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Concomitant chemoradiotherapy (CRT) is extensively used as primary organ preservation treatment for selected advanced laryngeal squamous cell carcinomas (LSCC). The oncologic outcomes of such regimens are comparable to those of total laryngectomy followed by adjuvant radiotherapy. However, the management of loco-regional recurrences after CRT remains a challenge, with salvage total laryngectomy being the only curative option. Furthermore, the decision whether to perform an elective neck dissection (END) in patients with rN0 necks, and the extent of the neck dissection in patients with rN + necks is still, a matter of debate. For rN0 patients, meta-analyses have reported occult metastasis rates ranging from 0 to 31 %, but no survival advantage for END. In addition, meta-analyses also showed a higher incidence of complications in patients who received an END. Therefore, END is not routinely recommended in addition to salvage laryngectomy. Although some evidence suggests a potential role of END for supraglottic and locally advanced cases, the decision to perform END should weigh benefits against potential complications. In rN + patients, several studies suggested that selective neck dissection (SND) is oncologically safe for patients with specific conditions: when lymph node metastases are not fixed and are absent at level IV or V. Super-selective neck dissection (SSND) may be an option when nodes are confined to one level. In conclusion, current evidence suggests that in rN0 necks routine END is not necessary and that in rN + necks with limited nodal recurrences SND or a SSND could be sufficient. [ABSTRACT FROM AUTHOR]

Patients who receive chemoradiotherapy or bioradiotherapy (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often experience high toxicity rates interfering with oral intake, causing tube feeding (TF) dependency. International guidelines recommend gastrostomy insertion when the expected use of TF exceeds 4 weeks. We aimed to develop and externally validate a prediction model to identify patients who need TF ≥ 4 weeks and would benefit from prophylactic gastrostomy insertion. A retrospective multicenter cohort study was performed in four tertiary head and neck cancer centers in the Netherlands. The prediction model was developed using data from University Medical Center Utrecht and the Netherlands Cancer Institute and externally validated using data from Maastricht University Medical Center and Radboud University Medical Center. The primary endpoint was TF dependency ≥4 weeks initiated during CRT/BRT or within 30 days after CRT/BRT completion. Potential predictors were extracted from electronic health records and radiotherapy dose–volume parameters were calculated. The developmental and validation cohort included 409 and 334 patients respectively. Multivariable analysis showed predictive value for pretreatment weight change, texture modified diet at baseline, ECOG performance status, tumor site, N classification, mean radiation dose to the contralateral parotid gland and oral cavity. The area under the receiver operating characteristics curve for this model was 0.73 and after external validation 0.62. Positive and negative predictive value for a risk of 90% or higher for TF dependency ≥4 weeks were 81.8% and 42.3% respectively. We developed and externally validated a prediction model to estimate TF-dependency ≥4 weeks in LAHNSCC patients treated with CRT/BRT. This model can be used to guide personalized decision-making on prophylactic gastrostomy insertion in clinical practice. [ABSTRACT FROM AUTHOR]

The Geriatric 8 (G8) has proven to be one of the most sensitive frailty-screening tools for older patients with cancer undergoing systemic treatment. In this study we validated whether the G8 is also suitable for identifying impairments in their comprehensive geriatric assessment (CGA) in older patients with cancer undergoing surgery. Thereby, we investigated the differences in postoperative outcomes between the fit and frail patients classified by the G8. Patients ≥70 years with a surgery indication because of a (suspected) malignant disease were prospectively enrolled. In all patients, a CGA was performed. The G8 results were assessed in parallel. The diagnostic value of the G8 was determined by comparing the result with the CGA as a reference test. Deficits in CGA was defined as ≥ two impairments of the CGA. Postoperative complications were retrospectively obtained from the medical record and compared between the fit and frail patients. In total, 143 patients were enrolled. The sensitivity, specificity, and negative predictive value of the G8 were 82% (95% CI 70–91), 63% (95% CI 52–73), and 85% (95% CI 75–91). In the patients with an impaired G8, a significantly prolonged hospital stay, higher rate of delirium, and higher 1-year mortality rate were seen. The G8 is a simple and useful screening tool for identifying deficits in CGA in older patients with cancer requiring surgery. Second, we concluded that patients with an impaired G8 are more at risk for a complicated recovery from surgery. [ABSTRACT FROM AUTHOR]

Patients with head and neck cancer (HNC) have a risk of sarcopenia which is associated with adverse health outcomes. Frailty is also associated with adverse outcomes and is diagnosed by a comprehensive geriatric assessment (CGA). Because a CGA is time-consuming and not all patients benefit from it, frailty screening questionnaires are used to select patients for CGA. Sarcopenia measurement may be a biomarker for frailty. Our objective was to examine the association between sarcopenia and a frailty screening questionnaire. In this single-center retrospective study, 150 patients (≥ 60-years old) with HNC were reviewed. Sarcopenia was defined as the combination of reduced handgrip strength and loss of skeletal muscle mass, calculated as skeletal muscle index (SMI), according to the EWGSOP-criteria. Frailty screening was performed using the Geriatrics 8 (G8) questionnaire. The 150 patients included 101 men and 49 women. Frail patients were more likely to be sarcopenic at diagnosis. G8 frailty score showed a significant though weak correlation with SMI. Univariate regression analysis with frailty as a dependent variable distinguished comorbidity score, handgrip strength, SMI, and sarcopenia as significant. These variables were subjected to a multivariate analysis in which comorbidity score and SMI remained significant. There is an association between sarcopenia and the G8 frailty screening questionnaire. Therefore, sarcopenia measurement could be interchangeable with the G8 frailty screening questionnaire. Further research should compare the gold standard for frailty, i.e. CGA, with sarcopenia. [ABSTRACT FROM AUTHOR]

Purpose: For planning of the surgical resection, computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used for the preoperative assessment of bone invasion of the maxilla. The purpose of this study was to compare the diagnostic test accuracy of CT and MRI for detecting bone invasion of the maxilla in patients with squamous cell carcinoma of the maxilla (MSCC).Materials and Methods: We conducted a retrospective cross-sectional study and enrolled a consecutive number of patients with primary MSCC between 2000 and 2017 who underwent either preoperative CT or MRI scans. The outcome variable was the absence or presence of bone invasion, with histopathologic examination of the resection specimen as the gold standard. The predictor variable was the imaging technique (CT and MRI). The imaging results on bone invasion were compared with the histopathologic results. Sensitivity and specificity were calculated, and the 2-sided Fisher exact test was used to calculate statistically significant differences between the unpaired CT and MRI results. Receiver operating characteristic curves were computed, and the area under the curve (AUC) was calculated.Results: The study included 72 patients (29 male and 43 female patients) with a mean age of 72 years. A total of 41 CT scans and 31 MRI scans were available. Histopathologic examination showed bone invasion in 45 cases: 26 of 41 patients with CT scans (63%) and 19 of 31 patients with MRI scans (61%). CT yielded 2 false-positive and 2 false-negative results, with a sensitivity of 92%, specificity of 87%, and AUC of 0.895. MRI yielded 5 false-positive and 2 false-negative results, with a sensitivity of 89%, specificity of 58%, and AUC of 0.739. No significant differences were observed for sensitivity (P > .999) and specificity (P = .185).Conclusions: In the absence of metallic dental restorations, CT could detect bone invasion more accurately than MRI in this study; however, the difference was not statistically significant. The imaging method of choice may depend on other situational factors. [ABSTRACT FROM AUTHOR]

Chemoradiation and bioradiation (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often comes with high toxicity rates, interfering with oral intake and leading to temporary tube feeding (TF) dependency. High-quality scientific evidence for indicators of prophylactic gastrostomy insertion is not available. The aim of this retrospective cohort study was to develop a prediction model to identify patients who need prophylactic gastrostomy insertion, defined as the expected use of TF for at least four weeks. Four-hundred-fifty LAHNSCC patients receiving CRT/BRT with curative intent between 2013 and 2016 were included in the study. Primary outcome was TF-dependency for four weeks or longer. Patient, tumor, and treatment characteristics were extracted from the medical records and their effects on the use of TF were analyzed using univariable and multivariable analysis. The prediction model was internally validated using bootstrapping techniques. Sixty-five percent (294/450 patients) required TF for four weeks or longer. Variables included in the model were: body mass index and adjusted diet at start of CRT/BRT, percentage weight change at baseline, World Health Organization performance status, tumor subsite, TNM-classification, CRT/BRT, mean radiation dose on the contralateral submandibular and parotid gland. The corrected Area Under the Curve after internal validation was 72.3%, indicating good discriminative properties of the prediction model. We developed and internally validated a prediction model that is intended to estimate TF-dependency for at least four weeks in LAHNSCC patients treated with CRT/BRT. This model can be used as a tool to support personalized decision making on prophylactic gastrostomy insertion. [ABSTRACT FROM AUTHOR]

In 1994 a decision analysis, based on the literature and utility ratings for outcome by a panel of experienced head and neck physicians, was presented which showed a threshold probability of occult metastases of 20% to recommend elective treatment of the neck. It was stated that recommendations for the management of the cN0 neck are not immutable and should be reconfigured to determine the optimal management based on different sets of underlying assumptions. Although much has changed and is published in the almost 25 years after its publication, up to date this figure is still mentioned in the context of decisions on treatment of the clinically negative (cN0) neck. Therefore, we critically reviewed the developments in diagnostics and therapy and modeling approaches in the context of decisions on treatment of the cN0 neck. However, the results of studies on treatment of the cN0 neck cannot be translated to other settings due to significant differences in relevant variables such as population, culture, diagnostic work-up, follow-up, costs, institutional preferences and other factors. Moreover, patients may have personal preferences and may weigh oncologic outcomes versus morbidity and quality of life differently. Therefore, instead of trying to establish "the" best strategy for the cN0 neck or "the" optimal cut-off point for elective neck treatment, the approach to optimize the management of the cN0 neck would be to develop and implement models and decision support systems that can serve to optimize choices depending on individual, institutional, population and other relevant variables. [ABSTRACT FROM AUTHOR]

Objectives: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is used for detection and (re)staging of prostate cancer. However, healthy salivary, seromucous, and lacrimal glands also have high PSMA-ligand uptake. This study aimed to describe physiologic PSMA-ligand uptake distribution characteristics in the head and neck to aid in PSMA PET/CT interpretation and to identify possible new clinical applications for PSMA-ligand imaging.Study Design: Thirty consecutive patients who underwent PSMA PET/CT for prostate cancer were evaluated. Tracer maximum standardized uptake values (SUVmax) in the salivary, seromucous, and lacrimal glands were determined visually and quantitatively. Overall and intraindividual variations were reported.Results: All gland locations had increased tracer uptake. The mean SUVmax ± standard deviation varied: parotid 12.3 ± 3.9; submandibular 11.7 ± 3.5; sublingual 4.5 ± 1.9; soft palate 2.4 ± 0.5; pharyngeal wall 4.3 ± 1.3; nasal mucosa 3.4 ± 0.9; supraglottic larynx 2.7 ± 0.7; and lacrimal 6.2 ± 2.2. The parotid had the largest overall variation in SUVmax (5.2-22.9), and the sublingual glands had the largest mean intraindividual difference (18.1%).Conclusions: Major and minor salivary and seromucous glands consistently have high PSMA-ligand uptake. Minor gland locations can be selectively visualized by this technique for the first time. This provides potential new applications such as quantification of present salivary gland tissues and individualization of radiotherapy for head and neck cancer or lutetium-177-PSMA radionuclide treatment. [ABSTRACT FROM AUTHOR]

Adequate treatment of lymph node metastases is essential for patients with head and neck squamous cell carcinoma (HNSCC). However, there is still no consensus on the optimal surgical treatment of the neck for patients with a clinically positive (cN+) neck. In this review, we analyzed current literature about the feasibility of selective neck dissection (SND) in surgically treated HNSCC patients with cN + neck using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. From the reviewed literature, it seems that SND is a valid option in patients with cN1 and selected cN2 neck disease (non-fixed nodes, absence of palpable metastases at level IV or V, or large volume ->3 cm-multiple lymph nodes at multiple levels). Adjuvant (chemo) radiotherapy is fundamental to achieve good control rates in pN2 cases. The use of SND instead a comprehensive neck dissection (CND) could result in reduced morbidity and better functional results. We conclude that SND could replace a CND without compromising oncologic efficacy in cN1 and cN2 cases with the above-mentioned characteristics. [ABSTRACT FROM AUTHOR]

Objective: The management of the clinically node negative (N0) neck in patients with squamous cell carcinoma of the maxilla (MSCC) is a matter of debate. In this retrospective cohort study the incidence of occult metastases is determined in clinically N0 MSCCs, as well as histopathological factors associated with occult metastases.Patients and Methods: 95 patients with clinically N0 MSCCs had maxillectomy. 18 patients with elective treatment of the neck were excluded. The remaining 77 patients followed a 'watch and wait' strategy for the neck and were included in this study. The incidence of occult metastases was calculated and Cox regression analysis was used to assess the predictive and prognostic value of clinical and histopathological parameters.Results: Occult metastases occurred in 14.3% (11/77) in the whole cohort and in 19.0% (11/58) in T2-T4 clinically N0 MSCC. Patients with T4 clinically N0 MSCC, showed the highest rate of occult metastases (24.1%). 45.5% of the occult metastases developed in the contralateral neck. The hazard ratio to develop occult metastasis was 5.39 (p=0.017) for perineural growth and 11.12 (p=0.003) for perivascular invasion. Salvage for cervical recurrence was poor at 40%.Conclusion: We recommend elective treatment of the neck or improved diagnostics to detect occult metastases in T2-T4 clinically N0 MSCC or when the biopsy specimen shows perineural growth or perivascular invasion. Since the contralateral neck was involved in 45.5% of the regional recurrences, we emphasize the importance of bilateral neck management. Improved diagnostics, like sentinel node biopsy, could possibly further reduce occult metastatic disease. [ABSTRACT FROM AUTHOR]

Objective: Assessment of the impact of a sentinel node biopsy (SNB)-based strategy in cT1/T2 N0 oral cancer on the course of health related quality of life, psychological distress, and shoulder disability, and evaluation of the patients' perspective on neck management strategies.Study Design: Fifty-two patients (39 SNB negative; 13 SNB positive) completed the European Organization for Research and Treatment of Cancer (EORTC) questionnaires-QLQ-C30 and QLQ-H&N35, and the HADS, IES, and SDQ questionnaires at baseline, after SNB diagnosis and at 6 months of follow-up. Objective shoulder measurements were performed after 2 years and interviews were conducted after 4.5 months of follow-up.Results: All the scores of the questionnaires were not significantly different between SNB negative and SNB positive patients. Objective shoulder functioning was similar. Most patients preferred a SNB-based strategy to an elective neck dissection strategy.Conclusions: The impact of a SNB-based strategy in patients with cT1/T2 N0 oral cancer is comparable for SNB-negative and SNB-positive patients in terms of health-related quality of life, psychological distress and shoulder functioning. Most patients preferred the SNB-based strategy over the elective neck dissection strategy. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study is to evaluate the efficacy of 18 F-FDG-PET as first-line diagnostic investigation, prior to performing a direct laryngoscopy with biopsy under general anesthesia, in patients suspected of recurrent laryngeal carcinoma after radiotherapy. Patients and methods 150 patients suspected of recurrent T2–4 laryngeal carcinoma at least two months after prior (chemo)radiotherapy with curative intent for resectable disease were randomized to direct laryngoscopy (CWU: conventional workup strategy) or to 18 F-FDG-PET only followed by direct laryngoscopy if PET was assessed ‘positive’ or ‘equivocal’ (PWU: PET based workup strategy), to compare the effectiveness of these strategies. Primary endpoint was the number of indications for direct laryngoscopies classified as unnecessary based on absence of recurrence, both on direct laryngoscopy and on six month follow up. Safety endpoints comprised resectability of recurrent lesions and completeness of surgical margins following salvage laryngectomy. Results Intention-to-treat analyses were performed on all randomized patients (CWU: n = 74, PWU: n = 76). Tumor recurrence was similar in both groups: 45 patients (30%; 21 CWU, 24 PWU) within six months. In 53 patients in the CWU arm (72%, 95% CI: 60–81) unnecessary direct laryngoscopies were performed compared to 22 in the PWU arm (29%, 95% CI: 19–40) ( p < 0·0001). The percentage of salvage laryngectomies (resectability) and positive surgical margins were similar between CWU and PWU (81%, 63% respectively, p = 0·17, and 29%, 7%, respectively, p = 0.20). The prevalence of the combination of local unresectability and positive margins is in the CWU group 24% and in the PWU group 8%. No difference ( p = 0.32) in disease specific survival between both groups was found. Conclusion In patients with suspected laryngeal carcinoma after radiotherapy, PET as the first diagnostic procedure can reduce the need for direct laryngoscopy by more than 50% without jeopardizing quality of treatment. [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]

Purpose: Due to the rarity and the variety of histological types of sinonasal cancers, there is a paucity of data regarding strategy for their optimal treatment. Generally, outcomes of advanced and higher grade tumors remain unsatisfactory, despite the employment of sophisticated surgical approaches, technical advances in radiation techniques and the use of heavy ion particles. In this context, we critically evaluated the role of systemic therapy as part of a multidisciplinary approach to locally advanced disease.Results: Induction chemotherapy has shown encouraging activity and could have a role in the multimodal treatment of patients with advanced sinonasal tumors. For epithelial tumors, the most frequently employed chemotherapy is cisplatin, in combination with either 5-fluorouracil, taxane, ifosfamide, or vincristine. Only limited experiences with concurrent chemoradiation exist with sinonasal cancer. The role of systemic treatment for each histological type (intestinal-type adenocarcinoma, sinonasal undifferentiated carcinoma, sinonasal neuroendocrine carcinoma, olfactory neuroblastoma, sinonasal primary mucosal melanoma, sarcoma) is discussed.Conclusions: The treatment of SNC requires a multimodal approach. Employment of systemic therapy for locally advanced disease could result in better outcomes, and optimize the therapeutic armamentarium. Further studies are needed to precisely define the role of systemic therapy and identify the optimal sequencing for its administration in relation to local therapies. [ABSTRACT FROM AUTHOR]

Summary The aim of this report is to describe the history of sentinel node biopsy in head and neck cancer. Sentinel node biopsy is a minimally invasive technique to select patients for treatment of metastatic lymph nodes in the neck. Although this procedure has only recently been accepted for early oral cancer, the first studies on visualization of the cervical lymphatic vessels were reported in the 1960s. In the 1980s mapping of lymphatic drainage from specific head and neck sites was introduced. Sentinel node biopsy was further developed in the 1990s and after validation in this century the procedure is routinely performed in early oral cancer in several head and neck centers. New techniques may improve the accuracy of sentinel node biopsy further, particularly in difficult subsites like the floor of mouth. [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]

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]

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]

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: Adult soft tissue sarcoma of the head and neck are rare and represent a heterogeneous group of tumours of different histological variants. Management of these neoplasms presents a great challenge. Malignant fibrous histiocytoma, fibrosarcoma, angiosarcoma and malignant peripheral nerve sheath tumour are the most frequently found sarcoma types in the head and neck. Although traditional morphological assessment is the foundation of clinical decision making, the role of immunohistochemistry and molecular biology are useful for diagnosis, prognosis and identification of possible targets for molecular therapy. The most frequently involved tumour sites are scalp/face, sinonasal tract/anterior skull base and parotid/neck. The management of soft tissue sarcomas in the head and neck is primarily surgical. Since it is difficult to obtain wide margins during surgical treatment in head and neck sarcomas, because of anatomic constraints, most patients undergo post-operative irradiation. Survival varies from 50 to 80%. Prognostic factors are tumour grade, margin status and tumour size. With further insight into the biology of soft tissue sarcoma, modern imaging techniques and new treatment options, we will most certainly be able to improve clinical outcome in patients with soft tissue sarcoma in the upcoming years. [ABSTRACT FROM AUTHOR]

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]

Summary: Accurate staging at the time of the diagnosis of head and neck squamous cell carcinoma (HNSCC) is critical for selection of the appropriate treatment strategy. Therefore, optimizing pre-treatment imaging in the diagnostic work-up is of great importance. CT and MRI are the corner stones of diagnostic work-up. Technical improvements will increase the value of these techniques even further. PET and PET-CT became a standard imaging techniques for HNSCC patients. It may be helpful for the detection of occult primary tumours, but its sensitivity for the detection of occult lymph node metastases is too low. Alternatively, the sentinel node procedure may be sufficiently accurate to avoid elective treatment of the neck. Screening for distant metastases should be performed only in HNSCC patients with high risk factors by FDG-PET-CT. [Copyright &y& Elsevier]

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]

Abstract: Background and purpose: Reports on shoulder function after non-surgical treatment are not available. In the present study shoulder morbidity after surgical and non-surgical treatment of the neck is determined and compared. Materials and methods: In 100 head and neck cancer patients 174 neck sides were treated by surgery (n =51) or (chemo)radiation (n =123). Abduction, anteflexion, endorotation and exorotation were assessed. Subjective measurements were performed using the Visual Analogue Scale for pain, the Shoulder Disability Questionnaire (SDQ) and stiffness reporting. Results: Predictive factors for SDQ-score>0 (n =54) were VAS pain score, stiffness, abduction, anteflexion, physiotherapy, low shoulder position and surgical treatment. The SDQ, stiffness and pain scores were significantly higher in the surgically treated group than in the non-surgical group (p <0.01). Anteflexion, abduction and exorotation were less impaired in the non-surgically treated group than in the surgically treated group (p <0.01). No differences between neck dissection and neck dissection with post-operative radiotherapy, and radiotherapy and chemoradiation were found for these movements. Conclusions: Shoulder morbidity is often present after non-surgical treatment of the neck, but to a lesser extent compared to surgical treatment. Radiotherapy adds no morbidity to neck dissection and chemotherapy does not add extra morbidity to primary radiation. [Copyright &y& Elsevier]

Summary: Background: Head and neck cancer (HNC) is the 5th most common cancer worldwide. As good locoregional tumor control can be achieved with current treatment strategies, patients who develop second primary tumors from field cancerization have poorer prognosis. Objectives: To determine if autofluorescence bronchoscopy (AF) played a role in the detection of second primary lung cancer (SPLC), and impact of SPLC on survival of patients with HNC and no cervical lymph node metastasis (N0). Methods: Patients with HNC(N0) referred for symptoms and/or radiology suspicious for lung cancer were assessed with AF. Data on patient demographics, smoking, cancer characteristics, and outcome were prospectively collected. Results: Fifty-one patients (44 males) with curatively treated HNC(N0) were evaluated. Median age was 70 years, all were current or former smokers of 35 pack years, and 25 had chronic obstructive lung disease. Over a median follow up of 60 months, 8 patients were diagnosed with synchronous and 26 with metachronous SPLC. Forty-two SPLC were found; 12 (29%) affected the tracheobronchial tree and 30 (71%) involved the lung parenchyma. Median time to metachronous SPLC was 22 months. Most of SPLC were surgically resectable. Five radiographically occult lung cancers detected by AF were successfully treated with endobronchial therapy. Lung cancer mortality was 24%. HNC patients who developed synchronous and metachronous SPLCs had significantly shorter survival (51 and 144 months) compared to those without (240 months) (p =0.0005). Conclusion: SPLC impacted negatively on the survival of patients with HNC. Close surveillance with AF and CT for SPLC combined with aggressive treatment of early stage lung cancer might be a strategy to improve outcome. [Copyright &y& Elsevier]

Summary: Hereditary retinoblastoma patients are at an increased risk for subsequent primary tumors after successful treatment for their initial cancer. Two mechanisms may be responsible for this increased incidence of second malignancies: genetic susceptibility (RB1 gene alterations) and induction by radiation that is frequently used as treatment for retinoblastoma. Because of the high cure rates obtained in the treatment of retinoblastoma, the risk of subsequent primary tumors is substantial, especially in the radiation field. We present four retinoblastoma survivors who developed multiple subsequent primary tumors. Two retinoblastoma survivors developed one and the other two patients two subsequent primary tumors. Despite extensive treatments two patients died of their second primary tumor in the head and neck region. The head and neck surgeon has an increasingly important role in the diagnosis and management of subsequent primary tumors in retinoblastoma survivors. [Copyright &y& Elsevier]

Abstract: Background and purpose: The aim of the study was to define the added value of whole body FDG-PET in screening for distant metastases in patients with head and neck squamous cell carcinoma and risk factors. Materials and methods: In a multi-center prospective study between 1998 and 2003, 145 consecutive HNSCC patients with risk factors for distant metastases underwent chest CT and whole body FDG-PET for screening of distant metastases. The data of 92 evaluable patients who developed distant metastases or who had a follow-up of at least 12 months were analyzed. Besides their performance in clinical practice, the operational characteristics of PET and CT using ROC analyses were investigated. Results: Pretreatment screening identified distant metastases in 19 patients (21%). FDG-PET had a higher sensitivity (53% vs. 37%) and positive predictive value (80% vs. 75%) than CT. The combination of CT and FDG-PET had the highest sensitivity (63%). The ROC analyses of the five point ordinal scales revealed that the “area under the curve” (AUC) of FDG-PET was significantly higher as compared to CT. Conclusion: In HNSCC patients with risk factors, pretreatment screening for distant metastases by chest CT is improved by FDG-PET. [Copyright &y& Elsevier]

Abstract: Background and purpose: Timely detection of recurrent laryngeal tumor after radiation is an important predictive factor for curation as well as preservation of laryngeal function. Direct laryngoscopy under general anesthesia with taking of biopsies is the standard diagnostic procedure to detect recurrence when suspicion is raised. This, however, is an invasive and potentially damaging technique. Hence, a non-invasive diagnostic procedure, such as 18FDG-PET to stratify patients for direct laryngoscopy could be useful. 18FDG-PET is interpreted visually so that observer variation may affect clinical practice. In the present study, we therefore investigated this aspect of reproducibility. Patients and methods: Thirty consecutive patients suspected of recurrent laryngeal carcinoma after radiotherapy underwent 18FDG-PET and direct laryngoscopy under general anesthesia with taking of biopsies. 18FDG-PET scans were reported by nine nuclear medicine physicians and residents, using a three-point scaling system. The reference was the absence or appearance of a local recurrence in the 12 months following 18FDG-PET. Results: Eight patients had biopsy proven recurrent laryngeal carcinoma. Sensitivity of 18FDG-PET was 88% (95% CI 53–98%) and specificity was 82% (95% CI 62–93%). The observers had a moderate to reasonable agreement (weighted kappa 0.45 (95% CI 0.20–0.69)) vs. the clinical gold standard and interobserver kappa was 0.54 (95% CI 0.40–0.69). Conclusion: 18FDG-PET seems to be a promising technique to detect recurrent laryngeal carcinoma after radiotherapy, and selecting patients for direct laryngoscopy. This will avoid futile invasive procedures. Interobserver agreement and variability is reasonable using this technique, but training is necessary. Studies comparing different strategies to select patients for direct laryngoscopy in case of suspected recurrence are warranted. [Copyright &y& Elsevier]

Abstract: The RELAPS study (REcurrent LAryngeal carcinoma PET Study) was designed to determine whether FDG–PET is of value in the selection of patients for direct laryngoscopy under general anesthesia in patients with suspicion of recurrent laryngeal carcinoma after radiotherapy. In a randomized controlled clinical trial the current diagnostic practice, i.e. all patients undergo direct laryngoscopy, will be compared to a strategy in which FDG–PET selects the patients for laryngoscopy. All eight head and neck cancer centers of the Dutch Head and Neck Oncology Cooperative Group NWHHT will participate in this multicenter trial. The study population consists of patients with clinical suspicion of recurrent T2–T4 laryngeal carcinoma after radiotherapy (without obvious signs of tumor) in whom a direct laryngoscopy under general anesthesia with taking of biopsies is indicated by the local physician. The primary efficacy endpoint is the difference in the number of futile indications for direct laryngoscopy between the conventional diagnostic arm and the FDG–PET based diagnostic arm. An indication for laryngoscopy is classified as futile if this laryngoscopy was negative and no recurrence was diagnosed within 6 months follow-up (gold standard). The FDG–PET based strategy may increase the risk of missing recurrent tumor compared to current practice. Safety endpoints include survival and morbidity due to laryngoscopy with taking of biopsies. Survival rates of both groups will have to be collected outside the time frame of the funded trial. Resectability of recurrent tumor and tumor negative surgical margins after total laryngectomy will be used as proxy endpoints. The trial will also compare quality of life and direct medical costs between both arms. [Copyright &y& Elsevier]

Summary: Adult soft tissue sarcomas of the head and neck are rare and consist of a variety of histopathological subtypes and sites. The purpose of this study was to review patients treated for adult soft tissue sarcomas of the head and neck at our institute. The medical records of 41 adult patients treated for head and neck soft tissue sarcomas between 1983 and 2004 were reviewed. Thirty-six tumours were histologically reviewed. Histopathological revision showed that 7% of the original sarcomas were found not to be sarcomas and 39% of the sarcoma subtypes changed. Multivariate analysis showed that surgical margin status and lymph node metastases are the most important prognostic factors. Review of histopathological examination of tumours showed a change in subtype in a substantial number of head and neck sarcomas. Negative surgical margins are an important prognostic factor, but are difficult to obtain in head and neck sarcomas. [Copyright &y& Elsevier]

The free radial forearm flap is the most frequently used free flap for head and neck reconstructions. Survival of free flaps is dependent on adequate blood supply. A 69-year old woman was scheduled for excision of a T3N0M0 oropharyngeal carcinoma, neck dissections and reconstruction with a free vascularized radial forearm flap. During the operation it appeared that the entire radial artery was almost completely obstructed by atherosclerotic plaques precluding microvascular anastomosis. Despite systemic risk factors certain artery types are more prone to develop clinically manifest atherosclerosis. There are no reports on the pathology of the radial artery in free flap reconstructions. In head and neck cancer patients severe atherosclerosis of the radial artery is very rare, but if present makes free radial forearm flap reconstruction impossible. Therefore, in patients with risk factors for peripheral vascular disease screening for radial artery stenosis should be considered. [Copyright &y& Elsevier]

A 74-year-old man presented with a small locoregional, histopathologically proven, fluorodeoxyglucose positron emission tomography/computed tomography-avid recurrence of follicular thyroid carcinoma in the left subglottic space after extensive surgical resection, adjuvant radioactive iodine therapy, and external beam radiation therapy. Because all established focal therapies were contraindicated, percutaneous irreversible electroporation was performed without complications. Follow-up imaging at 7 months showed a small ablation scar without signs for residual vital tumor tissue. Irreversible electroporation may be a viable treatment option for selected cases of recurring head and neck tumors that are unsuitable for other local treatments. [ABSTRACT FROM AUTHOR]

B Background: b Reliable identification of lymph node (LN) metastases is one of the most important prognostic factors to stratify the treatment in oral cancer (OC). This pilot study identifies LN metastases in OC patients using a magnetic approach for sentinel lymph node biopsy (SLNB) procedure. A total of 26 SLN were pathologically evaluated (8 LN in 0.4ml, and 18 in 0.8ml dose group), and yielded three patients with a metastatic LN (3/26 LN in total). [Extracted from the article]

Summary: Second primary tumours in patients treated for oral cancer occur at a rate of 3% to 7% per year. The majority of these tumours show up at least six months after the detection of the primary and are often located in the upper aerodigestive tract. Cessation of smoking habits may reduce the risk of the development of a second primary. There is no statistical significance between the oral subsite of the primary and the occurence of a second primary. There are conflicting views in the literature on the survival rate of patients treated for a second primary in the head and neck region. [Copyright &y& Elsevier]

The purpose of this study was to review the outcomes of the different therapies for extracranial head and neck arteriovenous malformations (AVMs). AVMs are high-flow congenital vascular anomalies. They are composed of a complex system of vessels directly connecting feeding arteries to draining veins forming a nidus. They may be potentially life-threatening due to progressive symptoms and infiltrative disease. Extracranial AVMs most commonly affect the head and neck area (47.4%) followed by the extremities (28.5%). AVMs are best characterized as being either focal or diffuse. Focal AVMs have good outcomes following adequate treatment. Diffuse lesions have multiple feeding vessel, which results in high rates of recurrence despite treatment. The management of AVMs includes conventional surgery and endovascular techniques. A combination of embolization and surgical resection has become the treatment of choice over the last years. The main goal of both forms of treatment being the complete blockage or resection of the nidus. Transcatheter embolization of vessels has evolved over the years and new embolic agents have emerged. The types of materials available for embolization are classified into mechanical devices, liquid agents and particulates. Efficacy, rate of recurrence and most common complications were evaluated. AVMs recurrence after embolization or resection is reported in up to 80% of cases. Incomplete resection and embolization can induce aggressive growth of the remaining nidus and the risk of progression is up to 50% within the first 5 years and recurrences can occur up to 10 years later. Although ethanol seems to be associated with the highest degree of cure and permanent occlusion, the overall complication rate reported was 48%. Other materials, such as cyanoacrylate, have obtained modest rates of complete remission, while the reported rates of complete regression of AVMs with Fibrin glue and Polyvinyl alcohol are above 50%. At present, there are no unified agreement on the ideal embolic agent. Therefore, a multidisciplinary approach is recommended to support decision making about the best therapeutic approach and to achieve optimal outcome. A long-term post-treatment follow-up is recommended to recognize early recurrence. [ABSTRACT FROM AUTHOR]

Objective: Diagnosing residual malignancy after (chemo)radiotherapy presents a diagnostic challenge because of overlapping symptoms and imaging characteristics. We assessed the added diagnostic value of diffusion-weighted imaging (DWI) to positron emission tomography combined with computed tomography (PET-CT) in patients with head and neck squamous cell carcinoma (HNSCC) with residual fluorodeoxyglucose (18F-FDG) uptake at the primary tumor site 3 months after (chemo)radiotherapy.Study Design: For this retrospective study from January 2010 to June 2012, 22 cases (median patient age of 61 years; range 41-77 years) were included for analysis. Both PET-CT and magnetic resonance imaging (MRI), including DWI, were performed as part of the institutional protocol and were qualitatively assessed for the presence of residual malignancy at the primary tumor site.Results: The sensitivity and specificity of PET-CT were 100% and 47%, respectively. For DWI, sensitivity and specificity were 80% and 82%, respectively. When DWI was added to PET-CT with residual 18F-FDG uptake, and only a positive read on both PET-CT and DWI was considered to be overall positive, sensitivity remained 80% (95% confidence interval [CI] 28%-99%), and specificity was 88% (95% CI 64%-99%).Conclusions: In this pilot study of the selected patients with residual 18F-FDG uptake at the primary tumor site 3 months after (chemo)radiotherapy, we demonstrated that the addition of DWI to PET-CT has the potential to increase the specificity of the response evaluation with limited decrease in sensitivity. [ABSTRACT FROM AUTHOR]

The preferred treatment for oral squamous cell carcinoma is complete surgical tumour resection to achieve local-regional control. [1] Complete surgical removal requires an adequate resection margin of at least 5 mm of healthy tissue around the tumour. Unfortunately, international literature reports 30% to 85% inadequate resection margins (i.e., positive and close margins). [2] This study aims to investigate whether adequate tongue cancer resection margins can accurately be determined using ex-vivo high-field magnetic resonance imaging (MRI). This proposed technique could help improve the localisation of inadequate margins during surgery. Nine fresh resection specimens of tongue cancer patients were scanned with a small-bore 7 Tesla (7T) MRI scanner (Biospec 70/20, Bruker, Ettlingen, Germany) interfaced with a Philips console. For each resection specimen, four MRI scans were obtained: a 3D T2-weighted (T2W) Turbo Spin Echo (TSE) scan with an isotropic voxel size of 0.3 mm3 and three orthogonal multi-slice T2W TSE scans with an in-plane resolution of 0.125 mm2 and a slice thickness of 1 mm. After completion of the MR protocol, the resection specimens were processed according to routine clinical histopathological workup. The tumour was delineated by a histopathologist (HP) on the hematoxylin and eosin (HE) stained histopathological slices and by two independent radiologists (R1 and R2) on the coronal multi-slice MR scan. For each patient, a 3D representation of the resection specimen was created using the following three steps: 1) For each HE-slice, the MR-slice with the highest resemblance was found by visual inspection (Fig. 1A, 1B). 2) These corresponding slices were registered using point-based registration based on visual corresponding anatomical points (e.g., specimen contour, tumour-protrusions, mucosa) (Fig. 1C). 3) The registered HE-slices were digitally stacked to create a 3D-specimen of all HE-slices (Fig. 1D). This method to create the 3D-specimen was previously discussed and used in the work by Caldas-Magalhaes et al. [3] The delineated tumour created by the radiologists (tR1 and tR2) and histopathologist (tHP) were interpolated and mapped to the other MRI-scans (i.e., sagittal, axial, and 3D TSE scan) (Fig. 1D). The accuracy of the inadequate margin detection by R1 and R2 was determined using two different methods. First, the minimal resection margins in all five directions (anterior, posterior, craniomedial, caudolateral and central) were measured based on tR1 and tR2 and compared to the measurements reported by the HP. Second, the 95th percentile Hausdorff distance (HD95) of the overestimation (O-HD 95) and underestimation (U-HD 95) of tR1 and tR2 was calculated with respect to the ground truth (tHP) in all five directions. The relationship between the measured resection margins based on tR1, tR2 and tHP was evaluated using Pearson's correlation coefficient (PCC). Only the craniomedial, caudolateral, and central resection margins were included in the PCC analysis. [Display omitted] According to the histological report, one of the nine resection specimens was adequately resected. Based on the in-plane measurements, R1 and R2 were able to accurately determine which tumours were (in)adequately removed in 7/9 and 8/9 cases. Two of these cases were inadequate but considered adequate by the radiologists, and the other case was determined inadequate by R1 but adequate according to the HP. All these three incorrect cases had a T-stage of 1. Based on the tumour segmentation, the sensitivity and specificity of the detection of inadequate margins with respect to the final histopathological report were 77% and 50% for R1 and 65% and 57% for R2, respectively. The median U-HD95 and O-HD95 for R1 were 0.9 mm (range: 0.0-1.7 mm) and 2.5 mm (range: 0.6-11.8 mm). For R2, the median U-HD95 and O-HD95 were 0.5 mm (range: 0.3-5.3 mm) and 2.5 mm (range: 1.2-6.6 mm). [Display omitted] The PCC of the measured margins between the HP and two radiologists was 0.67 and 0.71 for R1 and R2, respectively. Between both radiologists, the PCC of the measured margins was 0.75. Figure 2 shows an example of a 3D-specimen and the corresponding MRI-slices. Ex-vivo 7T MRI enables accurate margin predictions for tongue cancer resection specimens. The radiologists' assessment of in- and adequate resections based on ex-vivo 7T MRI generally aligns with the histopathology reports. The sensitivity of both radiologists for adequate margin detection is reasonable. However, the specificity is low, which might be caused by the radiologists' overestimation of the tumour on ex-vivo 7T MRI. This study offers a proof of principle for future studies to validate and further improve the detection of inadequate margins for oral cavity resection specimens using ex-vivo 7T MRI. This technique could provide guidance for surgeons to localise inadequate margins and enable them to perform accurate re-resections during surgery. [ABSTRACT FROM AUTHOR]

Background: Loco-regional treatment failure after radiotherapy with or without chemotherapy and/or prior surgery represents a significant portion of head and neck cancer patients. Due to a wide array of biological interactions, these patients have a significantly increased risk of complications related to wound healing.Methods: Review of the current literature was performed for wound healing pathophysiology, head and neck salvage surgery, and wound therapy.Results: The biology of altered wound healing in the face of previous surgery and chemoradiotherapy is well described in the literature. This is reflected in multiple clinical studies demonstrating increased rates of wound healing complications in salvage surgery, most commonly in the context of previous irradiation. Despite these disadvantages, multiple studies have described strategies to optimize healing outcomes. The literature supports preoperative optimization of known wound healing factors, adjunctive wound care modalities, and microvascular free tissue transfer for salvage surgery defects and wounds.Conclusion: Previously treated head and neck patients requiring salvage surgery have had a variety of disadvantages related to wound healing. Recognition and treatment of these factors can help to reverse adverse tissue conditions. A well-informed approach to salvage surgery with utilization of free vascularized or pedicled tissue transfer as well as optimizing wound healing factors is essential to obtaining favorable outcomes. [ABSTRACT FROM AUTHOR]