The Use of Carbon-ions for Treatment of Cancer | Hailu

The Use of Carbon-ions for Treatment of Cancer ___________________________________________________ A Comparative Study of Carbon-ion Radiotherapy vs Photon Radiotherapy BY FIKADU HAILU THE OHIO STATE UNIVERSITY
Abstract: This study explores the use of Carbon-ion for the treatment of cancer in radiation therapy. The use of heavy charged particles for radiotherapy has grown in popularity over the years and Carbon-ions are now being implemented in the field. This study compares the rate of treatment complications, side effects, among patients treated with Carbon-ions and Conventional Photon therapy. Data will be collected from treatment centers across the nation that utilize Carbon-ions and will be analyzed to see if there is statistically significant difference between Carbon-ion radiotherapy and Photon therapy with respect to side effects. The side effects, toxicity, that were compared in this study are general fatigue, skin erythema and specific reactions. We used matched groups for this study.

Introduction Radiation therapy is the use of very high energy radiation to treat cancer. It utilizes the energy of the radiation being used to break the DNA strands of a cancer cell, thereby effectively killing it. The use of radiation therapy along with surgery and chemotherapy has become very effective in controlling the growth of cancer cells.

Just like advancements in Surgery and chemotherapy, radiotherapy has gotten better at delivering the intended damage to cancer cells while minimizing the side effects to normal surrounding cells. This is due to different reasons including better understanding of the effects of radiation leading to better fractionations, better immobilization devices leading to better
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The Use of Carbon-ions for Treatment of Cancer | Hailu

reproducibility of treatments, better techniques as IMRT and SBRT to avoid critical structures and the use of newer sources of radiation with unique characteristics as Heavy charged particle. For years photon energy has been used to deliver radiation treatments. Gamma ray sources and Linear accelerator capable of producing photons have been the primary mechanisms used in the application of radiotherapy. But over the past few decades, the use of heavy charged particle for cancer treatment has grown in popularity. As R. Wilson stated for the first time in the year 1946, Heavy charged particle have a special characteristics called Bragg Peak which can be used to deliver a high amount of dose to a small volume while maintaining the dose to the surround tissue very minimal.1 With Bragg Peak, most of the energy of the charged particle is deposited at the end of the track of the charged particle along its path.2 Bragg Peak is a very important concept as it delivers a direct damage to the DNA strands of cancer cells. With Bragg
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Peak, three-dimensional dose formation is possible with high precision by controlling the incident energy.3 Photons, unlike heavy charged particles, utilize indirect methods of destroying the DNA of cancer cells by creating charged particles (free radicals) within tissue which in turn cause the damage. The problem with free radicals is the fact that they affect normal cells as they bounce around in tissues. Due to their size, heavy charged particle do not bounce around, so they deposit their energy in relatively straight path. As most of the energy is deposited at the end of the path of the particle, Bragg Peak, by planning so that the tumor lies right at the end of the path, the highest direct damage can be obtained without affecting normal surrounding cells. With any new technique come the obvious question, is it better than the current techniques? Can we see improvements when it comes to side effects as compared to photon treatments? Research Question This study tries to see if the side effects of Carbon-ion treatments is any

Wilson R (1946) Radiological use of fast protons. Radiology 47: 487491.

Radiation Therapy for Cancer. National Cancer Institute Web site. Kanematsu N, Koba Y, Ogata R. Page | 2

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The Use of Carbon-ions for Treatment of Cancer | Hailu

different than photon treatments for the same disease and site. Is there statistically significant difference between the frequency of side effects between photon treatments and Carbon-ion treatments? Due to the very different nature of heavy charged particles like Carbon-ions and photons, a significant reduction in the frequency and severity of side effects by utilizing Carbon-ion radiotherapy is expected. So this study is set out to find if available data supports this claim.

patients.4 The mean age of the patients was 46.2 years. The study was performed from the year 2001 to 2008. Efficancy of treatment was compared with previous results. The study did find that less complications and superior survival rate with Carbon-ion radiotherapy than any other therapy whether Heavy charged therapy or conventional photon radiotherapy. However, this study was only done on patients with unresectable adult bone and soft tissue sarcoma of head and neck. This study tries to look further and see if the use of Carbon-ions for radiotherapy can improve treatment effectiveness by

Review of Literature Studies have been done to see the effectiveness of Carbon-ions for radiotherapy but very few studies exist comparing the side effects of this treatment with conventional photon treatment. To evaluate the effectiveness of Carbon-ion treatment in improving the prognosis of unresectable adult bone and soft tissue sarcoma of head and neck, researchers from the Research Center for Charged Particle Therapy, National Institute of Radiological Science (NIRS) of Chiba, Japan did a prospective study on 27
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minimizing side effects for other types of cancer. Researchers from Department of Radiation Oncology, University Hospital of Heidelberg, Germany performed a study on 118 patients to assess early toxicity and response in patients treated with Heavy ions.5 The research which took place between November 2009 and June 2010 included subjects with chondro-sarcoma, salivary gland tumors and gliomas. Early toxicity was evaluated within six weeks. Their findings not only confirmed Carbon-ions to be safe, but

Jingu K, Tsujii H, Yamada S, et al. Rieken S, Habermehl D, Combs S, et al.

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The Use of Carbon-ions for Treatment of Cancer | Hailu

also the side effects with carbon-ions to be very rare.

of each side effect was compared for each treatment type, Carbon-ion therapy or conventional photon therapy. Common

Methods For this study data was collected from multiple institutions across the nation who were willing to participate in the study. The data collected did include the type of treatment, the site being treated, the type of disease, the length of fractions. Since photon energy is widely used, the data collected for photon treatments was very specific. Only data from patients of similar disease site and type as those treated with Carbon-ions was selected from the photon group. For a patient being treated for thyroid cancer with Carbonion radiotherapy, we did search for a patient with similar traits that was being treated with photon and compared the side effects. Age of patients with similar trait was + or - 5 years. For every phone treatment selected, a Carbonion treatment of same site with similar dose in Gray equivalent (GyE) was compared for side effect. Early toxicity was measured on the sixth week of the start of a treatment. The components compared include, general disorder, fatigue, skin redness of treated area and site specific side effects. The frequency

Terminology Criteria Adverse Events was used to grade each side effect in order to standardize the measuring scale. The number of data collected was limited by the number of participating institutes that were treating with Carbon-ions. The data was entered into a statistical program called Math-lab to find the p value. A p value of less than 0.05 was required to claim that there is statistically significant difference between the frequency of the side effects observed for Carbon-ion radiotherapy and the frequency of the side effects observed for conventional photon therapy.

Results The calculated p value was 0.7 > 0.05. As a result, we our study was not able to find any improvements with Carbon-ion treatments with respect to side effects. This could be due to selection bias, as we had to select patients being treated with photon manually in order to get the closest attributes to patients with Carbon-ion treatment. Due to small participating institutions, perhaps our sample was not large enough to show any

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significant difference. This was just a study and one could possibly perform experimental

study to investigate further.

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The Use of Carbon-ions for Treatment of Cancer | Hailu

References
1. Wilson R (1946) Radiological use of fast protons. Radiology 47: 487491. 2. Radiation Therapy for Cancer. National Cancer Institute Web site. http://www.cancer.gov/ cancertopics/factsheet/Therapy/radiation Updated June 30, 2010. Accessed June 22, 2013. 3. Kanematsu N, Koba Y, Ogata R. Evaluation of Plastic Materials for Range Shifting, Range Compensation, and Solid-Phantom Dosimetry in Carbon-ion Radiotherapy. Available at: http://link.aip.org/getpdf/servlet/GetPDFServlet? filetype=pdf&id=MPHYA6000040000004041724000001. Accessed June 15, 2013. 4. Jingu K, Tsujii H, Yamada S, et al. Carbon ion radiation therapy improves the prognosis of unresectable adult bone and soft-tissue sarcoma of the head and neck. International Journal Of Radiation Oncology, Biology, Physics [serial online]. April 2012;82(5):2125-2131. Available from: CINAHL Plus with Full Text, Ipswich, MA. Accessed June 15, 2013. 5. Rieken S, Habermehl D, Combs S, et al. Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the heidelberg ion therapy center using the raster scanning technique. International Journal Of Radiation Oncology, Biology, Physics [serial online]. December 2011;81(5):e793-801. Available from: CINAHL Plus with Full Text, Ipswich, MA. Accessed June 22, 2013.

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