Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: a combined SIOP and AIEOP study.

BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is an uncommon paediatric renal tumour. Relapses occur in about 15% of the patients. Since detailed clinical information on relapsed CCSK is scarce, the current study aims to describe outcome of patients with relapsed CCSK treated according to recent European protocols. PATIENTS AND METHODS: We analysed prospectively collected data of all CCSK patients who developed a relapse after complete remission at the end of primary treatment, entered onto SIOP and AIEOP trials between 1992 and 2012. RESULTS: Thirty-seven of 237 CCSK patients (16%) treated according to SIOP and AIEOP protocols developed a relapse. Median time from initial diagnosis to relapse was 17 months (range, 5.5 months - 6.6 years). Thirt-five out of thirty-seven relapses (95%) were metastatic; the most common sites of relapse were the brain (n=13), lungs (n=7) and bone (n=5). Relapse treatment consisted of chemotherapy (n=30), surgery (n=19) and/or radiotherapy (n=18), followed by high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14 patients. Twenty-two out of thirty-seven patients (59%) achieved a second complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year event-free survival (EFS) after relapse was 18% (95% CI: 4%-32%), and 5-year overall survival (OS) was 26% (95% CI: 10%-42%). CONCLUSIONS: In this largest series of relapsed CCSK patients ever described, overall outcome is poor. Most relapses are metastatic and brain relapses are more common than previously recognised. Intensive treatment aiming for local control, followed by high dose chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel development of targeted therapy is urgently required.

Incidence and outcomes of patients with late recurrence of Wilms' tumor.

BACKGROUND: Most relapses from Wilms' tumor occur within 2 years from diagnosis. This study aims to describe the incidence and outcome of patients who experienced a late recurrence (LR) more than 5 years after diagnosis across several clinical trials, and to develop evidence-based recommendations for follow-up surveillance. METHODS: Available records on children with Wilms' tumor enrolled onto 10 national or international cooperative clinical trials were reviewed to identify patients who experienced a LR. RESULTS: Seventy of 13,330 (0.5%) patients with Wilms' tumor experienced a LR. No gender bias was observed. Median time elapsing between initial Wilms' tumor diagnosis and first recurrence was 13.2 years (range: 5.1-17.3 years). Initial tumor stage was: stage I (15); stage II (19); stage III (14); stage IV (8); bilateral disease stage V (14). The most frequent sites of relapse were--abdomen: 21, lungs: 20, and contralateral kidney: 15. Thirty-five children died of disease progression. Recurrence in the contralateral kidney was associated with a better outcome (13/15 patients alive), while initial tumor stage did not seem to influence the post-recurrence outcome. Therapies administered at recurrence varied between centers, preventing any conclusion about the best salvage treatment. CONCLUSIONS: LR of Wilms' tumor is rare and associated with similar outcome to those experiencing earlier recurrence. The low rate of LR does not justify prolonged monitoring. Further study of the biology of these tumors may give us some insights in regards to mechanisms on tumor cell dormancy or cancer stem cell maintenance.

Allelic loss of chromosome 1p36 in neuroblastoma is of preferential maternal origin and correlates with N-myc amplification.

Neuroblastomas frequently have deletions of chromosome 1p and amplification of the N-myc oncogene. We analysed 53 neuroblastomas for the N-myc copy number, loss of heterozygosity (LOH) of chromosome 1p36 and the parental origin of the lost alleles. Allelic loss of 1p36 was found in 15 tumours. All N-myc amplified tumours belonged to this subset. In 13/15 tumours with LOH of 1p36 the lost allele was of maternal origin. This non-random distribution implies that the two alleles of the putative neuroblastoma suppressor gene on chromosome 1p36 are functionally different, depending on their parental origin. This is the first evidence as far as we know for genomic imprinting on chromosome 1p.

Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group.

Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6-97) and 98.9% (95% CI: 97.7-100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2-89.5; OS 93.2%, 95% CI: 88.7-97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse.

Sustainability assessment as problem structuring: three typical ways.

Sustainability assessment (SA) is an increasingly popular term referring to a broad range of approaches to align decision-making with the principles of sustainability. Nevertheless, in public and private sectors sustainability results are still disappointing, and this paper reflects on this problem and proposes a way forward. We argue that, because sustainability issues are generally wicked problems (i.e. a 'complex of interconnected factors in a pluralistic context'), effective assessments need to be reflexive about the definition of the issue and about the criteria for sustainable solutions. Based on a distinction of policy problems, we characterize SA as a form of problem structuring, and we distinguish three typical ways of problem structuring, corresponding to three different ways of integrating reflexivity in the assessment. We illustrate these routes in three examples. We discuss the way reflexivity is integrated in each example by discussing the mix of methods, SA process and epistemological balance. Rather than merely calling for more stakeholder participation, our aim is to call for more reflexivity integrated into the SA approach, and we conclude by proposing a process map for reflexive sustainability assessment to support this.

Loss of heterozygosity in Wilms' tumors, studied for six putative tumor suppressor regions, is limited to chromosome 11.

Studies on the loss of heterozygosity (LOH) in human malignancies have shown that a number of different chromosomal regions associated with putative tumor suppressor genes may be involved in any one given tumor. We have carried out a similar study on Wilms' tumor using a range of DNA markers for a number of tumor suppressor regions. We tested a total of 44 Wilms' tumors including material from bilateral cases and from patients with Beckwith-Wiedemann syndrome, Drash syndrome, Perlman syndrome, and hemihypertrophy. In 11 of 36 informative tumors we found LOH for markers for the short arm of chromosome 11; only one of these tumors had additional LOH for regions 5q and 17p. No LOH was found for regions 3p, 13q, and 22q. Thus our findings support a major role for chromosome 11p in Wilms' tumor development and apparent noninvolvement of other tumor suppressor genes. No correlation was found between allelic losses and the International Society of Paediatric Oncology tumor stage or histology.

A lack of neuroblastoma in Down syndrome: a study from 11 European countries.

An epidemiological investigation in 11 European countries comprising a total childhood population of 54.1 million children and using 8 separate data sources was conducted to evaluate the occurrence of neuroblastoma in Down syndrome (DS). No cases of DS were detected among 6724 infants and children with neuroblastoma, although more than five were expected. This highly significant result (P = 0.0045 according to the Poisson test) is consistent with data in the literature, which contains only two poorly detailed cases in epidemiological studies and one ganglioneuroma in a DS mosaic patient. Like other tumors, such as leukemias, testicular germ cell tumors and lymphomas are in excess in DS patients; the lack of neuroblastomas does not reflect a general decreased incidence of cancer but rather a specific underrepresentation of this precise tumor. S-100 b protein, the gene for which maps to the long arm of chromosome 21, (a) is overproduced in DS patients, (b) produces growth inhibition and differentiation of neural cells in vitro, (c) is abundant in good-prognosis neuroblastomas, and (d) has been shown to induce growth inhibition and differentiation and cell death in several human and murine neuroblastoma cell lines and could be responsible for this variation. Additional epidemiological and experimental studies are warranted to confirm our interpretation of these data.

Wilm's tumor with pulmonary metastases at diagnosis: the significance of primary chemotherapy. International Society of Pediatric Oncology Nephroblastoma Trial and Study Committee.

Data from patients with pulmonary metastases (PM) from Wilms' tumor at diagnosis (stage IV) were collected from six European centers. All patients were pretreated with a chemotherapy (CT) regimen consisting of vincristine (VCR), dactinomycin (AD), and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH). After nephrectomy, local therapy for residual pulmonary disease was considered to avoid whole-lung irradiation. Only four of 36 patients still had multiple inoperable metastases after preoperative CT. Thirty patients survived. Four of them were irradiated. Of the six patients who died, four died of PM, one died of abdominal recurrence, and one of therapy-related disease. Disease-free survival and actuarial survival rates are 83% with a mean follow-up of 4 years postnephrectomy.

Results of the Sixth International Society of Pediatric Oncology Wilms' Tumor Trial and Study: a risk-adapted therapeutic approach in Wilms' tumor.

PURPOSE: The Sixth International Society of Pediatric Oncology study (SIOP6) concerned Wilms' tumor with favorable histology, preoperatively treated to obtain a high rate of stage I patients, and sought to reduce treatment for patients with stage I and stage II negative nodes (IIN0) tumors and to find better therapy to prevent relapses in stage II positive nodes (IIN1) and stage III patients. PATIENTS AND METHODS: Eligible patients (N = 509) had received four weekly doses of vincristine (VCR) and two courses of dactinomycin (AMD) preoperatively and were assigned after surgery, according to stage and lymph node involvement, to three different prognostic groups, which were to be randomized. Stage I patients (n = 303) received VCR and AMD either for 17 weeks (S) or 38 weeks (L). Stage IIN0 patients (n = 123) received either 20 Gy irradiation (R+) or no irradiation (R-) and received VCR and AMD for 38 weeks. Stage IIN1 and III patients (n = 83) received intensified VCR and AMD (INTVCR) versus VCR, AMD, and Adriamycin (ADRIA; Doxorubicin Farmitalia Carbo Erba, Rueil, Malmaison, France; doxorubicin). Assessment criteria were 2-year disease-free survival (DFS) and 5-year survival (SURV) percentages. A stopping rule was added that took into account abdominal recurrences for the stage IIN0 trial. RESULT: A 52% rate of stage I tumors was obtained, with a low rate of ruptures (7%). The 2-year DFS and 5-year SURV rates according to the different therapeutic groups were stage I, 92% versus 88% (equivalent) and 95% versus 92% for S and L, respectively; stage IIN0, 72% versus 78% (stage equivalent) and 88% versus 85% for R+ and R-, respectively; and stage IIN1 and stage III, 49% versus 74% (P < .029) and 77% versus 80% for INTVCR and ADRIA, respectively, which results in an 82% DFS and 89% SURV rate for the entire trial population. However, six abdominal metastases observed during the first year of follow-up (FU) in the R- group versus none in the R+ group resulted in discontinuation of the stage IIN0 trial. CONCLUSION: Risk-adapted therapy to limit risk of sequelae is possible. More intensive chemotherapy is necessary to prevent abdominal recurrences in nonirradiated stage IIN0 patients treated preoperatively. A three-drug protocol is necessary in stage IIN1 and stage III patients.

Optimal duration of preoperative therapy in unilateral and nonmetastatic Wilms' tumor in children older than 6 months: results of the Ninth International Society of Pediatric Oncology Wilms' Tumor Trial and Study.

PURPOSE: To determine the optimal duration of preoperative chemotherapy to further increase the proportion of stage I tumors by comparison of two regimens in the treatment of patients older than 6 months who have unilateral Wilms' tumor. PATIENTS AND METHODS: Eligible patients (n = 382) initially received four weekly doses of vincristine (VCR) and two courses of actinomycin D (AMD) and were randomized either to be operated on (4-week group [n = 193]) or to receive 4 more weeks of the same chemotherapy regimen (8-week group [n = 189]). The assessment criterion was the observed percentage of stage I tumors. After surgery, patients were assigned according to tumor stage and histology to four different treatment groups: stage I and favorable histology (n = 5) were to have no further treatment (NFT); stage I and standard histology or anaplasia (n = 244), VCR and AMD for 17 weeks (AV); stages II and III and favorable or standard histology, VCR, AMD, and an anthracycline for 27 weeks (AVE) with no abdominal radiotherapy for stage II N0 disease (n = 75) or with a 15-Gy dose of abdominal irradiation (RTH) in case of stages IIN1 and III (n = 56). Anaplastic tumors staged higher than I or clear-cell sarcoma of the kidney (14), AMD, VCR, an anthracycline, and ifosfamide for 36 weeks (DEVI). RESULTS: No advantage was found in favor of prolonged preoperative treatment. The percentages obtained for the 4-week and the 8-week groups, respectively, were as follows: stage I, 64% versus 62%; intraoperative tumor rupture rate, 1% versus 3%; 2-year EFS, 84% versus 83%; and 5-year OS, 92% versus 87%. Two-year EFS and 5-year OS rates, respectively, of the different treatment groups were as follows: NFT, 100% for both EFS and OS; AV, 88% and 93%; AVE, 84% and 88%; AVE RTH, 71% and 85%; and DEVI, 71% and 71%. The rate of abdominal recurrences in stage II N0 nonirradiated patients was 6.6%. CONCLUSION: The 4-week schedule pre-nephrectomy chemotherapy regimen should be considered the standard treatment. Clinical trials should continue to improve the cure rate of high-risk patients and the quality of life of children with a more favorable prognosis.

Bilateral Wilms' tumor: long-term survival and some epidemiological features.

Sixty-seven children with a bilateral Wilms' tumor (BWT) who were registered to the International Society of Pediatric Oncology (SIOP) nephroblastoma trial and studies 1, 2, and 5, conducted between 1971 and 1980, were analyzed. The overall 10-year survival was 64%. While most deaths due to tumor occurred within 3 years after diagnosis of bilateral disease, five patients died after 3 years (20%), three with synchronous and two with metachronous BWT. The survival rates for the 42 children with synchronous BWT (follow-up time, 6 1/2 to 14 years) and the 25 children with metachronous BWT (follow-up time, 5 to 13 years) were 69% and 56%, respectively. Due to an improvement in the synchronous group, overall survival improved over the years: 47%, 72%, and 70%, in SIOP 1, 2, and 5, respectively. Age at diagnosis and most advanced tumor stage affected prognosis. Children presenting a tumor manifestation before the age of 2 years had better prognosis than older children. This difference is significant in synchronous BWT. Prognosis for children with local stage 1 or 2 was better than for those with local stage 3. Median age at initial presentation in BWT was lower than in unilateral nephroblastoma and lower in metachronous BWT than in synchronous BWT. Young children presenting with unilateral nephroblastoma should have a careful follow-up of the contralateral kidney for at least the next 3 1/2 years, as most contralateral tumors will develop during this period.

Reduction of postoperative chemotherapy in children with stage I intermediate-risk and anaplastic Wilms' tumour (SIOP 93-01 trial): a randomised controlled trial.

BACKGROUND: Present treatment for Wilms' tumour is very successful. Now, efforts are aimed at reducing toxicity and burden of treatment by shortening schedules without loss of effectiveness. The objective of this randomised trial was to assess whether postoperative chemotherapy for patients with stage I intermediate-risk and anaplastic Wilms' tumour could be shortened to only 4 weeks from the standard 18 weeks, while maintaining equivalent event-free survival. METHODS: Between June, 1993, and June, 2000, 410 patients were randomly assigned after four doses of vincristine plus one course of dactinomycin postoperatively either to stop further adjuvant chemotherapy (no further chemotherapy group, n=200), or to receive a further two courses of the same chemotherapy (standard group, n=210). Previous treatment consisted of chemotherapy before nephrectomy of four doses of vincristine and two courses of dactinomycin followed by surgical resection of the tumour. Eligible patients were at least 6 months old and had stage I tumours with either intermediate-risk histology or anaplasia. The primary endpoint of this equivalence trial was 2-year event-free survival. Both per-protocol and intention-to-treat analyses were done. FINDINGS: By 2 years, 18 recurrences were reported in the standard group, and 22 in the no further chemotherapy group. Event-free survival was 91.4% (95% CI 87.5-95.2) for the no further chemotherapy group and 88.8% (84.3-93.2) for the standard group (difference=2.6%, upper 97.5% confidence limit 8.4%). The null hypothesis, that experimental treatment is less effective than standard treatment, could be rejected (p=0.008). CONCLUSIONS: Shortening duration of chemotherapy could reduce acute and late side-effects and inconvenience for patient and parents while maintaining effectiveness, and could be beneficial in terms of health costs.

Endocrine late effects from multi-modality treatment of neuroblastoma.

Thyroid dysfunction has been reported after 131I-MIBG-treatment for neuroblastoma. In this study, we have evaluated all endocrine functions from patients who were given multi-modality treatment including 131I-MIBG. Twenty-five neuroblastoma survivors who were off therapy for a median period of 6.0 years (range 1.3-11.1) were evaluated and their median age was 8.1 years (range 2.2-14.7). All patients had received 131I-MIBG, 16 chemotherapy, and 16 surgery. Fourteen patients (56%) had permanently elevated thyrotropin levels and 9 received thyroxine. Two patients had a small thyroid volume while 6 had thyroid nodules or cysts. Two boys showed hypergonadotropic hypogonadism. Growth was retarded in 39% of children. Mean Target Height Standard Deviation Score of patients with thyrotropin elevation was lower than those without (P=0.019). Children treated for neuroblastoma with 131I-MIBG, chemotherapy and surgery were seen to be at risk from developing irreversible thyroid function loss, thyroid nodules, hypergonadotropic hypogonadism, and growth retardation. We recommend that during follow-up of neuroblastoma children, special attention should be paid to their endocrine state.

Outcome of localised blastemal-type Wilms tumour patients treated according to intensified treatment in the SIOP WT 2001 protocol, a report of the SIOP Renal Tumour Study Group (SIOP-RTSG).

Blastemal-type Wilms tumour (BT-WT) has been identified as a high risk histological subgroup in WT assessed after pre-nephrectomy chemotherapy in trials of the International Society of Paediatric Oncology (SIOP) Renal Tumour Study Group. Therefore, in SIOPWT2001, post-operative chemotherapy for BT-WT was intensified aiming to improve survival. Survival analysis of all unilateral BT-WT patients (SIOPWT2001) (n=238), was compared with historical BT-WT controls (SIOP93-01) (n=113). 351/4061 (8.6%) unilateral non-metastatic BT-WT patients (SIOP93-01/SIOPWT2001) were studied. Median age at diagnosis was 43 months (Inter Quartile Range (IQR) 24-68 months), stages: I (n=140, 40%), II (n=106, 30%), III (n=105, 30%). BT-WTs were higher staged, showed greater volume decrease after pre-operative chemotherapy and were diagnosed at an older median age compared to other WT patients. Patient characteristics did not differ substantially between SIOP93-01 and SIOPWT2001. Univariate analysis showed a 5-year event-free survival (EFS) of 80% (95% confidence interval (CI): 75-86%) (SIOPWT2001) compared to 67% in SIOP93-01 (95% CI: 59-76%; p=0.006) and overall survival (OS) of 88% (95% CI: 83-93%) (SIOPWT2001) compared to 84% (95% CI: 77-91%; p=0.4) in SIOP93-01. 95% of relapses were distant metastases (SIOP93-01/SIOPWT2001). Treatment protocol, age at diagnosis, tumour stage (III versus I/II) and volume (at surgery), were prognostic variables for EFS (uni- and multivariate Cox regression analysis). Independent prognosticators for OS were age at diagnosis, tumour stage and volume (at surgery). The most significant survival benefit of intensified treatment, was observed in Stage I (EFS 96% in SIOPWT2001 (OS 100%), 71% in SIOP93-01 (OS 90%)). BT-WT derived benefits from more intensive chemotherapy as reflected by a reduction in relapse risk. However, the benefit of the more intensive chemotherapy to improve OS was only observed in stage I BT-WTs, by adding doxorubicin.

131I-rose bengal therapy in hepatoblastoma patients.

If conventional treatment modalities have failed in hepatoblastoma patients and no distant metastases can be demonstrated therapy with radionuclide agents can be considered. In 6 patients diagnostic technetium-99m (99mTc)-disofenin and two iodine-131 (131I)-rose bengal scans were made. 2 patients demonstrated specific uptake of disofenin. One of these had a positive scintigram with radiolabelled rose bengal. This patient was subsequently treated with 1.1 GBq 131I-rose bengal. No toxicity was observed. A clear decrease in the level of alpha-fetoprotein indicated a response and demonstrated that this radiopharmaceutical can be used for tumour targeted radiation therapy in selected patients with therapy resistant tumours.

Fetal rhabdomyomatous nephroblastoma: a tumour of good prognosis but resistant to chemotherapy.

Fetal rhabdomyomatous nephroblastoma (FRN) is a rare variant of Wilms' tumour. The tumour chiefly consists of fetal striated muscle with particularly distinct striations and central nuclei. To determine the effect of (preoperative) chemotherapy in the treatment of this subtype of nephroblastoma, a retrospective analysis was performed. By 1 November 1991, SIOP 9 had registered 852 patients (pts) from 55 centres. We report on 13 children diagnosed with FRN between 1988 and 1992 with a median age of 2 years and 1 month (range 1 month-8 years 6 months). There were 7 boys and 6 girls. 9 patients were classified as stage I, 2 as stage II, 1 as stage III and 1 as stage V. 12 patients received preoperative chemotheraphy with actinomycin-D and vincristine for 2 weeks (1 pt), 4 weeks (5 pts) and 8 weeks (6 pts) respectively. The average tumour volume at registration (determined by ultrasonography) in 12/13 patients was 965 cm3 (range 17.3-2520 cm3). 3/7 of the FRN patients showed no tumour regression after 4 weeks preoperative CT and 4/8 after 8 weeks preoperative chemotheraphy (compared with only 28 and 34%, after 4 and 8 weeks CT, of all trial patients). Of 13 patients, 10% are alive and free of disease with a mean follow up of 4 years. This variant of Wilms' tumour is a poor responder to preoperative chemotherapy and is associated with a generally favourable outcome in most of all unilateral cases when treated by surgery.

Radioimmunoscintigraphy using [111In]antimyosin Fab fragments for the diagnosis and follow-up of rhabdomyosarcoma.

Between 1987 and 1992, 39 radioimmunoscintigraphic studies using 111In-labelled antimyosin Fab fragments were performed in 27 patients with rhabdomyosarcoma (RMS), 2 patients with leiomyosarcoma (LMS) and 1 with alveolar soft tissue sarcoma. 21 patients were children aged 3-14 years. These patients, who had histologically proven myosarcoma, were examined scintigraphically to search for local recurrences or metastases and to determine the response to treatment. The results of immunoscintigraphy were compared with histopathological parameters and other imaging modalities. The sensitivity of antimyosin scintigraphy in this series was 82% and the specificity was 73%. Although the technique appears to be not highly specific for RMS, it was found to be useful for the early detection of local recurrence and metastases, as well as for the evaluation of the response to therapy.

Clinical experience with radiation enhancement by hyperbaric oxygen in children with recurrent neuroblastoma stage IV.

The high risk group of patients with neuroblastoma are children over 1 year with stage IV disease. Most series report a maximum of 20% survival at 5 years. For recurrent neuroblastoma stage IV, cure rates are not reported in the literature, but they are nil. Any treatment for recurrent neuroblastoma stage IV remains a therapeutic dilemma. The outcome of radiation therapy is variable. A very important factor in tumour treatment remains tumour hypoxia, and others, such as metabolic factors, also play a role. Combined application of radiation modifiers may influence the final survival rate. In an attempt to improve the survival of recurrent neuroblastoma stage IV, hyperbaric oxygen and radioionated meta-Iodobenzylguanidine (MIBG) was used in a clinical setting. Although survival may not be used as a determinant of the usefulness of a treatment for stage IV neuroblastoma disease, a better one is not available. In this study, at 28 months, a cumulative probability of survival of 32% was recorded for patients treated with [131I]MIBG and hyperbaric oxygen compared to 12% for [131I]MIBG treatment alone. These preliminary results are promising but further studies are needed to reveal substantial therapeutic gain.

First line targeted radiotherapy, a new concept in the treatment of advanced stage neuroblastoma.

33 previously untreated advanced stage neuroblastoma patients were treated with [131I]meta-iodobenzylguanidine (MIBG). The number of treatments varied between 2 and 7 per patient (mean 3). Toxicity was seldom severe. Only thrombocytopenia WHO-grade 4 was noticed. Response was documented before surgery for the primary tumour was performed. There was one complete response (CR), 18 partial responses (PR), 11 had stable disease (SD) and 3 had progressive disease (PD). After MIBG therapy and surgery, 12 of 33 patients achieved a CR. This approach is feasible, comparable to multidrug chemotherapy in efficacy and less toxic. Long term results are not known yet.

Ewing's sarcoma of the pelvis: changes over 25 years in treatment and results.

The pelvic localisations of Ewing's sarcoma have the worst prognosis due to large size at diagnosis, frequent distant metastases, radiosensitive organs next to the tumour and difficult surgery. The purpose of the present study was to analyse treatment results over a period of 25 years and to investigate the impact of newer chemotherapy schedules, improved radiotherapy techniques and newer surgical methods on the prognosis. 35 children and young adults were identified from 1967 to 1994 for whom diagnosis, presentation, performed treatment and outcome were available. Tumour size, as measured from CT scans, response to chemotherapy and radiotherapy target volume, could be reviewed in the later years. Actuarial 5-year survival for the whole group was 31% and for the 24 non-metastatic patients 40%, with a disease-free interval of 19%. Tumour size could be measured in 27 patients and ranged from 36 to 1540 cm3. There were 12 local recurrences, 1 in the 4 patients treated with surgery. After 1983, 9 out of 17 irradiated patients developed local failure. 3 patients had adequate fields and one a close field which did not cover completely the prechemotherapy extent and 3 of these recurred. All 4 patients with stable disease after neoadjuvant CT failed locally, not withstanding high-dose radiotherapy. The mean length of neoadjuvant CT tended to be shorter in patients without local relapse. There was no significant difference in survival before and after 1983.