Association of genetic variants in plastin family genes with tumor recurrence in stage II/III colon cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14031-e14031
Author(s):  
Yan Ning ◽  
Thomas Winder ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
Fotios Loupakis ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Recurrence ◽  
Cox Regression ◽  
Stage Ii ◽  
In Vivo Studies ◽  
Actin Binding ◽  
Comprehensive Cancer Center ◽  
Rank Test ◽  
Cancer Center ◽  
Log Rank Test

e14031 Background: Plastins belong to a subclass of actin-binding proteins known as actin bundling proteins. Plastins family constitute of two isoforms in human as T-plastin (PLS3) and L-plastin (LCP1). Recent in vitro and in vivo studies found plastin genes are overexpressed in colon cancer cells and can lead to increased proliferation, invasion and metastasis. Here we tested the hypothesis whether potential functional tagging polymorphisms in PLS3 (rs6643869, rs5987947, rs2522188) and LCP1 (rs4941543, rs1409429, rs11342) may predict tumor recurrence in adjuvant colon cancer patients. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 years (range 22–78 years)) with stage II (105 patients) or III (129 patients) colon cancer at the University of Southern California/Norris Comprehensive Cancer Center. The median follow-up was 4.4 years. PLS3 and LCP1 SNPs were determined by PCR-RFLP or PCR-based direct sequence. The primary endpoint of the study was time to tumor recurrence (TTR). Results: In univariable analysis, PLS3 rs6643869 and LCP1 rs4941543 were significantly associated with time to tumor recurrence (TTR). Patients with PLS3 AA genotype had shortest median TTR 3.2 years (95% C.I: 1.5-10.7) compared to those with AG or GG genotype, which had median TTR 9.4 years (95% C.I: 5.7-12.2) (p=0.012, log-rank test). Patients with LCP1 CC genotype had longer median TTR 10.7 years (95% C.I: 5.7-16.8+) compared to those with CT and TT genotypes, which had shorter median TTR 4.9 years (95% C.I: 1.4-9.0+)(p=0.040, log-rank test). PLS3 rs6643869 remained significant in the multivariate Cox regression model adjusted by stage and type of adjuvant therapy and stratified by race (p=0.021). Conclusions: Our preliminary results demonstrated that polymorphisms in plastin family genes PLS3 and LCP1 might be potential molecular markers to predict TTR in adjuvant colon cancer. Further large and biomarker embedded trial needed to confirm our findings.

Association of genetic variants in obesity-related genes with tumor recurrence in stage II/III colon cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3584-3584
Author(s):  
Robert D. Ladner ◽  
Armin Gerger ◽  
Wu Zhang ◽  
Melissa Janae Labonte ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Tumor Recurrence ◽  
High Body Mass Index ◽  
Stage Ii ◽  
Comprehensive Cancer Center ◽  
Rank Test ◽  
Cancer Center ◽  
Related Gene ◽  
Log Rank Test

3584 Background: High body mass index (BMI) is an established risk factor for colorectal cancer incidence and death. Recent studies found obesity before the diagnosis of colon cancer was associated with worse survival compared with normal weight. Single nucleotide polymorphisms (SNPs) of obesity-related gene have been related with different cancer risk including colorectal cancer. Here we tested the hypothesis whether SNPs in obesity-related genes (PPAR, LEP, NFKB, CD36, DRG1, NGAL, REGIA and DSCR1) may predict tumor recurrence in adjuvant colon cancer. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 years (range 22–78 years)) with stage II (105 patients) or III (129 patients) colon cancer at the University of Southern California/Norris Comprehensive Cancer Center. The median follow-up was 4.4 years. SNPs in obesity-related genes were determined by PCR-RFLP or PCR-based direct sequence. The primary endpoint of the study was time to tumor recurrence (TTR). Results: in univariable analysis, PPAR rs1801282 and DSCR1 rs6517239 were independently associated with time to tumor recurrence (TTR). Patients with PPAR CC genotype had longer median TTR 9.4 months (95% C.I: 5.6, 12.4+) compared to those with CG genotype, had median TTR 3.4 months (95% C.I: 1.7, 16.8+)(p=0.04, log-rank test). Patients with DSCR1 AA genotype had shorter median TTR 6.6 months (95% C.I: 4.0, 16.8+) compared to those with AG and GG genotypes, which had longer median TTR 9.4 months (95% C.I: 5.7, 10.7+)(p=0.027, log-rank test). The multivariate analysis adjusting for stage and type of adjuvant therapy showed a trend in the association between PPAR rs1801282 and DSCR1 rs6517239 and time to recurrence (Wald test p=0.08 and 0.058, respectively). Conclusions: Our preliminary results demonstrated polymorphisms in obesity-related gene might be potential molecular markers to predict TTR in adjuvant colon cancer. Further large and biomarker embedded trial needed to confirm our findings.

VEGF and VEGF receptor-2 (VEGFR2) gene polymorphisms predict tumor recurrence in stage II and III colon cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4004-4004 ◽  
Author(s):  
G. Lurje ◽  
A. M. Schultheis ◽  
A. E. Hendifar ◽  
S. Ashouri ◽  
W. Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Tumor Recurrence ◽  
Stage Ii ◽  
Stage Iii ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Vegf Receptor ◽  
Stage Iii Colon Cancer ◽  
Increased Risk

4004 Background: Despite recent advances in the treatment of metastatic colorectal cancer, tailoring adjuvant treatment of stage II and III colon cancer patients remains controversial. Identifying a reliable panel of prognostic and predictive markers for tumor recurrence is critical in selecting an individualized and tailored chemotherapy. Tumor angiogenesis plays an important role in tumor development, progression and metastasis. In this retrospective study, we tested whether a specific pattern of 40 functionally significant polymorphisms in 37 genes involved in angiogenesis and tumor microenvironment will predict the risk of tumor recurrence in stage II and III colon cancer patients treated with adjuvant chemotherapy. Methods: Between 1999 and 2006 blood specimens from 140 patients (69 females and 71 males with a median age of 59 years; range=28–86) were obtained at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC). Sixty-three patients had stage II and 77 had stage III colon cancer. The median follow-up was 5.4 years (range=2.0–16.8). 51 of 140 patients (36.4%) developed tumor recurrence with a 5-year probability of 0.28 ± 0.06 for stage II and 0.40 ± 0.06 for stage III colon cancer patients. Genomic DNA was extracted from peripheral blood and genotypes were determined using PCR based RFLP. Results: Polymorphisms in VEGF (C936T; p=0.009, log-rank) and VEGFR2 (+4422 AC- repeat; p=0.04, log-rank and +1416 T/A; p=0.0009, log-rank) were associated with risk of tumor recurrence in stage III colon cancer patients (n=77). VEGFR2 AC-repeat polymorphisms were additionally associated with risk of recurrence in Stage II colon cancer patients (n=63, p=0.02, log-rank). Conclusion: VEGF C936T and VEGFR2 (+4422 AC-repeat and +1416 T/A) polymorphisms may help to identify Stage II and III colon cancer patients who are at increased risk for developing tumor recurrence. Angiogenesis seems to play a crucial role in tumor recurrence, thus targeting VEGF and VEGFR2 may be of clinical benefit for stage II and stage III colon cancer patients. Large prospective trials are needed to validate these preliminary data. No significant financial relationships to disclose.

Benefit of fluorouracil and folinic acid adjuvant in colon cancer elderly patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13564-13564 ◽  
Author(s):  
S. Lonardi ◽  
M. Stefani ◽  
A. Jirillo ◽  
C. Ghiotto ◽  
L. M. Pasetto ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Recurrence ◽  
Progression Free Survival ◽  
Tnm Stage ◽  
Stage Ii ◽  
Rank Test ◽  
Log Rank Test ◽  
Significant Difference ◽  
Unselected Population

13564 Background: Retrospective analyses on elderly people enrolled in clinical trials of adjuvant chemotherapy for colon cancer indicated the maintenance of the efficacy in that subset of patients (pts). However, data on the benefit of the routinely used adjuvant treatment in an unselected population of pts aged more than 65 years are few. Methods: All the charts of pts radically operated for colon cancer from 1996–2001 at Medical Oncology, Padua Hospital, were retrospectively analysed. 147 out of 330 pts consecutively treated with fluorouracil (FU)-based chemotherapy was aged 65 years or more at the time of diagnosis. Kaplan-Meyer progression-free-survival (PFS) and overall survival (OS) of stage II and III pts were calculated. Results: Pts characteristics were: males/females: 87/60, median age 71 (range 65–87), ECOG PS 0/1: 124/23, right/left colon primary tumor: 62/85, TNM stage: 24/63/60. 86 out of 147 pts were treated with the following regimen of adjuvant chemotherapy: FU 370 mg/mq + leucovorin (LV) 20 mg/mq day 1–5 q 28 for 6 cycles (Machover regimen, n=69), or FU 500 mg/mq + LV 250 mg/mq weekly × 6 q 56 for 4 cycles (Roswell Park regimen, n=17). Treated pts were staged as follows: TNM stage I/II/III: 1/38/47. No toxic death were observed and only nine of 86 pts (10.4%) stopped the treatment due to acute grade III gastrointestinal toxicity. At a median follow-up of 73.2 months, 19 out of 86 pts (22%) developed cancer recurrence (3-y PFS: 82.2%, 5-y PFS: 80.3%). Seventeen pts (19.7%) died, 13 (15.1%) due to tumor progression, 3 (3.4%) due to acute heart failure, and 1 (1.1%) due to chronic pulmonary disease (3-y OS: 88.8%, 5-y OS: 82.4%). No statistically significant difference in survival was observed comparing pts aged 65–70 (n=41) with pts more than 70 years old (n=45): 5-y OS 84.1% vs 77.8%, respectively (p=2.23, log rank test). A separate survival analysis on stage II pts was performed (n=63). 5 of 38 (13.1) treated pts dead, compared to 9 of 25 (36%) non treated pts; 5-y survival in the two groups were 86.6% and 60.8%, respectively (p= 0.03, log-rank test). Conclusions: The efficacy of adjuvant chemotherapy appears maintained in an unselected population of elderly pts. Surprisingly, our retrospective analysis suggest that even stage II pts may benefit of a fluorouracil-based well tolerated chemotherapy. No significant financial relationships to disclose.

Association of gender-related tumor recurrence with a polymorphic variant of LMTK3 in stage II and III colon cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 454-454
Author(s):  
Wu Zhang ◽  
Armin Gerger ◽  
Melissa Janae Labonte ◽  
Dongyun Yang ◽  
Pierre Oliver Bohanes ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Recurrence ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage Ii ◽  
In Vivo Studies

454 Background: Recent evidence suggests that Lemur Tyrosine Kinase 3 (LMTK3) activates estrogen receptor alpha (ERα) transcriptional activity in breast cancer. The mutant variants of two single nucleotide polymorphisms (SNPs) in LMTK3 (rs8108419 and rs9989661) were independently associated with reduced time to tumor recurrence (TTR), suggesting these SNPs were functionally significant. In colon cancer (CC), ERβ expression has been shown to be predominant with low levels of ERα also expressed. ERα stimulates cell proliferation, while ERβ negatively regulates the estrogen-dependent activity of ERα. Based on these previous findings, we hypothesized that LMTK3 rs808419 and rs9989661 may predict TTR in stage II and III CC. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 yrs (range 22–78 yrs)) with stage II (105 pts) or III (129 pts) CC at the University of Southern California. The median follow-up was 4.4 years. LMTK3 rs8108419 and rs9989661 were determined by PCR-RFLP. The primary endpoint of the study was TTR. This study was conducted adhering to the reporting recommendations for tumor marker prognostic studies (REMARK). Results: The minor allele of LMTK3 rs9989661 (C; frequency=30.5%) showed significantly longer median TTR (5.9 vs 12.2+ yrs; HR: 0.41, 95%CI: 0.15-1.18, log-rank p=0.086; univariate analysis) in female CC patients. After Cox proportional hazards model adjustment for stage and type of adjuvant chemotherapy, this result remained significant (HR: 0.25, 95%CI: 0.077-0.778, Wald test p=0.017). No significant association was found between TTR and LMTK3 rs9989661 in men and rs8108419 in both genders. Conclusions: This is the first report demonstrating LMTK3 rs9989661 associations with gender-related TTR in CC. We hypothesize that there is an ERα-dependent loop mechanism with higher estrogen levels in females exerting the effect on ERβ. Larger prospective trials are warranted to confirm these findings, and in vitro and in vivo studies are needed to identify the underlying biological mechanism.

Impact of comorbidities using Adult Comorbidity Evaluation-27 (ACE-27) score on survival in stage II colon cancer: Age, TNM staging, and pathological high risk-disease.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 659-659
Author(s):  
Manik A. Amin ◽  
Andrea Wang-Gillam ◽  
Benjamin R. Tan ◽  
Rama Suresh ◽  
Joel Picus ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Tnm Staging ◽  
Stage Ii ◽  
Cancer Center ◽  
Cancer History ◽  
Comorbidity Score ◽  
High Risk Disease ◽  
Stage Ii Colon Cancer

659 Background: Impact of comorbidities is identified in stage III colon cancer patients (CCPs) receiving adjuvant chemotherapy (Wildes et al, PMID 21113435) but is not well defined in predicting overall survival (OS) in stage II CCPs undergoing either adjuvant treatment or observation depending upon high-risk disease. The goal of this study was to identify impact of comorbidities on OS in this potentially curable disease using ACE-27 score, which uses 27 different patient comorbid conditions has been developed and validated by Piccirrillo et al at Barnes Jewish Hospital (BJH) (PMID: 24933715). Methods: We identified stage II CCPs treated at BJH, Siteman cancer center from January 1, 1996 to October 31st, 2013 from BJH oncology data cancer registry. The primary outcome was OS, defined as the time from date of surgery to death from any cause, censored at the time of last follow-up. Patient comorbidities at diagnosis were recorded using ACE-27 score, assigning a comorbidity score of none, mild, moderate and severe to the patients. Survival analysis was done using Cox proportional hazard modelling using STATA/SE 11.2 software. Pathological high risk features such as T4 lesions, < 12 LN, perineural, lymphovascular invasion, positive margins & perforation/obstruction were identified. Results: Out of 579 stage II CCPs, 48% male and 51% were females. High risk features were identified in 45% of patients. ACE-27 comorbidity score of none (n = 146), mild (n = 229), moderate (n = 132) and severe (n = 72) was calculated. 497 patients had T3N0M0 and 82 had T4N0M0 staging. Cox regression hazard model using histological prognostic factors, age at surgery, sex, race, prior cancer history and TNM staging showed that ACE-27 score of moderate and severe were independent predictors of OS with a hazard ratio of 1.6 (95% CI 1.0-2.4), P = 0.036 and 2.5 (95% CI 1.5-4.0), P = 0.00 respectively. Conclusions: Highest commodity burden using ACE-27 comorbidity score was associated with poor OS in stage II CCPs and was independent of other prognostic risk factors including high-risk features. Treatment related mortality will be calculated in patients with high risk disease.

Use of germ-line variants in the WNT/β-CATENIN pathway to predict tumor recurrence in adjuvant colon cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14034-e14034
Author(s):  
Peter M.D. Wilson ◽  
David Páez ◽  
Armin Gerger ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Tumor Recurrence ◽  
Cox Regression ◽  
Germ Line ◽  
Stage Ii ◽  
Cox Regression Analysis ◽  
Direct Dna Sequencing ◽  
Stage Ii Colon Cancer

e14034 Background: The Wnt/β-catenin signaling plays a central role in the development and progression of most colon cancers. Germline variants in Wnt/β-catenin pathway genes may result in altered gene function and/or activity, thereby causing inter-individual differences in relation to tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of Wnt/β-catenin pathway genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II colon cancer. Methods: A total of 234 patients treated with 5-fluorouracil-based chemotherapy at the University of Southern California were included in this study. Whole blood samples were analyzed for putative functional germline polymorphisms in SFRP3, SFRP4, DKK2, DKK3, Axin2, APC, TCF7L2, WNT5B, CXXC4 genes by PCR-RFLP or direct DNA-sequencing. We also included NOTCH2 and GLI1 variants which belong to the Notch and Hedgehog pathways respectively. Results: The minor allele of WNT5B rs2010851 T>G was significantly associated with a shorter TTR (4.9vs10.7 years; HR: 2.48; 95%CI, (0.96, 6.38); p=0.044) in high-risk stage II colon cancer patients. This result remained significant in the multivariate Cox regression analysis. Conclusions: Despite the importance of Wnt/β-catenin pathway in the development of cancer, only the WNT5B germline variant rs2010851 was significantly identified as a stage-dependent prognostic marker for colon cancer patients after 5-fluorouracil-based adjuvant therapy.

LMTK3 polymorphism in patients with metastatic colon cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 471-471 ◽  
Author(s):  
Fotios Loupakis ◽  
Wu Zhang ◽  
Armin Gerger ◽  
Dongyun Yang ◽  
Pierre Oliver Bohanes ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Estrogen Receptor ◽  
Prognostic Factor ◽  
Cox Model ◽  
White Blood Cells ◽  
Comprehensive Cancer Center ◽  
Rank Test ◽  
Cancer Center ◽  
Metastatic Colon Cancer

471 Background: LMTKs are a family of serine-threonine-tyrosine kinases. LMTK3 isoform is a potent regulator of estrogen receptor activity LMTK3 gene polymorphisms affect DFS and OS of breast cancer patients. Cumulative evidence implies that estrogen receptor signalling plays a role in colon carcinoma development and progression. We investigated whether the LMTK3 rs9989661 SNP is a prognostic factor in patients with advanced colon cancer. Methods: 318 patients with metastatic colon cancer treated at the USC/Norris Comprehensive Cancer Center or the LA County/USC Medical Center were included in this study. Genomic DNA was extracted from white blood cells of peripheral blood samples using the QiaAmp kit (Qiagen, Valencia, CA). The LMTK3 polymorphism was genotyped by PCR-RFLP. The association between the LMTK3 polymorphism and overall survival was examined using the log-rank test and multivariate Cox-model. Results: There were 141 females and 177 males, with a median age of 58 years (range 25-86). The cohort comprised 234 whites, 43 Asians, 15 Blacks, 24 Hispanics, and 2 Native Americans. The median survival was 13.7 months with a median follow-up of 2.3 years. The median overall survival was 16.6 vs. 12.8 months for patients with C/- vs. patients with T/T (HR=0.78; 95% CI: 0.56-1.08; p=0.055). At a multivariate analysis restricted to subjects with left-sided disease (n=126) the median OS for patients with C/- genotype was 23.8 months compared to 14.9 months of T/T patients (HR=0.51; 95%CI: 0.28-0.91; p=0.014). Conclusions: This study suggests that LMTK3 may be an independent prognostic factor for patients with metastatic colon cancer and raise the issue of possible disparities according to primary tumor location. Our group produced similar results also in the adjuvant setting. Functional correlative preclinical analyses and external clinical validation studies are currently ongoing.

Prediction of tumor recurrence by tumor location in stage II and III colon cancer patients through common germ-line variants of genes involved in wnt signaling pathway.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14714-e14714
Author(s):  
Wu Zhang ◽  
Yan Ning ◽  
Dongyun Yang ◽  
Takeru Wakatsuki ◽  
Sebastian Stintzing ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Wnt Signaling ◽  
Cancer Patients ◽  
Signaling Pathway ◽  
Tumor Recurrence ◽  
Wnt Signaling Pathway ◽  
Tumor Location ◽  
Stage Ii ◽  
Comprehensive Cancer Center ◽  
Tcf7l2 Rs7903146

e14714 Background: Wnt signaling is essential for embryonic development, stem cells and tissue regeneration. The Wnt signaling pathway was found to be deregulated in 93% of colorectal cancer (CRC). Tumor recurrence after curative resection is still a major problem in the management of adjuvant CRC, with recurrence rate approximately 30-40%. Identifying molecular markers for tumor recurrence is critical for successfully selecting patients who are more likely to benefit from adjuvant chemotherapy. In this study, our group tested whether gene polymorphisms [TCF7L2 rs7903146, AXIN2 (rs2240308, rs3923087) and P300 (rs7286979, rs220551 and rs5782022)] involved in Wnt signaling pathway could predict the risk of tumor recurrence in stage II and III CRC patients. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 years (range 22–78 years)) with stage II (105 patients) or III (129 patients) colon cancer at the University of Southern California/Norris Comprehensive Cancer Center. The median follow-up was 4.4 years. TCF7L2, AXIN2 and p300 SNPs were determined by PCR-RFLP or PCR-based direct sequence. The primary endpoint of the study was time to tumor recurrence (TTR). Results: In univariate analysis, patients with TCF7L2 rs7903146 TT genotype had significantly longer TTR (median=10.7 months, 95%CI 4.9,10.7 +) compared with those harboring CT (median=3.9months, 95% CI 2.4, 10.7) or CC genotype (median=5.9months, 95% CI 2.8, 11.4+) patients (p=0.042, log-rank test). In multivariate analysis, left-side tumor patients with p300 rs7286979 AA genotype had highest risk of TTR (HR=2.85, 95% CI 1.03,7.89) compared to those carring GA (HR=0.81, 95% CI 0.35,1.84) or AA genotype (p=0.048, Wald test). Conclusions: Our results show that germline polymorphisms profiling of Wnt signaling pathway TCF7L2 rs7903146, p300 rs7286979 may predict tumor recurrence risk in adjuvant colon cancer patients, and may dependent on tumor location. Our exploratory data warrants further validation.

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

Survival Outcomes for Induction vs Adjuvant Chemotherapy in Squamous Cell Carcinoma of the Maxillary Sinus

2018 ◽  
Vol 160 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Phoebe Kuo ◽  
Sina J. Torabi ◽  
Dennis Kraus ◽  
Benjamin L. Judson
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Maxillary Sinus ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Cox Regression ◽  
Rank Test ◽  
Controlled Clinical Trial ◽  
Log Rank Test ◽  
Kaplan Meier

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.

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