Dataset Information

Association of Delayed Time to Treatment Initiation With Overall Survival and Recurrence Among Patients With Head and Neck Squamous Cell Carcinoma in an Underserved Urban Population.

ABSTRACT: Importance:Delay in time to treatment initiation (TTI) can alter survival and oncologic outcomes. There is a need to characterize these consequences and identify risk factors and reasons for treatment delay, particularly in underserved urban populations. Objectives:To investigate the association of delayed treatment initiation with outcomes of overall survival and recurrence among patients with head and neck squamous cell carcinoma (HNSCC), to analyze factors that are predictive of delayed treatment initiation, and to identify specific reasons for delayed treatment initiation. Design, Setting, and Participants:Retrospective cohort study at an urban community-based academic center. Participants were 956 patients with primary HNSCC treated between February 8, 2005, and July 17, 2017, identified through the Montefiore Medical Center Cancer Registry. Exposures:The primary exposure was TTI, defined as the duration between histopathological diagnosis and initial treatment. The threshold for delayed treatment initiation was determined by recursive partitioning analysis. Main Outcomes and Measures:Overall survival, recurrence, and reasons for treatment delay. Results:Among 956 patients with HNSCC (mean [SD] age, 60.8 [18.2] years; 72.6% male), the median TTI was 40 days (interquartile range, 28-56 days). The optimal TTI threshold to differentiate overall survival was greater than 60 days (20.8% [199 of 956] of patients in our cohort). Independent of other relevant factors, patients with HNSCC with TTI exceeding 60 days had poorer survival (hazard ratio, 1.69; 95% CI, 1.32-2.18). Similarly, TTI exceeding 60 days was associated with greater risk of recurrence (odds ratio, 1.77; 95% CI, 1.07-2.93). Predictors of delayed TTI included African American race/ethnicity, Medicaid insurance, body mass index less than 18.5, and initial diagnosis at a different institution. Commonly identified individual reasons for treatment delay were missed appointments (21.2% [14 of 66]), extensive pretreatment evaluation (21.2% [14 of 66]), and treatment refusal (13.6% [9 of 66]). Conclusions and Relevance:Delaying TTI beyond 60 days was associated with decreased overall survival and increased HNSCC recurrence. Identification of predictive factors and reasons for treatment delay will help target at-risk patients and facilitate intervention in hospitals with underserved urban populations.

SUBMITTER: Liao DZ

PROVIDER: S-EPMC6743055 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Association of Delayed Time to Treatment Initiation With Overall Survival and Recurrence Among Patients With Head and Neck Squamous Cell Carcinoma in an Underserved Urban Population.

Liao David Z DZ Schlecht Nicolas F NF Rosenblatt Gregory G Kinkhabwala Corin M CM Leonard James A JA Ference Ryan S RS Prystowsky Michael B MB Ow Thomas J TJ Schiff Bradley A BA Smith Richard V RV Mehta Vikas V

JAMA otolaryngology-- head & neck surgery 20191101 11

<h4>Importance</h4>Delay in time to treatment initiation (TTI) can alter survival and oncologic outcomes. There is a need to characterize these consequences and identify risk factors and reasons for treatment delay, particularly in underserved urban populations.<h4>Objectives</h4>To investigate the association of delayed treatment initiation with outcomes of overall survival and recurrence among patients with head and neck squamous cell carcinoma (HNSCC), to analyze factors that are predictive o ...[more]

PMID: 31513264

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Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is a common malignancy that emanates from the lips, mouth, paranasal sinuses, oropharynx, larynx, nasopharynx, and from other pharyngeal cancers. The availability of high-throughput expression data has made it possible to use global gene expression data to analyze the relationship between metabolic-related gene expression and clinical outcomes in HNSCC patients.MethodIn this study, we used RNA sequencing (RNA-seq) data from the cancer genome atlas (TCGA), with validation in the GEO dataset to profile the metabolic microenvironment and define potential biomarkers for metabolic therapy.ResultsWe extracted data for 529 patients and 327 metabolic genes (198 upregulated and 129 downregulated genes) in the TCGA database. Carbonic anhydrase 9 (CA9) and CA6 had the largest logFCs in the upregulated and downregulated genes, respectively. Our Cox regression model data showed 51 prognostic-related genes with lysocardiolipin acyltransferase 1 (LCLAT1) and choline dehydrogenase (CHDH) being associated with the highest risk (HR = 1.144, 95% CI = 1.044 ~ 1.251) and the lowest risk (HR = 0.580, 95% CI = 0.400 ~ 0.839) in HNSCC, respectively. We next used the ROC curve to evaluate whether the differentially expressed metabolic-related genes could serve as early predictors of HNSCC. The findings showed an AUC of 0.745 and 0.618 in the TCGA and GEO analysis, respectively. Besides, the ability for the genes to predict clinicopathological HNSCC status was analyzed and the data showed that the AUC for age, gender, grade, stage, T, M, and N was 0.520, 0.495, 0.568, 0.606, 0.577, 0.476, and 0.673, respectively, in the TCGA dataset. On the other hand, the AUC for age, gender, stage, T, M, N, smoking, and HPV16-pos was 0.599, 0.531, 0.622, 0.606, 0.616, 0.550, 0.614, 0.519, and 0.397, respectively, in the GEO dataset.ConclusionTaken together, our study unearths a novel metabolic gene signature for the prediction of HNSCC prognosis based on the TCGA dataset. Our signature might point out the metabolic microenvironment disorders and provides potential treatment targets and prognostic biomarkers.

Project description:ImportanceThe standard of care for initiation of postoperative radiotherapy (PORT) in head and neck squamous cell carcinoma (HNSCC) is within 6 weeks of surgical treatment. Delays in guideline-adherent PORT initiation are common, associated with mortality, and a measure of quality care, but patient-specific tools to estimate the risk of these delays are lacking.ObjectiveTo develop and validate 2 nomograms (that use presurgical and postsurgical data) for predicting delayed PORT initiation.Design, setting, and participantsThis cohort study obtained patient data from January 1, 2004, to December 31, 2015, from the National Cancer Database. Adults aged 18 years or older with a newly diagnosed HNSCC who underwent surgical treatment and PORT at a Commission on Cancer-accredited facility were included. Data analysis was conducted from June 2, 2019, to January 29, 2020.ExposuresSurgical treatment and PORT.Main outcomes and measuresThe primary outcome measure was PORT initiation more than 6 weeks after the surgical intervention. Multivariable logistic regression models were created in a random selection of 80% of the sample (derivation cohort) and were internally validated with bootstrapping, assessed for discrimination by calibration plots and the concordance (C) index, and externally validated in the remaining 20% of the sample (validation cohort).ResultsThe study included 60 766 adults with HNSCC who were grouped into derivation and validation cohorts. The derivation cohort comprised 48 625 patients (mean [SD] age, 59.59 [11.3] years; 36 825 men [75.7%]) selected randomly from the full sample, whereas 12 151 patients (mean [SD] age, 59.63 [11.2] years; 9266 men [76.3%]) composed the validation cohort. The rate of PORT delay was 55.8% (n=27140) in the derivation cohort and 56.7% (n=6900) in the validation cohort. Both nomograms created to predict the risk of PORT initiation delay used variables, including race/ethnicity, insurance type, tumor site, and facility type. The nomogram based on presurgical variables included clinical stage and severity of comorbidity, whereas the nomogram with postsurgical variables included US region, length of stay, and care fragmentation between surgical and radiotherapy facilities. For the presurgical nomogram, the concordance indices were 0.670 (95% CI, 0.664-0.676) in the derivation cohort and 0.674 (95% CI, 0.662-0.685) in the validation cohort. For the nomogram with postsurgical variables, the concordance indices were 0.691 (95% CI, 0.686-0.696) in the derivation cohort and 0.694 (95% CI, 0.685-0.704) in the validation cohort.Conclusions and relevanceThis study found that a nomogram developed with presurgical data to generate personalized estimates of PORT initiation delay may improve pretreatment counseling and the delivery of interventions to patients at high risk for such a delay. A nomogram including postsurgical data can drive institutional quality improvement initiatives and enhance risk-adjusted comparisons of delay rates across facilities.

Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is a common cancer characterized by late diagnosis and poor prognosis. The aim of this study was to identify a novel ferroptosis-related DNA methylation signature as an alternative diagnosis index for patients with HNSCC.MethodsMethylome and transcriptome data of 499 HNSCC patients, including 275 oral squamous cell carcinoma (OSCC) samples, were obtained from The Cancer Genome Atlas (TCGA). An additional independent methylation dataset of 50 OSCC patients from the NCBI Gene Expression Omnibus (GEO) database was used for validation. As an index of ferroptosis activity, the ferroptosis score (FS) of each patient was inferred from the transcriptome data using single-sample gene set enrichment analysis. Univariate, multivariate, and LASSO Cox regression analyses were used to select CpG sites for the construction of a ferroptosis-related DNA methylation signature for diagnosis of patients.ResultsWe initially inferred the FS of each TCGA HNSCC patient and divided the samples into high- and low-FS subgroups. Results showed that the high-FS subgroup displayed poor overall survival. Moreover, 378 differentially methylated CpG sites (DMCs) were identified between the two HNSCC subgroups, with 16 selected to construct a 16-DNA methylation signature for risk prediction in HNSCC patients using the LASSO and multivariate Cox regression models. Relative operating characteristic (ROC) curve analysis showed great predictive efficiency for 1-, 3-, and 5-year HNSCC survival using the 16-DNA methylation signature. Its predictive efficiency was also observed in OSCC patients from the TCGA and GEO databases. In addition, we found that the signature was associated with the fractions of immune types in the tumor immune microenvironment (TIME), suggesting potential interactions between ferroptosis and TIME in HNSCC progression.ConclusionsWe established a novel ferroptosis-related 16-DNA methylation signature that could be applied as an alternative tool to predict prognosis outcome in patients with HNSCC, including OSCC.

Dataset Information

Association of Delayed Time to Treatment Initiation With Overall Survival and Recurrence Among Patients With Head and Neck Squamous Cell Carcinoma in an Underserved Urban Population.

Publications

Association of Delayed Time to Treatment Initiation With Overall Survival and Recurrence Among Patients With Head and Neck Squamous Cell Carcinoma in an Underserved Urban Population.

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