[Panniculectomy as first part of colorectal resection for cancer in a morbidly obese patient]. / La panniculectomie première comme voie d'abord dans la résection colorectale pour cancer chez le grand obèse.

We reported the case of a patient presenting a rectal cancer of the upper part with a BMI at 59 which was previously considered as a contraindication to surgery. To perform the operation we had to make as first step of the procedure a panniculectomy. The technique made possible the rectal resection under good conditions, without blood transfusion. The post-operative course was uneventful except a pulmonary embolism controlled with medical treatment. This procedure is feasible in colorectal surgery.

Soft tissue sarcoma or malignant mesenchymal tumors in the first year of life: experience of the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Committee.

PURPOSE: To describe the outcome of infants with a histologically confirmed diagnosis of malignant mesenchymal tumor (MMT) included in the International Society of Paediatric Oncology studies MMT 84 and MMT 89. PATIENTS AND METHODS: One hundred two infants (< or = 12 months old) were included. Twenty-four children were less than 3 months old, and 16 were less than 1 month old. Sixty-four patients had rhabdomyosarcoma (RMS), 26 had undifferentiated sarcoma, and 12 had other histology. Clinical TNM stage was stage I (41%), II (39%), III (6%), and IV (14%). First-line treatment was ifosfamide, vincristine, dactinomycin, whereas the second-line combination consisted of either cisplatin and doxorubicin (in MMT 84) or vincristine, carboplatin, etoposide/teniposide (in MMT 89). Chemotherapy doses were adapted to age. Local therapy was conservative surgery as often as possible. RESULTS: After a median follow-up of 7.8 years (range, 0.1 to 13 years), 5-year overall survival (OS) and event-free survival rates were 66% and 55% for the total study population and 72% and 60% for nonmetastatic patients, respectively. Only two of 13 stage IV patients survived. Sixty-seven percent of newborn infants survived. Infants with alveolar subtype had a poorer survival than those with non-RMS MMT or nonalveolar RMS (5-year OS, 37% v 75% or 82%, respectively; P = .002). When compared with older children with MMT, young age does not seem to be an important prognostic factor. CONCLUSION: OS was satisfactory even when local treatment was not aggressive, although the prognosis was poor for infants with alveolar RMS or metastatic tumors. Chemotherapy toxicity was manageable with appropriate dose modification.

No topoisomerase I alteration in a neuroblastoma model with in vivo acquired resistance to irinotecan.

CPT-11 (irinotecan) is a DNA-topoisomerase I inhibitor with preclinical activity against neuroblastoma (NB) xenografts. The aim was to establish in vivo an NB xenograft resistant to CPT-11 in order to study the resistance mechanisms acquired in a therapeutic setting. IGR-NB8 is an immature NB xenograft with MYCN amplification and 1p deletion, which is sensitive to CPT-11. Athymic mice bearing advanced-stage subcutaneous tumours were treated with CPT-11 (27 mg kg(-1) day(-1) x 5) every 21 days (1 cycle) for a maximum of four cycles. After tumour regrowth, a new in vivo passage was performed and the CPT-11 treatment was repeated. After the third passage, a resistant xenograft was obtained (IGRNB8-R). The tumour growth delay (TGD) was reduced from 115 at passage 1 to 40 at passage 4 and no complete or partial regression was observed. After further exposure to the drug, up to 28 passages, the resistant xenograft was definitively established with a TGD from 17 at passage 28. Resistant tumours reverted to sensitive tumours after 15 passages without treatment. IGR-NB8-R remained sensitive to cyclophosphamide and cisplatin and cross-resistance was observed with the topoisomerase I inhibitor topotecan. No quantitative or qualitative topoisomerase I modifications were observed. The level of expression of multidrug resistance 1 (MDR1), MDR-associated protein 1 (MRP1) and, breast cancer resistance protein, three members of the ATP-binding cassette transporter family was not modified over passages. Our results suggest a novel resistance mechanism, probably not involving the mechanisms usually observed in vitro.

Bilateral germ-cell tumours: 22-year experience at the Institut Gustave Roussy.

The aim of this study was to describe the incidence, clinical and histological characteristics, treatment and long-term follow-up of bilateral germ-cell tumours (BGCT) of the testis in order to determine in what respects they differ significantly from unilateral germ-cell tumours. In all, 31 patients with BGCT had metachronous tumours and 14 had synchronous tumours. Among the metachronous tumours, 61% occurred more than 5 years after the first tumour. The overall incidence of BGCT in patients with testicular germ-cell tumours (TGCT) was 1.9%. The incidence was 3.2% in patients presenting with a seminoma and 1.4 % in patients presenting with a nonseminomatous germ-cell tumour (NSGCT). Patients under 30 years of age at the time of the initial diagnosis had a higher incidence of bilateral tumours compared with older men. The outcome of BGCT was excellent. A high association was found between BGCT, sterility and suspected genetic risk factors for TGCT. These results argue against a systematic contralateral biopsy at diagnosis of first TGCT in all patients, but emphasise the importance of patient education and of the need to better identify patients at risk for a second TGCT. Therapeutic indications for synchronous BGCT, including conservative treatment, need to be better defined.

Lymphocyte-predominant Hodgkin's lymphoma in children: therapeutic abstention after initial lymph node resection--a Study of the French Society of Pediatric Oncology.

PURPOSE: To clarify treatment strategy for lymphocyte-predominant Hodgkin's lymphoma (LPHL), the French Society of Pediatric Oncology initiated a prospective, nonrandomized study in 1988. Patients received either standard treatment for Hodgkin's lymphoma or were not treated beyond initial adenectomy. PATIENTS AND METHODS: From 1988 to 1998, 27 patients were available for study. Twenty-four patients were male, and median age was 10 years (range, 4 to 16 years). Twenty-two, two, and three patients had stage I, II, and III disease, respectively. Thirteen patients (stage I, n = 11; stage III, n = 2) received no further treatment after initial surgical adenectomy (SA). Fourteen patients received combined treatment (CT; n = 10), involved-field radiotherapy alone (n = 1), or chemotherapy alone (n = 3). The two groups were comparable for clinical status, treatment, and follow-up. RESULTS: Twenty-three of 27 patients achieved complete remission (CR). With a median follow-up time of 70 months (range, 32 to 214 months), overall survival to date is 100%, and overall event-free survival (EFS) is 69% +/- 10% (SA, 42% +/- 16%; CT, 90% +/- 8.6%; P <.04). If we considered only the patients in CR after initial surgery (n = 12), EFS was no longer significantly different between the two groups. Patients with residual mass after initial surgery (n = 15) had worse EFS if they did not receive complementary treatment (P <.05). CONCLUSION: Although based on a small number of patients, our study showed that (1). no further therapy is a valid therapeutic approach in LPHL patient in CR after initial lymph node resection, and (2). complementary treatment diminishes relapse frequency but has no impact on survival.

Doxorubicin and ifosfamide in patients with metastatic sarcomatoid renal cell carcinoma: a phase II study of the Genitourinary Group of the French Federation of Cancer Centers.

PURPOSE: We assessed the efficacy and toxicity of a chemotherapy regimen combining doxorubicin and ifosfamide in patients with metastatic sarcomatoid renal cell carcinoma. MATERIALS AND METHODS: Of the 25 patients included in a prospective multicenter phase II trial 23 were evaluable for efficacy and toxicity studies after pathological review. RESULTS: A median of 3 cycles per patient (range 1 to 8) was administered. No objective response was observed. Median time to progression was 2.2 months and median overall survival was 3.9 months. A single patient died of toxicity. CONCLUSIONS: The results do not support the standard use of doxorubicin/ifosfamide chemotherapy in patients with metastatic sarcomatoid renal cell carcinoma.

Non-Hodgkin's lymphoma of the testis: a retrospective study of 84 patients treated in the French anticancer centres.

Primary non-Hodgkin's lymphoma of the testicle is rare. We analysed cases treated in French anticancer centres from 1969 to 1995. All cases were reviewed and classified according to the R.E.A.L. Classification. Eighty-four cases were included in this study. The median age was 67 years (17-85). Disease was classified as stages I in 42 cases, stages II in 19 and stages III-IV in 23. Diffuse large B-cell lymphoma was diagnosed in 75% of cases. Treatment included orchidectomy and radiotherapy and/or chemotherapy. A complete response was obtained in 72.6% of the patient population and in 100%, 68% and 33% of stage I, II and III-IV disease respectively. Recurrence occurred in 32 cases and the most frequent site was the central nervous system: six of these patients presented stage I disease. Median overall survival was 32 months for the entire population, 52 months for stage I, 32 months for stage II, and 12 months for stage III-IV cases (P < 0.0001). Among patients presenting stage I disease, no difference was found between those treated with combined surgery and chemotherapy or surgery followed or not followed by radiotherapy. This study confirms that non-Hodgkin's lymphoma of the testicle carries a poor prognosis. Systemic adjuvant chemotherapy should be discussed because of the high recurrence rate. Inclusion of these cases in large co-operative prospective studies is recommended.

Patterns of specific genomic alterations associated with poor prognosis in high-grade renal cell carcinomas.

A series of 13 sporadic renal cell carcinomas was analyzed for the specific chromosome rearrangements after serial xenografting into immunodeficient mice. Seven tumors displayed genetic traits of the conventional subtype and 5 showed genetic features of the papillary subtype. In all the xenografted conventional tumors, we observed loss of 3p, as well as loss of the 9p21 region and of the long arm of chromosome 14, both considered as markers of a poor prognosis. In the xenografted papillary tumors, a duplication of chromosome arm 8q was observed concomitant with the duplication of the 7q31 region. The association of the 7q31 and 8q22 approximately qter duplicated regions was also observed for one conventional tumor. The latency of tumor take was found to be reduced and the median time to passage statistically shorter for all tumors which presented the associated duplication of the 7q31 and 8q22 approximately qter regions. The proto-oncogene NOV (nephroblastoma overexpressed gene) maps to 8q24.1 and is overexpressed in some Wilms tumors. It could be an interesting candidate gene, since its level of expression and release in the culture medium was found to be increased in all of the fast growing tumors analyzed.

Genomic and allelic expression status of the p73 gene in human neuroblastoma.

BACKGROUND AND PROCEDURE: The p53 gene homologue, p73, is located on the 1p36-3 locus, which is frequently deleted in human neuroblastoma (NB). A survey of 61 NB showed that among 33% of informative cases, p73 loss of heterozygosity (LOH) occurred in 7 of 20 (35%). RESULTS: LOH pattern of vicinal markers suggested that the p73 gene could not be considered as the candidate NB suppressor gene. Moreover, comparative measurements of allelic expression in tumors and corresponding patient lymphocytes indicate that pure biallelism is much more frequent in lymphocytes than in tumors (71% vs 30%, P= 0.05), which suggests that disequilibrated allelic expression is associated with NB disease. CONCLUSION: Therefore, in the p73 LOH NBs, the p73 gene could be altered in the maintained allele not by mutations [Ishimiya et al.: Med Pediatr Oncol, this issue], but rather by an abnormal transcription.

In vivo elimination of acentric double minutes containing amplified MYCN from neuroblastoma tumor cells through the formation of micronuclei.

Neuroblastoma, the most common solid extracranial neoplasm in children, shows an appreciable variability in clinical evolution. Amplification of the MYCN oncogene in this tumor is detected in 25 to 30% of cases and is associated with poor clinical outcome. In this study, quantitative polymerase chain reaction and fluorescence in situ hybridization were used to determine MYCN amplification status in 46 neuroblastoma tumors. MYCN amplification was detected in tumors from 11 patients. Fluorescence in situ hybridization revealed the presence of micronuclei containing amplified MYCN sequences in 8 of the 11 tumors. Micronuclei are indicative of spontaneous elimination or loss of amplified sequences by tumor cells. Because the elimination of amplified sequences can be enhanced in vitro by specific drugs such as hydroxyurea, our observations suggest a new therapeutic strategy specifically targeted to cells with amplified genes.

Association between germ cell tumours, large numbers of naevi, atypical naevi and melanoma.

Identifying groups of subjects at high risk for the development of melanoma is crucial for the early diagnosis of curable tumours. In the present study, we performed a skin examination in a group of 63 patients followed up after treatment of germ cell tumours (GCTs) who were referred to the dermatologist for multiple pigmented cutaneous spots. Forty-nine patients bearing a great number of naevi or atypical naevi were included in the study. Two thin cutaneous melanomas were discovered in two patients. In addition, a third patient had had a conjunctival melanoma since treatment of the GCT. Our study confirms the presence of atypical naevi in a subgroup of GCT patients, who are shown to be at high risk of developing melanoma. Patients harbouring multiple pigmented spots should be referred for a skin examination aimed at early detection of curable melanomas, and should be advised to protect themselves from sun exposure.

The Société Française d'Oncologie Pédiatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia.

This study was undertaken to show that a high survival rate can be obtained in B-cell (Burkitt and large B-cell) lymphoma and L3 leukemia with multiagent chemotherapy adapted to the tumor burden (stage, resection status, percentage of blasts in bone marrow, and central nervous system [CNS] involvement) and early response to chemotherapy, to investigate actual prognostic factors, and to see if large B-cell lymphoma can be treated with the same regimen as Burkitt lymphoma. Patients were classified into 3 risk groups. Group A (resected stage I and abdominal stage II) received 2 courses of vincristine, cyclophosphamide, doxorubicin, and prednisone. Group B (patients not eligible for groups A or C) received 5 courses of chemotherapy with, in addition, high-dose methotrexate, 3 g/m(2) over 3 hours; infusional cytarabine; and intrathecal (IT) methotrexate. Group C (patients with CNS involvement and acute lymphoblastic leukemia with at least 70% of blasts in bone marrow) received 8 courses with, in addition, high-dose methotrexate, 8 g/m(2); high-dose cytarabine; etoposide; and triple IT. Except in group A, treatment started with a prephase (COP, low-dose vincristine and cyclophosphamide). It was intensified for patients who did not respond to COP in group B and any patient with residual viable cells after the consolidation phase. A total of 561 patients were enrolled in the SFOP LMB89 protocol (July 1989-June 1996). Five-year survival is 92.5% (95% confidence interval [CI], 90%-94%) and event-free survival (EFS) 91% (95% CI, 89%-93%). EFS is 98% (95% CI, 90%-100%), 92% (95% CI, 89%-95%), and 84% (95% CI, 77%-90%) for group A, B, and C, respectively. In group B, multivariate analysis of prognostic factors showed that a lactate dehydrogenase level more than 2-fold the normal value, no response after COP, and age of at least 15 years were associated with a lower EFS. CNS involvement was the only prognostic factor in group C. (Blood. 2001;97:3370-3379)

Stage I non-seminomatous germ-cell tumours of the testis: identification of a subgroup of patients with a very low risk of relapse.

There is no consensus about a reproducible prognostic model capable of distinguishing between clinical stage I non-seminomatous germ cell tumour (NSGCT) carrying a high and low risk of relapse. The aim of this study was to assess the prognostic value of histological parameters in patients with stage I NSGCT undergoing surveillance after orchiectomy. We retrospectively evaluated tumour specimens from 88 consecutive stage I NSGCT patients undergoing surveillance in our institution between 1984 and 1996. 24 patients relapsed (27%). Multivariate analysis singled out vessel invasion (VI) (relative risk (RR)=3.8; 95% confidence interval (CI) 1.4-10.4) and the presence of mature teratoma (RR= 0.2; 95% CI 0.1-0.6) as independently correlated with relapse-free survival (RFS). Patients can be classified accordingly into three prognostic groups with a low (27 patients with mature teratoma but without VI), intermediate (34 patients with both VI and mature teratoma or with neither VI or mature teratoma) and a high risk (23 patients with VI, but without mature teratoma) of relapse. Relapse rates in these three groups were 0%, 29% (95% CI: 23-35%) and 61% (95% CI: 55-67%), respectively. This prognostic index, based on two standard pathological parameters, identified a subgroup with a very low risk of relapse that represents approximately one third of stage I patients. Patients who belong to this subgroup should be managed by surveillance only, instead of retroperitoneal lymph node dissection (RPLND) or adjuvant chemotherapy.

[Standards, options, and recommendations for radiotherapy of kidney cancer]. / Standards, Options et Recommandations pour la radiothérapie du cancer du rein.

CONTEXT: The "Standards, Options and Recommendations" (SOR), initiated in 1993, is a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary expert group, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for the diagnosis, management and treatment of patients with renal cancer. This review is part of previously published complete guidelines and focuses on the place of radiotherapy in this disease. METHODS: The data was identified by literature search using Medline (up to June 1999) and personal reference lists. The main endpoints considered were survival, risk factors for late effects of radiotherapy, safety and quality of life. RESULTS: The key recommendations are: 1) In localised renal cancer, adjuvant radiotherapy has a limited role: it is not indicated for T1 and T2 tumours and there is no proof of a survival benefit for T3 N1-N2 tumours. Postoperative radiotherapy can be considered in young patients without risk factors for the development of post-radiotherapy complications and without loco-regional invasion (renal capsule, renal pelvis, vena cava, regional lymph nodes); 2) For metastatic tumours, the multidisciplinary team must decide whether palliative radiotherapy is appropriate after consideration of the prognostic factors. An isolated metastasis can be treated by radiosurgery and stereotaxic radiosurgery may be of benefit in the case of one or two cerebral metastasis. The optimal dose for palliative treatment is not known. Radiotherapy followed by immunotherapy can also be considered if the patient has no contraindication to such treatments.

Immunohistochemical expression of WT1 by desmoplastic small round cell tumor: a comparative study with other small round cell tumors.

Desmoplastic small round cell tumors (DSRCTs) present a reciprocal chromosomal translocation, t(11;22)(p13;q12), that results in fusion of Ewing's sarcoma and Wilms' tumor (WT1) genes. The authors evaluated 15 DSRCTs and 71 other tumors often considered in the differential diagnosis for immunoreactivity using a polyclonal antibody directed against the WT1 part of the chimeric protein resulting from this translocation. WT1 immunostaining was performed on paraffin material using the WT(C-19) antibody after heat-antigen retrieval. All the DSRCTs (15 of 15, 100%) demonstrated strong WT1 nuclear immunoreactivity. Ten of 14 nephroblastomas (71%) disclosed WT1-positive nuclei in accordance with the staining reported by others, and rare and focal nuclear positivity was detected in two of 17 rhabdomyosarcomas. WT1 immunoreactivity was not observed in Ewing's sarcoma/primitive neuroectodermal tumors (zero of 21, 0%), neuroblastomas (zero of 17, 0%), or rhabdoid tumors of the kidney (zero of two, 0%). In nephroblastoma, differential diagnosis with DSRCT was not difficult: Clinical and morphologic data are not similar for these two entities. The current study validates WT1 immunoreactivity as a useful marker to separate DSRCT from other small round cell tumors.

Localized childhood Hodgkin's disease: response-adapted chemotherapy with etoposide, bleomycin, vinblastine, and prednisone before low-dose radiation therapy-results of the French Society of Pediatric Oncology Study MDH90.

PURPOSE: The French Society of Pediatric Oncology MDH82 study demonstrated the effectiveness of 20 Gy irradiation of involved fields after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, vincristine, procarbazine, and prednisone/ABVD chemotherapy in children with localized Hodgkin's disease (HD). The response to primary chemotherapy was the only predictor of survival. To reduce long-term treatment complications without compromising efficacy, the MDH90 study was based on a new chemotherapy regimen devoid of both alkylating agents and anthracycline, followed by 20 Gy of radiotherapy (RT) for good responders. PATIENTS AND METHODS: From January 1990 to July 1996, 202 children were enrolled from 30 institutions. Good responders to four cycles of vinblastine, bleomycin, etoposide (VP16), and prednisone (VBVP) were given 20 Gy of RT and no further therapy. Poor responders were given vincristine, procarbazine, prednisone, and doxorubicin. After a second evaluation, good responders were given 20 Gy of RT, and poor responders were given 40 Gy of RT. RESULTS: One hundred seventy-one patients (85%) were good responders to VBVP, 27 (15%) were poor responders, and four did not respond. With a median follow-up of 74 months (range, 25 to 117 months), the 5-year overall survival rate (mean +/- SD) is 97.5% +/- 2.1%, and the event-free survival rate (mean +/- SD) is 91.1% +/- 1.8%. Significant predictors of worse event-free survival in multivariate analysis were hemoglobin < 10.5 g/L, "b" biologic class, and nodular sclerosis. CONCLUSION: These results suggest that most children with clinical stage I and II HD can be treated with chemotherapy devoid of alkylating agents and anthracycline, followed by low-dose RT.

Relapses of childhood anaplastic large-cell lymphoma: treatment results in a series of 41 children--a report from the French Society of Pediatric Oncology.

PURPOSE: To study response to chemotherapy and the outcome of children treated for a relapsed anaplastic large-cell lymphoma (ALCL) and to evaluate the role of bone marrow transplantation (BMT) in these patients. PATIENTS AND METHODS: Clinical data concerning the 41 relapses that occurred in 119 patients with ALCL enrolled in 3 consecutive studies since 1975 were analysed. First-line treatment consisted of intensive chemotherapy according to the COPAD protocol for the first series of 12 patients treated between 1975 and 1989 and to the SFOP (French Society of Pediatric Oncology) HM protocols for the 30 patients treated between 1989 and 1997. Twenty-eight patients were treated with CV(B)A (CCNU, vinblastine, ara-C with or without bleomycin), and the others with miscellaneous protocols for recurrent disease. Fifteen patients underwent autologous BMT and 1 allogeneic BMT while in CR2. RESULTS: Thirty-six of forty-one (88%) patients achieved CR2. With a median follow-up of 5 years, 12 patients died, 9 of their disease and 29 patients are alive in CR2 (20 patients), CR3 (5 patients), CR4 (2 patients), CR5 (1 patient) or CR6 (1 patient). Overall and disease-free survival are respectively 69% (53%-82%) and 44% (29%-61%) at three years. In univariate analysis, patients treated with ABMT while in CR2 did not appear to have a better outcome than the other. Remarkably, a long-lasting remission was obtained in 8 of 13 patients treated with weekly vinblastine for a relapse including 6 relapses occurring after ABMT. CONCLUSIONS: Relapsed ALCL are highly chemosensitive but over 40% of the patients experience several relapses. Prolonged conventional chemotherapy based on vinblastine might, in some cases, be as efficient as short intensive treatment with ABMT.

[Brachytherapy in the treatment of vesicoprostatic rhabdomyosarcomas in children]. / Curiethérapie dans le traitement des rhabdomyosarcomes vésicoprostatiques de l'enfant.

Brachytherapy has been widely used at the Institut Gustave-Roussy since 1972 in pediatric oncology. In genitourinary rhabdomyosarcoma, because of its ballistic and physical characteristics, it represents the optimal treatment whenever irradiation is required and brachytherapy feasible. Between 1976 and 1998, 23 children with bladder or prostate rhabdomyosarcoma were treated with a protocol including brachytherapy, with five of them treated with a salvage brachytherapy. All but one brachytherapy was performed during the surgery. Among the 18 brachytherapies performed as a first-line treatment, eight presented a tumoral evolution: five presented a local evolution, one a local and nodal evolution and two a nodal evolution. Brachytherapy allowed a conservative treatment among ten out of 11 children alive with no evidence of disease. Among the five patients with salvage brachytherapy, two presented a second recurrence. Sequelae were minimal, consisting of one grade I rectitis and one asymptomatic vesical and ureteral reflux. These results are consistent with the published data using more radical treatment. Brachytherapy can represent an alternative to radical surgery, when indications are clearly defined in bladder or prostate rhabdomyosarcoma. This type of treatment can be performed only integrated with other treatments, more particularly with surgery. This approach requires a close cooperation between the different specialists: pediatricians, surgeons and brachytherapists.

Conservative treatment for girls with nonmetastatic rhabdomyosarcoma of the genital tract: A report from the Study Committee of the International Society of Pediatric Oncology.

PURPOSE: To report the results of a conservative multimodal approach in girls with nonmetastatic rhabdomyosarcoma (RMS) of the genital tract, treated in International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumors 84 and 89 protocols. PATIENTS AND METHODS: From 1984 to 1994, 38 girls with RMS of the genital tract (vulva, vagina, uterus) were treated in SIOP protocols. With the exception of patients with rare small tumors, which were resected at the start of the studies, all patients received initial chemotherapy (CHT) (ifosfamide, vincristine, and actinomycin D). Local treatment including surgery, brachytherapy (BT), and external-beam radiotherapy (ERT) was given only to girls who did not achieve complete remission (CR) with CHT or who subsequently relapsed. RESULTS: The primary tumor originated in the vulva or vagina in 27 girls and in the uterus in 11. The overall survival rate (+/- SE) was 91% +/- 6% at 5 years, and the event-free survival rate was 78% +/- 7%. At a median follow-up of 5 years, 30 girls were alive and in first CR and five were alive and in second CR. Four patients treated with complete resection of the tumor at diagnosis received less CHT. Thirteen patients were treated with CHT alone. In 17 patients, local treatment was necessary to achieve complete local control, for a residual mass after initial CHT (10 patients), for viable tumor on biopsy (three patients), or for local relapse (four patients). The local treatment used was radiotherapy (RT) (ERT in three patients, BT in seven), radical surgery with uterine ablation (three patients), RT and radical surgery (three patients), and conservative surgery with RT (one patient). CONCLUSION: Girls with nonmetastatic RMS of the genital tract have an excellent prognosis. We found no difference in outcome between uterine and vulvovaginal RMS. Local treatment does not seem necessary in patients who have a complete response to CHT. When a local treatment is needed, BT may be an alternative to radical surgery or ERT.