Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement

Abstract

Purpose To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. Methods and Materials We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. Results At a median follow-up of 4.5years, 26patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gy with respect to local relapse—free survival (P = .55), disease-free survival (P = .22), or OS (P= .72). With respect to local relapse—free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. Conclusions Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.

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

“…Our study adds to the scant proton literature and is consistent with the existing proton and photon literature with longer follow-up. [1][2][3][4]8,10 The predominant site of failure is progression in post-induction non-MIBG-avid distant sites, similar to previously published reports. 3,11,12 Although proton therapy provides high rates of local control with acceptable toxicity for neuroblastoma, our results suggest that advances in systemic therapy are needed for improved control of systemic disease.…”

“…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 .…”

“…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 .…”

“…primary and persistent MIBG-avid metastatic sites, and hence RT has been an essential part of therapy for this group of patients. [1][2][3][4] With the increasing number of proton centers, proton therapy has been used instead of photons to minimize the late effects of RT. 5,6 Because of the lack of an exit dose compared with photons, proton therapy delivers less low-dose radiation to surrounding normal tissues beyond the target.…”

Analysis of the risk factor for the poor prognosis of localized neuroblastoma after the surgical

“…[ 31 ] Studies have demonstrated that patients with low risk disease can be treated with surgery alone and supported a role for >90% resection of the primary tumor in high-risk patients. [ 32 ] Although overall survival is excellent for patients who have low- and intermediate-risk neuroblastoma with a general trend toward minimization of therapy, mortality rate is still high for high-risk patients. [ 33 ] Thus it is of importance to identify the characteristics which could predict the outcomes of patients.…”