Differences in Survival Rates for Patients with Hodgkin Lymphoma, Who Were Treated Inside vs. Outside Therapy Optimisation Protocols in Germany.

Abstract Introduction: Despite the improvements and knowledge brought by clinical trials to cancer treatment, it remained unclear how beneficial participation in a clinical trial with Therapy Optimisation Protocol (TOP) is for patients (pts) with Hodgkin Lymphoma (HL) in relation to pts treated outside of trials. In the TOPiCS project, trial participants (TOP) were compared with non-trial pts (non-TOP). Methods: In the population-based survey NLL, which aimed to register all incident HL-cases 356 pts were recorded in six counties of northern Germany with a first diagnosis of HL in 1988–1998. Data on staging, therapy, adverse events and survival were collected. The dataset was additionally screened for patients fulfilling inclusion and exclusion criteria for clinical trials of the German Hodgkin Study Group (GHSG). A total of 328 pts were documented of whom 198 pts (60%) met the inclusion criteria of the GHSG. Of these, 125 pts (63%) have not been recruited into GHSG trials (non-TOP pts). They were compared retrospectively with 4963 TOP pts randomised nation-wide between 1988–1998 in the GHSG trials HD4-HD9. Endpoints were Overall Survival (OS) and Progression Free Survival (PFS) which considered progression, relapse and death of any cause as events. Survival analysis was performed using Kaplan-Meier method and log-rank tests. Cox regression analysis was used for multivariable modelling of risk of death or progression and included 118 non-TOP pts and 4958 TOP pts. Results: The demographic parameters were not well balanced between the two groups: TOP pts were younger, had more often advanced stage and diagnosis in the later study generation than the non-TOP pts. The median observation time for OS was 7 yrs for the TOP group and 10 yrs for the non-TOP group. The 5-yrs OS for TOP pts is 89% (95%–CI [88–90]) and for non-TOP 89% (95%-CI [82–94])(p=0.63). The 5-year PFS for TOP pts is 79% (95%–CI [78–80]) and for non-TOP pts 68% (95%–CI [59–76])(p<0.001). According to Cox-regression analysis, 5 parameters were significantly (p<0.01) associated with poor OS and PFS: male sex, older age, advanced stage (according to DHSG classification considering Ann Arbor stage, B-symptoms and risk factors) and earlier study generation. Participation in a TOP-trial did not contribute independently for OS (Hazard Ratio (HR)=1.12, 95%–CI [0.71–1.79]) but contributed independently and positively for PFS (HR=0.66, 95%–CI [0.49–0.89]). The difference is mainly due to a higher number of relapses. Conclusion: For German patients fulfilling inclusion and exclusion criteria for TOP, a participation in therapy optimisation protocols results in a higher PFS, allowing for the influence of other factors, than for patients who were treated outside of TOP-trials. However, no difference was observed in OS.

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Identification and Analysis of Three Hub Prognostic Genes Related to Osteosarcoma Metastasis

Journal of Oncology ◽

10.1155/2021/6646459 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Jianye Tan ◽

Haofeng Liang ◽

Bingsheng Yang ◽

Shuang Zhu ◽

Guofeng Wu ◽

...

Keyword(s):

Regression Analysis ◽

Cox Regression ◽

Survival Rates ◽

Prognostic Biomarkers ◽

Messenger Rnas ◽

Hub Genes ◽

Cox Regression Analysis ◽

Expression Levels ◽

Kaplan Meier ◽

Before And After

Osteosarcoma (OS) often occurs in children and often undergoes metastasis, resulting in lower survival rates. Information on the complexity and pathogenic mechanism of OS is limited, and thus, the development of treatments involving alternative molecular and genetic targets is hampered. We categorized transcriptome data into metastasis and nonmetastasis groups, and 400 differential RNAs (230 messenger RNAs (mRNAs) and 170 long noncoding RNAs (lncRNAs)) were obtained by the edgeR package. Prognostic genes were identified by performing univariate Cox regression analysis and the Kaplan–Meier (KM) survival analysis. We then examined the correlation between the expression level of prognostic lncRNAs and mRNAs. Furthermore, microRNAs (miRNAs) corresponding to the coexpression of lncRNA-mRNA was predicted, which was used to construct a competitive endogenous RNA (ceRNA) regulatory network. Finally, multivariate Cox proportional risk regression analysis was used to identify hub prognostic genes. Three hub prognostic genes (ABCG8, LOXL4, and PDE1B) were identified as potential prognostic biomarkers and therapeutic targets for OS. Furthermore, transcriptions factors (TFs) (DBP, ESX1, FOS, FOXI1, MEF2C, NFE2, and OTX2) and lncRNAs (RP11-357H14.16, RP11-284N8.3, and RP11-629G13.1) that were able to affect the expression levels of genes before and after transcription were found to regulate the prognostic hub genes. In addition, we identified drugs related to the prognostic hub genes, which may have potential clinical applications. Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that the expression levels of ABCG8, LOXL4, and PDE1B coincided with the results of bioinformatics analysis. Moreover, the relationship between the hub prognostic gene expression and patient prognosis was also validated. Our study elucidated the roles of three novel prognostic biomarkers in the pathogenesis of OS as well as presenting a potential clinical treatment for OS.

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Prognostic Factors and Treatment Outcome in Lymphocyte Predominant and Classical Hodgkin’s Lymphoma: A Comprehensive Analysis of the German Hodgkin Study Group.

Blood ◽

10.1182/blood.v108.11.97.97 ◽

2006 ◽

Vol 108 (11) ◽

pp. 97-97

Author(s):

Lucia Nogova ◽

Thorsten Reineke ◽

Corinne Brillant ◽

Thomas Ruediger ◽

Hans K. Mueller-Hermelink ◽

...

Keyword(s):

Treatment Outcome ◽

Prognostic Factors ◽

Hodgkin Lymphoma ◽

Cox Regression ◽

White Cell Count ◽

Advanced Stage ◽

Treatment Protocols ◽

Cox Regression Analysis ◽

Negative Factor ◽

Advanced Stages

Abstract Introduction: Lymphocyte predominant Hodgkin lymphoma (LPHL) differs in histological and clinical presentation from classical Hodgkin lymphoma (cHL). Treatment of LPHL patients using standard approaches leads to complete remission (CR) in more than 95% of patients. However, differences in terms of relapse rates, overall survival (OS) and freedom from treatment failure (FFTF) between LPHL and cHL patients were suggested by a recent intergroup analysis. To obtain a more comprehensive picture, we reviewed all LPHL-cases registered in the GHSG database comparing patient characteristics and treatment outcome with cHL patients. Patients and methods: We retrospectively analyzed 8298 HL patients treated within the GHSG trials (HD4 to HD12). 394 patients had LPHL and 7904 cHL. From 394 LPHL patients, 63% were in early favorable stage, 16% in early unfavorable and 21% in advanced stage of disease. Of the 7904 cHL patients analyzed, 22% were in early favorable, 39% in early unfavorable and 39% in advanced stages. 9% of LPHL patients had B symptoms compared to 40% in cHL patients. Results: 91% LPHL vs. 86% cHL patients in early favorable stages, 86% vs. 83% in early unfavorable and 79% vs. 75% in advanced stages reached CR/CRu. 0.3% LPHL patients developed progressive disease (PD) compared to 3.7% cHL patients. The relapse rate of LPHL patients was very similar to cHL (8.1% vs. 7.9%). There were 2.5% secondary malignancies in LPHL and 3.7% in cHL patients. 4.3% LPHL patients and 8.8% cHL patients died. The FFTF rates for LPHL and cHL patients at a median observation of 41 or 48 months were 88% and 82% (p=0.0093), respectively. The OS for LPHL and cHL patients was 96% and 92%, respectively (p=0.0166). The analysis between LPHL stages showed significant differences in FFTF (p=0.0239). According to a multiple Cox-regression analysis, advanced stage (p=0.0089) and lymphocytes < 8% of white cell count was shown as negative prognostic factors for FFTF and age ≥ 45 years (p=0.008) as negative factor for OS in LPHL patients. Hb value < 10.5 g/dl was shown as negative factor for both, FFTF and OS (p=0.0125, p=0.0002). Conclusion: This is the largest analysis comparing LPHL and cHL patients. We found differences in FFTF and OS rates between both groups and differences in FFTF between LPHL stages. New treatment protocols for LPHL patients with reduced intensity schedules are to be discussed.

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Dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio as prognostic biomarkers in COVID-19

10.21203/rs.3.rs-21984/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Wenjing Ye ◽

Guoxi Chen ◽

Xiaopan Li ◽

Xing Lan ◽

Chen Ji ◽

...

Keyword(s):

Regression Analysis ◽

Lymphocyte Count ◽

Cox Regression ◽

Roc Curves ◽

Critical Value ◽

Dynamic Changes ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Count Ratio ◽

D Dimer

Abstract Background Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use.Methods In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR.Results 349 participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors (P<0.001). There was a more significant upward trend of D-Dimer and NLR during hospitalization in the deceased patients, initial D-Dimer and NLR were lower than the peak tests (MD) -25.23, 95% CI:-31.81- -18.64, P <0.001; (MD) -43.73, 95% CI:-59.28- -31.17, P <0.001. The test showed a stronger correlation between hospitalization days, PCT and peak D-Dimer than initial D-Dimer. The areas under the ROC curves of peak D-Dimer and peak NLR tests were higher than the initial tests (0.94(95%CI: 0.90-0.98) vs. 0.80 (95% CI: 0.73-0.87); 0.93 (95%CI:0.90-0.96) vs. 0.86 (95%CI:0.82-0.91). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR was 0.73 mg/L, 3.78 mg/L,7.13 and 14.31 respectively. The multivariable Cox regression analysis showed that age (HR 1.04, 95% CI 1.00-1.07, P=0.01), the peak D-Dimer (HR 1.03, 95% CI 1.01-1.04, P<0.001) were prognostic factors for COVID-19 patients’ death.Conclusions To dynamically observe the ratio of D-Dimer and NLR was more valuable during the prognosis of COVID-19. The rising trend in D-Dimer and NLR, or the test results higher than the critical values may indicate a risk of death for participants with COVID-19.

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P6331Influence of dynapenia and obesity on prognoses of elderly heart failure patients

European Heart Journal ◽

10.1093/eurheartj/ehz746.0928 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

S Uchida ◽

K Kamiya ◽

N Hamazaki ◽

R Matsuzawa ◽

K Nozaki ◽

...

Keyword(s):

Heart Failure ◽

Regression Analysis ◽

Muscle Strength ◽

Cox Regression ◽

Handgrip Strength ◽

Survival Rates ◽

The Other ◽

Rank Test ◽

Protective Effects ◽

Cox Regression Analysis

Abstract Background In elderly people, a decline in activities of daily living is more closely associated with low muscle strength (dynapenia) than with low muscle mass. Moreover, the combination of low muscle strength and obesity (dynapenic obesity) is associated with a higher risk of mortality than dynapenia or obesity alone, but its influence on prognosis is still unknown in elderly heart failure (HF) patients. To clarify these relationships may contribute to the development of rehabilitation programs for elderly HF patients and the improvement their prognoses in the future. Purpose We aimed to investigate the influence of dynapenia and obesity on prognoses of elderly HF patients. Methods We evaluated 1006 elderly HF patients aged ≥65 years (76.5±6.9 years, 579 males) who were admitted to our hospital and participated in an inpatient cardiac rehabilitation program. We assessed patients' characteristics, including body mass index (BMI) and handgrip strength during hospitalization. Patients with low handgrip strength (<26 kg and <18 kg in males and females, respectively) and high BMI (≥25 kg/m2) were considered to have dynapenia and obesity, respectively. Moreover, patients fulfilling the above two criteria (dynapenia, obesity) were considered to have dynapenic obesity. Patients were divided into four groups: normal, dynapenia only, obesity only, and dynapenic obesity. We compared survival rates among the four groups using the Kaplan-Meier method and log-rank test. To identify predictors for all-cause mortality, we performed Cox regression analysis. Results During the 8-year follow-up period, 228 patients (21.2%) died. Eight-year cumulative incidences of mortality were 35.4%, 26.0%, 62.6%, and 33.1% in the normal, obesity only, dynapenia only, and dynapenic obesity groups, respectively. Significantly lower survival rates were observed in the dynapenia only group than in the other 3 groups (log-rank: 28.893, P<0.001). Cox regression analysis, after adjusting for age and sex, showed significantly poor prognosis in the dyanapenia only group than in the other 3 groups (normal group, hazard ratio [HR] = 0.684, 95% confidence interval [CI] = 0.488–0.959, P=0.028; obesity only group, HR = 0.330, 95% CI = 0.182–0.598, P<0.001; dynapenic obesity group, HR = 0.390, 95% CI = 0.206–0.739, P=0.004). Conclusion Elderly HF patients with dynapenia alone had poor prognoses. Obesity may have protective effects on the survival of dynapenia patients with HF.

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Chromogranine A and neuron-specific enolase as the main predictors of survival for hormone-refractory prostate cancer (HRPC) patients

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15594 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15594-15594

Author(s):

A. Banu ◽

E. Banu ◽

D. Dionysopoulos ◽

J. Medioni ◽

F. Scotte ◽

...

Keyword(s):

Prostate Cancer ◽

Regression Analysis ◽

Gleason Score ◽

Cox Regression ◽

Neuron Specific Enolase ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Metastatic Sites ◽

Ecog Ps ◽

The Impact

15594 Background: Clinical studies suggested that the extent of neuro-endocrine differentiation in prostate cancer increases with tumor progression and the development of androgen refractory status. Chromogranine (CgA) and neuron-specific enolase (NSE) are currently explored as surrogate markers. Methods: Eligible chemonaive HRPC patients (pts) were required to have an ECOG performance status (PS) ≤ 2. Before chemotherapy initiation, we quantified NSE, CgA and PSA in the venous blood using commercial kits. We evaluated the impact of baseline NSE, CgA and PSA on overall survival (OS) using multivariate Cox regression analysis, stratified by chemotherapy regimen. Secondary, we studied the correlation between NSE, CgA, PSA and other important variables as age, Gleason score, hemoglobin, number of metastatic sites and ECOG PS. Results: Data of 39 consecutive HRPC pts treated between December 01–06 in a single French center were analyzed. Chemotherapy was docetaxel-based in 92% of pts. Median age was 71 years (range 51–86) and 79% of pts had bone metastases. Elevated NSE, CgA and PSA were observed in 6, 9 and 30% of pts and median levels were 10.8, 67 and 23.3 ng/mL, respectively. Gleason 8–10 was present in 49% of pts. Significant correlations were observed between NSE and the number of metastatic sites and between CgA and age, hemoglobin and ECOG PS. The baseline PSA was only correlated with Gleason score. Median OS for the entire cohort was 24.4 months (95% CI, 18.8–29.9). Two-year OS was 15% and only 19% of patients are dead. Univariate Cox regression analysis showed only a significant relationship between OS and baseline NSE: hazard ratio= 1.09 (95% CI, 1.03–1.16), P=0.006. No other known prognostic factors are related to outcome. A multivariate model including baseline NSE, CgA, ECOG PS and Gleason score showed a 15% rise of the risk of death related to NSE (borderline P value). Conclusions: NSE was the most powerful predictor of survival for HRPC pts. Our results emphasize the theory that cells secreting NSE are chemoresistant, with a negative impact on OS. No significant financial relationships to disclose.

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Comparison of the effects of primary somatostatin analogue therapy and pituitary adenomectomy on survival in patients with acromegaly: a retrospective cohort study

Acta Endocrinologica ◽

10.1530/eje-13-0166 ◽

2013 ◽

Vol 169 (3) ◽

pp. 367-376 ◽

Cited By ~ 17

Author(s):

Fausto Bogazzi ◽

Annamaria Colao ◽

Giuseppe Rossi ◽

Martina Lombardi ◽

Claudio Urbani ◽

...

Keyword(s):

Regression Analysis ◽

Mortality Rate ◽

Cox Regression ◽

Diabetic Patients ◽

Somatostatin Analogue ◽

Primary Therapy ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Risk Of Mortality ◽

Increased Risk

ObjectiveAcromegalic patients have an increased risk of mortality. The objective of this study was to compare the effect of different therapies for acromegaly on mortality.Design and methodsThe mortality rate of 438 consecutive acromegalic patients was compared with that of the general population using the standardized mortality ratio (SMR); the effect of different therapies on survival was evaluated using Cox regression analysis.ResultsTwenty patients (4.5%) died between 1999 and 2009. Age- and sex-adjusted SMR was 0.70 (95% CI 0.43–1.08). The Cox regression analysis revealed that, in the whole population, both general risk factors (age and physical status) and specific factors for acromegaly (macroadenoma, hypopituitarism and uncontrolled disease) were associated with death. The most compromised patients at diagnosis had a higher mortality rate (P=0.001), which also occurred in patients with controlled acromegaly. Death occurred in 2.4% (adenomectomy), 2.6% (adenomectomy followed by somatostatin analogue (SSA) therapy) and 11.4% (SSA therapy as the primary therapy) of the patients. The risk of death was higher in patients receiving SSA therapy as the primary therapy (hazard ratio (HR) 5.52, 95% CI 1.06–28.77,P=0.043) than in all patients submitted to adenomectomy; however, a higher risk of death occurred only in diabetic patients treated with SSAs alone (HR 21.94, 95% CI 1.56–309.04,P=0.022). Radiotherapy was associated with an increased risk of mortality, which occurred in patients with the more locally advanced disease.ConclusionsTherapies for acromegaly and comorbidities have lowered the risk of mortality to the level of the general population; the effect of SSA therapy alone or that following pituitary adenomectomy was comparable to that of curative neurosurgery on survival in non-diabetic patients; on the contrary, SSA therapy as the primary therapy may be less effective than adenomectomy in reducing mortality rate in diabetic patients.

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Outcomes of Patients With Advanced Gastrointestinal Cancer in Relationship to Opioid Use: Findings From Eight Clinical Trials

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2019.7382 ◽

2020 ◽

Vol 18 (5) ◽

pp. 575-581

Author(s):

Omar Abdel-Rahman ◽

Hatim Karachiwala ◽

Jacob C. Easaw

Keyword(s):

Clinical Trials ◽

Regression Analysis ◽

Cox Regression ◽

Survival Outcomes ◽

Disease Entity ◽

Gastrointestinal Cancers ◽

Opioid Use ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

The Impact

Background: This study assessed the patterns of opioid use among patients with advanced gastrointestinal cancers who were included in 8 clinical trials and evaluated the impact of opioid use on survival outcomes of included patients. Methods: Deidentified datasets from 8 clinical trials evaluating first-line systemic treatment of advanced gastrointestinal cancers were accessed from the Project Data Sphere platform (ClinicalTrial.gov identifiers: NCT01124786, NCT00844649, NCT00290966, NCT00678535, NCT00699374, NCT00272051, NCT00305188, and NCT00384176). These trials evaluated patients with pancreatic carcinoma, gastric carcinoma, hepatocellular carcinoma (HCC), and colorectal carcinoma. Multivariable logistic regression analysis was used to evaluate factors predicting the use of opioids. Kaplan-Meier survival estimates were used to compare survival outcomes in each disease entity among patients who did or did not receive opioid treatment. Multivariable Cox regression analysis was then used to further assess the impact of opioid use on survival outcomes in each disease entity. Results: A total of 3,441 participants were included in the current analysis. The following factors predicted a higher probability of opioid use within logistic regression analysis: younger age at diagnosis (odds ratio [OR], 0.990; 95% CI, 0.984–0.997; P=.004), nonwhite race (OR for white vs nonwhite, 0.749; 95% CI, 0.600–0.933; P=.010), higher ECOG score (OR for 1 vs 0, 1.751; 95% CI, 1.490–2.058; P<.001), and pancreatic primary site (OR for colorectal vs pancreatic, 0.241; 95% CI, 0.198–0.295; P<.001). Use of opioids was consistently associated with worse overall survival (OS) in Kaplan-Meier survival estimates of each disease entity (P=.008 for pancreatic cancer; P<.001 for gastric cancer, HCC, and colorectal cancer). In multivariable Cox regression analysis, opioid use was associated with worse OS among patients with pancreatic cancer (hazard ratio [HR], 1.245; 95% CI, 1.063–1.459; P=.007), gastric cancer (HR, 1.725; 95% CI, 1.403–2.122; P<.001), HCC (HR, 1.841; 95% CI, 1.480–2.290; P<.001), and colorectal cancer (HR, 1.651; 95% CI, 1.380–1.975; P<.001). Conclusions: Study findings suggest that opioid use is consistently associated with worse OS among patients with different gastrointestinal cancers. Further studies are needed to understand the underlying mechanisms of this observation and its potential implications.

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А New Combination of Prognostic Markers in Follicular Lymphoma That Influences the Choice of Therapy

Blood ◽

10.1182/blood-2021-145104 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4520-4520

Author(s):

Ekaterina S. Nesterova ◽

Nataliya A. Severina ◽

Bella V. Biderman ◽

Andrey B. Sudarikov ◽

Tatiana N. Obukhova ◽

...

Keyword(s):

Risk Factors ◽

Regression Analysis ◽

Follicular Lymphoma ◽

Tumor Size ◽

Cox Regression ◽

Proliferation Index ◽

Ki 67 ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Probability Of Death

Abstract Background: Follicular lymphoma (FL) is characterized by clinical and morphological heterogeneity. It is based on the pathogenetic mechanisms of the development of tumor cells. The identification and assessment of risk factors associated with the course of the disease and treatment outcome in FL is an important task, as it allows to evaluate and predict the effectiveness of therapy. Objective: Identify and estimate risk factors for overall survival (OS) and progression free survival (PFS) in FL. Patients and Methods: The prospective exploratory study conducted at National Research Center for Hematology (Moscow) from 01/2017 to 04/2021 included patients (pts)(in total, 80) with FL. Morpho-immunohistochemical, cytogenetic and molecular studies were performed on biopsies of lymph nodes taken before the start of therapy. The mutational status of exon 16 and intron polymorphism rs_2072407 of the EZH2 gene were investigated by Sanger sequencing. 18q21/BCL-2 rearrangements were determined by conventional cytogenetic analysis and/or FISH study. The results obtained in a blind study were compared with the effect of the therapy. Results: Of the 80 pts 34 were male: Me (median) age 50 years (range 30-72) and 46 were female: Me 56 (range 21-81). The median follow-up (FU) time was 53 months. As a result of the study in the multivariate Cox regression model (likelihood-ratio test, p=0.01) of significant factors, selected in the previously univariate analysis, the following statistically significant (Wald test) risk factors for OS and PFS (the events: progression, relapse, or death) were obtained: • BCL-2 gene rearrangements (no vs yes) • EZH2 gene genotypes (AA/AG vs GG) • proliferation index Ki-67 (>35%) • morphological grade (3А vs 1/2) • tumor size (>6 cm /bulky/) (Tab. 1, Fig. 1) The BCL-2 rearrangements were found in 45 from 80 pts (56%; 95 % CI 45-66). The probability of BCL-2 rearrangements is estimated to be about 0.5 (50%). According to the results of Cox-regression analysis (by OS) in the absence of BCL-2 rearrangements, the risk of death in FL was generally significantly (p = 0.01) higher than in the group with its presence: HR = 4.3 (95 % CI 1.5-13.0) (Fig. 2) Mutations in the 16th exon of the EZH2 gene (mutEZH2) were found in 10/80 (13%) pts. Analysis of EZH2 gene mutations with BCL-2 rearrangements revealed that in the mutEZH2 group with the presence of BCL-2 rearrangements, the number of deaths associated with progression is significantly less than in the control initial groups (mutEZH2 with BCL-2 rearrangements - 0/6, mutEZH2 without BCL-2 rearrangements - 2/4, wEZH2 with BCL-2 rearrangements - 3/39 (8%), wEZH2 without BCL-2 rearrangements - 11/31 (35%)) . The prognostic significance of EZH2 genotypes in lymphomas was studied for the first time in this study. The frequencies of rs_2072407 genotypes were: AA - 24% (19), AG - 42% (34), and GG - 34% (27). AA and AG genotypes of the EZH2 gene in pts with FL were associated with an increased risk of death (compared to the GG genotype) : HR = 2.9 (95% CI: 1.2-10.6), p = 0.01 (Fig. 3). The GG variant in most cases was associated with wEZH2 (26/27 (96%)) with BCL-2 rearrangements (16/26 (62%)) and a favorable prognosis (26/27 (96%)) (p = 0.01). Index of proliferative activity Ki-67> 35% (n = 40) and Ki-67 ≤ 35% (n = 40) were equally common in the study group. With a Ki-67> 35%, the probability of death is 2.9 (95% CI 1.1-9.7) times higher. The frequency distribution of morphological grade was as follows: grade 3A - 53% (n = 43) and grade 1-2 - 47% (n = 37). At grade 3A, the probability of death is 2.5 (95% CI 1.1-7.8) times higher. The number of pts with tumor size >6 cm (bulky) and ≤ 6 cm in the sample is approximately the same (41 and 39, respectively), the presence of bulky increased the mortality risk by 2.1 (95% CI 1.0-6.5) times. A short time from the manifestation of the disease to appeal to medical care is a predictor of poor prognosis, but this result we received earlier on a large sample of pts was not significant on a smaller sample. Conclusions: As a result of the multivariable Cox regression analysis, we identified and confirmed the previously obtained factors (bulky, grade 3A, Ki-67 > 35%, short medical history), and discovered new biogenetic factors (BCL-2 rearrangements and the GG rs2072407 genotype of the EZH2 gene). The model based on these independent risk factors improves the accuracy of predicting adverse events and allows to use more personalized treatment options for patients with FL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Glycemic Control and Risk of Sepsis and Subsequent Mortality in Type 2 Diabetes

10.2337/figshare.16775743 ◽

2021 ◽

Author(s):

Anca Balintescu ◽

Marcus Lind ◽

Mikael Andersson Franko ◽

Anders Oldner ◽

Maria Cronhjort ◽

...

Keyword(s):

Type 2 Diabetes ◽

Regression Analysis ◽

Cox Regression ◽

Cubic Spline ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Increased Risk

Objective To investigate the nature of the relationship between HbA1c and sepsis among individuals with type 2 diabetes and to assess the association of sepsis and all-cause mortality in such patients. Research design and methods We included 502,871 individuals with type 2 diabetes recorded in the Swedish National Diabetes Register and used multivariable Cox regression and restricted cubic spline analyses to assess the association between time-updated HbA1c values and sepsis occurrence between January 1, 2005 and December 31, 2015. The association between sepsis and death was examined using multivariable Cox regression analysis. Result Overall, 14,534 (2.9%) patients developed sepsis during the study period. On multivariable Cox regression analysis, compared with an HbA1c of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was 1.15 (95% CI 1.07-1.24) for HbA1c <43 mmol/mol (6.1%); 0.93 (0.87-0.99) for HbA1c 53-62 mmol/mol (7.0-7.8%); 1.05 (0.97-1.13) for HbA1c 63-72 mmol/mol (7.9-8.7%); 1.14 (1.04-1.25) for HbA1c 73-82 mmol/mol (8.8-9.7%); and 1.52 (1.37-1.68) for HbA1c >82 mmol/mol (9.7%). In the cubic spline model, a reduction of the adjusted risk was observed within the lower HbA1c range until 53 mmol/mol (7.0%), with a hazard ratio of 0.78 (0.73-0.82) per standard deviation, and increased thereafter (P for non-linearity <0.001). As compared to patients without sepsis, the adjusted hazard ratio for death among patients with sepsis was 4.16 (4.03-4.30). Conclusions In a nationwide cohort of individuals with type 2 diabetes, we found a U-shaped association between HbA1c and sepsis and a four-fold increased risk of death among those developing sepsis.

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Does in-house availability of multidisciplinary teams increase survival in upper GI cancer?

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.4066 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 4066-4066

Author(s):

Christian Kersten ◽

Milada Cvancarova ◽

Geir Boehler ◽

Svein Mjaaland ◽

Odd Mjaaland

Keyword(s):

Cox Regression ◽

Survival Rates ◽

Fold Increase ◽

Primary Objective ◽

Multidisciplinary Teams ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Pancreatic Cancers ◽

Administrative Institution ◽

Upper Gi Cancer

4066 Background: Treatment of esophageal, gastric and pancreatic cancers (UGI) is recommended to be discussed by a multidisciplinary team (MDT), despite lack of evidence that this approach leads to increased survival. In 2001, a cancer centre with irradiation and chemotherapy facilities was established in the Norwegian county of West Agder (WA), providing the potential for local in-house MDT meetings. Our primary objective was to evaluate the effect of the establishment of in-house MDT availability (iMDTa) on survival in a cohort of UGI patients in WA. We compared survival figures for WA with those of other Norwegian counties with complete, less complete and without iMDTa. Methods: We defined “iMDTa” as a single administrative institution with all departments on one campus, serving the population of one county. We compared cause-specific survival rates for 2000-04 and 2005-08 for UGI patients living in counties with (MDT-Yes), without (MDT-No) and with a mix (MDT-mix) of iMDTa, with the county of WA which had a change in iMDTa (MDT-Change) during the study period. Crude survival was modelled with Kaplan-Meier method and Cox regression analysis was used to adjust for age and region (sex and stage distributions were similar in all counties). Results: We analyzed 12530 UGI patients living in five Norwegian regions. Median age was 74 (17-98) yrs and median follow-up was 5 (0-138) months. The regions with the highest level of iMDTa achieved the largest increases in survival, compared to the counties with limited or no iMDTa. Median overall survival for all UGI patients in WA/MDT-Change increased from 129 to 300 days from 2000-8, p=0.001. Compared to the county with MDT-Mix, the county with MDT-Change reached a statistically significant reduction in the risk of death (HR) for both esophageal (1.12- 0.60) and stomach cancers (0.87-0.63), but not for pancreatic cancers (1.04-1.01). Conclusions: In parallel with an increasing use of in-house MDT, we found a striking and more than two-fold increase in survival in the Norwegian county of WA/MDT-Change. This survival gain is partly explained by increased use of chemotherapy. During the same time period, no increase in survival was found in the MDT-No or MDT-Mix counties.

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