Artificial Intelligence-Driven Radiomics in Head and Neck Cancer: Current Status and Future Prospects.

BACKGROUND: Radiomics is a rapidly growing field used to leverage medical radiological images by extracting quantitative features. These are supposed to characterize a patient's phenotype, and when combined with artificial intelligence techniques, to improve the accuracy of diagnostic models and clinical outcome prediction. OBJECTIVES: This review aims at examining the application areas of artificial intelligence-based radiomics (AI-based radiomics) for the management of head and neck cancer (HNC). It further explores the workflow of AI-based radiomics for personalized and precision oncology in HNC. Finally, it examines the current challenges of AI-based radiomics in daily clinical oncology and offers possible solutions to these challenges. METHODS: Comprehensive electronic databases (PubMed, Medline via Ovid, Scopus, Web of Science, CINAHL, and Cochrane Library) were searched following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The quality of included studies and their risk of biases were evaluated using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD)and Prediction Model Risk of Bias Assessment Tool (PROBAST). RESULTS: Out of the 659 search hits retrieved, 45 fulfilled the inclusion criteria. Our review revealed that the application of AI-based radiomics model as an ancillary tool for improved decision-making in HNC management includes radiomics-based cancer diagnosis and radiomics-based cancer prognosis. The radiomics-based cancer diagnosis includes tumor staging, tumor grading, and classification of malignant and benign tumors. Similarly, radiomics-based cancer prognosis includes prediction for treatment response, recurrence, metastasis, and survival. In addition, the challenges in the implementation of these models for clinical evaluations include data imbalance, feature engineering (extraction and selection), model generalizability, multi-modal fusion, and model interpretability. CONCLUSION: Considering the highly subjective and interobserver variability that is peculiar to the interpretation of medical images by expert clinicians, AI-based radiomics seeks to offer potentially useful quantitative information, which is not visible to the human eye or unintentionally often remain ignored during clinical imaging practice. By enabling the extraction of this type of information, AI-based radiomics has the potential to revolutionize HNC oncology, providing a platform for more personalized, higher quality, and cost-effective care for HNC patients.

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

INTRODUCTION: Locally advanced oral cavity carcinoma (LAOCSCC) is primarily treated with surgery followed by radiotherapy with or without chemotherapy. METHODS: A review of literature using PubMED was performed for studies reporting the management of LAOCSCC. Based on the reviewed literature and opinions of experts in the field, recommendations were made. RESULTS: Studies have shown that outcomes following resection of T4a and infranotch (inferior to mandibular notch) T4b are comparable. We discuss the concept of compartmental resection of LAOCSCC and issues concerning the management of the neck. Further, patients who refuse or are unable to undergo surgery can be treated with chemoradiotherapy with uncertain outcomes. The role of neoadjuvant chemotherapy has shown promise for organ (mandibular) preservation in a select subset of patients. CONCLUSION: The management strategy for LAOCSCC should be determined in a multidisciplinary setting with emphasis on tumor control, functional preservation, and quality of life of the patient.

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.

Lower Rates of Hypocalcemia Following Near-Infrared Autofluorescence Use in Thyroidectomy: A Meta-Analysis of RCTs.

BACKGROUND: Iatrogenic injury of the parathyroid glands is the most frequent complication after total thyroidectomy. OBJECTIVE: To determine the effectiveness of near-infrared autofluorescence (NIRAF) in reducing postoperative hypocalcemia following total thyroidectomy. METHODS: PubMed, Scopus, and Google Scholar databases were searched. Randomised trials reporting at least one hypocalcemia outcome following total thyroidectomy using NIRAF were included. RESULTS: The qualitative data synthesis comprised 1363 patients from nine randomised studies, NIRAF arm = 636 cases and non-NIRAF arm = 637 cases. There was a statistically significant difference in the overall rate of hypocalcemia log(OR) = -0.7 [(-1.01, -0.40), M-H, REM, CI = 95%] and temporary hypocalcemia log(OR) = -0.8 [(-1.01, -0.59), M-H, REM, CI = 95%] favouring the NIRAF. The difference in the rate of permanent hypocalcemia log(OR) = -1.09 [(-2.34, 0.17), M-H, REM, CI = 95%] between the two arms was lower in the NIRAF arm but was not statistically significant. CONCLUSIONS: NIRAF during total thyroidectomy helps in reducing postoperative hypocalcemia. Level of evidence-1.

Neurological complications of modern radiotherapy for head and neck cancer.

Radiotherapy is one of the mainstay treatment modalities for the management of non-metastatic head and neck cancer (HNC). Notable improvements in treatment outcomes have been observed in the recent decades. Modern radiotherapy techniques, such as intensity-modulated radiotherapy and charged particle therapy, have significantly improved tumor target conformity and enabled better preservation of normal structures. However, because of the intricate anatomy of the head and neck region, multiple critical neurological structures such as the brain, brainstem, spinal cord, cranial nerves, nerve plexuses, autonomic pathways, brain vasculature, and neurosensory organs, are variably irradiated during treatment, particularly when tumor targets are in close proximity. Consequently, a diverse spectrum of late neurological sequelae may manifest in HNC survivors. These neurological complications commonly result in irreversible symptoms, impair patients' quality of life, and contribute to a substantial proportion of non-cancer deaths. Although the relationship between radiation dose and toxicity has not been fully elucidated for all complications, appropriate application of dosimetric constraints during radiotherapy planning may reduce their incidence. Vigilant surveillance during the course of survivorship also enables early detection and intervention. This article endeavors to provide a comprehensive review of the various neurological complications of modern radiotherapy for HNC, summarize the current incidence data, discuss methods to minimize their risks during radiotherapy planning, and highlight potential strategies for managing these debilitating toxicities.

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.

IgG4-related disease: an update on pathology and diagnostic criteria with a focus on salivary gland manifestations.

Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ disorder characterized by a highly variable clinical presentation depending on the affected organ/s, extent of tumefactive fibroinflammatory lesions, and associated functional impairment. The disease pursues a chronic, relapsing, often asymptomatic course and hence may pose a significant diagnostic challenge. Diagnostic delay can lead to progressive fibrosis and irreversible organ damage resulting into significant morbidity and even mortality. Given its broad clinical spectrum, physicians of all specialties may be the first clinicians facing this diagnostic challenge. Outside the pancreatobiliary system, the head and neck represents the major site of IgG4-RD with variable organ-specific diffuse or mass-forming lesions. In up to 75% of cases, elevated serum IgG4 levels are observed, but this figure possibly underestimates the fraction of seronegative cases, as the disease manifestations may present metachronously with significant intervals. Together with negative serology, this can lead to misdiagnosis of seronegative cases. A standardized nomenclature and diagnostic criteria for IgG4-RD were established in 2012 and revised in 2020 facilitating scientific research and expanding the range of diseases associated with IgG4 abnormalities. In addition to orbital pseudotumor, dacryoadenitis, Riedel thyroiditis, sinonasal manifestations, and rare miscellaneous conditions, IgG4-related sialadenitis is one of the most frequent presentations in the head and neck region. However, controversy still exists regarding the relationship between sialadenitis and IgG4-RD. This review focuses on the clinicopathological features of IgG4-related sialadenitis and its contemporary diagnostic criteria.

Poorly differentiated thyroid carcinomas: conceptual controversy and clinical impact.

Poorly differentiated thyroid carcinomas (PDTC) are rare diseases; nevertheless, they account for the majority of deaths from non-anaplastic follicular cell-derived thyroid carcinomas. Establishing the diagnosis and treatment of PDTC is challenging given the low incidence and the lack of standardization of diagnostic criteria. These limitations hamper the ability to compare therapeutic modalities and outcomes between recent and older studies. Recently, the 5th edition of the classification of endocrine tumors has been published, which includes changes in nomenclature and the addition of the disease entity of "differentiated high-grade follicular cell-derived carcinomas". On the other hand, the recently witnessed advances in molecular diagnostics have enriched therapeutic options and improved prognosis for patients. We herein review the various historical variations and evolution in the diagnostic criteria for PDTC. This systematic review attempts to clarify the evolution of the histological and molecular characteristics of this disease, its prognosis, as well as its treatment options.

Update on olfactory neuroblastoma.

Olfactory neuroblastomas are uncommon malignancies that arise from olfactory receptor cells located high in the nasal cavity. Accurate diagnosis plays a crucial role in determining clinical results and guiding treatment decisions. Diagnosis can be a major challenge for pathologists, especially when dealing with tumours with poor differentiation. The discovery of several molecular and immunohistochemical markers would help to overcome classification difficulties. Due to the paucity of large-scale studies, standardisation of diagnosis, treatment and prediction of outcome remains a challenge. Surgical resection by endoscopic techniques with the addition of postoperative irradiation is the treatment of choice. In addition, it is advisable to consider elective neck irradiation to minimise the risk of nodal recurrence. Molecular characterisation will help not only to make more accurate diagnoses but also to identify specific molecular targets that can be used to develop personalised treatment options tailored to each patient. The present review aims to summarise the current state of knowledge on histopathological diagnosis, the molecular biology and management of this disease.

The prognostic role of single cell invasion and nuclear diameter in early oral tongue squamous cell carcinoma.

BACKGROUND: The clinical significance of single cell invasion and large nuclear diameter is not well documented in early-stage oral tongue squamous cell carcinoma (OTSCC). METHODS: We used hematoxylin and eosin-stained sections to evaluate the presence of single cell invasion and large nuclei in a multicenter cohort of 311 cases treated for early-stage OTSCC. RESULTS: Single cell invasion was associated in multivariable analysis with poor disease-specific survival (DSS) with a hazard ratio (HR) of 2.089 (95% CI 1.224-3.566, P = 0.007), as well as with disease-free survival (DFS) with a HR of 1.666 (95% CI 1.080-2.571, P = 0.021). Furthermore, large nuclei were associated with worse DSS (HR 2.070, 95% CI 1.216-3.523, P = 0.007) and with DFS in multivariable analysis (HR 1.645, 95% CI 1.067-2.538, P = 0.024). CONCLUSION: Single cell invasion and large nuclei can be utilized for classifying early OTSCC into risk groups.

Liprin-α1 contributes to oncogenic MAPK signaling by counteracting ERK activity.

PTPRF interacting protein alpha 1 (PPFIA1) encodes for liprin-α1, a member of the leukocyte common antigen-related protein tyrosine phosphatase (LAR-RPTPs)-interacting protein family. Liprin-α1 localizes to adhesive and invasive structures in the periphery of cancer cells, where it modulates migration and invasion in head and neck squamous cell carcinoma (HNSCC) and breast cancer. To study the possible role of liprin-α1 in anticancer drug responses, we screened a library of oncology compounds in cell lines with high endogenous PPFIA1 expression. The compounds with the highest differential responses between high PPFIA1-expressing and silenced cells across cell lines were inhibitors targeting mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinases (ERK) signaling. KRAS proto-oncogene, GTPase (KRAS)-mutated MDA-MB-231 cells were more resistant to trametinib upon PPFIA1 knockdown compared with control cells. In contrast, liprin-α1-depleted HNSCC cells with low RAS activity showed a context-dependent response to MEK/ERK inhibitors. Importantly, we showed that liprin-α1 depletion leads to increased p-ERK1/2 levels in all our studied cell lines independent of KRAS mutational status, suggesting a role of liprin-α1 in the regulation of MAPK oncogenic signaling. Furthermore, liprin-α1 depletion led to more pronounced redistribution of RAS proteins to the cell membrane. Our data suggest that liprin-α1 is an important contributor to oncogenic RAS/MAPK signaling, and the status of liprin-α1 may assist in predicting drug responses in cancer cells in a context-dependent manner.

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.

Interpretable machine learning model for prediction of overall survival in laryngeal cancer.

Background: The mortality rates of laryngeal squamous cell carcinoma cancer (LSCC) have not significantly decreased in the last decades.Objectives: We primarily aimed to compare the predictive performance of DeepTables with the state-of-the-art machine learning (ML) algorithms (Voting ensemble, Stack ensemble, and XGBoost) to stratify patients with LSCC into chance of overall survival (OS). In addition, we complemented the developed model by providing interpretability using both global and local model-agnostic techniques.Methods: A total of 2792 patients in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with LSCC were reviewed. The global model-agnostic interpretability was examined using SHapley Additive exPlanations (SHAP) technique. Likewise, individual interpretation of the prediction was made using Local Interpretable Model Agnostic Explanations (LIME).Results: The state-of-the-art ML ensemble algorithms outperformed DeepTables. Specifically, the examined ensemble algorithms showed comparable weighted area under receiving curve of 76.9, 76.8, and 76.1 with an accuracy of 71.2%, 70.2%, and 71.8%, respectively. The global methods of interpretability (SHAP) demonstrated that the age of the patient at diagnosis, N-stage, T-stage, tumor grade, and marital status are among the prominent parameters.Conclusions: A ML model for OS prediction may serve as an ancillary tool for treatment planning of LSCC patients.

Prognostic Significance of Tumor-associated Stroma in Nasopharyngeal Carcinoma: A Multicenter Study.

Assessment of tumor-associated stroma has shown a reliable prognostic value in recent research. We evaluated the prognostic value of tumor-stroma ratio (TSR) in a large multicenter cohort of nasopharyngeal carcinoma (NPC). We used the conventional hematoxylin and eosin-stained slides of 115 cases of NPC to assess TSR as described in recent guidelines. The amount of tumor-associated stroma was assessed as a percentage and then tumors were classified as stroma-high (>50%) or stroma-low (≤50%). Kaplan-Meier curves, χ 2 test, and Cox regression univariable and multivariable analyses were carried out. A total of 48 (41.7%) tumors were stroma-high and 67 (58.3%) tumors were stroma-low. In the Cox regression multivariable analysis, the tumors categorized as stroma-high were associated with a worse overall survival with a hazard ratio of 2.30 (95% CI: 1.27-4.15, P =0.006) and with poor disease-specific survival (hazard ratio=1.87, 95% CI: 1.07-3.28, P =0.029). The assessment of TSR in NPC is simple and cost-effective, and it has a significant prognostic value. TSR can aid in risk stratification and clinical decision-making in NPC.

Comparing Mohs micrographic surgery and wide local excision in the management of head and neck dermatofibrosarcoma protuberans: a scoping review.

Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma with a propensity for recurrence. Its management, particularly in the head and neck (H&N) region, presents unique challenges. This study aimed to evaluate the effectiveness of Mohs micrographic surgery (MMS) compared to wide local excision (WLE) in treating H&N DFSP and its impact on recurrence rates and tissue preservation. A comprehensive search was conducted in PubMed/MEDLINE, yielding 29 relevant studies. We included studies comparing MMS and WLE in adult patients with H&N DFSP and reporting local recurrence outcomes. Data were analyzed using random effects analysis, with a meta-analysis performed for comparative studies. Analysis of studies demonstrated a lower recurrence for MMS. Comparative analysis of five studies involving 117 patients showed a significantly lower recurrence rate in the MMS group (2%) compared to the WLE group (19%). Margin status varied between studies, with some achieving negative margins at shorter distances. In the management of H&N DFSP, MMS has emerged as a superior surgical technique, consistently associated with reduced recurrence rates and the potential for tissue preservation. The adoption of MMS should be considered for its capacity to achieve negative margins with fewer processing steps, particularly in anatomically complex regions like the H&N.

A Meta-analysis of Surgical Outcomes of T4a and Infranotch T4b Oral Cancers.

OBJECTIVE: To determine the overall surgical outcomes of infranotch T4b oral cancers and compare them with T4a oral cancers. METHODS: PubMed, EMBASE and Cochrane databases from 2000 to 2022 were systematically searched. Clinical studies reporting at least one outcome following curative surgery and adjuvant therapy for comparison of patients with either infranotch T4b (IN-T4b) or T4a tumour. The heterogeneity of the included studies was determined using Tau-squared, Chi-squared, and the Higgins I2 test. The random effects model was used to determine the log odds ratio (logOR). RESULTS: The systematic review comprised 11,790 patients from 16 included studies. Seven studies were included in the meta-analysis (n = 11,381). For IN-T4b patients, the pooled 2 and 5 year overall survival (OS) were 59.3% and 53.2%, 2 and 5 year disease-free survival (DFS) 57.9% and 48.4%, 2 and 5 year disease-specific survival (DSS) 72% and 68%, and 2 and 5 year local control (LC), 47% and 56%, respectively. There was no statistically significant difference in 2 year OS [logOR = 0.28 (-0.47, 1.03), p = 0.46, confidence interval (CI) = 95%], 5 year OS [logOR = 0.7 (-0.4, 1.8), p = 0.54, CI = 95%], 2 year DFS [logOR = 0.22 (-0.35, 0.79), p = 0.45, CI = 95%], 5 year DFS [logOR = 0.17 (-0.42, 0.77), p = 0.57, CI = 95%], 2 year LC [logOR = 0.47 (-0.33, 1.26), p = 0.25, CI = 95%] and 5 year LC [logOR = 0.34 (-0.31, 0.99), p = 0.31, CI = 95%] between IN-T4b and T4a oral cancers. CONCLUSION: Results of this meta-analysis suggest that IN-T4b oral cancers have similar outcomes to T4a oral cancers, which supports down-staging IN-T4b cancers to T4a cancers.

Review of Outcomes after Salvage Surgery for Recurrent Squamous Cell Carcinoma of the Head and Neck.

Surgery with adjuvant chemoradiotherapy or chemoradiotherapy is the mainstay in treatment for advanced stage head and neck squamous cell carcinoma; however, locoregional recurrences are frequent. Salvage surgery could be proposed in selected patients to improve local control, disease-free, and overall survival. Factors for improved disease-free and overall survival in patients treated with salvage surgery include age, tumor location, the initial T stage, HPV status, resection margins, and the time elapsing from the initial treatment. Clinical trials with adjuvant therapies have shown promise after salvage surgery in terms of tolerance and response, but clinical guidelines for using these adjuvant treatments are currently lacking. The aim of this review is to present current knowledge concerning the incidence and management of recurrent head and neck squamous cell carcinoma and current data concerning survival and morbidity after salvage surgery.

Iron, Ferroptosis, and Head and Neck Cancer.

Ferroptosis is an iron-dependent regulatory form of cell death characterized by the accumulation of intracellular reactive oxygen species and lipid peroxidation. It plays a critical role not only in promoting drug resistance in tumors, but also in shaping therapeutic approaches for various malignancies. This review aims to elucidate the relationship between ferroptosis and head and neck cancer treatment by discussing its conceptual framework, mechanism of action, functional aspects, and implications for tumor therapy. In addition, this review consolidates strategies aimed at improving the efficacy of head and neck cancer treatment through modulation of ferroptosis, herein serving as a valuable reference for advancing the treatment landscape for this patient population.