Abstract: BACKGROUND: A 4-week course of high-dose glucocorticoids may cause prolonged adrenal suppression even after a 9-day tapering phase. In this study, adrenal function and signs and symptoms of adrenal insufficiency were prospectively assessed in children with acute lymphoblastic leukemia (ALL) after induction treatment including high-dose prednisone (PDN) or dexamethasone (DXM). PROCEDURES: Sixty-four children with ALL, treated according to the AIEOP ALL 2000 Study protocol, underwent low dose ACTH (LD-ACTH) stimulation 24 hr after the last tapered steroid dose. In those with impaired cortisol response, additional LD ACTH tests were performed every 1-2 weeks until cortisol levels normalized. Signs and symptoms of adrenal insufficiency were recorded during the observation period. RESULTS: All patients had normal basal cortisol values at diagnosis. Twenty-four hours after last glucocorticoid dose, morning cortisol was reduced in 40/64 (62.5%) patients. LD-ACTH testing showed adrenal suppression in 52/64 (81.5%) patients. At the following ACTH test 7-14 days later, morning cortisol values were reduced in 8/52 (15.4%) patients and response to the test was impaired in 12/52 (23%). Adrenal function completely recovered in all patients within 10 weeks. No difference was found between patients treated with PDN or DXM. Almost 35% of children with impaired cortisol values at the first test developed signs or symptoms of adrenal insufficiency. One child developed a severe adrenal crisis during adrenal suppression. CONCLUSIONS: High-dose glucocorticoid therapy in ALL children may cause prolonged adrenal suppression and related clinical symptoms. Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated.

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Abstract: Tertiary care centres, grouped in the Italian Association of Paediatric Haematology and Oncology (AIEOP) are unevenly distributed across the country. In an attempt to describe their perceived efficacy, we matched the residence and the location of the treatment centre in 18,441 patients aged 15 years treated in the AIEOP network between 1989 and 2005. Overall, centres located in the central and southern regions were less appealing than those located in the North, although this trend decreased over the study period. Patients with solid tumours migrated more frequently than those with leukaemia or lymphoma. Information resulting from better knowledge of the non-random migrations for treatment of children with cancer will be useful to refine planning of the national paediatric haematology-oncology network with social and economic implications.

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Abstract: We describe the survival patterns of 10,791 Italian children (age 0-14) diagnosed with cancer during 1989-1998 and who were included in the hospital-based registry of the Italian Association of Paediatric Haematology and Oncology. Five-year cumulative survival percentages were 76% for lymphoproliferative disorders and 68% for solid tumours. Survival rates in 1994-1998 significantly improved for acute lymphocytic leukaemia (ALL), acute non-lymphocytic leukaemia, Hodgkin's lymphoma and Wilms' tumour. Gender and age were determinants of survival for some specific types of cancer. Girls with ALL and neuroblastoma exhibited a significant advantage (hazard ratio HR 0.72, 0.62-0.83) and disadvantage (HR 0.73, 0.59-0.90) over boys, respectively. Children with a Wilms' tumour diagnosed above age 3 had a worse prognosis than younger children (HR 2.3, 1.4-4.1). The persisting gender-related difference in survival rate for ALL requires understanding as to whether it is attributable to delays in the adoption of more recent therapeutic protocols, while the corresponding findings for Wilms' tumour and neuroblastoma deserve further biological interpretation.

Abstract: PURPOSE: The aim of this study was to assess the risk of second malignant neoplasms (SMNs) other than central nervous system (CNS) neoplasms after childhood CNS cancer in an international multicentre study. METHODS: Individual data on cases of CNS cancer in children (0-14 years) and on subsequent SMNs were obtained from 13 population-based cancer registries contributing data for different time periods in 1943-2000. Standardised incidence ratios (SIRs) with 95% confidence intervals (CI), absolute excess risk and cumulative incidence of SMNs were computed. RESULTS: We observed 43 SMNs in 8431 CNS cancer survivors. The SIR was 10.6 (4.85-20.1) for thyroid cancer (nine cases), 2.75 (1.01-5.99) for leukaemia (six cases) and 2.47 (0.90-5.37) for lymphoma (six cases). The SIRs were highest in the first 10 years after CNS cancer diagnosis. The cumulative incidence of non-CNS SMNs was 3.30% (0.95-5.65%) within 45 years after a CNS cancer diagnosis. Within 15 years, the cumulative incidence was highest for cases diagnosed after 1980 (0.56%, 95% CI: 0.29-0.82%). CONCLUSION: This population-based study indicates that about one every 180 survivors of a childhood CNS cancer will develop a non-CNS SMN within the following 15 years. The excess is higher after glioma and embryonal malignant tumour than after another CNS tumour.

Abstract: The total number of children with incident cancer in Italy has never been specifically estimated. Specialized population-based Childhood Cancer Registries have only been operating in Piedmont (CCRP) and in the Marche region, while general population cancer registries cover about 20% of the Italian population. The number of expected cases of childhood cancer (0-14 years) in Italy in the period 2001-2015 has been estimated using CCRP incidence rates and annual percentage changes. The expected number of cases of all cancer types were 8,132, 8,672 and 8,944 in the periods 2001-2005, 2006-2010 and 2011-2015 respectively. These figures help evaluate the allocation of resources for the care of child cancer patients in Italy, and to estimate the number of cases expected to enter clinical trials.

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Abstract: BACKGROUND: Prognosis for most types of childhood tumours has improved during the last few decades. In this article we estimate up-to-date period survival for less common, but important childhood malignancies in Europe. METHODS: Using the database of the Automated Childhood Cancer Information System we calculated period estimates of 10-year survival for the 1995-1999 period for children aged 0-14 years diagnosed during 1985-1999 with tumours of the sympathetic nervous system (NS), retinoblastoma, renal tumours, bone tumours and soft tissue sarcomas in four European regions. RESULTS: Ten-year period survival for 1995-1999 was 66% in children with tumours of the sympathetic NS, 96% for retinoblastoma, 87% for renal tumours, 58% for bone tumours and 61% for soft tissue sarcomas. The higher period estimates, as compared with cohort and complete estimates indicate recent improvement in survival for tumours of the sympathetic NS and to a lesser extent for retinoblastoma and renal tumours. Region-specific period survival estimates were lowest for Eastern Europe for renal, bone and soft tissue tumours, but not for the other two tumour groups. CONCLUSION: There have been further improvements in the 1990s in long-term survival of children diagnosed with several malignancies, albeit to a different extent in different European regions.

Abstract: BACKGROUND: Survivors of childhood leukemia and lymphoma experience high risks of second malignant neoplasms. We quantified such risk using a large dataset from 13 population-based cancer registries. METHODS: The registries provided individual data on cases of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma occurring in children aged 0-14 years and on subsequent second malignant neoplasms for different time periods from 1943 to 2000. Risks of second malignant neoplasms were assessed through standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (CIs), using the incidence rates in the general populations covered by the registries as a reference. Cumulative absolute risks were also calculated. RESULTS: A total of 133 second malignant neoplasms were observed in 16,540 patients (12,731 leukemias, 1246 Hodgkin lymphomas, and 2563 non-Hodgkin lymphomas) after an average follow-up of 6.5 years. The most frequent second malignancies after leukemia were brain cancer (19 cases, SIR = 8.52, 95% CI = 5.13 to 13.3), non-Hodgkin lymphoma (nine cases, SIR = 9.41, 95% CI = 4.30 to 17.9), and thyroid cancer (nine cases, SIR = 18.8, 95% CI = 8.60 to 35.7); the most frequent after Hodgkin lymphoma were thyroid cancer (nine cases, SIR = 52.5, 95% CI = 24.0 to 99.6), breast cancer (six cases, SIR = 20.9, 95% CI = 7.66 to 45.4), and neoplasms of skin (non-melanoma) (six cases, SIR = 34.0, 95% CI = 12.5 to 74.0); and the most frequent after non-Hodgkin lymphoma were thyroid cancer (six cases, SIR = 40.4, 95% CI = 14.8 to 88.0) and brain cancer (four cases, SIR = 6.97, 95% CI = 1.90 to 17.9). Cumulative incidence of any second malignant neoplasm was 2.43% (95% CI = 1.09 to 3.78), 12.7% (95% CI = 8.29 to 17.2), and 2.50% (95% CI = 1.04 to 3.96) within 30 years from diagnosis of leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma, respectively. CONCLUSIONS: This population-based study provides, to our knowledge, the most precise and up-to-date estimates for relative and absolute risks of second malignant neoplasms after childhood leukemia and lymphoma.

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Abstract: Several studies report increasing trends in the incidence of childhood acute lymphoblastic leukemia (ALL). Because ALL may generate in utero, this study investigated if maternal age and birth cohort influence ALL temporal trends. Data on 252 ALL cases in children ages 1 to 5 years were extracted from the population-based Childhood Cancer Registry of Piedmont, Italy. Information on cases' maternal age and year of birth was obtained from the registry, whereas population data were obtained for children born in 1980 to 1997. Incidence rates were analyzed using an age-period-cohort approach, in which the period effect was represented by the child year of birth, the age effect by the maternal age at the time of delivery, and the cohort effect by the maternal birth cohort. ALL incidence increased over the study period [annual percentage change 2.49%; 95% confidence interval (95% CI), 0.09-4.93]. A linear effect of the maternal time variables (P = 0.012) was found, which was equally described by maternal age (direct association) and maternal birth cohort (inverse association). The annual percentage change was 1.83% (95% CI, -0.59-4.31), when maternal age was included in the model, and 5.72% (95% CI, 2.29-9.27), when maternal year of birth was included. In conclusion, maternal characteristics substantially affect temporal trends in childhood ALL incidence.

Abstract: The aim of this study was to estimate how many deaths have been avoided because of the substantial improvement in childhood cancer survival both in Piedmont (2769 incident cases) and in Italy during 1970-1999. For each time period of diagnosis, the number of avoided deaths within 5 years after diagnosis was estimated as the difference between the observed number of deaths and the number of deaths that would have been observed if the patients had experienced the same mortality as in the reference period of 1970-1974. The national estimate of the number of avoided deaths was calculated by applying Piedmont cumulative mortality to the expected number of incident cases in Italy. An increase in the number of avoided deaths from 103 (95% confidence interval: 65-140) in 1975-1979 to 239 (95% confidence interval: 209-268) in 1995-1999 was observed in Piedmont. In Italy, the number of avoided deaths was 3880 in 1995-1999, with respect to 1970-1974. Results of these analyses provide an effective way to quantify the improvement in the quality of care for children with childhood cancer.

Abstract: The aim of this study was to compare the characteristics of respondents and nonrespondents in a survey of childhood cancer survivors recorded in the Childhood Cancer Registry of Piedmont and their current primary care general practitioners. Eligible subjects were identified from the Childhood Cancer Registry of Piedmont and the referring general practitioners were traced through the National Health Service. A postal questionnaire was sent both to childhood cancer survivors and to their general practitioners. Prevalence odds ratios were estimated for demographic and clinical characteristics in survivors and for demographic characteristics in general practitioners. A total of 1005 childhood cancer survivors and 857 general practitioners (132 of them had two or more cancer survivors in care) were included in the study. Completed questionnaires were obtained from 691 survivors (69%) and 615 general practitioners (72%). For survivors, the only associations with nonresponse were for age 35-44 years [prevalence odds ratio: 0.53 (95% confidence interval: 0.33-0.85)], being married [prevalence odds ratio: 1.45 (95% confidence interval: 0.96-2.18)] and diagnosis after 1977 [prevalence odds ratio: 0.66 (95% confidence interval: 0.42-1.03)]. For general practitioners, the only associations were for male sex [prevalence odds ratio: 1.62 (95% confidence interval: 1.13-2.32)] and place of work outside of the city of Turin [prevalence odds ratio: 1.93 (95% confidence interval: 1.07-3.47)]; furthermore associations were relatively weak. An association was also found between nonresponse in survivors and nonresponse in their general practitioners [prevalence odds ratio: 3.40 (95% confidence interval: 2.54-4.56)]. In conclusion, apart from age, marital status and period of diagnosis, there were little differences between respondent and nonrespondents, for the considered clinical and demographical characteristics. Participation of survivors and their general practitioners correlated, suggesting that involvement of the general practitioners in the study may be a method to increase participation of survivors of childhood cancers.

Abstract: This population-based study (the largest on this issue conducted in Southern Europe) has examined mortality among the parents of 2622 children diagnosed with cancer in Piedmont during 1967-1994. Parents were followed up from the date of the index child's birth until the end of 2000, yielding a total of 118 090.7 person-years of observation. Standardized mortality ratios (SMRs) were estimated using mortality rates for the whole population of Piedmont as the reference. Among mothers, total mortality was similar to that expected [SMR 1.02, 95% confidence interval (CI) 0.85-1.23, 117 cases]. A reduced risk of mortality was seen in fathers (SMR 0.91, 95% CI 0.81-1.02, 293 cases); this was largely due to causes other than cancer and the reduction in risk disappeared after the index child's death (SMR 0.98, 95% CI 0.84-1.15, 168 cases). Deaths from cancers of the lymphohaematopoietic system were in excess among mothers (SMR=2.13, 95% CI 1.02-3.92, 10 cases) and breast cancer deaths were in excess specifically among mothers of leukaemic children (SMR 2.32, 95% CI 1.16-4.14, 11 cases). Three mothers dying with breast cancer had index children who had been diagnosed with a bone sarcoma. Parental cancer of the respiratory tract was significantly associated with both tumours of the central nervous system and Hodgkin's lymphoma in the index child. The excess risks identified here may be due to genetic factors or due to parental psychological stress consequent to cancer in a child that may lead to increased mortality either through the direct effects of stress or through consequent changes in lifestyle.

Abstract: We report on 12 near-term babies from three families in which an unexplained transient respiratory distress was observed. No known risk factor was present in any family and no sequelae were recorded at follow-up. The most common causes of respiratory distress at birth are Neonatal Respiratory Distress Syndrome (NRD) and Transient Tachypnea of the Newborn (TTN), and their cumulative incidence is estimated to be about 2%. Genetic factors have been identified in NRD (surfactant genes) or suggested for TTN (genes affecting lung liquid clearance). Survivors from NRD may develop clinically relevant sequelae, while TTN does not cause any problem later in life. Our cases do not immediately fit NRD or TTN, while familial recurrence suggests the existence of a previously unreported subgroup on patients with respiratory distress for which autosomal-recessive inheritance is likely.

Abstract: AIM OF THE STUDY: To determine the Health Related Quality of Life (HRQL) in a population-based cohort of long-term survivors of childhood cancer in Piedmont, northwestern Italy. PATIENTS AND METHODS: During 2003, a 15-item Health Utilities Index questionnaire was mailed to 1005 5-year survivors, identified from the population-based Childhood Cancer Registry of Piedmont, to derive scores for overall HRQL and for eight single attributes of health. Score differences were estimated as adjusted prevalence odds ratios. RESULTS: A large majority of long-term survivors had moderately high scores for overall HRQL and for each of the single attributes. Males reported better overall HRQL and less morbidity with respect to dexterity, emotion and pain than females. Survivors diagnosed when they were 10-14 years of age had better overall HRQL and less morbidity with respect to emotion, cognition and pain than younger persons. Long-term survivors of central nervous system (CNS) tumours, retinoblastoma and bone tumours had greater impairment of overall HRQL, vision, ambulation, dexterity, cognition and pain than survivors of other forms of cancer. CONCLUSION: Many survivors of childhood cancer in Piedmont had fairly good overall HRQL. Greater probability of impaired HRQL was seen for females, survivors of CNS tumours, retinoblastoma and bone tumours, and persons diagnosed before 10 years of age.

Abstract: An empirical evaluation of long-term period survival analysis was performed using data from the Childhood Cancer Registry of Piedmont, Italy. The aim was to update survival time trends and provide 25-year projections for children currently diagnosed with cancer. The observed survival experiences up to 15 years after diagnosis of five quinquennial cohorts (cohort analysis) were compared to the corresponding estimates obtained by period analysis. The two methods generally produced very similar findings, although period analysis estimates were slightly lower than those obtained from cohort analysis. We then used mixed analysis to assess time trends in long-term survival. This showed that the probability of surviving 25 years after a cancer in childhood has more than doubled compared to cohort analysis estimates from patients diagnosed more than 25 years ago (73% vs. 32%), providing further evidence of an ongoing improvement in prognosis.

Abstract: The aim of this report is to provide an update on the natural history of the Cri du Chat Syndrome by means of the Italian Register (I.R.). Two hundred twenty patients were diagnosed by standard cytogenetic methods and 112 of these were also characterised by molecular-cytogenetic investigation (FISH). FISH analysis showed interstitial deletions, short terminal deletions and other rare rearrangements not previously correctly diagnosed by standard cytogenetics. The diagnosis was made in the first month of life in 42% and within first year in 82% of cases. The remaining 18% were diagnosed at an age ranging from 13 months to 47 years. At the last follow-up, patient age ranged from 8 months to 61 years. Mortality, already low, has decreased over time as it is lower between 1984-2002 compared to 1965-1983. Mortality was higher in patients with unbalanced translocations resulting in 5p deletions. Our data confirm that the cat-like cry and peculiar timbre of voice are the most typical signs of the syndrome, not only at birth but also later and these are the only signs which might suggest the diagnosis in patients with small deletions and mild clinical picture. A cytogenetic and clinical variability must be underlined. Cardiac, cerebral, renal and gastrointestinal malformations were more frequent in the patients with unbalanced translocations resulting in 5p deletions. Sucking and feeding difficulties and respiratory infections are frequent in the first months or years of life. Intubation difficulties linked to larynx anomalies must be considered. Psychomotor development is delayed in all patients but there is a variability related to deletion size and type as well as other genetic and environmental factors. However, the results showed an improvement in the acquisition of the development skills and progress in social introduction which should encourage caregivers and parents to work together in carrying out the rehabilitative and educational interventions.

Abstract: Published data on time trends in the incidence of childhood leukaemia show inconsistent patterns, with some studies showing increases and others showing relatively stable incidence rates. Data on time trends in childhood cancer incidence from the Childhood Cancer Registry of Piedmont, Italy were analysed using two different approaches: standard Poisson regression and a Bayesian regression approach including an autoregressive component. Our focus was on acute lymphoblastic leukaemia (ALL), since this is hypothesised to have an infectious aetiology, but for purposes of comparison we also conducted similar analyses for selected other childhood cancer sites (acute non-lymphoblastic leukaemia (AnLL), central nervous system (CNS) tumours and neuroblastoma (NB)). The two models fitted the data equally well, but led to different interpretations of the time trends. The first produced ever-increasing rates, while the latter produced non-monotonic patterns, particularly for ALL, which showed evidence of a cyclical pattern. The Bayesian analysis produced findings that are consistent with the hypothesis of an infectious aetiology for ALL, but not for AnLL or for solid tumours (CNS and NB). Although sudden changes in time trends should be interpreted with caution, the results of the Bayesian approach are consistent with current knowledge of the natural history of childhood ALL, including a short latency time and the postulated infectious aetiology of the disease.

Abstract: BACKGROUND: Survival analysis is a standard methodology to assess progress in oncology disease treatment. However, survival analysis commonly only measures survival during the treatment period (and the period immediately afterwards), and does not provide an estimate of life expectancy, which is often of more interest to patients and to health policy makers. In this paper we propose a method to estimate childhood acute lymphoblastic leukemia (ALL) life expectancy through the integration of traditional survival analysis and life expectancy tables. PATIENTS AND METHODS: The study included 305 incident cases registered by the Childhood Cancer Registry of Piedmont in 1979-1991. Vital status on 30 June 2004 was known for 304 cases. Survival analyses were carried out using the Kaplan-Meier method and the Gompertz model, according to the time period of diagnosis and gender. RESULTS: Cumulative survival at 5 years increased from 58.6% (95% CI 48.9-68.3) for cases diagnosed in March 1979-July 1982 to 79.1% (95% CI 70.8-87.5) in March 1987-February 1991 (P = 0.002). Average life expectancy increased from 46.1 years for boys and 42.6 years for girls diagnosed in March 1979-July 1982 to 58.3 and 69.1, respectively, in March 1987-February 1991. CONCLUSIONS: These analyses show an improvement over the time period of diagnosis of life expectancy for children with ALL.

Abstract: BACKGROUND AND OBJECTIVES: The aim of this study was to analyze late mortality among 5-year survivors of childhood cancer, in Piedmont (Italy), in terms of risk factors and causes of death. DESIGN AND METHODS: From 1967 to 1999, the Childhood Cancer Registry of Piedmont recorded 3164 incident cases. Patients identified only by a death certificate (n = 59), lost to follow-up (n = 32), alive with a period of observation shorter than 5 years at the end of follow-up (n = 65) and records corresponding to a second malignant tumor during childhood (n = 9) were excluded from the analyses. RESULTS: Within 5 years after diagnosis, 1301 children died, and among the 1698 5- year survivors, 144 children subsequently died. Among 5-year survivors, cumulative mortality percentages increased from 5.1% (95% CI 4.0-6.2) at 10 years after diagnosis to 16.0% (12.2-19.8) at 35 years. Period of diagnosis (p = 0.006), age at diagnosis (p = 0.002), and tumor type (p = 0.003) were associated with late mortality. Most deaths were related to cancer recurrence (62.2%) and treatment-related sequelae (22.4%), including second malignant neoplasms, cardiac diseases and other late effects. Compared to the general population, children included in this study had a 9-fold increased risk of overall mortality, and experienced an absolute excess of 4.4 deaths per 1000 person-years. INTERPRETATION AND CONCLUSIONS: Among 5-year survivors, patients treated more recently (after 1979) had a statistically significant lower risk of late death than those treated earlier. However, long-term survivors still experienced higher mortality rates than those in the general population, and recurrence or progression of the primary tumor was the first cause of death.

Abstract: Survival after childhood cancer has been improving since the late 1970s in most developed countries. The Childhood Cancer Registry of Piedmont has been recording malignant tumors in children (0-14 years) throughout Piedmont since 1967. The present paper is based on the records of the 2,970 children diagnosed during the period 1970-2001; survival rates are estimated up to June 30, 2004. Based on records from the Registrar Offices of the relevant towns of residence, 1,698 children were reported to be alive, 1,252 deceased, and 20 were of unknown vital status. Over the period 1970-2001, 5-year survival rates for all tumor types combined showed a statistically significant increasing trend (p<0.0001). For acute lymphocytic leukemia, the survival rate increased steadily from 24.7% (95% CI 15.0-34.3) in 1970-1974 to 87.8% (82.1-93.6) in 1995-1999. Five-year survival rates for central nervous system tumors increased from 32.8% (21.0-44.6) in 1970-1974 to 80.3% (72.6-88.0) in 1990-1994 and decreased thereafter. Age of less than 1 year at time of diagnosis was a favorable prognostic factor for neuroblastoma and ganglioneuroblastoma. The extent of disease at diagnosis was related to prognosis for neuroblastoma and ganglioneuroblastoma and other selected solid tumors. A white blood cell count greater than 50,000 x 10(6) cells/l was associated with decreased survival in children with acute lymphocytic leukemia and acute non-lymphocytic leukemia. We have found positive trends in survival for all tumor types in Piedmont, similar to those reported by other population-based cancer registries. Age, extent of disease, and white blood cell count at diagnosis are prognostic factors for selected cancer sites.

Abstract: The Automated Childhood Cancer Information System (ACCIS) collects and presents data on childhood cancer in Europe. This report describes trends (1978-1997) and geographical differences (1988-1997) in incidence and survival for 6202 children with neuroblastoma from 59 registries in 19 countries, grouped into five regions (British Isles, West, East, North, and South). The age-standardised incidence rate (ASR) of neuroblastoma in Europe in 1988-1997 was 10.9 cases per million children, being highest in infants (52.6). The ASR of neuroblastoma increased in Europe from 8.4 in 1978-1982 to 11.6 in 1993-1997, mostly due to an increase in infants (from 35.4 to 57.8). Overall 5-year survival was 59%, ranging from 47% (East) to 67% (West). It improved markedly from 37% in 1978-1982 to 66% in 1993-1997, especially in infants. A certain amount of overdiagnosis in children under 2 years of age may explain the increased incidence rates and partially the increase in survival. Survival of older children (aged 2-14 years), which is likely to be largely affected by therapy, has also improved from 21% to 45%.

Abstract: Survivors of retinoblastoma (Rb) are at high risk of dying from second malignant tumour. The occurrence of second malignant neoplasm (SMN) and related mortality in a cohort of 1111 cases from the Italian Retinoblastoma Registry was analysed, considering the possible role of both genetic and iatrogenic causes. Rb patients had a greater than 10-fold excess in overall mortality compared with the general population (standardized mortality ratio (SMR) 10.73, 95% CI 9.00-12.80). Their excess risk attributable to cancers other than Rb was 14.93 95% CI 10.38-21.49). Survivors of hereditary Rb had an SMR for all causes of 16.25 (95% CI 13.20-20.00), whereas their SMR for all cancers was 25.72 (95% CI 17.38-38.07). Survivors of unilateral sporadic Rb had an SMR of 4.12 from all cancers (95% CI 1.55-10.98) and a much higher excess for overall mortality (SMR 13.34, 95% CI 10.74-16.56). As expected, survivors of hereditary Rb had higher mortality from cancers of the bone (SMR 391.90, 95% CI 203.90-753.20) and soft tissue (SMR 453.00, 95% CI 203.50-1008.40), small intestine (SMR 1375.50, 95% CI 344.00-5499.70), nasal cavity (SMR 13.71, 95% CI 1.93-97.35) and cancers of the brain and central nervous system (SMR 41.14, 95% CI 13.2-127.55).

Abstract: This study, originating in the Automated Childhood Cancer Information System (ACCIS), evaluated the time trend in survival after childhood cancer in Europe. The study included more than 72,000 childhood cancer cases aged 0-14 years diagnosed in 1978-1997 and followed-up in 30 population-based cancer registries with a long history of registration and follow-up, in 15 European countries. Survival was analysed using an actuarial life-table method. Five-year cumulative survival probability increased significantly over the study period for all tumour types combined, from 54% for cases diagnosed in the period 1978-1982 to 75% in 1993-1997. Significant improvement was also observed in 10-year survival. Comparing the results for the period 1993-1997 with those for 1978-1982, the largest relative increase in survival was seen for hepatic tumours (32%) and the largest reduction in mortality for non-Hodgkin's lymphomas (60%). Least progress was seen for central nervous system (CNS) tumours. The improvement was statistically significant in all European regions and was most rapid in the East. The ranking among the European regions did not change over the study period, with highest survival in the North and the West and lowest in the East. Extended data collection is necessary to evaluate future time trends and changes in differences between European regions.

Abstract: This population-based study is based on 5802 cases of soft tissue sarcomas (STS) in children aged 0-14 years extracted from the database of the Automated Childhood Cancer Information System (ACCIS) and registered in population-based cancer registries in Europe for the period 1978-1997. STS represent almost 8% of neoplasms in children, almost half of whom are less than 5 years at diagnosis. Rhabdomyosarcoma is the most frequent childhood STS (50%). During 1988-1997 the age-standardised incidence of STS in Europe was 9.1 per million children, lowest in the West and East and highest in the North. The incidence of STS increased almost 2% per year over the period 1978-1997, attributable mostly to increase in genito-urinary rhabdomyosarcoma. Prognosis of children with STS was related to age and site of tumour. Five-year survival of children with STS increased from 46% in 1978-1977 to 66% in 1993-1997, reaching 74% in the North for those diagnosed in 1993-1997. This improvement is ascribed to therapy advances.

Abstract: More than 5000 cases of malignant renal tumour diagnosed in children under the age of 15 years during the period 1978-1997 in Europe, were extracted from the database of the Automated Childhood Cancer Information System (ACCIS). In 1988-1997 the age-standardised incidence rate of childhood renal tumours in Europe was 8.8 per million, with significant differences between regions. Wilms' tumour (WT, M-8960) accounted for 93% of renal tumours and about 7% were bilateral. The incidence rates of WT increased over the 20 years, by 0.7% per year. European 5-year survival for children diagnosed with WT in 1988-1997 was 85%, ranging from 73% in the East to 91% in the North. Patients in the age group 0-3 years at diagnosis had a more favourable prognosis (5-year survival 87%) than those diagnosed later (81%), P<0.0001. Patients with unilateral WT (n=2085) had better 5-year survival (85%) than 154 patients with bilateral tumours (76%), P=0.003. Five-year survival for 64 patients with clear cell sarcoma of kidney was 68%, for 43 patients with rhabdoid tumour of kidney it was 23%, and for 56 patients with renal cell carcinoma it was 87%. For combined European data, 5-year survival for WT increased from 73% in 1978-1982 to 87% in 1993-1997 and the increase was significant in three out of five regions (East, North and West). Further development and exploitation of the ACCIS database will benefit clinical management and aetiological studies.

Abstract: Hypospadias, when the urethra opens on the ventral side of the penis, is a common malformation seen in about 3 per 1,000 male births. It is a complex disorder associated with genetic and environmental factors and can be part of genetic syndromes. Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype, Hirschsprung disease, microcephaly and mental retardation. It is caused by mutations in the zinc finger homeo box 1B gene, ZFHX1B (SIP1). To date, 68 deletion/mutation-positive cases have been reported. Genitourinary anomalies are common in MWS. Here we report that hypospadias is common in males with this syndrome. In 39 patients where this information was available, hypospadias was present in 46% of patients (18/39). In the 3 Italian male cases reported here, hypospadias was always present. MWS should be considered by endocrinologists in patients with hypospadias associated with developmental delays/mental retardation, in particular in the presence of a distinct facial phenotype.

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Abstract: Children with acute lymphoblastic leukemia (ALL) receive as part of induction therapy a 4-week course of high-dose glucocorticoid, which is either abruptly discontinued or shortly tapered. The aim of this study was to evaluate the signs and symptoms of steroid withdrawal syndrome and performance status (according to Lansky scale) during the 9-day tapering period and 1 week after withdrawal of the steroid in 63 children randomly allocated to receive prednisone or dexamethasone as part of induction treatment according the AIEOP ALL 2000 protocol. Twenty of 28 (75%) patients on dexamethasone versus 18 of 35 (51.4%) on prednisone (P < 0.05) developed at least one steroid withdrawal symptom during the study period. Three or more symptoms were observed in 39.3% (11/28) of the dexamethasone group and 8.6% (3/35) of the prednisone group (P < 0.05). Dexamethasone patients developed clinical signs earlier (within 3 days from the steroid tapering) than symptomatic prednisone patients. In the prednisone group, the symptoms were less severe and the performance status was higher (P < 0.05). Steroid withdrawal morbidity in ALL children during induction is a frequent and clinically relevant complaint. A more gradual (for dexamethasone) or a more prolonged (for prednisone) tapering might be suggested.

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Abstract: OBJECTIVE: Identification of a rapid and noninvasive test for the follow-up of aplastic anemia (AA) patients during immunosuppressive therapy (IST) to evaluate its functional effect on hematopoietic progenitors (HPC) and for early detection of progression to myelodysplasia or relapse. MATERIALS AND METHODS: Absolute count and apoptotic rate (AR) of peripheral blood (PB) CD34+ cells were evaluated by three-color flow cytometry for CD45, CD34, and annexin V in cord blood (CB), normal children, and adults, as well as in pediatric patients with AA at diagnosis and during IST, Fanconi anemia (FA), chronic immune cytopenia, and refractory anemia with excess blasts (RAEB). RESULTS: In normal subjects, the AR of PB CD34+ cells showed a progressive increase (p < 0.05), while their counts decreased (p < 0.05) from birth to adulthood. In very severe AA (vSAA) and severe AA (SAA) at diagnosis, the AR was 91.6% +/- 2.8%, higher than controls (p < 0.05), and PB CD34+ cell count was 2.6 +/- 2.4/microL. In FA patients, the PB CD34+ AR was again significantly increased (54.2% +/- 13.7%) with an absolute count of 3.7 +/- 1.2/microL. Conversely, in RAEB the AR was 11.7% +/- 3.5% and the absolute count 85.1 +/- 48.2/microL (p < 0.05). Chronic immune cytopenias did not significantly differ from controls. CONCLUSIONS: Flow cytometry evaluation of PB CD34+ AR and counts is a noninvasive and feasible first-step method for the differentiation of AA and myelodysplasia (MDS), and it might be useful for monitoring AA during IST to secure the early detection of relapse or transformation to MDS.

Abstract: OBJECTIVES: To record the prevalence of the sleeping position of sucklings living in the ASL 11-Regione Piemonte; to make an information campaign about the utility of sleeping in the supine position (most important protection factor against the SIDS); to find out its efficacy for a short or long time. METHODS: During the first two months of 2002 all the parents coming to the consulting rooms for the compulsory vaccinations of their 3 and 5 months old babies have been interviewed about the position of their babies during sleep. The same recording has been made in the first two months of 2003 and 2004. During 2002 various consciousness campaigns have been made, above all for medical operators of hospital nurseries and of Mother-and-Child Departments and Prevention Departments in ASL 11 area. RESULTS: Before the consciousness campaign the percentage of 3 months old sucklings sleeping in the supine position was 62,3% and 55% for the 5 months old suckings; after the campaign the percentage has grown to 77,4% for 3 months old sucklings and 74,5% for 5 months old sucklings during 2003 and during 2004 the percentage has grown to 80,3% and 74,2%, respectively. CONCLUSIONS: A simple and not expensive but capillary consciousness and information campaign addressed to medical operators has obtained valid and statistically relevant results in a short time.

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Abstract: BACKGROUND: Care procedures for preventing neonatal diseases are carried out according to nurseries' traditions and may be not consistent with the evidence based medicine issues. METHODS: A multi-centric survey was conducted in 2 Regions located in NW Italy (Piedmont and Aosta Valley) in order to collect information on some healthy newborn care procedures. During 2001, a questionnaire was sent to the chief pediatrician in charge to the all 33 nurseries of the region asking the methods used during 2000 as prevention of ophthalmia neonatorum, early and late hemorrhagic disease of newborn, umbilical cord care and recommendations of vitamin D administration. Thereafter, during 2004 the same questionnaire was sent to the 34 chief pediatrician of nurseries to evaluate if the procedures were changed during 2003 according to guidelines. The nurseries care for 32,516 newborns in 2000 and 37,414 in 2003. RESULTS: Aminoglycoside eyes drops as prevention of ophthalmia neonatorum were the first choice in both periods (23 out 33 nurseries in 2000 and 24 out 34 in 2003 p > 0.05; the corresponding figures for newborns were 18,984 out 32,516 newborns vs. 28,180 out of 37,414 p < 0.05). The umbilical cord care was carried out with alcohol in 12/33 centers (13,248 newborns) and dry gauze in 3/33 centers (2,130 newborns) in 2000, the corresponding figures in 2003 were 6/34 centers (p > 0.05), (6,380 newborns, p < 0.05) and 12/34 centers (p < 0.05), (18,123 newborns, p < 0.05). The percentage of newborns receiving of i.m. vitamin K. at birth increased during the study period (15,923/32,104 in 2000 vs. 19,684/37,414 in 2003, p < 0.01), but not the number of nurseries (16 in 2000 and 17 in 2003 p > 0.05). The numbers of parents of newborns who receive the recommendations of oral vitamin K during the first months life decreased from 2000 (25,516/30,606) to 2003 (29,808/37,414, p < 0.01) as well as for Vitamin D recommendation (14,582/30,616 in 2000 vs. 11,051/37,414 in 2003, p < 0.01). Oral vitamin K during the first months of life was recommended by 25 nurseries in 2000 and 27 in 2003 (p > 0.05), the corresponding figures for Vitamin D were 15 and 14 (p > 0.05). CONCLUSION: In the present study a large variability of procedures among the nurseries was observed. During the study periods, guidelines and evidence based medicine issues have only partially modified the neonatal care procedures In Piedmont and Aosta Valley nurseries. These observations suggest to implement local forum/consensus conference to standardized procedures as much as possible.

Abstract: BACKGROUND AND OBJECTIVES: Several studies have been published on trends in childhood cancer incidence, with different patterns being reported. We present an analysis of cancer incidence trends in Piedmont (Italy) in 1967-2001 for the major categories of childhood malignant neoplasms. DESIGN AND METHODS: The population-based Childhood Cancer Registry of Piedmont has recorded incident cases of malignant neoplasm in children (age 0-14) since 1967. Procedures for data collection and coding have been uniform throughout the study period. We calculated incidence rates per million children per year by sex and age-group. Trends were estimated using Poisson regression analysis, adjusted for age and sex and presented as the annual percent change (APC). RESULTS: Significant increases were observed for all malignant neoplasms combined (3360 cases, APC:1.3%, 95% CI:1.0% to 1.6%), leukemia (APC: 1.0%, 95% CI: 0.4% to 1.6%), central nervous system (CNS) tumors (APC of 2.3%, 95% CI: 1.6% to 3.1%) and neuroblastoma (APC: 2.3%, 95% CI: 1.0% to 3.5%). Acute lymphoblastic leukemia (APC 1.2%, 95% CI: 0.2% to 2.3%), and Acute non-lymphoblastic leukemia (APC 1.7%, 95% CI-0.6%, 4.1) both increased over time. Differences by age groups were observed for some tumor types, such as for neuroblastoma in infants (4.8% increase per year), leukemia in children aged 1-4 years (1.2%) and CNS tumors in children aged 10-14 (3.4%). INTERPRETATION AND CONCLUSIONS: Our data suggest an increasing incidence of childhood cancer in general, and specifically for leukemia, CNS tumors and neuroblastoma in Piedmont in 1967-2001. The observed trends are unlikely to be explained by random variation, changes in exhaustiveness or quality of data collection and registration.

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Abstract: The population-based Childhood Cancer Registry of Piedmont (CCRP) has collected data on incidence since 1967. The occurrence of early death (i.e. within 30 days of diagnosis) was investigated in 3006 cases of childhood cancer diagnosed during the period 1967-1998. The proportion of early deaths (178 of the 3006 cases) was analysed by period of diagnosis (three decennial periods), age group, major diagnostic group and hospital category, with univariate statistics and logistic regression. The proportion of children with cancer who died within 1 month of diagnosis was 10.8%, 5.3% and 1.8% for cases diagnosed during 1967-1978, 1979-1988 and 1989-1998, respectively. This trend may reflect earlier diagnosis, improved diagnosis, more effective therapy or more frequent referral to specialised centres. The risk factors for early death were: age <1 year and diffuse disease at diagnosis, diagnosis during 1967-1978, a diagnosis of acute non lymphocytic leukaemia, non-Hodgkin lymphoma, central nervous system tumour or hepatic tumour. Early death was not related to the sex of the child. Care in an extra-regional specialised centre was associated with lower risk of early death. CONCLUSION: No temporal changes in early mortality were found among children with acute non lymphocytic leukaemia diagnosed in the first, second or third decade of activity of the CCRP, the percentages of children dying within 1 month being 12.8%, 10.7% and 12.8%, respectively. This pattern clearly differed from the corresponding trend for acute lymphoid leukaemia (6.4%, 2.0%, 0.4%).

Abstract: Time changes in mortality rates can be used to suggest future trends in the prognosis of childhood cancer. Estimates provided from recent studies led to divergent previsions of future trends. In this study we used data from the population-based Childhood Cancer Registry of Piedmont (CCRP) in order to measure the decrease in mortality. The study included 1,060 deaths in the period 1971-1998. Analyses were carried out using Poisson regression models and considered separately the total tumours, acute lymphoblastic leukaemia (ALL) and tumours of the central nervous system (CNS). We observed a progressive decline in the mortality rates: for all tumours the estimated annual percentage change was -3.6% (P < 0.05), for ALL it was -5.2%, (P < 0.05) and for CNS tumours it was -3.8% (P < 0.05). The statistical test for effect modification due to age at death was not significant. For all cancer types, the Poisson model fits the data well, corresponding to an exponential decrease of mortality rates and leading to the conclusion that current therapies, despite their proven effectiveness, are not sufficient to cure all cases of childhood cancer.

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Abstract: Usually survival studies evaluate the percentage of subjects alive or disease-free at a given point in time (cumulative survival percentage). These studies require a lengthy period both for follow up and for the collection of an exhaustive number of cases. In addition, for cancer types with a sharp gradient of cumulative mortality, the estimate may be unstable. On the database of children with Acute Lymphoblastic Leukaemia (ALL) collected by the Childhood Cancer Registry of Piedmont (CCRP) in 1979-1991, we have estimated an alternative time-dimensional index to estimate both patients' life expectancy of patient and number of years gained to death. These estimates have been compared in subsets of the database corresponding to different periods of diagnosis and efficacy of treatment. Life expectancy has been evaluated as the area under the survival curve, on the assumption that after a number of years since diagnosis, survivors have the same mortality rates of the general population. Clinicians are invited to take into consideration the approach described in the present note.

Abstract: This study evaluated the outcome after childhood acute lymphoblastic leukaemia (ALL) in a population aged 0-14 years served by the Childhood Cancer Registry of Piedmont (CCRP) during the accrual periods to nationwide clinical studies run by the Italian Association for Paediatric Haematology and Oncology (AIEOP). In the time period considered (March 1979-December 1998) the CCRP recorded 498 incident cases of ALL. The living status on 31 December 2000 was known for 497 cases. Overall survival at 5 years was 74.1% standard error (S.E.) 2.0%). It increased from 58.6% (S.E. 4.9%) for cases diagnosed in March 1979-July 1982 to 87.3 (S.E. 3.6) in May 1995-December 1998. Results observed from data in our population-based study in Piedmont were similar to those presented in the nationwide clinical trials. Survival was better (statistically significant) for children aged 1-4 years, with a white blood cell (WBC) count lower than 10 000 x 10(3) cells/litre and for B-precursor ALL. Differences by immunophenotype were statistically significant only in the univariate analyses. Girls showed a non-statistically significant survival advantage over boys. Results of the present study show the impact on the population of recent clinical trials and emphasise the role of population-based cancer registries in evaluating childhood cancer care delivery in a given population.

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Abstract: A group of 1.085 students (582 M, 503 F) attending high school (742) and nursing school (343) filled in an anonymous questionnaire on their sexual habits and their knowledge of contraception and sexually transmitted diseases. Overall, 57% of the study population had already a complete sexual intercourse at a mean age of 16,4 (SD +/- 1,8). 74% had 1-3 sexual partners, whereas 28% had more than 3. All students affirmed that it was possible to prevent sexually transmitted diseases and 92,6% indicated correct methods. However 10% of students did not know that AIDS is transmitted sexually as 47% hepatitis B. The responses made by nursing students were more correct that those of high school students.

Abstract: BACKGROUND AND OBJECTIVES: Survival after childhood cancer has shown a steady improvement from the late 1970s in most developed countries. Since 1967 the Childhood Cancer Registry of Piedmont has been collecting cases of malignant tumor, diagnosed in children aged 0-14 years, living in Piedmont. This work aims to update survival rates to 31.12.2000. DESIGN AND METHODS: This study includes 2,678 children diagnosed between 1970-98. Vital status was assessed at the Registry Office of the town of residence. One thousand four-hundred ninety cases were reported to be alive, 1170 dead and for 18 the status was unknown. Thirty-three cases registered with a death certificate only were excluded. Completeness of follow-up was 99.3%. All tumor types were classified according to the Birch-Marsden classification. Histologic verification was available for 94.4% of cases. RESULTS: Survival at 5 years increased over the period 1970-98 for all tumor types with a statistically significant trend over time (p<0.0001). The 5 year survival rate for acute lymphoblastic leukemia (ALL) increased steadily from 24.7% (95%CI 15.0-34.3) to 87.6% (80.9-94.3), for acute non-lymphoblastic leukemia (ANLL) from 0.0% to 38.1% (17.3-58.9), and for non-Hodgkin's lymphomas from 25.2% (0.6-49.8) to 79.7% (61.9-97.5). Five year survival rates of children with central nervous system tumors increased from 33.4% in 1970-74 to 78.5% in 1990-94 and decreased in 1995-98 to 70.9%. Age <1 year and >50,000x10(6) cells/L at diagnosis were negative prognostic factors for ALL. Age <1 year was a favorable prognostic factor for neuroblastoma. INTERPRETATION AND CONCLUSIONS: Survival of children with all types of tumors improved in Piedmont. This improved survival is comparable to that reported by other European and North American population-based cancer registries.

Abstract: Although some childhood cancer registries reported increasing incidence, the evidence and magnitude of time trends in the incidence of childhood leukemia are debated and the scientific evidence is conflicting. Only limited data have so far been supplied from Southern European countries. We present an analysis of the incidence trend of childhood leukemia in Piedmont (NW Italy) in 1975-98, based on data from the population-based childhood cancer registry. The Childhood Cancer Registry of Piedmont has been recording cases of childhood neoplasms since 1967. Procedures have been uniform and are based on an active search for cases and relevant information. Only cases with confirmed residence in Piedmont at diagnosis are included. Eight hundred cases of leukemia (622 acute lymphoblastic [ALL], 133 acute nonlymphoblastic [AnLL], 45 other and unspecified) were recorded in the period 1975-98 considered in our study. Incidence trends were analyzed using piecewise regression and Poisson regression, based on annual incidence rates. As results from the 2 analyses were similar, only the former were reported. In the age group 1-4 years, a statistically significant annual 2.6% increase in incidence rate of ALL (adjusted by age and gender; 95% confidence interval [CI] 1.13-4.13) was estimated. There was no evidence of increase in other age groups. During 1980-98, a statistically significant 4.4% annual increase (95% CI 1.86-6.90) was seen for pre-B-All in the age group 1-4 years. An increase was also seen for T-ALL that was not statistically significant. Sensitivity analyses were conducted, with no relevant differences from the main results. Our data suggest an increasing trend in ALL incidence for children between the ages of 1 and 4 years. These results are unlikely to be explained by changes in quality of data or exhaustiveness in reporting in the study period. The results were not changed in the sensitivity analyses we conducted. Possible causes to be investigated include environmental factors, changes in family size and parental age, socioeconomic conditions and geographical distribution of cases.

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Abstract: The aim of this study was to provide a comparative description of geographical variations and time trends in the population-based survival of European children with acute lymphoblastic leukaemia (ALL). Data on 13344 newly diagnosed children (0--14 years) with ALL were included in the EUROCARE study and were collected were collected by 34 population-based cancer registries (four comprising only childhood malignancies), operating in 17 countries (four in Scandinavia, two in Southern Europe, three in Eastern Europe, six in Continental Europe and two in the UK). Age-specific crude survival rates were estimated for boys and girls according to country for the period 1985--1989 and in adjusted form to attain comparability. Overall pooled and weighted rates were estimated as European standards. Children dead at diagnosis or diagnosed only through a death certificate were excluded. Geographical variation was also estimated by calculating the relative death rate with respect to the pooled overall European rate. After adjustment for age, gender and country, a Cox regression analysis was used to estimate time trends in survival. Survival was compared with that in the USA, Japan, Canada and Australia. During 1985--1989, the 1-year survival rate varied from 99 to 79%, the 5-year survival rate from over 80 to 56% (with the exception of Estonia; 34%; 95% confidence interval (CI) 20--52) among the various countries; the European weighted means were 90 (95% CI 87--93) and 72% (95% CI 69--75), respectively. Survival was particularly favourable in (south) Sweden, Finland, Germany and The Netherlands and rather unfavourable in Estonia and (surprisingly) France, where only 4% of its population was covered by the participating registries. Compared with the period 1978--1981, the hazard ratio for the period 1986--1989 decreased to 0.59 (95% CI 0.54--0.64) and -- in a smaller set of registries -- to 0.49 (0.45--0.55) for 1990-1992, an annual decrease in this rate of approximately 3.5%. During 1985--1989, the 5-year survival rates for European children were largely similar to those found in the USA, Canada and Australia, but markedly better than those in Japan. Higher survival rates were found for countries with 'good' access to centrally organised diagnostic and treatment facilities which stimulated 'aggressive' treatments according to a protocol. However, a subdivision according to risk profiles, e.g. according to the initial white blood cell count at diagnosis, could not be made and this might have explained partially the geographical differences in survival, because a positive association appeared between incidence at age 1--4 years and 5-year survival in most countries.

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Abstract: This paper describes the database of children with cancer in the EUROCARE study and the methodology used to analyse and report survival. This is the first systematic evaluation of survival after childhood cancer on a large scale in Europe: approximately 45,000 cases were included, diagnosed between 1978 and 1992 (34,814 cases diagnosed in 1978--1989 and an additional set of 9495 cases diagnosed in 1990--1992) and followed-up until 1995. Data were provided from 34 population-based registries (four specialised for childhood cancer registrations and one specialised registry for childhood leukaemia) in 17 countries of Europe (where there was national coverage in 10 countries). Quality of the data was fairly good, given the general differences among the countries and their health systems, thereby allowing for comparisons between them. Among cases diagnosed in 1978--1989, overall 2.0% were lost to follow-up, 91.8% were microscopically diagnosed and 93.4% of alive cases had at least 5 years of observation. Survival proportions (observed survival) were calculated for each of the countries involved, by age group (0, 1--4, 5--9, 10--14 years), gender, different time periods and selected diagnostic groups. Age-standardised cumulative survival rates and European averages (weighted and pooled) were also computed. Cox regression models were used to evaluate geographical and temporal differences. The EUROCARE database represents a unique source of information on survival of childhood cancer patients in Europe, intercountry differences and time trends in survival.

Abstract: BACKGROUND: The Childhood Cancer Registry of Piedmont (CCRP) started its activity in 1967. It is population based and covers the Piedmont Region (population 4,500,000; NW Italy). This article reports on time trends in survival after a childhood cancer diagnosed during 1970-1994. PROCEDURE: During 1970-1994, 2,329 incident cases were registered at CCRP on the basis of histological and/or clinical information, excluding 30 cases reported only by death certificate. Histological or hematological diagnosis was available for 2,067 cases. Vital status was assessed through the offices of the town of residence. At the end of follow-up, 1,202 cases were alive, 1,084 dead and 43 were not traceable. Survival was measured for the major diagnostic groups using both univariate and multivariate statistics. RESULTS: The 5-yr survival rate for acute lymphoblastic leukemia (ALL) improved regularly from 24.7% in 1970-1974 to 81.1% in 1990-1994, for acute nonlymphoblastic leukemia (ANLL) from 0% to 38.1%, for non-Hodgkin lymphoma (NHL) from 25.2% to 67.7%, for tumors of the central nervous system (CNS) (all types) from 33.4% to 75.9% and for Ewing tumor from 0% to 90%. Focusing on survival by period of diagnosis, the highest 5-year survival rate was observed for children diagnosed during 1985-1989 for medulloblastoma, neuroblastoma (NB), retinoblastoma, Wilms tumor, osteosarcoma, and rhabdomyosarcoma and for children diagnosed in 1990-1994 for the remaining sites. The trend over time was statistically significant for ALL, ANLL, NHL, CNS tumors, NB, and osteosarcoma as well as for all malignancies together. CONCLUSIONS: Population-based survival studies are useful complements to clinical studies. Survival results in the present study are similar to those presented for other European countries and the United States. For most types of neoplasm (except CNS) survival probability appears to stabilize 5-10 years after diagnosis.

Abstract: The majority of deletions of the short arm of chromosome 5 are associated with cri du chat syndrome (CdCS) and patients show phenotypic and cytogenetic variability. To perform a genotype-phenotype correlation, 80 patients from the Italian CdCS Register were analysed. Molecular cytogenetic analysis showed that 62 patients (77.50%) had a 5p terminal deletion characterised by breakpoint intervals ranging from p13 (D5S763) to p15.2 (D5S18). Seven patients (8.75%) had a 5p interstitial deletion, four (5%) a de novo translocation, and three (3.75%) a familial translocation. Of the remaining four patients, three (3.75%) had de novo 5p anomalies involving two rearranged cell lines and one (1.25%) had a 5p deletion originating from a paternal inversion. The origin of the deleted chromosome 5 was paternal in 55 out of 61 patients (90.2%). Genotype-phenotype correlation in 62 patients with terminal deletions highlighted a progressive severity of clinical manifestation and psychomotor retardation related to the size of the deletion. The analysis of seven patients with interstitial deletions and one with a small terminal deletion confirmed the existence of two critical regions, one for dysmorphism and mental retardation in p15.2 and the other for the cat cry in p15.3. Results from one patient permitted the cat cry region to be distally narrowed from D5S13 to D5S731. Furthermore, this study lends support to the hypothesis of a separate region in p15.3 for the speech delay.

Abstract: In most developed countries, malignant lymphomas account for 10--15% of all cancers occurring among children aged 0--14 years. The present study estimates survival after a diagnosis of lymphoma in childhood, based on the EUROCARE II database which includes 34 population-based cancer registries from 17 European countries. The survival pattern of children with malignant lymphoma diagnosed in 1985--1989 is reported, as well as the time trends since 1978. The analyses focus on Hodgkin's disease (HD, 1696 cases) and on non-Hodgkin's lymphoma (NHL, 2255 cases including Burkitt's lymphoma and unspecified lymphomas). For HD, the European weighted average 5-year survival rate was 93% (95% confidence interval (CI) 82--98) in 1985--1989. The survival rates were not affected by either age or gender. 5-year survival rates ranged from 68% (95% CI 34--90) in Estonia to 96% (95% CI 92--98) in Germany and 100% (95% CI 57--100) in Slovenia. Multivariate analyses for the time period 1978--1989 gave little suggestion of an improvement in survival over the later time periods of diagnosis. For NHL, the European weighted average 5-year survival rate was 74% (95% CI 67--80) in 1985--1989. Gender did not influence the survival rate. Children in the age group 0--4 years had a poorer prognosis compared with older cases (5-year rate: 66% versus 77% in the pool). 5-year survival rates ranged from 53% (95% CI 30--76) (Estonia) to 83% (95% CI 62--94) in France and 83% (95% CI 66--92) in Scotland. Multivariate analysis show a decreasing HR for the more recent periods of diagnosis from 1 in 1978--1981 to 0.67 (95% CI 0.56--0.79) in 1982--1985 to 0.48 (95% CI 0.40--0.57) in 1986--1989. Exploratory analysis, conducted including the cancer registries which provided cases diagnosed until 1992, show a positive trend over time for both types of lymphoma.

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Abstract: This article shows the survival trends of childhood cancers diagnosed from 1978 to 1994 in Italy. A first analysis presents a survival increase for all the diagnostic categories and in both sexes, with the exception of Hodgkin's disease, for which five-year survival is stable at 97%. The results of this analysis show that five-year survival changes from 54% to 72% for all cancers, from 56% to 70% for non Hodgkin's lymphomas, from 53% to 64% for central nervous system tumours, from 59% to 78% for acute lymphatic leukaemia, from 18% to 42% for acute non lymphatic leukaemia, from 30% to 62% for neuroblastoma and from 33% to 71% for malignant bone tumours. Concerning international comparisons, the overall Italian rates and their increases are very similar to the USA ones. Instead, if we consider a comparison between survival trends in Italy and survival trends observed in some European countries, like Great Britain, Slovakia and Denmark, it is evident that in Italy there is a faster improvement of prognosis for almost all diagnostic categories.

Abstract: AIMS AND BACKGROUND: The study describes the health status and the attainment of life goals in the adult survivors of childhood cancer recorded at the Childhood Cancer Registry of Piedmont. METHODS AND STUDY DESIGN: A postal questionnaire was sent to the general practitioner of the 690 cases born before 1976 and alive in 1991 after at least 5 years from diagnosis.The answer was received for 485 (72.9%) included in the analyses. Items in the questionnaire were: sequelae related to cancer and its treatment, health-related quality of life (according to Bloom's criteria), educational level attained, and employment status. RESULTS: Vital and marital status were obtained for all 690 cases at the offices of the town of residence. No medical condition was reported for 309 cases (63.7%). The overall proportion with a high school or university education was compared to corresponding figures for Piedmont in 1991, adjusted by age, and was as high as in the general population. Similar results are observed for occupation. Patients of both genders were married less than expected. Patients with leukemia (112 cases), non-Hodgkin's lymphoma (34) or Hodgkin's lymphoma (52) were reported to have the highest quality of life. In contrast, patients with tumors of the central nervous system (151) had the highest frequency of sequelae and the lowest score for health-related quality of life. They-also presented the lowest educational achievement, the lowest proportion of employment and, among males, the lowest frequency of marriage. CONCLUSIONS: Our study shows a good social adjustment of adult survivors from childhood cancer, with the exception of central nervous system tumors. From the methodologic point of view, the present study shows the feasibility of surveillance surveys on health-related quality of life with the contribution of general practitioners.

Abstract: EUROCARE is a population-based survival study including data from European Cancer Registries. The present paper analyses survival after a malignant neoplasm of the central nervous system (CNS) in childhood (aged 0--14 years at diagnosis). The database includes 6130 cases from 34 population-based registries in 17 countries: 1558 were primitive neuroectodermal tumours (PNET) and 4087 astrocytoma, ependymoma or other gliomas: these morphologies were grouped in the analyses in order to reduce the diagnostic variability among the registries. 87% of cases were microscopically diagnosed (range among registries 71--100%) and losses to follow-up were limited to 2% (range 0--14%). Actuarial analyses indicate that the European (weighted) average of 5 years cumulative survival for cases diagnosed in 1978--1989 was 53% (95% confidence interval (CI) 49--57) for CNS neoplasms, 44% (95% CI 37--50) for PNET and 60% (95% CI 55--65) for the glioma-related types. Analysis of the sub-set of cases diagnosed in 1985--1989 revealed better results: cumulative survival at 5 years was 61% (95% CI: 55--65) for all CNS neoplasms; 48% (95% CI 41--56) for PNET and 68% (95% CI 62--73) for glioma-related types. Compared with older children, infants showed poorer prognosis: in 1978--1989 the 5-year survival rate was 33% (95% CI 23--45) and in 1985--1989 it was 46% (95% CI 34--59). Variability among countries was very large, with 5-year survival for CNS tumours diagnosed in 1985--1989 ranging from 28% in Estonia (95% CI 17--43) to 73% Sweden (95% CI 59--83) and 75% in Iceland (95% CI 35--95) and 73% in Finland (95% CI 66--79). Time trends were studied in a multivariate analysis observing a reduction in the risk of death in periods of diagnosis 1982--1985 (hazard ratio (HR)=0.85; 95% CI 0.78--0.93) and 1986--1989 (HR=0.70; 95% CI 0.64--0.77) compared with 1978--1981. The analysis were extended to 1990--1992 for the countries whose registries provided data for that period did not indicate any further progress. Results of this study confirm the large variability in European countries and indicate a positive trend in the survival probability for cases diagnosed in the 1980s.

Abstract: This study shows the childhood cancer survival rates of 1,315 cases incident in the 1990-1994 period in Italy. The observed survival shows an increase over the previous period in almost all diagnostic groups. In particular, 5-year survival attained 72% overall, 78% for acute lymphatic leukaemia, about 100% for Hodgkin's disease, 70% for non Hodgkin's lymphomas, 64% for central nervous system tumours, 87% for retinoblastoma, 80% for renal tumours, 67% for hepatic tumours, 71% for bone tumours, and 70% for soft tissue sarcomas. Finally, the findings are comparable to those in other countries (USA, Great Britain, Australia, Slovakia) and they show a progressive improvement in survival.

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Abstract: BACKGROUND: To evaluate the effect of different oral glucose or sucrose solutions on the pain response to heelstick in newborns. METHODS: DESIGN: randomised double blind placebo controlled trial of water (control) versus one of three solutions of glucose - namely 5, 33 and 50% - or one of two solutions of sucrose (33% and 50%) or nothing. SETTING: postnatal ward. PATIENTS: seven groups of 20 healthy newborns (gestational age 38-41, weighing over 2500 g) were randomised to receive 2 ml of one of the six solutions on the tongue inmediately before heelstick procedure. Main outcome measure: heart rate before, during and three minutes after the procedure. RESULTS: Even if the trend of the cardiac rates did not reach statistic significance, glucose solution 33 and 50% proved to be the most effective in reducing pain response. CONCLUSIONS: Sweet solutions may be an easy, useful, safe and cheap analgesic for minor invasive procedures in newborns.

Abstract: BACKGROUND AND OBJECTIVE: Transplantation of hematopoietic stem cells from different sources is being increasingly used to treat a variety of diseases in children. Transplant procedures and indications have changed considerably during recent years. Monitoring of information about these changes is useful for interpretation of nationwide collected data. DESIGN AND METHODS: Since 1985, Centers belonging to the AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica), performing hematopoietic stem cell transplants (HSCT) in children, and members of the AIEOP-Bone Marrow Transplant (BMT) Group annually report data on their transplant activity to the AIEOP-BMT Registry employing specially prepared patient-oriented forms. RESULTS: From January 1985 to December 1998, a total of 2,474 bone marrow (BM), peripheral blood (PB) or umbilical cord blood (CB) transplants were reported: 1,296 (52%) were allogeneic (Allo) and 1,178 (48%) autologous (Auto) transplants. These transplants were performed in 19 Italian Centers on 2,249 patients aged less than 17 years. Among Allo-transplants, 1,198 (92%) were performed using BM progenitor cells, whereas 49 (4%) CB, 42 (3%) were PB, 4 BM plus PB, and 3 BM plus CB allografts; they were performed using HLA-identical sibling donors in 867 cases (67%) and alternative donors (i.e. partially-matched relatives or unrelated donors) in the remaining 429 (33%) cases. Allogeneic transplants were performed on 786 (67%) patients with malignancy and on 395 (33%) patients with non-malignant disorders. In the last 6 years, the number of Allo-transplants per year exceeded that of Auto-transplants. Of the Auto-transplants, 775 (66%) were performed using BM, and 403 (34%) using PB alone or combined with BM hematopoietic stem cells. Indications for Auto-BMT were myelo-lymphoproliferative disorders in 524 (49%) cases, solid tumor in 533 (50%) cases and non-malignant disease in 11 (1%) cases. In the last 5 years, the use of PB for autografts has increased from 7% to 70%. INTERPRETATION AND CONCLUSIONS: These data reflect the development and present status of HSCT in Italy and provide a basis for patient counseling and health care planning.

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Abstract: Low birth weight and slow growth are frequently observed in the patients with cri-du-chat syndrome. To provide a growth reference standard for children with cri-du-chat syndrome, syndrome-specific growth charts have been developed from a combination of cross-sectional and longitudinal measurements on 374 patients from North America, Italy, Australia, and the British Isles. The data were obtained from pediatric records, parent reporting, and personal examinations at national 5p- parent support group meetings in the U.S., Italy, U.K., and Australia. The growth curves include height and weight measurements for patients ages 0 to 18 years and head circumference measurements for patients ages 0 to 15 years. Birth weight was above the 5th percentile of general population in 50% of cases: mean weight 2.8 kg +/- 1.85 SD for males and 2.6 kg +/- 1.51 SD for females. Growth curve medians were usually at or below the 5th centile of reference populations throughout life. The median head circumference falls below the 2nd centile, and this change increases with age. The charts show that compared with the standard population, most children with cri-du-chat syndrome are small at birth and as they grow most, but not all, have significant microcephaly and compromised weight for age, and to a lesser extent, compromised height for age. Am. J. Med. Genet. 94:153-162, 2000.

Abstract: Since 1967, the Childhood Cancer Registry of Piedmont measures cancer incidence and lethality among children aged 0-14 residents in the Region. Two thousand seven hundred twenty cases were recorded in the period 1967-94. Males were 55.4%. The highest frequency was observed in the age class 0-4 including 41.3% of cases. The most frequent malignancies were: Acute Lymphocytic Leukemias, CNS Tumours and Lymphomas. Incidence rates showed limited variation, both for total neoplasm and for the largest diagnostic categories. On the contrary, lethality decreased markedly: rate (per million children years) was 77.2 in 1967-69 and 59.4 in 1988-94. This trend as more evident for acute leukemias and CNS tumours. Better diagnostic techniques, anticancer and support therapies are the likely explanation for the improved prognosis. Prevalence increased, as a consequence of improved survival and curability: in the Province of Torino it increased from 62 cases per 100,000 children (age 0-14) in 1980 to 98 cases in 1994.

Abstract: AIMS AND BACKGROUND: A cohort study was conducted in order to measure cause-specific mortality among parents of children recorded in the Childhood Cancer Registry of Piedmont. It is the first study carried out on the subject in southern Europe. METHODS AND STUDY DESIGN: The study comprised the 740 children resident in Turin and in whom a cancer had been diagnosed in the period 1967-1991. Nominal data were obtained for 723 fathers and 733 mothers. At the end of the follow-up in 1995, 645 fathers were alive, 68 dead and 10 untraceable. Corresponding figures for mothers were 700, 28 and 5. Cause of death was known for 91 of 96 parents. RESULTS: The period of observation of parents started on the birth of the index child, however mortality analyses were restricted to the period after 1965 because of limited availability of local reference rates. Total mortality was lower than expected among fathers (66 observed deaths vs 88.2 expected, P <0.05) and mothers (28 vs 31.4). Fathers showed deficits (not statistically significant) of lung neoplasms (4 vs 9.9), cardiovascular diseases (18 vs 27.1) and hepatic cirrhosis (2 vs 6.6). No statistically significant variations in mortality were observed with time from diagnosis or according to life status of the children. No cancer deaths occurred among the mothers of sarcoma cases whereas 1.9 were expected. CONCLUSIONS: The data do not indicate any increase in mortality from cancer or other causes end, on the contrary, show a reduction in mortality which was more evident for the causes related to life style.

Abstract: In the framework of the ITACARE project, a cooperative investigation conducted on the data from the Italian population-based cancer registries, survival of patients with childhood malignant neoplasms was studied. The study included 1,768 cases diagnosed at age 0-14 plus 29 osteosarcoma cases diagnosed at age 15-19. Cases were collected over the period 1978-1989, or more limited periods for some participating registries. A total of 1,138 cases were from the Childhood Cancer Registry of Piedmont and 659 from the registries operating in the provinces of Varese, Parma, Modena, Forli and Ravenna, Florence, Latina, Ragusa and in the cities of Genova and Torino (the last contributed only for bone neoplasm diagnosed at age 15-19). Overall 5-year survival was 54% for malignancies diagnosed in 1978-1981, 60% for the period 1982-1985; and 69% for the period 1986-1989. The range among registries of 5-year survival for cases diagnosed in 1986-1989 was 55-78%. Most diagnostic categories presented an improved prognosis for the cases diagnosed more recently. For cases diagnosed in 1986-1989, 5-year survival was: 74% for acute lymphatic leukaemia, 40% for acute non-lymphatic leukaemia, 65% for central nervous system neoplasms (76% for astrocytoma, 75% for ependymoma and 85% for medulloblastoma), 66% for osteosarcoma, 55% for Ewing's sarcoma, 87% for Hodgkin's disease, 64% for non-Hodgkin's lymphoma, 74% for rhabdomyosarcoma, 64% for neuroblastoma, 78% for nephroblastoma and 100% for retinoblastoma. Italian survival was similar to that observed in other population-based surveys in the UK and USA.

Abstract: Defects of the middle line are an heterogeneous group of congenital malformations due to commune pathogenetic mechanisms. We have made a case-control study about 150 newborns, who have at least 1 defect of the middle line. Results prove an excess of males between the cases, due mostly to hypospadias. We haven't found families with defects of the middle line with x-linked manner of hereditary transmission. We haven't found any particular risk present in cases and not in controls. We haven't found any case with 2 or more middle line defects.

Abstract: We have studied the frequency of second primary malignancies (SPM) among the 2,328 children registered in 1967-1969 at the Childhood Cancer Registry of Piedmont, the largest population-based childhood cancer registry in Southern Europe. Since the population of Piedmont is not served by a conventional cancer registry covering all ages, SPMs were identified through a number of ad hoc surveys within a variety of sources. Eighteen SPM (all histologically diagnosed) were observed after a thorough survey conducted in the ontological departments in Piedmont and after a postal questionnaire addressed to general practitioners. Death certificates were also examined. The crude incidence rate was 116.5 per 100,000 person-years. Risk was higher among children whose first malignancy was diagnosed more recently (SIR = 9.8 for diagnoses in 1983-1989 vs. 4.5 for diagnoses in 1967-1974). The same tendency was confirmed in analyses restricted to children in whom leukemia was diagnosed as the first cancer. Clinical data regarding the treatment of the first malignancy were available for 16 children out of 18: 15 had received chemotherapy and 12 radiotherapy (9 SPM originated in the irradiation field). The interest of measuring the risk of SPM on a population basis (and not only in clinical series) and the advantage of close cooperation between epidemiologists and clinical oncologists are underlined.

Abstract: A survey was carried out within the framework of the Association of Hospital Pediatricians (APO) on the implementation of the pediatric structure in Pediatric hospitals wards in Piedmont during 1990. There was a 100% adhesion rate. It was found that only in 7 out of 36 hospitals were children always admitted to the Pediatric Division irrespective of symptoms. In all remaining cases, hospitalisation was based on the pathology and therefore children were spread between pediatric and adult wards with a percentage of over 30% (it was only possible to verify this figure in a small number of hospitals). Children with surgical symptoms were admitted to adult wards for the entire duration of their hospital stay in 17 hospitals. Only in 7 hospitals were children with surgical problems given pre- and postoperative treatment in pediatric wards. In 18 out of 36 hospitals children undergoing surgery were not even examined before the operation by a pediatrician. The implementation of the pediatric structure mainly depended on the behaviour of the PS DEA and therefore the fact that when a child entered hospital he immediately came into contact with the pediatrician. It was also found that average hospital stay in pediatric wards was 4.4 days (range 2.1-7.4); the mean index of bed occupation was 50% (range 27.5-83.4). A pediatric doctor was on duty round the clock only in 10 out of 36 centres. In the majority of hospitals the number of beds destined for day-hospital activities was not specified. It is also worth pointing out that the number of neonatal cradles is never specified by the Regional Health Plan and there is no legal recognition of neonates admitted to the Nursery and, as a result, the number of neonatal medical staff is not quantified. A greater incisiveness of the current statutory requirements for the implementation of the pediatric structure might improve the level of assistance for children admitted to hospital.

Abstract: AIMS AND BACKGROUND: The Childhood Cancer Registry of Piedmont (RTI) periodically updates the life status of each registered child. Given its size, the RTI is the major (albeit geographically limited) Italian source of population-based survival rates of cancer in children. The present report describes time trends in survival of children with acute lymphocytic leukemia (ALL). METHODS: During 1970-87, 429 residents in Piedmont aged 0-14 were diagnosed as having ALL: they have been followed up until 1991. RESULTS: Five-year survival rates increased from 21% to 72% for children diagnosed ALL respectively in 1970-72 and 1985-87. Major improvements occurred up to the mid-seventies and again between cases diagnosed in the early and late eighties. Improvement in survival was statistically significant for children belonging to classes comprised between 2 and 10 years of age at diagnosis. Period of diagnosis was unrelated to probability of survival among the 13 cases diagnosed ALL at age 0. Survival was unrelated to sex, even in the early seventies and even after consideration of children dying more than 5 years after diagnosis. Between 1976-81 and 1982-87, an improvement in survival was found in all categories of WBC count at diagnosis: the ratio between the two estimates was somewhat higher for children with more than 50,000 WBC/mm3 at diagnosis than for other children. CONCLUSIONS: Present data are compared with those resulting from other population-based series: this exercise can be useful for an overall evaluation of delivery of cancer therapy at the population basis.

Abstract: The outcome of 171 children with ALL who relapsed for the first time after elective cessation of therapy (1-86 mo) and followed over 10 years (median 60 mo; range 1-232 mo) has been evaluated. One hundred and three patients relapsed in the bone marrow (BM), 29 in the testis (T), 21 in the central nervous system (CNS), 14 in the BM plus another site and 4 in other sites. Second remission was achieved in 97% of patients (97% BM, 100% T, 90% CNS, respectively) with reinduction schedules including three or more drugs. All but 4 out of 100 patients who relapsed in the BM received cranial reprophylaxis with intrathecal CT alone or CT plus radiotherapy. Seven patients in second CR underwent allogeneic bone marrow transplantation from an HLA matched sibling. The overall survival was 34% and disease-free survival (DFS) probability at 100 years was 22%. A second relapse was observed in 73% of patients. Forty children are alive in second continuous remission and 24 are alive after a second or subsequent relapse. Patients with isolated T relapse showed a significant better outcome than those with BM or CNS involvement. Most patients (62%) with isolated BM relapse showed a further disease recurrence in BM, and DFS was shorter when relapse occurred within 12 months from off-therapy. Eighty-two patients in second CR stopped the treatment a second time and showed a survival and DFS probabilities, respectively, of 69% and 43%. Thus, children with ALL who relapse after cessation of therapy still have a high risk of further late relapses and should be treated with intensive chemotherapy and CNS reprophylaxis. BMT must be considered for all patients relapsing in the BM within 12 months from off-therapy.

Abstract: In recent years several cases of anemia (iron deficiency) have been reported in adults who participate in long-distance running although its etiology has not been entirely explained. We report the case of a 16-year-old girl who had participated in middle-distance running at a competitive level for about three years and who had been admitted to hospital because of a progressive weakness and a reduction in her sporting performance. Evaluation revealed that the patient had a balanced diet, normal menstrual cycles and slight abdominal pain. The objective examination were negative except for the presence of a pronounced pallor of the skin and the mucous membranes. The blood count revealed Hb 7.5 g%, Ht 26%, GV 63 mu 3, the reticulocyte count was 10%, serum iron 9 micrograms/dl, serum transferrin 450 micrograms/dl and serum ferritin 4 ng/ml. All tests for constitutional anemia proved negative. Stool Hemoccult tests proved negative (these tests were carried out some weeks after the patient had stopped running). Her symptoms resolved after the beginning of iron treatment and her blood test results returned to normal. This case has been reported to draw attention to the existence of this problem in adolescents who practice sport. The knowledge of the problem night lead to a preventive scanning of young athletes and the presence of clinical manifestations would reduce the need for invasive tests.

Abstract: Incident childhood cancers in the Province of Torino, Italy (population aged 0 to 14 years averaging 0.5 million) have been registered since 1967. Four population-based exhaustive surveys have been done to collect cases diagnosed during the periods 1967 to 1969, 1970 to 1975, 1976 to 1981, and 1982 to 1986. For each registered child, vital status on June 30, 1988 was assessed. This article reports incidence, mortality, and survival rates over a 20-year period. A statistically significant trend toward an increased incidence of soft tissue sarcomas was identified. Statistically insignificant trends included an increased incidence of brain tumors (probably reflecting improved diagnostic procedures) and a decreased incidence of thyroid tumors. Incidence rates of leukemias in the first year of life tended to decrease. As expected, survival rates of some childhood cancers dramatically improved throughout the 20-year period; this occurred in leukemias, brain tumors, soft tissue sarcomas, and renal tumors. Survival rates are compared with observations in comparable population-based series.

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Abstract: The clinical report is one of the most useful ways of cooperation between the hospital doctors and general practitioners. This paper is aimed at checking the accuracy of clinical reports in an Italian children's hospital. The authors examined 200 clinical reports after establishing some criteria to be fulfilled in order to write a good clinical report. Only 18 reports were considered good; the results were discussed with the physicians who had written the reports. At a second evaluation, the authors checked the efficacy of the proposed changes: 97 clinical reports were considered good.

Abstract: The goal of this study was to measure the incidence of insulin-dependent diabetes mellitus (IDDM) during 1984-1986 in residents of Turin, Italy, aged less than 30 yr. The primary data source was the list of all subjects diagnosed with IDDM who attended diabetes clinics in Turin. Other data sources were the general register of death certificates, the list of hospital discharges, and the computerized data base of insulin prescriptions. Eighty incident cases of IDDM were identified during the study in 1,130,284 person-yr for those less than 30 yr of age. Age-adjusted (world standard) incidence rates were 8.05, 8.10, and 6.96/100,000 in the age-groups 0-14, 0-19, and 0-29 yr, respectively. Estimated completeness of the primary data source compared with all other data sources was 91%, whereas the estimated completeness of ascertainment of the registry was 99%. Incidence rates of IDDM in northern Italy compare with those of European countries with low-medium incidence. A population-based register is being established for the province of Turin (951,445 inhabitants aged 0-29 yr) for the collection of incident cases since 1984.

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Abstract: We report the results of a hospital-based, case-control study on acute lymphocytic leukemia (ALL), acute non-lymphocytic leukemia (AnLL) and non-Hodgkin lymphoma (NHL) in childhood. The study was conducted from 1981 to 1984 in Turin (Italy). One hundred and forty-two children with ALL, 22 with AnLL and 19 with NHL were included, as well as 307 controls. Information on parental smoking habits, parental occupation, ionizing radiation and childhood diseases were collected using a standard questionnaire during a personal interview of the relative attending the child in the hospital. The odds ratios for antenatal diagnostic radiation were 1.1 (NS) for ALL and 2.4 (NS) for AnLL. No association was found with diseases in childhood. Paternal and maternal smoking habits were similar for ALL cases and controls. Both maternal and paternal smoking were associated with NHL: for paternal smoking, odds ratios were around 5, but without a correlation with number of cigarettes. Positive associations observed with maternal employment were: ALL with teacher and cleaner; AnLL and textile worker; NHL and baker. Corresponding association with paternal jobs were: ALL with clerks, farmers and employment in office equipment production; AnLL and workers in building, tire or textile industries; NHL and lorry drivers, workers in the building or in the wood and furniture industry.

Abstract: A hospital-based case-control study on soft tissue sarcomas (STS) was conducted in 1983-84 in Torino and in Padova (Italy). Cases (36 children with rhabdomyosarcoma (RMS) and 16 non RMS-STS) were compared to 326 controls. Histories of parental smoking habits and occupations, parental and children's exposure to ionizing radiation, children's diseases and some other variables were collected through interviews to the relatives attending the child in the hospital. A non statistically significant association was observed with both maternal age above 30 at child's birth (STS: OR = 1.5, C.I. = 0.8-2.9; RMS: OR = 1.9, C.I. = 0.9-4.0) and "in utero" exposure to diagnostic radiation (STS: OR = 1.9, C.I. = 0.5-6.5, based on 4 cases). No association was found with children's previous diseases. Paternal and maternal smoking habits were similar for RMS and STS cases and controls. Some positive associations with either maternal or paternal occupational histories were identified. They are difficult to interpret in view of the large number of comparisons and small absolute figures. They included maternal employment as medical doctor and nurse, farmer, textile worker and machine tool operator. An association was also observed with paternal occupation as butcher, building worker or employment in the production of domestic appliances. One case and no controls reported a maternal aunt affected by breast cancer.

Abstract: The aim of this study was to evaluate the antitumor effect and toxicity of a single course of Peptichemio at high dose (450 mg/sq m) given to children with neuroblastoma resistant to first line treatment or at relapse. A total of 28 children were treated. Seven children showed partial response, 4 minor response, 8 had stable disease, and in 8 the tumor progressed. The principal toxic effect was myelosuppression. Hemorrhagic enteritis with liver failure and toxic death occurred in 1 patient. High dose Peptichemio can be administered with tolerable toxicity, inducing tumor regression in one third of previously treated patients.

Abstract: This descriptive epidemiology study of 1,040 children with Wilms' tumor (WT) registered in the International Society of Paediatric Oncology (SIOP) clinical trials confirms the findings reported by the National Wilms' Tumor Study. The male:female rate was 0.89:1. The mean age at diagnosis of the 43 bilateral cases was significantly younger than children with unilateral renal involvement (32.4 vs 45 months). However, the mean ages of diagnosis for unilateral multicentric and for unicentric WT were very similar. On the other hand, the mean age at diagnosis of children with sporadic aniridia and hypospadias was younger than the mean age of patients with or without other congenital malformations. Thus aniridia as well as hypospadias could be indices of the first mutation, according to the Knudson and Stron hypothesis. WT was reported in two members of each of five families. However, these familial cases were comparable in terms of demographic and clinical features to the nonfamilial ones. These data suggest that the heritable fraction of WT is relatively small and that genetic and environmental factors interact in the development of WT.

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Abstract: This report deals with a randomized prospective multicentric clinical trial in childhood rhabdomyosarcoma (RMS) conducted to evaluate the toxicity and the effectiveness of dactinomycin (ACT-D) administered as high, single doses v five-day, divided doses administered in combination with vincristine (VCR) and cyclophosphamide (CYC). Fifty-five group III evaluable patients (pts) less than 15 years of age with tumor size greater than 5 cm in diameter, without high-risk features of CNS involvement, and 15 group IV RMS pts were randomized to receive VAC as primary chemotherapy (CT): VCR, 1.5 mg/m2 intravenously (IV) days 1 and 8; CYC, 275 mg/m2 IV days 1 through 5; and ACT-D, 0.45 mg/m2 IV days 1 through 5 every 28 days for three cycles (33 pts), or VAC-M: CYC, 150 mg/m2 intramuscularly (IM) days 1 through 7; VCR, 2.0 mg/m2 IV day 8; and ACT-D, 1.7 mg/m2 IV day 8 every 21 days for four cycles (37 pts). Major responses (complete plus partial responses [PR]) were obtained in 67% of the VAC pts and in 70% of the VAC-M pts. Toxic effects were low, and no increased toxicity was observed in pts treated with high, single-dose ACT-D. These results confirm the effectiveness and feasibility of single, high doses of ACT-D with the advantage of requiring less pt hospitalization.

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Abstract: Information was obtained on the living status or cause of death of 2223 close relatives of 195 children with soft-tissue sarcomas (STS) diagnosed under age 15. Three-hundred nine relatives had died, from all causes, before STS diagnosis in the index child. The expected figure estimated from age- and sex-specific mortality rates in Italy was 293.3. Cancer was reported as cause of death in 76 relatives (75.1 expected). Seven grandmothers, 2 aunts, 1 uncle and 0 mothers died from breast cancer vs. 4.6, 0.9, 0.0 and 0.2 expected. Three siblings died from cancer (0.2 expected, P less than 0.01), i.e. STS, ependymoma and non-Hodgkin lymphoma. These results confirm and expand previous observations that STS in children are associated with other cancers, particularly childhood and breast cancer, in members of the same family.

Abstract: A multicentre registry of children who had been successfully removed from therapy for some common childhood cancers (Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, nephroblastoma, acute lymphatic leukaemia and other leukaemias) was established in Italy in 1981. The present study describes mortality and occurrence of second primary malignancies (SPMs) among 1467 children who were alive when the registry was established. Follow-up ended on December 31, 1983 for mortality and 1 year later for the occurrence of SPMs. Sixty-seven deaths were recorded, 11 of which were due to causes other than progression of the original disease. Eleven incident SPMs were identified (i.e. 3 acute myeloid leukaemias, 3 thyroid carcinomas, 1 bilateral breast carcinoma, 1 liver malignant mesenchymoma, 1 astrocytoma, 1 chondrosarcoma and 1 osteosarcoma) corresponding to an incidence rate of 2.1/1000 patient-years at risk. Anecdotal reports were collected regarding 2 further SPMs (a thyroid carcinoma and a myeloid leukaemia) as well as several benign tumours, including 2 mammary fibroadenomas.

Abstract: Neural tumors, Wilms' tumor, rhabdomyosarcoma and several types of leukemia have been previously described in association with neurofibromatosis (NF). In a nation-wide collection of cases in Italy, 15 children (0-14 years of age) with NF and cancer or leukemia were identified; 13 of them had been diagnosed with cancer between 1976-83. The expected number of children with cancer and NF in 1976-83 was 4.48. The distribution of tumor types was different from that found in the general population, with a higher proportion of tumors of neural crest origin as well as soft tissue sarcomas. In 7/15 the family history was positive for NF; in 5/7 the individuals affected included the mother and/or a maternal relative.

Abstract: Sixty-five children with neuroblastoma without evidence of distant metastases underwent initial tumor resection. Seventeen with no evidence of lymph node involvement in whom tumor resection was complete (Group 1) received no further antitumor therapy. One child died postoperatively; disease recurred in the bone marrow of one child at 52 months, the child subsequently died. Fifteen were alive without disease, giving an 82% actuarial five year survival. Forty-eight children with minimal residual tumor and/or regional lymph node involvement (Group 2) received two 5-day courses of Peptichemio (1.2 mg/kg/d) and the 29 children in this group who were older than 1 year of age at diagnosis were randomized to receive either radiotherapy to the tumor bed in addition or no radiotherapy. In Group 2, ten of the 48 have relapsed: six of 17 with initial lymph node involvement, three of four with tumor rupture at operation, and one of eight with tumor extension to the intervertebral foramen. No relapses were seen in the 19 children with minimal residual tumor confined to the tumor bed. Only one of the 18 Group 2 children who were younger than 1 year of age at diagnosis relapsed. Of the 29 Group 2 children who were older than 1 year of age at diagnosis, five relapses occurred in the 14 who received radiotherapy and four relapses in the 15 who did not receive radiotherapy. All six children with disseminated relapse died. Actuarial 5-year survival in Group 2 is 87%, and actuarial relapse-free survival, 76%.

Abstract: This paper reports late effects and health status of 198 children who had cancer or leukemia diagnosed under 2 years of age and their therapies electively withdrawn. This series (92 neuroblastoma [NBL], 57 Wilms' tumor [WT], 46 acute lymphoblastic leukemia [ALL], and 3 non-Hodgkin's lymphoma) was followed for 1-12 years after discontinuation of therapy. Thirty-three children were diagnosed before 1973, 92 between 1973 and 1977, and 73 after 1977 in 16 Italian Pediatric Oncology Centers. As of December 1983, 176 children were reported to be alive and without evidence of primary cancer by physicians responsible for their care. One child died from a second primary tumor, two from late recurrences of the primary cancer, and three from other causes; eight were alive with evidence of primary cancer; and eight were lost to follow-up. Kyphoscoliosis was found in 22 children and other musculoskeletal anomalies in 8. Neurological sequelae were observed in 8 out 35 children with ALL treated with radiotherapy (RT) and intrathecal methotrexate. All but one were in continuous complete remission when they developed seizures (three cases), leukoencephalopathy (three cases), or intracerebral calcifications (two cases). One child had cardiomyopathy and subsequently died from cardiac failure: he had received doxorubicin (400 mg/m2) and mediastinal RT (13 Gy) for NBL. Growth impairments were observed in children with NBL and WT.

Abstract: The Italian Registry of Off-Therapy patients after childhood tumors now includes 760 subjects with acute lymphoblastic leukemia. These patients were all removed from treatment by December 31, 1981, and were followed in 35 different institutions. All the children have received multiple-drug treatment, combined, in 79.7% of the cases, with cranial irradiation. Thirty-nine (5%) experienced a relapse before treatment suspension. Total duration of antileukemic therapy ranges between 18 and 131 months (median, 38). At the last updating (December 31, 1981), 699 subjects were alive, 6 were lost to follow-up, and 55 had died. Life-table analysis shows that 90.8% were alive and 77% were alive in continuous complete remission at 36 months, whereas at 66 months, the cumulative proportions were 88% and 75.5%, respectively. One hundred thirty-six of 760 relapses after therapy suspension were reported: 83 in male patients and 53 in female patients (P less than 0.01). The longest interval between relapse and treatment suspension was 64 months. Six of 55 died in continuous complete remission 3 to 44 months after treatment suspension. Five births of apparently normal babies to female patients have been reported. A general outline of the project and the future program are given.

Abstract: This paper reviews a series of 70 consecutive children with rhabdomyosarcoma (RMS) diagnosed during 1971-1978 and treated in five Italian institutions. Thirteen were classified as group I, 12 as group II, 37 as group III, and 8 as group IV according to the Intergroup RMS Study staging system. Survival was influenced by tumor extension at diagnosis, primary site, and response to therapy. The 5-year-survival rate was 92% for group I patients, 67% for group II, 44% for group III, and 0% for group IV. Thirty-four children had all therapy stopped after 12-32 months of complete remission, 7 had late recurrences, and 3 died from disease. Musculoskeletal sequelae were diagnosed in 11 children, short stature in 3, corneal opacity in 2, and cardiac failure in 1.

Abstract: Hemostatic changes in 20 children with acute lymphoblastic leukemia (ALL) who were induced with L-asparaginase (L-asp), vincristine (VCR), and prednisone (PDN) (Group A) were prospectively evaluated. These data were compared with those of a previous group of ALL patients who received L-asp as a single agent during consolidation (Group B). In Group A patients, mean plasma antithrombin activity decreased in the first 2 weeks, though not significantly. Relative to pretreatment values, mean fibrinogen concentration diminished particularly by week 3 (p less than 0.001). Activated partial thromboplastin time (APTT) decreased in the last week as well as after cessation of therapy with L-asp (p less than 0.05). Mean platelet count increased significantly by week 3 (p less than 0.05). Thromboelastograms performed in seven patients confirmed the tendency for thrombosis evidenced by a decreased APTT. Patients in Group B (L-asp alone during consolidation) had decreased concentrations of fibrinogen, AT, and Factors IX and X after L-asp therapy. APTT was prolonged. Our data demonstrate that the tendency for thrombosis is the predominant manifestation of L-asp induced coagulopathy, when the drug is associated with VCR and PDN. Thus the risk/benefit ratio for the use of L-asp early in induction in children with low risk ALL needs to be further evaluated.

Abstract: It has been inquired into the possibility of the resumption of breast feeding in low birth weight babies, in the 101 survivors of the 128 infants weighing less than 2000 g at birth, who were born at St. Andrea Hospital in Vercelli between 1974-82. 86% of the mothers accepted to attempt breast feeding after the separation period for intensive care and the attempt the successful in 85% of the cases (73 infants). The resumption was successful with more than 90% of the infants weighting more than 1250 g at birth and 68.6% of these infants were exclusively breast-fed. 57% of those infants weighting less than 1250 g at birth resumed breast feeding. No infant developed an infectious disease nor necrotizing enterocolitis. Almost all of the mothers succeeded in maintaining breast feeding for a mean period of 5 months and all of them considered the experience extremely positive. The study demonstrated that it is possible to resume breast feeding in low birth weight babies with suitable encouragement and care on the part of the family, the doctors and the nurses.

Abstract: During 1967-1981, the population-based Childhood (ages 0-14 years) Cancer Registry of the Province of Torino has recorded 1057 resident children with incident cancer. The life status of each child has been ascertained as of December 31, 1983. Sex- and age-specific incidence rates have been stable throughout the period. Annual mortality rates (per million) from leukemias (all types) decreased from 34.0 in 1967-69 to 19.4 in 1979-81. Correspondingly, the survival percentage cumulative of leukemic children at 3 years after diagnosis increased from 16 for children diagnosed in 1967-69 to 57 for those diagnosed in 1979-81. For other cancer types, no increases or debatable decreases in mortality rates and increases in survival rates were recognized.

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Abstract: This study examines differences between cancer centers (CC) and noncancer centers (NCC) in terms of management procedures and outcomes for three pediatric solid tumors: Wilms' tumor (N = 147), rhabdomyosarcoma (N = 87), and medulloblastoma (N = 76). Data were derived for the period 1970-1979 from the population-based Greater Delaware Valley Pediatric Tumor Registry maintained at the Children's Cancer Research Center, which routinely collects data on all childhood neoplasms that occur in a 31-county region. Management measures reviewed included the degree to which important pretreatment evaluations were performed, types of therapy used, and extent of follow-up examinations conducted. Outcome variables were three-year disease-free survival and frequency of deaths related to complications of therapy. Differences in three-year disease-free survival between CC and NCC were noted for medulloblastoma (52% v 24%) and rhabdomyosarcoma (48% v 10%), but not for Wilms' tumor (79% v 68%). Among medulloblastoma patients, differences were detected in the frequency of pretreatment evaluations and in the therapy used. The principal management contrast found in rhabdomyosarcoma was that multiagent chemotherapy was used less often in NCC. Wilms' tumor patients were evaluated and treated similarly in the community versus the CC, except for some contrasts in the surgical approach and the frequency of follow-up for the detection of late complications.

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Abstract: Oral glucose tolerance tests were performed in 47 children with acute lymphoblastic leukemia (ALL), treated according to 2 consecutive protocols. Glucose and insulin values were assessed before and after L-asparaginase (L-asp). 30 children (group A) received L-asp as a single-agent consolidation course, after achieving remission with vincristine (VCR) and prednisone (PDN). Normal insulin and glucose levels were found in all patients before L-asp; 4 children (13%) had a transient impaired glucose tolerance (IGT) after completing L-asp therapy. 17 children (group B) were given L-asp during induction therapy with VCR and PDN, and all achieved complete remission. 5 patients (23%) had IGT, without hypoinsulinemia, before L-asp administration. IGT normalized in 4 patients after L-asp, the other children developed a diabetes mellitus. Only 1 patient, with a normal IGT test before L-asp therapy, showed a transient IGT after L-asp. In patients with ALL, the presence of IGT before treatment may be related to leukemia. The concomitant use of steroids does not influence the incidence of IGT in our series. Our data reveal normal insulinemia in patients with IGT. Thus, the leukemic process itself may play a much more significant role in inducing abnormalities in carbohydrate metabolism.

Abstract: Peptichemio (PTC), a multipeptidic complex of m-L-phenyl-alanine mustard, was administered to 39 children with neuroblastoma at relapse. The compound was given in two 5-day cycles at dosages varying from 1.0-1.5 mg/kg/day. We were able to evaluate 29 of the initial 39 children for PTC effect; 21 of them had received PTC as first therapy following diagnosis. Ten patients underwent other chemotherapy for relapse before PTC. Three patients were off therapy when relapse occurred. Subjective improvement was observed in 18 cases (62%). Eleven patients (38%) experienced an objective regression, which was scored as complete response in three cases, partial response in two, mixed response in six. In ten children no significant disease change was observed; the remaining eight had a progression of their disease while receiving PTC. The incidence of responses has been higher in patients off therapy at moment of relapse, and lower in those pretreated for their relapse. Previous administration of PTC did not reduce the chance of response at relapse. Major toxic effects were transient, mostly moderate myelodepression and phlebosclerosis. Allergic reactions, nausea, and vomiting, occurred in a few patients. These data indicate that PTC may exert objective antitumor activity in approximately one-third of neuroblastoma patients at relapse.

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Abstract: 40 children (23 males, 17 females) have been diagnosed have ANLL during the period from february 1970 to september 1981. According to FAB classification, 24 cases were M1,-M2, 9 M3, 3 M4, 3 M5 and 1 M6. At diagnosis, 20 patients (50%) had leukocytes less than 10.000/mmc, 6 (15%) had leukocytes greater than 50.000mmc. Hb levels was 7 g% in 16 patients (40%); 10 children had hepatosplenomegaly (25%), 7 splenomegaly (18%) and 5 lymphoadenomegaly (13%). 4 patients had cutaneous or mucous infiltrates. None had meningeal involvement at diagnosis. According to the year of diagnosis, 3 groups can be identified. In the group I (1970-73), 11 patients have been treated with not codified combination chemotherapy as ARA-C, 6-TG, DNR, CTX, Metil-GAG. In the group II (1974-76) and in the group III (1977-81), the patients (respectively 12 and 17) have been treated according to the following protocols: LAM-5 (3), TRAP (5), COAP (1), LAM 80 (2), AIL 7402 (8), AIL 7604, AIL 7801 (6). Immunotherapy has been performed in 7 cases. CNS prophylaxis (MTX i.t. +/-ARA-C +/- RT) was given in 5 patients of group II and in 6 of group III. I patients of group I (45%), 6 of group II (50%) and 13 of group III (76%) achieved CR. Median duration of remission was 5 months in the group I and in 17 in group II and III.(ABSTRACT TRUNCATED AT 250 WORDS)

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Abstract: During 1967-78, cancer was diagnosed in 870 children living in the Province of Torino. Survival until the end of 1978 is reported separately for cases diagnosed in 1967-70, in 1971-74, and in 1975-78. Comparisons between the three series indicate a statistically significant (p less than 0.05) increase in survival rates for children with leukemia and cancer of the central nervous system as well as a nonstatistically significant increase for children with lymphoma (both Hodgkin's and non-Hodgkin's). No consistent changes in time were noticed for neuroblastomas, nephroblastomas, soft tissue sarcomas, and retinoblastomas. Survival rates for both types of lymphomas and for leukemias (at least for cases diagnosed after 1975) were very similar to corresponding population-derived data from the U.S. and other Western countries. Rates for other cancers were relatively poor in the Province of Torino. It is suggested that relatively high care standards are easier to achieve in the case of childhood cancers requiring chemotherapy than in cancers commonly treated through radiotherapy and/or surgery.

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Abstract: Seven epidemiologic studies on the possible association between parental occupations and cancer in childhood are reviewed. Most were based on the hypothesis of an etiologic role of parental occupations, involving exposure to the broad category of "hydrocarbons". The relevant observations were contradictory, possibly because of the vagueness of the definition of the risk factor. Some findings were significant in at least two studies, such as an excess of machinists and mechanics among fathers of children with Wilms' tumor and an excess of occupations with exposure to paints among children with brain cancer. These and other findings should be considered as hypotheses for further studies.

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Abstract: Eighty-six children were diagnosed with cancer in infancy, followed for at lest 5 years, and assessed for late effects of disease and therapy. One child subsequently died from respiratory failure and 3 died from second primary cancers. Another patient survived second primary cancers of the skin. The high frequency of new cancers (4 observed, 0.09 expected) was attributable to host susceptibility factors and treatment effects. Kyphoscoliosis was diagnosed in 44 patients, 40 of whom had received radiotherapy to the spine. Other patients had neurologic deficits, pulmonary fibrosis, hypoplastic breasts, bowel adhesions, thyroid nodules, musculoskeletal defects, and liver fibrosis associated with tumor therapy. Sequelae of cancer were more common after treatment in infancy than in later childhood. Improved treatments and knowledge of natural history can reduce adverse effects of therapy.

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Abstract: PTC, a mixture of oligopeptides of m-L-sarcholysin, acting primarily as an alkylating agent, was utilized as initial therapy following diagnosis in 80 children with nonlocalized neuroblastoma. Of the 67 evaluable patients (21 Stage III, 41 Stage IV and five Stage IV-S), 51 had measurable lesions allowing to evaluate PTC activity; objective tumor responses to the drug were recorded in 45 of these 51 cases (88.2%); 5/5 Stage III, 37/41 Stage IV, 3/5 Stage IV-S. Complete responses were obtained in seven patients (13.7%), partial responses in 32 (62.7%), objective improvement in six (11.8%). Four patients (7.8%) had either no tumor change, or tumor progression. There have been two early drug-related deaths (3.9%). Stage III and IV patients responding to PTC were then treated by irradiation + VCR, followed by cycles of a combination of ADriamycin, vincristine, and cyclophosphamide. Stage IV-S patients received no further therapy. Thirteen of 21 Stage III (61.9%), five of 41 Stage IV (12.2%) and four of five Stage IV-S (80%) are presently alive from 19-48 months (median, 27 months). PTC is an effective agent in advanced neuroblastoma. However, the results of this report do not indicate that its addition to a "standard" treatment, at least in the schedule adopted in this protocol, has improved the final outcome of children with nonlocalized disease.

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Abstract: Thirty-four infants under 1 year of age with Wilms' tumor were diagnosed and treated in 14 Italian pediatric oncology units during 1970-79. The 3-year survival rates decreased with higher group unilateral tumors: 95% in group I Wilms' tumor, 75% in group II and 20% in group III. The survival rates for children with group I and II Wilms' tumor were similar for those who were treated with surgery and chemotherapy and those who also received postoperative radiotherapy. During 1975-79 fewer patients with group I Wilms' tumor received radiotherapy (1 of 11) than during 1970-74 (4 of 6, p less than 0.05). All these children are alive at this writing.

Abstract: Two girls with homozygous beta-thalassaemia developed acute lymphoblastic leukaemia. In the first case the two disorders were diagnosed at the same time, when the infant was 11 months old. In the second girl the thalassaemia was diagnosed at the age of 5 months. The patient received monthly packed red cell transfusion. At the age of 3 years she developed the leukaemia. Both the patients achieved a complete remission and are alive after 73 and 5 months from the diagnosis of the leukaemia. The authors discuss the possible relationship between the two haematological diseases.

Abstract: Six children with yolk sac tumor, 3 occurring in gonadal sites and 3 in extragonadal ones, were studied with respect to pathological features, laboratory findings and clinical course. Their histological appearance was similar regardless of the site of origin. The prognosis was poor, but all the cases exhibited objective response to chemotherapy. Two children are alive and off therapy from 27 and 60 months. Three of the six patients in which serum alfa-fetoprotein determinations were performed showed positive results. The demonstration of alfa-fetoprotein in the serum of these patients could prove to be of prognostic value, indicating the presence of residual or recurrent disease. It is advisable to gather cases from many Institutions in order to specify prognostic factors, to know the natural history of this tumor and to prepare an effective therapeutic program.

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Abstract: We report a new case of ataxia-telangiectasia (AT) and acute lymphoblastic leukemia (ALL) and review all 21 known cases of AT and ALL. Leukemia in these patients is associated with a male predominance, age older than 10 years at diagnosis, a white blood cell count higher than 50,000 mm3, and a fatal course. Four patients have been reported who developed T-cell leukemia, 3 null-cell leukemia and 1 B-cell leukemia. The AT-ALL patients appear to be at risk for infections related to their immunodeficient status and ALL chemotherapy. In addition, neurologic deterioration has been noted during the early phase of therapy.

Abstract: The results of discontinuing therapy in children with acute lymphocytic leukemia observed at four associated institutions are presented. Of the 247 patients who achieved complete remission, 122 (49.3%) reached the point of discontinuing therapy after 2-4 years of continuous remission. The median period off therapy was 13 months with a range of 1-69 months. Of the 122 children removed from therapy, 27 (22.1%) relapsed, mainly in the bone marrow; relapses occurred 1-32 months after cessation of therapy (median ten months) with only two relapses occurring later than two years. By actuarial analysis, 57% of the patients are projected in continuous remission after five years from cessation of therapy. Neither selected features at diagnosis nor single modalities of treatment were found to predict whether relapse would occur after discontinuing therapy. Long-term remission and possibly cure can be expected in over one-third of newly diagnosed children with ALL after 2-4 years of antileukemic treatment.

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Abstract: The influence on the duration of CR and survival of 2 modalities (MTX + hydrocortisone IT, with and without TCT) for the prevention of meningeal CNS involvement was assessed in 24 children with acute lymphoblastic leukemia. Of the 9 subjects who received MTX and hydrocortisone only, 42% were still in CR 33 months after its attainment, as opposed to 75% of the 15 who also received TCT. Survival at 33 months after diagnosis was 89% and 82% in the 2 groups. The results are compared with those obtained in an earlier series of 14 children who received no prophylactic treatment. Here CR at 45 months was 25% and survival 46%. Eight subjects died, as opposed to 3 (1 in CR) in the present series.

Abstract: The survival of children with Wilms' tumour is evaluated in 11 males and 12 females treated between 1967 and 1975 in the light of the clinical stage, age at diagnosis, and sex. The subjects were aged from 4 months to 6 years. Six were in stage I, 4 in stage II, 4 in stage III, 7 in stage IV, and 2 in stage V. Survival in stage I was 100% at 36 months and gradually decreased with the stage. Patients aged less than 2 years presented a survival of 50% two years after diagnosis, compared to 24% in those over 2 years old. Sex appears to be irrelevant to prognosis.

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Abstract: Piemonte and Valle d'Aosta are in the NW part of Italy. In 1967 total population and population aged 0-14 were respectively 4.338.000 and 841.000. During the period 1965-69 a total of 688 cases of cancer (including leukemia) were diagnosed inchildren under 15 years of age resident in this area. The Cancer Registry of Piedmont and Valle d'Aosta (RTP) provided information on 465 children; the other 223 were collected through additional investigation in the files of 31 university of hospital departments of the region and 5 extraregional hospitals. Distribution through the 5 years covered by the investigation is shown in Table 1. Histological or hematological confirmation of the diagnosis was available in 499 cases (73%). The 688 cases included 216 leukemias, 131 tumors of the central nervous system, 40 neuroblastomas, 82 lymphomas (including 34 cases of Hodgkin's disease), 46 nephroblastomas, 32 soft-tissue sarcomas, 29 bone sarcomas (including 5 cases of Ewing's disease), 25 retinoblastomas, 12 thyroid tumors, 10 extragenital teratomas, 5 ovarian dysgerminomas, 4 tumours of the testes, 4 hepatoblastomas and 52 other tumours (Table 2). The number of children under 15 years of age dying of cancer during 1965-69 was 341 (Table 2). Incidence and mortality rates by age groups are given in Tables 3 and 4. The rates were of the same order as those observed in the U.S. and in other European cancer registries during the same period (Tables 4,5 and 6). The mortality rate for nephroblastomas at age 0-4 was 1,09/100.000/year, i.e. slightly higher than that observed in the U.S. in 1960 but about twice as high as that observed in the U.S. in 1967 (14). Incidence and mortality rates for both Hodgkin's and non-Hodgkin's lymphomas were about 3 times higher in males than in females (Table 3). The difference was less obvious during the first five years of life, in which the total number of diagnosed lymphomas was 16.

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