Search

Aim: To investigate the possible role of imatinib, an inhibitor of the tyrosine kinase activity of PDGF-R, in desmoplastic small round cell tumor (DSRCT). Patients & methods: From August 2005 to June 2009, DSRCT patients refractory to conventional treatment were enrolled. Patients received imatinib 400 mg daily. Primary end point of this open label, prospective, Phase II trial was objective response rate. Results: Of the 13 enrolled patients, eight were evaluable for response. Median age was 20 years (range: 9–32). Objective responses at 3 months were: stable disease in one patient and progressive disease in seven patients. Conclusion: Imatinib showed no efficacy in the treatment of DSRCT unresponsive to conventional therapy, despite molecular-based selection of patients.

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.

To assess post-traumatic stress symptoms (PTSS) in mothers of children over 2 years of leukemia treatment, to identify possible early family and child predictors of this symptomatology and to indicate the temporal trajectory of PTSS.Participants were 76 Italian mothers (mean age = 37.30 years; SD = 6.07) of children receiving treatment for acute lymphoblastic (n = 69) or myeloid (n = 7) leukemia. Mothers had 12.05 years of education (SD = 3.87), and their incomes were average (52.1%), high (26%) and low (21.9%) for Italian norms, never in poverty. The pediatric patients with leukemia were equally distributed by gender with their mean age of 7.10 years (SD = 4.18). Post-traumatic stress symptoms were measured by a 17-item checklist. Scales assessing anxiety, depression, physical (Brief Symptom Inventory 18) and cognitive functioning (Problem Scale), and life evaluation were also used. There were five assessment points: 1 week (T1), 1 month (T2), 6 months (T3), 12 months (T4) and 24 months post-diagnosis (T5).The main results indicated moderate presence of clinical PTSS (≥9 symptoms: 24% at T2, 18% at T3, 16% at T4 and 19% at T5) that remained stable across time points, whereas Brief Symptom Inventory 18 Global score decreased and life evaluation improved. A series of hierarchical regression models identified cognitive functioning early after the diagnosis as the best predictive factor of PTSS across time points.Specific psychological interventions could be devised for mothers at risk for short and long-term PTSS just after the diagnosis.

Summary: Aggressive fibromatosis is a rare tumor of borderline malignancy with a marked local aggressiveness. Surgery is the mainstay of treatment but complete tumor resection is often not easy to achieve without functional and cosmetic sequelae. We report a case of a pretreated child with aggressive fibromatosis who responded to hydroxyurea, avoiding the need for demolitive surgery.

Previous studies have reported a poor outcome for synovial sarcoma patients whose tumours relapse.This study analysed 44 relapsing cases in a series of 118 consecutive patients21 yr of age with non-metastatic synovial sarcoma prospectively enrolled in Italian paediatric protocols between 1979 and 2006. In an effort to identify a possible risk-adapted stratification enabling a better planning of second-line treatment, the relapsing patients' outcome was analysed vis-à-vis their clinical picture at onset, first-line treatments, clinical findings at the time of first relapse and second-line treatment modalities.The first event was a local recurrence in only 15 cases, and metastatic in 29 (associated with local relapse too in 7 cases). The time to relapse ranged from 4 to 108 months (median 20 months). Overall survival was 29.7% and 21.0% five and ten years after relapsing, respectively. The variables influencing survival were the timing and type of relapse (combined) and the chances of a secondary remission, which correlated strongly with the feasibility of complete surgery.Our study confirmed a largely unsatisfactory prognosis after recurrences in children and adolescents with synovial sarcoma: the chances of survival can be estimated on the basis of several variables for the purposes of planning risk-adapted salvage protocols. An aggressive surgical approach should be recommended. New effective systemic agents are warranted, and experimental therapies can be offered to patients with little chance of salvage.

The results obtained by protocols for children with rhabdomyosarcoma (RMS) have improved in recent decades. Survival curves usually reach a plateau 3 years after the diagnosis, suggesting that long-term survival can be expected, but late events are known to occur. We analyzed the long-term results of the RMS 79 protocol to investigate the type and impact of such events.From 1979 to 1987, 163 children with RMS diagnosed at 21 Italian institutions were registered. Each institution was contacted every year to record patients' status after the end of treatment. When patients were lost to follow-up, their status was checked by inquiring at the Registry Offices of the towns of residence and the cause of death or occurrence of second cancers was investigated by contacting the patients or their family by phone.Overall, 16 patients had late events, that is, 7 tumor recurrences, 6 second tumors, and 3 deaths due to treatment-related complications. The overall survival rates dropped from 62.6 at 3 years to 52.8 at 20 years. By multivariate analysis, the characteristics influencing long-term survival were histology, tumor site and size, and IRS group. Factors predictive of any kind of late event were tumor site and IRS group.Major late events can significantly affect the long-term survival of children with RMS. Modern protocols should provide for a much longer follow-up than is usually considered to confirm the results achieved and enable possible correlations between primary treatment and late events to be investigated.

Background: The outcome of patients with non-extremity synovial sarcoma (SS) is generally worse than that of patients with limb tumours. Methods: The present study analysed a series of 115 consecutive SS patients treated in Italian paediatric protocols (period 1979–2005), mainly focusing on the 30 cases arising from ‘axial’ sites (16 head–neck, 8 trunk, 4 lung-pleura and 2 retroperitoneum). Results: Initial gross resection was achieved in 40% of axial cases and in 80% of limb SS (p < 0.0001). Five-year EFS and overall survival (OS) were, respectively, 43.3% and 55.1% for axial SS, and 69.6% (p = 0.0068) and 84.0% (p = 0.0004) for extremity SS. Local progression/ recurrence was the cause of treatment failure in 75% of relapsing patients axial disease. Conclusions: Our findings emphasise that children and adolescents with SS originating at non-extremity locations have a worse prognosis than those with limb SS. Tumour site should be considered when defining a risk-adapted treatment strategy for SS.

Recent reports have suggested that Helicobacter pylori infection may be a causative agent of adult chronic idiopathic thrombocytopenic purpura (cITP) and antimicrobial treatment may increase platelet counts. As there is limited experience in pediatric age, we investigated the prevalence of H. pylori infection and the effects of H. pylori eradication therapy in a series of children with cITP. Twenty-four children with cITP were investigated for H. pylori infection using the C-urea breath test or H. pylori fecal antigen. In cases of H. pylori infection, antimicrobial treatment was given with amoxicillin, clarithromycin, and proton pump inhibitors. Response was assessed at 6 months and defined as complete (platelet count >150x10/L) or partial (platelet count between 50 and 150x10/L). H. pylori infection was found in 8 patients (33%) and 3 of them showed a response after eradication therapy, but 2 of them relapsed later on. Two patients had a spontaneous increase in platelet count in the group of H. pylori-negative patients. Given that spontaneous improvements in platelet count can occur in children with cITP, we were unable to demonstrate that H. pylori plays a major role in cITP occurring in pediatric age.

A reliable diagnosis of invasive aspergillosis (IA) is hampered by the difficulty in obtaining suitable tissue samples. To evaluate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the LightCycler PCR for the diagnosis of IA, 536 blood samples were collected over a 22-month period from 62 paediatric patients (median age 10 years, range 1-18) considered at risk of IA. The galactomannan antigen (GM) and fungal DNA were assessed on serial blood samples. IA was diagnosed in eight of 62 patients (13%): proven, five, probable, three. Sensitivity, specificity, PPV and NPV of LightCycler PCR varied according to the number of positive samples used to define positivity: 88%; 37%; 17% and 95% for single sample positivity; and 63%, 81%, 33% and 94% for serial sample positivity respectively. The concordance between positivity of LightCycler PCR assay and the diagnosis of IA was 79%. The single positivity of LightCycler PCR assay showed a good sensitivity for the diagnosis of IA in paediatric patients. The high NPV makes LightCycler PCR a promising tool in addition to GM testing to design a strategy of pre-emptive antifungal therapy, although further validation studies are needed.

Acute GVHD (aGVHD) is a major cause of morbidity and mortality after unrelated BMT (UBMT). Our purpose was to analyze the role of extracorporeal photochemotherapy (ECP) in controlling grade II-IV aGVHD in children given UBMT. Of 41 consecutive children, 31 developed grade II-IV aGVHD after UBMT: 16 had a good response to steroids (GR group), whereas 15 underwent ECP (ECP group) within 100 days of UBMT. Eligibility criteria for starting ECP were steroid resistance, dependence or viral reactivations. Criteria for judging response to aGVHD treatment were that the resolution of all signs were considered a complete response (CR), at least a 50% improvement was classified as a partial response (PR) and stable or progressive disease was judged as no response (NR). On completing ECP, the CR rate was 73%, whereas the GR group had a CR rate of 56% by day 100. The 2-year overall survival and progression-free survival rates were 57 and 67% in the GR group vs 85 and 87% in the ECP group. Our data seem to suggest that ECP may improve outcome in patients after UBMT. These findings need to be confirmed in a larger population.

We report a simplified method of performing antibiotic lock therapy (ALT) based on a disposable central venous catheter (CVC) hub device, CLC 2000, enabling an open-ended CVC to be flushed with normal saline solution without heparin.ALT was administered through a CLC 2000 connector for recurrent CVC-bloodstream infections (BSI) by the same organism in four patients and for CVC colonization in five patients.The antibiotic concentration obtained in the lumen of the CVC with ALT was 2,500-fold higher than the minimum inhibiting concentration of targeted bacteria for patients treated with vancomycin, 2,500-80,000-fold higher for patients treated with teicoplanin, and 10,000-fold higher for the patient treated with amikacin. All CVC-BSIs treated with ALT resulted in complete clinical and microbiological responses. No case of malfunction in withdrawing or flushing the CVC and no precipitation during the administration of the antibiotic solution was observed. No recurrence of CVC-BSI or CVC colonization by the same organism was diagnosed during subsequent follow-up, despite the fact that all patients had further periods of severe neutropenia. At the last follow-up, three CVCs had been removed for other infections (fever of unknown origin in two; fungemia in one), four CVCs had been removed at the end of therapy, and one CVC is still in situ 20 months after ALT.In conclusion, a course of ALT is feasible in cancer patients with infected but much-needed CVCs before resorting to removal. The use of the CLC 2000 connector device simplifies the procedure for preparation and administration of ALT without compromising its efficacy.

BACKGROUND. The purpose of the current study was to analyze the influence of the initial surgical approach (biopsy vs resection with macroscopic residual tumors) on the outcome of patients with localized Intergroup Rhabdomyosarcoma Study (IRS) Group III rhabdomyosarcoma (RMS) enrolled in the Italian studies between 1979 and 2003. METHODS. Among the 394 patients evaluated, 323 underwent biopsy, as recommended by the protocols, and 71 patients underwent surgical resection with macroscopic residual tumors (debulking operation [DO]), although this procedure was discouraged. All these patients were classified at the same risk group and received the same treatment. The different characteristics (patient age, tumor site, T classification and size, histology) and outcome in the 2 groups were considered. RESULTS. The estimated 5-year overall survival (OS) rates were 68.4% and 72.6%, respectively, after biopsy and DO(P = .38), and the rates of progression-free survival (PFS) were 56.5% and 61.7%, respectively, after biopsy and DO (P = .41). The outcome did not differ significantly when considering other variables such as tumor site, size, and histology. Age > 10 years appeared to have little benefit in patients with DO; the OS was 62% after biopsy and 83.1% after DO (P = .06); the PFS was 49.7% and 72.8%, respectively after biopsy and DO (P = .04). No surgical complications due to the 2 procedures were reported, but in 2 cases the initial DO resulted in a mutilation. CONCLUSIONS. No significant advantages of DO versus biopsy were detected with regard to patient outcome. Biopsy, which is less aggressive, appears to be thebest option for patients with IRS Group III RMS. Cancer 2007. © 2007 American Cancer Society.

Purpose To assess the value of chemotherapy and radiotherapy in children with malignant peripheral nerve sheath tumors (MPNSTs) and to identify risk factors associated with outcome. Patients and Methods A total of 167 untreated eligible patients enrolled onto the Italian and German studies between 1975 and 1998 entered this analysis. Seventeen percent of patients had neurofibromatosis type 1 (NF1). Chemotherapy was administered to 74% of patients; radiotherapy was administered to 38% of patients. Results With a median follow-up of 7 years, 5-year overall survival (OS) and progression-free survival (PFS) were 51% and 37%, respectively. The 5-year OS and PFS by Intergroup Rhabdomyosarcoma Study (IRS) groupings were as follows: group I, 82% and 61%; group II, 62% and 37%; group III, 32% and 27%; group IV, 26% and 21%, respectively. Univariate analysis identified IRS groups, size, invasiveness, primary site, age, and presence of NF1 as prognostic factors; multivariate analysis identified absence of NF1, tumor invasiveness T1, IRS groups I to II and extremity of primary site as independent favorable factors for OS. A trend was observed toward a benefit from radiotherapy after initial gross resection. The overall response rate to primary chemotherapy, including minor responses, in group III patients was 45%. Conclusion MPNST is an aggressive tumor for which complete surgical resection is the mainstay of successful treatment. Postoperative radiotherapy may have a role in improving local control in patients with minimal residual tumor. The reported responses to primary chemotherapy suggest that it may be effective in patients with tumor considered unresectable at diagnosis.

This paper describes the case of a male child with acute lymphoblastic leukemia who developed cerebral sinovenous thrombosis on day 6 of induction therapy with intrathecal methotrexate and methylprednisolone. A central venous catheter had been implanted the day before. The heterozygous prothrombin G20210A variant was found together with acquired activated protein C resistance and a reduced activated partial thromboplastin time. Clinical course and magnetic resonance imaging with magnetic resonance venography gradually improved over the following days after starting anticoagulant therapy (heparin and nadroparin). Cerebral sinovenous thrombosis is a serious disease in leukemic children, occurring in up to 6% of these patients. Data from the literature are in favor of anti-coagulant treatment, even though the efficacy and safety of thromboprophylaxis during chemotherapy in leukemic children with inherited thrombophilic conditions remain to be demonstrated.

Survivors of childhood cancer risk developing second malignant neoplasms (SMN). a small proportion of SMNs is represented by soft tissue sarcoma (STS), including leiomyosarcoma. The files of the STS Italian Cooperative Group (ICG) were reviewed and 4 patients with secondary leiomyosarcoma were identified, only two of them still alive. In 3 cases, the leiomyosarcoma occurred in the radiation field. The authors found no clear differences between primary and secondary leiomyosarcomas, but leiomyosarcoma proved to be the most frequent SMN registered by the ICG, confirming the need for further studies to identify any distinctive features or syndromes.

BACKGROUND Following their previous report on the activity of vinorelbine in the treatment of rhabdomyosarcoma, the authors report the results of a pilot study aimed at defining the optimal dose of vinorelbine when this agent is used in conjunction with continuous, orally administered low-dose cyclophosphamide to treat patients with refractory or recurrent sarcoma. It is hoped that the combination of vinorelbine and low-dose cyclophosphamide can be used as a maintenance regimen in an upcoming European trial involving high-risk patients with rhabdomyosarcoma. METHODS In the current pilot study, the cyclophosphamide dose was fixed at 25 mg/m2 per day for 28 days. Vinorelbine was administered intravenously on Days 1, 8, and 15, with trial doses escalated from an initial level of 15 mg/m2 in steps of 5 mg/m2; intrapatient dose escalation was not allowed. RESULTS Between April 2002 and November 2003, 18 patients ages 2–23 years were treated with the study regimen after having received 1–4 (median, 2) other regimens previously. Ninety cycles were administered in total (median, 5 cycles per patient; range, 1–10 cycles per patient). Two cases of dose-limiting toxicity (Grade 4 neutropenia in both cases) were observed among the 5 patients who received vinorelbine at a dose of 30 mg/m2. Of the 41 cycles in which vinorelbine was administered at a dose of 25 mg/m2, Grade ≥ 3 neutropenia was observed in 15 (37%); no other major toxicity was documented in association with these cycles. One complete remission and 6 partial remissions were noted among the 17 patients who had measurable disease. Three of the eight assessable patients with rhabdomyosarcoma (which was embryonal in two cases and alveolar in one) had responses to treatment. CONCLUSIONS Combination therapy involving vinorelbine and low-dose cyclophosphamide was found to be feasible and to possess activity against recurrent sarcomas. The maintenance therapy doses recommended for use in the upcoming European trial are cyclophosphamide 25 mg/m2 per day for 28 days and vinorelbine 25 mg/m2 on Days 1, 8, and 15. Cancer 2004. © 2004 American Cancer Society.

BACKGROUND. Survivors of childhood malignancies have an increased risk of developing second malignant neoplasms (SMN) due to their prior treatment and/or genetic susceptibility. A small proportion of SMNs are soft tissue sarcomas (STS), whose prognosis is generally thought to be poor, though publications on such patients’ treatment and outcome is limited. METHODS. The authors analyzed 25 patients who were registered for the Italian Cooperative Group protocols for pediatric STS from 1979 to 2000. The primary tumor was STS in five patients; Hodgkin disease in five patients; leukemia in four patients; retinoblastoma, neuroblastoma, and Wilms tumor in two patients each; and other tumor types in five patients. SMNs occurred after a median of 8 years (range, 1.9 –15.0 years) and included rhabdomyosarcoma (RMS) in 4 patients, malignant peripheral nerve sheath tumor in 4 patients, extraosseous Ewing family tumor (EFT) in 4 patients, leiomyosarcoma in 3 patients, fibrosarcoma in 2 patients, synovial sarcoma in 2 patients, and other tumor types in 6 patients. Treatment generally was administered according to the guidelines for primary STS. RESULTS. Seven non-RMS patients with STS underwent surgery alone, whereas 18 patients received chemotherapy and 8 patients received radiotherapy. Retreatment was feasible with acceptable toxicity. Fifteen patients were alive in complete remission of their SMN at the time of last follow-up. Responses to chemotherapy and survival were satisfactory for patients with tumors such as RMS and EFT. Complete tumor resection was correlated with a favorable prognosis in patients with other types of STS and in patients with postirradiation sarcoma. Two patients developed a third malignancy. CONCLUSIONS. Although prior treatment may hinder the management of these patients, pediatric STS second malignancies can be cured using the same strategies used for de novo pediatric sarcomas. Long-term follow-up is mandatory given the risks of further malignancies and more severe, treatment-related side effects. Cancer 2004;100:1758–65. © 2004 American Cancer Society. KEYWORDS: soft tissue sarcoma, second malignancy, rhabdomyosarcoma, malignant peripheral nerve sheath tumor, leiomyosarcoma, children.

Purpose Final results are presented from two consecutive European studies for patients with metastatic rhabdomyosarcoma (RMS) to identify prognostic variables and determine the value of high-dose chemotherapy (HDCT) in complete remission. Patients and Methods A total of 174 patients aged 3 months to 18 years participated. From 1989 to 1991, patients received four cycles of intensive multiagent chemotherapy. From 1991 to 1995, patients achieving complete remission received consolidation with HDCT. All received local therapy (surgery, radiation therapy) according to response. Results At a median follow-up of 8 years, 5-year overall survival (OS) and event-free survival (EFS) for the whole group were 24% and 20%, respectively. No statistical difference was found between HDCT and standard chemotherapy (5-year OS, 36% v 27%; EFS 29% v 23%). Univariate analysis identified primary tumor in parameningeal, extremity, or other sites; age younger than 1 year and older than 10 years; bone or bone marrow metastases; multiple metastases; and multiple sites of metastases as unfavorable prognostic factors for OS and EFS. Multivariate analysis identified unfavorable site, bone or bone marrow involvement, and unfavorable age as independently unfavorable factors. Two subgroups were identified. Those with fewer than two unfavorable factors had 5-year EFS and OS of 40% and 47%, respectively. Patients with ≥ two unfavorable factors had 5-year EFS and OS of 7.5% and 9%, respectively. Conclusion A minority of patients with metastatic RMS have better survival than overall results for this population suggest. Those in the highest risk group have such poor survival that they are candidates for first-line novel therapies. There is no evidence that consolidation with HDCT improves outcome.

BACKGROUND The management of rhabdomyosarcoma (RMS) in patients age < 1 year is particularly problematic and requires a tailored therapeutic approach. We report on the Italian Cooperative Group's 20-year study of 50 children with RMS who were age < 1 year at diagnosis. METHODS Patients were treated using multimodality therapeutic approaches that were based on three consecutive protocols. Chemotherapy was administered to all patients, with dosages calculated according to body weight; calculated doses subsequently were reduced by 33–50%. Radiotherapy was administered to 10 patients. RESULTS With a median follow-up of 76 months, 5-year event-free survival and overall survival rates were 42.3% and 61.7%, respectively. Local recurrence was the major reason for treatment failure. In particular, the local recurrence rate was high in patients who warranted radiotherapy but received none due to their age. Completeness of surgery and nodal involvement were the most significant prognostic factors. After a suitable reduction in dosage was made, acute toxicity was no different from what has been observed in older children. The most relevant toxic event was cardiotoxic death in a newborn (n = 1). CONCLUSIONS The current study confirmed that the outcome for infants with RMS is less satisfactory than for older children and that infants with RMS require more careful monitoring and specific treatment guidelines. The absence of local control is the major cause of treatment failure; aggressive conservative surgery should be encouraged, but more radiotherapy may be advisable in selected cases. Intensive chemotherapy is essential; a 33% dose reduction may ensure adequate tolerance. In addition, patients age < 3 months should not receive anthracyclines. Cancer 2003;10:2597–604. © 2003 American Cancer Society. DOI 10.1002/cncr.11357

Purpose: To identify the prognostic factors, treatment, and outcome of children affected by renal cell carcinoma (RCC). Patients and Methods: The series included 41 patients (18 males and 23 females) with a median age of 124 months observed at the 11 Italian Association for Pediatric Hematology and Oncology centers from January 1973 to January 2001. Clinical data, surgical notes, pathologic findings, and summaries of therapy were taken from the charts. Results: Seven (17%) of the 41 patients had a papillary histology, and 34 (82.4%) had nonpapillary histology. Eighteen patients (43.9%) had stage I, one patient (2.4%) had stage II, two patients (4.8%) had stage IIIA, 10 patients (24.3%) had stage IIIB, and nine patients (21.9%) had stage IV disease. One patient had a bilateral involvement at diagnosis. Seven patients experienced disease recurrence. Lung and liver were the most common distant lesions and usually were fatal. In this study, the major factor influencing the prognosis was the stage. Event-free survival at 20 years was 53.5% for all patients. Overall survival at 20 years was 54.9% for all patients. Conclusion: RCC is a rare disease in children and adolescents. This neoplasm has a different clinical presentation in children compared with adults but the same outcome. In our experience, patients with localized disease could be cured by nephrectomy alone. Prospective studies in a larger number of patients are needed to confirm radiation therapy and biologic response modifiers as effective adjunct therapy in RCC stage III. The alternative therapy seems warranted in patients with advanced disease.

BACKGROUND Clear cell sarcoma (CCS) of tendons and aponeuroses is extremely rare in childhood and little information is available on its clinical management. Originally believed to be a type of melanoma of soft tissue origin, CCS is now considered a distinct clinicopathologic entity that behaves like a high-grade soft tissue sarcoma. We report on a series of 28 pediatric patients treated from 1980 to 2000 by the Soft Tissue Sarcoma Italian Cooperative Group and the German Cooperative Group. METHODS Patients were treated with a multimodality therapeutic approach. Surgical resection was complete in 17 patients (mutilating in 3), radiotherapy was administered to 8 patients, and 20 patients received chemotherapy. RESULTS After a median follow-up of 102 months (range, 19–238 months), the 5-year and event-free survival rates were 66.4% and 63.3%, respectively. Seventeen patients were alive in first remission, two were alive in second remission, and nine had died of disease. The response to chemotherapy in the 7 evaluable patients included one partial remission, one minor response, and five no responses. Radiotherapy contributed to achieving local control in four of six Intergroup Rhabdomyosarcoma Study (IRS) Group II patients. Statistically significant differences in outcome were evident according to IRS group, tumor size, and site. CONCLUSIONS Our study confirms the aggressive behavior of CCS. Complete surgical resection represents the mainstay of treatment, and even the only treatment for patients with small tumors. Radiotherapy may control microscopic residual disease after surgery. Chemotherapy is ineffective and the prognosis is unfavorable for patients with unresectable and large tumors. Cancer 2002;94:3269–76. © 2002 American Cancer Society. DOI 10.1002/cncr.10597

BACKGROUND Hemangiopericytoma (HPC) is very uncommon in childhood and comprises two different clinical entities, the adult type and the infantile type, occurring in the first year of age. We report on a series of 27 pediatric patients treated from 1978 to 1999 by the Italian and German Soft Tissue Sarcoma Cooperative Group. METHODS Seven patients had infantile HPC; complete resection was achieved in the tumors of five patients and chemotherapy was given to four patients. Twenty children had adult type HPC; nine received complete tumor resection (four patients at diagnosis and five at delayed surgery). Post-operative radiotherapy was administered to 15 patients, chemotherapy to 19. RESULTS Six of seven patients with infantile HPC were alive in first remission; one patient died of disease. Chemotherapy achieved an objective response in four of four patients. Among the adult type HPC cases, 5-year event free survival was 64% (median follow-up 125 months); 12 patients were alive in first remission, eight patients relapsed and died of disease. Seven of 10 evaluable patients showed good response to chemotherapy. Statistically significant differences in outcome were observed in relation to Intergroup Rhabdomyosarcoma Study grouping, size, local invasiveness, and gender. CONCLUSIONS Infantile HPC is a unique entity probably related to infantile myofibroblastic lesions and characterized by a high response to chemotherapy, which is required in case of unresectable, life-threatening tumors. In children over 1 year of age, HPC behaves like its adult counterpart; complete surgical resection remains the mainstay of treatment, but chemotherapy and radiotherapy seem effective and are recommended in all patients with incomplete tumor resection and/or locally invasive, large tumors. Cancer 2001;92:2692–8. © 2001 American Cancer Society.

Background and Objectives Fibrosarcoma is a rare soft tissue sarcoma (STS) that has two peaks of incidence in pediatric patients: one in infants and young childern (infantile fibrosarcoma), another in older children (“adult type” fibrosarcoma). The purpose of this study was to describe the clinical features and the treatment results in patients affected by fibrosarcoma enrolled in two consecutive studies run by the STS-Italian Cooperative Group (ICG) between 1979 and 1995. Patients and Methods Twenty-five evaluable patients were grouped according the intergroup rhabdomyosarcoma staging (IRS) system: 12 Gr I, 5 Gr II, 8 Gr III. The cut-off point between the two forms was considered the age of 2 years: 14 patients were affected by infantile and 11 by adult type of fibrosarcoma. The therapeutic guidelines were not strict and not different for the two forms: patients with initial macroscopic excision (Gr I–II) were given IVA or VAC; Gr III had VAC or VAIA and subsequent excision, if feasible. Radiation therapy (RT) was delivered in patients > 3 years with microscopic (42 Gy) and macroscopic (54 Gy) residuals. Results Thirteen patients are alive without evidence of disease: 10 in first complete remission (CR), 7 Gr I, 1 Gr II, 2 Gr III, 3 in second CR after local relapse (LR) (2 Gr I, 1 Gr II). Two Gr I patients are alive with metastatic relapse. Nine patients died: six of progressive disease (PD) (three Gr II, three Gr III), two because of a second tumor (one Gr I, one Gr III) and one because of other causes (Gr III). One Gr III patient was lost at follow up, 2 years from diagnosis. The 10 years overall survival (OS) is 67.4% and the progression-free survival (PFS) is 52.2%. The OS for patients 2 years (5 of 11). Conclusions The complete excision at diagnosis was the treatment of choice and was related to the best outcome. Microscopical residuals were difficult to treat with chemo-radiotherapy in both forms of fibrosarcoma. Neoadjuvant chemotherapy (CT) obtained a partial remission (PR) only in three of eight cases, while no conclusions concerning the efficacy of CT for infantile forms are possible. Patients

To evaluate the incidence of second malignant tumors in a cohort of subjects previously treated for childhood cancer, we analyzed data from the Off-Therapy Registry (OTR) of the Italian Association of Pediatric Hematology/Oncology, which collects information on children treated for Hodgkin's disease, non-Hodgkin's lymphoma, Wilms' tumor, acute lymphoblastic leukemia (ALL) and acute non-lymphatic leukemia and who had been removed from treatment in the absence of clinical signs of disease, i.e. the off-therapy stage. Second malignant tumors (SMT), diagnosed before December 31, 1988, were identified through a special enquiry to the 36 institutions cooperating in the registry. Observed cases were compared to expected numbers estimated from age- and sex-specific incidence rates derived from the Cancer Registry of the Province of Varese. In a total of 3,310 study subjects, 27 SMTs have been registered. The Cumulative Risk (CR) of SMT was 2.9% 15 years after the end of treatment and the Standard Incidence Ratio (SIR) was 10.8. The ALL sub-cohort had the highest risk of SMT (SIR 13.6) and 9 cases of CNS tumor occurred in this group (SIR 58.9). All 9 had received prophylactic cranial radiotherapy (CRT) and 5 had been treated on one protocol, characterized by low-dose intrathecal methotrexate (IT MTX) given monthly for 2 years after CRT. The Off-Therapy Registry has unique criteria for inclusion; direct comparisons with similar studies are therefore somewhat problematic. However, our data suggest that the risk of SMT in childhood ALL cancer survivors may be greater than previously reported, and that CNS tumors are the most common SMT in this group. The administration schedule of IT MTX may be an important risk factor.

Thirty-four infants under 1 year of age with Wilms’ tumor were diagnosed and treated in 14 Italian pediatric oncology units during 1970-79. The 3-year survival rates decreased with higher group unilateral tumors: 95% in group I Wilms’ tumor, 75% in group II and 20% in group III. The survival rates for children with group I and II Wilms’ tumor were similar for those who were treated with surgery and chemotherapy and those who also received postoperative radiotherapy. During 1975-79 fewer patients with group I Wilms’ tumor received radiotherapy (1 of 11) than during 1970-74 (4 of 6, p < 0.05). All these children are alive at this writing.