Outcomes in AML patients age ≥70: A very large single institution experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7031-7031
Author(s):  
Jeffrey E. Lancet ◽  
Jongphil Kim ◽  
Najla Al Ali ◽  
Marina Sehovic ◽  
Tea Reljic ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Propensity Score ◽  
De Novo ◽  
Older Age ◽  
Rank Test ◽  
Term Survival ◽  
Poor Risk ◽  
Log Rank Test ◽  
Significant Difference ◽  
Ecog Ps

7031 Background: AML in older adults is associated with poor outcomes. The Moffitt Cancer Center AML Database was used to evaluate a very large cohort of patients (pts) age ≥ 70 with untreated AML to identify key prognostic variables affecting outcome. Methods: Overall survival (OS): Kaplan-Meier method and was compared across groups using the log-rank test. Association between OS and predictors: Cox regression model. Impact of participation of initial clinical trial on OS: Propensity score with stratified log-rank test. A predictive model for 12 month OS was developed using multiple logistic regression with backward elimination method. Results: Nine hundred eighty (980) pts were identified. M/F(%): 66/34. Median age at diagnosis: 75.7 years (range 70 – 95.7 years). De novo/secondary (%): 43/57. Fifty two % of pts had prior hematologic disease (AHD). Baseline karyotype at AML diagnosis: adverse in 31% and non-adverse in 58%. Baseline ECOG PS: 0-1 in 79%; ≥2 in 19%. Median OS was 7.1 months (95% CI 6.4 – 7.9) for the entire cohort. In the univariable model, factors associated with inferior survival included: secondary AML (sAML) status, poor-risk karyotype, ECOG ≥2, non HMA therapy (including clinical trials), Charlson Comorbidity Index ≥3, older age, increased WBC, decreased platelets (plts), and decreased hemoglobin (hgb). Independent negative predictors for OS in the multivariate model included sAML, poor-risk karyotype, ECOG ≥2, non-HMA initial therapy, older age, increased WBC, decreased plts, and decreased hgb. Propensity score matching revealed no significant difference in OS amongst pts receiving initial treatment on a clinical trial (median 7.8 months, 95% CI 6.4 – 10.4) vs not (median 7.0 months, 95% CI 6 –7.9). A model to predict OS at 12 month was developed in a subset of 446 pts. Independent predictive variables included karyotype, ECOG PS, AML type (de novo vs sAML), age, and WBC, with AUC of 0.78, indicating strong discriminatory capacity. Conclusions: In this largest reported cohort of AML pts age ≥ 70, prognostic modeling identifies differences in longer-term survival with conventional therapies, discriminating the highest risk subsets. Decision modeling to further assist choice of optimal therapies for these pts is in progress.

Comparison of de novo and upgrade to resynchronization therapy: a propensity-score matched analysis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Brandao ◽  
J Goncalves Almeida ◽  
J Monteiro ◽  
F Montenegro Sa ◽  
P Fonseca ◽  
...  
Keyword(s):  
New York ◽  
Propensity Score ◽  
De Novo ◽  
Heart Association ◽  
Rank Test ◽  
Resynchronization Therapy ◽  
Cardiac Events ◽  
Systolic Volume ◽  
Log Rank Test ◽  
All Cause Mortality

Abstract Background Upgrade to resynchronization therapy (CRT) from conventional pacemaker (P) or defibrillator (D) is common practice in Europe. However, guidelines (GL) are discordant: Pacing GL give a class I recommendation, while Heart Failure (HF) GL provide a class IIb indication. Previous studies suggested worse outcomes in upgraded patients (pts). Aim To compare response rate and clinical outcomes in a cohort of pts receiving de novo or upgrade to CRT. Methods Single-center retrospective study of consecutive pts submitted to CRT implantation (2007–2017). Major adverse cardiac events (MACE) included HF hospitalization (HHF) or all-cause mortality. Clinical response was defined as New York Heart Association class improvement without MACE in the first year of follow-up (FU). Left ventricle end-systolic volume reduction of >15% denoted echocardiographic (echo) response. Survival analysis with Kaplan-Meier method and Log-rank test was performed. Propensity-score matching (PSM) analysis was made to adjust for possible confounder variables. Results 230 CRT recipients (70.9% male, mean age 67±11 years, 71.5% non-ischemic cardiomyopathy, 39.6% CRT-P) were included, of whom 46 (20%) underwent an upgrade. Upgraded pts were older (69.8 vs 65.9 years, p=0.015), with higher rates of permanent atrial fibrillation (37.0% vs 12.7%, p=0.001), moderate to severe valve disease (45.7% vs 22.3%, p=0.002), chronic kidney disease (37.0% vs 17.2%, p=0.005) and treatment with mineralocorticoid receptor antagonists (79.1% vs 52.0%, p=0.002). They were more likely to receive CRT-P (65.2% vs 33.2%, p<0.001) and CRT-D were more often implanted for secondary prevention (60.0% vs 17.9%, p=0.001). No differences emerged in procedural complications, clinical (74.4% vs 71.4%, p=0.712) or echo (66.7% vs 69.7%, p=0.822) response rates. During a median FU of 3±4 years, all-cause mortality was similar among groups (Log Rank test, p=0.522, unadjusted hazard ratio [HR] 1.25, confidence interval [CI] 95% 0.62–2.49, p=0.534). There was a statistical tendency for higher MACE rate in the upgrade group (Log Rank test, p=0.064, HR 1.66, CI 95% 0.95–2,91, p=0.076). No differences were found in lead dislodgement (10.9% vs 7.1%, p=0.368) or endocarditis (2.2% vs 4.3%, p=0.692) rates. PSM analysis identified 88 matched pairs (46 upgrade/42 de novo pts). In this cohort, all-cause mortality (Log Rank test, p=0.77, HR 0.89, CI 95% 0.39–2.03, p=0.78) and MACE (Log Rank test, p=0.36, HR 1.38, CI 95% 0.68–2.81, p=0.37) were comparable between groups [graph no. 1]. Conclusion Upgrade to CRT was similar to de novo implantation in terms of complications and clinical and echo response, in this cohort. The risk for MACE and mortality was also comparable. Graph 1 Funding Acknowledgement Type of funding source: None

scholarly journals Factors Determining Survival and Retention among HIV-Infected Children and Adolescents in a Community Home-Based Care and a Facility-Based Family-Centred Approach in Kampala, Uganda: A Cohort Study

ISRN AIDS ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
W. Massavon ◽  
L. Barlow-Mosha ◽  
L. Mugenyi ◽  
W. McFarland ◽  
G. Gray ◽  
...  
Keyword(s):  
Cohort Study ◽  
Children And Adolescents ◽  
Care Delivery ◽  
Rank Test ◽  
Term Survival ◽  
Log Rank Test ◽  
Home Based ◽  
Significant Difference ◽  
Home Based Care

We describe factors determining retention and survival among HIV-infected children and adolescents engaged in two health care delivery models in Kampala, Uganda: one is a community home-based care (CHBC) and the other is a facility-based family-centred approach (FBFCA). This retrospective cohort study reviewed records from children aged from 0 to 18 years engaged in the two models from 2003 to 2010 focussing on retention/loss to follow-up, mortality, use of antiretroviral therapy (ART), and clinical characteristics. Kaplan Meier survival curves with log rank tests were used to describe and compare retention and survival. Overall, 1,623 children were included, 90.0% (1460/1623) from the CHBC. Children completed an average of 4.2 years of follow-up (maximum 7.7 years). Median age was 53 (IQR: 11–109) months at enrolment. In the CHBC, retention differed significantly between patients on ART and those not (log-rank test, adjusted, P<0.001). Comparing ART patients in both models, there was no significant difference in long-term survival (log-rank test, P=0.308, adjusted, P=0.489), while retention was higher in the CHBC: 94.8% versus 84.7% in the FBFCA (log-rank test, P<0.001, adjusted P=0.006). Irrespective of model of care, children receiving ART had better retention in care and survival.

scholarly journals Clinical outcomes after upgrade to resynchronization therapy: a propensity-score matched comparative analysis

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
M Brandao ◽  
J Goncalves Almeida ◽  
P Fonseca ◽  
F Rosas ◽  
E Santos ◽  
...  
Keyword(s):  
Propensity Score ◽  
Clinical Outcomes ◽  
De Novo ◽  
Nyha Class ◽  
Rank Test ◽  
Complication Rates ◽  
Resynchronization Therapy ◽  
Log Rank Test ◽  
Device Infection ◽  
All Cause Mortality

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Upgrade to resynchronization therapy (CRT) is common practice in Europe. However, guideline recommendations are discordant and randomized trials are lacking. Previous studies have shown worse outcomes in upgraded patients. AIM To compare clinical outcomes in a cohort of patients receiving de novo or upgrade to CRT. METHODS Single-center retrospective study of consecutive patients submitted to CRT implantation (2007-2018). Major adverse cardiac events (MACE) included heart failure hospitalization or all-cause mortality. Clinical response was defined as NYHA class improvement without MACE in the 1st year of follow-up (FU). Left ventricle end-systolic volume reduction of &gt;15% designated echocardiographic (echo) response. Survival analysis with Kaplan-Meier method and Log-rank test was performed. Propensity-score matching (PSM) analysis was performed to adjust for possible confounder variables. RESULTS 295 CRT patients (70.5% male, mean age 67 ± 11 years, 72.5% non-ischemic cardiomyopathy, 54.6% implanted with CRT-D) were included. Fifty-six patients (19%) underwent an upgrade: 43 (78.2%) from a pacemaker and 12 (21.8%) from a defibrillator device.  Indications for upgrade were mainly pacemaker dependency or pacing-induced LV dysfunction (76.6%) and de novo left bundle branch block (23.4%). Upgraded patients were older (70 vs 66 years, p=.034), with larger baseline QRS (185 ± 25 vs 163 ± 30 ms, p&lt;.001) and higher rates of atrial fibrillation (58.2% vs 26.7%, p&lt;.001), coronary artery disease (41.8% vs 26.2%, p=.033), moderate to severe valve disease (42.9% vs 22.6%, p=.003) and chronic kidney disease (36.4% vs 18.7%, p=.008). Upgraded patients more frequently received CRT-P (71.4% vs 39.3%, p&lt;.001). CRT-D were more often implanted for secondary prevention (53.3% vs 20.2%, p=.011) in the upgrade group. There were no differences in procedural complications, clinical (59.3 vs 62.6%, p=.765) or echo (72.2% vs 71.9%, p=.970) response rates. During a median FU of 3 ± 5 years, all-cause mortality was similar among groups (Log-rank test, p=.688). MACE occurred more frequently in the upgrade group (Log-rank test, p=.025). No differences emerged in lead complications (8.9% vs 8.4%, p=.892) or device infection (1.8% vs 2.9%, p=.986). PSM analysis identified 106 matched pairs (56 upgrade/50 de novo patients), without baseline statistical differences. All-cause mortality (Log-rank test, p=.555) and MACE (Log-rank test, p=.574)  were comparable between groups. CONCLUSION In this cohort, upgrade to CRT was comparable to de novo implantation in terms of clinical and echo response. Moreover, upgrade to CRT was not associated with higher complication rates. All-cause mortality and MACE were similar between groups.

scholarly journals Female Sex and Outcomes after Endovascular Aneurysm Repair for Abdominal Aortic Aneurysm: A Propensity Score Matched Cohort Analysis

2021 ◽  
Vol 10 (1) ◽  
pp. 162
Author(s):  
Christian-Alexander Behrendt ◽  
Thea Kreutzburg ◽  
Jenny Kuchenbecker ◽  
Giuseppe Panuccio ◽  
Mark Dankhoff ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Propensity Score ◽  
Acute Limb Ischemia ◽  
Insurance Claims ◽  
Long Term Outcomes ◽  
Term Survival ◽  
Abdominal Aortic ◽  
Significant Difference

Objective: Previous studies have showed a potential disadvantage of female patients who underwent abdominal aortic aneurysm (AAA) repair. The current study aims to determine sex-specific perioperative and long-term outcomes using propensity score matched unselected nationwide health insurance claims data. Methods: Insurance claims from a large German fund were used, covering around 8% of the insured German population. Patients who underwent endovascular aortic repair (EVAR) for intact AAA from 1 January 2011 to 30 April 2017 were included in the cohort. A 1:2 female to male propensity score matching was applied to adjust for confounding variables. Perioperative and long-term outcomes after 5 years were determined using matching and regression methods. Results: Among a total of 3736 patients (19.3% females, mean 75 years) undergoing EVAR for intact AAA, we identified 1863 matched patients. Before matching, females were more likely to be previously diagnosed with hypothyroidism, electrolyte disorders, rheumatoid disorders, and depression, while males were more often diabetics. In the matched sample, 23.4% of the females and 25.8% of the males died during a median follow-up of 776 and 792 days, respectively. Perioperatively, females were more likely to exhibit acute limb ischemia (5.3% vs. 3.2%, p = 0.031) and major bleeding (22.0% vs. 15.9%, p = 0.001) before they were discharged to rehabilitation (5.5% vs. 1.5%, p < 0.001) when compared to males. No statistically significant difference in perioperative (odds ratio 1.12, 95% CI 0.54–2.16) or long-term mortality (hazard ratio 0.91, 95% CI 0.76–1.08) was observed between sexes. This was also true regarding aortic reintervention rates after 1 year (2.0% vs. 2.9%) and 5 years (10.9% vs. 8.1%). Conclusion: The current retrospective matched analysis of insurance claims revealed high early access-related morbidity in females when compared to their male counterparts. Short-term or long-term survival and reintervention outcomes were similar between sexes.

Bioinformatics Analysis of The Expression of ATP Binding Cassette Transporters and The Screening of Regulatory Genes in PTEN/PI3K/Akt/mTOR Signaling Pathway in The Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Tingdan Zheng ◽  
Wuqi Song ◽  
Aiying Yang
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Bioinformatics Analysis ◽  
Wilcoxon Test ◽  
Rank Test ◽  
Short Term ◽  
Term Survival ◽  
Log Rank Test ◽  
Short Term Survival

Abstract Objective Here we performed the Bioinformatics analysis on the data from The Cancer Genome Atlas (TCGA), in order to find the correlation between the expression of ATP Binding Cassette (ABC) Transporters’ genes and hepatocellular carcinoma (HCC) prognosis; Methods Transcriptome profiles and clinical data of HCC were obtained from TCGA database. Package edgeR was used to analyze differential gene expression. Patients were divided into low-ABC expression and high-ABC expression groups based on the median expression level of ABC genes in cancer. The overall survival and short-term survival (n= 341) of the two groups was analyzed using the log-rank test and Wilcoxon test; Results We found that ABC gene expression was correlated with the expression of PIK3C2B (p<0.001, ABCC1: r=0.27; ABCC10: r=0.57; ABCC4: r=0.20; ABCC5: r=0.28; ABCB9: r=0.17; ABCD1: r=0.21). All patients with low-ABC expression showed significantly increased overall survival. Significantly decreased overall survival (Log-rank test: p<0.05, Wilcoxon test: p<0.05) was found in patients with high expression of ABCC1 (HR=1.58), ABCD1 (HR=1.45), ABCC4 (HR=1.56), and ABCC5 (HR=1.64), while decreased short-term survival (Log-rank test: p>0.05, Wilcoxon test: p<0.05) was correlated with the increased expression of ABCC10 (HR=1.29), PIK3C2B (HR=1.29) and ABCB9 (HR=1.23); Conclusions Our findings indicate that the specific ABC gene expression correlates with the prognosis of HCC. Therefore, ABC expression profile could be a potential indicator for HCC patients.

scholarly journals Clinical evaluation of the failure rate of metallic brackets bonded with orthodontic composites

2012 ◽  
Vol 23 (4) ◽  
pp. 399-402 ◽  
Author(s):  
Fábio Lourenço Romano ◽  
Rodrigo Alexandre Valério ◽  
Jaciara Miranda Gomes-Silva ◽  
José Tarcísio Lima Ferreira ◽  
Gisele Faria ◽  
...  
Keyword(s):  
Failure Rate ◽  
Orthodontic Treatment ◽  
Color Change ◽  
Rank Test ◽  
Initial Alignment ◽  
Bond Failure ◽  
Log Rank Test ◽  
Significant Difference ◽  
Mandibular Teeth

The purpose of the present study was to evaluate in vivo the failure rate of metallic brackets bonded with two orthodontic composites. Nineteen patients with ages ranging from 10.5 to 38.7 years needing corrective orthodontic treatment were selected for study. The enamel surfaces from second premolars to second premolars were treated with Transbond Plus-Self Etching Primer (3M Unitek). Next, 380 orthodontic brackets were bonded on maxillary and mandibular teeth, as follows: 190 with Transbond XT composite (3M Unitek) (control) and 190 with Transbond Plus Color Change (3M Unitek) (experimental) in contralateral quadrants. The bonded brackets were light cured for 40 s, and initial alignment archwires were inserted. Bond failure rates were recorded over a six-month period. At the end of the evaluation, six bond failures occurred, three for each composite. Kaplan-Meyer method and log-rank test (Mantel-Cox) was used for statistical analysis, and no statistically significant difference was found between the materials (p=0.999). Both Transbond XT and Transbond Plus Color Change composites had low debonding rates over the study period.

Effectiveness of the Bactiseal Universal Shunt for reducing shunt infection in a sub-Saharan African context: a retrospective cohort study in 160 Ugandan children

2014 ◽  
Vol 13 (2) ◽  
pp. 140-144 ◽  
Author(s):  
Jordan D. Lane ◽  
John Mugamba ◽  
Peter Ssenyonga ◽  
Benjamin C. Warf
Keyword(s):  
Cohort Study ◽  
Low Income ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Shunt Infection ◽  
Low Income Countries ◽  
Rank Test ◽  
Log Rank Test ◽  
Significant Difference ◽  
Chi Square Analysis

Object Antibiotic-impregnated shunts have yet to find widespread use in the developing world, largely due to cost. Given potential differences in the microbial spectrum, their effectiveness in preventing shunt infection for populations in low-income countries may differ and has not been demonstrated. This study is the first to compare the efficacy of a Bactiseal shunt system with a non–antibiotic-impregnated system in a developing country. Methods The Bactiseal Universal Shunt (BUS) was placed in 80 consecutive Ugandan children who required a shunt. In this retrospective cohort study, the outcome for that group was compared with the outcome for the immediately preceding 80 consecutive children in whom a Chhabra shunt had been placed. The primary end points were shunt failure, shunt infection, and death. Shunt survival was analyzed using the Kaplan-Meier method. Significance of differences between groups was tested using the log-rank test, chi-square analysis, Fisher's exact test, and t-test. Results There was no difference between groups in regard to age, sex, or etiology of hydrocephalus. Mean follow-up for cases of nonfailure was 7.6 months (median 7.8 months, interquartile range 6.5–9.5 months). There was no significant difference between groups for any end point. The BUS group had fewer infections (4 vs 11), but the difference was not significant (p = 0.086, log-rank test). Gram-positive cocci were the most common culturable pathogens in the Chhabra group, while the only positive culture in the BUS group was a gram-negative rod. Conclusions These results provide equipoise for a randomized controlled trial in the same population and this has been initiated. It is possible that the observed trends may become significant in a larger study. The more complex task will involve determining not only the efficacy, but also the cost-effectiveness of using antibiotic-impregnated shunt components in limited-resource settings.

scholarly journals The relationship of the prolonged PR interval with the long-term survival in patients with heart failure undergoing cardiac resynchronization therapy

2020 ◽  
Vol 25 (1) ◽  
pp. 33-38
Author(s):  
A. M. Soldatova ◽  
V. A. Kuznetsov ◽  
T. P. Gizatulina ◽  
L. M. Malishevsky ◽  
S. M. Dyachkov
Keyword(s):  
Cardiac Resynchronization ◽  
Rank Test ◽  
Term Survival ◽  
Log Rank Test ◽  
Group I ◽  
Pr Interval ◽  
Qrs Duration ◽  
Group Ii ◽  
The Relationship

Aim. To assess the relationship between the prolonged PR interval (≥200 ms) and the long-term survival of patients undergoing cardiac resynchronization therapy (CRT).Material and methods. A total of 85 patients (mean age — 55,1Ѓ}9,9 years; men — 81,2%) with NYHA class II-IV heart failure (HF) were examined. The mean follow-up was 34,0Ѓ}21,2 months. Patients with PR<200 ms (n=52) made up group I, with PR≥200 ms (n=33) — group II. Then the patients were divided into subgroups depending on the QRS duration: ≥150 ms (n=33 in group I and n=14 in group II, respectively) <150 ms (n=19 in group I and n=19 in group II, respectively).Results. In patients of group II, a history of myocardial infarction (MI) was more often registered (p=0,005), left ventricular ejection fraction (LVEF) was lower (p=0,032). In a multivariate analysis, MI (OR 3,217; CI 95% 1,188-8,712; p=0,022) and LVEF value (OR 0,869; CI 95% 0,780-0,968; p=0,011) had a significant relationship with the PR interval prolongation (≥200 ms). The survival of patients of group I was 59,6%, group II — 18,2% (Log-rank test p<0,001). According to Cox regression model, the initial left ventricle end-systolic volume (OR 1,012; 95% CI 1,006-1,017; p<0,001), inferior wall MI (OR 1,690; 95% CI 1,131-2,527; p=0,011) and PR interval ≥200 ms (OR 2,179; 95% CI 1,213–3,915; p=0,009) were associated with long-term mortality. In patients with PR≥200 ms, survival rate was low, regardless of the QRS duration (21,4% in patients with QRS≥150 ms, 15,8% in patients with QRS<150 ms; Log-rank test p=0,698) In patients with PR<200 ms, the survival rate of patients with QRS≥150 ms was 72,7%, and for patients with QRS<150 ms — 36,8% (Log-rank test p=0,031).Conclusion. In HF patients, PR interval prolongation (≥200 ms) is associated with long-term mortality increase. The highest survival rates were observed in patients with PR<200 ms and QRS≥150 ms. In patients with QRS≥150 ms, the presence of PR≥200 ms should be considered as an additional criterion for CRT.

Craniopharyngioma: a comparison of tumor control with various treatment strategies

2010 ◽  
Vol 28 (4) ◽  
pp. E5 ◽  
Author(s):  
Isaac Yang ◽  
Michael E. Sughrue ◽  
Martin J. Rutkowski ◽  
Rajwant Kaur ◽  
Michael E. Ivan ◽  
...  
Keyword(s):  
Tumor Resection ◽  
Treatment Strategies ◽  
Group Versus ◽  
Outcome Data ◽  
Treatment Modalities ◽  
Rank Test ◽  
Tumor Control ◽  
Subtotal Resection ◽  
Log Rank Test ◽  
Significant Difference

Object Craniopharyngiomas have a propensity to recur after resection, potentially causing death through their aggressive local behavior in their critical site of origin. Recent data suggest that subtotal resection (STR) followed by adjuvant radiotherapy (XRT) may be an appealing substitute for gross-total resection (GTR), providing similar rates of tumor control without the morbidity associated with aggressive resection. Here, the authors summarize the published literature regarding rates of tumor control with various treatment modalities for craniopharyngiomas. Methods The authors performed a comprehensive search of the English language literature to identify studies publishing outcome data on patients undergoing surgery for craniopharyngioma. Rates of progression-free survival (PFS) and overall survival (OS) were determined through Kaplan-Meier analysis. Results There were 442 patients who underwent tumor resection. Among these patients, GTR was achieved in 256 cases (58%), STR in 101 cases (23%), and STR+XRT in 85 cases (19%). The 2- and 5-year PFS rates for the GTR group versus the STR+XRT group were 88 versus 91%, and 67 versus 69%, respectively. The 5- and 10-year OS rates for the GTR group versus the STR+XRT group were 98 versus 99%, and 98 versus 95%, respectively. There was no significant difference in PFS (log-rank test) or OS with GTR (log-rank test). Conclusions Given the relative rarity of craniopharyngioma, this study provides estimates of outcome for a variety of treatment combinations, as not all treatments are an option for all patients with these tumors.

CDKN2A or CDKN2B homozygous deletion with high-immune infiltration as a favorable prognostic factor for lung adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20543-e20543
Author(s):  
Benxu Tan ◽  
Yonghong Chen ◽  
Lei Xia ◽  
Xian Yu ◽  
Yusheng Huang ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Lung Adenocarcinoma ◽  
Homozygous Deletion ◽  
Hazard Ratio ◽  
Gene Set Enrichment Analysis ◽  
Rank Test ◽  
Immune Infiltration ◽  
Log Rank Test ◽  
Significant Difference ◽  
Wild Group

e20543 Background: CDKN2A and CDKN2B both acted as tumor suppressor genes by regulating the cell cycle, which in humans were located at chromosome 9, band p21.3. The frequencies of homozygous deletion (HomDel) in CDKN2A and CDKN2B in lung adenocarcinoma (LUAD) were 12.5% and 12.1%, respectively. However, the genomic, immunogenomic features and impact on the prognosis of LUAD patients with CDKN2A/B HomDel were still unclear. Methods: The cohort of this study was from The Cancer Genome Atlas (TCGA). A total of 508 LUAD patients, including 99 CDKN2A/B HomDel (homdel) and 509 CDKN2A/B wild (wild). This study explored the difference of genomic and immunogenomic landscape between homdel and wild by analysis of whole-exome sequencing (WES) and RNA sequencing data. Results: The most frequently mutated genes were TP53, TTN, MUC16, and CSMD3. Their frequencies in homdel and wild are 46% and 48%, 43% and 46%, 35% and 41%, 33% and 38%, respectively. There was no significant difference of tumor mutational burden (TMB) between homdel and wild (median TMB, 133 in homdel vs 177 in wild; Wilcoxon test, p = 0.11), and clinical characteristics including age, gender, smoking history, and tumor stage were not significantly different between homdel and wild. Homdel had a shorter overall survival (OS) than wild (Log-rank test, p = 0.04, Hazard Ratio: 0.7, 95% CI: 0.49-1.02), but there was no significant difference in progression-free survival (PFS) (Log-rank test, p = 0.05, Hazard Ratio: 0.73, 95% CI: 0.51-1.04). We used single sample gene set enrichment analysis (ssGSEA) to calculate the enrichment score (ES) of 25 immune-related pathways such as antigen presentation and T cell-mediated immunity, and then used the consensus clustering algorithm (ConsensusClusterPlus) to cluster homdel and wild respectively, and both clustered into low and high immune infiltration groups. For the high immune infiltration and low immune infiltration in homdel and wild, high immune infiltration had a longer OS (Log-rank test, p = 0.009, Hazard Ratio: 2.19, 95% CI: 1.22-3.94) and PFS (Log-rank test, p = 0.044, Hazard Ratio: 1.8, 95% CI: 1.01-3.2) than low immune infiltration in homdel. However, there was no significant heterogeneity between high and immune infiltration in terms of PFS (Log-rank test, p = 0.28, Hazard Ratio: 1.21, 95% CI: 0.87-1.68) and OS (Log-rank test, p = 0.96, Hazard Ratio: 1.01, 95% CI: 0.71-1.44) in the wild group, the wild group had longer OS than homdel group with low immune infiltration (Log-rank test, p = 0.003, Hazard Ratio: 0.5, 95% CI: 0.29-0.88), while had the same OS with homdel with high immune infiltration, irrespective of immune infiltration. And so was PFS (Log-rank test, p = 0.005, Hazard Ratio: 0.48, 95% CI: 0.27-0.82). Conclusions: CDKN2A/B homdel was an unfavorable prognostic factor for LUAD, but which with high immune infiltration might improve patient survival time.

Sign in / Sign up

Export Citation Format

Share Document