First effective immunotherapy for high-risk neuroblastoma

A team led by San Diego medical researcher Alice Yu published in New England Journal of Medicine their break-through results of the first ever immunotherapy proved to be effective for high-risk neuroblastoma patients. This new treatment was first announced in the 2009 edition of ASCO meeting (see previous post). Children with this disease normally have a grim prognosis. Yu's group treated children after standard high-dose chemotherapy and stem cell rescue with a monoclonal antibody against a surface molecule commonly found in neuroblastomas - the disialoganglioside GD2. Anti-GD2 therapy along with isotretinoin and IL-2 boosted patients' disease-free survival by 20% (44 to 64% 2 years after diagnosis). This result is superior to conventional treatment. The only drawback was the high amount of toxicity in immunotherapy-treated patients. Read the article here.

Intermediate-risk neuroblastoma has good prognosis

Neuroblastoma, a tumor that affects mostly young children and has a very high mortality rate when advanced, has been shown in a study published in 2010 that can have good prognosis with reduced chemotherapy. The study, announced for the first time in 2007 (see this previous post) was led by a team from Perth, Australia and endorsed by Childrens Oncology Group. They used the COG risk stratification system that uses clinical and tumor biological data to assign children to one of 3 risk groups: low, intermediate and high. Only intermediate-risk patients were included in this study. Results have shown that a short, reduced chemotherapy made up of 4 or 8 cycles and lower doses than previous treatment regimens yielded high survival rates. This regimen reduced toxicity as well, while maintaining a very good result. In this present study, 100% of INSS stage 3 patients achieved prolonged cure. Read the complete article here.

High-dose chemotherapy and stem cell transplant for advanced neuroblastoma

Results from a french pilot trial testing very high dose chemotherapy followed by autologous transplantation in children with advanced neuroblastoma were not different from previous trials with other approaches. Survival in this group of patients remained between 30-40% in 5 years. New treatments are needed for kids with advanced neuroblastoma.

A dose-intensive approach (NB96) for induction therapy utilizing sequential high-dose chemotherapy and stem cell rescue in high-risk neuroblastoma in children over 1 year of age - Monnereau-Laborde - 2011 - Pediatric Blood & Cancer - Wiley Online Library

Advanced neuroblastoma treated with 131I-MIBG and combined chemotherapy

A group from Italy has just published results from a trial using Radio-iodine MIBG to treat kids with advanced neuroblastoma. They report better results with association to chemotherapy. This initial report may yield new clinical trials using this combination to test it's efficacy against this grim disease.

Treatment of advanced neuroblastoma in children over 1 year of age: The critical role of 131I-metaiodobenzylguanidine combined with chemotherapy in a rapid induction regimen - Mastrangelo - 2011 - Pediatric Blood & Cancer - Wiley Online Library

Neuroblastoma e VEGF - um relacionamento maligno

Altos níveis de expressão do fator de crescimento endotelial vascular (VEGF) no neuroblastoma são associadas a um estágio avançado do tumor e sobrevida reduzida para crianças com mais de 18 meses de idade.
Dr. Jakovljevic e colegas avaliaram a expressão de VEGF em amostras de tecido neuroblastoma de 56 crianças para determinar se este se correlaciona com outros fatores de prognóstico e resposta ao tratamento.
Cinqüenta e quatro dos 56 tumores foram positivos para a coloração de VEGF, e somente 2 tumores mostraram imunorreatividade negativa para VEGF. Doze tumores tiveram baixos escores na expressão de VEGF e outros 44 apresentaram altas pontuações na expressão de VEGF. Houve uma correlação significativa entre a expressão do VEGF alta e estágio avançado do tumor.
Comparado com os pacientes que sobreviveram mais de cinco anos, aqueles que não sobreviveram tinham expressão de VEGF significativamente maior, enquanto todos os pacientes com baixa expressão de VEGF sobreviveram. Este relacionamento só estava presente em pacientes com idade superior a 18 meses.
Artigo completo aqui.

Novo tratamento para neuroblastoma

Este vídeo da Cancer Research UK no YouTube mostra novidades no tratamento do neuroblastoma, um dos tipos de tumores sólidos mais frequentes nas crianças.
http://www.youtube.com/watch?v=ILIS2bOaj00

Dr Juliet Gray and Professor Martin Glennie - new treatment for neuroblastoma

ASCO 2009: Immunotherapy Prolongs Survival in High-risk Pediatric Neuroblastoma

An experimental immunotherapy product has been shown to improve overall survival and to reduce the risk for relapse in children with high-risk neuroblastoma. The results from a phase 3 clinical trial are due to be presented at the upcoming 2009 Annual Meeting of the American Society of Clinical Oncologists (ASCO). The new product is a chimeric antibody directed against a glycolipid known as GD2, which sits on the surface of neuroblastoma cells and protects them from attack by the immune system. When the antibody binds to GD2, it provokes an attack by different types of immune cells against the cancer. This is the first time that an antibody directed against a glycolipid has shown clinical efficacy and an improvement in survival, Dr. Yu noted. Most antibody therapies are directed against proteins, she pointed out.
The trial was conducted by the Children's Oncology Group in 226 newly diagnosed high-risk neuroblastoma patients who had achieved a complete or partial response to induction therapy and had received myeloablative consolidation with stem-cell rescue. All received standard treatment with 13-cis-retinoic acid for 6 cycles, and half the patients also received 5 concomitant cycles of the antibody. The antibody was administered along with 1 of 2 cytokines — granulocyte macrophage colony-stimulating factor and interleukin-2 — given in alternating cycles, as preclinical studies had shown an enhanced efficacy. After 2 years, overall survival was 86% in the immunotherapy group and 75% in the standard-treatment group, and event-free survival was 66% and 46%, respectively. The study was terminated early because of the benefit seen in interim analyses.
Read more on Medscape.

Myeloablative therapy and cis-retinoic acid confer better survival to high-risk neuroblastoma patients

The results of study CCG-3891 were published in March 2009 on Journal of Clinical Oncology. The multicentric study has shown that high-dose myeloablative chemotherapy followed by stem-cell rescue is better than conventional chemotherapy for high-risk neuroblastoma patients. Moreover, addition of cis-retinoic acid treatment after chemotherapy could boost survival in both groups. Standard therapy for high-risk neuroblastoma patients should be therefore myeloablative chemotherapy with autologous stem cell rescue followed by cis-retinoic acid treatment.
Read the article here.

Scientists Discover Neuroblastoma Gene

Scientists have discovered that mutations in a gene called anaplastic lymphoma kinase (ALK) are a major cause of neuroblastoma in both inherited and noninherited forms of neuroblastoma. Previous to this finding, it was known that numerous chromosomal abnormalities, including deletions of chromosome arms 1p, 11q, and 14q, were associated with neuroblastoma, though no specific drug targets had been identified. ALK is a tyrosine kinase, one of a family of proteins that add phosphate groups to other proteins. These phosphate groups act as switches that regulate the activity of other proteins. Thus, the phosphotransferase activity of tyrosine kinases is strictly controlled in normal cells. Mutations that abnormally activate the phosphotransferase activity of tyrosine kinases are a major cause of cancer in numerous tumor types. ALK, like MYCN, can be amplified in neuroblastoma. The discovery of ALK mutations in neuroblastoma provides an exciting opportunity to develop new approaches for therapy, and an ALK inhibitor has been tested for efficacy in non-small-cell lung cancer.
Read more in Medscape.
Article here.

Effectiveness of screening for neuroblastoma

A japanese group has published a retrospective evaluation of neuroblastoma mass-screening program that was performed between 1984 and 2003. They reported that this program was effective for more neuroblastoma diagnosis and less mortality, suggesting that previous accounts that it did not affect patients mortality were not true. These results indicate that neuroblastoma mass-screening with quantitative methods can effectively diminish the diagnosis of late-stage disease and help reduce mortality in children with this disease. Read the article here.

Portal Oncopediatria - Neuroblastoma

A tese de doutorado “Estudo Comparativo para o Tratamento de Crianças com Neuroblastama Avançado” da médica Lilian Maria Cristofani é mais um trabalho disponivel no portal Oncopediatria.
A tese descreve o estudo que a especialista realizou tratando 36 crianças com neuroblastoma avançado com quimioterapia de altas doses seguida de transplante autólogo de medula óssea. O resultado, infelizmente, não logrou obter melhor sobrevida do que o tratamento convencional, mostrando a necessidade de novas e melhores abordagens terapêuticas para estes pacientes.
Texto da tese na íntegra aqui.

Less aggressive approach to neuroblastoma still effective

In infants and children with intermediate risk neuroblastoma, a reduced-intensity chemotherapy regimen yields survival rates comparable to or better than a more aggressive regimen typically used in this patient population, researchers report.

In a study of 467 neuroblastoma patients, 192 received 4 cycles of chemotherapy in 64 days (the less intense arm) and 275 received 8 cycles in 168 days (the standard arm), following surgery. Chemotherapy consisted of 2 to 3 drug combinations of carboplatin, etoposide, cyclophosphamide and doxorubicin.

"The bottom line is that with significantly less intense chemotherapy, we achieved 3-year overall survival of 96%," Dr. David L. Baker told the 43rd annual meeting of the American Society of Clinical Oncology.