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    Proton Therapy:


    In proton radiotherapy, a particle accelerator is used to target the tumor with a beam of protons. These charged particles damage the DNA of cells, ultimately causing their death or interfering with their ability to reproduce. Cancer cells, because of their high rate of division and the reduced ability to repair damaged DNA are particularly unable to resist this attack on the DNA. For patients with a relatively well defined superficial tumor mass, all protons are of a single energy that has well defined range characteristics. With single beam proton radiotherapy, very few protons will penetrate beyond the distance determined by the physical characteristics of proton energy. A single beam treatment delivers dose to the tissues at a maximum just over the last few mm of the protons particles range. This range of maximum dose is called the BRAGG peak. Physical characteristics made proton beam useful for rare tumors that were generally superficially located, included melanomas of the eye, tumors arising near the spinal cord and at the skull base.

    The first treatments were performed at particle accelerators built for Physics research. Berkeley Radiation Laboratory in California started treating patients in 1954 for limited disease indications. Subsequently, the Harvard Cyclotron Laboratory collaborative program between the Harvard Cyclotron and the Massachusetts General, started in 1961. The treatment facility was shut down, and the programs in Boston were transferred to the Northeast Proton Therapy facility at Massachusetts General Hospital in 2001. Loma Linda University Medical Center in Loma Linda, California was built in 1990. For decades, there were three operating programs in the United States; Boston, Berkeley and Loma Linda. These facilities concentrated most of their attention to tumors of the eye, skull base and paraspinal tumors, as well as unresectable sarcomas.

    Modern Day: As of today, 7 proton beam radiotherapy facilities are operating in the United States and four more are planned, or are under construction. With little data from randomized control demonstrating better cancer control with lower side effects, the Centers have continued to build and open new proton beam facilities at costs between $100 million and $225 million each. As for tumors of the eye and skull base, the skull base and paraspinal areas, the traditional realm of protons are typically relatively uncommon tumors, Proton centers are now concentrating on more common malignancies including adenocarcinoma of the prostate. Despite the massive cost involved with building and maintaining these facilities, very little has actually been done to compare results with technologically advanced modern radiotherapy techniques, including IMRT and Rapid Arc.

    Lack of Comparisons: A report in the Annuals of Internal Medicine in the fall of 2009 (Volume 151, pages 556 – 565) presented a systemic review of 243 studies of any design, evaluating clinical outcomes and adverse affects, in patients treated with charged particle radiotherapy (includes proton). Of the 243 studies (the studies must have had at least 10 patients in the final analysis and many were small), only 8 of the studies were randomized and 9 were non-randomized trials comparing treatments with or without charged particle radiotherapy. The authors concluded no comparative study reported showed statistical improvement of important differences in overall or cancer-specific survival rates or in serious adverse events.

    The classic indication for proton radiotherapy is involved in the globe ocular tumors (the eye), which are small, shallow and thin. This presents the perfect therapeutic environment for proton beam. Tumors such as the prostate are deep seated, with the target region much thicker. This necessitates the use of the spread out BRAGG peak (SOBP). It is important to understand that tissues deep to the tumor, receive little or no radiation from single beam proton therapy. The tissues in front are irradiated while the tumor receives the prescribed radiation dosage, based on the spread out BRAGG peak. When prostates are treated, two large lateral fields, one from the left and one from the right are utilized. The net result of this is that the tissue on both sides of the prostate will receive radiation dosage.

    Cancer killing ability: Proton beam is a relative biological effect (RBE) cancer killing ability which is similar to that of photons used. Proton dose is often described in centigrade equivalent (CGE). A misconception exists that protons are more effective at destroying cancer when centigrade equivalent dose is compared. This is not true. That is the case of prostate cancer.

    Prostate cancer: There is very little published information about the efficacy and safety of proton therapy on a long term basis. In 2004, the experience of Loma Linda University was published in the International Journal of Radiation Oncology biology Physics (Volume 59, pages 348 – 352). The study evaluated 1,255 patients treated at their facility. Some received protons and 3-D conformal radiation. Others received protons alone. The patients treated with protons and 3-D conformal radiotherapy (Photons) typically received an older form of treatment delivery using a four field set up which is no longer utilized for the treatment of prostate cancer and is outdated technology. The field technique that they used does not have the ability to spare normal tissues to the extent that modern image-guided radiotherapy techniques do today.

    The provision of the authors was that “no difference was seen in toxicity between those treated with combined protons and photons, and those with protons alone”. Because of the very small incidence of Grade III and Grade IV side effects (no statistically significant prognostic variables for toxicity could be found). These results, when accounting for length of follow up, compare favorably with conformal photon therapy and intensity modulated radiotherapy. The only long term study of proton beam radiotherapy for prostate cancer has failed to show any improvement in results in terms of cancer control or side effects.

    The prostate cancer therapy stirs debate on cost and efficacy. An article ran in the Wall Street Journal on September 23, 2008. This article addresses the debate of costly proton beam radiotherapy. There have been no clinical trials showing that proton beam is more effective with fewer side effects than other prostate treatments. “I think there was a time 10 years ago when proton had fewer risks. Other treatments have gotten better and the gap may no longer exist,” according to Andrew Zeitman, M.D. a Radiation Oncologist at the Harvard Medical School at Massachusetts General who treats prostate cancer with protons and other therapies.

    Summary. Comparisons of proton beam radiotherapy with older forms of photon radiotherapy have not indicated that there is an improvement in cancer outcomes or a reduction in side effects. More modern, technologically advanced forms of radiotherapy, such as Rapid Arc IMRT have not been compared with protons. Based on the lack of proven benefit of protons compared with outdated modalities for prostate cancer, proton facilities must show some benefit to modern up-to-date treatment techniques in order to justify the high cost and inconvenience of their treatment.


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