ORLANDO--A new high dose rate/intraoperative radiation therapy (HDR-IORT) delivery system utilizing the Harrison, Anderson, Mick (HAM) applicator is proving effective in treating primary unresectable and locally advanced, recurrent rectal cancer.
The HAM applicator is combined with an HDR remote afterloader for use in a special shielded operating room (see figure). One of its inventors, Louis B. Harrison, MD, presented the results of a 2-year study of HDR-IORT with the new applicator at the American Society for Therapeutic Radiology and Oncology (ASTRO) annual meeting.
The advantage of IORT is that normal organs can be moved out of the way and the radiation focused on the exact area to be treated, thus providing greater accuracy and allowing for dose escalation. However, most medical centers do not have an operating room equipped with a dedicated linear accelerator, and moving a patient intraoperatively is not the optimum choice in most situations, Dr. Harrison said.
"We developed the concept of bringing this machine into the operating room, and we developed a place to do that," he said, referring to the special shielded brachytherapy suite that was set up at Memorial Sloan-Kettering to deliver HDR-IORT to rectal cancer patients in the trial.
The study addressed the problems posed by primary unresectable rectal cancer patients, who face a 40% recurrence rate (even when use of preoperative radiation and chemotherapy allows conversion to resectable disease), and by those with recurrent disease, many of whom have had prior radiation therapy so that external beam radiation therapy is not an option.
"Intraoperative radiation therapy thus becomes an interesting avenue of investigation as a means of dose escalation in the primary unresectable group and of retreatment in the recurrent group," said Dr. Harrison, chairman of the Department of Radiation Oncology, Beth Israel Health Care System, New York.
The Study Patients
Of 112 rectal cancer patients who were explored in the operating room, 68 were considered eligible for HDR-IORT treatment--38 males and 30 females. Their ages ranged from 30 to 80 years with a median of 61. Twenty-two of the patients had primary unresectable disease and 46 had recurrent disease. Of the recurrent group, 42 were evaluable at the time of study.
The primary unresectable group received preoperative chemotherapy and external beam radiation therapy to convert their condition to resectable disease. 	In the recurrent group, 12 had not received radiation therapy previously, and they received a regimen similar to that of the primary unresectable group.
Both groups of patients underwent surgery in the shielded brachytherapy operating room.
In this protocol, after resection, the surgeon and the radiation oncologist map out the tumor bed. Normal tissue is displaced from the treatment field to prepare for the administration of HDR-IORT.
The HAM applicator is connected to an HDR remote afterloader by customized tubes and positioned on the surface of the target area, generally including the presacral region and pelvic side walls, Dr. Harrison said. It is kept in place by packing or silk sutures, and the prescribed dose is delivered to a tissue depth of 5 mL from the surface of the applicator.
The applicator consists of a flat pad with radiation source tubes, or channels, running through it spaced 1 cm apart. One of the advantages of the HAM applicator, Dr. Harrison said, is that it comes in various sizes and can be cut down in size to fit the target area. In addition, not all of the channels need to be loaded, which makes treating specific areas very easy, he said. With traditional IORT, the electron cones often do not conform well to the area to be treated, he added.
While the intraoperative procedure added to the operation time, it did not add to the overall hospital stay, Dr. Harrison said. "We believe that HDR-IORT is feasible and applicable to all the situations we encountered," he said.
Study Results
In the patients with primary unre-sectable disease, the actuarial 2-year local control rate was 81%. Margin status was a critical predictor of local control; for patients with negative margins, local control was 92% vs 38% for those with positive margins (P = .002).
In recurrent disease patients, the actuarial 2-year local control rate was 63%. Those with negative margins achieved a local control rate of 82% vs 19% for those with positive margins (P = .02).
Actuarial 2-year disease-free survival was 77% in the patients with primary unresectable disease who had negative margins vs 38% for those with positive margins. Patients with recurrent disease with negative margins had a 2-year disease-free rate of 71% vs 0% for those with positive margins.
"Within the common cohort of patients for whom IORT is useful, especially colorectal cancer patients, the preliminary data at 2 years look very encouraging for both patients with recurrent rectal cancer and those with locally advanced primary cancer," Dr. Harrison said.
He added that the procedure is cost effective, making it especially suitable in the era of managed care. "This approach to IORT is an example of how you can make a treatment better and more cost effective at the same time," Dr. Harrison said.
The HAM applicator has been FDA approved and is commercially available. It is named after its developers--Dr. Harrison; Lowell Anderson, MD, chief of Brachytherapy Physics, Memorial Sloan-Kettering; and Felix Mick, president of Mick Radionuclear Instruments, New York.
