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Second malignant neoplasm risk after craniospinal irradiation in X-ray-based techniques compared to proton therapy

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Abstract

Cranio-spinal irradiation (CSI) is widely used for treating medulloblastoma cases in children. Radiation-induced second malignancy is of grave concern; especially in children due to their long-life expectancy and higher radiosensitivity of tissues at young age. Several techniques can be employed for CSI including 3DCRT, IMRT, VMAT and tomotherapy. However, these techniques are associated with higher risk of second malignancy due to the physical characteristics of photon irradiation which deliver moderately higher doses to normal tissues. On the other hand, proton beam therapy delivers substantially lesser dose to normal tissues due to the sharp dose fall off beyond Bragg peak compared to photon therapy. The aim of this work is to quantify the relative decrease in the risk with proton therapy compared to other photon treatments for CSI. Ten anonymized patient DICOM datasets treated previously were selected for this study. 3DCRT, IMRT, VMAT, tomotherapy and proton therapy with pencil beam scanning (PBS) plans were generated. The prescription dose was 36 Gy in 20 fractions. PBS was chosen due to substantially lesser neutron dose compared to passive scattering. The age of the patients ranged from 3 to 12 with a median age of eight with six male and four female patients. Commonly used linear and a mechanistic doseresponse models (DRM) were used for the analyses. Dose-volume histograms (DVH) were calculated for critical structures to calculate organ equivalent doses (OED) to obtain excess absolute risk (EAR), life-time attributable risk (LAR) and other risk relevant parameters. A α′ value of 0.018 Gy−1 and a repopulation factor R of 0.93 was used in the mechanistic model for carcinoma induction. Gender specific correction factor of 0.17 and − 0.17 for females and males were used for the EAR calculation. The relative integral dose of all critical structures averaged were 6.3, 4.8, 4.5 and 4.7 times higher in 3DCRT, IMRT, VMAT and tomotherapy respectively compared to proton therapy. The mean relative LAR calculated from the mean EAR of all organs with linear DRM were 4.0, 2.9, 2.9, 2.7 higher for male and 4.0, 2.9, 2.8 and 2.7 times higher for female patients compared to proton therapy. The same values with the mechanistic model were 2.2, 3.6, 3.2, 3.8 and 2.2, 3.5, 3.2, 3.8 times higher compared to proton therapy for male and female patients respectively. All critical structures except lungs and kidneys considered in this study had a substantially lower OED in proton plans. Risk of radiation-induced second malignancy in Proton PBS compared to conventional photon treatments were up to three and four times lesser for male and female patients respectively with the linear DRM. Using the mechanistic DRM these were up to two and three times lesser in proton plans for male and female patients respectively.

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References

  1. Frühwald MC, Rutkowski S (2011) Tumors of the central nervous system in children and adolescents. Dtsch Arztebl Int 108(22):390–397

    PubMed  PubMed Central  Google Scholar 

  2. Slampa P, Pavelka Z, Dusek L, Hynkova L, Sterba J, Ondrova B, Princ D, Novotny T, Kostakova S (2007) Longterm treatment results of childhood medulloblastoma by craniospinal irradiation in supine position. Neoplasma 54(1):62–67

    CAS  PubMed  Google Scholar 

  3. Athiyaman H, Mayilvaganan A, Singh D (2014) A simple planning technique of craniospinal irradiation in the eclipse treatment planning system. J Med Phys 39(4):251–258

    Article  PubMed  PubMed Central  Google Scholar 

  4. Seppälä J, Kulmala J, Lindholm P, Minn H (2010) A method to improve target dose homogeneity of craniospinal irradiation using dynamic split field IMRT. Radiother Oncol 96(2):209–215

    Article  PubMed  Google Scholar 

  5. Peñagarícano J, Moros E, Corry P, Saylors R, Ratanatharathorn V (2009) Pediatric craniospinal axis irradiation with helical tomotherapy: patient outcome and lack of acute pulmonary toxicity. Int J Radiation Oncol Biol Phys 75:1155–1161

    Article  Google Scholar 

  6. Kunos CA, Dobbins DC, Kulasekere R, Latimer B, Kinsella TJ (2008) Comparison of helical tomotherapy versus conventional radiation to deliver craniospinal radiation. Technol Cancer Res Treat 7(3):227–233

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  8. Lindell B et al (1990) International Commission on Radiological Protection. Recommendations. Annals of the ICRP Publication 60. Pergamon Press, Oxford

    Google Scholar 

  9. Friedman DL et al (2010)) Subsequent neoplasms in 5year survivors of childhood cancer: the childhood cancer survivor study. J Natl Cancer Inst 102:1083–1095

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hall EJ, Wuu C (2003) Radiation-induced second cancers: the impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys 56:83–88

    Article  PubMed  Google Scholar 

  11. Smith MA et al (2010) Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28:2625–2634

    Article  PubMed  PubMed Central  Google Scholar 

  12. Tubiana M (2009) Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review. Radiother Oncol 91:4–15

    Article  PubMed  Google Scholar 

  13. Yan X, Titt U, Koehler AM et al (2002) Measurement of neutron dose equivalent to proton therapy patients outside of the proton radiation field. Nucl Instrum Method Phys Res A476:429–434

    Article  Google Scholar 

  14. Newhauser WD, Durante M (2011) Assessing the risk of second malignancies after modern radiotherapy. Nat Rev Cancer 11(6):438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhang R et al (2013) Comparison of risk of radiogenic second cancer following photon and proton craniospinal irradiation for a pediatric medulloblastoma patient. Phys Med Biol 58(4):807–823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Schneider U, Antony L, Norbert L (2000) Comparative risk assessment of secondary cancer incidence after treatment of Hodgkin’s disease with photon and proton radiation. Radiat Res 154(4):382–388

    Article  CAS  PubMed  Google Scholar 

  17. Grantzau T, Lene M, Jens O (2013) Second primary cancers after adjuvant radiotherapy in early breast cancer patients: a national population based study under the Danish Breast Cancer Cooperative Group (DBCG). Radiother Oncol 106(1):42–49

    Article  PubMed  Google Scholar 

  18. Moteabbed M, Yock TI, Paganetti H (2014) The risk of radiation-induced second cancers in the high to medium dose region: a comparison between passive and scanned proton therapy, IMRT and VMAT for pediatric patients with brain tumors. Phys Med Biol 59(12):2883

    Article  PubMed  Google Scholar 

  19. Jarlskog CZ, Harald P (2008) Risk of developing second cancer from neutron dose in proton therapy as function of field characteristics, organ, and patient age. Int J Radiat Oncol Biol Phys 72(1):228–235

    Article  CAS  Google Scholar 

  20. Athar BS, Paganetti H (2011) Comparison of second cancer risk due to out-of-field doses from 6-MV IMRT and proton therapy based on 6 pediatric patient treatment plans. Radiother Oncol 98(1):87–92

    Article  PubMed  Google Scholar 

  21. Sakthivel V, Mani GK, Mani S, Boopathy R, Selvaraj J (2017) Estimating second malignancy risk in intensity-modulated radiotherapy and volumetric-modulated arc therapy using a mechanistic radiobiological model in radiotherapy for carcinoma of left breast. J Med Phys 42(4):234

    Article  PubMed  PubMed Central  Google Scholar 

  22. Daşu A, Toma-Daşu I, Olofsson J, Karlsson M (2005) The use of risk estimation models for the induction of secondary cancers following radiotherapy. Acta Oncol 44(4):339–347

    Article  PubMed  Google Scholar 

  23. Kumar S (2012) Second malignant neoplasms following radiotherapy. Int J Environ Res Public Health 9(12):4744–4759

    Article  PubMed  PubMed Central  Google Scholar 

  24. Armstrong GT, Sklar CA, Hudson MM, Robison LL (2007) Long-term health status among survivors of childhood cancer: does sex matter? J Clin Oncol 25(28):4477–4489

    Article  PubMed  Google Scholar 

  25. BEIR (2006) Health risks from exposure to low levels of ionizing radiation BEIR VII phase 2. National Research Council, National Academy of Science, Washington

    Google Scholar 

  26. Taddei PJ, Mahajan A, Mirkovic D, Zhang R, Giebeler A, Kornguth D, Harvey M, Woo S, Newhauser WD (2010) Predicted risks of second malignant neoplasm incidence and mortality due to secondary neutrons in a girl and boy receiving proton craniospinal irradiation. Phys Med Biol 55(23):7067

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sharma DS, Gupta T, Jalali R, Master Z, Phurailatpam RD, Sarin R (2009) High-precision radiotherapy for craniospinal irradiation: evaluation of three-dimensional conformal radiotherapy, intensity-modulated radiation therapy and helical Tomo therapy. Br J Radiol 82(984):1000–1009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Brown AP, Barney CL, Grosshans DR, McAleer MF, De Groot JF, Puduvalli VK, Tucker SL, Crawford CN, Khan M, Khatua S, Gilbert MR (2013) Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma. Int J Radiat Oncol Biol Phys 86(2):277–2784

    Article  PubMed  PubMed Central  Google Scholar 

  29. Schneider U (2009) Mechanistic model of radiation-induced cancer after fractionated radiotherapy using the linear-quadratic formula. Med Phys 36(4):1138–1143

    Article  PubMed  Google Scholar 

  30. Anderson RN, DeTurk PB (2002) United States life tables 1999. Natl Vital Stat Rep 50:1–39

    PubMed  Google Scholar 

  31. Miralbell R, Lomax A, Cella L, Schneider U (2002) 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 54(3):824–829

    Article  PubMed  Google Scholar 

  32. Schneider U, Marcin S, Judith R (2011) Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy. Theor Biol Med Model 8(1):27

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Advanced Medical Physics, Houston, USA

    Vasanthan Sakthivel & Raghavendiran Boopathy

  2. Research and Development Centre, Bharathiar University, Coimbatore, India

    Vasanthan Sakthivel & Kadirampatti M. Ganesh

  3. Department of Radiation Physics, Kidwai Memorial Institute of Oncology, Bengaluru, India

    Kadirampatti M. Ganesh

  4. Department of Radiation Oncology, Miami Cancer Institute, Miami, USA

    Craig McKenzie

  5. RaySearch Laboratories, New York, USA

    Craig McKenzie

  6. Medical Physics & Radiation Engineering, Canberra Hospital, Garran, ACT, Australia

    Jothybasu Selvaraj

  7. South West Clinical School, University of New South Wales, Sydney, Australia

    Jothybasu Selvaraj

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  1. Vasanthan Sakthivel
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  2. Kadirampatti M. Ganesh
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  3. Craig McKenzie
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  4. Raghavendiran Boopathy
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  5. Jothybasu Selvaraj
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Correspondence to Jothybasu Selvaraj.

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Sakthivel, V., Ganesh, K.M., McKenzie, C. et al. Second malignant neoplasm risk after craniospinal irradiation in X-ray-based techniques compared to proton therapy. Australas Phys Eng Sci Med 42, 201–209 (2019). https://doi.org/10.1007/s13246-019-00731-y

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  • DOI: https://doi.org/10.1007/s13246-019-00731-y

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