Twelve years after: The french national network on rare head and neck tumours (REFCOR).

BACKGROUND: Rare cancers constitute less than 10% of head and neck cancers and lack sufficient evidence for standardized care. The French Rare Head and Neck Cancer Expert Network (REFCOR) as established a national database to collect data on these rare cancers. This study aims to describe patient and tumour characteristics in this database. METHODS: Prospective data collection was conducted across multiple centers. Survival analyses were performed using Kaplan Meier method and Log Rank test. Odds ratios were used for comparing proportions. RESULTS: A total of 7208 patients were included over a period of 10 years. The most frequent histologies were: Not Otherwise Specified (NOS) adenocarcinoma 13 %, adenoid cystic carcinoma 12 %, squamous cell carcinoma of rare locations 10 %, mucoepidermoid carcinoma 9 %, intestinal-type adenocarcinoma (8 %). Tumours were located in sinonasal area (38 %); salivary glands (32 %); oral cavity / oropharynx / nasopharynx (16 %); larynx / hypopharynx (3 %); ears (1 %); others (3 %). Tumours were predominantly classified as T4 (23 %), N0 (54 %), and M0 (62 %). Primary treatment approach involved tumour resection (78 %) and / or radiotherapy (63 %). Patients with salivary gland cancers exhibited better 5-year overall survival (OS) rates (p < 0.05), and lower recurrence rates compared to patients with sinonasal, laryngeal/ hypopharyngeal cancers. No significant differences were observed in the other comparisons. Acinar cell carcinoma demonstrated the best OS while mucous melanoma had the poorest prognosis. CONCLUSION: Melanoma, carcinoma NOS, and sinonasal undifferenciated carcinoma still have poor prognoses. Efforts are being made, including training and guidelines, to expand network coverage (REFCOR, EURACAN), improve data collection and contribute to personalized therapies.

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.

Functional or radical surgical treatment of laryngeal chondrosarcoma, analysis of survival and prognostic factors: A REFCOR and NetSarc-ResOs multicenter study of 74 cases.

INTRODUCTION: Laryngeal chondrosarcoma (LCS) is a rare tumor of slow evolution whose treatment is poorly codified. For a long time, a radical treatment by total laryngectomy (TL) was proposed. More recent studies tend to propose a conservative surgical approach of the larynx. The objective of this study was to compare the overall survival (OS) of total laryngectomized patients (TL+) versus non-laryngectomized patients (TL-). The secondary objectives were to analyse the reoperation free survival (RFS), the total laryngectomy free survival (TLFS) and to identify the preoperative factors leading surgeons to propose TL. MATERIALS AND METHODS: A retrospective analysis of prospectively collected incident cases from the REFCOR and NetSarc-ResOs multicenter databases between March 1997 and June 2021 was conducted. A propensity score matching analysis was performed to compare the OS of TL+ and TL-patients. RESULTS: 74 patients were included. After propensity score, the 5-year OS of TL+ and TL-patients was comparable (100 %, p = 1). The 5-year RFS rate was 69.2 % (95 % CI [57.5-83.4]) and the 5-year TLFS was 61.7 % (95 % CI [50.4-75.5]). Cricoid involvement greater than 50 % (HR 3.58; IC 95 % [1.61-7.92] p < 0.001), an ASA score of 3 or 4 (HR 5.07; IC 95 % [1.64-15.67] p = 0.009) and involvement of several cartilages (HR 5.26; IC 95 % [1.17-23.6] p = 0.04) are prognostic factors for TL. Dyspnea caused by the tumour is a prognostic factor for reoperation (HR 2.59; IC 95 % [1.04-6.45] p = 0.03). CONCLUSION: These results demonstrate that conservative treatment should be considered as first-line treatment for laryngeal chondrosarcoma.

Side-door temporoparietal fascia flap: First experience with a novel technique for anterior skull base reconstruction.

BACKGROUND: Modern achievements in transnasal endoscopic skull base (SB) surgery have led to complex resections that render reconstruction a challenge. Temporoparietal fascia flap (TPFF) is a suitable option for SB reconstruction. The side-door TPFF technique for anterior SB reconstruction is described here for the first time in a real-life surgical setting. METHODS: Patients affected by a SB malignancy who underwent cranioendoscopic resection were included. For reconstruction, a multilayer reconstruction technique including side-door TPFF transposition was employed. RESULTS: TPFF transposition was performed in five patients. The TPFF could be easily transposed via a side-door approach. It adequately covered the edges of the defect and supported optimal healing of the surgical site. During follow-up, vitality and integration of the TPFF were assessed endoscopically and radiologically. CONCLUSIONS: The TPFF side-door transposition technique is a valuable option in anterior SB reconstruction that can provide fast and effective healing, especially in patients needing adjuvant radiotherapy.

The "Gift Wrap" Technique - A Method that Simplifies the Placement of Fascia Lata in the Reconstruction of the Skull Base Following Endoscopic Endonasal Surgery: A Technical Note.

BACKGROUND: With the advancement of endoscopic endonasal surgery in the treatment of anterior skull base (ASB) pathologies, extended, watertight reconstructions are needed to prevent cerebrospinal fluid (CSF) leakage. This often involves the use of multilayers closure, with free fascia lata (FL) graft frequently used as an in- and/or outlay. However, positioning the FL properly can be challenging and time-consuming, particularly on wider defects. In this technical note, we present an easier and faster way to position FL using a silicone sheet. METHODS: FL graft is harvested using a standard technique. The required dimensions are evaluated depending on the extent of the dural defect taking in consideration that FL graft should exceed the edges of the dural defect especially laterally. It is then wrapped around a semi rigid pattern (Silastic sheet) and secured with several monofilament 5/0 sutures. The "package" is transferred through the endonasal corridor to the defect. The sutures are divided and taken out; the fascia is unfolded, and its edges are inserted into the subdural space without any twisting or folding of the flap. Finally, the silicone sheet is withdrawn from the nasal cavity, leaving the FL well-stretched in perfect position. RESULTS: We illustrate this technique in the management of a large anterior skull base chondrosarcoma, which necessitated significant bone and dural resection. CONCLUSIONS: The "Gift wrap" technique offers an alternative approach for positioning the FL, which is less time-consuming compared to the traditional technique. Moreover, it enables improved placement of the FL, enhancing its efficacy.

Management of 80 sinonasal undifferentiated carcinomas. Retrospective multicentre study of the French Network of Rare Head and Neck Cancers (REFCOR).

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive disease requiring multimodal treatment, and multiple new entities once included in the spectrum of SNUC, such as SWI/SNF-deficient carcinomas, are emerging. We aimed to provide new data regarding the role of chemotherapy and surgery and the prognostic factors of disease-free survival. METHODS: This study was based on data from the REFCOR database and included patients with SNUC treated with curative intent from 2007 to 2021 across 22 centres in France. RESULTS: A total of 80 patients were included in the analysis. Among the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58% and 63%, respectively. Of 100% of the patients treated with irradiation, 29% underwent surgery, 56% neoadjuvant chemotherapy (82% had either a partial or a complete response) and 76% chemoradiotherapy. No treatment modality was associated with a better OS or DFS, including surgery (p = 0.34). There was a trend for a better DFS for the patients treated with chemotherapy (neoadjuvant or concomitant, p = 0.062). Overall survival at 3 years was 58% for SWI/SNF deficient group and 86% for non deficient group (p = 0.14). The locoregional relapse rate without distant metastases was 21% in the exclusive radiotherapy group and 26% in the surgery group. Grade 3 or higher toxicities concerned 9%, 32% and 29% of patients for surgery, radiotherapy and chemotherapy respectively. CONCLUSION: In the management of localised SNUC among all patients treated with irradiation, surgery yielded no benefit, whereas the addition of chemotherapy tended to improve disease-free survival.

Reconstruction of subtotal pharyngolaryngectomy using a fasciocutaneous free flap with cartilage graft: A case series of 17 patients.

INTRODUCTION: Subcricoid-hemilaryngopharyngectomy (SCHLP) with a reconstruction using a fasciocutaneous free flap armed with cartilage graft (FFACG) aims to avoid permanent tracheostomy while still maintaining the laryngopharyngeal functions. The purpose of this study is to report the outcome of this surgical approach. MATERIALS AND METHODS: Retrospective study including 17 men operated between 2001 and 2019. Specific survival rate included death caused by cancer or SCHLP complications. Complications, functional and oncological outcomes were evaluated retrospectively. RESULTS: There were no locoregional recurrences. One patient died due to inhalation pneumonia 3 years after surgery. Tracheostomy was closed in 13 patients (76.5%). Mean decannulation time was at six [1-14] months after surgery. CONCLUSION: SCHPL with FFACG could avoid total pharyngolaryngectomy with good oncologic results. However, tracheotomy is extended and deglutition recovery is long with high risk of aspirations. These complications justify that such surgery should be realized only on selected patients by experienced surgical teams. Expertise of the surgical team is critical.

High Frequency Jet Ventilation or Mechanical Ventilation for Panendoscopy for Cervicofacial Cancer: A Retrospective Study.

Introduction-the upper airway panendoscopy, performed under general anesthesia, is mandatory for the diagnosis of cervicofacial cancer. It is a challenging procedure because the anesthesiologist and the surgeon have to share the airway space together. There is no consensus about the ventilation strategy to adopt. Transtracheal high frequency jet ventilation (HFJV) is the traditional method in our institution. However, the COVID-19 pandemic forced us to change our practices because HFJV is a high risk for viral dissemination. Tracheal intubation and mechanical ventilation were recommended for all patients. Our retrospective study compares the two ventilation strategies for panendoscopy: high frequency jet ventilation (HFJV) and mechanical ventilation with orotracheal intubation (MVOI). Methods-we reviewed all panendoscopies performed before the pandemic in January and February 2020 (HFJV) and during the pandemic in April and May 2020 (MVOI). Minor patients, patients with a tracheotomy before or after, were excluded. We performed a multivariate analysis adjusted on unbalanced parameters between the two groups to compare the risk of desaturation. Results-we included 182 patients: 81 patients in the HFJV group and 80 in the MVOI group. After adjustments based on BMI, tumor localization, history of cervicofacial cancer surgery, and use of muscle relaxants, the patients from the HFJV group showed significantly less desaturation than the intubation group (9.9% vs. 17.5%, ORa = 0.18, p = 0.047). Conclusion-HFJV limited the incidence of desaturation during upper airway panendoscopies in comparison to oral intubation.

[Rare cancers of the head and neck on behalf of the REFCOR, part 2]. / Cancers rares de la tête et du cou sous l'égide du REFCOR, partie 2.

Among the 16,000 new cases of malignant tumors of the head and neck diagnosed in France each year, 10% are not conventional squamous cell carcinomas. These so-called rare cancers are distinguished by their presentation and patterns of failure, which is important to recognize in order to offer specific adapted management and maximize the chances of tumor control. These cancers can be rare by their histology as well as their anatomical location when arising from the paranasal sinuses, salivary glands and ear. The management of these heterogeneous rare diseases of complex treatment has considerably been structured over the last 15 years, in particular via the French ENT Cancer Expertise Network (REFCOR) and international networks and registries (EURACAN, etc.). Structuration also favors research with identification of new entities and setting up of specific therapeutic trials. A first article (part 1) discusses the diagnostic and therapeutic specificities of these rare cancers, and develops the recommendations of the REFCOR concerning rare epithelial tumors, i.e., salivary tumors, sinonasal tumors, variants of conventional squamous cell carcinomas, neuroendocrine carcinomas, malignant odontogenic tumors, and ear tumors. This second article (part 2) is focused on non-epithelial tumors (sarcomas, mucosal melanomas, lymphomas, tumors of uncertain or undetermined malignancy) and describes the organization and missions of the REFCOR.

[Rare cancers of the head and neck on behalf of the REFCOR, part 1]. / Cancers rares de la tête et du cou sous l'égide du REFCOR, partie 1.

Among the 16,000 new cases of malignant tumors of the head and neck diagnosed in France each year, 10% are not conventional squamous cell carcinomas. These so-called rare cancers are distinguished by their presentation and patterns of failure, which is important to recognize in order to offer specific adapted management and maximize the chances of tumor control. These cancers can be rare by their histology, which determines their local invasiveness, and their hematogenous/nodal spread. Their diagnosis can be difficult and often requires comprehensive immunohistochemistry and genomic techniques. Expert pathology review is recommended in the cases of undifferentiated tumors, sarcomas and at the slightest diagnostic doubt. These rare cancers can also be rare by their anatomical location when arising from the paranasal sinuses, salivary glands and ear. Their location requires knowledge of their specific extension routes, and may call for a specific surgical technique (skull base endoscopic sinus surgery, extended total parotidectomy, etc.) and adapted radiotherapy to spare healthy organs surrounding the tumor. This article (part 1) discusses the diagnostic and therapeutic specificities of these rare cancers, and develops the recommendations of the French ENT Cancer Expertise Network (REFCOR) concerning rare epithelial tumors, i.e., salivary tumors, sinonasal tumors, variants of conventional squamous cell carcinomas, neuroendocrine carcinomas, malignant odontogenic tumors, and ear tumors. A second article (part 2) is focused on non-epithelial tumors (sarcomas, mucosal melanomas, lymphomas, tumors of uncertain or undetermined malignancy) and describes the organization and missions of the REFCOR.

How I do it: epidural transposition of the temporoparietal fascia flap for anterior skull base reconstruction.

BACKGROUND: Multilayer closures and the use of vascularized flaps have been showed to be very effective in the reconstruction of the anterior skull base (ASB) after extended endonasal approaches resulting in large bone and dural defects. In the case of unavailability of a local flap, regional ones like the temporoparietal fascia flap (TPFF), used until now via a transpterygoïd route (Bolzoni Villaret et al. in Eur Arch Otorhinolaryngol 270(4):1473-1479, 2023; Fortes et al. in Laryngoscope 117(6):970-976, 2017; Veyrat et al. in Acta Neurochir (Wien) 158(12):2291-2294, 2016), can be an effective alternative. METHOD: We describe a step-by-step technique of TPFF transposition via an epidural supraorbital corridor for the reconstruction of a large midline ASB defect. CONCLUSION: TPFF is a promising alternative for the reconstruction of the ASB defects.

Intraoperative Autofluorescence Imaging for Parathyroid Gland Identification during Total Laryngectomy with Thyroidectomy.

OBJECTIVE: Hypoparathyroidism is a known complication of total laryngectomy, although parathyroid preservation and/or reimplantation are not routine. Autofluorescence is a new technique for identifying parathyroid glands intraoperatively. The aim of this study was to evaluate the feasibility of autofluorescence in this context. MATERIALS AND METHODS: A retrospective study of patients undergoing total laryngectomy/pharyngectomy with concomitant thyroidectomy using the Fluobeam® (Fluoptics, Grenoble, France) and frozen section of a parathyroid fragment in case of reimplantation. The rates of identification using autofluorescence, reimplantation, and hypoparathyroidism were evaluated. RESULTS: Eighteen patients (16 males, median age 67) underwent total laryngectomy/pharyngectomy with total thyroidectomy (n = 12) or hemithyroidectomy (n = 6). A median of 2 parathyroid glands were identified per patient. Ninety-two percent were identified by autofluorescence before visualisation. All parathyroids were reimplanted due to devascularization. Temporary hypoparathyroidism occurred in nine patients, and was permanent in one patient. After 34 months of median follow-up (range 1-49), no tumor recurrence was observed in the reimplantation sites. CONCLUSIONS: To our knowledge, this is the largest study to evaluate autofluorescence during total laryngectomy with thyroidectomy. No tumor recurrence occurred in the sites of parathyroid reimplantation.

Outcomes of mandibular reconstruction using three-dimensional custom-made porous titanium prostheses.

BACKGROUND: Our aim was to report the long-term outcomes of mandibular reconstruction using CAD-CAM-designed 3D-printed porous titanium implants in patients not amenable to a free vascularized fibula flap reconstruction. METHODS: The implants were designed with ProPlan CMF® 2.2 software and manufactured with a Selective Laser Melting (SLM) "layer-by-layer" 3D-printing of pure porous titanium powder beds. Primary endpoints were implant exposure and implant removal calculated using Gray's tests. Secondary endpoints were predictive factors of implant exposure and implant removal, and rates of dental rehabilitation. RESULTS: Thirty-six patients were operated between 2015 and 2017 and were included in this study. Reconstruction using a porous titanium 3D-printed implant was proposed due to medical contraindication for a fibula free flap (n = 13), due to the failure of a previous fibula free flap reconstruction (n = 7), or due to refusal of a fibula free flap reconstruction by the patient (n = 16). The medical indications for mandibular reconstruction were a primary tumor requiring mandibulectomy in nine patients, mandibular osteoradionecrosis requiring mandibulectomy in nineteen patients, and secondary reconstruction in eight patients. The 2-year rates of implant exposure and implant removal were 69.4% and 52.8%. Reconstruction of the symphysis was a high-risk exposure variable (OR 30; p = 0.0003). Only one patient underwent a successful dental rehabilitation. CONCLUSION: The use of a porous titanium 3D- implant for mandibular reconstruction in head and neck cancer patients resulted in high rates of implant exposure and of implant removal, notably when symphysis involvement.

Multicenter study to assess surgical treatments of 452 sinonasal intestinal-type adenocarcinomas: A REFCOR study.

PURPOSE: The objective was to assess the local oncological outcomes of endoscopic versus external surgical treatment of sinonasal intestinal-type adenocarcinomas (ITAC) and the factors of recurrence. METHODS: a retrospective non-randomized case-control multicenter study was carried out, including 452 untreated sinonasal ITACs recruited from 10 tertiary referral centers. The tumors were re-classified according to the UICC 2017 (pT). Survival curves were obtained using the Kaplan-Meier method. Univariate analysis was done with the log-rank test. Multivariate analysis was performed with a Cox model adjusted for age, T stage, and radiotherapy. A binary logistic regression compared surgical complications and performed two supplementary analyses on positive margins. RESULTS: We compared 195 and 257 patients operated by the external and endoscopic approach, respectively. The mean follow-up was 59.2 ± 48.7 months. Post-operative margins were invaded in 30.6 versus 18.9% of patients, respectively (p = 0.007). The overall recurrence rate was 33.8 versus 24.6%, respectively (p = 0.034). There was a significant difference in favor of the endoscopic approach regarding local recurrence-free survival thanks to better surgical margins in univariate and multivariate analysis (Odd Ratio = 2.01 (1.2-3.36) p = 0.0087). The complication rate (Odds Ratio = 3.4 (1.79-6.32) p < 0.001) was significantly lower in the endoscopic group. The histological positivity of signet-ring cells shows a statistically significant difference in recurrence-free survival (p = 0.0028). CONCLUSION: the oncological control of ITAC is better through the endoscopic approach, with negative margins and the absence of signet-ring-cells, two independent factors of recurrence.

NUT Carcinoma in Children and Adolescents: The Expert European Standard Clinical Practice Harmonized Recommendations.

BACKGROUND AND AIMS: Nuclear protein of the testis ( NUT ) carcinoma (NC) is a rare and highly aggressive tumor mainly occurring in adolescents and young adults, defined by the presence of a somatic NUTM1 rearrangement. The aim is to establish internationally harmonized consensus recommendations for the diagnosis and treatment of adolescents and young adults with NC in the framework of the European Reference Network for Paediatric Oncology. METHODS: The European Cooperative Study Group for Pediatric Rare Tumors developed recommendations according to the Consensus Conference Standard Operating procedure methodology and reviewed by external "experts." No evidence of level I to II exists. Recommendations were developed based on published prospective (level III), but more frequently retrospective series (level IV), case reports (level V), and personal expertise (level V). In addition, "strength" of recommendations were categorized by grading (grade A to E). RESULTS: Histology is mandatory for the diagnosis of NC, including immunolabeling with anti-NUT antibodies and molecular biology ( NUTM1 rearrangement) (level V; grade A). Treatment of NC usually combines aggressive approaches in multimodal regimens. Chemotherapy should be considered as first-line treatment (neoadjuvant vincristine-adriamycin-ifosfamide/cisplatin-adriamycin-ifsofamide or vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide) for unresectable or metastatic tumor (ie, 3 courses), rapidly followed by local treatment (level IV; grade B). Referral to a specialized surgical oncology center is highly recommended (level V; grade A). In localized NC, a complete microscopic surgical resection should be attempted whenever and as soon as possible, followed by primary irradiation (60 to 70 Gy) and involved lymph nodes area (level IV; grade B). For head and neck tumors, a systematic neck dissection might be considered, even if N0 (level V; grade C). Adjuvant postirradiation chemotherapy is recommended, for a total of 9 to 12 courses (level IV; grade B). For first-line resected tumors, concomitant adjuvant chemotherapy to radiotherapy may be discussed (level IV; grade B). Targeted therapies and immunotherapeutic regimens should be delivered in the setting of prospective trials (level V; grade B). CONCLUSIONS: This project leads to a consensus strategy based on international experience with this very rare disease.

Hippocrates: father of mini-invasive nasal surgery.

Hippocrates, a Greek physician during the fifth century BC., is often considered the father of medicine. The Corpus Hippocraticum comprising of 58 volumes was writing between 450 and 150 BC. The objective of our study was to detail the management of nasal polyps during this period. We read and analyzed all volumes of the Corpus Hippocraticum in French translation and extracted all passages dealing with nasal polyps (n = 6). Surgical procedures in the Corpus Hippocraticum are described in great detail. The first surgical strategy for the removal of nasal polyps was by mini-invasive nasal approach: the lopping method and the sponge method. We explain the two mini-invasive nasal approaches with drawings. The meticulously detailed observations of the corpus give us a precious insight into the early perception of diseases, their progression and early attempts of treatment.

Association between human papillomavirus infection and malignant transformation of sinonasal inverted papilloma: A systematic review and meta-analysis.

PURPOSE: Although sinonasal inverted papilloma malignant transformation has not been entirely understood, some studies have suggested that human papillomavirus acts as a potential oncogenic agent in the progression of sinonasal inverted papilloma to squamous cell carcinoma. The purpose of this study was to assess the association between human papillomavirus infection and sinonasal inverted papilloma transformation, taking also into account human papillomavirus types and their distribution in different geographic areas. MATERIALS AND METHODS: The literature from the last 25 years was examined. The systematic review and meta-analysis were performed according to the PRISMA guidelines. RESULTS: A total of 163 malignant sinonasal inverted papilloma and 961 non-malignant sinonasal inverted papilloma were included in the overall analysis. From this sample it was possible to recognize a statistically significant increase in risk of malignancy of sinonasal inverted papilloma for human papillomavirus infection (OR = 2.43, 95 % CI: 1.45-4.08, I2 = 14.0 %). A positive association for patients with high-risk human papillomavirus types was noted (OR = 10.20, 95 % CI: 3.66-28.42, I2 = 15.9 %). In all the 3 geographical areas analyzed the presence of high-risk human papillomavirus significantly increased the probability of malignant transformation. CONCLUSIONS: High-risk human papillomavirus infection plays a key role in the malignant transformation of sinonasal inverted papilloma and its research during histological examination can be of paramount importance. More prospective studies are needed to help further tease out this association.

Events prediction after treatment in HPV-driven oropharyngeal carcinoma using machine learning.

OBJECTIVES: Our objective was to develop a predictive model using a machine learning signature to identify patients at high risk of relapse or death after treatment for HPV-positive oropharyngeal carcinoma. MATERIALS AND METHODS: Pre-treatment variables of 450 patients with HPV-positive oropharyngeal carcinoma treated with a curative intent comprised clinical items, imaging parameters and histological findings. The events considered were progression or residual disease after treatment, the recurrent disease after a disease-free interval and death. The endpoints were the prediction of events and progression-free survival. After feature Z-score normalisation and selection, random forest classifier models were trained. The best models were evaluated on recall, the F-score, and the ROC AUC metric. The clinical relevance of the best prediction model was evaluated using Kaplan-Meier analysis with a log-rank test. RESULTS: The best random forest model predicted the 5-year risk of relapse-free survival with a recall of 79.1%, an F1-score of 81.08%, and an AUC of the ROC curve of 0.89. The models performed poorly for the prediction of specific events of progression only, recurrence only or death only. The clinical relevance of the model was validated with a 5-year relapse-free survival of high-risk patients versus low-risk patients of 23.5% and 80%, respectively (p < 0.0001). CONCLUSION: Patients with HPV-driven oropharyngeal carcinoma at high risk of relapse-free survival could be identified with a predictive machine learning model using patient data before treatment.