Teruhiko Terasawa, MD; Tomas Dvorak, MD; Stanley Ip, MD; Gowri Raman, MD; Joseph Lau, MD; Thomas A. Trikalinos, MD, PhD
Radiation therapy with charged particles can potentially deliver maximum doses while minimizing irradiation of surrounding tissues, and it may be more effective or less harmful than other forms of radiation therapy.
To review evidence about the benefits and harms of charged-particle radiation therapy for patients with cancer.
MEDLINE (inception to 11 July 2009) was searched for publications in English, German, French, Italian, and Japanese. Web sites of manufacturers, treatment centers, and professional organizations were searched for relevant information.
Four reviewers identified studies of any design that described clinical outcomes or adverse events in 10 or more patients with cancer treated with charged-particle radiation therapy.
The 4 reviewers extracted study, patient, and treatment characteristics; clinical outcomes; and adverse events for nonoverlapping sets of articles. A fifth reviewer verified data on comparative studies.
Currently, 7 centers in the United States have facilities for particle (proton)â€“beam irradiation, and at least 4 are under construction, each costing between $100 and $225 million. In 243 eligible articles, charged-particle radiation therapy was used alone or in combination with other interventions for common (for example, lung, prostate, or breast) or uncommon (for example, skull-base tumors or uveal melanomas) types of cancer. Of 243 articles, 185 were single-group retrospective studies. Eight randomized and 9 nonrandomized clinical trials compared treatments with or without charged particles. No comparative study reported statistically significant or important differences in overall or cancer-specific survival or in total serious adverse events.
Few studies directly compared treatments with or without particle irradiation.
Evidence on the comparative effectiveness and safety of charged-particle radiation therapy in cancer is needed to assess the benefits, risks, and costs of treatment alternatives.
Agency for Healthcare Research and Quality.
Charged-particle radiation therapy is an alternative mode of radiation delivery for patients with cancer. This treatment is expensive but is becoming increasingly available.
This review found that published evidence about the benefits and harms of charged-particle radiation therapy was derived mostly from small, single-group, retrospective studies. Of the 17 studies that compared treatments with or without charged particles, none reported statistically significant or important differences in overall or cancer-specific survival or in total serious adverse events.
We need better evidence to guide decision making about the indications for and the relative safety of charged-particle radiation therapy for cancer.
The dotted line shows the dose distribution of a spread-out Bragg peak of a particle beam. The dose distribution is created by adding the contributions of the 12 “pristine” Bragg peaks (solid lines). The dashed line shows the depth–dose distribution of a 10-MV photon beam. By varying the intensity and the energy (speed) of the charged particles, the width of the spread-out Bragg peak can be modulated. In this example, there is no dose beyond the distal end of the spread-out Bragg peak at a depth of approximately 150 mm, and the smaller dose is delivered to the entrance tissues compared with the spread-out Bragg peak. In contrast, the photon beam delivers the maximum dose to the entry tissues, as well as a substantial dose to tissues beyond a depth of 150 mm. Adapted by permission from MacMillan Publishers Ltd: British Journal of Cancer (reference 3), copyright 2005.
Appendix Table 1.
Each circle represents 1 study; the size of the circle is proportional to the logarithm of the total number of participants in the study. The number in each cell indicates the total number of studies. Each row shows studies addressing 1 type of cancer, and the columns show study designs with reported clinical outcomes. The “Other” row includes studies reporting on multiple types of cancer. The “Other” columns include studies that reported clinical outcomes other than OS or CSS (for example, disease-free survival, progression-free survival, tumor response rate, or quality of life). CSS = cancer-specific survival; GI = gastrointestinal; OS = overall survival.
Appendix Table 2.
Appendix Table 3.
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Terasawa T, Dvorak T, Ip S, Raman G, Lau J, Trikalinos TA. Systematic Review: Charged-Particle Radiation Therapy for Cancer. Ann Intern Med. 2009;151:556-565. doi: 10.7326/0003-4819-151-8-200910200-00145
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Published: Ann Intern Med. 2009;151(8):556-565.
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