scholarly journals Heregulin expression and its clinical implication for patients with EGFR-mutant non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kimio Yonesaka ◽  
Eiji Iwama ◽  
Hidetoshi Hayashi ◽  
Shinichiro Suzuki ◽  
Ryoji Kato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Cox Proportional Hazards Model ◽  
Small Cell Lung ◽  
Hazards Model ◽  
Egfr Tkis

AbstractEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard therapy for EGFR-mutant non-small cell lung cancer (NSCLC). Preclinically, HER3 ligand heregulin induces resistance to EGFR-TKIs, whereas the pan-human EGFR family inhibitor afatinib remains effective. Here, we examined whether soluble heregulin levels have clinical implications for EGFR-mutant NSCLC treated with EGFR-TKIs. Soluble heregulin was immunologically measured in plasma from EGFR-mutant NSCLC patients. Cutoff values were determined by 1-year PFS ROC curve. The relationship between soluble heregulin and PFS following EGFR-TKI therapy was analyzed by Cox proportional hazards model. Seventy-three patients were enrolled: 44 were treated with 1st-generation and 29 with 2nd-generation EGFR-TKIs. Soluble heregulin levels varied (range: 274–7,138 pg/mL, median: 739 pg/mL). Among patients treated with 1st-generation EGFR-TKIs, those with high heregulin (n = 20, >800 pg/mL) had a tendency for shorter PFS than those with low heregulin (n = 24, <800 pg/mL), with median PFS of 322 and 671 days, respectively. Cox proportional hazards model also indicated a trend toward resistance against 1st-generation EGFR-TKIs (HR: 1.825, 95% CI: 0.865–4.318) but not against 2nd-generation EGFR-TKIs. Soluble heregulin potentially correlates with resistance to EGFR-TKIs but not 2nd-generation EGFR-TKIs in patients with EGFR-mutant NSCLC.

Immune Checkpoint Inhibitor for Non-small Cell Lung Cancer With Negative or Low Tumor PD-L1 Expression

2021 ◽  
Vol 1 (3) ◽  
pp. 173-177
Author(s):  
MINEHIKO INOMATA ◽  
NAOKI TAKATA ◽  
ISAMI MIZUSHIMA ◽  
KENJI AZECHI ◽  
KANA HAYASHI ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Cox Proportional Hazards Model ◽  
Small Cell Lung ◽  
Hazards Model

Background/Aim: We conducted a retrospective analysis of the survival durations of 25 patients diagnosed as having non-squamous cell non-small cell lung cancer with negative or low tumor programmed death-ligand 1 (PD-L1) expression treated with immune checkpoint inhibitor (ICI) monotherapy. Patients and Methods: The progression-free (PFS) and overall (OS) survival were calculated from the initiation of ICI monotherapy. The association between the patient characteristics and the PFS was analyzed using Cox proportional hazards model. Results: The median PFS was 2.6 months, and the 12-month PFS rate was 9.3%. The median OS was 5.5 months, and the 12-month OS rate was 39.8%. A Cox proportional hazards model identified the neutrophil/lymphocyte ratio and presence of liver metastasis as being significantly associated with PFS. Conclusion: Our findings suggest that a subset of patients with non-squamous cell non-small cell lung cancer who show negative or low tumor PD-L1 expression could benefit from ICI monotherapy.

Therapeutic effect of cranial radiotherapy with or without anlotinib treatment for lung cancer patients with brain metastasis and non-EGFR/ALK-TKIs indication

2020 ◽  
Author(s):  
Zelai He ◽  
Jia Liu ◽  
Hongwei Li ◽  
Jing Qian ◽  
Zhen Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Brain Metastasis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Cox Proportional Hazards Model ◽  
Cranial Radiotherapy ◽  
Hazards Model

Abstract Background: Cranial radiotherapy (CRT) is the main treatment for lung malignant tumor with brain metastasis (BM) and lacking EGFR/ALK-TKIs indication. For non-small cell lung cancer with BM, anlotinib can improve progression free survival (PFS). We retrospectively analyzed the clinical effects of anlotinib + CRT versus CRT alone.Methods: In patients with lung cancer (adenocarcinoma, squamous carcinoma, or small cell carcinoma) with BM and non-EGFR/ALK-TKIs indication, the overall survival (OS) and PFS of anlotinib + CRT treatment versus CRT treatment alone were separately calculated and compared. The Cox proportional hazards model was used to analyze the independent prognostic factors for intracranial PFS (iPFS) and OS. All confounding factors were adjusted, including age, gender, Karnofsky Performance Status (KPS) score, smoking history, physiological characteristics, T/N stage, histology, metastases, and pathological characteristics. Subgroup analysis for iPFS and OS was performed to assess the effects on BM of treatment pattern.Results: The study included 100 patients with BM at baseline and the follow-up data. Of the 100 patients, 67 patients received CRT treatment alone and 33 patients received CRT + anlotinib treatment. The overall response rates of the CRT + anlotinib group and the CRT alone group were 90.91% and 83.58%, respectively. There was significantly more iPFS in the CRT + anlotinib group compared to CRT alone (median iPFS [miPFS]: 9.0 vs 3.0 months; hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.01-2.52; p = 0.038). The OS, extracranial PFS (ePFS), and systematic PFS (sPFS) of CRT + anlotinib group were longer than those of the CRT alone group, but there was no significant statistical difference (median OS [mOS]: 9.0 vs 7.0 months, HR 1.17, 95% CI 0.74-1.85; median ePFS [mePFS]: 9.0 vs 7.0 months, HR 1.23, 95% CI 0.72-2.11; median sPFS [msPFS]: 7.0 vs 4.0 months, HR 1.37, 95% CI 0.82-2.30). The Cox proportional hazards model analysis revealed that age was an independent prognostic factor of iPFS (HR 1.65, 95% CI 1.05-2.59, p = 0.03). Age (HR 1.74, 95% CI 1.09-2.77, p = 0.02) and KPS score (HR 1.88, 95% CI 1.17-3.01, p = 0.01) were identified as independent prognostic factors of OS. Further subgroup analysis of iPFS showed that when the number of BM in the CRT + anlotinib group was less than or equal to three lesions (≤ 3), the miPFS (12.0 months) was significantly longer than that for CRT alone (> 3) (3.0 months), for CRT alone (≤ 3) (3.0 months), and for CRT + anlotinib (> 3) (7.0 months) (p = 0.014). The OS of the CRT + anlotinib group (≤ 3) (mOS 37.0 months) was much longer than that in CRT alone (> 3) (mOS 6.0 months), CRT alone (≤ 3) (mOS 7.5 months), and CRT + anlotinib (> 3) (mOS 8.5 months) groups, but this difference was not statistically significant (p = 0.051).Conclusion: Anlotinib can improve the survival of patients with lung cancer BM, with better efficacy of a combined treatment of anlotinib + CRT compared to that of CRT alone, especially for the iPFS of patients with BM ≤ 3.

scholarly journals Analysis of Prognostic Factors of Patients with Small Cell Lung Cancer using Cox's Proportional Hazards Model.

Haigan ◽  
1993 ◽  
Vol 33 (7) ◽  
pp. 1011-1016
Author(s):  
Masahiko Takenaka ◽  
Noriaki Iwahashi ◽  
Takashi Nakano ◽  
Juichiro Maeda ◽  
Nobuyuki Aihara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Small Cell ◽  
Small Cell Lung ◽  
Hazards Model ◽  
Cox's Proportional Hazards Model

scholarly journals Real-World Use of FLT3 Tyrosine Kinase Inhibitors in Patients with Relapsed/Refractory FLT3 mutation-Positive Acute Myeloid Leukemia in the United States

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5033-5033
Author(s):  
David L. Grinblatt ◽  
Wei Han ◽  
David Nimke ◽  
Qi Feng ◽  
Loretta Sullivan ◽  
...  
Keyword(s):  
Real World ◽  
Treatment Duration ◽  
Kinase Inhibitors ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Treatment Patterns ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Tki Treatment

Abstract Background: FLT3 tyrosine kinase inhibitors (TKIs) have improved outcomes in clinical trials for patients with FLT3 mutation-positive acute myeloid leukemia (FLT3mut+ AML). Gilteritinib is the first FDA-approved (11/28/2018) targeted therapy for relapsed/refractory (R/R) FLT3mut+ AML in adults, although two other multikinase inhibitors, midostaurin and sorafenib, are used off-label in this population. This analysis characterized treatment duration for these three drugs in R/R FLT3mut+ AML, as little is known about the treatment of patients receiving a FLT3 inhibitor in the real world. Aim/Objective: To describe real-world treatment patterns of patients newly initiating a FLT3 TKI for R/R AML following the launch of gilteritinib. Methods: This was a post hoc analysis of a US-based retrospective cohort study using IBM MarketScan claims data (1/1/2007-10/30/2020) to evaluate real-world treatment patterns. Adult patients (≥18 years) with R/R AML who newly initiated a FLT3 TKI (ie, ≥1 claim for gilteritinib, midostaurin, or sorafenib) on or after 12/1/2018 were eligible for inclusion. Included patients were required to have continuous enrollment starting 180 days prior to first AML diagnosis through first FLT3 TKI initiated for R/R AML on or after 12/1/2018 (index date). FLT3 TKI treatment duration was calculated as the difference between the first claim and the last day of supply or end of enrollment/study, whichever occurred first. Treatments that were not discontinued prior to the end of the study period (10/30/2020) were censored. Treatment duration was estimated using Kaplan-Meier analysis, and the hazard ratio for discontinuation was estimated with a Cox proportional hazards model. Additional subgroup analyses were conducted based on prior FLT3 TKI exposure for R/R AML and use of FLT3 TKI therapy alone or in combination with chemotherapy. Data from the ProMetrics specialty pharmacy database (12/6/2018-3/3/2021) were also analyzed to establish a benchmark for gilteritinib and validate the treatment duration in the MarketScan results. Results: A total of 65 patients newly initiating FLT3 TKIs for R/R AML were identified in the MarketScan database. Mean patient age was 53.4 years and mean Quan-Charlson Comorbidity index score at baseline was 5.1. Most patients initiating FLT3 TKI therapy received gilteritinib (n=44 [68%]). Patients initiating gilteritinib compared with other FLT3 TKIs had the highest prior history of high-intensity chemotherapy (n=24 [47%]) and hematopoietic stem cell transplantation (n=16 [31%]). Midostaurin was the most common prior TKI for patients who initiated sorafenib (n=6 [50%]) or gilteritinib (n=28 [55%]). The median (95% CI) treatment duration was 150 (73-260) days for gilteritinib (n=51), 60 (15-210) days for sorafenib (n=12), and 54 (28-268) days for midostaurin (n=12). Treatment duration was significantly longer for patients receiving gilteritinib compared with midostaurin (P=.0018) and sorafenib (P=.0016) in the Cox proportional hazards model (Table) and the Kaplan-Meier analysis (P=.0021) (Figure). Differences in gilteritinib duration in patients with prior TKI treatment versus no prior TKI treatment and patients who used a FLT3 TKI alone versus in combination with chemotherapy were not statistically significant (Table). The median gilteritinib treatment duration in the MarketScan data (150 days) was aligned with the median duration in the ProMetrics specialty pharmacy data (154 days), which validates the MarketScan results. Conclusions: This early look at treatment patterns suggests a median duration of therapy for gilteritinib of 150 days. Importantly, gilteritinib treatment duration does not appear to differ based on prior TKI treatment or overlapping use with chemotherapy. Small sample sizes precluded adjusted comparisons between the treatments. Gilteritinib was the most commonly used treatment. The availability of new targeted therapies such as gilteritinib is promising for patients with R/R FLT3mut+ AML and is changing the therapeutic landscape for this aggressive AML subtype. Figure 1 Figure 1. Disclosures Grinblatt: Astellas Pharma, Inc.: Consultancy; Bristol Myers Squibb: Consultancy; Astra Zeneca: Consultancy; AbbVie: Consultancy. Han: Astellas Pharma, Inc.: Current Employment. Nimke: Astellas Pharma, Inc.: Current Employment. Feng: Astellas Pharma, Inc.: Current Employment. Sullivan: Astellas Pharma, Inc.: Current Employment. Pandya: Astellas Pharma, Inc.: Current Employment.

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&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.

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 &lt;.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.

scholarly journals Evaluation of Changes on World Stock Exchanges in Connection with the SARS-CoV-2 Pandemic. Survival Analysis Methods

Risks ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 121
Author(s):  
Beata Bieszk-Stolorz ◽  
Krzysztof Dmytrów
Keyword(s):  
Survival Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Stock Exchange ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stock Exchanges ◽  
Analysis Methods ◽  
Hazards Model ◽  
Kaplan Meier

The aim of our research was to compare the intensity of decline and then increase in the value of basic stock indices during the SARS-CoV-2 coronavirus pandemic in 2020. The survival analysis methods used to assess the risk of decline and chance of rise of the indices were: Kaplan–Meier estimator, logit model, and the Cox proportional hazards model. We observed the highest intensity of decline in the European stock exchanges, followed by the American and Asian plus Australian ones (after the fourth and eighth week since the peak). The highest risk of decline was in America, then in Europe, followed by Asia and Australia. The lowest risk was in Africa. The intensity of increase was the highest in the fourth and eleventh week since the minimal value had been reached. The highest odds of increase were in the American stock exchanges, followed by the European and Asian (including Australia and Oceania), and the lowest in the African ones. The odds and intensity of increase in the stock exchange indices varied from continent to continent. The increase was faster than the initial decline.

scholarly journals Association between milk and yogurt intake and mortality: a community-based cohort study (Yamagata study)

BMC Nutrition ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Akiko Nakanishi ◽  
Erika Homma ◽  
Tsukasa Osaki ◽  
Ri Sho ◽  
Masayoshi Souri ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Hazard Analysis ◽  
Total Mortality ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Milk Intake ◽  
Community Based ◽  
Hazards Model ◽  
Kaplan Meier

Abstract Background Dairy products are known as health-promoting foods. This study prospectively examined the association between milk and yogurt intake and mortality in a community-based population. Methods The study population comprised of 14,264 subjects aged 40–74 years who participated in an annual health checkup. The frequency of yogurt and milk intake was categorized as none (< 1/month), low (< 1/week), moderate (1–6/week), and high (> 1/day) intake. The association between yogurt and milk intake and total, cardiovascular, and cancer-related mortalities was determined using the Cox proportional hazards model. Results During the follow-up period, there were 265 total deaths, 40 cardiovascular deaths and 90 cancer-related deaths. Kaplan–Meier analysis showed that the total mortality in high/moderate/low yogurt intake and moderate/low milk intake groups was lower than that in none group (log-rank, P < 0.01). In the multivariate Cox proportional hazard analysis adjusted for possible confounders, the hazard ratio (HR) for total mortality significantly decreased in high/moderate yogurt intake group (HR: 0.62, 95% confidence interval [CI]: 0.42–0.91 for high intake, HR: 0.70, 95%CI: 0.49–0.99 for moderate intake) and moderate milk intake group (HR: 0.67, 95% CI: 0.46–0.97) compared with the none yogurt and milk intake groups. A similar association was observed for cancer-related mortality, but not for cardiovascular mortality. Conclusions Our study showed that yogurt and milk intake was independently associated with a decrease in total and cancer-related mortalities in the Japanese population.

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