Long-term health-care utilisation in older patients with cancer and the association with the Geriatric 8 screening tool: a retrospective analysis using linked clinical and population-based data in Belgium.

peer reviewed[en] BACKGROUND: Little evidence is available on the long-term health-care utilisation of older patients with cancer and whether this is associated with geriatric screening results. We aimed to evaluate long-term health-care utilisation among older patients after cancer diagnosis and the association with baseline Geriatric 8 (G8) screening results. METHODS: For this retrospective analysis, we included data from three cohort studies for patients (aged ≥70 years) with a new cancer diagnosis who underwent G8 screening between Oct 19, 2009 and Feb 27, 2015, and who survived more than 3 months after G8 screening. The clinical data were linked to cancer registry and health-care reimbursement data for long-term follow-up. The occurrence of outcomes (inpatient hospital admissions, emergency department visits, use of intensive care, contacts with general practitioner [GP], contacts with a specialist, use of home care, and nursing home admissions) was assessed in the 3 years after G8 screening. We assessed the association between outcomes and baseline G8 score (normal score [>14] or abnormal [≤14]) using adjusted rate ratios (aRRs) calculated from Poisson regression and using cumulative incidence calculated as a time-to-event analysis with the Kaplan-Meier method. FINDINGS: 7556 patients had a new cancer diagnosis, of whom 6391 patients (median age 77 years [IQR 74-82]) met inclusion criteria and were included. 4110 (64·3%) of 6391 patients had an abnormal baseline G8 score (≤14 of 17 points). In the first 3 months after G8 screening, health-care utilisation peaked and then decreased over time, with the exception of GP contacts and home care days, which remained high throughout the 3-year follow-up period. Compared with patients with a normal baseline G8 score, patients with an abnormal baseline G8 score had more hospital admissions (aRR 1·20 [95% CI 1·15-1·25]; p<0·0001), hospital days (1·66 [1·64-1·68]; p<0·0001), emergency department visits (1·42 [1·34-1·52]; p<0·0001), intensive care days (1·49 [1·39-1·60]; p<0·0001), general practitioner contacts (1·19 [1·17-1·20]; p<0·0001), home care days (1·59 [1·58-1·60]; p<0·0001), and nursing home admissions (16·7% vs 3·1%; p<0·0001) in the 3-year follow-up period. At 3 years, of the 2281 patients with a normal baseline G8 score, 1421 (62·3%) continued to live at home independently and 503 (22·0%) had died. Of the 4110 patients with an abnormal baseline G8 score, 1057 (25·7%) continued to live at home independently and 2191 (53·3%) had died. INTERPRETATION: An abnormal G8 score at cancer diagnosis was associated with increased health-care utilisation in the subsequent 3 years among patients who survived longer than 3 months. FUNDING: Stand up to Cancer, the Flemish Cancer Society

reMelting Curve Analysis as a Tool for Enrichment Monitoring in the SELEX Process

Current aptamer selection procedures enable limited control and transparency on how the DNA selection pool is evolving. Affinity tests and binding analysis are not always as informative. Here we show that real-time PCR provides a valuable tool for the follow-up of aptamer selection. Limited time, work and amount of amplified ssDNA make this an interesting instrument to set-up a SELEX design and monitor the enrichment of oligonucleotides. reMelting Curve Analysis (rMCA) after reannealing at stringent conditions provides information about enrichment, compared to a random library. Monitoring the SELEX process and optimizing conditions by means of the proposed methods can increase the selection efficiency in a controlled way. rMCA is applied in enrichment simulations and three different selection procedures. Our results imply that rMCA can be used for different SELEX designs and different targets. SELEX pool diversity analysis by rMCA is proven to be a useful, reproducible tool to detect and evaluate enrichment of specific binding aptamers while the selection procedure is performed.status: publishe

Cancer registration, molecular marker status and adherence to the WHO 2016 classification of pathology reports for glioma diagnosed during 2017-2019 in Belgium

Introduction:The objective of this study is to cross-check and if necessary, adjust registered ICD-O-3 topography and morphology codes with the findings in pathology reports available at the Belgian Cancer Registry (BCR) for glioma patients. Additionally, integration of molecular markers in the pathological diagnosis and concordance with WHO 2016 classification is investigated. Methods:Since information regarding molecular tests and corresponding conclusions are not available as structured data at population level, a manual screening of all pseudonymized pathology reports available at the BCR for registered glioma patients (2017-2019) was conducted. ICD-O-3 morphology and topography codes from the BCR database (based on information as provided by hospital oncological care programs and pathology labs), were, at tumour level, cross-checked with the data from the pathology reports and, if needed, specified or corrected. Relevant molecular markers (IDH-1/2, 1p19q codeletion, MGMTp) were manually extracted from the pathology reports. Results:In 95,3% of gliomas, the ICD-O-3 morphology code was correct. Non-specific topography codes were specified in 9,3%, while 3,3% of specific codes were corrected. The IDH status was known in 75,2% of astrocytic tumours. The rate of correct integrated diagnoses varies from 47,6% to 56,4% among different gliomas. MGMTp methylation status is available in 32,2% of glioblastomas. Conclusion:Both the integration of molecular markers in the conclusion of the pathology reports and the delivery of those reports to the BCR can be improved. The availability of distinct ICD-O-3 codes for each molecularly defined tumour entity within the WHO classification would increase the consistency of cancer registration, facilitate population level research and international benchmarking

Enhanced Biosensor Platforms for Detecting the Atherosclerotic Biomarker VCAM1 Based on Bioconjugation with Uniformly Oriented VCAM1-Targeting Nanobodies

Surface bioconjugation of biomolecules has gained enormous attention for developing advanced biomaterials including biosensors. While conventional immobilization (by physisorption or covalent couplings using the functional groups of the endogenous amino acids) usually results in surfaces with low activity, reproducibility and reusability, the application of methods that allow for a covalent and uniformly oriented coupling can circumvent these limitations. In this study, the nanobody targeting Vascular Cell Adhesion Molecule-1 (NbVCAM1), an atherosclerotic biomarker, is engineered with a C-terminal alkyne function via Expressed Protein Ligation (EPL). Conjugation of this nanobody to azidified silicon wafers and Biacore™ C1 sensor chips is achieved via Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) “click” chemistry to detect VCAM1 binding via ellipsometry and surface plasmon resonance (SPR), respectively. The resulting surfaces, covered with uniformly oriented nanobodies, clearly show an increased antigen binding affinity, sensitivity, detection limit, quantitation limit and reusability as compared to surfaces prepared by random conjugation. These findings demonstrate the added value of a combined EPL and CuAAC approach as it results in strong control over the surface orientation of the nanobodies and an improved detecting power of their targets—a must for the development of advanced miniaturized, multi-biomarker biosensor platforms

Epidemiology and survival of adult-type diffuse glioma in Belgium during the molecular era

Background Survival data of diffuse adult-type glioma is mostly based on prospective clinical trials or small retrospective cohort studies. Real-world data with large patient cohorts is currently lacking.Methods Using the nationwide, population-based Belgian Cancer Registry, all known histological reports of patients diagnosed with an adult-type diffuse glioma in Belgium between 2017 and 2019 were reviewed. The ICD-O-3 morphology codes were matched with the histological diagnosis. The gathered data were transformed into the 2021 World Health Organization classification of CNS tumors using the IDH- and 1p/19q-mutation status.Results Between 2017 and 2019, 2233 diffuse adult-type gliomas were diagnosed in Belgium. Full molecular status was available in 67.1% of identified cases. The age-standardized incidence rate of diffuse adult-type glioma in Belgium was estimated at 8.55 per 100 000 person-years and 6.72 per 100 000 person-years for grade 4 lesions. Median overall survival time in IDH-wild-type glioblastoma was 9.3 months, significantly shorter compared to grade 4 IDH-mutant astrocytoma (median survival time: 25.9 months). The 3-year survival probability was 86.0% and 75.7% for grades 2 and 3 IDH-mutated astrocytoma. IDH-wild-type astrocytoma has a worse prognosis with a 3-year survival probability of 31.6% for grade 2 and 5.7% for grade 3 lesions.Conclusions This registry-based study presents a large cohort of adult-type diffuse glioma with known molecular status and uses real-world survival data. It adds to the current literature which is mainly based on historical landmark trials and smaller retrospective cohort studies

Comorbidity in head and neck cancer: Is it associated with therapeutic delay, post-treatment mortality and survival in a population-based study?

OBJECTIVES: This study aims to investigate the relationship between comorbidities and therapeutic delay, post-treatment mortality, overall and relative survival in patients diagnosed with squamous cell carcinoma of the head and neck (HNSCC). PATIENTS AND METHODS: 9245 patients with a single HNSCC diagnosed between 2009 and 2014 were identified in the Belgian Cancer Registry. The Charlson Comorbidity Index (CCI) was calculated for 8812 patients (95.3%), distinguishing patients having none (0), mild (1-2), moderate (3-4) or severe comorbidity (>4). The relationship between CCI and therapeutic delay was evaluated using the Spearman correlation. Post-treatment mortality was modelled with logistic regression, using death within 30 days as the event. The association between comorbidity and survival was assessed using Cox proportional hazard models. RESULTS: Among 8812 patients with a known CCI, 39.2% had at least one comorbidity. Therapeutic delay increased from 31 to 36 days when the CCI worsened from 0 to 4 (rho = 0.087). After case-mix adjustment, higher baseline comorbidity was associated with increased post-surgery mortality (mild, OR 3.52 [95% CI 1.91-6.49]; severe, OR 18.71 [95% CI 6.85-51.12]) and post-radiotherapy mortality (mild, OR 2.23 [95% CI 1.56-3.19]; severe, OR 9.33 [95% CI 4.83-18.01]) and with reduced overall survival (mild, HR 1.39, [95% CI 1.31-1.48]; severe, HR 2.41 [95% CI 2.00-2.90]). That was also the case for relative survival in unadjusted analyses (mild, EHR 1.77 [95% CI 1.64-1.92]; severe, EHR = 4.15 [95% CI 3.43-5.02]). CONCLUSION: Comorbidity is significantly related to therapeutic delay, post-treatment mortality, 5-year overall and relative survival in HNSCC patients. Therapeutic decision support tools should optimally integrate comorbidity.status: publishe

Comorbidity in head and neck cancer : is it associated with therapeutic delay, post-treatment mortality and survival in a population-based study?

OBJECTIVES: This study aims to investigate the relationship between comorbidities and therapeutic delay, post-treatment mortality, overall and relative survival in patients diagnosed with squamous cell carcinoma of the head and neck (HNSCC). PATIENTS AND METHODS: 9245 patients with a single HNSCC diagnosed between 2009 and 2014 were identified in the Belgian Cancer Registry. The Charlson Comorbidity Index (CCI) was calculated for 8812 patients (95.3%), distinguishing patients having none (0), mild (1-2), moderate (3-4) or severe comorbidity (>4). The relationship between CCI and therapeutic delay was evaluated using the Spearman correlation. Post-treatment mortality was modelled with logistic regression, using death within 30 days as the event. The association between comorbidity and survival was assessed using Cox proportional hazard models. RESULTS: Among 8812 patients with a known CCI, 39.2% had at least one comorbidity. Therapeutic delay increased from 31 to 36 days when the CCI worsened from 0 to 4 (rho = 0.087). After case-mix adjustment, higher baseline comorbidity was associated with increased post-surgery mortality (mild, OR 3.52 [95% CI 1.91-6.49]; severe, OR 18.71 [95% CI 6.85-51.12]) and post-radiotherapy mortality (mild, OR 2.23 [95% CI 1.56-3.19]; severe, OR 9.33 [95% CI 4.83-18.01]) and with reduced overall survival (mild, HR 1.39, [95% CI 1.31-1.48]; severe, HR 2.41 [95% CI 2.00-2.90]). That was also the case for relative survival in unadjusted analyses (mild, EHR 1.77 [95% CI 1.64-1.92]; severe, EHR = 4.15 [95% CI 3.43-5.02]). CONCLUSION: Comorbidity is significantly related to therapeutic delay, post-treatment mortality, 5-year overall and relative survival in HNSCC patients. Therapeutic decision support tools should optimally integrate comorbidity

Comorbidities, timing of treatments, and chemotherapy use influence outcomes in stage III colon cancer: a population-based European study

For stage III colon cancer (CC), surgery followed by chemotherapy is the main curative approach, although optimum times between diagnosis and surgery, and surgery and chemotherapy, have not been established. We analysed a population-based sample of 1912 stage III CC cases diagnosed in eight European countries in 2009–2013 aiming to estimate: (i) odds of receiving postoperative chemotherapy, overall and within eight weeks of surgery; (ii) risks of death/relapse, according to treatment, Charlson Comorbidity Index, time from diagnosis to surgery for emergency and elective cases, and time from surgery to chemotherapy; and (iii) time-trends in chemotherapy use