Cancer in adolescents and young adults aged 15-24 years: a report from the North of England young person's malignant disease registry, UK.

BACKGROUND: Descriptions of population-based data have rarely been published specifically for adolescents and young adults with cancer. PROCEDURE: Data on young adults (15-24 years) diagnosed with cancer in the North of England from 1968 to 1997 were obtained from the Northern Region Young Person's Malignant Disease Registry. Temporal changes in incidence and survival rates were investigated. RESULTS: There were 2,329 first cancers diagnosed over the study period (M:F 1.22:1). Overall age standardized incidence was 174 cases per million 15-24 years old, per year, 190 for males and 157 for females. The most common cancers in young adults were Hodgkin disease (19%), carcinomas (15%), central nervous system tumors (14%), germ cell tumors (13%), and leukemia (11%). Comparing incidence for 1968-1977 with 1988-1997 there were significant increases in the incidence of bone tumors (rate ratio 1.72, 95% CI 1.10-2.68), testicular tumors (rate ratio 1.64, 95% CI 1.16-2.32), thyroid cancer (rate ratio 2.63, 95% CI 1.37-5.02), and malignant melanoma (rate ratio 2.04, 95% CI 1.36-3.08). Survival rates improved significantly (P < 0.001) over the study period; 5-year survival rates over the three time periods 1968-1977, 1978-1987, 1988-1997 for all cancers were 45% (95% CI 41%-49%), 62% (95% CI 58%-65%), and 74% (95% CI 71%-77%) respectively. CONCLUSIONS: Survival rates improved and there were significant increases in incidence for specific cancers in young adults in the North of England. Further research is required to identify the reasons for changing incidence and to investigate the late effects of treatment among survivors.

High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group.

BACKGROUND: High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. PROCEDURE: In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative "megatherapy" was evaluated in a randomised, multi-centre trial. Between 1982 and 1985, 167 children with stages IV and III neuroblastoma (123 stage IV > 1 year old at diagnosis and 44 stage III and stage IV from 6 to 12 months old at diagnosis) were treated with oncovin, cisplatin, epipodophyllotoxin, and cyclophosphamide (OPEC) induction chemotherapy every 3 weeks. After surgical excision of primary tumour, the 90 patients (69% of the total) who achieved complete response (CR) or good partial response (GPR) were eligible for randomisation either to high dose melphalan (180 mg per square meter) with autologous bone marrow support or to no further treatment. RESULTS: Sixty-five (72%) of eligible children were actually randomised and 21 of these patients were surviving at time of this analysis, with median follow-up from randomisation of 14.3 years. Five year event-free survival (EFS) was 38% (95% confidence interval (CI) 21-54%) in the melphalan-treated group and 27% (95% CI 12-42%) in the "no-melphalan" group. This difference was not statistically significant (P = 0.08, log rank test) but for the 48 randomised stage IV patients aged >1 year at diagnosis outcome was significantly better in the melphalan-treated group-5 year EFS 33% versus 17% (P = 0.01, log rank test). CONCLUSIONS: In this trial, high dose melphalan improved the length of EFS and overall survival of children with stage IV neuroblastoma >1 year of age who achieved CR or GPR after OPEC induction therapy and surgery. Multi-agent myeloablative regimens are now widely used as consolidation therapy for children with stage IV disease and in those with other disease stages when the MYCN gene copy number in tumour cells is amplified. Because they are more toxic, complex, and costly these combination megatherapy regimens should be compared with single agent melphalan in randomised clinical trials.

Fathers' occupational contacts and risk of childhood leukemia and non-hodgkin lymphoma.

BACKGROUND: There is evidence to suggest that childhood leukemia and non-Hodgkin lymphoma have an infective etiology. We investigated the risk of childhood leukemia and non-Hodgkin lymphoma in relation to paternal occupational contact with other individuals, a surrogate for potential exposure to infection. METHODS: We carried out a case-control study using 792 cases from the Northern Region Young Persons' Malignant Disease Registry, United Kingdom, 1968-1997, and 2 large population-based control groups. Paternal occupations at birth were classified as having standard, high, or very high levels of contact. Conditional logistic regression was used in the analysis. RESULTS: There was an increased risk of childhood leukemia and non-Hodgkin lymphoma in those children whose fathers' occupational contacts were high or very high compared with standard (odds ratio = 1.3; 95% confidence interval = 1.0-1.5). The excess risk in the very high group was most pronounced for 245 cases of acute lymphoblastic leukemia aged 2 to 5 years at diagnosis (1.5; 1.1-2.1). The risk with paternal occupational contacts was greater in rural areas, although it was also present in urban areas. The risks of leukemia and non-Hodgkin lymphoma were also higher among the offspring of men employed as policemen, sales representatives, or teachers. CONCLUSIONS: Our findings are consistent with the hypothesis of an infective etiology for childhood leukemia and non-Hodgkin lymphoma, and they add to the evidence that infections could be transmitted to children by adults.

Stature of young people with malignant bone tumors.

BACKGROUND: Little is known about the aetiology of primary bone tumours. There have been conflicting reports relating to stature in young people with bone cancer. PATIENTS: We analysed height data at diagnosis for 364 patients with osteosarcoma and 356 patients with Ewing sarcoma registered on clinical trials run by the Medical Research Council (MRC) and the United Kingdom Children's Cancer Study Group (UKCCSG). MAIN OUTCOME MEASURES: Height at diagnosis for each patient was standardised for age and sex compared to national reference data with a standard deviation score (SDS) calculated for each subject. RESULTS: Those with osteosarcoma were significantly taller than the general population (mean height SDS 0.2, P=0.001). Patients with osteosarcoma of the femur were significantly taller than patients with other primary sites (mean height SDS 0.45 vs. -0.06, P=0.0001). Overall those with Ewing sarcoma were not significantly taller than the general population (mean height SDS 0.09, P=0.1), but children presenting under 15 years were taller (SDS 0.2, P=0.004) whilst older patients were not (SDS -0.07, P=0.4). In both osteosarcoma and Ewing sarcoma the mean age at diagnosis for females was significantly younger than for males. CONCLUSIONS: This study suggests that tall stature and an earlier pubertal growth spurt may be important factors in the aetiology of both osteosarcoma and Ewing sarcoma.

Skin cancer in children and young adults: 28 years' experience from the Northern Region Young Person's Malignant Disease Registry, UK.

Little population-based data has been published about skin cancers in children and young adults. In this study, 200 cases of melanoma and non-melanoma skin cancers diagnosed under 25 years of age in the North of England from 1968-1995 were obtained from the Northern Region Young Persons' Malignant Disease Registry. The incidence was 1.2 cases per million per year for children (aged 0-14 years) and was 13 cases per million per year for young adults (aged 15-24 years). Melanoma accounted for 138 cases, of which 16 were in subjects aged < 15 years at diagnosis. The incidence of melanoma increased in females at a rate of 5.6 per million per decade (95% confidence interval [CI] 2.2-8.9, P = 0.002), largely due to an increased incidence of primary lower limb tumours. The incidence for males was unchanged. Survival improved significantly over time for both males and females (P < or = 0.02). Of the 62 patients with non-melanoma skin cancers, 66% were diagnosed with primary non-basal cell carcinoma, 13% with dermatofibrosarcoma protuberans, 10% with squamous cell carcinoma and 11% with other tumours. Two cases were iatrogenic second malignancies following treatment for an earlier primary brain tumour. The incidence of non-melanoma skin cancers was significantly higher during 1982-1995 than during 1968-1981 (rate ratio 1.7, 95% CI 1.0-2.8). There were three deaths from non-melanoma skin cancer, and the overall 5 year survival rate was 98% (95% CI 89-100%). The reason for the increasing incidence of both melanoma and non-melanoma skin cancer in young people is unknown, but it is likely that ultraviolet exposure plays an aetiological role. It is important that families continue to be advised of the need for vigilance with regard to childhood sun exposure.

Cytogenetic abnormalities and clinical outcome in Wilms tumor: a study by the U.K. cancer cytogenetics group and the U.K. Children's Cancer Study Group.

BACKGROUND: Tumor genetic features reported to correlate with adverse outcome in Wilms tumor include karyotype complexity, losses of material from the short arm of chromosome 1 and from the long arms of chromosomes 11, 16 and 22 and gain of material from the long arm of chromosome 1. This study sought to test these associations in a large series of tumors studied by cytogenetic analysis. Identification of markers associated with elevated risk of relapse and fatal outcome could allow more effective treatment stratification at presentation. PROCEDURE: Thirteen member laboratories of the U.K. Cancer Cytogenetics Group provided results from a 12-year period. Karyotype abnormalities were correlated with clinical data (age, tumor stage, and histology) and outcome data provided by the central register of the U.K. Children's Cancer Study Group. RESULTS: Of 127 abnormal karyotypes, 78 included a reputedly "poor prognosis" feature. Univariate survival analysis showed no significant adverse effect for karyotype complexity, 1p loss or 11q loss. The poor outcome of cases with 16q loss was of borderline significance, but this effect was restricted to those tumors with unbalanced translocation der(16)t(1q;16q). The association between relapse risk and gain of 1q material was not significant. Only monosomy 22 was a significant marker of poor outcome in univariate analysis (13 cases showing 50% relapse free survival at 5 years compared to 79% survival for the remaining 114 cases, P = 0.02). In multivariate analysis, significant independent predictors of poor outcome were 1q gain (Hazard Ratio 3.4), stage IV disease (HR 5.0), and monosomy 22 (HR 5.9). CONCLUSIONS: Loss of chromosome 22 identifies high risk Wilms tumors. The prognostic significance of 1q gain, 16q loss and unbalanced translocation der(16)t(1q;16q) is unresolved and warrants further investigation.