Submandibular gland involvement in oral cavity squamous cell carcinoma: a retrospective multicenter study.

BACKGROUND: The submandibular gland (SMG) is routinely excised during neck dissection. Given the importance of the SMG in saliva production, it is important to understand its involvement rate by cancer tissue and the feasibility of its preservation. METHODS: Retrospective data were collected from five academic centers in Europe. The study involved adult patients affected by primary oral cavity carcinoma (OCC) undergoing tumor excision and neck dissection. The main outcome analyzed was the SMG involvement rate. A systematic review and a meta-analysis were also conducted to provide an updated synthesis of the topic. RESULTS: A total of 642 patients were enrolled. The SMG involvement rate was 12/642 (1.9%; 95% CI 1.0-3.2) when considered per patient, and 12/852 (1.4%; 95% CI 0.6-2.1) when considered per gland. All the glands involved were ipsilateral to the tumor. Statistical analysis showed that predictive factors for gland invasion were: advanced pT status, advanced nodal involvement, presence of extracapsular spread and perivascular invasion. The involvement of level I lymph nodes was associated with gland invasion in 9 out of 12 cases. pN0 cases were correlated with a reduced risk of SMG involvement. The review of the literature and the meta-analysis confirmed the rare involvement of the SMG: on the 4458 patients and 5037 glands analyzed, the involvement rate was 1.8% (99% CI 1.1-2.7) and 1.6% (99% CI 1.0-2.4), respectively. CONCLUSIONS: The incidence of SMG involvement in primary OCC is rare. Therefore, exploring gland preservation as an option in selected cases would be reasonable. Future prospective studies are needed to investigate the oncological safety and the real impact on quality of life of SMG preservation.

Lymphoepithelial carcinoma of larynx and hypopharynx: a systematic review and pooled analysis.

PURPOSE: To define the oncologic outcomes and the prognostic factors of laryngeal and hypopharyngeal lymphoepithelial carcinoma (LEC). METHODS: A systematic review and individual patient data analysis were performed according to the PRISMA guidelines. A total of 41 patients (males: 37; mean age: 63.1, standard deviation: 10.0) were included. RESULTS: The median follow-up time was 36.0 months (interquartile range, IQR: 11.5-73.5), while the median overall survival (OS) time was 96 months (IQR: 39.0-120.0). Estimated disease-specific survival (DSS) rates (95% Confidence Interval, CI; number still at risk) at 1, 3, and 5 years were 94.4% (79.5-98.6; 31), 82.7% (62.7-92.5; 21), and 78.1% (56.8-89.7; 13), respectively. Estimated disease-free survival (DFS) rates (95% CI; number still at risk) at 1, 3, and 5 years were 92.1% (77.4-97.4; 31), 74.9% (55.6-86.8; 21), and 66.6% (46.1-80.8; 13), respectively. Patients undergoing primary surgery had a reduced chance of death from cancer than patients receiving primary radiotherapy (5-year DSS 85.6 vs. 56.2%; p = 0.04), while EBV positivity tend to be a negative prognostic factor (5-year DSS 100 vs. 66.7%; p = 0.05). CONCLUSIONS: Laryngeal and hypopharyngeal LEC is a rare disease with favorable survival. Further prospective multicenter studies are needed to make a reliable statement on prognosis and outcome, stratifying patients for different therapy regimens and tumor stages.

Acinic cell carcinoma of the parotid gland: Timeo Danaos et dona ferentes? A multicenter retrospective analysis focusing on survival outcome.

OBJECTIVES: To analyze the demographic data, surgical and adjuvant treatment data and the survival outcomes in adult patients affected by acinic cell carcinoma of the parotid gland (AciCC). METHODS: A retrospective multicenter analysis of patients treated for AciCC of the parotid gland from 2000 to 2021 was performed. Exclusion criteria were pediatric (0-18 years) patients, the absence of follow-up and patients with secondary metastatic disease to the parotid gland. Multivariable logistic regression was used to determine factors associated with survival. RESULTS: The study included 81 adult patients with AciCC of the parotid gland. The median age was 46.3 years (SD 15.81, range 19-84 years), with a gender female prevalence (F = 48, M = 33). The mean follow-up was 77.7 months (min 4-max 361, SD 72.46). The 5 years overall survival (OS) was 97.5%. The 5 years disease-free survival (DFS) was 60%. No statistical differences have been found in prognosis for age (< 65 or ≥ 65 years), sex, surgery type (superficial vs profound parotid surgery), radicality (R0 vs R1 + Rclose), neck dissection, early pathologic T and N stages and adjuvant therapy (p > 0.05). CONCLUSION: This study did not find prognostic factor for poorest outcome. In contrast with the existing literature, our results showed how also high-grade tumours cannot be considered predictive of recurrence or aggressive behaviour.

Sarcomatoid larynx carcinoma differential clinical evolution, on field statistical considerations.

Spindle cell larynx carcinoma (SpCC) represents around 3% of laryngeal cancers. It is originated by a single cancer stem cell undergoing epithelial to mesenchymal transition. This explains the aggressiveness, the peculiar resistance to conventional therapy and the frequent relapses. We focused on this particular cancer subset characteristics in patients, in early and advanced stages primarily aiming to define and highlight the differences with Laryngeal Squamous Cell Carcinoma (LSCC) focusing on clinical features, treatments, follow-up and survival in a patient's cohort composed by comparable cases from two subgroups.

Transoral robotic surgery and intensity-modulated radiotherapy in the treatment of the oropharyngeal carcinoma: a systematic review and meta-analysis.

PURPOSE: To perform a meta-analysis evaluating trans-oral robotic surgery (TORS), and intensity-modulated radiation therapy (IMRT) in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). METHODS: This study adhered to the PRISMA guidelines. RESULTS: A total of 5624 patients (IMRT, n = 4322; TORS, n = 1302) were included in this meta-analysis. The majority of patients in the IMRT cohort were treated with concurrent CT (n = 3433, 81.3%). On the other hand, the majority of patients in the TORS cohort was treated with an adjuvant treatment (n = 826, 67.8%). IMRT subgroup showed a cumulative survival rate of 83.6% (99% CI 76.9-89.3%), while it was 91.3% (99% CI 81.2-97.8%) in the TORS subgroup. Disease-free survival was significantly different between IMRT (79.6%, 99% CI 70.6-87.3%), and TORS (89.4%, 99% CI 82.7-94.5%). IMRT subgroup showed a feeding tube dependence rate of 4.0% (99% CI 1.1-8.4%), but it was not significantly different from the TORS subgroup (1.3%, 99% CI 0-4.9%). Tracheostomy dependence rates were similar among the two subgroups (IMRT, 0.7%, 99% CI 0-1.1%; TORS, 0.2%, 99% CI 0-1.1%). CONCLUSIONS: TORS appears to be a consolidated effective surgical approach in the management of OPSCC, according to both oncologic and functional outcomes. Further RCTs comparing TORS and IMRT with homogeneous cohorts in terms of tumor staging and HPV status are advisable.

Open partial horizontal laryngectomy and adjuvant (chemo)radiotherapy for laryngeal squamous cell carcinoma: results from a multicenter Italian experience.

PURPOSE: To evaluate the functional and oncologic outcomes of adjuvant (chemo)radiation [(C)RT] after open partial horizontal laryngectomies (OPHLs). METHODS: Multicenter retrospective evaluation of 130 patients (116 males, 14 females) submitted between 1995 and 2017 to OPHL Types II and III for laryngeal cancer and receiving adjuvant (C)RT for one or more of the following risk factors at histopathologic examination of the surgical specimen: pT4a and/or > pN2a categories, close/positive resection margins, or presence of both perineural (PNI) and lympho-vascular invasion (LVI). The primary study endpoints were evaluation of the presence of tracheostomy and/or gastrostomy at last follow-up, and calculation of laryngo-esophageal dysfunction-free survival (LEDFS). RESULTS: Mean age of the study cohort was 60.8 ± 8.9 years (median, 62; interquartile range [IQR], 13). Mean follow-up was 50.7 ± 39.4 months (range 24-188; median, 38; IQR, 51). Adjuvant therapy consisted of CRT in 53 (41%) patients, and RT alone in 77 (59%). Five-year LEDFS was 85%. Overall survival was 71.5%, while 13% of patients remained tracheostomy- and 3% gastrostomy-dependent at the last follow-up. The only significant variable in predicting survival (p = 0.020) was tracheostomy dependence: it was maintained in 7.5% of subjects after OPHL Type II and in 34% of those submitted to OHPL Type III (p < 0.001). CONCLUSIONS: In selected patients affected by advanced laryngeal cancer, OPHLs Type II and III have a relatively good laryngeal safety profile and provide favorable oncologic outcomes even in case of need for adjuvant (C)RT.

Preliminary Functional Outcomes and Quality of Life after Tongue Reconstruction with the Vastus Lateralis Myofascial Free Flap.

The aim of the present study is to report our preliminary experience with the vastus lateralis myofascial free flap (VLMFF) for tongue reconstruction according to tongue and donor site functional outcomes. Twelve consecutive patients (F: 5; median age: 54.0 years, interquartile range or IQR 42.75-69.0) were included. The validated European Organization for Research and Treatment of Cancer of the Head and Neck 35 Quality of Life Questionnaire (EORTC QLQ-H&N35) and the performance status scale for head and neck cancer (PSS-HN) questionnaires were used to assess the health-related quality of life (HRQOL). The lower extremity functional scale (LEFS) was used to self-report the donor area function. All patients were successfully treated, and no VLMFF failure was detected during a median follow-up period of 10.5 months (IQR: 6.5-33.0). The HRQOL showed a median EORTC QLQ-H&N35 score of 56.0 (IQR: 50.0-72.5). The median PSS-HN score was 80.0 (IQR: 45.0-95.0), 75.0 (IQR: 62.5-100.0), 75.0 (IQR: 62.5-100.0) for "Normalcy of Diet," "Public Eating," and "Understandability of Speech," respectively. The self-reported function of the lower extremities (donor area) showed a median LEFS of 59.0 (IQR: 32.5-74.0). This study reports optimistic data regarding the functional and quality of life outcomes after tongue reconstruction using VLMFF. Prospective controlled studies are needed to demonstrate advantages and disadvantages when compared with other reconstructive techniques.

Surgeons reaching satisfying outcomes without surgery: nasal dorsum skin cancer recurrence treated with electrochemotherapy.

Cutaneous squamous cell carcinoma of the head and neck district are generally treated with surgery. Surgery is the standard treatment in early stages and local advanced tumors, followed by adjuvant therapy, radiation or concurrent chemoradiation therapy. Local recurrence treatment depends on previous therapies, though radical surgery is often the first choice at the expense of anatomy preservation. We present the case of a patient with cutaneous squamous cell carcinoma of the nasal dorsum which relapsed after surgery and radiation therapy. The patient refused radical surgery and electrochemotherapy under general anesthesia was administered. After 6 months from treatment, the patient showed a complete clinical response. Electrochemotherapy could be considered as an alternative to surgery in small lesion when other approaches are refused.

Present and Future of De-intensification Strategies in the Treatment of Oropharyngeal Carcinoma.

PURPOSE OF REVIEW: The treatment of patients with squamous cell carcinoma of the oropharynx (OPSCC) remains controversial. HPV positivity is widely accepted as a favorable prognostic factor, and HPV+ OPSCC is considered a distinct pathological entity with dedicated NCCN guidelines and may deserve a more personalized therapeutic strategy. The possibility to reduce surgical invasiveness and acute and late toxicity of radiotherapy/chemotherapy has led to the new concept of de-escalation treatment strategies. In particular, several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease's control and survival. The aim of the present review is to systematically illustrate the current status of research in de-intensification surgical and non-surgical strategies in the treatment of the OPSCC. RECENT FINDINGS: We categorized all completed and on-going trials on the basis of the specific de-escalated treatment protocol. Several de-intensified approaches have been investigated with the aim to give patients less toxic treatments, while maintaining comparable results in terms of disease's control and survival. Considering the conflicting results reported so far by preliminary studies, it is necessary to wait for the final results of the on-going trials to better clarify which is the best de-intensified strategy and which patients would really benefit from it.

Trans-Oral Robotic Surgery in the Management of a Supraglottic Solitary Fibrous Tumor.

Trans-oral robotic surgery (TORS) has become increasingly widespread for the head and neck surgery procedures. In this paper, the authors describe the first reported TORS in the management of a laryngeal solitary fibrous tumor (SFT). A 77-year-old woman suffered from progressive dysphonia lasting 2 years and occasional dyspnea. A submucosal mass of about 4 cm in diameter involving the left supraglottis and left aryepiglottic fold was detected during the flexible fibre-optic laryngeal examination. Magnetic resonance imaging revealed a solid, well-demarcated mass (36 × 25 mm), hyperintense with nonhomogeneous contrast enhancement in T2-weighted sequences. The lesion was successfully removed en bloc using the daVinci Xi system (Intuitive Surgical, Sunnyvale, CA) equipped with 3 robotic arms (1 3-dimensional endoscopic arm, 1 monopolar cautery, 1 bipolar Maryland forceps). The postoperative course was regular, and the endoscopic examination at 1 month showed normal laryngeal morphology and function. Trans-oral robotic surgery has proved to be a good alternative to conventional trans-oral approaches in the treatment of laryngeal SFT. The lesion was completely removed without intraoperative complications, and postoperative morbidity was minimized. Further comparative studies are recommended to define if TORS could become the gold standard for the surgical treatment of laryngeal SFTs.

Transoral Robotic Surgery in the Management of a Tongue Base Schwannoma.

Schwannomas are the most common benign tumors arising from the peripheral nerve sheath, and the intraoral location is very atypical, representing less than 1% of all cases. Surgical excision is the treatment of choice, and a variety of surgical approaches have been described. The authors report the first described case of tongue base schwannoma treated with transoral robotic surgery (TORS). A 47-years-old female patient complaining mild dysphagia and snoring, presented a submucosal swelling at the right side of the tongue base. MRI showed a large well-circumscribed solid mass, homogeneously isointense in T1WI and hyperintense on T2WI, with no lymph node metastasis. According to size, location and radiological characteristic of the mass a TORS approach was chosen. An extracapsular dissection was performed, and the lesion was completely removed with no intraoperative complications. The final diagnosis based on histopathological examination and IHC analysis (S-100 positive) was a schwannoma of the tongue base. The post-operative course was uneventful, and no recurrence was observed after 6 months of follow-up. This study demonstrates the feasibility of TORS in the treatment of a tongue base schwannoma. This is a valid alternative to the common transoral approach in order to avoid more invasive external approaches, and further studies are recommended in order to clarify if this approach could be proposed as the first line treatment in selected cases.

Myxoid Liposarcoma Metastasizing to the Parotid Gland.

Localization of metastases into the parotid gland is a very uncommon event. Usually they arise from primary tumors located in the head and neck, mainly melanoma or epidermoid carcinoma of the skin, while other histotypes, from others anatomical districts, hardly have a metastatic spread to the parotid. Myxoid liposarcoma (MLS) is a rare malignant tumor of the soft tissue that mainly occurs in the extremities, representing the second most common subtype of liposarcoma. Although it is typical for liposarcomas to metastasize to the lungs, it is known that MLS can spread also to extra pulmonary sites. The authors report a case of myxoid liposarcoma of the left thigh in a 64-year-old man, with an unusual metastatic double presentation to the contralateral forearm first and to the parotid gland then. MLS with metastatic disease to the parotid gland is an extremely rare event with very few cases reported in the English literature.

Procalcitonin for Early Detection of Pharyngocutaneous Fistula after Total Laryngectomy: A Pilot Study.

OBJECTIVES: The aim of this prospective study was to investigate the role of procalcitonin as an early diagnostic marker of pharyngocutaneous fistula (PCF) in a cohort of head and neck patients treated with total laryngectomy for squamous cell carcinoma. METHODS: This prospective study was conducted on a sample of patients enrolled from January 2019 to March 2022. All patients were subjected to a "protocol" of blood chemistry investigations, scheduled as follows: complete blood count with formula, ESR dosage, CPR, and PCT. PCT was also dosed by salivary sampling and a pharyngo-cutaneous swab in patients who presented with PCF. The dosage scheme was systematically repeated: the day before the intervention (t0); the 5th day postoperative (t1); the 20th day postoperative (t2); and at time X, the day of the eventual appearance of the pharyngocutaneous fistula. RESULTS: A total of 36 patients met the inclusion criteria. The patients enrolled in the study were subsequently divided into two groups: 27 patients underwent total laryngectomy (TL) for laryngeal cancer without postoperative complications, and 9 patients were undergoing TL with postoperative PCF. Using the Cochran's Q test, statistical significance was found for PCT among T0, T1, Tx, and T2 (p-value < 0.001) between the PCF and non-PCF groups. The Z test demonstrated that there is a difference in PCT levels at T1 and T2 and that this difference is statistically significant (p < 0.001). CONCLUSIONS: PCT could be considered an early marker of complications in open laryngeal surgery. According to our results, it could be useful in the precocious detection of pharyngocutaneous fistulas and in the management of antibiotic therapy.

Impact of Adjuvant Radiotherapy in Squamous Cell Carcinoma of the Oral Cavity with Perineural Invasion.

OBJECTIVE: Current guidelines indicate postoperative radiotherapy (PORT) in oral squamous cell carcinoma (OSCC) with perineural invasion (PNI), however, its real benefit has never been proven. The aim of our study is to investigate the benefit of PORT in OSCC patients with PNI in terms of survival and disease control. DATA SOURCES: The Pubmed/MEDLINE, Cochrane Library, and Scopus databases. REVIEW METHODS: Patients with PNI + OSCC treated with primary surgery were extracted from the included studies. The pooled logHR was calculated by comparing patients who underwent PORT to those who underwent only observation for overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and locoregional control (LRC). RESULTS: About 690 patients with primary OSCC and PNI were included from nine studies. 374 (54.2%) patients underwent PORT, while 316 (45.8%) underwent observation. Analyses showed non-significant difference between the two groups for OS (HR: 1.01; 95% CI: 0.38-2.69), DSS (HR: 2.03; 95% CI: 0.54-7.56), and LRC (HR: 0.89; 95% CI: 0.53-1.50). They showed a significant difference in terms of DFS (HR: 0.86; 95% CI: 0.77-0.97). CONCLUSION: The real benefit of PORT in OSCC patients with PNI is still unclear, although it may have a positive impact on DFS. Clinicians should consider individual patient's characteristics, tumor factors, and treatment goals when deciding whether to recommend PORT. Further studies are needed to clarify which entity of PNI really benefits from PORT. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2019-2027, 2024.

A multicenter protocol to assess the prognostic significance of the tumor microenvironment in patients with squamous cell carcinoma of the larynx.

BACKGROUND: The purpose of this multicenter study was to retrospectively investigate the prognostic significance of the tumor microenvironment, in relation to survival in a large cohort of patients with laryngeal squamous cell carcinoma (LSCC), using the method proposed by the International TILs Working Group in breast cancer. METHODS: All consecutive patients with biopsy-proven LSCC who underwent total laryngectomy (TL) between January 2014 and January 2023 were retrospectively included in the study. A retrospective review of medical records including surgical, pathological and follow-up reports was performed. The density of TILs was determined according to the recommendations of the International TILs Working Group. RESULTS: The study group included 186 patients with LSCC. High TILs were statistically correlated with reduced size and extension of primary tumor (pT stage) with a statistically significant value (S: p = 0.01; P: p = 0.0003) and without needs of salvage therapy (S: p = 0.03; P: p = 0.004). Low TILs were indicative of worse prognosis. CONCLUSIONS: Our study confirmed the protective value of TILs and the prognostic role of the tumor microenvironment in LSCC; furthermore, our results showed that the score proposed by the International TILs Working Group for breast cancer can be applied to LSCC.

Role of Tumor-Infiltrating Lymphocytes and the Tumor Microenvironment in the Survival of Malignant Parotid Gland Tumors: A Two-Centre Retrospective Analysis of 107 Patients.

Background: This study aims to retrospectively investigate the prognostic significance of the tumor microenvironment, with a focus on TILs (tumor-infiltrating lymphocytes), in relation to survival in a large cohort of patients with parotid gland cancer, and it uses the method proposed by the International TILs Working Group in breast cancer. Methods: We included a cohort of consecutive patients with biopsy-proven parotid cancer who underwent surgery between January 2010 and September 2023. A retrospective review of medical records, including surgical, pathological and follow-up reports, was performed. The density of TILs was determined according to the recommendations of the International TILs Working Group for breast cancer. Results: A weak negative correlation (p = 0.3) between TILs and time of survival and a weak positive correlation (p = 0.05) between TILs and months of survival (high TILs were correlated with longer survival in months) were identified. High TILs were weakly negatively, but not statistically significantly p (0.7), correlated with the grading of tumor; this means that high TILs were associated with low-grade tumors. Conclusions: Contrary to previous preliminary reports, this retrospective work found no statistically significant prognostic role of TILs in parotid gland malignancies. This case series represents the largest cohort ever reported in the literature and includes all malignant histological types. Future larger molecular studies may be useful in this regard.

Subglottic Mass as Isolated Manifestation of Relapsing Polychondritis at Presentation.

Relapsing polychondritis (RP) is a rare systemic disease that is characterized by recurrent episodic inflammation of the cartilaginous structures of the body, resulting in their progressive destruction and subsequent replacement with fibrotic scar. We present a case of RP that initially manifested with subglottic involvement and we propose an innovative strategy for the treatment for laryngeal RP in phase of active inflammation. A multidisciplinary approach (rheumatologist, otolaryngologist, immunologist, internist, cardiologist, etc) and adequate follow-up are essential. The timeliness of the diagnosis is fundamental to contain the destructive effects on the cartilages involved.

Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer. METHODS: PubMed/MEDLINE, Cochrane Library, and Scopus databases were searched. English language, original studies investigating oncological outcomes of TLM in adult patients with recurrent laryngeal cancer were included. Data were pooled using a distribution-free approach for estimating summary local control (LC), disease-specific survival (DSS), and overall survival (OS) curves with random effects. RESULTS: Two hundred and thirty-five patients underwent salvage TLM after primary (chemo)radiotherapy. The mean follow-up time was 60.8 months (95% CI: 32.7-88.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 74.2% (61.7-89.4), 53.9% (38.5-75.3), and 39.1% (25.2-60.8). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 88.4% (82.0-95.3), 67.8% (50.9-90.3), and 58.9% (42.7-81.1). Two hundred and seventy-one patients underwent TLM after primary laser treatment. The mean follow-up time was 70.9 months (95% CI: 36.9-104.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 72.2% (64.7-80.6), 53.2% (42.2-66.9), and 40.4% (29.6-55.2). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 92.1% (85.5-99.1), 77.0% (64.4-92.0), and 67.1% (51.6-87.3). CONCLUSIONS: TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1425-1433, 2023.

Machine learning in laryngeal cancer: A pilot study to predict oncological outcomes and the role of adverse features.

BACKGROUND: Laryngeal carcinoma (LC) remains a significant economic and emotional problem to the healthcare system and severe social morbidity. New tools as Machine Learning could allow clinicians to develop accurate and reproducible treatments. METHODS: This study aims to evaluate the performance of a ML-algorithm in predicting 1- and 3-year overall survival (OS) in a cohort of patients surgical treated for LC. Moreover, the impact of different adverse features on prognosis will be investigated. Data was collected on oncological FU of 132 patients. A retrospective review was performed to create a dataset of 23 variables for each patient. RESULTS: The decision-tree algorithm is highly effective in predicting the prognosis, with a 95% accuracy in predicting the 1-year survival and 82.5% in 3-year survival; The measured AUC area is 0.886 at 1-year Test and 0.871 at 3-years Test. The measured AUC area is 0.917 at 1-year Training set and 0.964 at 3-years Training set. Factors that affected 1yOS are: LNR, type of surgery, and subsite. The most significant variables at 3yOS are: number of metastasis, perineural invasion and Grading. CONCLUSIONS: The integration of ML in medical practices could revolutionize our approach on cancer pathology.