Ultrasound dye-assisted parathyroidectomy (USDAP): Experience of a tertiary center.

BACKGROUND: Primary hyperparathyroidism is primarily caused by parathyroid adenoma, followed by hyperplasia and parathyroid carcinoma. In the era of minimally invasive, targeted parathyroidectomy, the main challenge remains that of distinguishing intraoperatively pathological parathyroid from normal glands and peri-thyroid fat tissue. The aim of this study is to evaluate the surgical outcomes of a novel minimally invasive technique called ultrasound-guided dye-assisted parathyroidectomy (USDAP). METHODS: We perform a retrospective analysis of patients affected by parathyroid adenoma, treated with USDAP at our institution between 2014 and 2019. Data were collected on patient age and sex, tumor location and size, preoperative investigations, histopathology, perioperative complications and surgical outcomes. RESULTS: Between January 2014 and June 2019, 43 patients underwent parathyroidectomy in our Institute. Each case was discussed by the Institutional Multidisciplinary Board. All patients undergoing thyroidectomy together with USDAP or patients undergoing USDAP under endoscopic control were excluded from the present study. The final cohort, the largest to our knowledge, consisted of 29 patients. All patients were successfully treated with USDAP and remained disease-free during follow up. In all cases, pathological parathyroid was correctly identified and removed. There was no postoperative allergic reaction, nor were there neurotoxicity complications. USDAP permitted a shortening of operative and hospitalization time. CONCLUSIONS: USDAP is an effective and safe procedure both as first line treatment and as a re-operative procedure after previous surgical failures in selected cases.

Minimally-invasive treatments for benign thyroid nodules: a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group.

Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS ≤3) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and ≥80% nodule volume ablation is expected (LoE = 3).

From transmandibular to transoral robotic approach for parapharyngeal space tumors.

PURPOSE: Parapharyngeal space (PPS) tumors are rare, accounting for 0.5% of all head-and-neck masses. Surgery remains the standard treatment for most cases, including different approaches (cervical approach, parotidectomy, mandibulotomy, transoral/robotic). We report our experience in the management of PPS tumors, aiming to create a surgical algorithm on the base of tumor's radiological and clinical characteristics. MATERIALS AND METHODS: Critical retrospective analysis of patients with PPS neoplasms who underwent surgery at our Institute. Data were collected on patient age and sex, tumor location and size, preoperative investigations, surgical approaches, histopathology, complications and outcomes. RESULTS: Between January 2000 and July 2015, 53 patients were treated at our Institute. Salivary gland tumors were the most common neoplasms followed by neurogenic tumors. CT scan/MRI were the most used preoperative imaging studies. The cervical approach with or without parotidectomy is the most used, providing the best compromise between the need for radicality and low risk of damage to the neurovascular structures. Mandibulotomy is used whenever the mass extends to the cranial base, assuming a higher morbidity, a slower functional recovery and the need for tracheotomy. Recently, TORS has been used for tumors of the PPS with promising outcomes. CONCLUSIONS: PPS surgery includes a wide spectrum of approaches but it is still a matter of debate which one guarantees better functional and oncological outcomes. We report a surgical algorithm based on surgical invasiveness and tumor characteristics to standardize PPS tumors management. We also highlight the upcoming role of TORS in this field.

Small tongue squamous cell carcinoma with neck metastasis at diagnosis: operative insights and surgical technique.

BACKGROUND: The treatment of tongue tumors includes different surgical procedures ranging from a simple mucosal resection to complex combined resection depending on the tumor stage and size. In 2019 we reported an international glossectomy classification with the purpose of standardizing all the different types of surgical procedures adopted for tongue cancer. METHODS: The present communication aims at providing further insight into the glossectomy classification. More specifically, it is intended to better specify the indications to glossectomy type IIIA and B in selected tongue cancers, with positive cervical lymph nodes at the diagnosis. RESULTS AND CONCLUSIONS: Type IIIA glossectomy permits a high function sparing surgery in selected cases, with better postoperative functional outcomes. From an oncological perspective, it permits a radical surgery, avoiding postoperative radiation in the absence of extracapsular spread, multiple nodal metastases or T-N tract involvement.

Tongue cancer treatment and oncological outcomes: The role of glossectomy classification.

BACKGROUND: Nowadays surgery remains the gold standard of treatment for tongue cancer. Via a more clear and precise terminology, the glossectomy classification by Ansarin et al. facilitates shared communication between surgeons, allowing comparison between published research and improving surgical practice and patient care. To establish the association of glossectomies, according to their classification by Ansarin et al. with overall survival (OS), disease-free survival (DSF), and cause-specific survival (CSS) in tongue cancer, we conducted a systemic retrospective study on 300 consecutive patients affected by primary oral tongue cancer and treated with surgery at the European Institute of Oncology, IRCCS (IEO). METHODS: Three hundred patients with tongue squamous cell carcinoma and treated at the Division of Otorhinolaryngology and Head and Neck Surgery of the European Institute of Oncology, IRCCS were cataloged according to the glossectomy classification. OS, DFS, and CSS were compared by surgical treatments. RESULTS: OS-5yrs was 80% for the type I glossectomy group, 75% for type II, 65% for type III, and 35% for type IV-V. DFS-5yrs was 74%, 60%, 55%, and 27%, respectively for I, II, III, and IV-V glossectomy group; CSS-5yrs was 82%, 80%, 72%, and 48%, respectively for I, II, III, and IV-V glossectomy group (p < 0.01). CONCLUSIONS: This study confirmed that the application of the glossectomy classification was statistically correlated with patients' oncological outcomes.

Outcomes of head and neck cancer management from two cancer centres in Southern and Northern Europe during the first wave of COVID-19.

OBJECTIVE: To describe the approach and outcomes from two cancer centres in Southern and Northern Europe during the first wave of coronavirus disease 2019 (COVID-19) of patients with head and neck cancer (HNC). METHODS: Data collection was performed on a retrospective cohort of patients surgically treated for primary HNC between March and May 2020, using data from two tertiary hospitals: the European Institute of Oncology (Milan) and Guy's & St Thomas' NHS Foundation Trust (London). RESULTS: We included 77 patients with HNC. More patients with COVID-19 were taking angiotensin-converting enzyme (ACE) inhibitors and had Clavien-Dindo Classification grade I compared to negative patients, respectively (60% vs 22% [p = 0.058] and 40% vs 8% [p = 0.025]). Multivariate logistic regression analyses confirmed our data (p = 0.05 and 0.03, respectively). Sex and age were statistically significantly different (p = 0.05 and <0.001 respectively), showing more male patients (75% vs 53.66%, respectively) and more elderly patients in Italy than in the United Kingdom (patients aged >63 years: 69.44% vs 29.27%). CONCLUSIONS: This study presents a large cohort of patients with HNC with nasopharyngeal swab during the first peak of the COVID-19 pandemic in Europe. Patients with HNC with COVID-19 appeared more likely to develop postsurgical complications and to be taking ACE inhibitors. The preventive measures adopted guaranteed the continuation of therapeutic surgical intervention.

Prospective study on the dose distribution to the acoustic structures during postoperative 3D conformal radiotherapy for parotid tumors: dosimetric and audiometric aspects.

BACKGROUND AND PURPOSE: To analyze dose distribution in the hearing organ and to evaluate the dose effect on the hearing thresholds in patients treated with post-parotidectomy 3-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: A total of 17 patients received post-parotidectomy 3D-CRT (median dose: 63 Gy). The audiometric evaluation comprised pure tone audiometry and tympanometry performed before radiotherapy (RT) and 3, 6, and 24 months after RT. The ear structures were delineated on planning computer tomography scans. Mean and maximum doses were calculated and dose-volume histograms were plotted. RESULTS: Before RT, the median baseline audiometric thresholds were normal. At 3 months post-RT, 3 patients were diagnosed as having middle ear underpressure and/or effusion that resolved completely by 6 months. During 2-year follow-up, none of the ears showed perceptive hearing loss at speech frequencies. The mean doses at ipsilateral external auditory canal, mastoids cells, tympanic case, Eustachian tube, semicircular canals, and cochlea were 44.8 Gy, 39.0 Gy, 30.9 Gy, 33.0 Gy, 19.6 Gy, and 19.2 Gy, respectively. The doses to the contralateral ear were negligible, except for the Eustachian tube (up to 28.2 Gy). CONCLUSION: Post-parotidectomy 3D-CRT is associated with relatively low doses to the ear and the surrounding structures. Post-RT audiometry did not show any permanent (neither conductive nor perceptive) hearing impairment. Only in 3 patients were there signs of transient unilateral dysfunction of the Eustachian tube observed during the first few months after RT. Longer follow-up and larger patient series are warranted to confirm these preliminary findings.

Functional base of tongue fat injection in a patient with severe postradiation Dysphagia.

Lipofilling is a well-established technique in reconstructive plastic surgery. It is used primarily in recontouring of the body and face to correct post-traumatic and congenital defects. The regenerative properties of adipose tissue have allowed the use of the lipofilling technique for the treatment of burn sequelae and irradiated breast to improve tissue quality and elasticity. We report on the case of a patient treated with radiation therapy for a nasopharyngeal carcinoma who presented with severe postradiation dysphagia. The lipofilling technique was successfully used to improve abnormal swallowing. The technical details and functional outcomes are discussed.

Three-dimensional conformal postoperative radiotherapy in patients with parotid tumors: 10 years' experience at the European Institute of Oncology.

AIMS AND BACKGROUND: Salivary gland malignancies are rare. The aim of our study was to investigate radiotherapy-related toxicity and clinical outcome in patients treated at our division with postoperative radiotherapy (pRT) for parotid tumors. METHODS AND STUDY DESIGN: Forty-three consecutive patients (32 with primary parotid tumors, 9 with parotid metastases and 2 with recurrent benign diseases) were retrospectively analyzed. RESULTS: The median follow-up was 28 months. Twenty and 5 patients had a follow-up longer than 2 and 5 years, respectively. Thirty-seven patients were alive and most of them (78%) were free from disease. The local and distant control rates were higher in patients with primary parotid tumors (94% and 87.5%) than in patients with parotid metastases (87.5% and 75%). Grade 3 radiotherapy-related acute toxicity of skin and mucosa was recorded in 20.9% and 28% of patients, respectively. Two patients (4.7%) had grade 4 skin toxicity. Late toxicity data were available for 33 (77%) patients. None of the patients developed severe (grade 3 and 4) late toxicity of soft tissues, skin or temporomandibular joints. CONCLUSIONS: Postoperative radiotherapy is a feasible treatment that was found to be effective mainly in patients with primary parotid tumors. Toxicity was acceptable but could probably be further reduced using more advanced radiotherapy techniques. Longer follow-up is required to achieve definitive results.

An innovative tool for mandibular reconstruction in oral malignancies: A pictorial essay.

Mandibular reconstruction is challenging for most head and neck surgeons. Technological advances have led to the development of a new innovative procedure based on the concepts of computer-assisted design (CAD) and virtual surgical planning (VSP). The main disadvantage of this technique is the lack of flexibility, especially in oncology. A possible solution is the development of a semi-standardized mandible and fibula resection cutting guide: the L1® mandible ReconGuide. We provided a step-by-step description of the operative technique for mandibular reconstruction with the L1® mandible ReconGuide. The L1® mandible ReconGuide is a guiding force toward mandibular reconstruction. Moreover, the tool has been designed to suit the needs of the patients, particularly those with oral cancer, thereby permitting intraoperative planning and increasing time and cost effectiveness. In this pictorial essay, we have presented the operative techniques of using the L1® mandible ReconGuide for reconstruction.

Oral cancer: changing the aim of the biopsy in the age of precision medicine. A review.

Oral cancer is a heterogeneous disease that develops through a complex, multi-step process. Precision medicine should help to better understand its molecular basis, integrate traditional classifications and have a positive impact on cancer management. To apply this information in clinical practice, we need to define its histology and identify biomarkers expressed by the tumour that provide useful information for planning tailored treatment. The most reliable information currently derives from evaluation of biomarkers on post-operative samples. To plan personalised treatment, oncologists need to assess these markers on biopsy samples. We reviewed the recent literature and identified 6 of 184 publications that compared markers measured on biopsy and post-operative samples or assessed their predictivity for the development of lymph node metastases. Data from these studies suggest that markers measured on biopsy samples can provide useful indications for tailoring treatments. However, due to their heterogeneity and low level of evidence, these results need to be confirmed by clinical studies on a large population to standardise and validate biomarkers in biopsies and to assess their reliability in other diagnostic mini-invasive procedures such as radiomics and liquid biopsy.^ieng

Il cancro orale è una malattia eterogenea che origina ed evolve con un processo complesso e multifasico. La medicina di precisione permette di pianificare un trattamento personalizzato sulla base delle caratteristiche biologiche e molecolari delle singole neoplasie. Le informazioni oggi più affidabili sono fornite dalla valutazione post-operatoria dei biomarcatori, ma per pianificare un trattamento personalizzato è necessario valutare questi marcatori sulla biopsia. Per questo abbiamo rivisto la letteratura dell'ultimo quinquennio ed abbiamo identificato 6/184 articoli che valutano i marcatori sulla biopsia confrontandone i valori con quelli misurati sul pezzo operatorio di ciascun paziente o valutandone la predittività per lo sviluppo di metastasi linfonodali. I dati che emergono da questi studi suggeriscono che la valutazione dei marcatori sul campione bioptico potrebbe fornire indicazioni utili per programmare trattamenti personalizzati. Tuttavia, a causa della eterogeneità e del basso livello di evidenza dei lavori considerati, questi risultati devono essere confermati da studi clinici su un'ampia popolazione per standardizzare e validare i biomarcatori e la loro affidabilità in altre procedure mini-invasive, ad esempio radiomica e biopsia liquida.

Prevalence of Central Compartment Lymph Node Metastases in Papillary Thyroid Micro-Carcinoma: A Retrospective Evaluation of Predictive Preoperative Features.

Papillary thyroid micro-carcinomas are considered relatively indolent carcinomas, often occult and incidental, with good prognosis and favorable outcomes. Despite these findings, central lymph node metastases are common, and are related to a poor prognosis for the patient. We performed a retrospective analysis on patients treated with surgery for stage pT1a papillary thyroid micro-carcinomas. One hundred ninety-five patients were included in the analyses. The presence of central lymph node metastases was identified and studied. A multivariate analysis employing binary logistic regression was used to calculate adjusted odds ratios with 95% confidence intervals of possible central lymph node metastases risk factors. In the performed multivariate analysis, male gender, younger age, and histopathological characteristics, such as a tumor sub-capsular localization, were significantly associated with central lymph node metastases in pT1a patients. Central compartment lymph node metastases are present in a non-negligible number of cases in patients with papillary thyroid micro-carcinoma undergoing surgical resection. Studying these factors could be an effective tool for predicting patients' central lymph node metastases in papillary thyroid micro-carcinomas, defining a tailored surgical treatment in the future.

Survival Outcomes in Oral Tongue Cancer: A Mono-Institutional Experience Focusing on Age.

OBJECTIVE: The prognostic role of age among patients affected by Oral Tongue Squamous Cell Carcinoma (OTSCC) is a topic of debate. Recent cohort studies have found that patients diagnosed at 40 years of age or younger have a better prognosis. The aim of this cohort study was to clarify whether age is an independent prognostic factor and discuss heterogeneity of outcomes by stage and treatments in different age groups. METHODS: We performed a study on 577 consecutive patients affected by primary tongue cancer and treated with surgery and adjuvant therapy according to stage, at European Institute of Oncology, IRCCS. Patients with age at diagnosis below 40 years totaled 109 (19%). Overall survival (OS), disease-free survival (DFS), tongue specific free survival (TSFS) and cause-specific survival (CSS) were compared by age groups. Multivariate Cox proportional hazards models were used to assess the independent role of age. RESULTS: The median follow-up time was 5.01 years (range 0-18.68) years with follow-up recorded up to February 2020. After adjustment for all the significant confounding and prognostic factors, age remained independently associated with OS and DSF (respectively, p = 0.002 and p = 0.02). In CSS and TSFS curves, the role of age seems less evident (respectively, p = 0.14 and p = 0.0.37). In the advanced stage sub-group (stages III-IV), age was significantly associated with OS and CSS with almost double increased risk of dying (OS) and dying from tongue cancer (CSS) in elderly compared to younger groups (OS: HR = 2.16 95%, CI: 1.33-3.51, p= 0.001; CSS: HR = 1.76 95%, CI: 1.03-3.01, p = 0.02, respectively). In our study, young patients were more likely to be treated with intensified therapies (glossectomies types III-V and adjuvant radio-chemotherapy). Age was found as a prognostic factor, independently of other significant factors and treatment. Also the T-N tract involved by disease and neutrophil-to-lymphocyte ratio ≥3 were independent prognostic factors. CONCLUSIONS: Young age at diagnosis is associated with a better overall survival. Fewer younger people than older people died from tongue cancer in advanced stages.

Image-Guided Thermal Ablation as an Alternative to Surgery for Papillary Thyroid Microcarcinoma: Preliminary Results of an Italian Experience.

Purpose: To report the results of our preliminary experience in treating patients with papillary thyroid microcarcinoma (PTMC) with image-guided thermal ablation, in particular estimating the feasibility, safety and short-term efficacy. Materials and Methods: From 2018 patients with cytologically proven PTMC < 10 mm were discussed in a multidisciplinary team and evaluated for feasibility of image-guided thermal ablation. In case of technical feasibility, the three possible alternatives (i.e., image-guided thermal ablation, surgery, and active surveillance) were discussed with patients. Patients who agreed to be treated with image guided thermal ablation underwent radiofrequency (RFA) or laser ablation under local anesthesia and conscious sedation. Treatment feasibility, technical success, technique efficacy, change in thyroid function tests, side effects, minor and major complications, patients satisfaction and pain/discomfort perception during and after treatment, and disease recurrence during follow-up were recorded. Results: A total of 13 patients were evaluated, and 11/13 (84.6%) patients (9 female, 2 male, mean age 49.3 ± 8.7 years) resulted suitable for image-guided thermal ablation. All 11 patients agreed to be treated with image-guided thermal ablation. In addition, 3/11 (27.3%) were treated with laser ablation and 8/11 (72.7%) with RFA. All procedures were completed as preoperatively planned (technical success 100%). Technique efficacy was achieved in all 11/11 (100%) cases. Ablated volume significantly reduced from 0.87 ± 0.67 ml at first follow-up to 0.17 ± 0.36 at last follow-up (p = 0.003). No change in thyroid function tests occurred. No minor or major complications occurred. All patients graded 10 the satisfaction for the treatment, and mean pain after the procedure was reported as 1.4 ± 1.7, and mean pain after the procedure as 1.2 ± 1.1 At a median follow-up of 10.2 months (range 1.5-12 months), no local recurrence or distant metastases were found. Conclusions: Image guided thermal ablations appear to be feasible and safe in the treatment of PTMC. These techniques hold the potential to offer patients a minimally invasive curative alternative to surgical resection or active surveillance. These techniques appear to be largely preferred by patients.

Perfusion computed tomography for monitoring induction chemotherapy in patients with squamous cell carcinoma of the upper aerodigestive tract: correlation between changes in tumor perfusion and tumor volume.

OBJECTIVE: The aim of this study was to assess the potential of perfusion computed tomography (CTp) for monitoring induction chemotherapy in patients with squamous cell carcinoma (SCCA) of the upper aerodigestive tract. MATERIALS AND METHODS: Twenty-five patients with advanced SCCA underwent CTp and volumetric CT before and after induction chemotherapy. Perfusion CT parameters were calculated in the tumor, normal tissue, and muscles and correlated with tumor volume. RESULTS: The blood flow (BF), blood volume (BV), and permeability surface were significantly higher, and the mean transit time was significantly lower in the tumor than in the normal tissue. The tumor BF and BV significantly decreased, and the mean transit time significantly increased after the therapy; decrease in BF and BV correlated with tumor volume reduction after chemotherapy. The baseline tumor BV was significantly lower in nonresponders compared with that in responders. CONCLUSIONS: In patients with SCCA, CTp showed potential for monitoring induction chemotherapy, reduction in tumor BF and BV correlated with reduction of tumor volume after chemotherapy, and baseline tumor BV may predict response to chemotherapy.

Classification of GLOSSECTOMIES: Proposal for tongue cancer resections.

BACKGROUND: Surgery of tongue tumors includes different procedures ranging from mucosal resection to complex combined resection. Numerous terms have been used to describe such procedures, but there is no consensus between the terminology and the extent of resection. METHODS AND RESULTS: We searched the medical literature and found a lack of published information. We undertook to describe a new classification of surgical procedures for tongue tumor resection. We based it upon the surgical anatomy of the tongue and the spread of the cancer. We posited that there were five major types of glossectomy embracing all the methods of tongue cancer resection. This classification was reviewed and endorsed by an international team of experts. CONCLUSION: We propose a more precise classification than that currently in practice, thereby bringing clarity and consistency to the terminology, facilitating shared communication between surgeons, comparison between published research, and ultimately improving surgical practice and patient care.

The role of the T-N tract in advanced stage tongue cancer.

BACKGROUND: We investigated the role of the soft tissue tract between the primary tumor and the neck lymph nodes, the "T-N tract," in patients with tongue squamous cell carcinoma at an advanced stage. METHODS: We performed a compartmental tongue surgery in 233 patients. Cumulative incidence of relapses and overall survival curves were compared by T-N tract involvement. Multivariate Cox proportional hazards models were used to assess the independent role of T-N tract. RESULTS: At 4 years of follow-up, patients with disease in the T-N tract experienced a significantly more distant recurrence (40%) than did patients without T-N tract involvement (22%; P = .02). Multivariate Cox models indicate a significant almost triple risk of distant metastases (hazard ratio [HR], 2.70; 95% CI, 1.01-7.19; P = .05) and double risk of death (HR, 2.09; 95%CI, 1.13-3.85; P = .02) in patients with "T-N tract involvement." CONCLUSIONS: Our data show that the T-N tract plays an important role in prognosis and survival in patients with tongue cancer.

Role of EGFR as prognostic factor in head and neck cancer patients treated with surgery and postoperative radiotherapy: proposal of a new approach behind the EGFR overexpression.

In an era of personalized treatment, there is a great interest in identifying factors which might predict patient response to radiotherapy (RT). The role of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) remains still controversial. We performed a retrospective analysis on the prognostic value of EGFR in HNSCC patients treated with surgery and postoperative RT through a semiquantitative immunohistochemical analysis of EGFR membrane expression. We retrospectively analyzed 65 HNSCC patients treated in our Institute from 1997 to 2003 who underwent adjuvant RT after surgery. Median follow-up was 43.5 months (range 0.2-173 months). None of these patients were treated with postoperative concomitant chemotherapy. Tumor samples were obtained from surgical specimens. Membrane features (intensity, extension) of EGFR expression were evaluated, and a statistical analysis (univariate and multivariate) was conducted to correlate these parameters with overall survival (OS) and disease-free survival (DFS). Patients with an intense and complete labeling of EGFR presented worse OS and DFS compared with groups obtained by all other possible combination, and the difference was borderline statistically significant (P = 0.08 for OS and P = 0.006 for DFS). Moreover, a stratification of patients was performed considering EGFR expression on the tumor tissue and classifying its distribution as "homogeneous" or "heterogeneous." We found that patients showing an "heterogeneous" EGFR expression distribution had worse OS and DFS compared to the "homogeneous" group of patients. Based on our results, EGFR expression, especially referring to membrane features (semiquantitative analysis), might have a prognostic value for OS and DFS in locally advanced HNSCC treated with surgery and adjuvant RT. Prospective trials could be useful to confirm the prognostic role of EGFR expression and also to assess a predictive role to select that might benefit from more aggressive treatments.