The complementary value of intraoperative fluorescence imaging and Raman spectroscopy for cancer surgery: combining the incompatibles.

A clear margin is an important prognostic factor for most solid tumours treated by surgery. Intraoperative fluorescence imaging using exogenous tumour-specific fluorescent agents has shown particular benefit in improving complete resection of tumour tissue. However, signal processing for fluorescence imaging is complex, and fluorescence signal intensity does not always perfectly correlate with tumour location. Raman spectroscopy has the capacity to accurately differentiate between malignant and healthy tissue based on their molecular composition. In Raman spectroscopy, specificity is uniquely high, but signal intensity is weak and Raman measurements are mainly performed in a point-wise manner on microscopic tissue volumes, making whole-field assessment temporally unfeasible. In this review, we describe the state-of-the-art of both optical techniques, paying special attention to the combined intraoperative application of fluorescence imaging and Raman spectroscopy in current clinical research. We demonstrate how these techniques are complementary and address the technical challenges that have traditionally led them to be considered mutually exclusive for clinical implementation. Finally, we present a novel strategy that exploits the optimal characteristics of both modalities to facilitate resection with clear surgical margins.

Quality improvements of healthcare trajectories by learning from aggregated patient-reported outcomes: a mixed-methods systematic literature review.

BACKGROUND: In healthcare, analysing patient-reported outcome measures (PROMs) on an aggregated level can improve and regulate healthcare for specific patient populations (meso level). This mixed-methods systematic review aimed to summarize and describe the effectiveness of quality improvement methods based on aggregated PROMs. Additionally, it aimed to describe barriers, facilitators and lessons learned when using these quality improvement methods. METHODS: A mixed-methods systematic review was conducted. Embase, MEDLINE, CINAHL and the Cochrane Library were searched for studies that described, implemented or evaluated a quality improvement method based on aggregated PROMs in the curative hospital setting. Quality assessment was conducted via the Mixed Methods Appraisal Tool. Quantitative data were synthesized into a narrative summary of the characteristics and findings. For the qualitative analysis, a thematic synthesis was conducted. RESULTS: From 2360 unique search records, 13 quantitative and three qualitative studies were included. Four quality improvement methods were identified: benchmarking, plan-do-study-act cycle, dashboards and internal statistical analysis. Five studies reported on the effectiveness of the use of aggregated PROMs, of which four identified no effect and one a positive effect. The qualitative analysis identified the following themes for facilitators and barriers: (1) conceptual (i.e. stakeholders, subjectivity of PROMs, aligning PROMs with clinical data, PROMs versus patient-reported experience measures [PREMs]); (2a) methodological-data collection (i.e. choice, timing, response rate and focus); (2b) methodological-data processing (i.e. representativeness, responsibility, case-mix control, interpretation); (3) practical (i.e. resources). CONCLUSION: The results showed little to no effect of quality improvement methods based on aggregated PROMs, but more empirical research is needed to investigate different quality improvement methods. A shared stakeholder vision, selection of PROMs, timing of measurement and feedback, information on interpretation of data, reduction of missing data, and resources for data collection and feedback infrastructure are important to consider when implementing and evaluating quality improvement methods in future research.

The eHealth self-management application 'Oncokompas' that supports cancer survivors to improve health-related quality of life and reduce symptoms: which groups benefit most?

BACKGROUND: Oncokompas is a web-based self-management application that supports cancer survivors to monitor their health-related quality of life (HRQOL) and symptoms, and to obtain personalised feedback and tailored options for supportive care. In a large randomised controlled trial among survivors of head and neck cancer, colorectal cancer, and breast cancer and (non-)Hodgkin lymphoma, Oncokompas proved to improve HRQOL, and to reduce several tumour-specific symptoms. Effect sizes were however small, and no effect was observed on the primary outcome patient activation. Therefore, this study aims to explore which subgroups of cancer survivors may especially benefit from Oncokompas. MATERIALS AND METHODS: Cancer survivors (n = 625) were randomly assigned to the intervention group (access to Oncokompas, n = 320) or control group (6 months waiting list, n = 305). Outcome measures were HRQOL, tumour-specific symptoms, and patient activation. Potential moderators included socio-demographic (sex, age, marital status, education, employment), clinical (tumour type, stage, time since diagnosis, treatment modality, comorbidities), and personal factors (self-efficacy, personal control, health literacy, Internet use), and patient activation, mental adjustment to cancer, HRQOL, symptoms, and need for supportive care, measured at baseline. Linear mixed models were performed to investigate potential moderators. RESULTS: The intervention effect on HRQOL was the largest among cancer survivors with low to moderate self-efficacy, and among those with high personal control and those with high health literacy scores. Cancer survivors with higher baseline symptom scores benefitted more on head and neck (pain in the mouth, social eating, swallowing, coughing, trismus), and colorectal cancer (weight) specific symptoms. DISCUSSION: Oncokompas seems most effective in reducing symptoms in head and neck cancer and colorectal cancer survivors who report a higher burden of tumour-specific symptoms. Oncokompas seems most effective in improving HRQOL in cancer survivors with lower self-efficacy, and in cancer survivors with higher personal control, and higher health literacy.

Demographic, clinical and lifestyle-related correlates of accelerometer assessed physical activity and fitness in newly diagnosed patients with head and neck cancer.

Introduction: Objective measurements of levels of physical activity and fitness in patients with head and neck cancer (HNC) are lacking. Furthermore, demographic, clinical and lifestyle-related correlates of low levels of physical activity and fitness in patients with HNC are unknown. This study aims to investigate the levels of accelerometer that assessed physical activity and fitness in patients with HNC and to identify their demographical, clinical and lifestyle-related correlates.Methods: Two hundred and fifty-four patients who were recently diagnosed with HNC and participated in the NETherlands QUality of life and Biomedical cohort studies In head and neck Cancer (NET-QUBIC) study were included. Physical activity (accelerometer), cardiorespiratory fitness (Chester Step Test), hand grip strength (hand dynamometer) and lower body muscle function (30-second chair-stand test) were assessed. Multivariable linear regression analyses with a stepwise forward selection procedure were used.Results: Patients spent 229 min/d in physical activity of which 18 min/d in moderate-to-vigorous physical activity. The mean predicted VO2max was 27.9 ml/kg/min, the mean hand grip strength was 38.1 kg and the mean number of standings was 14.3. Patients with lower educational level, more comorbidity and higher tumor stage spent significantly less time in physical activity. Older patients, females and patients with a higher tumor stage had significantly lower cardiorespiratory fitness levels. Older patients, females, patients with more comorbidity, patients with normal weight and patients who have never smoked had significantly lower hand grip strength. Older patients, patients with lower educational level, smokers and patients with more comorbidity had a significantly lower function of lower body muscle.Conclusions: Pre-treatment levels of physical activity, cardiorespiratory fitness and lower body muscle function are low in patients with HNC. Based on this study, exercise programs targeted and tailored to patients with low levels of physical activity and fitness can be developed.

Advancing interdisciplinary research in head and neck cancer through a multicenter longitudinal prospective cohort study: the NETherlands QUality of life and BIomedical Cohort (NET-QUBIC) data warehouse and biobank.

BACKGROUND: Worldwide, over 500,000 people are diagnosed with head and neck cancer each year, a disease with major impact on life expectancy and quality of life. The purpose of the Netherlands Quality of life and Biomedical Cohort study (NET-QUBIC) is to advance interdisciplinary research that aims to optimize diagnosis, treatment, and supportive care for head and neck cancer patients and their informal caregivers. METHODS: Using an extensive assessment protocol (electronic clinical record form, patient reported outcome measures and fieldwork (interviews and physical tests)), clinical data and data on quality of life, demographic and personal factors, psychosocial (depression, anxiety, fatigue, pain, sleep, mental adjustment to cancer, posttraumatic stress), physical (speech, swallowing, oral function, malnutrition, physical fitness, neurocognitive function, sexual function), lifestyle (physical activity, nutrition, smoking, alcohol, drugs), and social factors (social function, social support, work, health care use, and costs) are collected and stored in the data warehouse. A longitudinal biobank is built with tumor tissue, blood and blood components, saliva samples, and oral rinses. An infrastructure for fieldwork and laboratory protocols is established at all participating centers. All patients fill out patient reported outcome measures before treatment and at 3, 6, 12, 24, 36, 48, and 60 months follow-up. The interviews, physical tests and biological sample collection are at baseline and 6, 12, and 24 months follow-up. The protocol for caregivers includes blood sampling and oral rinses at baseline and a tailored list of questionnaires, administered at the same time points as the patients. In total, 739 HNC patients and 262 informal caregivers have been included in 5 out of the 8 HNC centers in the Netherlands. DISCUSSION: By granting access to researchers to the NET-QUBIC data warehouse and biobank, we enable new research lines in clinical (e.g. treatment optimization in elderly patients), biological (e.g. liquid biopsy analysis for relapse detection), health related quality of life (e.g. the impact of toxicity on quality of life), and interrelated research (e.g. health related quality of life in relation to biomarkers and survival).

Correction to: Advancing interdisciplinary research in head and neck cancer through a multicenter longitudinal prospective cohort study: the NETherlands QUality of life and BIomedical Cohort (NET-QUBIC) data warehouse and biobank.

Following publication of the original article [1], the authors reported the name of R.J. Baatenburg de Jong was incorrectly tagged in the HTML version of the article.

Evaluation of the eighth TNM classification on p16-positive oropharyngeal squamous cell carcinomas in the Netherlands and the importance of additional HPV DNA testing.

Background: Oropharyngeal squamous cell carcinomas (OPSCCs) are traditionally caused by smoking and excessive alcohol consumption. However, in the last decades high-risk human papillomavirus (HPV) infections play an increasingly important role in tumorigenesis. HPV-driven OPSCCs are known to have a more favorable prognosis, which has led to important and marked changes in the recently released TNM-8. In this 8th edition, OPSCCs are divided based on p16 immunostaining, with p16 overexpression as surrogate marker for the presence of HPV. The aims of this study are to evaluate TNM-8 on a Dutch consecutive cohort of patients with p16-positive OPSCC and to determine the relevance of additional HPV DNA testing. Patients and methods: All OPSCC patients without distant metastases at diagnosis and treated with curative intent at VU University Medical Center (2000-2015) and Erasmus Medical Center (2000-2006) were included (N = 1204). HPV status was determined by p16 immunostaining followed by HPV DNA PCR on the p16-immunopositive cases. We compared TNM-7 and TNM-8 using the Harrell's C index. Results: In total, 388 of 1204 (32.2%) patients were p16-immunopositive. In these patients, TNM-8 had a markedly better predictive prognostic power than TNM-7 (Harrell's C index 0.63 versus 0.53). Of the 388 p16-positive OPSCCs, 48 tumors (12.4%) were HPV DNA-negative. This subgroup had distinct demographic, clinical and morphologic characteristics and showed a significantly worse five-year overall survival compared with the HPV DNA-positive tumors (P < 0.001). Conclusions: TNM-8 has a better predictive prognostic power than TNM-7 in patients with p16-positive OPSCC. However, within p16-positive OPSCCs, there is an HPV DNA-negative subgroup with distinct features and a worse overall survival, indicating the importance to perform additional HPV DNA testing when predicting prognosis and particularly for selecting patients for de-intensified treatment regimens.

Raman spectroscopic analysis of the molecular composition of oral cavity squamous cell carcinoma and healthy tongue tissue.

A Raman tissue spectrum is a quantitative representation of the overall molecular composition of that tissue. Raman spectra are often used as tissue fingerprints without further interpretation of the specific information that they contain about the tissue's molecular composition. In this study, we analyzed the differences in molecular composition between oral cavity squamous cell carcinoma (OCSCC) and healthy tissue structures in tongue, based on their Raman spectra. A total of 1087 histopathologically annotated spectra (142 OCSCC, 202 surface squamous epithelium, 61 muscle, 65 adipose tissue, 581 connective tissue, 26 gland, and 10 nerve) were obtained from Raman maps of 44 tongue samples from 21 patients. A characteristic, average spectrum of each tissue structure was fitted with a set of 55 pure-compound reference spectra, to define the best library of fit-spectra. Reference spectra represented proteins, lipids, nucleic acids, carbohydrates, amino acids and other miscellaneous molecules. A non-negative least-squares algorithm was used for fitting. Individual spectra per histopathological annotation were then fitted with this selected library in order to determine the molecular composition per tissue structure. The spectral contribution per chemical class was calculated. The results show that all characteristic tissue-type spectra could be fitted with a low residual of <4.82%. The content of carbohydrates, proteins and amino acids was the strongest discriminator between OCSCC and healthy tissue. The combination of carbohydrates, proteins and amino acids was used for a classification model of 'tumor' versus 'healthy tissue'. Validation of this model on an independent dataset showed a specificity of 93% at a sensitivity of 100%.

Adjuvant radiotherapy in sinonasal mucosal melanoma: A retrospective analysis.

OBJECTIVES: Evaluation of outcome after curative treatment for sinonasal mucosal melanoma focused on the effect of adjuvant radiotherapy on recurrence and survival. DESIGN: Retrospective chart analysis. SETTING: Tertiary referral hospital. PARTICIPANTS: Fifty-one patients with primary sinonasal mucosal melanoma who underwent surgical resection with curative intention between 1980 and 2016 at Erasmus Medical Center, Rotterdam. MAIN OUTCOME MEASURES: Patients were categorised into 2 groups: surgery alone and surgery with adjuvant radiotherapy. Log-rank test was used to compare rates of recurrence and survival between treatment groups. Predictors for treatment modality, recurrence and survival were assessed with multivariate statistical analysis. RESULTS: Of all patients, 23.5% developed local recurrence and 47.1% developed distant metastasis. Estimated 5-year disease-free survival was 25.2%, and 5-year overall survival (OS) was 38.1%. Forty-three patients (84.3%) were treated with post-operative radiotherapy. Patients who underwent surgery with adjuvant radiotherapy presented more often with high tumour stage, tumour involving multiple sites and positive margins. Post-operative radiotherapy seemed to be associated with better local control (P = .549). No effect was found on occurrence of distant metastasis and OS. Positive margin status was an independent negative predictor for distant metastasis-free survival and overall survival. CONCLUSIONS: Our treatment outcomes are consistent with literature. Post-operative radiotherapy seems to be associated with improved local control despite advanced disease and positive margin status in this treatment group.

Postoperative value of serum squamous cell carcinoma antigen as a predictor of recurrence in sinonasal inverted papilloma.

OBJECTIVES: Sinonasal inverted papilloma (IP) has several unfavourable characteristics and therefore requires careful monitoring. The goal of this study was to identify whether serum squamous cell carcinoma antigen (SCCa) could predict IP recurrence. DESIGN: A retrospective cohort study. SETTING: Department of otolaryngology/head and neck surgery, Erasmus Medical Centre, Rotterdam, the Netherlands. PARTICIPANTS: One hundred and thirty patients with IP treated at our centre with SCCa measurements available were included. MAIN OUTCOME MEASUREMENTS: Follow-up of patients with IP since 2005, recurrence was defined as new disease within primary localisation at least 3 months after adequate surgical removal. We analysed the association between IP recurrence and serum SCCa values measured preoperatively, postoperatively and during follow-up. RESULTS: Preoperative SCCa values or values measured during follow-up were not associated with risk of recurrence. Postoperative SCCa was positively associated with the risk of recurrence (P < 0.001). Postoperative SCCa had a good discriminative ability for the identification of recurrence with an area under the curve of 80.9%. CONCLUSION: Postoperative SCCa is strongly associated with risk of recurrence. This might help the surgeon in the postoperative setting by identifying high-risk patients and planning follow-up strategy tailored to the individual patient.

Zenker's diverticulum: Rotterdam experience.

Different surgical techniques exist for the treatment of Zenker's diverticulum (ZD), of which minimally invasive techniques have become the standard. We reviewed our experience with management and treatment of ZD and sought to determine what type of treatment is most effective and efficient. We selected patients who underwent treatment for ZD between January 2004 and January 2014 at our tertiary referral center. All procedures were performed by ENT surgeons. The medical records were reviewed for pre- and intraoperative characteristics and follow-up. Of our 94 patients (58 male, 36 female), 75 underwent endoscopic cricopharyngeal myotomy (42 stapler, 33 laser) and 6 received treatment via transcervical approach. 13 interventions were aborted. Mean operating time was 49.0 min for stapler, 68.3 for laser and 124.0 for the transcervical approach. Its respective median post-operative admission durations were 2.0, 3.0 and 3.0 days. After the first treatment, of the 75 endoscopic procedures, 45 patients (23 stapler, 22 laser) had complete symptom resolution. In the transcervical group 4 (67 %) patients were symptom free and one patient died of complications. In the endoscopically treated patients, ten complications occurred, of which 8 G1 and 2 G2 (Clavien Dindo classification). In the transcervical group 2 complications occurred, 1 G3b and 1 G5. Both endoscopic techniques provide efficient management of Zenker's diverticulum with the stapler-assisted modality providing a shorter surgery duration and hospital admission. Although there is no significant difference in terms of complications or recurrence rates for both endoscopic techniques, it seems that stapler patients are at higher risk of having a re-intervention and of having more severe complications.

Discrimination between oral cancer and healthy tissue based on water content determined by Raman spectroscopy.

Tumor-positive resection margins are a major problem in oral cancer surgery. High-wavenumber Raman spectroscopy is a reliable technique to determine the water content of tissues, which may contribute to differentiate between tumor and healthy tissue. The aim of this study was to examine the use of Raman spectroscopy to differentiate tumor from surrounding healthy tissue in oral squamous cell carcinoma. From 14 patients undergoing tongue resection for squamous cell carcinoma, the water content was determined at 170 locations on freshly excised tongue specimens using the Raman bands of the OH-stretching vibrations (3350-3550 cm(-1)) and of the CH-stretching vibrations (2910-2965 cm(-1)). The results were correlated with histopathological assessment of hematoxylin and eosin stained thin tissue sections obtained from the Raman measurement locations. The water content values from squamous cell carcinoma measurements were significantly higher than from surrounding healthy tissue (p-value < 0.0001). Tumor tissue could be detected with a sensitivity of 99% and a specificity of 92% using a cutoff water content value of 69%. Because the Raman measurements are fast and can be carried out on freshly excised tissue without any tissue preparation, this finding signifies an important step toward the development of an intraoperative tool for tumor resection guidance with the aim of enabling oncological radical surgery and improvement of patient outcome.

Management of the neck in T1 and T2 buccal squamous cell carcinoma.

Buccal squamous cell carcinoma (SCC) appears to behave more aggressively than other oral subsites, in particular with regards to regional disease at presentation and regional recurrence. Adequate management of the neck is of the utmost importance but is still the subject of debate. An international multicentre retrospective review of 101 patients treated for T1-T2 buccal SCC was performed. Twenty-four were staged clinical node positive (cN+) and underwent therapeutic neck dissection, while 77 were node negative (cN0), with 32 undergoing elective neck dissection (END), with an occult nodal metastasis rate of 28.1%. Depth of invasion (DOI) < 4 mm was associated with a significantly lower rate of cervical nodal metastasis (87.5% versus 12.5%; P = 0.033). END demonstrated a non-significantly lower regional recurrence rate compared to observation (6.3% versus 8.9%, P = 0.670). Regional recurrence was more common in pN+ (24%) and undissected cases (8.9%) than in pN0 patients (0%) (P = 0.011) and was associated with DOI > 5 mm (P = 0.002). Regional recurrence resulted in a reduction in survival (24 versus 93 months, P < 0.001). In the pT2cN0 group, END improved survival (123 versus 26 months, P = 0.009). It is suggested that END be performed in cT2N0 buccal SCC, particularly for tumours with DOI > 4 mm.

Human papillomavirus detection and comorbidity: critical issues in selection of patients with oropharyngeal cancer for treatment De-escalation trials.

BACKGROUND: The presence of human papillomavirus (HPV)-infection in oropharyngeal squamous cell carcinoma (OPSCC) is a major determinant in prognostic risk modeling. However, most risk models are based on clinical trials which only include a selected patient population. The clinical significance of HPV and other prognostic factors in patients with OPSCC remains to be evaluated in a large, unselected cohort, which also includes patients with stage I/II disease and patients with severe comorbidity. PATIENTS AND METHODS: All patients diagnosed with OPSCC in 2000-2006 in two Dutch university hospitals were included. The presence of an oncogenic HPV infection was determined by p16-immunostaining, followed by a high-risk HPV general primer 5+/6+ DNA PCR on the p16-positive cases. Cox regression analysis was carried out to compare survival rates between HPV-positive and HPV-negative patients and a prognostic model was generated by recursive partitioning. RESULTS: In total, 163 of 841 (19.4%) tumors were HPV-positive. Patients with HPV-positive OPSCC had a more favorable overall survival [73.5% versus 40.9% after 5 years; P < 0.001; hazard ratio = 0.34, 95% confidence interval (CI) 0.25-0.48] compared with patients with HPV-negative OPSCC. Patients with p16-positive but HPV DNA-negative tumors showed a significantly less favorable survival than patients with p16-positive and HPV DNA-positive tumors (P < 0.001). A prognostic model was developed in which patients were classified into three risk groups according to HPV status, nodal stage and comorbidity. [Harrell's concordance index of 0.68 (95% CI 0.65-0.71)]. CONCLUSIONS: Tumor HPV status is a strong and independent prognostic factor for survival among patients with OPSCC. A prognostic risk model was proposed, based on our large, unselected cohort of patients with HPV status, comorbidity and nodal stage being the important prognostic factors. In addition, this study emphasizes the importance of performing an HPV DNA-specific test besides p16-immunostaining.

Radiotherapy for T1-2N0 glottic cancer: a multivariate analysis of predictive factors for the long-term outcome in 1050 patients and a prospective assessment of quality of life and voice handicap index in a subset of 233 patients.

OBJECTIVES: To evaluate the outcomes of patients with early stage glottic cancer (GC) treated with radiotherapy (RT). DESIGN, SETTING AND PARTICIPANTS: The current study report on a retrospective analysis of oncologic outcome of 1050 patients with T1-2N0 glottic cancer treated with radiotherapy. Prospective assessment of quality of life (QoL) and voice handicap index (VHI) was performed in all patients treated from 2006 onwards (n = 233). MAIN OUTCOME MEASURES: Local control (LC), regional control (RC), disease-free survival (DFS), overall survival (OS), quality of life and voice handicap index. RESULTS: After a median follow-up of 90 months (range 3-309), the actuarial rates of local control, regional control, disease-free survival and overall survival were 85%, 99%, 84% and 81% at 5 years and 82%, 98%, 80% and 61% at 10 years, respectively. On multivariate analysis, T2 tumours, smoking after radiotherapy and conventional radiation scheme correlated significantly with poor local control. Patients who continued smoking after radiotherapy had also significantly lower overall survival rates (OR 4.3, P < 0.001). Hypothyroidism was reported in 18% of patients. Slight and temporary deterioration of quality of life scores was reported. Patient-reported xerostomia and dysphagia at 48 months were -7.1 and -6.5, compared with baseline, respectively. Voice handicap index improved significantly from 37 at baseline to 18 at 48 months. Patients with T2b and those who continued smoking had significantly worse voice handicap index. CONCLUSIONS: In the current study, excellent outcome with good quality of life and voice handicap index scores were reported. T2 tumours, in particular T2b, and continuing smoking after radiotherapy correlated significantly with poor local control and worse voice handicap index.

B-cell clusters at the invasive margin associate with longer survival in early-stage oral-tongue cancer patients.

In oral-cancer, the number of tumor-infiltrating lymphocytes (TILs) associates with improved survival, yet the prognostic value of the cellular composition and localization of TILs is not defined. We quantified densities, localizations, and cellular networks of lymphocyte populations in 138 patients with T1-T2 primary oral-tongue squamous cell carcinoma treated with surgical resections without any perioperative (chemo)radiotherapy, and correlated outcomes to overall survival (OS). Multiplexed in-situ immunofluorescence was performed for DAPI, CD4, CD8, CD20, and pan-cytokeratin using formalin-fixed paraffin-embedded sections, and spatial distributions of lymphocyte populations were assessed in the tumor and stroma compartments at the invasive margin (IM) as well as the center of tumors. We observed a high density of CD4, CD8, and CD20 cells in the stroma compartment at the IM, but neither lymphocyte densities nor networks as single parameters associated with OS. In contrast, assessment of two contextual parameters within the stroma IM region of tumors, i.e., the number of CD20 cells within 20 µm radii of CD20 and CD4 cells, termed the CD20 Cluster Score, yielded a highly significant association with OS (HR 0.38; p = .003). Notably, the CD20 Cluster Score significantly correlated with better OS and disease-free survival in multivariate analysis (HR 0.34 and 0.47; p = .001 and 0.019) as well as with lower local recurrence rate (OR: 0.13; p = .028). Taken together, our study showed that the presence of stromal B-cell clusters at IM, in the co-presence of CD4 T-cells, associates with good prognosis in early oral-tongue cancer patients.

Reasons for not reaching or using web-based self-management applications, and the use and evaluation of Oncokompas among cancer survivors, in the context of a randomised controlled trial.

INTRODUCTION: The web-based self-management application Oncokompas was developed to support cancer survivors to monitor health-related quality of life and symptoms (Measure) and to provide tailored information (Learn) and supportive care options (Act). In a previously reported randomised controlled trial (RCT), 68% of 655 recruited survivors were eligible, and of those 45% participated in the RCT. Among participants of the RCT that were randomised to the intervention group, 52% used Oncokompas as intended. The aim of this study was to explore reasons for not participating in the RCT, and reasons for not using Oncokompas among non-users, and the use and evaluation of Oncokompas among users. METHODS: Reasons for not participating were assessed with a study-specific questionnaire among 243 survivors who declined participation. Usage was investigated among 320 participants randomised to the intervention group of the RCT via system data and a study-specific questionnaire that was assessed during the 1 week follow-up (T1) assessment. RESULTS: Main reasons for not participating were not interested in participation in scientific research (40%) and not interested in scientific research and Oncokompas (28%). Main reasons for not being interested in Oncokompas were wanting to leave the period of being ill behind (29%), no symptom burden (23%), or lacking internet skills (18%). Out of the 320 participants in the intervention group 167 (52%) used Oncokompas as intended. Among 72 non-users, main reasons for not using Oncokompas were no symptom burden (32%) or lack of time (26%). Among 248 survivors that activated their account, satisfaction and user-friendliness were rated with a 7 (scale 0-10). Within 3 (IQR 1-4) sessions, users selected 32 (IQR 6-37) topics. Main reasons for not using healthcare options in Act were that the information in Learn was already sufficient (44%) or no supportive care needs (32%). DISCUSSION: Main reasons for not reaching or using Oncokompas were no symptom burden, no supportive care needs, or lack of time. Users selected many cancer-generic and tumour-specific topics to address, indicating added value of the wide range of available topics.

Structural brain differences in pre-adolescents who persist in and recover from stuttering.

BACKGROUND: Stuttering is a complex speech fluency disorder occurring in childhood. In young children, stuttering has been associated with speech-related auditory and motor areas of the brain. During transition into adolescence, the majority of children who stutter (75-80%) will experience remission of their symptoms. The current study evaluated brain (micro-)structural differences between pre-adolescents who persisted in stuttering, those who recovered, and fluently speaking controls. METHODS: This study was embedded in the Generation R Study, a population-based cohort in the Netherlands of children followed from pregnancy onwards. Neuroimaging was performed in 2211 children (mean age: 10 years, range 8-12), of whom 20 persisted in and 77 recovered from stuttering. Brain structure (e.g., gray matter) and microstructure (e.g., diffusion tensor imaging) differences between groups were tested using multiple linear regression. RESULTS: Pre-adolescents who persisted in stuttering had marginally lower left superior frontal gray matter volume compared to those with no history of stuttering (ß -1344, 95%CI -2407;-280), and those who recovered (ß -1825, 95%CI -2999;-650). Pre-adolescents who recovered, compared to those with no history of stuttering, had higher mean diffusivity in the forceps major (ß 0.002, 95%CI 0.001;0.004), bilateral superior longitudinal fasciculi (ß 0.001, 95%CI 0.000;0.001), left corticospinal tract (ß 0.003, 95%CI 0.002;0.004), and right inferior longitudinal fasciculus (ß 0.001, 95%CI 0.000;0.001). CONCLUSION: Findings suggest that relatively small difference in prefrontal gray matter volume is associated with persistent stuttering, and alterations in white matter tracts are apparent in individuals who recovered. The findings further strengthen the potential relevance of brain (micro-)structure in persistence and recovery from stuttering in pre-adolescents.

Screening for head and neck second primary tumors in patients with esophageal squamous cell cancer: A systematic review and meta-analysis.

Background: Esophageal squamous cell carcinomas (ESCCs) are often accompanied by head and neck second primary tumors (HNSPTs). The prognosis of patients with an additional HNSPT is worse compared with patients with only ESCC. Therefore, early detection of HNSPTs may improve the overall outcome of patients with ESCC. The purpose of this study was to investigate the yield of endoscopic screening for HNSPTs in patients with primary ESCC. Methods: We conducted a systematic literature search of all available databases. Studies were included if ESCC patients were endoscopically screened for HNSPT. The primary outcome was the pooled prevalence of HNSPTs. Results: Twelve studies, all performed in Japan, were included in this systematic review with a total of 6483 patients. The pooled prevalence of HNSPTs was 6.7% (95% confidence interval: 4.9-8.4). The overall heterogeneity was high across the studies (I2 = 89.0%, p < 0.001). Most HNSPTs were low stage (85.3%) and located in the hypopharynx (60.3%). The proportion of synchronous (48.2%) and metachronous (51.8%) HNSPTs was comparable. Conclusion: Based on our results, HNSPT screening could be considered in patients with primary ESCC. All studies were performed in Japan; it is therefore not clear whether this consideration applies to the Western world.

Stuttering and gray matter morphometry: A population-based neuroimaging study in young children.

Stuttering is a developmental speech disorder originating in early childhood. We aimed to replicate the association of stuttering and structural morphometry using a large, population-based prospective cohort, the Generation R Study, and explore the neurobiological mechanism of stuttering in children. Twenty-six children with a history of stuttering and 489 fluent speaking peers (ages 6-9) were included in the MRI sub-study. Cortical and subcortical regions of interest were analyzed using linear regression models. Compared to fluent speakers, children with a history of stuttering had less gray matter volume in the left inferior frontal gyrus and supplementary motor area. Exploratory surface-based brain analysis showed thinner cortex in the left inferior frontal gyrus, and in bilateral frontal and parietal areas. These findings corroborate previous studies that reported aberrant brain morphometry in speech motor and auditory regions in children who stutter. Future research is needed to explore the causal nature of this association.