Abstract

Background. Intensive multimodal treatment can improve survival in patients with high-risk neuroblastoma, and consolidative radiation therapy has contributed to local control. We examined the clinical outcomes of patients who underwent consolidative radiation therapy at our institution.

Methods. We retrospectively reviewed the records of patients with high-risk neuroblastoma who underwent consolidative radiation therapy from March 2001 to March 2021 at Asan Medical Center. Patients underwent multimodal treatment including high-dose chemotherapy, surgery, stem cell transplantation, and maintenance therapy. Radiation (median, 21.0 Gy; range, 14–36) was administered to the primary site and surrounding lymph nodes.

Results. This study included 37 patients, and the median age at diagnosis was 2.8 years (range, 1.3–10.0). Four patients exhibited local failure, and 5-year free-from locoregional failure rate was 88.7%, with a median follow-up period of 5.7 years. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 59.1% and 83.6%, respectively. Univariate analysis revealed that patients with neuron-specific enolase levels >100 ng/mL had significantly worse DFS and OS (P = 0.036, 0.048), and patients with no residual disease before radiation therapy showed superior OS (P = 0.029). Furthermore, patients with 11q deletion or 17q gain exhibited poor DFS and OS, respectively (P = 0.021, 0.011). Six patients experienced grade 1 acute toxicity. Late toxicity was confirmed in children with long-term survival, predominantly hypothyroidism and hypogonadism, typically < grade 3, possibly attributed to combination treatment. Four patients experienced late toxicity ≥ grade 3 with chronic kidney disease, growth hormone abnormality, ileus, premature epiphyseal closure, and secondary tumor, and recovered by hospitalization or surgical treatment.

Conclusions. In patients with high-risk neuroblastoma, consolidative radiotherapy to the primary tumor site resulted in excellent local control and a tolerable safety profile.

Keywords: neuroblastoma, radiation therapy, combined modality therapy, treatment outcome, toxicity

Copyright and license

How to cite

1.
Jang JY, Park J-H, Kim YJ, et al. Local control and toxicity outcomes following consolidative radiation therapy in patients with high-risk neuroblastoma: a 20-year experience at a single center. Turk J Pediatr 2024; 66: 99-109. https://doi.org/10.24953/turkjped.2023.575

References

  1. Bhatnagar SN, Sarin YK. Neuroblastoma: a review of management and outcome. Indian J Pediatr 2012; 79: 787-792. https://doi.org/10.1007/s12098-012-0748-2
  2. Irwin MS, Naranjo A, Zhang FF, et al. Revised neuroblastoma risk classification system: a report from the Children’s Oncology Group. J Clin Oncol 2021; 39: 3229-3241. https://doi.org/10.1200/JCO.21.00278
  3. Smith V, Foster J. High-risk neuroblastoma treatment review. Children (Basel) 2018; 5: 114. https://doi.org/10.3390/children5090114
  4. Kushner BH, Wolden S, LaQuaglia MP, et al. Hyperfractionated low-dose radiotherapy for high-risk neuroblastoma after intensive chemotherapy and surgery. J Clin Oncol 2001; 19: 2821-2828. https://doi.org/10.1200/JCO.2001.19.11.2821
  5. Fish JD, Grupp SA. Stem cell transplantation for neuroblastoma. Bone Marrow Transplant 2008; 41: 159-165. https://doi.org/10.1038/sj.bmt.1705929
  6. Pinto NR, Applebaum MA, Volchenboum SL, et al. Advances in risk classification and treatment strategies for neuroblastoma. J Clin Oncol 2015; 33: 3008-3017. https://doi.org/10.1200/JCO.2014.59.4648
  7. Gatcombe HG, Marcus RB, Katzenstein HM, Tighiouart M, Esiashvili N. Excellent local control from radiation therapy for high-risk neuroblastoma. Int J Radiat Oncol Biol Phys 2009; 74: 1549-1554. https://doi.org/10.1016/j.ijrobp.2008.10.069
  8. Casey DL, Kushner BH, Cheung NK, Modak S, LaQuaglia MP, Wolden SL. Local control with 21-Gy radiation therapy for high-risk neuroblastoma. Int J Radiat Oncol Biol Phys 2016; 96: 393-400. https://doi.org/10.1016/j.ijrobp.2016.05.020
  9. Chen GY, Cheng JC, Chen YH, et al. Local control and clinical outcome of high-risk pediatric neuroblastoma patients after receiving multimodality treatment and helical tomotherapy. Anticancer Res 2019; 39: 2207-2215. https://doi.org/10.21873/anticanres.13336
  10. Hosaka S, Fukushima H, Nakao T, et al. Patient transfer to receive proton beam therapy during intensive multimodal therapy is safe and feasible for patients with newly diagnosed high-risk neuroblastoma. J Pediatr Hematol Oncol 2020; 42: e18-e24. https://doi.org/10.1097/MPH.0000000000001570
  11. Hessels AC, Langendijk JA, Gawryszuk A, et al. Review - Late toxicity of abdominal and pelvic radiotherapy for childhood cancer. Radiother Oncol 2022; 170: 27-36. https://doi.org/10.1016/j.radonc.2022.02.029
  12. Palmer JD, Tsang DS, Tinkle CL, et al. Late effects of radiation therapy in pediatric patients and survivorship. Pediatr Blood Cancer 2021; 68(Suppl 2): e28349. https://doi.org/10.1002/pbc.28349
  13. Jo JH, Ahn SD, Koh M, et al. Patterns of recurrence after radiation therapy for high-risk neuroblastoma. Radiat Oncol J 2019; 37: 224-231. https://doi.org/10.3857/roj.2019.00353
  14. Park JR, Bagatell R, Cohn SL, et al. Revisions to the International neuroblastoma response criteria: a consensus statement from the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol 2017; 35: 2580-2587. https://doi.org/10.1200/JCO.2016.72.0177
  15. Ferris MJ, Danish H, Switchenko JM, et al. Favorable local control from consolidative radiation therapy in high-risk neuroblastoma despite gross residual disease, positive margins, or nodal involvement. Int J Radiat Oncol Biol Phys 2017; 97: 806-812. https://doi.org/10.1016/j.ijrobp.2016.11.043
  16. Casey DL, Kushner BH, Cheung NV, Modak S, LaQuaglia MP, Wolden SL. Dose-escalation is needed for gross disease in high-risk neuroblastoma. Pediatr Blood Cancer 2018; 65: e27009. https://doi.org/10.1002/pbc.27009
  17. Liu KX, Naranjo A, Zhang FF, et al. Prospective evaluation of radiation dose escalation in patients with high-risk neuroblastoma and gross residual disease after surgery: a report from the Children’s Oncology Group ANBL0532 Study. J Clin Oncol 2020; 38: 2741-2752. https://doi.org/10.1200/JCO.19.03316
  18. Lucas JT, McCarville MB, Cooper DA, et al. Implications of image-defined risk factors and primary-site response on local control and radiation treatment delivery in the management of high-risk neuroblastoma: is there a role for de-escalation of adjuvant primary-site radiation therapy? Int J Radiat Oncol Biol Phys 2019; 103: 869-877. https://doi.org/10.1016/j.ijrobp.2018.11.041
  19. Mallepalli S, Gupta MK, Vadde R. Neuroblastoma: an updated review on biology and treatment. Curr Drug Metab 2019; 20: 1014-1022. https://doi.org/10.2174/1389200221666191226102231
  20. Su Y, Qin H, Chen C, et al. Treatment and outcomes of 1041 pediatric patients with neuroblastoma who received multidisciplinary care in China. Pediatr Investig 2020; 4: 157-167. https://doi.org/10.1002/ped4.12214
  21. Yu AL, Gilman AL, Ozkaynak MF, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 2010; 363: 1324-1334. https://doi.org/10.1056/NEJMoa0911123
  22. Georgantzi K, Sköldenberg EG, Stridsberg M, et al. Chromogranin A and neuron-specific enolase in neuroblastoma: correlation to stage and prognostic factors. Pediatr Hematol Oncol 2018; 35: 156-165. https://doi.org/10.1080/08880018.2018.1464087
  23. Cangemi G, Reggiardo G, Barco S, et al. Prognostic value of ferritin, neuron-specific enolase, lactate dehydrogenase, and urinary and plasmatic catecholamine metabolites in children with neuroblastoma. Onco Targets Ther 2012; 5: 417-423. https://doi.org/10.2147/OTT.S36366
  24. Decaesteker B, De Preter K, Speleman F. DREAM target reactivation by core transcriptional regulators supports neuroblastoma growth. Mol Cell Oncol 2019; 6: 1565470. https://doi.org/10.1080/23723556.2019.1565470
  25. Guan J, Hallberg B, Palmer RH. Chromosome Imbalances in Neuroblastoma-Recent Molecular Insight into Chromosome 1p-deletion, 2p-gain, and 11q-deletion Identifies New Friends and Foes for the Future. Cancers (Basel) 2021; 13: 5897. https://doi.org/10.3390/cancers13235897
  26. Hagemann S, Misiak D, Bell JL, et al. IGF2BP1 induces neuroblastoma via a druggable feedforward loop with MYCN promoting 17q oncogene expression. Mol Cancer 2023; 22: 88. https://doi.org/10.1186/s12943-023-01792-0
  27. Yoshimoto Suzuki Y, Yamanaka J, Miyazaki O, et al. Infantile wtage M neuroblastoma with 11q deletion, mimicking stage MS. J Pediatr Hematol Oncol 2022; 44: e779-e781. https://doi.org/10.1097/MPH.0000000000002398
  28. Geurten C, Geurten M, Hoyoux C, Lebrethon MC. Endocrine consequences of neuroblastoma treatment in children: 20 years’ experience of a single center. J Pediatr Endocrinol Metab 2019; 32: 347-354. https://doi.org/10.1515/jpem-2018-0273
  29. Nandagopal R, Laverdière C, Mulrooney D, Hudson MM, Meacham L. Endocrine late effects of childhood cancer therapy: a report from the Children’s Oncology Group. Horm Res 2008; 69: 65-74. https://doi.org/10.1159/000111809
  30. Laverdière C, Liu Q, Yasui Y, et al. Long-term outcomes in survivors of neuroblastoma: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst 2009; 101: 1131-1140. https://doi.org/10.1093/jnci/djp230
  31. Westerveld ASR, van Dalen EC, Asogwa OA, et al. Neuroblastoma survivors at risk for developing subsequent neoplasms: a systematic review. Cancer Treat Rev 2022; 104: 102355. https://doi.org/10.1016/j.ctrv.2022.102355
  32. Applebaum MA, Henderson TO, Lee SM, Pinto N, Volchenboum SL, Cohn SL. Second malignancies in patients with neuroblastoma: the effects of risk-based therapy. Pediatr Blood Cancer 2015; 62: 128-133. https://doi.org/10.1002/pbc.25249
  33. Dalianis T, Lukoseviciute M, Holzhauser S, Kostopoulou ON. New approaches towards targeted therapy for childhood neuroblastoma. Anticancer Res 2023; 43: 3829-3839. https://doi.org/10.21873/anticanres.16570