 5 year survival following cancer diagnosis is about two thirds. Among patients with various chronic diseases, improved survival is known to be associated with higher income and education. The aim of the current study is to assess the influence of income and education on survival following cancer diagnosis in Israel. Methods: Retrospective cohort study, using baseline measurement from the 1995 census conducted by the Central Bureau of Statistics in Israel. Cancer data were obtained from the Israel Cancer Registry. Cox proportional hazards ratios were calculated for mortality among cancer patients and adjusted for age, sex, religious, income and education years. The first model excluded cancers associated with early detection (breast, prostate, colorectal and cervix), and a second model excluded also lung cancer in order to control for smoking which is common in lower socioeconomic status. Results: A total of 3,712 cases of cancer and 1,252 deaths were reported during the study period. Higher income (HR=0.985 per 1000NIS, approximately 330$ in 1995's value, p=0.016) and education (HR=0.957 per year of education, p<0.001) were associated with decreased risk of death after cancer diagnosis. Jews had better prognosis than non-Jews following cancer diagnosis (HR=0.62, p<0.001), while males (HR=1.54, p<0.001) and age (HR=1.036 per year, p<0.001) had been associated with worse prognosis. The association between higher income and education was not changed in a model which excluded lung cancer. Conclusions: Higher income and education are associated with improved survival after cancer diagnosis. In the light of current study, further studies are needed to depict the variation in cancer incidence, stage at diagnosis and treatment disparities related to socioeconomic variables.

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Prognosis of Women With Metastatic Breast Cancer by HER2 Status and Trastuzumab Treatment: An Institutional-Based Review

Journal of Clinical Oncology ◽

10.1200/jco.2008.19.9844 ◽

2010 ◽

Vol 28 (1) ◽

pp. 92-98 ◽

Cited By ~ 463

Author(s):

Shaheenah Dawood ◽

Kristine Broglio ◽

Aman U. Buzdar ◽

Gabriel N. Hortobagyi ◽

Sharon H. Giordano

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Proportional Hazards ◽

Metastatic Breast ◽

Cox Proportional Hazards ◽

Rank Test ◽

Her2 Status ◽

First Line ◽

Risk Of Death ◽

Trastuzumab Treatment

Purpose The purpose of this study was to determine whether trastuzumab improves prognosis of women with metastatic human epidermal growth factor receptor 2 (HER2)/neu –positive breast cancer beyond that of women with HER2/neu-negative disease. Patients and Methods Two thousand ninety-one women with metastatic breast cancer diagnosed from 1991 to 2007, with known HER2/neu status and who had not received trastuzumab in the adjuvant setting, were identified. Disease was classified into the following three groups: HER2/neu negative, HER2/neu positive without first-line trastuzumab treatment, and HER2/neu positive with first-line trastuzumab treatment. Overall survival (OS) was estimated using the Kaplan-Meier product-limit method and compared between groups with the log-rank test. Cox proportional hazards models were used to determine associations between OS and HER2/neu status after controlling for patient characteristics. Results One hundred eighteen patients (5.6%) had HER2/neu-positive disease without trastuzumab treatment, 191 (9.1%) had HER2/neu-positive disease and received trastuzumab treatment, and 1,782 (85.3%) had HER2/neu-negative disease. Median-follow-up was 16.9 months. One-year survival rates among patients with HER2/neu-negative disease, HER2/neu-positive disease and trastuzumab treatment, and HER2/neu-positive disease and no trastuzumab treatment were 75.1% (95% CI, 72.9% to 77.2%), 86.6% (95% CI, 80.8% to 90.8%), and 70.2% (95% CI, 60.3% to 78.1%), respectively. In a multivariable model, women with HER2/neu-positive disease who received trastuzumab had a 44% reduction in the risk of death compared with women with HER2/neu-negative disease (hazard ratio [HR] = 0.56; 95% CI, 0.45 to 0.69; P < .0001). This HR varied with time and was significant for the first 24 months and not significant after 24 months. Conclusion Our results show that women with HER2/neu-positive disease who received trastuzumab had improved prognosis compared with women with HER2/neu-negative disease.

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CMET-12. EFFICACY OF UPFRONT IMMUNE CHECKPOINT INHIBITORS IN LUNG CANCER BRAIN METASTASIS

Neuro-Oncology ◽

10.1093/neuonc/noz175.213 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi53-vi53

Author(s):

Addison Barnett ◽

Adam Lauko ◽

Hong Li ◽

Assad Ali ◽

Soumya Sagar ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastasis ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Proportional Hazards ◽

Checkpoint Inhibitors ◽

Tertiary Care ◽

Cox Proportional Hazards ◽

Rank Test ◽

Cox Proportional Hazards Models

Abstract INTRO/OBJECTIVE Immune checkpoint inhibitors (ICI) have improved outcomes in a subset of patients with lung cancer. However, data describing the efficacy of ICI in lung cancer brain metastasis (LCBM) is limited. We analyzed overall survival (OS) in patients with LCBM treated with upfront ICI, defined as having received ICI within 90-days of LCBM diagnosis, compared to non-ICI therapies. METHODS We reviewed 665 patients with LCBM diagnosed between 2000 and 2018 at a major tertiary care institution. Of those patients, 240 received ICI, 164 of which received ICI after 90-days and 76 received ICI within 90-days. Propensity score (PS) was calculated by logistic regression model including age, KPS, number of baseline brain lesions, and presence of extra-cranial metastasis (ECM) at time of LCBM diagnosis. OS from LCBM diagnosis between PS matched cohorts were compared using Kaplan-Meier, the Log-Rank test, and Cox proportional hazards models. RESULTS Prior to PS matching, median survival between ICI and non-ICI cohorts was not significantly different (10.9 months for both, p=0.81), although more ICI patients had ECM (57.1% vs 40.9%, p=0.006). Following PS matching, the ICI (n=76) and non-ICI (n=76) cohorts had median age (62.4 vs 62.3 years), KPS (80 for both), lesion number (2 for both), and ECM (56.6% for both). Of matched patients, 94% received SRS, 52% received WBRT, and 29% underwent surgical resection. Compared to non-ICI, the ICI cohort had a 2-year OS hazard ratio=0.87 (95% CI=0.58–1.31, p=0.51). Median and 1-year survival were not significantly different between ICI and non-ICI cohorts (median: 10.9 vs 9.1 months; 1-yr: 43.0% vs 42.4%). CONCLUSION Patients with LCBM who received ICI within 90-days of their diagnosis did not have improvement in OS compared to patients who received non-ICI therapies. Evaluation of clinical factors that may affect the efficacy and durability of immunotherapy is ongoing and will be presented.

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Hepatic Resection Versus Transarterial Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma: A Cohort Study

Frontiers in Oncology ◽

10.3389/fonc.2021.618937 ◽

2021 ◽

Vol 11 ◽

Author(s):

Linbin Lu ◽

Peichan Zheng ◽

Zhixian Wu ◽

Xiong Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatic Resection ◽

Transarterial Chemoembolization ◽

Proportional Hazards ◽

Intermediate Stage ◽

Cox Proportional Hazards ◽

Rank Test ◽

Real World Data ◽

Risk Of Death ◽

The Impact

BackgroundThe selection criteria for hepatic resection (HR) in intermediate-stage (IM) hepatocellular carcinoma (HCC) are still controversial. We used real-world data to evaluate the overall survival (OS) in treatment with HR or transarterial chemoembolization (TACE).MethodsIn total, 942 patients with IM-HCC were categorized into the HR group and the TACE group. OS was analyzed using the Kaplan–Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched (PSM) analysis. Curve smoothing was performed through the generalized additive model. The interaction test was performed to evaluate the impact of HR on OS concerning risk factors. Also, we used multiple imputation to deal with missing data.ResultsIn total, 23.0% (n = 225) of patients received HR. At a median OS of 23.7 months, HR was associated with improved OS in the multivariate analysis [hazard ratio (HzR) = 0.45, 95%CI = 0.35–0.58; after PSM: HzR = 0.56, 95%CI = 0.41–0.77]. Landmark analyses limited to long-term survivors of ≥6 months, ≥1 year, and ≥2 years demonstrated better OS with HR in all subsets (all p < 0.05). After PSM analysis, however, HR increased the risk of death by 20% (HzR = 1.20, 95%CI = 0.67–2.15) in the subgroup of patients with lactate dehydrogenase (LDH) ≤192 U/L (p for interaction = 0.037). Furthermore, the significant interaction was robust between the LDH and HR with respect to the 1-, 3-, and 5-year observed survival rates (all p < 0.05).ConclusionHR was superior to TACE for intermediate-stage HCC in patients with LDH levels >192 U/L. Moreover, TACE might be suitable for patients with LDH levels ≤192 U/L.

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Adaptive metabolic and inflammatory responses identified using accelerated aging metrics are linked to adverse outcomes in severe SARS-CoV-2 infection

The Journals of Gerontology Series A ◽

10.1093/gerona/glab078 ◽

2021 ◽

Author(s):

Alejandro Márquez-Salinas ◽

Carlos A Fermín-Martínez ◽

Neftalí Eduardo Antonio-Villa ◽

Arsenio Vargas-Vázquez ◽

Enrique C. Guerra ◽

...

Keyword(s):

Critical Illness ◽

Proportional Hazards ◽

Inflammatory Responses ◽

Age Groups ◽

Accelerated Aging ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Adaptive Responses ◽

Predictive Capacity ◽

Risk Of Death

Abstract Background Chronological age (CA) is a predictor of adverse COVID-19 outcomes; however, CA alone does not capture individual responses to SARS-CoV-2 infection. Here, we evaluated the influence of aging metrics PhenoAge and PhenoAgeAccel to predict adverse COVID-19 outcomes. Furthermore, we sought to model adaptive metabolic and inflammatory responses to severe SARS-CoV-2 infection using individual PhenoAge components. Methods In this retrospective cohort study, we assessed cases admitted to a COVID-19 reference center in Mexico City. PhenoAge and PhenoAgeAccel were estimated using laboratory values at admission. Cox proportional hazards models were fitted to estimate risk for COVID-19 lethality and adverse outcomes (ICU admission, intubation, or death). To explore reproducible patterns which model adaptive responses to SARS-CoV-2 infection, we used k-means clustering using PhenoAge components. Results We included 1068 subjects of whom 222 presented critical illness and 218 died. PhenoAge was a better predictor of adverse outcomes and lethality compared to CA and SpO2 and its predictive capacity was sustained for all age groups. Patients with responses associated to PhenoAgeAccel>0 had higher risk of death and critical illness compared to those with lower values (log-rank p<0.001). Using unsupervised clustering we identified four adaptive responses to SARS-CoV-2 infection: 1) Inflammaging associated with CA, 2) metabolic dysfunction associated with cardio-metabolic comorbidities, 3) unfavorable hematological response, and 4) response associated with favorable outcomes. Conclusions Adaptive responses related to accelerated aging metrics are linked to adverse COVID-19 outcomes and have unique and distinguishable features. PhenoAge is a better predictor of adverse outcomes compared to CA.

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Epilepsy as a Comorbidity in Polymyositis and Dermatomyositis—A Cross-Sectional Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18083983 ◽

2021 ◽

Vol 18 (8) ◽

pp. 3983

Author(s):

Ella Nissan ◽

Abdulla Watad ◽

Arnon D. Cohen ◽

Kassem Sharif ◽

Johnatan Nissan ◽

...

Keyword(s):

Proportional Hazards ◽

Cross Sectional Study ◽

Cox Proportional Hazards ◽

Categorical Variables ◽

Rank Test ◽

Control Group ◽

Multivariable Logistic Regression Analysis ◽

Positive Trend ◽

Continuous Variables ◽

Cross Sectional

Polymyositis (PM) and dermatomyositis (DM) are autoimmune-mediated multisystemic myopathies, characterized mainly by proximal muscle weakness. A connection between epilepsy and PM/DM has not been reported previously. Our study aim is to evaluate this association. A case–control study was conducted, enrolling a total of 12,278 patients with 2085 cases (17.0%) and 10,193 subjects in the control group (83.0%). Student’s t-test was used to evaluate continuous variables, while the chi-square test was applied for the distribution of categorical variables. Log-rank test, Kaplan–Meier curves and multivariate Cox proportional hazards method were performed for the analysis regarding survival. Of the studied 2085 cases, 1475 subjects (70.7%) were diagnosed with DM, and 610 patients (29.3%) with PM. Participants enrolled as cases had a significantly higher rate of epilepsy (n = 48 [2.3%]) as compared to controls (n = 141 [1.4%], p < 0.0005). Using multivariable logistic regression analysis, PM was found only to be significantly associated with epilepsy (OR 2.2 [95%CI 1.36 to 3.55], p = 0.0014), whereas a non-significant positive trend was noted in DM (OR 1.51 [95%CI 0.99 to 2.30], p = 0.0547). Our data suggest that PM is associated with a higher rate of epilepsy compared to controls. Physicians should be aware of this comorbidity in patients with immune-mediated myopathies.

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Influence of Smoking Habits on the Prevalence of Dental Caries: A Register-Based Cohort Study

European Journal of Dentistry ◽

10.1055/s-0041-1729458 ◽

2021 ◽

Author(s):

Miguel A. de Araújo Nobre ◽

Ana M. Sezinando ◽

Inês C. Fernandes ◽

Andreia C. Araújo

Keyword(s):

Dental Caries ◽

Proportional Hazards ◽

Smoking Habit ◽

Cox Proportional Hazards ◽

Radiographic Examination ◽

Rank Test ◽

Significance Level ◽

Cumulative Survival ◽

Caries Lesions

Abstract Objective The study aimed to evaluate the influence of smoking habit on the prevalence of dental caries lesions in a follow-up study. Materials and Methods A total of 3,675 patients (2,186 females and 1,489 males) with an average age of 51.4 years were included. Outcome measures were the incidence of dental caries defined as incipient noncavitated, microcavitated, or cavitated lesions which had been diagnosed through clinical observation with mouth mirror and probe examination evaluating change of texture, translucency, and color; radiographic examination through bitewing radiographs; or secondary caries through placement of a new restoration during the follow-up of the study. Statistical Analysis Cumulative survival (time elapsed with absence of dental caries) was estimated through the Kaplan–Meier product limit estimator with comparison of survival curves (log-rank test). A multivariable Cox proportional hazards regression model was used to evaluate the effect of smoking on the incidence of dental caries lesions when controlled to age, gender, systemic status, frequency of dental hygiene appointments, and socioeconomic status. The significance level was set at 5%. Results Eight hundred sixty-three patients developed caries (23.5% incidence rate). The cumulative survival estimation was 81.8% and 48% survival rate for nonsmokers and smokers, respectively (p < 0.001), with an average of 13.5 months between the healthy and diseased state diagnosis. Smokers registered a hazard ratio for dental caries lesions of 1.32 (p = 0.001) when controlled for the other variables of interest. Conclusion Within the limitations of this study, it was concluded that smoking habit might be a predictor for dental caries.

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Pre-diagnosis neutrophil-to-lymphocyte ratio and mortality in individuals who develop lung cancer

Cancer Causes & Control ◽

10.1007/s10552-021-01469-3 ◽

2021 ◽

Author(s):

Laurie Grieshober ◽

Stefan Graw ◽

Matt J. Barnett ◽

Gary E. Goodman ◽

Chu Chen ◽

...

Keyword(s):

Lung Cancer ◽

Proportional Hazards ◽

Smoking Status ◽

Cox Proportional Hazards ◽

Neutrophil To Lymphocyte Ratio ◽

Blood Draw ◽

Lymphocyte Ratio ◽

Cox Proportional Hazards Models ◽

Inflammatory Profile ◽

Heavy Smokers

Abstract Purpose The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been reported to be associated with survival after chronic disease diagnoses, including lung cancer. We hypothesized that the inflammatory profile reflected by pre-diagnosis NLR, rather than the well-studied pre-treatment NLR at diagnosis, may be associated with increased mortality after lung cancer is diagnosed in high-risk heavy smokers. Methods We examined associations between pre-diagnosis methylation-derived NLR (mdNLR) and lung cancer-specific and all-cause mortality in 279 non-small lung cancer (NSCLC) and 81 small cell lung cancer (SCLC) cases from the β-Carotene and Retinol Efficacy Trial (CARET). Cox proportional hazards models were adjusted for age, sex, smoking status, pack years, and time between blood draw and diagnosis, and stratified by stage of disease. Models were run separately by histotype. Results Among SCLC cases, those with pre-diagnosis mdNLR in the highest quartile had 2.5-fold increased mortality compared to those in the lowest quartile. For each unit increase in pre-diagnosis mdNLR, we observed 22–23% increased mortality (SCLC-specific hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.02, 1.48; all-cause HR = 1.22, 95% CI 1.01, 1.46). SCLC associations were strongest for current smokers at blood draw (Interaction Ps = 0.03). Increasing mdNLR was not associated with mortality among NSCLC overall, nor within adenocarcinoma (N = 148) or squamous cell carcinoma (N = 115) case groups. Conclusion Our findings suggest that increased mdNLR, representing a systemic inflammatory profile on average 4.5 years before a SCLC diagnosis, may be associated with mortality in heavy smokers who go on to develop SCLC but not NSCLC.

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The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

Acta Haematologica ◽

10.1159/000514920 ◽

2021 ◽

pp. 1-9

Author(s):

Leonard Naymagon ◽

Douglas Tremblay ◽

John Mascarenhas

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Proportional Hazards ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Rank Test ◽

Kaplan Meier ◽

Hazard Ratios ◽

Significant Difference ◽

The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

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