RESEARCH
The Clinical Science Section     

The Clinical Science Section, in cooperation with Prof. Quynh-Thu Le of Stanford University(SU), has been engaging in the development of imaging technology to determine positioning of patients in order to improve treatment delivery accuracy with X-ray therapy and proton beam therapy systems. Currently, a team led by Assoc. Prof. Billy W Loo, Assist. Prof. Maximilian Diehn, Prof. Hiroki Shirato and Assist. Prof. Tetsuya Inoue is now ready to enroll the first patient for an international clinical trial to be conducted by SU to test the role of stereotactic ablative radiotherapy (SABR) in improving the survival rates of the patients with lung cancer.

For liver cancer, Prof. Albert Koong, Assoc. Prof. Daniel Chang and Assoc. Prof. Nishita Kothary have also been leading an international clinical study with cooperation from Assist. Prof. Norio Katoh of Hokkaido University(HU) and this team is now making final preparations for the clinical trial to measure cDNA (cancer cell gene in the blood) developed by Assist. Prof. Maximilian Diehn of SU to monitor tumor burden.

To learn essential knowledge for the collaborative clinical research and conducting joint clinical trials, Assist. Prof. Daisuke Abo of HU studied at SU Hospital for three months in 2015 and engaged in joint research between interventional radiology and radiation oncology, focusing on trans-arterial tumor embolization and intratumoral fiducial marker placement. Assoc. Prof. Shinichi Shimizu has also led research to develop state-of-the-art technology, minimally invasive, advanced radiotherapy using proton beam therapy. Dr. Shimizu has published papers and made presentations at academic conferences related to the development of proton beam therapy with real-time tumor tracking technology and simulations of clinical applications.

A team led by Assoc. Prof. Kohsuke Kudo, and Senior Assist. Prof. Khin Khin Tha, is engaging in research related to accurate imaging of hypoxic tumor cells in vivo. Another team led by Senior Assist. Prof. Noriko Manabe and research fellow, Jeffrey Wang, in collaboration with Assist. Prof. Ruijiang Li of the Medical Physics Section of SU, is conducting radiomics research, and developing innovative quantitative image analysis technology. For radiomics, which is an innovative quantitative image analysis technology, publication of papers and presentation of research results at academic conferences has been conducted jointly between HU and SU. Clinical studies on real-time-image gated proton beam therapy (RGPT) are also being conducted by the HU unit. The results of these clinical studies will enable clinical research to realize new treatments that are aimed at avoiding recurrence and metastasis.

The Medical Physics Section

The Medical Physics Section has worked on developing new technology to improve the treatment accuracy of proton therapy, something that has attracted a great deal of public attention in recent years. Assoc. Prof. Taeko Matsuura of Hokkaido University(HU), Instructor Magdalena Bazalova (currently serving as an Assistant Professor at University of Victoria), and Prof. Lei Xing of Stanford University(SU) developed technology to depict and outline the two dimensional gold concentration distributions in objects using the proton beam therapy system of HU (M. Bazalova et al., Med. Phys. 2015). Currently, a further study using this technology is being developed by Assist. Prof. Hao Peng, a doubly appointed Stanford researcher who stayed at HU for three months in 2016. Many specialists have pointed out the importance of developing technology to verify the proton beam range during treatment. The team led by Dr. Matsuura and post-doctoral researcher Moiz Ahmad of SU is engaging in developing technology to determine the range of the proton beam in real-time using ultrasonic waveforms emitted by the irradiated target during treatment (M. Ahmad et al., Med. Phys. 2015). Since 2015, a team led by Assist. Prof. Seishin Takao, Prof. Kikuo Umegaki, and Dr. Ruud Vinke, a doubly appointed Stanford researcher who stayed at HU for three months in 2015, has been engaged in the development of technology to make it easier to acquire CBCT with multiplex X-ray energy levels compared to the existing single energy approach. We can expect that this technology will improve resolution of the obtained CT images and enable more accurate calculations of doses. The Matsuura team has also developed a device to decrease the duration of irradiation needed when the target moves due to respiration (T. Matsuura et al., Phys. Med. Biol. 2016).

In addition to these research activities, Assist. Prof. Ruijiang Li who spent six months at HU and post-doctoral researcher Yi Cui (currently serving as an Associate Researcher at SU) who spent twelve months at GSQ of HU, performed radiomics study using the clinical imaging data of brain and pancreatic tumors treated at SU and HU. They published their results in the top journal in this field (Radiology, 2015). Prof. Lei Xing, Prof. Kikuo Umegaki, Prof. Masayori Ishikawa and Assist. Prof. Kenneth Lee Sutherland of HU are engaging in the summer school sessions at HU as a part of the global educational outreach in collaboration with SU. Assoc. Prof. Edward Graves of SU visited HU in 2015 and gave a lecture titled “The Effects of Radiation on Cell Migration” at the seminar held by GSQ. Clinical Assoc. Prof. Yong Yang of SU visited HU in 2016 and collaborated with medical physics team at HU and Assist. Prof. Hao Peng on development of dual-energy CT based proton therapy dose calculation strategy. Assoc. Prof. Yang also gave a lecture titled “Stereotactic Body Radiation Therapy: Simulation, Planning and Delivery” to the graduate students of HU.

With the growing adoption of proton beam therapy, there is an increasing need for effective and user-friendly tools for performing quality assurance (QA) measurements. The phosphor coated phantom developed by a SU researcher, Cesare Jenkins, would be one of the promising tools to meet this goal. Since the phosphor emits the visible light when the proton beam passes through it, we can visualize the delivery of individual spots in real-time. He came to HU and performed the first experimental study with Assist. Prof. Yuka Matsuzaki. The preliminary data has been submitted to the 2016 Annual Meeting of AAPM.

medical physics
 The Radiation Biology Section

Since 2014, the Radiation Biology Section has worked to prepare the work environment for carrying out radiation biology research with Stanford University(SU) including wet laboratory space, an office, and research facilities on the 4th floor of the Graduate School of Medicine of Hokkaido University(HU).

The radiation biology research team led by Prof. Amato J. Giaccia of SU, including Assist. Prof. Erinn B. Rankin, Assist. Prof. Jin-Min Nam, and post-doctoral researcher, Frances C. Recuenco have been conducting collaborative research. This team has been investigating ways to improve the efficacy of radiation treatment on cancer by analyzing the molecular changes on the cell surface receptors after radiation treatment while taking into account the effect of the tumor microenvironment. Assist. Prof. Koichi Yasuda visited SU for five months in 2015 to conduct collaborative research focusing on enhancing tumor radiosensitivity in the Rankin’s lab. Dr. Giaccia has given three state-of-the-art special lectures on radiation biology and the tumor microenvironment in the annual GI-CoRE International Symposium. Drs. Le, Giaccia, Koong and Shirato have put together a review on emerging treatment paradigm in radiation oncology in a prestigious American Association for Cancer Research journal (Le QT et al, Clin Cancer Res, 2015). Drs. Rankin, Nam and Giaccia published a review regarding “Hypoxia: Signaling the Metastatic Cascade” in a Cell Press Reviews journal (Rankin et al, Trends in Cancer, 2016)

In addition to collaboration between SU and HU, the Radiation Biology Section has also been conducting collaborative research projects with groups of the Graduate School of Medicine, HU, and focused on the molecular mechanisms of cancer cell invasion (Hashimoto A et al, J Cell Biol, 2016).

Among educational activities under the supervision of Dr. Nam, Ping-Hsiu Wu (MD), a graduate student of the Graduate School of Medicine of HU, is engaging in research related to the application of radiation sensitizers targeting cell surface receptors which are involved in cancer cell invasion. He presented the research at international conferences: ASCB Meeting (San Diego, 2015), The 3rd GI-CoRE Medical Science and Engineering Symposium (Sapporo, 2016), and will present at ASTRO Meeting (Boston, 2016). Dr. Wu also visited the laboratories of Drs. Giaccia and Graves at SU to learn how to conduct in vivo experiments in mice. Dr. Recuenco has developed and mastered the experimental system of in vivo imaging to analyze the effect of radiation using animal models. Besides, faculty members of GSQ, undergraduate and graduate students have a monthly journal club in English for learning recent knowledge and researches of radiation biology. The Radiation Biology teams of HU and SU have monthly lab meetings via Skype to plan collaborative projects and report progress.

 

HU=Hokkaido University, SU=Stanford University