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Sexuality and sexual intimacy are important aspects of cancer survivorship. In head and neck cancer (HNC), concerns around sexual health, sexuality and sexual intimacy are infrequently raised or addressed in standard HNC consultations, either before embarking on treatment or during survivorship. The changing demographic of HNC patients, largely due to the increasing proportion of patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPVOPSCC), has driven renewed interest in some specific survivorship issues, including sexual behaviours and lifestyles, which may account for both the primary mode of HPV transmission and the younger and less comorbid population affected by this disease. While HNC survivors may have many complex needs in the short and longer term, some patients may prioritise preserving sexual function above other more HNC-specific issues, such as swallowing and xerostomia. Beyond HPVOPSCC, there is evidence to suggest that impairment of sexual health is a pervasive survivorship issue across all HNC cancer types, and this narrative review article highlights publications reporting quantitative assessments of sexual health outcomes in HNC patients. There are also limited studies evaluating whether current sexual health models of care are adequate for HNC patients or whether new or adapted models are needed. Future research will also need to define the impact of our treatments on the sexuality and sexual intimacy concerns of specific HNC cohorts with more granularity to enhance pre- and post-treatment counselling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The primary objectives were to describe the longitudinal course of sexual health in people undergoing curative (chemo)radiation therapy ([C)RT) for human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPVOPSCC) and identify factors associated with higher sexual satisfaction 12 months after (C)RT., Methods and Materials: Eligible participants from 3 sites were recruited to a prospective observational study between October 2020 and November 2021. Measures of sexual health (22-item European Organization for Research and Treatment of Cancer Sexual Health Questionnaire), treatment outcome priorities (Chicago Priorities Scale), quality of life (30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire), symptom burden (MD Anderson Symptom Inventory-Head and Neck), emotional distress (Patient-Reported Outcomes Measurement Information System - Anxiety and Depression), and facial appearance and appearance distress (FACE-Q) were administered before, at the end, and 3 and 12 months after (C)RT., Results: Of 128 eligible participants, 100 were recruited; sexual health measure data were available for 89 of 98 patients alive at 12 months. Mean sexual satisfaction scores were 51.8 (SD = 26.6) before (C)RT. Mixed model results indicated a clinically significant reduction in sexual satisfaction by the end of (-25.4; 95% CI, -30.7 to -20.2) and 3 months after CRT (-12.2; -17.3 to -7.0) but not 12 months after CRT (-3.8; 95% CI, -9.0 to 1.4). Of 13 treatment outcome priorities, "keeping sexual function" had a median rank of 10 and 9 before and 12 months after (C)RT, respectively; 24% and 26% identified it as a top priority at these times. Cohabiting, having a sexual partner, being sexually active, higher global health status, lower sexual health issues, lower depression, and considering sexual function a top priority were associated with higher sexual satisfaction scores 12 months after (C)RT., Conclusions: Although affected acutely by (C)RT, average sexual satisfaction returned to near pretreatment levels after 12 months. Sexual function is considered a top survivorship priority by approximately one-quarter of patients with HPVOPSCC., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To develop consensus on patient characteristics and disease-related factors considered in deciding treatment approaches for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) based on real-world treatment patterns in 4 territories in Asia-Pacific., Methods: A three-round modified Delphi involving a multidisciplinary panel of HN surgeons, medical oncologists, and radiation oncologists was used. Of 41 panelists recruited, responses of 26 from Australia, Japan, Singapore, and Taiwan were analyzed. All panelists had ≥five years' experience managing LA-HNSCC patients and treated ≥15 patients with LA-HNSCC annually., Results: All statements on definitions of LA-HNSCC, treatment intolerance and cisplatin dosing reached consensus. 4 of 7 statements on unresectability, 2 of 4 on adjuvant chemoradiotherapy, 7 of 13 on induction chemotherapy, 1 of 8 on absolute contraindications and 7 of 11 on relative contraindications to high-dose cisplatin did not reach consensus. In all territories except Taiwan, high-dose cisplatin was preferred in definitive and adjuvant settings for patients with no contraindications to cisplatin; weekly cisplatin (40 mg/m 2 ) preferred for patients with relative contraindications to high-dose cisplatin. For Taiwan, the main treatment option was weekly cisplatin. For patients with absolute contraindications to cisplatin, carboplatin ± 5-fluorouracil or radiotherapy alone were preferred alternatives in both definitive and adjuvant settings., Conclusion: This multidisciplinary consensus provides insights into management of LA-HNSCC in Asia-Pacific based on patient- and disease-related factors that guide selection of treatment modality and systemic treatment. Despite strong consensus on use of cisplatin-based regimens, areas of non-consensus showed that variability in practice exists where there is limited evidence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: This secondary analysis of clinical trial TROG 12.01, involving patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma, aimed to identify patient-reported outcome (PRO) trajectories before, during, and after chemoradiotherapy., Methods and Materials: Head and neck cancer symptom severity (HNSS) and interference (HNSI), generic health-related quality of life (HRQL), and emotional distress were assessed with the MD Anderson Symptom Inventory-Head and Neck, Functional Assessment of Cancer Therapy-General, and Hospital Anxiety and Depression Scale questionnaires, respectively. Latent class growth mixture modeling (LCGMM) was used to identify distinct underlying trajectories. Baseline and treatment variables were compared between trajectory groups., Results: The LCGMM identified latent trajectories for all PROs: HNSS, HNSI, HRQL, anxiety, and depression. Four HNSS trajectories (HNSS1-4) were identified, distinguished by differences in HNSS at baseline, during the peak of treatment symptoms, and during early and intermediate recovery. All trajectories were stable beyond 12 months. The reference trajectory (HNSS4, n = 74) score was 0.1 (95% confidence interval [CI], 0.1-0.2) at baseline, peaking at 4.6 (95% CI, 4.2-5.0), with rapid early recovery (1.1; 95% CI, 0.8-2.2) and gradual improvement to 12 months (0.6; 95% CI, 0.5-0.8). Patients in HNSS2 (high baseline, n = 30) reported higher baseline scores (1.4; 95% CI, 0.8-2.0) but were otherwise similar to HNSS4. Patients in HNSS3 (low acute, n = 53) reported reduced acute symptoms (2.5; 95% CI, 2.2-2.9) with stable scores beyond 9 weeks after chemoradiotherapy (1.1; 95% CI, 0.9-1.4). Patients in HNSS1 (slow recovery, n = 25) had slower recovery from an acute peak of 4.9 (95% CI, 4.3-5.6) to 0.9 (95% CI, 0.6-1.3) at 12 months. Age, performance status, education, receipt of cetuximab, and baseline anxiety varied between trajectories. The other PRO models demonstrated clinically relevant trajectories, with distinct associations with baseline factors., Conclusions: LCGMM identified distinct PRO trajectories during and after chemoradiotherapy. These and their associations with variations in the characteristics and treatment factors of patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma provide clinically relevant insights into identifying patients who may require increased support before, during, or after chemoradiotherapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Radiotherapy (RT) continues to play a key role in the management of head and neck cancer (HNC). Xerostomia remains a principal detriment to the quality of life (QoL) for 80 % of surviving patients receiving head and neck radiation. Radiation-induced injury to the salivary glands is dose-dependent, and thus efforts have been focused on decreasing radiation to the salivary glands. Decreased saliva production reduces both short-term and long-term quality of life in head and neck survivors by impacting on taste and contributing to dysphagia. Several radioprotective agents to the salivary gland have been investigated. Although not widely practiced, surgical transfer of the submandibular gland prior to RT is the mainstay of surgical options in preventing xerostomia. This review focuses on the strategies to improve xerostomia following radiation therapy in head and neck cancers., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: High CD103 + intratumoral immune cell (ITIC) abundance is associated with better prognosis in unselected patients with human papilloma virus-associated oropharyngeal squamous cell carcinoma (HPV-associated OPSCC) treated with cisplatin and radiotherapy (CIS/RT). Substituting cetuximab (CETUX) for CIS with RT in HPV-associated OPSCC resulted in inferior efficacy. Our aim was to determine whether quantification of CD103 ITIC could be used to identify a population of HPV-associated OPSCC with superior prognosis., Patients and Methods: We pooled data from the TROG 12.01 and De-ESCALaTE randomized trials that compared CETUX/70GyRT with CIS/70GyRT in low-risk HPV-associated OPSCC: American Joint Committee on Cancer 7 stage III (excluding T1-2N1) or stage IV (excluding N2b-c if smoking history >10 pack-years and/or distant metastases), including all patients with available tumor samples. The primary endpoint was failure-free survival (FFS) in patients receiving CETUX/RT comparing CD103 + ITIC high (≥30%) versus low (<30%). High and low CD103 were compared using Cox regression adjusting for age, stage and trial., Results: Tumor samples were available in 159/182 patients on TROG 12.01 and 145/334 on De-ESCALaTE. CD103 + ITIC abundance was high in 27% of patients. The median follow-up was 3.2 years. The 3-year FFS in patients treated with CETUX/RT was 93% [95% confidence interval (CI) 79% to 98%] in high CD103 and 74% (95% CI 63% to 81%) in low CD103 [adjusted hazard ratio = 0.22 (95% CI 0.12-0.41), P < 0.001]. The 3-year overall survival in patients treated with CETUX/RT was 100% in high CD103 and 86% (95% CI 76% to 92%) in low CD103, P < 0.001. In patients treated with CIS/RT, there was no significant difference in FFS., Conclusions: CD103 + ITIC expression separates CETUX/RT-treated low-risk HPV-associated OPSCC into excellent and poor prognosis subgroups. The high CD103 population is a rational target for de-intensification trials., Competing Interests: Disclosure DR—grants from Merck Sharp & Dohme, grants from Merck KGaA, grants from Bristol-Myers Squibb, grants from GSK, grants from Roche, grants from Regeneron, grants from Kura Oncology, grants from ALX Oncology, trial steering committees and/or advisory boards (all uncompensated)—MSD, GSK, Regeneron, Sanofi; HM—grants from Astra Zeneca, grants from GSK Biologicals, grants from GSK, trial steering committees and/or advisory boards—Astra Zeneca, Merck Sharp and Dohme, Merck KGaA and GSK; JC—grants from Merck KGgA, advisory board Merck KGgA Sandro Porceddu—advisory boards Merck Sharp & Dohme, Merck KGgA, Steering Committee Regeneron; CW—advisory board Merck KGgA; BJS—research grant from Sanofi-Regeneron; advisory boards or consultancies—Bristol-Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Pfizer, Roche/Genentech, Amgen, Lilly, Sanofi, Glaxo-Smith Kline, Takeda and BeiGene; has been compensated for royalties UpToDate. All other authors have declared no conflicts of interest., (Copyright © 2022 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Background: Several reports have suggested that radiotherapy after reconstructive surgery for head and neck cancer (HNC), could have deleterious effects on the flaps with respect to functional outcomes. To predict and prevent toxicities, flap delineation should be accurate and reproducible. The objective of the present study was to evaluate the interobserver variability of frequent types of flaps used in HNC, based on the recent GORTEC atlas. Materials and methods: Each member of an international working group (WG) consisting of 14 experts delineated the flaps on a CT set from six patients. Each patient had one of the five most commonly used flaps in HNC: a regional pedicled pectoralis major myocutaneous flap, a local pedicled rotational soft tissue facial artery musculo-mucosal (FAMM) (2 patients), a fasciocutaneous radial forearm free flap, a soft tissue anterolateral thigh (ALT) free flap, or a fibular free flap. The WG's contours were compared to a reference contour, validated by a surgeon and a radiologist specializing in HNC. Contours were considered as reproducible if the median Dice Similarity Coefficient (DSC) was > 0.7. Results: The median volumes of the six flaps delineated by the WG were close to the reference contour value, with approximately 50 cc for the pectoral, fibula, and ALT flaps, 20 cc for the radial forearm, and up to 10 cc for the FAMM. The volumetric ratio was thus close to the optimal value of 100% for all flaps. The median DSC obtained by the WG compared to the reference for the pectoralis flap, the FAMM, the radial forearm flap, ALT flap, and the fibular flap were 0.82, 0.40, 0.76, 0.81, and 0.76, respectively. Conclusions: This study showed that the delineation of four main flaps used for HNC was reproducible. The delineation of the FAMM, however, requires close cooperation between radiologist, surgeon and radiation oncologist because of the poor visibility of this flap on CT and its small size.

Within the global head and neck cancer population, there are subgroups of patients with poorer cancer outcomes independent from tumor characteristics. In this article, we review three such groups. The first group comprises patients with nasopharyngeal cancer in low- and middle-income countries where access to high-volume, well-resourced radiotherapy centers is limited. We discuss a recent study that is aiming to improve outcomes through the instigation of a comprehensive radiotherapy quality assurance program. The second group comprises patients with low socioeconomic status in a high-income country who experience substantial financial toxicity, defined as financial hardship for patients due to health care costs. We review causes and consequences of financial toxicity and discuss how it can be mitigated. The third group comprises older patients who may poorly tolerate and not benefit from intensive standard-of-care treatment. We discuss the role of geriatric assessment, particularly in relation to the use of chemotherapy. Through better recognition and understanding of disadvantaged groups within the global head and neck cancer population, we will be better placed to instigate the necessary changes to improve outcomes and quality of life for patients with head and neck cancer.

Purpose: The excellent prognosis of patients with low-risk human papillomavirus (HPV)- associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiation therapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an epidermal growth factor receptor targeting antibody, when combined with radiation therapy would result in a decrease in symptom burden and toxicity with similar efficacy compared with weekly cisplatin., Methods and Materials: TROG12.01, a randomized, multicenter trial involving 15 sites in Australia and New Zealand enrolled patients with HPV-associated oropharyngeal squamous cell carcinoma, American Joint Committee on Cancer 7th edition stage III (excluding T1-2N1) or stage IV (excluding T4 and/or N3 and/or N2b-c if smoking history >10 pack years and/or distant metastases). Patients were randomized (1:1) to receive radiation therapy (70 Gy in 35 fractions) with either weekly cisplatin, 7 doses of 40 mg/m 2 , or cetuximab, loading dose of 400 mg/m 2 followed by 7 weekly doses of 250 mg/m 2 . The primary outcome was symptom severity assessed by the MD Anderson Symptom Inventory Head and Neck Symptom Severity Scale from baseline to 13 weeks postcompletion of radiation therapy using the area under the curve. Trial was registered on ClinicalTrials.gov: NCT01855451., Results: Between June 17, 2013, and June 7, 2018, 189 patients were enrolled, with 92 in cisplatin arm and 90 in cetuximab included in the main analysis. There was no difference in the primary endpoint of symptom severity; difference in area under the curve cetuximab-cisplatin was 0.05 (95% confidence interval [CI], -0.19, 0.30), P = .66. The T-score (mean number of ≥grade 3 acute adverse events) was 4.35 (standard deviation 2.48) in the cisplatin arm and 3.82 (standard deviation 1.8) in the cetuximab arm, P = .108. The 3-year failure-free survival rates were 93% (95% CI, 86%-97%) in the cisplatin arm and 80% (95% CI, 70%-87%) in the cetuximab arm (hazard ratio = 3.0 [95% CI, 1.2-7.7]); P = .015., Conclusions: For patients with low-risk HPV-associated oropharyngeal cancer, radiation therapy and cetuximab had inferior failure-free survival without improvement in symptom burden or toxicity compared with radiation therapy and weekly cisplatin. Radiation therapy and cisplatin remain the standard of care., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cancers of the head and neck region often present with nodal involvement. There is a long-standing convention within the community of head and neck radiation oncology to irradiate both sides of the neck electively in almost all cases to include both macroscopic and microscopic disease extension (so called elective nodal volume). International guidelines for the selection and delineation of the elective lymph nodes were published in the early 2000s and were updated recently. However, diagnostic imaging techniques have improved the accuracy and reliability of nodal staging and as a result, small metastases that used to remain undetected and were thus in the past included in the elective nodal volume, will now be included in high-dose volumes. Furthermore, the elective nodal areas are situated close to the parotid glands, the submandibular glands and the swallowing muscles. Therefore, irradiation of a smaller, more selected volume of the elective nodes could reduce treatment-related toxicity. Several researchers consider the current bilateral elective neck irradiation strategies an overtreatment and show growing interest in a unilateral nodal irradiation in selected patients. The aim of this article is to give an overview of the current evidence about the indications and benefits of unilateral nodal irradiation and the use of SPECT/CT-guided nodal irradiation in squamous cell carcinomas of the head and neck., (© 2021 Wiley Periodicals LLC.)

Introduction: As a result of the increased use of radiotherapy (RT) and improved long-term overall survival of patients with cancers of the head and neck (HN), the frequency of radiation-induced sarcomas of the head and neck (RISHN) may be increasing. The main objective of this systematic review was to determine the existing evidence on the frequency, treatment, and outcome of RISHN., Methods: Using PRISMA guidelines we conducted a systematic review of the literature published from 2000 to 2020., Results: Our review includes data of 560 patients from 64 articles. The total frequency of RISHNs among the reviewed series was 0.15%. The most frequent location of the primary tumor treated by RT was the nasopharynx. The mean RT dose used was 62 Gy, mean latency interval between irradiation and occurrence of RISHN was 11.1 years, and the most common RISHN location was the sinonasal region. Osteosarcoma was the principal histology, followed by fibrosarcoma. Surgery was the most frequently applied treatment modality. Of all patients with RISHN, 40.7% died of this disease after a mean interval of 13.9 months., Conclusions: Notwithstanding the increased use of RT, the number of reported RISHNs has not increased substantially during the past two decades. Surgery with wide margins forms the best therapeutic option for these cases, but the outcome remains poor.

Purpose: Because of the unprecedented disruption of health care services caused by the COVID-19 pandemic, the American Society of Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) identified an urgent need to issue practice recommendations for radiation oncologists treating head and neck cancer (HNC) in a time of limited resources and heightened risk for patients and staff., Methods and Materials: A panel of international experts from ASTRO, ESTRO, and select Asia-Pacific countries completed a modified rapid Delphi process. Topics and questions were presented to the group, and subsequent questions were developed from iterative feedback. Each survey was open online for 24 hours, and successive rounds started within 24 hours of the previous round. The chosen cutoffs for strong agreement (≥80%) and agreement (≥66%) were extrapolated from the RAND methodology. Two pandemic scenarios, early (risk mitigation) and late (severely reduced radiation therapy resources), were evaluated. The panel developed treatment recommendations for 5 HNC cases., Results: In total, 29 of 31 of those invited (94%) accepted, and after a replacement 30 of 30 completed all 3 surveys (100% response rate). There was agreement or strong agreement across a number of practice areas, including treatment prioritization, whether to delay initiation or interrupt radiation therapy for intercurrent SARS-CoV-2 infection, approaches to treatment (radiation dose-fractionation schedules and use of chemotherapy in each pandemic scenario), management of surgical cases in event of operating room closures, and recommended adjustments to outpatient clinic appointments and supportive care., Conclusions: This urgent practice recommendation was issued in the knowledge of the very difficult circumstances in which our patients find themselves at present, navigating strained health care systems functioning with limited resources and at heightened risk to their health during the COVID-19 pandemic. The aim of this consensus statement is to ensure high-quality HNC treatments continue, to save lives and for symptomatic benefit., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Appropriate selection of head and neck squamous cell cancer (HNSCC) patients for curative treatment is difficult, and it is a very understudied issue. The aim of this study was to review the outcomes of curative intent treatment in non-p16 positive HNSCC patients assessed as having borderline curability., Methods: A single institution retrospective review of the clinical outcomes of non-p16 positive HNSCC patients with borderline curability. Predefined criteria for borderline curability were as follows: (i) T4 and/or N3 disease; or (ii) ECOG status ≥2; or (iii) age ≥75 years., Results: A total of 114 patients were identified. A total of 56 had N3/T4, 32 were >ECOG 2 and 57 were >75 years. A total of 29 had two or more borderline curability criteria. Progression-free survival rate (PFS) at 1 and 2 years was 72% (95% confidence interval (CI), 63-79) and 53% (95% CI, 43-62), respectively. Overall survival (OS) at 1 and 2 years was 76% (95% CI, 67-83) and 61% (95% CI, 51-69), respectively. On multivariable analysis, the only independent prognostic factor for OS was the adult comorbidity evaluation-27 (ACE-27) grade (HR 1.4; 95% CI, 1.1-1.8; P = 0.018)., Conclusions: Patients with borderline curability criteria treated with curative intent achieved good PFS and OS. ACE-27 was an important prognostic factor in this population., (© 2020 The Royal Australian and New Zealand College of Radiologists.)

Purpose: Treatment package time (TPT) prolongation is associated with lower overall survival and locoregional control in mucosal head and neck squamous cell carcinoma (SCC), but there are few reports in cutaneous HNSCC (cHNSCC). We sought to test the effect of TPT in a cohort of patients with cHNSCC., Methods: This is a single institution retrospective study of node-positive cHNSCC patients involving either the parotid or cervical nodes treated with curative intent surgery with macroscopic tumor clearance followed by standard fractionation postoperative radiation therapy (PORT) from 2001 to 2014. We assessed the effect of TPT and other prognostic variables on overall survival (OS), cHNSCC specific survival (CSS) progression free survival (PFS), and freedom from locoregional failure (FFLRF)., Results: In the present study, 152 patients met the inclusion criteria. The 5-year OS, CSS, PFS, and FFLRF were 62% (95% confidence interval [CI], 54-71), 78% (95% CI, 71-87), 54% (95% CI, 46-64), and 76% (95% CI ,68-85), respectively. In a multivariable model, TPT ≥14 weeks was associated with worse outcomes in all endpoints (OS [hazard ratio (HR) 4.93; 95% CI, 2.54-9.56, P < .001], CSS [HR 6.09; 95% CI, 2.33-15.92; P = .001], PFS [HR 4.29; 95% CI, 2.21-8.34; P < .001], and FFLRF [HR 4.63; 95% CI, 1.71-12.51; P = .007]). Immunosuppression and the presence of ≥2 pathologically involved lymph nodes were also significant adverse factors for both OS and FFLRF, although extracapsular extension was also associated with lower FFRLF. Delays to commencing PORT rather than treatment breaks accounted for the majority of cases with prolonged TPT., Conclusions: Prolongation of TPT to 14 weeks or longer may confer a lower probability of locoregional control and survival in patients with lymph node-positive cHNSCC treated with surgery and PORT. Timely referral and commencement of PORT is necessary to maximize long-term disease outcomes., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Head and Neck Cancer (HNC) radiation oncologists (ROs) enjoy the immense pleasure of curing patients, working within a large multidisciplinary team to effectively deliver curative intent treatment whilst also aiming to minimise late treatment toxicity. Secondary analyses of large-scale HNC clinical trials have shown the critical impact of the quality of radiotherapy plans, where protocol non-compliant plans have yielded inferior survival rates approximating 20%. The peer review process in routine day-to-day HNC practice shows that even in major academic centers a significant proportion of RT plans may require changes to the radiotherapy planning volume. Optimising the therapeutic ratio in HNC has been dramatically facilitated by intensity modulated radiotherapy (IMRT), but that technology has also increased the complexity of HNC radiotherapy treatment and high-volume centers with experienced clinicians may be best placed to deliver this most accurately. International consensus guidelines to standardise or benchmark best practice with respect to the RT-QA process in HNC are needed. The aim of this paper is to highlight the importance of the RT-QA process in the HNC treatment process and to make some recommendations for its inclusion in both clinical trials and routine clinical practice., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Objectives/hypothesis: The outcomes of unilateral radiotherapy treatment for patients with p16/HPV-positive squamous cell carcinomas of unknown primary (SCCUP) affecting cervical lymph nodes are under-reported. Compared to radiating large volumes of the pharyngeal axis (the more common approach), this is potentially a much less toxic treatment for a good prognosis group., Study Design: Retrospective cohort study., Methods: We identified patients with SCCUP who were treated radically at our center and did not have parotid or isolated level IV or V nodal involvement. Failure-free and overall survivals were calculated using Kaplan-Meier methods., Results: From 2004 to 2012, there were 49 radically treated patients with SCCUP. Fourteen patients had bilateral neck treatment (they had bilateral nodal disease or suspected lesions in the base of tongue, though not proven with biopsy), two had surgery alone, whereas 33 had unilateral radiotherapy (after neck dissection, excisional biopsy, or definitively with concurrent chemotherapy). Of the 33 patients, 21 tested positive to p16/HPV and had median follow-up of 57 months. In this group, no isolated contralateral neck failures or putative primaries emerged. There was 1/21 (4.3%) ipsilateral neck failure, 1/21 (4.3%) concurrent contralateral neck and distant failure, and 1/21 (4.3%) patient with distant failure. The 5-year freedom from failure was 78% (95% confidence interval [CI]: 56%-100%) and overall survival was 90% (95% CI: 79%-100%)., Conclusions: With no emergence of putative primaries and no isolated contralateral neck failures, this single-institution experience in p16/HPV-positive SCCUP patients suggests that unilateral radiotherapy may be an underutilized management strategy., Levels of Evidence: 4 Laryngoscope, 128:2076-2083, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Radiotherapy (RT) is used to treat approximately 80% of patients with cancer of the head and neck. Despite enormous advances in RT planning and delivery, a significant number of patients will experience radiation-associated toxicities, especially those treated with concurrent systemic agents. Many effective management options are available for acute RT-associated toxicities, but treatment options are much more limited and of variable benefit among patients who develop late sequelae after RT. The adverse impact of developing late tissue damage in irradiated patients may range from bothersome symptoms that negatively affect their quality of life to severe life-threatening complications. In the region of the head and neck, among the most problematic late effects are impaired function of the salivary glands and swallowing apparatus. Other tissues and structures in the region may be at risk, depending mainly on the location of the irradiated tumor relative to the mandible and hearing apparatus. Here, we review the available evidence on the use of different therapeutic strategies to alleviate common late sequelae of RT in head and neck cancer patients, with a focus on the critical assessment of the treatment options for xerostomia, dysphagia, mandibular osteoradionecrosis, trismus, and hearing loss., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To report on the outcomes of a novel treatment regimen for patients with locally advanced head and neck squamous cell carcinoma who were fit for curative treatment but not fit for cisplatin., Methods and Materials: Single-arm phase 1/2 study of previously untreated patients with biopsy-proven SCC of the oropharynx, larynx, or hypopharynx. The primary endpoint was feasibility of the regimen, defined as the proportion of patients successfully completing treatment. Secondary endpoints were locoregional control (LRC), failure-free survival (FFS), overall survival (OS), and treatment toxicities., Results: Sixty patients were included in the study. Their mean age was 66 years (range, 42-87 years); 28% of patients were >70 years. The median follow-up time was 4 years. Compliance with treatment was very high: feasibility was 55/60 (91.7%, 90% CI: 83.3%-96.7%), which satisfied the predefined criteria. The 4-year LRC was 82% (95% CI: 71-94), the FFS was 72% (95% CI: 60-85), and the OS was 77% (95% CI: 66-90). The cumulative incidences of first failure of any type at 4 years were 5.2% local, 1.8% local and distant, 8.5% regional, 1.7% regional and distant, 3.5% distant, and 7.7% death (any cause). The 4-year FFS in the patients aged ≤70 years and >70 years were 71% (95% CI: 58-88) and 73% (95% CI: 54-100), respectively (log-rank P=.801). Their 4-year OS was 79% (95% CI: 66-93) and 73% (95% CI: 53-100), respectively (log-rank P=.708). Significant late treatment toxicities were very few., Conclusion: This treatment regimen was feasible and safe in this patient cohort unfit for cisplatin, 28% of whom were older than 70 years. Carboplatin-based and cetuximab-based chemoradiation regimens warrant further investigation in patients with a contraindication to cisplatin., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The primary endpoint was to ascertain whether the percentage of major changes implemented from our routine intensity modulated radiation therapy (IMRT) quality assurance (QA) process was more than 10%. The secondary endpoints were to document the percentage of minor changes, ascertain the time taken to perform the IMRT QA process, evaluate potential predictors for major changes, and ascertain the perceived value of the program by the compliance of radiation oncologists (ROs) treating head and neck cancer (HNC)., Methods and Materials: This was a retrospective analysis of a prospective database for all radically treated HNC patients. Recommended changes were predefined with criteria as either "major changes" or "minor changes.", Results: Of 595 patients treated radically between May 21, 2012, and May 21, 2014, 548 patients were entered, giving a compliance of 92.1%. The vast majority were treated with IMRT (470/548, 89%), 49.3% treated definitively and 50.7% treated adjuvantly; overall, 63% had stage IV disease. Eighty-one patients (14.8%) had 1 or more major changes recommended and implemented, and 21 patients (3.8%) had major changes recommended but not implemented because of a lack of consensus. Of minor recommendations, in 115 patients (21%) they were implemented and in 13 patients (2.4%) they were not implemented. No changes were recommended in the remaining 324 patients (59.1%). The only factor correlating with the likelihood of a major change was treatment with IMRT (P=.001). In the vast majority of cases (85%), the time taken for IMRT QA was less than 20 minutes., Conclusions: Our routine HNC IMRT QA program resulted in the implementation of a significant number of major changes. The high compliance with the program is indicative of the belief in its clinical value. This study can inform discussion on optimal RT QA processes in routine clinical practice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The minority of head and neck cutaneous squamous cell carcinomas (SCC) metastasize to regional lymph nodes. The purpose of this study was to describe the clinical outcomes and prognostic factors for patients with node-positive head and neck cutaneous SCC who underwent lymphadenectomy., Methods: We conducted a retrospective single center study using the Kaplan-Meier method for the investigation of the overall survival (OS) and locoregional control rates. The Cox proportional hazards model was evaluated to identify prognostic factors., Results: The median number of positive lymph nodes from 149 lymphadenectomies was 2 in the neck and 1 in the parotid gland. The 5-year OS and locoregional control rates were 50% and 77%, respectively. OS was worse among older patients (hazard ratio [HR], 1.04; p = .015), immunosuppressed patients (HR, 2.06; p = .034), and patients with a high total lymph node ratio (calculated from the number of positive lymph nodes divided by the total number of nodes; multivariate analysis [MVA]; HR, 1.13; p = .019)., Conclusion: Low total lymph node ratio is associated with improved outcomes in node-positive head and neck cutaneous SCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 772-778, 2017., (© 2017 Wiley Periodicals, Inc.)

People with head and neck cancer (HNC) experience elevated symptom toxicity and co-morbidity as a result of treatment, which is associated with poorer psychosocial and quality-of-life (QoL) outcomes. This Phase I study examined whether an individualised mindfulness-based stress reduction (IMBSR) programme could be successfully used with HNC patients undergoing curative treatment. Primary aims were to explore feasibility, compliance, acceptability and fidelity. Secondary aims were to determine whether (1) participation in the intervention was associated with changes in post-intervention mindfulness and (2) post-intervention mindfulness was associated with post-intervention distress and QoL. Nineteen HNC patients participated in a seven-session IMBSR programme with pre- and post-test outcome measures of psychological distress, depression, anxiety and QoL. Primary aims were assessed by therapists or participants. Mindfulness, distress and QoL were assessed using self-report questionnaires at pre- and post-intervention. Longer time spent meditating daily was associated with higher post-intervention mindfulness. After controlling for pre-intervention mindfulness, there was an association between higher post-intervention mindfulness and lower psychological distress and higher total, social and emotional QoL. This study offers important preliminary evidence than an IMBSR intervention can be administered to HNC patients during active cancer treatment. A randomised controlled trial is warranted to confirm these findings., (© 2016 John Wiley & Sons Ltd.)

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., (© 2016 The Royal Australian and New Zealand College of Radiologists.)

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., (© 2016 American Cancer Society.)

Background: This prospective study evaluated long-term swallowing outcomes and associated risk factors 5 years postchemoradiotherapy for head and neck cancer., Methods: Following an earlier study of 69 patients, 39 patients had patient-reported activity and quality of life (QOL) data collected. Twenty-one patients also underwent a videofluoroscopy swallowing study (VFSS)., Results: Between 6 months and 5 years posttreatment, patient-reported activity for solid foods significantly improved (p < .001), returning to pretreatment levels for 74% of patients. On VFSS, swallowing function for semisolids declined, with 5 patients demonstrating a clinically significant deterioration. Factors that predicted poorer long-term swallowing were the same as at 6 months, with the addition of older age and disease stage., Conclusion: Although long-term patient-reported activity improves and swallowing-related QOL is high, up to 24% of patients may demonstrate a clinically significant deterioration in swallowing function at 5 years posttreatment. This divergence suggests a degree of adaptation that patients develop, which warrants further investigation. © 2015 Wiley Periodicals, Inc. Head Neck 38: E307-E315, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Prognostic information can rationalise clinical follow-up after radical cancer treatment. This retrospective cohort study of radical head and neck (chemo)radiotherapy patients examines the clinical safety and cost implications of stratifying follow-up intensity by post-treatment (18)FDG-PET-CT response., Methods: In 2008 clinical review after radical head and neck radiotherapy was reduced from 3- to 6-monthly for patients with complete (18)FDG-PET-CT response at 3months. 184 patients treated after this change ("PET Stratified", 2009-11) were compared to 178 patients treated before ("Standard", 2005-7). Clinical safety was assessed by the time to detection of recurrence, overall survival and potential for radical treatment of recurrence. A hospital cost analysis was performed using individual patient data., Results: 127 of 178 Standard and 148 of 184 PET Stratified patients achieved complete response on post-treatment imaging. Baseline clinical characteristics were comparable. Median follow-up from response assessment was 4.8years in the Standard cohort and 2.1years for PET Stratified. PET Stratified patients had a mean 4.4 outpatient visits in 2years, compared to 7.0 among Standard patients. Over 90% of patients remained free of recurrence at 2years in both cohorts. Time to detection of recurrence was similar between two cohorts (HR1.05, 95%CI 0.45-2.52), as was overall survival (HR0.91, 95%CI 0.36-2.29). The proportion of radically treatable recurrences was also similar (42% Standard vs. 47% PET Stratified). The hospital cost savings per patient from reduced review were AUD$2606 over 2years, AUD$5012 over five., Conclusion: (18)FDG-PET-CT to stratify follow-up intensity after radical radiotherapy for head and neck cancer reduces costs with no apparent clinical detriment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Human papillomavirus (HPV) infection is a powerful prognostic biomarker in a subset of head and neck squamous cell carcinomas, specifically oropharyngeal cancers. However, the role of HPV in non-oropharyngeal sites, such as the larynx, remains unconfirmed., Methods: We evaluated a cohort of 324 laryngeal squamous cell carcinoma (LSCC) patients for the expression of p16(INK4A) (p16) protein by immunohistochemistry (IHC) and for high-risk HPV E6 and E7 mRNA transcripts by RNA in situ hybridisation (ISH). p16 expression and HPV status were correlated with clinicopathological features and outcomes., Results: Of 307 patients assessable for p16 IHC, 20 (6.5%) were p16 positive. Females and node-positive patients were more likely to be p16 positive (P<0.05). There were no other significant clinical or demographic differences between p16-positive and -negative cases. There was no difference in overall survival (OS) between p16-positive and -negative patients with 2-year survival of 79% in each group (HR=0.83, 95% CI 0.36-1.89, P=0.65). There was no statistically significant difference in failure-free survival (FFS) with 2-year FFS of 79% and 66% for p16-positive and -negative patients, respectively (HR=0.60, 95% CI 0.26-1.36, P=0.22). Only seven cases were found to be HPV RNA ISH positive, all of which were p16 IHC positive. There was no statistically significant difference in OS between patients with HPV RNA ISH-positive tumours compared with -negative tumours with 2-year survival of 86% and 71%, respectively (HR=0.76, 95% CI 0.23-2.5, P=0.65). The 2-year FFS was 86% and 59%, respectively (HR=0.62, 95% CI 0.19-2.03, P=0.43)., Conclusions: p16 overexpression is infrequent in LSCC and the proportion of cases with high-risk HPV transcripts is even lower. There are no statistically significant correlations between p16 IHC or HPV RNA ISH status and OS or disease outcomes.

Background: Local and/or regional recurrence and metachronous primary tumor arising in a previously irradiated area are rather frequent events in patients with head and neck squamous cell carcinoma (HNSCC). Re-treatment is associated with an increased risk of serious toxicity and impaired quality of life (QOL) with an uncertain survival advantage., Methods: We analyzed the literature on the efficacy and toxicity of photon/electron-based external beam reirradiation for previously irradiated patients with HNSCC of non-nasopharyngeal origin. Studies were grouped according to the radiotherapy technique used for reirradiation. Patient selection criteria, target volume identification method, tumor dose, fractionation schedule, systemic therapy administration, and toxicities were reviewed., Results: In addition to disease-related factors, current comorbidities and preexisting organ dysfunction must be considered when selecting patients for reirradiation. As morbidity from re-treatment may be considerable and differ depending on which mode of re-treatment is used, it is important to give patients information on potential morbidity outcomes so that an informed choice can be made within a shared decision-making context. With improved dose distribution and adequate imaging support, including positron emission tomography-CT, modern radiotherapy techniques may improve local control and reduce toxicity of reirradiation. A reirradiation dose of ≥60 Gy and a volume encompassing the gross tumor with up to a 5-mm margin are recommended. Concomitant administration of systemic therapeutics and reirradiation is likely to be of similar benefit as observed in large randomized studies of upfront therapy., Conclusion: Reirradiation, administered either with or without concurrent systemic therapy, is feasible and tolerable in properly selected patients with recurrent or a new primary tumor in a previously irradiated area of the head and neck, offering a meaningful survival (in the range of 10% to 30% at 2 years). Whenever feasible, salvage surgery is the method of choice for curative intent; patients at high-risk for local recurrence should be advised that postoperative reirradiation is expected to increase locoregional control at the expense of higher toxicity and without survival advantage compared to salvage surgery without reirradiation. © 2014 Wiley Periodicals, Inc. Head Neck 37: 134-150, 2015., (© 2014 Wiley Periodicals, Inc.)

Background: The impact of primary tumor volume (pTV) on local control after definitive radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) is unclear., Methods: Pertinent literature was reviewed to address the impact of pTV on local control after definitive RT for HNSCC., Results: Reproducibility of pTV calculations is probably influenced by interobserver variability and may be reduced by relying on experienced observers. The impact of pTV on local control after definitive RT is probably influenced by primary site. A relatively limited impact of pTV on local control after RT for oropharyngeal squamous cell carcinomas (SCCs) might be attributable to human papillomavirus (HPV) positivity., Conclusion: pTV may be a useful parameter to select patients for treatment with definitive RT, particularly for those with laryngeal SCCs. Patients with high-volume primary cancers, in which the probability of local control with a functional larynx is low, are likely better treated with surgery., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: The primary purpose of this study was to review the efficacy of unilateral treatment of lateralized tonsil primaries, in particular whether laterality of the primary is a more powerful determinant of contralateral neck failure than advanced ipsilateral nodal classification., Methods: A retrospective study of all patients with tonsillar cancer treated with curative intent between January 1990 and December 2002 was performed., Results: There were 167 patients, 76% men, median age 58 years, 86% current or ex-smokers. The majority of patients (58%) had stage IV disease. Five-year local, nodal, locoregional, and distant failure rates were 14%, 4%, 18%, and 8%, respectively. Of the 58 patients treated unilaterally, 33% had N2a, N2b, or N3 nodal disease. There were no contralateral nodal failures in the unilaterally treated group., Conclusion: These results support the potential use of unilateral radiation therapy (RT) for lateralized tonsil primaries even with advanced ipsilateral nodal disease., (Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.)

Background: Swallowing dysfunction following chemoradiation for head and neck cancer is a major cause of morbidity and reduced quality of life. This review discusses 3 strategies that may improve posttreatment swallowing function., Methods: The literature was assessed by a multiauthor team that produced evidence-based recommendations., Results: (1) Prospective and randomized studies with small cohorts show a trend toward benefits for a preventative exercise program addressing oral and pharyngeal structures. (2) Prospective and retrospective data indicate that better swallowing outcomes are likely when nasogastric tubes are used in preference to gastrostomy tubes to supplement enteral nutrition during chemoradiation. (3) Emerging prospective data with mature results on small cohorts support the hypothesis that radiation dose restriction to swallowing structures using intensity-modulated radiation therapy techniques leads to better swallow outcomes., Conclusions: This study discusses 3 strategies for improving swallow-related outcomes in patients undergoing chemoradiation for head and neck cancer and identifies areas for future research., (Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.)

Introduction: We investigated the relationship between hypoxia, human papillomavirus (HPV) status and outcome in head and neck squamous cell carcinoma., Methods: Patients with stage III and IV head and neck squamous cell carcinoma treated on phase I and II chemoradiation trials with 70-Gy radiation combined with tirapazamine/cisplatin or cisplatin/fluorouracil (5FU), hypoxic imaging using [18F]-misonidazole positron emission tomography and known HPV status (by p16 immunohistochemistry) were included in this sub-study. Separate analyses were conducted to consider the impact of tirapazamine on HPV-negative tumours in the phase II trial., Results: Both p16-positive oropharyngeal tumours and p16-negative head and neck squamous cell carcinoma tumours had a high prevalence of tumour hypoxia; 14/19 (74%) and 35/44 (80%), respectively. The distribution of hypoxia (primary, nodal) was similar. On phase II, trial patients with p16-negative hypoxic tumours had worse loco-regional control with cisplatin and 5FU compared with tirapazamine and cisplatin (P < 0.001) and worse failure-free survival (hazard ratio = 5.18; 95% confidence interval, 1.98-13.55; P = 0.001). Only 1 out of 14 p16-positive patients on the phase II trial experienced loco-regional failure., Conclusion: Hypoxia, as assessed by [18F]-misonidazole positron emission tomography, is frequently present in both p16-positive and negative head and neck cancer. Further research is required to determine whether hypoxic imaging can be used to predict benefit from hypoxia-targeting therapies in patients with p16-negative tumours., (© 2014 The Royal Australian and New Zealand College of Radiologists.)

Purpose: Cutaneous squamous cell carcinoma (cSCC) behaves aggressively in patients with chronic lymphocytic leukemia (CLL). Lymphadenopathy due to CLL can obscure the clinical and radiological assessment of nodal involvement by cSCC. This study aimed to evaluate whether functional imaging with positron emission tomography (PET)/computed tomography (CT) may clarify the clinical picture., Methods: Five consecutive patients with cSCC and CLL who had a PET/CT scan for the purposes of cSCC staging between July 2000 and July 2010 were analyzed. PET/CT findings were compared to histopathology from subsequent neck dissection., Results: PET/CT can distinguish nodal cSCC from leukemic infiltration with high specificity, allowing prompt appropriate management of nodal disease., Conclusions: PET/CT is a promising modality for nodal staging in patients with cSCC and CLL, with the potential to improve outcomes in this poor prognosis group. Larger confirmatory studies are needed., (© 2013.)

Adequate resection margins are critical to the treatment decisions and prognosis of patients with head and neck squamous cell carcinoma (HNSCC). However, there are numerous controversies regarding reporting and interpretation of the status of resection margins. Fundamental issues relating to the basic definition of margin adequacy, uniform reporting standards for margins, optimal method of specimen dissection, and the role of intraoperative frozen section evaluation, all require further clarification and standardization. Future horizons for margin surveillance offer the possible use of novel methods such as "molecular margins" and contact microscopic endoscopy, However, the limitations of these approaches need to be understood. The goal of this review was to evaluate these issues to define a more rational, standardized approach for achieving resection margin adequacy for patients with HNSCC undergoing curative resection., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Health literacy is the capacity to seek, understand and utilise health information to make informed health decisions. Suboptimal health literacy has been linked to poor health outcomes. This study assessed health literacy in patients treated for head and neck or lung cancer and associations between health literacy and demographic factors and distress levels., Methods: Consecutive English-speaking patients were approached at Peter MacCallum Cancer Centre. Face-to-face interviews were conducted. Health literacy was assessed using the Shortened Test of Functional Health Literacy in Adults (S-TOFHLA) and Health Literacy Management Scale (HeLMS). Distress was assessed by the Distress Thermometer., Results: Response rate was 73 % (n = 93). Using S-TOFHLA, prevalence of inadequate and marginal health literacy was 5.4 and 6.5 % respectively, and both groups were associated with older age (p = 0.043) and low education level (p = 0.009). Specific assessment of S-TOFHLA revealed that 70 % could not interpret prescription labels. HeLMS reported that 17 % had health literacy difficulties. Low scores on domains of HeLMS were associated with lower education level (p < 0.05) but younger age (p < 0.05). Distress was not associated with S-TOFHLA scores but related to low scores in two domains of HeLMS (p < 0.05)., Conclusion: Using two different measures, a substantial proportion of patients have poor health literacy abilities and may experience difficulties in accessing health services.

Objective: The aim of the study was to assess symptoms of depression and anxiety in patients with head and neck cancer up to 18 months after radiotherapy., Methods: Prospective observational study of consecutive head and neck outpatients was conducted at a tertiary cancer centre (n = 101). Eligibility included diagnosis of cancer in the head and neck region, where the patient agreed to radiotherapy with curative intent. Data were collected before commencement of radiotherapy and 3 weeks and 18 months after completion. Symptoms of depression and anxiety were assessed by the Hospital Anxiety and Depression Scale. Tumour/treatment-related physical symptoms were assessed using the 'Additional Concerns' subscale of the Functional Assessment of Chronic Illness Therapy for Head and Neck Cancer., Results: The prevalence of identified probable cases of depression was 15% at baseline, increasing to 29% 3 weeks post-treatment, falling to 8% at 18-month follow-up. The number of probable cases of anxiety was 20% at baseline, 17% at 3 weeks post-treatment and 22% at 18-month follow-up. Depression scores significantly increased from baseline to 3 weeks post-treatment and decreased at 18-month follow-up. Variability in depression scores was accounted for by tumour/treatment-related physical symptoms. Anxiety scores significantly decreased between baseline and 3-week post-treatment and increased at 18-month follow-up. Younger age and more tumour/treatment-related physical symptoms predicted anxiety scores., Conclusions: The rates of depression in head and neck cancer patients increase following cancer treatment and are related to tumour/treatment-related physical symptoms. Anxiety levels are higher pre-treatment, lower immediately following cancer treatment but rise to near pre-treatment levels more than a year after completion of cancer treatment., (Copyright © 2012 John Wiley & Sons, Ltd.)

Although uncommon, cancer of an unknown primary (CUP) metastatic to cervical lymph nodes poses a range of dilemmas relating to optimal treatment. The ideal resolution would be a properly designed prospective randomized trial, but it is unlikely that this will ever be conducted in this group of patients. Accordingly, knowledge gained from retrospective studies and experience from treating patients with known head and neck primary tumors form the basis of therapeutic strategies in CUP. This review provides a critical appraisal of various treatment approaches described in the literature. Emerging treatment options for CUP with metastases to cervical lymph nodes are discussed in view of recent innovations in the field of head and neck oncology and suitable therapeutic strategies for particular clinical scenarios are presented. For pN1 or cN1 disease without extracapsular extension (ECE), selective neck dissection or radiotherapy offer high rates of regional control. For more advanced neck disease, intensive combined treatment is required, either a combination of neck dissection and radiotherapy, or initial (chemo)radiotherapy followed by neck dissection if a complete response is not recorded on imaging. Each of these approaches seems to be equally effective. Use of extensive bilateral neck/mucosal irradiation must be weighed against toxicity, availability of close follow-up with elective neck imaging and guided fine-needle aspiration biopsy (FNAB) when appropriate, the human papillomavirus (HPV) status of the tumor, and particularly against the distribution pattern (oropharynx in the majority of cases) and the emergence rate of hidden primary lesions (<10% after comprehensive workup). The addition of systemic agents is expected to yield similar improvement in outcome as has been observed for known head and neck primary tumors., (Copyright © 2011 Wiley Periodicals, Inc.)

In an era of advanced diagnostics, metastasis to cervical lymph nodes from an occult primary tumor is a rare clinical entity and accounts for approximately 3% of head and neck malignancies. Histologically, two thirds of cases are squamous cell carcinomas (SCCs), with other tissue types less common in the neck. With modern imaging and tissue examinations, a primary tumor initially undetected on physical examination is revealed in >50% of patients and the site of the index primary can be predicted with a high level of probability. In the present review, the range and limitations of diagnostic procedures are summarized and the optimal diagnostic workup is proposed. Initial preferred diagnostic procedures are a fine-needle aspiration biopsy (FNAB) and imaging. This allows directed surgical biopsy (such as tonsillectomy), based on the preliminary findings, and prevents misinterpretation of postsurgical images. When no primary lesion is suggested after imaging and panendoscopy, and for patients without a history of smoking and alcohol abuse, molecular profiling of an FNAB sample for human papillomavirus (HPV) and/or Epstein-Barr virus (EBV) is important., (Copyright © 2011 Wiley Periodicals, Inc.)

Perineural invasion (PNI) occurs in 2% to 6% of cutaneous head and neck basal and squamous cell carcinomas (SCCs) and is associated with mid-face location, recurrent tumors, high histologic grade, and increasing tumor size. Patients may be asymptomatic with PNI appreciated on pathologic examination of the surgical specimen (microscopic), or may present with cranial nerve (CN) deficits (clinical). The V and VII CNs are most commonly involved. Magnetic resonance imaging (MRI) may be obtained to detect and define the extent of PNI; computed tomography (CT) or ultrasound-guided fine needle aspiration cytology (UGFNAC) may assist with detecting or excluding regional lymph node metastases. Patients with apparently resectable cancers undergo surgery, usually followed by postoperative radiotherapy (RT). Patients with unresectable cancers are treated with definitive RT. Moreover, RT may be considered if significant functional or cosmetic impairment is expected after surgical treatment. The 5-year outcomes after treatment for clinically unsuspected microscopic compared with clinical PNI are: local control, 80% and 55%; cause-specific survival, 75% and 65%; and overall survival, 55% and 50%, respectively. The incidence of grade ≥ 3 complications is higher after treatment for clinical PNI versus microscopic PNI; approximately 35% compared with 15%, respectively. Proton beam RT may be used to reduce the risk of late complications by reducing RT dose to the visual apparatus and central nervous system (CNS)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: Malnutrition is prevalent in head and neck cancer patients and is associated with poorer outcomes and increased health care costs. This study aimed to evaluate the acceptability, organisational efficiency and clinical outcomes of a dietitian-led head and neck cancer clinic., Methods: Two consecutive, independent, patient cohorts were studied with a pre-post-test design of 98 patients prior to the introduction of a dietitian-led clinic (DLC) and the subsequent 100 patients who attended the newly formulated DLC. The two groups were compared for frequency of dietitian intervention, weight loss, enteral feeding, hospital admissions and post-treatment medical follow-up requirements., Results: Nutritional management in a DLC was associated with reduced nutrition-related admissions from 12% to 4.5% (p = 0.0029), unplanned nasogastric tube insertions from 75% to 39% (p = 0.02), improved transition to oral diet post-radiotherapy from 68.3% to 76.7% (p = 0.10) and reduced radiation oncologist review at 2 weeks post-radiotherapy from 32% to 15% patients (p = 0.009) compared to the cohort prior to the DLC., Conclusions: A dietitian-led head and neck cancer clinic is associated with improved efficiency and nutritional management of head and neck cancer patients and offers a feasible model of care.

Concurrent chemotherapy and radiotherapy (CRT) has become standard treatment for many patients with advanced head and neck squamous cell carcinoma (HNSCC). This has led to controversy concerning the role of neck dissection (ND) in this setting. The current debate is focused on N2-N3 disease and the ability of a clinical complete response to predict the absence of viable cells in the ND specimen. Proponents of a systematic planned ND argue that it improves regional control and possibly disease-specific survival. They assert that a clinical response does not predict the pathologic response, and that in the event of recurrence in the neck, a surgical salvage procedure is unlikely to succeed. Conversely, there are many arguments in favor of performing ND only for patients who have evidence of residual neck disease because of the very low probability of isolated neck recurrence following a complete response. Proponents argue that for complete responders, planned ND is associated with no survival benefit. As planned surgery will only benefit patients with residual disease in the neck alone, there is a high rate of unnecessary ND with its associated morbidity. Another question concerns the appropriate type of ND to be performed. Even if required after chemoradiation, selective ND is oncologically feasible with minimal morbidity. Lastly, robust data from a randomized trial demonstrating the superiority of one approach vs. the other are lacking. After conducting a review of recent literature on the subject, the authors conclude that planned ND is not necessary for patients with complete response because of the availability of improved diagnostic follow up modalities, and the increased sensitivity to CRT of HNSCC, particularly HPV associated tumors., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The established and emerging roles of FDG positron-emission tomography/computed tomography (PET/CT) in the evaluation of squamous cell carcinoma of head and neck region is reviewed with a strong clinical focus on recommended applications and methodologies. In the staging of newly diagnosed disease, detection of cervical nodal involvement is the major indication but exclusion of distant metastases and of synchronous primary malignancy is also a valuable adjunct. Use in radiotherapy planning is advantageous for locally-advanced disease. Although there are few data yet to assess the use of FDG PET/CT to assess response during therapy, there is good evidence that this technique can accurately assess the post-treatment neck to identify those who might benefit from salvage therapy and those in whom observation or palliative treatment might be more appropriate. Although more expensive than other imaging modalities used for assessing this disease, the superior diagnostic accuracy and impact of incremental information provided by this technology has been shown to be cost-effective in several clinical scenarios.

Background: Human papilloma virus (HPV) infection is a powerful prognostic biomarker in head and neck squamous cell carcinoma (HNSCC). Increased epidermal growth factor receptor (EGFR) gene copy number and protein expression have been reported to be negative predictors of outcome. This study examined the relationship between HPV status, EGFR gene copy number, EGFR protein expression, and clinical outcome in HNSCC patients treated with chemoradiation., Methods: HPV status was determined using p16(INK4A) immunohistochemistry (IHC), EGFR gene copy number was evaluated with FISH, and EGFR protein expression by IHC in 212 subjects., Results: EGFR FISH was positive in 41 of 204 (20%) patients and was negatively correlated with failure-free survival (FFS; HR = 1.84, P = 0.027) and overall survival (OS; HR = 1.78, P = 0.082). For p16(INK4A), 85 of 200 (42.5%) patients were found to be p16 positive, including 75 of 131 (57%) with oropharyngeal cancer. Patients with p16-positive oropharyngeal cancer had significantly improved FFS (HR = 0.28, P < 0.001) and OS (HR = 0.31, P = 0.002). Only 2 of 126 (1.6%) oropharyngeal cancer patients were found to be p16+/EGFR FISH+. EGFR IHC was positive in 81 of 93 (87%) of patients and was associated with poorer FFS (HR = 1.98, P = 0.35) and OS (HR = 2.52, P = 0.22)., Conclusions: Increased EGFR gene copy number is largely restricted to p16(INK4A)-negative oropharyngeal cancer. Although p16(INK4A) and EGFR FISH are both predictive of outcome in univariate analyses, only p16(INK4A) remains independently predictive., Impact: Knowledge of HPV and EGFR status can have implications for treatment options and prognosis in HNSCC.

Objective: To assess symptoms of depression and anxiety in patients with head and neck cancers (HNCs) before and after radiotherapy., Design, Participants and Setting: Prospective observational study of 102 outpatients with HNCs at a tertiary cancer centre in Melbourne between 1 May 2008 and 30 May 2009. Eligibility criteria were a first-time diagnosis of HNC, age over 17 years, and agreement to undergo cancer treatment involving radiotherapy with curative intent. Data were collected before commencement of radiotherapy and again 3 weeks after completing treatment., Main Outcome Measures: Symptoms of depression and anxiety as assessed by the Hospital Anxiety and Depression Scale (HADS); physical and psychosocial aspects of quality of life as assessed by the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N)., Results: Seventy-five participants completed pretreatment and posttreatment questionnaires. Mean depression scores increased significantly from before to after treatment, while anxiety scores decreased significantly over the same period. The prevalence of mild to severe depression was 15% before treatment and 31% after treatment. The prevalence of mild to severe symptoms of anxiety was 30% before treatment, reducing to 17% after treatment. Posttreatment depression was predicted by pretreatment depression and receiving chemotherapy. Posttreatment anxiety was predicted by pretreatment anxiety and male sex., Conclusions: These findings suggest that rates of depression in patients with HNCs increase after cancer treatment, with a third of patients experiencing clinically significant symptoms of depression after radiotherapy.

Background: This prospective study evaluated the impact of patient demographics, tumor characteristics, and radiotherapy treatment on swallowing before and after radiotherapy or chemoradiotherapy., Methods: Eighty-one patients with head and neck cancer were examined using videofluoroscopy swallowing studies (VFSS) before treatment and again at 3 and 6 months after treatment., Results: Swallowing was best at baseline, significantly worse 3 months posttreatment, and improved by 6 months posttreatment. Worse swallowing was associated with: living in rural areas; ex-heavy alcohol consumption; hypopharyngeal tumor site; large (particularly T4) tumors; nonconformal radiotherapy; bilateral radiation to the pharynx; and longer radiotherapy fields. Through the use of multiple regression analysis, previous swallowing was determined to be the most common predictor of swallowing outcomes, followed by T classification, alcohol history, and radiotherapy technique., Conclusions: The pretreatment and treatment factors that influenced swallowing in this cohort should be considered when planning treatment, in discussing potential side effects with patients, and when developing and testing future treatment techniques.