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From 1984 to 1997, 57 consecutive patients with non-metastatic Ewing's sarcoma of the ribs were treated according to multimodal French Society of Pediatric Oncology (SFOP) protocols EW 84, EW 88 and EW 93. The results of treatment were reviewed and analysed. Median age was 12 years. 34 patients had large tumours (greatest tumour dimension > or = 8 cm); pleural effusion was noted in 26. A tumour-positive margin after surgery was noted in 15 patients. Histological response after chemotherapy was assessed in 34 patients. 34 patients received radiation therapy. With a median follow-up of 5 years, the projected overall and relapse-free survival rates were 69 and 62%, respectively. The major site of relapse was local. None of the following was significant in predicting relapse: tumour size, gender, age at diagnosis, existence of pleural effusion, level of rib tumour, rib component, type of local control, surgical margin (positive or negative). Response to chemotherapy was the sole significant prognostic factor (P=0.004). Patients with pleural effusion had a higher percentage of relapse if they were treated without local radiation therapy. Our study confirms the prognostic significance of response to initial chemotherapy. Radiation therapy may be withheld in selected cases, but seems necessary in patients with pleural effusion.

Unlabelled: This study evaluates histological response, long-term outcome, and toxicity in an intensive chemotherapy program given before surgery., Patients and Methods: Sixty-two patients (39 males, 23 females: median age 14) with biopsy, chest computerised-tomography, technetium bone-scan and magnetic resonance imaging, were enrolled. Primary localisations were femur (44%) and tibia (26%). Induction chemotherapy involved seven courses of high-dose methotrexate and two courses of HELP (ifosfamide, eldesine (vindesine), cisplatin (platinum)-doxorubicin. After surgery, patients received six courses of high-dose methotrexate and two courses of HELP-doxorubicin., Results: Pre- and postoperative toxicities were similar. Fifty-nine patients underwent surgery; histological response was good in thirty-eight patients (64%) and poor in twenty-one (36%). Median follow-up is 57 months (range 30-80), with 77% overall survival and 59% progression-free survival. In a multivariate analysis, age under 10 years is the only prognostic factor that significantly correlates with outcome., Conclusions: This regimen appears to increase histological necrosis, but associates with severe toxicity. Results for patients with less necrosis at surgery are encouraging. Future trials should determine the minimum effective doses to reduce toxicity. New drugs should be added.

Ewing's sarcoma is the second most common malignant bone tumor of childhood, yet it is a rare tumor. Primary maxillary localization is unusual and occur in only 1-2% of cases, mostly in the mandible. The prognosis of Ewing's sarcoma has been improving considerably since the introduction of combined modality treatment. The estimated overall survival at 4 years is 75%. It is widely accepted that prompt chemotherapy is necessary to treat occult micrometastasis, present in over 80% of cases at time of diagnosis, and to reduce the tumor size. Prognostic factors correlated with a poor overall survival are large tumor size and poor histologic response to initial chemotherapy. Adequate local control of Ewing's sarcoma can be achieved after chemotherapy, with radical or conservative surgery and radiotherapy. Surgery was recommended whenever possible. Radiation dosage and fields are based upon the quality of surgery and histological response to chemotherapy. Concern has been raised, however, regarding deleterious late effects of radiation in this young population. Conservative surgery and reconstruction are often used to improve functional outcome. We report four cases of Ewing's sarcoma localized to jaw bone and mandible, successfully treated by combined modality treatment.

Early detection of relapse has been advocated to improve survival in children with recurrent medulloblastoma. However, the prognostic factors and the longer term outcome of these patients remains unclear. Pattern of recurrences were analysed in three consecutive protocols of the Société Française d'Oncologie Pédiatrique (1985-91). A uniform surveillance programme including repeated lumbar puncture combined with computerized tomography (CT) or magnetic resonance imaging (MRI) scan was applied for all registered patients. Forty-six out of 116 patients had progressive or recurrent disease. The median time from diagnosis to recurrence was 10.5 months and 76% relapses occurred during the first 2 years. Seventeen patients had asymptomatic relapses that were detected by the surveillance protocol. Forty-one patients were treated at time of progression. Twenty-three responded to salvage therapy and 11 achieved a second complete remission. The median survival time after progression was 5 months (<1-41 months), and only two patients remained alive at time of follow-up. Length of survival is primarily related to some specific patterns of relapse (time from diagnosis to recurrence, circumstances of relapse, extent of relapse) and to the response to salvage therapy. No evidence of long-term benefit appeared from any form of treatment.

Ifosfamide is one of the most efficient antimitotic in soft tissue sarcoma. To try to find a possible dose-effect, 10 patients with advanced pretraited relapsed soft tissue sarcoma received 15 g/m2/cycle ifosfamide in continuous infusion during 5 days. A pharmacokinetic study was done for 2 patients. All patients received growth factors, ondansetron and 8 clonazepam. Renal toxicity was evaluated after the first and the second cycle. Twenty two cycles were delivered to patients who have been already treated with ifosfamid (10 patients with 15 g/m2 to 54 g/m2, median 27 g/m2) or cis platinum (2 patients). No major renal or neurologic toxicity was observed; only subclinical modifications of urinary enzymes excretion were found. Two patients had visual hallucinations at the end of a cycle and just in the 2 following days; another presented a neuropathy of inferior limbs. Hematological toxicity was very limited. Pharmacokinetic study did not show induction mechanism at this dosage and with this type of administration. So ifosfamide 3 g/m2 during 5 days is feasible. The few level of complications observed is perhaps linked to the daily dose of 3 g/m2 instead of 4 g/m2 or more used in the other studies.

The aim of this phase II study was to determine the efficacy of high-dose ifosfamide with moderate dose etoposide in childhood osteosarcoma. From January 1992 to January 1995, 27 children (15 male, 12 female) with relapsed or refractory evaluable osteosarcoma were included in a phase II study of two courses of ifosfamide 3g/m2/day and etoposide 75 mg/m2/day for 4 days. Median age was 14 years (7-19 years). All but one had received high-dose methotrexate and doxorubicin as first-line treatment. 22 patients had previously received ifosfamide. This regimen was given as first-line in 1 patient, second-line in 23 and third-line in 3. Evaluable disease was lung metastases in 21 patients, local relapse in 5 and adenopathy in 1. There were six complete responses, seven partial responses, three minor responses, six stable disease and five progressive disease (including one mixed response). Response rate was 48% (95% confidence interval, 29-67%). Duration of response was not available (10 responding patients had other treatments). Response rate was equivalent in the subgroup of 22 patients who had previously received ifosfamide (4 CR, 6 PR). Among 3 patients who received the phase II regimen as third-line chemotherapy, there was 1 PR. All but 4 patients had a well tolerated grade 4 neutropenia. Transient mild confusion or seizures were each observed once. 5 patients are alive 15-31 months after the beginning of chemotherapy. This combination of drugs at this dosage has tolerable toxicity, is efficient and deserves evaluation in phase III studies.

Atypical decubital fibroplasia (FAD) occurs especially in elderly and physically debilited or immobilized patients. We report one observation which is peculiar due to the patient's young age and its circumstances. The painless mass is situated in hyperpressure areas (shoulder, posterior or lateral chest wall, sacrum). The lesion is situated in the deep subcutis and has ill defined limits; it is characterized by zones of fibrinoid necrosis and fibrosis and a prominent myxoid stroma. The differential diagnoses includes mesenchymatous malignant tumors and non neoplastic fibroblastic proliferations such as proliferative fasciitis and decubitus ulcer. The prominent underlying factor and the initial event contributing to its pathogenesis seems to be ischemia. Although some recurrent cases have been reported, FAD is a benign lesion whose treatment is surgical removal.

Objective: The aim of this study was to know the wishes of our patients for information and to compare them with the point of view of our colleagues in a cancer center., Methods: We gave 100 consecutive new patients with breast cancer a questionnaire about their needs. The same questionnaire was given in duplicate to all our colleagues in the cancer center (n = 53) asking: 1) their own needs of information if they had breast cancer 2) how they thought the patients would answer., Results: Seventy-five percent of the patients and 81% of the doctors returned the questionnaire (28 were men and 15 women; 81% were involved in the management of breast cancer). On one hand, concerning information about the disease and about the treatment, there was no difference between the needs expressed by patients of doctors (as patients). As expected, the two groups wanted to be well informed. On the other hand, there was always a statistically significant difference between the needs expressed by patients and the opinion of doctors who systematically underestimated them. Concerning information to the family, 21% of doctors and only 4% of patients didn't want any information to be given to their family. Interestingly, 67% of the patients thought the decision had to be taken together with the doctor and 56% of the doctors (as patients) wished the decision to be taken by the doctor., Conclusion: Patients and physicians if they were patients, expressed the same high level need of information, but the patients needs seemed underestimated by the majority of doctors.

A prospective study about the development of the mandibular second right molar, has been performed with 17 chemotherapy treated children in the Paediatric Oncology department of the Centre Oscar-Lambret (Lille). Our method is based upon the measure of the crown or root length for different periods: periods with or without chemotherapy. These measurements have been performed every 6 months for 18 months with orthopantomograms. We notice for both the crown and the root: a significant difference in growing speed between periods with an without chemotherapy; a speeding up of the mineralization at the end of the treatment rejoining the average figures of a healthy test population.

Background: Medulloblastoma is a rare disease in adult patients, with an annual incidence rate of 0.05 per 100,000 per year. Results are, therefore, sparse and comprise small series over long periods. The real survival rate, the prognostic factors, the optimal postoperative radiation dose, and the role of adjuvant chemotherapy are still unknown for this disease in adults., Methods: The authors collected 156 cases of histologically proven medulloblastoma in patients older than 18 years of age who were treated between January 1975 and December 1991 in 13 French institutions. They analyzed the prognostic factors for survival and the impact of postoperative treatment on survival., Results: The 5- and 10-year event free survival rates, 61 and 48%, respectively, are similar to those observed in children. The median time to recurrence is 30 months, but late relapses after 5 years remain frequent. Multivariate analysis identified postoperative performance status, spinal axis radiation dose, fourth ventricular floor involvement, and desmoplastic histologic subtype as factors significantly correlated with event free survival. No benefit of concomitant chemotherapy was demonstrated, and complete resection resulted only in severely reduced postoperative performance status., Conclusions: The prognostic factors in adult medulloblastoma are comparable to those of medulloblastoma in children, but a new parameter, postoperative performance status, was identified in this adult series. Postoperative craniospinal irradiation remains the standard treatment for adults with medulloblastoma. A reduced dose to the supratentorial compartment should be tested in a prospective protocol.

Malignant germinal tumours of the thyroid gland are exceptional. Two cases are reported here. The first case concerned an 8-year old girl who had a teratoma; she was treated by surgery and adjuvant chemotherapy; 4 years after the diagnosis she is still alive and in complete remission. The second case is that of a 21-year old woman with a vitelline sac tumour treated by surgery and radiotherapy; she soon had lung metastases and died. The diagnostic, prognostic and therapeutic aspects of malignant germinal tumours of the thyroid gland are presented, together with data from a review of the literature. The authors insist on the importance of marker assays for all thyroid tumours with suspicious cytology. These tumours should be treated by surgery and initial chemotherapy combined, just as malignant germinal tumours located in other organs.

A serum assay of CA 549 (Hybri-BREScan CA 549 degrees, Hybritech), a new tumor marker, was performed in 129 patients with breast cancer and 35 healthy women, in parallel with CA 15.3 (ELSA-CA 15.3 degrees, CIS Biointernational). Comparing 95 women with primary breast carcinoma and 35 controls, Relative (or Receiver) Operating Characteristic (ROC) analysis revealed that the Area Under ROC Curve (AUC) of CA 15.3 was significantly higher than that of CA 549, indicating that, for our population, the first marker was more effective. Parallel and series analyses were also performed using ROC AUC and revealed that the combination of these two tests did not give more information than the CA 15.3 test alone; however, they did not in any way constitute diagnostic tools. In our experience, the best field of application for CA 549 seems to be the therapeutic monitoring and early detection of breast cancer recurrences. However, further investigations on a larger scale are necessary to assess more precisely the place of CA 549 in following the clinical course of breast cancer patients.

14 adult patients between 16 and 50 years old with small non-cleaved cell lymphoma (Burkitt's lymphoma) were prospectively treated from 1982 to 1990 with the LMB protocols of the Société Française d'Oncologie Pédiatrique (SFOP). No HIV-positive patients were included. All patients had extensive disease with bad prognosis factors, i.e. 10 patients had Murphy stage III and 4 had stage IV with bone marrow involvement. The LMB protocols were characterised by high-dose fractionated cyclophosphamide, high-dose methotrexate (HD-MTX), and cytosine arabinoside. No local or central nervous system irradiation was used. Treatment duration ranged from 5 (LMB 84) to 12 (LMB 81) months. There were no therapy-related deaths. All patients achieved complete remission (CR). 6 patients relapsed between 2 and 30 months following CR. 8 of the 14 patients (57%) are still alive and disease-free after treatment by LMB protocol alone. 2 patients were salvaged with bone marrow transplantation after relapse and a total of 10 out of 14 patients (71%) are disease-free at the time of this report. Our results showed the high curability of advanced Burkitt's lymphoma using a paediatric protocol, even in adult patients. The LMB protocol may be applied to adult patients but requires intensive care during the induction period.

Twenty-five children or adolescents with relapsed or refractory non-Hodgkin's lymphoma (NHL) were included in this phase II study of the combination of cytarabine (ARA-C) 50 mg/m2/d by 12 hours continuous infusion day 1 to day 5, ARA-C 3 g/m2/d in 3 hours day 1 to day 4, and etoposide (VP 16) 200 mg/m2 daily from day 1 to day 4. Twelve patients had B-cell, 12 T-cell, and one non-T, non-B-cell lymphoma; according to Murphy's staging system, 15 had stage III and nine stage IV disease with bone marrow involvement at diagnosis. All had previously received ARA-C by push or continuous infusion. Two patients had received epipodophyllotoxins. At the time of the study, three children had initial refractory disease, 18 were in first relapse (14 on therapy), two in first refractory relapse, and two in second relapse (on therapy). The overall response rate (RR) was 60%: eight complete responses (CRs), seven partial responses (PRs) (two became CRs after a second course). The RR was 66% (four CRs plus four PRs) in B-cell and 54% (four CRs, three PRs) in non-B-cell NHL. It was 20% (one PR per five patients) in initial or relapsed refractory disease. In four patients with measurable CNS disease, there were three CRs. Duration of response was nonassessable since all the responding patients received high-dose polychemotherapy followed by autologous bone marrow transplantation (ABMT) (five are alive with long follow-up [FU]). Toxicity was marked mostly by pancytopenia for 2 weeks, and half the patients encountered a grade-3 infection. One severe diarrhea was observed. In conclusion, high-dose ARA-C (HD-ARA-C) and VP 16 are an effective regimen in relapsed NHL, especially with CNS disease, and its toxicity is acceptable with regards to the prognosis of the disease.

The marker CA-125 is not specific of malignant ovarian tumors but, when its titration is positive, its evolution permits to follow correctly the development of the tumor. The authors report their experience with 180 titrations coupled with the titration of inflammation markers.

From 1970 to 1982, 79 cases of nasopharyngeal carcinomas were treated at the Regional Cancer Center of Lille (France). At the term of the study, it appears that patients of Central Europe origin have a rather high risk of NPC (17% of cases, that ethnic population representing about 8% of all superior aerodigestive tract carcinomas). The classical differences between well and undifferentiated tumors are founded, the first presenting local spread the other general involvement.

The authors treated 188 patients with osteosarcoma by chemotherapy followed by surgery and additional chemotherapy (Rosen's T regimen). In 14% of cases, infectious, neurologic or cardiac complications were observed, which resulted in death in 2% of the patients. Forty-six per cent responded well to the primary chemotherapy, 76% of which are alive and disease-free, as opposed to merely 42% of the bad responders.

In this paper we apply decision theory to evaluate the efficiency of diagnostic procedures. In the case we discuss, we compute the value of scintigraphy and radiography used separately or in combination in the diagnosis and treatment of bony metastases after breast cancer.

The main tumor markers used in breast and gynaecological neoplasias are reviewed with their individual characteristics: carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP), chorionic gonadotropin hormone (CGH), CA 125, CA 15.3 and Squamous Cell Carcinoma Antigen (SCC). Their indications are specified according to the following cancer locations: breast, trophoblast, ovary, endometrium and cervix. The major clinical applications of the tumor markers routinely used are emphasized.

Eight cases of malignant melanoma developed during childhood have been recorded over a 35-year period. Treatment and course of the disease were extremely variable. Melanomas developed on giant pigmented naevi had a particularly somber prognosis: death occurred within 6, 7 and 3 months respectively in the 3 cases observed. In the 5 remaining cases, the course of the melanoma seemed to be about the same as in adults. The main difficulty resides in the clinical and histopathological diagnosis at that age: although most lesions are benign, uncertainty is not permissible, and in doubtful cases the tumour must be rapidly removed and examined.

Forty cases of carcinoma in situ of the cervix were seen in the "Center Oscar Labret" of Lille between 1953 and 1978. The best treatment appears to be only simple total hysterectomy. Twenty patients underwent such an operation. seven In the course attended of follow-up, among 36 patients who regularly the out-patient clinic, there was one case of persistent progression and one early vaginal recurrence of the carcinoma in situ.

Peripheral lymphocyte chromosomes were analyzed in 55 consecutive patients with complete remission after treatment for Hodgkin's disease. In 8 patients, observed metaphases were too few in number. The other 47 patients, 29 men and 18 women, had been off all therapy for 53 months (median 41, ext. 1 to 250 months). The mean interval since the diagnosis was 78 months (median: 73 months) and the mean age at the time of chromosome analysis was 38 years (median: 34, ext. 10-78 years). No patient had either a preleukemic syndrome or leukemia. In contrast to karyotypes in normal controls and previously untreated patients, abnormal cells, hypodiploid, hyperdiploid and tetradiploid cells were more frequent. But neither monosomy 5 or 7 nor trisomy 8 were observed. Intrachromosomal rearrangements (gaps, breaks...) were significantly more frequent (12% vs 5% in untreated patients) particularly on chromosomes 1 and 2. Interchromosomal rearrangements were also numerous (1,25%) but no cells showed any specific translocation for malignant hemopathy. Chromosomal aberrations do not seem closely associated with treatments but influenced by the post-diagnosis interval and the factors present at the time of primary treatment.

The steroid receptor (ER, PgR) content of breast cancer specimens is now widely used as an indicator for hormone sensitivity which is a prerequisite for endocrine therapy. Is it conceivable to extend this steroid receptor determination to other types of tumors in order to select patients who would eventually benefit from an hormonal therapy? It seems that most normal or tumoral tissues contain detectable amount of steroid receptors. The values of each receptor comprise a continuum from very low to relatively high, suggesting that previous considerations of hormone dependence on the basis of presence or absence of hormone receptors may be oversimplified. The steroid receptor concentrations are however higher in target tissues, and could be of clinical interest in endometrium and prostatic cancers. The date are however insufficient to draw firm conclusions regarding their usefulness for treatment.

The authors report a series of 120 cerebellar medulloblastomas. All patients were operated on between 1953 and 1982. Among them, 88 completed the treatment with radiotherapy, and 32 had additional chemotherapy. The operative mortality was 22.5%. The 5-year survival rate was 30% in the whole series. Recurrences occurred in 35 patients, associated with supratentorial or spinal metastasis in 60% of cases.

Ninety-five children with localized Ewing's sarcoma were included in a prospective cooperative study. All patients received initial chemotherapy with the purpose of early prevention of metastases and improvement of the conditions of the subsequent local therapy, radiotherapy in all cases, surgical resection in selected cases. Clinical response to initial chemotherapy was evaluated in 67 patients who had measurable soft tissue mass or functional symptoms. This response appeared highly correlated with outcome as the disease-free survival was 57.3% for the 41 good responders and 9% for the 26 bad responders (P less than 0.00001), though 23 of these bad responders reached complete remission with radiotherapy. This study also confirms the prognostic significance for survival of the site of the primary tumor on axial skeleton or on limbs. Nevertheless, this factor had no predictive value for response to chemotherapy, which thus appears to be an independent factor.

A series of 132 female patients with carcinoma of upper respiratory and digestive tracts, and examined successively, is reviewed. The mean age of the group was sensibly higher than that of the group of male patients used as reference. Progressive stages of the disease were similar in the female and male groups. The must frequent localization was buccopharyngeal, naso-sinusal and nasopharyngeal lesions being observed more frequently than in men. Alcohol and smoking were perhaps less important factors in women. Overall prognosis was better in the female group. Detailed epidemiologic surveys involving. This population would appear to be essential.

In order to define the influence of intraarterial administration of cis-platinum in tumors of the cervix, a preliminary crossover study was performed to measure and compare the intratumoral concentrations (ITC) of platinum obtained respectively after intravenous (iv) and intraarterial (ia) (both bilateral hypogastric arteries) injection. The results in nine patients demonstrate that higher (P = 0.05) intratumoral concentrations are obtained after intraarterial injection of cis-platinum: 10; 3.7-23.7 ng Pt/mg of dry tissue after ia (median; range) 6.9; 4.1-23.6 ng Pt/mg tissue after iv. This difference is probably too small to be of clinical significance and a comparative clinical trial does not seem to be warranted. The results also show a large intersubject variation in intratumoral platinum concentration which are reproducible in patients whatever route of administration is used. Thus the observed differences in ITC are more related to the variability of the tumor properties than to the route of administration.

Intratumoral (cervix uterine tumors) distribution of platinum was studied in ten patients after IV administration of CDDP. Sequential tumoral measurement of platinum was carried out 4, 24, and 48 h after the IV infusion. Platinum concentration in the tumor samples ranged from 0 to 29,5 ng/mg tissue. For all patients, there was no definite evolution of the tumoral concentration with time and there was no good relation for the same patient between the platinum concentration in three successive biopsies. These results involve uncertainty in studies attempting to relate CDDP tumor levels (measured in one biopsy) and tumor response to chemotherapy.

Multiple osteosarcoma is a rare tumour which usually has a poor prognosis. We report the case of a 14-year old girl who developed successively, at 2 1/2 years' interval, one osteosarcoma of the right radius bone, then one of the left radius bone. The tumours were strictly symmetrical. Each time, the patient was treated with chemotherapy of the Rosen type and underwent conservative surgery. At present, 5 years after the first treatment, she is in good health. This case is remarkable on several scores: chemotherapy was feasible and well tolerated, the multiple osteosarcoma had a favourable outcome, and conservative surgery of both radius bones gave satisfactory functional results.

The squamous cell carcinoma (SCC) antigen was assayed by radioimmunoassay in patients with squamous cell carcinoma of the uterine cervix at different stages before any treatment and in patients under treatment. Low levels of SCC antigen were detected in the early stages of the disease, showing that this antigen cannot be considered an aid to diagnosis. In the more advanced cancers, an increase of SCC antigen levels proportional to the stage of the disease was observed. However, SCC antigen assays are mainly useful in the follow-up of patients to evaluate therapeutic effectiveness.

The authors report a series of 17 non-seminomatous malignant germ cell tumours of the gonads in children, seen over a period of 18 years. 10 of these tumours were located in the ovaries and 7 were testicular. These are rare tumours with a highly polymorphous histological appearance. The overall 3-year survival was 10 (15 girls and 5 boys) out of 17. Choriocarcinomas and stage IV tumours have a very poor prognosis. Among the testicular tumours, the embryonal tumours have the most reserved prognosis. Whether the tumour arises in the ovary or in the testis, surgery is essential in order to define the therapeutic strategy.