Web-based return of individual patient-reported outcome results among patients with lymphoma:Randomized controlled trial

BACKGROUND: There has been a cultural shift toward patient engagement in health, with a growing demand from patients to access their results. OBJECTIVE: The Lymphoma Intervention (LIVE) trial is conducted to examine the impact of return of individual patient-reported outcome (PRO) results and a web-based self-management intervention on psychological distress, self-management, satisfaction with information, and health care use in a population-based setting. METHODS: Return of PRO results included comparison with age- and sex-matched peers and was built into the Patient-Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship registry. The self-management intervention is an adaptation of a fully automated evidence-based intervention for breast cancer survivors. Patients with lymphoma who completed the web-based questionnaire were equally randomized to care as usual, return of PRO results, and return of PRO results plus self-management intervention. Patients completed questionnaires 9 to 18 months after diagnosis (T0; n=227), 4 months (T1; n=190), 12 months (T2; n=170), and 24 months (T3; n=98). RESULTS: Of all invited patients, 51.1% (456/892) responded and web-based participants (n=227) were randomly assigned to care as usual (n=76), return of PRO results (n=74), or return of PRO results and access to Living with lymphoma (n=77). Return of PRO results was viewed by 76.7% (115/150) of those with access. No statistically significant differences were observed for psychological distress, self-management, satisfaction with information provision, and health care use between patients who received PRO results and those who did not (P>.05). Use of the self-management intervention was low (2/76, 3%), and an effect could therefore not be determined. CONCLUSIONS: Return of individual PRO results seems to meet patients’ wishes but had no beneficial effects on patient outcome. No negative effects were found when individual PRO results were disclosed, and the return of individual PRO results can therefore be safely implemented in daily clinical practice. TRIAL REGISTRATION: Netherlands Trial Register NTR5953; https://www.trialregister.nl/trial/5790 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-017-1943-

Single Nucleotide Polymorphism (SNP)-Based Loss of Heterozygosity (LOH) Testing by Real Time PCR in Patients Suspect of Myeloproliferative Disease

During tumor development, loss of heterozygosity (LOH) often occurs. When LOH is preceded by an oncogene activating mutation, the mutant allele may be further potentiated if the wild-type allele is lost or inactivated. In myeloproliferative neoplasms (MPN) somatic acquisition of JAK2V617F may be followed by LOH resulting in loss of the wild type allele. The occurrence of LOH in MPN and other proliferative diseases may lead to a further potentiating the mutant allele and thereby increasing morbidity. A real time PCR based SNP profiling assay was developed and validated for LOH detection of the JAK2 region (JAK2LOH). Blood of a cohort of 12 JAK2V617F-positive patients (n = 6 25–50% and n = 6>50% JAK2V617F) and a cohort of 81 patients suspected of MPN was stored with EDTA and subsequently used for validation. To generate germ-line profiles, non-neoplastic formalin-fixed paraffin-embedded tissue from each patient was analyzed. Results of the SNP assay were compared to those of an established Short Tandem Repeat (STR) assay. Both assays revealed JAK2LOH in 1/6 patients with 25–50% JAK2V617F. In patients with >50% JAK2V617F, JAK2LOH was detected in 6/6 by the SNP assay and 5/6 patients by the STR assay. Of the 81 patients suspected of MPN, 18 patients carried JAK2V617F. Both the SNP and STR assay demonstrated the occurrence of JAK2LOH in 5 of them. In the 63 JAK2V617F-negative patients, no JAK2LOH was observed by SNP and STR analyses. The presented SNP assay reliably detects JAK2LOH and is a fast and easy to perform alternative for STR analyses. We therefore anticipate the SNP approach as a proof of principle for the development of LOH SNP-assays for other clinically relevant LOH loci

The Prospective Dutch Colorectal Cancer (PLCRC) cohort: real-world data facilitating research and clinical care

Real-world data (RWD) sources are important to advance clinical oncology research and evaluate treatments in daily practice. Since 2013, the Prospective Dutch Colorectal Cancer (PLCRC) cohort, linked to the Netherlands Cancer Registry, serves as an infrastructure for scientific research collecting additional patient-reported outcomes (PRO) and biospecimens. Here we report on cohort developments and investigate to what extent PLCRC reflects the “real-world”. Clinical and demographic characteristics of PLCRC participants were compared with the general Dutch CRC population (n = 74,692, Dutch-ref). To study representativeness, standardized differences between PLCRC and Dutch-ref were calculated, and logistic regression models were evaluated on their ability to distinguish cohort participants from the Dutch-ref (AU-ROC 0.5 = preferred, implying participation independent of patient characteristics). Stratified analyses by stage and time-period (2013–2016 and 2017–Aug 2019) were performed to study the evolution towards RWD. In August 2019, 5744 patients were enrolled. Enrollment increased steeply, from 129 participants (1 hospital) in 2013 to 2136 (50 of 75 Dutch hospitals) in 2018. Low AU-ROC (0.65, 95% CI: 0.64–0.65) indicates limited ability to distinguish cohort participants from the Dutch-ref. Characteristics that remained imbalanced in the period 2017–Aug’19 compared with the Dutch-ref were age (65.0 years in PLCRC, 69.3 in the Dutch-ref) and tumor stage (40% stage-III in PLCRC, 30% in the Dutch-ref). PLCRC approaches to represent the Dutch CRC population and will ultimately meet the current demand for high-quality RWD. Efforts are ongoing to improve multidisciplinary recruitment which will further enhance PLCRC’s representativeness and its contribution to a learning healthcare system

Clinical comparison of new monoclonal antibody-based nephelometric assays for free light chain kappa and lambda to polyclonal antibody-based assays and immunofixation electrophoresis

Background: New monoclonal antibody-based assays for serum-free light chains (FLC) have become available. Methods: In a clinical study with 541 patients, the new N Latex FLC assays were compared with the Freelite (TM) FLC assays and immunofixation electrophoresis (IF). Results: Comparison of the different FLC kappa (kappa) assays showed a slope of 0.99 with a deviation of 5.0%, r(s)=0.92, for FLC lambda (lambda) a slope of 1.22, deviation 13.8%, r(s)=0.90 and for the kappa/lambda ratio a slope of 0.72, deviation -4.6%, r(s)=0.72. The concordance for the FLC kappa assays was 91%, for FLC lambda 85% and kappa/lambda ratio 95%. The clinical sensitivity and specificity of the kappa/lambda ratios in the study were comparable: 60% and 99% for the N Latex FLC assay and 61% and 97% for the Freelite (TM) assay. In IF-FLC positive samples, the N Latex FLC kappa/lambda ratio scored 20/23 (87%) samples outside the reference range and Freelite (TM) 21/23 (91%). For IF-FLC negative samples, N Latex FLC assay kappa/lambda ratio scored 338/350 (97%) within the reference range and Freelite (TM) scored 332/350 (95%). Conclusions: The concordance scores and the clinical sensitivity and specificity of the new N Latex FLC assays and Freelite (TM) assays appeared comparable, but there are some differences in measurement of concentrations between the method

Prevalence and treatment of anemia and secondary iron overload in patients with a myelodysplastic syndrome: Real-world data from a multicenter cohort study

Background: anemia is the most common finding in patients with a myelodysplastic syndrome (MDS). Repetitive red blood cell (RBC) transfusions and disease-related low hepcidin levels induce secondary iron overload. Real-world data on the prevalence and treatment strategies of anemia and secondary iron overload in MDS patients, is limited. Methods: three years of data on MDS diagnosis, anemia and ferritin management was collected in 230 MDS patients from seven non-academic hospitals in the Netherlands. Descriptive statistics and linear mixed models were used to analyze the data. Results: transfusion dependent (TD) patients (n = 49) needed 1–3 RBC transfusions per month. Serum hemoglobin remained stable in both TD and transfusion-independent (TI) patients over 3 years. In the TD patients, serum ferritin increased 63 pmol/L/month. Overall, 19 (39%) were diagnosed with secondary hemochromatosis, of which 13 (68%) received chelation therapy with a heterogeneous response. Conclusions: mean hemoglobin remains stable over time in both TD and TI MDS patients. Approximately 40% of TD patients develop secondary hemochromatosis. Treatment and monitoring of secondary hemochromatosis as well as the response on chelation therapy vary substantially

Cross table of <i>JAK2</i> region loss of heterozygosity results of the patients suspect of MPN cohort, generated by the Short Tandem Repeat (STR) assay and the Single Nucleotide Polymorphism (SNP) based assay.

D<p> =  patients 15, 39, 41, 44 and 61.</p><p><i>JAK2</i>LOH  =  loss of heterozygosity on the <i>JAK2</i> region, <i>JAK2</i>ROH  =  retention of heterozygosity on the <i>JAK2</i> region. MPN  =  myeloproliferative neoplasm.</p

Panel of selected Single Nucleotide Polymorphisms (SNPs).

<p>SNP-ID (hCV)  =  Celera SNP ID. SNP-ID (rs)  =  reference SNP ID number. Base (9p)  =  the nucleotide position on chromosome 9(p). The particular nucleotide variation is referenced in “SNP”-column. Minor allele frequencies are indicated for different populations: CEU, CEPH (Centre d’Etude du Polymorphisme Humain) from Utah; CHB, Chinese from Beijing; JPT, Japanse from Tokyo and YRI, Yoruba from Ibadan Nigeria.</p>*<p>SNP rs7862852 is excluded from the panel of recommended SNPs. NA  =  not applicable.</p

Visualization of FAM/VIC ratios generated by representative SNP rs3780378

<p><b>A.</b>Scatterplot of SNP rs3780378 analyses of paired EDTA-blood and formalin-fixed paraffin-embedded (FFPE)-tissues of 93 patients (12 patients from <i>JAK2V617F</i>-positive cohort and 81 sample pairs from the MPN suspect patient cohort). X-axis: Delta Rn VIC (T  =  Thymine), Y-axis: Delta Rn FAM (C  =  Cytosine). White squares (bl-M1&2)  =  EDTA-blood samples amplified using ABI7500FAST machines 1 and 2, grey squares (bl-M3)  =  EDTA-blood samples amplified using ABI7500FAST machine 3, white triangles (par-M1&2)  =  FFPE-tissue samples amplified using ABI7500FAST machines 1 and 2 and grey triangles (par-M3)  =  FFPE-tissue samples amplified using ABI7500FAST machine 3. <b>B.</b> Representative box-and-whisker plot generated using the SNP rs3780378 VIC/FAM ratios of the EDTA-blood samples of all heterozygous patients from the patient cohort analyzed with ABI7500FAST machines 1 and 2. Stars represent extremes (>3× IQR  =  <i>JAK2</i>LOH).</p