Correlation-based joint feature screening for semi-competing risks outcomes with application to breast cancer data

2021 ◽  
pp. 096228022110370
Author(s):  
Mengjiao Peng ◽  
Liming Xiang
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Overall Survival ◽  
Competing Risks ◽  
Distant Metastasis ◽  
Finite Sample ◽  
Breast Cancer Data ◽  
Free Survival ◽  
Cancer Data ◽  
Distant Metastasis Free Survival

Ultrahigh-dimensional gene features are often collected in modern cancer studies in which the number of gene features [Formula: see text] is extremely larger than sample size [Formula: see text]. While gene expression patterns have been shown to be related to patients’ survival in microarray-based gene expression studies, one has to deal with the challenges of ultrahigh-dimensional genetic predictors for survival predicting and genetic understanding of the disease in precision medicine. The problem becomes more complicated when two types of survival endpoints, distant metastasis-free survival and overall survival, are of interest in the study and outcome data can be subject to semi-competing risks due to the fact that distant metastasis-free survival is possibly censored by overall survival but not vice versa. Our focus in this paper is to extract important features, which have great impacts on both distant metastasis-free survival and overall survival jointly, from massive gene expression data in the semi-competing risks setting. We propose a model-free screening method based on the ranking of the correlation between gene features and the joint survival function of two endpoints. The method accounts for the relationship between two endpoints in a simply defined utility measure that is easy to understand and calculate. We show its favorable theoretical properties such as the sure screening and ranking consistency, and evaluate its finite sample performance through extensive simulation studies. Finally, an application to classifying breast cancer data clearly demonstrates the utility of the proposed method in practice.

scholarly journals Impact of an MT-RNR1 Gene Polymorphism on Hepatocellular Carcinoma Progression and Clinical Characteristics

2021 ◽  
Vol 22 (3) ◽  
pp. 1119
Author(s):  
Yang-Hsiang Lin ◽  
Yu-De Chu ◽  
Siew-Na Lim ◽  
Chun-Wei Chen ◽  
Chau-Ting Yeh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Risk Factor ◽  
Distant Metastasis ◽  
Tumor Metastasis ◽  
12S Rrna ◽  
Potential Candidate ◽  
Free Survival ◽  
Mtdna Mutations ◽  
Distant Metastasis Free Survival

Mitochondrial DNA (mtDNA) mutations are highly associated with cancer progression. The poor prognosis of hepatocellular carcinoma (HCC) is largely due to high rates of tumor metastasis. This emphasizes the urgency of identifying these patients in advance and developing new therapeutic targets for successful intervention. However, the issue of whether mtDNA influences tumor metastasis in hepatoma remains unclear. In the current study, multiple mutations in mtDNA were identified by sequencing HCC samples. Among these mutations, mitochondrially encoded 12S rRNA (MT-RNR1) G709A was identified as a novel potential candidate. The MT-RNR1 G709A polymorphism was an independent risk factor for overall survival and distant metastasis-free survival. Subgroup analysis showed that in patients with cirrhosis, HBV-related HCC, α-fetoprotein ≥ 400 ng/mL, aspartate transaminase ≥ 31 IU/L, tumor number > 1, tumor size ≥ 5 cm, and histology grade 3-4, MT-RNR1 G709A was associated with both shorter overall survival and distant metastasis-free survival. Mechanistically, MT-RNR1 G709A was clearly associated with hexokinase 2 (HK2) expression and unfavorable prognosis in HCC patients. Our data collectively highlight that novel associations among MT-RNR1 G709A and HK2 are an important risk factor in HCC patients.

Comparison of Survival Outcomes for Axillary Surgery Extent Based on Intraoperative Sentinel Lymph Node Biopsy Result After Neoadjuvant Chemotherapy for Breast Cancer

2021 ◽  
Author(s):  
Jung Whan Chun ◽  
Jisun Kim ◽  
Il Yong Chung ◽  
Beom Seok Ko ◽  
Hee Jeong Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Neoadjuvant Chemotherapy ◽  
Axillary Recurrence ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Axillary Surgery ◽  
Distant Metastasis Free Survival

Abstract PurposeTo investigate the survival difference between limited axillary surgery and full axillary lymph node dissection (ALND) in patients with 1-3 positive sentinel lymph node biopsies (SLNBs) after neoadjuvant chemotherapy (NAC).MethodWe retrospectively analyzed data from 676 patients who underwent surgery between 2007 and 2017 with cT1-4, cN0-3, cM0 breast cancer at the time of diagnosis and 1-3 positive SLNBs after NAC. The patients received either SLNB only or completed level I or II ALND based on SLNB results. After propensity score matching, 483 patients who had undergone SLNB only (n=188) and ALND (n=295) were included. We examined overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival and compared them between the subgroups.ResultAt a median follow-up of 59.4 months, no significant statistical difference was observed in overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival between SLNB only and ALND. No significant differences were observed in the 5-year axillary recurrence-free survival (93.1% vs. 94.0%, hazard ratio [HR]=0.94, 95% confidence interval [CI]=0.43-2.05, p=0.876) and 5-year overall survival (97.7% vs. 97.3%, HR=1.65, 95% CI=0.58-4.65, p=0.347) between the two groups.ConclusionOur analysis suggests that SLNB alone may be a possible option for patients with 1-3 sentinel node-positive breast cancer following NAC without significant compromise of recurrence or overall survival.

Multicenter Validation of a Gene Expression–Based Prognostic Signature in Lymph Node–Negative Primary Breast Cancer

2006 ◽  
Vol 24 (11) ◽  
pp. 1665-1671 ◽  
Author(s):  
John A. Foekens ◽  
David Atkins ◽  
Yi Zhang ◽  
Fred C.G.J. Sweep ◽  
Nadia Harbeck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Distant Metastasis ◽  
Gene Signature ◽  
Breast Cancer Patients ◽  
Prognostic Signature ◽  
Free Survival ◽  
Node Negative ◽  
Distant Metastasis Free Survival ◽  
Multicenter Validation

Purpose We previously identified in a single-center study a 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients. The aim of this study was to validate this gene signature in an independent more diverse population of LNN patients from multiple institutions. Patients and Methods Using custom-designed DNA chips we analyzed the expression of the 76 genes in RNA of frozen tumor samples from 180 LNN patients who did not receive adjuvant systemic treatment. Results In this independent validation, the 76-gene signature was highly informative in identifying patients with distant metastasis within 5 years (hazard ratio, [HR], 7.41; 95% CI, 2.63 to 20.9), even when corrected for traditional prognostic factors in multivariate analysis (HR, 11.36; 95% CI, 2.67 to 48.4). The actuarial 5- and 10-year distant metastasis-free survival were 96% (95% CI, 89% to 99%) and 94% (95% CI, 83% to 98%), respectively, for the good profile group and 74% (95% CI, 64% to 81%) and 65% (53% to 74%), respectively for the poor profile group. The sensitivity for 5-yr distant metastasis-free survival was 90%, and the specificity was 50%. The positive and negative predictive values were 38% (95% CI, 29% to 47%) and 94% (95% CI, 86% to 97%), respectively. The 76-gene signature was confirmed as a strong prognostic factor in subgroups of estrogen receptor-positive patients, pre- and postmenopausal patients, and patients with tumor sizes 20 mm or smaller. The subgroup of patients with estrogen receptor-negative tumors was considered too small to perform a separate analysis. Conclusion Our data provide a strong methodologic and clinical multicenter validation of the predefined prognostic 76-gene signature in LNN breast cancer patients.

scholarly journals Clinical Study of Nasopharyngeal Carcinoma Treated by Helical Tomotherapy in China: 5-Year Outcomes

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Lei Du ◽  
Xin-Xin Zhang ◽  
Lin Ma ◽  
Lin-Chun Feng ◽  
Fang Li ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Overall Survival ◽  
Nasopharyngeal Carcinoma ◽  
Distant Metastasis ◽  
Helical Tomotherapy ◽  
Antibody Therapy ◽  
Monoclonal Antibody Therapy ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Distant Metastasis Free Survival

Background.To evaluate the outcomes of nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT).Methods.Between September 2007 and August 2012, 190 newly diagnosed NPC patients were treated with HT. Thirty-one patients were treated with radiation therapy as single modality, 129 with additional cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody therapy, and 30 with concurrent anti-EGFR monoclonal antibody therapy.Results.Acute radiation related side effects were mainly grade 1 or 2. Grade 3 and greater toxicities were rarely noted. The median followup was 32 (3–38) months. The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 96.1%, 98.2%, 92.0%, and 86.3%, respectively, at 3 years. Cox multivariate regression analysis showed that age and T stage were independent predictors for 3-year OS.Conclusions.Helical tomotherapy for NPC patients achieved excellent 3-year locoregional control, distant metastasis-free survival, and overall survival, with relatively minor acute and late toxicities. Age and T stage were the main prognosis factors.

Single-center experiences of neoadjuvant systemic therapy in breast cancer: Individualization of the treatment

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11628-e11628
Author(s):  
M. Gumus ◽  
B. O. Ustaalioglu ◽  
M. Seker ◽  
A. Bilici ◽  
T. Salman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Neoadjuvant Chemotherapy ◽  
Distant Metastasis ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

e11628 Background: Neoadjuvant chemotherapy is one of the standard treatment options for patients with locally advanced breast cancer for twenty five years. In this study, we evaluate results of neoadjuvant chemotherapy in breast cancer patients. Methods: We retrospectively analyzed 68 patients with locally advanced breast cancer. Anthracycline/taxane-based chemotherapy regimens were prescribed mostly for neoadjuvant chemotherapy. Before chemotherapy was given, patients were examined for distant metastasis by radiologic methods thereafter if patient had distant metastasis, they were excluded. Patients with breast cancer received neoadjuvant chemotherapy were analyzed according to age, menopausal status, type of surgery, response to the treatment, histopathological properties and survival. After 3 to 6 cycle of chemotherapy patients were reevaluated by clinically and radiologically for response. Surgery was performed for appropriate patient thereafter adjuvant locoregional and systemic chemotherapy were continued. Results: Median age was 47 (29–43) years. 17,6 % of them were younger than 35 years and 42,6 % were premenopausal. Median follow-up time was 19 month. After 3 to 6 cycle of neoadjuvant chemotherapy 64 of patients responded to therapy (94,1 %). Breast conserving surgery was performed for 15,6 % patients. In histopathologic analysis most of patients were invasive ductal carcinoma and there was lymph node invasion for 84,9 %. Estrogen and progesterone receptor status were negative for 18,6 % of patients and cerbB2 was positive for 14,8 % of patients. Median disease free survival time was 44 month (SE: 9; 95% CI: 25–62) but median overall survival time could not be reached. Three years disease free survival rate and overall survival rate were 55,3% and 90,1% respectively. According to Cox regression analyses; we did not find any demographic and pathologic characteristic of breast cancer that is related to prognosis. Conclusions: In recent years neoadjuvant chemotherapy in breast cancer is increasingly being used for early stage disease. Further study will be facilitated establishment of guidelines for preselecting patients for neoadjuvant chemotherapy and will provide beneficial effect on treatment option and survival. No significant financial relationships to disclose.

HSD3B1 and resistance to androgen deprivation therapy in prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 156-156 ◽  
Author(s):  
Jason W.D. Hearn ◽  
Ghada AbuAli ◽  
Cristina Magi-Galluzzi ◽  
Chandana A. Reddy ◽  
Kai-Hsiung Chang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Deprivation Therapy ◽  
Distant Metastasis ◽  
Progression Free Survival ◽  
Wild Type ◽  
Free Survival ◽  
Homozygous Variant ◽  
Distant Metastasis Free Survival ◽  
Variant Alleles

156 Background: The somatic mutation HSD3B1(1245A>C) has been mechanistically linked to castration-resistant prostate cancer by encoding a mutant enzyme that augments intratumoral dihydrotestosterone synthesis. Given the HSD3B1(1245C) allele is also frequently found in the germline, we hypothesized men inheriting this variant allele would exhibit resistance to androgen deprivation therapy (ADT), as manifested by worse clinical outcomes. Methods: We used a prospectively maintained prostate cancer registry to identify men treated with ADT for biochemical failure in the post-prostatectomy setting who were without evidence of metastatic disease at the time of ADT initiation. We analyzed progression-free survival, distant metastasis-free survival, and overall survival according to HSD3B1 genotype using Kaplan-Meier methods. Cox proportional hazards regression was performed to evaluate potential gene-dosage effects, with homozygous wild-type men serving as the reference group. Demographic and treatment characteristics were compared across genotypes to assess for possible confounders using Fisher’s exact test and Kruskal-Wallis analysis of variance. Results: Of 118 men genotyped, 37% were homozygous wild-type, 53% were heterozygous, and 10% were homozygous variant. Demographic and treatment characteristics did not differ across groups. Median progression-free survival diminished as a function of the number of variant alleles inherited (6.6 years in homozygous wild-type men, 4.1 years in heterozygotes, and 2.5 years in homozygous variant men; P=0.01). Median distant metastasis-free survival likewise decreased according to the number of variant alleles inherited (9.1 years in homozygous wild-type men, 6.8 years in heterozygotes, and 3.6 years in homozygous variant men; P=0.01). Finally, overall survival also diminished with the number of variant alleles inherited (5-year and 10-year overall survival: 82% and 55% in homozygous wild-type men, 74% and 35% in heterozygotes, and 58% and 0% in homozygous variant men; P=0.006). Conclusions: Inheritance of the variant HSD3B1(1245C) allele that enhances dihydrotestosterone synthesis may predict resistance to ADT for prostate cancer. These findings require validation.

Sign in / Sign up

Export Citation Format

Share Document