High-Dose-Rate Intraoperative Radiation Therapy For Colorectal Cancer

Introduction

The efforts of radiation oncologists have long been thwarted by the therapeutic ratio. This ratio, which is expressed as the required dose to eradicate tumor divided by the tolerance dose of the surrounding normal tissues, often dictates the potential for tumor control with radiation therapy. When the required radiation dose exceeds the tolerance dose of the surrounding normal tissues, it becomes either difficult or impossible to control the tumor using conventional radiation therapy techniques. Such cancers as advanced pelvic tumors, abdominal and retroperitoneal tumors, liver tumors, certain pediatric tumors, and selected thoracic tumors frequently pose this therapeutic dilemma.

Over the years, radiation oncologists have developed numerous novel strategies to overcome the constraints of the therapeutic ratio and to increase the biologic effectiveness of radiation. These include radiation sensitizers, radiation protectors, brachytherapy, intra-operative radiation therapy (IORT), three-dimensional conformal external-beam irradiation, heavy-charged-particle irradiation, and various combinations of these techniques.

At Memorial Sloan-Kettering Cancer Center, we have developed a new program for intraoperative radiation therapy: high-dose-rate intraoperative radiation therapy (HDR-IORT), that attempts to combine the technical and dosimetric advantages of brachytherapy with the conceptual and logistic advantages of intraoperative electron-beam irradiation. The entire procedure is performed in a specially designed operating room. Thus, no intraoperative patient transportation is required.

For intraoperative radiation therapy delivery, we use an HDR remote afterloader, a device that advances a cable-mounted radioactive (iridium-192) source out of its shield into proximity with the tissue to be treated. The machine permits stopping the source for prescribed "dwell" times at regularly spaced positions in one or more catheters. This equipment is far less expensive than a linear accelerator, allowing the treatment to be given in a more cost-effective manner. Because the remote after- loader is portable, it can also be utilized for other procedures in the outpatient facility when it is not needed for intraoperative cases. This further enhances the cost effectiveness of the program.

Advantages and Limitations of Novel Strategies

Conventional Brachytherapy

Brachytherapy involves the placement of interstitial or intracavitary sources of radioactive material either into or against the desired target region. This permits high doses of radiation to be successfully and safely delivered to tumors, with acceptable toxicity to the surrounding normal structures. For this reason, brachytherapy has become a standard part of the sophisticated management of a wide variety of tumors, such as cancers of the oral cavity, oropharynx, nasopharynx, rectum, cervix, vagina, endometrium, prostate, brain, and eye and soft-tissue sarcoma.

Conventional brachytherapy is not always feasible, however. Advanced tumors of the pelvis or retroperitoneum require a large surface area to be irradiated after appropriate tumor resection. Interstitial techniques are often suboptimal in these anatomic regions, as they fail to cover the complex surfaces adequately with permanent or temporary implants. Catheter movement, risk of infection related to indwelling catheters, risk that normal tissues, such as the large and small bowel, will fall in close proximity to the implanted isotopes (increasing complications), and suboptimal implant geometry are all potential obstacles to adequate conventional brachytherapy.

Intraoperative External-Beam Radiation Therapy

Intraoperative external-beam irradiation has been explored for most of this decade in an attempt to improve the therapeutic ratio [1-3]. The concept on which this technique is based is quite simple. During an operation, the normal organs are physically moved out of the pathway of the radiation beam. A large, single fraction of radiation is directed onto the target surface during the operative procedure, with the normal tissues physically distanced and protected from the beam.

Although conceptually attractive, intraoperative external-beam irradiation also has several limitations:

1) The most common technique for administering this treatment, a linear accelerator, is quite expensive to install in a dedicated operating room. This expense has seriously limited the number of medical centers in this country that use this form of therapy.

Electron-beam irradiation can also be administered intraoperatively by transporting the patient from the main operating room to the radiation therapy facility. Afterward, the patient is either closed in the radiation therapy facility or transported back to the main operating room. There are obvious safety and logistic concerns about subjecting anesthetized patients to this process. It is also quite disruptive to the outpatient radiation therapy schedule.

2) It can be difficult to target complex surfaces, particularly in the pelvis, retroperitoneum, or chest, with available electron cones. Although the use of beveled cones enhances the capability to treat most anatomic surfaces, in many cases effective intraoperative orientation can prove quite awkward with the available or appropriate electron cones.

3) Available electron cones have size limitations. When a large surface requires treatment, it becomes necessary to use abutting electron fields. This introduces the potential both for underdosage and for overdosage at the junction of these fields [4]. Because relatively large fractions are delivered (1,000 to 2,000 cGy), the dose in an overlapped region can be substantial, increasing the risk of toxicity.

4) The electron beam delivers a relatively homogeneous dosimetry. Although not inherently disadvantageous, homogeneous dosimetry does not allow for dose intensification within the treatment volume that can be accomplished with brachytherapy.

All these issues notwithstanding, selected institutions have had substantial success using the intraoperative electron beam [1-3].

High-Dose-Rate Intraoperative Radiation

At Memorial Sloan-Kettering Cancer Center, we have developed a new program for intraoperative radiation therapy, high-dose-rate intraoperative radiation therapy (HDR-IORT), that attempts to combine the technical and dosimetric advantages of brachytherapy with the conceptual and logistic advantages of intraoperative electron-beam irradiation. The entire procedure is performed in a specially designed OR. Thus, no intraoperative patient transportation is required.

For radiation therapy delivery, we use an HDR remote afterloader. This equipment is far less expensive than a linear accelerator, allowing the treatment to be given in a more cost-effective manner. Because the remote afterloader is portable, it can also be utilized for other procedures in the outpatient facility when it is not needed for intraoperative cases. This further enhances the cost effectiveness of the program.

We have developed an applicator system that employs flexible, intraoperative applicators of various sizes designed to contour to any surface within the body (Figure 1). These applicators are connected to the HDR remote afterloader using customized source guide tubes. With this applicator system, a large, single fraction of radiation therapy can be delivered to any tumor bed during the surgical procedure.

Our new facility opened in November 1992. In the following sections, we will describe the treatment facility, surgical procedure, and HDR-IORT equipment and technique. We will also outline our preliminary results using HDR-IORT in patients with locally advanced or recurrent colorectal cancer-the predominant area of investigation to date. Results of treatment in other tumors under study, including retroperitoneal sarcoma, selected pediatric tumors, advanced or recurrent gynecologic malignancies, and malignant pleural mesothelioma, will not be discussed.

Treatment Facility

As mentioned above, all HDR-IORT procedures take place in an operating room located in the Brachytherapy Suite in the Department of Radiation Oncology. This facility was designed and constructed under the auspices of a multidisciplinary group of radiation oncologists, surgical oncologists, anesthesiologists, nurses, physicists, and hospital administration personnel. The operating room is a full-service facility, allowing for the performance of all major operative procedures, and has all of the necessary support services of the main operating room. It is fully shielded for the delivery of radiation therapy.

During the actual radiation therapy delivery, all personnel obviously must leave the room, and thus, the anesthetized patient remains alone in the operating room for an extended period. Our facility has a remote-control station with a duplicate set of monitors immediately outside of the operating room in an area where the radiation oncologist, surgeon, and operating nurse can remain gowned and gloved. This station allows for identical monitoring of the patient during the delivery of radiation therapy as is possible in the operating room.

Video cameras, installed in several strategic locations in the operating room, can be controlled by the anesthesiologist, who sits at the monitoring station just outside the operating room. They provide complete, consistent visual backup to the online monitoring of the patient's vital signs, ECG tracing, arterial or central line, endotracheal tube, and face. A remote, computer-controlled software system regulates the rate of infusion of two intravenous fluids, three syringes with drugs, and blood products.

Using a separate video system, the radiation oncologist and surgeon can remain scrubbed and view the operative field and brachytherapy application. Any malfunction of the remote afterloader, movement of the applicator or disruption of the source guide tubing, or obvious bleeding would be immediately observed on the color video monitor. For any reason, whether related to anesthesia, radiation, or surgery, the treatment can be instantaneously interrupted by the press of a button. When the button is pressed, the radioactive source is immediately retracted, the door to the room opens, and the patient's needs can be handled literally within seconds. Once these needs have been satisfied, radiation treatment can be resumed.

Patients who undergo major operations and intraoperative radiation procedures recover in the main recovery room. They are transported from the Brachytherapy Suite to the recovery room on a life-support gurney that allows for full monitoring and resuscitation of the patient. Total transport time is 5 to 8 minutes.