A pilot randomized controlled trial of an online intervention for Hodgkin lymphoma survivors to increase knowledge about late effects and recommended screening.

BACKGROUND: Hodgkin lymphoma (HL) survivors who received chest radiotherapy are at risk for breast cancer and cardiovascular disease, but screening adherence is low. We assessed the acceptability/feasibility of a web-based educational intervention and its impact on knowledge of health risks and screening. METHODS: HL survivors were randomized to either an interactive online educational intervention or handouts only. Surveys were completed at baseline and 3 months post-intervention. We described the acceptability/feasibility of the intervention and compared knowledge between groups. RESULTS: Fifty-two HL survivors participated; 27 in the intervention group and 25 in the control group. Eighteen (66%) intervention participants completed the intervention and reported high acceptability (89-100%). At baseline, adherence to breast cancer screening was low across all participants. Post-intervention, those in the intervention group more often than controls correctly identified breast cancer and echocardiogram screening guidelines (35% vs. 28%, P = 0.02 and 82% vs. 52%, P = 0.04) and reported knowing how to address potential complications from cancer treatments (87% vs. 64%, P = 0.03). We detected no increase in screening behavior post-intervention. CONCLUSION: Online education modules for high-risk HL survivors are an acceptable method to improve knowledge of health risks and screening guidelines. Future interventions should focus on improving screening uptake in this population. IMPLICATIONS FOR CANCER SURVIVORS: Web-based learning can be useful in increasing cancer survivor knowledge of their unique risks and screening recommendations but does not necessarily change patient behavior. Involvement in a cancer survivorship program can help assess individual barriers and monitor uptake of screening.

The Feasibility and Acceptability of a Data Capture Methodology in Pediatric Cancer Patients Treated with Targeted Agents and Immunotherapies.

As childhood cancer treatments have improved to include new and innovative agents, the need for more advanced monitoring of their long-term effects and related research has increased. This has resulted in a need for evidence-based research methodologies for the longitudinal care of childhood cancer patients treated with targeted agents and immunotherapies. The rationale for this pilot study was to determine the feasibility and acceptability of a data capture methodology for pediatric, adolescent, and young adult cancer patients treated with targeted agents and immunotherapy as there is little research to inform this delivery of care. Data were collected from thirty-two patients and two providers for descriptive statistics and thematic analyses. Feasibility was characterized by expected participant attrition. Key drivers of acceptability were (1) providers' language and clarity of communication and (2) convenient participation requirements. Long-term follow-up research practices developed with input from key stakeholders, including patients, caregivers, and providers, can lead to acceptable and feasible research protocols that optimize successful participant recruitment. These evidence-based research practices can result in high participant satisfaction and can be implemented as program development initiatives across centers caring for childhood cancer survivors.

Utility of apical four-chamber longitudinal strain in the assessment of childhood cancer survivors: A multicenter study.

BACKGROUND: A previous multicenter study showed that longitudinal changes in standard cardiac functional parameters were associated with the development of cardiomyopathy in childhood cancer survivors (CCS). Evaluation of the relationship between global longitudinal strain (GLS) changes and cardiomyopathy risk was limited, largely due to lack of quality apical 2- and 3-chamber views in addition to 4-chamber view. We sought to determine whether apical 4-chamber longitudinal strain (A4LS) alone can serve as a suitable surrogate for GLS in this population. METHODS: A4LS and GLS were measured in echocardiograms with acceptable apical 2-, 3-, and 4-chamber views. Correlation was evaluated using Pearson and Spearman coefficients, and agreement was evaluated with Bland-Altman plots. The ability of A4LS to identify normal and abnormal values compared to GLS as the reference was evaluated. RESULTS: Among a total of 632 reviewed echocardiograms, we identified 130 echocardiograms from 56 patients with adequate views (38% female; mean age at cancer diagnosis 8.3 years; mean follow-up 9.4 years). Correlation coefficients between A4LS and GLS were .89 (Pearson) and .85 (Spearman), with Bland-Altman plot of GLS-A4LS showing a mean difference of -.71 ± 1.8. Compared with GLS as the gold standard, A4LS had a sensitivity of 86% (95% CI 79%-93%) and specificity of 82% (69%-95%) when using normal range cutoffs and 90% (82%-97%) and 70% (58%-81%) when using ±2 standard deviations. CONCLUSION: A4LS performs well when compared with GLS in this population. Given the more recent adoption of apical 2- and 3-chamber views in most pediatric echocardiography laboratories, A4LS is a reasonable stand-alone measurement in retrospective analyses of older study cohorts and echocardiogram biorepositories.

The development and flux of the University of Minnesota Survivorship Program: progress, challenges, and opportunities.

For the past 30 years, the University of Minnesota's Cancer Survivorship Program has been dedicated to providing exceptional care to patients who have lived the cancer experience. Our model is consultative, risk-stratified, and oncologist-led but executed predominately by advanced practice providers. Care is personalized and serves three survivor populations: children, adults, and patients who received BMT with over 500 new patients evaluated annually. As guidelines and survivorship standards have changed, our clinical programs have evolved from a focus on survivorship care plans to supportive care. The program offers a wide range of supportive services from acupuncture to nutritional services as well as several educational programs for patients. The program has a strong research legacy, notably as the birthplace of research that led to the Children's Oncology Group Guidelines as well as advancements in cardio-oncology and frailty after bone marrow transplantation. In 2021, we hosted the first annual Survivorship Research Forum, providing the opportunity and space for experts across disciplines to exchange ideas on a broad range of survivorship topics not possible at other national cancer-related conferences. With successes and challenges, we have identified opportunities for growth as our program continues to evolve and grow in our goal to improve cancer outcomes along a wide spectrum of physical, emotional, functional, and social dimensions. IMPLICATIONS FOR CANCER SURVIVORS: The University of Minnesota Cancer Survivorship Program provides care, education, and research opportunities for patients across the cancer continuum.

Perspectives on Virtual Care for Childhood Cancer Survivors in Non-Metropolitan Areas during the COVID-19 Pandemic.

The COVID-19 pandemic paved the way for the widespread use of virtual care for childhood cancer survivors (CCSs). CCSs were virtual recipients of diverse care, including long-term follow-up (LTFU), primary care, mental health care, and several others. Virtual care comes with well-documented benefits and challenges. These are further magnified for CCSs living in rural or non-metropolitan areas. Here, we describe the virtual care of CCSs from two Upper Midwest cities with well-established childhood cancer survivor programs within large comprehensive cancer centers in the United States. CCSs from non-metropolitan areas, especially CCSs with two or more late effects, used virtual care more often during the COVID-19 pandemic compared to CCSs from metropolitan areas. A review of the related literature is also included and the identified challenges in providing virtual care, such as privacy concerns, technology-connectivity constraints, and medical license restrictions. Despite these limitations, the care of CCSs has evolved to leverage virtual care and its ability to increase access for patients and promote continuity of care for CCSs living in rural areas.

Usability and Satisfaction Testing of Game-Based Learning Avatar-Navigated Mobile (GLAm), an App for Cervical Cancer Screening: Mixed Methods Study.

BACKGROUND: Barriers to cervical cancer screening in young adults include a lack of knowledge and negative perceptions of testing. Evidence shows that mobile technology reduces these barriers; thus, we developed a web app, Game-based Learning Avatar-navigated mobile (GLAm), to educate and motivate cervical cancer screening using the Fogg Behavioral Model as a theoretic guide. Users create avatars to navigate the app, answer short quizzes with education about cervical cancer and screening, watch videos of the screening process, and earn digital trophies. OBJECTIVE: We tested ease of use, usefulness, and satisfaction with the GLAm app among young adults. METHODS: This mixed methods study comprised a qualitative think-aloud play interview session and a quantitative survey study. Participants were cervical cancer screening-eligible US residents aged 21 to 29 years recruited through social media. Qualitative study participants explored the app in a think-aloud play session conducted through videoconference. Data were analyzed using directed content analysis to identify themes of ease of use, usefulness, and content satisfaction. Qualitative study participants and additional participants then used the app independently for 1 week and completed a web-based survey (the quantitative study). Ease of use, usefulness, and satisfaction were assessed using the validated Technology Acceptance Model and Computer System Usability Questionnaire adapted to use of an app. Mean (SD) scores (range 1-7) are presented. RESULTS: A total of 23 individuals participated in one or both study components. The mean age was 25.6 years. A majority were cisgender women (21/23, 91%) and White (18/23, 78%), and 83% (19/23) had at least some secondary education. Nine participants completed the think-aloud play session. Direct content analysis showed desire for content that is concise, eases anxiety around screenings, and uses game features (avatars and rewards). Twenty-three individuals completed the quantitative survey study. Mean scores showed the app was perceived to be easy to use (mean score 6.17, SD 0.27) and moderately useful to increase cervical cancer screening knowledge and uptake (mean score 4.94, SD 0.27). Participants were highly satisfied with the app (mean score 6.21, SD 1.20). CONCLUSIONS: Survey results showed participants were satisfied with the app format and found it easy to use. The app was perceived to be moderately useful to inform and motivate cervical cancer screening; notably, the screening reminder function was not tested in this study. Qualitative study results demonstrated the app's ability to ease anxiety about screening through demonstration of the screening process, and brevity of app components was favored. Interpretation of results is limited by the predominantly cisgender, White, and educated study population; additional testing in populations which historically have lower cervical cancer screening uptake is needed. A modified version of the app is undergoing efficacy testing in a randomized clinical trial.

Transition practices for survivors of childhood cancer: a report from the Children's Oncology Group.

PURPOSE: Pediatric healthcare systems must support childhood cancer survivors to optimize their transition to adult care. This study aimed to assess the state of healthcare transition services provided by Children's Oncology Group (COG) institutions. METHODS: A 190-question online survey was distributed to 209 COG institutions to assess survivor services, including transition practices, barriers, and implementation of services aligned with the six core elements of Health Care Transition 2.0 from the US Center for Health Care Transition Improvement. RESULTS: Representatives from 137 COG sites reported on institutional transition practices. Two-thirds (66.4%) of site discharge survivors to another institution for cancer-related follow-up care in adulthood. Transfer to primary care (33.6%) was a commonly reported model of care for young adult-aged survivors. Site transfer at ≤ 18 years (8.0%), ≤ 21 years (13.1%), ≤ 25 years (7.3%), ≥ 26 years (12.4%), or when survivors are "ready" (25.5%). Few institutions reported offering services aligned with the structured transition process from the six core elements (Median = 1, Mean = 1.56, SD = 1.54, range: 0-5). The most prevalent barriers to transitioning survivors to adult care were perceived lack of late-effects knowledge among clinicians (39.6%) and perceived lack of survivor desire to transfer care (31.9%). CONCLUSIONS: Most COG institutions transfer adult-aged survivors of childhood cancer elsewhere for survivor care, yet few programs report delivering recognized standards for quality healthcare transition programming to support survivors. IMPLICATIONS FOR CANCER SURVIVORS: Development of best practices for survivor transition is needed to help promote increased early detection and treatment of late effects among adult survivors of childhood cancer.

Growth Hormone Deficiency in Childhood Intracranial Germ Cell Tumor Survivors.

Background and Aims: Intracranial germ cell tumor (iGCT) survivors have multiple risk factors for growth hormone (GH) deficiency, a commonly reported late effect in childhood cancer survivors. The objective of this study is to examine the prevalence of GH deficiency among childhood iGCT survivors. Methods: Participants were previously enrolled in the Germ Cell Tumor Epidemiology Study (GaMETES), a case parent triad study conducted using the Children's Oncology Group registry protocols, including 216 cases with iGCTs. Data on late effects and outcomes are available for 129 iGCT cases who consented for a follow-up study including a self-administered questionnaire and medical record retrieval. GH deficiency was identified via self-report and validated through medical record review. Chi-squared and Fisher's exact tests were used to examine cases with GH deficiency predating iGCT detection. Logistic regression was used to identify predictors of GH deficiency as a late effect. Results: Of 129 iGCT cases who participated in the late effects study, 45% had GH deficiency; 18% had GH deficiency predating the iGCT and 27% developed GH deficiency within a median of 19 months after diagnosis. Younger age at diagnosis, suprasellar location, and higher radiation doses were associated with GH deficiency as a late effect. Conclusions: GH deficiency is highly prevalent as an early clinical sign for iGCT and frequently arises as an early late effect after treatment. Additional investigation is needed to address earlier detection and treatment for this highly prevalent late effect in iGCT survivors.

HPV vaccination coverage for pediatric, adolescent and young adult patients receiving care in a childhood cancer survivor program.

Pediatric, adolescent and young adult patients undergoing cancer treatment and/or hematopoietic stem cell transplant are at increased risk for developing a secondary human papillomavirus (HPV)-associated malignancy. The objective of this study was to determine HPV vaccination coverage among individuals participating in a childhood cancer survivor program (CCSP). A retrospective cohort study was conducted among CCSP patients age 11-26 years attending a CCSP visit between 2014 and 2019. Survivors were age-, sex-, and race-matched 1:2 with controls without cancer. Data were abstracted from the electronic health record and state-based vaccination registry. Analysis was limited to Minnesota residents to minimize missing vaccination data. Survivorship care plans (SCPs) were reviewed for vaccine recommendations. 592 patients were included in the analyses (200 CCSP patients; 392 controls). By study design, mean age (18.4 years), race (72 % white), and sex (49 % female) were similar in the two groups. Among CCSP patients 22 % resided in a rural area compared to 3.8 % of controls. Vaccination coverage among CCSP patients was not statistically significantly different from controls [60.0 % vs 66.3 %, OR = 0.82, 95 % CI: (0.55, 1.23), p = 0.35]. Completion of 3 doses was not different between groups even though 3 doses is recommended for all CCSP patients regardless of age at initiation (28.5 % vs 30.1 %, p = 0.09). Only 8.0 % of SCPs recommended HPV vaccination. Although patients participating in a CCSP did not have significantly different HPV vaccination coverage compared to controls, HPV vaccination initiation and 3-dose series completion are still suboptimal in a patient population at high-risk of a secondary HPV-associated cancer.

Late-onset toxicities of monoclonal antibodies in cancer patients.

Cancer therapy duration is variable and may take years, adding a new challenge of maintaining the best life quality for cancer survivors. In cancer patients, late-onset toxicities have been reported with monoclonal antibodies and may involve several body organs or systems. They are defined as an autoimmune illnesses that can happen months to years after treatment discontinuation. Late-onset toxicities have become a focus of clinical care and related research. After cancer therapy is completed, the patient should receive longitudinal follow-up to detect these late effects as early as possible. The current review summarizes the recently reported late-onset toxicities of four classes of monoclonal antibodies (anti-CD52, anti-CTLA-4, anti-PD-1 and anti-CD20) with guidance for the diagnostic tools, appropriate management and treatment.

Late-onset toxicities have been reported in cancer patients with monoclonal antibodies therapy and may involve several body organs or systems. They are defined as autoimmune illnesses that can happen months to years after treatment discontinuation. The reported late-onset toxicities include; bruises due to decreased platelet count associated with alemtuzumab, ipilimumab-induced pneumonitis, hepatitis, gastrointestinal disorders, cardiovascular complications and neurosarcoidosis. Moreover, endocrinal side effects of nivolumab, pembrolizumab-induced colitis, dermatological toxicities and acute encephalopathy, and rituximab-induced late-onset decrease in neutrophils count. Several treatment options are available for managing late-onset toxicities, including corticosteroids. After monoclonal antibodies therapy is completed in cancer patients, they should receive a longitudinal follow-up to detect these late effects as early as possible.

Identifying metrics of success for transitional care practices in childhood cancer survivorship: A qualitative interview study of parents.

BACKGROUND: Survivor-focused care for adolescent and young adult (AYA) childhood cancer survivors (CCS) often involves their parents. Recognizing the importance of parents in the ongoing care of CCS, our study sought to identify key aspects of a successful transition for CCS from pediatric- to adult-centered care from the parent perspective. METHODS: We conducted qualitative interviews with 26 parents of CCS who were receiving care in the long-term follow-up (LTFU) clinic at a single institution. We used a semi-structured interview protocol with the parents and conducted a thematic content analysis. RESULTS: Using a constant comparison approach, data revealed three primary themes regarding parents' perspectives toward ensuring a seamless transition from pediatric- to adult-centered follow-up care: (1) the transition needs to include seamless communication between all involved parties, (2) survivors need to demonstrate sufficient health care self-efficacy in order to achieve a successful transition, and (3) the survivor-focused care should include support for survivors' overall well-being, including financial and health insurance literacy. CONCLUSIONS: For parents of AYA CCS, the optimal pediatric to adult care transition model should include mechanisms that facilitate communication between parents, CCS, and survivor-focused providers while also supporting self-efficacy and financial literacy as it relates to health insurance.

Challenges associated with retrospective analysis of left ventricular function using clinical echocardiograms from a multicenter research study.

BACKGROUND: Retrospective multicenter research using echocardiograms obtained for routine clinical care can be hampered by issues of individual center quality. We sought to evaluate imaging and patient characteristics associated with poorer quality of archived echocardiograms from a cohort of childhood cancer survivors. METHODS: A single blinded reviewer at a central core laboratory graded quality of clinical echocardiograms from five centers focusing on images to derive 2D and M-mode fractional shortening (FS), biplane Simpson's ejection fraction (EF), myocardial performance index (MPI), tissue Doppler imaging (TDI)-derived velocities, and global longitudinal strain (GLS). RESULTS: Of 535 studies analyzed in 102 subjects from 2004 to 2017, all measures of cardiac function could be assessed in only 7%. While FS by 2D or M-mode, MPI, and septal E/E' could be measured in >80% studies, mitral E/E' was less consistent (69%), but better than EF (52%) and GLS (10%). 66% of studies had ≥1 issue, with technical issues (eg, lung artifact, poor endocardial definition) being the most common (33%). Lack of 2- and 3-chamber views was associated with the performing center. Patient age <5 years had a higher chance of apex cutoff in 4-chamber views compared with 16-35 years old. Overall, for any quality issue, earlier era of echo and center were the only significant risk factors. CONCLUSION: Assessment of cardiac function using pooled multicenter archived echocardiograms was significantly limited. Efforts to standardize clinical echocardiographic protocols to include apical 2- and 3-chamber views and TDI will improve the ability to quantitate LV function.

Cancer survivors exercise at higher intensity in outdoor settings: The GECCOS trial.

PURPOSE: This randomized cross-over group pilot trial assessed feasibility of recruiting survivors from a long-term follow-up clinic to an exercise group and measured whether outdoor or indoor exercise sessions better supported exercise motivation and behaviors in survivors of cancer. METHODS: Sixteen adolescent and young adult survivors of any cancer completed indoor and outdoor exercise sessions in this randomized cross-over pilot trial. Measures of physical activity, motivation, and fatigue were taken 2 weeks before and 2 weeks after indoor sessions and 2 weeks before and 2 weeks after outdoor sessions. Measures of physical activity and fatigue were also taken during each exercise session. RESULTS: Initial recruiting of 19 participants met recruiting goals. Survivors who attended the most sessions lived an average of 8.7 km closer to the clinic. Objectively measured physical activity intensity was 0.63 metabolic equivalents of a task (METs) per minute greater during outdoor exercise sessions as compared to indoor exercise sessions. There were no meaningful differences in long term, habitual physical activity behavior, motivation, or fatigue in the weeks following the outdoor exercise sessions as compared to the indoor exercise sessions. CONCLUSIONS: This study shows the feasibility of recruiting survivors from a long-term follow-up clinic to community-based exercise groups. Although this brief pilot intervention did not show significant effects on habitual physical activity behavior or motivation in adolescent and young adult survivors of cancer, the greater exercise intensity during the outdoor exercise sessions indicate that holding group exercise sessions for survivors outdoors may promote greater intensity during exercise.

Molecular mechanisms and cardiovascular implications of cancer therapy-induced senescence.

Cancer treatment has been associated with accelerated aging that can lead to early-onset health complications typically experienced by older populations. In particular, cancer survivors have an increased risk of developing premature cardiovascular complications. In the last two decades, cellular senescence has been proposed as an important mechanism of premature cardiovascular diseases. Cancer treatments, specifically anthracyclines and radiation, have been shown to induce senescence in different types of cardiovascular cells. Additionally, clinical studies identified increased systemic markers of senescence in cancer survivors. Preclinical research has demonstrated the potential of several approaches to mitigate cancer therapy-induced senescence. However, strategies to prevent and/or treat therapy-induced cardiovascular senescence have not yet been translated to the clinic. In this review, we will discuss how therapy-induced senescence can contribute to cardiovascular complications. Thereafter, we will summarize the current in vitro, in vivo, and clinical evidence regarding cancer therapy-induced cardiovascular senescence. Then, we will discuss interventional strategies that have the potential to protect against therapy-induced cardiovascular senescence. To conclude, we will highlight challenges and future research directions to mitigate therapy-induced cardiovascular senescence in cancer survivors.

Identifying metrics of success for transitional care practices in childhood cancer survivorship: a qualitative interview study of survivors.

BACKGROUND: Adolescent and young adult (AYA) childhood cancer survivors (CCS) should be empowered to continue their survivor-focused care as they transition into adult medicine. However, the majority of AYA-aged survivors become lost to follow up around the age of typical transition to adulthood. The purpose of this study was to identify, from the patient's perspective, key factors that facilitate successful transitions to adult-centered survivorship care. METHODS: A qualitative study was conducted with AYA CCS (n = 29) from the survivorship clinic of a single institution as key informants. Data were collected through a series of structured phone interviews and subjected to thematic content analysis. RESULTS: Four major themes with multiple subthemes were identified: (1) transition practices need to be flexible and individually tailored; (2) effective communication is critical to a successful transition; (3) continuity in providers is needed during the transition; and (4) comprehensive care means care that also addresses psycho-social well-being. CONCLUSIONS: From the perspective of AYA CCS, the ideal model of transitional survivorship care could include a patient navigator who promotes provider flexibility, consistent communication, and pro-active comprehensive care that encompasses both medical and psycho-social well-being. Models of care for CCS should be built to provide, or seamlessly facilitate, continuous survivor-focused care across the age continuum. A longitudinal relationship with a survivor-focused provider can help promote the values that CCS' report as important in transitioning care from pediatric- to adult-centered care.

Longitudinal Changes in Echocardiographic Parameters of Cardiac Function in Pediatric Cancer Survivors.

BACKGROUND: Childhood cancer survivors undergo serial echocardiograms to screen for cardiotoxicity. It is not clear whether small longitudinal changes in functional or structural parameters over time have clinical significance. OBJECTIVES: To assess the timing of changes in serial echocardiographic parameters in pediatric age childhood cancer survivors and to evaluate their associations with cardiomyopathy development. METHODS: We performed a multi-center retrospective case-control study of ≥1-year survivors following the end of cancer therapy. Cardiomyopathy cases (fractional shortening (FS) ≤28% or ejection fraction (EF) ≤50% on ≥2 occasions) were matched to controls (FS ≥30%, EF ≥55%, not on cardiac medications) by cumulative anthracycline and chest radiation dose, follow-up duration, and age at diagnosis. Digitally archived clinical surveillance echocardiograms were quantified in a central core lab, blinded to patient characteristics. Using mixed models with interaction terms between time and case status, we estimated the least square mean differences of 2D, M-mode, pulsed wave Doppler and tissue Doppler imaging derived parameters across time between cases and controls. RESULTS: We identified 50 matched case-control pairs from 5 centers. Analysis of 412 echocardiograms (cases, n=181; controls, n=231) determined that indices of LV systolic function (FS, biplane EF), diastolic function (mitral E/A ratio), and LV size (end diastolic dimension z-scores) were significantly different between cases and controls, even four years prior to the development of cardiomyopathy. CONCLUSIONS: Longitudinal changes in cardiac functional parameters can occur relatively early in pediatric age childhood cancer survivors and are associated with the development of cardiomyopathy.

Henoch-Schönlein Purpura Presenting in Association With Neuroblastoma: A Case Report.

Henoch-Schönlein purpura (HSP) is a common systemic vasculitis affecting children. It is managed in the outpatient setting and rarely associated with malignancy. We present a case of neuroblastoma in a 7-year-old boy diagnosed after suspected HSP. Our case highlights the importance of maintaining a broad differential diagnosis in children with atypical HSP and performing a skin biopsy with immunofluorescence when a rash is present.