Randomized phase II study of preoperative afatinib in untreated head and neck cancers: predictive and pharmacodynamic biomarkers of activity.

There is no strong and reliable predictive biomarker in head and neck squamous cell carcinoma (HNSCC) for EGFR inhibitors. We aimed to identify predictive and pharmacodynamic biomarkers of efficacy of afatinib, a pan-HER tyrosine kinase inhibitor, in a window-of-opportunity trial (NCT01415674). Multi-omics analyses were carried out on pre-treatment biopsy and surgical specimen for biological assessment of afatinib activity. Sixty-one treatment-naïve and operable HNSCC patients were randomised to afatinib 40 mg/day for 21-28 days versus no treatment. Afatinib produced a high rate of metabolic response. Responders had a higher expression of pERK1/2 (P = 0.02) and lower expressions of pHER4 (P = 0.03) and pRB1 (P = 0.002) in pre-treatment biopsy compared to non-responders. At the cellular level, responders displayed an enrichment of tumor-infiltrating B cells under afatinib (P = 0.02). At the molecular level, NF-kappa B signaling was over-represented among upregulated genes in non-responders (P < 0.001; FDR = 0.01). Although exploratory, phosphoproteomics-based biomarkers deserve further investigations as predictors of afatinib efficacy.

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.

Development and External Validation of a PET Radiomic Model for Prognostication of Head and Neck Cancer.

AIM: To build and externally validate an [18F]FDG PET radiomic model to predict overall survival in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Two multicentre datasets of patients with operable HNSCC treated with preoperative afatinib who underwent a baseline and evaluation [18F]FDG PET/CT scan were included (EORTC: n = 20, Unicancer: n = 34). Tumours were delineated, and radiomic features were extracted. Each cohort served once as a training and once as an external validation set for the prediction of overall survival. Supervised feature selection was performed using variable hunting with variable importance, selecting the top two features. A Cox proportional hazards regression model using selected radiomic features and clinical characteristics was fitted on the training dataset and validated in the external validation set. Model performances are expressed by the concordance index (C-index). RESULTS: In both models, the radiomic model surpassed the clinical model with validation C-indices of 0.69 and 0.79 vs. 0.60 and 0.67, respectively. The model that combined the radiomic features and clinical variables performed best, with validation C-indices of 0.71 and 0.82. CONCLUSION: Although assessed in two small but independent cohorts, an [18F]FDG-PET radiomic signature based on the evaluation scan seems promising for the prediction of overall survival for HNSSC treated with preoperative afatinib. The robustness and clinical applicability of this radiomic signature should be assessed in a larger cohort.

Swallowing outcomes over time after total pharyngolaryngectomy and free flap reconstruction.

BACKGROUND: One of the challenges after total pharyngolaryngectomy (TPL) is to restore the swallowing function. The aim of this study was to compare swallowing outcomes between patients who underwent reconstruction with jejunum free flap (JFF) and other free flaps (OFFs). METHODS: This retrospective study included patients who underwent TPL and free flap reconstruction. The endpoints were the evolution of swallowing outcomes during the first five years after treatment assessed by the Functional Oral Intake Scale (FOIS), and outcomes associated with complications. RESULTS: One hundred and eleven patients were included, 84 patients in the JFF group and 27 in the OFF group. The patients in the OFF group experienced more chronic pharyngostoma (p = 0.001) and pharyngoesophageal stricture (p = 0.008). During the first year, a lower FOIS score tended to be associated with OFF (p = 0.137), and this result remained stable over time. CONCLUSIONS: This study suggests that JFF reconstruction provides better swallowing outcomes than OFF reconstruction, stable over time.

Enteral Nutrition during Radiotherapy for Oropharyngeal Cancers: Prevalence and Prognostic Factors Based on HPV Status (A GETTEC Study).

Nutritional support during radiotherapy is crucial to tolerating and completing oropharyngeal squamous cell carcinoma (OPSCC) treatment. The impact of HPV status on nutritional support is debated. The objective was to evaluate the rate of Reactive Feeding Tube (RFT) use and determine its prognostic factors during definitive radiotherapy for OPSCC. All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. The impact of tumor p16 status on the risk of RFT was assessed through multivariate analyses. Among the 543 patients, 103 patients required an RFT (19.0%). The use of RFT differed between centers (5% to 32.4%). In multivariate analysis, only tongue base involvement and concurrent chemotherapy were significantly associated with RFT (OR = 2.18 and 3.7, respectively). Tongue base involvement and concomitant chemotherapy were prognostic factors for RFT. HPV status was not a prognostic factor for enteral nutrition during radiotherapy for OPSCC.

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.

Influence of Different Measurement Methods of Arterial Input Function on Quantitative Dynamic Contrast-Enhanced MRI Parameters in Head and Neck Cancer.

BACKGROUND: Head and neck cancer (HNC) is the sixth most prevalent cancer worldwide. Dynamic contrast-enhanced MRI (DCE-MRI) helps in diagnosis and prognosis. Quantitative DCE-MRI requires an arterial input function (AIF), which affects the values of pharmacokinetic parameters (PKP). PURPOSE: To evaluate influence of four individual AIF measurement methods on quantitative DCE-MRI parameters values (Ktrans , ve , kep , and vp ), for HNC and muscle. STUDY TYPE: Prospective. POPULATION: A total of 34 HNC patients (23 males, 11 females, age range 24-91) FIELD STRENGTH/SEQUENCE: A 3 T; 3D SPGR gradient echo sequence with partial saturation of inflowing spins. ASSESSMENT: Four AIF methods were applied: automatic AIF (AIFa) with up to 50 voxels selected from the whole FOV, manual AIF (AIFm) with four voxels selected from the internal carotid artery, both conditions without (Mc-) or with (Mc+) motion correction. Comparison endpoints were peak AIF values, PKP values in tumor and muscle, and tumor/muscle PKP ratios. STATISTICAL TESTS: Nonparametric Friedman test for multiple comparisons. Nonparametric Wilcoxon test, without and with Benjamini Hochberg correction, for pairwise comparison of AIF peak values and PKP values for tumor, muscle and tumor/muscle ratio, P value ≤ 0.05 was considered statistically significant. RESULTS: Peak AIF values differed significantly for all AIF methods, with mean AIFmMc+ peaks being up to 66.4% higher than those for AIFaMc+. Almost all PKP values were significantly higher for AIFa in both, tumor and muscle, up to 76% for mean Ktrans values. Motion correction effect was smaller. Considering tumor/muscle parameter ratios, most differences were not significant (0.068 ≤ Wilcoxon P value ≤ 0.8). DATA CONCLUSION: We observed important differences in PKP values when using either AIFa or AIFm, consequently choice of a standardized AIF method is mandatory for DCE-MRI on HNC. From the study findings, AIFm and inflow compensation are recommended. The use of the tumor/muscle PKP ratio should be of interest for multicenter studies. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

2011-2021 rising prevalence of HPV infection among oropharyngeal carcinoma in France.

BACKGROUND: The objective of our study was to investigate changes over the past decade in patient age and the prevalence of HPV in the population of patients with oropharyngeal carcinoma (OPC) treated at our center. METHODS: We performed a retrospective cohort study of patients treated at our cancer center for OPC between 2011 and 2021. Tissue biopsies were assessed for HPV status based on p16 staining for all patients. RESULTS: There were 1,365 treated patients. The proportion of p16-positive patients increased from 43% in 2011 to 57.3% in 2021 (p = 0.01). The sex ratio was 3.6 M/1F for p16-positive and 3.7 M/1F for p16-negative patients (p = 0.94). The mean age increased from 60.2 y in 2011 to 63.6 y in 2021. The mean ages were 61.9 y for p16-positive and 61.7 y for p16-negative patients (p = 0.71), but there was a broader age distribution for the p16-positive patients (p = 0.03). The proportion of patients older than 70 y increased from 11% in 2011 to 28.2% in 2021, and this aging was similar between p16-positive (30.7% in 2021) and p16-negative (26.3% in 2021) patients. The 2-year and 5-year OS rates were 73.7% and 56.5% for the entire cohort. p16-positive patients had 2-year and 5-year OS rates of 86.8% and 77.4%, respectively, whereas p16-negative patients had 2-year and 5-year OS rates of 63.9% and 40.5%. CONCLUSIONS: Assessment of the change over the past decade in the population of patients with OPC at our center showed that HPV-positive OPC now appear to have overtaken HPV-negative cases in France, with 57.3% in 2021, and showed significant aging, with almost thirty percent of patients now older than 70 years. Those combined changes emphasize some of the challenges to be addressed in future OPC management.

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.

A prospective longitudinal study of quality of life in robotic-assisted salvage surgery for oropharyngeal cancer.

OBJECTIVE: We investigated the quality of life (QoL), functional, and oncological outcomes after robotic-assisted transoral or combined cervical-transoral salvage surgery for oropharyngeal carcinoma following radiotherapy. MATERIAL AND METHODS: We performed a single tertiary referral center, prospective, observational cohort study of all consecutive patients who underwent salvage robotic-assisted surgery for oropharyngeal carcinoma between 2015 and 2021. The primary outcomes were quality of life assessments using the MDADI, EORTC-QLQC30, and EORTC-QLQH&N35. Secondary endpoints were the functional and oncological outcomes based on overall survival, disease-free survival, and local control. RESULTS: A consecutive cohort of 53 patients were included. The median Charlson comorbidity index was 5. The p16 status was negative in 87%, and 22.6% were T3-4. A flap reconstruction was performed in 90.6%, with a free flap in 67.9%. Margins were negative in 81.1%. The preoperative, 1-year, and 2-year MDADI total scores were 71.4, 64.3, and 57.5, respectively. The preoperative, 1-year, and 2-year QLQ-C30 global scores were 61.2, 59.4, and 80.6, respectively. Decannulation was possible in 97.1% of the tracheotomized patients. The two-year enteral tube dependence was 23.1%. The two-year overall survival, disease-free survival, and local control rates were 59%, 46.1%, and 80.9%, respectively. CONCLUSION: Robotic-assisted salvage surgery for oropharyngeal carcinoma following radiotherapy demonstrated a very satisfactory quality of life, good functional sequelae, and good oncological outcomes compared to historical approaches.

Patterns of disease events and causes of death in patients with HPV-positive versus HPV-negative oropharyngeal carcinoma.

BACKGROUND AND PURPOSE: There have been no studies to date of patterns of events after oropharyngeal squamous cell carcinoma (OPC) treatment comprising disease progression immediately after treatment or after a disease-free interval (DFI), and causes of death, according to HPV status. MATERIALS AND METHODS: Patients with a T1-4, N0-3, M0 OPC who completed treatment in a curative intent at our center between 2011 and 2020 were analyzed. A DFI was defined as the absence of the disease confirmed by both physical and radiological evaluation. RESULTS: We analyzed 888 patients, of who 451 were p16-positive and 437 were p16-negative. The 5-year survival rates were 82.4% vs. 44%, respectively (p < 0.0001, HR 0.24). The rates of disease progression at the end of the treatment without a DFI were 7.8% vs. 21.1% in the p16-positive vs. the p16-negative patients (p < 0.0001, OR 0.38). The 5-year competing risks of disease recurrence after a DFI were 5.6% vs. 20.5%, respectively (p < 0.0001, HR 0.26). Patients who were p16-positive had a lower risk of death from OPC disease (p < 0.0001, HR 0.23). The 5-year competing risks of a second primary cancer during follow-up were 16.1% vs. 49.9% (p = 0.0002) in the p16-positive vs. the p16- negative patients. Patients who were p16-positive had a lower risk of death from intercurrent causes (p < 0.0001, HR 0.17). CONCLUSION: Clinical trials and medical interventions dedicated to each category of events and causes of death are needed to improve survival in HPV-positive and HPV-negative OPC patients.

Head and neck Ewing sarcoma: French surgical practice analysis pleads for surgery centralization.

This study aimed to analyze surgical procedures for head and neck Ewing sarcoma (HNES) with regard to oncological, functional, and esthetic outcomes. A blinded multidisciplinary retrospective chart review of operated French HNES patients (Euro-EWING 99 trial, 1999-2014) was performed to assess patient/tumor characteristics, treatment details, and outcomes. Primary surgery without reconstruction was undertaken in 13 patients (emergency context/misdiagnosis). However, because of contaminated surgical margins, all patients had to undergo systematic postoperative radiotherapy. Twenty-six patients underwent multidisciplinary evaluation and were scheduled to undergo postchemotherapy surgery, with 19 patients scheduled for immediate reconstruction. All cases showed R0 margins after postchemotherapy surgery of the initial tumor bed by multidisciplinary surgical teams, while n = 3/4 of local relapses (very poor prognosis) had R1a margins after surgery of the residual tumor volume following chemotherapy. Only three surgical expertise centers operated on ≥ 4 patients over the 15-year period. Thirty patients developed long-term sequelae, with increased complications following radiotherapy. Referring patients to surgical expertise centers following a suspected diagnosis, with planned postchemotherapy surgery of the initial tumor bed at these centers, might limit the need for intralesional resections, allowing radical R0 resections and thus reducing long-term sequelae as well as the risk of secondary radio-induced malignancy by limiting the need for postoperative radiotherapy.

Delto-acromial artery perforator flap combined with a radial forearm free flap as a "vascular bridge" for nasal reconstruction.

Nasal reconstruction for total rhinectomy is challenging, especially if locoregional flaps are unavailable. Herein, we report the case of a nasal reconstruction combining a forearm free flap as "vascular bridge" and a Delto-Acromial Artery Perforator (DAAP) flap in its free form. The forearm free flap was used to restore missing elements of the nasal lining while the distal part of the radial pedicle has served as a donor vessel for the DAAP free flap which restores the nasal covering. A chondrocostal graft was used as a nasal framework. The nasal aspect at 24 months postop support the patient's satisfaction. The main advantages of the DAAP Flap are the pliability, relative hairless nature, skin thinness and its geographical proximity with the nose avoiding major dyschromia. Moreover, the anatomy consistency makes it easier to harvest, the underlying muscles are respected, and it allows for tension free primary closure without shoulder movement limitation.

Vestibuloplasty for immediate dental implantation in fibular free flap for oral cancer patients undergoing mandibulectomy reconstruction: A technical note.

Vestibuloplasty is fundamental to restore an oral vestibule for immediate dental implantation in fibular free flap (FFF) for oral cancer patients undergoing mandibulectomy reconstruction. Double surgical team including reconstructive head and neck surgeon and a dental surgeon is fundamental. The first step of the vestibuloplasty is to identify the skin perforator. The second step is to thin the FFF skin island as much as necessary to facilitate: i-the reinset into the gingivobuccal sulcus while creating enough space in the oral vestibule for the future dental prosthesis and ii-the exposition of dental implants. The third step is to create a percutaneous access to the implants through the FFF skin paddle using a dermatologic punch while preserving a large oral vestibule. The fourth step is the skin reinsertion into the gingivobuccal sulcus and closure. Realizing vestibuloplasty before radiotherapy allows prevention of soft tissue contraction and osteoradionecrosis while reducing the necessary time for a complete dental rehabilitation and improving patient quality of life.

18F-FDG PET/CT for early response assessment of jaw osteoradionecrosis after the PENTOCLO protocol: A promising imaging modality.

INTRODUCTION: The Pentoxifylline, Tocopherol and Clodronate protocol (PENTOCLO) showed promising results for jaw osteoradionecrosis (ORN) management. However, the clinical and radiological improvements are often delayed, leading to unwanted long-term treatment, with potential loss of opportunity for more radical surgical treatments. Our objective was to assess the diagnosis performance of 18F-FDG PET/CT to early predict ORN response to the PENTOCLO protocol. MATERIALS AND METHODS: All patients from our center who were treated with the PENTOCLO protocol and with a 18F-FDG PET/CT performed at diagnosis and three months after the end of antibiotherapy were retrospectively included. The PENTOCLO protocol was always combined with prior appropriate antibiotherapy for six weeks. The healing endpoint was divided into healing, stability or worsening, according to the combination of clinical and radiological assessments at the date of last follow-up. For each patient, the difference between the maximal standardized uptake value (ΔSUVmax) of the ORN lesion at three months and baseline were computed. Diagnostic performance of 18F-FDG PET/CT was evaluated by sensitivity, specificity and the area under the receiver operating characteristic curve (ROC-AUC) of ΔSUVmax. RESULTS: 24 patients were included with an average follow-up of 29.3 months. The healing, stability and worsening rate were 25%, 62.5% and 12.5% respectively. The AUC for discriminating worsening vs stability or healing was 0.92 (IC95 [0.81-1.00]). A ΔSUVmax greater than or equal to 0 was predictive of a worsening with a sensitivity and specificity of 84 and 66% respectively. CONCLUSION: 18F-FDG PET/CT imaging could be useful for early prediction of PENTOCLO treatment resistance with appropriate antibiotherapy.

Exploratory window-of-opportunity trial to investigate the tumor pharmacokinetics/pharmacodynamics of the IAP antagonist Debio 1143 in patients with head and neck cancer.

Inhibitor of apoptosis proteins (IAPs) regulate apoptosis and modulate NF-κB signaling thereby driving expression of genes involved in immune/inflammatory responses. The orally available IAP antagonist Debio 1143 has potential to enhance tumor response to chemoradiotherapy and/or immunotherapy. Patients with pre-operative squamous cell carcinomas of the head and neck (SCCHN) received: Debio 1143 monotherapy (200 mg/day [D]1-15 +/- 2); Debio 1143 (200 mg/day D1-15 +/- 2) plus cisplatin (40 mg/m2 D 1 and 8); cisplatin alone (40 mg/m2 D 1 and 8; EudraCT: 2014-004655-31). Pharmacokinetic/pharmacodynamic effects were assessed in plasma and resected tumors. Primary end point; effect of Debio 1143 on cellular IAP-1 (cIAP-1). Levels of cIAP-1/-2, X-linked inhibitor of apoptosis protein (XIAP), tumor infiltrating lymphocytes (TILs), including CD8+ T cells, programmed cell death protein 1 (PD-1), PD-ligand 1 (PD-L1), and gene expression were also analyzed. Twenty-three of 26 patients completed treatment. In the Debio 1143 monotherapy cohort (n = 13), mean tumor concentrations of Debio 1143 were 18-fold (maximum 55.2-fold) greater than in plasma, exceeding the half-maximal inhibitory concentration for cIAPs and XIAP by 100 to 1000-fold, with significant engagement/degradation of cIAP-1 (p < 0.05). Overall, levels of CD8+ TILs, PD-1, and PD-L1 positive immune cells increased significantly (p < 0.05) following Debio 1143 treatment. Changes were observed in the expression of genes related to NF-κB signaling. Treatments were well-tolerated. Debio 1143 penetrated SCCHN tumors, engaged cIAP-1, and induced immune inflammatory changes in the tumor microenvironment. Based on the mode of action demonstrated here and in previous studies, these data support future combinations of Debio 1143 with immune-checkpoint agents.

Disease-free time stratification in locally recurrent head and neck carcinoma after definitive radiotherapy or chemoradiotherapy.

PURPOSE: There is no standard definition of disease-free interval before local recurrence after treatment in head and neck carcinoma (HNSCC). We evaluated an easy-to-use stratification and its association with survival in a large cohort of patients. METHODS: We performed a retrospective cohort analysis of prognostic variables in 325 HNSCC patients with a local recurrence after definitive radiotherapy or concurrent chemoradiotherapy. Endpoints were overall survival (OS) and post-recurrence survival (PRS). RESULTS: Variables associated with the survival were the patient age (OS p < 0.0001, PRS p < 0.0001), the initial disease stage (OS p = 0.24, PRS p = 0.0358), localization (OS p = 0.012, PRS p = 0.0002), a complete initial response to treatment (OS p < 0.0001, PRS p = 0.019), synchronous regional or distant metastatic disease (OS p = 0.0094, PRS p < 0.0001), a salvage surgery (OS p < 0.0001, PRS p < 0.0001) and time to recurrence (OS p = 0.0002, PRS p = 0.0029). Time to recurrence could be stratified between specific prognostic time categories that comprised disease persistence, early recurrence (< 12 months), standard recurrence (12 months-5 years) and late recurrence (> 5 years). CONCLUSION: In HNSCC patients, time to local recurrence is a prognostic variable that can be defined using an easy-to-use stratification.

Diagnostic accuracy of in vivo early tumor imaging from probe-based confocal laser endomicroscopy versus histologic examination in head and neck squamous cell carcinoma.

OBJECTIVES: Probe-based confocal laser endomicroscopy (pCLE) is a noninvasive and real-time imaging technique allowing acquisition of in situ images of the tissue microarchitecture during oral surgery. We aimed to assess the diagnostic performance of pCLE combined with patent blue V (PB) in improving the management of early oral cavity, oro/hypopharyngeal, and laryngeal cancer by imaging squamous cell carcinoma in vivo. MATERIALS AND METHODS: The prospective study enrolled 44 patients with early head and neck lesions. All patients underwent white-light inspection or panendoscopy depending on the lesion's location, followed by pCLE imaging of the tumor core and its margins after topical application of PB. Each zone imaged by pCLE was interpreted at distance of the exam by three pathologists blinded to final histology. RESULTS: Most imaged zones could be presented to pathologists; the final sensitivity and specificity of pCLE imaging in head and neck cancers was 73.2-75% and 30-57.4%, respectively. During imaging, head and neck surgeons encountered some challenges that required resolving, such as accessing lesions with the flexible optical probe, achieving sufficiently precise imaging on the targeted tissues, and heterogeneous tissue staining by fluorescent dye. CONCLUSION: Final sensitivity scores were reasonable but final specificity scores were low. pCLE zones used to calculate specificity were acquired in areas of tumor margins, and the poor quality of the images acquired in these areas explains the final low specificity scores. CLINICAL RELEVANCE: Practical adjustments and technical training are needed to analyze head and neck lesions in various anatomical sites in real-time by pCLE.

Metachronous second primary neoplasia in oropharyngeal cancer patients: Impact of tumor HPV status. A GETTEC multicentric study.

INTRODUCTION: Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk to develop a metachronous second primary neoplasia (MSPN). HPV and non-HPV-related OPSCC are 2 distinct entities with biological, clinical and prognostic differences. The aims of our study were to analyze the impact of tumor HPV status and other relevant clinical factors, such as tobacco and/or alcohol (T/A) consumption, on the risk and distribution of MSPN in OPSCC patients and to assess the impact of MSPN on patient survival. MATERIAL AND METHODS: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. P16 immunohistochemical expression was used as a surrogate maker of tumor HPV status. The impact of tumor p16 status on the risk of MSPN was assessed in uni- and multivariate analyses. Overall survival (OS) was determined by Kaplan-Meier analysis. RESULTS: Among the 1291 patients included in this study, 138 (10.7%) displayed a MSPN which was preferentially located in the head and neck area (H&N), lung and esophagus. Multivariate analyses showed that p16- tumor status (p = 0.003), T/A consumption (p = 0.005) and soft palate tumor site (p = 0.009) were significantly associated with a higher risk of MSPN. We found no impact of p16 tumor status on the median time between index OPSCC diagnosis and MSPN development, but a higher proportion of MSPN arising outside the H&N, lung and esophagus was found in p16 + than in p16- patients. MSPN development had an unfavorable impact (p = 0.04) on OS only in the p16 + patient group. CONCLUSION: P16 tumor status and T/A consumption were the main predictive factors of MSPN in OPSCC patients. This study provides crucial results with a view to tailoring global management and follow-up of OPSCC patients.

Outcomes after pulmonary lobectomy in patients with history of head and neck carcinoma.

BACKGROUND: We aimed to determine whether video assisted thoracic surgery (VATS) was associated with better short-term outcomes compared to open approach and to determine factors affecting long term survival after lobectomy in patients with history of head and neck carcinoma (HNC). METHODS: We performed a retrospective monocentric analysis of consecutive standard lobectomies performed for lung cancer in patients with history of HNC between 2010 and 2017. Patients' characteristics, surgical approach, lung tumor histology, in-hospital and 90-days morbi-mortality and long term survival were analyzed; VATS and open lobectomy groups were compared. RESULTS: Among 85 patients, 52 underwent an open lobectomy and 33 a VATS lobectomy. There was no significant difference between the two groups regarding age, preoperative characteristics, pathology and stage of lung cancer (All p = NS). In the VATS group, there was a significant decrease in proportion of in-hospital postoperative life-threatening complications requiring hospitalization in intensive care unit (12/52 vs. 1/33, p = 0.01). The 90-days postoperative comprehensive complication index was significantly increased in the open thoracotomy group (median (interquartile range):33.5 (0-53.5) vs. 8.7 (0-34.1), p = 0.018). Long term survival was not significantly different between the 2 groups - Log-rank test comparison, p = NS). Patients with squamous cell histology presented a significantly poorer survival (both Log-rank test comparison, p < 0.01). CONCLUSIONS: Minimally invasive approach improved in-hospital and 90-days outcomes compared to open surgery for lung cancer resection in patients with history of HNC. The poor long-term results in patients with squamous cell carcinoma highlight the need to improve therapeutic strategies for this subset of patients.