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      Development and Validation of Nomograms for Predicting Delayed Postoperative Radiotherapy Initiation in Head and Neck Squamous Cell Carcinoma

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          Abstract

          The 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. To develop and validate 2 nomograms (that use presurgical and postsurgical data) for predicting delayed PORT initiation. This 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. Surgical treatment and PORT. The 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). The study included 60766 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, whereas12 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. This 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.

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          Most cited references18

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          American Joint Committee on Cancer acceptance criteria for inclusion of risk models for individualized prognosis in the practice of precision medicine.

          The American Joint Committee on Cancer (AJCC) has increasingly recognized the need for more personalized probabilistic predictions than those delivered by ordinal staging systems, particularly through the use of accurate risk models or calculators. However, judging the quality and acceptability of a risk model is complex. The AJCC Precision Medicine Core conducted a 2-day meeting to discuss characteristics necessary for a quality risk model in cancer patients. More specifically, the committee established inclusion and exclusion criteria necessary for a risk model to potentially be endorsed by the AJCC. This committee reviewed and discussed relevant literature before creating a checklist unique to this need of AJCC risk model endorsement. The committee identified 13 inclusion and 3 exclusion criteria for AJCC risk model endorsement in cancer. The emphasis centered on performance metrics, implementation clarity, and clinical relevance. The facilitation of personalized probabilistic predictions for cancer patients holds tremendous promise, and these criteria will hopefully greatly accelerate this process. Moreover, these criteria might be useful for a general audience when trying to judge the potential applicability of a published risk model in any clinical domain. CA Cancer J Clin 2016;66:370-374. © 2016 American Cancer Society.
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            Association of Treatment Delays With Survival for Patients With Head and Neck Cancer

            Delays in the delivery of care for head and neck cancer (HNC) are a key driver of poor oncologic outcomes and thus represent an important therapeutic target.
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              Development and Validation of Nomograms Predictive of Overall and Progression-Free Survival in Patients With Oropharyngeal Cancer

              Purpose Treatment of oropharyngeal squamous cell carcinoma (OPSCC) is evolving toward risk-based modification of therapeutic intensity, which requires patient-specific estimates of overall survival (OS) and progression-free survival (PFS). Methods To develop and validate nomograms for OS and PFS, we used a derivation cohort of 493 patients with OPSCC with known p16 tumor status (surrogate of human papillomavirus) and cigarette smoking history (pack-years) randomly assigned to clinical trials using platinum-based chemoradiotherapy (NRG Oncology Radiation Therapy Oncology Group [RTOG] 0129 and 0522). Nomograms were created from Cox models and internally validated by use of bootstrap and cross-validation. Model discrimination was measured by calibration plots and the concordance index. Nomograms were externally validated in a cohort of 153 patients with OPSCC randomly assigned to a third trial, NRG Oncology RTOG 9003. Results Both models included age, Zubrod performance status, pack-years, education, p16 status, and T and N stage; the OS model also included anemia and age × pack-years interaction; and the PFS model also included marital status, weight loss, and p16 × Zubrod interaction. Predictions correlated well with observed 2-year and 5-year outcomes. The uncorrected concordance index was 0.76 (95% CI, 0.72 to 0.80) for OS and 0.70 (95% CI, 0.66 to 0.74) for PFS, and bias-corrected indices were similar. In the validation set, OS and PFS models were well calibrated, and OS and PFS were significantly different across tertiles of nomogram scores (log-rank P = .003;< .001). Conclusion The validated nomograms provided useful prediction of OS and PFS for patients with OPSCC treated with primary radiation-based therapy.
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                Author and article information

                Journal
                JAMA Otolaryngology–Head & Neck Surgery
                JAMA Otolaryngol Head Neck Surg
                American Medical Association (AMA)
                2168-6181
                April 02 2020
                Affiliations
                [1 ]Department of Otolaryngology–Head & Neck Surgery, Medical University of South Carolina, Charleston
                [2 ]Department of Public Health Sciences, Medical University of South Carolina, Charleston
                [3 ]Hollings Cancer Center, Medical University of South Carolina, Charleston
                [4 ]Department of Psychiatry & Behavioral Sciences, Medical University of South Carolina, Charleston
                [5 ]Department of Radiation Oncology, Medical University of South Carolina, Charleston
                [6 ]Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston
                [7 ]American Board of Otolaryngology–Head & Neck Surgery, Houston, Texas
                [8 ]Arnold School of Public Health, Department of Epidemiology and Biostatistics, University of South Carolina, Columbia
                Article
                10.1001/jamaoto.2020.0222
                7118672
                32239201
                3deb1a25-b689-4afd-91c1-ed1176d188f1
                © 2020
                History

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