Association Between Aryl Hydrocarbon Receptor Genotype and Survival in Soft Tissue Sarcoma

2004 ◽  
Vol 22 (19) ◽  
pp. 3997-4001 ◽  
Author(s):  
Marianne Berwick ◽  
Giuseppe Matullo ◽  
Yan Shuang Song ◽  
Simonetta Guarrera ◽  
Gemma Dominguez ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Aryl Hydrocarbon Receptor ◽  
Proportional Hazards ◽  
Tumor Grade ◽  
Cox Proportional Hazards ◽  
Nucleotide Polymorphisms ◽  
Anatomic Site ◽  
Aryl Hydrocarbon ◽  
Cox Proportional Hazards Models

Purpose Accumulating evidence shows that germline polymorphisms may affect survival in cancer. The purpose of this study was to investigate the association between polymorphisms in a group of candidate genes and survival with soft tissue sarcoma. Patients and Methods We measured single nucleotide polymorphisms in the metabolizing, detoxifying, and DNA repair pathways in 120 newly diagnosed patients with soft tissue sarcoma. We assessed polymorphisms in the aryl hydrocarbon receptor (AhR-Arg554Lys), null variants of the glutathione S-transferase superfamily (GSTM1 and GSTT1), x-ray repair cross-complementing 1 and 3, and Xeroderma pigmentosum, group D (XRCC1-Arg399Gln, XRCC3-Thr241Met, XPD-Lys751Gln). We followed the patients for survival for a median of 7.6 years. Results Cox proportional hazards models demonstrated that a polymorphism at codon 554 in exon 10 of the AhR was significantly and adversely associated with survival (hazard ratio, 2.2; 95% CI, 1.3 to 3.9; P < .01), even while accounting for major clinical characteristics such as tumor grade, tumor size, anatomic site, and patient age. Conclusion Further study of the role of the AhR polymorphism is warranted.

Adverse Effect of Older Age on the Recurrence of Soft Tissue Sarcoma of the Extremities and Trunk

2011 ◽  
Vol 29 (30) ◽  
pp. 4029-4035 ◽  
Author(s):  
David J. Biau ◽  
Peter C. Ferguson ◽  
Robert E. Turcotte ◽  
Peter Chung ◽  
Marc H. Isler ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Local Recurrence ◽  
Soft Tissue Sarcoma ◽  
Older Patients ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Hazard Ratios ◽  
Age At Surgery ◽  
Effect Of Age

Purpose To examine the effect of age on the recurrence of soft tissue sarcoma in the extremities and trunk. Patients and Methods This was a multicenter study that included 2,385 patients with median age at surgery of 57 years. The end points considered were local recurrence and metastasis. Cox proportional hazards models were used to estimate hazard ratios across the age ranges with and without adjustment for known confounding factors. Results Older patients presented with tumors that were larger (P < .001) and of higher grade (P < .001). The proportion of positive margins increased significantly as patients age (P < .001), but radiation therapy was relatively underused in patients older than age 60 years. The 5-year cumulative incidences of local recurrence were 7.2% (95% CI, 4% to 11.7%) for patients age 30 years or younger and 12.9% (95% CI, 9.1% to 17.5%) for patients age 75 years or older. The corresponding 5-year cumulative incidences of metastasis were 17.5% (95% CI, 12.1% to 23.7%) and 33.9% (95% CI, 28.1% to 39.8%) for the same groups. Regression models showed that age was significantly associated with local recurrence (P < .001) and metastasis (P < .001) in nonadjusted models. After adjusting for imbalance in presentation and treatment variables, age remained significantly associated with local recurrence (P = .031) and metastasis (P = .019). Conclusion Older patients have worse outcomes because they tend to present with worse tumors and are treated less aggressively. However, there remained a significant increase in the risk of both local and systemic recurrence associated with increasing age that could not be explained by tumor or treatment characteristics.

Current treatments, determinants of use, and survival for patients with hepatoma in the United States from 1998–2002

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4138-4138
Author(s):  
A. B. Siegel ◽  
R. McBride ◽  
D. Hershman ◽  
R. S. Brown ◽  
J. Emond ◽  
...  
Keyword(s):  
Tumor Size ◽  
Proportional Hazards ◽  
Case Series ◽  
Tumor Grade ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Data Set ◽  
Cox Proportional Hazards Models ◽  
Highly Correlated ◽  
The Impact

4138 Background: Multiple case series have described the use of current therapies for hepatocellular carcinoma (HCC), but recent estimates of treatment utilization in the general population and the impact of various treatments on survival are not known. Methods: We first identified 2898 adults diagnosed with HCC with known tumor size and stage in the Surveillance, Epidemiology, and End-Results Program (SEER), from 1998–2002. Treatment was categorized as transplant, resection, ablation, or none of these. We created a second data set of 1856 HCC patients who were potentially operable, as defined by SEER. We used these patients to construct Kaplan-Meier survival curves and adjusted Cox proportional hazards models. Results: The median age of the larger cohort at HCC diagnosis was 62 (range:18–96). Approximately 42% were white, 32% Asian, 16% Hispanic, and 10% African American. Overall, 10% received a transplant, 18% resection, 8% ablation, and 65% none of these. Only 5% of African Americans with HCC received a transplant, versus 12% of whites, 10% of Hispanics, and 8% of Asians. Asians were most likely to receive resection (24%) and ablation (9%), and least likely to have non-surgical treatment (60%). Using the restricted cohort, improved survival in the multivariate analysis was seen with later year of diagnosis, younger age, female sex, Asian race, smaller tumor size, lower tumor grade, and localized disease. Treatment was highly correlated with survival. This was greatest in the transplanted group (1, 3, and 5-year survivals 93%, 79%, and 71%), followed by resection (70%, 45%, and 29%), and ablation (71%, 33%, and 18%). The non-surgical group had poor survival (33%, 9%, and 0%). Conclusions: Transplantation yields excellent survival on a population scale, similar to reported series, and resection gives relatively good outcomes as well. Asians are more likely to be resected and ablated than other groups. They also had better survival than other groups, perhaps due to underlying etiology of HCC (hepatitis B) and better preserved liver function. No significant financial relationships to disclose.

scholarly journals Pulmonary metastasectomy in bone and soft tissue sarcoma with metastasis to the lung

2021 ◽  
Author(s):  
Charles A Gusho ◽  
Christopher W Seder ◽  
Nicolas Lopez-Hisijos ◽  
Alan T Blank ◽  
Marta Batus
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Medical Management ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Interquartile Range ◽  
Cox Proportional Hazards Model ◽  
Pulmonary Metastasectomy ◽  
Hazards Model

Abstract OBJECTIVES This study investigated the outcomes of sarcoma patients with lung metastases who underwent pulmonary metastasectomy (PM), compared to patients who underwent medical management alone. The secondary objective was to compare survival after PM between variables of interest. METHODS This was a retrospective review of 565 sarcoma patients with confirmed, isolated pulmonary metastasis identified from the Surveillance, Epidemiology and End Results database between 2010 and 2015. 1:4 propensity score matching was used to select PM and non-PM groups. The multivariable Cox proportional hazards model was used to analyse prognostic factors of disease-free survival (DFS). RESULTS Of the eligible 565 patients, 59 PM patients were matched to 202 non-PM patients in a final ratio of 3.4. After propensity matching, there were no significant differences in baseline characteristics between PM and non-PM patients. The median DFS after PM was 32 months (interquartile range 18–59), compared to 20 months (interquartile range 7–40) in patients without PM (P = 0.032). Using a multivariable Cox proportional hazards model, metastasectomy (hazard ratio 0.536, 95% confidence interval 0.33–0.85; P = 0.008) was associated with improved DFS. In a subset analysis of patients who underwent PM only, the median DFS was longer in males compared to females (P = 0.021), as well as in bone sarcoma compared to soft tissue sarcoma (P = 0.014). CONCLUSIONS For sarcoma patients with metastatic lung disease, PM appears to improve the prognosis compared to medical management. Furthermore, there may be a survival association with gender and tumour origin in patients who underwent PM. These data may be used to inform the surgical indications and eligibility criteria for metastasectomy in this setting.

Sunitinib in patients with pancreatic neuroendocrine tumors (panNETs): Exploratory pharmacogenomic analyses.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 255-255
Author(s):  
Nicola Fazio ◽  
Jean-Francois Martini ◽  
Adina-Emilia Croitoru ◽  
Michael Schenker ◽  
Sherry Li ◽  
...  
Keyword(s):  
Protein Transport ◽  
Proportional Hazards ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Nucleotide Polymorphisms ◽  
Exact Test ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Treatment Naïve

255 Background: In a phase IV trial (NCT01525550), median progression-free survival (PFS) was 13.2 mo in sunitinib-treated patients (pts) with well-differentiated panNETs. Objective response rate (ORR) was 24.5% and median overall survival (OS) was 37.8 mo. Exploratory analyses evaluated potential associations between single nucleotide polymorphisms (SNP) in genes involved in angiogenesis, protein transport or inflammatory response and clinical outcomes. Methods: Blood samples were genotyped using TaqMan assays for 12 SNPs previously associated with panNET risk, prognosis or drug effect. Associations between SNP and PFS or OS were assessed by comparing genotypes within treatment-naïve (TN), previously treated (PT) and combined groups, and within a genotype between treatment groups, using Kaplan-Meier analysis and Cox proportional hazards models. Fisher’s exact test was used for association between ORR and genotype. PFS and ORR were investigator-assessed. P values displayed are unadjusted and Bonferroni method was used for multiplicity adjustment. Results: 56 pts were genotyped: 25 TN and 31 PT. There were no significant associations between genotype and PFS or OS but there was a trend toward shorter PFS in pts with VEGFR1 rs9554320 C/A versus C/C (hazard ratio [HR] 1.78; 95% confidence interval [CI] 0.83–3.82; p = 0.117) and VEGFR1 rs9582036 A/C versus A/A (HR 1.88; 95% CI 0.9–3.93; p = 0.102). The genotypes G/G of VEGFA rs2010963 (p = 0.041) , G/G of VEGFA rs833068 (p = 0.041) and A/C of VEGFR1 rs9582036 (p = 0.046) showed a trend toward a higher ORR in the PT versus TN group. Genotype T/T of VEGFR2 rs7692791 (p = 0.103) showed a trend toward to a lower ORR in the TN versus PT group. Higher ORR was associated with IL1B rs16944 G/A versus G/G (46.4% vs 4.5%; p = 0.001) in the combined group. Conclusions: Potential associations between ORR and VEGFA rs2010963 and rs833068, VEGFR1 rs9582036 and VEGFR2 rs7692791 were observed. IL1B rs16944 was significantly associated with ORR, consistent with the role of IL1B in panNET etiology and development. Most correlations were not significant after adjustment for multiplicity. Clinical trial information: NCT01525550.

scholarly journals Chemotherapy and Survival in Patients with Primary High-Grade Extremity and Trunk Soft Tissue Sarcoma

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2389
Author(s):  
Danielle S. Graham ◽  
Ritchell van Dams ◽  
Nicholas J. Jackson ◽  
Mykola Onyshchenko ◽  
Mark A. Eckardt ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
High Volume ◽  
The Elderly ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Multi Agent

The use of upfront chemotherapy for primary localized soft tissue sarcoma (STS) of the extremity and trunk is debated. It remains unclear if chemotherapy adds clinical benefit, which patients are likely to benefit, and whether the timing of therapy affects outcomes. We used the National Cancer Database (NCDB) to examine the association between overall survival (OS) and chemotherapy in 5436 patients with the five most common subtypes of STS with primary disease localized to the extremity or trunk, mirroring the patient population of a modern phase 3 clinical trial of neoadjuvant chemotherapy. We then examined associations between timing of multi-agent chemotherapy (neoadjuvant or adjuvant) and OS. We used a Cox proportional hazards model and propensity score matching (PSM) to account for covariates including demographic, patient, clinical, treatment, and facility factors. In the overall cohort, we observed no association between multi-agent chemotherapy or its timing and improved OS. Multi-agent chemotherapy was associated with improved OS in several subgroups, including patients with larger tumors (>5 cm), those treated at high-volume centers, or those who received radiation. We also identified an OS benefit to multi-agent chemotherapy among the elderly (>70 years) and African American patients. Multi-agent chemotherapy was associated with improved survival for patients with tumors >5 cm, who receive radiation, or who receive care at high-volume centers. Neither younger age nor chemotherapy timing was associated with better outcomes. These ‘real-world’ findings align with recent randomized trial data supporting the use of multi-agent chemotherapy in high-risk patients with localized STS.

scholarly journals Improvement in Overall Survival from Extremity Soft Tissue Sarcoma over Twenty Years

Sarcoma ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Andrew J. Jacobs ◽  
Ryan Michels ◽  
Joanna Stein ◽  
Adam S. Levin
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Proportional Hazards ◽  
Large Population ◽  
Survival Rates ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
Extremity Soft Tissue Sarcoma ◽  
Study Population

Several patient demographic factors, including marital status, have been demonstrated to have prognostic significance for survival in extremity soft tissue sarcoma (ESTS). A study population of 12,546 adult patients diagnosed with ESTS from 1991 to 2010 was identified from the SEER database, a large population-based registry, in order to determine whether overall survival had changed over this recent 20-year period. The study population was divided into three groups by year of diagnosis: 1991–1996, 1997–2003, and 2004–2010. We used the Kaplan-Meier method and Cox proportional hazards regression to assess survival differences between different demographic groups and prognostic clinical characteristics. Over the course of time, the 5-year overall survival rates have increased from 28% in the earliest time period to 62% in the latest(P<0.0001). On multivariate analysis, the mortality rate progressively declined from the 1991–1996 group (HR: 3.02, CI: 2.78–3.29) to the 1997–2003 group (HR: 2.21, CI: 2.06–2.37), with the 2004–2010 group having the best overall survival, despite increases in the proportion of patients with tumors greater than 5 cm in size(P<0.0001), and those presenting with metastasis(P<0.0001).

Appraisal of prognostic interaction between sidedness and histology in colon cancer: A population-based study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 649-649
Author(s):  
Lu-Ping Yang ◽  
Zi-Xian Wang ◽  
Ying-Nan Wang ◽  
Feng Wang ◽  
Rui-hua Xu
Keyword(s):  
Proportional Hazards ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Stage Ii ◽  
Stage Iii ◽  
Prognostic Impact ◽  
Cox Proportional Hazards Models ◽  
The Right

649 Background: It is reported that sidedness (right vs. left) and histology (mucinous vs. non-mucinous) of CC is predictive of survival. We investigated whether the prognostic values of sidedness and histology were affected by each other. Methods: We identified 81342 patients with stage II–IV CC between 2004 and 2012 from the Surveillance, Epidemiology, and End Results database. Inverse probability propensity score weighting was used to balance the clinical features (i.e., age, sex, race, marital status, year of diagnosis, registry, tumor grade, and T and N stage) between the non-mucinous right-sided, non-mucinous left-sided, mucinous right-sided, and mucinous left-sided subgroups with stratification for tumor stage. Afterwards, overall survival (OS) was compared between these subgroups using univariable Cox proportional hazards models. Results: In stage III/IV CC, the prognosis for non-mucinous left-sided tumors was significantly better than that for non-mucinous right-sided tumors and that for mucinous left-sided tumors, whereas the survival was similar between left-sided and right-sided tumors with the mucinous subtype and between mucinous and non-mucinous tumors in the right-sided colon (Table; test for interaction between sidedness and histology, P < 0.001 in both stages). In stage II CC, the weighted 5-year OS rates were comparable among the four sidedness-histology subgroups (range, 70.3%–72.6%; P= 0.159 and Pinteraction= 0.466). Conclusions: In stage III/IV CC, the prognostic impact of sidedness differed according to histology, and vice versa. By contrast, neither should be considered in risk stratification for stage II CC. [Table: see text]

Primary Adult Soft Tissue Sarcoma: Time-Dependent Influence of Prognostic Variables

2002 ◽  
Vol 20 (21) ◽  
pp. 4344-4352 ◽  
Author(s):  
Alexander Stojadinovic ◽  
Denis H.Y. Leung ◽  
Peter Allen ◽  
Jonathan J. Lewis ◽  
David P. Jaques ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Tumor Size ◽  
Proportional Hazards ◽  
Resection Margin ◽  
Cox Proportional Hazards ◽  
Complete Resection ◽  
Time Dependent ◽  
Rank Test

PURPOSE: To define prognostic factors for postrelapse survival and their time-dependent influence for adult soft tissue sarcoma (STS).PATIENTS AND METHODS: We analyzed 2,123 patients with completely resected localized primary STS treated from 1982 to 1999. Variables studied included tumor site, size, depth, grade, and resection margin but not treatment other than resection. Landmark time frames were used to assess the influence of disease-free interval (DFI) on disease-specific survival (DSS). DSS was estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed using log-rank test and the Cox proportional hazards regression model. Time-dependent stepwise regression analysis evaluated the time-dependent influence of each variable.RESULTS: Two thirds of recurrences developed within 2 years of initial resection. Tumor size (P < .001), grade (P < .001), and microscopic resection margin (P < .001) independently predicted DSS for all STS. Size and grade independently predicted early (DFI ≤ 3 years) and margin late (DFI > 3 years) DSS. Risk of tumor-related death was the same across all sites 3 years postresection and decreased significantly for extremity/trunk STS when DFI exceeded 3 years (P < .001). Influence of initial high-risk factors for tumor-related mortality in extremity/trunk STS decreased by 40% 3 years postresection, but their influence over DSS for non–extremity/trunk sites remained constant over time. Likelihood of complete resection after recurrence (all sites) increased with DFI (9% and 33% for DFI < 6 and > 36 months, respectively).CONCLUSION: Tumor size, grade, and resection margin predict outcome for completely resected STS, and their influence for DSS is time- and site-dependent. The influence of prognostic factors changes over the natural history of extremity/trunk STS. Time to recurrence exerts significant influence over complete resection rates for recurrent disease.

Safety of Ovarian Preservation in Premenopausal Women With Endometrial Cancer

2009 ◽  
Vol 27 (8) ◽  
pp. 1214-1219 ◽  
Author(s):  
Jason D. Wright ◽  
Adam M. Buck ◽  
Monjri Shah ◽  
William M. Burke ◽  
Peter B. Schiff ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Proportional Hazards ◽  
Early Stage ◽  
Cox Model ◽  
Premenopausal Women ◽  
Tumor Grade ◽  
Cox Proportional Hazards ◽  
Eastern United States ◽  
Ovarian Preservation ◽  
Cox Proportional Hazards Models

Purpose Oophorectomy is commonly performed in premenopausal women with endometrial cancer who undergo hysterectomy. The benefits of oophorectomy in this setting are unknown, and the procedure subjects women to the long-term sequelae of estrogen deprivation. We examined the safety of ovarian preservation in young women with endometrial cancer who underwent hysterectomy. Patients and Methods Women ≤ 45 years of age with stage I endometrial cancer recorded from 1988 to 2004 in the Surveillance, Epidemiology, and End Results Database were examined. We developed Cox proportional hazards models and Kaplan-Meier curves to compare women who underwent oophorectomy with those who had ovarian preservation. Results A total of 3,269 women, including 402 patients (12%) who had ovarian preservation, were identified. Younger age (P < .0001), later year of diagnosis (P = .04), residence in the eastern United States (P = .02), and low tumor grade (P < .0001) were associated with ovarian preservation. In a multivariate Cox model, ovarian preservation had no effect on either cancer-specific (hazard ratio [HR] = 0.58; 95% CI, 0.14 to 2.44) or overall (HR = 0.68; 95% CI, 0.34 to 1.35) survival. The findings were unchanged when women who received pelvic radiotherapy were excluded. Conclusion Ovarian preservation in premenopausal women with early-stage endometrial cancer may be safe and not associated with an increase in cancer-related mortality.

scholarly journals A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems

JAMIA Open ◽  
2020 ◽  
Author(s):  
Spiros Denaxas ◽  
Anoop D Shah ◽  
Bilal A Mateen ◽  
Valerie Kuan ◽  
Jennifer K Quint ◽  
...  
Keyword(s):  
Primary Care ◽  
Proportional Hazards ◽  
Biomarker Discovery ◽  
Data Extraction ◽  
Cox Proportional Hazards ◽  
Research Quality ◽  
Uk Biobank ◽  
Expert Review ◽  
Cox Proportional Hazards Models ◽  
The Uk

Abstract Objectives The UK Biobank (UKB) is making primary care electronic health records (EHRs) for 500 000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: (a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and (b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers. Materials and Methods We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving (a) bootstrapping definitions using existing phenotypes, (b) excluding generic, rare, or semantically distant terms, (c) forward-mapping terminology terms, (d) expert review, and (e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models. Results We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications, for example diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38 190 682 events and identified 220 978 participants with at least one biomarker measured. Discussion and conclusion Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.

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