Cannabidiol protects C2C12 myotubes against cisplatin-induced atrophy by regulating oxidative stress.

Cancer and chemotherapy induce a severe loss of muscle mass (known as cachexia), which negatively impact cancer treatment and patient survival. The aim of the present study was to investigate whether cannabidiol (CBD) administration may potentially antagonize the effects of cisplatin in inducing muscle atrophy, using a model of myotubes in culture. Cisplatin treatment resulted in a reduction of myotube diameter (15.7 ± 0.3 vs. 22.2 ± 0.5 µm, P < 0.01) that was restored to control level with 5 µM CBD (20.1 ± 0.4 µM, P < 0.01). Protein homeostasis was severely altered with a ≈70% reduction in protein synthesis (P < 0.01) and a twofold increase in proteolysis (P < 0.05) in response to cisplatin. Both parameters were dose dependently restored by CBD cotreatment. Cisplatin treatment was associated with increased thiobarbituric acid reactive substances (TBARS) content (0.21 ± 0.03 to 0.48 ± 0.03 nmol/mg prot, P < 0.05), catalase activity (0.24 ± 0.01 vs. 0.13 ± 0.02 nmol/min/µg prot, P < 0.01), whereas CBD cotreatment normalized TBARS content to control values (0.22 ± 0.01 nmol/mg prot, P < 0.01) and reduced catalase activity (0.17 ± 0.01 nmol/min/µg prot, P < 0.05). These changes were associated with increased mRNA expression of GPX1, SOD1, SOD2, and CAT mRNA expression in response to cisplatin (P < 0.01), which was corrected by CBD cotreatment (P < 0.05). Finally, cisplatin treatment increased the mitochondrial protein content of NDUFB8, UQCRC2, COX4, and VDAC1 (involved in mitochondrial respiration and apoptosis), and CBD cotreatment restored their expression to control values. Altogether, our results demonstrated that CBD antagonize the cisplatin-induced C2C12 myotube atrophy and could be used as an adjuvant in the treatment of cancer cachexia to help maintain muscle mass and improve patient quality of life.NEW & NOTEWORTHY In an in vitro model, cisplatin treatment led to myotube atrophy associated with dysregulation of protein homeostasis and increased oxidative stress, resulting in increased apoptosis. Cotreatment with cannabidiol was able to prevent this phenotype by promoting protein homeostasis and reducing oxidative stress.

Efficacy and safety of intravenous bevacizumab on severe bleeding associated with hemorrhagic hereditary telangiectasia: A national, randomized multicenter trial.

BACKGROUND: Bevacizumab-a humanized monoclonal antibody-has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been conducted. METHODS: This study is a double-blind multicenter randomized phase 2 trial with a 1:1 active-treatment-to-placebo ratio. We included patients over the age of 18 with a confirmed diagnosis and the need for at least four red blood cell (RBC) units transfused in the 3 months before study enrollment. Bevacizumab was administered at a dose of 5 mg/kg every 14 days with a total of six injections. The primary efficacy criterion was a decrease of at least 50% in the cumulative number of RBC units transfused in a 3-month period before and after treatment. RESULTS: A total of 24 patients (12 in each group) were included and randomized at 4 different centers. In intention-to-treat analysis, 63.6% of patients (7/11) in the bevacizumab group versus 33.3% of patients (4/12) in the placebo group decreased the number of blood transfusions by at least 50% (p = 0.22). Hemoglobin levels significantly improved at 6 months in the bevacizumab versus placebo group (p = 0.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in RBC transfusions (p = 0.03). Fifty-nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm. CONCLUSION: Though the present trial was underpowered, patients with HHT receiving bevacizumab required numerically fewer red blood cell transfusions than those receiving placebo, particularly those with high exposure.

Prediction of residual disease using circulating DNA detection after potentiated radiotherapy for locally advanced head and neck cancer (NeckTAR): a study protocol for a prospective, multicentre trial.

BACKGROUND: Sensitive and reproducible detection of residual disease after treatment is a major challenge for patients with locally advanced head and neck cancer. Indeed, the current imaging techniques are not always reliable enough to determine the presence of residual disease. The aim of the NeckTAR trial is to assess the ability of circulating DNA (cDNA), both tumoral and viral, at three months post-treatment, to predict residual disease, at the time of the neck dissection, among patients with partial cervical lymph node response on PET-CT, after potentiated radiotherapy. METHODS: This will be an interventional, multicentre, single-arm, open-label, prospective study. A blood sample will be screened for cDNA before potentiated radiotherapy and after 3 months if adenomegaly persists on the CT scan 3 months after the end of treatment. Patients will be enrolled in 4 sites in France. Evaluable patients, i.e. those with presence of cDNA at inclusion, an indication for neck dissection, and a blood sample at M3, will be followed for 30 months. Thirty-two evaluable patients are expected to be recruited in the study. DISCUSSION: The decision to perform neck dissection in case of persistent cervical adenopathy after radio-chemotherapy for locally advanced head and neck cancer is not always straightforward. Although studies have shown that circulating tumour DNA is detectable in a large proportion of patients with head and neck cancer, enabling the monitoring of response, the current data is insufficient to allow routine use of this marker. Our study could lead to better identification of patients who do not have residual lymph node disease in order to avoid neck dissection and preserve their quality-of-life while maintaining their prospects of survival. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05710679, registered on 02/02/2023, https://clinicaltrials.gov/ct2/show/ . Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°ID RCB 2022-A01668-35, registered on July 15th, 2022.

Prevention of cerebrospinal fluid leak after vestibular schwannoma surgery: a case-series focus on mastoid air cells' partition.

BACKGROUND: Petrous bone pneumatization may be related to cerebrospinal fluid (CSF) leak secondary to vestibular schwannoma surgery. OBJECTIVE: To assess the association between petrous bone pneumatization and CSF leak in vestibular schwannoma surgery. METHODS: A retrospective study included 222 consecutive vestibular schwannoma patients treated via a retrosigmoid or translabyrinthine approach in a 17-year period in one University Hospital. Association of CSF leak and petrous bone pneumatization, as seen on CT scans, was assessed on ANOVA and Student's t or Chi-squared test in case of non-parametric distribution. RESULTS: One hundred and 75 resections were performed on a retrosigmoid approach and 47 on a translabyrinthine approach. Mean age was 53.6 ± 12.9 years. Mean follow-up was 5 years 6 months. Twenty-six patients (11.7%) showed CSF leak and 8 (3.6%) meningitis. Approach (p = 0.800), gender (p = 0.904), age (p = 0.234), body-mass index (p = 0.462), tumor stage (p = 0.681) and history of schwannoma surgery (p = 0.192) did not increase the risk of CSF leak. This risk was unrelated to mastoid pneumatization (p = 0.266). There was a highly significant correlation between internal acousticus meatus (IAM) posterior wall pneumatization and CSF leak after retrosigmoid surgery (p = 0.008). Eustachian tube packing in the translabyrinthine approach did not decrease risk of CSF leak (p = 0.571). CONCLUSION: Degree of petrous bone pneumatization was not significantly related to risk of CSF leak, but pneumatization of the posterior IAM wall increased this risk in retrosigmoid surgery. Eustachian tube packing in the translabyrinthine approach is not sufficient to prevent postoperative CSF leak. Both approaches had similar rates of CSF leaks, around 12%.

Poor dental condition is a factor of imbalance of the nutritional status at the outset of management of head and neck cancer.

OBJECTIVES: To determine whether deterioration of dental condition at the outset of management of head and neck cancer (HNC) is a nutritional risk and whether social deprivation is a cause of the poor dental condition observed in HNC patients. MATERIAL AND METHODS: A nutritional assessment form (NAF) and the Nutrition Risk Index (NRI) were used to standardize the nutritional status of 108 patients at the outset of management of HNC (2017-2019). The NAF includes assessment of weight loss over the past 3 months, the amount and difficulty of food intake, and the presence of digestive disorders. Dental condition was assessed by the decayed, filled, and missing teeth acopre (DFM) index and the masticatory coefficient (MC). Dental status and social deprivation were correlated with the EPICES score. RESULTS: A correlation was found between the extent of weight loss and dental condition. The MC was higher in absence of weight loss (46% vs. 27%, p = 0.03) and the DMF lower when weight loss was less than 5% (22.3 vs. 26.9 if > 5% loss of weight, p = 0.005). No correlation was found between dental status and nutritional status. Social deprivation was associated with a lower MC (26% vs. 50%, p < 0.001). CONCLUSION: Dental condition is a risk factor for weight loss at the outset of management of HNC but is not a determinant of nutritional status. Clinical relevance Dental condition is no longer considered simply as a source of potential complications after radiotherapy but also as an important factor for nutritional status.

Predictive factors of toxicity of TPF induction chemotherapy for locally advanced head and neck cancers.

BACKGROUND: The rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is however highly effective in terms of rate and speed of response. The purpose of the study was to investigate predictive factors of toxicity of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC). METHODS: Between June 2009 and December 2017, 113 patients treated consecutively with TPF were included retrospectively. Patients were receiving induction chemotherapy for either an inoperable cancer or laryngeal preservation. For inoperable cancer, induction chemotherapy was proposed to patients presenting either a large tumor with strong symptoms (dyspnea, dysphagia, pain) or a tumor with rapid progression. Risk factors were chosen among the initial patient and tumour characteristics and chemotherapy modalities. RESULTS: Eighty-nine patients (79%) were male; the median age was 58 years [32-71]. Sixty-nine (61%) patients were treated for inoperable cancer and 44 (39%) for laryngeal preservation. 45% had stage IVa cancer, 28% stage III and 25% stage IVb. Sixty percent of patients had a partial response after TPF, 22% had a complete response, 12% were stable, 5% were progressing, and 1% had a discordant response. Thirty-four patients (30%) received enteral feeding during induction chemotherapy with TPF. The possibility of oral feeding without a tube was predictive of a better response (p = 0.003). Seven (6%) patients died during TPF. There was an increased risk of death with preexisting liver dysfunction (liver dysmorphia on imaging or decrease prothrombin rate) (p = 0.032). There was an increased risk of grade ≥ 3 infection if an enteral feeding occurred during the period of induction chemotherapy (p = 0.03). CONCLUSIONS: TPF induction chemotherapy had an 82% objective response rate with 6% toxic deaths. Nutritional status and the presence of hepatic dysfunction are significant risk factors to be taken into account in therapeutic decisions.

Fluoroscopy guided electrode-array insertion for cochlear implantation with straight electrode-arrays: a valuable tool in most cases.

PURPOSE: To highlight the advantages of real time fluoroscopy guided electrode-array (EA) insertion (FGI) during cochlear implants surgery. METHODS: All surgical procedures were performed in a dedicated operating room equipped with a robotic C-arm cone beam device, allowing for intraoperative real time 2D FGI and postoperative 3D imaging. Only straight EAs were used. Patients were sorted out in three groups: ANAT, with anatomical concerns; HP, with residual hearing; NPR: patients with no particular reason for FGI. In all cases the angle of EA-insertion was measured. In the HP group pre and postoperative hearing were compared. The radiation delivered to the patient was recorded. RESULTS: Fifty-three cochlear implantation procedures were achieved under fluoroscopy in 50 patients from November 2015 to January 2020 (HP group: n = 10; ANAT group: n = 13; NPR group: n = 27). In the ANAT group, FGI proved to be helpful in 8 cases (61.5%), successfully guiding the surgeon during EA -insertion. On average, the angle of insertion was at 424° ± 55°. In the HP group, a controlled smooth EA-insertion was carried out in all cases but one. The targeted 360° angle of insertion was always reached. Hearing preservation was possible with an eventual average drop of 30 ± 1.5 dB. In the NPR group, FGI helped control the quality of insertion in all cases and appeared very informative in five (17.8%): one EA-misrouting, three stuck EAs, and one case with hidden electrodes out of the cochlea in revision surgery. Final 3D cone beam CT scan double-checked the EA position in all adults. The radiation dose was equivalent to a bit less than four digital subtract radiographs. CONCLUSION: The FGI is a very useful adjunct in cochlear implantation in all cases of expected surgical pitfalls, in patients with residual hearing, and even in case without preoperative particular reason, with low irradiation.

Donor site sequelae and patient satisfaction after head and neck reconstruction with a radial forearm free flap.

PURPOSE: Radial forearm free flap (RFFF) being a workhorse flap in head and neck reconstruction, we investigated its donor site delayed consequences. METHODS: Multicentric case series evaluating 189 patients who underwent RFFF for carcinologic reasons at least 6 months before. Patients and surgeon's appreciation regarding the aesthetic and functional consequences of the flap harvest on their daily life were evaluated by questionnaires using likert scales. Medical data were collected from patients' charts retrospectively. RESULTS: Thirty percent of patients had at least one sequelae. Experiencing a graft necrosis did not worsen long-term results. Cosmetic satisfaction was significantly worst for women, according to patients' and surgeons' opinion. For 81% and 92% patients, respectively, the flap harvest had no impact on daily life nor sport practice. Ratio between the benefits of reconstruction and the sequelae at the donor site was judged "excellent" for 77% patients. CONCLUSIONS: Although objectively important, RFFF morbidity has little impact in head and neck cancer patient's life.

A multicenter prospective phase II study of postoperative hypofractionated stereotactic body radiotherapy (SBRT) in the treatment of early-stage oropharyngeal and oral cavity cancers with high risk margins: the STEREO POSTOP GORTEC 2017-03 trial.

BACKGROUND: Primary surgery is usually the mainstay treatment in early-stage oropharyngeal and oral cavity cancer. Typically, neck surgery is performed. Negative tumor margins are recommended (> 5 mm). If feasible, re-resection of any positive margin is preferred. Otherwise, postoperative radiotherapy is required. Adjuvant postoperative radiotherapy can be limited to the primary site for patients with pT1-T2 tumors and negative neck exploration. Currently, both fractionated external beam radiotherapy and brachytherapy can have a role in the postoperative management of early-stage oropharyngeal and oral cavity cancer with high risk margins. Another possible alternative could be postoperative stereotactic body radiotherapy (SBRT). The aim of this study is to evaluate postoperative SBRT in the treatment of early-stage oropharyngeal and oral cavity cancer with high risk margins. METHODS: The STEREO POSTOP study is a national, open-label, non-randomized phase II trial within the GORTEC network. Patients with early-stage oropharyngeal and oral cavity cancers with high risk margins indicating the need for postoperative radiation are eligible for enrollment. SBRT consists of a total dose of 36 Gy in 6 fractions over 2 weeks. The primary endpoint is severe late toxicity defined as 2-year toxicity of grade ≥ 3 according to CTCAE V4.03 classification. The secondary endpoints include acute toxicity (≤ 3 months), local and locoregional control, disease-free and overall survival, quality of life of patients, nutritional impact and predictive factors of toxicity. The experimental design chosen is a one-step Fleming plan design without interim analysis as the primary endpoint will be evaluated at a 2-year follow-up. Ninety patients will be recruited. The study was started in January 2018 with a 4-year enrollment period and an estimated completion in January 2024. DISCUSSION: This study is the first prospective trial to evaluate head and neck cancer postoperative SBRT in the setting of early-stage oropharyngeal and oral cavity cancers with high risk margins. SBRT is an attractive option because it delivers a highly conformal dose of radiation in a limited number of fractions (like brachytherapy but with less contraindication), with steep dose gradients resulting in reduced normal tissue irradiation and with a short overall treatment time. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03401840 , registered on 17-1-2018. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°ID - RCB 2017-A02058-45, registered on July 2017. Protocol version: Version 3 dated from 25th November 2019.

Cochlear implantation through the round window with a straight slotted electrode array: optimizing the surgical procedure.

The question addressed here is how optimizing the quality of insertion through the round window with the lower morbidity, when using a straight and slotted electrode array of regular length. This retrospective analysis includes all cases implanted with a cochlear implant Digisonic SP (Neurelec-Oticon Medical) since 2004. We checked the operative charts, the depth of insertion, and the follow-up. For comparisons, contingency tables were used and a Chi-square test was performed. A p value <0.05 was considered significant. 126 cases of patients with non-malformed cochleas were implanted through the round window. The mean age was 53.8 ± 16.2 for adults and 3.6 ± 2.6 for children (24 cases). The mean follow-up was 33 ± 22 months. The straight electrode array had either a square or a soft pointed tip (n = 84). Full insertion was achieved in 79 out of 84 cases with a soft tip vs. 18 out of 42 square tips (χ (2) = 41.41, DOF = 1, p < 0.0001). Two cases were stuck at the round window niche by a prominent crista fenestrae. In all cases but one, the chorda tympany was preserved. In one case, a misrouting to the vestibule required a revision surgery. Implantation through the round window with a straight and slotted electrode array with a soft tip (Digisonic SP, Neurelec-Oticon Medical) can lead to a full insertion in 94 % of cases. Drilling out a prominent crista fenestrae is recommended.

Preliminary trials of trackerless augmented reality in endoscopic endonasal surgery.

PURPOSE: We present a novel method for augmented reality in endoscopic endonasal surgery. Our method does not require the use of external tracking devices and can show hidden anatomical structures relevant to the surgical intervention. METHODS: Our method registers a preoperative 3D model of the nasal cavity to an intraoperative 3D model by estimating a scaled-rigid transformation. Registration is based on a two-stage ICP approach on the reconstructed nasal cavity. The hidden structures are then transferred from the preoperative 3D model to the intraoperative one using the estimated transformation, projected and overlaid into the endoscopic images to obtain the augmented reality. RESULTS: We performed qualitative and quantitative validation of our method on 12 clinical cases. Qualitative results were obtained from an ENT surgeon from visual inspection of the hidden structures in the augmented images. Quantitative results were obtained by measuring a target registration error using a novel transillumination-based approach. The results show that the hidden structures of interest are augmented at the expected locations in most cases. CONCLUSION: Our method was able to augment the endoscopic images in a sufficiently precise manner when the intraoperative nasal cavity did not deform considerably with respect to its preoperative state. This is a promising step towards trackerless augmented reality in endonasal surgery.

Pathophysiology of Postoperative Hearing Disorders after Vestibular Schwannoma Resection: Insights from Auditory Brainstem Response and Otoacoustic Emissions.

Background: In order to better understand the pathophysiology of surgically induced hearing loss after vestibular schwannoma (VS) surgery, we postoperatively analyzed the hearing status in a series of patients where hearing was at least partially preserved. Methods: Hearing was assessed through tonal audiometry, speech discrimination score, maximum word recognition score (dissyllabic word lists-MaxIS), otoacoustic emissions (OAEs), and auditory brainstem response (ABR). The magnetic resonance imaging (MRI) tumor characterization was also noted. Results: In a series of 24 patients operated on for VS over 5 years, depending on the results of this triple hearing exploration, we could identify, after surgery, patients with either a myelin alteration or partial damage to the acoustic fibers, others with a likely partial cochlear ischemia, and some with partial cochlear nerve ischemia. One case with persisting OAEs and no preoperative ABR recovered hearing and ABR after surgery. Long follow-up (73 ± 57 months) revealed a mean hearing loss of 30 ± 20 dB with a drastic drop of MaxIS. MRI revealed only 25% of fundus invasion. Conclusion: a precise analysis of hearing function, not only with classic audiometry but also with ABR and OEAs, allows for a better understanding of hearing damage in VS surgery.

Comparison of the microvascular anastomotic Coupler™ system with hand-sewn suture for end to end veno-venous anastomosis for head and neck reconstruction with free flap transfer: Medico-economic retrospective case-control study.

The aim of this study was to assess the medico-economic impact of the MACD Coupler™ system in comparison with HSA for end to end veno-venous anastomosis during free flap transfer. A retrospective case-control study was performed in an academic institution, from March 2019 through July 2021, to analyze medical and economic outcomes of patients managed for head and neck reconstruction with free flap transfer. 43 patients per group were analyzed. Rates of initial success, re-intervention, complications and flap transfer failure were not different between groups. Use of MACD increased the cost of medical devices between Coupler and Control groups with respectively K€ 0.7 [0.5; 0.8] and K€ 0.1 [0.5; 0.8] (p = 0.001) and decreased the cost for operating staff with respectively K€ 4.0 [3.4; 5.2] and K€ 5.1 [3.8; 5.4] (p = 0.03). The total management costs were not different between groups with respectively a total median cost of K€ 18.4 [14.3; 27.2] and K€ 17.3 [14.1; 23.7] (p = 0.03). In conclusion, the cost of the Coupler™ is significant but is partly offset by the decrease in operating staff costs. The choice of one or the other technique can be left to the discretion of the surgeon.

Study protocol: the biologics in severe chronic rhinosinusitis with nasal polyps survey.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of intranasal corticosteroids and short-term use of oral corticosteroids, in adjunct with saline solution rinses. Surgical management is proposed in patients who failed after medical treatment. In France, two biologics are reimbursed in case of severe uncontrolled CRSwNP despite medical treatment and endoscopic sinus surgery. Waiting for head-to-head biologics comparison, studies should report the efficacy and safety of biologics in large real-life cohorts. This study protocol describes the aims and methods of a prospective, observational, national, multicentric cohort of patients with CRSwNP treated with biologics. METHODS AND ANALYSIS: The BIOlogics in severe nasal POlyposis SurvEy is a French multicentre prospective observational cohort study. The main aim is to assess the efficacy and tolerance of biologics in patients with CRSwNP, with or without association with other type 2 diseases, and to determine the strategies in case of uncontrolled disease under biologics. Patients over 18 years old requiring biologics for CRSwNP in accordance with its marketing approval in France (ie, severe nasal polyposis, with lack of control under nasal corticosteroid, systemic corticosteroids and surgery) are invited to participate. Collected data include topical history of surgical procedures and biologics, medication and use of systemic corticosteroids, visual analogical scales for specific symptoms, Sino-Nasal Outcome Test-22 questionnaire, nasal polyp score, asthma control test, Lund-Mackay score on CT scan and IgE concentration and eosinophilic count on blood sample. TRIAL REGISTRATION: NCT05228041/DRI_2021/0030.

Carcinomas of the external auditory canal: Management and results: A multicenter REFCOR propensity score matching study.

OBJECTIVES: To analyse prognostic factors and survival outcomes of malignant tumors of the external auditory canal, to investigate the role of regional surgery, and adjuvant radiotherapy in early stages and to investigate the role of surgery in operable T4 stage. SETTING: A retrospective analysis was conducted on all patients prospectively included in the national database of the French Expertize Network for Rare ENT Cancers (REFCOR) from January 2000 to December 2016. PARTICIPANTS: 103 patients from 19 reference centers were included. A propensity score matching analysis was applied to enable comparisons between treatments. MAIN OUTCOMES AND MEASURES: Event-free survival, overall survival and factors of poor prognosis of the cohort were described. The interest of local and regional surgery and postoperative radiotherapy were evaluated. RESULTS: The factors of poor prognosis on event-free survival were immunosuppression (p = 0.002), Karnofsky status less than 90% (p = 0.02), body mass index less than 19 Kg / m2 (p = 0.0009), peripheric facial palsy (p = 0.0016), and positive margin (p = 0.0006). In early stages, locoregional surgery was associated with an increase in event-free survival (p = 0.003, HR = 0.21) versus local surgery alone, while postoperative radiotherapy was not associated with an increase in event-free survival (p = 0.86, HR = 0.91) or overall (p = 0.86, HR = 0.91). In locally advanced stages, locoregional surgery followed by radiotherapy was associated with an increase in event-free survival (p = 0.03, HR = 0.39) and overall (p = 0.02, HR = 0.34) versus chemoradiotherapy alone. CONCLUSION AND RELEVANCE: Regional surgery is recommended for early stages of cancers of the external auditory canal. In operable cases, locoregional surgery followed by radiotherapy is recommended.

The Prognostic Value of Olfactory Dysfunction in Patients with COVID-19: The COVIDORA Study.

BACKGROUND: Among all studies describing COVID-19 clinical features during the first wave of the pandemic, only a few retrospective studies have assessed the correlation between olfac-tory dysfunction (OD) and the evolution of disease severity. The main aim was to assess whether OD is a predictive factor of COVID-19 severity based on the patient's medical management (outpa-tient care, standard hospital admission, and ICU admission). METHODS: A national, prospective, mul-ticenter cohort study was conducted in 20 public hospitals and a public center for COVID-19 screen-ing. During the first wave of the pandemic, from 6 April to 11 May 2020, all patients tested positive for COVID-19 confirmed by RT-PCR underwent two follow-up ENT consultations within 10 days of symptom onset. The main outcome measures were the evolution of medical management (out-patient care, standard hospital admission, and ICU admission) at diagnosis and along the clinical course of COVID-19 disease. RESULTS: Among 481 patients included, the prevalence of OD was 60.7%, and it affected mostly female patients (74.3%) under 65 years old (92.5%), with fewer comor-bidities than patients with normal olfactory function. Here, 99.3% (290/292) of patients with OD presented with non-severe COVID-19 disease. Patients reporting OD were significantly less hospi-talized than the ones managed as outpatients, in either a standard medical unit or an ICU. Conclu-sions: As regards the clinical course of COVID-19 disease, OD could predict a decreased risk of hospitalization during the first wave of the pandemic.

Postoperative SBRT in the treatment of early-stage oropharyngeal and oral cavity cancers with high-risk margins: A dosimetric comparison of volumetric modulated arc therapy with or without non-coplanar arcs and acute toxicity outcomes from the STEREOPOSTOP GORTEC 2017-03 phase 2 trial.

Background and purpose: The STEREO POSTOP GORTEC 2017-03 phase 2 trial (NCT03401840) evaluates postoperative stereotactic body radiotherapy (SBRT) in case of high-risk margins for pT1-T2/N0 oropharyngeal and oral cavity tumors. The present ancillary study aimed to compare the dosimetric impact of adding non-coplanar arcs to the volumetric modulated arc therapy (VMAT) technique and to evaluate acute toxicities on the first patients included in this trial. Materials and methods: Ten patients were included. Patients were treated with Novalis TX®. The total dose was 36 Gy (100 % isodose line) in 6 fractions, treated every other day. Two treatment plans were created for each patient: one plan using 2 coplanar arcs only (VMATc) and one plan using coplanar and 3 non-coplanar arcs (VMATc + nc). Acute toxicity was evaluated according to NCI CTCAE criteria V4.03. Results: Median age was 62 years. Localization of tumor was the mobile tongue for 6 patients, floor of mouth for 2, cheek for 1, and gingiva for 1. Six patients had pT2N0 tumors (AJCC 7th edition) and 4 had pT1N0. Mean CTV and PTV volumes were 36.4 and 56.1 cc respectively. Mean PTV coverage by the 36 Gy isodose was 98.2 % for both techniques (p = ns), with comparable conformity indexes (1.1 for VMATc vs 1.07 for VMATc + nc; p = 0.23). VMATc + nc had a significantly better gradient index (3.45 vs 2.97; p = 0.01), resulting in a significantly better sparing of most organs at risk. For example, mean Dmean to the oral cavity, lips, and homolateral parotid were respectively of 16.8 Gy, 11.1 Gy, and 10.4 Gy for VMATc vs 14.8 Gy (p = 0.005), 8.1 Gy (p = 0.001), 6.5 Gy (p = 0.04) for VMATc + nc. No grade ≥ 4 or higher acute toxicity was reported. The most common acute toxicity was grade ≥ 2 mucositis. Conclusion: VMATc + nc had better dosimetric outcomes than VMATc and has become the standard technique for patients treated in the STEREO POSTOP GORTEC 2017-03 trial (NCT03401840) in our institution. Acute toxicity appears acceptable.

Early detection of pharyngocutaneous fistulae after total laryngectomy by cytokine in drainage: A pilot study (DEFILAC).

BACKGROUND: The determination of cytokines in the postoperative drainage (POD) fluid could be a method for early detection of the development of a pharyngocutaneous fistula (PCF). MATERIALS AND METHODS: We conducted a prospective two-center study involving 28 patients. PODs were collected on Day 1 (D1) and Day 2 (D2) postoperatively for determination of a cytokine panel and cytobacteriological examination. RESULTS: Eleven (39%) patients presented with PCF on average 13 ± 5.5 days after surgery. Patients with PCF had higher IL-10 (121 vs. 40.3, p = 0.04, effect size (ES) = 0.98 [0.16, 1.79]) and TNFα level (21.2 vs. 2.2, p = 0.02, ES = 0.83 [0.03, 1.63]) on D2. An IL-10 threshold of 72 pg/mL on D2 was diagnostic of the occurrence of PCF with a sensibility of 70%, specificity of 88%. CONCLUSION: The determination of cytokines in POD fluid on D2 is a reliable tool for predicting the development of a PCF after total laryngectomy.