The antitumor effect of static and extremely low frequency magnetic fields against nephroblastoma and neuroblastoma.

Certain magnetic fields (MF) have potential therapeutic antitumor effect whereas the underlying mechanism remains undefined. In this study, a well-characterized MF was applied to two common childhood malignancies, nephroblastoma and neuroblastoma. This MF has a time-averaged total intensity of 5.1 militesla (mT), and was generated as a superimposition of a static and an extremely low frequency (ELF) MF in 50 Hertz (Hz). In nephroblastoma and neuroblastoma cell lines including G401, CHLA255, and N2a, after MF exposure of 2 h per day, the cell viability decreased significantly after 2 days. After 3 days, inhibition rates of 17-22% were achieved in these cell lines. Furthermore, the inhibition rate was positively associated with exposure time. On the other hand, when using static MF only while maintaining the same time-averaged intensity of 5.1 mT, the inhibition rate was decreased. Thus, both time and combination of ELF field were positively associated with the inhibitory effect of this MF. Exposure to the field decreased cell proliferation and induced apoptosis. Combinational use of MF together with chemotherapeutics cisplatin (DDP) was performed in both in vitro and in vivo experiments. In cell lines, combinational treatment further increased the inhibition rate compared with single use of either DDP or MF. In G401 nephroblastoma tumor model in nude mice, combination of MF and DDP resulted in significant decrease of tumor mass, and the side effect was limited in mild liver injury. MF exposure by itself did not hamper liver or kidney functions. In summary, the antitumor effect of an established MF against neuroblastoma and nephroblastoma is reported, and this field has the potential to be used in combination with DDP to achieve increased efficacy and reduce side effects in these two childhood malignancies. Bioelectromagnetics. 39:375-385, 2018. © 2018 Wiley Periodicals, Inc.

Results of Therapy for Wilms Tumor and Other Malignant Kidney Tumors: A Report From the Chilean Pediatric National Cancer Program (PINDA).

OBJECTIVE: The aim of this study was to analyze the survival of children with Wilms tumor and other malignant renal tumors treated with the TWPINDA-99 protocol. MATERIALS AND METHODS: Between January 1999 and December 2013, 226 patients were registered on this trial, based on National Wilms Tumor Study-5. Patient characteristics and survival were evaluated. RESULTS: Two hundred seven patients were diagnosed with Wilms tumor, which represented 91.6% of renal tumors. The male to female ratio was 0.7:1. The median age at diagnosis was 3.3 years. Stage III was the most frequent (39.2%). Metastatic disease was present in 16.7% of the cases. Synchronous bilateral disease was observed in 9.3% of the cases. Favorable histology was diagnosed in 93.6% and anaplastic histology in 6.4% of the patients. Median follow-up was 7.5 years. Ten-year event-free survival and overall survival (OS) for assessable patients with Wilms tumor (n=192) were 82.0% and 89.9%, respectively. OS for patients with stage I was 100% (n=36), stage II: 97.1% (n=35), stage III: 88.6% (n=71), stage IV: 77.9% (n=32), and stage V: 80.8% (n=18). OS for favorable histology (n=180) and anaplastic histology tumors (n=12) were 91.0% and 72.9%, respectively. Other malignant renal tumors had a poorer survival. CONCLUSION: Prognosis for patients with Wilms tumor treated on TWPINDA-99 seems to be better than previous national trials and is similar to developed countries.

The oral health needs of children after treatment for a solid tumour or lymphoma.

BACKGROUND: With increasing survival rates for childhood cancer, late effects are of growing importance. Oral health is central to general health, level of nutrition, quality of life, and is significant in the holistic care of children during cancer therapy. HYPOTHESIS: The oral health needs of children treated for solid tumours/lymphoma will be greater than the general population, groups will differ according to tumour and treatment. DESIGN: One hundred and twenty patients, 0-17 years, under follow-up from 01/07/06 to 07/02/07 were investigated for caries, opacities, microdontia, and gingivitis. Analysis was performed with stratification according to tumour and treatment. Comparisons made with the UK 2003 Child Dental Health Survey. RESULTS: The neuroblastoma group and high-dose chemotherapy with stem-cell rescue (HDCSCR) therapy group had increased caries of the primary teeth. Chi-squared analysis revealed a statistically significant relationship (P < 0.03) between the age at receipt of chemotherapy (<3.5 years) and the presence of microdont teeth. CONCLUSION: Oral health care is important for all patients particularly those with a neuroblastoma, or who received HDCSCR. Patients should be advised about the possibility of microdontia in the permanent dentition following chemotherapy under 3.5 years.

A pilot study of addition of amifostine to melphalan, carboplatin, etoposide, and cyclophosphamide with autologous hematopoietic stem cell transplantation in pediatric solid tumors-A pediatric blood and marrow transplant consortium study.

Limited information is available regarding the use of amifostine in pediatric hematopoietic stem cell transplant (HSCT) patients. Melphalan, carboplatin, etoposide +/- cyclophosphamide is a commonly used preparatory regimen in pediatric solid tumor HSCT. Therefore, we decided to determine the feasibility of the addition of amifostine (750 mg/m b.i.d. x 4 d) to melphalan (200 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) (level 1) and escalating doses of cyclophosphamide (3000 mg/m and 3800 mg/m, levels 2 and 3, respectively) followed by autologous HSCT. Thirty-two patients with a variety of pediatric solid tumors were studied. Seventeen patients were accrued at level 1, 9 at level 2, and 6 at level 3. Major toxicities during the administration of the preparatory regimen were hypocalcemia, emesis, and hypotension. Hypocalcemia required aggressive calcium supplementation during the conditioning phase. No dose limiting toxicities were encountered at level 3. Amifostine at 750 mg/m b.i.d. for 4 days can be administered with a double alkylator regimen consisting of melphalan (200 mg/m), cyclophosphamide (up to 3800 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) with manageable toxicities.

[Understanding nephroblastoma. Information dedicated to parents and relatives]. / Comprendre le néphroblastome. Information à l'usage des parents et des proches d'un enfant malade.

In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives, the SOR SAVOIR PATIENT program. The methodology of this program adheres to established quality criteria regarding the elaboration of patient information. Cancer patient information developed in this program is based on clinical practice guidelines produced by the FNCLCC and the twenty French regional cancer centres,the National League against Cancer, The National Cancer Institute, the French Hospital Federation, the National Oncology Federation of Regional and University Hospitals, the French Oncology Federation of General Hospitals, many learned societies, as well as an active participation of patients, former patients and caregivers. The handbook SOR SAVOIR PATIENT Understanding nephroblastoma is an adapted version of various scientific publications and international clinical practice guidelines, validated by oncology experts and by the Nephroblastoma Committee of the French Society against Cancers and Leukaemias in children and adolescents (SFCE). It was elaborated with the active participation of parents and other family members. It is meant to provide a basis for the explanation of the disease, to help parents asking questions, and to facilitate discussions with the healthcare team. It is available from the FNCLCC (101, rue de Tolbiac, 75013 PARIS, Tel. (0033)1 76 64 78 00, www.fnclcc.fr). This document was validated at the end of 2005 and published in May 2006. SOR SAVOIR PATIENT guides are systematically updated when new research becomes available. Information leaflets, extracted from the handbook SOR SAVOIR PATIENT Understanding nephroblastoma and published in this edition of the Cancer et Radiothérapie, describe the physiopathology of nephroblastoma, as well as treatments and follow-up. The guide allows parents and relatives to better understand the disease and the treatments proposed. It also offers health professionals a synthetic evidence-based patient information source which facilitates discussions with the patient.

[Treatment of advanced Wilms' tumor].

OBJECTIVE: To improve prognosis of the patients with advanced Wilms' tumor, the authors compared different therapeutic strategies including preoperative transcatheter arterial chemoembolization (TACE), conventional preoperative chemotherapy and initial surgery. METHODS: Sixty-two patients aged from 5 months to 10 years (mean 3.2 years) were identified from medical records to have histologically confirmed advanced Wilms' tumor during the period from January 1993 to December 2002. The criteria for choice were huge tumor size with a volume more than 550 ml or the mass extending beyond the midline, involvement of vital structures, inferior vena cava invasion, distal metastasis or bilateral Wilms' tumor judged by imaging examination. All cases were divided into 3 groups according to the treatment received: 31 cases in group TACE received preoperative transcatheter arterial chemoembolization with Lipiodol-Epirubicin (EPI)-Vincristine emulsion. One week after TACE, systemic chemotherapy with Actinomycin D (ACTD) was administered and tumor resected at two weeks after TACE. 20 cases in group PC received conventional preoperative chemotherapy with VCR, ACTD plus EPI for 4-5 weeks, and 11 cases in group IS underwent initial surgery. Postoperative treatment for all patients was based on the postoperative staging and tumor histology. RESULTS: In the patients treated with TACE, no drug-induced complications such as cardiotoxicity, nephrotoxicity, hepatic dysfunction or bone marrow suppression were observed except for mild fever due to tumor necrosis. The percentages of tumor size shrinkage were 32.4% and 20.3% in group TACE and group PC, respectively (P < 0.05). Complete surgical removal of the tumor was achieved in 27 patients (87.1%) in group TACE, significantly higher in comparison with 14 in group PC (70.0%, P < 0.05) and 2 in group IS (18.2%, P < 0.01). Event-free survival (EFS) at 2 years was 87.1% (27/ 31), 60.0% (12/20) and 18.2% (2/11), respectivrely. EFS at 4 years was 84.6% (11/13), 56.3% (9/16 ) and 18.2% (2/11) in groups TACE, PC and IS, respectively. CONCLUSION: The present study has shown that both preoperative TACE and conventional preoperative chemotherapy can be applied to the patients with advanced Wilms' tumor who are not candidates for immediately surgical resection. The survival is significantly increased in the patients undergoing preoperativeTACE when compared with conventional preoperative chemotherapy and initial surgery.

[Leptin, body composition and bone mineralization in children after treatment for Wilms tumor]. / Leptyna, skladowe masy ciala oraz mineralizacja ukladu kostnego u dzieci po zakonczonym leczeniu guza Wilmsa.

UNLABELLED: Advances in diagnosis and improved methods of treatment have resulted in increasing number of long-term survivors in children with Wilms tumor. Growth and puberty are important for accumulation of bone mass; chemotherapy nad radiotherapy used in treatment for Wilms tumor can influence bone structure and physical development. Leptin plays an important role in metabolism of adipose tissue and bone mineralization. Considering that neoplasm and its treatment can affect normal development in childhood, we analysed the influence of antineoplastic treatment on bone mineralization and the correlations between serum leptin levels, body composition and bone mineral density in survivors of Wilms tumor. Twenty subjects (12 boys) treated for Wilms tumor at the mean age of 10.9 (range 3-20 years) participated in this study. Mean follow up period after discontinuation of therapy was 5.6 years (range 2 months - 13.5 years). Mean age of diagnosis was 3.9 years (range 1 month - 12.6 years). 18 patients received chemotherapy, 7 - additionally radiotherapy and 2 infants had only surgery treatment. We measured fat mass - FM, fat free mass - FFM, bone mineral density - BMD total and BMD spine using dual energy x-ray absorptiometry (DXA) and compared to the results obtained for healthy references (SD score). Leptin levels were measured with RIA method. RESULTS: 1. No difference was found in leptin levels, body mass index, FM, FFM, BMD total and spine in relation to sex. 2. Means of SDS BMI, FM, FFM, BMD and leptin were in the normal range for the age and sex matched controls. 3. We found the correlation between leptin level and BMI, FM, FFM and BMD total and spine, no correlation was found between SDS values. 4. We observed a positive correlation between SDS BMD and SDS BMI, FM, FFM, BMD spine. 5. BMI, FM and leptin levels were higher in children treated with radiotherapy and chemotherapy than in children treated with only chemotherapy. However, the SDS values were comparable with the healthy controls. 6. SDS BMD total was decreased in 5/20 subjects (25% of all studied patients) compared with healthy controls. CONCLUSIONS: The results demonstrated the risk of osteopenia in the group of children treated for Wilms tumor and the necessity for long-term monitoring of bone mineralization.

[A century of progress in the knowledge and treatment of nephroblastoma]. / Un siècle de progrès dans la connaissance et le traitement du néphroblastome.

Since its initial description by Max Wilms over a century ago, nephroblastoma has benefited from considerable improvements both in terms of basic knowledge about it and management of it. Today, the majority of these very young patients can expect a long-term survival in excess of 90% at the price of a light therapy that combines surgical resection, chemotherapy based on ill-toxic agents, and in selected cases, radiotherapy of remarkably low toxicity. The contribution of large international studies will be emphasized here.

Activation of multiple effector mechanisms to enhance tumor immunotherapy.

Recent technical advances have enabled the generation of clinical reagents for immunotherapy. Currently, treatment protocols combining both interleukin-2 (IL-2) and tumor-specific monoclonal antibody are underway at the University of Wisconsin Comprehensive Cancer Center and elsewhere. These approaches are based on the hypothesis that IL-2-activated lymphocytes will use tumor-reactive antibody to more selectively and effectively destroy tumor in vivo. Just as IL-2 can activate lymphocytes to destroy antibody-coated tumor cells, other agents can activate neutrophils and monocytes to destroy antibody-treated tumor cells. We are investigating, in laboratory and clinic, approaches aimed at eventually using combinations of distinct antibody-based tumor recognition mechanisms in patients whose monocytes, neutrophils, and lymphocytes have been simultaneously activated with multiple biologic agents.

The use of magnetic resonance imaging in diagnosing Wilms' tumor mimicking a lumbosacral strain and sprain.

Wilms' tumor is the most common tumor of the kidney in childhood. This article discusses the case of a young adult with a Wilms' tumor whose initial presentation appeared similar to a lumbosacral strain. The use of magnetic resonance imaging in diagnosing Wilms' tumor is discussed, along with the common clinical picture of the disease.

[Chemoembolization of blood vessels in the complex treatment of children with nephroblastoma]. / Khimioémbolizatsiia sosudov v komplekse lecheniia detei s nefroblastomoi.

The results of roentgeno-endovascular intervention in nephroblastoma in 31 child are presented. For chemoembolization, suspension of lipiodol and adriamycin was used, for control of the effectiveness of the intervention--the radiopharmaceutical preparation pyrophosphate. After embolization, the decrease in tumor size was noted. This made easier the performance of nephrectomy, the volume of blood loss reduced. Pathomorphism of neuroblastoma induced by chemoembolization was studied. No complications were noted.

Integration of nutrition support into oncologic treatment protocols for high and low nutritional risk children with Wilms' tumor. A prospective randomized study.

Benefits and risks of nutrition support were evaluated in 31 malnourished children with newly diagnosed Wilms' tumor managed according to the third National Wilms' Tumor Study protocol. Patients were classified at diagnosis as being at high nutritional risk (HNR, n = 19) or low nutritional risk (LNR, n = 12). Ten HNR patients were randomized to central parenteral nutrition (CPN) and nine HNR patients were randomized to peripheral parenteral nutrition (PPN) plus enteral nutrition (EN) for 4 weeks of initial intense treatment and EN (nutritional counseling, oral foods and supplements) thereafter. Thirteen HNR patients (seven CPN, six PPN) completed the protocol. Twelve LNR patients received EN; 11 Stage I malnourished patients were randomized to 10 or 26 weeks of chemotherapy. Dietary, anthropometric, and biochemical data were determined for HNR patients at weeks 0-4, 6, 13, 19, and 26 and for LNR patients at weeks 1, 2, 5, and 26. In HNR patients, adequate parenteral nutrition support reversed protein energy malnutrition (PEM), and prevented chemotherapy and radiotherapy delays due to granulocytopenia. CPN was superior to PPN in reversing PEM: energy intake, weight gain, and retinol binding protein were higher (P less than 0.05). LNR patients lost weight and fat reserves in the first 2 weeks of treatment; depletion persisted at week 5, and 25% had chemotherapy delays. Thereafter, EN reversed PEM in patients with both chemotherapy regimens. These data suggest that CPN is preferable during initial intense treatment for HNR patients, and that, although EN is ineffective in preventing depletion and treatment delays in the first 5 weeks of treatment for LNR patients, it is effective thereafter.

Self-regulation treatment to reduce the aversiveness of cancer chemotherapy.

In an A-B design, the effectiveness of a multicomponent intervention for reducing chemotherapy-associated nausea and emesis in an 11-year-old cancer patient was evaluated. A highly structured, time-limited, self-regulation treatment was implemented that consisted of patient and parent instruction in self-hypnotic methods, cue-controlled relaxation, and guided imagery. Practice of the self-regulation methods at home and in vivo (clinic setting) in the absence of chemotherapy infusion were emphasized to promote skill acquisition and cross-setting generalization. Dependent variables included self-reported nausea intensity and parental report of duration of the patient's sleep and vomiting frequency. Data were obtained before, during, and following chemotherapy for baseline and self-regulation treatment phases across five cycles of chemotherapy that occurred over a 5-month period. During the intervention phase, a marked and clinically significant reduction in self-reported nausea and parent-observed vomiting were noted as well as a concurrent increase in sleep duration. The integrity of patient self-report and parental observations were supported by clinic staff anecdotal data. Treatment limitations and cost-effectiveness are discussed as well as the use of this intervention with adolescent patients.

Glutathione peroxidase activity, selenium and lipid peroxides levels in blood of cancer children.

The concentrations of whole blood and plasma selenium, plasma lipid peroxides and the glutathione peroxidase activity in plasma and erythrocytes were measured in untreated and treated children with neuro- (n = 23) and nephroblastoma (n = 32) aged 6 months to 15 years. The patients were divided into the following groups: 0.5-1, 1-3, 3.5-6 and 8-15 years old. In all the groups of cancer patients investigated selenium concentration in whole blood and plasma and glutathione peroxidase activity in erythrocytes and plasma were significantly lower than in the age-matched healthy children. The concentrations of lipid peroxides in plasma of children with cancer was higher than in the age-matched control group. No differences were observed between the levels of the determined parameters in children with neuro- and nephroblastoma. Nor were there any differences in the determined parameters between children before and during treatment with cytostatics and between children at different stages of the disease. A significant linear correlation was found between plasma selenium concentration and glutathione peroxidase activity in the erythrocytes and plasma of children with cancer.