Association of HPV status with survival after surgical salvage of oropharyngeal cancers.

OBJECTIVES: This study used the National Cancer Database to determine the effect of human papillomavirus (HPV) on survival outcomes for recurrent oropharyngeal cancer treated with salvage surgery after initial treatment with radiation therapy or chemoradiation therapy. METHODS: Patients with recurrent oropharyngeal cancer receiving salvage surgery after initial treatment with adjuvant therapy were identified through the National Cancer Database. Demographics, tumor characteristics, and survival data were collected. The data were analyzed to identify factors that may be associated with survival. RESULTS: A total of 169 patients were included, 59% of which were HPV-positive cases and 41% were HPV-negative. On univariate analysis, HPV-positive cases had higher overall survival compared to HPV-negative cases. However, on multivariate analysis, the association with HPV status was no longer statistically significant while positive surgical margins, higher T-stage at initial diagnosis, and a greater comorbidity burden were significantly associated with poorer survival. CONCLUSION: In the salvage setting for treatment of recurrent oropharyngeal squamous cell carcinoma, HPV status may not be associated with improved survival.

Effect of histopathological grade on treatment and survival in base of tongue adenocarcinoma.

OBJECTIVES: The purpose of this study was to investigate survival differences between low-grade and high-grade base of tongue (BOT) adenocarcinoma by examining demographics, tumor characteristics, and treatment modalities. METHODS: The National Cancer Database was queried for patients with BOT adenocarcinoma between 2004 and 2017. Univariate and multivariate analyses were performed for all cases of BOT adenocarcinoma. Subsequent analysis focused on low-grade (grade 1 and grade 2) and high-grade (grade 3 and grade 4) BOT adenocarcinoma. RESULTS: A total of 286 patients with BOT adenocarcinoma were included in the main cohort and divided into low grade (n = 137) and high grade (n = 66). The 5-year overall survival for all patients, low-grade, and high-grade was 67%, 85%, and 58%, respectively. Prognostic factors associated with decreased survival for the main cohort include advanced age (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02-1.06), non-white race (HR: 1.79; 95% CI: 1.04-3.25), public insurance (HR: 1.79; 95% CI: 1.02-3.14) and high-grade 3,4 (HR: 2.63; 95% CI: 1.51-4.56). The prognostic factor associated with increased survival for the main cohort was surgery (HR: 0.59; 95% CI: 0.36-0.96). Radiotherapy was associated with improved overall survival for high-grade BOT adenocarcinoma (HR: 0.09; 95% CI: 0.02-0.49) but not for low-grade BOT adenocarcinoma (HR: 0.93; 95% CI: 0.38-2.32). CONCLUSIONS: This investigation is the largest to date analyzing the association of treatment modalities with overall survival in BOT adenocarcinoma. Surgery remains standard of treatment, particularly in low-grade cases, with radiotherapy offering additional survival benefit for high-grade BOT adenocarcinoma.

Voice-related quality of life: Relation to objective spirometry measures in subglottic stenosis.

OBJECTIVES: The current study seeks to identify the correlation between in-office spirometry data and voice-related quality of life in patients with subglottic stenosis (SGS). METHODS: Patients with SGS of any etiology were included when in-office spirometric data was available in addition to voice-related patient-reported outcomes (PROM) data in the form of the Voice Handicap Index-10 (VHI-10) and/or the Voice-Related Quality of Life (V-RQOL) survey. Overall survey scores and individual question responses were assessed for degree of correlation to spirometric data. RESULTS: Twenty-nine patients were included in the final analysis. Overall mean total VHI-10 scores totaled 7.15 (SD 9.11), while mean overall V-RQOL scores totaled 78.41 (SD 16.45). Both PEF and PIF rates correlated to total scores on the VHI and V-RQOL surveys. This correlation was stronger with PIF than with PEF, and with the V-RQOL than with the VHI. Questions related to breathlessness most closely correlated with spirometric data. CONCLUSION: Voice-related QOL is impacted in patients with SGS in a predictable way. Breathlessness while speaking may be more impactful than inability to produce speech in this population.

Panniculectomy Performed in Conjunction With Gynecologic Surgery in Obese and Morbidly Obese Patients: A National Surgical Quality Improvement Program Analysis and Systematic Review of the Literature.

INTRODUCTION: Panniculectomy is a common procedure in plastic surgery, often performed after massive weight loss and in morbidly obese patients. It is also performed in combination with various gynecologic procedures based on the rational that it will reduce complication rates and benefit the patient (Am J Obstet Gynecol, 2000. 182, 1502-1505; J Gynecol Technol, 1997;3:9-16; J Am Coll Surg, 1995). These and other studies fail to provide proof of these claims for a number of reasons, including study design, lack of a control group and the inclusion of nonmorbidly obese patients (J Am Coll Surg, 1995; Gynecol Oncol, 1998, 70, 80-86; Int J Gynecol Cancer, 2015;25(8):1503-1512). Recent medical practice has focused increasingly on minimizing patient morbidity and trends in reimbursement are moving toward penalizing practices, which increase complications. The aim of this study was to evaluate the premise that the addition of panniculectomy to gynecologic surgery in the obese and morbidly obese patient population results in a statistically significant improvement in measureable outcomes. METHODS/RESULTS: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was reviewed to assess the association of complications with panniculectomy combined with gynecologic surgery in the morbidly obese patient population. The query identified 296 patients with a body mass index greater than 30 who had panniculectomy concomitant with gynecologic surgery. The results demonstrated a statistically significant relationship (P < 0.05) of these concomitant procedures with superficial infection, wound infection, pulmonary embolism, systemic sepsis, return to operating room, length of operation and length of stay. A systematic review of the literature was then performed which identified only 5 studies that included comparative cohorts of those with gynecologic surgery, with and without panniculectomy. There was no significant benefit across the studies in measured paramters. CONCLUSIONS: This NSQIP study and systematic review of the existing literature does not support the premise that there is a statistically significant benefit associated with performing panniculectomy in conjunction with gynecologic surgery in the morbidly obese patient population. The NSQIP data demonstrate significant elevation of negative outcomes in morbidly obese patients undergoing combined procedures. In the light of the risks to patients and current direction of medical practice the addition of elective panniculectomy to gynecologic surgery should be reevaluated in the a patient population with a body mass index greater than 30.

Characterizing models of adolescent and youth-friendly health services in sub-Saharan Africa: a scoping review.

This scoping review provides an up-to-date overview of the evidence on adolescent and youth-friendly health services (AYFHS) in sub-Saharan African countries. We conducted a search of four databases and grey literature sources to identify English language publications from January 1, 2005, to December 14th, 2022. The review synthesized evidence on the models and characteristics of AYFHS, the application of World Health Organization (WHO) standards, and whether AYFHS have improved young people's health outcomes. In total, 77 sources were included in the review, representing 47 AYFHS initiatives spanning 19 countries, and three multi-country reports. Most commonly, AYFHS were delivered in public health facilities and focused on sexual and reproductive health, with limited application of WHO standards. Some evidence suggested that AYFHS increased young people's health service utilization and contraceptives uptake. There is a clear need to strengthen and develop innovative and multi-pronged approaches to delivering and evaluating AYFHS in this region.

Shortcut learning in medical AI hinders generalization: method for estimating AI model generalization without external data.

Healthcare datasets are becoming larger and more complex, necessitating the development of accurate and generalizable AI models for medical applications. Unstructured datasets, including medical imaging, electrocardiograms, and natural language data, are gaining attention with advancements in deep convolutional neural networks and large language models. However, estimating the generalizability of these models to new healthcare settings without extensive validation on external data remains challenging. In experiments across 13 datasets including X-rays, CTs, ECGs, clinical discharge summaries, and lung auscultation data, our results demonstrate that model performance is frequently overestimated by up to 20% on average due to shortcut learning of hidden data acquisition biases (DAB). Shortcut learning refers to a phenomenon in which an AI model learns to solve a task based on spurious correlations present in the data as opposed to features directly related to the task itself. We propose an open source, bias-corrected external accuracy estimate, PEst, that better estimates external accuracy to within 4% on average by measuring and calibrating for DAB-induced shortcut learning.

RADCURE: An open-source head and neck cancer CT dataset for clinical radiation therapy insights.

PURPOSE: This manuscript presents RADCURE, one of the most extensive head and neck cancer (HNC) imaging datasets accessible to the public. Initially collected for clinical radiation therapy (RT) treatment planning, this dataset has been retrospectively reconstructed for use in imaging research. ACQUISITION AND VALIDATION METHODS: RADCURE encompasses data from 3346 patients, featuring computed tomography (CT) RT simulation images with corresponding target and organ-at-risk contours. These CT scans were collected using systems from three different manufacturers. Standard clinical imaging protocols were followed, and contours were manually generated and reviewed at weekly RT quality assurance rounds. RADCURE imaging and structure set data was extracted from our institution's radiation treatment planning and oncology information systems using a custom-built data mining and processing system. Furthermore, images were linked to our clinical anthology of outcomes data for each patient and includes demographic, clinical and treatment information based on the 7th edition TNM staging system (Tumor-Node-Metastasis Classification System of Malignant Tumors). The median patient age is 63, with the final dataset including 80% males. Half of the cohort is diagnosed with oropharyngeal cancer, while laryngeal, nasopharyngeal, and hypopharyngeal cancers account for 25%, 12%, and 5% of cases, respectively. The median duration of follow-up is five years, with 60% of the cohort surviving until the last follow-up point. DATA FORMAT AND USAGE NOTES: The dataset provides images and contours in DICOM CT and RT-STRUCT formats, respectively. We have standardized the nomenclature for individual contours-such as the gross primary tumor, gross nodal volumes, and 19 organs-at-risk-to enhance the RT-STRUCT files' utility. Accompanying demographic, clinical, and treatment data are supplied in a comma-separated values (CSV) file format. This comprehensive dataset is publicly accessible via The Cancer Imaging Archive. POTENTIAL APPLICATIONS: RADCURE's amalgamation of imaging, clinical, demographic, and treatment data renders it an invaluable resource for a broad spectrum of radiomics image analysis research endeavors. Researchers can utilize this dataset to advance routine clinical procedures using machine learning or artificial intelligence, to identify new non-invasive biomarkers, or to forge prognostic models.

Repeatability and reproducibility of prostate apparent diffusion coefficient values on a 1.5 T magnetic resonance linear accelerator.

Background and Purpose: Integrated magnetic resonance linear accelerator (MR-Linac) systems offer potential for biologically based adaptive radiation therapy using apparent diffusion coefficient (ADC). Accurate tracking of longitudinal ADC changes is key to establishing ADC-driven dose adaptation. Here, we report repeatability and reproducibility of intraprostatic ADC using deformable image registration (DIR) to correct for inter-fraction prostate changes. Materials and Methods: The study included within-fraction repeat ADC measurements for three consecutive fractions for 20 patients with prostate cancer treated on a 1.5 T MR-Linac. We deformably registered successive fraction T2-weighted images and applied the deformation vector field to corresponding ADC maps to align to fraction 2. We delineated gross tumour volume (GTV), peripheral zone (PZ) and prostate clinical target volume (CTV) regions-of-interest (ROIs) on T2-weighted MRI and copied to ADC maps. We computed intraclass correlation coefficients (ICC) and percent repeatability coefficient (%RC) to determine within-fraction repeatability and between-fraction reproducibility for individual voxels, mean and 10th percentile ADC values per ROI. Results: The ICC between repeats and fractions was excellent for mean and 10th percentile ADC in all ROIs (ICC > 0.86), and moderate repeatability and reproducibility existed for individual voxels (ICC > 0.542). Similarly, low %RC within-fraction (4.2-17.9 %) mean and 10th percentile ADC existed, with greater %RC between fractions (10.2-36.8 %). Higher %RC existed for individual voxel within-fraction (21.7-30.6 %) and between-fraction (32.1-34.5 %) ADC. Conclusions: Results suggest excellent ADC repeatability and reproducibility in clinically relevant ROIs using DIR to correct between-fraction anatomical changes. We established the precision of voxel-level ADC tracking for future biologically based adaptation implementation.

Development of a Sentence Verification Task to Measure Speech Comprehension and Listening Effort in Cochlear Implant Users.

PURPOSE: Tests measuring speech comprehension and listening effort for cochlear implant (CI) users may reflect important aspects of real-world speech communication. In this study, we describe the development of a multiple-talker, English-language sentence verification task (SVT) for use in adult CI users to measure speech comprehension and listening effort. We also examine whether talker differences affect speech comprehension and listening effort. METHOD: Thirteen experienced adult CI users participated in the study and underwent testing using a newly developed multiple-talker SVT. Participants were sequentially presented with audio recordings of unique sentences spoken in English by six different talkers. Participants classified each sentence as either true or false. Accuracy of classification and the response time (RT) for correct responses were used as measures of comprehension and listening effort, respectively. The effect of talker on the results was further analyzed. RESULTS: All 13 participants successfully completed the SVT. The mean verification accuracy for participants was 87.2% ± 8.8%. The mean RT for correct responses across participants was 1,050 ms ± 391 ms. When stratified by talker, verification accuracy ranged from 83.7% to 95.2% and mean RTs across participant ranged from 786 ms to 1,254 ms. Talker did not have a significant effect on sentence classification accuracy, but it did have a significant effect on RTs (p < .001). CONCLUSIONS: The SVT is an easily implemented test that can assess speech comprehension and listening effort simultaneously. CI users may experience increased effort for comprehending certain talkers' speech, despite showing similar levels of comprehension accuracy. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24126630.

Resection of Intracochlear Schwannomas With Immediate Cochlear Implantation.

INTRODUCTION: Intralabyrinthine schwannomas, including the intracochlear variety, are rare benign tumors. They can cause a number of symptoms and have the potential to grow to involve other critical structures of the inner ear and skull base. While surgical resection is feasible, there is typically permanent hearing dysfunction as a result of resection and subsequent fibrosis. Here, we present 2 cases of intracochlear schwannomas (ICS) that were successfully resected with simultaneous cochlear implant placement. METHODS: Patient 1 presented with an intravestibulocochlear schwannoma. This patient underwent a translabyrinthine approach. Endoscopic assistance was used to dissect the tumor from the vestibule and basal turn of the cochlea, through an enlarged round window approach. A cochlear implant was placed via a round window cochleostomy. Patient 2 presented with an intracochlear schwannoma involving the basal and middle turns of the cochlea. The patient underwent a trans-otic approach for resection. A large portion of the cochlear promontory required unroofing for complete exposure of the tumor. A cochlear implant was then placed via a round window cochleostomy. RESULTS: Upon cochlear implant activation, Patient 1's sound field thresholds using the implant were near the normal range of hearing, ranging from 25 to 50 dB HL from 250 to 6000 Hz. Patient 2's 6-month post-operative cochlear implant sound field testing ranged from 20 to 30 dB HL from 250 to 6000 Hz and speech recognition testing revealed 59% on AZ Bio sentences compared to 0% pre-operatively. CONCLUSION: Simultaneous cochlear implantation after resection of intracochlear schwannomas is safe and successful in restoring hearing. Attention to adequate exposure and endoscopic assistance, when required, allow for gross total resection while minimizing trauma to cochlear structures. In such cases, immediate cochlear implantation allows for hearing rehabilitation before likely cochlear fibrosis can occur.

Open reduction internal fixation of rib fractures: a biomechanical comparison between the RibLoc U Plus® system and anterior plate in rib implants.

OBJECTIVES: In this study, we assessed the bending strength of two surgical repairs of rib fracture using RibLoc® U Plus system made by Acute Innovations and the anterior plate by Synthes. METHODS: After a rib fracture was created in seven pairs of cadaveric rib specimens, one side was repaired with the anterior plate and the other side repaired with the RibLoc U Plus® plate. Each of the rib is loaded using a custom device over 360,000 bending cycles to simulate in vivo fatiguing related to respiration. Upon completion of the cyclic loading, the specimens were compressively loaded to failure and the failure bending moment was determined. RESULTS: The ribs repaired with the RibLoc U Plus® system showed 79% higher failure bending moment than that of the anterior plate, with a p value of 0.033. The ribs repaired with RibLoc U Plus® showed a trend of less stiffness reduction over the 360,000 loading cycles. CONCLUSION: The biomechanical study showed that the RibLoc U Plus® system is stronger in the bending moment loading of repaired ribs, possibly due to the U-shape structure supporting both the inner and outer cortices of a repaired rib.

Jugular Foramen Cerebrospinal Fluid Leak Repaired Via the Infralaybryinthine Approach With Adjunct Use of Intrathecal Fluorescein and Stereotactic Navigation.

OBJECTIVE: This report describes a case of a spontaneous cerebrospinal fluid leak at the jugular foramen that was surgically repaired via the infralabyrinthine approach with adjunct use of intrathecal fluorescein and stereotactic navigation. PATIENTS: A 39-year-old woman presenting with clear otorrhea confirmed to be cerebrospinal fluid (CSF) emanating from a defect in the jugular foramen. INTERVENTION: Surgical repair of the skull base defect using an infralabyrinthine approach to the jugular foramen. During surgery, intrathecal fluorescein and stereotactic navigation were used to localize the defect and confirm a successful repair. MAIN OUTCOME MEASURE: Recurrence of a CSF leak. RESULTS: The defect was successfully repaired using the techniques described, resulting in cessation of the patient's CSF leak. There was no recurrence of the CSF leak up to a 4-month postoperative outpatient follow-up. CONCLUSIONS: Diagnosis and repair of spontaneous otogenic CSF leaks in an uncommon location like the jugular foramen are challenging. This report demonstrates the successful use of the infralabyrinthine approach for control of a CSF from the jugular foramen. In addition, use of techniques, such as intrathecal fluorescein and stereotactic navigation that are not routinely used in otology and neurotology allowed for safe, effective repair of the leak in this case.

Role of the otologist/neurotologist in managing auricular and periauricular cutaneous malignancies: A 10-year otologic oncology experience.

Objective: Auricular/periauricular cutaneous malignancies can be challenging to manage surgically due to the complex anatomy of the region. Otologists/neurotologists have unique skillsets that are well-suited to surgically treat these patients. We aim to highlight the role of otologists and neurotologists in providing surgical care of patients with auricular and periauricular malignancies by describing the experience of a single fellowship-trained neurotologist over a 10-year period. Methods: Retrospective chart review of 387 patients with auricular and periauricular malignancy treated by a single neurotologist between 2012 and 2022 was completed. Tumor histology and procedures performed for each patient were extracted. Additional data was collected for a subset of 84 patients with complex cases requiring selective neck dissection, parotidectomy, lateral temporal bone resection, regional advancement or rotational flap reconstruction, and/or free tissue transfer reconstruction. Results: Within the series of 387 patients, squamous cell carcinoma was the most common histology (42.6%, n = 165), followed by basal cell carcinoma (40.8%, n = 158), and melanoma (9.8%, n = 38). Common surgical procedures included wide local excision (61.8%, n = 239), partial/sub-total auriculectomy 18.3% (n = 71), or total auriculectomy 5.2% (n = 20). Within the 84-patient subset, median age at diagnosis was 71.9 years. Dermatologists provided most patient referrals (50.0%, n = 42). Most common tumor locations included: auricular (58.3%, n = 49), pre-auricular (21.4%, n = 18), and parotid (27.4%, n = 23). Revision surgery occurred in 22.6% of cases (n = 19), of which 26.3% (n = 5) for positive margins and 31.6% (n = 6) for recurrence. Mean follow-up was 22.8 months. Disease-specific 5-year survival was 91%. Conclusions: We demonstrate the feasibility of an otologist/neurotologist incorporating the surgical management of auricular and periauricular malignancies into their practice. Level of Evidence: 4.

Delayed presentation of biopsy-proven eosinophilic myocarditis following COVID-19 mRNA vaccine.

Myopericarditis associated with COVID-19 mRNA vaccines has been recognized as an uncommon adverse reaction, especially among young, healthy adult males. Eosinophilic myocarditis is a rare form of inflammation reflecting a hypersensitivity reaction following an inciting event commonly caused by drugs including vaccines. Eosinophilic myocarditis, a subtype of myocarditis, is characterized by eosinophilic myocardial infiltrates. It is usually accompanied by systemic eosinophilia in the form of a drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and is rarely associated with myocyte fibrosis and/or necrosis. In this report, we present a case of biopsy-proven eosinophilic myocarditis in a 24-year-old male patient, likely secondary to COVID-19 mRNA vaccination. To our knowledge, this is the first report to describe delayed eosinophilic myocarditis following the COVID-19 mRNA vaccine. Clinicians should be aware of possible delayed presentation to avoid associated morbidity.

Postoperative protocols following endoscopic skull base surgery: An evidence-based review with recommendations.

BACKGROUND: Postoperative management strategies for endoscopic skull base surgery (ESBS) vary widely because of limited evidence-based guidance. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from January 1990 through February 2022 to examine 18 postoperative considerations for ESBS. Nonhuman studies, articles written in a language other than English, and case reports were excluded. Studies were assessed for levels of evidence, and each topic's aggregate grade of evidence was evaluated. RESULTS: A total of 74 studies reporting on 18 postoperative practices were reviewed. Postoperative pain management, prophylactic antibiotics, and lumbar drain use had the highest grades of evidence (B). The literature currently lacks high quality evidence for a majority of the reviewed ESBS precautions. There were no relevant studies to address postoperative urinary catheter use and medical intracranial pressure reduction. CONCLUSION: The evidence for postoperative ESBS precautions is heterogeneous, scarce, and generally of low quality. Although this review identified the best evidence available in the literature, it suggests the urgent need for more robust evidence. Therefore, additional high-quality studies are needed in order to devise optimal postoperative ESBS protocols.

Transesophageal Echocardiography vs. Transthoracic Echocardiography for Methicillin-Sensitive Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus Endocarditis.

Infective endocarditis is an infection of the inner layers of the heart, seen often in intravenous drug users and patients with valvular lesions or prosthetic heart valves. This entity has high mortality and morbidity. The most common causative microorganism is Staphylococcus aureus. In this comprehensive literature review, we focused on both Staphylococcus aureus infections, i.e., methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) endocarditis, demographics, use of transthoracic echocardiogram and/or transesophageal echocardiogram for diagnostics, and treatments. Although clinical criteria are relevant, transesophageal echocardiogram plays a vital role in establishing and identifying the presence of infective endocarditis and its local complications, with higher sensitivity in patients with prosthetic valves. The antibiotic selection posed a great challenge for clinicians due to antibiotic resistance and the aggressive nature of Staphylococcus aureus. Early diagnosis of infective endocarditis, when suspected, and effective management by a multispecialty team can improve the outcome for the patients.

Evaluation of dosimetric predictors of toxicity after IMRT with concurrent chemotherapy for anal cancer.

BACKGROUND: This study investigates the impact of dosimetric parameters on acute and late toxicity for patients with anal squamous cell carcinoma (SCC) treated with image-guided intensity modulated radiation therapy (IG-IMRT) and concurrent chemotherapy. MATERIALS AND METHODS: Patients were enrolled in an observational cohort study between 2008 and 2013 (median follow-up 3.4 years). They were treated with standardized target and organ-at-risk (OAR) contouring, planning, and IG-IMRT. Radiotherapy dose, based on clinicopathologic features, ranged from 45 Gy to 63 Gy to gross targets and 27 Gy to 36 Gy to elective targets. Chemotherapy was concurrent 5-fluorouracil and mitomycin C (weeks 1&5). Toxicity was prospectively graded using NCI CTCAE v.3 and RTOG scales. Logistic regression was used to assess the association between dose/volume parameters (e.g small bowel V5) and corresponding grade 2 + and 3+ (G2+/3 + ) toxicities (e.g. diarrhea). RESULTS: In total, 87 and 79 patients were included in the acute and late toxicity analyses, respectively. The most common acute G2 + toxicities were skin (dermatitis in 87 % [inguino-genital skin], 91 % [perianal skin]) and hematologic in 58 %. G2 + late anal toxicity (sphincter dysfunction), gastrointestinal toxicity, and skin toxicity were respectively experienced by 49 %, 38 %, and 44 % of patients. Statistically significant associations were observed between: G2 + acute diarrhea and small bowel V35; G2 + acute genitourinary toxicity and bladder D0.5cc; G2 + inguino-genital skin toxicity and anterior skin V35; G2 + perianal skin toxicity and posterior skin V15; G2 + anemia and lower pelvis bone V45. D0.5 cc was significantly predictive of late toxicity (G2 + anal dysfunction, intestinal toxicity, and inguino-genital/perianal dermatitis). Maximum skin toxicity grade was significantly correlated with the requirement for a treatment break. CONCLUSION: Statistically significant dose-volume parameters were identified and may be used to offer individualized risk prediction and to inform treatment planning. Additional validation of the results is required.

Multi-institutional Prognostic Modeling in Head and Neck Cancer: Evaluating Impact and Generalizability of Deep Learning and Radiomics.

Artificial intelligence (AI) and machine learning (ML) are becoming critical in developing and deploying personalized medicine and targeted clinical trials. Recent advances in ML have enabled the integration of wider ranges of data including both medical records and imaging (radiomics). However, the development of prognostic models is complex as no modeling strategy is universally superior to others and validation of developed models requires large and diverse datasets to demonstrate that prognostic models developed (regardless of method) from one dataset are applicable to other datasets both internally and externally. Using a retrospective dataset of 2,552 patients from a single institution and a strict evaluation framework that included external validation on three external patient cohorts (873 patients), we crowdsourced the development of ML models to predict overall survival in head and neck cancer (HNC) using electronic medical records (EMR) and pretreatment radiological images. To assess the relative contributions of radiomics in predicting HNC prognosis, we compared 12 different models using imaging and/or EMR data. The model with the highest accuracy used multitask learning on clinical data and tumor volume, achieving high prognostic accuracy for 2-year and lifetime survival prediction, outperforming models relying on clinical data only, engineered radiomics, or complex deep neural network architecture. However, when we attempted to extend the best performing models from this large training dataset to other institutions, we observed significant reductions in the performance of the model in those datasets, highlighting the importance of detailed population-based reporting for AI/ML model utility and stronger validation frameworks. We have developed highly prognostic models for overall survival in HNC using EMRs and pretreatment radiological images based on a large, retrospective dataset of 2,552 patients from our institution.Diverse ML approaches were used by independent investigators. The model with the highest accuracy used multitask learning on clinical data and tumor volume.External validation of the top three performing models on three datasets (873 patients) with significant differences in the distributions of clinical and demographic variables demonstrated significant decreases in model performance. Significance: ML combined with simple prognostic factors outperformed multiple advanced CT radiomics and deep learning methods. ML models provided diverse solutions for prognosis of patients with HNC but their prognostic value is affected by differences in patient populations and require extensive validation.

An astrocyte BMAL1-BAG3 axis protects against alpha-synuclein and tau pathology.

The circadian clock protein BMAL1 modulates glial activation and amyloid-beta deposition in mice. However, the effects of BMAL1 on other aspects of neurodegenerative pathology are unknown. Here, we show that global post-natal deletion of Bmal1 in mouse tauopathy or alpha-synucleinopathy models unexpectedly suppresses both tau and alpha-synuclein (αSyn) aggregation and related pathology. Astrocyte-specific Bmal1 deletion is sufficient to prevent both αSyn and tau pathology in vivo and induces astrocyte activation and the expression of Bag3, a chaperone critical for macroautophagy. Astrocyte Bmal1 deletion enhances phagocytosis of αSyn and tau in a Bag3-dependent manner, and astrocyte Bag3 overexpression is sufficient to mitigate αSyn spreading in vivo. In humans, BAG3 is increased in patients with AD and is highly expressed in disease-associated astrocytes (DAAs). Our results suggest that early activation of astrocytes via Bmal1 deletion induces Bag3 to protect against tau and αSyn pathologies, providing new insights into astrocyte-specific therapies for neurodegeneration.