International Journal of Clinical Oncology

, Volume 23, Issue 2, pp 353–360 | Cite as

Acute toxicity of image-guided hypofractionated proton therapy for localized prostate cancer

  • Koichiro NakajimaEmail author
  • Hiromitsu Iwata
  • Hiroyuki Ogino
  • Yukiko Hattori
  • Shingo Hashimoto
  • Mikiko Nakanishi
  • Toshiyuki Toshito
  • Yukihiro Umemoto
  • Shoichiro Iwatsuki
  • Yuta Shibamoto
  • Jun-etsu Mizoe
Original Article



Hypofractionated proton therapy (HFPT) is expected to become an effective treatment approach for localized prostate cancer (PCa). The purpose of this study was to evaluate differences in acute toxicity among patients with localized PCa treated with either conventional fractionated proton therapy (CFPT) or HFPT.


A total of 526 eligible patients treated with proton therapy between February 2013 and May 2016 in three phase II trials were analyzed. We prescribed 74 gray relative biological effectiveness equivalents [Gy (RBE)]/37 fractions for low-risk patients and 78 Gy (RBE)/39 fractions for intermediate- and high-risk patients in the CFPT group (n = 254) and 60 Gy (RBE)/20 fractions for low-risk and 63 Gy (RBE)/21 fractions for intermediate- and high-risk patients in the HFPT group (n = 272). Patients were evaluated for acute toxicity with the Common Terminology Criteria for Adverse Events, version 4.0, and urinary quality-of-life change using the International Prostate Symptom Score (IPSS).


No grade ≥3 acute toxicity was observed in either group. Among acute genitourinary toxicities, grade 2 rates were 15% (n = 38) in CFPT and 5.9% (n = 16) in HFPT (P ≤ 0.001). The median baseline IPSSs of the CFPT and HFPT groups were 7 (0–29) and 6 (0–31), respectively (P = 0.70). One-month post-treatment scores were 9 (0–32) and 11 (0–32), respectively (P = 0.036), and 6-month post-treatment scores were 7 (0–30) and 7 (0–33), respectively (P = 0.88). There were no significant differences in acute gastrointestinal toxicity between the two groups.


Our results demonstrated the safety of HFPT for localized PCa patients in terms of acute toxicity.


Prostate cancer Proton therapy Hypofractionation Acute toxicity International Prostate Symptom Score (IPSS) 



The authors thank Dr. Chihiro Omachi as a member of proton therapy physics, and Dr. Keisuke Yasui and Mr. Kensuke Hayashi as a member of proton therapy technology, for their valuable help in this research.

Compliance with ethical standards

Conflict of interest

All authors have read the journal’s policy on conflicts of interest and have none to declare.


No specific funding was disclosed.

Ethics approval

The data of this study were extracted from ongoing prospective phase II clinical trials based on protocols approved by the Institutional Review Board (IRB) of Nagoya City Hospital. The IRB numbers are 14-02-17 (14) and 14-02-18 (15) and 14-02-19 (16).

Informed consent

Informed consent was obtained from each participant.


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Copyright information

© Japan Society of Clinical Oncology 2017

Authors and Affiliations

  • Koichiro Nakajima
    • 1
    Email author
  • Hiromitsu Iwata
    • 1
    • 2
  • Hiroyuki Ogino
    • 1
  • Yukiko Hattori
    • 1
    • 2
  • Shingo Hashimoto
    • 1
    • 2
  • Mikiko Nakanishi
    • 1
    • 2
  • Toshiyuki Toshito
    • 3
  • Yukihiro Umemoto
    • 4
  • Shoichiro Iwatsuki
    • 4
  • Yuta Shibamoto
    • 2
  • Jun-etsu Mizoe
    • 1
  1. 1.Department of Radiation OncologyNagoya Proton Therapy Center, Nagoya City West Medical CenterNagoyaJapan
  2. 2.Department of RadiologyNagoya City University Graduate School of Medical SciencesNagoyaJapan
  3. 3.Proton Therapy Physics, Nagoya Proton Therapy CenterNagoyaJapan
  4. 4.Department of Nephro-UrologyNagoya City West Medical CenterNagoyaJapan

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