Abstract：High-risk neuroblastoma (NB) is highly aggressive and has poor prognosis. Treatment of NB mainly includes comprehensive therapies, of which radiotherapy serves as a part of consolidation therapy. For patients who receive complete resection of the primary lesion, usually an irradiation dose of 21-23.4 Gy is given; for patients with incomplete resection, further study focused on radiation dose is necessary. Recurrence is most commonly observed in the bone lesions involved at presentation. Currently, the principle of irradiation to the metastatic sites is to treat lesions where metaio-dobenzylguanidine (MIBG) uptake remains positive after induction chemotherapy, or those become negative uptake but still at high risk of recurrence. On the premise of lacking of MIBG imaging, positron emission tomography CT (PET-CT) may assist in screening for metastatic sites requiring irradiation. The late side effects of radiotherapy are mainly mild musculoskeletal abnormalities. No significant increase is observed in the incidence of second primary tumor during short-term follow-up.
Zhang Shidi,Bai Yongrui,Chen Haiyan. Research progress on radiotherapy and radiation-associated adverse effects of high-risk neuroblastoma[J]. Chinese Journal of Radiation Oncology, 2023, 32(2): 174-178.
[1] Pinto NR, Applebaum MA, Volchenboum SL, et al.Advances in risk classification and treatment strategies for neuroblastoma[J]. J Clin Oncol, 2015,33(27):3008-3017. DOI: 10.1200/JCO.2014.59.4648. [2] Casey DL, Pitter KL, Kushner BH, et al.Radiation therapy to sites of metastatic disease as part of consolidation in high-risk neuroblastoma: can long-term control be achieved?[J]. Int J Radiat Oncol Biol Phys, 2018,100(5):1204-1209. DOI: 10.1016/j.ijrobp.2018.01.008. [3] Mazloom A, Louis CU, Nuchtern J, et al.Radiation therapy to the primary and postinduction chemotherapy MIBG-avid sites in high-risk neuroblastoma[J]. Int J Radiat Oncol Biol Phys, 2014,90(4):858-862. DOI: 10.1016/j.ijrobp.2014.07.019. [4] 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]. J Clin Oncol, 2020,38(24):2741-2752. DOI: 10.1200/JCO.19.03316. [5] Rosen EM, Cassady JR, Frantz CN, et al.Neuroblastoma: the joint center for radiation therapy/dana-farber cancer institute/children's hospital experience[J]. J Clin Oncol, 1984,2(7):719-732. DOI: 10.1200/JCO.1984.2.7.719. [6] Halperin EC, Cox EB.Radiation therapy in the management of neuroblastoma: the Duke University Medical Center experience 1967-1984[J]. Int J Radiat Oncol Biol Phys, 1986,12(10):1829-1837. DOI: 10.1016/0360-3016(86)90326-3. [7] Castleberry RP, Kun LE, Shuster JJ, et al.Radiotherapy improves the outlook for patients older than 1 year with pediatric oncology group stage C neuroblastoma[J]. J Clin Oncol, 1991,9(5):789-795. DOI: 10.1200/JCO.1991. 9.5.789. [8] Matthay KK, Villablanca JG, Seeger RC, et al.Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. children's cancer group[J]. N Engl J Med, 1999,341(16):1165-1173. DOI: 10.1056/NEJM199910143411601. [9] Arumugam S, Manning-Cork NJ, Gains JE, et al.The evidence for external beam radiotherapy in high-risk neuroblastoma of childhood: a systematic review[J]. Clin Oncol (R Coll Radiol), 2019,31(3):182-190. DOI: 10.1016/j.clon.2018.11.031. [10] Gatcombe HG, Marcus RB, Katzenstein HM, et al.Excellent local control from radiation therapy for high-risk neuroblastoma[J]. Int J Radiat Oncol Biol Phys, 2009,74(5):1549-1554. DOI: 10.1016/j.ijrobp.2008.10.069. [11] Kushner BH, Wolden S, LaQuaglia MP, et al. Hyperfractionated low-dose radiotherapy for high-risk neuroblastoma after intensive chemotherapy and surgery[J]. J Clin Oncol, 2001,19(11):2821-2828. DOI: 10.1200/JCO.2001.19.11.2821. [12] Casey DL, Kushner BH, Cheung NK, et al.Local control with 21-Gy radiation therapy for high-risk neuroblastoma[J]. Int J Radiat Oncol Biol Phys, 2016,96(2):393-400. DOI: 10.1016/j.ijrobp.2016.05.020. [13] 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[J]. Int J Radiat Oncol Biol Phys, 2017,97(4):806-812. DOI: 10.1016/j.ijrobp.2016. 11.043. [14] Pai Panandiker AS, Beltran C, Billups CA, et al.Intensity modulated radiation therapy provides excellent local control in high-risk abdominal neuroblastoma[J]. Pediatr Blood Cancer, 2013,60(5):761-765. DOI: 10.1002/pbc. 24350. [15] Bradfield SM, Douglas JG, Hawkins DS, et al.Fractionated low-dose radiotherapy after myeloablative stem cell transplantation for local control in patients with high-risk neuroblastoma[J]. Cancer, 2004,100(6):1268-1275. DOI: 10.1002/cncr.20091. [16] Casey DL, Kushner BH, Cheung NV, et al.Reduced-dose radiation therapy to the primary site is effective for high-risk neuroblastoma: results from a prospective trial[J]. Int J Radiat Oncol Biol Phys, 2019,104(2):409-414. DOI: 10.1016/j.ijrobp.2019.02.004. [17] 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?[J]. Int J Radiat Oncol Biol Phys, 2019,103(4):869-877. DOI: 10.1016/j.ijrobp.2018.11.041. [18] Casey DL, Kushner BH, Cheung NV, et al.Dose-escalation is needed for gross disease in high-risk neuroblastoma[J]. Pediatr Blood Cancer, 2018,65(7):e27009. DOI: 10.1002/pbc.27009. [19] Haas-Kogan DA, Swift PS, Selch M, et al.Impact of radiotherapy for high-risk neuroblastoma: a children's cancer group study[J]. Int J Radiat Oncol Biol Phys, 2003,56(1):28-39. DOI: 10.1016/s0360-3016(02)04506-6. [20] Simon T, Hero B, Bongartz R, et al.Intensified external-beam radiation therapy improves the outcome of stage 4 neuroblastoma in children > 1 year with residual local disease[J]. Strahlenther Onkol, 2006,182(7):389-394. DOI: 10.1007/s00066-006-1498-8. [21] Hattangadi JA, Rombi B, Yock TI, et al.Proton radiotherapy for high-risk pediatric neuroblastoma: early outcomes and dose comparison[J]. Int J Radiat Oncol Biol Phys, 2012,83(3):1015-1022. DOI: 10.1016/j.ijrobp.2011. 08.035. [22] Park JR, Kreissman SG, London WB, et al.Effect of tandem autologous stem cell transplant vs single transplant on event-free survival in patients with high-risk neuroblastoma: a randomized clinical trial[J]. JAMA, 2019,322(8):746-755. DOI: 10.1001/jama.2019.11642. [23] Memorial Sloan Kettering Cancer Center. Local control with reduced-dose radiotherapy for high-risk neuroblastoma[EB/OL]. (2014-09-22)[2021-11-01]. https://clinicaltrials.gov/ct2/show/NCT02245997?term=0224 5997&draw=2&rank=1. [24] Polishchuk AL, Li R, Hill-Kayser C, et al.Likelihood of bone recurrence in prior sites of metastasis in patients with high-risk neuroblastoma[J]. Int J Radiat Oncol Biol Phys, 2014,89(4):839-845. DOI: 10.1016/j.ijrobp.2014. 04.004. [25] Kushner BH, Yeung HW, Larson SM, et al.Extending positron emission tomography scan utility to high-risk neuroblastoma: fluorine-18 fluorodeoxyglucose positron emission tomography as sole imaging modality in follow-up of patients[J]. J Clin Oncol, 2001,19(14):3397-3405. DOI: 10.1200/JCO.2001.19.14.3397. [26] Papathanasiou ND, Gaze MN, Sullivan K, et al.18F-FDG PET/CT and 123I-metaiodobenzylguanidine imaging in high-risk neuroblastoma: diagnostic comparison and survival analysis[J]. J Nucl Med, 2011,52(4):519-525. DOI: 10.2967/jnumed.110.083303. [27] Taggart DR, Han MM, Quach A, et al.Comparison of iodine-123 metaiodobenzylguanidine (MIBG) scan and [18F]fluorodeoxyglucose positron emission tomography to evaluate response after iodine-131 MIBG therapy for relapsed neuroblastoma[J]. J Clin Oncol, 2009,27(32):5343-5349. DOI: 10.1200/JCO.2008.20.5732. [28] Piccardo A, Morana G, Puntoni M, et al.Diagnosis, treatment response, and prognosis: the role of 18f-dopa pet/ct in children affected by neuroblastoma in comparison with 123I-mibg scan: the first prospective study[J]. J Nucl Med, 2020,61(3):367-374. DOI: 10.2967/jnumed.119.232553. [29] Beckham TH, Casey DL, LaQuaglia MP, et al. Renal function outcomes of high-risk neuroblastoma patients undergoing radiation therapy[J]. Int J Radiat Oncol Biol Phys, 2017,99(2):486-493. DOI: 10.1016/j.ijrobp.2017. 04.003. [30] Hoeben BA, Carrie C, Timmermann B, et al.Management of vertebral radiotherapy dose in paediatric patients with cancer: consensus recommendations from the SIOPE radiotherapy working group[J]. Lancet Oncol, 2019,20(3):e155-e166. DOI: 10.1016/S1470-2045(19)30034-8. [31] Meacham LR, Sklar CA, Li S, et al.Diabetes mellitus in long-term survivors of childhood cancer. Increased risk associated with radiation therapy: a report for the childhood cancer survivor study[J]. Arch Intern Med, 2009,169(15):1381-1388. DOI: 10.1001/archinternmed. 2009.209. [32] Casey DL, Friedman DN, Moskowitz CS, et al.Second cancer risk in childhood cancer survivors treated with intensity-modulated radiation therapy (IMRT)[J]. Pediatr Blood Cancer, 2015,62(2):311-316. DOI: 10.1002/pbc. 25285. [33] Zichová A, Eckschlager T, Ganevová M, et al.Subsequent neoplasms in childhood cancer survivors[J]. Cancer Epidemiol, 2020,68:101779. DOI: 10.1016/j.canep.2020. 101779. [34] Meadows AT, Friedman DL, Neglia JP, et al.Second neoplasms in survivors of childhood cancer: findings from the Childhood Cancer Survivor Study cohort[J]. J Clin Oncol, 2009,27(14):2356-2362. DOI: 10.1200/JCO.2008. 21.1920.
2023, Vol. 32 
