Vitamin K and childhood cancer: a population based case-control study in Lower Saxony,Germany.

OBJECTIVE--To confirm or refute a possible association of parenteral vitamin K prophylaxis and childhood cancer. DESIGN--Population based case-control study. Comparison of vitamin K exposure in children with leukaemia or other common tumours with two control groups. SETTING--State of Lower Saxony (north western part of Germany); case recruitment from the German childhood cancer registry. SUBJECTS--272 children with leukaemia, nephroblastoma, neuroblastoma, rhabdomyosarcoma, and tumours of the central nervous system diagnosed between 1 July 1988 and 30 June 1993; children were aged between 30 days and 15 years at diagnosis. 334 population based controls without diagnoses of cancer matched to the leukaemia cases for age and sex. MAIN EXPOSURE MEASURES--Parenteral vitamin K prophylaxis (intramuscular and subcutaneous) versus oral and no vitamin K prophylaxis. RESULTS--An association between parenteral vitamin K exposure and childhood cancer (leukaemias and other tumours combined) could not be confirmed (odds ratio 1.04, 95% confidence interval 0.74 to 1.48). For leukaemias the observed odds ratio was only 0.98 (0.64 to 1.50) (comparison of leukaemia cases with local controls 1.24 (0.68 to 2.25); state controls 0.82 (0.50 to 1.36)). These odds ratios remained almost unchanged when several potential confounders were considered in the logistic regression model. CONCLUSIONS--This population based study adds substantial evidence that there is no association between parenteral vitamin K and childhood cancer.     

Use of Primary Care during the Year before Childhood Cancer Diagnosis: A Nationwide Population-Based Matched Comparative Study

Objective

Childhood cancer is rare and symptoms tend to be unspecific and vague. Using the utilization of health care services as a proxy for symptoms, the present study seeks to determine when early symptoms of childhood cancer are seen in general practice.

Methods

A population-based matched comparative study was conducted using nationwide registry data. As cases, all children in Denmark below 16 years of age (N = 1,278) diagnosed with cancer (Jan 2002-Dec 2008) were included. As controls, 10 children per case matched on gender and date of birth (N = 12,780) were randomly selected. The utilization of primary health care services (daytime contacts, out-of-hours contacts and diagnostic procedures) during the year preceding diagnosis/index date was measured for cases and controls.

Results

During the six months before diagnosis, children with cancer used primary care more than the control cohort. This excess use grew consistently and steadily towards the time of diagnosis with an IRR = 3.19 (95%CI: 2.99–3.39) (p<0.0001) during the last three months before diagnosis. Children with Central Nervous System (CNS) tumours had more contacts than other children during the entire study period. The use of practice-based diagnostic tests and the number of out-of-hours contacts began to increase four to five months before cancer diagnosis.

Conclusions

The study shows that excess health care use, a proxy for symptoms of childhood cancer, occurs months before the diagnosis is established. Children with lymphoma, bone tumour or other solid tumours had higher consultation rates than the controls in the last five months before diagnosis, whereas children with CNS tumour had higher consultation rates in all twelve months before diagnosis. More knowledge about early symptoms and the diagnostic pathway for childhood cancer would be clinically relevant.     

The immune system and cancers of foetal origin

Summary Evidence of early loss of immunological competence in cases of neoplasms occurring in juveniles was found in an analysis of OSCC data (Oxford Survey of Childhood Cancers). The effects observed included heightened sensitivity to infection from birth onwards for all types of childhood cancer, higher levels of sensitivity for leukaemia than for lymphomas, and higher levels for lymphomas than for other solid tumours. The findings as a whole are consistent with in utero loss of immunological competence, which is an essential promoter of cancers of foetal origin and thus allows the outcome of an in utero cancer induction to be influenced both by maternal levels of immunological competence and postnatal infection.     

Incidence and survival of childhood cancer in the French islands of Reunion and Mayotte (2005–2011)

The aim of this study is to describe childhood cancer incidence and survival in the French islands of Reunion and Mayotte for the period 2005–2011. Data were taken from the population-based Cancer Registry of Reunion Island. All incident cases of malignant tumours and benign tumours of the Central Nervous System diagnosed between 2005 and 2011 in children under the age of 15 and living in Reunion or Mayotte were included. A total of 236 cases were registered (176 in Reunion, 60 in Mayotte). Age-standardised incidence rates (ASRs, world standard) for all cancers were 125.0 and 101.8 per million for Reunion and Mayotte, respectively. ASRs for the main cancer groups were lower than those described in mainland France for the same period. The 5-year overall survival rate for all patients was 78.5% (95%CI 71.9- 83.7), slightly lower than that reported in mainland France.     

Childhood cancer and residential radon exposure – results of a population-based case-control study in Lower Saxony (Germany)

A population-based case-control study on risk factors for childhood malignancies was used to investigate a previously reported association between elevated indoor radon concentrations and childhood cancer, with special regard to leukaemia. The patients were all children suffering from leukaemia and common solid tumours (nephroblastoma, neuroblastoma, rhabdomyosarcoma, central nervous system (CNS) tumours) diagnosed between July 1988 and June 1993 in Lower Saxony (Germany) and aged less than 15 years. Two population-based control groups were matched by age and gender to the leukaemia patients. Long-term (1 year) radon measurements were performed in those homes where the children had been living for at least 1 year, with particular attention being paid to those rooms where they had stayed most of the time. Due to the sequential study design, radon measurements in these rooms could only be done for 36% (82 leukaemias, 82 solid tumours and 209 controls) of the 1038 families initially contacted. Overall mean indoor radon concentrations (27 Bq m^–3) were low compared with the measured levels in other studies. Using a prespecified cutpoint of 70 Bq m^–3, no association with indoor radon concentrations was seen for the leukaemias (odds ratio (OR): 1.30; 95% confidence interval (95% CI): 0.32–5.33); however, the risk estimates were elevated for the solid tumours (OR: 2.61; 95% CI: 0.96–7.13), mainly based on 6 CNS tumours. We did not find any evidence for an association between indoor radon and childhood leukaemia, which is in line with a recently published American case-control study. There is little support for an association with CNS tumours in the literature. Received: 14 December 1998 / Accepted in revised form: 10 June 1999     

Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case-control study.

OBJECTIVE: To explore the possible association between intramuscular vitamin K given to neonates and the subsequent development of childhood cancer. DESIGN: Retrospective case-control study on the basis of hospital records. SETTING: The former Northern Health region of England. SUBJECTS: 685 children who were born and lived in the region and who developed cancer before their 15th birthday, and 3442 controls also born between 1960 and 1991 and matched only for date and hospital of birth. The notes of a further 701 index cases were untraceable. MAIN EXPOSURE MEASURE: Administration of intramuscular vitamin K versus no exposure to vitamin K. RESULTS: There was no association between the administration of vitamin K and the development of all childhood cancers (unadjusted odds ratio 0.89; 95% confidence interval 0.69 to 1.15) or for all acute lymphoblastic leukaemia (1.20; 0.75 to 1.92), but there was a raised odds ratio for acute lymphoblastic leukaemia developing 1-6 years after birth (1.79; 1.02 to 3.15). No such association was seen in a separate cohort-based study not dependent on case note retrieval in which the rates of acute lymphoblastic leukaemia in children born in hospital units where all babies received vitamin K were compared with those born in units where less than a third received prophylaxis. CONCLUSIONS: It is not possible, on the basis of currently published evidence, to refute the suggestion that neonatal intramuscular vitamin K administration increases the risk of early childhood leukaemia. Any association may have been masked in earlier studies that did not use controls matched for time and locality by other unidentified factors affecting the spatiotemporal variations in incidence of leukaemia.     

Do Maternal Knowledge and Attitudes towards Childhood Immunizations in Rural Uganda Correlate with Complete Childhood Vaccination?

Improving childhood vaccination coverage and timeliness is a key health policy objective in many developing countries such as Uganda. Of the many factors known to influence uptake of childhood immunizations in under resourced settings, parents’ understanding and perception of childhood immunizations has largely been overlooked. The aims of this study were to survey mothers’ knowledge and attitudes towards childhood immunizations and then determine if these variables correlate with the timely vaccination coverage of their children. From September to December 2013, we conducted a cross-sectional survey of 1,000 parous women in rural Sheema district in southwest Uganda. The survey collected socio-demographic data and knowledge and attitudes towards childhood immunizations. For the women with at least one child between the age of one month and five years who also had a vaccination card available for the child (N = 302), the vaccination status of this child was assessed. 88% of these children received age-appropriate, on-time immunizations. 93.5% of the women were able to state that childhood immunizations protect children from diseases. The women not able to point this out were significantly more likely to have an under-vaccinated child (PR 1.354: 95% CI 1.018–1.802). When asked why vaccination rates may be low in their community, the two most common responses were “fearful of side effects” and “ignorance/disinterest/laziness” (44% each). The factors influencing caregivers’ demand for childhood immunizations vary widely between, and also within, developing countries. Research that elucidates local knowledge and attitudes, like this study, allows for decisions and policy pertaining to vaccination programs to be more effective at improving child vaccination rates.     

Risk of cancer in Finnish children living close to power lines.

OBJECTIVE--To investigate the risk of cancer in children living close to overhead power lines with magnetic fields of > or = 0.01 microteslas (microT). DESIGN--Cohort study. SETTING--The whole of Finland. SUBJECTS--68,300 boys and 66,500 girls aged 0-19 years living during 1970-89 within 500 m of overhead power lines of 110-400 kV in magnetic fields calculated to be > or = 0.01 microT. Subjects were identified by record linkages of nationwide registers. MAIN OUTCOME MEASURES--Numbers of observed cases in follow up for cancer and standardised incidence ratios for all cancers and particularly for nervous system tumours, leukaemia, and lymphoma. RESULTS--In the whole cohort 140 cases of cancer were observed (145 expected; standardised incidence ratio 0.97, 95% confidence interval 0.81 to 1.1). No statistically significant increases in all cancers and in leukaemia and lymphoma were found in children at any exposure level. A statistically significant excess of nervous system tumours was found in boys (but not in girls) who were exposed to magnetic fields of > or = 0.20 microT or cumulative exposure of > or = 0.40 microT years. CONCLUSIONS--Residentia magnetic fields of transmission power lines do not constitute a major public health problem regarding childhood cancer. The small numbers do not allow further conclusions about the risk of cancer in stronger magnetic fields.     

Reliability of recording uterine cancer in death certification in France and age-specific proportions of deaths from cervix and corpus uteri

French uterine cancer recordings in death certificates include 60% of "uterine cancer, Not Otherwise Specified (NOS)"; this hampers the estimation of mortalities from cervix and corpus uteri cancers. The aims of this work were to study the reliability of uterine cancer recordings in death certificates using a case matching with cancer registries and estimate age-specific proportions of deaths from cervix and corpus uteri cancers among all uterine cancer deaths by a statistical approach that uses incidence and survival data. Deaths from uterine cancer between 1989 and 2001 were extracted from the French National database of causes of death and case-to-case matched to women diagnosed with uterine cancer between 1989 and 1997 in 8 cancer registries. Registry data were considered as "gold-standard". Among the 1825 matched deaths, cancer registries recorded 830 cervix and 995 corpus uteri cancers. In death certificates, 5% and 40% of "true" cervix cancers were respectively coded "corpus" and "uterus, NOS" and 5% and 59% of "true" corpus cancers respectively coded "cervix" and "uterus, NOS". Miscoding cervix cancers was more frequent at advanced ages at death and in deaths at home or in small urban areas. Miscoding corpus cancers was more frequent in deaths at home or in small urban areas. From the statistical method, the estimated proportion of deaths from cervix cancer among all uterine cancer deaths was higher than 95% in women aged 30-40 years old but declined to 35% in women older than 70 years. The study clarifies the reason for poor encoding of uterus cancer mortality and refines the estimation of mortalities from cervix and corpus uteri cancers allowing future studies on the efficacy of cervical cancer screening.     

Cancer chemotherapy: identifying novel anticancer drugs.

There are now around 60 cytotoxic drugs licensed for use in cancer therapy in the United Kingdom. For certain malignancies such as childhood cancers, haematological malignancies, and germ cell tumours chemotherapy has been pivotal to the substantial improvement in therapeutic outcome achieved over the past 10 years. In contrast, improvements in the systemic management of adult solid tumours have been less dramatic. There is a clear and urgent need for new, more effective drugs for lung, breast, and colorectal malignancies. This paper examines the processes in identifying, developing, and evaluating new drugs with anticancer activity.     

A double immunochemical method for detecting faecal haemoglobin and albumin in rectal screening

Undoubtedly, colonoscopy is the "gold standard" in the diagnosis of colorectal cancers. Sophisticated bowel preparation and risk of bowel perforation and bleeding, as well as the patient's discomfort during examination lead to low compliance in screening. Therefore, alternative non-invasive screening methods tend to come into the fore. In this study we compared the sensitivity and specificity of the double immunochemical FECA test for the haemoglobin + albumin content of the faeces with those of control colonoscopy in the detection of colorectal neoplasms. In a 3-year period 154 patients (69 males and 85 females) were scheduled for colonoscopy with previously collected stool samples. The sensitivity and specificity of the double immunochemical test for faecal haemoglobin + albumin content were determined in colorectal neoplasms of different severity. Colonoscopy served as a control examination. Colonoscopy identified in 77 cases benign lesions, and in 10 cases malignant tumours. The double immunochemical test for faecal blood and protein successfully used in model screening population showed in our present study 52.7% sensitivity and 92.3% specificity for significant neoplastic lesions (high-risk polyps and tumours). When the evaluation was limited to the high-risk polyps, the sensitivity was modified to 45.5% and the specificity to 92.3% and in case of invasive tumours to 90% and 100%, respectively. If only faecal haemoglobin content was measured, the overall sensitivity for polyps of any size and sort was 15.7% which, however, increased to 27.63% if faecal albumin was also measured. Based on relevant literature, the sensitivity of the FECA test for colorectal polyp and cancer is more favourable than that of other FITs. However, the increased sensitivity of the double faecal protein test falls short of the standard colonoscopy. Therefore, in certain cases the latter might be considered as a primary screening method.     

Determination of Ki67 Growth Fraction and Oestrogen Receptors In Screen-Detected Breast Cancer Using Cytological Preparations

Oestrogen receptor (ER) status of 77 cases of screen-detected breast cancer has been determined using cytological preparations. In 48% ER status was positive, which was the same proportion as that formed in a control group of age-matched patients with symptomatic breast carcinoma. Since the screen-detected group contained more low grade tumours, the percentage of ER-positive cases would be expected to be higher. the reasons for the discrepancy are discussed. Ki67 score has been determined for 41 cases of screen-detected cancer. Ki67 score showed a positive correlation with histological tumour grade and a negative correlation with ER status. However, there was no correlation with tumour size or lymph node status. the Ki67 scores in the screen-detected cancers were essentially similar to those found in an age-matched symptomatic group, but the very low scores were only found in the screened group.     

Patterns and temporal trends in the incidence of childhood and adolescence cancer in Cyprus 1998–2017: A population-based study from the Cyprus Paediatric Oncology Registry

BackgroundDespite its rarity, cancer in children and adolescents (CAC) is a major health issue worldwide. The lack of appropriate cancer registries is an obstacle for defining its incidence and survival, and informing cancer control. As in Cyprus, CAC epidemiology has not previously been comprehensively examined, we determined incidence rates and temporal trends of cancer in the 0–19 age group during 1998–2017.MethodsWe established the population based Paediatric Oncology Registry of Cyprus (PORCY) for the period 1998–2017. World age standardised incidence rate per million children and adolescents per year (ASRW) were calculated and time trends were assessed using Joinpoint regression analysis. Comparisons were made with other countries using the International Incidence of Childhood Cancer, third volume.ResultsFor all cancers combined, for ages 0–19-years, ASRW was 203.54 (95% CI 189.49, 217.59) one of the highest rates globally. The most frequent CAC were leukaemias followed by lymphomas, specified epithelial neoplasms and central nervous system tumours, differing to what is described in most other countries. For all cancers, both combined and individual types, except thyroid carcinoma (where incidence was rising), no significant temporal variation was found.ConclusionsTo inform cancer control activities, we conducted the first ever population-based epidemiological study of childhood and adolescent cancer (0–19 years) in Cyprus. The striking findings indicate high overall incidence rates that are among the world’s highest, a higher frequency of lymphomas and thyroid cancer than brain tumours, and rising incidence for thyroid, but not for other, cancers. These novel findings, will help the formulation of hypotheses to provide explanation for the high rates for all CAC in Cyprus and may contribute to the global efforts for improving prevention of cancer in this age group.     

ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer

Several studies have suggested ERBB3/HER3 may be a useful prognostic marker for colorectal cancer. Tumours with an intestinal stem cell signature have also been shown to be more aggressive. Here, we investigate whether ERBB3 is associated with intestinal stem cell markers in colorectal cancer and if cancer stem cells within tumours are marked by expression of ERBB3. Expression of ERBB3 and intestinal stem cell markers (LGR5, EPHB2, CD44s and CD44v6) was assessed by qRT-PCR in primary colorectal tumours (stages 0 to IV) and matched normal tissues from 53 patients. The localisation of ERBB3, EPHB2 and KI-67 within tumours was investigated using co-immunofluorescence. Expression of ERBB3 and intestinal stem cell markers were significantly elevated in adenomas and colorectal tumours compared to normal tissue. Positive correlations were found between ERBB3 and intestinal stem cell markers. However, co-immunofluorescence analysis showed that ERBB3 and EPHB2 marked specific cell populations that were mutually exclusive within tumours with distinct proliferative potentials, the majority of ERBB3+ve cells being non-proliferative. This pattern resembles cellular organisation within normal colonic epithelium where EPHB2 labelled proliferative cells reside at the crypt base and ERBB3+ve cells mark differentiated cells at the top of crypts. Our results show that ERBB3 and intestinal stem cell markers correlate in colorectal cancers. ERBB3 localises to differentiated cell populations within tumours that are non-proliferative and distinct from cancer stem cells. These data support the concept that tumours contain discrete stem, proliferative and differentiation compartments similar to that present in normal crypts.     

Evaluation of heterogeneity of DNA ploidy in early gastric cancers.

DNA ploidy has been shown to be a predictive parameter for prognosis in various solid tumours. The prognostic value of DNA-ploidy in gastric cancers is still a matter of controversy. A possible explanation for the discrepant results reported in the literature could be sampling error in tumours with multiple stemlines differing in DNA-ploidy. In order to determine whether or not such heterogeneity exists in early gastric carcinoma, we have performed DNA cytophotometry on multiple samples of a group of 17 early gastric carcinomas, of which 8 were pure intramucosal and 9 were infiltrating into the submucosa. We found an aneuploid DNA-stemline in 8 (47%) early gastric cancers, more often in tumours invading into the submucosa (5/9) than in purely mucosal tumours (3/8). Multiple DNA-stemlines were found more frequently in submucosally infiltrating tumours (4/5). These results confirm the presence of DNA-aneuploid early gastric carcinoma which are frequently heterogeneous and suggest that heterogeneity occurs more frequently in tumours invading the submucosa. This heterogeneity is best detected by analysing multiple samples of tumours for DNA-ploidy.     

Radiotherapy in thyroid cancer.

Although resection is the mainstay of treatment of thyroid cancer, and radioactive iodine (131-1) is curative in a small number of patients with differentiated cancers, external irradiation is much more effective than is generally believed. This has been clearly shown in a review of 138 patients with thyroid cancer referred to a cancer centre, in most cases after an initial operation. External irradiation should be considered in all patients except those with pure papillary tumours that have been completely excised. It should be used (a) in conjunction with surgery if there is even a remote doubt as to the completeness of excision; (b) in conjunction with 131-1 in treating inoperable primary tumours or metastatic lesions; () alone for differentiated tumours (primary or metastatic) that do not take up 131-1; and, (d) perhaps combined with chemotherapy, for medullary and anaplastic tumours.     

Canadian survey of thyroid cancer

We report the results of a multicentre retrospective chart review of 2214 patients with thyroid cancer registered at 13 radiotherapy centres between 1958 and 1978. The data analysed included sex, age at the time of diagnosis, pathological diagnosis, extent of disease before treatment, types of treatment and their complications, and the rates of recurrence and survival up to 24 years after diagnosis. Although papillary cancers were most common, anaplastic and miscellaneous tumours were more frequent than expected, which reflects the type of patients referred by endocrinologists and surgeons to radiotherapy centres. There were marked differences in patterns of referral to the centres. Some patients with papillary and follicular thyroid cancers died of these cancers up to 20 years after diagnosis. The clinical manifestations, treatment and outcome of the rarer types of thyroid malignant tumours were of particular interest. The influence of age at the time of diagnosis on survival rates for patients with papillary or follicular thyroid cancer was highly significant, indicating much more aggressive behaviour of these cancers in older patients, particularly those beyond the age of 60 years. A more detailed analysis of tumour subtypes should provide new information on their natural history and lead to better management.     

Lack of Genomic Heterogeneity at High-Resolution aCGH between Primary Breast Cancers and Their Paired Lymph Node Metastases

Lymph-node metastasis (LNM) predict high recurrence rates in breast cancer patients. Systemic treatment aims to eliminate (micro)metastatic cells. However decisions regarding systemic treatment depend largely on clinical and molecular characteristics of primary tumours. It remains, however, unclear to what extent metastases resemble the cognate primary breast tumours, especially on a genomic level, and as such will be eradicated by the systemic therapy chosen. In this study we used high-resolution aCGH to investigate DNA copy number differences between primary breast cancers and their paired LNMs. To date, no recurrent LNM-specific genomic aberrations have been identified using array comparative genomic hybridization (aCGH) analysis. In our study we employ a high-resolution platform and we stratify on different breast cancer subtypes, both aspects that might have underpowered previously performed studies.To test the possibility that genomic instability in triple-negative breast cancers (TNBCs) might cause increased random and potentially also recurrent copy number aberrations (CNAs) in their LNMs, we studied 10 primary TNBC–LNM pairs and 10 ER-positive (ER+) pairs and verified our findings adding additionally 5 TNBC-LNM and 22 ER+-LNM pairs. We found that all LNMs clustered nearest to their matched tumour except for two cases, of which one was due to the presence of two distinct histological components in one tumour. We found no significantly altered CNAs between tumour and their LNMs in the entire group or in the subgroups. Within the TNBC subgroup, no absolute increase in CNAs was found in the LNMs compared to their primary tumours, suggesting that increased genomic instability does not lead to more CNAs in LNMs. Our findings suggest a high clonal relationship between primary breast tumours and its LNMs, at least prior to treatment, and support the use of primary tumour characteristics to guide adjuvant systemic chemotherapy in breast cancer patients.     

Serum metallothionein in newly diagnosed patients with childhood solid tumours

Tumour markers are substances produced by malignant cells or by the organism as a response to cancer development. Determination of their levels can, therefore, be used to monitor the risk, presence and prognosis of a cancer disease or to monitor the therapeutic response or early detection of residual disease. Time-consuming imaging methods, examination of cerebrospinal fluid or tumour tissue and assays for hormones and tumour markers have been used for cancer diagnosis. However, no specific marker for diagnosis of childhood solid tumours has been discovered yet. In this study, metallothionein (MT) was evaluated as a prospective marker for such diseases. Serum metallothionein levels of patients with childhood solid tumours were determined using differential pulse voltammetry - Brdicka reaction. A more than 5-fold increase in the amount of metallothionein was found in sera of patients suffering from cancer disease, compared with those in sera of healthy donors. The average metallothionein level in the sera of healthy volunteers was 0.5 ± 0.2 μmol ? dm?3 and was significantly different (p<0.05, determined using the Schefe test) from the average MT level found in serum samples of patients suffering from childhood solid tumours (3.4 ± 0.8 μmol ? dm?3). Results found in this work indicate that the MT level in blood serum can be considered as a promising marker for diagnostics, prognosis and estimation of therapy efficiency of childhood tumours.     

Improvements in survival from childhood cancer: results of a population based survey over 30 years

Survival from cancer of children whose cancer was diagnosed during the 30 years 1954-83 was analysed. The study was population based with nearly 3000 cases covering about 30 million child years at risk. When survival during the three decades 1954-63, 1964-73, and 1974-83 was compared striking improvements were observed. For all childhood cancer five year survival increased from 21% in the first decade to 49% in the third decade. During the first and third decades five year survival rates for acute lymphocytic leukaemia increased from 2% to 47%, Hodgkin''s disease from 44% to 91%, non-Hodgkin''s lymphoma from 18% to 45%, Wilms''s tumour from 31% to 85%, and germ cell tumours from 10% to 64%. Twenty patients developed second primary tumours, but otherwise there were few late deaths. Less than 1% of children who survived without a relapse for 10 years subsequently died of their initial cancer.Survival from childhood cancer is no longer rare, and people who have been cured of cancer during childhood should be accepted as normal members of society.