Imagine, Discover, Inspire: Proceedings of the 4th International Conference of the Trisomy 21 Research Society.

Down syndrome (DS) or trisomy 21 (T21) is present in a significant number of children and adults around the world and is associated with cognitive and medical challenges. Through research, the T21 Research Society (T21RS), established in 2014, unites a worldwide community dedicated to understanding the impact of T21 on biological systems and improving the quality of life of people with DS across the lifespan. T21RS hosts an international conference every two years to support collaboration, dissemination, and information sharing for this goal.

The prognostic value of image-identified extranodal extension in laryngeal and hypopharyngeal carcinoma following definitive (chemo-)radiotherapy.

Objectives: Clinical extranodal extension (cENE) is a cN modifier in TNM-8 for laryngo-hypopharygeal carcinoma (LHC). We hypothesize that image-detected ENE (iENE) can provide additional prognostic value over cENE in LHC.

Methods: Baseline CTs/MRIs of cN+ LHC patients treated with definitive (chemo-)radiotherapy between 2010-2019 were re-reviewed by a neuroradiologist using internationally accepted criteria for iENE-positive/negative (iENE+/iENE-).

Criteria for the diagnosis of extranodal extension detected on radiological imaging in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Extranodal extension of tumour on histopathology is known to be a negative prognostic factor in head and neck cancer. Compelling evidence suggests that extranodal extension detected on radiological imaging is also a negative prognostic factor. Furthermore, if imaging detected extranodal extension could be identified reliably before the start of treatment, it could be used to guide treatment selection, as patients might be better managed with non-surgical approaches to avoid the toxicity and cost of trimodality therapy (surgery, chemotherapy, and radiotherapy together).

Radiology-Pathology Concordance and Prognostication of Nodal Features in pN+ Oral Cavity Cancer.

Background And Purpose: The aims of our study are to evaluate the diagnostic performance and prognostic value of radiological lymph node (LN) characteristics in pN+ oral cavity squamous carcinoma (OSCC).

Materials And Methods: pN+ OSCC treated between 2012 and 2020 were included. Preoperative imaging was reviewed by a single radiologist blinded to pathologic findings for the following nodal features: imaging-positive LN (iN+), laterality and total number, and image-identified extranodal extension (iENE).

Transoral Robotic Surgery and Radiation Volume Deintensification in Unknown Primary Squamous Cell Carcinoma of the Neck: The Phase 2 FIND Nonrandomized Controlled Trial.

Importance: Patients with unknown primary squamous cell carcinoma (CUP) with cervical metastases typically receive comprehensive radiotherapy (RT) of the pharynx and bilateral neck. Typically, these patients receive comprehensive RT of the pharynx and bilateral neck that may produce treatment-related toxic effects.

Objective: To determine whether localization of occult oropharyngeal cancers with transoral robotic surgery (TORS) combined with reduced pharyngeal and neck RT volumes provides acceptable disease control.

Altered tongue muscle contractile properties coincide with altered swallow function in the adult Ts65Dn mouse model of down syndrome.

Purpose: Down syndrome (DS) is a developmental disability associated with difficulties in deglutition. The adult Ts65Dn mouse model of DS has been previously shown to have differences in measures of swallowing compared with euploid controls. However, the putative mechanisms of these differences in swallowing function are unclear.

SARS-CoV-2 Infection Causes Heightened Disease Severity and Mortality in a Mouse Model of Down Syndrome.

Recent epidemiological studies suggest that individuals with Down syndrome are more susceptible to SARS-CoV-2 infection and have higher rates of hospitalization and mortality than the general population. However, the main drivers behind these disparate health outcomes remain unknown. Herein, we performed experimental infections with SARS-CoV-2 in a well-established mouse model of Down syndrome.

The Quantification of Radiation Fibrosis Using Clinically Indicated Magnetic Resonance Imaging for Head and Neck Cancer Patients.

Currently, no objective method exists to measure the extent of fibrosis in swallowing musculature in head and neck cancer (HNC) patients. We developed and psychometrically tested a method of quantifying fibrosis volume using magnetic resonance imaging (MRI). The overall aim of this study was to determine if clinical MRI is a reliable tool to measure fibrosis of the pharyngeal musculature in patients with HNC managed with RT and to assess its potential to capture changes in fibrosis over time.

Dissection of a Down syndrome-associated trisomy to separate the gene dosage-dependent and -independent effects of an extra chromosome.

As an aneuploidy, trisomy is associated with mammalian embryonic and postnatal abnormalities. Understanding the underlying mechanisms involved in mutant phenotypes is broadly important and may lead to new strategies to treat clinical manifestations in individuals with trisomies, such as trisomy 21 [Down syndrome (DS)]. Although increased gene dosage effects because of a trisomy may account for the mutant phenotypes, there is also the possibility that phenotypic consequences of a trisomy can arise because of the presence of a freely segregating extra chromosome with its own centromere, i.

Association of Primary Tumor Volume With Survival in Patients With T3 Glottic Cancer Treated With Radiotherapy: A Study of the Canadian Head & Neck Collaborative Research Initiative.

Importance: The association of primary tumor volume with outcomes in T3 glottic cancers treated with radiotherapy with concurrent chemotherapy remains unclear, with some evidence suggesting worse locoregional control in larger tumors.

Objective: To evaluate the association of primary tumor volume with oncologic outcomes in patients with T3 N0-N3 M0 glottic cancer treated with primary (chemo)radiotherapy in a large multi-institutional study.

Design, Setting, And Participants: This multi-institutional retrospective cohort study involved 7 Canadian cancer centers from 2002 to 2018.

Hearing impairment in murine model of Down syndrome.

Hearing impairment is a cardinal feature of Down syndrome (DS), but its clinical manifestations have been attributed to multiple factors. Murine models could provide mechanistic insights on various causes of hearing loss in DS. To investigate mechanisms of hearing loss in DS in the absence of the cadherin 23 mutation, we backcrossed our DS mice, Dp(16)1Yey, onto normal-hearing CBA/J mice and evaluated their auditory function.

Nasopharyngeal Carcinoma Radiomic Evaluation with Serial PET/CT: Exploring Features Predictive of Survival in Patients with Long-Term Follow-Up.

Purpose: We aim determine the value of PET and CT radiomic parameters on survival with serial follow-up PET/CT in patients with nasopharyngeal carcinoma (NPC) for which curative intent therapy is undertaken.

Methods: Patients with NPC and available pre-treatment as well as follow up PET/CT were included from 2005 to 2006 and were followed to 2021. Baseline demographic, radiological and outcome data were collected.

Augmenting inter-rater concordance of radiologic extranodal extension in HPV-positive oropharyngeal carcinoma: A multicenter study.

Objectives: To assess intra- and inter-institutional concordance and identify methods to increase precision in radiologic extranodal extension (rENE) ascertainment in HPV+ oropharyngeal carcinoma.

Methods: Six radiologists, blinded to clinical outcomes, from three centers assessed rENE in two phases: Phase-I (20 cases) utilized each individual's a priori appreciation of the literature. Phase-II (30 additional cases) was performed after deliberating experience and consolidating operating definitions.

Clinical presentation and outcome of human papillomavirus-positive nasopharyngeal carcinoma in a North American cohort.

Background: The objective of this study was to describe the clinical presentation and outcomes of human papillomavirus (HPV)-positive nasopharyngeal cancer (NPC) versus Epstein-Barr virus (EBV)-positive NPC and HPV-positive oropharyngeal cancer (OPC).

Methods: Clinical characteristics and presenting signs/symptoms were compared between patients who had viral-related NPC versus viral-related OPC treated with intensity-modulated radiotherapy from 2005 to 2020 and who were matched 1:1 (by tumor and lymph node categories, smoking, age, sex, histology, and year of diagnosis). Locoregional control (LRC), distant control (DC), and overall survival (OS) were compared using the 2005-2018 cohort to maintain 2 years of minimum follow-up.

Radiologic-pathologic correlation of major versus minor extranodal extension in oral cavity cancer.

Background: To evaluate the diagnostic performance of radiologic extranodal extension (rENE) in predicting major (>2 mm) and minor (≤2 mm) pathologic ENE (pENE).

Methods: All oral cavity squamous cell carcinoma patients who underwent neck dissection with pathological nodal disease (pN+) between 2010 and 2015 were reviewed. Preoperative computed tomography and/or magnetic resonance imaging were reviewed by two head and neck neuroradiologists.

Inter-rater concordance and operating definitions of radiologic nodal feature assessment in human papillomavirus-positive oropharyngeal carcinoma.

Background And Purpose: This study aims to evaluate the reliability of radiologic nodal feature assessment in clinical node-positive human papillomavirus-positive oropharyngeal carcinoma.

Materials And Methods: Baseline CTs or MRIs of clinical node-positive human papillomavirus-positive oropharyngeal carcinoma diagnosed between 2012 and 2015 were reviewed independently by two neuroradiologists for seven nodal features: radiologic nodal involvement, cystic change, presence of necrosis, clustering, conglomeration, coalescence, and extranodal extension. Consensus operating definitions were derived after discussion.

Regional Recurrences and Hyams Grade in Esthesioneuroblastoma.

 The aim of this study is to determine if Hyams grade may help predict which patients with esthesioneuroblastoma (ENB) tumors are likely to develop regional recurrences, and to determine the impact of tumor extent on regional failure in ENB patients without evidence of nodal disease at presentation.  The study was designed as a retrospective review for ENB patients.  The study was prepared at tertiary care academic center for ENB patients.

Prognostic importance of radiologic extranodal extension in nasopharyngeal carcinoma treated in a Canadian cohort.

Purpose: To confirm the prognostic value of radiologic extranodal extension (rENE) and its role in clinical-N classification in nasopharyngeal carcinoma (NPC) treated in a western institution.

Methods And Materials: NPC treated between 2010 and 2017 were included. Pre-treatment MRI were reviewed for unequivocal rENE and its grade: grade-1: tumour invading through any nodal capsule but confined to perinodal fat; grade-2: ≥2 adjacent nodes forming a coalescent nodal mass; grade-3: tumour extending beyond perinodal fat to invade/encase adjacent structures.