Occurrence of comorbidity following osteoarthritis diagnosis: a cohort study in the Netherlands.

OBJECTIVE: To determine the risk of comorbidity following diagnosis of knee or hip osteoarthritis (OA). DESIGN: A cohort study was conducted using the Integrated Primary Care Information database, containing electronic health records of 2.5 million patients from the Netherlands. Adults at risk for OA were included. Diagnosis of knee or hip OA (=exposure) and 58 long-term comorbidities (=outcome) were defined by diagnostic codes following the International Classification of Primary Care coding system. Time between the start of follow-up and incident diagnosis of OA was defined as unexposed, and between diagnosis of OA and the end of follow-up as exposed. Age and sex adjusted hazard ratios (HRs) comparing comorbidity rates in exposed and unexposed patient time were estimated with 99.9% confidence intervals (CI). RESULTS: The study population consisted of 1,890,712 patients. For 30 of the 58 studied comorbidities, exposure to knee OA showed a HR larger than 1. Largest positive associations (HR with (99.9% CIs)) were found for obesity 2.55 (2.29-2.84) and fibromyalgia 2.06 (1.53-2.77). For two conditions a HR < 1 was found, other comorbidities showed no association with exposure to knee OA. For 26 comorbidities, exposure to hip OA showed a HR larger than 1. The largest were found for polymyalgia rheumatica 1.81 (1.41-2.32) and fibromyalgia 1.70 (1.10-2.63). All other comorbidities showed no associations with hip OA. CONCLUSION: This study showed that many comorbidities were diagnosed more often in patients with knee or hip OA. This suggests that the management of OA should consider the risk of other long-term-conditions.

The effect of emergency department pharmacists on drug overuse and drug underuse in patients with an ADE-related hospitalisation: a controlled intervention study.

BACKGROUND: Drug overuse or drug underuse are the most common causes of adverse drug events and can lead to hospital admissions. Using clinical pharmacists in the emergency department may improve patient safety as they are specialised in recognising of adverse drug events and tackling drug overuse and drug underuse. This study tested the effect of an emergency department pharmacist on the number of medication changes for drug overuse and drug underuse taking place in patients with an adverse drug event-related hospitalisation following an emergency department visit. METHODS: A multicenter prospective non-randomized controlled intervention study was conducted in a university hospital and a general teaching hospital. Trained emergency department pharmacists included patients in the intervention group with a hospital admission related to an adverse drug event. The interdisciplinary intervention consisted of a pharmacist-led medication review, patient counselling regarding medication, and information transmission to general practitioners and community pharmacies after discharge. The control patients were also admitted after an emergency department visit and received the usual care. The primary outcome was the number of medication changes for drug overuse and drug underuse that took place during hospital admission and persisted 6 months thereafter. Poisson regression analysis was used to estimate the difference in these medication changes between the intervention group and the control group. RESULTS: A total of 216 patients were included (intervention group 104, control group 112). In the intervention group, 156 medication changes for drug overuse and drug underuse persisted 6 months after admission compared to 59 in the control group (adjusted rate ratio 1.22 [95%CI 1.01-1.49] p = 0.039). CONCLUSION: Emergency department pharmacists do contribute to reduction of drug overuse and drug underuse of medication in patients with a hospitalisation related to adverse drug events after an emergency department visit.

The impact of vestibular schwannoma and its management on employment.

BACKGROUND: Employment is an important factor in quality of life. For vestibular schwannoma (VS) patients, employment is not self-evident, because of the sequelae of the disease or its treatment and their effects on daily life. OBJECTIVES: This study assessed employment status, sick leave (absenteeism) and being less productive at work (presenteeism) in the long-term follow-up of VS patients, and evaluated the impact of treatment strategy (active surveillance, surgery or radiotherapy). METHODS: A cross-sectional survey study was performed in a tertiary university hospital in the Netherlands. Patients completed the iMTA-post productivity questionnaire (iPCQ). Employment status was compared to that of the general Dutch population. Employment, absenteeism and presenteeism were compared between patients under active surveillance, patients after radiotherapy and post-surgical patients. RESULT: In total 239 patients participated, of which 67% were employed at the time of the study. Only 14% had a disability pension, which was comparable to the age-matched general Dutch population. The proportion of patients with absenteeism was 8%, resulting in a 4% reduction of working hours. Presenteeism was reported by 14% of patients, resulting in a 2% reduction of working hours. The median number of working hours per week was 36, and since the diagnosis, these hours had been reduced by 6%. There were no significant differences between treatment modalities. CONCLUSION: On average, long-term employment status and working hours of VS patients are comparable to the age-matched general population. Treatment strategies do not seem to differentially impact on long-term employment of VS patients.

The ALPACA study: (In)Appropriate LAMA prescribing in asthma: A cohort analysis.

INTRODUCTION: Since long-acting muscarinic antagonists (LAMA) are only indicated as add-on therapy in subjects with moderate-to-severe asthma, there are concerns whether LAMA monotherapy is associated with worse asthma control. AIM: To study the prevalence of LAMA monotherapy and its potential association with severe asthma exacerbations (SAE) in patients with asthma. METHODS: A cohort study (2007-2017) in the IPCI primary care database, in asthma patients aged 6-50, using LAMA during follow-up. Respiratory prescriptions were retrieved from the electronic medical records based on ATC code. Asthma treatment periods were created and categorized as LAMA mono, dual (LAMA + ICS), or triple therapy (LAMA + ICS + LABA). Relative rates (RR) of SAE, adjusting for patient characteristics, were estimated to compare treatments. RESULTS: From a total of 66,508 asthma patients, 1236 (1.9%) LAMA users were identified. Median age was 41 years, 65.9% were females. LAMA users were responsible for 3596 LAMA treatment periods of which 1390 (38.7%) were LAMA monotherapy, 553 (15.4%) dual therapy and 1653 (46.0%) triple therapy. The RR of SAE during LAMA monotherapy compared to dual therapy was 1.5 (95% CI 0.6-3.8). In patients alternating between mono and dual therapy (but never triple therapy), the RR for LAMA monotherapy increased to 5.7 (95% CI 1.4-23.6). CONCLUSIONS: This observational study shows that when LAMA is prescribed, it is often prescribed without concurrent ICS (LAMA monotherapy). LAMA monotherapy was associated with an increased risk of exacerbations when not used concurrently with ICS. This emphasizes the importance that LAMA should never be prescribed without concomitant ICS use in patients with asthma.

[18 years old: choose wisely! Provision of information about changing health insurance status]. / 18 Jaar: verstandig kiezen! Informatievoorziening rond veranderende verzekeringsstatus.

From the age of 18, dental care is no longer covered by basic healthcare insurance [in the Netherlands]. Individuals can voluntarily take out additional insurance however. The aim of this study was to map out what information those nearly 18 years old receive about the changes in coverage of dental care (Part A) and what their preferences were concerning information on this topic (Part B). Part A consisted of desk research on the websites of 4 health insurers and government agencies, complemented with interviews with portfolio holders. Part B consisted of a questionnaire survey among 18-year-old secondary school pupils training for university and vocational students (n = 106).The websites of health insurers and government agencies contained some information, 2 health insurers sent information by post about dental insurance and 1 also got in touch by phone. The level of knowledge about the insurance system among 18-year-olds was low, information often did not seem to have been received and they did not look for information themselves. Secondary school pupils training for university preferred to receive written information, vocational students preferred to receive it orally. Conclusion: Information about the changing health insurance status is available but does not reach those nearly 18 years old effectively. Cooperation and clarity on the responsibilities regarding the provision of information is recommended.

Pulmonary function changes following helical tomotherapy in patients with inoperable, locally advanced non-small cell lung cancer.

PURPOSE: To evaluate alterations in pulmonary function indices after helical tomotherapy and explore potential associations with biologically corrected dosimetric parameters. PATIENTS AND METHODS: In 64 patients with inoperable locally advanced non-small cell lung cancer, pulmonary function tests before and within 6 months after radiotherapy were evaluated retrospectively. In the case of concurrent chemotherapy a total dose of 67.2 Gy was delivered, otherwise 70.5 Gy was provided. In 44 patients, late pulmonary function changes (≥6 months after radiotherapy) could also be assessed. RESULTS: In the entire patient group, there were significant declines in forced expiratory volume in 1s (FEV1) (average change -4.1% predicted; P = 0.007), in forced vital capacity (FVC) (-4.9% predicted; P = 0.002), total lung capacity (TLC) (-5.8% predicted; P = 0.0016) and DLCO (diffusing capacity of the lung for carbon monoxide corrected for hemoglobin level) (-8.6% predicted; P < 0.001) during the first 6 months. Corresponding FEV1, FVC, TLC and DLCO declines in the subgroup with late measurements (after 11.3 months on average) were -5.7, -7.4, -7.0, -9.8% predicted. A multivariate analysis including V5 Gy, V10 Gy, V20 Gy, V40 Gy, V60 Gy, mean lung dose (MLD), gross tumor volume (GTV) and planning target volume (PTV) as potential covariates showed that GTV was the most consistent contributor, being significant for ∆FEV1 (P = 0.003), ∆FVC (P = 0.003), ∆TLC (P = 0.001) and ∆DLCO (P = 0.01). V5 Gy or V10 Gy did not contribute to any of the lung function changes. CONCLUSIONS: The decline in pulmonary function indices after helical tomotherapy was of similar magnitude to that observed in studies reporting the effect of conformal radiotherapy on lung function. Diffusion capacity was the parameter showing the largest decrease following radiation therapy as compared to baseline and correlated with gross tumor volume. None of the alterations in pulmonary function tests were associated with the lung volume receiving low-dose radiation.

Health-related quality of life, emotional burden, and neurocognitive function in the first generation of metastatic melanoma survivors treated with pembrolizumab: a longitudinal pilot study.

PURPOSE: The aim of this study was to assess the evolution of health-related quality of Life (HRQoL), emotional burden, and neurocognitive function in the first-generation metastatic melanoma survivors treated with pembrolizumab. METHODS: Survivors were defined as patients who achieved a durable remission for at least 6 months after initiating pembrolizumab in a single-center observational study (N = 141). A semi-structured interview was performed at baseline. Neurocognitive computerized testing and patient-reported outcomes were collected at 4 time points to assess HRQoL using the EORTC QLQ-C30 and the HADS to assess anxiety and depression. RESULTS: Out of 35 eligible patients, 25 were recruited and completed baseline assessment (18 female; median age 58 years [range 28-86]; 24 completed the 1-year follow-up phase. Median time since diagnosis was 30 months (range 12-84); median time since initiation of pembrolizumab was 19 months (range 6-42). At all visits, survivors reported a significantly lower global HRQoL, lower physical, emotional, cognitive, role, and social functioning compared with the European Mean of the healthy population. Fifteen patients (64%) had clinical levels of anxiety/depression at one time point during follow-up. The clinical interview revealed that 12 patients (48%) suffered from Cancer-Related-Post-Traumatic-Stress disorder, of whom 7 (28%) developed transient suicidal ideation, 1 patient made a suicide attempt. Neurocognitive testing revealed cognitive impairment in 8 patients (32%). CONCLUSIONS: Metastatic melanoma survivors, treated successfully with pembrolizumab, are at risk for suffering from emotional distress and neurocognitive impairment with a persistent impact on their HRQOL. Timely detection in order to offer tailored care is indicated.

Use of antihistamines and risk of ventricular tachyarrhythmia: a nested case-control study in five European countries from the ARITMO project.

PURPOSE: After regulatory restrictions for terfenadine and astemizole in '90s, only scarce evidence on proarrhythmic potential of antihistamines has been published. We evaluate the risk of ventricular tachyarrhythmia (VA) related to the use of individual antihistamines. METHODS: A matched case-control study nested in a cohort of new users of antihistamines was conducted within the EU-funded ARITMO project. Data on 1997-2010 were retrieved from seven healthcare databases: AARHUS (Denmark), GEPARD (Germany), HSD and ERD (Italy), PHARMO and IPCI (Netherlands) and THIN (UK). Cases of VA were selected and up to 100 controls were matched to each case. The odds ratio (OR) of current use for individual antihistamines (AHs) was estimated using conditional logistic regression. RESULTS: For agents largely used to prevent allergic symptoms, such as cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, we found no VA risk. A statistically significant, increased risk of VA was found only for current use of cyclizine in the pooled analysis (ORadj, 5.3; 3.6-7.6) and in THIN (ORadj, 5.3; 95% CI, 3.7-7.6), for dimetindene in GEPARD (ORadj, 3.9; 1.1-14.7) and for ebastine in GEPARD (ORadj, 3.3; 1.1-10.8) and PHARMO (ORadj, 4.6; 1.3-16.2). CONCLUSIONS: The risk of VA associated with a few specific antihistamines could be ascribable to heterogeneity in pattern of use or in receptor binding profile.

The impact of cumulative dose of cisplatin on outcome of patients with head and neck squamous cell carcinoma.

Despite the wide use of cisplatin-based concomitant chemoradiotherapy (CCRT) for head and neck squamous cell carcinoma (HNSCC), data on the optimal regimen and cumulative dose are scarce and frequently conflicting. We aimed to evaluate the compliance and the impact of the cumulative dose of cisplatin on overall survival (OS), disease-free survival (DFS), loco-regional control (LRC), and distant-metastasis-free survival (DMFS) in a retrospective study. Between 2008 and 2015, 279 patients with HNSCC scheduled for CCRT (three courses of 3-week 100 mg/m2 cisplatin) were identified. Of the whole group, 14% did not receive any cisplatin and 26% received daily cisplatin. In patients planned for three courses (n = 167), 56% received 3, 20% received 2, and 24% received one course. After median follow-up of 31.6 months, the actuarial OS, DFS, LRC, and DMFS rates at 3 years for patients received cumulative dose of ≥200 mg/m2 were significantly better compared to those received <200 mg/m2; 74 vs. 51% for OS, 73 vs. 49% for DFS, 80 vs. 58% for LRC (p < 0.001), and 85 vs. 76% for DMFS (p = 0.034). At multivariate analysis, the cumulative cisplatin dose (≥200 vs. <200 mg/m2) was significantly predictive for OS (HR 2.05; 95% CI 1.35-3.13, p = <0.001). Borderline GFR (60-70 mL/min) at baseline predicts compliance for ≥two courses (p = 0.003). In conclusion, considerable proportion of patients did not receive all pre-planned courses of cisplatin. Patients receiving cumulative cisplatin dose ≥200 mg/m2 had significantly better outcome than those receiving <200 mg/m2 and cumulative dose <200 mg/m2 might even be detrimental. These findings increased the bulk of slowly growing evidence on the optimal cumulative dose of cisplatin. Baseline GFR might predict compliance.

Recurrent oropharyngeal cancer after organ preserving treatment: pattern of failure and survival.

The objectives is to thoroughly analyze the pattern of failure and oncologic outcome in recurrent oropharyngeal cancer (OPC) after (chemo)radiotherapy and correlate the site of failure to the planned radiation dose. Between January 2010 and April 2014, 57 patients with recurrent OPC after (chemo)radiotherapy were analyzed. Endpoints were pattern of failure and overall survival (OS). Local (LF) and regional failure (RF) were classified as in-field [>50% within gross tumor volume (GTV)], marginal [<50% within GTV but >50% within clinical target volume (CTV)], or out-of-field (>50% outside CTV) recurrences. In the whole group, 70 recurrences were reported. Of the 31 LF, 29 (93.5%) were in-field and 2 (6.5%) were marginal. No out-field LF was reported. Of the 21 RF, 13 RF (62%) were in-field, 6 (28.5%) marginal, and 2 (9.5%) out-of-field recurrences. Forty-three percent of RF was developed in an electively treated neck level, and 2 of them were contralateral. OS at 2 years in recurrent HPV positive, compared to HPV-negative OPC, were 66 and 18%, respectively (p = 0.011). OS was also significantly better in patients that were salvage treatment which was possible (70 vs. 6%, p < 0.001). Median survival after distant failure was 3.6 months. The great majority of LFs were located within the GTV and 43% of RFs developed in an electively treated neck level. The currently used margins and dose recipe and the indication for bilateral nodal irradiation need to be reevaluated. OS was significantly better in recurrent HPV-positive OPC and in patients, where salvage treatment was possible.

Risk of cardiac valvulopathy with use of bisphosphonates: a population-based, multi-country case-control study.

UNLABELLED: Analyses of healthcare data from 30 million individuals in three countries showed that current use of bisphosphonates may be associated with a small increased risk of cardiac valvulopathy (vs. those not exposed within the previous year), although confounding cannot be entirely ruled out. The observed tendency for decreased valvulopathy risk with cumulative duration of bisphosphonate use >6 months may even indicate a protective effect with prolonged use. Further studies are still needed to evaluate whether bisphosphonates increase or decrease the risk of valvulopathy. INTRODUCTION: A signal of cardiac valve disorders with use of bisphosphonates was identified in the literature and EudraVigilance database, which contains reports of suspected adverse drug reactions from worldwide sources. The aim of this study was to evaluate the association using population-based healthcare data. METHODS: This was a case-control study among users of bisphosphonates and other drugs for osteoporosis in six healthcare databases covering over 30 million individuals in Italy, Netherlands and the UK from 1996 to 2012. Prescriptions/dispensations were used to assess drug exposure. Newly diagnosed cases of cardiac valvulopathy were identified via disease codes/free-text search. Controls were matched to each case by age, sex, database and index date. Adjusted odds ratios (ORs) were estimated using conditional logistic regression for the pooled data and meta-analysis of individual database risk estimates. RESULTS: A small but statistically significant association was found between exposure to bisphosphonates as a class and risk of valvulopathy. Overall risk was 18 % higher (95 % CI 12-23 %) in those currently exposed to any bisphosphonate (mainly alendronate and risedronate) vs. those not exposed within the previous year. Risk of valve regurgitation was 14 % higher (95 % CI 7-22 %). Decreased valvulopathy risk was observed with longer cumulative duration of bisphosphonate use, compared to use of less than 6 months. Meta-analyses of database-specific estimates confirmed results from pooled analyses. CONCLUSIONS: The observed increased risks of cardiac valvulopathy with bisphosphonate use, although statistically significant, were quite small and unlikely to be clinically significant. Further studies are still needed to evaluate whether bisphosphonates increase or decrease the risk of valvulopathy and to investigate possible mechanisms for the association.

Hypertension in older patients, a retrospective cohort study.

BACKGROUND: It is unknown to what extent General Practitioners (GPs) manage hypertension (HT) differently in older patients, as compared to younger age groups. The purpose of our study was to compare HT management in older patients to younger age groups. METHODS: We performed a retrospective cohort study of patients of 159 GP's practices in the Integrated Primary Care Information (IPCI) database. The study period lasted from September 2010 through December 2012. The study population consisted of all patients aged 60 years or older with at least one blood pressure (BP) measurement during the inclusion period, without pre-existent HT, diabetes mellitus (DM) or atherosclerotic cardiovascular disease at time of study start. Study outcomes were a diagnosis of HT within one month after cohort entry and the use of antihypertensive medication within 4 months after cohort entry in HT diagnosed patients. We compared the incidence of outcomes between the age groups, stratified by systolic blood pressure (SBP). Logistic regression analysis was used to assess the influence of age-adjusted SBP Z-scores, age and gender on the outcomes. RESULTS: We included 19,500 patients from 159 GP's practices of whom 1,181 (6.1 %) were newly diagnosed with HT. Corrected for age-adjusted SBP, older patients were less likely to be diagnosed with HT (odds ratio per year age increase 0.98, p < 0.001). Corrected for age-adjusted SBP, no significant effect of age on the probability of treatment in newly diagnosed HT patients was observed (p = 0.82). CONCLUSIONS: This study showed that GPs are less inclined to diagnose HT with increasing patient age, but do not withhold treatment when they diagnose HT in older patients.

New insights into factors influencing adult height in short SGA children: Results of a large multicentre growth hormone trial.

BACKGROUND: Growth hormone (GH) treatment is effective in improving adult height (AH) in short children born SGA. However, there is a wide variation in height gain, even after adjustment for predictive variables. It is therefore important to investigate new factors which can influence the response to GH. OBJECTIVE: To investigate the efficacy of GH treatment (1 mg/m(2/) day) in short SGA children on AH. To assess the relation between spontaneous catch-up growth after birth and growth during puberty on the total height gain SDS to AH. PATIENTS: Longitudinal GH trial in 170 children. RESULTS: Median age at start of GH was 7·1 years and height -3·0 SDS. AH was -1·8 SDS (TH-corrected AH -1·1 SDS) in boys and -1·9 SDS (TH-corrected AH -1·3 SDS) in girls. Spontaneous catch-up growth after birth was ≥0·5 SDS in 42% of children. In contrast to expectation, spontaneous catch-up growth was negatively correlated with total height gain SDS during GH (P = 0·009). During puberty, height SDS declined (-0·4 SDS in boys and -0·5 SDS in girls) resulting in a lower total height gain SDS than expected. Pubertal height gain was 25·5 cm in boys and 15·3 cm in girls, significantly lower compared to AGA children (P < 0·001). At onset of puberty, BA for boys and girls was moderately advanced (P = 0·02 and P < 0·001, respectively). Growth velocity was comparable to AGA children during the first two years of puberty, but thereafter significantly lower until reaching AH (P < 0·001). CONCLUSION: In contrast to our hypothesis, children with greater spontaneous catch-up growth after birth show a lower total height gain SDS during GH. Height SDS declines from mid-puberty, due to a marked early deceleration of growth velocity.

Examining a possible association between human papilloma virus (HPV) vaccination and migraine: results of a cohort study in the Netherlands.

UNLABELLED: Since the introduction of the bivalent human papilloma virus (HPV) vaccine in the Netherlands, migraine has been reported as a notable event in the passive safety surveillance system. Research on the association between HPV vaccination and migraine is needed. Therefore, potential migraine cases in 2008-2010 were selected from a group of general practitioners and linked to the vaccination registry. Data were analysed in three ways: (i) incidences of migraine postvaccination (2009/2010) were compared to pre-vaccination incidences (2008); (ii) in a cohort, incidence rates of migraine in vaccinated and unvaccinated girls were compared and (iii) in a self-controlled case series analysis, the relative incidence of migraine in potentially high-risk periods was compared to non-high-risk periods. Incidence rates of migraine for 12- to 16-year-old girls and boys postvaccination were slightly higher than pre-vaccination incidence rates. Incidence rate ratios (IRRs) for vaccinated compared to unvaccinated girls were not statistically significantly higher. Furthermore, the RR for migraine in the high-risk period of 6 weeks following each dose versus non-high-risk period was 4.3 (95% confidence interval (CI) 0.69-26.6) for certain migraine. CONCLUSION: Using different methods, no statistically significant association between HPV vaccination and incident migraine was found. However, the number of cases was low; to definitively exclude the risk, an increased sample size is needed.

Stereotactic radiotherapy for oligometastatic cancer: a prognostic model for survival.

BACKGROUND: Stereotactic radiotherapy (SRT) is a safe and locally effective treatment for patients with inoperable oligometastases. The challenge remains identifying subsets of patients that benefit in terms of overall survival (OS). PATIENTS AND METHODS: Between 2005 and 2011, 309 patients with ≤5 metastases were treated by stereotactic body radiotherapy (n=209) and/or by intracranial single or fractionated stereotactic radiotherapy (n=107). We analyzed OS and carried out a risk factor analysis. RESULTS: The median survival of all patients was 24 months. The 3-, 4- and 5-year OS rates were 32%, 25% and 19%, respectively. The following four risk factors were independently associated with impaired OS: nonadenocarcinoma histology (P<0.01), intracranial metastases (P<0.01), synchronous oligometastatic disease (P<0.01) and male gender (P=0.02). Patients with 0, 1 and 2 risk factors displayed a median survival (95% CI) of 40 (24-63), 29 (23-35) and 23 (16-29) months, respectively, and are defined as patients with good prognosis. Patients with 3 and 4 risk factors had a median survival of 9 (6-11) and 4 (1-7) months only and are defined as bad prognostic patients. CONCLUSIONS: We identified subsets of oligometastatic cancer patients with good prognosis after SRT. These patients are candidates for inclusion in prospective randomized trials for defining the role of SRT in the management of oligometastases.

Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall-cell lung cancer patients.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has emerged as a treatment modality in patients presenting with oligometastatic nonsmall-cell lung cancer (NSCLC). SBRT is used as a local consolidative treatment to metastatic disease sites. The majority of patients included in SBRT trials for oligometastatic NSCLC have controlled primary tumors and brain metastases. PATIENTS AND METHODS: Oligometastatic NSCLC patients with ≤5 metastatic lesions were included in a prospective phase II trial to evaluate efficacy and toxicity of SBRT to all disease sites, primary tumor and metastatic locations. SBRT to a dose of 50 Gy in 10 fractions was delivered. Positron emission tomography-computed tomography (PET-CT) was carried out at baseline and 3 months after SBRT to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST). The progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier method from start of chemotherapy or radiotherapy. Side-effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. RESULTS: Twenty-six patients received SBRT after induction chemotherapy (n = 17) or as a primary treatment (n = 9). Median follow-up was 16.4 months. Overall metabolic response rate was 60% with seven patients (30%) achieving a complete metabolic remission and 7 (30%) a partial metabolic response. Any acute grade 2 toxicity was observed in four patients (15%) and grade 3 pulmonary toxicity in two patients (8%). Median PFS and OS were 11.2 and 23 months. The 1-year PFS and 1-year OS rate were 45% and 67%, respectively. CONCLUSION: SBRT to all disease sites, primary tumor and metastatic locations, in oligometastatic NSCLC patients produced an acceptable median PFS of 11.2 months.

Characterization of the long-term effects of lethal total body irradiation followed by bone marrow transplantation on the brain of C57BL/6 mice.

PURPOSE: Total body irradiation (TBI) followed by bone marrow transplantation (BMT) is used in pre-clinical research to generate mouse chimeras that allow to study the function of a protein specifically on immune cells. Adverse consequences of irradiation on the juvenile body and brain are well described and include general fatigue, neuroinflammation, neurodegeneration and cognitive impairment. Yet, the long-term consequences of TBI/BMT performed on healthy adult mice have been poorly investigated. MATERIAL AND METHODS: We developed a robust protocol to achieve near complete bone marrow replacement in mice using 2x550cGy TBI and evaluated the impact of the procedure on their general health, mood disturbances, memory, brain atrophy, neurogenesis, neuroinflammation and blood-brain barrier (BBB) permeability 2 and/or 16 months post-BMT. RESULTS: We found a persistent decrease in weight along with long-term impact on locomotion after TBI and BMT. Although the TBI/BMT procedure did not lead to anxiety- or depressive-like behavior 2- or 16-months post-BMT, long-term spatial memory of the irradiated mice was impaired. We also observed radiation-induced impaired neurogenesis and cortical microglia activation 2 months post-BMT. Moreover, higher levels of hippocampal IgG in aged BMT mice suggest an enhanced age-related increase in BBB permeability that could potentially contribute to the observed memory deficit. CONCLUSIONS: Overall health of the mice did not seem to be majorly impacted by TBI followed by BMT during adulthood. Yet, TBI-induced alterations in the brain and behavior could lead to erroneous conclusions on the function of a protein on immune cells when comparing mouse chimeras with different genetic backgrounds that might display altered susceptibility to radiation-induced damage. Ultimately, the BMT model we here present could also be used to study the related long-term consequences of TBI and BMT seen in patients.

Computer-aided design and fabrication of nasal prostheses: a semi-automated algorithm using statistical shape modeling.

PURPOSE: This research aimed to develop an innovative method for designing and fabricating nasal prostheses that reduces anaplastologist expertise dependency while maintaining quality and appearance, allowing patients to regain their normal facial appearance. METHODS: The method involved statistical shape modeling using a morphable face model and 3D data acquired through optical scanning or CT. An automated design process generated patient-specific fits and appearances using regular prosthesis materials and 3D printing of molds. Manual input was required for specific case-related details. RESULTS: The developed method met all predefined requirements, replacing analog impression-making and offering compatibility with various data acquisition methods. Prostheses created through this method exhibited equivalent aesthetics to conventionally fabricated ones while reducing the skill dependency typically associated with prosthetic design and fabrication. CONCLUSIONS: This method provides a promising approach for both temporary and definitive nasal prostheses, with the potential for remote prosthesis fabrication in areas lacking anaplastology care. While new skills are required for data acquisition and algorithm control, these technologies are increasingly accessible. Further clinical studies will help validate its effectiveness, and ongoing technological advancements may lead to even more advanced and skill-independent prosthesis fabrication methods in the future.

Personalized neck irradiation guided by sentinel lymph node biopsy in patients with squamous cell carcinoma of the oropharynx, larynx or hypopharynx with a clinically negative neck: (Chemo)radiotherapy to the PRIMary tumor only. Protocol of the PRIMO study.

Background: Elective neck irradiation (ENI) is performed in head and neck cancer patients treated with definitive (chemo)radiotherapy. The aim is to eradicate nodal metastases that are not detectable by pretreatment imaging techniques. It is conceivable that personalized neck irradiation can be performed guided by the results of sentinel lymph node biopsy (SLNB). It is expected that ENI can be omitted to one or both sides of the neck in 9 out of 10 patients, resulting in less radiation side effects with better quality of life. Methods/design: This is a multicenter randomized controlled trial aiming to compare safety and efficacy of treatment with SLNB guided neck irradiation versus standard bilateral ENI in 242 patients with cN0 squamous cell carcinoma of the oropharynx, larynx or hypopharynx for whom bilateral ENI is indicated. Patients randomized to the experimental-arm will undergo SLNB. Based on the histopathologic status of the SLNs, patients will receive no ENI (if all SLNs are negative), unilateral neck irradiation only (if a SLN is positive at one side of the neck) or bilateral neck irradiation (if SLNs are positive at both sides of the neck). Patients randomized to the control arm will not undergo SLNB but will receive standard bilateral ENI. The primary safety endpoint is the number of patients with recurrence in regional lymph nodes within 2 years after treatment. The primary efficacy endpoint is patient reported xerostomia-related quality of life at 6 months after treatment. Discussion: If this trial demonstrates that the experimental treatment is non-inferior to the standard treatment in terms of regional recurrence and is superior in terms of xerostomia-related quality of life, this will become the new standard of care.

Cognition: development of a cognitive testing battery on the iPad for the evaluation of patients with brain Mets.

To make assessment of neurocognitive decline in patients with brain metastases more reliable and feasible, Brainlab AG developed an application 'Cognition' for the iPad by gamifying validated paper and pencil tests. This study aims at validating the computerized tests. We assessed reliability and comparability of 'Cognition' with similar well-established paper and pencil tests in two consecutive sessions per participant. The electronic tests used the same assignments with different stimuli than the paper and pencil tests. Domains involved are learning and memory, attention and processing speed, verbal fluency and executive functions. In total 5 employees and 25 cancer patients without disease in the CNS participated, of whom 24 completed both sessions. Reliability was found satisfying for the domains learning and memory (p = 0.08; p = 0.612; p = 0.4445) and verbal fluency (p = 0.064). A learning effect showed for attention and processing speed (p = 0.001) while executive functioning showed a significant decline, possibly due to radiotherapy-related fatigue (p = 0.013). Concerning comparability between electronic and paper results, a significant correlation was found for attention and processing speed (p = 0.000), for verbal fluency (p = 0.03), for executive functions (p = 0.000), but not for learning and memory (p = 0.41; p = 0.25). Overall 'Cognition' showed moderate comparability, probably caused by the consecution of tests during sessions and the unfamiliarity with electronic test in older patients. After improving its functionality, the application needs to be validated in patients with brain metastases before it can detect cognitive decline and possible early radiation toxicity or relapses.