Goal-Focused Emotion-Regulation Therapy (GET) for young adult survivors of testicular cancer: a pilot randomized controlled trial of a biobehavioral intervention protocol.

BackgroundTesticular cancer diagnosis and treatment, especially given its threat to sexuality and reproductive health, can be distressing in the formative period of young adulthood and the majority of young survivors experience impairing, distressing, and modifiable adverse outcomes that can persist long after medical treatment. These include psychological distress, impairment in pursuit of life goals, persistent physical side effects, elevated risk of secondary malignancies and chronic illness, and biobehavioral burden (e.g., enhanced inflammation, dysregulated diurnal stress hormones). However, few targeted interventions exist to assist young survivors in renegotiating life goals and regulating cancer-related emotions, and none focus on reducing the burden of morbidity via biobehavioral mechanisms. This paper describes the methodology of a randomized controlled biobehavioral trial designed to investigate the feasibility and preliminary impact of a novel intervention, Goal-focused Emotion-Regulation Therapy (GET), aimed at improving distress symptoms, emotion regulation, goal navigation skills, and stress-sensitive biomarkers in young adult testicular cancer patients.MethodsParticipants will be randomized to receive six sessions of GET or Individual Supportive Therapy (ISP) delivered over 8 weeks. In addition to indicators of intervention feasibility, we will measure primary (depressive and anxiety symptoms) and secondary (emotion regulation and goal navigation skills, career confusion) psychological outcomes prior to (T0), immediately after (T1), and 12 weeks after (T2) intervention. Additionally, identified biomarkers will be measured at baseline and at T2.DiscussionGET may have the potential to improve self-regulation across biobehavioral domains, improve overall cancer adjustment, and address the need for targeted supportive care interventions for young adult cancer survivors.Trial registrationClinicaltrials.gov, NCT04150848. Registered on 28 October 2019

Colorectal cancer surveillance in Hodgkin lymphoma survivors at increased risk of therapy-related colorectal cancer: Study design

Background: Second primary malignancies are a major cause of excess morbidity and mortality in cancer survivors. Hodgkin lymphoma survivors who were treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine have an increased risk to develop colorectal cancer. Colonoscopy surveillance plays an important role in colorectal cancer prevention by removal of the precursor lesions (adenomas) and early detection of cancer, resulting in improved survival rates. Therefore, Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine could benefit from colonoscopy, or other surveillance modalities, which are expected to reduce colorectal cancer incidence and mortality. Current knowledge on clinicopathological and molecular characteristics of therapy-related colorectal cancer is limited. The pathogenesis of such colorectal cancers might be different from the pathogenesis in the general population and therefore these patients might require a different clinical approach. We designed a study with the primary aim to assess the diagnostic yield of a first surveillance colonoscopy among Hodgkin lymphoma survivors at increased risk of colorectal cancer and to compare these results with different screening modalities in the general population. Secondary aims include assessment of the test characteristics of stool tests and evaluation of burden, acceptance and satisfaction of CRC surveillance through two questionnaires. Methods/Design: This prospective multicenter cohort study will include Hodgkin lymphoma survivors who survived =8years after treatment with infradiaphragmatic radiotherapy and/or procarbazine (planned inclusion of 259 participants). Study procedures will consist of a surveillance colonoscopy with removal of precursor lesions (adenomas) and 6-8 normal colonic tissue biopsies, a fecal immunochemical test and a stool DNA test. All neoplastic lesions encountered will be classified using relevant histomorphological, immunohistochemical and molecular analyses in order to obtain more insight into colorectal carcinogenesis in Hodgkin lymphoma survivors. The Miscan-model will be used for cost-effectiveness analyses. Discussion: Evaluation of the diagnostic performance, patient acceptance and burden of colorectal cancer surveillance is necessary for future implementation of an individualized colorectal cancer surveillance program for Hodgkin lymphoma survivors. In addition, more insight into treatment-induced colorectal carcinogenesis will provide the first step towards prevention and personalized treatment. This information may be extrapolated to other groups of cancer survivors. Trial registration: Registered at the Dutch Trial Registry (NTR): NTR4961

Pulmonary disease, its risk factors and necessity for long-term follow-up care in childhood cancer survivors.

Treatment for childhood cancer puts the young patients at risk to develop adverse health outcomes. These adverse health outcomes can develop acute, already during treatment, or slowly over years to decades after completion of treatment. They can be of transient nature or long-lasting and chronic. Adverse health outcomes can potentially affect every organ system, including the lung. The term late effects is used to describe this heterogeneity of adverse health outcomes. Pulmonary late effects contribute to a higher morbidity and mortality in childhood cancer survivors compared to siblings or the general population

Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus

Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment

Assessment of sexual difficulties associated with multi-modal treatment for cervical or endometrial cancer: A systematic review of measurement instruments

Background: Practitioners and researchers require an outcome measure that accurately identifies the range of common treatment-induced changes in sexual function and well-being experienced by women after cervical or endometrial cancer. This systematic review critically appraised the measurement properties and clinical utility of instruments validated for the measurement of female sexual dysfunction (FSD) in this clinical population. Methods: A bibliographic database search for questionnaire development or validation papers was completed and methodological quality and measurement properties of selected studies rated using the Consensus-based Standards for the selection of health Measurement Instrument (COSMIN) checklist. Results: 738 articles were screened, 13 articles retrieved for full text assessment and 7 studies excluded, resulting in evaluation of 6 papers; 2 QoL and 4 female sexual morbidity measures. Five of the six instruments omitted one or more dimension of female sexual function and only one instrument explicitly measured distress associated with sexual changes as per DSM V (APA 2013) diagnostic criteria. None of the papers reported measurement error, responsiveness data was available for only two instruments, three papers failed to report on criterion validity, and test-retest reliability reporting was inconsistent. Heterosexual penile-vaginal intercourse remains the dominant sexual activity focus for sexual morbidity PROMS terminology and instruments lack explicit reference to solo or non-coital sexual expression or validation in a non-heterosexual sample. Four out of six instruments included mediating treatment or illness items such as vaginal changes, menopause or altered body image. Conclusions: Findings suggest that the Female Sexual Function Index (FSFI) remains the most robust sexual morbidity outcome measure, for research or clinical use, in sexually active women treated for cervical or endometrial cancer

Prevalence of neoplasia at colonoscopy among testicular cancer survivors treated with platinum-based chemotherapy

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have an increased risk of colorectal cancer (CRC). We determined the yield of colonoscopy in TCS to assess its potential in reducing CRC incidence and mortality. We conducted a colonoscopy screening study among TCS in four Dutch hospitals to assess the yield of colorectal neoplasia. Neoplasia was defined as adenomas, serrated polyps (SPs), advanced adenomas (AAs: ≥10 mm diameter, high-grade dysplasia or ≥25% villous component), advanced serrated polyps (ASPs: ≥10 mm diameter or dysplasia) or CRC. Advanced neoplasia (AN) was defined as AA, ASP or CRC. Colonoscopy yield was compared to average-risk American males who underwent screening colonoscopy (n = 24,193) using a propensity score matched analysis, adjusted for age, smoking status, alcohol consumption and body mass index. A total of 137 TCS underwent colonoscopy. Median age was 50 years among TCS (IQR 43–57) vs 55 years (IQR 51–62) among American controls. A total of 126 TCS were matched to 602 controls. The prevalence of AN was higher in TCS than in controls (8.7% vs 1.7%; P =.0002). Nonadvanced adenomas and SPs were detected in 45.2% of TCS vs 5.5% of controls (P &lt;.0001). No lesions were detected in 46.0% of TCS vs 92.9% of controls (P &lt;.0001). TCS treated with platinum-based chemotherapy have a higher prevalence of neoplasia and AN than matched controls. These results support our hypothesis that platinum-based chemotherapy increases the risk of colorectal neoplasia in TCS. Cost-effectiveness studies are warranted to ascertain the threshold of AN prevalence that justifies the recommendation of colonoscopy for TCS.</p

Prevalence of neoplasia at colonoscopy among testicular cancer survivors treated with platinum-based chemotherapy

Testicular cancer survivors (TCS) treated with platinum-based chemotherapy have an increased risk of colorectal cancer (CRC). We determined the yield of colonoscopy in TCS to assess its potential in reducing CRC incidence and mortality. We conducted a colonoscopy screening study among TCS in four Dutch hospitals to assess the yield of colorectal neoplasia. Neoplasia was defined as adenomas, serrated polyps (SPs), advanced adenomas (AAs: ≥10 mm diameter, high-grade dysplasia or ≥25% villous component), advanced serrated polyps (ASPs: ≥10 mm diameter or dysplasia) or CRC. Advanced neoplasia (AN) was defined as AA, ASP or CRC. Colonoscopy yield was compared to average-risk American males who underwent screening colonoscopy (n = 24,193) using a propensity score matched analysis, adjusted for age, smoking status, alcohol consumption and body mass index. A total of 137 TCS underwent colonoscopy. Median age was 50 years among TCS (IQR 43–57) vs 55 years (IQR 51–62) among American controls. A total of 126 TCS were matched to 602 controls. The prevalence of AN was higher in TCS than in controls (8.7% vs 1.7%; P =.0002). Nonadvanced adenomas and SPs were detected in 45.2% of TCS vs 5.5% of controls (P &lt;.0001). No lesions were detected in 46.0% of TCS vs 92.9% of controls (P &lt;.0001). TCS treated with platinum-based chemotherapy have a higher prevalence of neoplasia and AN than matched controls. These results support our hypothesis that platinum-based chemotherapy increases the risk of colorectal neoplasia in TCS. Cost-effectiveness studies are warranted to ascertain the threshold of AN prevalence that justifies the recommendation of colonoscopy for TCS.</p

Implementation and evaluation of a physical activity counselling programme in primary care among cancer survivors:SoDA study protocol

INTRODUCTION: Physical activity (PA) favourably affects various health outcomes in cancer survivors, but little is known about how to implement a PA programme in primary care. We therefore aim to implement and evaluate such a programme for cancer survivors in general practice. METHODS AND ANALYSES: The Stimulation of Daily Activity study is an implementation study with a single-arm longitudinal design in 15 Dutch general practices. Patients aged ≥18 years who finished cancer treatment more than 6 months ago will be eligible for inclusion. The intervention will comprise six coaching sessions with the practice nurse in 9 months, seeking to increase PA in daily activities and using an activity tracker for goal setting and feedback. The Reach, Effectiveness, Adoption, Implementation and Maintenance framework will be used to evaluate implementation in terms of the health outcomes, extent of implementation and barriers and facilitators to implementation, using a mixed methods approach. Descriptive analyses and linear mixed model analyses will be performed on the quantitative data, while qualitative data from focus groups and interviews will be analysed by thematic analyses. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee of the University Medical Centre Groningen, the Netherlands, concluded that this study was not subject to the Dutch Medical Research Involving Human Subjects Act (registration number: 201900586). The study results will be made available to patients and general practitioners via (inter)national publications and conferences, newsletters, public summaries and via (social) media

Late effects of high-dose methotrexate treatment in childhood cancer survivors-a systematic review

BACKGROUND: High-dose methotrexate (HD-MTX) is used in the treatment of different childhood cancers, including leukemia, the most common cancer type and is commonly defined as an intravenous dose of at least 1 g/m$^{2}$ body surface area per application. A systematic review on late effects on different organs due to HD-MTX is lacking. METHOD: We conducted a systematic literature search in PubMed, including studies published in English or German between 1985 and 2020. The population of each study had to consist of at least 75% childhood cancer survivors (CCSs) who had completed the cancer treatment at least twelve months before late effects were assessed and who had received HD-MTX. The literature search was not restricted to specific cancer diagnosis or organ systems at risk for late effects. We excluded case reports, case series, commentaries, editorial letters, poster abstracts, narrative reviews and studies only reporting prevalence of late effects. We followed PRISMA guidelines, assessed the quality of the eligible studies according to GRADE criteria and registered the protocol on PROSPERO (ID: CRD42020212262). RESULTS: We included 15 out of 1731 identified studies. Most studies included CCSs diagnosed with acute lymphoblastic leukemia (n = 12). The included studies investigated late effects of HD-MTX on central nervous system (n = 10), renal (n = 2) and bone health (n = 3). Nine studies showed adverse outcomes in neuropsychological testing in exposed compared to non-exposed CCSs, healthy controls or reference values. No study revealed lower bone density or worse renal function in exposed CCSs. As a limitation, the overall quality of the studies per organ system was low to very low, mainly due to selection bias, missing adjustment for important confounders and low precision. CONCLUSIONS: CCSs treated with HD-MTX might benefit from neuropsychological testing, to intervene early in case of abnormal results. Methodological shortcomings and heterogeneity of the tests used made it impossible to determine the most appropriate test. Based on the few studies on renal function and bone health, regular screening for dysfunction seems not to be justified. Only screening for neurocognitive late effects is warranted in CCSs treated with HD-MTX