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.

Development and Validation of an Automated Image-Based Deep Learning Platform for Sarcopenia Assessment in Head and Neck Cancer.

Importance: Sarcopenia is an established prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC); the quantification of sarcopenia assessed by imaging is typically achieved through the skeletal muscle index (SMI), which can be derived from cervical skeletal muscle segmentation and cross-sectional area. However, manual muscle segmentation is labor intensive, prone to interobserver variability, and impractical for large-scale clinical use. Objective: To develop and externally validate a fully automated image-based deep learning platform for cervical vertebral muscle segmentation and SMI calculation and evaluate associations with survival and treatment toxicity outcomes. Design, Setting, and Participants: For this prognostic study, a model development data set was curated from publicly available and deidentified data from patients with HNSCC treated at MD Anderson Cancer Center between January 1, 2003, and December 31, 2013. A total of 899 patients undergoing primary radiation for HNSCC with abdominal computed tomography scans and complete clinical information were selected. An external validation data set was retrospectively collected from patients undergoing primary radiation therapy between January 1, 1996, and December 31, 2013, at Brigham and Women's Hospital. The data analysis was performed between May 1, 2022, and March 31, 2023. Exposure: C3 vertebral skeletal muscle segmentation during radiation therapy for HNSCC. Main Outcomes and Measures: Overall survival and treatment toxicity outcomes of HNSCC. Results: The total patient cohort comprised 899 patients with HNSCC (median [range] age, 58 [24-90] years; 140 female [15.6%] and 755 male [84.0%]). Dice similarity coefficients for the validation set (n = 96) and internal test set (n = 48) were 0.90 (95% CI, 0.90-0.91) and 0.90 (95% CI, 0.89-0.91), respectively, with a mean 96.2% acceptable rate between 2 reviewers on external clinical testing (n = 377). Estimated cross-sectional area and SMI values were associated with manually annotated values (Pearson r = 0.99; P < .001) across data sets. On multivariable Cox proportional hazards regression, SMI-derived sarcopenia was associated with worse overall survival (hazard ratio, 2.05; 95% CI, 1.04-4.04; P = .04) and longer feeding tube duration (median [range], 162 [6-1477] vs 134 [15-1255] days; hazard ratio, 0.66; 95% CI, 0.48-0.89; P = .006) than no sarcopenia. Conclusions and Relevance: This prognostic study's findings show external validation of a fully automated deep learning pipeline to accurately measure sarcopenia in HNSCC and an association with important disease outcomes. The pipeline could enable the integration of sarcopenia assessment into clinical decision making for individuals with HNSCC.

Fully-automated sarcopenia assessment in head and neck cancer: development and external validation of a deep learning pipeline.

Purpose: Sarcopenia is an established prognostic factor in patients diagnosed with head and neck squamous cell carcinoma (HNSCC). The quantification of sarcopenia assessed by imaging is typically achieved through the skeletal muscle index (SMI), which can be derived from cervical neck skeletal muscle (SM) segmentation and cross-sectional area. However, manual SM segmentation is labor-intensive, prone to inter-observer variability, and impractical for large-scale clinical use. To overcome this challenge, we have developed and externally validated a fully-automated image-based deep learning (DL) platform for cervical vertebral SM segmentation and SMI calculation, and evaluated the relevance of this with survival and toxicity outcomes. Materials and Methods: 899 patients diagnosed as having HNSCC with CT scans from multiple institutes were included, with 335 cases utilized for training, 96 for validation, 48 for internal testing and 393 for external testing. Ground truth single-slice segmentations of SM at the C3 vertebra level were manually generated by experienced radiation oncologists. To develop an efficient method of segmenting the SM, a multi-stage DL pipeline was implemented, consisting of a 2D convolutional neural network (CNN) to select the middle slice of C3 section and a 2D U-Net to segment SM areas. The model performance was evaluated using the Dice Similarity Coefficient (DSC) as the primary metric for the internal test set, and for the external test set the quality of automated segmentation was assessed manually by two experienced radiation oncologists. The L3 skeletal muscle area (SMA) and SMI were then calculated from the C3 cross sectional area (CSA) of the auto-segmented SM. Finally, established SMI cut-offs were used to perform further analyses to assess the correlation with survival and toxicity endpoints in the external institution with univariable and multivariable Cox regression. Results: DSCs for validation set (n = 96) and internal test set (n = 48) were 0.90 (95% CI: 0.90 - 0.91) and 0.90 (95% CI: 0.89 - 0.91), respectively. The predicted CSA is highly correlated with the ground-truth CSA in both validation (r = 0.99, p < 0.0001) and test sets (r = 0.96, p < 0.0001). In the external test set (n = 377), 96.2% of the SM segmentations were deemed acceptable by consensus expert review. Predicted SMA and SMI values were highly correlated with the ground-truth values, with Pearson r ß 0.99 (p < 0.0001) for both the female and male patients in all datasets. Sarcopenia was associated with worse OS (HR 2.05 [95% CI 1.04 - 4.04], p = 0.04) and longer PEG tube duration (median 162 days vs. 134 days, HR 1.51 [95% CI 1.12 - 2.08], p = 0.006 in multivariate analysis. Conclusion: We developed and externally validated a fully-automated platform that strongly correlates with imaging-assessed sarcopenia in patients with H&N cancer that correlates with survival and toxicity outcomes. This study constitutes a significant stride towards the integration of sarcopenia assessment into decision-making for individuals diagnosed with HNSCC. SUMMARY STATEMENT: In this study, we developed and externally validated a deep learning model to investigate the impact of sarcopenia, defined as the loss of skeletal muscle mass, on patients with head and neck squamous cell carcinoma (HNSCC) undergoing radiotherapy. We demonstrated an efficient, fullyautomated deep learning pipeline that can accurately segment C3 skeletal muscle area, calculate cross-sectional area, and derive a skeletal muscle index to diagnose sarcopenia from a standard of care CT scan. In multi-institutional data, we found that pre-treatment sarcopenia was associated with significantly reduced overall survival and an increased risk of adverse events. Given the increased vulnerability of patients with HNSCC, the assessment of sarcopenia prior to radiotherapy may aid in informed treatment decision-making and serve as a predictive marker for the necessity of early supportive measures.

Clinical significance of overall assessment of tumor-infiltrating lymphocytes in oropharyngeal cancer: A meta-analysis.

BACKGROUND: The overall assessment of tumor-infiltrating lymphocytes (TILs) evaluated using hematoxylin and eosin (HE) staining has been recently studied in oropharyngeal squamous cell carcinoma (OPSCC). METHODS: We conducted a systematic review of Scopus, Ovid Medline, PubMed, Web of Science, and Cochrane Library to retrieve studies assessing TILs in HE-stained sections of OPSCC. We used fixed-effect models and random-effect models to estimate the pooled hazard ratios (HRs) and confidence intervals (CIs) for disease-free survival (DFS), overall survival (OS) and disease-specific survival (DSS). RESULTS: Eleven studies were identified that had analyzed the prognostic significance of TILs in OPSCC using HE-stained specimens. Our meta-analyses showed that a high infiltration of TILs was significantly associated with improved DFS (HR 0.39, 95%CI 0.24-0.65, P = 0.0003), OS (HR 0.38, 95%CI 0.29-0.50, P < 0.0001), and DSS (HR 0.32, 95%CI 0.19-0.53, P < 0.0001). CONCLUSION: Findings of our meta-analysis support a growing body of evidence indicating that assessment of TILs in OPSCC using HE-stained sections has reliable prognostic value. The clinical significance of such assessment of TILs has been reported repeatedly in many studies on OPSCC. The assessment is cost-effective, feasible, easy to transfer from lab to clinic, and therefore can be incorporated in daily practice.

Overall assessment of tumor-infiltrating lymphocytes in head and neck squamous cell carcinoma: time to take notice.

Background: The immune response has an important role in cancer progression. At the same time, anti-tumor effect of the immune response has been speculated to cause destruction of cancer cells. Recent studies have highlighted the significance of tumor-infiltrating lymphocytes (TILs) in different cancers. The International Immuno-Oncology Biomarkers Working Group has in 2017 published a practical review proposing a standardized method to assess TILs in the routine hematoxylin and eosin (HE) stained sections.Aims/objectives: To discuss the association between TILs and survival in head and neck squamous cell carcinoma (HNSCC).Material and methods: We review recent studies having assessed TILs in HNSCC and showing that tumors having low TILs associate significantly with worse survival.Results: These findings underline that HNSCC cases with low TILs might benefit from multimodality treatment and might be indicated to receive immunotherapy.Conclusions: The evaluation of TILs using routine HE-stained sections is practical and can be considered in assessment of antitumor activity.Significance: Here, we highlight the impact of overall assessment of TILs using the routine HE-stained specimens in HNSCC.

Assessment of Tumor-infiltrating Lymphocytes Predicts the Behavior of Early-stage Oral Tongue Cancer.

Tumor-infiltrating lymphocytes (TILs) have shown a promising prognostic value in many epithelial cancers. We sought to assess the prognostic value of TILs in a multicenter cohort of early oral tongue squamous cell carcinoma (OTSCC). The percentage of TILs was assessed on the surgical resection slides stained with hematoxylin and eosin. The assessment of TILs was performed in the stromal compartment and in the intraepithelial compartment (at the invasive front and at the center of the tumor). We followed the method that was described recently by the International Immuno-Oncology Biomarker Working Group for the assessment of TILs. A total of 308 cases from the 5 Finnish university hospitals and from A.C. Camargo Cancer Center, São Paulo, Brazil, were included. We found a promising prognostic value for stromal TILs at the invasive front in the multivariable analysis with a hazard ratio of 2.61 (95% confidence interval [CI], 1.77-3.83; P<0.001) for overall survival, 1.99 (95% CI, 1.07-3.69; P=0.040) for disease-specific survival, and 1.94 (95% CI, 1.14-3.29; P=0.020) for disease-free survival. In conclusion, evaluation of TILs is simple and can aid in identifying the high-risk cases of early OTSCC. The method introduced by the International Immuno-Oncology Biomarker Working Group can be used for standardized determination of TILs in early OTSCC.

NRS-2002 for pre-treatment nutritional risk screening and nutritional status assessment in head and neck cancer patients.

BACKGROUND: The aim of this study was to assess the value of nutritional risk screening-2002 (NRS-2002) as a nutritional risk screening and status assessment method and to compare it with nutritional status assessed by subjective and objective methods in the screening of head and neck cancer patients. METHODS: Sixty-five consecutive patients (50 male), with a median age of 61 years (range, 33-77), with head and neck squamous cell carcinoma (HNSCC) were enrolled prior to cancer therapy. Nutritional status was assessed by NRS-2002, patient-generated subjective global assessment (PG-SGA), handgrip strength (HGS) and mid-arm muscle area (MAMA). RESULTS: Twenty-eight percent of patients were at nutritional risk based on NRS-2002, and 34 % were malnourished according to PG-SGA, while 43 % had low HGS. NRS-2002 cut-off score of ≥3 compared with the nutritional status according to PG-SGA showed 77 % specificity and 98 % sensitivity (K = 0.78). NRS-2002 was able to predict malnutrition (PG-SGA BC) both in men (p < 0.001) and in women (p < 0.05). NRS-2002 identified correctly patients with malnutrition with a score of ≥3 (p < 0.001) and risk patients with a score of ≥2 (p < 0.001). CONCLUSIONS: These results suggest that NRS-2002 seems to be a reliable indicator of malnutrition, while NRS-2002 with the cut-off score of ≥2 seems to be more reliable for nutrition screening in head and neck cancer patients prior to oncological treatment.

FDG-PET/CT in the Assessment of Treatment Response after Oncologic Treatment of Head and Neck Squamous Cell Carcinoma.

BACKGROUND: In many centers, (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used to monitor treatment response after definitive (chemo)radiotherapy [(C)RT] for head and neck squamous cell carcinoma (HNSCC), but its usefulness remains somewhat controversial. We aimed at assessing the accuracy of FDG-PET/CT in detecting residual disease after (C)RT. METHOD: All HNSCC patients with FDG-PET/CT performed to assess treatment response 10-18 weeks after definitive (C)RT at our institution during 2008-2010 were included. The patient charts were reviewed for FDG-PET/CT findings, histopathologic findings, and follow-up data. The median follow-up time for FDG-PET/CT negative patients was 26 months. RESULTS: Eighty-eight eligible patients were identified. The stage distribution was as follows: I, n = 1; II, n = 15; III, n = 17; IV, n = 55. The negative predictive value, positive predictive value, specificity, sensitivity, and accuracy of FDG-PET/CT in detecting residual disease were 87%, 81%, 94%, 65%, and 85%, respectively. The corresponding specific figures for the primary tumor site were 91%, 71%, 94%, 59%, and 86% and for the neck 93%, 100%, 100%, 75%, and 94%, respectively. CONCLUSIONS: In patients who have received definitive (C)RT for HNSCC, post-treatment FDG-PET/CT has good potential to guide clinical decision-making. Patients with negative scan can safely be followed up clinically only, while positive scan necessitates tissue biopsies or a neck dissection to rule out residual disease.

A novel classification and online platform for planning and documentation of medical applications of additive manufacturing.

Additive manufacturing technologies are widely used in industrial settings and now increasingly also in several areas of medicine. Various techniques and numerous types of materials are used for these applications. There is a clear need to unify and harmonize the patterns of their use worldwide. We present a 5-class system to aid planning of these applications and related scientific work as well as communication between various actors involved in this field. An online, matrix-based platform and a database were developed for planning and documentation of various solutions. This platform will help the medical community to structurally develop both research innovations and clinical applications of additive manufacturing. The online platform can be accessed through http://www.medicalam.info.

The impact of pretreatment assessment of oropharynx on interstitial soft palate radiofrequency surgery outcome--a multi-center study in patients with habitual snoring.

PURPOSE: Interstitial radiofrequency (RF) surgery of the soft palate (SP) is an established option in the treatment of habitual snoring. The decision-making process in the management of habitual snoring would benefit from diagnostic guidelines for oropharyngeal findings. Our aim was to investigate the correlation of systematic clinical pretreatment oropharyngeal examination scores with the efficacy of interstitial RF surgery of SP in a multi-center study. METHODS: Seventy-four patients (58 (78%) males and 16 (22%) females) with the median age of 42 years (range, 23-64), pre-treatment BMI of 25.6 kg/m(2) (range, 20.0-28.0), and preoperative AHI of three events/h (range, 0-10), received a single session of RF surgery. Thirty-two, five, 16, and 21 patients, respectively, were treated at the participating centers with a follow-up time of 13 weeks (range 12-16). The primary outcome measure was the efficacy of the treatment on snoring assessed by the patient and the bed partner with visual analog scale (VAS). RESULTS: The snoring showed a significant change demonstrating decreased snoring (VASpatpre 7 (range, 5-10) ≥VASpatpost 4.25 (range, 1-8), P < 0.001, VASbedppre 8 (range, 4-10) ≥VASbedppost 5 (range, 1-10), P < 0.001). Twenty-one patients (28.4%) experienced a successful treatment outcome. The increased grade of the uvula had a negative impact on the snoring results. CONCLUSION: Systematic clinical pretreatment oropharyngeal examination scores showed that the increasing grade of the uvula correlated significantly with the short-term post-treatment change in snoring. We suggest that patients with habitual snoring and uvula grade III should be initially treated with SP interstitial RF surgery and concomitant uvular surgery. A grading tool is proposed for oropharyngeal examination to help in the most appropriate treatment decision for each individual snoring patient.