The Dutch LATER physical outcomes set for self-reported data in survivors of childhood cancer

Purposes: Studies investigating self-reported long-term morbidity in childhood cancer survivors (CCS) are using heterogeneous outcome definitions, which compromises comparability and include (un)treated asymptomatic and symptomatic outcomes. We generated a Dutch LATER core set of clinically relevant physical outcomes, based on self-reported data. Clinically relevant outcomes were defined as outcomes associated with clinical symptoms or requiring medical treatment. Methods: First, we generated a draft outcome set based on existing questionnaires embedded in the Childhood Cancer Survivor Study, British Childhood Cancer Survivor Study, and Dutch LATER study. We added specific outcomes reported by survivors in the Dutch LATER questionnaire. Second, we selected a list of clinical relevant outcomes by agreement among a Dutch LATER experts team. Third, we compared the proposed clinically relevant outcomes to the severity grading of the Common Terminology Criteria for Adverse Events (CTCAE). Results: A core set of 74 self-reported long-term clinically relevant physical morbidity outcomes was established. Comparison to the CTCAE showed that 36% of these clinically relevant outcomes were missing in the CTCAE. Implications for Cancer Survivors: This proposed core outcome set of clinical relevant outcomes for self-reported data will be used to investigate the self-reported morbidity in the Dutch LATER study. Furthermore, this Dutch LATER outcome set can be used as a starting point for international harmonization for long-term outcomes in survivors of childhood cancer

The PanCareSurFup consortium:research and guidelines to improve lives for survivors of childhood cancer

Background: Second malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF. Methods: The PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public. Results: We identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case–control studies of subsequent malignancies and cardiac disease in 5-year survivors. Conclusions: PCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health

A new method to facilitate valid and consistent grading cardiac events in childhood cancer survivors using medical records

BACKGROUND Cardiac events (CEs) are among the most serious late effects following childhood cancer treatment. To establish accurate risk estimates for the occurrence of CEs it is essential that they are graded in a valid and consistent manner, especially for international studies. We therefore developed a data-extraction form and a set of flowcharts to grade CEs and tested the validity and consistency of this approach in a series of patients. METHODS The Common Terminology Criteria for Adverse Events version 3.0 and 4.0 were used to define the CEs. Forty patients were randomly selected from a cohort of 72 subjects with known CEs that had been graded by a physician for an earlier study. To establish whether the new method was valid for appropriate grading, a non-physician graded the CEs by using the new method. To evaluate consistency of the grading, the same charts were graded again by two other non-physicians, one with receiving brief introduction and one with receiving extensive training on the new method. We calculated weighted Kappa statistics to quantify inter-observer agreement. RESULTS The inter-observer agreement was 0.92 (95% CI 0.80-1.00) for validity, and 0.88 (0.79-0.98) and 0.99 (0.96-1.00) for consistency with the outcome assessors who had the brief introduction and the extensive training, respectively. CONCLUSIONS The newly developed standardized method to grade CEs using data from medical records has shown excellent validity and consistency. The study showed that the method can be correctly applied by researchers without a medical background, provided that they receive adequate training

Flowchart heart failure.

<p>1a. The first question is <i>“Symptoms¹?”</i>, “number 1″ refers to block 1 under the step diagram, in this block symptoms of heart failure are shown, so the user knows which symptoms could occur; When the answer is “NO”. 1b. Is the <i>“EF<40%-20% or the FS<15%”</i> YES grade 3 heart failure. NO grade ≤2 heart failure. When the answer is “YES” Go to question “Responsive to intervention²?” 2. Question <i>“Responsive to intervention²?”</i>, block 2 in which common interventions for heart failure are shown; When the answer is “NO” grade 4 heart failure. When the answer is “YES” grade 3 heart failure. When it is “UNKNOWN” go to question “ <i>Device³, life threatening consequences⁴ or heart transplant?”</i>. 3. Question “ Device³, life threatening consequences⁴ or heart transplant?”, block 3 under the step diagram, in this block devices used as treatment for heart failure are shown. In block 4 the life threatening consequences associated with heart failure are stated; When the answer is “NO” grade 3 heart failure. When the answer is “YES” grade 4 heart failure. Ref. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100432#pone.0100432-Dickstein1" target="_blank">[10]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100432#pone.0100432-McMurray1" target="_blank">[11]</a>. ICD-10 = International classification of disease version 10. EF = ejection fraction. SF = shortening fraction. CRT-P or D = cardiac resynchronisation therapy pacemaker or defibrillator. ICD = implantable cardioverse defibrillator. LVAD = left ventricular assistance device.</p

Definitions of cardiac events (using CTCAEv3.0 and CTCAEv4.0).

<p>Definitions of cardiac events (using CTCAEv3.0 and CTCAEv4.0).</p

Result second consistency assessment (non-physician (NP) vs non-physician (extensive training) (NPE)).

<p>Result second consistency assessment (non-physician (NP) vs non-physician (extensive training) (NPE)).</p

Large variation in assessment and outcome definitions to describe the burden of long-term morbidity in childhood cancer survivors: A systematic review

We systematically reviewed outcome assessment methods, outcome classification, and severity grading of reported outcomes in studies investigating the burden of physical long-term morbidity in childhood cancer survivors (CCS). A MEDLINE and EMBASE search identified 56 studies reporting on three or more types of health conditions in 5-year CCS, for which information was extracted on outcome types and classification, methods of outcome ascertainment, and severity grading. There was substantial variability in classification and types of health conditions reported and in methods of outcome ascertainment. Only 59% of the included studies applied severity grading, mainly the common terminology criteria of adverse events. This large variation in assessment and definition of the burden of physical long-term morbidity in CCS challenges interpretation, comparison, and pooling data across studies. Global collaboration is needed to standardize assessments and harmonize definitions of long-term physical morbidity and associated outcomes in childhood cancer survivorship research