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1.
Psychooncology ; 33(1): e6251, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37955598

ABSTRACT

OBJECTIVE: To investigate utilization of mental healthcare among head and neck cancer (HNC) patients from diagnosis to 2 years after treatment, in relation to psychological symptoms, mental disorders, need for mental healthcare, and sociodemographic, clinical and personal factors. METHODS: Netherlands Quality of life and Biomedical Cohort study data as measured before treatment, at 3 and 6 months, and at 1 and 2 years after treatment was used (n = 610). Data on mental healthcare utilization (iMCQ), psychological symptoms (Hospital Anxiety and Depression Scale, Cancer Worry Scale), mental disorders (CIDI interview), need for mental healthcare (Supportive Care Needs Survey Short-Form 34, either as continuous outcome indicating the level of need or dichotomized into unmet need (yes/no)) and several sociodemographic, clinical and personal factors were collected. Factors associated with mental healthcare utilization were investigated using generalized estimating equations (p < 0.05). RESULTS: Of all HNC patients, 5%-9% used mental healthcare per timepoint. This was 4%-14% in patients with mild-severe psychological symptoms, 4%-17% in patients with severe psychological symptoms, 15%-35% in patients with a mental disorder and 5%-16% in patients with an unmet need for mental healthcare. Among all patients, higher symptoms of anxiety, a higher need for mental healthcare, lower age, higher disease stage, lower self-efficacy and higher social support seeking were significantly associated with mental healthcare utilization. CONCLUSION: Mental health care utilization among HNC patients is limited, and is related to psychological symptoms, need for mental healthcare, and sociodemographic, clinical and personal factors.


Subject(s)
Head and Neck Neoplasms , Quality of Life , Humans , Longitudinal Studies , Cohort Studies , Quality of Life/psychology , Head and Neck Neoplasms/therapy , Patient Acceptance of Health Care , Surveys and Questionnaires
2.
BMC Palliat Care ; 23(1): 54, 2024 Feb 24.
Article in English | MEDLINE | ID: mdl-38395897

ABSTRACT

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) enter the palliative phase when cure is no longer possible or when they refuse curative treatment. The mean survival is five months, with a range of days until years. Realistic prognostic counseling enables patients to make well-considered end-of-life choices. However, physicians tend to overestimate survival. The aim of this study was to develop a prognostic model that calculates the overall survival (OS) probability of palliative HNSCC patients. METHODS: Patients diagnosed with incurable HNSCC or patients who refused curative treatment for HNSCC between January 1st 2006 and June 3rd 2019 were included (n = 659). Three patients were lost to follow-up. Patients were considered to have incurable HNSCC due to tumor factors (e.g. inoperability with no other curative treatment options, distant metastasis) or patient factors (e.g. the presence of severe comorbidity and/or poor performance status).Tumor and patients factors accounted for 574 patients. An additional 82 patients refused curative treatment and were also considered palliative. The effect of 17 candidate predictors was estimated in the univariable cox proportional hazard regression model. Using backwards selection with a cut-off P-value < 0.10 resulted in a final multivariable prediction model. The C-statistic was calculated to determine the discriminative performance of the model. The final model was internally validated using bootstrapping techniques. RESULTS: A total of 647 patients (98.6%) died during follow-up. Median OS time was 15.0 weeks (95% CI: 13.5;16.6). Of the 17 candidate predictors, seven were included in the final model: the reason for entering the palliative phase, the number of previous HNSCC, cT, cN, cM, weight loss in the 6 months before diagnosis, and the WHO performance status. The internally validated C-statistic was 0.66 indicating moderate discriminative ability. The model showed some optimism, with a shrinkage factor of 0.89. CONCLUSION: This study enabled the development and internal validation of a prognostic model that predicts the OS probability in HNSCC patients in the palliative phase. This model facilitates personalized prognostic counseling in the palliative phase. External validation and qualitative research are necessary before widespread use in patient counseling and end-of-life care.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/therapy , Prognosis , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/therapy , Proportional Hazards Models
3.
Endoscopy ; 55(11): 981-990, 2023 11.
Article in English | MEDLINE | ID: mdl-37328150

ABSTRACT

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) can develop second primary tumors (SPTs) in the esophagus. Endoscopic screening could lead to detection of SPTs at early stages and improve survival. METHODS: We performed a prospective endoscopic screening study in patients with curably treated HNSCC diagnosed between January 2017-July 2021 in a Western country. Screening was performed synchronously (< 6 months) or metachronously (≥ 6 months) after HNSCC diagnosis. Routine imaging for HNSCC consisted of flexible transnasal endoscopy with positron emission tomography/computed tomography or magnetic resonance imaging, depending on primary HNSCC location. The primary outcome was prevalence of SPTs, defined as presence of esophageal high grade dysplasia or squamous cell carcinoma. RESULTS: 202 patients (mean age 65 years, 80.7 % male) underwent 250 screening endoscopies. HNSCC was located in the oropharynx (31.9 %), hypopharynx (26.9 %), larynx (22.2 %), and oral cavity (18.5 %). Endoscopic screening was performed within 6 months (34.0 %), 6 months to 1 year (8.0 %), 1-2 years (33.6 %), and 2-5 years (24.4 %) after HNSCC diagnosis. We detected 11 SPTs in 10 patients (5.0 %, 95 %CI 2.4 %-8.9 %) during synchronous (6/85) and metachronous (5/165) screening. Most patients had early stage SPTs (90 %) and were treated with curative intent with endoscopic resection (80 %). No SPTs in screened patients were detected with routine imaging for HNSCC before endoscopic screening. CONCLUSION: In 5 % of patients with HNSCC, an SPT was detected with endoscopic screening. Endoscopic screening should be considered in selected HNSCC patients to detect early stage SPTs, based on highest SPT risk and life expectancy according to HNSCC and comorbidities.


Subject(s)
Head and Neck Neoplasms , Neoplasms, Second Primary , Upper Gastrointestinal Tract , Humans , Male , Aged , Female , Neoplasms, Second Primary/diagnostic imaging , Neoplasms, Second Primary/epidemiology , Squamous Cell Carcinoma of Head and Neck/diagnosis , Prospective Studies , Early Detection of Cancer/methods , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/epidemiology , Endoscopy , Upper Gastrointestinal Tract/diagnostic imaging , Upper Gastrointestinal Tract/pathology
4.
Analyst ; 148(12): 2676-2682, 2023 Jun 12.
Article in English | MEDLINE | ID: mdl-37077171

ABSTRACT

Near-infrared (NIR) fluorescence imaging using exogenous fluorescent agents provides whole-field images in real-time to assist the surgeon in the excision of a tumor. Although the method has high sensitivity, the specificity can sometimes be lower than expected. Raman spectroscopy can detect tumors with high specificity. Therefore, a combination of both techniques can be advantageous. A complication that must be addressed is that the NIR spectral region is favored by both techniques for (in vivo) tissue analysis. When fluorescence and Raman emissions spectrally overlap, it becomes challenging or impossible to detect the Raman signal. In this paper, by avoiding this overlap, we describe a Raman spectroscopy setup capable of recording high-quality Raman spectra from tissue containing NIR exogenous fluorescent agents. We identify an optimal wavelength interval (900-915 nm) for Raman excitation, which avoids both excitation of fluorescent dyes and Raman signal self-absorption by the tissue. In this way, Raman spectroscopy can be combined with the currently most-used NIR fluorescent dyes. This combined novel setup could pave the way for clinical trials benefiting from both fluorescence imaging and Raman spectroscopy to avoid positive margins in cancer surgery.


Subject(s)
Fluorescent Dyes , Neoplasms , Humans , Fluorescent Dyes/chemistry , Spectrum Analysis, Raman/methods , Spectroscopy, Near-Infrared/methods , Neoplasms/diagnostic imaging , Neoplasms/surgery , Optical Imaging
5.
Analyst ; 148(17): 4116-4126, 2023 Aug 21.
Article in English | MEDLINE | ID: mdl-37493462

ABSTRACT

Patients with oral cavity cancer are almost always treated with surgery. The goal is to remove the tumor with a margin of more than 5 mm of surrounding healthy tissue. Unfortunately, this is only achieved in about 15% to 26% of cases. Intraoperative assessment of tumor resection margins (IOARM) can dramatically improve surgical results. However, current methods are laborious, subjective, and logistically demanding. This hinders broad adoption of IOARM, to the detriment of patients. Here we present the development and validation of a high-wavenumber Raman spectroscopic technology, for quick and objective intraoperative measurement of resection margins on fresh specimens. It employs a thin fiber-optic needle probe, which is inserted into the tissue, to measure the distance between a resection surface and the tumor. A tissue classification model was developed to discriminate oral cavity squamous cell carcinoma (OCSCC) from healthy oral tissue, with a sensitivity of 0.85 and a specificity of 0.92. The tissue classification model was then used to develop a margin length prediction model, showing a mean difference between margin length predicted by Raman spectroscopy and histopathology of -0.17 mm.


Subject(s)
Mouth Neoplasms , Spectrum Analysis, Raman , Mouth Neoplasms/diagnosis , Mouth Neoplasms/surgery , Margins of Excision , Intraoperative Period , Spectrum Analysis, Raman/instrumentation , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/surgery , Humans
6.
Lasers Med Sci ; 38(1): 193, 2023 Aug 25.
Article in English | MEDLINE | ID: mdl-37624524

ABSTRACT

As for many solid cancers, laryngeal cancer is treated surgically, and adequate resection margins are critical for survival. Raman spectroscopy has the capacity to accurately differentiate between cancer and non-cancerous tissue based on their molecular composition, which has been proven in previous work. The aim of this study is to investigate whether Raman spectroscopy can be used to discriminate laryngeal cancer from surrounding non-cancerous tissue. Patients surgically treated for laryngeal cancer were included. Raman mapping experiments were performed ex vivo on resection specimens and correlated to histopathology. Water concentration analysis and CH-stretching region analysis were performed in the high wavenumber range of 2500-4000 cm-1. Thirty-four mapping experiments on 22 resection specimens were used for analysis. Both laryngeal cancer and all non-cancerous tissue structures showed high water concentrations of around 75%. Discriminative information was only found to be present in the CH-stretching region of the Raman spectra of the larynx (discriminative power of 0.87). High wavenumber region Raman spectroscopy can discriminate laryngeal cancer from non-cancerous tissue structures. Contrary to the findings for oral cavity cancer, water concentration is not a discriminating factor for laryngeal cancer.


Subject(s)
Head and Neck Neoplasms , Laryngeal Neoplasms , Humans , Laryngeal Neoplasms/diagnosis , Squamous Cell Carcinoma of Head and Neck , Spectrum Analysis, Raman , Water
7.
Lancet Oncol ; 22(5): e186-e195, 2021 05.
Article in English | MEDLINE | ID: mdl-33765422

ABSTRACT

Fluorescence-guided surgery is an intraoperative optical imaging method that provides surgeons with real-time guidance for the delineation of tumours. Currently, in phase 1 and 2 clinical trials, evaluation of fluorescence-guided surgery is primarily focused on its diagnostic performance, although the corresponding outcome variables do not inform about the added clinical benefit of fluorescence-guided surgery and are challenging to assess objectively. Nonetheless, the effect of fluorescence-guided surgery on intraoperative decision making is the most objective outcome measurement to assess the clinical value of this imaging method. In this Review, we explore the study designs of existing trials of fluorescence-guided surgery that allow us to extract information on potential changes in intraoperative decision making, such as additional or more conservative resections. On the basis of this analysis, we offer recommendations on how to report changes in intraoperative decision making that result from fluorescence imaging, which is of utmost importance for the widespread clinical implementation of fluorescence-guided surgery.


Subject(s)
Decision Making , Neoplasms/surgery , Optical Imaging/methods , Surgery, Computer-Assisted/methods , Clinical Trials as Topic , Fluorescence , Humans , Intraoperative Period , Research Design
8.
Oral Dis ; 27(1): 111-116, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32816373

ABSTRACT

With an incidence of 350.000 new cases per year, cancer of the oral cavity ranks among the 10 most common solid organ cancers. Most of these cancers are squamous cell carcinomas. Five-year survival is about 50%. It has been shown that clear resection margins (>5 mm healthy tissue surrounding the resected tumor) have a significant positive effect on locoregional control and survival. It is not uncommon that the resection margins of oral tumors are inadequate. However, when providing the surgeon with intraoperative feedback on the resection margin status, it is expected that obtaining adequate resection margins is improved. In this respect, it has been shown that specimen-driven intraoperative assessment of resection margins is superior to defect-driven intraoperative assessment of resection margins. In this concise report, it is described how a specimen-driven approach can increase the rate of adequate resections of oral cavity squamous cell carcinoma as well as that it is discussed how intraoperative assessment can be further improved with regard to the surgical treatment of oral cavity squamous cell carcinoma.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Carcinoma, Squamous Cell/surgery , Humans , Margins of Excision , Mouth Neoplasms/surgery , Standard of Care
9.
Dis Esophagus ; 34(10)2021 Oct 11.
Article in English | MEDLINE | ID: mdl-34075402

ABSTRACT

Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of developing esophageal second primary tumors (ESPTs). We aimed to determine the incidence, stage, and outcome of synchronous ESPTs in patients with HNSCC in a Western population. We performed a prospective, observational, and cohort study. Patients diagnosed with HNSCC in the oropharynx, hypopharynx, any other sub-location in combination with alcohol abuse, or patients with two synchronous HNSCCs, between February 2019 and February 2020 underwent screening esophagogastroduodenoscopy (EGD). ESPT was defined as presence of esophageal squamous cell carcinoma (ESCC) or high grade dysplasia (HGD). Eighty-five patients were included. A lesion suspected for ESPT was detected in 14 of 85 patients, which was pathologically confirmed in five patients (1 ESCC and 4 HGD). The radiotherapy field was extended to the esophagus in two of five patients, HGD was treated with endoscopic resection in three of five patients. None of the ESPTs were detected on MRI and/or CT-scan prior to EGD. Of the remaining nine patients, three had low grade dysplasia on histology whereas the other six patients had benign lesions. Incidence of synchronous ESPT was 5.9% in our cohort of HNSCC patients. All ESPTs were diagnosed at an early stage and treated with curative intent. We recommend that screening for synchronous ESPTs should be considered in a selected group of patients with HNSCC.


Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Head and Neck Neoplasms , Neoplasms, Multiple Primary , Neoplasms, Second Primary , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/therapy , Cohort Studies , Early Detection of Cancer , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/therapy , Esophagoscopy , Head and Neck Neoplasms/therapy , Humans , Neoplasms, Multiple Primary/epidemiology , Neoplasms, Second Primary/epidemiology , Prospective Studies
10.
Microsc Microanal ; 27(4): 878-888, 2021 08.
Article in English | MEDLINE | ID: mdl-34108070

ABSTRACT

A profound characteristic of field cancerization is alterations in chromatin packing. This study aimed to quantify these alterations using electron microscopy image analysis of buccal mucosa cells of laryngeal, esophageal, and lung cancer patients. Analysis was done on normal-appearing mucosa, believed to be within the cancerization field, and not tumor itself. Large-scale electron microscopy (nanotomy) images were acquired of cancer patients and controls. Within the nuclei, the chromatin packing of euchromatin and heterochromatin was characterized. Furthermore, the chromatin organization was quantified through chromatin packing density scaling. A significant difference was found between the cancer and control groups in the chromatin packing density scaling parameter for length scales below the optical diffraction limit (200 nm) in both the euchromatin (p = 0.002) and the heterochromatin (p = 0.006). The chromatin packing scaling analysis also indicated that the chromatin organization of cancer patients deviated significantly from the control group. They might allow for novel strategies for cancer risk stratification and diagnosis with high sensitivity. This could aid clinicians in personalizing screening strategies for high-risk patients and follow-up strategies for treated cancer patients.


Subject(s)
Chromatin , Mouth Mucosa , Mouth Neoplasms , Euchromatin , Heterochromatin , Humans , Microscopy, Electron , Mouth Mucosa/cytology , Mouth Neoplasms/diagnosis
11.
Lancet Oncol ; 21(1): 80-94, 2020 01.
Article in English | MEDLINE | ID: mdl-31838009

ABSTRACT

BACKGROUND: Knowledge about the efficacy of behavioural intervention technologies that can be used by cancer survivors independently from a health-care provider is scarce. We aimed to assess the efficacy, reach, and usage of Oncokompas, a web-based eHealth application that supports survivors in self-management by monitoring health-related quality of life (HRQOL) and cancer-generic and tumour-specific symptoms and obtaining tailored feedback with a personalised overview of supportive care options. METHODS: In this non-blinded, randomised, controlled trial, we recruited patients treated at 14 hospitals in the Netherlands for head and neck cancer, colorectal cancer, breast cancer, Hodgkin lymphoma, or non-Hodgkin lymphoma. Adult survivors (aged ≥18 years) were recruited through the Netherlands Cancer Registry (NCR) and invited by their treating physician through the Patient Reported Outcomes Following Initial Treatment and Long term Evaluation of Survivorship (PROFILES) registry. Participants were randomly assigned (1:1) by an independent researcher to the intervention group (access to Oncokompas) or control group (access to Oncokompas after 6 months), by use of block randomisation (block length of 68), stratified by tumour type. The primary outcome was patient activation (knowledge, skills, and confidence for self-management), assessed at baseline, post-intervention, and 3-month and 6-month follow-up. Linear mixed models (intention-to-treat) were used to assess group differences over time from baseline to 6-month follow-up. The trial is registered in the Netherlands Trial Register, NTR5774 and is completed. FINDINGS: Between Oct 12, 2016, and May 24, 2018, 625 (21%) of 2953 survivors assessed for eligibility were recruited and randomly assigned to the intervention (320) or control group (305). Median follow-up was 6 months (IQR 6-6). Patient activation was not significantly different between intervention and control group over time (difference at 6-month follow-up 1·7 [95% CI -0·8-4·1], p=0·41). INTERPRETATION: Oncokompas did not improve the amount of knowledge, skills, and confidence for self-management in cancer survivors. This study contributes to the evidence for the development of tailored strategies for development and implementation of behavioural intervention technologies among cancer survivors. FUNDING: Dutch Cancer Society (KWF Kankerbestrijding).


Subject(s)
Cancer Survivors/psychology , Neoplasms/therapy , Patient Reported Outcome Measures , Quality of Life , Self-Management/methods , Telemedicine/methods , Telemedicine/statistics & numerical data , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasms/psychology , Neoplasms/rehabilitation , Prognosis , Self-Management/psychology , Surveys and Questionnaires , Survival Rate
12.
Mod Pathol ; 33(6): 1015-1032, 2020 06.
Article in English | MEDLINE | ID: mdl-31857683

ABSTRACT

Ectodomain shedding unleashes the aggressive nature of the MET oncogene product. Using specific C- and N-terminal MET antibodies (D1C2 and A2H2-3), MET protein status (i.e., no MET, decoy MET, transmembranous C-terminal MET with or without the ectodomain) was investigated in oral squamous cell carcinoma. For the cancers showing transmembranous C-terminal MET, the impact of ectodomain shedding on prognosis was investigated. To examine ectodomain shedding, reduced lysates of oral squamous cell carcinoma cell lines were immunoblotted using D1C2 and an ELISA was performed on culture media using A2H2-3. In addition, reduced lysates of fresh frozen tissues of 30 oral squamous cell carcinoma were immunoblotted using D1C2 and immunohistochemistry was performed on corresponding formalin-fixed paraffin-embedded tissues using both antibodies on parallel sections. To examine MET protein status, differences between membranous D1C2 and A2H2-3 immunoreactivities were scored using parallel tissue microarray sections representing 156 oral squamous cell carcinoma. The prognostic value of ectodomain shedding was examined using Cox regression analysis for disease-free survival and overall survival. Ectodomain shedding was observed in all cell lines, 43% (n = 13) of fresh frozen and 50% (n = 15) of formalin-fixed paraffin-embedded cancers (27% overlap, n = 8). The tissue microarray showed no MET in 23% (n = 36), decoy MET in 9% (n = 14), and transmembranous C-terminal MET in 68% (n = 106) of examined cancers. Within the latter group, ectodomain shedding occurs in 36% (n = 38) of the cases and is independently associated with poor disease-free survival (HR = 2.41; 95% CI, 1.35-4.30 and P = 0.003)-though not overall survival (HR = 1.64; 95% CI, 0.92-2.94 and P = 0.095)-after correcting for factors known to influence survival. In conclusion, MET ectodomain shedding occurs in transmembranous C-terminal MET positive oral squamous cell carcinoma and is independently associated with disease-free survival. These findings might aid in designing companion diagnostics for targeted therapies directed against MET.


Subject(s)
Mouth Neoplasms/metabolism , Proto-Oncogene Proteins c-met/metabolism , Squamous Cell Carcinoma of Head and Neck/metabolism , Cell Line, Tumor , Disease-Free Survival , Humans , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Prognosis , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/pathology , Survival Rate
13.
BMC Cancer ; 20(1): 399, 2020 May 07.
Article in English | MEDLINE | ID: mdl-32380962

ABSTRACT

BACKGROUND: Head and Neck cancer (HNC) is characterized by significant mortality and morbidity. Treatment is often invasive and interferes with vital functions, resulting in a delicate balance between survival benefit and deterioration in quality of life (QoL). Therefore, including prognostic information during patient counseling can be of great importance. The first aim of this study was to explore HNC patients' preferences for receiving prognostic information: both qualitative (general terms like "curable cancer"), and quantitative information (numbers, percentages). The second aim of this study was to explore patients' views on "OncologIQ", a prognostic model developed to estimate overall survival in newly diagnosed HNC patients. METHODS: We conducted a single center qualitative study by organizing five focus groups with HNC patients (n = 21) and their caregivers (n = 19), categorized in: 1) small laryngeal carcinomas treated with radiotherapy or laser, 2) extensive oral cavity procedures, 3) total laryngectomy, 4) chemoradiation, 5) other treatments. The patients' perspective was the main focus. The interview guide consisted of two main topics: life-expectancy and the prognostic model OncologIQ. All focus groups were recorded, transcribed and coded. Themes were derived using content analysis. RESULTS: While all patients considered it somewhat to very important to receive information about their life-expectancy, only some of them wanted to receive quantitative information. Disclosing qualitative prognostic information like "the cancer is curable" would give enough reassurance for most patients. Overall, patients thought life-expectancy should not be discussed shortly after cancer diagnosis disclosure, as a certain time is needed to process the first shock. They had a stronger preference for receiving prognostic information in case of a poor prognosis. Prognostic information should also include information on the expected QoL. The pie chart was the most preferred chart for discussing survival rates. CONCLUSIONS: The participants found it important to receive information on their life-expectancy. While most patients were enough reassured by qualitative prognostic information, some wanted to receive quantitative information like OncologIQs' estimates. A tailor-made approach is necessary to provide customized prognostic information. A clinical practice guideline was developed to support professionals in sharing prognostic information, aiming to improve shared decision making and patient-centered care.


Subject(s)
Decision Making , Focus Groups/statistics & numerical data , Head and Neck Neoplasms/psychology , Life Expectancy/trends , Patient Preference/psychology , Patient-Centered Care/methods , Quality of Life/psychology , Adult , Aged , Caregivers/standards , Female , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/therapy , Humans , Male , Middle Aged , Prognosis , Qualitative Research , Survival Rate
14.
Int J Hyperthermia ; 34(4): 407-414, 2018 06.
Article in English | MEDLINE | ID: mdl-28705099

ABSTRACT

PURPOSE: Hyperthermia (40-44 °C) effectively sensitises tumours to radiotherapy by locally altering tumour biology. One of the effects of heat at the cellular level is inhibition of DNA repair by homologous recombination via degradation of the BRCA2-protein. This suggests that hyperthermia can expand the group of patients that benefit from PARP-inhibitors, a drug exploiting homologous recombination deficiency. Here, we explore whether the molecular mechanisms that cause heat-mediated degradation of BRCA2 are conserved in cell lines from various origins and, most importantly, whether, BRCA2 protein levels can be attenuated by heat in freshly biopted human tumours. EXPERIMENTAL DESIGN: Cells from four established cell lines and from freshly biopsied material of cervical (15), head- and neck (9) or bladder tumours (27) were heated to 42 °C for 60 min ex vivo. In vivo hyperthermia was studied by taking two biopsies of the same breast or cervical tumour: one before and one after treatment. BRCA2 protein levels were measured by immunoblotting. RESULTS: We found decreased BRCA2-levels after hyperthermia in all established cell lines and in 91% of all tumours treated ex vivo. For tumours treated with hyperthermia in vivo, technical issues and intra-tumour heterogeneity prevented obtaining interpretable results. CONCLUSIONS: This study demonstrates that heat-mediated degradation of BRCA2 occurs in tumour material directly derived from patients. Although BRCA2-degradation may not be a practical biomarker for heat deposition in situ, it does suggest that application of hyperthermia could be an effective method to expand the patient group that could benefit from PARP-inhibitors.


Subject(s)
BRCA2 Protein/metabolism , Hyperthermia, Induced , Neoplasms/metabolism , Neoplasms/therapy , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Cell Line, Tumor , Combined Modality Therapy , Female , Hot Temperature , Humans , Proteolysis
15.
Analyst ; 142(17): 3025-3047, 2017 Aug 21.
Article in English | MEDLINE | ID: mdl-28726868

ABSTRACT

Oncological applications of Raman spectroscopy have been contemplated, pursued, and developed at academic level for at least 25 years. Published studies aim to detect pre-malignant lesions, detect cancer in less invasive stages, reduce the number of unnecessary biopsies and guide surgery towards the complete removal of the tumour with adequate tumour resection margins. This review summarizes actual clinical needs in oncology that can be addressed by spontaneous Raman spectroscopy and it provides an overview over the results that have been published between 2007 and 2017. An analysis is made of the current status of translation of these results into clinical practice. Despite many promising results, most of the applications addressed in scientific studies are still far from clinical adoption and commercialization. The main hurdles are identified, which need to be overcome to ensure that in the near future we will see the first Raman spectroscopy-based solutions being used in routine oncologic diagnostic and surgical procedures.


Subject(s)
Neoplasms/diagnostic imaging , Neoplasms/surgery , Spectrum Analysis, Raman , Humans
16.
BMC Cancer ; 16: 580, 2016 08 02.
Article in English | MEDLINE | ID: mdl-27484126

ABSTRACT

BACKGROUND: Total laryngectomy with or without adjuvant (chemo)radiation often induces speech, swallowing and neck and shoulder problems. Speech, swallowing and shoulder exercises may prevent or diminish these problems. The aim of the present paper is to describe the study, which is designed to investigate the effectiveness and cost-utility of a guided self-help exercise program built into the application "In Tune without Cords" among patients treated with total laryngectomy. METHODS/DESIGN: Patients, up to 5 years earlier treated with total laryngectomy with or without (chemo)radiation will be recruited for participation in this study. Patients willing to participate will be randomized to the intervention or control group (1:1). Patients in the intervention group will be provided access to a guided self-help exercise program and a self-care education program built into the application "In Tune without Cords". Patients in the control group will only be provided access to the self-care education program. The primary outcome is the difference in swallowing quality (SWAL-QOL) between the intervention and control group. Secondary outcome measures address speech problems (SHI), shoulder disability (SDQ), quality of life (EORTC QLQ-C30, QLQ-H&N35 and EQ-5D), direct and indirect costs (adjusted iMCQ and iPCQ measures) and self-management (PAM). Patients will be asked to complete these outcome measures at baseline, immediately after the intervention or control period (i.e. at 3 months follow-up) and at 6 months follow-up. DISCUSSION: This randomized controlled trial will provide knowledge on the effectiveness of a guided self-help exercise program for patients treated with total laryngectomy. In addition, information on the value for money of such an exercise program will be provided. If this guided self-help program is (cost)effective for patients treated with total laryngectomy, the next step will be to implement this exercise program in current clinical practice. TRIAL REGISTRATION: NTR5255 Protocol version 4 date September 2015.


Subject(s)
Deglutition Disorders/rehabilitation , Exercise Therapy/economics , Laryngectomy/adverse effects , Patient Education as Topic/methods , Self Care/methods , Speech Disorders/rehabilitation , Cost-Benefit Analysis , Deglutition Disorders/etiology , Female , Humans , Male , Patient Education as Topic/economics , Prospective Studies , Quality of Life , Research Design , Self Care/economics , Speech Disorders/genetics , Treatment Outcome
17.
Support Care Cancer ; 24(3): 1261-8, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26306518

ABSTRACT

PURPOSE: The purpose of this study was to investigate the feasibility of an online self-care education program supporting early rehabilitation of patients after total laryngectomy (TLPs) and factors associated with satisfaction. METHODS: Health care professionals (HCPs) were invited to participate and to recruit TLPs. TLPs were informed on the self-care education program "In Tune without Cords" (ITwC) after which they gained access. A study specific survey was used (at baseline T0 and postintervention T1) on TLPs' uptake. Usage, satisfaction (general impression, willingness to use, user-friendliness, satisfaction with self-care advice and strategies, Net Promoter Score (NPS)), sociodemographic, and clinical factors were analyzed. RESULTS: HCPs of 6 out of 9 centers (67% uptake rate) agreed to participate and recruited TLPs. In total, 55 of 75 TLPs returned informed consent and the baseline T0 survey and were provided access to ITwC (73% uptake rate). Thirty-eight of these 55 TLPs used ITwC and completed the T1 survey (69% usage rate). Most (66%) TLPs were satisfied (i.e., score ≥7 (scale 1-10) on 4 survey items) with the self-care education program (mean score 7.2, SD 1.1). NPS was positive (+5). Satisfaction with the self-care education program was significantly associated with (higher) educational level and health literacy skills (P = .004, P = .038, respectively). No significant association was found with gender, age, marital status, employment status, Internet use, Internet literacy, treatment modality, time since total laryngectomy, and quality of life. CONCLUSION: The online self-care education program ITwC supporting early rehabilitation was feasible in clinical practice. In general, TLPs were satisfied with the program.


Subject(s)
Health Literacy/methods , Laryngeal Neoplasms/surgery , Laryngectomy/rehabilitation , Patient Education as Topic/methods , Self Care/methods , Adult , Aged , Cross-Sectional Studies , Employment , Female , Humans , Internet , Male , Middle Aged , Patient Satisfaction/statistics & numerical data , Quality of Life , Surveys and Questionnaires
18.
Lab Invest ; 95(10): 1186-96, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26237270

ABSTRACT

The poor prognosis of oral cavity squamous cell carcinoma (OCSCC) patients is associated with residual tumor after surgery. Raman spectroscopy has the potential to provide an objective intra-operative evaluation of the surgical margins. Our aim was to understand the discriminatory basis of Raman spectroscopy at a histological level. In total, 127 pseudo-color Raman images were generated from unstained thin tissue sections of 25 samples (11 OCSCC and 14 healthy) of 10 patients. These images were clearly linked to the histopathological evaluation of the same sections after hematoxylin and eosin-staining. In this way, Raman spectra were annotated as OCSCC or as a surrounding healthy tissue structure (i.e., squamous epithelium, connective tissue (CT), adipose tissue, muscle, gland, or nerve). These annotated spectra were used as input for linear discriminant analysis (LDA) models to discriminate between OCSCC spectra and healthy tissue spectra. A database was acquired with 88 spectra of OCSCC and 632 spectra of healthy tissue. The LDA models could distinguish OCSCC spectra from the spectra of adipose tissue, nerve, muscle, gland, CT, and squamous epithelium in 100%, 100%, 97%, 94%, 93%, and 75% of the cases, respectively. More specifically, the structures that were most often confused with OCSCC were dysplastic epithelium, basal layers of epithelium, inflammation- and capillary-rich CT, and connective and glandular tissue close to OCSCC. Our study shows how well Raman spectroscopy enables discrimination between OCSCC and surrounding healthy tissue structures. This knowledge supports the development of robust and reliable classification algorithms for future implementation of Raman spectroscopy in clinical practice.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Intraoperative Care , Mouth Mucosa/pathology , Tongue Neoplasms/diagnosis , Tongue/pathology , Academic Medical Centers , Cancer Care Facilities , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Cluster Analysis , Databases, Factual , Discriminant Analysis , Humans , Mouth Mucosa/surgery , Neoplasm Grading , Neoplasm, Residual , Netherlands , Spectrum Analysis, Raman , Tongue/surgery , Tongue Neoplasms/pathology , Tongue Neoplasms/surgery
19.
Otolaryngol Head Neck Surg ; 170(3): 766-775, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37747035

ABSTRACT

OBJECTIVE: Timely treatment initiation in head and neck cancer (HNC) care is of great importance regarding survival, oncological, functional, and psychological outcomes. Therefore, waiting times are assessed in the Dutch Head and Neck Audit (DHNA). This audit aims to assess and improve the quality of care through feedback and benchmarking. For this study, we examined how waiting times evolved since the start of the DHNA. STUDY DESIGN: Prospective cohort study. SETTING: National multicentre study. METHODS: The DHNA was established in 2014 and reached national coverage of all patients treated for primary HNC in 2019. DHNA data on curative patients from 2015 to 2021 was extracted on national (benchmark) and hospital level. We determined 3 measures for waiting time: (1) the care pathway interval (CPI, first visit to start treatment), (2) the time to treatment interval (TTI, biopsy to start treatment), and (3) CPI-/TTI-indicators (percentage of patients starting treatment ≤30 days). The Dutch national quality norm for the CPI-indicator is 80%. RESULTS: The benchmark median CPI and TTI improved between 2015 and 2021 from 37 to 26 days and 37 to 33 days, respectively. Correspondingly, the CPI- and TTI-indicators, respectively, increased from 39% to 64% and 35% to 40% in 2015 to 2021. Outcomes for all hospitals improved and dispersion between hospitals declined. Four hospitals exceeded the 80% quality norm in 2021. CONCLUSION: Waiting times improved gradually over time, with 4 hospitals exceeding the quality standard in 2021. On the hospital-level, process improvement plans have been initiated. Systematic registration, auditing, and feedback of data support the improvement of quality of care.


Subject(s)
Head and Neck Neoplasms , Waiting Lists , Humans , Prospective Studies , Head and Neck Neoplasms/therapy , Benchmarking , Biopsy
20.
Laryngoscope ; 134(7): 3170-3176, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38326981

ABSTRACT

OBJECTIVE: Evidence suggests that distant metastasis in head and neck squamous cell carcinoma is a spectrum of disease. Previous studies show that oligometastasis has favorable survival compared with polymetastasis. The quality of life of patients with oligometastasis remains unknown. To further solidify the position of oligometastasis as a separate entity, we hypothesized that oligometastatic patients experience better quality of life than polymetastatic patients. METHODS: Patients with distant metastasis were stratified into three groups: oligometastasis (≤3 metastatic foci in ≤2 anatomic sites), explosive metastasis (≥4 metastatic foci at one anatomic site), and explosive-disseminating metastasis (spread to ≥3 anatomic sites). Quality of life was assessed every 2 months post distant metastasis diagnosis. RESULTS: Between January 1, 2016, and December 31, 2021, a total of 161 patients with distant metastasis were identified, with a total of 397 measurements. In this group, 57 (35.4%) patients had oligometastasis, 35 (21.7%) patients had explosive metastasis, and 69 (42.9%) patients had explosive-disseminating metastasis. Their median post-distant metastasis survivals were 8.5 months, 3.2 months, and 3.2 months respectively (p < 0.001). A significantly better overall quality of life was observed in the oligometastasis group compared with the polymetastatic groups (+0.75 out of 7, p < 0.05). Furthermore, oligometastatic patients performed better in the subdomains of "physical functioning," "fatigue," and "pain." CONCLUSION: Results from this study underscore that subgroups exist regarding quality of life and survival within distant metastasis, with polymetastatic patients performing worse than oligometastatic patients. This highlights the significance of tailored interventions that consider the unique challenges faced by each metastatic group of patients. LEVEL OF EVIDENCE: 3, retrospective cohort study Laryngoscope, 134:3170-3176, 2024.


Subject(s)
Head and Neck Neoplasms , Neoplasm Metastasis , Quality of Life , Squamous Cell Carcinoma of Head and Neck , Humans , Male , Female , Middle Aged , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/secondary , Squamous Cell Carcinoma of Head and Neck/therapy , Squamous Cell Carcinoma of Head and Neck/pathology , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/psychology , Head and Neck Neoplasms/secondary , Aged , Retrospective Studies , Adult
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