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Background This study tackles the challenge of developing reliable prognostic models for time-to-event (TTE) outcomes using high-dimensional omics data in head and neck cancers. Resampling methods, particularly nested cross-validation, are considered as standard for model hyperparameter selection and performance evaluation. When handling clustered data, balancing the random partition of the cross-validation folds to minimize optimism bias and instability could be tested. This work compares the performance of three nested cross-validation implementations, including random assignment of the folds, clustering-based resampling, and internal-external validation using an hold out approach. Method We analyzed two head and neck squamous cell carcinoma (HNSCC) cohorts: The Cancer Genome Atlas (TCGA) and SCANDARE (NCT03017573), with clinical data and transcriptomic data normalized as log-transcripts per million. Three model selection methods LASSO, IPF-Lasso, and Priority-LASSO were evaluated within five nested cross-validation frameworks: Standard nested cross-validation, Clustering-based nested-cross validation, nested-cross validation with Combat correction, Nested cross-validation for optimization combined with hold-out for validation, Nested cross-validation for optimization combined with hold-out and ComBat correction for validation. Predictive performance was assessed using 3-year AUC and Integrated Brier Score (IBS). Results We analyzed data from 581 patients (mean age 61.0 years, 33.6% female) across TCGA-HNSC ( n  = 505) and SCANDARE ( n  = 76). Clustering analyses, using UMAP and k-means, identified three transcriptomic clusters. Validation strategies demonstrated reduced instability for Lasso ( p  < 0.001), IPF-Lasso ( p  < 0.001) and Priority-lasso ( p  < 0.001) without apparent optimism in discrimination and calibration metrics with stratified nested cross-validation (SNCV), supporting its utility. As an application using IPF-Lasso Cox models with SNCV, we integrated clinical and transcriptomic data, selecting 35 prognosis variables of head and neck carcinomas. This model achieved a 3-year AUC of 0.71 and IBS of 0.08. Conclusion Clustering-based nested cross-validation combined with stratified cross-validation offers a robust compromise for developing high-dimensional survival models and evaluating their predictive performance. This approach leverages clustering-derived stratification to balance heterogeneity in the dataset within cross-validation folds, although the training and test sets remain derived from the pooled dataset rather than fully independent cohorts.

Background: Recent advances in understanding the biology of cancer have resulted in an extensive armamentarium of new therapeutic agents, most often tested on various tumor types at the earliest stages of drug development. However, the clinical impact of these therapies on patients with head and neck cancer (HNC) remains underexplored and requires further evaluation. Objectives: To investigate the clinical outcomes and toxicity profiles of patients with HNC enrolled in phase I trials (Ph1t) at a tertiary referral center over the last decade. Design: A retrospective cohort study was conducted, analyzing data from HNC patients enrolled in phase I trials at the Curie Institute between October 2011 and January 2024. Methods: Data on baseline characteristics, hematologic biomarkers, and outcomes were extracted from medical records. Objective response rate (ORR) and Kaplan–Meier estimates of progression-free survival (PFS) and overall survival (OS) were analyzed. A Cox model was used for the identification of prognostic factors. Results: One hundred and thirty patients were enrolled in Ph1t for recurrent/metastatic (R/M) setting (66.9%), including 20.8% of patients being treated with more than two lines of therapy, followed by locally advanced (LA) treated with radical surgery or exclusive chemo/radiotherapy (17.7%), neoadjuvant (10.0%), and adjuvant (5.4%) Ph1t. Patients were treated with immunotherapy (53.8%), targeted therapy (23.1%), bispecific antibody (8.5%), antibody–drug conjugate (4.6%), and other agents (10.0%). In 122 patients evaluable for response, ORR were 16.5%, 87.0%, and 92.3% in R/M, LA, and neoadjuvant Ph1t, respectively. Median PFS/OS rates were 2.0/8.3, 21.5/38.3, and 20.0/27.4 months in R/M, LA, and neoadjuvant Ph1t, respectively. At multivariable analysis, lower lymphocytes (HR = 0.144; 95% CI: 0.052–0.399; p < 0.001) and lower albumin levels (HR = 0.922; 95% CI: 0.879–0.966; p < 0.001) remained associated with poorer OS. Grade 3–4 adverse events were recorded in 27/130 patients (20.8%). The most frequent were hematologic and gastrointestinal disorders. No treatment-related deaths occurred. Conclusion: HNC Ph1t show encouraging results in terms of early efficacy signals and safety profiles, emphasizing their value across a variety of clinical settings.

Background SMARCB1, also known as INI1, is a member of a large protein complex involved in chromatin remodeling and thus the regulation of gene expression. It is located on chromosome 22q11.2. SMARCB1 tumors have been found in various locations, including the sinonasal region, gastrointestinal tract, central nervous system (in atypical teratoid and rhabdoid tumors), and perirenal region (in malignant rhabdoid tumors) in both adults and children. Case presentation We describe here the first case in the literature of an INI1-deficient neck carcinoma without a primary tumor managed with surgical therapy and neck dissection in a young Caucasian woman of 29 years old, followed by chemotherapy before radiotherapy, with regional control after 18 months of follow-up. Histologic analysis showed an undifferentiated carcinoma without glandular or epidermoid differentiation. Biomolecular analysis of the tumor revealed a homozygous deletion of the SMARCB1 gene on RNA sequencing. Conclusion Research of INI1 deletion should be performed for undifferentiated carcinoma of young patients because of possibilities of molecular therapies such as autophagy inhibitors or proteasome inhibitors could be used in clinical trials.

Objective Surgical (SS) and non-surgical strategies (NSS) are both considered as valid options in the therapeutic management of oropharyngeal squamous cell carcinoma (OPSCC) because of the absence of randomized control trial. Method The objective of this retrospective cohort study was to compare the efficacy of SS versus NSS on overall survival (OS) and disease-free survival (DFS) in non-metastatic OPSCC. The study included patients treated in two centers between 2012 and 2020 treated by upfront surgery in SS group and other therapies in NSS. A Cox model allowed to estimate hazard ratios and 95%CI., Weighting by the inverse probability of a propensity score was applied due to the absence of randomization. Results We analyzed 432 patients with a majority (71%) of male patients and a mean age of 62.6 (SD10.1), HPV prevalence of 70%, 61% were smokers. The 5-year OS and DFS were 59% (95%CI 54–64) and 61% (95% CI 56–66), respectively. The sample was split into SS ( n  = 254) and NSS ( n  = 178). Patients exposed to SS were statistically younger ( p  < 0.001), with a better performance status (PS) ( p  < 0.001), and less advanced TNM stage ( p  < 0.001). After weighting, the two groups were comparable. The weighted HR of SS versus NSS were 0.65 (95%CI 0.45–0.95, p  = 0.02) and 0.67 (95%CI 0.47–0.94, p  = 0.02) for OS and DFS respectively. Further sensitivity analysis confirmed these results. Conclusions While our findings suggest potential benefits of SS, ongoing controlled randomized trials are essential to conform these observations.

Anatomical variations of the stylohyoid apparatus are frequent. Two types can occur: an elongation of the stylohyoid ligament, from a long styloid process to a complete ossified structure connecting the skull base to the lesser horn of the hyoid bone, or the existence of supernumerary bones in the stylohyoid fibrous matrix, which sometimes resembles phalanges. These variations are in the majority of cases bilateral and symmetrical. The authors report the case of a 43-year-old male patient who presented with an unusual unilateral complete ossification of the stylohyoid apparatus, associated with vertebral and laryngeal calcifications. Original latest generation CT scan and three-dimensional MRI imagery are provided to illustrate this rare case.

BackgroundOur study aims to identify predictive factors of moderate to severe (grade ≥ 2) late toxicity after reirradiation (reRT) of recurrent head and neck carcinoma (HNC) and explore the correlations between dose organs at risk (OAR) and grade ≥ 2 toxicity.Material and methodsBetween 09/2007 and 09/2019, 55 patients were re-irradiated with IMRT or proton therapy with curative intent for advanced HNC. Our study included all patients for whom data from the first and second irradiations were available. Co-variables, including interval to reRT, size of re-irradiated PTV, and dose to OAR, were analyzed as potential predictors for developing moderate to severe long-term toxicity with death as a competing risk. Receiver-operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity.ResultsTwenty-three patients participated in our study. After a median follow-up of 41 months, 65% of the patients experienced grade ≥ 2 late toxicity. The average dose to pharyngeal constrictor muscles (PCM) at the time of reRT showed an association with the risk of grade ≥ 2 dysphagia: AUC = 0.78 (95% CI: 0.53–1), optimal cut-off value = 36.7 Gy (sensitivity 62%/specificity 100%). The average dose to the oral cavity at the time of reRT showed an association with the risk of grade ≥ 2 dysgeusia: AUC = 0.96 (0.89–1), optimal cut-off value = 20.5 Gy (sensitivity 100%/specificity 88%).ConclusionOur analysis depicted an association between the dose to OAR and the risk of developing moderate to severe dysphagia and dysgeusia and proposed new dose constraints for PCM (36.7 Gy) and oral cavity (20.5 Gy).

Purpose This study was designed to assess the efficacy and morbidity of the endoscopic endonasal approach for the treatment of sinonasal adenocarcinomas. Methods This was a retrospective, multicenter study of nine French tertiary referral centers, including untreated patients. All patients were operated by an endoscopic approach. Tumors were classified according to the UICC 2002. Demographic, therapeutic, histological, morbidity data, and the course of the disease were recorded. Survival rates were obtained using the Kaplan-Meier method. Results A total of 159 patients were included with a mean age of 69 years. There were 19T1, 62T2 (1M1), 36T3 (1N1), 26T4a, and 16T4b (1N2a-1N2c). The mean duration of hospitalization was 4.4 days. The histologic outcomes showed that the olfactory cleft, the posterior and anterior ethmoid sinus, and the sphenoid, maxillary, and frontal sinuses were invaded in 95, 64, 55, 19, 7, and 3 % of cases, respectively. Histologic margins were positive in 17 % (1T1, 4T2, 3T3, 2T4a, and 8T4b). In total, 130 patients received adjuvant radiotherapy on the primary tumor site (58 Gy), 24 cases were not irradiated, and 5 refused treatment. The mean follow-up was 32.5 ± 24 months. The complication rate was 19 %: 6 epistaxis, 3 meningitis, 6 CSF leaks, 2 dacryocystitis, and 8 septoplasties. The recurrence rate was 17.6 % (28 cases) within 23 ± 21 months. Eleven patients underwent a second surgical procedure. Nine patients died of their disease (3T2, 2T3, 4T4b). The global and disease-specific, recurrence-free survival rate at 3 years was 74 and 84 % respectively. Conclusions The endoscopic approach seems to be efficient to remove sinonasal adenocarcinoma with low morbidity.

Epiphora has traditionally fallen under the purview of ophthalmologists. However, owing to the development of endoscopic dacryocystorhinostomy, this condition has been increasingly observed in otolaryngologic practice. We report the case of a woman with a 4-month history of right epiphora and dacryocystitis. Nasal endoscopy revealed the presence of a tumor at the inferior meatus. Histopathologic examination of a biopsy specimen identified the tumor as an oncocytoma. Surgical excision via a lateral rhinotomy approach was performed. At 3 years postoperatively, the patient was disease-free. Lacrimal sac and nasolacrimal duct tumors are rare, but they should be considered as a possible etiology in patients with acquired epiphora because most of these tumors are malignant.

Objective: To assess the opinion, practices, and challenges of international key opinion leaders about two minimal invasive surgical techniques in supraglottic laryngeal tumours: transoral laser microsurgery (TLM) and the transoral robotic surgery (TORS). Methods: Design of a questionnaire composed of seven sections and fifty questions covering descriptive data of participants, practitioners experience procedural sequences, considerations related to airways, feeding, and voice, intraoperative haemorrhage, postoperative management, and a comparative analysis of TLM and TORS in treating supraglottic laryngeal cancer. Results: A total of 27 head and neck surgeons replied to the survey. The experts had an average experience in laryngeal surgery of 20.0 ± 9.4 years, ranging from 5 to 36 years. We noted a significantly shorter installation time in TLM compared to TORS (19% of experts estimated the installation time of over 20 min with TLM vs 44% with TORS; p = 0.02). According to complications, the experts considered that bleeding was the major concern with supraglottic laryngeal surgery, especially intraoperative bleeding in TLM (52% in TLM vs 26% in TORS) (p = 0.09) and postoperative bleeding in TORS (56% in TORS vs 44% in TLM). Conclusion: The experts did not identify a clear superiority of one technology (TLM) over the other (TORS). The two techniques seemed equivalent to the experts, except for the control of intraoperative haemostasis and visualisation of the surgical field, where TORS was perceived as superior to TLM.

Vagal paragangliomas are rare in the head and neck. Complementary use of computed tomography and magnetic resonance imaging can facilitate the diagnosis and help determine the best management approach. Most paragangliomas should be treated with surgery. We report a case of vagal paraganglioma of the neck in a 50-year-old man. The patient was treated with superficial parotidectomy via a transcervical approach. No postoperative morbidity was noted, and at 3 years of follow-up, he was free of disease.