We have studied the frequency of second primary malignancies (SPM) among the 2,328 children regis... more 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.
The study assesses the quantitative percentage use of second generation antidepressants (non-tric... more The study assesses the quantitative percentage use of second generation antidepressants (non-tricyclics or modified tricyclics) in clinical psychiatric practice in comparison with first generation products. The study was conducted on patients presenting in the surgery and psychiatric ward of Novara and in Turin Psychiatric Clinic in an-June 1987 and covers all patients receiving antidepressant drugs. For each individual given thymoanaleptic drugs, the type used and the reasons for its selection were examined as well as the combined use of antidepressants with other psychotherapeutic drugs. The data show that second generation antidepressants have come to play a major therapeutic role, though further research is needed to define their specific use and as far as possible to eliminate their use as a "vicarious" substitute for traditional drugs.
The influence on the duration of CR and survival of 2 modalities (MTX + hydrocortisone IT, with a... more 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.
We analyzed the clinical features and treatment of 23 hepatoblastomas (HPBs) and 16 hepatocellula... more We analyzed the clinical features and treatment of 23 hepatoblastomas (HPBs) and 16 hepatocellular carcinomas (HPCs) occurring in patients less than 19 years old, admitted to the Italian retrospective multicentric study, conducted between 1983 and 1985, on childhood malignant hepatic tumors. The median ages of the patients with HPB and HPC at diagnosis were 22.34 months and 96.23 months, respectively, with a male/female ratio of 0.7 and 1.7, respectively. Fourteen HPBs (61%) and 5 HPCs (31%) achieved surgical complete remission (CR). Of these, 11 HPB and all 5 HPC are still in CR with a median follow-up of 36 months and 3.5 years, respectively. One HPB and 1 HPC became resectable after a primary course of cis-platinum alone in the case of HPB and used with VP-16 in the case of HPC. All of the 9 HPBs and 11 HPCs, who never achieved CR, died of disease at a median interval from diagnosis of 5 and 2 months, respectively. The published therapeutic approaches for these tumors were also reviewed.
Background A 4‐week course of high‐dose glucocorticoids may cause prolonged adrenal suppression e... more 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 suppres...
Peptichemio (PTC), a multipeptidic complex of m-L-phenyl-alanine mustard, was administered to 39 ... more 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.
This descriptive epidemiology study of 1,040 children with Wilms' tumor (WT) registered in th... more 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 at diagnosis for unilateral multicentric and for unicen‐tric 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 Strong 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 nonfam...
This paper reports late effects and health status of 198 children who had cancer or leukemia diag... more 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 lymphomal 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 tr...
Children diagnosed with noncentral nervous system solid cancers (NCNSSC) experience several adver... more 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.
Sixty-five children with neuroblastoma without evidence of distant metastases underwent initial t... more 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%.
We have studied the frequency of second primary malignancies (SPM) among the 2,328 children regis... more 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.
The study assesses the quantitative percentage use of second generation antidepressants (non-tric... more The study assesses the quantitative percentage use of second generation antidepressants (non-tricyclics or modified tricyclics) in clinical psychiatric practice in comparison with first generation products. The study was conducted on patients presenting in the surgery and psychiatric ward of Novara and in Turin Psychiatric Clinic in an-June 1987 and covers all patients receiving antidepressant drugs. For each individual given thymoanaleptic drugs, the type used and the reasons for its selection were examined as well as the combined use of antidepressants with other psychotherapeutic drugs. The data show that second generation antidepressants have come to play a major therapeutic role, though further research is needed to define their specific use and as far as possible to eliminate their use as a "vicarious" substitute for traditional drugs.
The influence on the duration of CR and survival of 2 modalities (MTX + hydrocortisone IT, with a... more 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.
We analyzed the clinical features and treatment of 23 hepatoblastomas (HPBs) and 16 hepatocellula... more We analyzed the clinical features and treatment of 23 hepatoblastomas (HPBs) and 16 hepatocellular carcinomas (HPCs) occurring in patients less than 19 years old, admitted to the Italian retrospective multicentric study, conducted between 1983 and 1985, on childhood malignant hepatic tumors. The median ages of the patients with HPB and HPC at diagnosis were 22.34 months and 96.23 months, respectively, with a male/female ratio of 0.7 and 1.7, respectively. Fourteen HPBs (61%) and 5 HPCs (31%) achieved surgical complete remission (CR). Of these, 11 HPB and all 5 HPC are still in CR with a median follow-up of 36 months and 3.5 years, respectively. One HPB and 1 HPC became resectable after a primary course of cis-platinum alone in the case of HPB and used with VP-16 in the case of HPC. All of the 9 HPBs and 11 HPCs, who never achieved CR, died of disease at a median interval from diagnosis of 5 and 2 months, respectively. The published therapeutic approaches for these tumors were also reviewed.
Background A 4‐week course of high‐dose glucocorticoids may cause prolonged adrenal suppression e... more 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 suppres...
Peptichemio (PTC), a multipeptidic complex of m-L-phenyl-alanine mustard, was administered to 39 ... more 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.
This descriptive epidemiology study of 1,040 children with Wilms' tumor (WT) registered in th... more 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 at diagnosis for unilateral multicentric and for unicen‐tric 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 Strong 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 nonfam...
This paper reports late effects and health status of 198 children who had cancer or leukemia diag... more 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 lymphomal 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 tr...
Children diagnosed with noncentral nervous system solid cancers (NCNSSC) experience several adver... more 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.
Sixty-five children with neuroblastoma without evidence of distant metastases underwent initial t... more 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%.
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