Charlie Ma, PhD

Radiation therapy has long been an important treatment option for cancers of the prostate and lung. The proximity of critical normal structures to these organs and the fact that the tumors move make field design a challenge, however. Not surprisingly, for years, radiation treatment of prostate and lung tumors was associated with complications arising from damaged normal tissues.

To reduce morbidity, three-dimensional (3D) conformal therapy and its even more precise cousin, intensity-modulated radiation therapy (IMRT), were applied early in their development to the prostate and lung, although the narrower margins of these protocols made motion of these tumors even more troublesome. Attempts to refine treatment planning continue. One place that such research is being done is Fox Chase Cancer Center, Philadelphia.


Radiation therapy for prostate cancer traditionally has been used in older and sicker patients, but with the introduction of conformal and IMRT protocols, indications for its use have expanded. Conformal therapy proved superior to conventional external-beam radiation in obtaining local cancer control, as judged by serum prostate-specific antigen concentration, 1 and earlier work at Fox Chase Cancer Center showed that increasing the radiation dose to 75 Gy from the customary 65 to 70 Gy (which can be done safely, using a conformal protocol) improves the 5-year disease-free survival rate from 44% to 75% in patients with intermediate-risk tumors and from 14% to 29% in patients with high-risk disease. 2 IMRT is now the standard external-beam radiation treatment for prostate cancer, as it can permit further dose escalation, when appropriate, while keeping complications at an acceptable level.

Although designing an IMRT plan for a prostate tumor might seem straightforward, it is not: the gland can move significantly from day to day. “If the patient drank a great deal of liquid or ate a lot of beans, the prostate could move as much as 5 to 7 mm in relation to the bony structures in the pelvis,” according to Charlie Ma, PhD, director of radiation physics at Fox Chase Cancer Center, where a large proportion of the more than 1,200 IMRT treatments given have been performed for prostate cancer. “We call it prostate dancing. You, therefore, must determine how much to move the isocenter at the start of each session,” he says.

At Fox Chase Cancer Center, prostate IMRT is performed using a stereotactic body localizer. The protocol includes hypofractionation and use of a multileaf collimator having a leaf width of 4 mm. The radiation dose can be escalated by as much as 30 Gy without increasing the damage sustained by critical organs. 3

To establish the tumor position for each treatment session, two imaging methods are used. One is abdominal ultrasonography, but the resulting images may lack the desired clarity, especially in patients who have strong abdominal muscles or empty bladders. Moreover, in patients who have undergone prostatectomy and are scheduled for irradiation of the prostate bed to control extracapsular extension, ultrasonography may have an error of as much as 1 cm in locating the target, Ma notes.

The other localization technique used is CT. Since April 2003, Fox Chase Cancer Center has been using a Siemens PRIMATOM. A 3D locator data set is acquired with the patient immobilized in the treatment position, and the target is aligned with the radiation beam using an automated algorithm developed by the radiation physics department. The result is an accuracy of within 3 mm. 4


Eradication of microscopic lung cancers requires a radiation dose of 50 to 60 Gy, and treatment of gross lesions (of 1 to 3 cm) requires an even higher dose: 75 Gy. 5 It is possible to deliver doses of this size or more (up to 80 Gy) using 3D conformal protocols while exposing normal structures to doses that are no higher (and that may, in fact, be lower) than those applied by delivery of 70 Gy using classic techniques. 5 How, though, can the tumor be kept in the beam while the patient breathes?

Stereotactic hypofractionated IMRT using the PRIMATOM is being explored for lung cancer in a clinical trial at Fox Chase Cancer Center. Instead of the conventional 30 or 35 fractions, patients receive four fractions of 10 Gy per fraction; because of the close tracking of tumor position, the biologically effective dose is approximately 70 Gy. “You cannot even think of doing this protocol without the CT-on-rails function of the PRIMATOM,” Ma says. “In planning the treatment, we locate the tumor with CT and measure its volume at full inspiration and expiration. During this examination, we ask patients to hold their breaths, but many cannot do this well; therefore, the tumor is not exactly where we want it, so we scan immobilized patients for 3 minutes using a 0.23-T open MRI scanner, acquiring an image every 2 seconds, and displaying the 90 resulting images in the cine mode. During the portion of this display when the patient is relaxed, we measure the extent of tumor movement. Before a treatment session, we put the patient on the couch, find the skin markers and the bony structures, and use the PRIMATOM CT-on-rails to find the virtual isocenter. We add an appropriate margin. Then we know how to aim the radiation beams to ensure that the tumor will be inside. In this way, we can deliver radiation very accurately.” The time required to set up a treatment session is only 5 to 7 minutes, in most cases.

An alternative to this method is respiratory gating, but Ma points out that it has two significant drawbacks. “Treatment with gating takes four to eight times longer; also, it is not suitable for all patients because their breathing problems make it impossible to guarantee that they will hold their breaths at the right points in inspiration and expiration.” The method being used at Fox Chase is at least as accurate in focusing the radiation beam, Ma adds.

Accumulation of patients for the clinical trial of the Fox Chase protocol is going slowly. “In recent months, we have been treating fewer lung cancer patients,” Ma reports. “What we (and others) are finding is that when patients are staged with contemporary CT scanners or positron-emission tomography, many who would have been judged suitable for radiation, according to the staging methods of the past, are now found to be too full of tumor to be candidates. For patients who are suitable, howevernamely those with a primary tumor that is not enormous, or with no more than three positive lymph nodesyou can achieve a local control rate of 70% to 80% with conformal radiation therapy or IMRT. This is a considerable improvement over the traditional rate of 30% to 40%.”


Both prostate and lung cancers are common, and debate continues over the best approach to their treatment. Research such as that undertaken at Fox Chase ensures that the maximum achievable benefit from radiation will be obtained.

Judith Gunn Bronson, MS, is a contributing writer for Decisions in Axis Imaging News.


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