Safety and efficacy of bevacizumab biosimilar in glioma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14541-e14541
Author(s):  
Gunjesh Kumar Singh ◽  
Hollis D'souza ◽  
Sujay Srinivas ◽  
Dilip Harindran Vallathol ◽  
Mounika Boppana ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Cox Regression ◽  
Low Cost ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Recurrent Glioma ◽  
Rank Test ◽  
P Value ◽  
Cox Regression Analysis ◽  
Log Rank Test

e14541 Background: Anti-VEGF antibody Bevacizumab (Avastin: Roche Pharma AG) is the recommended drug for recurrent glioma. Multiple low-cost bio-similars of this drug are now available however their clinical efficacy has never been compared against the original molecule. The aim of the current analysis is to compare the overall survival (OS) between recurrent glioma patients with bio-similar and innovator molecule. Methods: Adult recurrent glioma patients treated with bevacizumab from 1st July 2015 to 30th July 2019 were identified from the Neuro-Medical Oncology database. These patients were either offered Avastin or Bevacizumab biosimilar (BevaciRel: Reliance Life sciences or Bryta: Zydus Oncosciences) depending upon the financial affordability. The primary endpoint of the study was OS. It was defined as the time in months from the start of bevacizumab to death. Progression-free survival (PFS) was defined as the time in months from the start of bevacizumab to progression or death. The time to event variables was estimated using Kaplan Meier method. The median with its 95% confidence interval (CI) was calculated using Brookmeyer and Crowley method. The estimates were compared between the original and bio-similar bevacizumab cohort using the log-rank test. The hazard ratio was calculated using COX regression analysis. Results: There were 82 patients, out of which 57 received innovator and 25 received bio-similar bevacizumab. At median follow up of 26 months, 76 patients had an event for progression. The median PFS was 3.66 (95% CI 2.08 to 5.25) and 3.3 months (95% CI 2.38 to 4.21) in innovator and bio-similar arm respectively (Log-rank test P-value = 0.072). The hazard ratio for progression was 0.61 (95% CI 0.35 to 1.05; P-value = 0.075). At the time of data cutoff, there were 69 deaths. The median OS was 5.53 (95% CI, 5.07 to 5.99) vs 7.33 months (95% CI, 5.63 to 9.03) in innovator and bio-similar arm respectively (Log-rank test P-value = 0.51). The hazard ratio for death was 1.21 (95% CI, 0.67 to 2.17; p-value = 0.51). Conclusions: In the brain tumor patients, both innovator and bio-similar bevacizumab seem to have similar clinical efficacy.

scholarly journals The prognostic value of lncRNA SNHG4 and its potential mechanism in liver cancer

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Yan Jiao ◽  
Yanqing Li ◽  
Baoxing Jia ◽  
Qingmin Chen ◽  
Guoqiang Pan ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
P Value ◽  
Expression Data ◽  
Potential Mechanism ◽  
Cox Regression Analysis ◽  
Cerna Network ◽  
Log Rank Test

Abstract Background and object: Emerging evidence shows that non-coding RNA functions as new gene regulators and prognostic markers in several cancers, including liver cancer. Here, we focused on the small nucleolar RNA host gene 4 (SNHG4) in liver cancer prognosis based on The Cancer Genome Atlas (TCGA) data. Methods: The expression data and clinical information were downloaded from TCGA. Chi-square tests evaluated the correlation between SNHG4 expression and clinical parameters. Differences in survival between high and low expression groups (optic cutoff value determined by ROC) from Cox regression analysis were compared, and P-value was calculated by a log-rank test. Kaplan–Meier curves were compared with the log-rank test. GSEA and ceRNA network were conducted to explore the potential mechanism. Results: Data mining of lncRNA expression data for 371 patients with primary tumor revealed overexpression of SNHG4 in liver cancer. High SNHG4 expression was correlated with histological type (P = 0.01), histologic grade (P = 0.001), stage (P = 0.01), T classification (P = 0.004) and survival status (P = 0.013). Patients with high SNHG4 expression had poor overall survival and relapse-free survival compared with those with low SNHG4 expression. Multivariate analysis identified SNHG4 as an independent prognostic factor of poor survival in liver cancer. GSEA revealed related signaling pathway and ceRNA network explored the further mechanism. Conclusion: High SNHG4 expression is an independent predictor of poor prognosis in liver cancer.

Exploratory analysis to investigate clinical factors that may influence trastsuzumab efficacy in patients with HER2-positive gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 169-169
Author(s):  
Takeru Wakatsuki ◽  
Keisho Chin ◽  
Satoshi Matsusaka ◽  
Mariko Ogura ◽  
Masato Ozaka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Exploratory Analysis ◽  
Rank Test ◽  
P Value ◽  
Clinical Factors ◽  
Her2 Positive ◽  
Cox Regression Analysis

169 Background: ToGA study showed significant survival benefit of trastuzumab in patients with HER2 positive gastric cancer (GC); however, clinical factors which can impact its efficacy prior to treatment are still unknown. Hence, we conducted this exploratory analysis whether clinical factors could influence trastuzumab efficacy in patients with HER2 positive GC. Methods: Thirty-three HER2 positive GC patients, who were treated by trastuzumab with chemotherapy in our institute from 2011 March to 2012 December, were enrolled. Clinical factors according to ToGA study and tumor markers were examined. We retrospectively analyzed whether these clinical factors were associated with progression-free survival (PFS) and overall survival (OS). These endpoints were estimated using by Kaplan-Meier methods and compared by the log-rank test. The Cox regression analysis including only clinical factors of which p-value was less than 0.02 was done. Results: Median follow-up period was 10.8 months. Median age was 63 y.o. and 64% of the patients were male. PS 0-1, GEJ cancer, visceral metastasis (lung or liver), previous gastorectomy, previous chemotherapy, number of metastatic site (1-2), and number of metastatic lesion (1-4) were found in 97%, 27%, 58%, 36%, 21%, 76%, and 27% of the patients, respectively. Sixty-seven% and 94% of the patients were differentiated type and HER2 3+ by IHC, respectively. Baseline median CEA and CA19-9 levels were 5.2 ng/ml and 109.4 U/ml, respectively. Median PFS was 9.5 months (95% CI: 5.5-13.5) and median OS was not reached. Overall response rate by RECIST was 71.4%. Lower CA19-9 levels were associated with longer PFS in univariate analysis. Patients who had lower CA 19-9 levels showed a median PFS of 12.2 months vs. 6.9 months for patients who had higher CA19-9 levels (HR: 0.41 [95%CI: 0.17-1.00], p=0.042), however this result was not conserved in multivariate analysis. No clinical factors were associated with OS. Conclusions: Lower CA19-9 levels were associated with favorable PFS in the patients with HER2 positive GC upon when treated by trastuzunab. External clinical validations and further molecular analyses are needed to validate this result.

scholarly journals 631 First vs. second generation drug-eluting STNET in heart transplant patients with cardiac allograft vasculopathy: a single centre experience

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Andrea Raffaele Munafò ◽  
Annalisa Turco ◽  
Giorgia Benzoni ◽  
Barbara Cattadori ◽  
Carlo Pellegrini ◽  
...  
Keyword(s):  
Heart Transplant ◽  
Cox Regression ◽  
Cardiovascular Death ◽  
Target Lesion ◽  
Rank Test ◽  
P Value ◽  
Syntax Score ◽  
Cox Regression Analysis ◽  
Transplant Patients ◽  
Log Rank Test

Abstract Aims Cardiac allograft vasculopathy (CAV) remains the ‘Achilles’ heel’ of successful long-term outcome after heart transplantation (HTx). Percutaneous coronary intervention (PCI) with bare-metal stents (BMS) and first (I) generation drug-eluting stents (DES) has been previously considered as a palliative treatment option in this setting, for the higher rate of restenosis and the lack of a survival benefit over medical therapy. Few data on the performance of second (II) generation DES in CAV are currently available. Our study aims to compare the efficacy and safety of PCI with I and II generation DES in patients with CAV. Methods and results All consecutive heart transplant patients who underwent urgent or elective PCI with I or II generation DES between 2003 and 2020 at Foundation IRCCS Polyclinic San Matteo (Pavia) were enrolled. The extent of revascularization for each patient was assessed calculating the post-procedural residual SYNTAX score. The primary endpoint was a composite of MACE [any myocardial infarction, cardiovascular death and target vessel revascularization (TVR)] at 3-year. The secondary endpoint was target lesion failure (TLF) at 3-year—composite of cardiovascular death, target vessel myocardial infarction (TV-MI) and target lesion revascularization (TLR). A total of 90 transplant patients (113 coronary lesions) were included: 28 patients (32 lesions) were treated with I generation DES and 62 patients (81 lesions) with II generation DES. No differences between the two study groups were identified in term of number of stents per patient implanted (overall 1.63 ± 0.87, P-value = 0.628), total stent length per patient [overall 26 (25th–75th : 18–44) mm, P-value = 0.486], pre-PCI [overall 8 (25th–75th: 5–15), P-value = 0.286], and post-PCI residual [overall 1.5 (25th–75th: 0–4), P-value = 0.187] SYNTAX score. In the whole study population, the primary and secondary endpoints occurred in 28 (33%) and 23 (27%) cases respectively, with a 3-year Kaplan–Meier estimate of freedom from MACE of 64%, and from TLF of 71%. No statistical differences between the two study arms were found (MACE log-rank test P-value = 0.269, TLF log-rank test P-value = 0.260). At multivariate Cox regression analysis, while treatment with II generation DES was confirmed to not predict the risk of MACE (HR: 0.70, CI: 0.32–1.5, P-value = 0.368), a borderline significant higher rate of events was found in patients with a post-PCI residual SYNTAX score >8 (HR: 2.37, CI: 0.98–5.73, P-value = 0.054). However, patients treated with II generation DES experienced a lower rate of TVR (3-year Kaplan-Meier estimate of freedom from TVR I generation DES 69% vs. II generation DES 85%, log-rank test P-value = 0.058, univariate Cox regression analysis HR: 0.4, CI: 0.13–1.07, P-value = 0.069). Conclusions In heart transplant patients with CAV, compared with I generation DES, PCI with II generation DES did not show to reduce the risk of MACE and TLF, guaranteeing however a lower rate of TVR. In this complex clinical scenario, incomplete revascularization (defined as a residual post-PCI SYNTAX score > 8) was associated with worse outcome at 3-year follow-up.

scholarly journals CILP2 overexpression predicts poor prognosis in colorectal cancer

2020 ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Rank Test ◽  
P Value ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Bioinformatical Analysis

Abstract Background: Cartilage Intermediate Layer Protein 2 (CILP2), a glycoprotein with mutations associated with abnormal blood lipid concentrations in normal and cardiovascular diseases patients, was barely reported with clinical features of tumors. We evaluated the role of CILP2 among all stages and histology in colorectal cancer (CRC) in the Cancer Genome Altas (TCGA), and furtherly verified using immunohistochemistry assay within human CRC tissues. Materials and methods : Clinical information and RNA-seq data were derived from TCGA colorectal carcinoma cohort. CILP2 expression at mRNA level was estimated by bioinformatical analysis of TCGA cases. Tissue microarray (TMA) was constructed containing paraffin-embedded 64 pairs of CRC and matched adjacent normal tissues. The expression at protein level was detected in 64 pairs of CRC and matched adjacent normal tissues by immunohistochemical analysis. CILP2 expression level and its clinical value were estimated by bioinformatical analysis with linear and logistic regression. Survival analysis was performed between high and low groups of CILP2 expression by Cox regression analysis, and P value was calculated by log-rank test. Kaplan-Meier curves were tested by log-rank test. Results : CILP2 was significantly higher expressed in the colorectal cancer tissues when compared with paired adjacent normal tissues in TCGA cohort ( P <0.001) and in TMA cohort ( P =0.001). In addition, CILP2 high-expression was strongly correlated with T3/4 stage ( P =0.001), N1/2/3 stage ( P =0.005), M1 stage ( P =0.048), and higher clinical stage (UICC 2010 stage) ( P <0.001) in TCGA cohort, and also positively associated with T3/4 stage ( P =0.022) and higher clinical stage (UICC 2010 stage) ( P =0.03) in TMA cohort. Furthermore, CILP2 overexpression predicted poor prognosis and could be as an independent prognostic factor ( P =0.003). Conclusion : We revealed that CILP2 is associated with advanced stages and could play a role as an independent predictor of poor survival in colorectal cancer. Key words: CILP2; Colorectal cancer; TCGA; Immunohistochemistry; Prognosis

scholarly journals Predictive impact of PVL assessments on clinical outcomes in patients undergoing TAVR

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Matsushita ◽  
B Marchandot ◽  
M Kibler ◽  
C Sato ◽  
J Heger ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Cox Regression ◽  
Adenosine Diphosphate ◽  
Rank Test ◽  
Multicenter Studies ◽  
Cox Regression Analysis ◽  
Paravalvular Leakage ◽  
Transcatheter Aortic Valve ◽  
Log Rank Test ◽  
Cerebrovascular Events

Abstract Introduction Paravalvular leakage (PVL) following transcatheter aortic valve replacement (TAVR) is associated with greater mortality. In clinical practice, determining PVL severity after TAVR remains challenging and often requires multiparametric assessment. Purpose This study sought to evaluate the respective value of various modalities of PVL assessments, including transthoracic echocardiography (TTE), cine-angiography, aortic regurgitation index (ARI), and closure time with adenosine diphosphate (CT-ADP), in the prediction of adverse clinical outcomes. Methods We included 1044 patients from our prospective TAVR registry between February 2010 and May 2019. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year. Established cutoff values of ARI (&lt;25) and CT-ADP (&gt;180 sec) were used to assess the presence of PVL after TAVR. Results Moderate to severe PVL occurred in 14.2% and 5.2% of patients as measured by TTE and angiography. The rate of patients with ARI &lt;25 and CT-ADP &gt;180 sec were 36.5% and 24.9%, respectively. Among the four modalities, PVL evaluated by angiography predicted poorer clinical outcomes (Log rank test; p=0.001), whereas TTE, ARI &lt;25, and CT-ADP &gt;180 sec were not associated with 1-year MACCE. By multivariate Cox regression analysis, moderate to severe PVL by angiography was an independent predictor of 1-year MACCE (hazard ratio: 1.96; 95% confidence interval: 1.22–3.00; p=0.007). Conclusions Paravalvular leakage measured by angiography was evidenced as the most meaningful modality in the prediction of adverse clinical outcomes. Future multicenter studies are warranted to ensure these findings in the current TAVR era. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals Tumor Volume Reduction Rate to Induction Chemotherapy Is a Prognostic Factor for Locally Advanced Head and Neck Squamous Cell Carcinoma: a Retrospective Cohort Study

2021 ◽  
Author(s):  
Chi-hsien Huang ◽  
Ting-Chun Lin ◽  
Ming-Yu Lien ◽  
Fu-Ming Cheng ◽  
Kai-Chiun Li ◽  
...  
Keyword(s):  
Tumor Volume ◽  
Cox Regression ◽  
Reduction Rate ◽  
Volume Reduction ◽  
Cancer Site ◽  
Rank Test ◽  
Primary Cancer ◽  
Cox Regression Analysis ◽  
Log Rank Test ◽  
Tumor Volume Reduction

Abstract BackgroundAim of this study was to evaluate the prognostic of tumor volume reduction rate (TVRR) status post induction chemotherapy (IC) in LA-HNSCC.MethodsPatients with newly diagnosed LA-HNSCC from year 2007 to 2016 at a single center were included in this retrospective study. All patients had received IC as TPF (taxotere, platinum, fluorouracil) followed by daily definitive intensity-modulated radiotherapy (IMRT) for 70 Gy in 35 fractions concurrent with or without cisplatin-based chemotherapy. Tumor volume reduction rate of the primary tumor (TVRR-T) and lymph node (TVRR-N) was measured and calculated by contrast-enhanced CT images at diagnosis, and one month after final IC cycle, and analyzed though a univariate and multivariate Cox regression model.ResultsNinety patients of the primary cancer sites at hypopharynx (31/90, 34.4%), oropharynx (29/90, 32.2%), oral cavity (19/90, 21.1%) and larynx (11/90, 12.2%) were included in this study, with a median follow-up time interval of 3.9 years. In univariate Cox regression analysis, the TVRR-T as the only variable showed a significant difference for disease-free survival (DFS) (hazard ratio [HR] 0.77, 95% confidence interval (CI) 0.63 to 0.96; P = 0.02), aside from cancer site, RECIST, age and IC dose. In multivariate Cox regression analysis, The TVRR-T was also an independently significant prognostic factor for DFS (HR 0.77, 95% CI 0.62 to 0.97; P = 0.02). At a cutoff value using TVRR-T of 50% in Kaplan-Meier survival analysis, the DFS was significant higher with TVRR-T ≥ 50% group (log-rank test, p = 0.024), and also a trend of improved OS. (log-rank test, p = 0.069).ConclusionsTVRR-T was related to improved DFS and trend of improved OS. Other factors including patient’s age at diagnosis, the primary cancer site, and RECIST, were not significantly related to DFS.

scholarly journals Clinical Value of lncRNA LUCAT1 Expression in Liver Cancer and its Potential Pathways

2019 ◽  
Vol 28 (4) ◽  
pp. 439-447 ◽  
Author(s):  
Yan Jiao ◽  
Yanqing Li ◽  
Bai Ji ◽  
Hongqiao Cai ◽  
Yahui Liu
Keyword(s):  
Liver Cancer ◽  
Roc Curve ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Rank Test ◽  
P Value ◽  
Rna Seq ◽  
Cox Regression Analysis

Background and Aims: Emerging studies indicate that long noncoding RNAs (lncRNAs) play a role as prognostic markers in many cancers, including liver cancer. Here, we focused on the lncRNA lung cancer-associated transcript 1 (LUCAT1) for liver cancer prognosis. Methods: RNA-seq and phenotype data were downloaded from the Cancer Genome Atlas (TCGA). Chisquare tests were used to evaluate the correlations between LUCAT1 expression and clinical features. Survival analysis and Cox regression analysis were used to compare different LUCAT1 expression groups (optimal cutoff value determined by ROC). The log-rank test was used to calculate the p-value of the Kaplan-Meier curves. A ROC curve was used to evaluate the diagnostic value. Gene Set Enrichment Analysis (GSEA) was performed, and competing endogenous RNA (ceRNA) networks were constructed to explore the potential mechanism. Results: Data mining of the TCGA -Liver Hepatocellular Carcinoma (LIHC) RNA-seq data of 371 patients showed the overexpression of LUCAT1 in cancerous tissue. High LUCAT1 expression was associated with age (p=0.007), histologic grade (p=0.009), T classification (p=0.022), and survival status (p=0.002). High LUCAT1 patients had a poorer overall survival and relapse-free survival than low LUCAT1 patients. Multivariate analysis identified LUCAT1 as an independent risk factor for poor survival. The ROC curve indicated modest diagnostic performance. GSEA revealed the related signaling pathways, and the ceRNA network uncovered the underlying mechanism. Conclusion: High LUCAT1 expression is an independent prognostic factor for liver cancer.

miR-181 Expression is Associated With The Prognosis in Lung Cancer.

2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Prognostic Value ◽  
Cox Regression ◽  
Suppressor Gene ◽  
Rank Test ◽  
High Morbidity ◽  
Cox Regression Analysis ◽  
Log Rank Test ◽  
Cancer Tissues

Abstract Background: Lung cancer is one of the most common cancers, with high morbidity and mortality. MiRNAs are proved to play important roles in various human cancers. In our study, we aimed to explore the prognostic value of miR-181 in lung cancerMethods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression level of miR-181 in lung cancer tissues and the paired non-cancerous tissues. The relationship between miR-181 expression and clinicopathologic parameters were analyzed by chi-square test. Kaplan-Meier method with log rank test was applied for overall survival analysis. Furthermore, the Cox regression analyses were performed to evaluate the prognostic value of miR-181 in lung cancer.Results: Down-regulated miR-181 expression was observed in lung cancer tissues (P<0.001), moreover, its expression was significantly correlated with TNM stage (P=0.015) and metastasis (P=0.000). In addition, lung cancer patients with lower miR-181 expression level had poorer overall survival than those with higher expression (log rank test, P=0.011). Cox regression analysis suggested that miR-181 was an independent prognostic factor for lung cancer (HR=1.961, 95%CI=1.135-3.388, P=0.016).Conclusion: MiR-181 may be a tumor suppressor gene in lung cancer, which can predict outcomes for the patients.

Phase III Study of VCAP-AMP-VECP vs. Biweekly CHOP in Aggressive Adult T-Cell Leukemia-Lymphoma (ATLL): Japan Clinical Oncology Group Study, JCOG9801.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 812-812 ◽  
Author(s):  
Kunihiro Tsukasaki ◽  
Takuya Fukushima ◽  
Atae Utsunomiya ◽  
Syuichi Ikeda ◽  
Masato Masuda ◽  
...  
Keyword(s):  
Cox Regression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Rank Test ◽  
P Value ◽  
Minimization Method ◽  
Adult T Cell Leukemia ◽  
Non Hodgkin Lymphoma

Abstract Background: In our study for non-Hodgkin lymphoma (NHL) in 1980’s (JCOG8701), human T-lymphotropic virus type-1- associated ATLL was the poorest prognostic subtype in NHL. The complete response (CR) rate was 42%, the median survival time (MST) was 8 months, and the 4-yr overall survival (OS) was 12% (Proc ASCO13:378, 1994). Our previous phase II study (JCOG9303) of G-CSF-supported, dose-intensified multi-agent chemotherapy with VCAP (vincristine, cyclophosphamide, doxorubicin, prednisolone), AMP (doxorubicin, ranimustine, prednisolone) and VECP (vindesine, etoposide, carboplatin, prednisolone) with intrathecal prophylaxis for aggressive ATLL, showed promising results with response rate (RR) of 81% and MST of 13 months (Br J Haematol113:375,2001). To test the superiority of this VCAP-AMP-VECP regimen over biweekly-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), we conducted a phase III trial. Methods: Previously untreated patients (pts) with aggressive ATLL, acute-, lymphoma- or unfavorable chronic-type, were randomized either to receive 6 courses of VCAP-AMP-VECP every 4 weeks (arm A) or 8 courses of biweekly-CHOP (arm B) with minimization method balancing performance status and institution. Both regimens were supported with G-CSF and intrathecal prophylaxis using cytarabine, methotrexate and prednisolone. Eligibility included preserved organ functions and aged 15–69 years. Primary endpoint was OS to be compared by log-rank test. Assuming 60 eligible pts in each arm, the study had 0.8 power to detect a 15% difference in 3-year OS at 0.05 one-sided alpha. Results: 118 pts (57 in arm A, 61 in arm B) were randomized between 07/98 and 10/03. Median follow-up time in all randomized pts was 11.0 months at 12/04. 72 % of the pts responded, with 23 pts achieving CR (40%) and 18 achieving partial response (PR; 32%) in arm A. The RR was 66%, with 15 pts achieving CR (25%) and 25 achieving PR (41%) in arm B. The median progression-free survival (PFS) time and PFS at one-year in arm A were 7.0 months and 28.1%, respectively, whereas 5.4 months and 16.2% in arm B. The MST and OS at 3 years in arm A were 12.7 months and 23.6%, respectively, whereas 10.9 months and 12.7% in arm B. Log-rank p-value for primary end point, OS, was 0.085. After adjustment of patients’ characteristics at registration by Cox regression, the p value became 0.029 because of unbalanced prognostic factors such as bulky lesion. In arm A vs. arm B, %G4 neutropenia, %G4 thrombocytopenia and %G4 infection were 98% vs. 83%, 74% vs. 17% and 7% vs. 3%, respectively. Three toxic deaths were reported in arm A. Conclusions: These results demonstrate that VCAP-AMP-VECP yields longer OS time than biweekly-CHOP but with higher toxicity profiles that are acceptable, and suggest that the former regimen should be the standard therapy for aggressive ATLL.

scholarly journals 551. Remdesivir and Tocilizumab for the Treatment of Severe COVID-19 in a Community Hospital: A Retrospective Cohort Study

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S378-S379
Author(s):  
Guillermo Rodriguez-Nava ◽  
Goar Egoryan ◽  
Daniela Patricia Trelles-Garcia ◽  
Maria Adriana Yanez-Bello ◽  
Qishuo Zhang ◽  
...  
Keyword(s):  
Regression Model ◽  
Community Hospital ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Rank Test ◽  
Hospital Death ◽  
P Value ◽  
Survival Curves ◽  
Cox Regression Model ◽  
Kaplan Meier

Abstract Background Growing evidence supports the use of remdesivir and tocilizumab for the treatment of hospitalized patients with severe COVID-19. The purpose of this study was to evaluate the use of remdesivir and tocilizumab for the treatment of severe COVID-19 in a community hospital setting. Methods We used a de-identified dataset of hospitalized adults with severe COVID-19 according to the National Institutes of Health definition (SpO2 &lt; 94% on room air, a PaO2/FiO2 &lt; 300 mm Hg, respiratory frequency &gt; 30/min, or lung infiltrates &gt; 50%) admitted to our community hospital located in Evanston Illinois, between March 1, 2020, and March 1, 2021. We performed a Cox proportional hazards regression model to examine the relationship between the use of remdesivir and tocilizumab and inpatient mortality. To minimize confounders, we adjusted for age, qSOFA score, noninvasive positive-pressure ventilation, invasive mechanical ventilation, and steroids, forcing these variables into the model. We implemented a sensitivity analysis calculating the E-value (with the lower confidence limit) for the obtained point estimates to assess the potential effect of unmeasured confounding. Figure 1. Kaplan–Meier survival curves for in-hospital death among patients treated with and without steroids The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. Figure 2. Kaplan–Meier survival curves for in-hospital death among patients treated with and without remdesivir The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. Results A total of 549 patients were included. The median age was 69 years (interquartile range, 59 – 80 years), 333 (59.6%) were male, 231 were White (41.3%), and 235 (42%) were admitted from long-term care facilities. 394 (70.5%) received steroids, 192 (34.3%) received remdesivir, and 49 (8.8%) received tocilizumab. By the cutoff date for data analysis, 389 (69.6%) patients survived, and 170 (30.4%) had died. The bivariable Cox regression models showed decreased hazard of in-hospital death associated with the administration of steroids (Figure 1), remdesivir (Figure 2), and tocilizumab (Figure 3). This association persisted in the multivariable Cox regression controlling for other predictors (Figure 4). The E value for the multivariable Cox regression point estimates and the lower confidence intervals are shown in Table 1. Figure 3. Kaplan–Meier survival curves for in-hospital death among patients treated with and without tocilizumab The hazard ratio was derived from a bivariable Cox regression model. The survival curves were compared with a log-rank test, where a two-sided P value of less than 0.05 was considered statistically significant. Figure 4. Forest plot on effect estimates and confidence intervals for treatments The hazard ratios were derived from a multivariable Cox regression model adjusting for age as a continuous variable, qSOFA score, noninvasive positive-pressure ventilation, and invasive mechanical ventilation. Table 1. Sensitivity analysis of unmeasured confounding using E-values CI, confidence interval. Point estimate from multivariable Cox regression model. The E value is defined as the minimum strength of association on the risk ratio scale that an unmeasured confounder would need to have with both the exposure and the outcome, conditional on the measured covariates, to explain away a specific exposure-outcome association fully: i.e., a confounder not included in the multivariable Cox regression model associated with remdesivir or tocilizumab use and in-hospital death in patients with severe COVID-19 by a hazard ratio of 1.64-fold or 1.54-fold each, respectively, could explain away the lower confidence limit, but weaker confounding could not. Conclusion For patients with severe COVID-19 admitted to our community hospital, the use of steroids, remdesivir, and tocilizumab were significantly associated with a slower progression to in-hospital death while controlling for other predictors included in the models. Disclosures All Authors: No reported disclosures

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