Patterns of Locoregional Relapse after Radiotherapy for High-Risk Neuroblastoma: A Multi-Institutional Study

Purpose/Objective(s)

In high-risk neuroblastoma (HRNBL), locoregional relapse (LRR) is a significant contributor to treatment failure despite intensive multimodal therapy, including radiotherapy (RT). A recent Children's Oncology Group study found no benefit to boost RT for gross residual disease. Thus, we sought to characterize patterns of LRR after RT for patients (pts) with HRNBL.

Materials/Methods

The Institutional Review Boards approved this multi-institutional retrospective cohort study of pts who received ≥1 autologous stem cell transplant (ASCT) and external beam RT for HRNBL from 1997-2021. Pts who progressed prior to ASCT were excluded. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis. In-field and marginal recurrences were defined as sites receiving >12 Gy and ≤12 Gy, respectively. Follow-up (FU) was from end of RT. Event-free survival (EFS) and overall survival (OS) were analyzed by Kaplan-Meier method. Cumulative incidence of locoregional progression (CILP) was analyzed using competing risks of distant-only relapse, secondary cancer, and death with Gray's test.

Results

We identified 311 pts with median age at diagnosis of 3.0 years (range: 0.02-28.7). The most common primary site was adrenal/abdominal (n=280, 90.0%). 271 (87.1%), 126 (40.5%) and 240 (77.2%) pts had metastatic disease at diagnosis, MYCN amplification, and unfavorable histology, respectively. 108 pts (34.7%) received proton RT. Of the 167 (53.7%) pts who underwent tandem ASCT, 68 (40.7%) received TBI-based conditioning. No pts received TBI after 2012. Of the 115 (37.0%) pts with subtotal resection (STR), 54 (47.0%) received ≥36 Gy. 202 (65.0%) received post-Consolidation anti-GD2 immunotherapy. Median FU was 6.5 years (range: 0.01-22.4). For the cohort, 5-year CILP, EFS and OS were 10.8%, 66.7% and 78.9%, respectively. After STR, ≥36 Gy did not decrease 5-year CILP (11.8% vs. 13.1%, p=0.80). 5-year CILP was significantly lower for pts receiving immunotherapy (6.4% vs. 21.5%, p<0.001). For pts receiving immunotherapy, 5-year CILP was similar for photon and proton RT (6.1% vs. 6.6%, p=0.78). Of the 29 pts with LRR and imaging for review, 13 (44.8%) were in-field only, 6 (20.7%) were marginal only, and 10 (34.5%) were both in-field and marginal. In pts receiving immunotherapy, 4 LRRs were in-field only, 3 were marginal only, and 4 were both in-field and marginal with 6/7 (85.7%) marginal recurrences occurring at sites of disease present at diagnosis with complete response after induction chemotherapy.

Conclusion

LRR contributes to treatment failure in HRNBL with most occurring in-field. CILP was lower for pts receiving immunotherapy and there was no difference in CILP between photon and proton RT. In pts receiving immunotherapy, approximately 25% of LRRs were marginal only. Future studies are needed to examine the optimal RT fields and dose in the era of anti-GD2 immunotherapy.