Alfio Ferlito’s research while affiliated with University of Udine and other places

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Publications (739)


Republication de : Deciding whether to do elective neck dissection in patients with salivary gland tumors with no evidence of neck lymph node metastasis
  • Article

June 2025

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17 Reads

Annales françaises d Oto-rhino-laryngologie et de Pathologie Cervico-faciale

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A. Ferlito

When Neck Dissection is Not Indicated in the Treatment of the Clinically Node-Negative Head and Neck Squamous Cell Carcinoma
  • Article
  • Full-text available

May 2025

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21 Reads

Oncology and Therapy

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The Limitations of Artificial Intelligence in Head and Neck Oncology

Advances in Therapy

Artificial intelligence (AI) is revolutionizing head and neck oncology, offering innovations in tumor detection, treatment planning, and patient management. However, its integration into clinical practice is hindered by several limitations. These include clinician mistrust due to a lack of understanding of AI mechanisms, biases in algorithm development, and the potential over-reliance on technology, which may undermine clinical expertise. Data-related challenges, such as inconsistent quality and limited representativeness of datasets, further complicate AI’s application. Ethical, legal, and privacy concerns also pose significant barriers. Addressing these issues through transparent AI systems, clinician education, and clear regulations is essential for ensuring responsible, equitable use in head and neck oncology. This manuscript explores the limitations of AI in head and neck oncology.


Older Patients with Head and Neck Cancer: A Scoping Review of Differences Regarding Diagnosis and Outcomes

April 2025

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66 Reads

Head & Neck

Background Understanding the relationship between age and diagnostic challenges, as well as outcomes in older patients with head and neck cancer, is crucial. The significance of age as a prognostic factor and how it should influence treatment decisions is debated, highlighting the need for tailored insights to help physicians make more informed choices. Objective This scoping review aims to address the diagnostic challenges/differences and patient outcomes as infection, pain, treatment‐related complications (either postmedical or postoperative), treatment toxicities, disease control, morbidity, and/or survival/mortality in older patients (above the cut‐off age of 60 years) with head and neck cancer. Methods PubMed, Embase, Scopus, Web of Science, and LILACS were searched, as well as gray literature and reference lists of included articles. Results A total of 5029 articles were retrieved and 57 studies were included, among which 5 appraised evidence on diagnostic challenges/differences, 53 addressed clinical (as postoperative complications, the impact of comorbidities in the occurrence of complications and treatment, postoperative delirium, swallowing outcomes, the correlation between age and infections, pain and opioid use, morbidity rates, treatment‐related toxicities), and 26 reported survival. Evidence on diagnostic challenges and outcomes between older and younger patients is mixed, but age, comorbidities, and complications must be considered. While many studies show no significant differences in complications according to age, comorbidities often correlate with worse outcomes and are more frequent in the older group. Despite variable age cut‐offs, survival rates between older and younger patients are similar. Conclusion Treatment decisions should be based on a thorough medical evaluation and patient preferences rather than chronological age alone, as age itself does not account for outcome differences.



Verrucous carcinoma: projections and invaginations of well-differentiated squamous epithelium with marked surface keratinisation, invading the subjacent stroma with well-defined pushing border
Basaloid squamous cell carcinoma: closely packed basaloid cells, with hyperchromatic nuclei and scant cytoplasm, with a lobular configuration
Papillary squamous cell carcinoma: exophytic growth, composed of papillae covered by atypical squamous epithelium, without invasion
Spindle cell carcinoma: biphasic tumour, composed of islands of squamous cell carcinoma and malignant spindle cells
Adenosquamous carcinoma: biphasic tumour, composed of squamous cell carcinoma and adenocarcinoma in close proximity, but separate and distinct

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The impact of histopathology on prognosis of squamous cell carcinoma of the larynx: can we do better?

Virchows Archiv

Despite decades of progress, laryngeal squamous cell carcinoma (SCC) is still associated with significant morbidity and mortality worldwide. Additional biomarkers are needed to apply precision medicine and predict the clinical course. We reviewed and summarised routinely reported histopathologic features (e.g. subtypes of laryngeal SCC) along with promising potential biomarkers not yet routinely assessed using international guidelines. These include extra- vs intratumoural vascular and perineural invasion, tumour budding, depth of invasion, and tumour-infiltrating lymphocytes. We also address the problem of specimen quality and type (open approach vs endoscopic surgery) and the related limitations. High-risk human papillomavirus infection is another controversial issue to be discussed, being rare in laryngeal SCC, with an indeterminate prognostic significance and less reliable p16 overexpression as a surrogate marker of HPV infection. Further studies are warranted to address the applicability and to see which of the described parameters may help to better stratify patients with laryngeal SCC and should therefore be included in the pathology report.


PRISMA flow diagram.
Risk of bias [12,13,14,15,16,17,18]: (A) graph; (B) summary.
Three-year OS forest plot [12,13,14,15,17] (A), three-year OS L’Abbé plot [12,13,14,15,17] (B), three-year OS funnel plot [12,13,14,15,17] (C), five-year OS forest plot [12,15,17] (D), five-year OS L’Abbé plot [12,15,17] (E), five-year OS funnel plot [12,15,17] (F).
Three-year DFS forest plot [12,15,16,17,18] (A), three-year DFS L’Abbé plot [12,15,16,17,18] (B), three-year DFS funnel plot [12,15,16,17,18] (C), five-year DFS forest plot [12,15,16,17,18] (D), five-year DFS L’Abbé plot [12,15,16,17,18] (E), five-year DFS funnel plot [12,15,16,17,18] (F).
Three-year LC forest plot [13,18] (A), three-year LC L’Abbé plot [13,18] (B), three-year LC funnel plot (C).
The Oncological Outcome of Postoperative Radiotherapy in Patients with Node-Negative Early-Stage (T1/T2/N0) Oral Squamous Cell Carcinoma and Perineural Invasion: A Meta-Analysis

Objective: To evaluate the impact of postoperative radiotherapy (PORT) on oncological outcomes in node-negative early-stage oral squamous cell carcinoma (OSCC) with perineural invasion (PNI). Methods: A systematic review and meta-analysis was conducted using the PubMed, EMBASE, and Scopus databases for the period from 2000 to 2024. Studies comparing PORT versus observation in pN0 early-stage OSCC with PNI were included. Oncological outcomes assessed included overall survival (OS), disease-free survival (DFS), and local control (LC). A random-effects model was used to calculate log odds ratios, and heterogeneity was assessed using tau², chi², and I² statistics. Results: Seven retrospective studies comprising 522 patients (281 PORT, 241 no-PORT) were included. The 3-year overall survival (OS) was 86.3% in the PORT group compared to 71.1% in the no-PORT group (logOR = −1.03, p = 0.0012), while the 5-year OS was 88.1% versus 77.3% (logOR = −0.97, p = 0.0061). Disease-free survival (DFS) also favored PORT, with 3-year DFS at 86.3% versus 58.1% (logOR = −1.19, p < 0.001) and 5-year DFS at 86.3% versus 55% (logOR = −0.78, p = 0.003). Local control (LC) was higher in the PORT group, with 3-year LC rates of 89% compared to 72.2% in the no-PORT group (logOR = −1.13, p = 0.025). Conclusions: PORT significantly improves OS, DFS, and LC in node-negative early-stage OSCC with PNI as the sole adverse feature.


Evidence Based Recommendations in Sinonasal Tumors Involving Orbit: Preservation or Exenteration? An IHNSG Guidelines

February 2025

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185 Reads

Advances in Therapy

Sinonasal tumors with orbital involvement present significant management challenges due to the complex anatomy of the orbital and sinonasal complex and the potential for severe tumor-and treatment-related morbidities. This comprehensive review examines evidence-based decision-making guidelines in the context of treating sinonasal malignancies involving the orbit. We evaluate pre-treatment assessment strategies, discuss the indications for orbital preservation versus its exenteration, explore Adv Ther the role of neo-adjuvant therapies, and analyze reconstruction techniques with ensuing rehabilitation approaches and quality of life. Our review underscores the need for a patient-centered multidisciplinary approach that optimizes treatment outcomes and quality of life for patients suffering from such advanced sinonasal malignancies with orbital involvement.



Post/Long COVID symptoms that should lead to a referral to an otorhinolaryngologist and treatment options.
International and national clinical guidelines screened for Post/Long COVID-related oto- rhinolaryngological symptoms.
Post COVID-19 and Long COVID Symptoms in Otorhinolaryngology—A Narrative Review

January 2025

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83 Reads

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1 Citation

Post/Long COVID (syndrome) is defined as a condition with symptoms persisting for more than 12 weeks after the onset of SARS-CoV-2 infection that cannot be explained otherwise. The prevalence of self-reported otorhinolaryngological Post/Long COVID symptoms is high. The aim of this review was to analyze the current literature regarding the actual prevalence, knowledge of the etiopathology, and evidence-based treatment recommendations of otorhinolaryngology-related Post/Long COVID symptoms. A systematic literature search of articles published since 2019 in PubMed and ScienceDirect was performed and resulted in 108 articles. These were the basis for this review and formed a comprehensive series of consented therapy statements on the most important of otorhinolaryngology-related Post/Long COVID symptoms. Otorhinolaryngological symptoms did not appear isolated but as part of a multi-organ syndrome. Self-reported otorhinolaryngology-related Post/Long COVID symptoms were often not confirmed by objective testing. The confirmed prevalence estimated for anosmia, dysgeusia, cough, facial palsy, hoarseness/dysphonia, acute hearing loss, tinnitus, and vertigo/dizziness was about 4%, 2%, 4–19%, 0%, 17–20%, 8%, 20%, and 5–26%, respectively. There are manifold theoretical concepts of the etiopathology of different symptoms, but there is no clear evidence-based proof. This certainly contributes to the fact that there is no effective specific treatment option for any of the symptoms mentioned. Healthcare pathways must be established so that otorhinolaryngological Post/Long COVID symptoms can be recognized and evaluated and otorhinolaryngologists can provide counseling. This would also help to establish and selectively include patients in clinical trials investigating specific therapeutic concepts.


Citations (76)


... I n patients with head and neck cancer (HNC), mental health disorders (MHDs) are highly prevalent and may influence postoperative outcomes. [1][2][3] Studies have reported up to 40% of HNC patients are affected by MHDs, most commonly major depressive disorder (MDD). [4][5][6] This may even be an underestimate, as a recent study using patient-reported surveys found that one in five patients with HNC has an undiagnosed MHD preoperatively. ...

Reference:

Mental Health Disorders and Pain in Patients Undergoing Head and Neck Free Flap Surgery
Psychological Factors Related to Treatment Outcomes in Head and Neck Cancer

Advances in Therapy

... Treatment modalities for LSCC include surgery, radiation therapy, chemotherapy, targeted therapy for specific genetic mutations, and immunotherapy. However, outcomes remain suboptimal, and LSCC continues to pose a substantial public health challenge [5]. Therefore, understanding the characteristics of LSCC is crucial for the comprehensive prevention and control of laryngeal cancer. ...

Treatment of the neck in residual/recurrent disease after chemoradiotherapy for advanced primary laryngeal cancer
  • Citing Article
  • May 2024

European Journal of Surgical Oncology

... The principle of "as low as reasonably achievable" (ALARA) is a fundamental tenet of radiation safety, and precision RT techniques typically reduce OAR doses. While some recent prospective work, especially in adaptive and MR-guided RT, has been confounded by the simultaneous deployment of adaptive techniques and target volume margin reduction, other studies of adaptive replanning, especially in the head and neck, have confirmed the ability of this technique to reduce the dose to the parotid glands and other critical structures [11][12][13]. Proton therapy can also substantially improve dose distribution in OARs near the target [14]. However, OAR dosing faces the same problem as tumor dosing: in most instances, the tolerance of OARs is not sufficiently well established to support the conjecture that modest reductions in specific dose metrics to OARs offered by advanced techniques will meaningfully decrease toxicity. ...

Adaptive radiotherapy for head and neck cancer: Pitfalls and possibilities from the radiation oncologist's point of view

... Oral squamous cell carcinoma (OSCC) is a significant health concern and ranks among the most common cancers worldwide [1]. According to the latest GLOBOCAN data, approximately 370,000 new cases of OSCC are diagnosed yearly [2]. ...

Primary Management of Operable Locally Advanced Oral Cavity Squamous Cell Carcinoma: Current Concepts and Strategies

Advances in Therapy

... it is also important in terms of prognosis and therapy [3]. SCC accounts for more than 90% of all malignant tumours, making it both the most significant and frequent malignant mucosal tumour to affect the head and neck [4]. ...

Metastatic cutaneous squamous cell carcinoma accounts for nearly all squamous cell carcinomas of the parotid gland

Virchows Archiv

... It is predominantly characterized by headache, insomnia, and emotional disorders, and REP usually occurs in the temporal lobe (2). The average crude incidence of temporal lobe necrosis in particular in the REP is approximately 14% (3). Although brain metastasis of nasopharyngeal carcinoma is the rarest mode of metastasis, both metastasis and recurrence are the most common causes of death in these patients (4). ...

Dosimetric parameters predict radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma patients: A systematic review and meta-analysis
  • Citing Article
  • March 2024

Radiotherapy and Oncology

... Tumors of the nasal cavity and paranasal sinuses are rare (account for 1-3% of malignant tumors of all localizations) and heterogeneous neoplasms that characterized by multifactorial etiology, including genetic predisposition (association with HLA-B17, HLA-Bw26), environmental factors and chronic viral infection (human papillomavirus, Epstein-Barr virus, etc.) [1,2,3]. Although tumors of nasal cavity and paranasal sinuses are presented with different histological features and clinical behavior, squamous cell carcinoma accounts for 90% of head and neck cancer [4]. ...

Molecularly defined sinonasal malignancies: an overview with focus on the current WHO classification and recently described provisional entities

Virchows Archiv

... The participants and patients remain anonymous, and all data are depersonalized to ensure that no patient's identity is revealed throughout the analysis. Informed consent is sought from the respective collegiate institutional review boards and the work conforms to the principles of researching people (Cohen et al., 2024) (Karcioglu et al., 2023). ...

Initial surgical management of sporadic medullary thyroid cancer: Guidelines based optimal care - A systematic review
  • Citing Article
  • March 2024

Clinical Endocrinology

... The treatment of H&N cancer remains one of the most challenging in RT for various reasons: the high prescription doses required for tumor control [9,10]; the intricate anatomy of the H&N district, with critical structures often in close proximity to target volumes and so irradiated with doses close to tolerance, thus requiring individual prescriptions to balance between the risk of complications and of local recurrence [10][11][12]; the high risk of malnutrition and weight loss during the treatment course [13]. Modern RT techniques reduced the risk of severe normal tissue toxicities, such as dysphagia, xerostomia or neurological complications [12,14,15], thus improving patients' quality of life. ...

Neurological complications of modern radiotherapy for head and neck cancer
  • Citing Article
  • March 2024

Radiotherapy and Oncology