Radiotherapy improves the outlook for patients older than 1 year with Pediatric Oncology Group stage C neuroblastoma.

Abstract

Children older than 1 year of age who have neuroblastoma with complete or partial removal of the primary tumor and positive intracavitary lymph nodes (Pediatric Oncology Group [POG] stage C) are a small but higher-risk subset of patients. To further evaluate the importance of identifying patients with POG stage C neuroblastoma and to assess the efficacy and toxicity of adding concurrent radiation therapy (RT) to chemotherapy (CT) in these children, a randomized study was conducted. Eligible patients received cyclophosphamide 150 mg/m2 orally days 1 to 7 and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) 35 mg/m2 intravenously (IV) on day 8 (CYC/ADR) every 3 weeks for five courses with or without RT to primary tumor and regional lymph nodes (24 to 30 Gy/16 to 20 fractions). Second-look surgery was advised to evaluate response and to remove residual disease. Continuation therapy alternated CYC/ADR every 3 weeks with cisplatin 90 mg/m2 day 1 followed by teniposide 100 mg/m2 day 3 (CDP/VM) for two courses each. Secondary CT with CDP/VM alone was available for patients not achieving complete response (CR) following induction treatment and second-look surgery. Of 29 eligible patients randomized to CT alone, 13 achieved CR, and nine are disease-free (NED) 1 to 52 months (median, 35 months) off therapy. Twenty-two of 33 eligible cases treated with CT/RT attained CR, and 19 are NED 1 to 77 months (median, 23 months) off therapy. Local and metastatic relapses occurred in both arms. Differences in CR, event-free survival, and survival rates were significant, P = .013, .009, and .008, respectively. Surgical compliance was excellent and complications uncommon. Therapy was tolerable in both groups but hematopoietic toxicity was more common in the CT/RT arm. We conclude that POG stage C neuroblastoma in children older than 1 year of age is a higher-risk group that should be identified, that CT/RT provides superior initial and long-term disease control compared with CT alone in this patient subset, and that the occurrence of metastatic failures in both treatment groups suggests a need for more aggressive chemotherapy.

High‐dose chemotherapy followed by locoregional irradiation improves the outcome of patients with international neuroblastoma staging system Stage II and III neuroblastoma with MYCN amplification

“…Although RT has shown no benefit in patients with Stage I and II, standard-risk NB, 20,36 adjuvant RT has a role in the treatment of patients with advancedstage and bulky disease, 21,[37][38][39] including Stage II NB with MNA. 40 In the current study, a striking observation was the absence of local recurrence in the HDC group.…”

131I-metaiodobenzylguanidine (131I-MIBG) therapy for residual neuroblastoma: a mono-institutional experience with 43 patients

“…Thus, until innovative and more effective therapies are developed the paediatric oncologist dealing with refractory or partially responsive neuroblastoma must struggle to optimize the therapeutic tools at his disposal (Castleberry et al, 1991;Gaze et al, 1995;Leavey et al, 1997).…”

Radiation-triggered Tumor Necrosis Factor (TNF) α-NFκB Cross-signaling Favors Survival Advantage in Human Neuroblastoma Cells

“…Seven-week-old athymic NCr-nu/nu nude mice (National Cancer Institute, Frederick, MD) received subcutaneous injections of SK-N-MC cells (5 ϫ 10 6 ) suspended in 100 l of medium into their right flank. Tumor growth was periodically monitored, tumor volume was calculated using the formula (28), and tumors were allowed to grow to a size of ϳ500 mm 3 . Xenografts were exposed to fractionated irradiation (FIR) of 2 Gy/day for 5 days.…”

“…Tumor cell repopulation may arise from remnant cells of the original neoplasm that have escaped therapeutic intervention and later become visible at the original site. RT is now widely used for high risk NB patients after chemotherapy, and the survival rate is significantly improved (76%) by using RT with chemotherapy, compared with chemotherapy alone (46%) (3). Overall goal of the RT is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue, a major complication with RT.…”