Hypofractionated Palliative Radiotherapy for Relapsed and Refractory High-Risk Neuroblastoma

Abstract

<h3>Purpose/Objective(s)</h3> While palliative radiation therapy (RT) is frequently used in the management of relapsed/refractory high-risk neuroblastoma (HR-NBL) in pediatric patients, few studies have examined the role of palliative hypofractionated RT (hypo-RT) in HR-NBL. We sought to characterize outcomes after palliative-intent RT using conventionally fractionated (conv-RT) and hypo-RT regimens for patients with relapsed/refractory HR-NBL. <h3>Materials/Methods</h3> The Institutional Review Board approved a retrospective study of 37 patients who were diagnosed with HR-NBL between 1997-2021 and received palliative RT at two institutions. Patients receiving RT for central nervous system and liver metastases were excluded. Hypo-RT was defined as treatment courses using dose >2 Gy per fraction. Clinical and treatment characteristics and outcomes, including dates and locations of progression, were recorded. Fisher exact tests were used for categorical variables. Follow-up time was defined from start of RT. Cumulative incidence of in-field progression was analyzed using Gray's test with death as competing risk. Univariate analyses (UVA) were performed using Cox proportional-hazards regression. <h3>Results</h3> When analyzing by first course of palliative RT, there were 16 courses of conv-RT (43.2%) and 21 courses of hypo-RT (56.8%). The distribution of patients having further progression of disease before palliative RT, receiving palliative RT to bony and soft tissue sites, and undergoing chemotherapy before, during, and after palliative RT were not different between the two groups. With median follow-up of 10.3 months (range: 0.3-104.0), cumulative incidence of in-field progression at 10 months was not different between hypo-RT and conv-RT (30.0% vs 20.1%, p=0.80). After RT, patients had similar clinical benefit, defined as symptomatic relief or decrease in size of lesion (92.3% conv-RT vs. 90.0% hypo-RT, p=1.00). On UVA, further progression of disease before palliative RT, bony vs. soft tissue sites, receipt of chemotherapy before RT, receipt of concurrent chemotherapy with RT, and receipt of chemotherapy after RT were not associated with time to in-field progression. In addition, hypo-RT (Hazard ratio [HR]: 1.50, 95% confidence interval [CI]: 0.47-4.76, p=0.49) and biologically equivalent dose (BED) ≥29 Gy (HR: 1.44, 95% CI: 0.43-4.82, p=0.55) were not associated with time to in-field progression. <h3>Conclusion</h3> We found no difference in cumulative incidence of in-field progression and clinical outcomes between the conv-RT and hypo-RT groups. On UVA, hypo-RT and BED ≥29 Gy were not associated with longer time to in-field recurrence. Palliative hypo-RT can be considered for relapsed/refractory HR-NBL, especially when quality of life from shorter treatments may be of benefit.