Patterns of recurrence after radiotherapy for high-risk neuroblastoma: Implications for radiation dose and field

Kevin X Liu; Sherif G Shaaban; Jie Jane Chen; Rochelle Bagatell; Benjamin J Lerman; Paul J Catalano; Steven G DuBois; Suzanne Shusterman; Myrsini Ioakeim-Ioannidou; Torunn I Yock; Robert C Shamberger; Peter Mattei; Lan Vu; Hesham Elhalawani; Kathryn E Dusenbery; Kieuhoa T Vo; Mary S Huang; Alison M Friedmann; Lisa R Diller; Karen J Marcus; Shannon M MacDonald; Stephanie A Terezakis; Steve E Braunstein; Christine E Hill-Kayser; Daphne A Haas-Kogan

doi:10.1016/j.radonc.2024.110384

Patterns of recurrence after radiotherapy for high-risk neuroblastoma: Implications for radiation dose and field

Radiother Oncol. 2024 Sep:198:110384. doi: 10.1016/j.radonc.2024.110384. Epub 2024 Jun 15.

Authors

Kevin X Liu¹, Sherif G Shaaban², Jie Jane Chen³, Rochelle Bagatell⁴, Benjamin J Lerman⁵, Paul J Catalano⁶, Steven G DuBois⁷, Suzanne Shusterman⁷, Myrsini Ioakeim-Ioannidou⁸, Torunn I Yock⁸, Robert C Shamberger⁹, Peter Mattei¹⁰, Lan Vu¹¹, Hesham Elhalawani¹, Kathryn E Dusenbery¹², Kieuhoa T Vo¹³, Mary S Huang¹⁴, Alison M Friedmann¹⁴, Lisa R Diller⁷, Karen J Marcus¹, Shannon M MacDonald⁸, Stephanie A Terezakis¹², Steve E Braunstein¹⁵, Christine E Hill-Kayser¹⁶, Daphne A Haas-Kogan¹⁷

Affiliations

¹ Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
² Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD, USA.
³ Department of Radiation Oncology, University of California at San Francisco, UCSF Benioff Children's Hospital, San Francisco, CA, USA; Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁵ Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pediatrics, UCSF Benioff Children's Hospital and UCSF School of Medicine, San Francisco, CA, USA.
⁶ Department of Biostatistics, Harvard T.H. Chan School of Public Health, and Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁷ Department of Pediatrics, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
⁸ Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Surgery, University of Pennsylvania and the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹¹ Department of Surgery, UCSF Benioff Children's Hospital and UCSF School of Medicine, San Francisco, CA, USA.
¹² Department of Radiation Oncology, University of Minnesota, Minneapolis, MN, USA.
¹³ Department of Pediatrics, UCSF Benioff Children's Hospital and UCSF School of Medicine, San Francisco, CA, USA.
¹⁴ Department of Pediatric Oncology, Massachusetts General Hospital, Boston, MA, USA.
¹⁵ Department of Radiation Oncology, University of California at San Francisco, UCSF Benioff Children's Hospital, San Francisco, CA, USA.
¹⁶ Department of Radiation Oncology, University of Pennsylvania and the Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹⁷ Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].

PMID: 38880415
DOI: 10.1016/j.radonc.2024.110384

Abstract

Background: Prognosis for patients with high-risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields.

Methods: Multi-institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997-2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis. Follow-up was defined from the end of EBRT. Event-free survival (EFS) and OS were analyzed by Kaplan-Meier method. Cumulative incidence of locoregional progression (CILP) was analyzed using competing risks of distant-only relapse and death with Gray's test.

Results: Median follow-up was 7.0 years (range: 0.01-22.4). Five-year CILP, EFS, and OS were 11.9 %, 65.2 %, and 77.5 %, respectively. Of the 31 patients with LRR and imaging review, 15 (48.4 %) had in-field recurrences (>12 Gy), 6 (19.4 %) had marginal failures (≤12 Gy), and 10 (32.3 %) had both in-field and marginal recurrences. No patients receiving total body irradiation (12 Gy) experienced marginal-only failures (p = 0.069). On multivariable analyses, MYCN amplification had higher risk of LRR (HR: 2.42, 95 % CI: 1.06-5.50, p = 0.035) and post-consolidation isotretinoin and anti-GD2 antibody therapy (HR: 0.42, 95 % CI: 0.19-0.94, p = 0.035) had lower risk of LRR.

Conclusions: Despite EBRT, LRR remains a contributor to treatment failure in HR-NBL with approximately half of LRRs including a component of marginal failure. Future prospective studies are needed to explore whether radiation fields and doses should be defined based on molecular features such as MYCN amplification, and/or response to chemotherapy.

Keywords: Autologous stem cell therapy; Dinutuximab; MYCN amplification; Photon radiotherapy; Proton radiotherapy; Total body irradiation.

Publication types

Multicenter Study

MeSH terms

Adolescent
Child
Child, Preschool
Female
Humans
Infant
Male
Neoplasm Recurrence, Local*
Neuroblastoma* / mortality
Neuroblastoma* / radiotherapy
Radiotherapy Dosage
Retrospective Studies

Grants and funding

U54 CA274516/CA/NCI NIH HHS/United States