Non-metastatic Ewing's sarcoma of the ribs: the French Society of Pediatric Oncology Experience.

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.

High-dose methotrexate and HELP [Holoxan (ifosfamide), eldesine (vindesine), platinum]--doxorubicin in non-metastatic osteosarcoma of the extremity: a French multicentre pilot study. Fédération Nationale des Centres de Lutte contre le Cancer and Société Française d'Oncologie Pédiatrique.

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 of the jaw. The value of multidisciplinary management. Apropos of 4 cases]. / Sarcome d'Ewing des maxillaires. Intérêt d'une prise en charge multidisciplinaire. A propos de 4 cas.

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.

Improving survival in recurrent medulloblastoma: earlier detection, better treatment or still an impasse?

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.

[High dose ifosfamide at 15 g/m2/cycle: a feasibility study in 10 patients]. / L'ifosfamide à hautes doses 15 g/m2/cure. Etude de faisabilité chez 10 patients.

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.

Ifosfamide and etoposide in childhood osteosarcoma. A phase II study of the French Society of Paediatric Oncology.

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 decubitus fibroplasia: a recent entity. Apropos of a case of an adolescent girl]. / La fibroplasie atypique de décubitus: une entité récente. A propos d'un cas chez une adolescente.

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.

[Breast neoplasms: information in question(s). A survey of patients and physicians at a cancer treatment center]. / Cancer du sein: l'information en question(s). Enquête auprès des patientes et des médecins d'un Centre de lutte contre le cancer.

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.

[Chemotherapy and dental growth]. / Chimiothérapie et croissance dentaire.

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.

Multivariate analysis of prognostic factors in adult patients with medulloblastoma. Retrospective study of 156 patients.

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 tumors of the thyroid. 2 cases]. / Tumeurs germinales malignes de la thyroïde 2 observations.

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.

An evaluation of CA 549, a circulating marker of breast cancer using a procedure for comparison with CA 15.3.

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.

Treatment of poor prognosis Burkitt's lymphoma in adults with the Société Française d'Oncologie Pédiatrique LMB Protocol--a study of the Federation Nationale des Centres de Lutte Contre le Cancer (FNLCC).

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.

Phase II study of cytarabine and etoposide in children with refractory or relapsed non-Hodgkin's lymphoma: a study of the French Society of Pediatric Oncology.

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.

[Mirror-image osteosarcoma of the radius. A case]. / Ostéosarcome en miroir du radius. Une observation.

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.

Comparative study of intravenous and intraarterial cis-platinum on intratumoral platinum concentration in carcinoma of the cervix.

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.

[The place of tumor markers in breast and gynecologic neoplasms]. / Place des marqueurs tumoraux dans les néoplasies mammaires et gynécologiques.

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.