Chronic neuroblastoma

Abstract

BACKGROUND An indolent course is associated with neuroblastoma (NB) in adolescents and adults. In the current study, the authors analyzed this phenomenon in a large series of children with metastatic NB. METHODS The authors studied 38 patients who were diagnosed with NB in the first decade of life and had metastatic disease 5 years or more from diagnosis. RESULTS The median age at diagnosis was 3 years 10 months. MYCN was amplified in 2 of 28 patients tested. Of 30 patients with classic Stage 4 NB, 9 had a late first recurrence of disease (4.3–13 years from diagnosis). Of eight patients who had atypical cases at diagnosis (one isolated mandibular lesion, two Stage 4‐N, five non‐Stage 4), six had a late first distant recurrence of disease (4 years 11 months–38 years 8 months). Nineteen patients were off therapy continuously for 3 years or more before disease recurred a first or second time. Myeloablative therapy was used to consolidate a first or second response in 27 patients. High‐dose conventional therapy helped to achieve a second remission of disease in 9 of 20 patients assessable for response of first recurrence but achieved no major responses of second or third relapse in 10 of 11 patients. The combination of anti‐GD2 immunotherapy and/or cis‐retinoic acid, targeted radiotherapy, and multiple cycles of chemotherapy with modest toxicity helped prolong survival. Twelve patients survive at 5 years 6 months+ to 19 years 4 months+ from diagnosis (median, 6 years 10 months+), including four with complete remission of disease; 10 received anti‐GD2 immunotherapy after recurrence. The other 26 patients died of disease (n = 22) or toxicity (n = 4) at 5 years–41 years 5 months from diagnosis (median, 6 years 5 months). CONCLUSIONS The concept of indolent or smoldering NB should not be limited to adolescents/adults. The expanding repertoire of anti‐NB treatments, including biologic therapies and chemotherapy regimens of modest toxicity, can convert childhood NB into a chronic disease with prolonged survival after recurrence. Cancer 2002;95:1366–75. © 2002 American Cancer Society. DOI 10.1002/cncr.10800

Molecular Characterization of the Anti-Idiotypic Immune Response of a Relapse-Free Neuroblastoma Patient following Antibody Therapy: A Possible Vaccine against Tumors of Neuroectodermal Origin?

“…Survival analysis of the remaining six patients shows two patients in complete remission for 5 and 7 years, respectively. Two patients relapsed, one with stable disease after surgery and radiotherapy and the other with progressive chronic neuroblastoma, and two patients died of progressive disease (67).…”

Recurrent Neuroblastoma

“…Isolated local relapse at the primary tumor site is uncommon (6%) and is generally confined to patients with non-metastatic disease at diagnosis. Bone and/or bone marrow disease are present in 75 to 85% of patients with recurrent disease (Kushner et al, 2002;Lau et al, 2004). As a result, bone pain from osteomedullary metastases represents the most common presenting symptom and is reported by 68% of patients with symptomatic relapse (Lau et al, 2004).…”

“…Children with chronic NB can be separated according to the timing of relapse. In a study by Kushner et al describing NB patients who were younger than 10 years old at diagnosis and had metastatic disease five years or more from diagnosis, 21 Stage 4 patients had first relapse <4 years from diagnosis (Kushner et al, 2002). All 21 patients had a second recurrence and 13 had a third recurrence.…”

“…One case was exceptional in that a man, who was 29 years old at diagnosis, relapsed 52 years later (Mir et al, 1987). Kushner et al also reported a man, who relapsed 38 years after he was diagnosed at age 8 years (Kushner et al, 2002).…”

“…Up to half of these patients achieve some response or stable disease, and survival after relapse is longer in patients who have received salvage therapy (Lau et al, 2004). Chronic NB is also an emerging phenomenon in a subset of patients (Kushner et al, 2002). The longer survival after relapse is also likely due to early detection of disease recurrence as a result of employing more sophisticated surveillance studies in recent years.…”