Franca Fossati Bellani

Wilms’ tumor: past, present and (possibly) future

Wilms’ tumor is one of the successes of pediatric oncology, with an overall cure rate of over 85%, using relatively simple therapies. This excellent outcome has been the result of collaborative efforts among surgeons, pediatricians, pathologists and radiation oncologists. The results that have been achieved in children with Wilms’ tumors support the strong value of the multidisciplinary team approach to cancer. The two largest cooperative groups that have studied the optimum treatment for Wilms’ tumor are the National Wilms’ Tumor Study group in North America and the International Society of Pediatric Oncology, involving European and other countries. The National Wilms’ Tumor Study group recommends primary surgery before any adjuvant treatment, whereas the International Society of Pediatric Oncology trials are based on the use of preoperative chemotherapy. The debate on primary chemotherapy versus primary nephrectomy appears to have been overcome, in the sense that the advantages and disadvantages of these two diverse methods have emerged from large and well-performed clinical trials, and comparably low doses of anthracyclines and radiotherapy are now used. Challenges remain in identifying novel molecular, histological and clinical risk factors for stratification of treatment intensity. This could allow a safe reduction in therapy for patients known to have an excellent chance of cure with the current therapy, while identifying, at diagnosis, the minority of children at risk of relapse, who will necessitate more aggressive treatments. Another positive factor is the substantial progress that has been made in the cure for recurrent patients, with long-term survivals shifting from 30 to almost 60% in more recently treated patients with intensive-dose chemotherapy regimens. The combination of lower relapses and higher salvage rates translated into significantly improved overall survival for Wilms’ tumor patients as a whole. This review covers current concepts on treatment strategies for Wilms’ tumor, with an overview of the results and achievements of the important clinical trials.

Vinorelbine in Previously Treated Advanced Childhood Sarcomas Evidence of Activity in Rhadbomyosarcoma

Vinca alkaloids have proved active against a number of pediatric malignancies. The aim of this study was to assess the feasibility and effectiveness of using vinorelbine in previously treated pediatric patients with advanced sarcomas.

Evidence for activation of KIT, PDGFRα, and PDGFRβ receptors in the Ewing sarcoma family of tumors

The Ewing sarcoma family of tumors (ESFT) is one of the most common malignant neoplasms of children and adolescents, characterized by nonrandom translocations involving the Ewing sarcoma (EWS) gene. Over the years the adoption of intensive multimodality treatment approaches has led to a gradual improvement in the survival of patients with ESFT. The prognosis is still unsatisfactory for high‐risk patients, however, and novel therapeutic approaches are desirable. The aim of the study was to investigate the expression/activation of KIT, PDGFRα, and PDGFRβ receptor tyrosine kinases (RTKs) as potential therapeutic targets in ESFT.

Immunomodulation in a treatment program including pre- and post-operative interleukin-2 and chemotherapy for childhood osteosarcoma

Aims and Background The treatment applied in our Institution to children with localized osteosarcoma between 1991 and 1999 consisted of four interleukin 2 (IL-2) courses (9 x 106 IU/mL/daily x 4), alternated with pre- and post-operative polichemotherapy. The aims of the present study were to quantify the modifications of some immunological parameters induced by IL-2 and to verify whether polychemotherapy could reduce them. An additional aim was to assess whether any correlation between the immune modifications and the clinical outcome could be found. Patients and Methods We evaluated in 18 consecutive patients the following changes, induced in blood by each IL-2 course: number of lymphocyte subpopulations and natural killer (NK) cells, lymphokine activated killer (LAK) and NK activities. Results Chemotherapy did not influence the modifications of the number of NK and CD4+ cells and of the LAK and NK activities, induced by each of the four courses of IL-2. The magnitudo of the NK activity and the peak of the NK absolute counts significantly correlated with the clinical outcome. Conclusions The results show that the use of IL-2 permitted a repeated immune activation despite the intensive chemotherapy. Furthermore, although the limited number of cases precludes any definitive conclusion, the results suggest a possible role of the NK cells in the control of osteosarcoma.

Neuron-Specific Enolase Evaluation in Patients with Neuroblastoma

Neuron-specific enolase (NSE) may be of interest for the prognostic evaluation and follow-up surveillance in patients with neuroblastoma. We evaluated NSE levels in 80 patients with neuroblastoma. The marker correlated with stage (in stage 1 patients, the median NSE level was 9.9 ng/ml, in stage 2, 45.1 ng/ml, in stage 3, 49 ng/ml, in stage 4, 93.9 ng/ml, in stage 4S, 53.4 ng/ml) and with survival. In patients with a favorable or a poor outcome, the difference in basal NSE serum levels was statistically significant (p = 0.0001). Serial measurements revealed that there was a good correlation between NSE levels and disease course. We concluded that NSE is a good marker for neuroblastoma and its quantitative determination in serum is valuable in the management of these patients to confirm the diagnosis, monitor the effect of treatment and detect recurrent disease.

Germ cell tumors of the ovary: The experience of the national cancer institute of milan. I. Dysgerminoma

The experience of the Istituto Nazionale Tumori of Milan on dysgerminoma is presented. Between 1970 and December of 1982, 25 patients were treated with a unique protocol which considered surgery and radiotherapy with different schedules according to the extension of the disease. With this treatment protocol all 13 patients at Stage I were alive and free of disease with a median follow-up of 77 months. Of 12 patients at Stage III (10 retroperitoneal and 2 retroperitoneal and peritoneal) 4 relapsed. The 5-year relapse-free survival of Stage III patients was 61.4% and the overall survival 89.5%. Amenorrhea due to radiation dose absorbed by the contralateral shielded ovary was found in 7.7%. The excellent results in Stage I patients were balanced by the unsatisfactory results in Stage III patients. A more aggressive treatment and the knowledge of other prognostic factors seem necessary.

Medulloblastoma. Results of a sequential combined treatment.

Actuarial progression‐free survival rate at 5 years of a series of 34 patients with medulloblastoma treated by combined surgery, radiotherapy, and chemotherapy was 71%. No relapses were observed in 14 patients followed for more than 5 years. Treatment consisted of a short postoperative course of vincristine (VCR) and intrathecal (IT) methotrexate (MTX) followed by irradiation to the entire cranio spinal axis. Maintenance chemotherapy (CCNU, VCR, and IT MTX) was then continued to encompass 2 years from surgery. Failure occurred in nine patients: four had local recurrence, four dissemination within the central nervous system, and one widespread skeletal metastases. Poor prognostic factors such as presence of malignant cells in the cerebrospinal fluid, non‐radical surgery, young age, and radiation doses less than 50 Gy to the tumor bed, did not adversely affect the outcome of patients in this series. Long‐term sequelae from the treatment program could be observed in all patients, and in 58% they were severe enough to interfere with normal, active life.

Clinical stage I nonseminomatous germ cell tumors of the testis in childhood and adolescence: an analysis of 31 cases.

A 20-year single-institution experience of clinical stage I nonseminomatous germ cell tumors of the testis (NSGCTT) in childhood and adolescents was reviewed in relation to clinical characteristics, treatment modalities, and survival. Thirty-one patients with clinical stage I NSGCTT were seen between 1980 and 2000: 14 children and 17 adolescents. Yolk sac tumors and/or teratomas occurred in the children, whereas mixed histologies, including embryonal carcinoma, were predominant in the adolescents. After orchiectomy, the children were assigned to surveillance and the adolescents to active treatment: 16 underwent retroperitoneal lymph node dissection (RPLND) and 1 had adjuvant cisplatin-based chemotherapy because of a high-risk histology. Three of the 14 children (21.4%) relapsed 3, 7, and 8 months after orchiectomy: all 3 had yolk sac tumors and presented with increased alpha-fetoprotein levels. No patients had retroperitoneal relapse; two recurred locally and one in the lung. All three children were treated with cisplatin-based chemotherapy with or without surgery. Among the 16 adolescents undergoing RPLND, 4 (25%) had nodal metastases. Three of the 12 patients (25%) who had negative nodes at RPLND relapsed in the lung 3, 7, and 8 months after RPLND. All were treated with cisplatin-based chemotherapy with or without surgery. Five-year relapse-free and overall survival rates for the whole series were 80.6% and 100%, respectively. This series enabled the authors to pinpoint several important aspects of stage I NSGCTT in children and adolescents. In particular, almost all the childhood cases had the same yolk sac tumor histology, the children tended to have localized disease, and an increased alpha-fetoprotein level had a very high predictive value, suggesting that follow-up should include AFP measurements. A conservative approach is the best option in children, while adolescent NSGCTT behaves like the adult disease and management must include similar treatment strategies.

Childhood non‐hodgkin's lymphoma: Long‐term results of an intensive chemotherapy regimen

Twenty‐nine consecutive children with untreated non‐Hodgkins malignant lymphoma were admitted to Istituto Nazionale Tumori of Milan during the period from 1974 through 1976 and underwent treatment with chemotherapeutic regimens consisting of Adriamycin, Cytoxan, vincristine, and prednisone (two month induction phase) and 6‐mercaptopurine, methotrexate, Adriamycin, vincristine, and prednisone (maintenance phase). Each patient, regardless of clinical stage or histologic subgroup, was given the same chemotherapy. The complete response rate was 66%. Due to the high incidence of recurrence of the initial bulky lymphomatous mass and of spread to the central nervous system (CNS), local radiotherapy was given to ten children and CNS prophylaxis (brain radiotherapy + intrathecal methotrexate) to 11 children. After a follow‐up period in excess of 40 months, there were five disease‐free survivors (17%). Each patient who had a relapse died from the disease. The main reason for first treatment failure was relapse at the level of the primary bulky tumor site or spread to the CNS. This type of CNS prophylaxis did not prevent relapse at this site.

End of life in children with cancer: experience at the pediatric oncology department of the istituto nazionale tumori in Milan.

Coping with end‐stage pediatric cancer patients and the related bereavement is a challenge for all the caregivers involved.