Liver involvement in neuroblastoma: the Memorial Sloan-Kettering Experience supports treatment reduction in young patients.
ABSTRACT We reviewed clinical and biologic findings in a series of infants with neuroblastoma (NB) in liver. The aim was to gain insights into improving therapy.
Among 19 newly or recently diagnosed infants with NB in liver, 1987-2002, those with stage 4 involving bone received chemotherapy, while those without bone or extensive bone marrow (BM) involvement were observed or received limited treatment if NB caused life-threatening symptoms. We assessed results in the context of NB treatment risk stratification, which is based on age, stage, and selected biologic features (MYCN, ploidy, histology).
Six of eight infants with bone involvement became long-term event-free survivors including 1/2 with MYCN amplification and four who received only 4-6 cycles of chemotherapy; at the end of treatment, four infants had abnormalities in liver +/- the primary site, but these resolved. All 11 infants without bone lesions became long-term survivors with either no cytotoxic therapy or only one cycle of chemotherapy (+/- radiotherapy to liver), including four who had stage 4 and one stage 4S patient who still had NB in BM at age 15 months.
Treatment reduction should be considered for subsets of infants with non-MYCN-amplified widespread NB: stage 4 without bone or extensive BM involvement may not require cytotoxic therapy, stage 4S with symptomatic hepatomegaly may not require multiple cycles of chemotherapy, and classic stage 4 may do well with limited chemotherapy. Persistent liver abnormalities post-treatment may not require continued therapy to achieve a radiologic complete remission.
Article: Malignant liver tumors[Show abstract] [Hide abstract]
ABSTRACT: Malignant tumors of the liver comprise a relatively small fraction of the total number of pediatric malignancies. However, these tumors can be a significant cause of morbidity and mortality, and there have been significant therapeutic gains during the past few decades through advances in systemic therapy and surgical treatment. Even in patients with advanced local disease, complete resection is now a possibility because of improvements in liver transplantation techniques. In this review, we will discuss the staging and treatment of common malignant tumors of the liver.Seminars in Pediatric Surgery 08/2012; 21(3):245-54. DOI:10.1053/j.sempedsurg.2012.05.007 · 1.94 Impact Factor
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ABSTRACT: Cancer in children has a low incidence. The type of malignancies differs substantially from tumors in adults. Since long-term event-free survival rates above 80% are noted in several tumors, it is estimated that in the future 1 in 750 adults will be a cancer survivor. Data on late effects are emerging and indicate that a large proportion of ex-patients has several and sometimes severe treatment sequelae. Minimizing treatment without loss of effectiveness in good risk cases and improving therapy in poor cases should be main goals in the future. In this review an update is given on tumor biology and treatment for several tumors, i.e. neuroblastoma, nephroblastoma, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, hepatoblastoma and germ cell tumors.Update on Cancer Therapeutics 12/2007; 2(4):177-191. DOI:10.1016/j.uct.2007.10.005
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ABSTRACT: Recent genomic and biological studies of neuroblastoma have shed light on the dramatic heterogeneity in the clinical behaviour of this disease, which spans from spontaneous regression or differentiation in some patients, to relentless disease progression in others, despite intensive multimodality therapy. This evidence also suggests several possible mechanisms to explain the phenomena of spontaneous regression in neuroblastomas, including neurotrophin deprivation, humoral or cellular immunity, loss of telomerase activity and alterations in epigenetic regulation. A better understanding of the mechanisms of spontaneous regression might help to identify optimal therapeutic approaches for patients with these tumours. Currently, the most druggable mechanism is the delayed activation of developmentally programmed cell death regulated by the tropomyosin receptor kinase A pathway. Indeed, targeted therapy aimed at inhibiting neurotrophin receptors might be used in lieu of conventional chemotherapy or radiation in infants with biologically favourable tumours that require treatment. Alternative approaches consist of breaking immune tolerance to tumour antigens or activating neurotrophin receptor pathways to induce neuronal differentiation. These approaches are likely to be most effective against biologically favourable tumours, but they might also provide insights into treatment of biologically unfavourable tumours. We describe the different mechanisms of spontaneous neuroblastoma regression and the consequent therapeutic approaches.Nature Reviews Clinical Oncology 10/2014; DOI:10.1038/nrclinonc.2014.168 · 15.70 Impact Factor