Vol 26, No 4 (2021)
Research paper
Published online: 2021-04-16

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Proton beam therapy with concurrent chemotherapy is feasible in children with newly diagnosed rhabdomyosarcoma

Ryoko Suzuki12, Hiroko Fukushima12, Hajime Okuwaki2, Masako Inaba2, Sho Hosaka2, Yuni Yamaki2, Takashi Fukushima3, Kouji Masumoto4, Masashi Mizumoto4, Hideyuki Sakurai4, Hidetoshi Takada12
DOI: 10.5603/RPOR.a2021.0082
Rep Pract Oncol Radiother 2021;26(4):616-625.


BACKGROUND: The optimal treatment for rhabdomyosarcoma (RMS) requires multidisciplinary treatment with chemotherapy, surgery, and radiotherapy. Surgery and radiotherapy are integral to the local control (LC) of RMS. However, postsurgical and radiotherapy-related complications could develop according to the local therapy and tumor location. In this study, we conducted a single-center analysis of the outcomes and toxicity of multidisciplinary treatment using proton beam therapy (PBT) for pediatric RMS.

MATERIALS AND METHODS: RMS patients aged younger than 20 years whose RMS was newly diagnosed and who underwent PBT at University of Tsukuba Hospital (UTH) during the period from 2009 to 2019 were enrolled in this study. The patients’ clinical information was collected by retrospective medical record review.

RESULTS: Forty-eight patients were included. The 3-year progression-free survival (PFS) and overall survival (OS) rates of all the patients were 68.8% and 94.2%, respectively. The 3-year PFS rates achieved with radical resection, conservative resection, and biopsy only were 65.3%, 83.3%, and 67.6%, respectively (p = 0.721). The 3-year LC rates achieved with radical resection, conservative resection, and biopsy only were 90.9%, 83.3%, and 72.9%, respectively (p = 0.548). Grade 3 or higher mucositis/dermatitis occurred in 14 patients. Although the days of opioid use due to mucositis/dermatitis during the chemotherapy with PBT were longer than those during the chemotherapy without PBT [6.1 and 1.6 (mean), respectively, p = 0.001], the frequencies of fever and elevation of C-reactive protein were equivalent.

CONCLUSIONS: Multidisciplinary therapy containing PBT was feasible and provided a relatively fair 3-year PFS, even in children with newly diagnosed RMS without severe toxicity.

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  1. Dasgupta R, Fuchs J, Rodeberg D. Rhabdomyosarcoma. Semin Pediatr Surg. 2016; 25(5): 276–283.
  2. Walterhouse DO, Pappo AS, Meza JL, et al. Shorter-duration therapy using vincristine, dactinomycin, and lower-dose cyclophosphamide with or without radiotherapy for patients with newly diagnosed low-risk rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol. 2014; 32(31): 3547–3552.
  3. Arndt CAS, Stoner JA, Hawkins DS, et al. Vincristine, actinomycin, and cyclophosphamide compared with vincristine, actinomycin, and cyclophosphamide alternating with vincristine, topotecan, and cyclophosphamide for intermediate-risk rhabdomyosarcoma: children's oncology group study D9803. J Clin Oncol. 2009; 27(31): 5182–5188.
  4. Weigel BJ, Lyden E, Anderson JR, et al. Intensive Multiagent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide and Vincristine/Doxorubicin/Cyclophosphamide, Irinotecan, and Radiation, in Patients With High-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2016; 34(2): 117–122.
  5. Fukushima H, Fukushima T, Suzuki R, et al. Comorbidity and quality of life in childhood cancer survivors treated with proton beam therapy. Pediatr Int. 2017; 59(10): 1039–1045.
  6. Munck af Rosenschold P, Engelholm SA, Brodin PN, et al. A Retrospective Evaluation of the Benefit of Referring Pediatric Cancer Patients to an External Proton Therapy Center. Pediatr Blood Cancer. 2016; 63(2): 262–269.
  7. Mizumoto M, Murayama S, Akimoto T, et al. Proton beam therapy for pediatric malignancies: a retrospective observational multicenter study in Japan. Cancer Med. 2016; 5(7): 1519–1525.
  8. Pixberg C, Koch R, Eich HT, et al. Acute Toxicity Grade 3 and 4 After Irradiation in Children and Adolescents: Results From the IPPARCA Collaboration. Int J Radiat Oncol Biol Phys. 2016; 94(4): 792–799.
  9. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
  10. Momo K, Nagaoka H, Kizawa Y, et al. Assessment of indomethacin oral spray for the treatment of oropharyngeal mucositis-induced pain during anticancer therapy. Support Care Cancer. 2017; 25(10): 2997–3000.
  11. Pizzo PA. Principles and Practice of Pediatric Oncology, 7th edition. Wolters Kluwer Health 2016: 803.
  12. Buszek SM, Ludmir EB, Grosshans DR, et al. Patterns of failure and toxicity profile following proton beam therapy for pediatric bladder and prostate rhabdomyosarcoma. Pediatr Blood Cancer. 2019; 66(11): e27952.
  13. Ladra MM, Szymonifka JD, Mahajan A, et al. Preliminary results of a phase II trial of proton radiotherapy for pediatric rhabdomyosarcoma. J Clin Oncol. 2014; 32(33): 3762–3770.
  14. Kozak KR, Smith BL, Adams J, et al. Accelerated partial-breast irradiation using proton beams: initial clinical experience. Int J Radiat Oncol Biol Phys. 2006; 66(3): 691–698.
  15. Huang A, Glick SA. Genetic susceptibility to cutaneous radiation injury. Arch Dermatol Res. 2017; 309(1): 1–10.
  16. Benitez CM, Knox SJ. Harnessing genome-wide association studies to minimize adverse radiation-induced side effects. Radiat Oncol J. 2020; 38(4): 226–235.
  17. Mizumoto M, Murayama S, Akimoto T, et al. Preliminary results of proton radiotherapy for pediatric rhabdomyosarcoma: a multi-institutional study in Japan. Cancer Med. 2018; 7(5): 1870–1874.
  18. Hays DM, Raney RB, Crist WM, et al. Secondary surgical procedures to evaluate primary tumor status in patients with chemotherapy-responsive stage III and IV sarcomas: a report from the Intergroup Rhabdomyosarcoma Study. J Pediatr Surg. 1990; 25(10): 1100–1105.
  19. Maurer HM, Beltangady M, Gehan EA, et al. The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer. 1988; 61(2): 209–220, doi: 10.1002/1097-0142(19880115)61:2<209::aid-cncr2820610202>3.0.co;2-l.
  20. Mizumoto M, Oshiro Y, Takizawa D, et al. Proton beam therapy for pediatric ependymoma. Pediatr Int. 2015; 57(4): 567–571.
  21. Takizawa D, Oshiro Y, Mizumoto M, et al. Proton beam therapy for a patient with large rhabdomyosarcoma of the body trunk. Ital J Pediatr. 2015; 41: 90.
  22. Friedman DL, Whitton J, Leisenring W, et al. Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2010; 102(14): 1083–1095.
  23. Wang Z, Wilson CL, Easton J, et al. Genetic Risk for Subsequent Neoplasms Among Long-Term Survivors of Childhood Cancer. J Clin Oncol. 2018; 36(20): 2078–2087.
  24. Bhatia S, Sklar C. Second cancers in survivors of childhood cancer. Nat Rev Cancer. 2002; 2(2): 124–132.
  25. Archer NM, Amorim RP, Naves R, et al. An Increased Risk of Second Malignant Neoplasms After Rhabdomyosarcoma: Population-Based Evidence for a Cancer Predisposition Syndrome? Pediatr Blood Cancer. 2016; 63(2): 196–201.