Is precision medicine the solution to improve organ preservation in laryngeal/hypopharyngeal cancer? A position paper by the Preserve Research Group.

In locally advanced (LA) laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC), larynx preservation (LP) strategies aim at the cure of the disease while preserving a functional larynx, thus avoiding total laryngectomy and the associated impact on the quality of life. In the last decades, apart from transoral and open-neck organ preservation approaches, several non-surgical regimens have been investigated: radiotherapy alone, alternate, concurrent or sequential chemoradiation, and bioradiotherapy. Despite major progress, the identification of reliable and effective predictors for treatment response remains a clinical challenge. This review examines the current state of LP in LA-LHSCC and the need for predictive factors, highlighting the importance of the PRESERVE trial in addressing this gap. The PRESERVE trial represents a pivotal initiative aimed at finding the optimal therapy for laryngeal preservation specific to each patient through a retrospective analysis of data from previous LP trials and prospectively validating findings. The goal of the PRESERVE trial is to develop a comprehensive predictive classifier that integrates clinical, molecular, and multi-omics data, thereby enhancing the precision and efficacy of patient selection for LP protocols.

Morbidity of multimodal treatments including endoscopic surgery for sinonasal malignancies: Results of an international collaborative study on 940 patients (MUSES).

INTRODUCTION: In the management of sinonasal malignancies treatment-induced morbidity and mortality is gaining relevance both for surgical approaches (endoscopic and open resection) and non-surgical therapies. The aim of this multicenter study is to assess complications associated with endoscopic surgery and non-surgical treatments (neoadjuvant and/or adjuvant) for malignant sinonasal tumors. METHODS: All patients with nasoethmoidal malignancies treated with curative intent with endoscopic or endoscopic-assisted surgery at three referral centers with uniform management policies were included. Neo- and/or adjuvant (chemo)radiotherapy was administered according to histology and pathological report. Demographics, treatment characteristics, and complications related both to the surgical and non-surgical approaches were retrieved. The data were analyzed with univariate and multivariate statistics to assess independent predictors of complications. RESULTS: Nine hundred and forty patients were included, 643 males (68%) and 297 females (32%). A total of 225 complications were identified in 187 patients (19.9%): cerebrospinal fluid (CSF) leak (3.5%), mucocele (2.3%), surgical site bleeding (2.0%), epiphora (2.0%), and radionecrosis (2.0%) were the most common. Treatment-related mortality was 0.4%. Variables independently associated with complications at multivariate analysis were principally dural resection (OR 1.92), cranioendoscopic or multiportal resection (OR 2.93), dural repair with multilayer technique with less than three layers (OR 2.17), and graft different from iliotibial tract (OR 3.29). CONCLUSION: Our study shows that modern endoscopic treatments and radiotherapy for sinonasal malignancies are associated with limited morbidity and treatment-related mortality. CSF leak and radionecrosis, although rare, remain the most frequent complications and should be further addressed by future research efforts.

The prognostic role of MRI-based radiomics in tongue carcinoma: a multicentric validation study.

PURPOSE: Radiomics is an emerging field that utilizes quantitative features extracted from medical images to predict clinically meaningful outcomes. Validating findings is crucial to assess radiomics applicability. We aimed to validate previously published magnetic resonance imaging (MRI) radiomics models to predict oncological outcomes in oral tongue squamous cell carcinoma (OTSCC). MATERIALS AND METHODS: Retrospective multicentric study on OTSCC surgically treated from 2010 to 2019. All patients performed preoperative MRI, including contrast-enhanced T1-weighted (CE-T1), diffusion-weighted sequences and apparent diffusion coefficient map. We evaluated overall survival (OS), locoregional recurrence-free survival (LRRFS), cause-specific mortality (CSM). We elaborated different models based on clinical and radiomic data. C-indexes assessed the prediction accuracy of the models. RESULTS: We collected 112 consecutive independent patients from three Italian Institutions to validate the previously published MRI radiomic models based on 79 different patients. The C-indexes for the hybrid clinical-radiomic models in the validation cohort were lower than those in the training cohort but remained > 0.5 in most cases. CE-T1 sequence provided the best fit to the models: the C-indexes obtained were 0.61, 0.59, 0.64 (pretreatment model) and 0.65, 0.69, 0.70 (posttreatment model) for OS, LRRFS and CSM, respectively. CONCLUSION: Our clinical-radiomic models retain a potential to predict OS, LRRFS and CSM in heterogeneous cohorts across different centers. These findings encourage further research, aimed at overcoming current limitations, due to the variability of imaging acquisition, processing and tumor volume delineation.

Artificial intelligence for automatic detection and segmentation of nasal polyposis: a pilot study.

PURPOSE: Accurate diagnosis and quantification of polyps and symptoms are pivotal for planning the therapeutic strategy of Chronic rhinosinusitis with nasal polyposis (CRSwNP). This pilot study aimed to develop an artificial intelligence (AI)-based image analysis system capable of segmenting nasal polyps from nasal endoscopy videos. METHODS: Recorded nasal videoendoscopies from 52 patients diagnosed with CRSwNP between 2019 and 2022 were retrospectively analyzed. Images extracted were manually segmented on the web application Roboflow. A dataset of 342 images was generated and divided into training (80%), validation (10%), and testing (10%) sets. The Ultralytics YOLOv8.0.28 model was employed for automated segmentation. RESULTS: The YOLOv8s-seg model consisted of 195 layers and required 42.4 GFLOPs for operation. When tested against the validation set, the algorithm achieved a precision of 0.91, recall of 0.839, and mean average precision at 50% IoU (mAP50) of 0.949. For the segmentation task, similar metrics were observed, including a mAP ranging from 0.675 to 0.679 for IoUs between 50% and 95%. CONCLUSIONS: The study shows that a carefully trained AI algorithm can effectively identify and delineate nasal polyps in patients with CRSwNP. Despite certain limitations like the focus on CRSwNP-specific samples, the algorithm presents a promising complementary tool to existing diagnostic methods.

Computer Vision Foundation Models in Endoscopy: Proof of Concept in Oropharyngeal Cancer.

OBJECTIVES: To evaluate the performance of vision transformer-derived image embeddings for distinguishing between normal and neoplastic tissues in the oropharynx and to investigate the potential of computer vision (CV) foundation models in medical imaging. METHODS: Computational study using endoscopic frames with a focus on the application of a self-supervised vision transformer model (DINOv2) for tissue classification. High-definition endoscopic images were used to extract image patches that were then normalized and processed using the DINOv2 model to obtain embeddings. These embeddings served as input for a standard support vector machine (SVM) to classify the tissues as neoplastic or normal. The model's discriminative performance was validated using an 80-20 train-validation split. RESULTS: From 38 endoscopic NBI videos, 327 image patches were analyzed. The classification results in the validation cohort demonstrated high accuracy (92%) and precision (89%), with a perfect recall (100%) and an F1-score of 94%. The receiver operating characteristic (ROC) curve yielded an area under the curve (AUC) of 0.96. CONCLUSION: The use of large vision model-derived embeddings effectively differentiated between neoplastic and normal oropharyngeal tissues. This study supports the feasibility of employing CV foundation models like DINOv2 in the endoscopic evaluation of mucosal lesions, potentially augmenting diagnostic precision in Otorhinolaryngology. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Skull base surgery for malignant tumors: The 2nd international collaborative study (1995-2015).

BACKGROUND: The current study presents the effort of a global collaborative group to review the management and outcomes of malignant tumors of the skull base worldwide. PATIENTS AND METHODS: A total of 28 institutions contributed data on 3061 patients. Analysis evaluated clinical variables, survival outcomes, and multivariable factors associated with outcomes. RESULTS: The median age was 56 years (IQR 44-67). The open surgical approach was used in 55% (n = 1680) of cases, endoscopic resection was performed in 36% (n = 1087), and the combined approach in 9.6% (n = 294). With a median follow-up of 7.1 years, the 5-year OS DSS and RFS were 65%, 71.7% and 53%, respectively. On multivariable analysis, older age, comorbidities, histology, dural/intracranial involvement, positive margins, advanced stage, and primary site were independent prognostic factors for OS, DSS, and RFS. Adjuvant RT was a protective prognostic factor. CONCLUSION: The progress across various disciplines may have contributed to improved OS and DSS in this study compared to previous reports.

Magnetic Resonance Imaging after Nasopharyngeal Endoscopic Resection and Skull Base Reconstruction.

Background: Postoperative imaging after nasopharyngeal endoscopic resection (NER) and skull base reconstruction is quite challenging due to the complexity of the post-surgical and regional anatomy. Methods: In this retrospective observational study, we included patients treated with NER from 2009 to 2019 and submitted to Magnetic Resonance Imaging (MRI) 6 and 12 months after surgery. A radiologist with 15 years of experience analyzed all MRI scans. Results: A total of 50 patients were considered in this study, 18 of whom were excluded due to imaging unavailability, and 16 of whom were not considered due to major complications and/or persistent disease. Sixteen patients were evaluated to identify the expected findings. Inflammatory changes were observed in 16/64 subsites, and regression of these changes was observed in 8/64 at 1 year. Fibrosis was observed in 5/64 subsites and was unmodified at 1 year. The nasoseptal flap showed homogeneous enhancement at 6 months (100%) and at 1 year. The temporo-parietal fascia flap (TPFF) showed a decrease in the T2- signal intensity of the mucosal layer in 57% of the patients at 1 year and a decrease in enhancement in 43%. Conclusions: Identifying the expected findings after NER and skull base reconstruction has a pivotal role in the identification of complications and recurrence.

Transoral laser exoscopic surgery of the larynx: state of the art and comparison with traditional transoral laser microsurgery.

Objective: To evaluate the efficacy of transoral laser exoscopic surgery (TOLES) in a unicentric series of patients affected by benign and malignant glottic and supraglottic lesions, and compare outcomes with those of transoral laser microsurgery (TOLMS). Methods: To demonstrate the non-inferiority of TOLES in terms of operative time, margin status and complication rates, we compared outcomes of 93 patients treated by TOLES between July 2021 and July 2023 with those of a match-paired group of 107 historical patients treated by TOLMS. To perform a multiparametric ergonomic evaluation of TOLES vs TOLMS, we used observational methods for biomechanical overload risk assessment and wearable technologies comparing 15 procedures with TOLES vs a paired match of 13 surgeries performed with TOLMS by the same surgeon. Results: No significant differences were found in terms of surgical duration, positive margins, or complications between TOLES and TOLMS. Ergonomics assessment by inertial measurement units and electromyographic surface electrodes demonstrated a reduced biomechanical overload with TOLES compared to TOLMS. Conclusions: The many advantages of TOLES, such as its superior didactic value, better digital control of light even through small-bored laryngoscopes, improved binocular vision, and increase in surgical performance by 3 or 4-hand techniques, are difficult to be quantified. In contrast, its non-inferiority in terms of oncological results and better ergonomics compared to TOLMS are demonstrated herein.

Recurrent Laryngeal Nerve Intraoperative Neuromonitoring Indications in Non-Thyroid and Non-Parathyroid Surgery.

Introperative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) is a well-established technique to aid in thyroid/parathyroid surgery. However, there is little evidence to support its use in non-thyroid or non-parathyroid surgery. The aim of this paper was to review the current evidence regarding the use of IONM in non-thyroid/non-parathyroid surgery in the head and neck and thorax. A literature search was performed from their inception up to January 2024, including the term "recurrent laryngeal nerve monitoring". IONM in non-thyroid/non-parathyroid surgery has mainly been previously described in oesophageal surgery and in tracheal resections. However, there is little published evidence on the role of IONM with other resections in the vicinity of the RLN. Current evidence is low-level for the use of RLN IONM in non-thyroid/non-parathyroid surgery. However, clinicians should consider its use in surgery for pathologies where the RLN is exposed and could be injured.

Initial surgical management of sporadic medullary thyroid cancer: Guidelines based optimal care - A systematic review.

INTRODUCTION: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor from parafollicular cells that produce calcitonin (Ct). Despite several existing guidelines for the surgical management of sporadic MTC (sMTC), optimal initial surgical management of the thyroid, the central and the lateral neck remains a matter of debate. METHODS: A systematic review in PubMed and Scopus for current guidelines addressing the surgical management of sMTC and its referenced citations was conducted as per the PRISMA guidelines. RESULTS: Two-hundred and one articles were identified, of which 7 met the inclusion criteria. Overall, guidelines vary significantly in their recommendations for the surgical management of sMTC. Only one guideline recommended partial thyroidectomy for limited disease, but the possibility to avoid completion thyroidectomy in selected cases is acknowledged in 42% (3/7) of the remaining guidelines. The majority of guidelines (71.4%; 5/7) recommended prophylactic central neck dissection (CND) for all patients while the remaining two guidelines recommended CND based on Ct level and tumor size. The role of prophylactic lateral neck dissection based on preoperative Ct levels was recommended by 42% (3/7) of guidelines. Overall, these guidelines are based on low-quality evidence, mostly single-center retrospective series, some of which are over 20 years old. CONCLUSION: Current surgical management guidelines of sMTC should be revised, and ought to be based on updated data challenging current recommendations, which are based on historic, low-quality evidence. Partial thyroidectomy may become a viable option for small, limited tumors. Prospective, multi-center studies may be useful to conclude whether prophylactic ND is necessary in all sMTC patients.

Measuring financial toxicity in head and neck cancer: a systematic review.

Objective: The current study systematically reviews the literature about financial toxicity (FT) in head and neck cancer patients. Three databases were reviewed: PubMed, Scopus and Web of Science. Methods: Full text English papers published from 2000 to 2022 reporting on quantitative results about FT in head and neck cancer survivors collected through structured questionnaires or interviews were included. Results: Twenty-seven articles were included. Most of the articles were published after 2015 and from United States. There was a slight prevalence of papers dealing with oropharyngeal cancer, squamous-cell carcinoma and locally advanced head and neck cancer. Measures of FT were obtained through validated questionnaires like COST, FIT and FDQ. Collected data were mostly referrable to financial spending, financial resources, psychosocial aspect, support seeking, coping care and coping lifestyle subdomain. FT scores by COST were found to be worse in the COVID era. Financial counseling and adequate information about the costs of treatment were two effective strategies to mitigate FT. Conclusions: FT is a relatively new challenge in head and neck cancer treatment, whose expenses are higher than therapies for other cancers. A universal method to assess FT and a unified guideline for the administration of questionnaires are needed to mitigate FT and to improve patient outcomes.

Evaluation of DNA methylation levels of SEPT9 and SHOX2 in plasma of patients with head and neck squamous cell carcinoma using droplet digital PCR.

Head and neck squamous cell carcinoma (HNSCC) is the seventh most commonly diagnosed cancer globally. HNSCC develops from the mucosa of the oral cavity, pharynx and larynx. Methylation levels of septin 9 (SEPT9) and short stature homeobox 2 (SHOX2) genes in circulating cell­free DNA (ccfDNA) are considered epigenetic biomarkers and have shown predictive value in preliminary reports in HNSCC. Liquid biopsy is a non­invasive procedure that collects tumor­derived molecules, including ccfDNA. In the present study, a droplet digital PCR (ddPCR)­based assay was developed to detect DNA methylation levels of circulating SEPT9 and SHOX2 in the plasma of patients with HNSCC. The assay was first set up using commercial methylated and unmethylated DNA. The dynamic changes in the methylation levels of SEPT9 and SHOX2 were then quantified in 20 patients with HNSCC during follow­up. The results highlighted: i) The ability of the ddPCR­based assay to detect very low copies of methylated molecules; ii) the significant decrease in SEPT9 and SHOX2 methylation levels in the plasma of patients with HNSCC at the first time points of follow­up with respect to T0; iii) a different trend of longitudinally DNA methylation variations in small groups of stratified patients. The absolute and precise quantification of SEPT9 and SHOX2 methylation levels in HNSCC may be useful for studies with translational potential.

Assessment of the risk of malignancy in Bethesda III thyroid nodules: a comprehensive review.

The increasing prevalence of thyroid cancer emphasizes the need for a thorough assessment of risk of malignancy in Bethesda III nodules. Various methods ranging commercial platforms of molecular genetic testing (including Afirma® GEC, Afirma® GSC, ThyroSeq® V3, RosettaGX®, ThyGeNEXT®/ThyraMIR®, ThyroidPRINT®) to radionuclide scans and ultrasonography have been investigated to provide a more nuanced comprehension of risk estimation. The integration of molecular studies and imaging techniques into clinical practice may provide clinicians with improved and personalized risk assessment. This integrated approach we feel may enable clinicians to carefully tailor interventions, thereby minimizing the likelihood of unnecessary thyroid surgeries and overall crafting the optimal treatment. By aligning with the evolving landscape of personalized healthcare, this comprehensive strategy ensures a patient-centric approach to thyroid nodule and thyroid cancer management.

Compartmental surgery for T4b oral squamous cell carcinoma involving the masticatory space.

PURPOSE OF REVIEW: This review aims to describe the oncological outcomes of T4b oral squamous cell carcinomas (OSCC) with masticatory space involvement as well as the surgical approaches that are able to achieve compartmental 'en bloc' resection of these lesions. RECENT FINDINGS: The masticatory space is subdivided into infra-notch and supra-notch spaces according to the axial plane passing through the mandibular notch between the coronoid process and the condyle neck. Compartmental resection for T4b OSCC with masticatory space invasion can be successfully achieved via purely external approaches or combining external and transnasal endoscopic routes. Infra-notch T4b OSCC showed survival outcomes comparable to T4a OSCC, thus prompting treatment with curative intent. SUMMARY: Compartmental resection of the masticatory space is technically feasible with comprehensive control of tumour margins. Use of a transnasal endoscopic anterior route within a multiportal approach may provide better control of margins at the level of the pterygo-maxillary fissure. Equivalent survival outcomes between T4a and infra-notch T4b OSCC are reported. Thus, a downstaging of the latter to T4a is advisable and compartmental surgery of such advanced lesions could be considered as a first-line treatment option in selected patients.

Head and neck nonmelanoma skin cancers: surgical management and debated issues.

PURPOSE OF REVIEW: This review critically assesses the current literature and guidelines, aiming to clarify some of the most important factors that impact surgical strategies of head and neck nonmelanoma skin cancers (NMSCs), focusing on squamous, basal, and Merkel cell carcinomas. RECENT FINDINGS: Recent developments underscore the complexity of treatment for NMSC, particularly in the head and neck region. There is a lack of high-level evidence for the management of these tumors, especially in advanced stages. The need to tailor the extent of surgical margins and parotid/neck management to different histotypes, considering the varying risk factors for recurrence, is beginning to emerge in the literature. Moreover, the role of immunotherapy and targeted therapies for locally advanced disease, alongside traditional treatment options, is progressively growing. SUMMARY: NMSCs represent a heterogeneous group of malignancies with varying treatment complexities and prognoses. Management of NMSC is evolving towards an increasingly personalized strategy within a multidisciplinary therapeutic framework.

Real-Time Laryngeal Cancer Boundaries Delineation on White Light and Narrow-Band Imaging Laryngoscopy with Deep Learning.

OBJECTIVE: To investigate the potential of deep learning for automatically delineating (segmenting) laryngeal cancer superficial extent on endoscopic images and videos. METHODS: A retrospective study was conducted extracting and annotating white light (WL) and Narrow-Band Imaging (NBI) frames to train a segmentation model (SegMENT-Plus). Two external datasets were used for validation. The model's performances were compared with those of two otolaryngology residents. In addition, the model was tested on real intraoperative laryngoscopy videos. RESULTS: A total of 3933 images of laryngeal cancer from 557 patients were used. The model achieved the following median values (interquartile range): Dice Similarity Coefficient (DSC) = 0.83 (0.70-0.90), Intersection over Union (IoU) = 0.83 (0.73-0.90), Accuracy = 0.97 (0.95-0.99), Inference Speed = 25.6 (25.1-26.1) frames per second. The external testing cohorts comprised 156 and 200 images. SegMENT-Plus performed similarly on all three datasets for DSC (p = 0.05) and IoU (p = 0.07). No significant differences were noticed when separately analyzing WL and NBI test images on DSC (p = 0.06) and IoU (p = 0.78) and when analyzing the model versus the two residents on DSC (p = 0.06) and IoU (Senior vs. SegMENT-Plus, p = 0.13; Junior vs. SegMENT-Plus, p = 1.00). The model was then tested on real intraoperative laryngoscopy videos. CONCLUSION: SegMENT-Plus can accurately delineate laryngeal cancer boundaries in endoscopic images, with performances equal to those of two otolaryngology residents. The results on the two external datasets demonstrate excellent generalization capabilities. The computation speed of the model allowed its application on videolaryngoscopies simulating real-time use. Clinical trials are needed to evaluate the role of this technology in surgical practice and resection margin improvement. LEVEL OF EVIDENCE: III Laryngoscope, 134:2826-2834, 2024.

Thyroid cartilage infiltration in advanced laryngeal cancer: prognostic implications and predictive modelling.

Objective: Detection of laryngeal cartilage invasion is of great importance in staging of laryngeal squamous cell carcinoma (LSCC). The role of prognosticators in locally advanced laryngeal cancer are still widely debated. This study aimed to assess the impact of volume of thyroid cartilage infiltration, as well as other histopathologic variables, on patient survival. Materials and methods: We retrospectively analysed 74 patients affected by pT4 LSCC and treated with total laryngectomy between 2005 and 2021 at the Department of Otorhinolaryngology - Head and Neck Surgery of the University of Brescia, Italy. We considered as potential prognosticators histological grade, perineural (PNI) and lympho-vascular invasion (LVI), thyroid cartilage infiltration, and pTN staging. Pre-operative CT or MRI were analysed to quantify the volume of cartilage infiltration using 3D Slicer software. Results: The 1-, 3-, and 5-year disease free survivals (DFS) were 76%, 66%, and 64%, respectively. Using machine learning models, we found that the volume of thyroid cartilage infiltration had high correlation with DFS. Patients with a higher volume (>670 mm3) of infiltration had a worse prognosis compared to those with a lower volume. Conclusions: Our study confirms the essential role of LVI as prognosticator in advanced LSCC and, more innovatively, highlights the volume of thyroid cartilage infiltration as another promising prognostic factor.

Malignant carotid body tumors: What we know, what we do, and what we need to achieve. A systematic review of the literature.

Malignant carotid body tumors (MCBT) are rare and diagnosed after detection of nodal or distant metastases. This systematic review (SR) focuses on MCBT initially approached by surgery. Preferred Reporting Items for SR and Meta-Analysis (MA) guided the articles search from 2000 to 2023 on PubMed, Scopus, and Web of Science. Among 3548 papers, 132 (337 patients) were considered for SR; of these, 20 (158 patients) for MA. Malignancy rate was 7.3%, succinate dehydrogenase (SDH) mutation 17%, age at diagnosis between 4th and 6th decades, with a higher prevalence of females. MCBTs were mostly Shamblin III, with nodal and distant metastasis in 79.7% and 44.7%, respectively. Malignancy should be suspected if CBT >4 cm, Shamblin III, painful or otherwise symptomatic, at the extremes of age, bilateral, with multifocal disease, and SDHx mutations. Levels II-III clearance should be performed to exclude nodal metastases and adjuvant treatments considered on a case-by-case basis.

Computer-aided designed 3D-printed polymeric scaffolds for personalized reconstruction of maxillary and mandibular defects: a proof-of-concept study.

PURPOSE: To investigate the potential reconstruction of complex maxillofacial defects using computer-aided design 3D-printed polymeric scaffolds by defining the production process, simulating the surgical procedure, and explore the feasibility and reproducibility of the whole algorithm. METHODS: This a preclinical study to investigate feasibility, reproducibility and efficacy of the reconstruction algorithm proposed. It encompassed 3 phases: (1) scaffold production (CAD and 3D-printing in polylactic acid); (2) surgical simulation on cadaver heads (navigation-guided osteotomies and scaffold fixation); (3) assessment of reconstruction (bone and occlusal morphological conformance, symmetry, and mechanical stress tests). RESULTS: Six cadaver heads were dissected. Six types of defects (3 mandibular and 3 maxillary) with different degree of complexity were tested. In all case the reconstruction algorithm could be successfully completed. Bone morphological conformance was optimal while the occlusal one was slightly higher. Mechanical stress tests were good (mean value, 318.6 and 286.4 N for maxillary and mandibular defects, respectively). CONCLUSIONS: Our reconstructive algorithm was feasible and reproducible in a preclinical setting. Functional and aesthetic outcomes were satisfactory independently of the complexity of the defect.

Prognostic Value of Anteroposterior Extension in Oral Tongue and Floor Squamous Cell Carcinoma.

Importance: The tongue and oral floor represent the most involved subsite by oral cancer, and there are no reported systems to classify anteroposterior tumor extension with prognostic effect. In other cancers, the anterior vs posterior tumor extension is a relevant prognostic factor. Objective: To establish whether anterior vs posterior tumor extension may represent a prognostic factor in oral tongue and floor squamous cell carcinoma (OTFSCC). Design, Setting, and Participants: This was a retrospective cohort study of patients who underwent surgery for OTFSCC from January 1, 2010, to December 31, 2021, at 2 tertiary-level academic institutions in Italy (University of Padua and University of Brescia). Patients eligible for the study had histologically proven primary OTFSCC; underwent surgery-based, curative treatment; and had available preoperative contrast-enhanced imaging. Exposures: Four anatomical lines were designed to assess tumor extension: (1) chin-palate line (CPL), (2) chin-basion line, (3) Stensen duct line, and (4) lingual septum line. Preoperative imaging was re-evaluated, and tumor extension was classified as either anterior or posterior according to the lines. Main Outcomes and Measures: Overall survival and time to recurrence (TTR) were evaluated according to tumor extension. These outcomes were reported as 5-year survival rates with 95% CIs. Results: Of the 133 patients included, 79 (59.4%) were male, and the mean (SD) age was 62.7 (15.4) years. The 5-year TTR difference was higher for posterior vs anterior OTFSCC classified according to CPL (21.0%; 95% CI, 8.3%-33.7%), Stensen duct line (15.5%; 95% CI, 1.0%-30.0%), and lingual septum line (17.2%; 95% CI, 2.2%-32.3%). Overall survival analysis showed similar results. At the multivariable analysis on TTR, N status (adjusted hazard ratio [HR], 3.0; 95% CI, 1.2-7.1) and anteroposterior classification according to CPL (adjusted HR, 7.1; 95% CI, 0.9-54.6) were the variables associated with the highest adjusted HRs. Conclusions and Relevance: In this cohort study, OTFSCC with a posterior extension to the CPL was associated with a higher risk of recurrence and death. This analysis suggests that the poor prognosis conveyed by the posterior tumor extension is independent of other relevant prognosticators except for the burden of nodal disease. This estimate is not precise and does not allow for definitive clinically important conclusions; therefore, further prospective studies are necessary to confirm these data.