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Background: Development of evidence‐based post‐treatment surveillance guidelines in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is limited by comprehensive documentation of patterns of recurrence and metastatic spread. Methods: A retrospective analysis of patients diagnosed with R/M HNSCC at a National Cancer Institute‐designated cancer center between 1998– 2019 was performed (n = 447). Univariate and multivariate analysis identified patterns of recurrence and predictors of survival. Results: Median overall survival (mOS) improved over time (6.7 months in 1998–2007 to 11.8 months in 2008–2019, p =.006). Predictors of worse mOS included human papillomavirus (HPV) negativity (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.2–2.6), high neutrophil/lymphocyte ratio (HR, 2.1 [1.4–3.0], disease‐free interval (DFI) ≤6 months (HR, 1.4 [1.02–2.0]), and poor performance status (Eastern Cooperative Oncology Group, ≥2; HR, 1.91.1–3.4). In this cohort, 50.6% of recurrences occurred within 6 months of treatment completion, 72.5% occurred within 1 year, and 88.6% occurred within 2 years. Metachronous distant metastases were more likely to occur in patients with HPV‐positive disease (odds ratio [OR], 2.3 [1.4–4.0]), DFI >6 months (OR, 2.4 [1.5–4.0]), and body mass index ≥30 (OR, 2.3 [1.1–4.8]). Oligometastatic disease treated with local ablative therapy was associated with improved survival over polymetastatic disease (HR, 0.36; 95% CI, 0.24–0.55). Conclusion: These data regarding patterns of distant metastasis in HNSCC support the clinical utility of early detection of recurrence. Patterns of recurrence in this population can be used to inform individualized surveillance programs as well as to risk‐stratify eligible patients for clinical trials. Plain Language Summary: After treatment for head and neck cancer (HNC), patients are at risk of recurrence at prior sites of disease or at distant sites in the body.This study includes a large group of patients with recurrent or metastatic HNC and examines factors associated with survival outcomes and recurrence patterns.Patients with human papillomavirus (HPV)‐positive HNC have good survival outcomes, but if they recur, this may be in distant regions of the body and may occur later than HPV‐negative patients.These data argue for personalized follow‐up schedules for patients with HNC, perhaps incorporating imaging studies or novel blood tests. Patterns of recurrence in recurrent/metastatic head and neck squamous cell carcinoma differ based on patient and tumor‐specific factors. These data can be used to guide personalized surveillance schedules. [ABSTRACT FROM AUTHOR]

PURPOSE: To use a hybrid method, combining statistical profiling, machine learning (ML), and clinical evaluation to predict emergency department (ED) visits among patients with head and neck cancer undergoing radiotherapy. MATERIALS AND METHODS: Patients with head and neck cancer treated with radiation therapy from 2015 to 2019 were identified using electronic health record data. Records from 60 days before 90 days after treatment were analyzed. Statistical profiling and ML were used to create a predictive model for ED visits during or after radiation therapy. A comprehensive set of variables were studied. Multiple ML models were developed including extreme gradient-boosted decision tree and generalized logistic regression with comparison of multiple predictive performance metrics. RESULTS: Of the 1,355 patients studied, 13% had an ED visit during or after treatment. Our hybrid methodology enabled evidence-based winnowing of candidate features from 141 to 11 with clinically applicable, evidence-based thresholds. Extreme gradient boosting had the highest area under the curve (0.81 ± 0.06) with a sensitivity of 0.89 ± 0.10 and exceeded generalized logistic regression (area under the curve 0.64 ± 0.02). Significant predictors of ED visits during treatment included increasingly complex opioid use, number of prior ED visits, tumor volume, rate of change of blood urea nitrogen, total bilirubin, body mass index, and distance from hospital. CONCLUSION: Our approach combining bootstrapped statistical profiling and ML importance analysis supported integration of clinician input to identify a distilled set of phenotypical characteristics for developing ML models predicting which patients undergoing head and neck cancer radiation therapy were at risk for ED visits. [ABSTRACT FROM AUTHOR]

PURPOSE Financial hardship is a growing concern for patients with cancer. Patients with head and neck cancer (HNC) are particularly vulnerable, given that a third leave the workforce following treatment. The goal of our study was to characterize financial hardship in the psychologic response (response to increased expenses) and coping behaviors (behaviors patients adopt to manage their care in the setting of increased expenses) domains in patients with HNC compared with patients with other cancers. METHODS This was a retrospective cohort study of nationally representative public survey data from 2013 to 2018 in the National Health Interviews Survey, an annual cross-sectional household survey. We included respondents age $ 18 years who reported a diagnosis of cancer and identified a subset of patients with HNC. Our main outcomes were financial hardship in the psychologic response and coping behaviors domains. RESULTS Our sample included a weighted population of 357,052 patients with HNC and 21.4 million patients with other cancers. Compared with patients with other cancers, patients with HNC reported greater levels of coping behaviors hardship (31% v 23%, P 5 .015), but similar levels of psychologic financial hardship (73% v 72%, P 5 .787). Medicaid or uninsured patients more often reported coping behaviors hardship. On multivariable analysis, HNC (odds ratio, 1.51; 95% CI, 1.01 to 2.24) was independently associated with coping behaviors hardship. CONCLUSION To our knowledge, this is the first study to evaluate financial hardship in patients with HNC compared with patients with other cancers that includes Medicaid and uninsured patients, who are more often to have financial hardship. Patients with HNC have greater levels of hardship in the coping behaviors domain compared with patients with other cancers, but similar levels in the psychologic response domain. [ABSTRACT FROM AUTHOR]

Background: Cutaneous squamous cell carcinoma of the head/neck (CSCCHN) is common due to chronic sun exposure. As CSCCHN highly expresses EGFR, we prospectively studied postoperative concurrent cetuximab with radiotherapy for locally advanced CSCCHN (LA‐CSCCHN). Materials and methods: Single‐institutional phase II trial of LA‐CSCCHN (NCT XXXX). Adjuvant radiation was given with concurrent cetuximab. Primary endpoint of 2‐year LRC and secondary objectives of 2‐year disease‐free survival (DFS) and 2‐year OS were assessed by Kaplan–Meier analysis. Results: Twenty‐four patients ages 47–88 (median 71 years) were treated from 2014 to 2017. Fourteen patients had T3/4 disease, 5 had N1 disease, and 7 were N2/3. At median follow‐up of 42 months, median OS and DFS was not reached and 64 months. Two‐year OS was 75%, 2‐year DFS was 70.8%. LRC was 91.1% at 2 years. All grade 3 adverse events were related to skin toxicity (12.5% radiation‐related dermatitis, 16.7% cetuximab‐related rash). Conclusions: LRC compares favorably to historical data examining postoperative radiation alone but requires further investigation. [ABSTRACT FROM AUTHOR]

Purpose: FDG-PET adds to clinical factors, such tumor stage and p16 status, in predicting local (LF), regional (RF), and distant failure (DF) in poor prognosis locally advanced head and neck cancer (HNC) treated with chemoradiation. We hypothesized that MRI-based quantitative imaging (QI) metrics could add to clinical predictors of treatment failure more significantly than FDG-PET metrics. Materials and methods: Fifty four patients with poor prognosis HNCs who were enrolled in an IRB approved prospective adaptive chemoradiotherapy trial were analyzed. MRI-derived gross tumor volume (GTV), blood volume (BV), and apparent diffusion coefficient (ADC) pre-treatment and mid-treatment (fraction 10), as well as pre-treatment FDG PET metrics, were analyzed in primary and individual nodal tumors. Cox proportional hazards models for prediction of LRF and DF free survival were used to test the additional value of QI metrics over dominant clinical predictors. Results: The mean ADC pre-RT and its change rate mid-treatment were significantly higher and lower in p16– than p16+ primary tumors, respectively. A Cox model identified that high mean ADC pre-RT had a high hazard for LF and RF in p16– but not p16+ tumors (p = 0.015). Most interesting, persisting subvolumes of low BV (TVbv) in primary and nodal tumors mid-treatment had high-risk for DF (p < 0.05). Also, total nodal GTV mid-treatment, mean/max SUV of FDG in all nodal tumors, and total nodal TLG were predictive for DF (p < 0.05). When including clinical stage (T4/N3) and total nodal GTV in the model, all nodal PET parameters had a p -value of >0.3, and only TVbv of primary tumors had a p -value of 0.06. Conclusion: MRI-defined biomarkers, especially persisting subvolumes of low BV, add predictive value to clinical variables and compare favorably with FDG-PET imaging markers. MRI could be well-integrated into the radiation therapy workflow for treatment planning, response assessment, and adaptive therapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Long non‐coding RNA (lncRNA) has emerged as a new avenue of interest due to its various biological functions in cancer. Abnormal expression of lncRNA has been reported in other malignancies but has been understudied in head and neck squamous cell carcinoma (HNSCC). Methods: The lncRNA expression was interrogated via quantitative real‐time polymerase chain reaction (qRT‐PCR) array for 19 human papillomavirus (HPV)‐negative HNSCC tumor‐normal pairs. The Cancer Genome Atlas (TCGA) was used to validate these results. The association between differentially expressed lncRNA and survival outcomes was analyzed. Results: Differential expression was validated for 5 lncRNA (SPRY4‐IT1, HEIH, LUCAT1, LINC00152, and HAND2‐AS1). There was also an inverse association between MEG3 expression (not significantly differentially expressed in TCGA tumors but highly variable expression) and 3‐year recurrence‐free survival (RFS). Conclusion: We identified and validated differential expression of 5 lncRNA in HPV‐negative HNSCC. Low MEG3 expression was associated with favorable 3‐year RFS, although the significance of this finding remains unclear. [ABSTRACT FROM AUTHOR]

Objectives: Financial toxicity (FT) is a significant barrier to high-quality cancer care, and patients with head and neck cancer (HNCA) are particularly vulnerable given their need for intensive support, daily radiotherapy (RT), and management of long-term physical, functional, and psychosocial morbidities following treatment. We aim to identify predictors of FT and adverse consequences in HNCA following RT.Materials and Methods: We performed a prospective survey study of patients with HNCA seen in follow-up at an academic comprehensive cancer center (CCC) or Veterans Affairs hospital between 05/2016 and 06/2018. Surveys included validated patient-reported functional outcomes and the COST measure, a validated instrument for measuring FT.Results: The response rate was 86% (n = 63). Younger age and lower median household income by county were associated with lower COST scores (i.e., worse FT) on multivariable analysis (p = .045 and p = .016, respectively). Patients with worse FT were more likely to skip clinic visits (RR (95% CI) 2.13 (1.23-3.67), p = .007), be noncompliant with recommended supplements or medications (1.24 (1.03-1.48), p = .02), and require supportive infusions (1.10 (1.02-1.20), p = .02). At the CCC, patients with worse FT were more likely to require feeding tubes (1.62 (1.14-2.31), p = .007). Overall, 36% reported that costs were higher than expected, 48% were worried about paying for treatment, and 33% reported at least a moderate financial burden from treatment.Conclusion: HNCA patients experience substantial FT from their diagnosis and/or therapy, with potential implications for medical compliance, QOL, and survivorship care. [ABSTRACT FROM AUTHOR]

Objectives: In an evolving era of immunotherapeutic options for persistent or recurrent laryngeal squamous cell carcinoma (LSCC), there is a need for improved biomarkers of treatment response and survival to inform optimal treatment selection and prognostication. Herein, our primary objective was to explore correlations between tumor infiltrating lymphocytes (TILs) and PD-L1 Combined Positive Score (CPS). Secondarily, we sought to explore their combined association with survival outcomes in patients with persistent or recurrent LSCC treated with salvage surgery.Materials and Methods: This was a retrospective cohort study at a single academic medical center. Immunohistochemistry staining for TILs and PD-L1 was performed on a tissue microarray of persistent or recurrent LSCC pathologic specimens. Correlations between TIL subsets and PD-L1 CPS were examined using Pearson's correlation coefficient and survival outcomes were analyzed with the Kaplan-Meier method and log-rank tests.Results: Only CD103+ TILs showed a statistically significant, weakly-positive correlation with PD-L1 CPS (r2 = 0.264, p < 0.015). No other TIL subsets correlated with PD-L1 CPS in our cohort. The most favorable survival outcomes were seen in patients with pathologic N0 tumors showing high CD103+ TILs and/or high PD-L1 CPS staining.Conclusion: Among patients with persistent or recurrent LSCC, CD103+ TILs only modestly correlated with PD-L1 CPS. A combined biomarker score incorporating CD103+ TILs and PD-L1 CPS greatly enhanced survival discrimination. This model may have additional utility in predicting the clinical benefit of immunotherapies in persistent or recurrent LSCC in the future. [ABSTRACT FROM AUTHOR]