RESUMEN
Because genetic predisposition probably plays an important role in the aetiology of most of childhood cancers, studies of second primaries occurring after these cancers may be particularly informative about possible common genetic mechanisms in both of these cancers. We have studied the incidence of thyroid tumours occurring after cancer in childhood in a cohort of 592 children treated before 1970. Among these children, six later developed a thyroid carcinoma, and 18 developed a thyroid adenoma. Radiation doses received to the thyroid by each of the irradiated children have been estimated using individual radiotherapeutic technical records. Thyroid carcinomas and thyroid adenomas were five times more frequent after irradiation for neuroblastoma than after irradiation for any other first cancer. This ratio did not depend on sex, nor on time elapsed since irradiation, nor on dose of radiation received for the thyroid gland. This result suggests that there is a common mechanism for the occurrence of neuroblastoma and of differentiated thyroid tumour.
Asunto(s)
Adenoma/etiología , Neoplasias Inducidas por Radiación , Neoplasias Primarias Secundarias/etiología , Neuroblastoma/etiología , Neoplasias de la Tiroides/etiología , Adenoma/epidemiología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Rayos gamma/efectos adversos , Humanos , Lactante , Recién Nacido , Masculino , Neoplasias Primarias Secundarias/epidemiología , Neuroblastoma/epidemiología , Riesgo , Neoplasias de la Tiroides/epidemiología , Rayos X/efectos adversosRESUMEN
Of a cohort of 634 children treated from 1942 to 1969 at the Gustave Roussy Institute for a first cancer and alive 5 years after treatment, 32 later developed second malignant neoplasms (SMN). A case-control study was performed to determine the relationship between the dose of radiotherapy received on a given anatomical site for the treatment of a first cancer, and the risk of SMN development at the same anatomical site. Another aim of the study was to analyse the effects of the association of radiotherapy with chemotherapy on the risk of SMN. The 32 cases of second malignant neoplasms were individually matched with one to nine patients of the cohort (a total of 162) who did not develop a SMN after a first cancer, matching on age, sex, type of first cancer and follow-up duration. The doses of radiotherapy delivered for the treatment of the first cancer were retrospectively estimated at the 26 anatomical sites of SMN. When the SMN was a leukaemia, the mean active bone-marrow dose was estimated as a weighted mean of the doses received by 20 bone sites. As compared to anatomical sites in children who had not received radiotherapy, the sites which had received 50 Gy or more had a relative risk of SMN of 5.8 (P less than 0.05). When taking into account the dose received at the site of the SMN, neither the number of fractions nor the type of radiations were related to the risk of SMN. Children who had received chemotherapy had a relative risk of SMN of 2.7 (95% CI: 1.2-6.4), adjusted for the dose of radiotherapy, as compared to those who had not. The relative risk of SMN did not vary with the dose nor the duration of the chemotherapy. Dactinomycin was found to increase the relative risk of second soft tissue and bone sarcomas. Cyclophosphamide was found to be less carcinogenic than the other alkylants. The relative risk of SMN was equal to 2.0 (n.s.) after radiotherapy of more than 25 Gy, to 4.4 (n.s.) after chemotherapy, and to 21.4 (P less than 0.01) after the combination of these two treatments modalities, as compared to patients treated by surgery alone. This study suggests that the oncogenic effect of radiations might be increased by chemotherapy, and that the combination of the two treatment modalities might be one of the major factors responsible for overall risk of SMN.
Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias Primarias Múltiples/etiología , Neoplasias Inducidas por Radiación/etiología , Radioterapia/efectos adversos , Adolescente , Niño , Preescolar , Estudios de Cohortes , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Neoplasias Primarias Múltiples/inducido químicamente , Dosificación Radioterapéutica , Factores de RiesgoRESUMEN
The risk of subsequent second malignant neoplasm was studied in a cohort of 634 patients, treated for a childhood cancer at the Gustave Roussy Institute between 1942 and 1969, and in complete remission five years after diagnosis. The most frequent types of first primary cancers (FPC) were Wilms' tumours (28% of the children), neuroblastomas (16%), lymphomas (12%) and soft tissue sarcomas (11%). Median follow-up duration after FPC was 19 years. Thirty-two patients (obs = 32) developed a total of 35 second cancers. Bone, thyroid, connective tissues and skin were the most frequent types of second cancer, with six patients for each type. The average annual incidence of second cancer was 0.36%. The average annual incidence for the periods 5-9, 10-14, 15-19, 20-24 and 25+ years after FPC was respectively 0.16%, 0.34%, 0.36%, 0.71% and 1.18%. The cumulative incidence of second cancer for the periods 5-20, 5-25 and 5-30 years after FPC was, respectively, 4.3% (95% CI: 2.8-6.6%), 7.8% (95% CI: 5.1-11.8%) and 13.0% (95% CI: 8.2-20.0%). The expected number of cancers in the cohort, computed from Danish cancer incidence data, was exp = 2.2. When compared to this expected number, the average annual excess incidence of second cancer, defined as obs-exp divided by the number of person years of observation, was 0.33%. This rose from 0.15% for the period 5-9 years after FPC to 1.09% for the period beginning 25 years after FPC. The standardised incidence ratio of second cancer (i.e. obs/exp) was 15 (95% CI: 10-21), and was fairly constant in the period extending from 15 to 20 years after FPC diagnosis. Obs/exp was equal to 25 for the patients who had had chemotherapy and equal to 9 for those who had not. Cyclophosphamide seemed less carcinogenic than the other alkylating agents. Obs/exp was similar for the patients who had received radiotherapy and for those who had not. The risk of cancer increased with age in the reference population and increased faster in the cohort, because the standardised incidence ratio is constant over a long period.
Asunto(s)
Neoplasias Primarias Múltiples/epidemiología , Adolescente , Factores de Edad , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Factores de Riesgo , Factores de TiempoRESUMEN
Ovarian function was investigated in 17 patients aged 13 5/12 to 30 years who had received various types of combined chemotherapy without any irradiation. Ovarian insufficiency was found in 6 cases with amenorrhea (n = 5) or irregular menstruations (n = 1). There is a high risk of sterility in these cases although as described in one case, a normal pregnancy occurred in spite of evidence of ovarian failure. Cyclophosphamide seemed to be less harmful when given before puberty. Great variations in individual susceptibility for relatively low doses were observed with this drug. The combination with other drugs in some protocols might play a role in these cases. At variance with results reported in adults, the MOPP chemotherapy used in children with Hodgkin's disease did not induce ovarian dysfunction.
Asunto(s)
Antineoplásicos/efectos adversos , Enfermedades del Ovario/inducido químicamente , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Preescolar , Ciclofosfamida/efectos adversos , Femenino , Enfermedades Hematológicas/tratamiento farmacológico , Humanos , Mecloretamina/efectos adversos , Neoplasias/tratamiento farmacológico , Prednisona/efectos adversos , Procarbazina/efectos adversos , Estudios Retrospectivos , Vincristina/efectos adversosRESUMEN
The socio-professional future of adults cured from a malignant solid tumor of childhood has been evaluated in 356 out of 476 patients followed 5 to 36 years after diagnosis (median: 17 years). Their professions appear similar to those observed in people of the same age, except for 2/3 of brain tumor patients who are more or less severely handicapped. Couples have been formed by 165 patients, 20 of them severely handicapped. Most of these people take an ardent interest in life, and part of them harbor a more or less secrete anguish of relapse. The conditions of their familial and socio-economic life play an important role in their adaptation to the life of a "cured from cancer patient".
Asunto(s)
Neoplasias/rehabilitación , Adolescente , Adulto , Niño , Preescolar , Personas con Discapacidad , Educación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Matrimonio , Neoplasias/psicología , Ocupaciones , Desarrollo de la Personalidad , Calidad de Vida , Ajuste SocialAsunto(s)
Pediatría , Rol del Médico , Rol , Adolescente , Niño , Preescolar , Ética Médica , Humanos , Lactante , Recién Nacido , Relaciones Médico-Paciente , Factores de TiempoRESUMEN
The 476 children treated for solid malignant tumor from 1947 to 1968 at the Institut Gustave-Roussy, and living NED at 5 years, were reviewed after 5 to 36 years of follow-up (median 17 years). Two children were affected in the sibship in 9 families. Thirty patients died after 7 to 32 years, 15 from late evolution of their primary tumor, 7 from second cancer, and 8 from other causes. Late sequellae (3 lethal), mainly neurologic, orthopedic, endocrine, and others were observed in 271 patients, and not known in 48. A second tumor (19 malignant, 46 benign) occurred from 7 to 26 years after treatment, more than half in the previously irradiated area. These patients have presently 164 known children; two died in infancy, two have malformations. None has had tumor up until now. The long-term cure of cancer remains true in 95% of cases in our span of follow-up, with sequellae compatible with a useful life in most cases.
Asunto(s)
Neoplasias/epidemiología , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/epidemiología , Neoplasias/genética , Neoplasias/mortalidad , Neoplasias/terapia , Neoplasias Primarias Múltiples/epidemiología , Neoplasias Inducidas por Radiación/epidemiología , Pronóstico , RiesgoRESUMEN
One hundred seventy-eight previously untreated children with biopsy-proven Hodgkin's disease of clinical Stages I and II were treated and followed between 1965 and 1978. Staging laparotomy was performed in 30 patients. Ninety-four percent of the patients obtained a complete remission; 24 patients have died. The actuarial survival rate for all patients was 90% at 5 years, and 81% at 10 years. The disease-free survival rate was 69% at 5 years, and 65% at 10 years. When nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) chemotherapy was added to either extended field or involved field irradiation, the relapse rate was significantly decreased as compared with the protocols without MOPP and prophylactic para-aortic irradiation. The authors believe that surgical staging may not be necessary as splenic involvement may be treated in some patients by MOPP chemotherapy alone or in association with splenic paraaortic radiotherapy. However, the side effects of MOPP need further study by other chemotherapy programs.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/radioterapia , Adolescente , Niño , Preescolar , Terapia Combinada , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Humanos , Lactante , Laparotomía , Masculino , Mecloretamina/administración & dosificación , Estadificación de Neoplasias , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Pronóstico , Distribución Aleatoria , Recurrencia , Estudios Retrospectivos , Esplenectomía , Vincristina/administración & dosificaciónRESUMEN
A series of 134 children, less than 15 years of age at the time of diagnosis of tumor, treated by one oncology group and one surgeon, have been submitted to thoracotomy for pulmonary metastatic disease between 1961 and 1976. Fifteen had a thoracic exploration only because of the extent of disease and died. Three had a nodule excised which proved to be nonmetastatic at histology and are alive. One hundred and sixteen underwent 152 excisional procedures with 2 operative deaths, 1 postpneumonectomy empyema, 2 transient postoperative complications, and 4 local relapses. Fifty-one are alive 4 to 15 years after the last surgical procedure. The results are best when a single (or a few) metastasis is removed as a primary treatment followed by chemotherapy and/or radiotherapy when indicated. Results are better in Wilms' tumors than in other tumors. Radiotherapy which can lead to long term pulmonary sequelae can be avoided in half of the patients (26/51). Thoracotomy is a safe and simple procedure in children, giving rewarding results when the indications of excision, among the different means of treatment, are carefully chosen.
Asunto(s)
Neoplasias Pulmonares/secundario , Adolescente , Niño , Preescolar , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia , Osteosarcoma/secundario , Osteosarcoma/cirugía , Pronóstico , Tumor de Wilms/secundario , Tumor de Wilms/cirugíaRESUMEN
To assess the value in Ewing's sarcoma of a new multiagent therapy (vincristine, cyclophosphamide, Adriamycin, (doxorubicin) procarbazine), 30 children with a localized tumor (eight distal, nine proximal, 13 central lesions) treated at the Institut Gustave-Roussy between 1973 and 1976 (E3), were pair-matched by site of primary with 30 control patients treated without intensive chemotherapy between 1967 and 1972 (E1) at the same institution, both groups having the same local radiotherapy. Actuarial survival and disease-free survival rates at six years were significantly higher in E3 at P less than 0.01, respectively, 58% and 49% versus 25% in E1. The prognostic value of the primary site was ascertained only in children under chemotherapy. In this group there were six early relapses with death within 14 months and nine late relapses at 21 to 38 months. Among these nine patients, six died, one is living with disease, and two are currently alive in second remission. Fifteen patients are continuously free of disease 50 to 90 months after first treatment (median, 69 months): functional sequelae are minimal in six, moderate in seven, and severe in two children with limb amputation. It is concluded that in future treatments chemotherapy must be intensified and begun prior to local treatment which has to be reevaluated for radiation modalities and for radical surgery indication.
Asunto(s)
Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Óseas/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Adolescente , Adulto , Antineoplásicos/efectos adversos , Neoplasias Óseas/patología , Neoplasias Óseas/radioterapia , Niño , Preescolar , Ensayos Clínicos como Asunto , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Lactante , Recuento de Leucocitos , Masculino , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Pronóstico , Sarcoma de Ewing/patología , Sarcoma de Ewing/radioterapia , Vincristina/administración & dosificación , Vincristina/efectos adversosAsunto(s)
Ganglioneuroma/terapia , Neuroblastoma/terapia , Neoplasias Torácicas/terapia , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , MasculinoAsunto(s)
Antineoplásicos/efectos adversos , Enfermedad de Hodgkin/tratamiento farmacológico , Leucemia Mieloide Aguda/inducido químicamente , Oligospermia/inducido químicamente , Enfermedades Testiculares/inducido químicamente , Adolescente , Adulto , Antineoplásicos/administración & dosificación , Niño , Quimioterapia Combinada , Humanos , MasculinoRESUMEN
Almost all malignant bone tumors in children are either osteogenic sarcomas or Ewing's sarcomas. Their origin and their site are different as well as the course of the disease and its treatment. Amputation or desarticulation in still the best local treatment for osteogenic sarcoma. Irradiation can benefit some patients. Conservative resection, followed by internal prosthesis, is still an experimental procedure. Results of chemotherapy combining high-dose methotrexate and adriamycin have been controversial. Prophylactic pulmonary irradiation seems to lessen the number of metastases. Controlled therapeutic trials are mandatory to assess the efficacy of these complementary treatments. Local cure is obtained in 90% of Ewing's sarcomas by high doses of radiotherapy but with a number of late sequellae. This tumor is also highly chemosensitive. Treatment of the infra-clinical disease by intensive chemotherapy has significantly increased the number of long-term cures. Other therapeutic regimens combining chemotherapy, radiotherapy and limited conservative surgery are now under investigation in an effort to diminish the sequellae without decreasing the number of cures.
Asunto(s)
Neoplasias Óseas/terapia , Osteosarcoma/terapia , Sarcoma de Ewing/terapia , Amputación Quirúrgica , Antineoplásicos/uso terapéutico , Neoplasias Óseas/radioterapia , Niño , Humanos , Metástasis de la Neoplasia , Osteosarcoma/radioterapia , Sarcoma de Ewing/radioterapiaRESUMEN
The case of a 2 month-old child with metastatic choriocarcinoma is reported. Death occurred rapidly and necropsy failed to find a primary tumor; the choriocarcinoma was therefore thought to be developed in the placenta. A year later, a uterine exploration was performed in the mother. In spite of normal chorionic gonadotrophin levels the histological findings were compatible with choriocarcinoma.
Asunto(s)
Coriocarcinoma/secundario , Placenta , Complicaciones del Embarazo , Neoplasias Uterinas , Femenino , Humanos , Lactante , Masculino , Intercambio Materno-Fetal , EmbarazoRESUMEN
A controlled clinical trial conducted by the European Organization for Research on Treatment of Cancer Radiotherapy Cooperative Group has shown that prophylactic lung irradiation is effective in preventing lung metastases in patients under 17 years of age. Recently, a new three-armed trial has started in which prophylactic chemotherapy and lung irradiation and chemotherapy combined with radiotherapy to the lungs will be compared for their ability to prevent the development of lung metastases.
Asunto(s)
Neoplasias Pulmonares/prevención & control , Pulmón/efectos de la radiación , Osteosarcoma/prevención & control , Adolescente , Brazo , Neoplasias Óseas/radioterapia , Neoplasias Óseas/cirugía , Niño , Preescolar , Ensayos Clínicos como Asunto , Humanos , Lactante , Pierna , Neoplasias Pulmonares/secundario , Osteosarcoma/radioterapia , Osteosarcoma/secundario , Osteosarcoma/cirugíaRESUMEN
Osteosarcoma or chondrosarcoma developed as a second malignant neoplasm (SMN) in 40 of 188 individuals with SMN whose first neoplasm occurred in childhood. A genetic susceptibility to cancer was found in 23; the SMN developed in an irradiated field in 32; both factors wer present in 16; neither in one. When a genetic predisposition was present, radiation shortened the interval to SMN. The intervals between tumors and the age at which the bone sarcomas developed in relation to genetic disease and therapy were analyzed by a two-mutation hypothesis. Studies of SMN in childhood permit us to make observation about the role of genetic factors and environmental mutagens in cancer etiology.