Top

Published in:

Open Access 01-12-2019 | Rhabdomyosarcoma | Review

Proton therapy in the most common pediatric non-central nervous system malignancies: an overview of clinical and dosimetric outcomes

Authors: Angela Sardaro, Roberta Carbonara, Maria Fonte Petruzzelli, Barbara Turi, Marco Moschetta, Arnaldo Scardapane, Amato Antonio Stabile Ianora

Published in: Italian Journal of Pediatrics | Issue 1/2019

Abstract

Radiation therapy represents an important approach in the therapeutic management of children and adolescents with malignant tumors and its application with modern techniques – including Proton Beam Therapy (PBT) – is of great interest. In particular, potential radiation-induced injuries and secondary malignancies – also associated to the prolonged life expectancy of patients – are still questions of concern that increase the debate on the usefulness of PBT in pediatric treatments. This paper presents a literary review of current applications of PBT in non-Central Nervous System pediatric tumors (such as retinoblastoma, Hodgkin Lymphoma, Wilms tumor, bone and soft tissues sarcomas). We specifically reported clinical results achieved with PBT and dosimetric comparisons between PBT and the most common photon-therapy techniques. The analysis emphasizes that PBT minimizes radiation doses to healthy growing organs, suggesting for reduced risks of late side-effects and radiation-induced secondary malignancies. Extended follow up and confirms by prospective clinical trials should support the effectiveness and long-term tolerance of PBT in the considered setting.

Spot-scanning is a PBT delivery method which provide a uniform and complex dose-distribution with the advantage of reduced neutron contamination [65]

Nowadays image-guidance is being used in association with current knowledge on optimization/reduction of exposure to imaging doses [70]

Levin W, Kooy H, Loeffler J, DeLaney T. Proton beam therapy. Br J Cancer. 2005;93(8):849–54. https://doi.org/10.1038/sj.bjc.6602754.CrossRefPubMedPubMedCentral

Greco C, Wolden S. Current status of radiotherapy with proton and light ion beams. Cancer. 2007;109(7):1227–38.PubMedCrossRef

Fuss M, Hug EB, Schaefer RA, Nevinny-Stickel M, Miller DW, Slater JM, Slater JD. Proton radiation therapy (PRT) for pediatric optic pathway gliomas: comparison with 3D planned conventional photons and a standard photon technique. Int J Radiat Oncol Biol Phys. 1999;45(5):1117–26.PubMedCrossRef

Hoppe BS, Flampouri S, Zaiden R, et al. Involved-node proton therapy in combined modality therapy for hodgkin lymphoma: results of a phase 2 study. Int J Radiat Oncol Biol Phys. 2014;89(5):1053–9.PubMedCrossRef

Allen AM, Pawlicki T, Dong L, et al. An evidence based review of proton beam therapy: the report of astros emerging technology committee. Radiother Oncol. 2012;103(1):8–11.PubMedCrossRef

Tian X, Liu K, Hou Y, Cheng J, Zhang J. The evolution of proton beam therapy: Current and future status. Mol Clin Oncol. 2018;8(1):15–21. https://doi.org/10.3892/mco.2017.1499.CrossRefPubMed

Archambeau JO, Slater JD, Slater JM, Tangeman R. Role for proton beam irradiation in treatment of pediatric cns malignancies. Int J Radiat Oncol Biol Phys. 1992;22(2):287–94.PubMedCrossRef

Palm A, Johansson KA. A review of the impact of photon and proton external beam radiotherapy treatment modalities on the dose distribution in field and out-of-field; implications for the long-term morbidity of cancer survivors. Acta Oncologica. 2007;46(4):462–73. https://doi.org/10.1080/02841860701218626.CrossRefPubMed

Lin R, Hug EB, Schaefer RA, Miller DW, Slater JM, Slater JD. Conformal proton radiation therapy of the posterior fossa: a study comparing protons with three-dimensional planned photons in limiting dose to auditory structures. Int J Radiat Oncol Biol Phys. 2000;48(4):1219–26.PubMedCrossRef

10.

Lomax AJ, Bortfeld T, Goitein G, et al. A treeatment planning inter-comparison of proton and intensity modulated photon radiotherapy. Radiother Oncol. 1999;51(3):257–71.PubMedCrossRef

11.

Weber DC, Habrand JL, Hoppe BS, et al. Proton therapy for pediatric malignancies: fact, figures and costs. A joint consensus statement from the pediatric subcommittee of PTCOG, PROS and EPTN. Radiother Oncol. 2018;128:44–55.PubMedCrossRef

12.

Sethi RV, Shih HA, Yeap BY, et al. Second nonocular tumors among survivors of retinoblastoma treated with contemporary photon and proton radiotherapy. Cancer. 2014;120(1):126–33.PubMedCrossRef

13.

Lodge M, Pijls-Johannesma M, Stirk L, Munro AJ, De Ruysscher D, Jefferson T. A systematic literature review of the clinical and cost-effectiveness of hadron therapy in cancer. Radiother Oncol. 2007;83(2):110–22.PubMedCrossRef

14.

Olsen DR, Bruland ØS, Frykholm G, Norderhaug IN. Proton therapy–a systematic review of clinical effectiveness. Radiother Oncol. 2007;83(2):123–32.PubMedCrossRef

15.

Brada M, Pijls-Johannesma M, De Ruysscher D. Proton therapy in clinical practice: current clinical evidence. J Clin Oncol. 2007;25(8):965–70.PubMedCrossRef

16.

Indelicato DJ, Merchant T, Laperriere N, et al. Consensus Report From the Stockholm Pediatric Proton Therapy Conference. Int J Radiat Oncol Biol Phys. 2016;96(2):387e392.CrossRef

17.

Krengli M, Hug EB, Adams JA, Smith AR, Tarbell NJ, Munzenrider JE. Proton radiation therapy for retinoblastoma: comparison of various intraocular tumor locations and beam arrangements. Int J Radiat Oncol Biol Phys. 2005;61(2):583–93.PubMedCrossRef

18.

Lee CT, Bilton SD, Famiglietti RM, et al. Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques? Int J Radiat Oncol Biol Phys. 2005;63(2):362–72.PubMedCrossRef

19.

Andolino DL, Hoene T, Xiao L, Buchsbaum J, Chang AL. Dosimetric comparison of involved-field three-dimensional conformal photon radio- therapy and breast-sparing proton therapy for the treatment of hodgkins lymphoma in female pediatric patients. Int J Radiat Oncol Biol Phys. 2011;81(4):e667–71.PubMedCrossRef

20.

Hoppe BS, Flampouri S, Su Z, et al. Effective dose reduction to cardiac structures using protons compared with 3DCRT and IMRT in mediastinal hodgkin lymphoma. Int J Radiat Oncol Biol Phys. 2012;84(2):449–55.PubMedCrossRef

21.

Hoppe BS, Flampouri S, Su Z, et al. Consolidative involved-node proton therapy for stage Ia-IIIb mediastinal hodgkin lymphoma: preliminary dosimetric outcomes from a phase ii study. Int J Radiat Oncol Biol Phys. 2012;83(1):260–7.PubMedCrossRef

22.

Knäusl B, Fuchs H, Dieckmann K, Georg D. Can particle beam therapy beimproved using helium ions? - a planning study focusing on pediatric patients. Acta Oncol. 2016;55(6):751–9. https://doi.org/10.3109/0284186X.2015.1125016.CrossRefPubMed

23.

Weber DC, Trofimov AV, Delaney TF, Bortfeld T. A treatment planning comparison of intensity modulated photon and proton therapy for paraspinal sarcomas. Int J Radiat Oncol Biol Phys. 2004;58(5):1596–606.PubMedCrossRef

24.

Miralbell R, Lomax A, Cella L, Schneider U. Potential reduction of the incidence of radiation-induced second cancers by using proton beams in the treatment of pediatric tumors. Int J Radiat Oncol Biol Phys. 2002;54(3):824–9.PubMedCrossRef

25.

Ladra MM, Edgington SK, Mahajan A, et al. A Dosimetric Comparison of Proton and Intensity Modulated Radiation Therapy in Pediatric Rhabdomyosarcoma Patients Enrolled on a Prospective Phase II Proton Study. Radiother Oncol. 2014;113(1):77–83. https://doi.org/10.1016/j.radonc.2014.08.033.CrossRefPubMedPubMedCentral

26.

Kozak KR, Adams J, Krejcarek SJ, Tarbell NJ, Yock TI. A dosimetric comparison of proton and intensity-modulated photon radiotherapy for pediatric parameningeal rhabdomyosarcomas. Int J Radiat Oncol Biol Phys. 2009;74(1):179–86.PubMedCrossRef

27.

Cotter SE, Herrup DA, Friedmann A, et al. Proton radiotherapy for pediatric bladder/prostate rhabdomyosarcoma: clinical outcomes and dosimetry compared to intensity-modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2011;81(5):1367–73.PubMedCrossRef

28.

Yock T, Schneider R, Friedmann A, Adams J, Fullerton B, Tarbell N. Proton radiotherapy for orbital rhabdomyosarcoma: clinical outcome and a dosimetric comparison with photons. Int J Radiat Oncol Biol Phys. 2005;63(4):1161–8.PubMedCrossRef

29.

Hillbrand M, Georg D, Gadner H, Pötter R, Dieckmann K. Abdominal cancer during early childhood: a dosimetric comparison of proton beams to standard and advanced photon radiotherapy. Radiother Oncol. 2008;89(2):141–9.PubMedCrossRef

30.

Mouw KW, Sethi RV, Yeap BY, et al. Proton radiation therapy for the treatment of retinoblastoma. Int J Radiat Oncol Biol Phys. 2014;90(4):863–9.PubMedPubMedCentralCrossRef

31.

Wray J, Flampouri S, Slayton W, et al. Proton therapy for pediatric Hodgkin lymphoma. Pediatr Blood Cancer. 2016;63(9):1522–6. https://doi.org/10.1002/pbc.26044.CrossRefPubMed

32.

Hug EB, Sweeney RA, Nurre PM, Holloway KC, Slater JD, Munzen-rider JE. Proton radiotherapy in management of pediatric base of skull tumors. Int J Radiat Oncol Biol Phys. 2002;52(4):1017–24.PubMedCrossRef

33.

Habrand JL, Schneider R, Alapetite C, et al. Proton therapy in pediatric skull base and cervical canal low-grade bone malignancies. Int J Radiat Oncol Biol Phys. 2008;71(3):672–5.PubMedCrossRef

34.

Rutz HP, Weber DC, Sugahara S, et al. Extracranial chordoma: outcome in patients treated with function-preserving surgery followed by spot-scanning proton beam irradiation. Int J Radiat Oncol Biol Phys. 2007;67(2):512–20.PubMedCrossRef

35.

Rutz HP, Weber DC, Goitein G, et al. Postoperative spot-scanning proton radiation therapy for chordoma and chondrosarcoma in children and adolescents: initial experience at Paul Scherrer Institute. Int J Radiat Oncol Biol Phys. 2008;71(1):220–5.PubMedCrossRef

36.

Ares C, Hug EB, Lomax AJ, et al. Effectiveness and safety of spot scanning proton radiation therapy for chordomas and chondrosarcomas of the skull base: first long-term report. Int J Radiat Oncol Biol Phys. 2009;75(4):1111–8.PubMedCrossRef

37.

Staab A, Rutz HP, Ares C, et al. Spot-scanning-based proton therapy for extracranial chordoma. Int J Radiat Oncol Biol Phys. 2011;81(4):e489–96.PubMedCrossRef

38.

Rombi B, Ares C, Hug EB, et al. Spot-scanning proton radiation therapy for pediatric chordoma and chondrosarcoma: clinical outcome of 26 patients treated at Paul Scherrer Institute. Int J Radiat Oncol Biol Phys. 2013;86(3):578–84.PubMedCrossRef

39.

Timmermann B, Schuck A, Niggli F, et al. Spot-scanning proton therapy for malignant soft tissue tumors in childhood: first experiences at the Paul Scherrer Institute. Int J Radiat Oncol Biol Phys. 2007;67(2):497–504.PubMedCrossRef

40.

Leiser D, Calaminus G, Malyapa R, et al. Tumour control and quality of life in children with rhabdomyosarcoma treated with pencil beam scanning proton therapy. Radiother Oncol. 2016;120(1):163–8.PubMedCrossRef

41.

Childs SK, Kozak KR, Friedmann AM, et al. Proton radiotherapy for Para- meningeal rhabdomyosarcoma: clinical outcomes and late effects. Int J Radiat Oncol Biol Phys. 2012;82(2):635–42.PubMedCrossRef

42.

Weber DC, Ares C, Albertini F, et al. Pencil beam scanning proton therapy for pediatric Parameningeal Rhabdomyosarcomas: clinical outcome of patients treated at the Paul Scherrer Institute. Pediatr Blood Cancer. 2016;63(10):1731–6. https://doi.org/10.1002/pbc.25864.CrossRefPubMed

43.

Vern-Gross TZ, Indelicato DJ, Bradley JA, Rotondo RL. Patterns of failure in pediatric Rhabdomyosarcoma after proton therapy. Int J Radiat Oncol Biol Phys. 2016;96(5):1070–7. https://doi.org/10.1016/j.ijrobp.2016.08.028.CrossRefPubMed

44.

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):1870–4. https://doi.org/10.1002/cam4.1464.CrossRefPubMedPubMedCentral

45.

Rombi B, DeLaney TF, MacDonald SM, et al. Proton radiotherapy for pediatric Ewing’s sarcoma: initial clinical outcomes. Int J Radiat Oncol Biol Phys. 2012;82(3):1142–8.PubMedCrossRef

46.

Leroy R, Benahmed N, Hulstaert F, Van Damme N, De Ruysscher D. Proton therapy in children: a systematic review of clinical effectiveness in 15 pediatric cancers. Int J Radiat Oncol Biol Phys. 2016;95(1):267–78.PubMedCrossRef

47.

Kaste SC, Chen G, Fontanesi J, Crom DB, Pratt CB. Orbital development in long-term survivors of retinoblastoma. J Clin Oncol. 1997;15(3):1183–9.PubMedCrossRef

48.

Schipper J, Tan KE, van Peperzeel HA. Treatment of retinoblastoma by precision megavoltage radiation therapy. Radiother Oncol. 1985;3:117–32.PubMedCrossRef

49.

Eldebawy E, Parker W, Rahman WA, Freeman CR. Dosimetric study of current treatment options for radiotherapy in retinoblastoma. Int J Radiat Oncol Biol Phys. 2012;82(3):e501–5.PubMedCrossRef

50.

Rombi B, Vennarini S, Vinante L, Ravanelli D, Amichetti M. Proton radiotherapy for pediatric tumors: review of first clinical results. Ital J Pediatr. 2014;40(1):74.PubMedPubMedCentralCrossRef

51.

Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277–300.PubMedCrossRef

52.

Kung FH, Schwartz CL, Ferree CR, et al. A randomized trial comparing chemotherapy with chemoradiotherapy for children and adolescents with stages I, IIa, IIIa1 hodgkin disease: a report from the children’s oncology group. J Pediatr Hematol Oncol. 2006;28(6):362–8.PubMedCrossRef

53.

Specht L, Yahalom J, Illidge T, et al. Modern radiation therapy for hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG). Int J Radiat Oncol Biol Phys. 2014;89(4):854–62.PubMedCrossRef

54.

Wolden SL, Chen L, Kelly KM, Nachman J, et al. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with hodgkin’s lymphoma – A report from the children’s oncology group. J Clin Oncol. 2012;30(26):3174.PubMedPubMedCentralCrossRef

55.

Holtzman A, Flampouri S, Li Z, Mendenhall NP, Hoppe BS. Proton therapy in a pediatric patient with stage III hodgkin lymphoma. Acta Oncol. 2013;52(3):592–4.PubMedCrossRef

56.

Oeffinger KC, Mertens AC, Sklar CA, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355(15):1572–82.PubMedCrossRef

57.

Bhatia S, Yasui Y, Robison LL, et al. High risk of subsequent neoplasms continues with extended follow-up of childhood hodgkins disease: report from the late effects study group. J Clin Oncol. 2003;21(23):4386–94.PubMedCrossRef

58.

Dores GM, Metayer C, Curtis RE, et al. Second malignant neoplasms among long-term survivors of hodgkins disease: a population-based evaluation over 25 years. J Clin Oncol. 2002;20(16):3484–94.PubMedCrossRef

59.

Travis LB, Hill DA, Dores GM, et al. Breast cancer following radiotherapy and chemotherapy among young women with hodgkin disease. Jama. 2003;290(4):465–75.PubMedCrossRef

60.

Girinsky T, van der Maazen R, Specht L, et al. Involved-node radiotherapy (INRT) in patients with early hodgkin lymphoma: concepts and guidelines. Radiother Oncol. 2006;79(3):270–7.PubMedCrossRef

61.

Eichenauer DA, Aleman BMP, Andrè M, et al. Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Supplement 4):iv19–29.PubMedCrossRef

62.

Tseng YD, Cutter DJ, Plastaras JP, et al. Evidence-based review on the use of proton therapy in lymphoma from the particle therapy cooperative group (PTCOG) lymphoma subcommittee. Int J Radiation Oncol Biol Phys. 2017;99(4):825e842.CrossRef

63.

Noël G, Feuvret L, Ferrand R, Boisserie G, Mazeron JJ, Habrand JL. Radiotherapeutic factors in the management of cervical-basal chordomas and chondrosarcomas. Neurosurgery. 2004;55(6):1252–62.PubMedCrossRef

64.

Catton C, O’Sullivan B, Bell R, et al. Chordoma: long-term follow-up after radical photon irradiation. Radiother Oncol. 1996;41(1):67–72.PubMedCrossRef

65.

Hall EJ. Intensity-modulated radiation therapy, proton, and the risk of second cancers. Int J Radiat Oncol Biol Phys. 2006;65(1):1–7.PubMedCrossRef

66.

Sangkhathat S. Current management of pediatric soft tissue sarcomas. World J Clin Pediatr. 2015;4(4):94–105.PubMedPubMedCentralCrossRef

67.

Pastore G, Peris-Bonet R, Carli M, Martínez-García C, de Toledo JS, Steliarova-Foucher E. Childhood soft tissue sarcomas incidence and survival in european children (1978–1997): report from the automated childhood cancer information system project. Eur J Cancer. 2006;42(13):2136–49.PubMedCrossRef

68.

Merchant TE. Clinical controversies: proton therapy for pediatric tumors. Semin Radiat Oncol. 2013;23, Elsevier:97–108.PubMedPubMedCentralCrossRef

69.

Waddle MR, Sio TT, Van Houten HK, et al. Photon and proton radiation therapy utilization in a population of more than 100 million commercially insured patients. Int J Radiat Oncol Biol Phys. 2017;99(5):1078–82.PubMedCrossRef

70.

Hess CB, Thompson HM, Benedict SH, et al. Exposure risks among children undergoing radiation therapy: considerations in the era of image guided radiation therapy. Int J Radiat Oncol Biol Phys. 2016;94(5):978–92. https://doi.org/10.1016/j.ijrobp.2015.12.372 Epub 2016 Jan 5.CrossRefPubMed

71.

Baues C, et al. Proton versus photon deep inspiration breath hold technique in patients with hodgkin lymphoma and mediastinal radiation. Radiat Oncol. 2018;13:122.PubMedPubMedCentralCrossRef

Title: Proton therapy in the most common pediatric non-central nervous system malignancies: an overview of clinical and dosimetric outcomes
Authors: Angela Sardaro
Roberta Carbonara
Maria Fonte Petruzzelli
Barbara Turi
Marco Moschetta
Arnaldo Scardapane
Amato Antonio Stabile Ianora
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Rhabdomyosarcoma
Hodgkin Lymphoma
Retinoblastoma
Radiotherapy
Chondrosarcoma
Retinoblastoma
Published in: Italian Journal of Pediatrics / Issue 1/2019
Electronic ISSN: 1824-7288
DOI: https://doi.org/10.1186/s13052-019-0763-2

At a glance: The STEP trials

Springer Medicine

Proton therapy in the most common pediatric non-central nervous system malignancies: an overview of clinical and dosimetric outcomes

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2019

Time to recovery and determinants of severe acute malnutrition among 6–59 months children treated at outpatient therapeutic programme in North Gondar zone, Northwest Ethiopia: a prospective follow up study

Congenital nephrotic syndrome associated with 22q11.2 duplication syndrome in a Chinese family and functional analysis of the intronic NPHS1 c. 3286 + 5G > A mutation

X-linked hypophosphatemic rickets: an Italian experts’ opinion survey

Early onset retinal dystrophies: clinical clues to diagnosis for pediatricians

Novel DNA variation of GPR54 gene in familial central precocious puberty

Factors affecting the catch-up growth of preterm infants after discharge in China: a multicenter study based on the health belief model