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Few studies have investigated the risks of subsequent primary neoplasms after adolescent and young adult (AYA) cancer. We investigated the risks of specific subsequent primary neoplasms after each of 16 types of AYA cancer.The Teenage and Young Adult Cancer Survivor Study is a population-based cohort of 200 945 survivors of cancer diagnosed when aged 15-39 years in England and Wales from Jan 1, 1971, to Dec 31, 2006. The cohort was established using cancer registrations from the Office for National Statistics and the Welsh Cancer registry. Follow-up was from 5-year survival until the first occurrence of death, emigration, or study end date (Dec 31, 2012). In this analysis, we focus on the risk of specific subsequent primary neoplasms after 16 types of AYA cancer: breast; cervical; testicular; Hodgkin lymphoma (female); Hodgkin lymphoma (male); melanoma; CNS (intracranial); colorectal; non-Hodgkin lymphoma; thyroid; soft-tissue sarcoma; ovarian; bladder; other female genital; leukaemia; and head and neck cancer. We report absolute excess risks (AERs; per 10 000 person-years) and cumulative incidence of specific types of subsequent primary neoplasm after each type of AYA cancer.During the 2 631 326 person-years of follow-up (median follow-up 16·8 years, IQR 10·5-25·2), 12 321 subsequent primary neoplasms were diagnosed in 11 565 survivors, most frequently among survivors of breast cancer, cervical cancer, testicular cancer, and Hodgkin lymphoma. AERs of any subsequent primary neoplasms were 19·5 per 10 000 person-years (95% CI 17·4-21·5) in survivors of breast cancer, 10·2 (8·0-12·4) in survivors of cervical cancer, 18·9 (16·6-21·1) in survivors of testicular cancer, 55·7 (50·4-61·1) in female survivors of Hodgkin lymphoma, and 29·9 (26·3-33·6) in male survivors of Hodgkin lymphoma. The cumulative incidence of all subsequent primary neoplasms 35 years after diagnosis was 11·9% (95% CI 11·3-12·6) in survivors of breast cancer, 15·8% (14·8-16·7) in survivors of cervical cancer, 20·2% (18·9-21·5) in survivors of testicular cancer, 26·6% (24·7-28·6) in female survivors of Hodgkin lymphoma, and 16·5% (15·2-18·0) in male survivors of Hodgkin lymphoma. In patients who had survived at least 30 years from diagnosis of cervical cancer, testicular cancer, Hodgkin lymphoma in women, breast cancer, and Hodgkin lymphoma in men, we identified a small number of specific subsequent primary neoplasms that account for 82%, 61%, 58%, 45%, and 41% of the total excess number of neoplasms, respectively. Lung cancer accounted for a notable proportion of the excess number of neoplasms across all AYA groups investigated.Our finding that a small number of specific subsequent primary neoplasms account for a large percentage of the total excess number of neoplasms in long-term survivors of cervical, breast, and testicular cancer, and Hodgkin lymphoma provides an evidence base to inform priorities for clinical long-term follow-up. The prominence of lung cancer after each of these AYA cancers indicates the need for further work aimed at preventing and reducing the burden of this cancer in future survivors of AYA cancer.Cancer Research UK, National Institute for Health Research, Academy of Medical Sciences, and Children with Cancer UK.

Background: Survivors of teenage and young adult cancer are at risk of cerebrovascular events, but the magnitude of and extent to which this risk varies by cancer type, decade of diagnosis, age at diagnosis, and attained age remains uncertain. This is the largest-ever cohort study to evaluate the risks of hospitalization for a cerebrovascular event among long-term survivors of teenage and young adult cancer. Methods: The population-based TYACSS (Teenage and Young Adult Cancer Survivor Study) (N=178,962) was linked to Hospital Episode Statistics data for England to investigate the risks of hospitalization for a cerebrovascular event among 5-year survivors of cancer diagnosed when 15 to 39 years of age. Observed numbers of first hospitalizations for cerebrovascular events were compared with that expected from the general population using standardized hospitalization ratios (SHRs) and absolute excess risks per 10 000 person-years. Cumulative incidence was calculated with death considered a competing risk. Results: Overall, 2782 cancer survivors were hospitalized for a cerebrovascular event—40% higher than expected (SHR=1.4, 95% confidence interval, 1.3–1.4). Survivors of central nervous system (CNS) tumors (SHR=4.6, 95% confidence interval, 4.3–5.0), head and neck tumors (SHR=2.6, 95% confidence interval, 2.2–3.1), and leukemia (SHR=2.5, 95% confidence interval, 1.9–3.1) were at greatest risk. Males had significantly higher absolute excess risks than females (absolute excess risks =7 versus 3), especially among head and neck tumor survivors (absolute excess risks =30 versus 11). By 60 years of age, 9%, 6%, and 5% of CNS tumor, head and neck tumor, and leukemia survivors, respectively, had been hospitalized for a cerebrovascular event. Beyond 60 years of age, every year, 0.4% of CNS tumor survivors were hospitalized for a cerebral infarction (versus 0.1% expected), whereas at any age, every year, 0.2% of head and neck tumor survivors were hospitalized for a cerebral infarction (versus 0.06% expected). Conclusions: Survivors of a CNS tumor, head and neck tumor, and leukemia are particularly at risk of hospitalization for a cerebrovascular event. The excess risk of cerebral infarction among CNS tumor survivors increases with attained age. For head and neck tumor survivors, this excess risk remains high across all ages. These groups of survivors, particularly males, should be considered for surveillance of cerebrovascular risk factors and potential pharmacological interventions for cerebral infarction prevention.

Background: Survivors of teenage and young adult cancer are acknowledged as understudied. Little is known about their long-term adverse health risks, particularly of cardiac disease that is increased in other cancer populations where cardiotoxic treatments have been used. Methods: The Teenage and Young Adult Cancer Survivor Study cohort comprises 200 945 5-year survivors of cancer diagnosed at 15 to 39 years of age in England and Wales from 1971 to 2006, and followed to 2014. Standardized mortality ratios, absolute excess risks, and cumulative risks were calculated. Results: Two thousand sixteen survivors died of cardiac disease. For all cancers combined, the standardized mortality ratios for all cardiac diseases combined was greatest for individuals diagnosed at 15 to 19 years of age (4.2; 95% confidence interval, 3.4–5.2) decreasing to 1.2 (95% confidence interval, 1.1–1.3) for individuals aged 35 to 39 years (2 P for trend Conclusions: This study of over 200 000 cancer survivors shows that age at cancer diagnosis was critical in determining subsequent cardiac mortality risk. For the first time, risk estimates of cardiac death after each cancer diagnosed between the ages of 15 and 39 years have been derived from a large population-based cohort with prolonged follow-up. The evidence here provides an initial basis for developing evidence-based follow-up guidelines.

Background: Survivors of childhood, adolescent, and young adult cancer are known to be at risk of late effects of their disease and its treatment. Most population-based studies of cancer survivors have reported on second primary cancers and mortality. The aim of this study was to research acute and psychiatric hospital admission rates and length of stay in 5-year survivors of cancer diagnosed before the age of 25 years. Methods: This was a population-based retrospective cohort study using linked national cancer registry, acute hospital discharge, psychiatric hospital, and mortality records. The study population consisted of 5229 individuals who were diagnosed with cancer before the age of 25 years between 1981 and 2003, and who survived at least 5 years after the date of diagnosis of their primary cancer. Indirect standardisation for age and sex was used to calculate standardised bed days and hospitalisation ratios (SBDR and SHR) for both acute and psychiatric hospital admissions, and absolute excess risks (AERs) compared with the general Scottish population. Results: Five-year survivors of cancer, diagnosed before the age of 25 years, are at increased risk of admission to acute hospitals (SHR 2.8; 95% confidence interval 2.7–2.9) and of spending more time in hospital (SBDR 3.7; 3.6–3.7). Corresponding AERs were 6.4 (6.0–6.6) admissions and 64.8 (64.4–66.9) bed days per 100 cancer survivors per year. In contrast, 5-year survivors were not at higher risk of admission to psychiatric hospital (SHR 0.9; 0.8–1.2), and they spent significantly less time as psychiatric in-patients (SBDR 0.4; 0.4–0.4) compared with the whole population. Conclusion: Using routinely collected linked records, our population-based study has demonstrated increased rates of hospitalisation in 5-year survivors of cancer diagnosed before the age of 25 years. Long-term clinical follow-up of survivors of cancer in this age group should focus on the prevention and treatment of the late effects of cancer in those patients at highest risk of hospitalisation.

Lifelong long-term follow-up (LTFU) is recommended for all survivors of childhood cancer. National guidelines recommend risk-stratified levels of follow-up by a multidisciplinary team, in an age-appropriate environment. Many survivors do not participate in long-term follow-up.To re-engage childhood cancer survivors lost to follow-up in late effects programmes by means of postal questionnaire.Retrospective cohort study of all children (19 years) diagnosed with cancer in a single institution in the UK between 1971 and 2003. All lost to follow-up survivors (not seen in clinic2 years) were sent a postal health and well-being questionnaire.831 patients were diagnosed with childhood cancer between 1971 and 2003, with 575 long-term survivors (overall survival rate 69%). Information was available on 550 survivors (males 290 (53%), median age (range) at review 18.8 (5.4-44.2) years and at diagnosis 5.0 (0.0-18.8) years, and disease free survival (range) was 10.8 (1.0-37.4) years. Of the 550 survivors, 256 (46%) were lost to follow-up. 99 (39%) of lost to follow-up survivors returned completed postal questionnaires (58% female). 45% of responders reported at least one late effect, 36% mild-moderate, and 8% severe-life threatening. 19% reported two or more late effects. 74% of all childhood cancer survivors are now in active follow-up.Almost half (46%) of all long-term survivors of childhood cancer are lost to follow-up, Postal follow-up is an effective means of re-engaging more than one third of survivors of childhood cancer in active long-term follow-up, half of whom had at least one late effect.

As the population of childhood cancer survivors steadily increases, currently estimated at 26,000 in the UK, investigators are focusing on improving our understanding of the late side effects associated with successful cancer therapy. Long-term survivors are at risk of developing a number of late sequelae including impaired fertility, adverse pregnancy outcomes and health problems in the offspring. Although not the highest priority at diagnosis, loss of fertility is one of the most devastating consequences of cytotoxic therapy for the long-term survivors. In this article we consider the late reproductive sequelae following treatment for childhood cancer and discuss the options for fertility preservation.

5 year survival for childhood and adolescent cancer in developed countries is now in excess of 80% and the number of survivors of cancer continues to increase worldwide. After completion of therapy, many of these survivors will face a lifelong risk of endocrine late effects. We summarise the available evidence related to the prevalence and risk factors for endocrine late effects among adult survivors of childhood and adolescent cancer. Present screening, surveillance, and treatment recommendations differ by country and region, so we also highlight the continued effort to harmonise the international guidelines for this population.

This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of ‘practical’ threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye.Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40–50 years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower.A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1–1.2, and in a few cases 1.5–2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors.Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5 Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

Today more than 75% of children treated for cancer will be cured, and attention is focusing on the late effects of treatments for these long-term survivors. Treatment-related morbidity is diverse, with potential effects on the endocrine system (growth, puberty, fertility, pituitary, thyroid and other disorders), cardiovascular, pulmonary and renal complications, second tumours, cognitive, education, neuropsychological and social manifestations. Multi-disciplinary long-term follow-up of these patients is essential to monitor, treat, and prevent morbidity. Depending on the nature of the treatment delivered, long-term follow-up of the survivor of childhood cancer can be individualised and delivered by a wide range of health professionals either in hospital or in primary care. In this review we describe the chronic health problems encountered by survivors and discuss the development of a long-term follow-up service for childhood cancer survivors.

Today more than 75% of children treated for cancer will be cured, and attention is focusing on the late effects of treatments for these long-term survivors. Treatment-related morbidity is diverse, wit

The majority of female cancer survivors will have normal reproductive function and would be expected to have a successful pregnancy. For the minority of young women who have received significant cytotoxic insult to the reproductive organs and yet still manage to conceive, pregnancy must be considered a high risk condition and these patients should be managed by a multidisciplinary specialist team. Female survivors of childhood cancer who are able to become pregnant carry an excess risk of preterm delivery and low birth weight baby. This restricted foetal growth and inability of the uterus to carry the foetus to term is associated with radiation-induced damage to the uterus. Chemotherapy does not appear to be associated with adverse pregnancy outcomes. However, prospective follow-up of cohorts of patients treated with contemporary therapies, frequently involving more intensive therapies are required to determine the risk. A number of large multi-centre studies, are underway and will provide new insights into pregnancy outcomes in survivors of childhood cancer.

Objective To determine the feasibility of therapy-based, risk-stratified follow-up guidelines for childhood and teenage cancer survivors by evaluating adverse health outcomes in a survivor cohort retrospectively assigned a risk category. Design Retrospective cohort study. Setting Tertiary level, single centre, paediatric cancer unit in South East Scotland. Participants All children and teenagers diagnosed with cancer (

Retinoblastoma is a childhood cancer that is now highly curable. Parents may be alerted to the disease when photographs of their child reveal a white pupil (leukocoria). In our case of a 15-month-old girl, one of her parents was a keen photographer and immediately noticed pupilliary abnormalities on digital photography (fi gure A). Application of red-eye reduction software improved the abnormal right pupil but the diseased left pupil remained white (fi gure B). Although the abnormal white refl ection from the retina was detected in this case, it is of note that the parent was easily able to