Progress in heavy ion cancer therapy at IMP and future development

Abstract

Basic research on heavy ion cancer therapy such as radiobiology, medical physics, and therapeutic technique has been conducted at the Institute of Modern Physics (IMP), Chinese Academy of Sciences since 1995. Based on the achievements acquired in the basic research and the requirements for a heavy ion accelerator for radiotherapy purposes, a dedicated heavy ion therapy facility named Heavy Ion Medical Machine (HIMM) was designed at IMP and constructed in Wuwei, China. The HIMM facility consists of two electron cyclotron resonance ion sources, one cyclotron as the injector and one synchrotron as the main accelerator, and four different treatment rooms equipped with passive or active beam delivery systems, and accelerates carbon ions up to 400 MeV/u. After the performance inspection of HIMM organized by the National Medical Device Inspection Center, preclinical tests like cell and animal radiobiological experiments and dosimetric verification using anthropomorphic phantoms for elucidating the biophysical properties of the carbon ion beams provided by HIMM were carried out. According to the Chinese medical device regulations, a clinical trial in which 46 tumor patients were recruited and two hospitals participated was conducted in the HIMM facility, aiming at evaluating the treatment safety and short-term efficacy of the medical device. The success of the clinical trial helped the HIMM facility be authorized by the Chinese government as a class III medical device. In this paper, all the aspects mentioned above are introduced and discussed, and implications for future improvements are also given.

Keywords

heavy ion cancer therapy / clinical trial / performance inspection / dosimetric verification / medical device

References

[1] Durante M, Loeffler JS. Charged particles in radiation oncology. Nat Rev Clin Oncol. 2010;7(1):37-43.

[2] Particle Therapy Co-Operative Group (PTCOG). Via the PTCOG website.

[3] Li Q, Dai Z, Yan Z, Jin X, Liu X, Xiao G. Heavy-ion conformal irradiation in the shallow-seated tumor therapy terminal at HIRFL. Med Biol Eng Comput. 2007;45(11):1037-1043.

[4] Li Q. Biomedical research with heavy ions at the IMP accelerators. Adv Space Res. 2007;40(4):455-460.

[5] Jin X, Liu Y, Ye F, et al. Role of autophagy in high linear energy transfer radiation-induced cytotoxicity to tumor cells. Cancer Sci. 2014;105(7):770-778.

[6] Jin X, Li F, Zheng X, et al. Carbon ions induce autophagy effectively through stimulating the unfolded protein response and subsequent inhibiting Akt phosphorylation in tumor cells. Sci Rep. 2015;5:13815.

[7] Jin X, Zheng X, Li F, et al. Fragmentation level determines mitochondrial damage response and subsequently the fate of cancer cells exposed to carbon ions. Radiother Oncol. 2018;129(1):75-83.

[8] Li Q, Sihver L. Therapeutic techniques applied in the heavy-ion therapy at IMP. Nucl Instr Meth Phys Res. 2011;269(7):664-670.

[9] Dai ZY, Li Q, Liu XG, Jin XD, Huang QY, Xiao GQ. Active spot-scanning test with heavy ions at HIRFL-CSR. Chin Phys C. 2012;36(8):784-791.

[10] He P, Li Q, Liu X, et al. Respiratory motion management using audio-visual biofeedback for respiratory-gated radiotherapy of synchrotron-based pulsed heavy-ion beam delivery. Med Phys. 2014;41(11):111708.

[11] Zhang H, Li S, Wang XH, et al. Results of carbon ion radiotherapy for skin carcinomas in 45 patients. Br J Dermatol. 2012;166(5):1100-1106.

[12] Yang JC, Shi J, Chai WP, Xia JW, Yuan YJ, Li Y. Design of a compact structure cancer therapy synchrotron. Nucl Instr Meth Phys Res A. 2014;756:19-22.

[13] Liu XG, Li Q, Du XG, et al. A preliminary version of heavy ion treatment planning system at IMP. Nucl Phys Rev. 2010;27(4):480-487.

[14] Karger CP, Peschke P. RBE and related modeling in carbon-ion therapy. Phys Med Biol. 2017;63(1):01TR02.

[15] Musolino SV. Absorbed dose determination in external beam radiotherapy: an international code of practice for dosimetry based on standards of absorbed dose to water. Technical reports series no. 398. Health Phys. 2001;81(5):592-593.

[16] Li Z, Li Q, Wang X, et al. Carbon ion radiotherapy acts as the optimal treatment strategy for unresectable liver cancer during the coronavirus disease 2019 crisis. Front Public Health. 2021;9:767617.

[17] Durante M, Formenti S. Harnessing radiation to improve immunotherapy: better with particles? Br J Radiol. 2020;93(1107).20190224.

[18] Matsunaga A, Ueda Y, Yamada S, et al. Carbon-ion beam treatment induces systemic antitumor immunity against murine squamous cell carcinoma. Cancer. 2010;116(15):3740-3748.

[19] Zhou P, Wang Y, Qin S, et al. Abscopal effect triggered by radiation sequential mono-immunotherapy resulted in a complete remission of PMMR sigmoid colon cancer. Front Immunol. 2023;14:1139527.

[20] Ollivier L, Moreau Bachelard C, Renaud E, Dhamelincourt E, Lucia F. The abscopal effect of immune-radiation therapy in recurrent and metastatic cervical cancer: a narrative review. Front Immunol. 2023;14:1201675.

[21] Viswanath D, Park J, Misra R, et al. Nanotechnology-enhanced radiotherapy and the abscopal effect: current status and challenges of nanomaterial-based radio-immunotherapy. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2023;15:e1924.

[22] Pangal DJ, Yarovinsky B, Cardinal T, et al. The abscopal effect: a systematic review in patients with brain and spine metastases. Neurooncol Adv. 2022;4(1):vdaC132.

[23] Craig DJ, Ambrose S, Stanbery L, Walter A, Nemunaitis J. Systemic benefit of radiation therapy via abscopal effect. Front Oncol. 2022;12:987142.

[24] Demaria S, Formenti SC. The abscopal effect 67 years later: from a side story to center stage. Br J Radiol. 2020;93(1109):20200042.

[25] Brenneman RJ, Sharifai N, Fischer-Valuck B, et al. Abscopal effect following proton beam radiotherapy in a patient with inoperable metastatic retroperitoneal sarcoma. Front Oncol. 2019;9:922.

[26] Ngwa W, Irabor OC, Schoenfeld JD, Hesser J, Demaria S, Formenti SC. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer. 2018;18(5):313-322.

[27] Demaria S, Golden EB, Formenti SC. Role of local radiation therapy in cancer immunotherapy. JAMA Oncol. 2015;1(9):1325-1332.

[28] Dai T, Li Q, Liu X, et al. Nanodosimetric quantities and RBE of a clinically relevant carbon-ion beam. Med Phys. 2020;47(2):772-780.

RIGHTS & PERMISSIONS

2024 2024 The Authors. Malignancy Spectrum published by John Wiley & Sons Australia, Ltd on behalf of Higher Education Press.