Odile Schweisguth

Bone sarcoma as a second malignant neoplasm in children: Influence of radiation and genetic predisposition

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 were 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 observations about the role of genetic factors and environmental mutagens in cancer etiology.

DECREASED RISK OF RADIATION-ASSOCIATED SECOND MALIGNANT NEOPLASMS IN ACTINOMYCIN-D-TREATED PATIENTS

One hundred two long‐term survivors of childhood cancers with second malignant neoplasms (SMNs) were collected from 10 institutions. Forty‐seven cases fulfilling study criteria were studied to determine the risk of developing a SMN in irradiated fields after exposure to various chemotherapeutic agents. The case control method was used. The risk of developing such tumors was decreased by a factor of 7 in patients receiving actinomycin‐D (AMD). The “protective” effect of AMD was more pronounced in patients receiving repeated courses of the agent. No change in relative risk was found for children given antifolates, the vinca alkaloids, or alkylating agents. AMD “protection” is an unexpected finding because the agent is an oncogen in animals and an enhancer of radiation, the latter being a known carcinogen. Possible mechanisms, which remain speculative, are discussed. These results indicate the need for careful long‐term observation of cancer survivors to gain understanding of the late effects of multimodal treatments.

Irradiation of the lungs as an adjuvant therapy in the treatment of osteosarcoma of the limbs: An E.O.R.T.C. randomized study

Abstract In 1970 a controlled clinical trial was started by the E.O.R.T.C. Radiotherapy Cooperative Group. The aim was to evaluate the effect on the development of lung metastases of an adjuvant irradiation of the lungs after “radical” treatment of primary osteosarcoma of the limbs. Five treatment Centers in France and two in The Netherlands have been participating in this trial. Early 1975 the trial was stopped. At that time 86 patients had been randomized into a group of 42 patients without any adjuvant therapy and a group of 44 patients with adjuvant lung irradiation to a dose of 2000 rad in 2 weeks. The results show that this dose of radiation can significantly decrease the percentage of cases in which metastases develop. This effect is especially seen in the group of patients under 17 yr of age, also resulting in a better survival rate for that group. Surprisingly it was found that in one of the participating Centers no beneficial effect from lung irradiation could be demonstrated. No other explanation could be found for this phenomenon than that a selection of patients with unfavourable prognosis is being referred to that Center. The results obtained make it necessary to include, apart from chemotherapy, lung irradiation in future trials on adjuvant therapy in osteosarcoma patients.

Lymphosarcoma and reticulum cell sarcoma in children. A retrospective study of 172 cases

The clinical features and survival rates of 112 cases of lymphosarcoma and 60 cases of reticulum cell sarcoma in children under 15 years of age, treated between 1950 and 1971, form the basis of this report. Some modifications of the Ann Arbor Classification are discussed, taking into account the local and distant dissemination of the disease and the importance of tumors arising outside the lymphatic organs. Forty of 91 Stage I and II patients, 5 of 44 Stage IVC patients, and 2 of 36 Stage IVD patients are living with a minimum followup period of 9 months. The over‐all survival rate is 27%. All deaths occurred before the 30th month following diagnosis, the survival curve not changing thereafter. A statistical analysis has been made. Age, sex, and his‐tologic type have not been found prognostically significant in this series. The initial stage has an independant significant prognostic value: The survival rate is 58% for the 54 Stage I patients, 24% for the 36 Stage II patients, and 8% for the 79 Stage IV patients. The 24 patients with non‐lymphatic forms have a 69% survival rate, as compared to 36% for the 67 patients with lymphatic forms.

Intensive systemic chemotherapy in localized Ewing's sarcoma in childhood. A historical trial

To assess the value in Ewings 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 pairmatched 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 < 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.

BILATERAL NON FUNCTIONNING THECOMA OF THE OVARY IN EPILEPTIC CHILDREN UNDER ANTICONVULSANT THERAPY

The peculiar features of two bilateral thecoma of the ovary are described. They were discovered because of a rapid enlargement of the abdomen with hemorrhagic ascites, but without any sign of precocious puberty. They occurred in young females treated with anti‐convulsant therapy for epilepsy. They have been cured with surgery alone.

Prognostic factors in malignant germ cell tumors of the ovary in children excluding pure dysgerminoma

Abstract Forty cases of malignant germ cell tumors of the ovary in children are presented, excluding pure dysgerminoma. They are classified according to the WHO classification. The histological typing and the stage have prognostic value, so they should be defined as accurately as possible. The choice of therapeutic should take these two prognostic factors into account.

A biochemical study of neuroblastoma in vivo and in vitro

Abstract Previous investigations on the metabolism in tissue culture of dl - 3 H-norepinephrine by tumors from patients with neuroblastoma have revealed that the tumor tissue itself is capable of converting the dl - 3 H-norepinephrine to 3 H-3-methoxy-4-hydroxyphenylglycol ( 3 H-MHPG). This report concerns studies on a patient with neuroblastoma whose tumor tissue showed the ability to carry out the above transformation. It was found that the levels of MHPG in the tumor and in the blood were higher that the levels of 3-methoxy-4-hydroxymandelic acid (VMA). In addition, the metabolism and excretion of dl -7- 3 H-MHPG in this patient have revealed that 34% of the administered compound was converted to 3 HVMA, 7.3% was excreted as the sulfate conjugate of MHPG, 39.7% was excreted as an unidentified compound, 15% of the tritium appears to be converted to tritium-labeled water, and only 3.6% was excreted as unchanged 3 HMHPG. These findings are consistent with the hypothesis that in those patients who have secreting neuroblastomas there appears to be synthesis of norepinephrine and metabolism of it to a significant extent to 3-methoxy-4-hydroxyphenylglycol which is then released into the blood and further metabolized to 3-methoxy-4-hydroxymandelic acid which is excreted in the urine.

Activité mono amine oxydase dans les tumeurs de la crête neurale

Mono Amine Oxidase activity in 54 fragments of neural crest tumors from 33 children (24 neuroblastomas, 4 ganglioneuroblastomas, 5 ganglioneuromas) and from 3 adults (3 pheochromocytomas), has been studied by the authors. 1. A. The repartition of the enzyme is heterogeneous and the values obtained in different parts of the tumors sometimes vary in the proportion of 1 to 5. The estimation of proteins in the tissues, necessary for calculating the specific activity can introduce an important error. 2. B. It seems there is no direct relationship between the level of catabolic enzyme (MAO) in the tumor and the levels of catabolites (vanillyl mandelic acid and homovanillic acid) found in the urine. 3. C. Pheochromocytomas have a very low Mono Amine Oxidase activity compared with neuroblastomas. The possibility of a competitive inhibition between the substrate (kynuramine) and catecholamines liberated by disruption of tumor cells is not excluded. 4. D. No MAO activity was found in four neuroblastomas examined, perhaps for the following reasons: inhibition of the enzyme by tyramine or dopamine liberated by disruption of cells an inhibitor of unknown nature masking of the enzyme a different cellular type.