Risk of second cancer after ion beam radiotherapy: insights from animal carcinogenesis studies

Abstract

Purpose: To review recent studies to better understand the risk of second cancer after ion beam radiotherapy and to clarify the importance of animal radiobiology therein.

Results: Risk of developing second cancer after radiotherapy is a concern, particularly for survivors of childhood tumors. Ion beam radiotherapy is expected to reduce the risk of second cancer by reducing exposure of normal tissues to radiation. Large uncertainty lies, however, in the choice of relative biological effectiveness (RBE) of high linear energy transfer (LET) radiation (e.g. carbon ions and neutrons) in cancer induction, especially for children. Studies have attempted to predict the risk of second cancer after ion beam radiotherapy based on an assessment of radiation dose, the risk of low LET radiation, and assumptions about RBE. Animal experiments have yielded RBE values for selected tissues, radiation types, and age at the time of irradiation; the results indicate potentially variable RBE which depends on tissues, ages, and dose levels. Animal studies have also attempted to identify genetic alterations in tumors induced by high LET radiation.

Conclusions: Estimating the RBE value for cancer induction is important for understanding the risk of second cancer after ion beam radiotherapy. More comprehensive animal radiobiology studies are needed.

Keywords:

• Second cancer
• carcinogenesis
• ion beam radiotherapy
• RBE
• animal experiments

Acknowledgements

The authors thank Dr. Naruhiro Matsufuji and Dr. Yusuke Koba (National Institutes for Quantum and Radiological Science and Technology) for critical reading of the manuscript.

Disclosure statement

The authors have no conflicts of interest to declare.

Additional information

Funding

This study was supported, in part, by MEXT via a Grant-in-aid for Scientific Research (B) (grant number JP15H02824).

Notes on contributors

Tatsuhiko Imaoka

Tatsuhiko Imaoka, PhD, 2016–present: Team Leader, QST, Japan; 2002–2016: Researcher, Senior Researcher and then Team Leader, NIRS, Japan; 2002: PhD in biological sciences, University of Tokyo, Japan; 2000–2001: Visiting Scientist, University of Cincinnati, USA.

Mayumi Nishimura

Mayumi Nishimura, 2016–present: Principal Researcher and then Senior Expert, QST, Japan; 1975–2016: Researcher and then Senior Researcher, NIRS, Japan.

Kazuhiro Daino

Kazuhiro Daino, PhD, 2016–present: Senior Researcher and then Section Manager, QST, Japan; 2008–2016: Postdoctoral Fellow, Researcher and then Senior Researcher, NIRS, Japan; 2005–2008: Postdoctoral Fellow, Atomic Energy Commission, France; 2005: PhD in biology, Chiba University, Japan.

Masaru Takabatake

Masaru Takabatake, PhD, 2016–present: Postdoctoral Fellow, QST, Japan; 2015–2016: Postdoctoral Fellow, NIRS, Japan; 2015: PhD in radiological science, Tokyo Metropolitan University, Japan.

Hitomi Moriyama

Hitomi Moriyama, MSc, 2015–present: Graduate Student, Tokyo Metropolitan University, Japan; 2013–2015: Radiological Technologist, Machida Municipal Hospital; 2013: BSc in radiological science, Tokyo Metropolitan University, Japan.

Yukiko Nishimura

Yukiko Nishimura, 2016–present: Technical Staff, QST, Japan; 2008–2016: Try Angle Inc., Japan; 2004–2008: Science Service Co., Ltd., Japan; 2002–2004: Assistant, NIRS, Japan.

Takamitsu Morioka

Takamitsu Morioka, PhD, 2016–present: Principal Researcher and then Section Manager, QST, Japan; 2010–2016: Postdoctoral Fellow and Senior Researcher, NIRS, Japan; 2007–2010: Assistant Professor, University of Ryukyus, Japan; 2007: PhD in medicine, University of Ryukyus, Japan.

Yoshiya Shimada

Yoshiya Shimada, PhD, 2016–present: Executive Director, QST, Japan; 1989–2016: Researcher, Senior Researcher, Team Leader and Director, NIRS, Japan; 1987–1989: Researcher, Tokyo Metropolitan Institute of Gerontology, Japan; 1985–1987: Postdoctoral Fellow, Japan Science and Technology Agency; 1985: PhD in biology, University of Tokyo, Japan.

Shizuko Kakinuma

Shizuko Kakinuma, PhD, 2016–present: Director, QST, Japan; 1999–2016: Visiting Researcher, Senior Researcher and Team Leader, NIRS, Japan; 1992–1999: Pharmaceutical industry and Kitasato Institute, Japan; 1992: PhD in pharmacy, Kitasato University; 1981–1992: Pharmaceutical industry in Japan and National Jewish Hospital Research Center, USA; 1981: BPharm, Kitasato University, Japan.