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Conformal Proton Beam Radiotherapy of Cancer

Carl J. Rossi, Jr., MD

Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, California

Originally Received March 4, 1995; Last Revised March 5, 1996.

Introduction | What is conformal PBRT? | Is PBRT new or experimental? | Where in the US can I receive PBRT? | Combining PBRT with other forms of radiotherapy | PBRT in prostate cancer | How is PBRT planned and delivered? | What happens in the treatment room? | Other cancers treated with PBRT | Editorial comment


This article is provided primarily for patients and family members in the hope that it will answer some of the most commonly asked questions about conformal proton beam radiotherapy, and to illustrate the usefulness of this form of radiation treatment in a variety of clinical situations. A separate article specifically addressing the use of this form of treatment for patients with prostate cancer is currently in development.

What is conformal proton beam radiotherapy?

Conformal proton beam radiotherapy (henceforth known as PBRT) is a form of external beam radiation treatment.

"External beam* refers to the fact that the radiation is generated and administered by a machine outside of the patient's body, as opposed to implanted sources of radiation, which either temporarily or permanently place radioactive sources within a person's body. Other forms of external beam radiotherapy include x-ray therapy and cobalt-60 gamma-ray therapy.

"Conformal" means that it is possible to shape or "conform" the beam in three dimensions to "fit" the shape of the organ or tumor to be radiated, so that the majority of the radiation is administered to the organ or tumor and not to the surrounding, normal tissue. It is this unique ability to conform a proton beam to a specific tumor or target which sets PBRT apart from other forms of external beam radiotherapy.

Is PBRT a new or experimental therapy for cancer?

The answer to this question is an emphatic "No" on both counts. The ability of PBRT to be shaped to particular targets within the human body was recognized in the 1940s when cyclotrons ("atom smashers") were being developed. The first scientific paper discussing their potential use in cancer treatment was published in the Journal of Radiology in July 1946. The author of the paper was Robert Wilson, a world-renowned physicist who was involved in early cyclotron development at the Donner (later Lawrence) radiation laboratory of the University of California. In this paper, Dr Wilson discussed how a proton beam could be manipulated to deliver high doses of radiation to a small target while at the same time sparing surrounding tissues.

As a direct outgrowth of this paper, scientists at the Harvard Cyclotron Laboratory and the Lawrence Berkeley Laboratory began to modify their research cyclotrons to permit human treatment. Initial treatments of intracranial sites began in the late 1950s. The results were so encouraging that, as the technology improved, modifications were made to existing machines to permit treatment of deep tumors in virtually any part of the body. Extensive studies were also carried out regarding the "radiobiology" of PBRT, or how protons interact with normal and malignant tissue. By the late 1980s, some 14,000 patients around the world had been treated with PBRT, and follow-up studies on some patients stretched back over 20 years.

Because of the significant number of patients treated, and the amount of follow-up data now available, it has become possible to assess the effectiveness of PBRT in cancer therapy. In virtually every tumor site examined, the higher tumor doses and lower normal tissue doses delivered by PBRT have been shown to improve local control and to reduce acute and late complications as compared with x-ray therapy. When the available data on PBRT was reviewed by the federal Medicare program and the National Cancer Institute in the early 1990s, it was decided that sufficient data existed to classify PBT as an accepted (i.e., non-experimental) treatment for any of a number of localized tumors and for treatment of intracranial aneurysms.

Loma Linda University and Harvard University are currently engaged in a series of studies sponsored by the National Cancer Institute to determine the "best" or optimal PBRT dose for certain cancers (such as prostate cancer and a variety of brain tumors). It is important to emphasize that these studies are not being done to see if PBRT is an effective therapy. This has already been established. What is being determined now is the optimal way to use this tool in the fight against cancer. Similar studies are performed all the time with other standard forms of cancer therapy such as chemotherapy and surgery.

Where in the US can I receive PBRT?

At the time of writing there are two facilities in the US treating patients with protons on a regular basis. The older facility is the Massachusetts General Hospital/Harvard Cyclotron Laboratory, which has been operational since 1957. Currently, that facility is limited to treating less than 10 patients per day, and cannot routinely irradiate many deep tumors. To overcome this problem, a new PBRT facility is being constructed at Massachusetts General Hospital. This new facility has been designed to treat up to 100 patients per day, and is scheduled to open in June 1998.

Loma Linda's PBRT center opened in 1990 and is now fully operational, with four rooms available for the treatment of patients and a fifth room for basic science research. The facility was designed to treat a maximum of approximately 100 patients per day and is currently averaging about 80 patient treatments per day.

Is PBRT ever combined with other forms of radiation therapy?

Conformal PBRT is often used in conjunction with x-ray therapy to "boost" the levels of radiation at sites of gross disease and to allow irradiation of a large volume of tissue at doses sufficient to sterilize microscopic cancer.

An example of this type of combination radiotherapy is available in the treatment of certain stages of prostate cancer. Depending on the amount of cancer within the gland, and the type of prostate cancer present, a patient may be at risk for harboring microscopic "nests" of prostate cancer cells within the pelvic lymph nodes. These nodes lie at some distance from the prostate, and will not be irradiated if conformal PBRT alone is delivered to the prostate gland. Similarly, the use of x-ray therapy alone will limit the total dose of radiation which can be given to the prostate because of the high doses which would be delivered to large amounts of normal tissue. The solution is to utilize conformal PBRT to treat the prostate gland and to follow this with x-ray therapy of the pelvic area to treat the lymph nodes. By giving some of the treatment with conformal PBRT, the total x-ray dose can be reduced substantially, thus reducing the risk of complications while simultaneously permitting treatment of potentially cancerous lymph nodes (which would be missed if x-rays were not used at all). An analogous situation is seen in the treatment of many head and neck cancers, when there is also a significant risk for lymph node involvement.

Why is there so much interest in using PBRT in prostate cancer?

The prostate gland lies deep within the pelvis and is surrounded by critical structures such as the bladder and the rectum. Cancer of the prostate is now the most common malignancy in males (excluding skin cancers). In 1996 it has been estimated by the American Cancer Society that over 300,000 new cases of prostate cancer will be diagnosed and that as many as 41,400 patients will die of this disease.

There is abundant evidence in the medical literature to demonstrate that radiation therapy or surgery (radical prostatectomy) are effective treatments for this disease. It has also been demonstrated that the ability of radiation therapy to control prostate cancer is highly dependent upon the total dose of radiation which is delivered. Higher doses equate to a higher degree of disease control. However, with normal external beam x-ray therapy alone (including three-dimensional conformal x-ray therapy) a point of diminishing returns is reached beyond which further dose escalation begins to cause unacceptable side effects.

This risk of unacceptable side effects can be reduced by using conformal PBRT for some or all of the treatment by virtue of the tissue-sparing capabilities of PBRT on normal tissue as compared to external beam x-radiation. You may remember that a proton beam has a well defined high-dose area which can be manipulated to surround an irregularly shaped target (like the prostate gland) and thus give comparatively low doses of protons to the nearby normal tissues. In the treatment of prostate cancer, this tissue-sparing capability allows for reductions in the dose of radiation which may be delivered to the bladder and the rectal area while permitting the necessary high doses to be delivered to the prostate. The outcome is a reduced risk of radiation damage to the bladder and the rectal area -- one of the major risks associated with conventional x-radiation therapy for prostate cancer.

How is PBRT planned and delivered?

It is impossible to deliver PBRT precisely without having (1) a three-dimensional reconstruction of the target organ or tumor and its relationship to the surrounding structures and (2) a reproducible treatment position to minimize movement errors (sometimes referred to as a "geographic miss").

The three-dimensional data are usually obtained by performing a computed tomography (CT) scan through the region of interest (chest, pelvis, etc.) with "slices" being taken at 3-5 mm intervals. Before the CT scan is performed, some type of immobilization device is constructed for the patient so that it is easy to reconstruct the patient's precise position each day during treatment. A typical immobilization device is a full-body "pod" constructed of a form-fitting foam liner surrounded by a rigid plastic (PVC) shell. For treatment of brain tumors, a custom-manufactured mask is utilized. The CT scan is obtained with the patient lying in the immobilization device so that the thickness of the immobilizing materials can be taken into account during the PBRT planning process.

Once the "pod" has been manufactured and the CT scan is complete, the treating physician sits down at a computer workstation and traces on the computer screen the tumor or organ to be irradiated and the surrounding normal tissue slice by slice. Next, a team of physicists and dosimetrists creates a proton beam treatment plan by generating a series of proton beams which are carefully designed to enter the patient at a variety of angles and by calculating the radiation dose being given to the tumor or target organ and the normal surrounding tissues. This plan is reviewed by the treating physician and, once approved, is electronically transferred to a series of automated machines which create the appropriate apertures and tissue compensating filters needed to turn the computer-generated plan into a treatment reality. All of these devices are calibrated by the physics support staff before the patient's first treatment to ensure that the planning and process of actual beam creation has been accomplished correctly.

What happens in the treatment room?

After changing into a gown, the patient enters the treatment room and lies down in the "pod" or puts on the mask. By utilizing a number of laser beams, the patient and the "pod" are moved to a position which is customarily within half a centimeter of the calculated optimal position. To further refine the patient's position, a series of low-power diagnostic radiographs are then taken. Distances from various bone landmarks to the "isocenter" are measured on these films each day and compared to identical measurements made on computer-generated films based on the planning CT scan. Usually, it is necessary to move the "pod" a few millimeters to make the daily position conform exactly with the ideal treatment position. These measurements and movements are performed by radiation therapy technologists and verified by a physician before each treatment.

After any necessary movements have been made, the treatment devices unique to each patient are loaded into the beam-line. All of these devices are identified by an individual bar-code which must be scanned by a laser scanner (similar to those you might see at a supermarket) before the computer will permit a treatment to take place. The purpose of this system is to minimize any risk that a particular patient might be treated with another patient's unique set of apertures and compensating filters.

At this point, the technologists and the physician retire to a control room located outside each treatment room and initiate the treatment. Protons enter the room as a series of discrete "spills" or "pulses" which (like x-rays) cannot be either seen or felt. Once the prescribed radiation dose has been delivered, the computer shuts off the proton beam, the technologists re-enter the room, and the patient gets out from the "pod" and changes back out of the gown.

Other cancers (and benign conditions) treated with PBRT

The following is a current list of the cancers and other benign conditions (listed by body site) which are currently being treated at Loma Linda using PBRT, either alone or in combination with x-ray therapy:

  • Brain and head/neck
    • Astrocytoma
    • Meningioma
    • Acoustic neuroma
    • Ocular melanoma
    • Subfoveal neurovascularization
    • Intracranial arteriovenous malformations
    • Brain metastases
    • Multiple head and neck sites (e.g., nasopharynx, tonsil, base of tongue, paranasal sinuses, etc.)

  • Spinal cord
    • Cordomas, including those involving the base of the skull
    • Chondrosarcomas

  • Chest
    • Medically inoperable non-small-cell lung cancer (usually stage I or stage II tumors which have not metastasized to any other site in patient's whose general health makes removal of the lung impossible)

  • Abdomen
    • Hepatocellular carcinoma
    • Liver metastasis (usually solitary)
    • Pancreatic cancer
    • Retroperitoneal sarcomas

  • Pelvis
    • Prostate cancer
    • Cervical cancer
    • Sacral cordomas

We are in the process of performing improvements to the synchrotron and the proton beam transport system to allow treatment of large fields such as those required to breast cancer and Hodgkin's disease. We anticipate that this capability will exist by the end of 1997.

Editorial comment

This article provides a useful introduction for the patient to the general principles behind the use of proton beam radiation therapy as well as some general comments on its relevance in the treatment of prostate cancer. Dr Rossi has agreed to a request from The Prostate Cancer InfoLink to develop an article which addresses more specifically issues regarding the use of PBRT in the treatment of prostate cancer in the near future.

The Prostate Cancer InfoLink would draw to the attention of its users that while the principles of the application of PBRT to prostate cancer are reasonably well defined, and the relative safety of this technique is well known, it will only be with the publication of data from treatment of a large, well documented series of prostate cancer patients at specific dose levels with a minimum mean follow-up of five years that we will truly begin to appreciate whether this technique can provide clinical efficacy and safety comparable to other forms of therapy. The Prostate Cancer InfoLink is of the opinion that PBRT represents a valid form of treatment for selected patients with prostate cancer at this time. It will be helpful when more prostate-specific data are available, particularly data regarding long-term disease-free survival and adverse reactions to treatment.

Other questions which may need to be asked about PBRT are whether (as appears to be the case with external beam radiotherapy) neoadjuvant and adjuvant hormone therapy can offer a significant disease-free survival benefit, and indeed whether such combination treatment might even offer an overall survival benefit compared to PBRT alone.

[This "editorial comment" was part of the original page.]

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