p16-positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high-risk human papillomavirus or prognosis and implications for the workup of the unknown primary.

BACKGROUND: The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear. METHODS: One hundred forty-three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high-risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes. RESULTS: The median follow-up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high-risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08; 95% confidence interval [CI], 0.85-1.36; P = .528), cancer-specific (hazard ratio, 1.12; 95% CI, 0.77-1.64; P = .542), or progression-free survival (hazard ratio, 1.03; 95% CI, 0.83-1.29; P = .783). Distant metastasis-free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status. CONCLUSIONS: p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High-risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site.

Essential data variables for a minimum dataset for head and neck cancer trials and clinical research: HNCIG consensus recommendations and database.

The Head and Neck Cancer International Group (HNCIG) has undertaken an international modified Delphi process to reach consensus on the essential data variables to be included in a minimum database for HNC research. Endorsed by 19 research organisations representing 34 countries, these recommendations provide the framework to facilitate and harmonise data collection and sharing for HNC research. These variables have also been incorporated into a ready to use downloadable HNCIG minimum database, available from the HNCIG website.

The Prevalence and Determinants of Return to Work in Nasopharyngeal Carcinoma Survivors.

PURPOSE: To assess the employment status in working-age survivors of nasopharyngeal carcinoma (NPC) and explore clinical, treatment, and sociodemographic factors that may facilitate or impede successful return to work (RTW). METHODS AND MATERIALS: This Canadian study was part of a larger cross-sectional study assessing late toxicities in 107 disease-free survivors of NPC who received curative-intent intensity modulated radiation therapy ≥4 years earlier. For this substudy, eligible participants were employed at diagnosis and were of working age (<65 years) at study enrollment. Patient-reported work status (modified Radiation Therapy Oncology Group Work Status Questionnaire), quality of life (Functional Assessment of Cancer Therapy-Head and Neck questionnaire), symptom burden (MD Anderson Symptom Inventory for head and neck cancer), anxiety and depression (Hospital Anxiety and Depression Scale), neurobehavioral functioning (Frontal Systems Behavior Scale), and neurocognitive function (Montreal Cognitive Assessment) were assessed. Univariable and multivariable logistic regression models were used to explore the impact of variables on RTW status. RESULTS: Among 73 eligible patients, the median age was 53 years (range, 32-64) and median time from intensity modulated radiation therapy completion was 7.3 years (range, 4.2-11.1). At enrollment, 45 (62%) were working, of whom 14 (31%) had reduced work hours from diagnosis by a median of 12 h/wk (range, 4-30). Overall, mean work hours decreased from 41.6 to 37.8 h/wk (P = .005). Currently employed (vs unemployed) patients were younger (P = .017) and reported better performance status (P = .013). They had higher quality of life (P = .044), lower symptom burden (P = .03), less significant change from their baseline neurobehavioral function (P = .008), and disability (P = .0025) or private health benefits (P = .035). Anxiety, depression, occupation type, income, and Montreal Cognitive Assessment score were not significantly associated with RTW in the univariable analysis. Age, change in baseline neurobehavioral function, and having private health benefits were all independent predictors of RTW. CONCLUSIONS: The majority of long-term survivors of NPC do RTW, although almost one-third report working fewer hours. Prospective research is needed to better understand and facilitate successful RTW in survivors of NPC.

A cross sectional study in cognitive and neurobehavioral impairment in long-term nasopharyngeal cancer survivors treated with intensity-modulated radiotherapy.

PURPOSE/OBJECTIVES: To determine neurocognitive and neurobehavioral impairment in long-term nasopharyngeal cancer survivors (NPC) treated with intensity-modulated radiotherapy (IMRT). MATERIALS/METHODS: A cross-sectional cohort of NPC ≥4 years (y) following IMRT was assessed. Objective cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and patient-reported memory was assessed with the MDASI-HN problems remembering item. Patient and family ratings of patients' neurobehavioral symptoms of apathy, disinhibition and executive dysfunction were assessed with the Frontal Systems Behavior Scale (FrSBe). Other patient-reported symptoms (MDASI-HN), mood (HADS), and quality of life (FACT-H&N) were also collected. RESULTS: Among 102 participants: M:F = 66:36; median age 56y (32-77); median time since IMRT 7.5y (4.2-11.1). Impaired MoCA scores (<23) were observed in 33 (32%). Patient and family ratings of pre-illness neurobehavioral symptoms were in the normal range (total FrSBe T-scores 53.3 and 59.0 respectively). In contrast, post-treatment patient and family T-scores were clinically impaired (64.7, 71.3 respectively), with apathy, disinhibition and executive dysfunction post-treatment ratings all significantly worse than pre-treatment (p < 0.001). Prevalence of clinically significant post-treatment disturbance was high by patient and family ratings (48%/66% apathy, 35%/53% disinhibition, 39%/56% executive dysfunction). Post-treatment neurobehavioral symptoms strongly correlated with lower quality of life (r = -0.62) and higher anxiety (r = 0.62) and depression scores (r = 0.67, all p < 0.001). Total MoCA scores did not correlate with RT dose. However, greater declines in apathy, disinhibition and executive dysfunction were associated with receiving >75 Gy to temporal lobes. CONCLUSION: NPC treated with IMRT had moderate to high rates of neurocognitive impairment and clinically significant apathy, disinhibition, and executive dysfunction.

Management of Parotid Metastatic Cutaneous Squamous Cell Carcinoma: Regional Recurrence Rates and Survival.

Objectives Extent of parotidectomy and neck dissection for metastatic cutaneous squamous cell carcinoma (cSCC) to the parotid is debated. We describe our experience, analyzing outcomes (overall survival and regional recurrence) associated with surgical extent and adjuvant treatment. Study Design A retrospective cohort study of parotidectomy with or without neck dissection for metastatic cSCC. Setting A tertiary referral cancer center in Australia. Subjects and Methods The study group consisted of patients with metastatic cSCC involving the parotid gland who underwent a curative-intent parotidectomy (superficial or total), with or without neck dissection, between 2003 and 2014. Demographic and clinical data, treatment modalities, and outcome parameters were collected from the electronic institutional database. Results Of 78 patients, 65 underwent superficial parotidectomy. Median follow-up was 6.5 years. Sixty-four patients (82%) patients received adjuvant radiotherapy. Cervical lymph nodes were involved in 6 (24%) elective neck dissections. Involved preauricular, facial, external jugular, and occipital nodes occurred in 36.9%. Adjuvant radiotherapy was associated with improved 5-year survival-50% (95% CI, 36%-69%) versus 20% (95% CI, 6%-70%)-and improved 2-year regional control: 89% (95% CI, 67%-100%) versus 40% (95% CI, 14%-100%). The ipsilateral parotid bed recurrence rate was 3.7% for those who received adjuvant radiotherapy and 27% for those who did not receive radiotherapy. Conclusion This study supports surgery plus adjuvant radiotherapy as a standard of care for metastatic cSCC. The low incidence of parotid bed recurrence with this approach suggests that routine elective deep lobe resection may not be required.

Long-Term Late Toxicity, Quality of Life, and Emotional Distress in Patients With Nasopharyngeal Carcinoma Treated With Intensity Modulated Radiation Therapy.

PURPOSE: To report long-term (>4 years) toxicity and quality of life (QoL) among patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy (IMRT) in a nonendemic center. METHODS AND MATERIALS: A cross-sectional cohort study enrolled patients with NPC who were disease-free and ≥4 years after IMRT ± chemotherapy. Physician-reported adverse events (Common Terminology Criteria for Adverse Events, version 4.03) and patient-reported QoL (Functional Assessment of Cancer Therapy-Head and Neck, Functional Assessment of Chronic Illness Therapy-Fatigue), utilities (EuroQOL-5D), head and neck symptoms (MD Anderson Symptom Inventory-Head and Neck), and emotional distress (Hospital Anxiety and Depression Scale) were collected. Consenting patients also underwent endocrine screening and audiometry. RESULTS: Among 107 patients enrolled, median age at enrollment and time since treatment were 57 (32-81) and 7.5 years (4.2-11.1), respectively. Most patients (99%) received 70 Gy in 35 fractions; the majority (93%) received concurrent chemotherapy. Mean scores for the Functional Assessment of Cancer Therapy-Head and Neck, Functional Assessment of Chronic Illness Therapy-Fatigue, and EuroQOL-5D were 105.0 (46-148), 116.6 (44-160), and 0.85 (0.29-1.00), respectively. Dry mouth, mucus, swallowing/chewing, memory, and teeth/gum problems were scored highest on the MD Anderson Symptom Inventory-Head and Neck; mean symptom severity and symptom interference scores were 2.3 and 2.4, respectively. Grade 3 or higher physician-reported adverse events were noted in 50 patients (47%), most frequently hearing problems (46, 43%). Audiometry revealed significant bilateral hearing loss (grade ≥3) in 68 patients (72%). Depression (25%), anxiety (37%), and fatigue (28%) were common and strongly correlated with QoL. Most patients (69%) developed hypothyroidism; 1 patient (1%) developed pituitary dysfunction requiring hormone replacement. V50 >90 and V45 >99 to the thyroid correlated with significantly higher rates of hypothyroidism. CONCLUSIONS: Despite the implementation of IMRT, survivors of NPC still experience many physical symptoms that affect long-term QoL many years after treatment. Depression, anxiety, and fatigue remain common in long-term survivors and are highly correlated with QoL.

High-dose intravenous steroid regimen for radiation-induced hypoglossal nerve palsy.

BACKGROUND: Hypoglossal nerve palsies are infrequent complications of head and neck radiotherapy. Treatments focus on maintaining function and prevention of abnormal airway-related swallowing events. METHODS: A patient with longstanding cranial neuropathies, including bilateral hypoglossal involvement, secondary to chemoradiotherapy for nasopharyngeal carcinoma, experienced repeated episodes of life-threatening complications. Initially, 2 courses of 2 weekly 24-hour intravenous methylprednisolone (IVMP) infusions were administered 2 years apart. We report the results of a third course comprising 5 weekly cycles. RESULTS: Patient-reported outcomes revealed significant improvement in swallowing function, speech, and psychosocial status. Airway invasion during swallowing and pharyngeal retention were assessed videofluoroscopically and evaluated using the Penetration-Aspiration Scale (PAS) and a residue rating scale, respectively. PAS ratings after infusions 2 and 5, improved dramatically from baseline and were maintained at 1-year follow-up. CONCLUSION: High doses of IVMP may improve radiation-induced neuropathies. Further testing in similar patients is needed to prove reproducibility. © 2016 Wiley Periodicals, Inc. Head Neck 39: E23-E28, 2017.

Effect of Intensity Modulated Radiation Therapy With Concurrent Chemotherapy on Survival for Patients With Cervical Esophageal Carcinoma.

PURPOSE: We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). METHODS AND MATERIALS: All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. RESULTS: Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age (P=.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P=.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P=.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P=.061). OS between P1 and P2 did not differ (P=.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P=.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P=.008). CONCLUSIONS: The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.

Outcomes of cutaneous squamous cell carcinoma of the head and neck with parotid metastases.

INTRODUCTION: Cutaneous squamous cell carcinoma of the head and neck (cHNSCC) metastatic to the parotid has a moderate risk of recurrence despite multimodality treatment. Immunosuppression is associated with lower rates of long-term cure. Our aim was to review outcomes of current management in a tertiary centre with a view to targeting future strategies. METHODS: A retrospective review of clinico-pathological data and outcomes for patients with metastatic cHNSCC involving the parotid gland, undergoing radical surgery and adjuvant radiotherapy during 2000-2014 was conducted. The Kaplan-Meier method was used to determine time-to-event outcomes. RESULTS: One hundred and thirty-two patients met the inclusion criteria. Median follow-up was 5.0 years. Five-year overall (OS), cancer-specific (CSS) and progression free survival (PFS) were 44% (95% Confidence Interval (CI) 34-53%), 64% (95% CI 52-74%) and 37% (95% CI 28-47%) respectively. Locoregional control (LRC) was 68% (95% CI 55-77%) at 5 years. Immunosuppressed patients fared worse (compared with immune-competent) with five-year OS, CSS, and PFS of 14% versus 53% (HR = 3.19; 95% CI 1.91-5.34), 40% versus 71% (Hazard Ratio (HR) = 2.92; 95% CI 1.38-6.19) and 10% versus 46% (HR = 2.51; 95% CI 1.52-4.14) respectively. On multivariate analysis, immune status strongly predicted OS (P < 0.001), CSS (P = 0.003), DMFS (P < 0.001) and PFS (P < 0.001), but not LRC. Largest lymph node size was the only significant factor predictive for LRC on multivariate analysis (P = 0.02). CONCLUSIONS: Despite multimodality treatment metastatic cHNSCC involving the parotid shows moderate rates of recurrence. Immunosuppressed patients with this disease have a particularly poor prognosis, demonstrating lower rates of CSS with similar rates of LRC compared to their immunocompetent counterparts.