The HLA ligandome of oropharyngeal squamous cell carcinomas reveals shared tumour-exclusive peptides for semi-personalised vaccination.

BACKGROUND: The immune peptidome of OPSCC has not previously been studied. Cancer-antigen specific vaccination may improve clinical outcome and efficacy of immune checkpoint inhibitors such as PD1/PD-L1 antibodies. METHODS: Mapping of the OPSCC HLA ligandome was performed by mass spectrometry (MS) based analysis of naturally presented HLA ligands isolated from tumour tissue samples (n = 40) using immunoaffinity purification. The cohort included 22 HPV-positive (primarily HPV-16) and 18 HPV-negative samples. A benign reference dataset comprised of the HLA ligandomes of benign haematological and tissue datasets was used to identify tumour-associated antigens. RESULTS: MS analysis led to the identification of naturally HLA-presented peptides in OPSCC tumour tissue. In total, 22,769 peptides from 9485 source proteins were detected on HLA class I. For HLA class II, 15,203 peptides from 4634 source proteins were discovered. By comparative profiling against the benign HLA ligandomic datasets, 29 OPSCC-associated HLA class I ligands covering 11 different HLA allotypes and nine HLA class II ligands were selected to create a peptide warehouse. CONCLUSION: Tumour-associated peptides are HLA-presented on the cell surfaces of OPSCCs. The established warehouse of OPSCC-associated peptides can be used for downstream immunogenicity testing and peptide-based immunotherapy in (semi)personalised strategies.

Apport de la tomodensitométrie dans la pathologie ORL non traumatique au centre hospitalier universitaire de Brazzaville / NA

Objectif: décrire l'apport de la tomodensitométrie dans la pathologie ORL non traumatique. Méthodologie : Il s'agissait d'une étude transversale et descriptive allant de mai 2003 à janvier 2017 soit 13 ans et 8 mois, au CHU de Brazzaville. Nous avons inclus dans notre étude tous les patients ayant présentés une pathologie ORL, pour laquelle le bilan diagnostique nécessitait la réalisation d'une tomodensitométrie. Résultats : la fréquence de prescription de la TDM en ORL représentait 3,5%. L'âge moyen 38,2 ± 18,2 ans. Le sexe masculin représentait 59%. La TDM était utile dans le diagnostic devant 51,90% des signes fonctionnels, 48,10% du syndrome tumoral. L'atteinte rhinosinusienne représentait 59,5% suivie du pharynx 17,8%. La pathologie infectieuse représentait 63% (sinusite 51%) et la pathologie tumorale 37% (tumeur du cavum 18%). Conclusion: La prescription de la tomodensitométrie dans les pathologies ORL reste faible. Les indications et les lésions observées sont multiples. La TDM reste un moyen d'exploration complémentaire utile dans la pathologie tumorale qu'infectieuse.

Objective: To describe the contribution of CT scans in non-traumatic ENT pathology. Methodology: This was a cross-sectional and descriptive study from May 2003 to January 2017 (13 years and 8 months), at the University Hospital of Brazzaville. We included in our study all patients who presented an ENT pathology for which the diagnostic work-up required a CT scan. Results: The frequency of prescription of CT in ENT represented 3.5%. The average age of the patients was 38.2 ± 18.2 years. Males accounted for 59%. CT was useful in the diagnosis of 51.90% of the functional signs and 48.10% of the tumour syndrom. Rhinosinus involvement accounted for 59.5%, followed by the pharynx for 17.8%. Infectious pathology represented 63% (sinusitis 51%) and tumour pathology 37% (cavum tumour 18%). Conclusion: The prescription of CT scans in ENT pathologies remains low. The indications and lesions observed are multiple. CT remains a useful complementary means of exploration in tumour and infectious pathology.

Impact of the first month of Covid-19 lockdown on oncologic surgical activity in the Ile de France region university hospital otorhinolaryngology departments.

OBJECTIVE: To evaluate the impact of the first month of lockdown related to the Covid-19 epidemic on the oncologic surgical activity in the Ile de France region university hospital otorhinolaryngology departments. MATERIAL AND METHODS: A multicenter prospective observational assessment was conducted in 6 university hospital otorhinolaryngology departments (Paris Centre, Nord, Est and Sorbonne) during the 1-month periods before (Month A) and after (Month B) lockdown on March 17, 2020. The main goal was to evaluate lockdown impact on oncologic surgical activity in the departments. Secondary goals were to report population characteristics, surgery conditions, postoperative course, progression of Covid status in patients and surgeons, and adverse events. RESULTS: 224 procedures were performed. There was 10.9% reduction in overall activity, without significant difference between departments. Squamous cell carcinoma and larynx, hypopharynx, oropharynx, oral cavity and nasal cavity and sinus locations were predominant, at 79% and 75.8% of cases respectively, with no significant differences between months. T3/4 and N2/3 tumors were more frequent in Month B (P=.002 and .0004). There was no significant difference between months regarding surgical approach, type of reconstruction, postoperative course, tracheotomy and nasogastric feeding-tube time, intensive care stay or hospital stay. None of the Month A patients were Covid-19-positive, versus 3 in Month B, without adverse events. None of the otorhinolaryngologists involved in the procedures developed symptoms suggesting Covid-19 infestation. CONCLUSION: The present study underscored the limited impact of the Covid-19 epidemic and lockdown on surgical diagnosis and cancer surgery in the Ile de France university otorhinolaryngology departments, maintaining chances for optimal survival without spreading the virus.

Interspecialty referral of oesophagogastric and pharyngolaryngeal cancers delays diagnosis and reduces patient survival: A matched case-control study.

OBJECTIVES: Pharyngolaryngeal and oesophagogastric cancers present with swallowing symptoms and as such, their clinical evaluation traverses boundaries between different specialties. We studied the incidence and significance of interspecialty cancer referrals (ICRs), that is, pharyngolaryngeal cancers first evaluated by gastroenterology and oesophagogastric cancers first evaluated by otolaryngology. DESIGN: A subset analysis of our Integrated Aerodigestive Partnership's audit dataset, of all ICR patients, and an equal number of controls matched for age, sex and cancer subsite. MAIN OUTCOME MEASURES: Information about patient age and presenting symptoms was recorded. The relationship between symptoms and ICR risk was examined with binary logistic regression. Referral-to-diagnosis latency was compared between ICR and control patients with unpaired Student's t test. Cox regression was used to identify independent predictors of overall survival. RESULTS: Of 1130 patients with pharyngolaryngeal and oesophagogastric cancers between 2008 and 2018, 60 diagnoses (5.3%) were preceded by an ICR. Referral-to-diagnosis latency increased from 43 ± 50 days for control patients to 115 ± 140 days for ICR patients (P < .0001). Dysphagia significantly increased the risk of an ICR (odds ratio 3.34; 95% CI 1.30-8.56), and presence of classic gastroesophageal reflux symptoms (heartburn or regurgitation; OR 0.25; 95% CI 0.08-0.83) and "distal" symptoms (nausea/vomiting, abdominal pain or dyspepsia; OR 0.23; 95% CI 0.08-068) significantly reduced the risk. Eleven pharyngolaryngeal cancers (of 26; 42%) were missed by gastroenterology, and eight (of 34; 24%) oesophageal cancers were missed by otolaryngology. An ICR was an independent adverse prognostic risk factor on multivariable analysis (hazard ratio 1.76; 95% CI 1.11-2.73; P < .02; log-rank test). Two systemic root causes were poor visualisation of pharynx and larynx by per-oral oesophago-gastro-duodenoscopy (OGD) for pharyngolaryngeal cancers, and poor sensitivity (62.5%) of barium swallow when it was used to 'evaluate' oesophageal mucosa. CONCLUSIONS: An interspecialty cancer referral occurs in a significant proportion of patients with foregut cancers. It almost triples the time to cancer diagnosis and is associated with a high incidence of missed cancers and diminished patient survival. It is a complex phenomenon, and its reduction requires an integrated approach between primary and secondary care, and within secondary care, to optimise referral pathways and ensure appropriate and expeditious specialist evaluation.

Single-cycle induction chemotherapy before chemoradiotherapy or surgery in functionally inoperable head and neck squamous cell carcinoma: 10-year results.

INTRODUCTION: The response to induction chemotherapy (IC) predicts local control after conservative treatment of laryngeal, meso- and hypopharyngeal head and neck squamous cell carcinoma (HNSCC) and can thus help to avoid surgery. Single-cycle induction chemotherapy may help to maintain a low local recurrence rate while keeping the overall toxicity manageable. However, long-term data on single-cycle IC response by tumor location is lacking. METHODS: N = 102 patients with functionally inoperable primary HNSCC of the larynx (n = 43), hypopharynx (n = 42) or mesopharynx/tongue (n = 17) received one cycle of docetaxel (75 mg/m2, d1) plus cisplatin (30 mg/m2, d1-3) or carboplatin (AUC 1.5, d1-3) and a response evaluation 3 weeks later. Responders (≥ 30% tumor size reduction and ≥ 20% SUVmax decrease in 18F-FDG PET/CT) were recommended chemoradiotherapy (CRT), and non-responders surgery. RESULTS: The overall response rate was 72.5%. All 74 responders and 10 non-responders received primary CRT, and 18 patients received primary surgery after single-cycle IC. Overall 10-year local recurrence-free survival (LRFS) was 73.7%. Three-year LRFS was 88.2% (mesopharynx/tongue), 88.2% (larynx), and 73.3% (hypopharynx); p = 0.17. 3-year distant metastasis-free survival (DMFS) was 94.1% (mesopharynx/tongue), 88.0% (larynx) and 76.4% (hypopharynx); p > 0.05. This influenced the 3-year cancer-specific survival (CSS) for larynx (91.2%) vs. hypopharynx tumors (60.8%); p = 0.003, but CSS was not different to tumors in the mesopharynx/tongue (81.4%); p > 0.05. CONCLUSIONS: A single-cycle induction chemotherapy for HNSCC enables surgery plus adjuvant therapy as well as chemoradiotherapy. The long-term local and distant disease control was good but varied between tumors in the larynx and mesopharynx/tongue vs. hypopharynx.

Low risk of contralateral lymph node recurrence in lateralized head and neck carcinoma after postoperative ipsilateral radiotherapy.

PURPOSE: The role of postoperative irradiation to contralateral non-involved neck nodes in lateralized carcinoma of the head and neck is not clear. The contralateral neck failure rate in head and neck carcinoma treated postoperatively with ipsilateral neck irradiation only was evaluated. METHODS: Patients with carcinoma of the oral cavity, oropharynx, or hypopharynx without midline extension treated between 1990 and 2016 were analyzed. After tumor resection and neck dissection (ND), radiotherapy was given to the primary tumor site and ipsilateral neck. High-risk patients additionally received concurrent chemotherapy. Freedom from contralateral neck recurrence (FCNR), locoregional control rate (LRC), overall survival (OS), and disease-free survival (DFS) were evaluated. RESULTS: 197 patients (median age 60.7 years, 66.5% males, 52.8% oropharyngeal carcinomas) were analyzed. Complete resection (R0) was achieved in 85.8% of cases. Ipsilateral ND was performed in all patients and contralateral ND in 144 patients (73.1%). Concurrent chemotherapy was given to 59 patients (30.0%). After a median follow-up of 45.5 months, OS and DFS of all patients were 73.6% and 70.9% at 5 years, respectively. A total of 45 patients (22.8%) suffered from a locoregional recurrence, lymph node metastases of the contralateral neck developed in 12 patients (6.1%) only. There was no significant difference in contralateral nodal failure rate with or without performance of contralateral ND. CONCLUSION: Regional failure of the contralateral neck was low after surgery and ipsilateral neck irradiation in head and neck carcinomas without midline extension, supporting evidence that contralateral neck radiotherapy can safely be omitted in selected cases.

Characterization of High-risk Oncogenic Human Papillomavirus Genotypes in Histologically Confirmed Ear, Nose and Throat (Ent) Cancers in Burkina Faso.

BACKGROUND: High-risk human papillomavirus (HPV-HR) infections are responsible for 99.99% of cervico-uterine cancers and 50% of carcinomas of the oropharynx. OBJECTIVE: To characterize high-risk HPV genotypes (HPV-HR) in histologically confirmed ear, nose and throat (ENT) cancers in Ouagadougou. METHODS: One hundred and twenty-eight archived tissues from the ENT sphere, obtained over the last ten years (2007 to 2017) and histologically diagnosed in anatomy and pathology-cytology laboratories in Ouagadougou were included. These tissues were dewaxed with xylene; HPV DNA extraction was performed and HPV-HR were researched by real-time multiplex PCR. RESULTS: Among the fourteen HPV-HR genotypes tested for, seven were identified. The prevalence of HPV-HR infection was 15.6%. The most common genotypes were: HPV56 (45%) and HPV33 (20%). Squamous cell carcinomas accounted for 75% of cases, followed by lymphomas for 10%. The age range was between 5 and 80 years. CONCLUSION: The results show the involvement of a diversity of HPV-HR genotypes and a high frequency of HPV56 and HPV33 in ENT cancers in Ouagadougou, Burkina Faso. The appropriate HPV vaccination will considerably reduce the number of these cancers.
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[Inter- and intrafraction imaging during stereotactic body radiation therapy: Which solutions for which tumours?] / Imagerie inter- et intrafractions en radiothérapie stéréotaxique extracrânienne : quelles solutions pour quelles tumeurs ?

Due to high dose gradients, stereotactic body radiation therapy requires high precision in the location of the tumour. Uncertainties in the positioning can introduce serious damage on organs at risk and consequently can reduce tumour local control. A better tumour location can be achieved by controlling its position with an efficient inter and intrafraction imaging procedure. The various imaging techniques available on treatment systems are presented and performances are discussed. Finally, propositions are given in terms of imaging system according to the location treated by stereotactic body radiation therapy.

Addition of chemotherapy to hyperfractionated radiotherapy in advanced head and neck cancer-a meta-analysis.

BACKGROUND: Adding concurrent chemotherapy (CTx) to definitive radiation therapy (RT) in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) improves overall survival. A comparable effect has been reported for hyperfractionated radiotherapy (HFX-RT) alone. Adding concurrent CTx to HFX-RT has been investigated in multiple trials, yet an evident effect on oncological outcomes and toxicity profile has not been established to date. Thus, the aim of the current study was to perform a meta-analysis on the clinical outcome and toxicity of the addition of CTx to HFX-RT. PATIENTS AND METHODS: We performed a literature search for randomized controlled trials comparing HFX-RT alone to HFX-RT + concurrent CTx in patients with LA-HNSCC undergoing definite RT. A meta-analysis was performed using the event rates and effect-sizes for overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), distant metastasis-free survival and distant recurrence-free interval (DMFS/DMFI) and locoregional recurrence (LRR) as investigated endpoints. Furthermore, we compared selected acute and late toxicities in the included studies. Statistical analysis was performed using the Microsoft Excel (Microsoft, Redmont, WA, USA) add-in MetaXL 5.3 (EpiGear International, Sunrise Beach, Australia), utilizing the inverse variance heterogeneity model. RESULTS: We identified six studies (n = 1280 patients) randomizing HFX-RT alone and the concurrent addition of CTx. OS was significantly improved in the HFX-RT + CTx group (HR = 0.77, CI95% = 0.66-0.89; p = <0.001). We found similar results in PFS (HR = 0.74, CI95% = 0.63-0.87; p < 0.001) and CSS (HR = 0.72, CI95% = 0.60-0.88; p = 0.001). In contrast, acute toxicities (≥grade 3 mucositis, ≥grade 3 dysphagia) and late adverse events including ≥grade 3 xerostomia, ≥grade 3 subcutaneous, ≥grade 3 bone, ≥grade 3 skin toxicity, and ≥grade 3 dysphagia did not significantly differ between the two groups. CONCLUSION: The addition of CTx to HFX-RT in the definitive treatment of advanced LA-HNSCC improves OS, CSS, PFS, and LRR without a significant increase in high-grade acute and late toxicities.

A clinicopathological study of upper aerodigestive tract cancers.

BACKGROUND: The upper aerodigestive tract (UAT) includes the nose and paranasal sinuses, oral cavity, pharynx, larynx, and salivary glands. Cancers of the UAT constitute approximately 4% of all malignancies. In this study, the varied nature of the UAT cancers was studied to find out their incidence, etiology, and clinicopathological correlations. MATERIALS AND METHODS: This prospective, observational, and clinicopathological study was conducted on 100 patients who were presented at outdoor in the Department of ENT, Government Medical College/Rajindra Hospital, Patiala, Punjab, India, from October 2016 to October 2018. Proven cases of UAT cancers were taken up and reviewed to gather data on multiple clinicopathological variables, such as age, sex, predisposing factors, and site of pathology. Histopathological differentiation was noted after conducting a biopsy. RESULTS: Most patients of UAT cancers were in the age group of 40-70 years. Maximum incidence was among males (82%) compared to females (28%). The most common predisposing factor was alcohol + smoking (28%), followed by alcohol + chewing tobacco (25%). The most common symptom in the oral cavity was ulcer and odynophagia (38%) each. In oropharyngeal cancers, dysphagia (92%) was the most common symptom. In laryngeal cancers, dyspnea (68%) and hoarseness of voice (32%) were the most common. The most common site involved in UAT cancers was the oral cavity (31%), followed by oropharynx (28%), larynx (22%), hypopharynx (7%), and salivary gland (5%). The most common histopathological type was squamous cell carcinoma (SCC) (90%). Most of the ulceroproliferative and exophytic growth was moderately differentiated SCC on histopathology. CONCLUSION: Studies are essential for education and awareness aimed at reducing exposure to habit-forming substances.

[Adaptive radiotherapy: Strategies and benefits depending on tumor localization]. / Radiothérapie adaptative : stratégies et bénéfices selon les localisations tumorales.

Adaptive radiotherapy (ART) is a complexe image-guided radiotherapy modality that comprises multiple planning to account for anatomical variations occurring during irradiation. Schematically, two strategies of RTA can be distinguished and combined according to tumor locations. One or more replanning can be proposed to correct systematic variations such as tumor shrinkage. A library of treatment plans with day-to-day plan selection from cone-beam CT imaging can also be proposed to correct random variations such as uterine motion or bladder/rectum volume changes. Because of strong anatomical variations occurring during irradiation, RTA appears therefore particularly justified in head and neck, lung, bladder, cervical and rectum and pancreas tumors, and to a lesser extent for prostate tumors and other digestive tumors. For these tumor locations, ART provides a fairly clear dosimetric benefit but a clinical benefit not yet formally demonstrated. ART cannot be proposed in a routine practice but must be evaluated medico-economically in the context of prospective trials. A rigorous quality control must be associated.

[Systemic treatments of metastatic or locally recurrent adenoid cystic carcinoma of the head and neck, a systematic review]. / Traitements systémiques du carcinome adénoïde kystique de la sphère ORL localement avancé ou métastatique, une revue systématique.

INTRODUCTION: Adenoid Cystic Carcinoma is a rare tumor of the head and neck sphere. The purpose of this review is a state of the art of systemic treatments (chemotherapies, targeted therapies, immunotherapies) for locally recurrent or metastatic disease. MATERIAL AND METHODS: Our inclusion criteria included head and neck adult patient, metastatic or locally advanced, treated by a systemic therapy, and with at least 10 or more patients. RESULTS: Forty articles have been selected in this review. The objective response rate under chemotherapy was predominantly<10% (0-70%) with objective responses in monotherapy with cisplatin, mitoxantrone, vinorelbine and eribuline, and with cisplatin-vinorelbine combination. EGFR inhibitors provided 40% objective responses only in combination. Inhibitors of VEGF and histone deacetylase have allowed disease stabilization in progressive patients, with about 10% of objective response. Inhibitors of c-KIT monotherapy yield objective response rates of<5%. Direct inhibitors of the PI3K/AKT/mTOR pathway display 0% objective response rate. CONCLUSION: The best objective response rates were obtained with cisplatin-vinorelbine combination. Many targetable molecular abnormalities have been identified and studies have shown prolonged stabilization with EGFR, VEGF and HDAC inhibitors. Multi-disciplinary collaborative consultation (MCC) meetings such as French network of experts in rare head and neck tumors (REFCOR) or Molecular MCC should be proposed and may allow referral to centers proposing specific therapeutic trials.

[Dihydropyrimidine dehydrogenase deficiency screening for management of patients receiving a fluoropyrimidine: Results of two national practice surveys addressed to clinicians and biologists]. / Intérêts et limites de la recherche du déficit en dihydropyrimidine déshydrogénase dans le suivi des patients traités par fluoropyrimidines : résultats de deux enquêtes nationales de pratiques réalisées auprès des médecins et des biologistes.

Dihydropyrimidine dehydrogenase (DPD) deficiency is the main cause of early severe toxicities induced by fluoropyrimidines (FP). The French Group of Clinical Oncopharmacology (GPCO)-Unicancer and the French Pharmacogenetics Network (RNPGx) initiated two surveys, one addressed to oncologists, the other to biologists, in order to evaluate routine practices regarding DPD deficiency screening at national level, as well as compliance, motivations and obstacles for implementation of these tests. These anonymized online surveys were performed with the logistic assistance of the Francophone Federation of Digestive Oncology (FFCD) and the support of numerous medical and biological societies. The surveys were conducted in 2016-2017 before the creation of the French INCa/HAS expert panel, which contributed to the drafting of rules and recommendations for DPD deficiency screening published in December 2018. In all, 554 questionnaires from clinicians were analyzed (23% participation) and 35 from biologists. The main arguments raised by clinicians for justifying the limited practice of DPD deficiency screening were: the lack of recommendations from medical societies or Health Authorities, delays in obtaining results, and the lack of adequate reimbursement by the health insurance system. The goal of these surveys was to provide the French Health Authorities with an overview on nationwide DPD-deficiency screening practices and thus help to design recommendations for the standardization and improvement of the management and safety of cancer patients receiving FP-based chemotherapy.

Predicting survival and local control after radiochemotherapy in locally advanced head and neck cancer by means of computed tomography based radiomics.

PURPOSE: To appraise the ability of a radiomics signature to predict clinical outcome after definitive radiochemotherapy (RCT) of stage III-IV head and neck cancer. METHODS: A cohort of 110 patients was included in a retrospective analysis. Radiomics texture features were extracted from the gross tumor volumes contoured on planning computed tomography (CT) images. The cohort of patients was randomly divided into a training (70 patients) and a validation (40 patients) cohorts. Textural features were correlated to survival and control data to build predictive models. All the significant predictors of the univariate analysis were included in a multivariate model. The quality of the models was appraised by means of the concordance index (CI). RESULTS: A signature with 3 features was identified as predictive of overall survival (OS) with CI = 0.88 and 0.90 for the training and validation cohorts, respectively. A signature with 2 features was identified for progression-free survival (PFS; CI = 0.72 and 0.80); 2 features also characterized the signature for local control (LC; CI = 0.72 and 0.82). In all cases, the stratification in high- and low-risk groups for the training and validation cohorts led to significant differences in the actuarial curves. In the validation cohort the mean OS times (in months) were 78.9 ± 2.1 vs 67.4 ± 6.0 in the low- and high-risk groups, respectively, the PFS was 73.1 ± 3.7 and 50.7 ± 7.2, while the LC was 78.7 ± 2.1 and 63.9 ± 6.5. CONCLUSION: CT-based radiomic signatures that correlate with survival and control after RCT were identified and allow low- and high-risk groups of patients to be identified.

The safety and benefit of using oxidized regenerated cellulose to position free flap pedicle in head and neck reconstruction.

BACKGROUND: Oxidized regenerated cellulose (ORC; Surgicel®; Ethicon, Neuchâtel, Switzerland) is an absorbable hemostatic agent used for hemostasis in operation, although some surgeons use it to position free flap pedicles. The increasing risk of vessel compromise is a huge concern. However, no scientific data to date demonstrate the safety and benefit of using ORC in microvascular surgery. In the present study, we compared the outcome of microvascular head and neck reconstruction with and without pedicle placement using ORC. MATERIALS AND METHODS: From January 2015 to December 2017, we reviewed patients undergoing microvascular surgery with free fibular osteocutaneous flap in our hospital. The patients were divided into the ORC group and non-ORC group and their baseline characteristics and outcomes were compared. RESULTS: In total, there were 27 patients in the ORC group and 67 in the non-ORC group. The non-ORC group had significantly higher cigarette consumption (70.4% vs. 89.6%; p = .022). The outcome of the ORC group was better regarding arterial thrombosis (0% vs. 3%), flap failure (0% vs. 4.5%), hematoma (7.4% vs. 10.4%), and wound complications (25.9% vs. 44.8%). The ORC group had a worse result than the non-ORC group for vein thrombosis (7.4% vs. 4.5%) and duration of hospitalization (24.111 days vs. 23.627 days). However, none of above results was significant. CONCLUSIONS: Though this study was underpowered to detect the differences, the results showed a trend toward better outcomes of flaps and wounds in the ORC group. It seems that using ORC in this field is safe and beneficial.

Association between operation- and operator-related factors and surgical complications among patients undergoing free-flap reconstruction for head and neck cancers: A propensity score-matched study of 1,865 free-flap reconstructions.

OBJECTIVE: Efforts have been devoted to clarify the possible factors related to postoperative complications in free-flap reconstruction. While patient-related factors have been widely discussed, studies regarding the operation/operator-related factors are rather limited in the literature. This study was designed to investigate the relationship between operation/operator-related factors and the surgical complications in free-flap reconstruction following head and neck cancer resection. METHODS: Data of 1,841 patients with a total of 1,865 free-flap reconstructions (24 double free-flap reconstructions) between March 2008 and February 2017 were retrieved from the registered microsurgery database of the hospital. The association of operation/operator-related factors (including flap length and length-width ratio, flap types, use of vein graft, opposite side microanastomosis, number of microanastomoses, operators, operator experience, and operation time) with surgical complications was assessed by 1:1 propensity score-matched study groups. RESULTS: After propensity score matching of the patient-related factors, the rate of vein grafting was significantly higher (0.6% vs. 2.2%, p = .038) and the operation time was longer (7.0 [5.8-8.5] vs. 7.4 [6.1-8.8] hr, p = .006) in the complication group. In addition, flap length and length-width ratio, flap types, opposite side microanastomosis, number of microanastomoses, operators, and operator experience were not associated with surgical complications. CONCLUSIONS: In a hospital that consisted of surgeons with high-volume or very-high-volume experience, the operators or operation experience were not significantly associated with the surgical complications. Only a longer operation time was associated with surgical complications in the patients who underwent free-flap reconstruction for head and neck cancer.

Radiogenomics in head and neck cancer: correlation of radiomic heterogeneity and somatic mutations in TP53, FAT1 and KMT2D.

PURPOSE: Genetic tumour profiles and radiomic features can be used to complement clinical information in head and neck squamous cell carcinoma (HNSCC) patients. Radiogenomics imply the potential to investigate complementarity or interrelations of radiomic and genomic features, and prognostic factors might be determined. The aim of our study was to explore radiogenomics in HNSCC. METHODS: For 20 HNSCC patients treated with primary radiochemotherapy, next-generation sequencing (NGS) of tumour and corresponding normal tissue was performed. In total, 327 genes were investigated by panel sequencing. Radiomic features were extracted from computed tomography data. A hypothesis-driven approach was used for radiogenomic correlations of selected image-based heterogeneity features and well-known driver gene mutations in HNSCC. RESULTS: The most frequently mutated driver genes in our cohort were TP53 (involved in cell cycle control), FAT1 (Wnt signalling, cell-cell contacts, migration) and KMT2D (chromatin modification). Radiomic features of heterogeneity did not correlate significantly with somatic mutations in TP53 or KMT2D. However, somatic mutations in FAT1 and smaller primary tumour volumes were associated with reduced radiomic intra-tumour heterogeneity. CONCLUSION: The landscape of somatic variants in our cohort is well in line with previous reports. An association of somatic mutations in FAT1 with reduced radiomic tumour heterogeneity could potentially elucidate the previously described favourable outcomes of these patients. Larger studies are needed to validate this exploratory data in the future.