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Calypso, according to Greek mythology, refers to a nymph who lived on the island of Ogygia. In this mini review, the Calypso (Varian Medical Systems, USA) is a motion management technology in radiation therapy which can perform internal electromagnetic motion monitoring. The special name derived from Greek mythology gives this technology a romantic feeling.

As shown in Figure 1, the Calypso system is composed of several parts, including beacon transponders, array, console, tracking station. Firstly, the array transmits electromagnetic signals to the beacon transponders. Secondly, the beacon transponders receive the waves and transmit Radio-Frequency (RF) signals at specific hertz. Lastly, the array detects the RF signal and converts their position displacements to movement curves. With the help of console and tracking station, therapists can observe the movement curves and recognize the real-time offsets of the tumor.

Figure 1: Calypso system components and accessories (Courtesy of Ref. [1]).

Compared to other motion management technologies, such as Active Breathing Coordinator™ (ABC, ELEKTA, Sweden) [2], Real-time Position Management™ (RPM, Varian Medical Systems, USA) [3], Optical Surface Management System (OSMS, Varian Medical Systems, USA) [4], etc. the Calypso system is a real-time and direct approach to localize and track tumors. Therefore, it is expected that this internal motion monitoring approach is more accurate than those external ones.

Due to the advantages of Calypso, the first internal electromagnetic motion monitoring implementation for stereotactic liver radiotherapy in China was successfully implemented and evaluated in our institution [5]. Preliminary research results had been reported. A thorough literature search was conducted with the keyword “calypso & radiotherapy” via the Web of Science, and current status of Calypso in China was briefly described. Nevertheless, it is necessary to investigate comprehensively the development of Calypso all over the world, which may facilitate the motion management-based radiotherapy methodologies and guide the way for its future applications.

By august 25th of 2021, a keyword of “((calypso & radiotherapy) or (electromagnetic tracking and radiotherapy) or (real-time tracking and radiotherapy and internal))” as topics were searched in web of science and refined by document types of articles and reviews only. Totally, 553 results were found. Although there were few papers related to gold and infrared marker, these literatures basically covered most aspects of Calypso through the years.

In this paper, a brief review of Calypso, including its past, present and future trend, was described. It is expected that this comprehensive retrospect, current status analysis and prospect can lead to an improvement in Calypso methodologies to different carcinoma characterization in different countries.

A statistic work was done in advance to reveal dependencies of number of papers, such as countries, years of publication and carcinoma types (Figure 2).

Figure 2: Number of papers with regard to Calypso in different countries.

Figure 2 shows the number of papers with regard to Calypso in different countries. It is clearly seen that there are huge differences among countries, especially the USA. The United States ranked the first and way out in front, followed by Australia, Germany, Japan, Canada, England, Denmark and China.

It can be seen that most countries in Figure 2 are developed countries, followed by developing countries. Furthermore, less Calypso cases were reported in some developed countries, such as New Zealand, than that of some developing countries, such as China and India.

It is assumed that availability of Calypso was related to not only economic development levels but also population bases. It is also expected that, with the economic growth, more Calypso cases will be reported especially in developing countries (Figure 3).

Figure 3: Number of articles and milestones of Calypso over the years.

Figure 3 shows the number of articles and milestones of Calypso over the years since it is invented. Although there were some records from 1997 to 2003, Calypso was actually emerged around 2004 [6]. At that time, other names such as wireless localization systems and nonionizing target localization systems were also used in addition to Calypso [7-9]. From 2004 to 2006, some QA (Quality Assurance) research papers were published, which were prepared for the following clinical trials [10,11]. Multi-centric clinical studies started from 2007 [12-15]. From 2004 to 2008, all the reports were revolving around prostate cancer.

Successively, the first case of pancreatic cancer with Calypso was reported in 2009 [16]. In the same time, results from clinical trials and multi-institutional studies kept coming out from 2009 [17-20]. Furthermore, the first case of cervical cancer and the first case of lung cancer based on Calypso were reported in 2010 and 2011, respectively [21,22]. The first case of liver cancer through the instrumentality of Calypso was reported in 2015 [23-25], which was closely following the Conformité Européenne marking and US Food and Drug Administration clearance for general implantation in soft issues in 2014.

In general, the number of articles about Calypso reached to its plateau during the period from 2012 to 2019. Possibly due to the COVID-19 pandemic, number of articles related to Calypso started to decrease since 2020. It can be predicted that more reports of Calypso will be published after the pandemic, when the traveling prohibition was released and risks of beacon implantation was lowered. It can also be noticed that Calypso was implemented in prostate cancer in the beginning and spread out to other types of carcinoma gradually, such as pancreatic cancer, cervical cancer, lung cancer and liver cancer. Thus, it is necessary to investigate the number of articles related to different carcinomas in order to recognize the current application status of Calypso (Figure 4).

Figure 4: Number of articles versus different carcinomas treated by Calypso.

Figure 4 shows the carcinoma type correlations of literature numbers related to Calypso. It can be seen that most of the reports were about prostate cancer and lung cancer, followed by liver cancer and breast cancer, etc. This may be attributed to that there is a high incidence of prostate cancer in western countries. It is also noticed that there are huge differences among carcinoma types. The number of liver cancer is about a quarter of prostate cancer. It is believed that, with the growing popularity of Calypso, more cases of liver cancer treated by this technology will be reported especially in East Asian countries as the incidence of liver cancer in this area higher than the rest of the world.

Future of calypso

According to the aforementioned retrospect and current status analysis of Calypso, several anticipations can be made. Firstly, Calypso will gradually spread to developing countries, especially those with large populations, such as China and India. Secondly, Calypso will be applied in more types of carcinoma, which are badly in need of motion management such as breast cancer. Thirdly and most importantly, the widespread implementation of Calypso must be based on the premise of the deliberate selection of appropriate patients and the adequate skills of beacon transponder implantation.

Furthermore, in addition to regular radiotherapy procedures, implementation of Calypso includes several extra steps such as CTguided beacon implantation and setup QA. These complicated steps hinder the installation of Calypso in junior hospitals, for instance, infirmaries. It can be anticipated that Calypso will be only applied in major hospitals in the foreseeable future.

It has been nearly two decades since the invention of Calypso. In the last seventeen years, Calypso has been booming in developed countries, especially in the United States. What is more, most of the Calypso application cases are in prostate cancers and lung cancers. Nowadays, it begins to spread to developing countries and be utilized in soft tissues such as liver cancer. It is believed that more cases will be reported in aspect of both countries and carcinoma types. To some extent, due to cumbersome and error-prone steps, Calypso is still restricted to be applied in major hospitals. Whereas, it is still promising and its bright future is glad to be prospected.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

This work was supported by the China Postdoctoral Science Foundation (Grant No. 2018M632263), Jiangsu Postdoctoral Research Funding Program (Grant No. 2021K422C), Southeast University- Nanjing Medical University Cooperative Research Project (Grant No. 2242018K3DN22) and Postdoctoral Foundation of Jiangsu Institute of Cancer Research (Grant No. SZL201715).

The authors thank the therapist group of the Radiotherapy Department of Jiangsu Cancer Hospital for their opinions and experiences in Calypso applications. The authors also thank Miss Vicky Chen for her careful proofreading.