Intraoperative radiotherapy in the treatment of gastrointestinal malignancies

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Intraoperative radiotherapy is a method of delivering one high dose of radiation to a specific area during a surgical procedure.

External beam radiation is the conventional therapy method, but intraoperative radiotherapy presents benefits over the conventional method that include the ability to limit toxicity by shielding or removing surrounding organs. 

In order to improve local control in patients with gastrointestinal tumors that are often associated with high rates of local failure, intraoperative radiotherapy has been studied as either a single treatment or an aspect of treatment within a combine modality approach.

The data related to pancreatic, rectal, and gastric cancers indicate that adding intraoperative radiotherapy to treatment displays a consistent improvement in local control. The data is inconsistent, however, in regards to the effect of intraoperative radiotherapy on survival.

Researchers also indicate that the mobility of modern intraoperative radiotherapy units will likely effect the use of this treatment method.

Continuing prospective evaluation will be necessary to determine efficacy, particularly as competing technology for dose escalation such as intensity modulated radiation therapy  and stereotactic body radiation therapy become more prevalent.

Also, as external beam radiation therapy continues to develop and improve in its technique, it will be necessary to continue to evaluate intraoperative radiotherapy in prospective trials. 

IORT has emerged as a technique to deliver a single high dose of radiation to a target volume at the time of an operation.
IORT has emerged as a technique to deliver a single high dose of radiation to a target volume at the time of an operation.

Abstract: Intraoperative radiotherapy (IORT) is a technique that allows delivery of a single high dose of radiation to a target volume during surgery. Where conventional external beam radiation therapy (EBRT) is limited by the normal tissue tolerance of abdominal and pelvic organs, IORT has an advantage that surrounding organs can be shielded or moved.

This approach permits delivery of a biologically potent dose of radiation with minimal toxicity. Many gastrointestinal malignancies are characterized by high rates of local failure, thus IORT has been investigated as a means to improve local control either alone or as part of a combined modality approach.

In pancreatic, gastric and rectal cancers, available data suggest that the addition of IORT consistently improves local control. The effect on survival has been variable in these cancers with a significant competing risk of distant failure. As EBRT techniques improve, the utility of IORT will need to be further validated in prospective trials.

Keywords: Intraoperative radiotherapy (IORT); radiotherapy; gastrointestinal malignancies

Submitted Apr 02, 2014. Accepted for publication Apr 25, 2014.

doi: 10.3978/j.issn.2218-676X.2014.04.05 

The treatment of gastrointestinal malignancies with external beam radiation therapy (EBRT) is limited by the normal tissue tolerance of various abdominal and pelvic organs including stomach, bowel, liver and kidneys. Intraoperative radiotherapy (IORT) has emerged as a technique to deliver a single high dose of radiation to a target volume at the time of an operation. IORT is typically performed in combination with EBRT, chemotherapy and surgical resection.

The advantage of this technique is the delivery of a biologically potent dose of radiation with rapid dose fall off and the ability to move and shield nearby organs at risk for normal tissue complication.

Delivery of IORT in the abdomen and pelvis is achieved primarily by two techniques: intraoperative electron radiation therapy (IOERT) and high-dose rate brachytherapy (HDR-IORT). IOERT previously required transporting a patient from the operating room (OR) to the radiation oncology department or having an OR equipped with a linear accelerator.

More recently, mobile units have been developed to increase the versatility of this therapy. The delivery of electrons to a discrete area necessitates the use of a rigid applicator or cone, a requirement that can be technically challenging depending on the target area and patient position. Multiple electron energies are available which allows the desired depth of treatment to be modified.

HDR-IORT uses an iridium-192 source housed in a remote afterloading device. The iridium source has a 74-day half-life and must be replaced throughout the year. High energy photons (370 keV) are emitted, thus facilities using this technique require appropriate shielding. HDR-IORT is accomplished by the placement of a flexible applicator with multiple channels in the operative bed (Figure 1).

The radioactive source passes from the remote afterloading device through catheters into the channels of the applicator at pre-determined positions and dwell times. The short range of these photons limits this technique primarily to superficial/microscopic disease only (0.5 cm thickness).

In both IOERT and HDR-IORT, close consultation and collaboration with the surgeon and pathologist are critical in defining the target volume.

The feasibility, volume and IORT dose given depend on normal tissue tolerance, initially derived from canine models at the National Cancer Institute (NCI) and Colorado State University.

These studies have demonstrated that gastrointestinal mucosa is particularly radiosensitive, and IORT doses of 15-20 Gy can result in strictures, obstructions, ulceration or perforations1. While many organs can be mobilized away from the treatment area and/or shielded, this is not feasible for deep nerves in the lumbar and sacral region where IORT may result in peripheral neuropathy.

A trial by the NCI randomized patients with resectable retroperitoneal sarcomas to 50-55 Gy postoperative EBRT alone or 20 Gy IOERT followed by 35-40 Gy EBRT. Radiation-related peripheral neuropathy was seen in 9 of 15 patients in the IOERT arm2. Peripheral nerves are therefore a dose limiting structure, with a maximum tolerated dose of approximately 15 Gy based on the previously mentioned studies3,4.

IORT has been used in the treatment of numerous gastrointestinal malignancies, primarily in disease sites with high rates of local failure. The majority of published experience has been in stomach, pancreatic and rectal cancers.

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