Discrete-choice experiment to analyse preferences for centralizing specialist cancer surgery services.

BACKGROUND: Centralizing specialist cancer surgery services aims to reduce variations in quality of care and improve patient outcomes, but increases travel demands on patients and families. This study aimed to evaluate preferences of patients, health professionals and members of the public for the characteristics associated with centralization. METHODS: A discrete-choice experiment was conducted, using paper and electronic surveys. Participants comprised: former and current patients (at any stage of treatment) with prostate, bladder, kidney or oesophagogastric cancer who previously participated in the National Cancer Patient Experience Survey; health professionals with experience of cancer care (11 types including surgeons, nurses and oncologists); and members of the public. Choice scenarios were based on the following attributes: travel time to hospital, risk of serious complications, risk of death, annual number of operations at the centre, access to a specialist multidisciplinary team (MDT) and specialist surgeon cover after surgery. RESULTS: Responses were obtained from 444 individuals (206 patients, 111 health professionals and 127 members of the public). The response rate was 52·8 per cent for the patient sample; it was unknown for the other groups as the survey was distributed via multiple overlapping methods. Preferences were particularly influenced by risk of complications, risk of death and access to a specialist MDT. Participants were willing to travel, on average, 75 min longer in order to reduce their risk of complications by 1 per cent, and over 5 h longer to reduce risk of death by 1 per cent. Findings were similar across groups. CONCLUSION: Respondents' preferences in this selected sample were consistent with centralization.

Congenital mesoblastic nephroma 50 years after its recognition: A narrative review.

Congenital mesoblastic nephroma (CMN) is a rare pediatric renal tumor with low malignant potential that most commonly occurs early in infancy. Treatment strategies are based on the few published CMN series, while a significant number of CMN patients have been described in case reports. The aim of this narrative review was to create an up-to-date overview of the literature. Complete surgical removal is curative in most cases. The risk of treatment-related mortality (both surgery- and chemotherapy-related) is relatively high in the first weeks of life, indicating that these young patients deserve special attention with respect to timing and type of treatment.

Treatment of relapsed Wilms tumour (WT) patients: experience with topotecan. A report from the SIOP Renal Tumour Study Group (RTSG).

BACKGROUND: Topotecan has been variably incorporated in the treatment of patients with relapsed Wilms tumour (WT) who failed initial treatment with three or more effective drugs. Our objective was to describe outcome and to retrospectively investigate the potential role of topotecan in relapsed WT patients. METHODS: Children who were treated with topotecan as part of their chemotherapeutic regimens for relapsed WT were identified and included in our retrospective study. Patient charts were reviewed for general patient characteristics, histology and stage at initial diagnosis, number and type of relapse, salvage treatment schedules, toxicity, response to treatment and outcome. RESULTS: From 2000 to 2012, 30 children (median age at relapse 5.5 years, range 1.6-14.5 years) were identified to have received topotecan as part of their salvage regimens (primary progressive disease n = 3, first, second and third relapse n = 13, 9 and 2 respectively, partial response n = 3). Topotecan was administered as a single agent (12 patients) or in combination with other drugs (18 patients). Sixteen patients had high-risk histology according to the SIOP classification, 15 died within 12 months because of progressive disease. Fourteen patients had SIOP intermediate-risk histology of which four patients displayed objective responses to topotecan. Overall, 6 out of 14 intermediate-risk patients survived (median follow up of 6 years), however, three of whom (stage V) had bilateral nephrectomy after topotecan treatment. CONCLUSIONS: Topotecan does not seem to show effectiveness in the treatment of relapsed WT patients with initial high-risk histology. In patients with intermediate-risk histology, the role of topotecan might deserve further attention, to prove its efficacy.

Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: a combined SIOP and AIEOP study.

BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is an uncommon paediatric renal tumour. Relapses occur in about 15% of the patients. Since detailed clinical information on relapsed CCSK is scarce, the current study aims to describe outcome of patients with relapsed CCSK treated according to recent European protocols. PATIENTS AND METHODS: We analysed prospectively collected data of all CCSK patients who developed a relapse after complete remission at the end of primary treatment, entered onto SIOP and AIEOP trials between 1992 and 2012. RESULTS: Thirty-seven of 237 CCSK patients (16%) treated according to SIOP and AIEOP protocols developed a relapse. Median time from initial diagnosis to relapse was 17 months (range, 5.5 months - 6.6 years). Thirt-five out of thirty-seven relapses (95%) were metastatic; the most common sites of relapse were the brain (n=13), lungs (n=7) and bone (n=5). Relapse treatment consisted of chemotherapy (n=30), surgery (n=19) and/or radiotherapy (n=18), followed by high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14 patients. Twenty-two out of thirty-seven patients (59%) achieved a second complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year event-free survival (EFS) after relapse was 18% (95% CI: 4%-32%), and 5-year overall survival (OS) was 26% (95% CI: 10%-42%). CONCLUSIONS: In this largest series of relapsed CCSK patients ever described, overall outcome is poor. Most relapses are metastatic and brain relapses are more common than previously recognised. Intensive treatment aiming for local control, followed by high dose chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel development of targeted therapy is urgently required.

Gain of 1q is a marker of poor prognosis in Wilms' tumors.

Wilms' tumor (WT) trials aim to better tailor treatment intensity to the risk of relapse and death. Currently, stage, histology, age (< or > 24 months), and combined loss of heterozygosity at 1p and 16q in chemotherapy-naïve WTs are the only risk factors used for treatment stratification. However, they predict only less than one-third of all relapsing patients, implying that other factors are involved in treatment failure. Previous studies have associated 1q gain with adverse outcome. Therefore, in this study, the role of 1q gain and other common cytogenetic aberrations (CAs) in WTs was investigated and related to follow-up data from patients with WT treated in the United Kingdom; 19% (64/331) had 1q gain. Gain of 1q was significantly associated with 16q loss (P < 0.001) and 1p loss (P < 0.001). In multivariate analysis taking account of age, tumor stage, anaplasia, and common CA (e.g., 1p loss and 16q loss), 1q gain was independently associated with adverse event-free survival [EFS; hazard ratio (HR) = 2.45, P = 0.02] and overall survival (HR = 4.28, P = 0.004). Loss of 14q was independently associated with an adverse EFS (HR = 4.0, P = 0.04). Gain of 1q is a marker of poor prognosis in WTs, independent of high tumor stage and anaplasia which remain the overarching adverse prognostic factors. Confirmation in other studies is necessary before future therapeutic studies can incorporate 1q gain into new risk stratification schema.

Incidence and outcomes of patients with late recurrence of Wilms' tumor.

BACKGROUND: Most relapses from Wilms' tumor occur within 2 years from diagnosis. This study aims to describe the incidence and outcome of patients who experienced a late recurrence (LR) more than 5 years after diagnosis across several clinical trials, and to develop evidence-based recommendations for follow-up surveillance. METHODS: Available records on children with Wilms' tumor enrolled onto 10 national or international cooperative clinical trials were reviewed to identify patients who experienced a LR. RESULTS: Seventy of 13,330 (0.5%) patients with Wilms' tumor experienced a LR. No gender bias was observed. Median time elapsing between initial Wilms' tumor diagnosis and first recurrence was 13.2 years (range: 5.1-17.3 years). Initial tumor stage was: stage I (15); stage II (19); stage III (14); stage IV (8); bilateral disease stage V (14). The most frequent sites of relapse were--abdomen: 21, lungs: 20, and contralateral kidney: 15. Thirty-five children died of disease progression. Recurrence in the contralateral kidney was associated with a better outcome (13/15 patients alive), while initial tumor stage did not seem to influence the post-recurrence outcome. Therapies administered at recurrence varied between centers, preventing any conclusion about the best salvage treatment. CONCLUSIONS: LR of Wilms' tumor is rare and associated with similar outcome to those experiencing earlier recurrence. The low rate of LR does not justify prolonged monitoring. Further study of the biology of these tumors may give us some insights in regards to mechanisms on tumor cell dormancy or cancer stem cell maintenance.

Evidence for a familial Wilms' tumour gene (FWT1) on chromosome 17q12-q21.

Wilms' tumour (WT) is one of the most common solid tumours of childhood, occurring in 1 in 10,000 children and accounting for 8% of childhood cancers. It is believed to result from malignant transformation of abnormally persistent renal stem cells (nephrogenic rests) which retain embryonic differentiation potential. Although WT is usually sporadic, approximately one percent occur in families in which susceptibility appears to be inherited as an autosomal dominant trait with incomplete penetrance. Predisposition to other cancers or to the developmental abnormalities associated with sporadic WT is not usually apparent in WT families. The WT1 gene at 11p13 (ref.2), and additional genes on chromosomes 11p15 (ref. 3) and 16q (ref. 4) have been implicated in the development of WT but are not responsible for familial WT. We have carried out a genome linkage search in a large Canadian family with seven confirmed cases of WT. Our results provide strong evidence for the localisation of a familial WT predisposition gene, FWT1, to an 18-centimorgan (cM) interval on chromosome 17q12-q21.

Population survival from childhood cancer in Britain during 1978-2005 by eras of entry to clinical trials.

BACKGROUND: Inclusion in clinical trials is generally viewed as best practice for most newly diagnosed childhood cancers, but the impact on population-based survival has rarely been examined. PATIENTS AND METHODS: The population-based data were analysed for 25 853 children (66% of all registered childhood cancers) diagnosed in Britain during 1978-2005 with acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), Hodgkin lymphoma, non-Hodgkin lymphoma, medulloblastoma, neuroblastoma, Wilms tumour, hepatoblastoma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and germ-cell tumours. The Kaplan-Meier survival curves were compared by log-rank tests. Time trends were analysed by Cox regression. Separate analyses were done for children with ALL, medulloblastoma and neuroblastoma according to clinically relevant age thresholds. RESULTS: Survival increased significantly during 1978-2005 for every diagnostic category; the annual reduction in risk of death ranged from 2.7% (rhabdomyosarcoma) to 12.0% (gonadal germ-cell tumours). Survival increased steadily between trial eras for ALL (age 1-14 years) and neuroblastoma (age 1-14 years), but changed little since the mid-1980s for medulloblastoma (age 0-2 years), osteosarcoma or Ewing sarcoma. CONCLUSIONS: Changes in survival between trial eras parallel those reported by the relevant clinical trials. The increasing level of participation in trials, facilitated by the organisation of specialist care, has underpinned the substantial improvements in survival seen at the population level.

Treatment and outcome of Wilms' tumour patients: an analysis of all cases registered in the UKW3 trial.

BACKGROUND: The randomised findings of the UKW3 trial were that preoperative chemotherapy was associated with a more advantageous stage distribution and reduction in therapy burden versus immediate nephrectomy without compromising outcome in localised Wilms' tumour (WT). We analysed outcome in all WT registered in UKW3. PATIENTS AND METHODS: Seven hundred and eighteen WT cases (7% anaplastic) were registered in UKW3. We assigned a treatment stage and conducted survival analysis. RESULTS: Five-year event-free survival (EFS) and overall survival (OS) were 77.2% [95% confidence interval (CI) 73.9-80.2] and 87.5% (95% CI 84.8-89.7) after median follow-up of 9.5 years and 10.0 years, respectively. Five-year OS in localised non-anaplastic cases was 92.9% (95% CI 90.2-94.9). Anaplasia was associated with adverse outcome compared with non-anaplastic cases: 5-year EFS of 42.0% (95% CI 28.3-55.1) versus 79.8% (95% CI 76.5-82.7) and 5-year OS of 60% (95% CI 45.1-72.0) versus 89.6% (95% CI 87.0-91.7), respectively. Outcomes were similar for non-anaplastic stage I or II but significantly poorer in stage III cases than stage I. Five-year OS after relapse was 54.1% (95% CI 44.5-62.8). Forty-seven percent of non-anaplastic WT received anthracycline; 27% were treated with radiotherapy first line. CONCLUSION: These outcomes provide a baseline for future comparisons of WT treatment approach, burden and patient outcome.

Constitutional translocation breakpoint mapping by genome-wide paired-end sequencing identifies HACE1 as a putative Wilms tumour susceptibility gene.

BACKGROUND: Localisation of the breakpoints of chromosomal translocations has aided the discovery of several disease genes but has traditionally required laborious investigation of chromosomes by fluorescent in situ hybridisation approaches. Here, a strategy that utilises genome-wide paired-end massively parallel DNA sequencing to rapidly map translocation breakpoints is reported. This method was used to fine map a de novo t(5;6)(q21;q21) translocation in a child with bilateral, young-onset Wilms tumour. METHODS AND RESULTS: Genome-wide paired-end sequencing was performed for approximately 6 million randomly generated approximately 3 kb fragments from constitutional DNA containing the translocation, and six fragments in which one end mapped to chromosome 5 and the other to chromosome 6 were identified. This mapped the translocation breakpoints to within 1.7 kb. Then, PCR assays that amplified across the rearrangement junction were designed to characterise the breakpoints at sequence-level resolution. The 6q21 breakpoint transects and truncates HACE1, an E3 ubiquitin-protein ligase that has been implicated as a somatically inactivated target in Wilms tumourigenesis. To evaluate the contribution of HACE1 to Wilms tumour predisposition, the gene was mutationally screened in 450 individuals with Wilms tumour. One child with unilateral Wilms tumour and a truncating HACE1 mutation was identified. CONCLUSIONS: These data indicate that constitutional disruption of HACE1 likely predisposes to Wilms tumour. However, HACE1 mutations are rare and therefore can only make a small contribution to Wilms tumour incidence. More broadly, this study demonstrates the utility of genome-wide paired-end sequencing in the delineation of apparently balanced chromosomal translocations, for which it is likely to become the method of choice.

MicroRNA-206 expression levels correlate with clinical behaviour of rhabdomyosarcomas.

BACKGROUND: Rhabdomyosarcomas (RMSs) are primarily paediatric sarcomas that resemble developing skeletal muscle. Our aim was to determine the effects of microRNAs (miRNA) that have been implicated in muscle development on the clinical behaviour of RMSs. METHODS: Expression levels of miR-1, miR-206, miR-133a and miR-133b were quantified by RT-PCR in 163 primary paediatric RMSs, plus control tissues, and correlated with clinico-pathological features. Correlations with parallel gene expression profiling data for 84 samples were used to identify pathways associated with miR-206. Synthetic miR-206 was transfected into RMS cell lines and phenotypic responses assessed. RESULTS: Muscle-specific miRNAs levels were lower in RMSs compared with skeletal muscle but generally higher than in other normal tissues. Low miR-206 expression correlated with poor overall survival and was an independent predictor of shorter survival in metastatic embryonal and alveolar cases without PAX3/7-FOXO1 fusion genes. Low miR-206 expression also significantly correlated with high SIOP stage and the presence of metastases at diagnosis. High miR-206 expression strongly correlated with genes linked to muscle differentiation and low expression was associated with genes linked to MAPkinase and NFKappaB pathway activation. Increasing miR-206 expression in cell lines inhibited cell growth and migration and induced apoptosis that was associated with myogenic differentiation in some, but not all, cell lines. CONCLUSION: miR-206 contributes to the clinical behaviour of RMSs and the pleiotropic effects of miR-206 supports therapeutic potential.

Seeking consent to tissue banking: a survey of health professionals in childhood cancer.

To identify the views of health professionals working in childhood cancer on seeking consent to tissue banking from potential donors. Self-completion questionnaires sent to 553 UK paediatric oncology health professionals. The response rate was 60%. Respondents (100%) were in favour of using tissue samples from children with cancer for research. A substantial minority (30%) had concerns about the impact of the law on their professional role in relation to tissue banking. Almost all (90%) reported that both the parent(s) and the child, if able, should be asked for consent, though the UK Human Tissue Act provides that a competent child's consent is sufficient. Most (94%) supported 'generic' rather than 'specific' consent. Barriers to obtaining consent included: (1) timing of the approach to families; (2) availability of suitable staff; (3) sensitivity of the issues; (4) difficulties of managing the process; and (5) problems of maintaining a paper trail. Many would welcome training on seeking consent. Personal knowledge and relationships with families are often seen as important in guiding the proper approach to consent rather than formalized rules. There is widespread support among health professionals for tissue banking in childhood cancer. In sensitive situations, disciplined exercise of professional discretion might better deliver on aspirations for regulation than rigid procedures.

Evidence-based data and rare cancers: The need for a new methodological approach in research and investigation.

Rare cancers are not so rare, their incidence is increasing and, as a group, they have worse survival than the common cancers. These factors emphasise the societal need to ensure sufficient focus on research into their biological basis, aetiological factors, new more effective therapies and organisation of healthcare to improve access to best practice and innovation. Accuracy of diagnosis is one of the first hurdles to be overcome, with around one third of tumours being reclassified - by type or risk group - when subject to a centralised pathology review process. Timely access to appropriate expert knowledge is a second challenge for patients - in Europe this is being addressed by the establishment of European Reference Networks (ERNs) as part of the EU cross border healthcare initiative. There are ERNs for adult solid and haematological cancers and childhood cancers, all of which are individually rare. These ERNs will facilitate creation of large databases of rare tumours that will incorporate knowledge of their molecular features and build an evidence base for the effectiveness of innovative, biology-directed therapies. With an increasing focus on 'real world' outcome data, research methodologies are evolving, to include randomised registry trials and data linkage approaches that exploit the ever-richer information held on patients in routine health care data. The inclusion of genomic analysis into cancer diagnosis, treatment and risk prediction raises many issues for the conduct of clinical research and cohort studies and personal data sharing. Sophisticated means of pseudonymisation, together with full involvement of affected and 'at risk' patients, are supporting novel research designs and access to data that will continue to build the evidence base to improve outcomes for patients with rare cancers.

Prognostic significance of age in 5631 patients with Wilms tumour prospectively registered in International Society of Paediatric Oncology (SIOP) 93-01 and 2001.

BACKGROUND: To enhance risk stratification for Wilms tumour (WT) in a pre-operative chemotherapy setting, we explored the prognostic significance and optimal age cutoffs in patients treated according to International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) protocols. METHODS: Patients(6 months-18 years) with unilateral WT were selected from prospective SIOP 93-01 and 2001 studies(1993-2016). Martingale residual analysis was used to explore optimal age cutoffs. Outcome according to age was analyzed by uni- and multivariable analysis, adjusted for sex, biopsy(yes/no), stage, histology and tumour volume at surgery. RESULTS: 5631 patients were included; median age was 3.4 years(IQR: 2-5.1). Estimated 5-year event-free survival (EFS) and overall survival (OS) were 85%(95%CI 83.5-85.5) and 93%(95%CI 92.0-93.4). Martingale residual plots detected no optimal age cutoffs. Multivariable analysis showed lower EFS with increasing age(linear trend P<0.001). Using previously described age categories, EFS was lower for patients aged 2-4(HR 1.34, P = 0.02), 4-10(HR 1.83, P<0.0001) and 10-18 years(HR 1.74, P = 0.01) as compared to patients aged 6 months-2 years. OS was lower for patients 4-10 years(HR 1.67, P = 0.01) and 10-18 years(HR 1.87, P = 0.04), but not for 2-4 years(HR 1.29, P = 0.23). Higher stage, histological risk group and tumour volume were independent adverse prognostic factors. CONCLUSION: Although optimal age cutoffs could not be identified, we demonstrated the prognostic significance of age as well as previously described cutoffs for EFS (2 and 4 years) and OS (4 years) in children with WT treated with pre-operative chemotherapy. These findings encourage the consideration of age in the design of future SIOP-RTSG protocols.

The European study on centralisation of childhood cancer treatment.

BACKGROUND: It is generally agreed to centralise treatment of childhood cancers (CCs). We analysed (1) the degree of centralisation of CCs in European countries and 2) the relations between centralisation and survival. PATIENTS AND METHODS: The analysis comprised 4415 CCs, diagnosed between 2000 and 2007 and followed up to the end of 2013, from Belgium, Bulgaria, Finland, Ireland, the Netherlands and Slovenia. All these countries had national population-based cancer registries and were able to provide information on diagnosis, treatment, treatment hospitals, and survival. Each case was then classified according to whether the patient was treated in a high- or a low-volume hospital among those providing CC treatment. A Cox proportional hazard model was used to calculate the relation between volume category and five-year survival, adjusting by age, sex and diagnostic group. RESULTS: The number of hospitals providing treatment for CCs ranged from six (Slovenia) to slightly more than 40 (the Netherlands and Belgium). We identified a single higher volume hospital in Ireland and in Slovenia, treating 80% and 97% of cases, respectively, and three to five major hospitals in the other countries, treating between 65% and 93% of cases. Outcome was significantly better when primary treatment was given in high-volume hospitals compared to low-volume hospitals for central nervous system tumours (relative risk [RR] = 0.71), haematologic tumours (RR = 0.74) and for all CC combined (RR = 0.83). CONCLUSION: Treatment centralisation is associated with survival benefits and should be further strengthened in these countries. New plans for centralisation should include ongoing evaluation.

T-cell responses in osteosarcoma patients vaccinated with an anti-idiotypic antibody, 105AD7, mimicking CD55.

We assessed T-cell responses in young osteosarcoma patients vaccinated with 105AD7, 1-6 months after having received chemotherapy. 105AD7 is a human anti-idiotypic antibody mimicking CD55, a glycoprotein that protects from attack by complement and which is overexpressed on osteosarcoma cells. Seven out of 21 investigated patients made a IFN-gamma T-cell response against the vaccine, 105AD7 as assessed by ELISPOT. Cytokine secretion was analysed using Luminex assays and revealed TNF-alpha and GM-CSF responses not only to the vaccine but also towards the native antigen, CD55, in 5 / 14 (36%) of investigated patients. Importantly, the Luminex assay was found to be more sensitive than the more established T-cell assays (ELISPOT and proliferation assay), since responses towards the native antigen were recorded in this assay. Clinical responses and induction of immune responses to both the anti-idiotype and the native CD55 antigen support the use of CD55 as a target in cancer treatment.

Dose finding study of oral PSC 833 combined with weekly intravenous etoposide in children with relapsed or refractory solid tumours.

PSC 833 is an effective MDR1 reversal agent in vitro, including studies with paediatric cancer cell lines such as neuroblastoma and rhabdomyosarcoma. This study was performed to determine the safety profile, dose limiting toxicity (DLT) and maximum tolerated dose (MTD) in children with solid tumours and to determine the influence of PSC 833 on the pharmacokinetics of co-administered etoposide. Each patient received one cycle of intravenous etoposide (100 mg/m2 daily for 3 days on three consecutive weeks) to document baseline pharmacokinetics, and subsequently the same schedule using a dose of 50 mg/m2 was given combined with PSC 833 given orally every 6h at a starting dose of 4 mg/kg. Thirty two eligible patients (23 male, median age 8.3 years) were enrolled. Neuroblastoma and rhabdomyosarcoma were the common disease types. Brain tumours were excluded. DLT was defined as any non-haematological grade 3-4 toxicity (common toxicity criteria) and using a specific toxicity scale for cerebellar toxicity. The MDT was defined as the first dose below which 2 or more patients per dose level experienced DLT. Grade 1-2 ataxia occurred in cohorts 2 and 3 (4 and 5 mg/kg, respectively). Three patients developed grade 3 neurotoxicity in the 6 mg/kg cohort and this defined the MTD. Six responses were observed (2 CR, 4 PR). Pharmacokinetic studies indicated that the clearance of etoposide was reduced by approximately 50% when combined with PSC 833. It is concluded that the toxicity profile and MDT is similar in both children and adults, as is the effect on etoposide metabolism. The study demonstrated the feasibility and safety of carrying out a paediatric phase 1 trial across European boundaries and acts as a model for future cooperative studies in rare cancers among children.

Geographical comparison of cancer survival in European children (1988-1997): report from the Automated Childhood Cancer Information System project.

The aim of this study was to assess regional survival differences among childhood cancer patients in Europe. For this exercise, the Automated Childhood Cancer Information System (ACCIS) database was utilised. Survival data from 54 population-based cancer registries on 49,651 childhood cancer patients aged 0-14 years and diagnosed in 1988-1997 were analysed using life-table method. Overall, the 5-year survival was 72% among all patients, varying from 62% to 77% between the five geographical regions. The East region generally had lower survival rates than the rest of Europe. The geographical differences indicate the need for more co-ordination, systematisation and standardisation in diagnosis, referral and the treatment of childhood cancers in Europe. Increase of resources is necessary to improve the lower survival in the East region. Continuing data collection on a European level will facilitate monitoring of population-based survival of childhood cancer patients.

Cancer in children and adolescents in Europe: developments over 20 years and future challenges.

This special issue contains 18 articles describing population-based analyses of incidence and survival for cancer among children and adolescents in Europe over the period 1978-1997. The analyses were derived from the large database of the ACCIS project (Automated Childhood Cancer Information System), which was built through collaboration of 62 population-based cancer registries in 19 European countries. Data on 88,465 cancers in children and 15,369 in adolescents (age 15-19 yrs) were included in the various analyses, making this the largest database on cancer in these age-groups in the world. National data were grouped into five European regions to allow comparisons of incidence and survival, for all cancers and by tumour type, including analysis of trends in both over time. This overview paper focuses on the comparability of the data from multiple registries and describes the potential confounding factors. Age-standardised annual incidence rates of many, but not all, cancers in children and adolescents are clearly rising. There are geographical differences in survival for the majority of tumour types. Survival rates increased for nearly all types of cancer in children and adolescents. The implications of these findings for aetiological factors and treatment delivery for cancer in children and adolescents are discussed.