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1.
Article in English | MEDLINE | ID: mdl-39001585

ABSTRACT

BACKGROUND: Measuring the swallowing muscle mass with volume measurements is complex and time intensive; therefore, it is not used in clinical practice. However, it can be clinically relevant, for instance, in the case of sarcopenic dysphagia. The aim of the study was to develop a feasible and clinically applicable method to measure swallowing muscle mass. METHODS: Data from 10 head and neck cancer patients were collected from the Oncological Life Study data-biobank of the University Medical Center Groningen. The pharyngeal constrictor, genioglossus, mylohyoid and geniohyoid complex muscles, as well as the tongue complex muscles, were delineated manually on routinely performed head and neck computed tomography scans. Axial and sagittal planes were used for volume and area measurements, respectively. Muscle density measurements were performed with and without Hounsfield unit thresholding. Correlations were assessed by Pearson correlation coefficients, and interobserver reliability was measured using intra-class correlation coefficients (ICCs). RESULTS: Significant differences were observed between sagittal area measurements with and without Hounsfield unit thresholds for pharyngeal constrictor, tongue complex and the sum of the swallowing muscles (t > 6; P-value < 0.001). Stronger correlations emerged without Hounsfield unit thresholding. Strong positive and significant correlations were found between the total swallowing muscle mass volume and the sagittal area of the tongue complex muscles (r = 0.87, P-value < 0.05) and the sum of the sagittal areas of the pharyngeal constrictor and tongue complex muscles (r = 0.85, P-value < 0.05). The use of the Hounsfield unit threshold weakened correlations. Interobserver reliability was assessed and found to be fair to good for the pharyngeal constrictor muscle (ICC = 0.68, P-value < 0.05), excellent for the tongue complex muscles (ICC = 0.98, P-value < 0.05) and excellent for the total swallowing muscle area (ICC = 0.96, P-value < 0.05). CONCLUSIONS: Single-slice delineation of the sagittal area of tongue complex muscle and pharyngeal constrictor muscle is a promising, fast, simple and clinically applicable method for measuring the total volume of the swallowing muscle mass in head and neck cancer patients without Hounsfield unit thresholding. These advancements and findings would help in the early and accurate diagnosis of definitive sarcopenic dysphagia.

2.
Oral Oncol ; 153: 106830, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38718459

ABSTRACT

BACKGROUND: Conventional clinicopathological characteristics insufficiently predict prognosis in oral squamous cell carcinoma (OSCC). We aimed to assess the added predictive value of tumor microenvironment immune cell composition (TMICC) in addition to conventional clinicopathological characteristics. METHODS: Primary tumor samples of 290 OSCC patients were immunohistochemically stained for CD4, CD8, CD20, CD68, CD163, CD57, FoxP3 and Programmed cell Death Ligand 1. Additionally, clinicopathological characteristics were obtained from patients' medical files. Predictive models were trained and validated by conducting Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses with cross-validation. To quantify the added predictive power of TMICC within models, receiver operating characteristic (ROC) analyses were used. RESULTS: Recurrence occurred in 74 patients (25.5%). Conventional clinicopathological characteristics (tumor localization, pathological T-stage, pathological N-stage, extracapsular spread, resection margin, differentiation grade, perineural invasion, lymphovascular invasion) and treatment modality, were used to build a LASSO logistic regression-based predictive model. Addition of TMICC to the model resulted in a comparable AUC of respectively 0.79 (±0.01) and 0.76 (±0.1) in the training and test sets. The model indicated that high numbers of CD4+ T cells protected against recurrence. Lymph node metastasis, extracapsular spread, perineural invasion, positive surgical margins and reception of adjuvant treatment were associated with increased risk for recurrence. CONCLUSIONS: The TMICC, specifically the number of CD4+ T cells, is an independent predictor , however, addition to conventional clinicopathological characteristics does not improve the performance of a predictive model for recurrence in OSCC.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Tumor Microenvironment , Humans , Tumor Microenvironment/immunology , Mouth Neoplasms/immunology , Mouth Neoplasms/pathology , Male , Female , Middle Aged , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Aged , Adult , Prognosis , Neoplasm Recurrence, Local/pathology , Aged, 80 and over
3.
Cancers (Basel) ; 16(8)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38672541

ABSTRACT

Transoral Robotic Surgery (TORS) is utilized for treating various malignancies, such as early-stage oropharyngeal cancer and lymph node metastasis of an unknown primary tumor (CUP), and also benign conditions, like obstructive sleep apnea (OSA) and chronic lingual tonsillitis. However, the success and failure of TORS have not been analyzed to date. In this retrospective observational multicenter cohort study, we evaluated patients treated with TORS using the da Vinci surgical system. Success criteria were defined as identification of the primary tumor for CUP, >2 mm resection margin for malignant conditions, and improvement on respiratory polygraphy and tonsillitis complaints for benign conditions. A total of 220 interventions in 211 patients were included. We identified predictors of success, such as low comorbidity status ACE-27, positive P16 status, and lower age for CUP, and female gender and OSA severity for benign conditions. For other malignancies, no predictors for success were found. Predictors of failure based on postoperative complications included high comorbidity scores (ASA) and anticoagulant use, and for postoperative pain, younger age and female gender were identified. This study provides valuable insights into the outcomes and predictors of success and failure in TORS procedures across various conditions and may also help in patient selection and counseling.

4.
Eur Arch Otorhinolaryngol ; 281(5): 2619-2626, 2024 May.
Article in English | MEDLINE | ID: mdl-38427043

ABSTRACT

OBJECTIVES: To identify associations between frailty and non-response to follow-up questionnaires, in a longitudinal head and neck cancer (HNC) study with patient-reported outcome measures (PROMs). MATERIALS AND METHODS: Patients referred with HNC were included in OncoLifeS, a prospective data-biobank, underwent Geriatric Assessment (GA) and frailty screening ahead of treatment, and were followed up at 3, 6, 12 and 24 months after treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Head and Neck 35. Statistical analysis for factors associated with non-response was done using Generalized Linear Mixed Models. RESULTS: 289 patients were eligible for analysis. Mean age was 68.4 years and 68.5% were male. Restrictions in Activities of Daily Living [OR 4.46 (2.04-9.78)] and Instrumental Activities of Daily Living [OR 4.33 (2.27-8.24)], impaired mobility on Timed Up and Go test [OR 3.95 (1.85-8.45)], cognitive decline [OR 4.85 (2.28-10.35)] and assisted living (OR 5.54 (2.63-11.67)] were significantly associated with non-response. Frailty screening, with Geriatric 8 and Groningen Frailty Indicator, was also associated with non-response [OR, respectively, 2.64 (1.51-4.59) and 2.52 (1.44-4.44)]. All findings remained significant when adjusted for other factors that were significantly associated with non-response, such as higher age, longer study duration and subsequent death. CONCLUSION: Frail HNC patients respond significantly worse to follow-up PROMs. The drop-out and underrepresentation of frail patients in studies may lead to attrition bias, and as a result underestimating the effect sizes of associations. This is of importance when handling and interpreting such data.


Subject(s)
Frailty , Head and Neck Neoplasms , Humans , Male , Aged , Female , Frailty/complications , Frailty/diagnosis , Frail Elderly , Quality of Life , Follow-Up Studies , Prospective Studies , Activities of Daily Living , Postural Balance , Time and Motion Studies , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/therapy , Geriatric Assessment
5.
Clin Otolaryngol ; 49(4): 429-435, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38400826

ABSTRACT

OBJECTIVE: To assess whether narrow band imaging (NBI) detects fields of cancerisation around suspicious lesions in the upper aerodigestive tract, which were undetected by white light imaging (WLI). METHODS: In 96 patients with laryngeal and pharyngeal lesions suspicious for malignancy, 206 biopsies were taken during laryngoscopy: 96 biopsies of suspicious lesions detected by both WLI and NBI (WLI+/NBI+), 60 biopsies adjacent mucosa only suspicious with NBI (WLI-/NBI+), and 46 biopsies of NBI and WLI unsuspicious mucosa (WLI-/NBI-) as negative controls. Optical diagnosis according to the Ni-classification was compared with histopathology. RESULTS: Signs of (pre)malignancy were found in 88% of WLI+/NBI+ biopsies, 32% of WLI-/NBI+ biopsies and 0% in WLI-/NBI- (p < .001). In 58% of the WLI-/NBI+ mucosa any form of dysplasia or carcinoma was detected. CONCLUSION: The use of additional NBI led to the detection of (pre)malignancy in 32% of the cases, that would have otherwise remained undetected with WLI alone. This highlights the potential of NBI as a valuable adjunct to WLI in the identification of suspicious lesions in the upper aerodigestive tract.


Subject(s)
Laryngeal Neoplasms , Laryngoscopy , Narrow Band Imaging , Humans , Narrow Band Imaging/methods , Female , Male , Laryngoscopy/methods , Middle Aged , Aged , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/diagnostic imaging , Laryngeal Neoplasms/diagnosis , Biopsy , Adult , Pharyngeal Neoplasms/pathology , Pharyngeal Neoplasms/diagnostic imaging , Pharyngeal Neoplasms/diagnosis , Precancerous Conditions/pathology , Precancerous Conditions/diagnostic imaging , Precancerous Conditions/diagnosis , Aged, 80 and over , White
6.
Laryngoscope ; 134(8): 3604-3610, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38366759

ABSTRACT

OBJECTIVES: Decision-making for patients with a locally advanced laryngeal carcinoma (T3 and T4) is challenging due to the treatment choice between organ preservation and laryngectomy, both with different and high impact on function and quality of life (QoL). The complexity of these treatment decisions and their possible consequences might lead to decisional conflict (DC). This study aimed to explore the level of DC in locally advanced laryngeal carcinoma patients facing curative decision-making, and to identify possible associated factors. METHODS: In this multicenter prospective cohort study, participants completed questionnaires on DC, level of shared decision-making (SDM), and a knowledge test directly after counseling and 6 months after treatment. Descriptive statistics and Spearman correlation tests were used to analyze the data. RESULTS: Directly after counseling, almost all participants (44/45; 98%) experienced Clinically Significant DC score (CSDC >25, scale 0-100). On average, patients scored 47% (SD 20%) correct on the knowledge test. Questions related to radiotherapy were answered best (69%, SD 29%), whilst only 35% (SD 29%) of the questions related to laryngectomy were answered correctly. Patients' perceived level of SDM (scale 0-100) was 70 (mean, SD 16.2), and for physicians this was 70 (SD 1.7). CONCLUSION: Most patients with advanced larynx cancer experience high levels of DC. Low knowledge levels regarding treatment aspects indicate a need for better patient counseling. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3604-3610, 2024.


Subject(s)
Laryngeal Neoplasms , Laryngectomy , Humans , Laryngeal Neoplasms/psychology , Laryngeal Neoplasms/therapy , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/surgery , Male , Female , Prospective Studies , Middle Aged , Aged , Laryngectomy/psychology , Surveys and Questionnaires , Conflict, Psychological , Decision Making, Shared , Quality of Life , Decision Making , Adult , Counseling
7.
J Laryngol Otol ; 138(6): 672-678, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38235588

ABSTRACT

OBJECTIVE: To determine oncological and functional outcomes in patients with T3 and T4 laryngeal carcinoma, in which choice of treatment was based on expected laryngeal function and not T classification. METHODS: Oncological outcomes (disease-specific survival and overall survival) as well as functional outcomes (larynx preservation and functional larynx preservation) were analysed. RESULTS: In 130 T3 and 59 T4 patients, there was no difference in disease-specific survival or overall survival rates after radiotherapy (RT) (107 patients), chemoradiotherapy (36 patients) and total laryngectomy (46 patients). The five-year disease-specific survival rates were 83 per cent after RT, 78 per cent after chemoradiotherapy and 69 per cent after total laryngectomy, whereas overall survival rates were 62, 54 and 60 per cent, respectively. Five-year larynx preservation and functional larynx preservation rates were comparable for RT (79 and 66 per cent, respectively) and chemoradiotherapy (86 and 62 per cent, respectively). CONCLUSION: There is no difference in oncological outcome after (chemo)radiotherapy or total laryngectomy in T3 and T4 laryngeal carcinoma patients whose choice of treatment was based on expected laryngeal function.


Subject(s)
Chemoradiotherapy , Laryngeal Neoplasms , Laryngectomy , Larynx , Neoplasm Staging , Humans , Laryngeal Neoplasms/surgery , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/therapy , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/radiotherapy , Laryngectomy/methods , Male , Middle Aged , Aged , Female , Larynx/surgery , Larynx/physiopathology , Chemoradiotherapy/methods , Treatment Outcome , Organ Sparing Treatments/methods , Adult , Retrospective Studies , Aged, 80 and over , Survival Rate , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy
8.
J Laryngol Otol ; 138(4): 425-430, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37880146

ABSTRACT

BACKGROUND: Fibre-optic laryngoscopy is still widely used in daily clinical practice; however, high-definition laryngoscopy using narrow band imaging could be more reliable in characterising pharyngeal and laryngeal lesions. METHODS: Endoscopic videos were assessed in a tertiary referral hospital by 12 observers with different levels of clinical experience. Thirty pairs of high-definition laryngoscopy with narrow band imaging and fibre-optic laryngoscopy videos were judged twice, with an interval of two to four weeks, in a random order. Inter- and intra-observer reliability, sensitivity and specificity were calculated in terms of detecting a malignant lesion and a specific histological entity, for beginners, trained observers and experts. RESULTS: Using high-definition laryngoscopy with narrow band imaging, inter-observer reliability for detecting malignant lesions increased from moderate to substantial in trained observers and experts (high-definition laryngoscopy with narrow band imaging κ = 0.66 and κ = 0.77 vs fibre-optic laryngoscopy κ = 0.51 and κ = 0.56, for trained observers and experts respectively) and sensitivity increased by 16 per cent. CONCLUSION: Inter-observer reliability increased with the level of clinical experience, especially when using high-definition laryngoscopy with narrow band imaging.


Subject(s)
Laryngeal Neoplasms , Larynx , Humans , Laryngoscopy/methods , Narrow Band Imaging/methods , Reproducibility of Results , Larynx/diagnostic imaging , Larynx/pathology , Endoscopy , Laryngeal Neoplasms/diagnostic imaging , Laryngeal Neoplasms/pathology
9.
Oral Oncol ; 149: 106677, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38142550

ABSTRACT

OBJECTIVE: The aim of this project is to create an interactive online patient decision aid (PDA) for oropharyngeal cancer (OPSCC) patients, eligible for transoral (robotic) surgery with an ultimate goal to assist both physicians and patients in making treatment choices. MATERIALS AND METHODS: Following the International Patient Decision Aid Standards, a mixed-methods approach was employed. The study involved semi-structured in-depth interviews with patients and physicians, thinking-out-loud sessions, and study-specific questionnaires. Thematic coding and analysis were conducted on verbatim transcriptions of audio-recorded interviews. RESULTS: The PDA drafts were evaluated by twenty OPSCC survivors and twenty multidisciplinary specialists. Significant revisions were made after phase 1 to enhance readability and reduce text, whilst incorporating videos and graphics. Following all phases, both patients and specialists rated the PDA as comprehensible, feasible, and a valuable addition to regular counseling. CONCLUSION: This study showcases the development of a PDA for early stage oropharyngeal cancer patients considering surgery and radiotherapy options. The decision aid emphasizes the disparities in short- and long-term side effects between the two treatments. Patients and physicians found the decision aid to be understandable, user-friendly, and helpful for future patients. The PDA is available on https://beslissamen.nl/.


Subject(s)
Carcinoma , Oropharyngeal Neoplasms , Robotic Surgical Procedures , Humans , Netherlands , Oropharyngeal Neoplasms/surgery , Oropharyngeal Neoplasms/radiotherapy , Decision Support Techniques
10.
Nat Commun ; 14(1): 4952, 2023 08 16.
Article in English | MEDLINE | ID: mdl-37587149

ABSTRACT

Inadequate surgical margins occur frequently in oral squamous cell carcinoma surgery. Fluorescence molecular imaging (FMI) has been explored for intraoperative margin assessment, but data are limited to phase-I studies. In this single-arm phase-II study (NCT03134846), our primary endpoints were to determine the sensitivity, specificity and positive predictive value of cetuximab-800CW for tumor-positive margins detection. Secondary endpoints were safety, close margin detection rate and intrinsic cetuximab-800CW fluorescence. In 65 patients with 66 tumors, cetuximab-800CW was well-tolerated. Fluorescent spots identified in the surgical margin with signal-to-background ratios (SBR) of ≥2 identify tumor-positive margins with 100% sensitivity, 85.9% specificity, 58.3% positive predictive value, and 100% negative predictive value. An SBR of ≥1.5 identifies close margins with 70.3% sensitivity, 76.1% specificity, 60.5% positive predictive value, and 83.1% negative predictive value. Performing frozen section analysis aimed at the fluorescent spots with an SBR of ≥1.5 enables safe, intraoperative adjustment of surgical margins.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/surgery , Cetuximab , Coloring Agents , ErbB Receptors , Margins of Excision , Molecular Imaging , Mouth Neoplasms/diagnostic imaging , Mouth Neoplasms/surgery , Radiopharmaceuticals
11.
Cancers (Basel) ; 15(12)2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37370810

ABSTRACT

One of the rare tumor entities present in the nose and paranasal sinuses is sinonasal (non-) intestinal-type adenocarcinoma (ITAC/non-ITAC). Currently, surgery with postoperative radiotherapy is the cornerstone of the treatment of these tumors. Systemic treatment is usually applied in a palliative setting. The prognosis of these tumors is very diverse. Biomarkers that may have prognostic value in these rare malignancies could help clinicians in decision-making. A systematic search of the literature was performed using the PubMed database. All studies investigating the prognostic significance of biomarkers in paranasal sinus ITAC/non-ITAC were retrieved. The findings were categorized within the hallmarks of cancer, to gain an understanding of the functions of possible prognostic biomarkers in the development of ITAC/non-ITAC. There were twenty-one studies reporting on twenty-one possible biomarkers included in the review. The expression of Mucin antigen sialosyl-Tn, C-erbB-2 oncoprotein, TIMP3 methylation, TP53, VEGF, ANXA2, MUC1 and the mucinous histological subtype were found to have a significant negative effect on survival. None of the biomarkers were found to have a positive effect on prognosis. The hallmarks 'activating invasion and metastasis' and 'sustaining proliferative signaling' seem to play the largest role in sinonasal (non-)ITAC. It could be concluded that there are multiple biomarkers foreboding a negative prognosis for ITAC/non-ITAC patients.

12.
J Clin Med ; 12(10)2023 May 13.
Article in English | MEDLINE | ID: mdl-37240550

ABSTRACT

The aim of this study was to evaluate whether radiologically defined sarcopenia, or a low skeletal muscle index (SMI), could be used as a practical biomarker for frailty and postoperative complications (POC) in patients with head and neck skin cancer (HNSC). This was a retrospective study on prospectively collected data. The L3 SMI (cm2/m2) was calculated with use of baseline CT or MRI neck scans and low SMIs were defined using sex-specific cut-off values. A geriatric assessment with a broad range of validated tools was performed at baseline. POC was graded with the Clavien-Dindo Classification (with a grade of > II as the cut-off). Univariate and multivariable regression analyses were performed with low SMIs and POC as the endpoints. The patients' (n = 57) mean age was 77.0 ± 9 years, 68.4% were male, and 50.9% had stage III-IV cancer. Frailty was determined according to Geriatric 8 (G8) score (OR 7.68, 95% CI 1.19-49.66, p = 0.032) and the risk of malnutrition was determined according to the Malnutrition Universal Screening Tool (OR 9.55, 95% CI 1.19-76.94, p = 0.034), and these were independently related to low SMIs. Frailty based on G8 score (OR 5.42, 95% CI 1.25-23.49, p = 0.024) was the only variable related to POC. However, POC was more prevalent in patients with low SMIs (∆ 19%, OR 1.8, 95% CI 0.5-6.0, p = 0.356).To conclude, a low SMI is a practical biomarker for frailty and malnutrition in HNSC. Future research should be focused on interventions based on low SMI scores and assess the effect of the intervention on SMI, frailty, malnutrition, and POC.

14.
Eur Arch Otorhinolaryngol ; 280(8): 3801-3809, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37029804

ABSTRACT

PURPOSE: Treatment decision-making in advanced-stage laryngeal squamous cell carcinoma (LSCC) is difficult due to the high recurrence rates and the desire to preserve laryngeal functions. New predictive markers for radiosensitivity are needed to facilitate treatment choices. In early stage glottic LSCC treated with primary radiotherapy, expression of hypoxia (HIF-1α and CA-IX) and proliferation (Ki-67) tumour markers showed prognostic value for local control. The objective of this study is to examine the prognostic value of tumour markers for hypoxia and proliferation on locoregional recurrent disease and disease-specific mortality in a well-defined cohort of patients with locally advanced LSCC treated with primary, curatively intended radiotherapy. METHODS: In pre-treatment biopsy tissues from a homogeneous cohort of 61 patients with advanced stage (T3-T4, M0) LSCC primarily treated with radiotherapy, expression of HIF-1α, CA-IX and Ki-67 was evaluated with immunohistochemistry. Demographic data (age and sex) and clinical data (T- and N-status) were retrospectively collected from the medical records. Cox regression analysis was performed to assess the relation between marker expression, demographic and clinical data, and locoregional recurrence and disease-specific mortality. RESULTS: Patients with high expression of HIF-1α developed significantly more often a locoregional recurrence (39%) compared to patients with a low expression (21%) (p = 0.002). The expression of CA-IX and Ki-67 showed no association with locoregional recurrent disease. HIF-1α, CA-IX and Ki-67 were not significantly related to disease-specific mortality. Clinical N-status was an independent predictor of recurrent disease (p < 0.001) and disease-specific mortality (p = 0.003). Age, sex and T-status were not related to locoregional recurrent disease or disease-specific mortality. CONCLUSION: HIF-1α overexpression and the presence of regional lymph node metastases at diagnosis were independent predictors of locoregional recurrent disease after primary treatment with curatively intended radiotherapy in patients with locally advanced LSCC.


Subject(s)
Carbonic Anhydrases , Carcinoma, Squamous Cell , Head and Neck Neoplasms , Laryngeal Neoplasms , Humans , Laryngeal Neoplasms/pathology , Retrospective Studies , Ki-67 Antigen , Carbonic Anhydrases/metabolism , Neoplasm Recurrence, Local/pathology , Prognosis , Squamous Cell Carcinoma of Head and Neck , Hypoxia , Biomarkers, Tumor/metabolism , Radiation Tolerance , Cell Proliferation , Hypoxia-Inducible Factor 1, alpha Subunit
15.
Theor Appl Genet ; 136(3): 64, 2023 Mar 21.
Article in English | MEDLINE | ID: mdl-36943531

ABSTRACT

KEY MESSAGE: The bs5 resistance gene against bacterial spot was identified by map-based cloning. The recessive bs5 gene of pepper (Capsicum annuum L.) conditions a non-hypersensitive resistance trait, characterized by a slightly swollen, pale green, photosynthetically active leaf tissue, following Xanthomonas euvesicatoria infection. The isolation of the bs5 gene by map-based cloning revealed that the bs5 protein was shorter by 2 amino acids as compared to the wild type Bs5 protein. The natural 2 amino acid deletion occurred in the cysteine-rich transmembrane domain of the tail-anchored (TA) protein, Ca_CYSTM1. The protein products of the wild type Bs5 and mutant bs5 genes were shown to be located in the cell membrane, indicating an unknown function in this membrane compartment. Successful infection of the Bs5 pepper lines was abolished by the 6 bp deletion in the TM encoding domain of the Ca_CYSTM1 gene in bs5 homozygotes, suggesting, that the resulting resistance might be explained by the lack of entry of the Xanthomonas specific effector molecules into the plant cells.


Subject(s)
Capsicum , Xanthomonas , Capsicum/genetics , Capsicum/metabolism , Alleles , Genes, Recessive , Cell Membrane/metabolism , Plant Diseases/genetics , Plant Diseases/microbiology , Plant Proteins/genetics , Gene Expression Regulation, Plant
16.
Biomedicines ; 11(3)2023 Mar 06.
Article in English | MEDLINE | ID: mdl-36979783

ABSTRACT

(1) Background: Hypopharyngeal squamous cell carcinomas usually present with locally advanced disease and a correspondingly poor prognosis. Currently, efforts are being made to improve tumor characterization and provide insightful information for outcome prediction. Radiomics is an emerging area of study that involves the conversion of medical images into mineable data; these data are then used to extract quantitative features based on shape, intensity, texture, and other parameters; (2) Methods: A systematic review of the peer-reviewed literature was conducted; (3) Results: A total of 437 manuscripts were identified. Fifteen manuscripts met the inclusion criteria. The main targets described were the evaluation of textural features to determine tumor-programmed death-ligand 1 expression; a surrogate for microvessel density and heterogeneity of perfusion; patient stratification into groups at high and low risk of progression; prediction of early recurrence, 1-year locoregional failure and survival outcome, including progression-free survival and overall survival, in patients with locally advanced HPSCC; thyroid cartilage invasion, early disease progression, recurrence, induction chemotherapy response, treatment response, and prognosis; and (4) Conclusions: our findings suggest that radiomics represents a potentially useful tool in the diagnostic workup as well as during the treatment and follow-up of patients with HPSCC. Large prospective studies are essential to validate this technology in these patients.

17.
Adv Ther ; 40(5): 1957-1974, 2023 05.
Article in English | MEDLINE | ID: mdl-36920746

ABSTRACT

The projected increase in life expectancy over the next few decades is expected to result in a rise in age-related diseases, including cancer. Head and neck cancer (HNC) is a worldwide health problem with high rates of morbidity and mortality. In this report, we have critically reviewed the literature reporting the management of older patients with HNC. Older adults are more prone to complications and toxicities secondary to HNC treatment, especially those patients who are frail or have comorbidities. Thus, this population should be screened prior to treatment for such predispositions to maximize medical management of comorbidities. Chronologic age itself is not a reason for choosing less intensive treatment for older HNC patients. Whenever possible, also older patients should be treated according to the best standard of care, as nonstandard approaches may result in increased treatment failure rates and mortality. The treatment plan is best established by a multidisciplinary tumor board with shared decision-making with patients and family. Treatment modifications should be considered for those patients who have severe comorbidities, evidence of frailty (low performance status), or low performance status or those who refuse the recommendations of the tumor board.


Subject(s)
Frailty , Head and Neck Neoplasms , Humans , Aged , Head and Neck Neoplasms/therapy , Frailty/complications , Comorbidity
18.
Otolaryngol Head Neck Surg ; 169(3): 606-614, 2023 09.
Article in English | MEDLINE | ID: mdl-36821814

ABSTRACT

OBJECTIVE: Assessing whether the additional use of narrow-band imaging (NBI) in transoral laser surgery (TOLS) for early laryngeal cancer improves clinical outcomes. STUDY DESIGN: Randomized controlled trial, performed between September 2015 and November 2022. SETTING: A tertiary referral hospital in The Netherlands. METHODS: TOLS was carried out in 113 patients. The procedure was performed with white light imaging (WLI, n = 56) alone, or combined with NBI (n = 57). Patients received frequent follow-up laryngoscopy. Resection margin status, recurrence rate, and recurrence-free survival at 12 months, 18 months, and after study termination (maximum 86 months) were analyzed. RESULTS: Thirty-one cases in the WLI group had a positive resection margin, versus 16 in the NBI group (p = .002). After 12 months, the recurrence-free survival was 92%: 87% for WLI versus 96% for NBI, p = .07. The recurrence rate was 7/56 (13%) for WLI, versus 2/57 (4%) for NBI, p = .09. After 18 months, the recurrence-free survival was 84% for WLI versus 96% for NBI, p = .02. The recurrence rate was 9/56 (16%) for WLI, versus 2/57 (4%) for NBI, p = .02. After study termination, the recurrence-free survival was 71% for WLI versus 83% for the NBI group (p = .08). The recurrence rate was 16/56 for WLI, versus 10/57 for NBI (p = .16). CONCLUSION: The additional use of NBI during TOLS significantly decreased the number of positive resection margins. Although not statistically significant at all time points, patients treated with NBI-supported TOLS showed a lower recurrence rate and better recurrence-free survival. Further studies in larger patient groups are needed to confirm these results.


Subject(s)
Laryngeal Neoplasms , Laser Therapy , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/surgery , Margins of Excision , Laryngeal Neoplasms/diagnostic imaging , Laryngeal Neoplasms/surgery , Narrow Band Imaging/methods
19.
Eur J Nucl Med Mol Imaging ; 50(6): 1735-1742, 2023 05.
Article in English | MEDLINE | ID: mdl-36781423

ABSTRACT

PURPOSE: Radiologically defined sarcopenia, or a low skeletal muscle index (SMI), is an emerging biomarker for adverse clinical outcomes in head and neck cancer (HNC) patients. Recently, SMI measurements have been validated at the level of the third cervical vertebra (C3) on diagnostic neck CT scans but are not yet validated on low-dose (LD) neck CT scans from the [18F]-FDG PET-CT. This hampers SMI analysis in HNC patients without a diagnostic neck CT but with a [18F]-FDG PET-CT scan. Therefore, the aim was to study whether (low) SMI based on LD CT scan from [18F]-FDG PET-CT is comparable to those derived from diagnostic neck CT scans. METHODS: HNC patients with both diagnostic CT and [18F]-FDG PET-CT of the neck were prospectively included into the OncoLifeS data-biobank. Skeletal muscle was retrospectively delineated at the level of the third cervical vertebra (C3), and (low) SMI (cm2/m2) was calculated for diagnostic and LD neck CTs. (Low) SMI from the diagnostic neck CT was considered the reference standard. Intra-class correlation coefficient (ICC), Bland-Altman plots, and Cohen's Kappa analysis were performed. RESULTS: The cohort (n = 233) mean age was 66.2 ± 12.8 years, and 74.2% of patients were male. Inter-rater reliability was excellent (ICC > 0.990, 95% confidence interval 0.975-0.996, p < 0.001). The agreement of SMI between both modalities was high according to the Bland-Altman plot (mean ΔSMI = - 0.19 cm2/m2), and there was no substantial bias. Cohen's Kappa analysis showed an almost perfect agreement of low SMI between the two modalities (κ = 0.911, p < 0.001). The position of arms didn't affect the high agreement of (low) SMI. CONCLUSION: Skeletal muscle mass, as measured with (low) SMI, remains constant irrespective of CT acquisition parameters (diagnostic neck CT scans versus LD neck scans of the [18F]-FDG PET-CT scan), positioning of arms, and observers. These findings contribute to the construction of a clinically useful radiological biomarker for SMI and therefore identify patients at risk for adverse clinical outcomes.


Subject(s)
Head and Neck Neoplasms , Positron Emission Tomography Computed Tomography , Humans , Male , Middle Aged , Aged , Female , Fluorodeoxyglucose F18 , Retrospective Studies , Reproducibility of Results , Tomography, X-Ray Computed , Muscle, Skeletal/diagnostic imaging , Head and Neck Neoplasms/diagnostic imaging
20.
Eur Arch Otorhinolaryngol ; 280(4): 1893-1902, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36484854

ABSTRACT

PURPOSE: Both malnutrition and frailty are associated with adverse treatment outcomes. Malnutrition (risk) and frailty are each commonly present in patients with head and neck cancer (HNC). However, their coexistence and association is unknown. Main goal of this study is to determine the coexistence of, and the association between malnutrition risk and frailty in patients with HNC. METHODS: In this retrospective analysis on prospectively collected data, newly diagnosed patients with HNC, enrolled in the OncoLifeS databiobank were included. The Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) was used to assess malnutrition risk. The Groningen Frailty Indicator (GFI) was used to assess frailty status. Multivariate logistic regression analyses were performed, taking into account several patient- and tumor-related factors. RESULTS: In total, 197 patients were included. Seventy-six patients (39%) had a medium or high malnutrition risk and 71 patients (36%) were frail. In 38 patients (19%), malnutrition risk coexisted with frailty. Patients with medium and high malnutrition risk were, respectively, 4.0 (95% CI 1.5-11.2) and 13.4 (95% CI 4.0-48.7) times more likely to be frail, compared to patients with low malnutrition risk. In turn, frail patients were 6.4 times (95% CI 2.6-14.9) more likely to have malnutrition risk compared to non-frail patients. CONCLUSIONS: Malnutrition risk and frailty frequently coexist but not fully overlap in newly diagnosed patients with HNC. Therefore, screening for both conditions is recommended.


Subject(s)
Frailty , Head and Neck Neoplasms , Malnutrition , Humans , Aged , Frailty/diagnosis , Frailty/epidemiology , Retrospective Studies , Malnutrition/diagnosis , Malnutrition/epidemiology , Malnutrition/etiology , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/epidemiology , Treatment Outcome , Nutritional Status , Geriatric Assessment , Nutrition Assessment
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