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C Rodary

Publications and source records attributed to C Rodary.

At least 37 records · Page 2Linked to original sources

Prognostic factors in 951 nonmetastatic rhabdomyosarcoma in children: a report from the International Rhabdomyosarcoma Workshop.

A total of 951 newly diagnosed patients with nonmetastatic rhabdomyosarcoma (RMS) under 21 years of age from four different cooperative study groups were analyzed to identify the most important pretreatment tumor characteristics in predicting survival. The patient characteristics considered were tumor invasiveness (T), tumor size, status of locoregional lymph nodes, and primary site. The cooperative groups and studies analyzed were: SIOP [RMS-75 (1975-1984)], the Intergroup Rhabdomyosarcoma Study [IRS-II (1978-1982)], Federal Republic of Germany [CWS-81 (1981-1986)] and Italy [RMS-79 (1979-1986), each study involving a different therapeutic protocol. Patient characteristics identified as having a significant relationship to survival by univariate analysis were (favorable features given in brackets): tumor invasiveness [T1], tumor size [less than or equal to 5 cm], status of locoregional lymph nodes [clinically negative], and primary site [orbit and genitourinary non-bladder prostate (GU-non-BP) sites]. T2 tumors tended to have large size (greater than 5 cm), to be associated with positive nodes, and to have a different distribution by primary site than T1 tumors. A multivariate Cox regression analysis of the pooled data identified tumor invasiveness (T), primary site, and the interaction between T and primary site as significant predictive factors for survival. The prognosis of orbital tumors was consistently favorable regardless of T status, whereas the prognosis for "other sites" was consistently unfavorable. International cooperation in this study has permitted the identification of good and poor risk patient subgroups, permitting the focusing of therapeutic protocols to particular risk groups and setting the stage for common future therapeutic protocols for rare subgroups of patients.

Child↗

High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS involvement with a short intensive polychemotherapy: results from the French Pediatric Oncology Society of a randomized trial of 216 children.

From April 1984 to December 1987, the French Pediatric Oncology Society (SFOP) organized a randomized trial for advanced-stage B-cell lymphoma without CNS involvement to study the possibility of reducing the length of treatment to 4 months. After receiving the same three intensive six-drug induction courses based on high-dose fractionated cyclophosphamide, high-dose methotrexate (HD MTX), and cytarabine in continuous infusion, patients were evaluated for remission. Those who achieved complete remission (CR) were randomized between a long arm (five additional courses with two additional drugs; 16 weeks of treatment) and a short arm (two additional courses; 5 weeks). For patients in partial remission (PR), intensification of treatment was indicated. Two hundred sixteen patients were registered: 15 stage II nasopharyngeal and extensive facial tumors, 167 stage III, and 34 stage IV, 20 of the latter having more than 25% blast cells in bone marrow. The primary sites of involvement were abdomen in 172, head and neck in 30, thorax in two, and other sites in 12. One hundred sixty-seven patients are alive in first CR with a minimum follow-up of 18 months; four are lost to follow-up. Eight patients died from initial treatment failure, 14 died from toxicity or deaths unrelated to tumor or treatment, and 27 relapsed. The event-free survival (EFS), with a median follow-up of 38 months, is 78% (SE 3) for all the patients, 73% (SE 11) for the stage II patients, 80% (SE 3) for the stage III patients, and 68% (SE 8) for the stage IV and acute lymphoblastic leukemia (ALL) patients. One hundred sixty-six patients were randomized: 82 in the short arm and 84 in the long arm. EFS is, respectively, 89% and 87%. Statistical analysis confirms equivalence of both treatment arms with regard to EFS. Moreover, morbidity was lower in the short arm. This study confirms the high survival rate obtained in the previous LMB 0281 study without radiotherapy or debulking surgery and demonstrates the effectiveness of short treatment.

Adolescent↗

Malignant histiocytosis: therapeutic results in 27 children treated with a single polychemotherapy regimen.

Twenty-seven children with histologically proven malignant histiocytosis were treated in the same institution from January, 1975 to December, 1986 with a combination chemotherapy regimen containing vincristine, cyclophosphamide, doxorubicine, and prednisone. Twenty-two patients achieved complete remission, one partial remission, and four no remission. Eight patients relapsed and were treated with Lomustine (CCNU), vinblastine, and bleomycin. In seven cases, a second complete remission was obtained. The overall survival rate is 81% at 5 years and the relapse-free survival rate is 54.5% at 5 years. Prognostic factors were fever and age under 10 at diagnosis, which were correlated with a higher incidence of relapse or no remission.

Adolescent↗

An attempt to use a common staging system in rhabdomyosarcoma: a report of an international workshop initiated by the International Society of Pediatric Oncology (SIOP).

One hundred medical records of children with rhabdomyosarcoma were reviewed independently by ten European and American specialists primarily concerned with pediatric cancer patients. Each specialist assessed the stage of disease using a pre-treatment staging system (International Society of Pediatric Oncology-Union Internationale Contre le Cancer TNM [SIOP-UICC TNM] and a post-surgical staging system (Inter-group Rhabdomyosarcoma [IRS] grouping system). These two prognostic systems are based on different criteria, and there is no simple correspondence between them. The reliability of the two systems, based on patients' characteristics extracted from medical records, was similar and satisfactory (Kappa index: 0.78 and 0.82 with the TNM system and with the IRS system, respectively). Nevertheless, the IRS grouping system, which considers a primary method of treatment: Surgery, is dependent upon the surgeon, the institution, and the current concept of treatment. We believe that the TNM system provides the best description of extent of disease and should be used for determining therapeutic options and comparing therapeutic results.

Child↗

Histopathological classification of childhood rhabdomyosarcoma: a report from the International Society of Pediatric Oncology pathology panel.

Five hundred thirteen soft tissue tumours of childhood referred to the International Society of Pediatric Oncology (SIOP) Rhabdomyosarcoma study have been reviewed. The period covered was from January 1975 to December 1983. Three hundred thirty-nine neoplasms were regarded as embryonal rhabdomyosarcoma. The histological diagnosis of all referred tumours is given, and a classification of rhabdomyosarcomas developed during the course of the study is described. The relationship between histological subtypes and aspects of clinical behaviour is presented. The classification is thought to be helpful in diagnosis and also in assessment of the likelihood of recurrence and/or metastasis of childhood rhabdomyosarcoma.

Adolescent↗

How to establish equivalence between treatments: a one-sided clinical trial in paediatric oncology.

The design of clinical trial to establish the equivalence of two treatments differs from that of an efficacy trial. The conventional null hypothesis of equivalent treatment efficacy is replaced by a null hypothesis of inequivalence which must be tested by appropriate statistics. In addition, the maximum allowable value of the true difference between the efficacy of two equivalent treatments must be specified. In oncology, such a trial is necessary when a standard treatment is replaced by a new less toxic one of equivalent efficacy. The statistical formulation is one-sided. A trial comparing two pre-operative treatments in childhood nephroblastoma is presented here and analysed according to this methodology.

Antineoplastic Combined Chemotherapy Protocols↗

Role of radiotherapy and chemotherapy in the risk of second malignant neoplasms after cancer in childhood.

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.

Adolescent↗

Long-term risk of second malignant neoplasm after a cancer in childhood.

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.

Adolescent↗

Prognostic factors in 281 children with nonmetastatic rhabdomyosarcoma (RMS) at diagnosis.

Pretreatment characteristics of 281 children with nonmetastatic rhabdomyosarcoma, included in the registry of the International Society of Pediatric Oncology (SIOP) between January 1975 and December 1983, were examined to study the children's prognosis. The multivariate statistical method (Cox regression model) was used for each of two endpoints: survival time and disease-free time. The three most important predictors for survival time were primary site (p less than .001), clinical stage (p = .009), and sex (p = .020). The best results involved paratesticular and orbital primary sites, regardless of the clinical stage; males fared slightly better than females. These same three factors were also significant predictors for disease-free time.

Adolescent↗

[Treatment of extensive B-cell lymphoma in children: studies of the French Pediatric Oncology Society].

Since 1981 in the French Pediatric Oncology Society, a multidrug intensive-pulsed chemotherapy was proposed for bad prognosis B-cell lymphomas (stage II ORL, III and IV) and for B acute lymphocytic leukemias (B-ALL). Between 1981 and 1984, the nine-drug regimen was based on high-dose cyclophosphamide, high-dose methotrexate and cytosine arabinoside in continuous infusion (regimen LMB-81). No irradiation was performed. CNS prophylaxis was made by high-dose methotrexate and by intrathecal injections. No debulking surgery was recommended. Since 1984, considering the high rate of continuous remission, some modifications were made for reducing the duration and toxicity of the treatment of most B-cell lymphomas without CNS involvement (regimen LMB-84). For B-cell lymphomas with CNS involvement and B-ALL, an intensive high-dose multidrug combination was proposed (regimen LMB-86). Between 1981 and 1984, 153 children (stage II ORL: 6%, III: 63%, IV: 31%) were treated with the LMB-81 regimen. The overall disease-free survival rate is 69%. No relapse occurred after 12 months. Only two CNS relapses were observed. Among stage IV, a worse prognosis was associated with initial CNS involvement (disease free survival: 19%). On the contrary, bone marrow involvement was not an adverse prognostic factor. With the LMB-84, the overall disease free survival rate is 74%. A noteworthy reduction of toxicity is observed.

Actuarial Analysis↗

[Prognostic factors in rhabdomyosarcomas in childhood. Study carried out with 253 children registered by the International Society of Pediatric Oncology].

Two hundred and fifty three children with newly diagnosed nonmetastatic rhabdomyosarcoma, from 30 European centers, were registered by the International Society of Pediatric Oncology (SIOP) between 1975 and 1982, and received a VAC-VAD chemotherapy. Multivariate statistical methods were used to study prognosis. The most important predictors for survival time were as follows: primary site (P less than 0.001), clinical stage (P = 0.02), and sex (P = 0.03). Three primary sites had a favourable prognosis (vagina, paratestis, orbit) as opposed to the most unfavorable ones (parameningeal head and neck sites). Clinical state I had better survival curves than stages II and III. Males had a better prognosis than females, regardless of stage and primary site. The analysis of the evolutive modes of the tumour showed that the lack of local control (no complete remission, local recurrence) was the first reason of failure.

Adolescent↗

[Review of statistical procedures for determining the equivalency of two treatments].

The absence of a significant difference in a classical efficacy trial testing the null hypothesis of equality between N and S does not allow us to conclude that the treatments are equivalent. Testing the null hypothesis of N not equivalent to S requires: specifying the definition of "equivalence" by choosing delta L, the upper allowable value of the actual difference between two equivalent treatments. The appropriate statistic D which evaluates the difference between N and S, has a non central distribution under the null hypothesis of inequivalence (Ko:[E(D)] greater than or equal to delta L, two-sided test). Under the null hypothesis for a two-sided test, parameters of noncentral distribution have to be estimated, and the critical p-value is obtained using some approximation. Confidence interval of the true difference delta can also provide a decision rule. Specific calculation of the minimum number of subjects is required when designing an equivalence trial.

Antihypertensive Agents↗

Improved survival rate in children with stage III and IV B cell non-Hodgkin's lymphoma and leukemia using multi-agent chemotherapy: results of a study of 114 children from the French Pediatric Oncology Society.

Children with B cell non-Hodgkin's lymphoma who have not relapsed 1 year after diagnosis and treatment are generally cured. We report here the results of treatment in 114 children who all had a minimum follow-up of 20 months. The protocol LMB 0281 from the French Pediatric Oncology Society was used. This nine-drug intensive-pulsed chemotherapy was based on high-dose cyclophosphamide, high-dose methotrexate (HD MTX), and cytosine arabinoside (ara-C) in continuous infusion. CNS prophylaxis was with chemotherapy only. No local irradiation was performed. No debulking surgery was recommended. There were 72 patients with stage III lymphoma and 42 patients with stage IV lymphoma or B cell acute lymphocytic leukemia (B-ALL). Among those 42 patients, seven had CNS involvement alone, 21 had bone marrow alone, and 14 had both; 26 had greater than 25% blast cells in bone marrow, 14 of whom had blast cells in blood. The primary site of involvement was the abdomen in 90 patients, the Waldeyer Ring in nine, and various sites in eight; seven patients presented without tumor. Seventy-seven patients are alive with a median follow-up of 2 years and 8 months. Seven patients died due to initial treatment failure, 11 died from toxicity, and 19 died after relapse. Among the 93 patients without initial CNS involvement, only one isolated relapse in CNS occurred. Survival and disease-free survival rates reached 67% and 64%, respectively, for all patients, 75% and 73% for stage III patients and 54% and 48% for stage IV and B-ALL patients. Bone marrow involvement was not an adverse prognostic factor. Contrary initial CNS involvement indicated a bad prognosis with a disease-free survival rate of 19% compared with 76% without CNS disease. This study showed that CNS prophylaxis and local control of the primary tumor can be achieved by intensive chemotherapy alone, without radiotherapy or debulking surgery.

Adolescent↗

Primary chemotherapy in the treatment of rhabdomyosarcoma in children: trial of the International Society of Pediatric Oncology (SIOP) preliminary results.

This therapeutic trial deals with 81 patients with stage III rhabdomyosarcoma (RMS), from different centers of the International Society of Pediatric Oncology. These patients were included between October 1975 and March 1983. The aim of this work is to minimize the sequelae of treatment without jeopardizing the survival rate. After a pretrial course of VAC, two groups of patients are compared: the first treated with systematic extensive surgery or radiotherapy on the initial tumor volume, and the second treated with combined chemotherapy using vincristine, dactinomycin, adriamycin, cyclophosphamide until maximum tumor reduction, followed by radiotherapy or surgery on the residual mass only. Eighty one patients were included in the trail; 15 patients were not randomized due to the failure of the pretrial course of chemotherapy, 3 were excluded after randomization (2 were found not to have RMS, and in one case the protocol was not observed). The preliminary results for the 63 patients show a survival rate of 40% at 3 years. The sequential scheme for patients at 3 years follow-up does not show a superiority in either arm.

Adolescent↗

The advantages of preoperative therapy in Wilms' tumour. A summarised report on clinical trials conducted by the International Society of Paediatric Oncology (SIOP).

During 1971-1980, three consecutive clinical studies on nephroblastoma were conducted by the International Society of Paediatric Oncology (SIOP). Besides several questions on different postoperative treatment modalities, the emphasis of these trials was to determine the role of preoperative therapy. In SIOP-1 (1971-1974) we compared preoperative radiotherapy to immediate surgery. There is no difference in survival or recurrence-free survival between both groups. Tumour ruptures, however, did occur significantly less in the pretreated group, and the recurrence-free survival is clearly lower in patients with intraoperative tumour rupture. These results were confirmed by SIOP-2, a non-randomised study conducted between 1974 and 1976. The question tackled by SIOP-5 (1977-1980) was whether preoperative chemotherapy could be a substitute for preoperative radiotherapy. The two preoperative therapies produced equally satisfactory results in terms of recurrence-free survival and 4-year survival rates, and the reduction in the number of operative ruptures. In addition, it was shown that with preoperative chemotherapy about 45% of an unselected population of patients with Wilms' tumour can be treated and cured without any irradiation and its well-known sequelae. The actual need for radiotherapy in stage II tumours with negative lymph node involvement (about 30% of the patients after pretreatment) is under investigation in SIOP-6. Cytohistological grading is equally possible after chemotherapy, and also without pretreatment. If antitumour treatment is begun before histopathological diagnosis, then the risk of overtreating patients with benign conditions, or of administering an inappropriate treatment to patients with malignant tumours of other types, is about 6%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effectiveness of preoperative chemotherapy in Wilms' tumor: results of an International Society of Paediatric Oncology (SIOP) clinical trial.

The results of a controlled clinical trial of preoperative radiotherapy compared to chemotherapy in patients with nephroblastoma are presented. Of 397 histologically proven cases of Wilms' tumor registered at 34 centers between January 1977 and July 1979, 164 were eligible for the trial and were randomized to receive preoperative radiotherapy and chemotherapy (group R, 76 patients) or preoperative chemotherapy (group C, 88 patients). The results were evaluated in terms of the number of surgical tumor ruptures and of local tumor extent at pathologic examination, reflecting the effectiveness of the preoperative treatment. Survival and recurrence-free survival in the two treatment groups were also taken into account. The stage distribution was comparable in the two groups, with 52% stage I tumors in group R, and 43% in group C. Significant changes in the pathologic pattern were more frequent in group R than in group C (53% versus 17%). From these data it is concluded that preoperative chemotherapy is as good as preoperative radiotherapy in terms of prevention of tumor rupture. In addition, it was shown that 43% of an unselected population of patients with Wilms' tumor could be treated without any radiotherapy when chemotherapy had been given preoperatively.

Adolescent↗