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Background To explore variation in numbers and treatment between hospitals that treat head and neck cancer (HNC) in the Netherlands. Material and methods Patient, tumor and treatment characteristics were collected from the Netherlands Cancer Registry, while histopathological features were obtained by linkage to the national pathology record register PALGA. Inter-hospital variation in volume, stage, treatment, pathologically confirmed loco-regional recurrence and overall survival rate was evaluated by tumor site. Results In total, 2094 newly diagnosed patients were included, ranging from 65 to 417 patients in participating hospitals treating HNC in 2008. Oral cavity cancer was mainly treated by surgery only, ranging from 46 to 82% per hospital, while the proportion of surgery with (chemo)radiotherapy ranged from 18 to 40%. Increasing age, male sex, and high stage were associated with a higher hazard of dying. In oropharynx cancer, the use of (chemo)radiotherapy varied from 31 to 82% between hospitals. We found an indication that higher volume was associated with a lower overall hazard of dying for the total group, but not by subsite. Low numbers, e.g. for salivary gland, nasopharynx, nasal cavity and paranasal sinus, did not permit all desired analyses. Conclusion This study revealed significant interhospital variation in numbers and treatment of especially oropharyngeal and oral cavity cancer. This study is limited because we had to rely on data recorded in the past for a different purpose. To understand whether this variation is unwanted, future research should be based on prospectively collected data, including detailed information on recurrences, additional case-mix information and cause of death. [ABSTRACT FROM AUTHOR]

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Abstract: Our aim was to develop a dynamic virtual model of the oral cavity and oropharynx so that we could incorporate patient-specific factors into the prediction of functional loss after advanced resections for oral cancer. After a virtual resection, functional consequences can be assessed, and a more substantiated decision about treatment can be made. In this study we used a finite element model of the tongue, which can be implemented in the total virtual environment in the future. We analysed the movements and changes in volume, and the effects of changes in the material variables, to mimic scar tissue. The observed movements were in accordance with descriptions of in vivo movements. Affected movements caused by the mimicked scar tissue were also similar to expectations. Some changes in volume were measured, particularly in individual elements. We have taken the first steps in the development of a finite element model of the tongue. Now, refinement is necessary to make the model suitable for future use in virtual surgery. [Copyright &y& Elsevier]

Abstract: Maxillectomy defects can be reconstructed by a prosthetic obturator or (free) flap transfer, but there is no consensus about the optimal method. This study evaluated 32 maxillectomy patients with prosthetic obturation regarding function (mastication, subjective oral and swallowing complaints and maximal mouth opening). Outcomes were related to the extent of the resection (Brown maxillectomy classification), dentition and history of adjuvant radiotherapy. Maxillectomy defects ranged from 2-1 to 4B on the Brown classification, and most had a defect graded as 2-A or 2-B. Mean mixing ability test after 10 chewing strokes was 24.2 and after 20 chewing strokes 19.7, which compares to edentulous healthy individuals. None of the outcomes was influenced by Brown classification. Radiotherapy negatively influenced mean maximal mouth opening (29.1mm versus 40.9mm, p =0.017) and subjective outcomes. Edentate obturated patients had worse outcomes than dentate patients, measured by mixing ability test and questionnaire. In conclusion, mastication after obturator reconstruction of a maxillectomy defect is comparable to mastication with full dentures. Size of the maxillectomy defect did not significantly influence functional outcome, but adjuvant radiotherapy resulted in worse mouth opening and self-reported oral and swallowing problems. Residual dentition had a positive influence on mastication and subjective outcomes. [Copyright &y& Elsevier]

Abstract: Aim: Description of an alternative surgical approach to the posterolateral maxillary and pterygoid region. Patients and method: Three patients with posterior maxillary/pterygoid lesions are described in whom a lower cheek flap was used to achieve optimal surgical exposure. After midline division of the soft tissues of the lower lip and chin, the incision is extended posteriorly in the inferior gingivobuccal sulcus and continued lateral from the retromolar trigone in the upward direction lateral from the maxillary tuberosity. The flap is elevated under the periosteum towards the angle of the mandible with detachment of the masseter muscle. By marginal resection of the anterior part of the ascending mandible, visualisation of the posterolateral maxillary and pterygoid region can be optimalized. Conclusion: As compared to the transoral approach, the lower cheek flap creates an optimal surgical exposure of the posterolateral maxillary sinus wall and pterygoid plates and should be considered for maxillary lesions extending into the pterygoid plate and pterygoid muscles. [Copyright &y& Elsevier]

Abstract: Aims: The aims of this study were to retrospectively evaluate incidence and patterns of lymph node metastases, surgical treatment and prognostic factors of medullary thyroid carcinoma. Methods: Out of a group of 70 MTC patients data of 67 patients were collected. Sixty-two of these patients underwent surgery. Apart from thyroidectomy, 16 patients underwent a bilateral neck dissection, 21 a unilateral neck dissection and 29 a paratracheal dissection or node-picking operation. Thirty-six patients were irradiated, of which 31 postoperatively and five with palliative intent. Results: Lymph node metastases were found in 91% of the ipsilateral neck dissection specimens, 91% of the paratracheal dissections and 63% of the contralateral dissections. Of the 12 elective neck dissections, 5 were tumor positive. Level VI was positive in 91% of the cases where a dissection was done, whereas preoperatively only 16% were scored tumor positive. During follow-up 22 of the 67 patients developed one or more locoregional recurrences (in total 28 recurrences). The most important factors that were correlated with a worse prognosis of survival were late stage of disease (stage III and IV) (p =0.0014), high number of positive lymph nodes (p =0.0023) and incomplete surgical resection (p =0.0002). Conclusions: The high rate of locoregional recurrences in this study are a strong argument for a more aggressive approach to the primary and neck. A routine central and ipsilateral selective neck dissection of levels II–V should be considered in all MTC patients based on the high incidence of metastases and the relative low morbidity of a unilateral neck dissection. Patients referred after thyroidectomy alone with elevated (stimulated) calcitonin levels should be re-operated, performing an elective or therapeutic central and unilateral neck dissection. [Copyright &y& Elsevier]

Summary: Cisplatin is one of the most commonly used cytotoxic agents. Ototoxicity is an important and dose-limiting side-effect of cisplatin therapy. It is believed that cisplatin suppresses the formation of endogenous anti-oxidants that normally prevent the inner ear against reactive oxygen species (ROS). These ROS affect the outer hair cells (OHCs) in the organ of Corti. Results from clinical trials with amifostine, an anti-oxidant with possible otoprotective action during cisplatin therapy, were disappointing. A variety of agents with chemoprotective action against cisplatin-induced ototoxicity were successfully tested in animal models. It is important to translate these promising results from animal models into clinical practice. The possible routes of administration are systemic and transtympanic. An important condition when using such an agent systemically is that the compound may not affect the anti-tumor effect of cisplatin. The critical step at transtympanic administration is the diffusion of the compound through the round window membrane (RWM). This diffusion depends on the characteristics of the medication as on the properties of the RWM. Positive results of an otoprotector in clinical practice may increase the effectiveness of cisplatin therapy and can improve the quality of life for a large group of patients. [Copyright &y& Elsevier]

Abstract: Aim: Description of a systematic approach to the neck for removal of lymph node bearing tissues in levels I–V. Method: A (modified) radical neck dissection is divided in three steps: (1) Dissection of levels I–IV, (2) dissection of level V and (3) transection of SCM bar and finalisation of the dissection. The sternocleidomastoid muscle (SCM) is used as a ‘bar’, around which the different neck levels can be systematically unwrapped, warranting permanent cranio-caudal tension of the neck specimen, while anatomical relations remain intact. Results: In a group of 115 (modified) radical en bloc neck dissections with or without post-operative radiotherapy 10% regional recurrences, 2% post-operative chylous fistulas and <5% post-operative wound infections occurred. The overall 5 years survival was 45% (95% confidence interval: 36–54%). Conclusion: A systematic unwrapping of lymph node levels around the sternocleidomastoid bar provides a reliable systematic method for performing (modified) radical neck dissections without a negative influence on clinical outcome. [Copyright &y& Elsevier]

• Locally advanced head and neck cancer is defined in various ways. • Netherlands Cancer Registry data show an increase of locally advanced oral and oropharynx cancer. • Standardized rates of locally advanced hypopharynx and larynx cancer have declined recent years. • The proportionate share of locally advanced larynx cancer has increased. • There is an urgent need for standardization of the definition locally advanced head and neck cancer. Several reports have indicated that locally advanced head and neck cancer (LAHNC) has increased in the past decade. However, incidence trends cannot be easily compared because slightly different definitions of LAHNC were used. To investigate if the incidence of locally advanced disease (LAD) in the oral cavity, oropharynx, hypopharynx and larynx is indeed increasing over time, considering the growing and ageing population in the Netherlands. Data were obtained from the Netherlands Cancer Registry (NCR). Primary head and neck squamous cell carcinomas of the oral cavity, oropharynx, hypopharynx and larynx diagnosed between 1989 and 2017 were included. Yearly numbers and European standardized incidence rates (ESRs) were reported by extent of disease. The annual percentage change (APC) over time in ESRs was calculated to assess trends. Absolute numbers and ESRs of LAD increased over time for oral cavity and most prominently for oropharynx carcinomas (before 1996, APC: 0.4, 95%CI: 0.1; 0.8 and APC: 5.7 (95%CI: 3.1; 8.4) after 1996: 1.5 (1.0; 2.0) respectively. For hypopharynx cancer the absolute number and ESR of LAD increased until 1997 and declined with 0.8% per year since 1997. Absolute numbers of patients with larynx cancer stayed stable over time, while ESR decreased (APC: −0.8 (95%CI: −1.1; −0.6)). The perception of an increasing trend in LAD in the Netherlands can be attributed to the increasing incidence of oral cavity and oropharynx carcinomas. For LAD of the hypopharynx a decreasing trend was observed. In larynx cancer, the proportional share of LAD of the larynx increased, even though incidence rates declined. [ABSTRACT FROM AUTHOR]

Introduction: Whereas salivary gland pleomorphic adenoma (SGPA) is the most common type of salivary gland tumor, little is known about its epidemiology because national cancer registries do not register this disease.Objectives: To establish SGPA incidence trends, rates of secondary malignant transformation and recurrence and associated factors in the Netherlands.Materials and Methods: Data on incidence, epidemiology, secondary malignant transformation and recurrence were retrieved from the Dutch pathology registry (PALGA) for the years 1992, 1997, 2002, 2007, and 2012. Multivariate analysis was performed to discover the risk factors for recurrence.Results: 3506 cases of SGPA were recorded implying an overall European standardized rate of 4.2-4.9 per 100,000 person-years. Our figures showed a female preponderance (1:1.43) with an annual 1% rise in female incidence (95% confidence interval [CI]: 0.2-1.8) and a bimodal age distribution in women (p<0.0001). The overall 20-year recurrence rate was 6.7%, and median time to first recurrence was 7years. Positive and uncertain resection margins and younger age at diagnosis were risk factors for recurrence, with odds ratios (ORs) of 4.62 (95%CI 2.84-7.51), 4.08 (95%CI 2.24-7.43), and 0.42 (95%CI 0.29-0.63) respectively. Tumor locations in the minor salivary glands had lower odds of recurrence than tumors in the parotid (OR 0.24; 95% CI: 0.07-0.77; p<0.016). Malignant transformation occurred in 0.15% of SGPAs (3.2% of recurrences).Conclusion: This first nationwide study clearly showed sex differences in SGPA epidemiology, possibly suggesting some underlying hormonal mechanism. Long-term recurrence risks were low, and secondary malignant transformation risks were very low. [ABSTRACT FROM AUTHOR]

Purpose Head and neck rhabdomyosarcoma (HNRMS) survivors are at increased risk of developing pituitary dysfunction as an adverse event of radiotherapy. Our aim was to investigate the frequency and risk factors for pituitary dysfunction in these survivors. Secondly, we aimed to compare the prevalence of pituitary dysfunction between survivors treated with external beam radiation therapy (EBRT) and survivors treated with the ablative surgery, moulage technique after loading brachytherapy, and surgical reconstruction (AMORE) procedure. Methods Eighty HNRMS survivors treated in London (EBRT based) and Amsterdam (AMORE based: AMORE if feasible, otherwise EBRT) in the period 1990–2010 and alive ≥2 years post-treatment were evaluated. Survivors were evaluated in multidisciplinary late-effects clinics, with measurement of linear growth, determination of thyroid function, and growth hormone parameters. Additional data, such as baseline characteristics, anthropometrics, pubertal stage, and the results of additional laboratory investigations, were retrieved from patient charts. Results Pituitary dysfunction was diagnosed in 24 in 80 (30%) survivors, after a median follow-up time of 11 years. Median time to develop pituitary dysfunction after HNRMS diagnosis was 3.0 years. Risk factors were EBRT-based therapy (odds ratio [OR] 2.06; 95% confidence interval [CI] 1.79–2.46), parameningeal tumour site (OR 1.83; 95% CI 1.60–2.17) and embryonal RMS histology (OR 1.49; 95% CI 1.19–1.90). Conclusions Radiotherapy used for the treatment of HNRMS confers a significant risk of the development of pituitary dysfunction. AMORE-based treatment in children with HNRMS resulted in less pituitary dysfunction than treatment with conventional EBRT. Our findings underscore the importance of routine early endocrine follow-up in this specific population. [ABSTRACT FROM AUTHOR]

Purpose: To assess cause-specific mortality in a large population-based cohort of 14,393 patients treated for squamous cell carcinoma of the oral cavity (OC) or oropharynx (OP) in The Netherlands between 1989 and 2006.Patients and Methods: Causes of death were obtained for 94.7% of 9620 patients who had died up to January 1, 2009. We assessed standardized mortality ratios (SMR) and absolute excess mortality (AEM), comparing observed cause-specific mortality with expected mortality for our cohort based on general population mortality rates.Results: Median survival was 3.9 years. Overall, the study population experienced a 6-fold higher (95% Confidence Interval (95% CI) 5.9-6.1) mortality risk compared with the general population. After three years, 41% of OP and 29% of OC patients had died due to cancer of the oral cavity and pharynx. Additionally, OC and OP patients experienced high excess mortality from esophageal (SMR 10.6 and 17.9) and lung cancer (SMR 4.6 and 6.3). With regard to non-cancer deaths, the highest AEMs were due to diseases of the circulatory system, with OC patients experiencing an AEM of 11.3 per 10,000 person-years for ischemic heart disease. OP patients experienced excess mortality due to pneumonia (AEM 22.1 per 10,000 person-years). The risk of death due to diseases of the digestive system was for OP and OC patients where about equal (AEM 28.7 and 23.80, respectively). The SMR for death due to pneumonia was more than two times higher (4.4 vs. 1.7) for OP patients than for OC patients (P<0.001). From 15 years after diagnosis, second tumors located outside the head and neck region accounted for most of the excess mortality.Conclusions: Excess mortality in OC and OP patients appears to be dominated by effects of heavy tobacco and alcohol use with high AEM due to second tumors, respiratory, cardiovascular and gastrointestinal diseases. Patients with OP experienced more than two times higher risk of death due to pneumonia than OC patients. Therefore, awareness of this potential complication should be raised along with development of prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Several recent studies have shown that incidence of oropharyngeal carcinomas is rising in the Western World. This increase has been attributed to changes in the etiology of oropharyngeal carcinomas with a growing role for infections with Human Papilloma viruses. This nationwide study evaluates and compares trends in incidence, clinical behavior and tumor characteristics of oropharyngeal and oral squamous cell cancer.Methods: This study comprised all 16,480 patients with primary squamous cell carcinoma of the oral tongue (OTSCC), oral cavity excluding oral tongue (OCSCC), and oropharynx (OPSCC) diagnosed from 1989 through 2008 in The Netherlands. We assessed trends in age-standardized incidence, second cancer risk and subsite specific relative survival (RS) over time.Results: Incidence of OTSCC and OPSCC in males and incidence of all subsites in females increased significantly from 1989 through 2008. In males increases in incidence were largely restricted to the 50-64 year age group (estimated annual percentage change 2.2% and 3.2% for OTSCC and OPSCC, respectively), while in females incidence increased for most age groups. The incidence of OCSCC (excl. oral tongue) and OPSCC before 50 years of age decreased. Patients with OPSCC showed the poorest prognosis with a relative survival of 41.6% after 5 years and 29.4% after 10 years (P<0.001) over the entire period 1989-2008. However survival increased substantially for OPSCC patients over time (5-year RS of 37.2% in 1989-1993 to 47.6% in 2004-2008, P<0.001).Conclusion: Although incidence of OPSCC did increase since 1989, especially in females, similar increases were seen for OCSCC (excl. oral tongue) and OTSCC. Our study does not appear to support that HPV is the main contributor to a rising incidence of OPSCC as the effects of changes in smoking and alcohol use cannot be discounted. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Recent studies suggest that lymph node ratio (LNR) is a strong prognostic factor in head and neck cancer. This study aims to determine if the yield of harvested lymph nodes (LNs) influences the LNR. Methods: The study included 522 head and neck cancer patients, undergoing 638 primary and salvage (selective) neck dissections between 2002 and 2012. Before 2007 the neck dissection specimens were macroscopically and microscopically examined by pathologists and after 2007 the macroscopic examination was performed by pathology technicians. For comparison of mean LN yields, univariate and multivariate analyses were performed. Results: The mean number of LNs among 374 specimens examined by pathologists was 24 (range 0–89) vs. 32 (range 2–89) among 264 specimens examined by pathology technicians (P <.001). This caused the mean LNR in the non pre-treated patient group to drop from 11.4% to 8.7%. The counts of LNs per type of neck dissection were significantly different and increased with the number of levels involved. However, there was no linear relationship and the higher yields could be mostly ascribed to LNs in level V. The LNR varied from 8.1% to 18.4% among the different types of neck dissections. Conclusions: A significant increase in the number of harvested LNs, but a decrease in LNR was observed after introducing pathology technicians for macroscopic examination. A clear association between the extent of the dissection and the number of harvested LNs was observed. LNR appears to be strongly dependent on the harvesting protocol and the extent of the dissection. [Copyright &y& Elsevier]

Summary: This systematic review addresses the prognostic significance of neck node volume in head and neck cancer. Primary tumor volume evolved as an independent significant factor for survival in head and neck cancer patients. Besides primary tumor volume, multiple prognostic features related to the regional lymph nodes were studied in literature. In literature, some authors showed the significance of total tumor volume/nodal volume for survival and loco-regional control. Articles reporting prognosis and survival in nodal tumor volumes were collected by systematically reviewing publications listed in the Pubmed and Embase databases. Publications were included when they at least reported on total tumor volume (TTV) or nodal volume and survival. In this systematic review we studied 21 articles. For measurement of nodal volume different formulas were used. Until now, there’s no clear statistical evidence for the use of either TTV or nodal volume versus primary tumor volume to predict the individual loco-regional control or survival after treatment. There is wide variety of tumor measuring systems in the literature. The cut-off value for local tumor response also shows large variation. Firstly consensus should be accomplished on standardization of volume measurements, preferably automatic, and secondly large study groups are needed with identical treatment modalities to further unravel the role of neck node volume as separate staging tool. [Copyright &y& Elsevier]

Tongue cancer treatment often results in impaired speech, swallowing, or mastication. Simulating the effect of treatments can help the patient and the treating physician to understand the effects and impact of the intervention. To simulate deformations of the tongue, identifying accurate mechanical properties of tissue is essential. However, not many succeeded in characterizing in-vivo tongue stiffness. Those who did, measured the tongue At Rest (AR), in which muscle tone subsides even if muscles are not willingly activated. We expected to find an absolute rest state in participants 'under General Anesthesia' (GA). We elaborated on previous work by measuring the mechanical behavior of the in-vivo tongue under aspiration using an improved volume-based method. Using this technique, 5 to 7 measurements were performed on 10 participants both AR and under GA. The obtained Pressure-Shape curves were first analyzed using the initial slope and its variations. Hereafter, an inverse Finite Element Analysis (FEA) was applied to identify the mechanical parameters using the Yeoh, Gent, and Ogden hyperelastic models. The measurements AR provided a mean Young's Modulus of 1638 Pa (min 1035 – max 2019) using the Yeoh constitutive model, which is in line with previous ex-vivo measurements. However, while hoping to find a rest state under GA, the tongue unexpectedly appeared to be approximately 2 to 2.5 times stiffer under GA than AR. Explanations for this were sought by examining drugs administered during GA, blood flow, perfusion, and upper airway reflexes, but neither of these explanations could be confirmed. [ABSTRACT FROM AUTHOR]