Advances and residual knowledge gaps in the neck management of head and neck squamous cell carcinoma patients with advanced nodal disease undergoing definitive (chemo)radiotherapy for their primary.

PURPOSE: Substantial changes have been made in the neck management of patients with head and neck squamous cell carcinomas (HNSCC) in the past century. These have been fostered by changes in cancer epidemiology and technological progress in imaging, surgery, or radiotherapy, as well as disruptive concepts in oncology. We aimed to review changes in nodal management, with a focus on HNSCC patients with nodal involvement (cN+) undergoing (chemo)radiotherapy. METHODS: A narrative review was conducted to review current advances and address knowledge gaps in the multidisciplinary management of the cN+ neck in the context of (chemo)radiotherapy. RESULTS: Metastatic neck nodes are associated with poorer prognosis and poorer response to radiotherapy, and have therefore been systematically treated by surgery. Radical neck dissection (ND) has gradually evolved toward more personalized and less morbid approaches, i.e., from functional to selective ND. Omission of ND has been made feasible by use of positron-emission tomography/computed tomography to monitor the radiation response in cN+ patients. Human papillomavirus-driven oropharyngeal cancers and their cystic nodes have shown dramatically better prognosis than tobacco-related cancers, justifying a specific prognostic classification (AJCC) creation. Finally, considering the role of lymph nodes in anti-tumor immunity, de-escalation of ND and prophylactic nodal irradiation in combination are intense areas of investigation. However, the management of bulky cN3 disease remains an issue, as aggressive multidisciplinary strategies or innovative combined treatments have not yet significantly improved their prognosis. CONCLUSION: Personalized neck management is an increasingly important aspect of the overall therapeutic strategies in cN+ HNSCC.

Peri-operative management of endoscopic endonasal cerebrospinal fluid leak repair: an international survey.

PURPOSE: Peri-operative management of nasal cerebrospinal fluid (CSF) leaks is not consensual due to limited evidence. The main aim of this study was to identify key factors in peri-operative management of endoscopic endonasal CSF leak repair among international experts. METHODS: A 60-item survey questionnaire collected opinions of members of international learned societies of ENT surgeons and neurosurgeons on nasal packing, post-operative instructions, antibiotic prophylaxis, and CSF volume depletion. RESULTS: The survey had 153 respondents (124 otorhinolaryngologists and 29 neurosurgeons). A resting position was recommended by 85% (130/151) of respondents for extended CSF leak of the anterior skull base, mainly in Fowler's position (72% (110/153)). Nasal packing was used by 85% (130/153) of respondents; 33.3% (51/153) used it to stabilize the reconstruction, and 22.2% (34/153) to prevent bleeding. It was usually removed after 48 h in 44.4% of cases (68/153). CSF depletion was considered by 47.1% (72/153) of respondents in case of CSF leak recurrence and by 34.6% (53/153) in cases of increased intracranial pressure. All respondents gave specific postoperative instructions to patients including driving, running, swimming, diving restrictions and flighting restrictions. In subgroup analysis, ENT surgeons more often recommended a resting position than neurosurgeons (71% vs. 37.9% ; p = 0.0008) and prescribed more antibiotics (82.3% vs. 21.4% ; p < 0.0001). CONCLUSION: Although postoperative management after CSF closure remains challenging and not codified, this international survey revealed some points of consensus concerning resting position and restriction of post-operative activities. Prospective clinical studies must be undertaken to evaluate their efficiency.

Chat GPT for the management of obstructive sleep apnea: do we have a polar star?

PURPOSE: This study explores the potential of the Chat-Generative Pre-Trained Transformer (Chat-GPT), a Large Language Model (LLM), in assisting healthcare professionals in the diagnosis of obstructive sleep apnea (OSA). It aims to assess the agreement between Chat-GPT's responses and those of expert otolaryngologists, shedding light on the role of AI-generated content in medical decision-making. METHODS: A prospective, cross-sectional study was conducted, involving 350 otolaryngologists from 25 countries who responded to a specialized OSA survey. Chat-GPT was tasked with providing answers to the same survey questions. Responses were assessed by both super-experts and statistically analyzed for agreement. RESULTS: The study revealed that Chat-GPT and expert responses shared a common answer in over 75% of cases for individual questions. However, the overall consensus was achieved in only four questions. Super-expert assessments showed a moderate agreement level, with Chat-GPT scoring slightly lower than experts. Statistically, Chat-GPT's responses differed significantly from experts' opinions (p = 0.0009). Sub-analysis revealed areas of improvement for Chat-GPT, particularly in questions where super-experts rated its responses lower than expert consensus. CONCLUSIONS: Chat-GPT demonstrates potential as a valuable resource for OSA diagnosis, especially where access to specialists is limited. The study emphasizes the importance of AI-human collaboration, with Chat-GPT serving as a complementary tool rather than a replacement for medical professionals. This research contributes to the discourse in otolaryngology and encourages further exploration of AI-driven healthcare applications. While Chat-GPT exhibits a commendable level of consensus with expert responses, ongoing refinements in AI-based healthcare tools hold significant promise for the future of medicine, addressing the underdiagnosis and undertreatment of OSA and improving patient outcomes.

Porcine model for tracheostomy training: evaluation of the content and construct validity.

PURPOSE: Tracheostomy is a key procedure that residents in Oto-Rhino-Laryngology, Head and Neck surgery must master as a fundamental component of their training. Swine is a potential model for tracheostomy training as it mimics human anatomy and provides realistic haptic feedback. The purpose of this study is to evaluate its content and construct validity in surgical tracheostomy training. METHODS: We carried out training sessions on dead swine with three groups of volunteers: young residents [postgraduate year (PGY)-1 to 3], experienced residents (PGY-4 to 6) and senior surgeons. Content validity was studied using questionnaires sent to senior surgeons. Construct validity was assessed by comparing the OSATS score on video analysis, between the three groups. RESULTS: 19 individuals participated in the training sessions. OSATS score were statistically different between groups (p < 0.05) with a mean score of 19 for young residents, 24.7 for experienced residents and 31.3 for senior surgeon, with a good inter-rater reliability (Pearson coefficient > 0.9). Experienced surgeons agreed that the model was a useful training tool, strongly agreed that it improved performance, and that it would be used to train their students. CONCLUSIONS: The dead pig is a suitable model to train for human tracheotomy, with good content and construction validity.

Impact of HPV status in T1-2 oropharyngeal squamous cell carcinoma with bulky N3 nodes: a multicenter GETTEC study.

PURPOSE: The purpose of our study was to investigate the impact of HPV status in oncologic outcomes in patients with T1-2 oropharyngeal SCC associated with bulky N3 nodes, and to determine progression prognosis factors aiming to define the best therapeutic strategies for these patients. METHODS: This multicenter retrospective study included patients with T1-2 oropharyngeal SCC with N3 nodes treated between 2010 and 2015 in 8 French comprehensive cancer centers. HPV status was determined with P16 hyperexpression in immunohistochemistry. HPV-positive patients were separated into 2 groups according to the associated smoking history (HPV + T +) or not (HPV + T-). We compared the oncological outcomes of patients according to HPV-status and smoking history. RESULTS: Of 67 patients with T1-2 N3 oropharyngeal SCC, 36 patients (53.7%) were HPV negative and 31 patients (46.3%) HPV positive. 2-year PFS was significantly better in HPV + T- group (p = 0.036). The risk of death or progression was significantly reduced in HPV + T- comparatively to HPV- (HR 0.25 95%CI [0.07; 0.89]). 2-year OS was significantly better in HPV + T- group than in the other two groups (p = 0.017). CONCLUSION: In patients with T1-2 oropharyngeal SCC associated with bulky N3 nodes, HPV positive patients without smoking history had better OS and PFS than HPV positive patients with smoking history and HPV negative patients. Thus, HPV status is a significant prognostic factor for survival but this benefit is altered when smoking history is associated. N3 HPV positive patients with smoking history have to be classified as high-risk.

Oncostatin M Contributes to Airway Epithelial Cell Dysfunction in Chronic Rhinosinusitis with Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a typical type-2 inflammation involving several cytokines and is associated with epithelial cell dysfunction. Oncostatin M (OSM) (belonging to the interleukin(IL)-6 family) could be a key driver of epithelial barrier dysfunction. Therefore, we investigated the presence of OSM and IL-6 and the expression pattern of tight junctions (TJs) in the nasal tissue of CRSwNP patients and controls using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Then, their potential role in the epithelial barrier was evaluated in vitro in 27 different primary cultures of human nasal epithelial cells (HNECs) by measuring TJ expression and transepithelial electric resistance (TEER) with or without OSM or IL-6 (1, 10, and 100 ng/mL). The effect on ciliary beating efficiency was evaluated by high-speed videomicroscopy and on repair mechanisms with a wound healing model with or without OSM. OSM and IL-6 were both overexpressed, and TJ (ZO-1 and occludin) expression was decreased in the nasal polyps compared to the control mucosa. OSM (100 ng/mL) but not IL-6 induced a significant decrease in TJ expression, TEER, and ciliary beating efficiency in HNECs. After 24 h, the wound repair rate was significantly higher in OSM-stimulated HNECs at 100 ng/mL. These results suggest that OSM could become a new target for monoclonal antibodies.

International assessment of interobserver reproducibility of flap delineation in head and neck carcinoma.

Background: Several reports have suggested that radiotherapy after reconstructive surgery for head and neck cancer (HNC), could have deleterious effects on the flaps with respect to functional outcomes. To predict and prevent toxicities, flap delineation should be accurate and reproducible. The objective of the present study was to evaluate the interobserver variability of frequent types of flaps used in HNC, based on the recent GORTEC atlas.Materials and methods: Each member of an international working group (WG) consisting of 14 experts delineated the flaps on a CT set from six patients. Each patient had one of the five most commonly used flaps in HNC: a regional pedicled pectoralis major myocutaneous flap, a local pedicled rotational soft tissue facial artery musculo-mucosal (FAMM) (2 patients), a fasciocutaneous radial forearm free flap, a soft tissue anterolateral thigh (ALT) free flap, or a fibular free flap. The WG's contours were compared to a reference contour, validated by a surgeon and a radiologist specializing in HNC. Contours were considered as reproducible if the median Dice Similarity Coefficient (DSC) was > 0.7.Results: The median volumes of the six flaps delineated by the WG were close to the reference contour value, with approximately 50 cc for the pectoral, fibula, and ALT flaps, 20 cc for the radial forearm, and up to 10 cc for the FAMM. The volumetric ratio was thus close to the optimal value of 100% for all flaps. The median DSC obtained by the WG compared to the reference for the pectoralis flap, the FAMM, the radial forearm flap, ALT flap, and the fibular flap were 0.82, 0.40, 0.76, 0.81, and 0.76, respectively.Conclusions: This study showed that the delineation of four main flaps used for HNC was reproducible. The delineation of the FAMM, however, requires close cooperation between radiologist, surgeon and radiation oncologist because of the poor visibility of this flap on CT and its small size.

Oncostatin M Counteracts the Fibrotic Effects of TGF-ß1 and IL-4 on Nasal-Polyp-Derived Fibroblasts: A Control of Fibrosis in Chronic Rhinosinusitis with Nasal Polyps?

Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with inflammation and tissue remodeling including myofibroblasts differentiation and extracellular matrix (ECM) deposition mediated by TGF-ß1 and IL-4. Oncostatin M (OSM) is a cytokine involved in fibrotic processes in other cellular subtypes. We investigated the mechanisms of action of OSM in the fibrosis process associated with CRSwNP. The expression of IL-4, OSM and TGF-ß1 was assessed by RT-qPCR. Primary human cultures of nasal-polyp-derived fibroblasts were established and stimulated by TGF-ß1 and/or IL-4 and/or OSM. The expression of ECM components and αSMA was determined by RT-qPCR and Western blot. TGF-ß1-Smad3 signaling was investigated by immunofluorescence. TGF-ß1, IL-4 and OSM as well as αSMA were overexpressed in nasal polyps when compared to noninflammatory nasal mucosa. In TGF-ß1-stimulated nasal-polyp-derived fibroblasts, ECM genes and αSMA gene and protein were overexpressed, as well as αSMA in IL-4-stimulated fibroblasts. OSM counteracted the profibrotic effect of TGF-ß1 on ECM components and αSMA. TGF-ß1-induced nuclear translocation of Smad3 was completely reversed by OSM. OSM counteracts the profibrotic effect of IL-4 and also TGF-ß1, by inhibiting the nuclear translocation of Smad3. We suggest OSM could be an efficient tool to protect against fibrosis in CRSwNP.

Cytokine Signature and Involvement in Chronic Rhinosinusitis with Nasal Polyps.

Cytokines are well known to play a central role in chronic rhinosinusitis with nasal polyps (CRSwNP), particularly in maintenance of the inflammatory response and the recruitment of eosinophils. The pathophysiological concepts concerning the involvement of inflammatory cytokines in CRSwNP have gradually evolved. Although the Th2 cytokines environment associated with an eosinophilic infiltration has retained a central role in the genesis of polyps, the role of other cytokine subpopulations has also and more recently been detailed, leading to a specific and complex signature in CRSwNP. The purpose of this review is to summarize the current state of knowledge about the cytokine signature in CRSwNP, the role of cytokines in the pathogenesis of this disease and in the intercellular dialog between epithelial cells, fibroblasts and inflammatory cells. Knowledge of this precise cytokine signature in CRSwNP is fundamental in the perspective of potential targeting biotherapies.

Locoregional control, progression-free survival and morbidity rates in N3 head and neck cancer patients with low primary tumour burden: A 301-patient study.

OBJECTIVES: In patients with N3 head and neck squamous cell carcinoma (HNSCC), N3 disease is associated with high regional relapse and metastatic risks. Patients with resectable N3 disease have better prognosis although their metastatic risk may be similar as in patients with unresectable disease. Neoadjuvant chemotherapy has been associated with lower metastatic rates, but N3 patients may die of rapid locoregional progression. We assessed outcomes with the three modalities in patients with low primary burden to better assess the specific prognosis of N3 disease. METHODS: This retrospective multicentric study included T0-2 N3 HNSCC patients. Outcomes and morbidity in upfront neck dissection (uND) vs non-surgical groups were analysed and oncological outcomes and morbidity compared between patients undergoing chemoradiation or neoadjuvant chemotherapy in patients with initially unresectable N3 nodes. RESULTS: Of 301 patients, 142 (47%) underwent uND, 68 (23%) neoadjuvant chemotherapy and 91 (30%) chemoradiation. The 24- and 60-month incidence of locoregional relapse was 23.2% [18.3%; 28.4%] and 27.4% [21.8%; 33.3%]; it was lower in patients undergoing uND (P = .006). In patients with non-surgical treatments, success rates were 57.8% [49.4%; 66.3%] after chemoradiation and 38.1% [29.6%; 46.7%] after neoadjuvant chemotherapy (P = .001). Overall morbidity was more frequent in patients undergoing uND (68.8%) (P < .001). CONCLUSION: uND improved locoregional control but increased morbidity and showed no survival benefit. Success rates were better after chemoradiation versus neoadjuvant chemotherapy. Neoadjuvant chemotherapy did not reduce metastatic rates but non-responders to chemoradiation had poor PFS and survival rate, suggesting that predictive criteria are warranted.

Surgery or Radiotherapy of the Primary Tumor in T1-2 Head and Neck Squamous Cell Carcinoma with Resectable N3 Nodes: A Multicenter GETTEC Study.

BACKGROUND: The prognosis of advanced nodal (N3) squamous cell carcinoma of the head and neck (HNSCC) is poor. We investigated whether surgery or radiotherapy of early (T1-2) primary stage HSNCC is preferable to limit the overall morbidity after upfront neck dissection (uND) for N3 disease. METHODS: This retrospective multicentric Groupe d'Étude des Tumeurs de la Tête Et du Cou study included patients undergoing uND and surgery or radiotherapy of their primary. Prognostic factors were evaluated using propensity score matching to account for biases in performing surgery depending on primary site and stage. RESULTS: Of 189 T1-2, N3 HNSCC patients, 70 (37.0%) underwent uND: 42 with surgery of their primary and 28 with radiotherapy only. Radiotherapy alone was more frequent in patients with hypopharyngeal primaries. All local (N = 3) and regional (N = 10) relapses (included 2 locoregional relapses) occurred within the first 2 years. There were 16 distant metastatic failures. Five-year locoregional relapse and survival incidences were 15.7% and 66.5% and were similar regardless of the treatment of the primary. The overall morbidity rate was 65.2% and was similar after weighting by the inverse propensity score (p = 0.148). The only prognostic factor for morbidity was the radicality of the uND. Prolonged parenteral feeding was not more frequent in patients only irradiated to their primary (p = 0.118). Prolonged tracheostomy was more frequent after surgery of the primary. CONCLUSIONS: In patients with T1-2, N3 HNSCC undergoing uND, radiotherapy and surgery of the primary yield similar oncological outcomes. Morbidity was related to the extent of neck dissection.

Obstructive sleep apnea syndrome: A frequent and difficult-to-detect complication of radiotherapy for oropharyngeal cancers.

This pilot study reveals a higher prevalence of obstructive sleep apnea syndrome (OSAS) in patients treated for oropharyngeal squamous cell carcinoma with radiotherapy compared to the general population. OSAS indicators such as the Epworth Sleepiness Scale seem insufficient in the diagnostic approach to OSAS in this population and systematic screenings should be considered.

[Prevention, diagnosis and management of osteoradionecrosis: Where do we stand?] / Prévention, diagnostic et prise en charge de l'ostéoradionécrose : où en est-on ?

Osteoradionecrosis (ORN) is a late secondary iatrogenic complication of external radiotherapy for cancers of the upper aero-digestive tract. Despite the systematization of intensity-modulated radiotherapy and its potential for preserving salivary secretion and limiting the dose delivered to the supporting bone, ORN remains a feared and frequent complication. The objective of this literature review was to provide an overview of the management of ORN and to determine the key points that would make it possible to improve patient care. The diagnosis of ORN requires to eliminate tumor recurrence then is based on clinical arguments and imaging by CT or Cone Beam evolving in a chronic mode (more than 3-6 months). The harmonization of its classifications aims to offer comprehensive and multidisciplinary care as early as possible. Primary prevention is based on pre-therapeutic oral and dental preparation, then associated with fluoroprophylaxis if salivary recovery is insufficient and requires supervision of invasive dental care and prosthetic rehabilitation. Semi-automatic contouring tools make it possible to identify doses delivered to dental sectors and guide dental care with personalized dosimetric mapping. Conservative medical treatment is offered at an early stage where innovative medical treatments, highlighted by early studies, could be of interest in the future. In the event of advanced ORN, a non-conservative treatment is then proposed and frequently consists of interruptive mandibulectomy associated with reconstruction by bony free flap, the conditions of implantation remaining to be defined with the support of prospective clinical trials.

Impact of hospital internships on success in university summative objective structured clinical examinations: Large-scale experience in a French medical school.

BACKGROUND: Objective structured clinical examinations (OSCEs) are extensively used in many medical schools worldwide with the stated objective to assess students' clinical skills acquired during internships. The objective of the present study was to assess the factors associated with success in university summative OSCEs, especially the impact of previous hospital internships in corresponding disciplines and supervision during internships. METHODS: This was a cross-sectional study assessing the results in the summative OSCEs of 4th year medical students during the 2021-2022 academic year in a French medical school. The summative OSCEs included five stations for each student. Each student answered a survey at the end of summative OSCEs about previous internships, the supervision they had and perceived difficulty levels for each station. The scores in each station were assessed according to previous hospital internships in the corresponding discipline. Analysis of predictive factors of success in OSCEs, defined by a score ≥ 10/20 at each station, were performed using univariate and multivariate logistic regression. RESULTS: Out of the 220 students participating in the summative OSCEs, 182 (83%) answered the survey. One hundred and forty-four (79%) of these students had carried out hospital internships in at least one of the disciplines evaluated during the OSCEs. Students having completed an internship in the corresponding discipline had significantly higher OSCEs scores for interrogation, communication, therapeutic education and procedure stations compared to those who had not. Previous internship in corresponding disciplines was independently associated with success in OSCEs in interrogation (OR 9.45 [1.34-66.8] p = 0.02), clinical examination (OR 6.93 [1.88-25.57] p = 0.004, and therapeutic education (OR 3.09 [1.22-7.82] p = 0.02) stations. CONCLUSION: Previous hospital internships in the discipline evaluated by the OSCEs are associated with success in summative OSCEs. This reinforces the importance of student involvement during their hospital internships.

Reconstructive flap surgery in head and neck cancer patients: an interdisciplinary view of the challenges encountered by radiation oncologists in postoperative radiotherapy.

Background: Major advances have been made in reconstructive surgery in the last decades to reduce morbidity in head and neck cancer. Flaps are now present in 80% of patients with oral cavity cancer to cover anatomic, functional, and cosmetic needs. However, gaps in interdisciplinary innovation transfer from surgery to postoperative radiotherapy (poRT) remain challenging. We aimed to provide an interdisciplinary view of the challenges encountered by radiation oncologists in planning head and neck postoperative radiotherapy. Methods: A systematic and critical review was conducted to address areas of optimization in surgery and radiology that may be relevant to poRT. Results: Despite extensive surgical literature on flap techniques and salvage surgery, 13 retrospective series were identified, where flap outcomes were indirectly compared between surgery alone or poRT. These low-evidence studies suggest that radiotherapy accelerates flap atrophy, fibrosis, and osteoradionecrosis and deteriorates functional outcomes. Preliminary evidence suggests that tumor spread occurs at the flap-tissue junction rather than in the flaps. One prospective 15-patient study showed 31.3% vs. 39.2% flap volume reduction without or with poRT. In an international consensus, experts recognized the needs for optimized flap-sparing poRT against flap-related functional deterioration and bone damage. CT, MRI, and PET-CT modalities show potential for the delineation of the junction area between native tissues and flap for flap segmentation and to characterize flap-specific changes quantitatively and correlate them with patterns of relapse or complications. Conclusion: Flap management in poRT is insufficiently documented, but poRT seems to damage flaps. Current gaps in knowledge underscore the need for prospective flap assessment and interdisciplinary trials investigating flap morbidity minimization by flap-sparing poRT planning.

SimLife®: A New Dynamic Model for Head and Neck Surgical Oncology Simulation.

The SimLife® model consists in a human cadaver dynamized by pulsatile vascularization. The objective was to evaluate the face, contents, and constructs validity of the SimLife® model in head and neck surgical oncology simulation. Head and neck surgical oncology simulation sessions on SimLife® models were organized with lateral neck dissection and total laryngectomy. Face and contents validity were addressed by questionnaires. Constructs validity was assessed by objective structured assessment of technical skills (OSATS) score. High realism was demonstrated for consistency of tissues (7.1 ± 1.4), color of arteries and veins (7.3 ± 1.9, 8.5 ± 1.1, respectively), and vein consistency (8.5 ± 1.2). The mean OSATS score was 19.7 ± 5.4 for residents and 32.7 ± 1.9 for senior surgeon (P = .0022). SimLife® is a hyperrealistic model for head and neck surgical oncology simulation and it might become a core component of the surgical resident curriculum.

Artificial Intelligence for Otosclerosis Detection: A Pilot Study.

The gold standard for otosclerosis diagnosis, aside from surgery, is high-resolution temporal bone computed tomography (TBCT), but it can be compromised by the small size of the lesions. Many artificial intelligence (AI) algorithms exist, but they are not yet used in daily practice for otosclerosis diagnosis. The aim was to evaluate the diagnostic performance of AI in the detection of otosclerosis. This case-control study included patients with otosclerosis surgically confirmed (2010-2020) and control patients who underwent TBCT and for whom radiological data were available. The AI algorithm interpreted the TBCT to assign a positive or negative diagnosis of otosclerosis. A double-blind reading was then performed by two trained radiologists, and the diagnostic performances were compared according to the best combination of sensitivity and specificity (Youden index). A total of 274 TBCT were included (174 TBCT cases and 100 TBCT controls). For the AI algorithm, the best combination of sensitivity and specificity was 79% and 98%, with an ideal diagnostic probability value estimated by the Youden index at 59%. For radiological analysis, sensitivity was 84% and specificity 98%. The diagnostic performance of the AI algorithm was comparable to that of a trained radiologist, although the sensitivity at the estimated ideal threshold was lower.

[Issues and implementation of postoperative radiotherapy after flap reconstructive surgery in head and neck cancers]. / Enjeux et mise en œuvre de radiothérapie postopératoire après chirurgie reconstructrice avec lambeau dans les cancers de la tête et du cou.

The management of head and neck cancers is multidisciplinary, often relying on the use of combined treatments to maximize the chances of cure. Combined treatments are however also responsible for cumulative side effects. The aim of reconstructive surgery with a flap is to restore a function lost with the loss of substance from the tumor resection. However, changes in reconstructive surgery have impact of postoperative radiotherapy planning. The optimization of imaging protocols for radiotherapy planning should make it possible to identify postoperative changes and to distinguish flaps from surrounding native tissues to delineate the flaps and document the spontaneous evolution of these flaps or dose-effect relationships in case of radiotherapy. Such changes include atrophy, fibrosis of soft tissue flaps and osteoradionecrosis of bone flaps. Radiotherapy optimization also involves standardization of the definition of target volumes in situations where a flap is present, a situation that is increasingly common in routine care. This evolution of practice, beyond the essential multidisciplinary consultation meetings defining treatment indications, requires a close radio surgical collaboration with respect to technical aspects of the two disciplines. Doing so, anticipation of relapse and toxicity profiles could possibly lead to propose strategies for personalized de-escalation of multimodal treatments through interdisciplinary trials.

Dupilumab prevents nasal epithelial function alteration by IL-4 in vitro: Evidence for its efficacy.

BACKGROUND: Chronic rhinosinusitis with nasal polyp (CRSwNP) is a typical type 2 inflammation involving interleukin (IL)-4 and IL-13. Dupilumab is a fully human monoclonal antibody targeting IL-4 receptor α subunit, thereby blocking signaling by both cytokines. Our hypothesis was that IL-4 and IL-13, by inducing a severe epithelial dysregulation, are involved in CRSwNP pathogenesis. This study aimed to evaluate the in vitro direct effect of IL-4, IL-13, and dupilumab on nasal epithelial functions. METHODS: Nasal polyps and control mucosa from 28 patients, as well as human nasal epithelial cells (HNEC) from 35 patients with CRSwNP were used. Three major epithelial functions were investigated: the epithelial barrier function (characterized by transepithelial electrical resistance measurements and tight junction protein expression), the ciliary motion (characterized by the ciliary beating efficiency index), and wound healing (characterized by the wound repair rate) under various stimulations (IL-4, IL-13, and dupilumab). The main outcome was a significant change in epithelial functions following exposure to IL-4, IL-13, and dupilumab for 48 h in the basal media. RESULTS: IL-4 (1, 10, and 100 ng/mL) but not IL-13 induced a significant decrease in occludin and zonula-occludens protein expression, ciliary beating efficiency, and wound repair rate in HNEC. Dupilumab (0.04 mg/mL) had no effect on HNEC and specifically restored all epithelial functions altered when cells were exposed to a 48-h IL-4 stimulation. CONCLUSION: Dupilumab, in vitro, restored epithelial integrity by counteracting the effect of IL-4 on the epithelial barrier (increased epithelial permeability, decreased ciliary beating efficiency, and decreased wound repair rate).