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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: This systematic review evaluates techniques defining adequate mucosal margins during the resection of oral squamous cell carcinoma (SCC). Residual SCC and dysplasia demand distinct adjuvant treatment, such as re-resection and radiation for SCC or CO2-laser evaporation for severe dysplasia, necessitating accurate differentiation between SCC and dysplasia during surgery. The study includes eight investigations into margin visualization techniques—autofluorescence, iodine staining, and narrow-band imaging—concluding that, except for autofluorescence, there is considerable variability in negative predictive values. Autofluorescence does not significantly enhance margin outcomes compared to conventional white light-guided surgery, while iodine does. Studies on narrow-band imaging did not report a comparison with a white light-guided surgery cohort. The review advocates for more comprehensive studies comparing the diagnostic accuracy of iodine staining or narrow-band imaging, with a specific focus on diagnostic accuracy and the discrimination between SCC and dysplasia. Background: This systematic review investigates techniques for determining adequate mucosal margins during the resection of oral squamous cell carcinoma (SCC). The primary treatment involves surgical removal with ≥5 mm margins, highlighting the importance of accurate differentiation between SCC and dysplasia during surgery. Methods: A comprehensive Embase and PubMed literature search was performed. Studies underwent quality assessment using QUADAS-2. Results: After the full-text screening and exclusion of studies exhibiting high bias, eight studies were included, focusing on three margin visualization techniques: autofluorescence, iodine staining, and narrow-band imaging (NBI). Negative predictive value (NPV) was calculable across the studies, though reference standards varied. Results indicated NPVs for autofluorescence, iodine, and NBI ranging from 61% to 100%, 92% to 99%, and 86% to 100%, respectively. Autofluorescence did not significantly enhance margins compared to white light-guided surgery, while iodine staining demonstrated improvement for mild or moderate dysplasia. NBI lacked comparison with a white light-guided surgery cohort. Conclusions: We recommend studying and comparing the diagnostic accuracy of iodine staining and NBI in larger cohorts of patients with oral SCC, focusing on discriminating between SCC and (severe) dysplasia. Furthermore, we advise reporting the diagnostic accuracy alongside the treatment effects to improve the assessment of these techniques. [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]

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: Swallowing rehabilitation in patients treated for oral cancer is a challenge. Different factors may influence these patients' swallowing function. Therefore, we aimed to identify factors related to swallowing function up to 5 years after oral cancer treatment. We found that patients who are older at diagnosis, women, and patients who regularly consume alcohol before their treatment may have poorer swallow functioning after oral cancer treatment. Patients that fit these criteria should have their swallowing evaluated during clinical follow-ups and sent to swallowing therapy when needed. During this therapy, optimizing tongue function needs attention to maintain an optimal swallowing function. Background: Swallowing rehabilitation in curative treated patients with oral cancer is still a challenge. Different factors may influence these patients' swallowing function. The aim of this study was to identify factors associated with swallowing function up to 5 years after cancer treatment. Methods: Swallowing duration and frequency of 5 mL water and 15 mL applesauce were measured in 123 patients treated for oral cancer. Mixed model analyses were performed to identify associated factors. Results: Age influenced all measured swallowing outcomes. Assessment moment, gender, tumor location, maximum tongue force, and tactile sensory function of the tongue were associated with both water and applesauce swallowing duration, tumor classification was associated with water swallowing duration, and alcohol consumption was associated with applesauce swallowing duration. Assessment moment, cancer treatment, maximum tongue force, and tactile sensory function of the tongue were associated with water and applesauce swallowing frequency. Conclusion: Patients who are older at diagnosis, women, and patients who regularly consume alcohol before their treatment may have poorer swallow functioning after curative oral cancer treatment. Patients that fit these criteria should have their swallowing evaluated during clinical follow-ups and sent to swallowing therapy when needed. During this therapy, optimizing tongue function needs attention to maintain an optimal swallowing function. [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: Cancer of the nasal vestibule is thought to be rare. Multiple staging systems exist for the staging of these tumors, which can lead to variability and, therefore, the poor reliability of data. This retrospective study aimed to evaluate these staging systems. One hundred and forty-eight patients with carcinoma of the nasal vestibule were included and re-staged per the available staging systems. Stage distribution varied widely between the four evaluated staging systems. The classification per Bussu et al. had the most balanced allocation of patients amongst the stages. The widespread adoption of a single system and the introduction of a designated topography code for this disease could lead to greater uniformity in data reporting and an improved understanding of the incidence and disease outcome. Further analysis of survival data is needed to assess which classification system is the best suited for nasal vestibule carcinoma. Squamous cell carcinoma of the nasal vestibule is reported to account for less than one percent of all head and neck malignancies. It lacks a designated WHO ICD-O topography code, and multiple systems are available for the staging of this disease, which results in unwanted variability and the subsequent poor reliability of data. The aim of this study was to evaluate the currently available staging systems for cancer of the nasal vestibule, including the recently introduced classification by Bussu et al., which built on Wang's original concept but with clearer anatomical cutoffs. Different staging systems for cancer of the nasal vestibule (UICC nasal cavity, UICC skin cancer of the head and neck, Wang and Bussu et al.) were evaluated via a retrospective analysis of 148 patients. The staging system, per Bussu et al., had the most balanced allocation of patients among the stages. When using the Wang classification as a reference, stage migration occurred less frequently with the Bussu classification. The widespread adoption of a single staging system, as well as the introduction of a designated topography code for cancer of the nasal vestibule, could lead to more uniformity in data reporting and improve an understanding of the incidence and disease outcome. The newly proposed carcinoma of the nasal vestibule classification by Bussu et al. has the potential to improve the staging and allocation among stages. Further analysis of survival data is needed to assess which classification system is best suited for nasal vestibule carcinoma. [ABSTRACT FROM AUTHOR]

(1) Background: Hypopharyngeal squamous cell carcinomas usually present with locally advanced disease and a correspondingly poor prognosis. Currently, efforts are being made to improve tumor characterization and provide insightful information for outcome prediction. Radiomics is an emerging area of study that involves the conversion of medical images into mineable data; these data are then used to extract quantitative features based on shape, intensity, texture, and other parameters; (2) Methods: A systematic review of the peer-reviewed literature was conducted; (3) Results: A total of 437 manuscripts were identified. Fifteen manuscripts met the inclusion criteria. The main targets described were the evaluation of textural features to determine tumor-programmed death-ligand 1 expression; a surrogate for microvessel density and heterogeneity of perfusion; patient stratification into groups at high and low risk of progression; prediction of early recurrence, 1-year locoregional failure and survival outcome, including progression-free survival and overall survival, in patients with locally advanced HPSCC; thyroid cartilage invasion, early disease progression, recurrence, induction chemotherapy response, treatment response, and prognosis; and (4) Conclusions: our findings suggest that radiomics represents a potentially useful tool in the diagnostic workup as well as during the treatment and follow-up of patients with HPSCC. Large prospective studies are essential to validate this technology in these patients. [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]

Simple Summary: Neutrophil-to-lymphocyte ratio (NLR) in peripheral blood samples has been associated with prognosis in several cancers, including head and neck cancer, but in oropharyngeal carcinomas its prognostic value, especially in relation to human papillomavirus (HPV) infection, has been little studied. This meta-analysis, including studies on the prognostic value of NLR in oropharyngeal carcinoma, shows that an elevated pretreatment NLR is associated with a worse prognosis in oropharyngeal cancer, regardless of the type of treatment performed, but this prognostic value appears to be specific to HPV-positive oropharyngeal carcinomas. NLR could be used as an affordable prognostic marker in this type of cancer. Neutrophil-to-lymphocyte ratio (NLR) has been associated with survival in various cancers, including head and neck cancer. However, there is limited information on its role in oropharyngeal squamous cell carcinomas (OPSCC) according to HPV status. This prompted the present meta-analysis. Studies were selected when the prognostic value of NLR prior to treatment was evaluated in OPSCC patients, the cutoff value of NLR was available, and the prognostic value of NLR was evaluated by time-to-event survival analysis. A total of 14 out of 492 articles, including 7647 patients, were analyzed. The results showed a worse prognosis for the patients with a high NLR: The combined hazard ratios (HR) for overall survival (OS) in patients with an elevated NLR was 1.56 (95% confidence interval (CI) 1.21–2.02; p = 0.0006), for disease-free survival was 1.52 (95% CI 1.34–1.73; p < 0.00001), and for recurrence-free survival was 1.86 (95% CI 1.50–2.30; p < 0.00001). This worse prognosis of high NLR was exclusive of HPV-positive patients: HR for OS in the HPV-positive subgroup was 4.05 (95% CI 1.90–8.62 (p = 0.0003), and in the HPV-negative subgroup 0.92 (95% CI 0.47–1.80; p = 0.82). The prognosis of NLR was not influenced by treatment: The HR for OS for patients treated with radiotherapy/chemoradiotherapy (RT/CRT) was 1.48 (95% CI 1.09–2.01; p = 0.01), and for patients treated with surgery (±RT/CRT) was 1.72 (95% CI 1.08–2.72; p = 0.02). In conclusion, an elevated NLR relates to worse outcomes in patients with HPV-positive OPSCC. [ABSTRACT FROM AUTHOR]

The choice for the most optimal strategy for patients with a cT1-2N0 carcinoma of the oral cavity, sentinel lymph node biopsy (SLNB) or elective neck dissection (END), is still open for debate in many head and neck cancer (HNC) treatment centers. One of the possible benefits of the less invasive SLNB could be reduced neck and shoulder morbidity. Recent studies have shown a benefit in favor of SLNB the first year after intervention, but the long-term consequences and differences in neck morbidity remain unclear. This cross-sectional study aimed to research differences in neck and shoulder morbidity and Health-Related Quality of Life (HR-QoL) in patients with a cT1-2N0 carcinoma of the oral cavity, treated with either END or SLNB. Neck and shoulder morbidity and HR-QOL were measured with patient-reported questionnaires (SDQ, SPADI, NDI, NDII, EORTC-QLQ-C30, EORTC-QLQ-HN35) and active range of motion (AROM) measurements. In total 18 patients with END and 20 patients with SLNB were included. We found no differences between END and SLNB for long-term neck morbidity, shoulder morbidity, and HR-QOL. The significant differences found in the rotation of the neck are small and not clinically relevant. [ABSTRACT FROM AUTHOR]

This study evaluated sentinel lymph node (SLN) identification with CT lymphography (CTL) following peritumoral administration of Lipiodol® relative to conventional 99mTc-nanocolloid lymphoscintigraphy (including SPECT/CT) in 10 early-stage oral cancer patients undergoing SLN biopsy. Patients first underwent early dynamic and static scintigraphy after peritumoral administration of 99mTc-nanocolloid. Subsequently, Lipiodol® was administered at the same injection sites, followed by fluoroscopy and CT acquisition. Finally, late scintigraphy and SPECT/CT were conducted, enabling the fusion of late CTL and SPECT imaging. The next day, designated SLNs were harvested, radiographically examined for Lipiodol® uptake and histopathologically assessed. Corresponding images of CT, 99mTc-nanocolloid lymphoscintigraphy and SPECT/late CTL fusion were evaluated. 99mTc-nanocolloid lymphoscintigraphy identified 21 SLNs, of which 7 were identified with CTL (33%). CTL identified no additional SLNs and failed to identify any SLNs in four patients (40%). Out of six histopathologically positive SLNs, two were identified by CTL (33%). Radiographic examination confirmed Lipiodol® uptake in seven harvested SLNs (24%), of which five were depicted by CTL. CTL using Lipiodol® reached a sensitivity of 50% and a negative predictive value (NPV) of 75% (median follow-up: 12.3 months). These results suggest that CTL using Lipiodol® is not a reliable technique for SLN mapping in early-stage oral cancer. [ABSTRACT FROM AUTHOR]

Evidence on the cost-effectiveness of eHealth in palliative care is scarce. Oncokompas, a fully automated behavioral intervention technology, aims to support self-management in cancer patients. This study aimed to assess the cost-utility of the eHealth application Oncokompas among incurably ill cancer patients, compared to care as usual. In this randomized controlled trial, patients were randomized into the intervention group (access to Oncokompas) or the waiting-list control group (access after three months). Healthcare costs, productivity losses, and health status were measured at baseline and three months. Intervention costs were also taken into account. Non-parametric bootstrapping with 5000 replications was used to obtain 95% confidence intervals around the incremental costs and quality-adjusted life years (QALYs). A probabilistic approach was used because of the skewness of cost data. Altogether, 138 patients completed the baseline questionnaire and were randomly assigned to the intervention group (69) or the control group (69). In the base case analysis, mean total costs and mean total effects were non-significantly lower in the intervention group (−€806 and −0.01 QALYs). The probability that the intervention was more effective and less costly was 4%, whereas the probability of being less effective and less costly was 74%. Among patients with incurable cancer, Oncokompas does not impact incremental costs and seems slightly less effective in terms of QALYs, compared to care as usual. Future research on the costs of eHealth in palliative cancer care is warranted to assess the generalizability of the findings of this study. [ABSTRACT FROM AUTHOR]

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]

The diagnosis is the art of determining the nature of a disease, and an accurate diagnosis is the true cornerstone on which rational treatment should be built. Within the workflow in the management of head and neck tumours, there are different types of diagnosis. The purpose of this work is to point out the differences and the aims of the different types of diagnoses and to highlight their importance in the management of patients with head and neck tumours. Qualitative diagnosis is performed by a pathologist and is essential in determining the management and can provide guidance on prognosis. The evolution of immunohistochemistry and molecular biology techniques has made it possible to obtain more precise diagnoses and to identify prognostic markers and precision factors. Quantitative diagnosis is made by the radiologist and consists of identifying a mass lesion and the estimation of the tumour volume and extent using imaging techniques, such as CT, MRI, and PET. The distinction between the two types of diagnosis is clear, as the methodology is different. The accurate establishment of both diagnoses plays an essential role in treatment planning. Getting the right diagnosis is a key aspect of health care, and it provides an explanation of a patient's health problem and informs subsequent decision. Deep learning and radiomics approaches hold promise for improving diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: To review the current options in the management of Warthin tumors (WTs) and to propose a working management protocol. Methods: A systematic literature search was conducted using PubMed and ScienceDirect database. A total of 141 publications were selected and have been included in this review. Publications were selected based on relevance, scientific evidence, and actuality. Results: The importance of parotid WTs is increasing due to its rising incidence in many countries, becoming the most frequently encountered benign parotid tumor in certain parts of the world. In the past, all WTs were treated with surgery, but because of their slow growth rate, often minimal clinical symptoms, and the advanced age of many patients, active observation has gradually become more widely used. In order to decide on active surveillance, the diagnosis of WT must be reliable, and clinical, imaging, and cytological data should be concordant. There are four clear indications for upfront surgery: uncertain diagnosis; cosmetic problems; clinical complaints, such as pain, ulceration, or recurrent infection; and the patient's wish to have the tumor removed. In the remaining cases, surgery can be elective. Active surveillance is often suggested as the first approach, with surgery being considered if the tumor progresses and/or causes clinical complaints. The extent of surgery is another controversial topic, and the current trend is to minimize the resection using partial parotidectomies and extracapsular dissections when possible. Recently, non-surgical options such as microwave ablation, radiofrequency ablation, and ultrasound-guided ethanol sclerotherapy have been proposed for selected cases. Conclusions: The management of WT is gradually shifting from superficial or total parotidectomy to more conservative approaches, with more limited resections, and to active surveillance in an increasing number of patients. Additionally, non-surgical treatments are emerging, but their role needs to be defined in future studies. [ABSTRACT FROM AUTHOR]

Low skeletal muscle mass (SMM) is associated with toxicities and decreased survival in head and neck cancer (HNC). Chemoradiotherapy (CRT) may exaggerate loss of SMM. We investigated the changes in SMM, their predictors, and prognostic impact of SMM in patients treated with CRT between 2012 and 2018. Skeletal muscle area (SMA) segmentation was performed on pre- and post-CRT imaging. Observed changes in SMM were categorized into: (I) Stable, (II) moderate gain (III), moderate loss, (IV) large gain, and (V) large loss. In total, 235 HNC patients were included, of which 39% had stable SMM, 55% moderate loss, 13% moderate gain, 0.4% large loss, and 0.4% large gain of SMM. After CRT, SMA decreased compared to pre-CRT (31.6 cm2 versus 33.3 cm2, p < 0.01). The key predictor was a body mass index (BMI) of ≥30 kg/m2 (OR 3.6, 95% CI 1.4–9.3, p < 0.01). Low SMM at diagnosis (HR 2.1; 95% CI 1.1–4.1, p = 0.03) and an HPV-positive oropharyngeal tumor (HR 0.1; 95% CI 0.01–0.9, p = 0.04) were prognostic for overall survival. Changes in SMM were not prognostic for survival. Loss of SMM is highly prevalent after CRT and a high BMI before treatment may aid in identifying patients at risk. [ABSTRACT FROM AUTHOR]

Low skeletal muscle mass (LSMM) is increasingly recognized for its predictive value for adverse events in cancer patients. In specific, the predictive value of LSMM has been demonstrated for anti-cancer drug toxicity in a variety of cancer types and anti-cancer drugs. However, due to the limited sample size and study populations focused on a single cancer type, an overall predictive value of LSMM for anti-cancer drug toxicity remains unknown. Therefore, this review aims to provide a comprehensive overview of the predictive value of LSMM and perform a meta-analysis to analyse the overall effect. A systematic search was conducted of MEDLINE, Scopus, EMBASE, and Cochrane. Inclusion criteria were skeletal muscle mass (SMM) evaluated with computed tomography (CT) or magnetic resonance imaging (MRI), articles published in English, SMM studied in humans, SMM measurement normalized for height, and patients did not receive an intervention to treat or prevent LSMM. A meta-analysis was performed using a random-effects model and expressed in odds ratio (OR) with 95% confidence interval (CI). Heterogeneity was assessed using χ2 and I2 statistics. The search yielded 907 studies. 31 studies were included in the systematic review. Sample sizes ranged from 21 to 414 patients. The occurrence of LSMM ranged from 12.2% to 89.0%. The most frequently studied cancer types were oesophageal, renal, colorectal, breast, and head and neck cancer. Patients with LSMM had a higher risk of severe toxicity (OR 4.08; 95% CI 2.48–6.70; p < 0.001) and dose-limiting toxicity (OR 2.24; 95% CI 1.28–3.92; p < 0.001) compared to patients without LSMM. To conclude, the predictive value of LSMM for anti-cancer drug toxicity can be observed across cancer types. This information increases the need for further research into interventions that could treat LSMM as well as the possibility to adapt treatment regimens based on the presence of LSMM. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with cervical lymph node metastasis from squamous cell carcinoma undergo extensive irradiation or surgery of the head and neck with higher treatment morbidity, recurrence rate and lower overall survival than patients with overt primary tumor. In order to enhance treatment efficiency and morbidity reduction, the primary tumor detection accuracy was evaluated by using Ultrafast-Dynamic Contrast-Enhancement (DCE-)MRI in addition to Diffusion-Weighted (DW-)MRI and 18F-FDG-PET/CT imaging. Ultrafast-DCE, with a temporal resolution of 4 s, enabled capturing lesions with increased neoangiogenesis or perfusion compared to normal tissue. The use of Ultra-fast DCE resulted in higher confidence for suspicious locations and high observer agreement. Ultrafast-DCE showed potential to improve detection of unknown primary tumors in addition to DWI and 18F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and 18F-FDG-PET/CT yielded highest sensitivity. To evaluate diagnostic accuracy of qualitative analysis and interobserver agreement of single ultrafast-DCE, DWI or 18F-FDG-PET and the combination of modalities for the detection of unknown primary tumor (UPT) in patients presenting with cervical lymph node metastasis from squamous cell carcinoma (SCC). Between 2014–2019, patients with histologically proven cervical lymph node metastasis of UPT SCC were prospectively included and underwent DWI, ultrafast-DCE, and 18F-FDG-PET/CT. Qualitative assessment was performed by two observers per modality. Interobserver agreement was calculated using the proportion specific agreement. Diagnostic accuracy of combined use of DWI, ultrafast-DCE and 18F-FDG-PET/CT was assessed. Twenty-nine patients were included (20 males. [68%], median age 60 years). Nine (31%) primary tumors remained occult. Ultrafast-DCE added reader confidence for suspicious locations (one additional true positive (5%), 2 decisive true malignant (10%). The per-location analysis showed highest specific positive agreement for ultrafast-DCE (77.6%). The per-location rating showed highest sensitivity (95%, 95%CI = 75.1–99.9, YI = 0.814) when either one of all modalities was scored positive, and 97.4% (95%CI = 93.5–99.3, YI = 0.774) specificity when co-detected on all. The per-patient analysis showed highest sensitivity (100%) for 18F-FDG-PET/CT (YI = 0.222) and either DWI or PET (YI = 0.111). Despite highest trends, no significant differences were found. The per-patient analysis showed highest specific positive agreement when co-detected on all modalities (55.6%, 95%CI = 21.2–86.3, YI = 0.456). Ultrafast-DCE showed potential to improve detection of unknown primary tumors in addition to DWI and 18F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and 18F-FDG-PET/CT yielded highest sensitivity. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node biopsy (SLNB) has been introduced as a diagnostic staging modality for detection of occult metastases in patients with early stage oral cancer. Comparisons regarding accuracy to the routinely used elective neck dissection (END) are lacking in literature. Methods: A retrospective, multicenter cohort study included 390 patients staged by END and 488 by SLNB. Results: The overall sensitivity (84% vs. 81%, p = 0.612) and negative predictive value (NPV) (93%, p = 1.000) were comparable between END and SLNB patients. The END cohort contained more pT2 tumours (51%) compared to the SLNB cohort (23%) (p < 0.001). No differences were found for sensitivity and NPV between SLNB and END divided by pT stage. In floor-of-mouth (FOM) tumours, SLNB had a lower sensitivity (63% vs. 92%, p = 0.006) and NPV (90% vs. 97%, p = 0.057) compared to END. Higher disease-specific survival (DSS) rates were found for pT1 SLNB patients compared to pT1 END patients (96% vs. 90%, p = 0.048). Conclusion: In the absence of randomized clinical trials, this study provides the highest available evidence that, in oral cancer, SLNB is as accurate as END in detecting occult lymph node metastases, except for floor-of-mouth tumours. [ABSTRACT FROM AUTHOR]

Background: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. Methods: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. Results: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4–23.4) and 8.0% (95% CI 2.7–13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0–6.1%), 2.0% (95% CI 0.9–3.1) and 0.4% (95% CI 0–1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0–1.3). Conclusions: The incidence of occult lymph node metastasis is higher in supraglottic and T3–4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors. [ABSTRACT FROM AUTHOR]

Patients diagnosed with head and neck squamous cell carcinoma (HNSCC) are currently treated with surgery and/or radio- and chemotherapy. Despite these therapeutic interventions, 40% of patients relapse, urging the need for more effective therapies. In photodynamic therapy (PDT), a light-activated photosensitizer produces reactive oxygen species that ultimately lead to cell death. Targeted PDT, using a photosensitizer conjugated to tumor-targeting molecules, has been explored as a more selective cancer therapy. Organoids are self-organizing three-dimensional structures that can be grown from both normal and tumor patient-material and have recently shown translational potential. Here, we explore the potential of a recently described HNSCC–organoid model to evaluate Epidermal Growth Factor Receptor (EGFR)-targeted PDT, through either antibody- or nanobody-photosensitizer conjugates. We find that EGFR expression levels differ between organoids derived from different donors, and recapitulate EGFR expression levels of patient material. EGFR expression levels were found to correlate with the response to EGFR-targeted PDT. Importantly, organoids grown from surrounding normal tissues showed lower EGFR expression levels than their tumor counterparts, and were not affected by the treatment. In general, nanobody-targeted PDT was more effective than antibody-targeted PDT. Taken together, patient-derived HNSCC organoids are a useful 3D model for testing in vitro targeted PDT. [ABSTRACT FROM AUTHOR]

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.

A magnetic sentinel lymph node biopsy ((SLN)B) procedure has recently been shown feasible in oral cancer patients. However, a grading system is absent for proper identification and classification, and thus for clinical reporting. Based on data from eight complete magnetic SLNB procedures, we propose a provisional grading system. This grading system includes: (1) a qualitative five-point grading scale for MRI evaluation to describe iron uptake by LNs; (2) an ex vivo count of resected SLN with a magnetic probe to quantify iron amount; and (3) a qualitative five-point grading scale for histopathologic examination of excised magnetic SLNs. Most SLNs with iron uptake were identified and detected in level II. In this level, most variance in grading was seen for MRI and histopathology; MRI and medullar sinus were especially highly graded, and cortical sinus was mainly low graded. On average 82 ± 58 µg iron accumulated in harvested SLNs, and there were no significant differences in injected tracer dose (22.4 mg or 11.2 mg iron). In conclusion, a first step was taken in defining a comprehensive grading system to gain more insight into the lymphatic draining system during a magnetic SLNB procedure.

Electrochemotherapy (ECT) is a local ablative treatment that is based on the reversible electroporation and intracellular accumulation of hydrophilic drug molecules, which greatly increases their cytotoxicity. In mucosal head and neck cancer (HNC), experience with ECT is limited due to the poor accessibility of tumors. In order to review the experience with ECT in mucosal HNC, we undertook a systematic review of the literature. In 22 articles, published between 1998 and 2020, 16 studies with 164 patients were described. Curative and palliative intent treatment were given to 36 (22%) and 128 patients (78%), respectively. The majority of tumors were squamous cell carcinomas (79.3%) and located in the oral cavity (62.8%). In the curative intent group, complete response after one ECT treatment was achieved in 80.5% of the patients, and in the palliative intent group, the objective (complete and partial) response rate was 73.1% (31.2% and 41.9%). No serious adverse events were reported during or soon after ECT and late effects were rare (19 events in 17 patients). The quality-of-life assessments did not show a significant deterioration at 12 months post-ECT. Provided these preliminary data are confirmed in randomized controlled trials, ECT may be an interesting treatment option in selected patients with HNC not amenable to standard local treatment.