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International Journal of Medical... Jul 2023In recent years, there has been a surge in machine learning-based models for diagnosis and prognostication of outcomes in oncology. However, there are concerns relating...
BACKGROUND
In recent years, there has been a surge in machine learning-based models for diagnosis and prognostication of outcomes in oncology. However, there are concerns relating to the model's reproducibility and generalizability to a separate patient cohort (i.e., external validation).
OBJECTIVES
This study primarily provides a validation study for a recently introduced and publicly available machine learning (ML) web-based prognostic tool (ProgTOOL) for overall survival risk stratification of oropharyngeal squamous cell carcinoma (OPSCC). Additionally, we reviewed the published studies that have utilized ML for outcome prognostication in OPSCC to examine how many of these models were externally validated, type of external validation, characteristics of the external dataset, and diagnostic performance characteristics on the internal validation (IV) and external validation (EV) datasets were extracted and compared.
METHODS
We used a total of 163 OPSCC patients obtained from the Helsinki University Hospital to externally validate the ProgTOOL for generalizability. In addition, PubMed, OvidMedline, Scopus, and Web of Science databases were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
The ProgTOOL produced a predictive performance of 86.5% balanced accuracy, Mathew's correlation coefficient of 0.78, Net Benefit (0.7) and Brier score (0.06) for overall survival stratification of OPSCC patients as either low-chance or high-chance. In addition, out of a total of 31 studies found to have used ML for the prognostication of outcomes in OPSCC, only seven (22.6%) reported a form of EV. Three studies (42.9%) each used either temporal EV or geographical EV while only one study (14.2%) used expert as a form of EV. Most of the studies reported a reduction in performance when externally validated.
CONCLUSION
The performance of the model in this validation study indicates that it may be generalized, therefore, bringing recommendations of the model for clinical evaluation closer to reality. However, the number of externally validated ML-based models for OPSCC is still relatively small. This significantly limits the transfer of these models for clinical evaluation and subsequently reduces the likelihood of the use of these models in daily clinical practice. As a gold standard, we recommend the use of geographical EV and validation studies to reveal biases and overfitting of these models. These recommendations are poised to facilitate the implementation of these models in clinical practice.
Topics: Humans; Artificial Intelligence; Reproducibility of Results; Prognosis; Oropharyngeal Neoplasms; Risk Assessment; Carcinoma
PubMed: 37094545
DOI: 10.1016/j.ijmedinf.2023.105064 -
Oral Oncology May 2023To estimate the prevalence of two most common and mutually exclusive -124 C > T and -146 C > T TERT promoter mutations in HNSCC and analyse their prognostic role. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To estimate the prevalence of two most common and mutually exclusive -124 C > T and -146 C > T TERT promoter mutations in HNSCC and analyse their prognostic role.
MATERIALS AND METHODS
The databases Medline (via Ovid), Embase (via Ovid), Cochrane Library, Scopus, and Web of Science (Core Collection) were searched from inception to December 2022 to identify studies analysing TERT promoter mutations in HNSCC. Pooled prevalence of TERT promoter mutations and hazard ratio (sHR) of death/progression, with corresponding confidence intervals (CI), were estimated.
RESULTS
The initial search returned 6416 articles, of which 17 studies, including 1830 patients, met the criteria for prevalence meta-analysis. Among them, 8 studies fitted the inclusion criterion to analyse the prognostic impact of TERT promoter mutations. Overall, 21% (95% CI: 12%-31%) of HNSCCs harboured TERT promoter mutation. TERT promoter mutations were more commonly found in oral cavity cancer (prevalence = 47%, 95% CI: 33%-61%), followed by laryngeal/hypopharyngeal cancer (prevalence = 12%, 95% CI: 4%-25%), while they were quite rare in oropharyngeal cancer (prevalence = 1%, 95% CI: 0%-4%). TERT promoter mutation -124 C > T was associated with a higher risk of death (sHR = 2.01, 95% CI: 1.25-3.23) and progression (sHR = 2.79, 95% CI: 1.77-4.40), while -146 C > T TERT promoter mutation did not show any significant correlation neither to overall nor progression-free survival.
CONCLUSION
TERT promoter mutations were mainly topographically restricted to oral cavity cancer. -124 C > T was the most common TERT promoter mutation and was significantly associated to worse outcome in HNSCC.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Prognosis; Prevalence; Mouth Neoplasms; Laryngeal Neoplasms; Telomerase; Head and Neck Neoplasms; Mutation
PubMed: 37075587
DOI: 10.1016/j.oraloncology.2023.106398 -
European Archives of... Jul 2023Minimally invasive surgery is today the main challenge of ENT surgeons who aim to achieve oncological radicality with less aesthetic and functional impact. This is the...
INTRODUCTION
Minimally invasive surgery is today the main challenge of ENT surgeons who aim to achieve oncological radicality with less aesthetic and functional impact. This is the basis for the widespread transoral surgical techniques, as the Thunderbeat.
OBJECTIVE
To date, the use of Thunderbeat in transoral surgery is still little known and widespread. So, this study analyzes, with a systematic review, current literature about the transoral use of Thunderbeat and shows our case studies.
METHODS
The research was carried out on Pubmed, Scopus, Web of Science and Cochrane databases using specific keywords. Then, a retrospective study was carried out on 10 patients who underwent transoral surgery by Thunderbeat in our ENT Clinic. Both in our cases and in the systematic review the following parameters have been evaluated: treated anatomical site and subsite, histological diagnosis, type of surgery, duration of nasogastric tube and hospitalization, post-operative complications, tracheostomy, resection margin status.
RESULTS
The review included 3 articles that described transoral use of Thunderbeat for a total of 31 patients suffering from oropharyngeal, hypopharyngeal and/or laryngeal carcinoma. Nasogastric tube was removed after 21.5 days on average, temporary tracheostomy was performed in 6 patients. The main complications were: bleeding (12.90%) and pharyngocutaneous fistula (29.03%). Thunderbeat shaft was 35 cm long and 5 mm large. Our case studies included 5 males and 5 females, mean age 64.4 ± 10.28, with oropharyngeal or supraglottic carcinoma, parapharyngeal pleomorphic adenoma and cavernous hemangioma of the tongue base. Temporary tracheostomy was performed in 8 patients. Free resection margins were achieved in all cases (100%). No peri-operative complications occurred. Nasogastric tube was removed after 5.3 ± 2 days on average. All patients were discharged without tracheal tube and NGT after 18.2 ± 4.72 days on average.
CONCLUSION
This study demonstrated that Thunderbeat has several advantages over other transoral surgical approaches, such as CO2 laser and robotic surgery, in terms of best combination of oncological and functional success, less post-operative complications and costs. So, it could represent a step forward in transoral surgery.
Topics: Male; Female; Humans; Middle Aged; Aged; Carcinoma, Squamous Cell; Retrospective Studies; Laryngeal Neoplasms; Hypopharynx; Larynx; Robotic Surgical Procedures; Postoperative Complications; Treatment Outcome
PubMed: 37014427
DOI: 10.1007/s00405-023-07944-8 -
JAMA Network Open Feb 2023Ipsilateral neck radiotherapy (RT) is controversial in some patients with tonsil cancer due to concern for nodal failure within the contralateral nonirradiated neck... (Meta-Analysis)
Meta-Analysis
Association of Unilateral Radiotherapy With Contralateral Lymph Node Failure Among Patients With Squamous Cell Carcinoma of the Tonsil: A Systematic Review and Meta-analysis.
IMPORTANCE
Ipsilateral neck radiotherapy (RT) is controversial in some patients with tonsil cancer due to concern for nodal failure within the contralateral nonirradiated neck (hereinafter referred to as contralateral neck failure [CNF]).
OBJECTIVE
To determine the rate of CNF following ipsilateral neck RT in patients with tonsil cancer.
DATA SOURCES
Databases including PubMed, Embase, Web of Science, and Cochrane Library were queried for peer-reviewed, English language articles published between January 1, 1980, and December 31, 2021.
STUDY SELECTION
Studies reporting rates of CNF from at least 20 patients treated with ipsilateral neck RT. Studies were excluded if they lacked full text, reported results from databases or systematic reviews, or did not provide RT details.
DATA EXTRACTION AND SYNTHESIS
Data were extracted following the PRISMA reporting guideline. Study quality was assessed using criteria from a methodological index for nonrandomized studies. Pooled outcomes were estimated using random-effects models.
MAIN OUTCOMES AND MEASURES
Primary outcome was the pooled rate of CNF following ipsilateral neck RT. Secondary outcomes were the pooled rates of CNF by tumor and nodal staging categories from the 7th edition of the AJCC Cancer Staging Manual and rates of toxic effects.
RESULTS
A total of 17 studies (16 retrospective and 1 prospective) including 1487 unique patients were identified. The pooled risk of CNF was 1.9% (95% CI, 1.2%-2.6%). The rate of CNF by tumor (T) category was as follows: 1.3% (95% CI, 0.3%-2.3%) for T1; 3.0% (95% CI, 1.6%-4.4%) for T2; 11.3% (95% CI, 3.3%-19.2%) for T3; and 16.0% (95% CI, -7.8% to 39.8%) for T4. Patients with T3 to T4 tumors had a significantly higher rate of CNF than those with T1 to T2 tumors (11.5% [95% CI, 3.9%-19.1%] vs 1.8% [95% CI, 1.0%-2.6%]; P < .001). The rate of CNF by nodal (N) category was 1.2% (95% CI, 0.1%-2.2%) for N0; 4.8% (95% CI, 2.4%-7.2%) for N1; 3.1% (95% CI, 0.4%-5.8%) for N2a; 3.1% (95% CI, 1.2%-4.9%) for N2b; and 0 (95% CI, not applicable) for N3. Rates of CNF were similar for patients with N2b to N3 and N0 to N2a disease (3.0% [95% CI, 1.2%-4.7%] vs 1.7% [95% CI, 0.6%-2.8%], respectively; P = .07). Compared with bilateral RT, ipsilateral RT was associated with increased risk of CNF (log odds ratio, 1.29 [95% CI, 0.09-2.48]; P = .04). The crude rates of xerostomia of grade 3 or greater and feeding tube use were 0.9% (95% CI, -0.2% to 1.9%) and 13.3% (95% CI, 8.3%-18.3%), respectively.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, ipsilateral neck RT was associated with a low rate of CNF in patients with small, lateralized tonsil cancers. Bilateral neck RT was associated with lower risk of CNF compared with ipsilateral neck RT. Patients with tumors of a higher T category were at increased risk for CNF following ipsilateral neck RT, and advanced nodal stage was not associated with CNF. Rates of toxic effects appeared favorable in patients treated with ipsilateral neck RT.
Topics: Humans; Tonsillar Neoplasms; Retrospective Studies; Palatine Tonsil; Prospective Studies; Neoplasm Staging; Lymph Nodes; Carcinoma, Squamous Cell
PubMed: 36753275
DOI: 10.1001/jamanetworkopen.2022.55209 -
JCO Global Oncology Jan 2023The proportion of head and neck cancers (HNCs) with human papillomavirus (HPV) positivity in sub-Saharan Africa (SSA) is poorly characterized. Characterizing this has...
PURPOSE
The proportion of head and neck cancers (HNCs) with human papillomavirus (HPV) positivity in sub-Saharan Africa (SSA) is poorly characterized. Characterizing this has implications in staging, prognosis, resource allocation, and vaccination policies. This study aims to determine the proportion of HPV-associated HNC in SSA.
MATERIALS AND METHODS
This systematic review included searches from PubMed, EMBASE, Web of Science, African Index Medicus, Google Scholar, and African Journals Online. All English publications reporting the proportion of HNC specimens from SSA patients who tested positive for HPV and/or p16 were included. Study quality was assessed using the National Institutes of Health Quality Assessment Tool for Case Series Studies.
RESULTS
In this systematic review of 31 studies and 3,850 patients, the overall p16 positivity was 13.6% (41 of 1,037 patients tested) with the highest proportion among oropharyngeal cancers (20.3%, 78 of 384 patients) and the overall HPV polymerase chain reaction positivity was 15.3% (542 of 3,548 samples tested) with the highest proportion among nasopharyngeal cancers (16.5%, 23 of 139 patients). Among the 369 HPV strains detected, the most common genotypes were HPV 16 (226 patients, 59.2%) and HPV 18 (78, 20.4%).
CONCLUSION
HPV was found to be associated with a significant proportion of HNC in SSA. The genotypes reported suggest that the nine-valent vaccine and gender-neutral vaccination policies should be considered. Given that these studies may not accurately capture prevalence nor causation of HPV in HNC subsites, additional research is needed to provide a more thorough epidemiologic understanding of HPV-associated HNC in SSA, including risk factors and clinical outcomes.
Topics: United States; Humans; Human Papillomavirus Viruses; Papillomavirus Infections; Head and Neck Neoplasms; Papillomaviridae; Risk Factors
PubMed: 36730877
DOI: 10.1200/GO.22.00259 -
International Journal of Molecular... Nov 2022Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is... (Review)
Review
Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is currently the gold standard for oropharyngeal cancers, but is technically demanding, invasive, and expensive. This systematic review aims to review current markers that are detectable in biofluids, which offer promising non-invasive alternatives in oropharyngeal carcinomas (OPCs). A total of 174 clinical trials from the PubMed search engine in the last 5 years were identified and screened by 4 independent reviewers. From these, 38 eligible clinical trials were found and subsequently reviewed. The biomarkers involved, categorized by human papillomavirus (HPV)-status, were further divided according to molecular and cellular levels. Recent trials investigating biomarkers for both HPV-positive and HPV-negative OPCs have approaches from various levels and different biofluids including plasma, oropharyngeal swabs, and oral rinse. Promising candidates have been found to aid in detection, staging, and predicting prognosis, in addition to well-established factors including HPV-status, drinking and smoking status. These studies also emphasize the possibility of enhancing prediction results and increasing statistical significance by multivariate analyses. Liquid biopsies offer promising assistance in enhancing personalized medicine for cancer treatment, from lowering barriers towards early screening, to facilitating de-escalation of treatment. However, further research is needed, and the combination of liquid biopsies with pre-existing methods, including in vivo imaging and invasive techniques such as neck dissections, could also be explored in future trials.
Topics: Humans; Alphapapillomavirus; Papillomaviridae; Oropharyngeal Neoplasms; Biomarkers; Carcinoma
PubMed: 36430813
DOI: 10.3390/ijms232214336 -
Cancers Nov 2022Locally-advanced head and neck squamous cell carcinoma (HNSCC) is mainly defined by the presence of pathologic cervical lymph nodes (LNs) with or without extracapsular... (Review)
Review
Locally-advanced head and neck squamous cell carcinoma (HNSCC) is mainly defined by the presence of pathologic cervical lymph nodes (LNs) with or without extracapsular spread (ECS). Current radiologic criteria to classify LNs as non-pathologic, pathologic, or pathologic with ECS are primarily shape-based. However, significantly more quantitative information is contained within imaging modalities. This quantitative information could be exploited for classification of LNs in patients with locally-advanced HNSCC by means of artificial intelligence (AI). Currently, various reviews exploring the role of AI in HNSCC are available. However, reviews specifically addressing the current role of AI to classify LN in HNSCC-patients are sparse. The present work systematically reviews original articles that specifically explore the role of AI to classify LNs in locally-advanced HNSCC applying Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and the Study Quality Assessment Tool of National Institute of Health (NIH). Between 2001 and 2022, out of 69 studies a total of 13 retrospective, mainly monocentric, studies were identified. The majority of the studies included patients with oropharyngeal and oral cavity (9 and 7 of 13 studies, respectively) HNSCC. Histopathologic findings were defined as reference in 9 of 13 studies. Machine learning was applied in 13 studies, 9 of them applying deep learning. The mean number of included patients was 75 (SD ± 72; range 10-258) and of LNs was 340 (SD ± 268; range 21-791). The mean diagnostic accuracy for the training sets was 86% (SD ± 14%; range: 43-99%) and for testing sets 86% (SD ± 5%; range 76-92%). Consequently, all of the identified studies concluded AI to be a potentially promising diagnostic support tool for LN-classification in HNSCC. However, adequately powered, prospective, and randomized control trials are urgently required to further assess AI's role in LN-classification in locally-advanced HNSCC.
PubMed: 36358815
DOI: 10.3390/cancers14215397 -
European Archives of... Mar 2023Voice training has been proposed as an intervention to improve swallowing function in patients with dysphagia. However, little is known about the effects of voice... (Review)
Review
BACKGROUND
Voice training has been proposed as an intervention to improve swallowing function in patients with dysphagia. However, little is known about the effects of voice training on swallowing physiology.
OBJECTIVES
This systematic review investigates the effect of voice training on the swallowing function of patients with oropharyngeal dysphagia and provides the theoretical basis for improving the swallowing function and life quality of patients with oropharyngeal dysphagia.
DATA SOURCES
A systematic review using a narrative synthesis approach of all published studies was sought with no date restrictions. Five electronic databases (EMBASE, PubMed, CINAHL, Web of Science, and The Cochrane Library) were searched from inception to April 2022.
STUDY SELECTION
Eight studies were included. Two researchers screened the literature according to inclusion and exclusion criteria, extracted data, and carried out quality control according to the Cochrane handbook5.1.0. Data were analyzed narratively and descriptively.
CONCLUSIONS
In general, statistically significant positive therapy effects were found. Voice training improves the oral and pharyngeal stages of swallowing in patients with neurological causes of dysphagia, such as stroke, and in patients with non-neurological causes of dysphagia, such as head and neck cancer. However, the current literature is limited and further primary research is required to provide more evidence to support voice training intervention in dysphagia. Future studies could further refine the content of voice training interventions, increase the number of patients enrolled, assess the long-term effects of voice training interventions and add associated assessments of the quality of life after treatment.
Topics: Humans; Deglutition Disorders; Quality of Life; Voice Training; Deglutition; Head and Neck Neoplasms
PubMed: 36342516
DOI: 10.1007/s00405-022-07719-7 -
International Journal of Molecular... Oct 2022Human papillomavirus type 16 (HPV-16) is a well-known etiological factor for cervical and oropharyngeal cancers. The E2 protein, the product of an early-transcribed gene... (Review)
Review
Human papillomavirus type 16 (HPV-16) is a well-known etiological factor for cervical and oropharyngeal cancers. The E2 protein, the product of an early-transcribed gene in HPV-16, is postulated to cause the death of cancerous cells via p53-dependent and p53-independent pathways. The main aim of the present systematic review was to study the HPV 16-E2 protein as an apoptosis-inducer agent. A thorough search of MEDLINE/PubMed, Science Direct, Scopus, and EBSCOhost databases was conducted for relevant studies on HPV AND apoptosis OR cell death where HPV 16-E2 was involved. The search identified 967 publications. Eleven records dated from 1 January 1997 to 16 February 2022 were found to meet the inclusion criteria and were eligible for data extraction and inclusion. All studies concluded that HPV 16-E2 was able to induce cell death in transfected cells. E2 proteins from the high-risk HPV-16 were able to induce apoptosis through different apoptotic pathways depending on the location of the expressed gene. However, the mechanism was still unclear, and further studies are warranted.
Topics: Humans; Female; Apoptosis Regulatory Proteins; Tumor Suppressor Protein p53; Oncogene Proteins, Viral; Human papillomavirus 16; Apoptosis; Papillomavirus Infections; Oropharyngeal Neoplasms; Uterine Cervical Neoplasms; Papillomaviridae
PubMed: 36293403
DOI: 10.3390/ijms232012554 -
Head & Neck Dec 2022Pretreatment determination of extranodal extension (ENE) has significant clinical implications in human papillomavirus positive (HPV+) oropharyngeal squamous cell... (Meta-Analysis)
Meta-Analysis Review
Pretreatment determination of extranodal extension (ENE) has significant clinical implications in human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). Unfortunately there is no gold-standard imaging modality for radiological assessment of ENE in HPV+ OPSCC, leading to subjective assessments and complex decision making concerning ENE. A systematic review of diagnostic test accuracy was therefore undertaken, with five databases systemically searched to evaluate the diagnostic performance of an imaging modality for detection of ENE in HPV+ OPSCC. A meta-analysis was conducted on four CT studies using a random-effects model. While a narrative synthesis was provided for the studies using PET/CT and "CT and MRI." Out of 1772 hits, six studies were included in the review. Meta-analysis on four CT studies showed CT had an overall sensitivity of 77% and specificity of 60%. PET/CT had a sensitivity of 37.5% and specificity of 97%. "CT and MRI" had a sensitivity of 62% and specificity of 78%. Further diagnostic studies involving CT, PET/CT and MRI are ultimately required.
Topics: Humans; Extranodal Extension; Papillomavirus Infections; Positron Emission Tomography Computed Tomography; Carcinoma, Squamous Cell; Neoplasm Staging; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms
PubMed: 36071683
DOI: 10.1002/hed.27183