Compartmental tongue surgery for intermediate-advanced squamous cell carcinoma: A multicentric study.

BACKGROUND: A multicentric study was conducted on technical reproducibility of compartmental tongue surgery (CTS) in advanced tongue cancers (OTSCC) and comparison to standard wide margin surgery (SWMS). METHODS: We studied 551 patients with OTSCC treated by CTS and 50 by SWMS. Oncological outcomes were analyzed. A propensity score was performed to compare survival endpoints for the two cohorts. RESULTS: In the CTS group, survival and prognosis were significantly associated with positive lymph-nodes, extranodal extension, depth of invasion and involvement of the soft tissue connecting the tongue primary tumor to neck lymph nodes (T-N tract), independently from the center performing the surgery. SWMS versus CTS showed a HR Cause-Specific Survival (CSS) of 3.24 (95% CI: 1.71-6.11; p < 0.001); HR Loco-Regional Recurrence Free Survival (LRRFS) of 2.54 (95% CI: 1.47-4.40; p < 0.001); HR Overall Survival (OS) of 0.11 (95% CI: 0.01-0.77; p = 0.03). CONCLUSION: Performing the CTS could provide better CSS and LRRFS than SWMS regardless of the center performing the surgery, in advanced OTSSC.

The T-N tract involvement as a new prognostic factor for PORT in locally advanced oral cavity tumors.

OBJECTIVE: The space comprised between tumor and neck lymph nodes (T-N tract) is one of the main routes of tumor spread in oral cavity tumors. Aim of the study was to investigate the impact of T-N tract involvement on the postoperative radiotherapy (PORT) outcomes. MATERIALS AND METHODS: Patients (pts) treated between 2000 and 2016 with indication to PORT were retrospectively retrieved. Inclusion criteria were: (a) locally advanced tumors of the oral cavity, (b) who received with indication to PORT (c) with a minimum follow-up of six months. RESULTS: One hundred and fifty-seven pts met the inclusion criteria (136 pts treated with PORT and 21 pts not treated with PORT). In the PORT cohort, the T-N tract involvement had no impact on both OS (p = .09) and LRFS (p = .2). Among the non-PORT cohort, both OS (p = .007) and LRFS (p = .017) were worse for pts with positive T-N tract compared to those with negative T-N tract. PORT improved both OS (p = .008) and LRFS (p = .003) in pts with positive T-N tract but not in those with negative T-N tract (p = .36 and p = .37, respectively). CONCLUSIONS: Our results suggest that involvement of T-N tract should be considered as prognostic factors informing the indication to PORT.

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.

Oral tongue carcinoma: prognostic changes according to the updated 2020 version of the AJCC/UICC TNM staging system.

Background: This study aimed to evaluate the performance of the 2017 8th TNM edition and the latest update in 2020 compared to the 7th in a large cohort of patients affected by oral tongue squamous cell carcinoma (OTSCC), considering all stages. Materials and methods: The cohort involved 300 patients affected by OTSCC treated with surgery. All cases were classified according to the 7th, 8th (2017), and the latest updated TNM edition (October 2020),. Patients were grouped based on the shift in tumour (T) category, lymph nodal (N) category and final pathological stage. Overall survival (OS) and disease-free survival (DFS) were calculated with the Kaplan-Meier method. Univariate and multivariate analyses were carried out. Results: According to the 7th edition, multivariate analysis OS revealed that stage IV patients had an almost 4-fold risk of death compared to stage I (HR = 3.81 95% CI: 2.32-6.25; p < 0.001). Regarding DFS, stage IV patients had a 2-fold greater risk of relapses, or second primary, than patients in stage I (HR = 2.51 95% CI: 1.68-3.74; p < 0.001). According to 2017 8th edition for OS, stage IV patients presented a 5-fold higher risk of death compared to patients in stage I (HR = 5.18 95% CI: 2.96-9.08; p < 0.001) and almost 4-old greater risk of relapses or second primary compared to patients in stage I considering DFS (HR = 3.61 95% CI: 2.28-5.71; p < 0.001). Regarding the recent edition of 8th TNM (2020), stage IV patients had an almost 5-fold greater risk of death compared to patients in stage I considering OS (HR = 4.84 95% CI: 2.74-8.55; p < 0.001), while for DFS they had 3-fold greater risk of relapse or second primary compared to patients in stage I (HR = 3.13 95% CI: 1.99-4.91; p < 0.001). Conclusions: This study confirmed that the recent update of the 8th edition of the TNM (2020) improves stratification and identification of advanced tumours, reducing the number of T3 compared to the 2017 edition and increasing the number of patients with pT4. This improvement made by the updated edition may reduce the risk of skipping adjuvant therapy.

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.

Indication to post-operative radiotherapy for oral cavity squamous cell carcinoma: what's new in the depth of infiltration (DOI) era?

OBJECTIVE: The last edition of the American Joint Committee on Cancer (AJCC eighth) has introduced the depth of infiltration (DOI) as a new prognostic parameter in oral cavity squamous cell carcinomas (OCSCCs). The aim of this study is to analyze the impact of stage migration on the indication to post-operative radiotherapy (PORT). METHODS: OCSCCs treated at two institutions between 2014 and 2019 were retrieved. As per the AJCC eighth, only pT3 primarily OCSCCs were considered; availability of the pathologic specimen was a further inclusion criterion. Risk factors considered for PORT were: pT3-pT4, nodal involvement, positive/close surgical margins, perineural and lymph vascular invasion. RESULTS: 149 patients staged as pT3 AJCC eighth were included. A four-fold increase in the number of patients staged as pT3 from the seventh to the eighth AJCC was found. Stage migration to pT3 was equally due to the downstaging from former pT4 (38%) and upstaging of former pT1-pT2 (35%). Considering the former pT1-pT2 53 patients, 13 (25%) had no risk factors for PORT other than DOI. Among 25 cases with former pT1-pT2 and negative lymph nodes, no additional risk factors were found in 11 (44%). CONCLUSION: 90% of patients had at least one risk factor besides DOI and would have received PORT also according to the AJCC seventh; notably, of former pT1-pT2N0, half of them have been upstaged to pT3 in the current TNM classification. The role of PORT in this cohort of patients has not been clarified yet. ADVANCES IN KNOWLEDGE: Other-than-DOI risk factors leading to PORT indication are highly prevalent in OCSSC patients classified as pT3 per the latest AJCC TNM staging system and should therefore be considered for a comprehensive oncological assessment.

The Impact of Post-Operative Radiotherapy in Early Stage (pT1-pT2N0M0) Oral Tongue Squamous Cell Carcinoma in Era of DOI.

Background: This study investigated the role of depth of infiltration (DOI) as an independent prognosticator in early stage (T1-T2N0M0) oral cavity tumors and to evaluate the need of postoperative radiotherapy in the case of patients upstaged to pT3 for DOI > 10 mm in the absence of other risk factors. Methods: We performed a retrospective analysis on patients treated with surgery and re-staged according to the 8th edition of malignant tumors classification (TNM). The role of DOI as well as other clinical/pathological features was investigated at both univariable and multivariable analyses on overall survival (OS), disease free survival (DFS), relapse free survival (RFS), and local RFS. Results: Among the 94 included patients, 23 would have been upstaged to pT3 based on DOI. Multivariable analysis showed that DOI was not an independent prognostic factor for any of the considered outcomes. The presence of perineural invasion was associated with a significant worse RFS (p = 0.02) and LRFS (p = 0.04). PORT was found to be significantly associated with DFS (p = 0.04) and RFS (p = 0.06). Conclusions: The increasing DOI alone was not sufficient to impact the prognosis, and therefore, should not be sufficient to dictate PORT indications in early-stage patients upstaged on the sole basis of DOI.

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.

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.

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.

Anatomically-based transoral surgical approach to early-stage oral tongue squamous cell carcinoma.

The mainstream of treatment of early-stage oral tongue squamous cell carcinoma (OTSCC) is represented by transoral resection with "adequate" free margins. Despite that, a precise and shared definition of "adequate margin" is lacking, and so is a standardized transoral surgical technique.The tongue is a symmetrically paired organ, consisting of intertwining intrinsic and extrinsic muscles, which can be distinguished during dissection. Routes of tumoral spread in oral tongue cancer are well-known and should be taken into account during resection. We propose herein a standardized and replicable surgical technique to resect early-stage OTSCC, based on rational anatomical considerations.

Soft tissue necrosis in patients treated with transoral robotic surgery and postoperative radiotherapy: preliminary results.

OBJECTIVE: Postoperative radiotherapy (PORT) is indicated in almost two-thirds of patients treated with transoral robotic surgery (TORS) for head and neck tumors. The aim of this study was to quantify the toxicity profile of patients treated with PORT after TORS in oropharyngeal and supraglottic laryngeal cancer focusing on soft tissue necrosis (STN). METHODS: We retrospectively reviewed 28 patients. Acute and late toxicity were examined. Incidence and severity of STN were recorded. RESULTS: No patient experienced acute grade 3 skin or mucosal toxicity; 1 patient had grade 3 dysphagia. At 12 months, no evaluated patient required enteral nutrition and 2 patients had tracheostomy. STN occurred in 4 (14%) patients: 3 out of 4 (75%) patients with STN had diabetes, whereas 6 out of 13 (25%) patients without STN had diabetes (p = 0.05). CONCLUSION: We found an acceptable toxicity profile of PORT performed after a TORS procedure. Diabetes mellitus might be a risk factor for STN.

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.

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.

Total glossectomy with preservation of the larynx: oncological and functional results.

Our aim was to analyse the overall and disease-free survival (DFS), time to recovery of oral feeding, and morbidity, in a consecutive series of patients who had total glossectomy with preservation of the larynx for advanced cancer of the tongue at the European institute of Oncology (Milan). From June 2002 to April 2011, 37 patients who were treated for advanced cancer of the tongue had total glossectomy, bilateral neck dissection, and preservation of the larynx. Various flaps were used for reconstruction. Overall and disease-free survival were assessed from the day of operation to the latest outpatient examination. Postoperative morbidity and rehabilitation of feeding were also assessed. Six patients had major complications, four of whom had a second operation for necrosis of the flap. Actuarial five-year overall survival (OS) and disease-free survival were 54% and 47%. Twenty-four patients (65%) were operated on as their first treatment, and had 79% five-year overall survival and 61% 5-year disease-free survival. Twenty-six patients were eventually able to feed orally postoperatively. Although this retrospective study include a limited number of patients, the results support the validity of total glossectomy as a safe procedure for advanced cancer of the tongue. Pretreated patient were previously treated with surgery, radiotherapy or chemoradiotherapy with curative purposes. Nevertheless, the long period required for recovery of oral feeding indicates that total glossectomy should be reserved for highly motivated patients.

High-dose-rate interstitial brachytherapy in early stage buccal mucosa and lip cancer: report on 12 consecutive patients and review of the literature.

AIMS AND BACKGROUND: To evaluate clinical outcome and toxicity using high-dose-rate brachytherapy as monotherapy in head and neck carcinomas. METHODS: Between September 2004 and April 2010, a series of 12 patients with lip (7 patients) or buccal mucosa (5 patients) cancers were treated by exclusive interstitial high-dose-rate brachytherapy. The median age of the patients was 71.5 years (range, 47-87). Stages were T1N0M0 and T2N0M0 in 6 and 6 patients, respectively. A dose of 27 to 54 Gy in 9 to 16 fractions, 3 to 4.5 Gy per fraction, 2 fractions per day with a minimal gap of 6 h in between was delivered. RESULTS: After a median follow-up of 46 months (range, 10-85), the disease-free and overall survival was 83% (10 of 12 patients) and 50% (6 of 12 patients), respectively. The crude local control in the lip cancer patients was 100% and in the buccal mucosa cancer patients was 60%. No severe toxicity was registered. CONCLUSIONS: High-dose-rate brachytherapy is feasible and safe and offers the possibility to treat patients in an outpatient regimen.

Future challenges in head and neck cancer: from the bench to the bedside?

HNC is the 11th most frequent carcinoma with a world-wide yearly incidence exceeding over half a million cases [1], a 10:1 male gender predilection and country specific variability [2]. The principal risk factors are tobacco and alcohol use and, in a growing population without these exposures, HPV infection. While much progress has been made in understanding the molecular basis of cancer, the 5-year mortality of head and neck cancer has remained approximately 50%. To this date we have not been able to translate as much of our basic science knowledge into significant disease altering therapeutic strategies in terms of local, loco-regional, functional and overall survival. Challenges remain in all aspects of head and neck cancer management: prevention, diagnosis, surgical and non-surgical treatment.