Initial Report of a Prospective Dosimetric and Clinical Feasibility Trial Demonstrates the Potential of Protons to Increase the Therapeutic Ratio in Breast Cancer Compared With Photons

Int J Radiat Oncol Biol Phys. 2016 May 1;95(1):411-421. doi: 10.1016/j.ijrobp.2015.09.018. Epub 2015 Sep 25.


Purpose: To compare dosimetric endpoints between proton therapy (PT) and conventional radiation and determine the feasibility of PT for regional nodal irradiation (RNI) in women with breast cancer.

Methods and materials: From 2012 to 2014, 18 women (stage IIA-IIIB) requiring RNI prospectively enrolled on a pilot study. Median age was 51.8 years (range, 42-73 years). The cohort included breast-conserving therapy (BCT) and mastectomy patients and right- and left-sided cancers. Treatment targets and organs at risk were delineated on computed tomography scans, and PT and conventional plans were developed. Toxicity was prospectively recorded using Common Terminology Criteria for Adverse Events version 4.0. A Wilcoxon signed-rank sum test compared the dose-volume parameters. The primary endpoint was a reduction in cardiac V5.

Results: Median follow-up was 20 months (range, 2-31 months). For all patients, the PT plan better met the dosimetric goals and was used for treatment. Proton therapy alone was used for 10 patients (9 postmastectomy, 1 after BCT) and combined proton-photon in 8 (6 BCT, 2 postmastectomy with immediate expander reconstruction). Proton therapy improved coverage of level 2 axilla (P=.0005). Adequate coverage of internal mammary nodes was consistently achieved with PT (median D95, 50.3 Gy; range, 46.6-52.1 Gy) but not with conventional radiation therapy (median D95, 48.2 Gy; range, 40.8-55 Gy; P=.0005). Median cardiac V5 was 0.6% with PT and 16.3% with conventional radiation (P<.0001). Median ipsilateral lung V5 and V20 were improved with PT (median V5 35.3% vs 60.5% [P<.0001]; and median V20, 21.6% vs 35.5% [P<.0001]). Grade 3 dermatitis developed in 4 patients (22%), which was the only grade 3 toxicity. No grade 4+ toxicities developed.

Conclusion: Proton therapy for RNI after mastectomy or BCT significantly improves cardiac dose, especially for left-sided patients, and lung V5 and V20 in all patients without excessive acute toxicity. Proton therapy simultaneously improves target coverage for the internal mammary nodes and level 2 axilla, which may positively impact long-term survival in breast cancer patients.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Axilla
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Heart / diagnostic imaging
  • Heart / radiation effects*
  • Humans
  • Lung / diagnostic imaging
  • Lung / radiation effects*
  • Lymphatic Irradiation / adverse effects
  • Lymphatic Irradiation / methods*
  • Mastectomy
  • Middle Aged
  • Organs at Risk / diagnostic imaging
  • Organs at Risk / radiation effects*
  • Photons / adverse effects
  • Photons / therapeutic use
  • Pilot Projects
  • Postoperative Care
  • Prospective Studies
  • Proton Therapy* / adverse effects
  • Proton Therapy* / methods*
  • Protons / adverse effects
  • Radiation Exposure / prevention & control
  • Radiodermatitis / pathology
  • Radiography
  • Radiotherapy Dosage
  • Time Factors
  • Unilateral Breast Neoplasms / diagnostic imaging
  • Unilateral Breast Neoplasms / pathology
  • Unilateral Breast Neoplasms / radiotherapy*


  • Protons