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Background: Squamous cell carcinoma of the nasal vestibule (SCCNV) is a rare disease, distinctly different in presentation, treatment, and outcome from squamous cell carcinoma (SCC) of the nasal cavity and paranasal sinuses. However, these are often not analyzed separately. Methods: The Netherlands Cancer Registry (NCR) and pathology reports from the Dutch Nationwide Pathology Databank (PALGA) were used to identify all newly diagnosed SCCNV cases in the Netherlands between 2008 and 2021. Results: A total of 763 patients were included. The yearly incidence rate displayed a significant downward trend with an annual percentage change (APC) of −3.9%. The 5‐year overall survival (OS) and disease‐free survival were 69.0% and 77.2%, respectively. The 5‐year relative survival was 77.9% and improved slightly over the inclusion period. OS for patients who were staged cT3 appeared to be worse than those staged cT4a, calling the applicability of the TNM‐classification into question. Conclusion: SCC of the nasal vestibule is rare, with declining incidence rates. Introducing a specific topography code for SCCNV is recommended to enhance registration accuracy. The TNM classification seems poorly applicable to SCCNV, suggesting the need to explore alternative staging methods. [ABSTRACT FROM AUTHOR]

The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional recurrence is a common cause of treatment failure, and few patients are suitable for salvage surgery. Reirradiation with conventional radiation techniques is challenging due to normal tissue tolerance limits and the risk of significant toxicities. Stereotactic body radiotherapy (SBRT) has emerged as a highly conformal modality that offers the potential for cure while limiting the dose to surrounding tissue. There is also growing research that shows that those with oligometastatic disease can benefit from curative intent local ablative therapies such as SBRT. This review will look at published evidence regarding the use of SBRT in locoregional recurrent and oligometastatic HNCs. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic body radiotherapy (SBRT) is a highly precise, non-invasive, and image-guided form of hypofractionated radiotherapy aimed at well-defined small targets. It is characterized by superior conformity of dose distribution, steep dose drop-off gradients, and short overall treatment time, which allow effective protection of surrounding normal tissue from high radiation doses, potentially resulting in lower toxicity and a more potent biological effect. Currently, SBRT is an established curative therapy for certain cancers and some benign tumors, as well as a valuable palliative option. There is limited experience with SBRT for de novo mucosal carcinoma of the head and neck. A systematic review of the literature and subsequent analysis of 124 patients from five studies treated between 2012 and 2020 confirmed that SBRT is an effective and relatively safe treatment for small tumor targets in de novo mucosal carcinoma of the head and neck. Standardization of SBRT practice and well-designed prospective clinical trials are highly needed. Stereotactic body radiotherapy (SBRT) is characterized by a high dose per fraction, well-defined small targets, superior dose conformity, and a steep off-target dose gradient. A literature search was conducted to examine the experience with SBRT as a curative treatment for newly diagnosed mucosal carcinoma of the head and neck (MCHN). Four retrospective case series and one prospective phase I clinical trial published between 2012 and 2020 described 124 patients. SBRT was mainly performed in older patients with different tumor sites. The median size of the planning target volumes ranged from 5.3 to 41 cm3. Different approaches were used to create margins. In two studies, limited elective nodal irradiation was performed. The equivalent doses used were 60–83.33 Gy delivered in five fractions. Considerable heterogeneity was observed in the radiation dose specification. The incidence of grade ≥3 late toxicity was 0–8.3%, with local and regional control ranging from 73% to 100%. Improved or stable quality of life after SBRT was reported in two studies. Curative-intent SBRT for de novo MCHN appears to be an effective and relatively safe treatment for small tumor targets, preferably without concomitant elective tissue irradiation. Standardization of SBRT practice and well-designed prospective clinical trials are needed to better define the role of SBRT in this setting. [ABSTRACT FROM AUTHOR]

Simple Summary: All patients suspected of having head and neck paragangliomas (HNPGLs) undergo magnetic resonance imaging (MRI) or computed tomography (CT) of the head and neck area as the standard imaging according to the Dutch guidelines. However, a relatively new imaging modality, [68Ga]Ga-DOTATOC PET/CT, has shown promising results in the detection of HNPGLs. In this pilot study, we aimed to compare the results of this new modality with the standard imaging. We compared both techniques in 25 patients at the University Medical Center Utrecht, The Netherlands. Twenty-eight percent of the patients had different outcomes between both modalities. In all cases, additional HNPGLs were identified using the [68Ga]Ga-DOTATOC PET/CT, suggesting the need for further prospective research to validate this finding. If confirmed, this modality could potentially be implemented as the standard of care for HNPGL detection in germline variant carriers. The Dutch guideline for patients suspected of head and neck paragangliomas (HNPGLs) recommends magnetic resonance imaging (MRI) and/or computed tomography (CT) of the head and neck area. Additionally, it suggests considering additional nuclear imaging. The aim of this study was to evaluate the outcomes of [68Ga]Ga-DOTATOC PET/CT compared to MRI in patients with suspected HNPGLs and carriers of genetic variations. Methods: In this single-center pilot study, retrospective data were obtained from consecutive patients between 2016 and 2023. Both MRI and [68Ga]Ga-DOTATOC PET/CT were performed within 12 months. The primary outcome was the location of HNPGLs. Results: A total of 25 consecutive patients were included, and 7 patients (28.0%, p = 0.5) showed differences between the imaging modalities, of whom 5 patients had unexpected localizations with additional uptake by somatostatin receptors (SSTR) on the [68Ga]Ga-DOTATOC PET/CT. Conclusions: The authors recommend performing baseline imaging with [68Ga]Ga-DOTATOC PET/CT (if available) in variant carriers and using MRI/CT for follow-up according to the regional protocol, thereby shifting the gold standard for baseline imaging from MRI/CT to [68Ga]Ga-DOTATOC PET/CT. [ABSTRACT FROM AUTHOR]

(1) Background: Chemoradiotherapy (CRT) for head and neck cancer (HNC) is associated with severe toxicity resulting in fatigue and weight loss, including loss of skeletal muscle mass. Exercise interventions might positively affect physical fitness and quality of life. Sufficient adherence and compliance rates are necessary for optimal effects. This study aimed to gain insight into expectations and experiences and factors influencing adherence, retention and compliance of HNC patients participating in exercise intervention during CRT. (2) Methods: Consecutive participants were invited for semi-structured interviews, conducted pre- and post-intervention. A deductive approach was used to identify themes and factors influencing adherence, retention and compliance. (3) Results: Thematic saturation was reached after interviewing 14 patients pre-intervention. Five themes were identified: planning and time management, treatment toxicity, motivation to exercise, exercise intervention and supervision by a physiotherapist. The intensity of the treatment schedule and treatment toxicity were important barriers. Facilitators mentioned were physical and emotional benefits, social support as well as the simplicity and home-based setting of the intervention. (4) Conclusions: A personalised approach, considering the individual facilitators and barriers of HNC patients, is important to increase adherence, retention and compliance to exercise intervention and to reap the optimal effects of the program. [ABSTRACT FROM AUTHOR]

Simple Summary: Nasal vestibule cancer is considered to be a rare form of cancer. There are several different staging systems in place for categorizing these tumors, which can result in inconsistencies and unreliable data due to variations in registration. The "Rome" classification is the most recent addition. This study aimed to assess the effectiveness of this new staging system and to compare it to the UICC/AJCC system. One hundred and forty-nine patients with a squamous cell carcinoma of the nasal vestibule were included. There was a significant association between an increased disease stage as staged per the Rome classification and decreased survival. This association persisted when correcting for various covariates (i.e., age at the time of diagnosis, sex, the presence of lymph node metastases, and treatment modality) in multivariable analysis. The Rome classification appears to be capable of adequately categorizing and stratifying patients for different outcome measures. Nevertheless, additional research with a larger number of patients is required before any definitive conclusions can be drawn. Squamous cell carcinoma of the nasal vestibule is considered a rare malignancy that differs from other sinonasal malignancies in many respects. Four staging systems currently exist for this disease, the most recent addition being the "Rome" classification. This study assesses the use of this new classification and its prognostic value regarding various outcome measures. A retrospective multicenter cohort study of patients with a primary squamous cell carcinoma of the nasal vestibule who were treated in three tertiary head and neck oncology referral centers was conducted. A total of 149 patients were included. The median follow-up duration was 27 months. Five-year locoregional control (LRC), disease-specific survival (DSS), and overall survival (OS) were 81.6%, 90.1, and 62.5% respectively. A statistically significant association was observed between the Rome classification and all survival outcomes in both univariable and multivariable analyses. Moreover, it appeared to perform better than the Union for International Cancer Control TNM classification for tumors of the nasal cavity and paranasal sinuses. The new Rome classification can be used effectively and is associated with LRC, DSS, and OS. However, it requires further validation in a larger (prospective) study population. [ABSTRACT FROM AUTHOR]

Objective: To investigate utilization of mental healthcare among head and neck cancer (HNC) patients from diagnosis to 2 years after treatment, in relation to psychological symptoms, mental disorders, need for mental healthcare, and sociodemographic, clinical and personal factors. Methods: Netherlands Quality of life and Biomedical Cohort study data as measured before treatment, at 3 and 6 months, and at 1 and 2 years after treatment was used (n = 610). Data on mental healthcare utilization (iMCQ), psychological symptoms (Hospital Anxiety and Depression Scale, Cancer Worry Scale), mental disorders (CIDI interview), need for mental healthcare (Supportive Care Needs Survey Short‐Form 34, either as continuous outcome indicating the level of need or dichotomized into unmet need (yes/no)) and several sociodemographic, clinical and personal factors were collected. Factors associated with mental healthcare utilization were investigated using generalized estimating equations (p < 0.05). Results: Of all HNC patients, 5%–9% used mental healthcare per timepoint. This was 4%–14% in patients with mild‐severe psychological symptoms, 4%–17% in patients with severe psychological symptoms, 15%–35% in patients with a mental disorder and 5%–16% in patients with an unmet need for mental healthcare. Among all patients, higher symptoms of anxiety, a higher need for mental healthcare, lower age, higher disease stage, lower self‐efficacy and higher social support seeking were significantly associated with mental healthcare utilization. Conclusion: Mental health care utilization among HNC patients is limited, and is related to psychological symptoms, need for mental healthcare, and sociodemographic, clinical and personal factors. [ABSTRACT FROM AUTHOR]

Chemoradiotherapy with cisplatin in a triweekly regimen of 100 mg/m2 body surface area, is used to treat locally advanced head and neck squamous cell carcinoma (HNSCC) with curative intent. Cisplatin dose limiting toxicity (CDLT) occurs often and impedes obtaining the planned cumulative cisplatin dose. A cumulative cisplatin dose of 200 mg/m2 or more is warranted for better survival and locoregional control. Patients with a low skeletal muscle mass (SMM) have a three-fold higher risk of developing CDLT than patients with a normal SMM. SMM can be assessed through measurements on routinely performed diagnostic head and neck CT- or MRI-scans. A weekly regimen of 40 mg/m2 body surface area cisplatin is proposed as a less toxic schedule, which possibly decreases the risk of developing CDLT and enables reaching a higher cumulative cisplatin dose. The aim of this multicenter randomized clinical trial (NL76533.041.21, registered in the Netherlands Trial Register) is to identify whether a regimen of weekly cisplatin increases compliance to the planned chemotherapy scheme in HNSCC patients with low SMM. The primary outcome is the difference in compliance rate, defined as absence of CDLT, between low SMM patients receiving either the weekly or triweekly regimen. Secondary outcomes consist of toxicities, the cumulative cisplatin dose, time to recurrence, incidence of recurrence at two years of follow-up, location of recurrence, 2-year overall, disease free and disease specific survival, quality of life, patient's experiences, and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Simple Summary: Many head and neck cancer patients report sexual problems. A deterioration in sexuality and sexual dysfunction from baseline to 3 months after treatment was observed especially in patients treated with chemoradiation. This effect seems to differ between men and women. Men reported change in erectile function, orgasm, satisfaction with intercourse, and overall satisfaction, while women reported change in desire, arousal, and orgasm. These findings are helpful to improve information on sexuality and sexual care in head and neck cancer patients. The aim of this study was to investigate changes in sexuality and sexual dysfunction in head and neck cancer (HNC) patients in the first two years after treatment, in relation to the type of treatment. Data were used of 588 HNC patients participating in the prospective NETherlands Quality of life and Biomedical Cohort Study (NET-QUBIC) from diagnosis to 3, 6, 12 and 24 months after treatment. Primary outcome measures were the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI). The total scores of the IIEF and FSFI were dichotomized into sexual (dys)function. In men, type of treatment was significantly associated with change in erectile function, orgasm, satisfaction with intercourse, and overall satisfaction. In women, type of treatment was significantly associated with change in desire, arousal, and orgasm. There were significant differences between treatment groups in change in dysfunctional sexuality. A deterioration in sexuality and sexual dysfunction from baseline to 3 months after treatment was observed especially in patients treated with chemoradiation. Changes in sexuality and sexual dysfunction in HNC patients were related to treatment, with an acute negative effect of chemoradiation. This effect on the various domains of sexuality seems to differ between men and women. [ABSTRACT FROM AUTHOR]

Simple Summary: Skin cancer, particularly non-melanoma skin cancer, is the most common malignancy in the world. There are both common and uncommon types that receive treatment every day. Despite their commonality, the management of each is not perfectly defined in the scientific literature. Many require surgical removal, but the management of regional metastasis (such as lymph nodes in the neck) may or may not require surgical removal, or even anything beyond observation. Further complicating matters, some may have microscopic regional metastases that cannot be detected with a physical exam or imaging. This article seeks to summarize the current literature on this topic and to offer specific insight on how to manage non-melanoma skin cancer that has migrated away from the primary site to the regional lymph nodes. Non-melanoma skin cancer (NMSC) represents the most common malignancy in the world, comprising exceedingly common lesions such as basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) and rare lesions such as Merkel cell carcinoma. Risk factors are widely recognized and include ultraviolet (UV) light exposure, radiation exposure, immunosuppression, and many others. As a whole, survival and functional outcomes are favorable, but each histopathological subtype of NMSC behaves differently. Treatment regimens for the primary site usually include wide surgical excision and neck dissection in cases of clinically involved metastatic lymph nodes. The elective management of draining nodal basins, however, is a contested topic. Nearly all subtypes, excluding BCC, have a significant risk of lymphatic metastases, and have been studied with regard to sentinel lymph node biopsy (SLNB) and elective neck dissection. To date, no studies have definitively established a true single standard of care, as exists for melanoma, for any of the NMSCs. As a result, the authors have sought to summarize the current literature and identify indications and management options for the management of the cervical lymphatics for each major subtype of NMSC. Further research remains critically necessary in order to develop complete treatment algorithms. [ABSTRACT FROM AUTHOR]

Background: The management of cT3 laryngeal cancers remains controversial, with studies recommending surgical or non-surgical approaches. Despite the many papers that have been published on the subject, there is a lack of studies showing which treatment has better results in terms of survival. Objective: To determine the difference in survival outcomes following total laryngectomy (TL), concurrent chemoradiation (CRT) or radiation therapy (RT) alone in T3 laryngeal cancers. Methods: Search of PubMed, Scopus, and Google Scholar databases from 1995 to 2023 employing specific keywords and Boolean operators to retrieve relevant articles. Statistical analysis was conducted using a random-effects model, and heterogeneity was evaluated using the Q-test and I2 statistic. Funnel plot asymmetry was assessed using rank correlation and regression tests. Results: The qualitative data synthesis comprised 10,940 patients from 16 included studies. TL was performed in 2149 (19.4%), CRT in 6723 (61.5%), RT in 295 (2.7%), while non-surgical treatment was not specified in 1773 (16.2%) patients. The pooled 2-year overall survival (OS) rates were TL = 73%, CRT = 74.7%, RT = 57.9%, 3-year OS rates were TL = 64.3%, CRT = 62.9%, RT = 52.4%, and 5-year OS rates were TL = 54.2%, CRT = 52.7%, RT = 40.8%. There was a significant heterogeneity in the included studies. There was no statistically significant difference in 2-year OS (logOR= −0.88 (95% confidence interval (CI): −1.99 to 0.23), p = 0.12), 3-year OS (logOR = −0.6 (95% CI: −1.34 to 0.15), p = 0.11), and 5-year OS (logOR = −0.54 (95% CI: −1.29 to 0.21), p = 0.16) between TL and CRT. Instead, there was significant difference in 2-year OS (logOR= −1.2383 (95% CI: −2.1679 to −0.3087), p = 0.009), 3-year OS (−1.1262 (95% CI: −1.6166 to −0.6358), p < 0.001), and 5-year OS (−0.99 (95% CI: −1.44 to −0.53)), p < 0.001) between TL and RT alone. Conclusions and Significance: TL followed with adjuvant (chemo)radiation on indication and CRT with salvage surgery in reserve appear to have similar OS outcomes. Both resulted in better OS outcomes compared to RT alone in the treatment of T3 laryngeal cancers. If patients are unfit for chemotherapy, making CRT impossible, surgery may become the choice of treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: In head and neck cancer, there are several treatment options. When surgical treatment is chosen, removal of the entire tumor is necessary for optimal therapy of the patient. This, however, is challenging in vulnerable areas of the body such as the mouth and throat, as a more radical resection leads to more severe functional limitations after surgery. Several imaging techniques facilitate the distinction of tumor versus adjacent healthy tissue during the operation, which can help the surgeon remove the entire tumor with optimal functional outcomes. In this paper, we aim to provide an overview of these imaging techniques applicable to oropharyngeal squamous cell carcinoma and discuss the possibilities for optimizing the surgical outcome of patients. Inadequate resection margins in head and neck squamous cell carcinoma surgery necessitate adjuvant therapies such as re-resection and radiotherapy with or without chemotherapy and imply increasing morbidity and worse prognosis. On the other hand, taking larger margins by extending the resection also leads to avoidable increased morbidity. Oropharyngeal squamous cell carcinomas (OPSCCs) are often difficult to access; resections are limited by anatomy and functionality and thus carry an increased risk for close or positive margins. Therefore, there is a need to improve intraoperative assessment of resection margins. Several intraoperative techniques are available, but these often lead to prolonged operative time and are only suitable for a subgroup of patients. In recent years, new diagnostic tools have been the subject of investigation. This study reviews the available literature on intraoperative techniques to improve resection margins for OPSCCs. A literature search was performed in Embase, PubMed, and Cochrane. Narrow band imaging (NBI), high-resolution microendoscopic imaging, confocal laser endomicroscopy, frozen section analysis (FSA), ultrasound (US), computed tomography scan (CT), (auto) fluorescence imaging (FI), and augmented reality (AR) have all been used for OPSCC. NBI, FSA, and US are most commonly used and increase the rate of negative margins. Other techniques will become available in the future, of which fluorescence imaging has high potential for use with OPSCC. [ABSTRACT FROM AUTHOR]

Objective: Chemoradiotherapy (CRT) for head and neck cancer (HNC) is associated with high toxicity that adversely affects physical functioning, body composition, fatigue, quality of life and treatment outcomes. Exercise interventions during treatment might counteract these negative effects. We therefore assessed the feasibility of an exercise programme for HNC patients during CRT. Methods: Forty patients were offered a tailored 10‐week endurance and resistance training with supervised and home‐based sessions. Feasibility endpoints were (1) adherence (main outcome): ≥60% attendance; (2) recruitment: ≥30%; (3) retention rate: ≥85% and (4) compliance rate: ≥60%. Physical performance, muscle strength, body composition, quality of life and fatigue were assessed pre‐ and post‐intervention. Results: Overall adherence was 54%. The recruitment rate was 36%, and the retention rate was 65%. Compliance to the supervised intervention protocol was 66%. Statistically significant decreases were found in mean grip strength, fat‐free mass and clinically relevant deteriorations on several domains of quality of life, and fatigue subscales were found. Conclusion: We conclude that this exercise programme for HNC patients during CRT in its current form is feasible for only a minority of patients. We suggest adaptations to improve adherence and retention rates for a definitive multicentre trial. Trial registration: This study is registered at the Netherlands Trial Register (NTR7305), 6 June 2018, retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle mass (SMM) and chronic inflammation are associated with postoperative complications and survival. Methods: Patients with head and neck cancer (HNC) undergoing microvascular free flap reconstruction were included. SMM and neutrophil‐to‐lymphocyte ratio (NLR) were measured and their association with treatment outcomes analyzed. Results: Five hundred and fifty‐four patients were included. Predictors for complications were elevated NLR in all flaps (OR 1.5), low SMM in radial forearm flap (OR 2.0), and elevated NLR combined with low SMM in fibula flap surgery (OR 4.3). Patients with solely elevated NLR were at risk for flap‐related complications (OR 3.0), severe complications (OR 2.2), and when combined with low SMM for increased length of hospital stays (LOS) (+3.9 days). In early‐stage HNC, low SMM (HR 2.3), and combined elevated NLR with low SMM (HR 2.6) were prognostics for decreased overall survival. Conclusions: SMM and NLR are predictive for poor outcomes in patients with HNC undergoing microvascular reconstruction. [ABSTRACT FROM AUTHOR]

Purpose: Evidence suggests that patients' skeletal muscle mass (SMM) can predict the patients at risk for cisplatin dose-limiting toxicities (DLT). Cisplatin is currently dosed on body surface area (BSA). The predictive value of SMM for cisplatin DLT in patients with locally advanced head and neck cancer (LA-HNC) is investigated. Methods: Patients with LA-HNC treated with cisplatin-based chemoradiotherapy (CRT) were included. SMM was measured using pre-treatment scans. Logistic regression analysis was performed to identify the predictive impact of low SMM for DLT. Results: In total, 343 patients were included of which 199 patients (58.0%) had low SMM and 154 patients (44.9%) experienced cisplatin DLT. In multivariate analysis, low SMM at diagnosis was the only predictive factor for DLT (HR 1.8, 95% CI 1.1–2.9). Conclusions: Low SMM was associated with an increased risk of DLT. Trials are needed to investigate cisplatin dosing with consideration of SMM rather than solely BSA. [ABSTRACT FROM AUTHOR]

Background: FDG-PET/CT has a high negative predictive value to detect residual nodal disease in patients with locally advanced squamous cell head and neck cancer after completing concurrent chemoradiotherapy (CCRT). However, the positive predictive value remains suboptimal due to inflammation after radiotherapy, generating unnecessary further investigations and possibly even surgery. We report the results of a preplanned secondary end point of the ECLYPS study regarding the potential advantages of dual time point FDG-PET/CT imaging (DTPI) in this setting. Standardized dedicated head and neck FDG-PET/CT images were obtained 12 weeks after CCRT at 60 and 120 min after tracer administration. We performed a semiquantitative assessment of lymph nodes, and the retention index (RI) was explored to optimize diagnostic performance. The reference standard was histology, negative FDG-PET/CT at 1 year, or > 2 years of clinical follow-up. The time-dependent area under the receiver operator characteristics (AUROC) curves was calculated. Results: In total, 102 subjects were eligible for analysis. SUV values increased in malignant nodes (median SUV1 = 2.6 vs. SUV2 = 2.7; P = 0.04) but not in benign nodes (median SUV1 = 1.8 vs. SUV2 = 1.7; P = 0.28). In benign nodes, RI was negative although highly variable (median RI = − 2.6; IQR 21.2), while in malignant nodes RI was positive (median RI = 12.3; IQR 37.2) and significantly higher (P = 0.018) compared to benign nodes. A combined threshold (SUV1 ≥ 2.2 + RI ≥ 3%) significantly reduced the amount of false-positive cases by 53% (P = 0.02) resulting in an increased specificity (90.8% vs. 80.5%) and PPV (52.9% vs. 37.0%), while sensitivity (60.0% vs. 66.7%) and NPV remained comparably high (92.9% vs. 93.3%). However, AUROC, as overall measure of benefit in diagnostic accuracy, did not significantly improve (P = 0.62). In HPV-related disease (n = 32), there was no significant difference between SUV1, SUV2, and RI in malignant and benign nodes, yet this subgroup was small. Conclusions: DTPI did not improve the overall diagnostic accuracy of FDG-PET/CT to detect residual disease 12 weeks after chemoradiation. Due to differences in tracer kinetics between malignant and benign nodes, DTPI improved the specificity, but at the expense of a loss in sensitivity, albeit minimal. Since false negatives at the 12 weeks PET/CT are mainly due to minimal residual disease, DTPI is not able to significantly improve sensitivity, but repeat scanning at a later time (e.g. after 12 months) could possibly solve this problem. Further study is required in HPV-associated disease. [ABSTRACT FROM AUTHOR]

In head and neck cancer (HNC) there is a need for more personalized treatment based on risk assessment for treatment related adverse events (i.e. toxicities and complications), expected survival and quality of life. Sarcopenia, defined as a condition characterized by loss of skeletal muscle mass and function, can predict adverse outcomes in HNC patients. A review of the literature on the measurement of sarcopenia in head and neck cancer patients and its association with frailty was performed. Skeletal muscle mass (SMM) measurement only is often used to determine if sarcopenia is present or not. SMM is most often assessed by measuring skeletal muscle cross-sectional area on CT or MRI at the level of the third lumbar vertebra. As abdominal scans are not always available in HNC patients, measurement of SMM at the third cervical vertebra has been developed and is frequently used. Frailty is often defined as an age-related cumulative decline across multiple physiologic systems, with impaired homeostatic reserve and a reduced capacity of the organism to withstand stress, leading to increased risk of adverse health outcomes. There is no international standard measure of frailty and there are multiple measures of frailty. Both sarcopenia and frailty can predict adverse outcomes and can be used to identify vulnerable patients, select treatment options, adjust treatments, improve patient counselling, improve preoperative nutritional status and anticipate early on complications, length of hospital stay and discharge. Depending on the definitions used for sarcopenia and frailty, there is more or less overlap between both conditions. However, it has yet to be determined if sarcopenia and frailty can be used interchangeably or that they have additional value and should be used in combination to optimize individualized treatment in HNC patients. [ABSTRACT FROM AUTHOR]

Keywords: Head and neck squamous cell carcinoma; distant metastases; metastasis directed therapy; oligometastases; metastasectomy; stereotactic body radiation therapy EN Head and neck squamous cell carcinoma distant metastases metastasis directed therapy oligometastases metastasectomy stereotactic body radiation therapy 1 3 3 02/01/23 20230101 NES 230101 Despite improvements in locoregional control due to developments in surgery, radiation therapy and systemic therapy, little improvement has been achieved in terms of survival rates for head and neck squamous cell carcinoma (HNSCC). Head and neck squamous cell carcinoma, distant metastases, metastasis directed therapy, metastasectomy, oligometastases, stereotactic body radiation therapy • This study showed that metastasis-directed stereotactic body radiation therapy in head and neck cancer patients with oligometastasis is safe 11 Schulz D, Wirth M, Piontek G, et al. Therefore, SBRT is a good option for metastases directed therapy in HNSCC patients. [Extracted from the article]

Introduction: Nasopharyngeal carcinoma (NPC) is endemic to Eastern and South-Eastern Asia, and, in 2020, 77% of global cases were diagnosed in these regions. Apart from its distinct epidemiology, the natural behavior, treatment, and prognosis are different from other head and neck cancers. With the growing trend of artificial intelligence (AI), especially deep learning (DL), in head and neck cancer care, we sought to explore the unique clinical application and implementation direction of AI in the management of NPC. Methods: The search protocol was performed to collect publications using AI, machine learning (ML) and DL in NPC management from PubMed, Scopus and Embase. The articles were filtered using inclusion and exclusion criteria, and the quality of the papers was assessed. Data were extracted from the finalized articles. Results: A total of 78 articles were reviewed after removing duplicates and papers that did not meet the inclusion and exclusion criteria. After quality assessment, 60 papers were included in the current study. There were four main types of applications, which were auto-contouring, diagnosis, prognosis, and miscellaneous applications (especially on radiotherapy planning). The different forms of convolutional neural networks (CNNs) accounted for the majority of DL algorithms used, while the artificial neural network (ANN) was the most frequent ML model implemented. Conclusion: There is an overall positive impact identified from AI implementation in the management of NPC. With improving AI algorithms, we envisage AI will be available as a routine application in a clinical setting soon. [ABSTRACT FROM AUTHOR]

Background: Low skeletal muscle mass (SMM) is an adverse prognostic factor for chemotherapy dose‐limiting toxicity (CDLT). In patients with locally advanced head and neck squamous cell carcinoma (HNSCC) undergoing chemoradiotherapy (CRT), low SMM is a predictor for CDLT. We aimed to validate these findings. Methods: Consecutive LA‐HNSCC patients treated with primary CRT with high‐dose cisplatin were retrospectively included. SMM was measured on pre‐treatment CT‐imaging. A cumulative cisplatin dose below 200 mg/m2 was defined as CDLT. Results: One hundred and fifty three patients were included; 37 (24.2%) experienced CDLT, and 84 had low SMM (54.9%). Patients with low SMM experienced more CDLT than patients with normal SMM (35.7% vs. 10.1%, p < 0.01). Low SMM (OR 3.99 [95% CI 1.56–10.23], p = 0.01) and an eGFR of 60–70 ml/min (OR 5.40 [95% CI 1.57–18.65], p < 0.01) were predictors for CDLT. Conclusion: Pre‐treatment low SMM is associated with CDLT in LA‐HNSCC patients treated with primary CRT. Routine SMM assessment may allow for CDLT risk assessment and treatment optimization. [ABSTRACT FROM AUTHOR]

The inherent variability in performing specific surgical procedures for head and neck cancer remains a barrier for accurately assessing treatment outcomes, particularly in clinical trials. While non-surgical modalities for cancer therapeutics have evolved to become far more uniform, there remains the challenge to standardize surgery. The purpose of this review is to identify the barriers in achieving uniformity and to highlight efforts by surgical groups to standardize selected operations and nomenclature. While further improvements in standardization will remain a challenge, we must encourage surgical groups to focus on strategies that provide such a level. [ABSTRACT FROM AUTHOR]

Keywords: [99mTc]Tc-tilmanocept; Lymph Node; Lymphoscintigraphy; metastasis; oral cancer; sentinel lymph node biopsy EN [99mTc]Tc-tilmanocept Lymph Node Lymphoscintigraphy metastasis oral cancer sentinel lymph node biopsy 1383 1388 6 10/14/21 20211101 NES 211101 KEY POINTS This study compares sentinel lymph node identification using [ SP 99m sp Tc]Tc-tilmanocept to [ SP 99m sp Tc]Tc-nanocolloid in early-stage oral cancer patients. Diagnostic accuracy of [99mTc]Tc-tilmanocept compared to [99mTc]Tc-nanocolloid for sentinel lymph node identification in early-stage oral cancer The prospective cohort has been described in the prequel study in detail.4 Patients underwent lymphoscintigraphy including SPECT-CT for both [ SP 99m sp Tc]Tc-tilmanocept and [ SP 99m sp Tc]Tc-nanocolloid. Besides, owing to relatively low activity residing in SLNs for [ SP 99m sp Tc]Tc-tilmanocept, intraoperative SLN localisation was challenging in some patients when using [ SP 99m sp Tc]Tc-tilmanocept for SLNB. [Extracted from the article]

Objective: Determine the presence and prognostic value of human papillomavirus (HPV), Epstein-Barr virus (EBV), Merkel cell polyomavirus (MCPyV), and cell cycle proteins in head and neck squamous cell carcinoma (HNSCC) of non-smokers and non-drinkers (NSND). Methods: Clinical characteristics and tumors of 119 NSND with HNSCC were retrospectively collected and analyzed on tissue microarrays. RNAscope in situ hybridization (ISH) was used to screen for the presence of HPV and MCPyV mRNA. Immunohistochemistry was performed for expression of p16 as surrogate marker for HPV, Large T-antigen for MCPyV, and cell cycle proteins p53 and pRb. Positive virus results were confirmed with polymerase chain reaction. For EBV, EBV encoded RNA ISH was performed. Differences in 5-year survival between virus positive and negative tumors were determined by log rank analysis. Results: All oropharyngeal tumors (OPSCC) (n = 10) were HPV-positive, in addition to one oral (OSCC) and one nasopharyngeal tumor (NPSCC). The other three NPSCC were EBV-positive. MCPyV was not detected. Patients with HPV or EBV positive tumors did not have a significantly better 5-year disease free or overall survival. Over 70% of virus negative OSCC showed mutant-type p53 expression. Conclusion: In this cohort, all OPSCC and NPSCC showed HPV or EBV presence. Besides one OSCC, all other oral (n = 94), hypopharyngeal (n = 1), and laryngeal (n = 9) tumors were HPV, EBV, and MCPyV negative. This argues against a central role of these viruses in the ethiopathogenesis of tumors outside the oro- and nasopharynx in NSND. So, for the majority of NSND with virus negative OSCC, more research is needed to understand the carcinogenic mechanisms in order to consider targeted therapeutic options. [ABSTRACT FROM AUTHOR]

Objectives: Head and neck squamous cell carcinoma (HNSCC) shows a remarkable heterogeneity between tumors, which may be captured by a variety of quantitative features extracted from diagnostic images, termed radiomics. The aim of this study was to develop and validate MRI-based radiomic prognostic models in oral and oropharyngeal cancer. Materials and Methods: Native T1-weighted images of four independent, retrospective (2005–2013), patient cohorts (n = 102, n = 76, n = 89, and n = 56) were used to delineate primary tumors, and to extract 545 quantitative features from. Subsequently, redundancy filtering and factor analysis were performed to handle collinearity in the data. Next, radiomic prognostic models were trained and validated to predict overall survival (OS) and relapse-free survival (RFS). Radiomic features were compared to and combined with prognostic models based on standard clinical parameters. Performance was assessed by integrated area under the curve (iAUC). Results: In oral cancer, the radiomic model showed an iAUC of 0.69 (OS) and 0.70 (RFS) in the validation cohort, whereas the iAUC in the oropharyngeal cancer validation cohort was 0.71 (OS) and 0.74 (RFS). By integration of radiomic and clinical variables, the most accurate models were defined (iAUC oral cavity, 0.72 (OS) and 0.74 (RFS); iAUC oropharynx, 0.81 (OS) and 0.78 (RFS)), and these combined models outperformed prognostic models based on standard clinical variables only (p < 0.001). Conclusions: MRI radiomics is feasible in HNSCC despite the known variability in MRI vendors and acquisition protocols, and radiomic features added information to prognostic models based on clinical parameters. Key Points: • MRI radiomics can predict overall survival and relapse-free survival in oral and HPV-negative oropharyngeal cancer. • MRI radiomics provides additional prognostic information to known clinical variables, with the best performance of the combined models. • Variation in MRI vendors and acquisition protocols did not influence performance of radiomic prognostic models. [ABSTRACT FROM AUTHOR]

Background: The Hopkins criteria were introduced for nodal response evaluation after therapy in head and neck cancer, but its superiority over quantification is not yet confirmed. Methods: SUVbody weight thresholds and lesion-to-background ratios were explored in a prospective multicenter study of standardized FDG-PET/CT 12 weeks after CRT in newly diagnosed locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients (ECLYPS). Reference standard was histology, negative FDG-PET/CT at 12 months after treatment or ≥ 2 years of negative follow-up. Area under the receiver operator characteristics curves (AUROC) were estimated and obtained thresholds were validated in an independent cohort of HNSCC patients (n = 127). Results: In ECLYPS, 124 patients were available for quantification. With a median follow-up of 20.4 months, 23 (18.5%) nodal neck recurrences were observed. A SUV70 threshold of 2.2 (AUROC = 0.89; sensitivity = 79.7%; specificity = 80.8%) was identified as optimal metric to identify nodal recurrence within 1 year after therapy. For lesion-to-background ratios, an SUV50/SUVliver threshold of 0.96 (AUROC = 0.89; sensitivity = 79.7%; specificity = 82.8%) had the best performance. Compared with Hopkins criteria (AUROC = 0.81), SUV70 and SUV50/SUVliver provided a borderline significant (p = 0.040 and p = 0.094, respectively) improvement. Validation of thresholds yielded similar AUROC values (SUV70 = 0.93, SUV50/SUVliver = 0.95), and were comparable to the Hopkins score (AUROC = 0.91; not statistically significant). Conclusion: FDG quantification detects nodal relapse in LAHNSCC patients. When using EARL standardized PET acquisitions and reconstruction, absolute SUV metrics (SUV70 threshold 2.2) prove robust, yet ratios (SUV50/SUVliver, threshold 0.96) may be more useful in routine clinical care. In this setting, the diagnostic value of quantification is comparable to the Hopkins criteria. Trial registration: US National Library for Medicine, NCT01179360. Registered 11 August 2010, https://clinicaltrials.gov/ct2/show/NCT01179360 [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the presence and prognostic value of tumor-infiltrating T cells in the tumor epithelium in advanced stage, HPV-negative head and neck squamous cell carcinoma (HNSCC) patients treated with primary chemoradiotherapy using digital pathology. Methods: Pre-treatment biopsies from 80 oropharyngeal, 52 hypopharyngeal, and 29 laryngeal cancer patients were collected in a tissue microarray (TMA) and immunohistochemically stained for T-cell markers CD3, CD4, CD8, FoxP3, and PD1, and for immune checkpoint PD-L1. For each marker, the number of positive tumor-infiltrating lymphocytes (TILs) per mm2 tumor epithelium was digitally quantified and correlated to overall survival (OS), disease-free survival (DFS), and locoregional control (LRC), as well as to clinicopathological characteristics. Differences in clinical outcome were estimated using Cox proportional hazard analysis and visualized using Kaplan–Meier curves. Results: The patient cohort had a 3-year OS of 58%, with a median follow-up of 53 months. None of the T-cell markers showed a correlation with OS, DFS or LRC. A low N stage was correlated to a better prognosis (OS: HR 0.39, p = 0.0028, DFS: HR 0.34, p = < 0.001, LRC: HR 0.24, p = 0.008). High TIL counts were more often observed in PD-L1-positive tumors (p < 0.05). Conclusion: This study showed an objective, digital pathology-aided method to assess TILs in the tumor epithelium. However, it did not provide evidence for a prognostic role of the presence of CD3 + , CD4 + , CD8 + , FoxP3 + , and PD1 + TILs in the tumor epithelium of advanced stage, HPV-negative HNSCC patients treated with primary chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Objectives: Pretreatment identification of radio-insensitive head and neck squamous cell carcinomas (HNSCC) would affect treatment modality selection. The apparent diffusion coefficient (ADC) of a tumor could be a predictor of local recurrence. However, little is known about its prognostic value next to known factors such as clinical T-stage. The aim of the present study is to determine the added value of pretreatment ADC to clinical T-stage as a prognostic factor for local recurrence.Methods: This retrospective cohort study included 217 patients with HNSCC treated with (chemo)radiotherapy between April 2009 and December 2015. All patients underwent diffusion-weighted MRI prior to treatment. Median ADC values of all tumors were obtained using a semi-automatic delineation method. Univariate models containing ADC and T-stage were compared with a multivariable model containing both variables.Results: Fifty-eight patients experienced a local recurrence within 3 years. On average, the ADC value in the group of patients with a recurrence was 1.01 versus 1.00 (10-3 mm2/s) in the group without a recurrence. Univariate analysis showed no significant association between tumor ADC and local recurrence within 3 years after (chemo)radiotherapy (p = 0.09). Cox regression showed that clinical T-stage was an independent predictor of local recurrence and adding ADC to the model did not increase its performance.Conclusion: Pretreatment ADC has no added value as a prognostic factor for local recurrence to clinical T-stage.Key Points: • Pretreatment identification of head and neck squamous cell carcinoma patients who do not benefit from (chemo)radiotherapy could improve personalized cancer care. • The apparent diffusion coefficient (ADC) obtained from diffusion-weighted MRI has been reported to be a prognostic factor for local recurrence. • In this study, ADC has no added value as a prognostic factor compared with clinical T-stage. [ABSTRACT FROM AUTHOR]

Purpose: Stepped care (SC), consisting of watchful waiting, guided self-help, problem-solving therapy, and psychotherapy/medication is, compared to care-as-usual (CAU), effective in improving psychological distress. This study presents secondary analyses on subgroups of patients who might specifically benefit from watchful waiting, guided self-help, or the entire SC program.Methods: In this randomized controlled trial, head and neck and lung cancer patients with distress (n = 156) were randomized to SC or CAU. Univariate logistic regression analyses were performed to investigate baseline factors associated with recovery after watchful waiting and guided self-help. Potential moderators of the effectiveness of SC compared to CAU were investigated using linear mixed models.Results: Patients without a psychiatric disorder, with better psychological outcomes (HADS: all scales) and better health-related quality of life (HRQOL) (EORTC QLQ-C30/H&N35: global QOL, all functioning, and several symptom domains) were more likely to recover after watchful waiting. Patients with better scores on distress, emotional functioning, and dyspnea were more likely to recover after guided self-help. Sex, time since treatment, anxiety or depressive disorder diagnosis, symptoms of anxiety, symptoms of depression, speech problems, and feeling ill at baseline moderated the efficacy of SC compared to CAU.Conclusions: Patients with distress but who are relatively doing well otherwise, benefit most from watchful waiting and guided self-help. The entire SC program is more effective in women, patients in the first year after treatment, patients with a higher level of distress or anxiety or depressive disorder, patients who are feeling ill, and patients with less speech problems.Trial: NTR1868. [ABSTRACT FROM AUTHOR]

Introduction: Management of clinically negative neck (cN0) in patients with parotid gland cancer is controversial. Treatment options can include observation, elective neck dissection or elective radiotherapy. Areas covered: We addressed the treatment options for cN0 patients with parotid gland cancer. A literature review was undertaken to determine the optimal management of this group of patients. Expert opinion: Patients with parotid carcinoma and clinically negative neck have various options for their management. The analysis of tumor stage, histology and grade is essential to better define patients at risk for occult lymph node metastasis. These patients can be managed by surgery, radiotherapy or their combination, depending on the presence of risk factors, the moment at which such risk factors are detected, patient-related clinical conditions, medical provider expertise and institutional facilities. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) represents a group of tumors arising in the oral cavity, oropharynx, and larynx. Although HNSCC is traditionally associated with tobacco and alcohol consumption, a growing proportion of head and neck tumors, mainly of the oropharynx, are associated with Human Papilloma Virus (HPV). Recurrent/metastatic disease is characterized by dismal prognosis and there is an unmet need for the development of biomarkers for detection of early disease, accurate prediction of prognosis, and appropriate selection of therapy. Based on the REMARK guidelines, a variety of diagnostic and prognostic biomarkers are being evaluated in clinical trials but their clinical significance is doubtful. Herein, we will focus on biomarkers in HNSCC used in the clinical setting and we will illustrate their clinical relevance. [ABSTRACT FROM AUTHOR]

Background Different clinical high-risk factors for the development of distant metastases have been identified but not tested in the same cohort of patients with head and neck squamous cell carcinoma (HNSCC). Methods In 145 patients with previously identified clinical high risk factors, the presence of extranodal spread (ENS) and matted node on pretreatment CT ( n = 96) and/or MRI ( n = 111) were determined. Results Of 145 patients, ENS was detected in 87 patients (60.0%) and matted nodes in 53 patients (36.6%). Kaplan-Meier curves for presence or absence of ENS (on CT and/or MRI) and matted nodes (on CT) differ significantly. In a Cox regression analysis, only ENS was a significant risk factor (hazard ratio [HR] = 3.3; 95% confidence interval [CI] = 2.0-5.5; p < .001). Conclusion In patients with high-risk HNSCC with clinically (palpably or radiologically) ENS and matted nodes, both determined radiologically, are high risk factors for development of distant metastases. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1452-E1458, 2016 [ABSTRACT FROM AUTHOR]

Background Early oral cavity squamous cell carcinoma (OCSCC) management appears to vary both within and between countries. Variation in practice can be an indicator of absence of evidence-based management and may negatively influence survival and morbidity. The exact variation and the relationship to differences in guidelines are unknown. This study aimed to report on these variations in the Netherlands, UK, and USA, and to evaluate them. Methods Information regarding the variation in OCSCC management strategies was obtained from a questionnaire sent to representatives of head and neck cancer centers in the Netherlands, UK, and USA. Within-country and between-country variations were also assessed in light of the different guidelines. Results In total, representatives of 45 centers completed the questionnaire; 10 from the Netherlands, 26 from the UK and 9 from the USA. Our results demonstrate a distinct variation in the diagnoses, treatment and follow-up of OCSCC, both within and between countries. Only a small amount of variation between countries could be linked to differences in guidelines. Conclusions There is high variation in the management of the neck in OCSCC. There seem to be a need for direct evidence about optimal management decisions to establish more evidence-based management and uniform practice. [ABSTRACT FROM AUTHOR]

Subash et al. [[1]] mentioned that the impact of micrometastases and ITC has not been established till now and that for studies looking at the role of sentinel lymph node biopsy (SLNB) in early OSCC, this may behold an unexplored arena [[1]]. Dear editor, With great interest we read the discussion on the impact of micrometastases and isolated tumor cells (ITC) in patients with early-stage (cT1-2N0) oral squamous cell carcinoma (OSCC). The results of these and other studies underline the clinical importance of reporting and detecting ITC and micrometastasis in early OSCC patients. [Extracted from the article]

Simple Summary: Therapies for squamous cell carcinomas of the head and neck (SCCHN) have been rapidly evolving, initially with the inclusion of immunotherapy, but more recently with the consideration of anti-angiogenic therapies. Recent preclinical and clinical data reveal a strong correlation between vascular endothelial growth factor (VEGF) and the progression of SCCHN, with nearly 90% of these malignancies expressing VEGF. Our review article not only elaborates on the utility of anti-VEGF therapies on SCCHN but also its interaction with the immune environment. Furthermore, we detailed the current data on immunotherapies targeting SCCHN and how this could be coupled with anti-angiogenics therapies. Despite the lack of approved anti-angiogenic therapies in squamous cell carcinoma of the head and neck (SCCHN), preclinical and more recent clinical evidence support the role of targeting the vascular endothelial growth factor (VEGF) in this disease. Targeting VEGF has gained even greater interest following the recent evidence supporting the role of immunotherapy in the management of advanced SCCHN. Preclinical evidence strongly suggests that VEGF plays a role in promoting the growth and progression of SCCHN, and clinical evidence exists as to the value of combining this strategy with immunotherapeutic agents. Close to 90% of SCCHNs express VEGF, which has been correlated with a worse clinical prognosis and an increased resistance to chemotherapeutic agents. As immunotherapy is currently at the forefront of the management of advanced SCCHN, revisiting the rationale for targeting angiogenesis in this disease has become an even more attractive proposition. [ABSTRACT FROM AUTHOR]

Objectives: This study analyzes the influence of the surgical setting, i.e. resection under local anesthesia versus resection under general anesthesia, on surgical margins in tumor resection of stage I and II oral squamous cell carcinoma (OSCC).Materials and Methods: Retrospective study on tumor resections of stage I or II OSCC performed between 2014 and 2020. Potential predictors associated with surgical margins were identified. Multinomial logistic regression was used to analyze the effect of type of anesthesia on surgical margins, adjusted for potential predictors.Results: In total, 109 cases were included: 54 tumor resections were performed under local anesthesia and 55 under general anesthesia. Histopathological examination showed 19 clear surgical margins, 54 close surgical margins, and 36 positive surgical margins. Compared to resection under general anesthesia, resection under local anesthesia increased the risk of close margins (adjusted OR = 6.26; 95 %CI 1.66-23.58; p = .01) and positive margins (adjusted OR = 6.81; 95 %Cl 1.70-27.27; p = .01). Tumor resection of the floor of mouth, buccal mucosa, gingiva, retromolar trigone, hard palate, and soft palate had a higher risk of close and positive margins than tumor resection of the tongue. Tumor resection of the tongue under local anesthesia was associated with an increased risk of positive margins compared to resection under general anesthesia.Conclusion: Tumor resection under local anesthesia of stage I and II OSCC increases the risk of close and positive surgical margins compared to tumor resection under general anesthesia. [ABSTRACT FROM AUTHOR]

Background The role of sentinel node biopsy in head and neck cancer is currently being explored. Patients with positive sentinel nodes were investigated to establish if additional metastases were present in the neck, their distribution, and their impact on outcome. Methods In all, 109 patients ( n = 109) from 15 European centers, with cT1/2,N0 tumors, and a positive sentinel lymph node were identified. Kaplan-Meier and univariate and multivariate logistic regression analysis were used to identify variables that predicted for additional positive nodes and their position within the neck. Results A total of 122 neck dissections were performed in 109 patients. Additional positive nodes were found in 34.4% of cases (42/122: 18 same, 21 adjacent, and 3 nonadjacent neck level). Additional nodes, especially if outside the sentinel node basin, had an impact on outcome. Conclusions The results are preliminary but suggest that both the number and the position of positive sentinel nodes may identify different prognostic groups that may allow further tailoring of management plans. © 2012 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

Summary: The detection of distant metastases is critical for prognostication and for the choice of treatment in patients with head and neck squamous cell carcinoma (HNSCC). Pretreatment screening for distant metastases should be conducted particularly for patients with high risk factors, prior to locoregional treatment decisions. Different diagnostic techniques are discussed. Unfortunately, most studies lack sufficient follow-up to reliably assess false-negative results. Moreover, the designs of most studies vary substantially with regard to homogeneity of groups (tumor types and stages), timing (pretreatment, follow-up) and definition of risk factors (patient selection). Therefore, only a few studies are comparable. The combination of F-18 fluoro-d-glucose-positron emission tomography (FDG-PET) and a dedicated CT (at least of the chest) is the most important imaging protocol at the present time. Eventually, whole-body-MRI (WB-MRI) may possibly replace PET-CT for screening patients for distant metastases. [ABSTRACT FROM AUTHOR]

Retropharyngeal lymph node (RPLN) metastasis of primary head and neck cancer often receives less consideration than lymph node metastasis in the neck. With improvements in imaging techniques and reports of surgical pathology, there is an improved understanding of the risk and subsequently the need for treatment of RPLNs. The rates of RPLN metastasis from carcinomas of the nasopharynx, oropharynx, hypopharynx, postcricoid region, maxillary sinus, and cervical esophagus are sufficiently high to warrant routine treatment, either electively or therapeutically, of this region. Through improved diagnostic techniques and heightened awareness of RPLN metastasis, patients at risk of having these metastases can be treated more effectively. © 2010 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

Summary: Currently, selection of lymph nodes for ultrasound-guided-fine-needle-aspiration cytology (USgFNAC) in patients with HNSCC relies mainly on size of lymph nodes. This retrospective study was undertaken to assess the potential value of size, laterality, level and changes in size as criteria for selection of nodes that need to be aspirated during follow-up of patients. We aim to reduce the number of unnecessary aspirations being performed without decreasing accuracy of USgFNAC. Eighty-one patients with oral cavity carcinoma (OCC) were eligible for observation-policy regarding treatment of the neck and received transoral excision of OCC. Selection of nodes for fine-needle-aspiration-cytology (FNAC) was based on size criterion. Localization (side and level) and size of aspirated lymph nodes were scored. Data on treatment and follow-up were collected and analyzed to assess the value of the used criteria. During follow-up all 17 positive nodes were found, of which 16 were ipsilateral. Contralateral metastasis was found in a patient with ipsilateral metastasis and a tumor crossing the midline. Minimal axial diameter (MAD) of all positive nodes was larger than 5.0mm in level II or 4.0mm in other levels. Follow-up aspirations in patients with OCC performed in the neck by USgFNAC can be reduced by 56% without increasing false-negative lymph nodes if follow-up aspirations would only be performed on the ipsilateral neck in lymph nodes with a MAD of 5mm in level II and 4mm in other levels or larger and in lymph nodes with rapid change of diameter. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to assess the interobserver variability in chest computed tomography (CT) and whole body 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography (FDG-PET) screening for distant metastases in head and neck squamous cell carcinoma (HNSCC) patients.Procedure: Chest CT and whole body FDG-PET of 69 HNSCC patients with high-risk factors who underwent screening for distant metastases were analyzed. All scans were independently read by two experienced radiologists or nuclear physicians who were blinded to the other examinations and follow-up results.Results: A kappa of 0.516 was found for assessment of size on CT. Kappa values for origin and susceptibility of 0.406 and 0.512 for CT and 0.834 and 0.939 for PET were found, respectively. The overall conclusions had a kappa of 0.517-0.634 for CT and 0.820-1.000 for PET.Conclusions: In screening for distant metastases in HNSCC patients with high-risk factors, chest CT readings had a reasonable to substantial agreement, while PET readings showed an almost perfect agreement. These findings suggest that for optimal assessment in clinical practice, PET most often can be scored by one observer, but CT should probably more often be scored by different observers in consensus or combined with PET. [ABSTRACT FROM AUTHOR]

Summary: Positron emission tomography (PET) is a functional imaging modality that is widely used in oncology. The integration of PET with CT (PET–CT) provides at the same time also detailed morphological information, which is especially attractive for the anatomically complex head and neck region. The most widely used PET-tracer for imaging the enhanced metabolism of tumours is 18F-fluorodeoxyglucose (18FDG), but several new tracers for imaging of metabolic features other than glucose consumption (non-FDG tracers) have been developed with the aim to perform better than 18FDG in specific indications. For initial staging of head and neck squamous cell carcinoma (HNSCC) these tracers until now did not show a better performance than 18FDG. Most data suggest a potential role for non-FDG metabolic tracers for treatment response prediction and surveillance of HNSCC. This information may provide a guide for further individualized treatment decisions. The possibility of PET to image biologic features and molecular targets as key drivers of malignant growth and survival provides another important tool for treatment guidance. The presence of the biologic feature hypoxia, a common phenomenon in head and neck cancer, is associated with a poor response to (chemo) radiotherapy. Therefore, knowledge of hypoxia may influence treatment decisions. Several candidate hypoxia PET tracers are discussed. With the increasing knowledge of critical molecular targets in head and neck cancer (e.g. the epidermal growth factor receptor), many novel targeted anticancer therapeutics become available among which monoclonal antibodies and small molecular tyrosin kinase inhibitors. Upon labelling of these drugs with a positron emitter, their distribution within the human body can be quantitatively imaged by PET. In this way, PET can be used for better understanding of in vivo tumour biology, guidance of drug development, and appropriate treatment selection for the individual patient (personalized medicine). Altogether, the potential role of non-FDG-PET in the management of HNSCC seems to be guidance and surveillance of treatment of the individual patient. [Copyright &y& Elsevier]

Summary: Radiation may cause radiation-induced cancers after a long latency period. In a group of 111 patients surgically treated for hypopharyngeal carcinoma, patients previously treated with radiotherapy for tuberculosis in the neck were compared to patients without previous radiotherapy. Seven patients (7.4%) underwent radiotherapy (median age 15years) and developed a hypopharyngeal carcinoma (median age 70years, median latency period 54.4year). Considering this long latency period and the localisation in the previous radiation field these tumours can be classified as potentially radiation-induced carcinomas. Patients with potentially radiation-induced carcinomas were significantly older when the hypopharyngeal carcinoma was diagnosed (p =0.048), were more frequently females (p =0.05) and had a worse 5-year regional control rate (p =0.048). When radiotherapy is considered in young patients the risk of induction of tumours has to be kept in mind. [ABSTRACT FROM AUTHOR]

A great disappointment in head and neck cancer surgery is that 10–30% of head and neck squamous cell carcinoma (HNSCC) patients develop local recurrences despite histopathologically tumor-free surgical margins. These recurrences result from either minimal residual cancer (MRC) or preneoplastic lesions that remain behind after tumor resection. Distinguishing MRC from preneoplasic lesions is important to tailor postoperative radiotherapy more adequately. Here we investigated the suitability of quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using human Ly-6D (hLy-6D) transcripts as molecular marker to detect MRC in surgical margins. Submucosal samples of deep surgical margins were collected from 18 non-cancer control patients and 67 HNSCC patients of whom eight had tumor-positive surgical margins. The samples were analyzed with hLy-6D qRT-PCR, and the data were analyzed in relation to the clinicohistological parameters. A significant difference was shown between the group of patients with histopathological tumor-positive surgical margins and the non-cancer control group (p<0.001), and the group of patients with histopathological tumor-free surgical margins (p=0.001). This study shows a novel approach for molecular analysis of deep surgical margins in head and neck cancer surgery. The preliminary data of this approach for detection of MRC in deep margins of HNSCC patients are promising. [ABSTRACT FROM AUTHOR]

Summary: After radiotherapy with or without chemotherapy differentiation between residual and recurrent head and neck cancer and (chemo)radiation sequelae is often difficult. Currently, most physicians aggressively pursue potential recurrences, leading to a high rate of futile invasive diagnostic, e.g. examinations under general anaesthesia with taking of biopsies, and surgical procedures, e.g. planned neck dissections, and a waste of health care resources. Therefore, diagnostic techniques which reliably select patients who should undergo these procedures are warranted. Conventional imaging techniques are not reliable enough for this purpose. Potential imaging techniques to detect residual and recurrent locoregional disease after chemoradiation are (serial) CT or MRI and FDG-PET, eventually in combination with specific response criteria or scoring systems. Diffusion MRI and PET/CT may further improve these techniques. FDG-PET may help to select patients clinically suspected of recurrent laryngeal carcinoma after radiotherapy for direct laryngoscopy under general anaesthesia. It is not yet clear whether FDG-PET can reliable avoid futile routine evaluation by examination under general anaesthesia in oral and oropharyngeal cancer and planned neck dissection when a residual mass persists in the neck after (chemo)radiation. The most reliable scoring criteria and the optimal time interval between completion of radiation and FDG-PET still has to be assessed. [Copyright &y& Elsevier]

Positron emission tomography (PET) using 18F-3′-deoxy-3′-fluorothymidine ([18F]FLT) allows noninvasive monitoring of tumour proliferation. For serial imaging in individual patients, good reproducibility is essential. The purpose of the present study was to evaluate the reproducibility of quantitative [18F]FLT measurements. Nine patients with non-small-cell lung cancer (NSCLC) and six with head-and-neck cancer (HNC) underwent [18F]FLT PET twice within 7 days prior to therapy. The maximum pixel value (SUVmax) and a threshold defined volume (SUV41%) were defined for all delineated lesions. The plasma to tumour transfer constant (Ki) was estimated using both Patlak graphical analysis and nonlinear regression (NLR). NLR was also used to estimate k3, which, at least in theory, selectively reflects thymidine kinase 1 activity. The level of agreement between test and retest values was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. All primary tumours and >90% of clinically suspected locoregional metastases could be delineated. In total, 24 lesions were defined. NLR-derived Ki, Patlak-derived Ki, SUV41% and SUVmax showed excellent reproducibility with ICCs of 0.92, 0.95, 0.98 and 0.93, and SDs of 16%, 12%, 7% and 11%, respectively. Reproducibility was poor for k3 with an ICC of 0.43 and SD of 38%. Quantitative [18F]FLT measurements are reproducible in both NSCLC and HNC patients. When monitoring response in individual patients, changes of more than 15% in SUV41%, 20–25% in SUVmax and Patlak-derived Ki, and 32% in NLR3k-derived Ki are likely to represent treatment effects. [ABSTRACT FROM AUTHOR]

Several techniques have been developed to reconstruct oral and pharyngeal defects following surgery, in order to restore function and cosmesis. These are primary closure, skin grafts, local transposition of skin, mucosa and/or muscle, regional flaps and free vascularized flaps. Because of the ‘bulky’, pedicled nature and problems with the donor area of locoregional flaps, and consequently frequently unsatisfactory functional results, free vascularized flaps have gained popularity during the last decade. The authors review the current options available to give physicians, who are not experienced in the field of reconstruction in the head and neck, an impression of the range of techniques available for reconstruction of oral and pharyngeal defects following tumor resection. For reconstruction of oral cavity and pharyngeal defects, fasciocutaneous (e.g. radial forearm and anterolateral thigh flaps) and myocutaneous free flaps (e.g. rectus abdominis and latissimus dorsi) have proven to be very reliable. Free vascularized osteocutaneous flaps (e.g. fibula and iliac crest) permit reconstructive options for bony defects of the mandible or maxilla that can be adapted to a variety of defects. Depending on the site, size and involved tissues of the surgical defect and patient factors, a variety of reconstructive options are available. For both soft tissue and bony defects of the upper aerodigestive tract, microvascular free flaps provide good functional outcomes. [ABSTRACT FROM AUTHOR]

Previous studies have shown the potential of murine and chimeric anti-CD44v6 monoclonal antibodies (MAbs) for radioimmunotherapy (RIT) of head and neck squamous cell carcinoma (HNSCC). A limitation of these MAbs, however, appeared to be their immunogenicity. Therefore, humanized monoclonal antibody BIWA 4 (bivatuzumab), with an intermediate affinity for CD44v6, was recently selected. As a prelude to RIT, we evaluated the safety, tumor-targeting potential, pharmacokinetics, and immunogenicity of technetium-99m-labeled BIWA 4 in patients undergoing operations for primary HNSCC in this study. Ten patients were treated at BIWA 4 dose levels of 25 mg (n=3), 50 mg (n=4), and 100 mg (n=3). Patients received 2 mg of 750 MBq 99mTc-BIWA 4, together with 23-, 48-, and 98-mg unlabeled BIWA 4, respectively. Radioimmunoscintigraphy (RIS) was performed within 1 h and after 21 h, and patients underwent surgery at 48 h after injection. Biodistribution of 99mTc-BIWA 4 was evaluated by radioactivity measurements in blood, bone marrow, and in biopsies of a surgical specimen obtained 48 h after injection. BIWA 4 concentration in blood was assessed by ELISA and high performance liquid chromatography and related to soluble CD44v6 levels in serum samples. The development of human anti–human antibody (HAHA) responses was determined. Administration of 99mTc-BIWA 4 was well tolerated by all patients and no HAHA responses were observed. A mean t1/2 in plasma of 54.8±11.5 h, 76.1±21.8 h, and 68.5±21.2 h was found for the 25-, 50-, and 100-mg dose group, respectively. No complex formation of BIWA 4 with soluble CD44v6 in blood was observed. RIS showed targeting of primary tumors and lymph node metastases in 8 of 10 and 1 of 5 patients, respectively. The highest tumor uptake and tumor to nontumor ratios were observed for the 50-mg dose group. Tumor uptake was 12.9±5.9, 26.2±3.1, and 15.4±1.9% of the injected dose (ID)/kg for the 25-, 50-, and 100-mg dose group, respectively, while the tumor to bone marrow ratios for these groups were 1.7±0.5, 3.2±1.1, and 2.0±0.6, respectively. Conclusion: 99mTc-BIWA 4 can safely be administered to patients with HNSCC, with absence of detectable HAHA responses. The 50-mg dose level showed the highest tumor uptake and tumor to nontumor ratios. These findings support the use of BIWA 4 for RIT studies in patients with HNSCC. [ABSTRACT FROM AUTHOR]