Conformal Method Of Neutron/Proton Radiation Promising

September 1, 1995

SEATTLE--A mixture of neutron radiation with conventional photon radiation, using a custom tailored pelvic template for each patient, appears to provide more effective therapy for prostate cancer than photon radiation alone (eg, external beam or I-125), while reducing the complications caused by neutron radiation alone, said Jeffrey Forman, MD, of Wayne State University, Detroit.

SEATTLE--A mixture of neutron radiation with conventional photonradiation, using a custom tailored pelvic template for each patient,appears to provide more effective therapy for prostate cancerthan photon radiation alone (eg, external beam or I-125), whilereducing the complications caused by neutron radiation alone,said Jeffrey Forman, MD, of Wayne State University, Detroit.

Dr. Forman discussed the technique, called three-dimensional conformalfast neutron irradiation, at the Pacific Northwest Cancer FoundationMeeting on Transperineal Brachytherapy for Early Stage ProstateCancer.

He has been studying neutron radiation for prostate cancer treatmentbecause, he said, "radiobiologic principles would suggestthat a slowly proliferating tumor, like prostate cancer, wouldbe advantageously treated by high LET (linear energy transfer)radiation."

This has indeed proved to be the case, with 70% vs 58% local controlof the tumor, and 53% vs 29% 10-year survival in favor of neutron/photonirradiation vs conventional external photon beam therapy alone(RTOG 77-04).

However, pelvic neutron irradiation has a high rate of complications,including rectal toxicity, bladder complications, and hip stiffness,progressing to pelvic bone necrosis in some patients. To addressthis problem, researchers have applied 3D conformal irradiationtechniques to neutron therapy (see below).

In this technique, the neutron beams are directed more preciselyto the confined area of the tumor, thus sparing adjacent radiosensitivestructures such as the bladder and rectal tissue.

Wayne State Study

In a series of phase II studies at Wayne State University, patientswere given 3D conformal radiation therapy in an alternating scheduleof neutrons and photons over the course of 5 weeks. Dr. Formangave a preliminary report of the first 151 patients.

By 18 months post-treatment, he said, 95% of the patients withlocalized tumors (all of whom were given a lower radiation dose)were predicted to have a PSA level of less than 4 ng/mL; 93% ofthe patients with locally advanced disease, who were given a higherdose, were predicted to reach 4 ng/mL.

Biopsies in the first 73 patients found that 85% were negativefor malignant cells at 12 to 18 months post-treatment, regardlessof clinical stage, Gleason score, pretreatment PSA volume, orneutron dose. These results were better than those for photonirradiation alone, he said. Up to 50% of biopsies are positivefollowing standard photon irradiation.

In addition, Dr. Forman said that the rates of chronic gastrointestinaland genitourinary morbidity in the low neutron dose arms werenot statistically different from those for 3D conformal photonirradiation alone, with 35% impotence and only 4% incontinence.

'Formidable Challenge'

Dr. Forman concluded that "improving the effectiveness ofradiation therapy for locally advanced prostate cancer, whilereducing the morbidity from treatment complications, remains aformidable challenge."

He asserted that, following photon radiation alone, 75% of patientshave clinical, radiographic, or biochemical evidence of failurewithin 3 years of treatment. In addition, he said, improvementsin disease-free survival with photon therapy alone have not yettranslated into an overall survival advantage.

On the other hand, there appears to be a significant improvementin both local control of the tumor and in survival for those patientstreated with the addition of neutrons. This suggests that photonirradiation alone may fail to fully eliminate locally advancedprostate cancer.

Unfortunately, Dr. Forman said, the major drawback to expandingthe use of this method is that only two facilities in the UnitedStates are currently capable of delivering conformal, isocentric,fully rotational, shaped neutron irradiation. Their capacity forpatients (approximately 300 per year) precludes this as a viableoption for most patients, he said.

The cost of developing new conformal neutron facilities is currentlyprohibitive, and significant expansion of the number of neutrontreatment facilities seems unlikely in the near future, he said.Dr. Forman suggested that using higher doses of photon irradiationand/or utilizing the concept of hyperfractionation might be aviable alternative to neutron therapy at this time.

3D Conformal Neutron Radiation

In the 3D conformal method, the neutrons are produced by a superconductingcyclotron that can rotate around the patient a full 360o. Thecyclotron contains a "multirod collimating system,"which pro-duces irregularly shaped and partial transmission fieldsby means of 12,000 independently moving tung-sten rods.

Two molded Styrofoam templates are custom designed to fit eachpatient, according to the

parameters of the prostate and the individual tumor to be irradiated,and the tungsten rods are moved pneumatically to conform to theshape of the templates.