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

Australas Phys Eng Sci Med. 2019 Mar;42(1):201-209. doi: 10.1007/s13246-019-00731-y. Epub 2019 Feb 6.


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.

Keywords: Childhood malignancy; Craniospinal irradiation; EAR; IMRT; LAR; Proton therapy; Second malignancy; Tomotheraspy; VMAT.

Publication types

  • Comparative Study

MeSH terms

  • Child
  • Child, Preschool
  • Craniospinal Irradiation / adverse effects*
  • Dose-Response Relationship, Radiation
  • Female
  • Humans
  • Male
  • Proton Therapy*
  • Risk Factors
  • X-Rays