Radiation Therapy to the Primary and Postinduction Chemotherapy MIBG-Avid Sites in High-Risk Neuroblastoma

Abstract

Purpose-Although it is generally accepted that consolidation therapy for neuroblastoma includes irradiation of the primary site and any remaining metaiodobenzylguanidine (MIBG)-avid metastatic sites, limited information has been published regarding the efficacy of this approach.Methods and Materials-Thirty patients with high-risk neuroblastoma were treated at 1 radiation therapy (RT) department after receiving 5 cycles of induction chemotherapy and resection. All patients had at least a partial response after induction therapy, based upon international neuroblastoma response criteria. The primary sites were treated with 24 to 30 Gy whereas the MIBG-avid metastatic sites were treated with 24 Gy. RT was followed by high-dose chemotherapy with autologous stem cell rescue and 6 months of cis-retinoic acid.Results-The 5-year progression-free survival (PFS) and overall survival (OS) rates were 48% and 59%, respectively. The 5-year locoregional control at the primary site was 84%. There were no differences in locoregional control according to degree of primary surgical resection. The 5-year local control rate for metastatic sites was 74%. The 5-year PFS rates for patients with 0, 1, 2, and >3 postinduction MIBG sites were 66%, 57%, 20%, and 0% (P<.0001), respectively, whereas 5-year OS rates were 80%, 57%, 50%, and 0%, respectively (P<.0001).Conclusions-RT to the primary site and postinduction MIBG-positive metastatic sites was associated with 84% and 74% local control, respectively. The number of MIBG-avid sites present after induction chemotherapy and surgery was predictive of progression-free and overall survival.

Efficacy of proton therapy in children with high‐risk and locally recurrent neuroblastoma

“…We did not exclude any patients with local failures occurring within 12 months. Our study adds to the scant proton literature and is consistent with the existing proton and photon literature with longer follow‐up . The predominant site of failure is progression in post‐induction non‐MIBG‐avid distant sites, similar to previously published reports .…”

“…Importantly, with this oligometastatic treatment approach, we did not observe any local failures at irradiated distant metastatic sites. Others have reported less favorable outcomes after RT for metastatic disease, with 23% to 26% failure rates in the irradiated sites …”

“…High‐risk neuroblastoma is currently treated with a multimodality approach, including induction chemotherapy, surgical resection, high‐dose chemotherapy with autologous stem cell rescue, radiotherapy (RT), cis‐retinoic acid, and immunotherapy. Locoregional control rates of 84% to 100% have been reported when RT is delivered to the primary and persistent MIBG‐avid metastatic sites, and hence RT has been an essential part of therapy for this group of patients . With the increasing number of proton centers, proton therapy has been used instead of photons to minimize the late effects of RT .…”

Dose‐escalation is needed for gross disease in high‐risk neuroblastoma

“…Although our cohort was small, we found a notable dose response relationship, with local control 70% in those who received 21–24 Gy versus 100% in those who received 30–36 Gy. Other small series including 7–13 patients with macroscopic disease at the time of RT have also demonstrated that patients treated with 30–36 Gy have improved local control compared to those treated with 21–24 Gy (Table ) . Thus, it appears that the current recommendation on modern protocols for 36 Gy is not only appropriate but likely necessary for optimal local control of macroscopic disease.…”

“…[1][2][3] Our institution and others have previously shown that a dose of 21 Gy RT provides excellent local control after gross total resection (GTR). [4][5][6][7] Although local failure (LF) is <10% among patients treated with 21 Gy RT after GTR, locoregional recurrence is much Abbreviations: CTV, clinical target volume; EFS, event-free survival; GTR, gross total resection; LF, local failure; MSK, Memorial Sloan Kettering; OS, overall survival; RT, radiation therapy more common among patients with macroscopic residual disease after surgical resection, with local recurrence rates approaching 50%. 8 There are no randomized trials that have directly addressed the role and optimal dose of RT to the primary site in high-risk neuroblastoma.…”