M. T. Di Tullio

Localized but unresectable neuroblastoma: treatment and outcome of 145 cases. Italian Cooperative Group for Neuroblastoma.

PURPOSE To define factors that influence outcome in children with localized but unresectable neuroblastoma by retrospective investigation of response to therapy and outcome in 21 Italian institutions. PATIENTS AND METHODS Of 145 assessable children diagnosed between 1979 and 1990, 77 were treated between 1979 and 1984 with three consecutive standard-dose (SD) protocols, and 68 between 1985 and 1990 with a high-dose (HD) protocol. All protocols included chemotherapy, followed by resection of primary tumor if feasible. If at least partial resection was achieved, consolidation therapy followed, except that from 1985 onward, patients considered disease-free following surgery received no further treatment. RESULTS Ninety-four of 145 patients (65%) achieved a complete response (CR) or partial response (PR) with chemotherapy and 75 (52%) subsequently underwent complete resection of the primary tumor. Eighty-one patients are alive (73 without disease, eight with disease), 63 have died, and one is lost to follow-up. The 5-year overall survival (OS) rate is 55% and progression-free survival (PFS) rate 50%. Both OS and PFS correlated with response to chemotherapy, removal of primary tumor, HD therapy, and serum lactate dehydrogenase (LDH) levels. Infants (< 1 year), independent of primary tumor site, and children aged 1 to 15 years with a nonabdominal primary tumor, did better compared with children aged 1 to 15 years with an abdominal primary tumor (PFS, 72% and 64% v 30%; P < .001 and < .01, respectively). Outcome of this last group improved with the HD protocol (PFS, 40% v 23%; P = .01). CONCLUSION In children with unresectable neuroblastoma, risk categories can be defined by age and primary tumor site. HD chemotherapy should be investigated for the poor-risk category age 1 to 15 years with an abdominal primary tumor.

Treatment of isolated testicular relapse in childhood acute lymphoblastic leukemia: an Italian multicenter study. Associazione Italiana Ematologia ed Oncologia Pediatrica.

Between May 1980 and April 1987, 49 children with acute lymphoblastic leukemia (ALL) in isolated testicular and first leukemia relapse (ITR) were enrolled in the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP) multicenter study REC80-ITR. According to the Rome Workshop criteria, 77% were at standard and 23% at high initial prognostic risk. In 33% of the cases, ITR occurred during first treatment. The REC80-ITR protocol consisted of an induction phase regimen of vincristine (VCR), cytarabine (ARA-C), methotrexate (MTX), and asparaginase (L-asp), and bilateral testicular irradiation, and CNS prophylaxis with intrathecal MTX and a maintenance phase with a multidrug rotating regimen. Total treatment duration was 30 months. The median time of observation after ITR was 51 months. The Kaplan-Meier estimates of survival and disease-free survival (DFS) at 4 years were 67.7% and 41%, respectively. Patients who had an ITR on therapy or within the first off-therapy year showed the poorest outcome. The DFS at 3 years was 20%, 47.6%, and 100%, respectively, for children who had an ITR on treatment (n = 16), within the first year of treatment withdrawal (n = 22), or later (n = 10) (P = .001). Patients with an asymptomatic occult testicular infiltrate at treatment discontinuation had a very unfavorable prognosis. Eighty-one percent of second relapses involved the bone marrow. In our experience, children presenting an early ITR (ie, within 6 months of treatment withdrawal) need a very aggressive treatment because of the high probability of an underlying systemic disease. On the other hand, patients with a late ITR seem to have a truly local recurrence and can apparently be cured by standard protocols, as shown in protocol REC80-ITR.

Tumor response and toxicity after single high-dose versus standard five-day divided-dose dactinomycin in childhood rhabdomyosarcoma.

This report deals with a randomized prospective multicentric clinical trial in childhood rhabdomyosarcoma (RMS) conducted to evaluate the toxicity and the effectiveness of dactinomycin (ACT-D) administered as high, single doses v five-day, divided doses administered in combination with vincristine (VCR) and cyclophosphamide (CYC). Fifty-five group III evaluable patients (pts) less than 15 years of age with tumor size greater than 5 cm in diameter, without high-risk features of CNS involvement, and 15 group IV RMS pts were randomized to receive VAC as primary chemotherapy (CT): VCR, 1.5 mg/m2 intravenously (IV) days 1 and 8; CYC, 275 mg/m2 IV days 1 through 5; and ACT-D, 0.45 mg/m2 IV days 1 through 5 every 28 days for three cycles (33 pts), or VAC-M: CYC, 150 mg/m2 intramuscularly (IM) days 1 through 7; VCR, 2.0 mg/m2 IV day 8; and ACT-D, 1.7 mg/m2 IV day 8 every 21 days for four cycles (37 pts). Major responses (complete plus partial responses [PR]) were obtained in 67% of the VAC pts and in 70% of the VAC-M pts. Toxic effects were low, and no increased toxicity was observed in pts treated with high, single-dose ACT-D. These results confirm the effectiveness and feasibility of single, high doses of ACT-D with the advantage of requiring less pt hospitalization.

Treatment of Poor-Risk Neuroblastoma with Intensive Chemotherapy and Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor

Advanced neuroblastoma is one of the most lethal pediatric malignancies. Several antitumor compounds are able to induce tumor regression, and a dose-response relationship has been demonstrated for some of them. A significant improvement in both response rate and duration of survival has thus been obtained by treatment intensification [1–4]. In the Italian experience, the median survival time of children treated with aggressive chemotherapy has been doubled compared with historical controls [5]. However, the higher initial response rate and the prolonged remission time has resulted in only a marginal improvement in cure rate, presently not exceeding 25% [6, 7]. Hematopoietic growth factors (colony-stimulating factors, CSFs), by mitigating the myelotoxic effect of chemotherapy, may reduce the treatment-related morbidity and thus permit the delivery of higher dosages and the shortening of intervals between chemotherapy courses [8, 9].

GERM CELL TUMOURS IN CHILDREN- A Report of 84 Cases

Publisher Summary This chapter discusses the results of a study examining germ cell tumors (GCTs) in children. In January 1991, a protocol for the diagnosis and treatment of GCTs in children was activated in 15 Italian pediatric centers. The diagnosis was made by the histological examination of a specimen obtained by surgical resection or biopsy and serum tumor marker positivity. Treatment was based on tumor site, histology, and stage. In the study, eighty-four patients were entered (40 males, 44 females), age range 0 to 14 years (median 5.1 years). The histological features were the following: (1) mature teratoma, 45 patients, (2) immature teratoma, 12 patients (eight grade II, four grade III), (3) MNSGCT 24 patients, including 2 cases of malignant relapse of one mature and one immature teratoma, and (4) seminomatous tumor, 5 patients. One patient with a SC tumor had a local malignant recurrence six months after surgical resection: the patient was disease-free 14 months after a second resection and 2 courses of chemotherapy (JE/IVA).

Soft Tissue Sarcomas in Infants Less than 1 Year Old: Experience of the Italian Cooperative Study RMS-791

Zusammenfassung18 Sauglinge wurde in der Italienischen Kooperativstudie RMS-79 registriert und behandelt. 10 Patienten hatten ein Rhabdomyosarkom (7 ein «embryonales», 3 ein «alveo-lares», 8 andere We