The risk for developing a secondary cancer after breast radiation therapy: Comparison of photon and proton techniques

Radiother Oncol. 2020 Aug;149:212-218. doi: 10.1016/j.radonc.2020.05.035. Epub 2020 May 25.


Background and purpose: To compare secondary malignancy risks of modern proton and photon therapy techniques for locally advanced breast cancer.

Methods and materials: We utilized dosimetric data from 34 [10 photon-VMAT, 10 photon-3DCRT, 14 pencil beam scanning proton (PBS)] breast cancer patients who received comprehensive nodal irradiation. Employing a model based on organ equivalent dose to account for both inhomogeneous organ dose distributions and non-linear functional dose relationships, we estimated excess absolute risk, excess relative risk, and lifetime attributable risk (LAR) for secondary malignancies. The model uses dose distribution, number of fractions, age at exposure, attained age, the linear-quadratic dose response relationship for cell survival, repopulation factor, as well as gender specific age dependencies, and initial slopes of dose response curves.

Results: The LAR for carcinoma at age 70 was estimated to be up to 3.64% for esophagus with an advantage of 3DCRT over PBS and VMAT. For the ipsilateral lung, risks were lowest for PBS (up to 5.56%), followed by 3DCRT (up to 6.54%) and VMAT (up to 7.7%). For the contralateral lung, there is a clear advantage of 3DCRT and PBS techniques (risk <0.86%) over VMAT (up to 4.4%). The risk for the contralateral breast is negligible for 3DCRT and PBS but was estimated as up to 1.2% for VMAT. Risks for the thyroid are overall negligible. Independently performed comparative treatment plans on 10 patients revealed that the risk for the contralateral lung and breast using VMAT can be more than an order of magnitude higher compared to PBS. Sarcoma risks were estimated as well showing similar trends but were overall lower compared to carcinoma.

Conclusion: Conventional (3DCRT) techniques led to the lowest estimated risks of, thyroid and esophageal secondary cancers while PBS demonstrated a benefit for secondary lung and contralateral breast cancer risks, with the highest risks overall associated with VMAT techniques.

Keywords: Breast cancer; Outcome modelling; Secondary malignancies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Breast Neoplasms* / etiology
  • Breast Neoplasms* / radiotherapy
  • Humans
  • Neoplasms, Second Primary* / epidemiology
  • Neoplasms, Second Primary* / etiology
  • Organs at Risk
  • Proton Therapy* / adverse effects
  • Protons
  • Radiotherapy Dosage
  • Radiotherapy Planning, Computer-Assisted
  • Radiotherapy, Intensity-Modulated* / adverse effects


  • Protons