The use of artificial intelligence in reconstructive surgery for head and neck cancer: a systematic review.

OBJECTIVES: The popularity of artificial intelligence (AI) in head and neck cancer (HNC) management is increasing, but postoperative complications remain prevalent and are the main factor that impact prognosis after surgery. Hence, recent studies aim to assess new AI models to evaluate their ability to predict free flap complications more effectively than traditional algorithms. This systematic review aims to summarize current evidence on the utilization of AI models to predict complications following reconstructive surgery for HNC. METHODS: A combination of MeSH terms and keywords was used to cover the following three subjects: "HNC," "artificial intelligence," and "free flap or reconstructive surgery." The electronic literature search was performed in three relevant databases: Medline (Ovid), Embase (Ovid), and Cochrane. Quality appraisal of the included study was conducted using the TRIPOD Statement. RESULTS: The review included a total of 5 manuscripts (n = 5) for a total of 7524 patients. Across studies, the highest area under the receiver operating characteristic (AUROC) value achieved was 0.824 by the Auto-WEKA model. However, only 20% of reported AUROCs exceeded 0.70. One study concluded that most AI models were comparable or inferior in performance to conventional logistic regression. The highest predictors of complications were flap type, smoking status, tumour location, and age. DISCUSSION: Some models showed promising results. Predictors identified across studies were different than those found in existing literature, showing the added value of AI models. However, the algorithms showed inconsistent results, underlying the need for better-powered studies with larger databases before clinical implementation.

Spatiotemporal Patterns of Reptile and Amphibian Road Fatalities in a Natura 2000 Area: A 12-Year Monitoring of the Lake Karla Mediterranean Wetland.

The pervasive expansion of human-engineered infrastructure, particularly roads, has fundamentally reshaped landscapes, profoundly affecting wildlife interactions. Wildlife-vehicle collisions, a common consequence of this intricate interplay, frequently result in fatalities, extending their detrimental impact within Protected Areas (PAs). Among the faunal groups most susceptible to road mortality, reptiles and amphibians stand at the forefront, highlighting the urgent need for global comprehensive mitigation strategies. In Greece, where road infrastructure expansion has encroached upon a significant portion of the nation's PAs, the plight of these road-vulnerable species demands immediate attention. To address this critical issue, we present a multifaceted and holistic approach to investigating and assessing the complex phenomenon of herpetofauna road mortality within the unique ecological context of the Lake Karla plain, a rehabilitated wetland complex within a PA. To unravel the intricacies of herpetofauna road mortality in the Lake Karla plain, we conducted a comprehensive 12-year investigation from 2008 to 2019. Employing a combination of statistical modeling and spatial analysis techniques, we aimed to identify the species most susceptible to these encounters, their temporal and seasonal variations, and the ecological determinants of their roadkill patterns. We documented a total of 340 roadkill incidents involving 14 herpetofauna species in the Lake Karla's plain, with reptiles, particularly snakes, being more susceptible, accounting for over 60% of roadkill occurrences. Moreover, we found that environmental and road-related factors play a crucial role in influencing roadkill incidents, while spatial analysis techniques, including Kernel Density Estimation, the Getis-Ord Gi*, and the Kernel Density Estimation plus methods revealed critical areas, particularly in the south-eastern region of Lake Karla's plain, offering guidance for targeted interventions to address both individual and collective risks associated with roadkill incidents.

Gut microbiome predicts gastrointestinal toxicity outcomes from chemoradiation therapy in patients with head and neck squamous cell carcinoma.

OBJECTIVES: Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut microbiome represents an emerging hallmark of cancer and a potentially important biomarker for CRT-related adverse events. This prospective study investigated the association between the gut microbiome composition and CRT-related toxicities in patients with HNSCC, including mucositis. MATERIALS AND METHODS: Stool samples from patients diagnosed with locally advanced HNSCC were prospectively collected prior to CRT initiation and analyzed using shotgun metagenomic sequencing to evaluate gut microbiome composition at baseline. Concurrently, clinicopathologic data, survival outcomes and the incidence and grading of CRT-emergent adverse events were documented in all patients. RESULTS: A total of 52 patients were included, of whom 47 had baseline stool samples available for metagenomic analysis. Median age was 62, 83 % patients were men and 54 % had stage III-IV disease. All patients developed CRT-induced mucositis, including 42 % with severe events (i.e. CTCAE v5.0 grade ≥ 3) and 25 % who required enteral feeding. With a median follow-up of 26.5 months, patients with severe mucositis had shorter overall survival (HR = 3.3, 95 %CI 1.0-10.6; p = 0.02) and numerically shorter progression-free survival (HR = 2.8, 95 %CI, 0.8-9.6; p = 0.09). The gut microbiome beta-diversity of patients with severe mucositis differed from patients with grades 1-2 mucositis (p = 0.04), with enrichment in Mediterraneibacter (Ruminococcus gnavus) and Clostridiaceae family members, including Hungatella hathewayi. Grade 1-2 mucositis was associated with enrichment in Eubacterium rectale, Alistipes putredinis and Ruminococcaceae family members. Similar bacterial profiles were observed in patients who required enteral feeding. CONCLUSION: Patients who developed severe mucositis had decreased survival and enrichment in specific bacteria associated with mucosal inflammation. Interestingly, these same bacteria have been linked to immune checkpoint inhibitor resistance.

Predictors of prolonged treatment time intervals in oral cavity cancer.

OBJECTIVES: Delays in treatment time intervals have been associated with overall survival in oral cavity squamous cell carcinoma (OCSCC). The aim of this study was to identify bottlenecks leading to prolonged treatment intervals. MATERIAL AND METHODS: A retrospective analysis was conducted using a cohort of OCSCC patients who underwent surgery and adjuvant radiation therapy. The endpoints of interest were prolonged treatment intervals. Multivariable logistic regression was used to adjust for patient and tumour characteristics. RESULTS: Median diagnosis-to-treatment interval (DTI) and surgery to initiation of postoperative radiation therapy interval (S-PORT) were 39 days (IQR 30-54) and 64 days (IQR 54-66), respectively. Prolonged DTI was associated with older age, worse Charlson Comorbidity index scores and worse T stages. Patients with prolonged DTI had longer times to preoperative imaging reports (25 vs 9 days; P < 0.01). Time to preoperative pathology did not differ. Prolonged S-PORT was associated with longer times to pathology report (28 vs 18 days; P < 0.01), to maxillofacial consult (38 vs 15 days; P < 0.01) and to maxillofacial approval of radiation (50 vs 28 days; P < 0.01). In patients requiring medical oncology consults, those with prolonged S-PORT had longer waiting times until consultation (58 vs 38 days; P = 0.02). Multivariate analysis showed independent predictors of prolonged DTI: time to preoperative imaging; and prolonged S-PORT: time to pathology report, time to maxillofacial consult, and time to medical oncology consult. CONCLUSIONS: Strategies targeting these organizational bottlenecks may be effective for shortening treatment time intervals, hence representing potential opportunities for improving oncological outcomes in OCSCC patients.

Patterns of alaryngeal voice adoption and predictive factors of vocal rehabilitation failure following total laryngectomy.

OBJECTIVE: We aimed to determine patterns of alaryngeal voice acquisition and predictive factors of vocal rehabilitation (VR) failure following total laryngectomy (TL) at a large Canadian tertiary care center. METHODS: All consecutive patients having undergone a TL between January 1st, 2011 and December 31st, 2019, at the Centre Hospitalier de l'Université de Montréal were included. RESULTS: One hundred and ninety-seven laryngectomized patients were identified. Successful VR was achieved in 86 (59.0%) patients, while 59 (41.0%) failed to use a method of alaryngeal voice as their principal means of communication at 1 year postoperatively. The use of tracheoesophageal puncture (TEP) was associated with higher VR success rates (70.6%) when compared with the artificial larynx (48.6%), and esophageal voice (18.8%). The only independent predictor of VR failure on multivariate analysis at all time points was a low socioeconomic status. CONCLUSION: Failure to adopt an alaryngeal voice following TL is highly prevalent, despite comprehensive and free speech language pathologist services being offered at our center. A low resort to TEP at our institution and a poor acceptability and accessibility of alternative VR methods may contribute to this trend. The challenges of VR may be further exacerbated by the barriers linked to a lower socioeconomic status, which in turn may contribute to reduced candidacy for TEP.

Oncologic Significance of Therapeutic Delays in Patients With Oral Cavity Cancer.

Importance: Oral cavity cancer often requires multidisciplinary management, subjecting patients to complex therapeutic trajectories. Prolonged treatment intervals in oral cavity cancer have been associated with poor oncological outcomes, but there has yet to be a study investigating treatment times in Canada. Objective: To report treatment delays for patients with oral cavity cancer in Canada and evaluate the outcomes of treatment delays on overall survival. Design, Setting, and Participants: This multicenter cohort study was performed at 8 Canadian academic centers from 2005 to 2019. Participants were patients with oral cavity cancer who underwent surgery and adjuvant radiation therapy. Analysis was performed in January 2023. Main Outcomes and Measures: Treatment intervals evaluated were surgery to initiation of postoperative radiation therapy interval (S-PORT) and radiation therapy interval (RTI). The exposure variables were prolonged intervals, respectively defined as index S-PORT greater than 42 days and RTI greater than 46 days. Patient demographics, Charlson Comorbidity Index, smoking status, alcohol status, and cancer staging were also considered. Univariate (log rank and Kaplan-Meier) and multivariate (Cox regression) analyses were performed to determine associations with overall survival (OS). Results: Overall, 1368 patients were included; median (IQR) age at diagnosis was 61 (54-70) years, and 896 (65%) were men. Median (IQR) S-PORT was 56 (46-68) days, with 1093 (80%) patients waiting greater than 42 days, and median (IQR) RTI was 43 (41-47) days, with 353 (26%) patients having treatment time interval greater than 46 days. There were variations in treatment time intervals between institutions for S-PORT (institution with longest vs shortest median S-PORT, 64 days vs 48 days; η2 = 0.023) and RTI (institution with longest vs shortest median RTI, 44 days vs 40 days; η2 = 0.022). Median follow-up was 34 months. The 3-year OS was 68%. In univariate analysis, patients with prolonged S-PORT had worse survival at 3 years (66% vs 77%; odds ratio 1.75; 95% CI, 1.27-2.42), whereas prolonged RTI (67% vs 69%; odds ratio 1.06; 95% CI, 0.81-1.38) was not associated with OS. Other factors associated with OS were age, Charlson Comorbidity Index, alcohol status, T category, N category, and institution. In the multivariate model, prolonged S-PORT remained independently associated with OS (hazard ratio, 1.39; 95% CI, 1.07-1.80). Conclusions and Relevance: In this multicenter cohort study of patients with oral cavity cancer requiring multimodal therapy, initiation of radiation therapy within 42 days from surgery was associated with improved survival. However, in Canada, only a minority completed S-PORT within the recommended time, whereas most had an appropriate RTI. An interinstitution variation existed in terms of treatment time intervals. Institutions should aim to identify reasons for delays in their respective centers, and efforts and resources should be directed toward achieving timely completion of S-PORT.

The protective role of postoperative radiation therapy in low and intermediate grade major salivary gland malignancies: A study of the Canadian Head and Neck Collaborative Research Initiative.

BACKGROUND: The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands. METHODS: The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution. RESULTS: In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10 years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10 years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins. CONCLUSIONS: Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins.

Preoperative evaluation of depth of invasion in oral tongue squamous cell carcinoma: A systematic review and meta-analysis.

The inclusion of depth of invasion (DOI) in the American Joint Committee on Cancer's staging system for oral cavity squamous cell carcinoma (SCC) has major clinical impacts. Recent studies have evaluated the reliability of imaging modalities and biopsy techniques to measure DOI preoperatively. The objective of this systematic review and meta-analysis was to comprehensively include all previously described methods to measure preoperative DOI in oral tongue SCC (OTSCC) and to compare their reliability. A systematic review was conducted on PubMed, Embase and Cochrane according to the PRISMA guidelines. Studies that evaluated the reliability of DOI measured on biopsy or imaging (rDOI) by comparing it to DOI on histopathology (pDOI) were included for extraction. A meta-analysis was conducted to obtain pooled correlation coefficients for each imaging modality. The pooled correlation coefficients between rDOI and pDOI were 0.86 (CI95% = [0.82-0.88]) and 0.80 (CI95% = [0.70-0.87]) for magnetic resonance imaging (MRI) studies and computed tomography (CT) studies, respectively. For ultrasound (US), the correlation coefficient could only be measured by including studies which measured not only DOI but also tumor thickness. It was 0.89 (CI95%= [0.82-0.94]). Overall, MRI is the better studied modality. It has a good reliability to measure preoperative rDOI in OTSCC. CT is less studied but appears to be less reliable. US cannot be compared to these imaging modality as it has been used more often to measure TT than DOI.

Quantification and visualization of aerosols in ear, nose, and throat exam and flexible laryngoscopy.

Objective: To measure and visualize aerosol generation during ear, nose, and throat (ENT) exam and flexible laryngoscopy, as safety recommendations are currently to defer routine and low-priority examinations. Methods: Aerosols generated during ENT examination and flexible laryngoscopy were quantified by laser aerosol spectrometry and visualized live by high-speed imaging during those procedures for three participants who were tested three times for each test. Results: Routine ENT examination and flexible laryngoscopy produce aerosols at levels comparable to normal breathing and speech. Conclusion: During ENT examination and flexible laryngoscopy, the practitioner should wear a surgical mask and potentially contaminated surfaces should be cleaned after the procedure. For flexible laryngoscopy, it is recommended in addition that the patient wear a mask over the mouth in case the procedure induces a sneeze. The time during which the patient is unmasked should be minimized. In these settings, the risk to the practitioner is minimal unless the patient is sneezing or symptomatic. Level of Evidence: 1.

Assessment of surgical competence for neck dissection: a pilot study.

BACKGROUND: Progressive implementation of the milestone competence-based curriculum has created a need for new objective and validated means to assess resident surgical proficiency. A previous systematic review of the literature by our group has highlighted a shortage of tools assessing surgical competence in oncologic procedures in otolaryngology - head and neck surgery. METHODS: We developed a procedure-specific assessment tool for neck dissection using a modified Delphi method. The 2-part design was modelled on the previously validated Objective Structured Assessment of Technical Skills checklist. The tool was then validated through a 1-year multicentric prospective study in collaboration with the residents and faculty from our academic centre. Additionally, we developed an online survey to assess the acceptability by residents and staff before and after the validation studies. RESULTS: A total of 29 evaluations were completed throughout the 2016-2017 academic year. Acceptability ranked high for both residents and staff, with a single discrepancy in responses regarding a potential formative as opposed to summative use of the tool. Validation study results showed significantly higher checklist scores among senior residents than junior residents, as well as a significant score progression over time (p < 0.05). Trends in scores on the task-specific tool correlated highly to results obtained on a validated global rating scale (p < 0.05). CONCLUSION: The first tool assessing surgical competence in oncologic otolaryngology - head and neck surgery has been developed and shows promising validity.

An (Un)Expected Threat for a Regionally Near-Threatened Species: A Predation Case of a Persian Squirrel on an Insular Ecosystem.

One of the most successful predators on island ecosystems is the domestic cat, which is considered responsible for the decline of numerous species' populations. This can be estimated by the analysis of cats' dietary habits, yet prey identification is not always possible, and thus, in cases where precise prey identification is required, one of the most accurate methods derives from observing the hunting process. However, the cryptic nature of the feral cats and the constant vigilance of the species that are preyed upon make the observation process difficult, especially when the prey has a low population density. Here, we report for the first time such a case: a feral cat that has ambushed, killed, and consumed a regionally near-threatened species, the Persian squirrel. This incidental observation happened in the squirrel's westernmost end of its distribution, the island of Lesvos, Greece. Due to the unexpectedness of the event, in the following days, we estimated both the squirrels' and cats' population density. Results showed that while the density of the squirrels is moderate, the population density of the feral cats is almost fifteen times higher. For this reason, management actions need to be taken in an effort to minimize the impacts of feral cats on the native species of the island.

Reconstruction of medium-size defects of the oral cavity: radial forearm free flap vs facial artery musculo-mucosal flap.

BACKGROUND: The radial forearm free flap (RFFF) is the most commonly used flap for defects of the oral cavity. The facial artery musculomucosal (FAMM) is a safe and effective method to reconstruct medium sized defects of the oral cavity. No comparison exists between the FAMM flap and RFFF. METHODS: 1) Retrospective chart review from 2007 to 2016. 2) Cost difference analysis. RESULTS: Thirteen FAMM flap cases and 18 RFFF met inclusion criteria. The FAMM flap showed a tendency to lower rates of return to the operating room (p = 0.065) as well as lower rates of complications not requiring return to the OR with 1 complication in 1 patient as opposed to 10 patients with 15 complications (p = 0.008). Also, FAMM flap had shorter operative times compared to the RFFF group (7.2HR and 8.9 HR respectively, p = 0.002). The average operative room related costs for a FAMM flap were 6510 CAD vs 10,703 CAD for RFFF (p < 0.0005). Speech and swallowing outcomes were similar (p > 0.05). CONCLUSION: The FAMM flap can be used for reconstruction of medium-size defects of the oral cavity with functional outcomes similar to the RFFF while decreasing the associated costs and morbidity.

DCBLD1 is associated with the integrin signaling pathway and has prognostic value in non-small cell lung and invasive breast carcinoma.

Germline single nucleotide polymorphisms in the promoter region of the DCBLD1 gene are associated with non-smoking cases of both non-small cell lung carcinoma (NSCLC) and human papillomavirus-negative head and neck cancer. However the clinical relevance and function of DCBLD1 remain unclear. This multicenter retrospective study was designed to evaluate the prognostic value and function of DCBLD1 in the four main solid cancers: NSCLC, invasive breast carcinoma, colorectal adenocarcinoma and prostate adenocarcinoma. We included the following cohorts: GSE81089 NSCLC, METABRIC invasive breast carcinoma, GSE14333 colorectal adenocarcinoma, GSE70770 prostate adenocarcinoma and The Cancer Genome Atlas (TCGA) Firehose Legacy cohorts of all four cancers. DCBLD1 gene expression was associated with a worse overall survival in multivariate analyses for both NSCLC cohorts (TCGA: P = 0.03 and GSE81089: P = 0.04) and both invasive breast carcinoma cohorts (TCGA: P = 0.02 and METABRIC: P < 0.001). Patients with high DCBLD1 expression showed an upregulation of the integrin signaling pathway in comparison to those with low DCBLD1 expression in the TCGA NSCLC cohort (FDR = 5.16 × 10-14) and TCGA invasive breast carcinoma cohort (FDR = 1.94 × 10-05).

Development, translation, and preliminary validation of the neck dissection assessment tool.

BACKGROUND: The objective was to develop an assessment tool to evaluate residents' competency for neck dissection and provide preliminary evidence of feasibility, reliability, and validity. METHODS: Six surgeons developed a neck dissection assessment tool using a modified Delphi method and evaluated 58 neck dissections from six junior and six senior otolaryngology residents. RESULTS: The assessment tool uses a double checklist: a previously validated global rating scale (GRS) and a task-specific checklist (TSC). Use of the instrument appeared feasible and the average scores on the GRS and TSC differed significantly between junior and senior residents. The Pearson correlation coefficient between both checklists was 0.87. Intraclass correlation (ICC) for inter-rater reliability was 0.69 for the GRS, and 0.80 for the TSC. CONCLUSION: This study provides preliminary evidence of feasibility, reliability, and validity for the first neck dissection assessment tool and provides a foundation for further psychometric analysis and research.

Université de Montréal Objective and Structured Checklist for Assessment of Audiovisual Recordings of Surgeries/ techniques (UM-OSCAARS): a validation study.

Background: Use of videos of surgical and medical techniques for educational purposes has grown over the last years. To our knowledge, there is no validated tool to specifically assess the quality of these types of videos. Our goal was to create an evaluation tool and study its intrarater and interrater reliability and its acceptability. We named our tool UM-OSCAARS (Université de Montréal Objective and Structured Checklist for Assessment of Audiovisual Recordings of Surgeries/techniques). Methods: UM-OSCAARS is a grid containing 10 criteria, each of which is graded on an ordinal Likert-type scale of 1 to 5 points. We tested the grid with the help of 4 voluntary otolaryngology - head and neck surgery specialists who individually viewed 10 preselected videos. The evaluators graded each criterion for each video. To evaluate intrarater reliability, the evaluation took place in 2 different phases separated by 4 weeks. Interrater reliability was assessed by comparing the 4 topranked videos of each evaluator. Results: There was almost-perfect agreement among the evaluators regarding the 4 videos that received the highest scores from the evaluators, demonstrating that the tool has excellent interrater reliability. There was excellent test-retest correlation, demonstrating the tool's intrarater reliability. Conclusion: The UM-OSCAARS has proven to be reliable and acceptable to use, but its validity needs to be more thoroughly assessed. We hope this tool will lead to an improvement in the quality of technical videos used for educational purposes.

Contexte: Au fil des ans, l'utilisation de vidéos pour l'enseignement de techniques chirurgicales et médicales s'est répandue. À notre connaissance, il n'existe aucun outil pour évaluer spécifiquement la qualité de ces types de vidéos. Notre objectif était de créer un outil d'évaluation et d'analyser sa fiabilité interévaluateurs et son acceptabilité. Notre outil a pour nom UM-OSCAARS (Université de Montréal Objective and Structured Checklist for Assessment of Audiovisual Recordings of Surgeries/Techniques). Méthodes: L'outil UM-OSCAARS est une grille qui contient 10 critères; chacun est noté sur une échelle de type Likert de 1 à 5 points. Nous avons testé la grille avec l'aide de 4 volontaires, spécialistes en otorhinolaryngologie/chirurgie de la tête et du cou, qui ont visionné 10 vidéos présélectionnées. Les évaluateurs ont noté chacun des critères pour chaque vidéo. Afin de vérifier la fiabilité interévaluateurs, l'évaluation s'est déroulée en 2 phases, à 4 semaines d'intervalle. La fiabilité interévaluateurs a été mesurée en comparant les 4 vidéos les mieux cotées par chaque évaluateur. Résultats: La concordance a été quasi parfaite entre les évaluateurs pour les 4 vidéos qu'ils ont les mieux cotées, ce qui montre que l'outil a une excellente fiabilité interévaluateurs. La corrélation test­retest a été excellente, ce qui démontre la fiabilité interévaluateurs de l'outil. Conclusion: L'outil UM-OSCAARS et son utilisation se sont révélés fiables et acceptables, mais il faut évaluer davantage sa validité. Nous espérons que cet outil permettra d'améliorer la qualité des vidéos techniques destinées à l'enseignement.

Vocal-cord Only vs. Complete Laryngeal radiation (VOCAL): a randomized multicentric Bayesian phase II trial.

BACKGROUND: Radiotherapy, along with laser surgery, is considered a standard treatment option for patients with early glottic squamous cell cancer (SCC). Historically, patients have received complete larynx radiotherapy (CL-RT) due to fear of swallowing and respiratory laryngeal motion and this remains the standard approach in many academic institutions. Local control (LC) rates with CL-RT have been excellent, however this treatment can carry significant toxicities include adverse voice and swallowing outcomes, along with increased long-term risk of cerebrovascular morbidity. A recent retrospective study reported improved voice quality and similar local control outcomes with focused vocal cord radiotherapy (VC-RT) compared to CL-RT. There is currently no prospective evidence on the safety of VC-RT. The primary objective of this Bayesian Phase II trial is to compare the LC of VC-RT to that of CL-RT in patients with T1N0 glottic SCC. METHODS: One hundred and fifty-five patients with T1a-b N0 SCC of the true vocal cords that are n ot candidate or declined laser surgery, will be randomized in a 1:3 ratio the control arm (CL-RT) and the experimental arm (VC-RT). Randomisation will be stratified by tumor stage (T1a/T1b) and by site (each site will be allowed to select one preferred radiation dose regimen, to be used in both arms). CL-RT volumes will correspond to the conventional RT volumes, with the planning target volume extending from the top of thyroid cartilage lamina superiorly to the bottom of the cricoid inferiorly. VC-RT volumes will include the involved vocal cord(s) and a margin accounting for respiration and set-up uncertainty. The primary endpoint will be LC at 2-years, while secondary endpoints will include patient-reported outcomes (voice impairment, dysphagia and symptom burden), acute and late toxicity radiation-induced toxicity, overall survival, progression free survival, as well as an optional component of acoustic and objective measures of voice analysis using the Consensus Auditory-Perceptual Evaluation of Voice. DISCUSSION: This study would constitute the first prospective evidence on the efficacy and safety of VC-RT in early glottic cancer. If positive, this study would result in the adoption of VC-RT as standard approach in early glottic cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759431 Registration date: November 30, 2018.

mTOR as a senescence manipulation target: A forked road.

Cellular senescence, cancer and aging are highly interconnected. Among many important molecular machines that lie at the intersection of this triad, the mechanistic (formerly mammalian) target of rapamycin (mTOR) is a central regulator of cell metabolism, proliferation, and survival. The mTOR signaling cascade is essential to maintain cellular homeostasis in normal biological processes or in response to stress, and its dysregulation is implicated in the progression of many disorders, including age-associated diseases. Accordingly, the pharmacological implications of mTOR inhibition using rapamycin or others rapalogs span the treatment of various human diseases from immune disorders to cancer. Importantly, rapamycin is one of the only known pan-species drugs that can extend lifespan. The molecular and cellular mechanisms explaining the phenotypic consequences of mTOR are vast and heavily studied. In this review, we will focus on the potential role of mTOR in the context of cellular senescence, a tumor suppressor mechanism and a pillar of aging. We will explore the link between senescence, autophagy and mTOR and discuss the opportunities to exploit senescence-associated mTOR functions to manipulate senescence phenotypes in age-associated diseases and cancer treatment.

Phase II study of de-intensified intensity-modulated radiotherapy and concurrent carboplatin/5-fluorouracil in lateralized p16-associated oropharyngeal carcinoma.

PURPOSE: To assess cancer control and patient-reported outcomes (PROs) after de-intensified intensity-modulated radiotherapy (IMRT) in lateralized p16-associated oropharyngeal cancer (p16-OPC). METHODS: Lateralized p16-OPC treated with radiotherapy and concurrent Carboplatin/5-fluorouracil between 2011 and 2014 were enrolled. De-intensified IMRT consisted in elective neck dose of 43.2 Gy/24 fractions and omission of contralateral retropharyngeal/level IV nodes. PROs were assessed using the EORTC QLC-C30 and QLQ-HN35 scales. RESULTS: Twenty-nine patients were included. Median follow-up was 44 months. As per AJCC 7th Ed, 7%, 83% and 10% of patients had stage III, IVa and IVb. 5-year locoregional control and overall survival rates were 100% and 100%, respectively. Rates of acute were 52% and 35%, respectively. At 2 years post-treatment, 50% and 14% of patients had grade 1 xerostomia and dysgueusia, respectively. Most PROs scores returned to baseline within 8 months post-treatment. CONCLUSION: De-intensified IMRT was associated with excellent cancer outcomes, and rapid recovery of PROs in lateralized p16-OPC.