Stage 4 neuroblastoma: sequential hemi-body irradiation or high-dose chemotherapy plus autologous haemopoietic stem cell transplantation to consolidate primary treatment

Abstract

The aim of the present study was to evaluate the effectiveness of two consecutive nonrandomised treatment programs applied between 1989 and 1999 at the Istituto Nazionale Tumori of Milan in an unselected cohort of 59 children over the age of one with stage 4 neuroblastoma. Both treatment programs consisted of two phases, the induction of the remission phase and the consolidation phase. The induction of the remission phase consisted of intensive chemotherapy, and remained the same throughout the study period. The consolidation phase consisted of sequential hemi-body irradiation (HBI) (10 Gy per session, 6 weeks apart) in the first period (1988( -June 1994 and sequential high-dose cyclophosphamide, etoposide, mitoxantrone þ L-PAM and autologous haemopoietic stem cell transplantation in the second (July 1994(July -1999. Intention-to-treat analysis revealed a significantly better outcome for patients treated with the second program, the 5-year event-free survival probability being 0.12 for program 1 and 0.31 for program 2 (P ¼ 0.03). This finding led us to conclude that sequential HBI is useless as consolidation treatment. The high-dose chemotherapy adopted in the second program enabled a proportion of patients to obtain long-term survival but, since the clinical results remain unsatisfactory, new treatment strategies are warranted.

Neuroblastoma in Patients over 12 Years Old: A 20-Year Experience at the Istituto Nazionale Tumori of Milan

“…Radiotherapy was employed in our study both as local treatment on the site of the primary tumor and as systemic treatment with sequential HBI. The small number of cases of the present series does not allow us to draw any conclusion about the impact of radiotherapy on local control, whereas the results of sequential HBI as consolidation therapy were worse than the results reported in other studies with myeloablative chemotherapy, a treatment modality that was abandoned 10,18,19 .…”

“…Patients with stage 4 neuroblastoma received the same treatment given for stage 3 neuroblastoma up until 1989. From 1989 to 1994, the treatment program for stage 4 cases was intensified and consisted of 8 monthly cycles with vincristine, etoposide, cisplatinum and epi-adriamycin alternated with ifosfamide, followed by a consolidation phase with 10 Gy HBI (1989)(1990)(1991)(1992)(1993)(1994), or sequential high-dose cyclophosphamide, etoposide, and myeloablative melphalan + mitoxantrone and autologous stem cell rescue (1995-2001) 10 . "Local" treatment on the primary tumor of patients with stage 4 neuroblastoma was scheduled after the 4 th cycle of chemotherapy and consisted of surgery or radiotherapy (35-45 Gy) decided on a case-by-case basis.…”

High CD133 expression levels in gastrointestinal stromal tumors

“…As both KIT and CD133 were PE-conjugated, CD34 FITC 7AADÀ (the R1 region in (F) was used as a secondary immunological gate to evaluate CD133 expression (G) of GIST cells. MSCs were obtained from the cryopreserved material of a patient participating in an investigative protocol (approved by our Institutional Ethics and Scientific Board) in which high-dose chemotherapy was used; informed consent for the use of the material was obtained as previously described (24). The c-kit (Hs00174029_m1 probe; Applied Biosystem), CD133 (Hs01009259_m1 probe; Applied Biosystem), CD90 (Hs00264235_m1 probe; Applied Biosystem), and beta 2 microglobulin cDNAs (Hs00187842_m1 probe; Applied Biosystem) used as endogenous controls were relatively quantified by means of real-time quantitative PCR (ABIPRISM 5700 PCR Sequence Detection Systems, Applied Biosystems) and a TaqMan-based analysis (User Bulletin No.…”

The Transcribed-Ultra Conserved Regions: Novel Non-Coding RNA Players in Neuroblastoma Progression

“…Neuroblastoma is a type of peripheral sympathetic nervous system cancer, affecting mostly infants and young children (95% of which are under the age of 5, and occurring 13% more frequently in males), which alters the growth and proliferation of neural crest cells (precursor nervous system cells) [1]. Neuroblastoma has a diverse clinical response to current treatments across the patient population and is quite rare, making research difficult.…”

“…Most often, neuroblastoma originates within either the adrenal glands, the paravertebral ganglia, and/or the neck as a solid tumor, and can potentially spread, although it is normally caught prior to widespread malignancy [2]. Surgery, chemotherapy, and radiotherapy are all current options for treatment depending upon the characteristics of the tumor’s presentation and behavior; however, chemotherapy is currently the main treatment option [1]. It was discovered that an amplification of the MYCN ( v-myc myelocytomatosis viral related oncogene, neuroblastoma derived ( avian )) gene in Neuroblastoma patients was correlated with an increased aggressive behavior of the tumor, leading to a poor prognosis [9,10].…”