Publications by authors named "Remco de Bree"

297 Publications

Comparison of different diagnostic approaches in the management of the clinically negative neck in early oral cancer patients.

Cancer 2021 Feb 26. Epub 2021 Feb 26.

Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, Netherlands.

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http://dx.doi.org/10.1002/cncr.33443DOI Listing
February 2021

Presence of Human Papillomavirus and Epstein-Barr Virus, but Absence of Merkel Cell Polyomavirus, in Head and Neck Cancer of Non-Smokers and Non-Drinkers.

Front Oncol 2020 20;10:560434. Epub 2021 Jan 20.

Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands.

Objective: Determine the presence and prognostic value of human papillomavirus (HPV), Epstein-Barr virus (EBV), Merkel cell polyomavirus (MCPyV), and cell cycle proteins in head and neck squamous cell carcinoma (HNSCC) of non-smokers and non-drinkers (NSND).

Methods: Clinical characteristics and tumors of 119 NSND with HNSCC were retrospectively collected and analyzed on tissue microarrays. RNAscope hybridization (ISH) was used to screen for the presence of HPV and MCPyV mRNA. Immunohistochemistry was performed for expression of p16 as surrogate marker for HPV, Large T-antigen for MCPyV, and cell cycle proteins p53 and pRb. Positive virus results were confirmed with polymerase chain reaction. For EBV, EBV encoded RNA ISH was performed. Differences in 5-year survival between virus positive and negative tumors were determined by log rank analysis.

Results: All oropharyngeal tumors (OPSCC) (n = 10) were HPV-positive, in addition to one oral (OSCC) and one nasopharyngeal tumor (NPSCC). The other three NPSCC were EBV-positive. MCPyV was not detected. Patients with HPV or EBV positive tumors did not have a significantly better 5-year disease free or overall survival. Over 70% of virus negative OSCC showed mutant-type p53 expression.

Conclusion: In this cohort, all OPSCC and NPSCC showed HPV or EBV presence. Besides one OSCC, all other oral (n = 94), hypopharyngeal (n = 1), and laryngeal (n = 9) tumors were HPV, EBV, and MCPyV negative. This argues against a central role of these viruses in the ethiopathogenesis of tumors outside the oro- and nasopharynx in NSND. So, for the majority of NSND with virus negative OSCC, more research is needed to understand the carcinogenic mechanisms in order to consider targeted therapeutic options.
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http://dx.doi.org/10.3389/fonc.2020.560434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855709PMC
January 2021

The prognostic impact of micrometastases and isolated tumor cells in early oral squamous cell carcinoma.

Eur Arch Otorhinolaryngol 2021 Jan 2. Epub 2021 Jan 2.

Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.

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http://dx.doi.org/10.1007/s00405-020-06500-yDOI Listing
January 2021

What is the role of sentinel lymph node biopsy in the management of oral cancer in 2020?

Eur Arch Otorhinolaryngol 2020 Dec 28. Epub 2020 Dec 28.

International Head and Neck Scientific Group, Padua, Italy.

Approximately 70-80% of patients with cT1-2N0 oral squamous cell carcinoma (OSCC) ultimately prove to have no cancer in the cervical lymphatics on final pathology after selective neck dissection. As a result, sentinel lymph node biopsy (SLNB) has been adopted during the last decade as a diagnostic staging method to intelligently identify patients who would benefit from formal selective lymphadenectomy or neck irradiation. While not yet universally accepted, SLNB is now incorporated in many national guidelines. SLNB offers a less invasive alternative to elective neck dissection (END), and has some advantages and disadvantages. SLNB can assess the individual drainage pattern and, with step serial sectioning and immunohistochemistry (IHC), can enable the accurate detection of micrometastases and isolated tumor cells (ITCs). Staging of the neck is improved relative to END with routine histopathological examination. The improvements in staging are particularly notable for the contralateral neck and the pretreated neck. However, for floor of mouth (FOM) tumors, occult metastases are frequently missed by SLNB due to the proximity of activity from the primary site to the lymphatics (the shine through phenomenon). For FOM cancers, it is advised to perform either elective neck dissection or superselective neck dissection of the preglandular triangle of level I. New tracers and techniques under development may improve the diagnostic accuracy of SLNB for early-stage OSCC, particularly for FOM tumors. Treatment of the neck (either neck dissection or radiotherapy), although limited to levels I-IV, remains mandatory for any positive category of metastasis (macrometastasis, micrometastasis, or ITCs). Recently, the updated EANM practical guidelines for SLN localization in OSCC and the surgical consensus guidelines on SLNB in patients with OSCC were published. In this review, the current evidence and results of SLNB in early OSCC are presented.
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http://dx.doi.org/10.1007/s00405-020-06538-yDOI Listing
December 2020

Metastatic Squamous Cell Carcinoma to the Cervical Lymph Nodes From an Unknown Primary Cancer: Management in the HPV Era.

Front Oncol 2020 10;10:593164. Epub 2020 Nov 10.

International Head and Neck Scientific Group, Padua, Italy.

Background: Patients with metastases in the lymph nodes of the neck and no obvious primary tumor, neck cancer with unknown primary (NCUP), represent a management challenge. A majority of patients have metastatic squamous cell carcinoma (SCC), although other histologies do occur.

Methods: We comprehensively reviewed the literature, compared available guidelines, and conferred with an international team of experts.

Results: Positron emission tomography-computed tomography (PET-CT) and fine needle aspiration (FNA) under ultrasound guidance increase accuracy of diagnosis. Immunohistochemistry (IHC), determination of human papilloma virus (HPV) status, by p16 staining or by hybridization (ISH), and next-generation gene sequencing can guide us regarding probable primary sites and tumor biology. Narrow Band Imaging (NBI) has been introduced for the early detection of subtle mucosal lesions. Direct laryngoscopy (DL) and tonsillectomy have long been procedures used in the search for a primary site. More recently, TransOral Robotic Surgery (TORS) or Transoral LASER Microsurgery (TLM) have been introduced for lingual tonsillectomy.

Conclusions: New technologies have been developed which can better detect, diagnose, and treat occult primary tumors. Decisions regarding therapy are based on the primary tumor site (if discovered) and N stage. Options include neck dissection with or without postoperative adjuvant therapy, primary irradiation, or combined chemotherapy with irradiation. The preferred treatment of patients whose primary remains unidentified is controversial.
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http://dx.doi.org/10.3389/fonc.2020.593164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685177PMC
November 2020

The Predictive Value of Low Skeletal Muscle Mass Assessed on Cross-Sectional Imaging for Anti-Cancer Drug Toxicity: A Systematic Review and Meta-Analysis.

J Clin Med 2020 Nov 23;9(11). Epub 2020 Nov 23.

Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.

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 χ and I 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; < 0.001) and dose-limiting toxicity (OR 2.24; 95% CI 1.28-3.92; < 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.
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http://dx.doi.org/10.3390/jcm9113780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700117PMC
November 2020

[Ga]Ga-tilmanocept PET/CT lymphoscintigraphy for sentinel lymph node detection in early-stage oral cavity carcinoma.

Eur J Nucl Med Mol Imaging 2020 Nov 13. Epub 2020 Nov 13.

Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands.

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http://dx.doi.org/10.1007/s00259-020-05060-xDOI Listing
November 2020

Validation of the G8 screening tool in older patients with cancer considered for surgical treatment.

J Geriatr Oncol 2020 Nov 7. Epub 2020 Nov 7.

Department of Geriatrics, University Medical Center Utrecht, Utrecht, the Netherlands.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1016/j.jgo.2020.10.017DOI Listing
November 2020

Prognostic role of intraparotid lymph node metastasis in primary parotid cancer: Systematic review.

Head Neck 2021 Mar 9;43(3):997-1008. Epub 2020 Nov 9.

Coordinator of the International Head and Neck Scientific Group, Padua, Italy.

Background: The prognostic importance of intraparotid lymph node metastasis (P+) in patients with primary parotid gland carcinoma is unclear.

Methods: Nineteen retrospective and noncomparative cohort studies, published between 1992 and 2020, met the inclusion criteria and included 2202 patients for this systematic review.

Results: The pooled prevalence of the P in adult patients in the unselected studies was 24.10% (95% confidence interval = 17.95-30.25). The number of P+ lymph nodes per patient was counted in only three studies and ranged from 1 to 11. The 5-year recurrence-free survival rate based on Kaplan-Meier analysis varied from 83% to 88% in P- patients compared to 36% to 54% in P+ patients. The average hazard ratio for tumor recurrence in patients with P+ compared to P- was 2.67 ± 0.58.

Conclusions: P+ is an independent negative prognostic factor in primary parotid gland cancer and should be included into the treatment planning.
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http://dx.doi.org/10.1002/hed.26541DOI Listing
March 2021

[Ga]Ga-tilmanocept PET/CT lymphoscintigraphy: a novel technique for sentinel lymph node imaging.

Eur J Nucl Med Mol Imaging 2020 Nov 6. Epub 2020 Nov 6.

Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

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http://dx.doi.org/10.1007/s00259-020-05101-5DOI Listing
November 2020

HIF-1a expression and differential effects on survival in patients with oral cavity, larynx, and oropharynx squamous cell carcinomas.

Head Neck 2021 Mar 5;43(3):745-756. Epub 2020 Nov 5.

Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands.

Background: Hypoxia is a negative prognostic factor in head and neck squamous cell carcinomas. Under hypoxia, the hypoxia-inducible factor (HIF)-1a transcription factor is overexpressed. We investigated whether there were site differences in HIF-1a expression and its effect on patient outcomes per subsite.

Design/method: A total of 941 patients with HNSCC in the squamous cell carcinoma of the oropharynx (OPSCC, n = 302), oral cavity (OSCC, n = 391), or larynx (LSCC, n = 248) were included. Expression of HIF-1a in tissue samples was investigated using immunohistochemistry. Overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were analyzed.

Results: HIF-1a expression was higher in OSCC than in LSCC and OPSCC. High HIF-1a expression led to worse prognosis in OPSCC (OS P = .029, DFS P = .085) and LSCC (OS P = .041, DFS P = .011) and better in OSCC (OS P = .055, DFS P = .012). There was no association between HIF-1a and LRC.

Conclusions: High HIF-1a expression is related to poor outcome in OPSCC and LSCC and better outcome in OSCC.
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http://dx.doi.org/10.1002/hed.26530DOI Listing
March 2021

New Developments in Imaging for Sentinel Lymph Node Biopsy in Early-Stage Oral Cavity Squamous Cell Carcinoma.

Cancers (Basel) 2020 Oct 20;12(10). Epub 2020 Oct 20.

Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, University of Utrecht, 3584 CX Utrecht, The Netherlands.

Sentinel lymph node biopsy (SLNB) is a diagnostic staging procedure that aims to identify the first draining lymph node(s) from the primary tumor, the sentinel lymph nodes (SLN), as their histopathological status reflects the histopathological status of the rest of the nodal basin. The routine SLNB procedure consists of peritumoral injections with a technetium-99m [Tc]-labelled radiotracer followed by lymphoscintigraphy and SPECT-CT imaging. Based on these imaging results, the identified SLNs are marked for surgical extirpation and are subjected to histopathological assessment. The routine SLNB procedure has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). However, an infamous limitation arises in situations where SLNs are located in close vicinity of the tracer injection site. In these cases, the hotspot of the injection site can hide adjacent SLNs and hamper the discrimination between tracer injection site and SLNs (shine-through phenomenon). Therefore, technical developments are needed to bring the diagnostic accuracy of SLNB for early-stage OSCC to a higher level. This review evaluates novel SLNB imaging techniques for early-stage OSCC: MR lymphography, CT lymphography, PET lymphoscintigraphy and contrast-enhanced lymphosonography. Furthermore, their reported diagnostic accuracy is described and their relative merits, disadvantages and potential applications are outlined.
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http://dx.doi.org/10.3390/cancers12103055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589685PMC
October 2020

Sarcopenia measured with handgrip strength and skeletal muscle mass to assess frailty in older patients with head and neck cancer.

J Geriatr Oncol 2020 Oct 13. Epub 2020 Oct 13.

Department of Head and Neck Surgical Oncology, Division of Imaging and Oncology Center, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands. Electronic address:

Objectives: 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.

Materials And Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1016/j.jgo.2020.10.002DOI Listing
October 2020

The Additional Value of Ultrafast DCE-MRI to DWI-MRI and 18F-FDG-PET to Detect Occult Primary Head and Neck Squamous Cell Carcinoma.

Cancers (Basel) 2020 Sep 30;12(10). Epub 2020 Sep 30.

Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

To evaluate diagnostic accuracy of qualitative analysis and interobserver agreement of single ultrafast-DCE, DWI or F-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 F-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 F-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 F-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 F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and F-FDG-PET/CT yielded highest sensitivity.
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http://dx.doi.org/10.3390/cancers12102826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600235PMC
September 2020

Depression and related factors after oral oncological treatment: a 5-year prospective cohort study.

Support Care Cancer 2020 Oct 1. Epub 2020 Oct 1.

Department of Oral and Maxillofacial Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.

Purposes: Being diagnosed with oral cancer is a life-threatening life event. It often induces social, emotional and psychological consequences and may cause depressive disorders. The primary aim of this study was to identify and quantify the personal and clinical characteristics involved in depression for patients who have been treated for oral cavity malignancies, with a 5-year follow-up period after treatment. The secondary aim of this study was to identify the clinical factors that increase a patient's risk of experiencing depression 5 years after treatment.

Methods: Patients with primary oral cancer were assessed for up to 5 years after primary treatment. A mixed-model analysis was performed, with depression measured by the Center for Epidemiologic Studies Depression Scale as outcome measure.

Results: A total of 141 patients were included in the study. Factors associated with depression were gender, tumour location and having an emotion-oriented coping style. The occurrence of depression within 5 years after treatment could be reliably predicted by a patient's gender, the location of their tumour and the extent to which they had an emotion-oriented coping style.

Conclusions: This study revealed that being female, having a maxillary tumour and having an emotion-oriented coping style are associated with higher levels of depressive symptoms in patients treated for oral cancer up to 5 years post-treatment. A substantial proportion of the patients with oral cancer experienced high levels of depression both before and after their treatment, suggesting that adequate diagnostics and care are needed to try to prevent severe depression in these patients.
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http://dx.doi.org/10.1007/s00520-020-05795-1DOI Listing
October 2020

Time interval between (chemo)radiotherapy and subsequent laryngectomy is not prognostic for post operative complications and survival.

Eur Arch Otorhinolaryngol 2020 Sep 29. Epub 2020 Sep 29.

Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.

Purpose: Pharyngocutaneous fistula (PCF) formation and swallowing difficulties are common and troublesome complications following total laryngectomy (TL). Prior (chemo)radiotherapy ((C)RT) is thought to be a risk factor for these complications, but there is conflicting evidence as to whether the time interval between (C)RT and TL is important. The impact of time interval on these complications and also its impact on overall survival are investigated.

Methods: This is a retrospective case note review of all patients undergoing TL at the University Medical Center, Utrecht, The Netherlands over the 10-year period from January 2008 to December 2017. The cohort was split into those who underwent TL within a year of finishing (C)RT and those longer than 1 year.

Results: One hundred and twenty-six patients (108 males, 18 females), with a mean age of 66 underwent total laryngectomy after prior (C)RT in the study period. Overall 5-year survival was 35% with a median follow-up of 30 months. Fifty-four patients underwent laryngectomy within a year of their (C)RT versus 72 patients who had a time interval of more than one year. No differences in PCF rate, risk of dilatation or overall survival could be found between the two groups.

Conclusions: In this modern cohort, time interval between (C)RT and surgery did not impact PCF rate, risk of dilatation or overall survival.
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http://dx.doi.org/10.1007/s00405-020-06384-yDOI Listing
September 2020

Considerations for environmentally sustainable head and neck surgical oncology practice.

Am J Otolaryngol 2020 Nov - Dec;41(6):102719. Epub 2020 Sep 12.

Coordinator of the International Head and Neck Scientific Group, Padua, Italy.

Objective: To evaluate the potential role of head and neck oncologic surgeons in environmental protection, sustainability of health-care systems and avoidance of procedures contributing to climate change in the future.

Review Methods: This literature review searched for relevant literature about the relevance of waste in surgical head and neck oncology practice and the innovative alternatives to decrease its effect on environment.

Conclusions: Head and neck oncologic surgeons have a role in environmental protection, sustainability of health-care systems and avoidance of procedures contributing to climate change in the future. However, there exist only limited data on waste management and other procedures in surgical oncology to promote these practices.

Implications For Practice: By increasing awareness of the corresponding issues of waste production within the healthcare environment, head and neck surgeons can have a pioneering role in considering how to reduce, recycle and reuse in a more efficient manner. As research in this field accumulates, healthcare providers can engage both managers and clinicians in this process. It remains imperative to provide these professionals opportunities for their work force to rethink current practices in a manner that prioritizes environmentally sustainable head and neck surgical practices.
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http://dx.doi.org/10.1016/j.amjoto.2020.102719DOI Listing
December 2020

Predictive value of quantitative F-FDG-PET radiomics analysis in patients with head and neck squamous cell carcinoma.

EJNMMI Res 2020 Sep 7;10(1):102. Epub 2020 Sep 7.

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, De Boelelaan 1117, PO Box 7057, 1007, Amsterdam, MB, Netherlands.

Background: Radiomics is aimed at image-based tumor phenotyping, enabling application within clinical-decision-support-systems to improve diagnostic accuracy and allow for personalized treatment. The purpose was to identify predictive 18-fluor-fluoro-2-deoxyglucose (F-FDG) positron-emission tomography (PET) radiomic features to predict recurrence, distant metastasis, and overall survival in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy.

Methods: Between 2012 and 2018, 103 retrospectively (training cohort) and 71 consecutively included patients (validation cohort) underwent F-FDG-PET/CT imaging. The 434 extracted radiomic features were subjected, after redundancy filtering, to a projection resulting in outcome-independent meta-features (factors). Correlations between clinical, first-order F-FDG-PET parameters (e.g., SUVmean), and factors were assessed. Factors were combined with F-FDG-PET and clinical parameters in a multivariable survival regression and validated. A clinically applicable risk-stratification was constructed for patients' outcome.

Results: Based on 124 retained radiomic features from 103 patients, 8 factors were constructed. Recurrence prediction was significantly most accurate by combining HPV-status, SUVmean, SUVpeak, factor 3 (histogram gradient and long-run-low-grey-level-emphasis), factor 4 (volume-difference, coarseness, and grey-level-non-uniformity), and factor 6 (histogram variation coefficient) (CI = 0.645). Distant metastasis prediction was most accurate assessing metabolic-active tumor volume (MATV)(CI = 0.627). Overall survival prediction was most accurate using HPV-status, SUVmean, SUVmax, factor 1 (least-axis-length, non-uniformity, high-dependence-of-high grey-levels), and factor 5 (aspherity, major-axis-length, inversed-compactness and, inversed-flatness) (CI = 0.764).

Conclusions: Combining HPV-status, first-order F-FDG-PET parameters, and complementary radiomic factors was most accurate for time-to-event prediction. Predictive phenotype-specific tumor characteristics and interactions might be captured and retained using radiomic factors, which allows for personalized risk stratification and optimizing personalized cancer care.

Trial Registration: Trial NL3946 (NTR4111), local ethics commission reference: Prediction 2013.191 and 2016.498. Registered 7 August 2013, https://www.trialregister.nl/trial/3946.
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http://dx.doi.org/10.1186/s13550-020-00686-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477048PMC
September 2020

Multiparametric functional MRI and F-FDG-PET for survival prediction in patients with head and neck squamous cell carcinoma treated with (chemo)radiation.

Eur Radiol 2021 Feb 26;31(2):616-628. Epub 2020 Aug 26.

Department of Radiology and Nuclear Medicine, Amsterdam UMC, De Boelelaan 1117, Amsterdam, The Netherlands.

Objectives: To assess (I) correlations between diffusion-weighted (DWI), intravoxel incoherent motion (IVIM), dynamic contrast-enhanced (DCE) MRI, and F-FDG-PET/CT imaging parameters capturing tumor characteristics and (II) their predictive value of locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy.

Methods: Between 2014 and 2018, patients with histopathologically proven HNSCC, planned for curative (chemo) radiotherapy, were prospectively included. Pretreatment clinical, anatomical, and functional imaging parameters (obtained by DWI/IVIM, DCE-MRI, and F-FDG-PET/CT) were extracted for primary tumors (PT) and lymph node metastases. Correlations and differences between parameters were assessed. The predictive value of LRFS and OS was assessed, performing univariable, multivariable Cox and CoxBoost regression analyses.

Results: In total, 70 patients were included. Significant correlations between F-FDG-PET parameters and DWI-/DCE volume parameters were found (r > 0.442, p < 0.002). The combination of HPV (HR = 0.903), intoxications (HR = 1.065), PT ADC (HR = 1.252), K (HR = 1.223), and V (HR = 1.215) was predictive for LRFS (C-index = 0.546; p = 0.023). N-stage (HR = 1.058), HPV positivity (HR = 0.886), hypopharyngeal tumor location (HR = 1.111), ADC (HR = 1.102), ADC (HR = 1.137), D* (HR = 0.862), K (HR = 1.106), V (HR = 1.195), SUV (HR = 1.094), and TLG (HR = 1.433) were predictive for OS (C-index = 0.664; p = 0.046).

Conclusions: Functional imaging parameters, performing DWI/IVIM, DCE-MRI, and F-FDG-PET/CT, yielded complementary value in capturing tumor characteristics. More specific, intoxications, HPV-negative status, large tumor volume-related parameters, high permeability (K), and high extravascular extracellular space (V) parameters were predictive for adverse locoregional recurrence-free survival and adverse overall survival. Low cellularity (high ADC) and high metabolism (high SUV) were additionally predictive for decreased overall survival. These different predictive factors added to estimated locoregional and overall survival.

Key Points: • Parameters of DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT were able to capture complementary tumor characteristics. • Multivariable analysis revealed that intoxications, HPV negativity, large tumor volume and high vascular permeability (K), and extravascular extracellular space (Ve) were complementary predictive for locoregional recurrence. • In addition to predictive parameters for locoregional recurrence, also high cellularity (low ADC) and high metabolism (high SUV) were complementary predictive for overall survival.
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http://dx.doi.org/10.1007/s00330-020-07163-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813703PMC
February 2021

Sentinel lymph node detection in oral cancer: a within-patient comparison between [Tc]Tc-tilmanocept and [Tc]Tc-nanocolloid.

Eur J Nucl Med Mol Imaging 2020 Aug 25. Epub 2020 Aug 25.

Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, the Netherlands, Heidelberglaan 100, 3584 CX, Utrecht, Netherlands.

Purpose: Sentinel lymph node (SLN) biopsy has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). [Tc]Tc-tilmanocept may be of benefit in OSCC with complex lymphatic drainage patterns and close spatial relation to SLNs.

Methods: A prospective within-patient evaluation study was designed to compare [Tc]Tc-tilmanocept with [Tc]Tc-nanocolloid for SLN detection. A total of 20 patients with early-stage OSCC were included, who underwent lymphoscintigraphy with both tracers. Both lymphoscintigraphic images of each patient were evaluated for SLN detection and radiotracer distribution at 2-4 h post-injection.

Results: The injection site's remaining radioactivity was significantly lower for [Tc]Tc-tilmanocept (29.9%), compared with [Tc]Tc-nanocolloid (60.9%; p < 0.001). Radioactive uptake in SLNs was significantly lower for [Tc]Tc-tilmanocept (1.95%) compared with [Tc]Tc-nanocolloid (3.16%; p = 0.010). No significant difference was seen in SLN to injection site ratio in radioactivity between [Tc]Tc-tilmanocept (0.066) and [Tc]Tc-nanocolloid (0.054; p = 0.232). A median of 3.0 and 2.5 SLNs were identified with [Tc]Tc-tilmanocept and [Tc]Tc-nanocolloid, respectively (p = 0.297). Radioactive uptake in higher echelon nodes was not significantly different between [Tc]Tc-tilmanocept (0.57%) and [Tc]Tc-nanocolloid (0.86%) (p = 0.052). A median of 2.0 and 2.5 higher echelon nodes was identified with [Tc]Tc-tilmanocept and [Tc]Tc-nanocolloid, respectively (p = 0.083).

Conclusion: [Tc]Tc-tilmanocept had a higher injection site clearance, but at the same time a lower uptake in the SLN, resulting in an SLN to injection site ratio, which was not significantly different from [Tc]Tc-nanocolloid. The relatively low-radioactive uptake in SLNs of [Tc]Tc-tilmanocept may limit intraoperative detection of SLNs, but can be overcome by a higher injection dose.
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http://dx.doi.org/10.1007/s00259-020-04984-8DOI Listing
August 2020

Adherence to pretreatment and intratreatment imaging of head and neck squamous cell carcinoma patients undergoing (chemo) radiotherapy in a research setting.

Clin Imaging 2021 Jan 9;69:82-90. Epub 2020 Jul 9.

Department of Radiology and Nuclear Medicine, Amsterdam UMC, De Boelelaan 1117, Amsterdam, Netherlands.

Purpose: The emerge of improved personalized treatment adaptations and outcome prediction is accompanied with increasing non-invasive assessments in early treatment phase, leading to increased patient burden. This study assessed the adherence of patients with head and neck squamous cell carcinoma (HNSCC) to undergo pretreatment and research-related intratreatment imaging, and assessed which factors caused drop-out.

Method: Between 2013 and 2019, advanced-staged HNSCC patients were prospectively included, underwent (chemo) radiotherapy with curative intent and planned for both pre-treatment and intratreatment sequential 18F-FDG-PET/CT, 18F-FDG-PET/MRI and thereafter MRI (including DWI/DCE). Drop-out-factors were described as healthcare-related (logistics and imaging-system defects) and patient-related (psychological, physical, not-specified). Common Toxicity Criteria (CTC) were routinely scored by radiation/medical oncologists throughout the first 3 weeks, and compared between patient drop-outs and who complete imaging.

Results: Ninety-seven patients (mean age 61 ± 6.8 years) were included; 95 patients (97.9%) underwent pretreatment imaging and 63 (64.9%) intratreatment imaging. For 18F-FDG-PET/CT, 18F-FDG-PET/MRI and MRI pretreatment drop-outs were 2, 10 and 3 patients and for intratreatment drop-outs were 34, 39 and 35 patients, respectively. Patient-related drop-out-factors were physical (n = 16, e.g. dysphagia), psychological (n = 6, e.g. claustrophobia) and non-specified (n = 12). Healthcare-related drop-out-factors were logistics (n = 6) and 18F-FDG-PET/CT-/MRI-system defects (n = 2). The CTC mucosal toxicity was significantly higher (p = 0.023) at week 2 of (chemo)radiotherapy in patient drop-outs than with complete imaging.

Conclusions: The drop-out frequency of advanced-staged HNSCC patients for imaging during (chemo)radiotherapy in a research-setting was high and mainly patient-related. Treatment of patient-related inconveniences, communication of rationale and healthcare-related imaging protocol efficiency improvements may contribute to improved adherence.
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http://dx.doi.org/10.1016/j.clinimag.2020.06.047DOI Listing
January 2021

Assessment of tumour depth in early tongue cancer: Accuracy of MRI and intraoral ultrasound.

Oral Oncol 2020 11 9;110:104895. Epub 2020 Jul 9.

Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, the Netherlands; Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, the Netherlands.

Objectives: Complete resection of tongue cancer is necessary to achieve local control. Unfortunately, deep resection margins are frequently inadequate. To improve deep margin control, accurate knowledge of tumour thickness is pivotal. Magnetic resonance imaging (MRI) and intraoral ultrasound (ioUS) are frequently applied for tumour staging. This study explores the accuracy of these techniques to estimate depth of invasion.

Materials And Methods: The data of patients with a T1-2 tongue cancer that had been treated surgically between 2014 and 2018 were retrospectively analysed. Measurements that had been taken by either MRI or ioUS were compared with those taken during histopathology.

Results: A total of 83 patients with tongue cancer had undergone a pre-operative MRI and 107 had been studied through an ioUS. Tumour thickness measured by MRI (r = 0.72) and ioUS (r = 0.78) correlated significantly (p < 0.001) with histopathological depth of invasion (DOI). In tumours with a DOI of 0-10 mm, MRI has a mean absolute difference with histopathology of 3.1 mm (SD 3.2 mm) and ioUS of 1.6 mm (SD 1.3 mm). In tumours with a DOI greater than 10 mm, MRI has a mean absolute difference of 3.5 mm (SD 3.0 mm) and ioUS of 4.7 mm (SD 3.5 mm).

Conclusion: Estimation of histopathological DOI in tongue cancers with DOI till 10 mm is very accurate through use of ioUS. ioUS tends to underestimate DOI in tumors exceeding 10 mm DOI. MRI tends to overestimate DOI in both thin and thick tumours. Since ultrasound measurements can be performed during surgery, ioUS could potentially guide the surgeon in the achievement of adequate resection margins.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104895DOI Listing
November 2020

Elective Neck Dissection or Sentinel Lymph Node Biopsy in Early Stage Oral Cavity Cancer Patients: The Dutch Experience.

Cancers (Basel) 2020 Jul 3;12(7). Epub 2020 Jul 3.

Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.

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%, = 0.612) and negative predictive value (NPV) (93%, = 1.000) were comparable between END and SLNB patients. The END cohort contained more pT2 tumours (51%) compared to the SLNB cohort (23%) ( < 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%, = 0.006) and NPV (90% vs. 97%, = 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%, = 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.
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http://dx.doi.org/10.3390/cancers12071783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407164PMC
July 2020

Locoregional recurrence rate and disease-specific survival following marginal vs segmental resection for oral squamous cell carcinoma with mandibular bone invasion.

J Surg Oncol 2020 Jun 9. Epub 2020 Jun 9.

Department of Oral and Maxillofacial Surgery and Special Dental Care, University Medical Center Utrecht, the Netherlands.

Background And Objectives: To determine locoregional recurrence rate (LRR) and disease-specific survival (DSS) following marginal vs segmental mandibulectomy.

Methods: Included were 210 patients, who had marginal or segmental mandibulectomy between 2000 and 2017. Marginal resection was performed when complete removal of the tumor was deemed feasible on the condition that at least 1 cm bone height of the inferior border of the mandible could be preserved. Segmental resection was performed in case less than 1 cm bone height of the mandible would remain. Clinical and histopathological data were collected from medical records. LRR and DSS were computed using Kaplan-Meier analysis. Cox-regression analysis was used to identify risk factors for LRR and DSS.

Results: A total of 59 marginal and 151 segmental resections had been performed. There was no significant difference in 3- and 5-year LRR (P = .904) and no significant difference in 3- and 5-year DSS (P = .362) between the marginal and segmental resection group. Cox-regression analysis showed a trend for surgical margin less than equal to 1 mm, to affect LRR (P = .05) and surgical margin less than equal 1 mm, perineural invasion and lymph node metastasis to affect DSS (P < .05).

Conclusions: There was no difference in outcome between the two types of mandibulectomy.
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http://dx.doi.org/10.1002/jso.26054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496367PMC
June 2020

Prostate-specific membrane antigen (PSMA) expression in adenoid cystic carcinoma of the head and neck.

BMC Cancer 2020 Jun 5;20(1):519. Epub 2020 Jun 5.

Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.

Background: Treatment options for advanced head and neck adenoid cystic carcinoma (AdCC) are limited. Prostate-Specific Membrane Antigen (PSMA), a transmembrane protein that is known for its use in diagnostics and targeted therapy in prostate cancer, is also expressed by AdCC. This study aimed to analyse PSMA expression in a large cohort of primary, recurrent and metastasized AdCC of the head and neck.

Methods: One hundred ten consecutive patients with histologically confirmed AdCC in the period 1990-2017 were included. An analysis was made of clinical details, revised pathology and semiquantitative immunohistochemical expression of PSMA on tissue microarray and whole slides. Associations of PSMA expression with clinicopathological parameters were explored and survival was analysed by multivariate Cox-proportional Hazard analysis.

Results: PSMA expression was present in 94% of the 110 primary tumours, with a median of 31% positive cells (IQR 15-60%). Primary tumours (n = 18) that recurred (n = 15) and/or had metastases (n = 10) demonstrated 40, 60 and 23% expression respectively. Expression was not independently related to increased pathological stage, tumour grade, and the occurrence of locoregional recurrence or metastasis. After dichotomization, only primary tumour PSMA expression ≤10% appeared to be associated with reduced 10-years recurrence-free survival (HR 3.0, 95% CI 1.1-8.5, p = .04).

Conclusions: PSMA is highly expressed in primary, recurrent and metastatic AdCC of the salivary and seromucous glands. PSMA expression has no value in predicting clinical behaviour of AdCC although low expression may indicate a reduced recurrence-free survival. This study provides supporting results to consider using PSMA as target for imaging and therapy when other diagnostic and palliative treatment options fail.
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http://dx.doi.org/10.1186/s12885-020-06847-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275445PMC
June 2020

Outcome prediction of head and neck squamous cell carcinoma by MRI radiomic signatures.

Eur Radiol 2020 Nov 4;30(11):6311-6321. Epub 2020 Jun 4.

Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

Objectives: Head and neck squamous cell carcinoma (HNSCC) shows a remarkable heterogeneity between tumors, which may be captured by a variety of quantitative features extracted from diagnostic images, termed radiomics. The aim of this study was to develop and validate MRI-based radiomic prognostic models in oral and oropharyngeal cancer.

Materials And Methods: Native T1-weighted images of four independent, retrospective (2005-2013), patient cohorts (n = 102, n = 76, n = 89, and n = 56) were used to delineate primary tumors, and to extract 545 quantitative features from. Subsequently, redundancy filtering and factor analysis were performed to handle collinearity in the data. Next, radiomic prognostic models were trained and validated to predict overall survival (OS) and relapse-free survival (RFS). Radiomic features were compared to and combined with prognostic models based on standard clinical parameters. Performance was assessed by integrated area under the curve (iAUC).

Results: In oral cancer, the radiomic model showed an iAUC of 0.69 (OS) and 0.70 (RFS) in the validation cohort, whereas the iAUC in the oropharyngeal cancer validation cohort was 0.71 (OS) and 0.74 (RFS). By integration of radiomic and clinical variables, the most accurate models were defined (iAUC oral cavity, 0.72 (OS) and 0.74 (RFS); iAUC oropharynx, 0.81 (OS) and 0.78 (RFS)), and these combined models outperformed prognostic models based on standard clinical variables only (p < 0.001).

Conclusions: MRI radiomics is feasible in HNSCC despite the known variability in MRI vendors and acquisition protocols, and radiomic features added information to prognostic models based on clinical parameters.

Key Points: • MRI radiomics can predict overall survival and relapse-free survival in oral and HPV-negative oropharyngeal cancer. • MRI radiomics provides additional prognostic information to known clinical variables, with the best performance of the combined models. • Variation in MRI vendors and acquisition protocols did not influence performance of radiomic prognostic models.
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http://dx.doi.org/10.1007/s00330-020-06962-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554007PMC
November 2020

Staging and grading of oral squamous cell carcinoma: An update.

Oral Oncol 2020 08 20;107:104799. Epub 2020 May 20.

Institute of Biomedicine, Pathology, University of Turku, Turku, Finland. Electronic address:

Oral squamous cell carcinoma (OSCC) is a common malignancy of the head and neck region. OSCC has a relatively low survival rate and the incidence of the disease is increasing in some geographic areas. Staging and grading of OSCC are established prerequisites for management, as they influence risk stratification and are the first step toward personalized treatment. The current AJCC/UICC TNM staging (8th edition, 2017) of OSCC has included significant modifications through the incorporation of depth of invasion in the T stage and extracapsular spread/extranodal extension in the N stage. Further modifications for AJCC 8 have been suggested. On the other hand, the World Health Organization (WHO) classification (4th edition, 2017) still endorses a simple, differentiation-based histopathologic grading system of OSCC (despite its low prognostic value) and ignores factors such as tumor growth pattern and dissociation, stromal reactions (desmoplasia, local immune response), and tumor-stroma ratio. The various controversies and possible developments of the current staging and grading criteria of OSCC are briefly discussed in this update together with possible applications of artificial intelligence in the context of screening and risk stratification.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104799DOI Listing
August 2020

Detecting Bone Invasion of the Maxilla by Oral Squamous Cell Carcinoma: Diagnostic Accuracy of Preoperative Computed Tomography Versus Magnetic Resonance Imaging.

J Oral Maxillofac Surg 2020 Sep 23;78(9):1645-1652. Epub 2020 Apr 23.

Head and Neck Surgeon, Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:

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.
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http://dx.doi.org/10.1016/j.joms.2020.04.019DOI Listing
September 2020

Incidence of Occult Lymph Node Metastasis in Primary Larynx Squamous Cell Carcinoma, by Subsite, T Classification and Neck Level: A Systematic Review.

Cancers (Basel) 2020 Apr 24;12(4). Epub 2020 Apr 24.

International Head and Neck Scientific Group, 35100 Padua, Italy.

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.
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http://dx.doi.org/10.3390/cancers12041059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225965PMC
April 2020

COVID-19 pandemic: Effects and evidence-based recommendations for otolaryngology and head and neck surgery practice.

Head Neck 2020 06 15;42(6):1259-1267. Epub 2020 Apr 15.

International Head and Neck Scientific Group, Udine, Italy.

The 2019 novel coronavirus disease (COVID-19) is a highly contagious zoonosis produced by SARS-CoV-2 that is spread human-to-human by respiratory secretions. It was declared by the WHO as a public health emergency. The most susceptible populations, needing mechanical ventilation, are the elderly and people with associated comorbidities. There is an important risk of contagion for anesthetists, dentists, head and neck surgeons, maxillofacial surgeons, ophthalmologists, and otolaryngologists. Health workers represent between 3.8% and 20% of the infected population; some 15% will develop severe complaints and among them, many will lose their lives. A large number of patients do not have overt signs and symptoms (fever/respiratory), yet pose a real risk to surgeons (who should know this fact and must therefore apply respiratory protective strategies for all patients they encounter). All interventions that have the potential to aerosolize aerodigestive secretions should be avoided or used only when mandatory. Health workers who are: pregnant, over 55 to 65 years of age, with a history of chronic diseases (uncontrolled hypertension, diabetes mellitus, chronic obstructive pulmonary diseases, and all clinical scenarios where immunosuppression is feasible, including that induced to treat chronic inflammatory conditions and organ transplants) should avoid the clinical attention of a potentially infected patient. Health care facilities should prioritize urgent and emergency visits and procedures until the present condition stabilizes; truly elective care should cease and discussed on a case-by-case basis for patients with cancer. For those who are working with COVID-19 infected patients' isolation is compulsory in the following settings: (a) unprotected close contact with COVID-19 pneumonia patients; (b) onset of fever, cough, shortness of breath, and other symptoms (gastrointestinal complaints, anosmia, and dysgeusia have been reported in a minority of cases). For any care or intervention in the upper aerodigestive tract region, irrespective of the setting and a confirmed diagnosis (eg, rhinoscopy or flexible laryngoscopy in the outpatient setting and tracheostomy or rigid endoscopy under anesthesia), it is strongly recommended that all health care personnel wear personal protective equipment such as N95, gown, cap, eye protection, and gloves. The procedures described are essential in trying to maintain safety of health care workers during COVID-19 pandemic. In particular, otolaryngologists, head and neck, and maxillofacial surgeons are per se exposed to the greatest risk of infection while caring for COVID-19 positive subjects, and their protection should be considered a priority in the present circumstances.
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http://dx.doi.org/10.1002/hed.26164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262203PMC
June 2020