Subsequent hospitalisation experience of 5-year survivors of childhood, adolescent, and young adult cancer in Scotland: a population based, retrospective cohort study.

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.

Can intensity of long-term follow-up for survivors of childhood and teenage cancer be determined by therapy-based risk stratification?

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 (<19 years) between 1 January 1971 and 31 July 2004, who were alive more than 5 years from diagnosis formed the study cohort. Each survivor was retrospectively assigned a level of follow-up, based on their predicted risk of developing treatment-related late effects (LEs; levels 1, 2 and 3 for low, medium and high risk, respectively). Adverse health outcomes were determined from review of medical records and postal questionnaires. LEs were graded using the Common Terminology Criteria for Adverse Event, V.3. RESULTS: 607 5-year survivors were identified. Risk stratification identified 86 (14.2%), 271 (44.6%) and 250 (41.2%) as levels 1, 2 and 3 survivors, respectively. The prevalence of LEs for level 1 survivors was 11.6% with only one patient with grade 3 or above toxicity. 35.8% of level 2 survivors had an LE, of whom 9.3%, 58.8%, 18.5%, 10.3% and 3% had grades 1, 2, 3, 4 and 5 toxicity, respectively. 65.2% of level 3 survivors had LE, of whom 5.5% (n=9), 34.4% (n=56), 36.2% (n=59), 22.1% (n=36) and 1.8% (n=3) had grades 1, 2, 3, 4 and 5 toxicity, respectively. CONCLUSIONS: Therapy-based risk stratification of survivors can predict which patients are at significant risk of developing moderate-to-severe LEs and require high-intensity long-term follow-up. Our findings will need confirmation in a prospective cohort study that has the power to adjust for all potentially confounding variables.

ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs--threshold doses for tissue reactions in a radiation protection context.

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 40-50years 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 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

Survivors of childhood cancer lost to follow-up can be re-engaged into active long-term follow-up by a postal health questionnaire intervention.

UNLABELLED: 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. OBJECTIVE: To re-engage childhood cancer survivors lost to follow-up in late effects programmes by means of postal questionnaire. POPULATION AND METHODS: 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 clinic >2 years) were sent a postal health and well-being questionnaire. RESULTS: 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. CONCLUSIONS: 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.