Locoregional control in high-risk neuroblastoma using highly-conformal image-guided radiotherapy, with reduced margins and a boost dose for residual lesions

Atia Samim; Annemieke S Littooij; Max Peters; Bart de Keizer; Alida F W van der Steeg; Raquel Dávila Fajardo; Kathelijne C J M Kraal; Miranda P Dierselhuis; Natasha K A van Eijkelenburg; Martine van Grotel; Roel Polak; Cornelis P van de Ven; Marc H W A Wijnen; Enrica Seravalli; Mirjam E Willemsen-Bosman; Max M van Noesel; Godelieve A M Tytgat; Geert O Janssens

doi:10.1016/j.radonc.2024.110604

Locoregional control in high-risk neuroblastoma using highly-conformal image-guided radiotherapy, with reduced margins and a boost dose for residual lesions

Radiother Oncol. 2024 Oct 29:202:110604. doi: 10.1016/j.radonc.2024.110604. Online ahead of print.

Authors

Atia Samim¹, Annemieke S Littooij², Max Peters³, Bart de Keizer², Alida F W van der Steeg⁴, Raquel Dávila Fajardo⁵, Kathelijne C J M Kraal⁴, Miranda P Dierselhuis⁴, Natasha K A van Eijkelenburg⁴, Martine van Grotel⁴, Roel Polak⁴, Cornelis P van de Ven⁴, Marc H W A Wijnen⁴, Enrica Seravalli³, Mirjam E Willemsen-Bosman³, Max M van Noesel¹, Godelieve A M Tytgat⁶, Geert O Janssens⁷

Affiliations

¹ Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
² Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
³ Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
⁴ Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
⁵ Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands.
⁶ Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
⁷ Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: G.O.R.Janssens@umcutrecht.nl.

PMID: 39481605
DOI: 10.1016/j.radonc.2024.110604

Abstract

Introduction: Radiotherapy protocols for high-risk neuroblastoma (HR-NBL) vary across international studies. The purpose of this study was to evaluate the locoregional control in a national HR-NBL cohort treated with highly-conformal image-guided radiotherapy (IGRT), using reduced margins, and a boost dose for residual lesions.

Materials and methods: Patients treated with radiotherapy as part of first-line HR-NBL treatment between 2015 and 2022 were eligible. To obtain clinical, internal, and planning target volumes, +0.5 cm, 4DCT-based, and + 0.3/0.5 cm margins, respectively, were added to the edited gross tumour volumes. Prescription dose was 21.6/1.8 Gy, followed by 14.4/1.8 Gy for any residual lesions measuring ≥ 1 cm³ at the time of radiotherapy planning. Intensity-modulated arc therapy was combined with daily cone beam CT-based online patient position verification. Locoregional failure (LRF) rates were compared for the presence of residual lesions < 1 cm³ vs. ≥ 1 cm³ (with/without locoregional activity on nuclear- and MRI[diffusion-weighted imaging]-scans) pre-radiotherapy, age at diagnosis, MYCN-status, [¹³¹I]mIBG therapy, response to induction chemotherapy, interval to radiotherapy onset, and metastatic site irradiation.

Results: Among the 77 included patients, 34 had residual lesions (median volume: 10.0 cm³, IQR 4.8-29.9) with activity visible on 17 nuclear- and 10 MRI-scans. Five-year LRF rate was 7.8 % (95 % confidence interval 1.8-13.8), and not significantly different between those with residual lesions < 1 cm³ vs. ≥ 1 cm³ (6.4 % vs. 14.3 %, respectively, p = 0.27), or any of the other variables. All 6 LRFs (2 isolated, 4 combined) occurred < 1.5 years post-radiotherapy.

Conclusion: In HR-NBL, IGRT with reduced margins and a boost dose for residual lesions ≥ 1 cm³ demonstrated excellent locoregional control, comparable to modern literature.

Keywords: Abdominal radiotherapy; High-risk neuroblastoma; Highly conformal radiotherapy; Image-guided radiotherapy; Locoregional failure; Pattern of failure; Radiotherapy boost; Residue; Tertiary hospital.