Clinical trials involving carbon‐ion radiation therapy and the path forward

Abstract

To describe the international landscape of clinical trials in carbon ion radiotherapy (CIRT), we reviewed the current status of 63 ongoing clinical trials (median: 47 subjects) involving CIRT identified from the clinicaltrials.gov trial registry and World Health Organization International Clinical Trials Platform Registry. We evaluated the potential for these trials to define the role of this modality in the treatment of specific cancer types, and to identify major challenges and opportunities to advance this technology. A significant body of literature suggests the potential for advantageous dose distributions and in preclinical biologic studies the enhanced effectiveness for CIRT compared to photons and protons. Additionally, clinical evidence, though limited, from phase I/II trials indicates the potential for CIRT to improve cancer outcomes. However, at present, high level phase III randomized clinical trial evidence does not exist. While there has been an increase in the number of trials investigating CIRT since 2010, and the number of countries and sites offering CIRT is slowly growing, this progress has excluded other countries. We propose several recommendations to study this modality in order to accelerate progress in the field, including to (1) increase the number of multi-national randomized clinical trials (2) leveraging existing CIRT facilities to launch larger multi-national trials directed at common cancers combined with high level quality assurance; and (3) developing more compact and less expensive “next generation” treatment systems integrated with radiobiological research and pre-clinical testing.

Carbon Ion Therapy: A Modern Review of an Emerging Technology

“…The National Institute of Radiologic Sciences (NIRS) opened the first heavy ion accelerator for clinical use in Chiba, Japan, in 1994 (2). Since that time, over 20,000 patients have been treated with carbon ion radiation therapy (CIRT) (3). Today, there are five countries and a total of 13 centers treating with CIRT (1,4).…”

Is there any benefit to particles over photon radiotherapy?

“…There are still no results available from RCTs. A review of clinicaltrial.gov in 2018 did not show any phase 3 RCT for carbon ion radiation therapy [16]. On the other side, there are several initiatives at a European level promoting research on particle therapy.…”

Three discipline collaborative radiation therapy (3DCRT) special debate: The United States needs at least one carbon ion facility

“…Ion therapy was pioneered at Lawrence Berkeley National Laboratory (LBNL) to investigate the clinical value of improved dose sparing, enhanced relative biological effectiveness (RBE), and lower oxygen enhancement ratio (OER) by using this form of radiotherapy. Despite the origins of carbon ion radiotherapy (CIRT) in the United States, initial phase I/II studies done in conjunction with the University of California, San Francisco (UCSF) were cut short because of the closure of the LBNL facility . Henceforth in the United States, clinical particle therapy has been restricted to proton therapy and we have had to rely on the experience of our colleagues outside the United States for clinical investigations of CIRT.…”

“…The authors acknowledge that although the current clinical evidence supporting the use of carbon ion therapy is compelling, it is incomplete . The pioneering investigations at LBNL showed that fractionated delivery of heavy ion therapy, generally as a boost at relatively low doses, was well tolerated across diverse tumor sites, including locally advanced prostate cancer, bone and soft tissue sarcomas, and head and neck tumors of the salivary gland and paranasal sinus .…”