Association between maternal education and survival after childhood cancer.

BACKGROUND: Several nonbiological factors, including socioeconomic status indicators and other family characteristics, influence survival from childhood cancers. Our study explores the association between parental education and childhood cancer survival. METHODS: The specialized Childhood Cancer Registry of the Piedmont region in Italy provided data on all the cases (aged 0-14) diagnosed with cancer in the period 1976-2011 who resided in the city of Turin (capital of the Piedmont region) at least once since 1971. Information on parental education was extracted from the Turin Longitudinal Study by record linkage. The association between parental educational level and survival was estimated using Cox regression. RESULTS: The study included 949 children. We observed a disadvantage in the overall survival for children of less educated mothers. No such effect was observed for paternal education. The effect of maternal education was particularly strong for central nervous system tumors (hazard ratios, 2.9; 95% confidence interval, 1.1-8.0). A similar effect, though smaller in magnitude, was observed for leukemia and embryonal tumors, whereas the estimates for lymphoma were imprecise. CONCLUSIONS: Our study shows an association between maternal educational level and survival in children with central nervous system tumors, a diagnosis that often requires long-lasting treatment and special care. Giving support to the families of affected children to provide them the optimal care has the potential to improve children's cancer treatment outcomes.

Lifetime growth and risk of testicular cancer.

Adult height is associated with testicular cancer risk. We studied to what extent this association is explained by parental height, childhood height and age at puberty. We conducted a case-control study on germ-cell testicular cancer patients diagnosed in 1997-2008 and resident in the Province of Turin. Information was collected using mailed questionnaires in 2008-2011. Specifically, we asked for adult height (in cm), height at age 9 and 13 (compared to peers) and age at puberty (compared to peers). We also asked for paternal and maternal height (in cm) as indicators of genetic components of adult height. The analysis included 255 cases and 459 controls. Odds ratios (ORs) of testicular cancer were estimated for the different anthropometric variables. Adult height was associated with testicular cancer risk [OR: 1.16, 95% confidence interval (CI): 1.03-1.31 per 5-cm increase]. The risk of testicular cancer was only slightly increased for being taller vs. shorter than peers at age 9 (OR: 1.55, 95% CI: 0.91-2.64) or age 13 (OR: 1.26, 95% CI: 0.78-2.01), and parental height was not associated with testicular cancer risk. The OR for adult height was 1.32 (95% CI: 1.12-1.56) after adjustment for parental height. Among participants with small average parental height (<167 cm or less), the OR of testicular cancer for tall (>180 cm) vs. short (<174 cm) subjects was 3.47 (95% CI: 1.60-7.51). These results suggest that the association between height and testicular cancer is likely to be explained by environmental factors affecting growth in early life, childhood and adolescence.

The economic burden of caregiving on families of children and adolescents with cancer: a population-based assessment.

BACKGROUND: Childhood cancer represents a relevant economic burden on families. The preferred tool to investigate family expenditure is the retrospective questionnaire, which is subject to recall errors and selection bias. Therefore, in the present study the economic burden of caregiving on families of children and adolescents (0-19 years of age) with cancer was analysed using administrative data as an alternative to retrospective questionnaires. PROCEDURE: Incident cases of cancer diagnosed in children and adolescents in 2000-2005 (N = 917) were identified from the Piedmont Childhood Cancer Registry and linked to available administrative databases to identify episodes of care during the 3 years after diagnosis (N = 13,433). The opportunity cost of informal caregiving was estimated as the value of the time spent by one of the parents, and was assumed to be equal to the number of days during which the child received inpatient care, day-care or outpatient radiotherapy. Factors affecting the level of economic burden of caregiving on families were analysed in a multivariable model. RESULTS: The economic burden of caregiving increased when care was supplied at the Regional Referral Centre, or when treatment complexity was high. Families with younger children had a higher level of economic burden of caregiving. Leukaemia required a higher family commitment than any other cancer considered. CONCLUSIONS: Estimates of the economic burden of caregiving on families of children and adolescents with cancer derived from administrative data should be considered a minimum burden. The estimated effect of the covariates is informative for healthcare decision-makers in planning support programmes.

Survival and cure trends for European children, adolescents and young adults diagnosed with acute lymphoblastic leukemia from 1982 to 2002.

Proportion cured is a potentially more informative cancer outcome measurement than 5-year survival. We present population-based estimates of cure for young patients diagnosed with acute lymphoblastic leukemia in Europe from 1982 to 2002. Thirty-five European cancer registries provided data. Survival was estimated by age, period of diagnosis and European region, and used as input for parametric cure models, which assume cured patients have the same mortality as the general population. For acute lymphoblastic leukemia diagnosed in 1-14 year olds in 2000-2002, over 77% were estimated cured. The proportion cured improved significantly over the study period: an impressive 26-58% in infants (up to 1 year), 70-90% in 1-4 year olds, 63-86% in 5-9 year olds, 52-77% in 10-14 year olds, and 44-50% in 15-24 year olds. Regional variations in proportion cured reduced over time for 1-14 year-olds, but persisted in infants and 15-24 year olds. Five-year survival was always slightly higher than proportion cured. Considerable proportions of young patients were estimated cured of acute lymphoblastic leukemia. Nevertheless, a small excess risk of death persisted beyond five years after diagnosis when patients remained at risk for late treatment effects, late relapses and second primaries.

Rhabdomyosarcoma in adolescents: a report from the AIEOP Soft Tissue Sarcoma Committee.

BACKGROUND: In many types of cancer, the survival rates are reported to be less favorable for adolescents compared with younger children. To investigate whether this is true for adolescents with rhabdomyosarcoma (RMS), the results obtained in patients enrolled in protocols run by the Italian Soft Tissue Sarcoma Committee (STSC) were analyzed. METHODS: From 1988 through 2005, 643 patients were registered (567 children ages birth-14 years and 76 adolescents ages 15-19 years) and treated in 4 STSC protocols. The number of patients enrolled was compared with the expected number calculated from incidence rates derived from the Italian network of cancer registries. RESULTS: Only 27% of the expected number of adolescents with RMS were enrolled in the STSC trials. Compared with children, adolescents were found to have a longer interval from initial symptoms to diagnosis (8 weeks vs 4.6 weeks), more alveolar RMS (47.4% vs 32.6%), lymph node infiltration (39.1% vs 23.3%), and metastases at the time of diagnosis (30.7% vs 17.8%). The 2 age groups received similar treatments. The 5-year overall survival (OS) rate was 68.9% in children versus 57.2% in adolescents (P = .006), and the progression-free survival (PFS) rate was 64.3% in children versus 48.1% in adolescents (P = .0237). On multivariate analysis, age, tumor site, lymph node involvement, and metastases were found to be significant prognostic factors for OS and PFS. CONCLUSIONS: Survival for adolescents with RMS enrolled in STSC protocols appears to be satisfactory. The higher prevalence of unfavorable tumor characteristics noted among adolescents seems to explain their worse outcome compared with children. However, the limited number of adolescents enrolled in STSC studies is worrisome, and cooperation with oncologists who treat adults needs to be improved.

Long-term results in childhood rhabdomyosarcoma: a report from the Italian Cooperative Study RMS 79.

BACKGROUND: The results obtained by protocols for children with rhabdomyosarcoma (RMS) have improved in recent decades. Survival curves usually reach a plateau 3 years after the diagnosis, suggesting that long-term survival can be expected, but late events are known to occur. We analyzed the long-term results of the RMS 79 protocol to investigate the type and impact of such events. PROCEDURE: From 1979 to 1987, 163 children with RMS diagnosed at 21 Italian institutions were registered. Each institution was contacted every year to record patients' status after the end of treatment. When patients were lost to follow-up, their status was checked by inquiring at the Registry Offices of the towns of residence and the cause of death or occurrence of second cancers was investigated by contacting the patients or their family by phone. RESULTS: Overall, 16 patients had late events, that is, 7 tumor recurrences, 6 second tumors, and 3 deaths due to treatment-related complications. The overall survival rates dropped from 62.6 at 3 years to 52.8 at 20 years. By multivariate analysis, the characteristics influencing long-term survival were histology, tumor site and size, and IRS group. Factors predictive of any kind of late event were tumor site and IRS group. CONCLUSIONS: Major late events can significantly affect the long-term survival of children with RMS. Modern protocols should provide for a much longer follow-up than is usually considered to confirm the results achieved and enable possible correlations between primary treatment and late events to be investigated.

Second malignancies after childhood noncentral nervous system solid cancer: Results from 13 cancer registries.

Children diagnosed with noncentral nervous system solid cancers (NCNSSC) experience several adverse late effects, including second malignant neoplasm. The aim of our study was to assess the risk of specific second malignancies after a childhood NCNSSC. Diagnosis and follow-up data on 10,988 cases of NCNSSC in children (0-14 years) were obtained from 13 registries. Standardized incidence ratios (SIRs) with 95% confidence intervals (CI) and cumulative incidence of second malignancies were computed. We observed 175 second malignant neoplasms, yielding a SIR of 4.6, 95% CI: 3.9-5.3. When considering second cancers with at least 10 occurrences, highest relative risks were found for second malignant bone tumors (SIR = 26.4, 16.6-40.0), soft tissue sarcomas (SIR = 14.1, 6.7-25.8) and myeloid leukemia (SIR = 12.7, 6.3-22.8). Significant increased risks for all malignancies combined were observed after sympathetic nervous system tumors (SIR = 11.4, 5.2-21.6), retinoblastomas (SIR = 7.3, 5.4-9.8), renal tumors (SIR = 5.7, 3.8-8.0), malignant bone tumors (SIR = 5.6, 3.7-8.2), soft tissue sarcomas (SIR = 4.7, 3.2-6.8), germ-cell, trophoblastic and other gonadal neoplasms (SIR = 2.5, 1.1-4.9), carcinomas and other malignant epithelial neoplasms (SIR = 2.2, 1.4-3.3). The highest risk of a second malignancy of any type occurred 5 to 9 years after NCNSSC (SIR = 9.9, 6.8-13.9). The cumulative incidence of second malignancies 10 years after the first neoplasm was eight times higher among NCNSSC survivors than in the general population, with the absolute difference between observed and expected cumulative incidence still increasing after 50 years of follow-up. Children who survived a NCNSSC experience a large increased risk of developing a new malignancy, even many years after their initial diagnosis.

Marriage and parenthood among childhood cancer survivors: a report from the Italian AIEOP Off-Therapy Registry.

BACKGROUND: The aim of this study was to describe the patterns of marriage and parenthood in a cohort of childhood cancer survivors included in the Off-Therapy Registry maintained by the Italian Association of Pediatric Hematology and Oncology. DESIGN AND METHODS: We analyzed a cohort of 6,044 patients diagnosed with cancer between 1960 and 1998, while aged 0 to 14 years and who were 18 years old or older by December 2003. They were followed up through the regional vital statistics registers until death or the end of follow up (October 30, 2006), whichever occurred first, and their marital status and date of birth of their children were recorded. The cumulative probabilities of being married and having a first child were computed by gender and compared by tumor type within the cohort. Marriage and fertility rates (the latter defined as the number of live births per woman-year) were compared with those of the Italian population of the same age, gender, area of residence and calendar period by means of the observed to expected (O/E) ratios. RESULTS: During the follow-up period, 4,633 (77%) subjects had not married. The marriage O/E ratios were 0.56 (95% CI: 0.51-0.61) and 0.70 (95% CI: 0.65-0.76) among men and women, respectively. Overall, 263 men had 367 liveborn children, and 473 women had 697 liveborn children. The female fertility O/E ratio was 0.57 (95% CI: 0.53-0.62) overall, and 1.08 (95% CI: 0.99-1.17) when analyses were restricted to married/cohabiting women CONCLUSIONS: Childhood cancer survivors are less likely to marry and to have children than the general population, confirming the life-long impact of their previous disease on their social behavior and choices. The inclusion of counseling in the strategies of management and long-term surveillance of childhood cancer patients could be beneficial to survivors as they approach adulthood.

Late sequelae of symptomatic epidural compression in children with localized neuroblastoma.

BACKGROUND: To describe late sequelae and their correlation with presenting clinical features and tumor treatment in children with symptomatic epidural compression (EC) secondary to localized neuroblastoma. PROCEDURES: A total of 98 evaluable children diagnosed with neuroblastoma and EC, who survived a minimum of 2 years were identified in two Italian and French neuroblastoma series. RESULTS: Symptoms of EC at diagnosis included motor deficit in 94 cases and sphincter deficits in 33. Initial treatment was chemotherapy in 66 cases, neurosurgical decompression in 29 and radiotherapy in 3. Chemotherapy was chosen more frequently for younger children and for those with stage 3 disease. Overall treatment consisted of chemotherapy alone in 44 cases, neurosurgery and chemotherapy in 38, radiotherapy and chemotherapy, with or without neurosurgery, in 16. After a median follow-up of 7.3 years, 57 children (58.2%) had one or more sequelae. Motor sequelae involved 50/57 of these children and correlated with age and severity of motor deficit at diagnosis and neurosurgical treatment. Spine deformities involved 27/57 children and were more frequent in those with severe motor deficit at diagnosis, or who were treated by neurosurgery or radiotherapy. Sphincter dysfunctions involved 31/57 children and were more frequent among children who presented with sphincter symptoms and severe motor deficit. CONCLUSIONS: Fifty-eight percent of the children with localized neuroblastoma and symptomatic EC registered in this study developed late sequelae. The severity of motor deficit at diagnosis was the main risk factor.

Evaluating access to pediatric cancer care centers of children and adolescents with rare tumors in Italy: the TREP project.

BACKGROUND: A national project focusing on rare malignant pediatric tumors (the TREP project) was launched in Italy in 2000. The present study compared the number of these tumors expected to be diagnosed in Italy with the number of cases actually enrolled in the TREP database in 2000-2006. METHODS: The predicted number of cases was calculated from incidence data from the Italian network of cancer registries (AIRTum). RESULTS: The TREP database included 336 patients under 18 years, that is, 261 children and 75 adolescents, as compared to 305 and 400 expected cases, respectively. For the 0-14 years old age-group, the ratio of observed to expected cases was 1:1 for nasopharyngeal carcinoma, adrenocortical tumors, renal cell carcinoma, and gonadal non-germ-cell tumors, while for the 15-17-year old individuals there was a statistically significant under-reporting for all tumor types. CONCLUSIONS: Our study showed that the TREP project succeeded in registering and treating the vast majority of the patients under 15 years of age with rare pediatric tumors, demonstrating the feasibility of cooperative protocols even for rare diseases. Conversely, there was a large gap between those registered compared to those expected for adolescents.

International collaborations in cancer control and the Third International Cancer Control Congress.

Over the past few decades, there has been growing support for the idea that cancer needs an interdisciplinary approach. Therefore, the international cancer community has developed several strategies as outlined in the WHO non-communicable diseases Action Plan (which includes cancer control) as the World Health Assembly and the UICC World Cancer Declaration, which both include primary prevention, early diagnosis, treatment, and palliative care. This paper highlights experiences/ideas in cancer control for international collaborations between low, middle, and high income countries, including collaborations between the European Union (EU) and African Union (AU) Member States, the Latin-American and Caribbean countries, and the Eastern Mediterranean countries. These proposals are presented within the context of the global vision on cancer control set forth by WHO in partnership with the International Union Against Cancer (UICC), in addition to issues that should be considered for collaborations at the global level: cancer survival (similar to the project CONCORD), cancer control for youth and adaptation of Clinical Practice Guidelines. Since cancer control is given lower priority on the health agenda of low and middle income countries and is less represented in global health efforts in those countries, EU and AU cancer stakeholders are working to put cancer control on the agenda of the EU-AU treaty for collaborations, and are proposing to consider palliative care, population-based cancer registration, and training and education focusing on primary prevention as core tools. A Community of Practice, such as the Third International Cancer Control Congress (ICCC-3), is an ideal place to share new proposals, learn from other experiences, and formulate new ideas. The aim of the ICCC-3 is to foster new international collaborations to promote cancer control actions in low and middle income countries. The development of supranational collaborations has been hindered by the fact that cancer control is not part of the objectives of the Millennium Development Goals (MGGs). As a consequence, less resources of development aids are allocated to control NCDs including cancer.

Survival of children with cancer in Italy, 1989-98. A report from the hospital based registry of the Italian Association of Paediatric Haematology and Oncology (AIEOP).

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.

Adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia.

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.

Effects of maternal age and cohort of birth on incidence time trends of childhood acute lymphoblastic leukemia.

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.

Health-related quality of life of long-term childhood cancer survivors: a population-based study from the Childhood Cancer Registry of Piedmont, Italy.

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.

Expected number of childhood cancers in Italy from 2001 to 2015.

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.

Mortality from cancer and other causes in parents of children with cancer: a population-based study in Piedmont, Italy.

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.

Analysis of nonresponse in the assessment of health-related quality of life of childhood cancer survivors.

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.

Avoided deaths as an indicator of improvement of childhood cancer treatment.

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.

Familial clustering of unexplained transient respiratory distress in 12 newborns from three unrelated families suggests an autosomal-recessive inheritance.

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.