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Survivors of childhood cancer treated with anthracycline chemotherapy or chest radiation are at an increased risk of developing congestive heart failure. In this population, congestive heart failure is well recognised as a progressive disorder, with a variable period of asymptomatic cardiomyopathy that precedes signs and symptoms. As a result, several clinical practice guidelines have been developed independently to help with detection and treatment of asymptomatic cardiomyopathy. These guidelines differ with regards to definitions of at-risk populations, surveillance modality and frequency, and recommendations for interventions. Differences between these guidelines could hinder the effective implementation of these recommendations. We report on the results of an international collaboration to harmonise existing cardiomyopathy surveillance recommendations using an evidence-based approach that relied on standardised definitions for outcomes of interest and transparent presentation of the quality of the evidence. The resultant recommendations were graded according to the quality of the evidence and the potential benefit gained from early detection and intervention.

Survivors of childhood, adolescent, and young adult (diagnosed when <25 years of age) cancer are at risk of mental health problems. The aim of this clinical practice guideline is to harmonise international recommendations for mental health surveillance in survivors of childhood, adolescent, and young adult cancer. This guideline was developed by a multidisciplinary panel of experts under the sponsorship of the International Guideline Harmonization Group. We evaluated concordance among existing survivorship clinical practice guidelines and conducted a systematic review following evidence-based methods. Of 7249 studies identified, 76 articles from 12 countries met the inclusion criteria. Recommendations were formulated on the basis of identified evidence in combination with clinical considerations. This international clinical practice guideline strongly recommends mental health surveillance for all survivors of childhood, adolescent, and young adult cancers at every follow-up visit and prompt referral to mental health specialists when problems are identified. Overall, the recommendations reflect the necessity of mental health surveillance as part of comprehensive survivor-focused health care.

Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research.

Historically, severe heart failure has been considered a contraindication for hematopoietic stem cell transplant (HSCT). Despite the growing use of the left ventricular assist device (LVAD), clinicians have avoided HSCT in patients with hematologic malignancies and an LVAD due to a multitude of potential complicating factors, including the use of cardiotoxic conditioning regimens and severe post-transplant thrombocytopenia requiring anticoagulation interruption. Currently, there are no published reports of a successful allogeneic HSCT in a patient with an LVAD. The case herein documents a 36-year-old man with acute myeloid leukemia (AML) and post-induction systolic heart failure necessitating LVAD (HeartMate 3) placement, who later successfully underwent allogeneic HSCT and is now in remission. We highlight preparative regimen considerations, the need to account for the effects of irradiation on the LVAD and external controller, and the importance of a multidisciplinary care team to demonstrate that the presence of an LVAD does not necessarily preclude patients with AML from potentially curative HSCT, particularly when managed with careful coordination and individualized risk-adapted strategies.

Female survivors of childhood, adolescent, and young adult (CAYA) cancer who were given radiation to fields that include breast tissue (ie, chest radiation) have an increased risk of breast cancer. Clinical practice guidelines are essential to ensure that these individuals receive optimum care and to reduce the detrimental consequences of cancer treatment; however, surveillance recommendations vary among the existing long-term follow-up guidelines. We applied evidence-based methods to develop international, harmonised recommendations for breast cancer surveillance among female survivors of CAYA cancer who were given chest radiation before age 30 years. The recommendations were formulated by an international, multidisciplinary panel and are graded according to the strength of the underlying evidence.

AbstractObjectiveTo investigate the impact of modifications to contemporary cancer protocols, which minimize exposures to cardiotoxic treatments and preserve long term health, on serious cardiac outcomes among adult survivors of childhood cancer.DesignRetrospective cohort study.Setting27 institutions participating in the Childhood Cancer Survivor Study.Participants23 462 five year survivors (6193 (26.4%) treated in the 1970s, 9363 (39.9%) treated in the 1980s, and 7906 (33.6%) treated in the 1990s) of leukemia, brain cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, renal tumors, neuroblastoma, soft tissue sarcomas, and bone sarcomas diagnosed prior to age 21 years between 1 January 1970 and 31 December 1999. Median age at diagnosis was 6.1 years (range 0-20.9) and 27.7 years (8.2-58.3) at last follow-up. A comparison group of 5057 siblings of cancer survivors were also included.Main outcome measuresCumulative incidence and 95% confidence intervals of reported heart failure, coronary artery disease, valvular heart disease, pericardial disease, and arrhythmias by treatment decade. Events were graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events. Multivariable subdistribution hazard models were used to estimate hazard ratios by decade, and mediation analysis examined risks with and without exposure to cardiotoxic treatments.ResultsThe 20 year cumulative incidence of heart failure (0.69% for those treated in the 1970s, 0.74% for those treated in the 1980s, 0.54% for those treated in the 1990s) and coronary artery disease (0.38%, 0.24%, 0.19%, respectively), decreased in more recent eras (P<0.01), though not for valvular disease (0.06%, 0.06%, 0.05%), pericardial disease (0.04%, 0.02%, 0.03%), or arrhythmias (0.08%, 0.09%, 0.13%). Compared with survivors with a diagnosis in the 1970s, the risk of heart failure, coronary artery disease, and valvular heart disease decreased in the 1980s and 1990s but only significantly for coronary artery disease (hazard ratio 0.65, 95% confidence interval 0.45 to 0.92 and 0.53, 0.36 to 0.77, respectively). The overall risk of coronary artery disease was attenuated by adjustment for cardiac radiation (0.90, 0.78 to 1.05), particularly among survivors of Hodgkin lymphoma (unadjusted for radiation: 0.77, 0.66 to 0.89; adjusted for radiation: 0.87, 0.69 to 1.10).ConclusionsHistorical reductions in exposure to cardiac radiation have been associated with a reduced risk of coronary artery disease among adult survivors of childhood cancer. Additional follow-up is needed to investigate risk reductions for other cardiac outcomes.Trial registrationClinicalTrials.gov NCT01120353.

Background Radiation‐related screening guidelines for survivors of childhood cancer currently use irradiated regions (IR) to determine risk for late effects. However, contemporary radiotherapy techniques utilize volumetric dosimetry (VD) to determine organ‐specific exposures, which could inform need for late effect surveillance. Methods This cross‐sectional cohort study involved patients treated for cancer using computerized tomography‐planned irradiation at Children's Hospital Los Angeles from 2000–2016. Organs at risk were identified using both VD and IR. Under each method, Children's Oncology Group Long‐Term Follow‐Up Guidelines were applied to determine radiation‐related potential late effects and their correlative recommended screening practices. Patients served as their own controls. Mean number of potential late effects per patient and recommended screening practices per patient per decade of follow‐up were compared using paired t‐tests; comparisons were adjusted for diagnosis and gender using random effects, repeated measure linear regression. Results In this cohort (n = 132), median age at end of treatment was 10.6 years (range, 1.4–20.4). Brain tumor was the most common diagnosis (45%) and head/brain the most common irradiated region (61%). Under IR and VD, the mean number of potential late effects flagged was 24.4 and 21.7, respectively (−11.3%, p < 0.001); concordance between the two methods was 6.1%. Under VD, the difference in mean number of recommended screening practices per patient was −7.4% in aggregate but as large as −37.0% for diagnostic imaging and procedures (p < 0.001 for both). Conclusion Use of VD rather than IR is feasible and enhances precision of guideline‐based screening for radiation‐related late effects in long‐term childhood cancer survivors. In this cross‐sectional cohort study of 132 eligible childhood cancer survivors treated with radiation therapy, we utilized current Children's Oncology Group Long‐term Follow‐Up Guidelines to compare the recommended screening practices triggered by use of conventional radiation fields (\"irradiated regions\") versus the more precise approach of volumetric dosimetry. This figure shows the number of recommended screening practices per patient per decade of follow‐up, by volumetric dosimetry (VD) compared with irradiated regions (IR). Each scatter plot point represents one patient with the number of recommended screening practices as determined by IR (x‐axis) versus VD (y‐axis); patients below the dotted line had fewer screening practices triggered using VD while those above it had more. Results are shown for all patients (A); by diagnosis (BSTT=bone/soft tissue tumor, LL=leukemia and lymphoma, CNS=central nervous system tumor) (B); by gender (C); and by age at end of therapy (D) Under IR and VD, the mean number of potential late effects flagged was 24.4 and 21.7, respectively (−11.3%, p < 0.001); full concordance between the two methods was 6.1%. We found that under VD, the difference in mean number of recommended screening practices per patient was −7.4% in aggregate but as large as −37.0% for diagnostic imaging and procedures (p < 0.001 for both). Study results show that use of VD rather than IR is feasible and enhances precision of guideline‐based screening for radiation‐related late effects in long‐term childhood cancer survivors.

Cranial radiation therapy (CRT) is commonly used to treat brain tumours but, in paediatric patients, this therapeutic strategy can lead to subsequent neurocognitive impairment. Padovani et al . discuss both the mechanisms underlying the effect of CRT on cognitive function and factors that can affect outcome. New approaches to correct or avoid CRT-induced neurotoxicity are also considered. The brain is highly vulnerable to neurotoxic agents during the prime learning period of a child's life. Paediatric patients with brain tumours who are treated with cranial radiation therapy (CRT) often go on to develop neurocognitive deficits, which are reflected in poor academic achievement and impaired memory, attention and processing speed. The extent of these delayed effects varies with radiation dose, brain volume irradiated, and age at treatment, and might also be influenced by genetic factors and individual susceptibility. CRT-induced impairment involves axonal damage and disruption of white matter growth, and can affect brain structures implicated in memory function and neurogenesis, such as the hippocampus. In this article, we review the underlying mechanisms and clinical consequences of CRT-induced neurocognitive damage in survivors of paediatric brain tumours. We discuss the recent application of neuroimaging technologies to identify white matter injury following CRT, and highlight new radiation techniques, pharmacological and neurological interventions, as well as rehabilitation programmes that have potential to minimize neurocognitive impairment following CRT. Key Points Cranial radiation therapy (CRT) for treatment of brain tumours in paediatric patients can cause subsequent neurocognitive impairment, particularly in patients who were very young at the time of irradiation CRT can impair development of white and grey matter, and can inhibit neurogenesis and synaptic plasticity—two processes that are crucial for learning and academic achievement Additional factors, such as the tumour itself, hydrocephalus, chemotherapy and other drugs, can contribute to cognitive impairment in survivors of paediatric brain tumours New strategies to prevent and treat CRT-induced neurocognitive damage, most notably new radiation techniques that spare healthy brain tissue, are increasingly used to avoid this adverse effect of radiotherapy Rehabilitation of paediatric patients treated with CRT is also possible through the child's school environment and cognitive training programmes

Although ionizing radiation is a known carcinogen, the long-term risk from relatively higher-dose diagnostic procedures during childhood is less well known. We evaluated this risk indirectly by assessing thyroid cancer incidence in a cohort treated with “lower-dose” chest radiotherapy more than 55 years ago. Between 2004 and 2008, we re-surveyed a population-based cohort of subjects treated with radiation for an enlarged thymus during infancy between 1926 and 1957 and their unexposed siblings. Thyroid cancer occurred in 50 irradiated subjects (mean thyroid dose, 1.29 Gy) and in 13 nonirradiated siblings during 334,347 person-years of follow-up. After adjusting for attained age, Jewish religion, sex and history of goiter, the rate ratio for thyroid cancer was 5.6 (95% CI: 3.1–10.8). The adjusted excess relative risk per gray was 3.2 (95% CI: 1.5–6.6). The adjusted excess absolute risk per gray was 2.2 cases (95% CI: 1.4–3.2) per 10,000 person-years. Cumulative thyroid cancer incidence remains elevated in this cohort after a median 57.5 years of follow-up and is dose-dependent. Although the incidence appeared to decrease after 40 years, increased risk remains a lifelong concern in those exposed to lower doses of medical radiation during early childhood.

Anthracycline-treated childhood cancer survivors experience cardiac damage that results in decreased left ventricular (LV) mass, leading to increased LV wall stress, which underlies their greater risk of cardiomyopathy. Many of these survivors also are at risk of growth hormone (GH) abnormalities from cranial irradiation exposure, although it is unknown whether such exposure is associated with cardiotoxicity. Echocardiograms and insulin-like growth factor-1 (IGF-1), a marker of GH, were measured in 130 anthracycline-treated childhood cancer survivors, 59 of whom had been exposed to cranial irradiation, a mean 10 years after their cancer diagnosis. Echocardiographic parameters and IGF-1 were standardized relative to age or body surface area using data from sibling control subjects and expressed as the percentage difference from normal values. The results showed that after adjustment for other risk factors, survivors exposed to cranial irradiation had an additional 12 % decrease in LV mass compared with unexposed survivors ( P  < 0.01) and an additional 3.6 % decrease in LV dimension ( P  = 0.03). Survivors exposed to cranial irradiation also had a 30.8 % decrease in IGF-1 relative to normal values, which was greater than the 10.5 % decrease in unexposed survivors ( P  < 0.01). The above findings led us to conclude that in anthracycline-treated childhood cancer survivors a mean 10 years after their diagnosis, those with cranial irradiation exposure had significantly greater decreases in LV mass and dimension. Because cranial irradiation also was associated with decreased IGF-1, it is possible that GH deficiencies mediated this effect, suggesting that GH replacement therapy may help to prevent the development of cardiotoxicity.