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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.
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.
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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