Intraoperative Radiotherapy (IORT)

23.1

Introduction

The goal of intraoperative radiotherapy (IORT) is to deliver a single high dose of radiation at the time of surgery to enhance tumor control. IORT is typically useful in cases where a complete surgical resection will be difficult. For example, a locally invasive tumor might surround a nerve or blood vessel that cannot be resected, or a tumor may invade into a bone that cannot be fully cut away. In such cases, irradiation of the tumor site during surgery may play a role in controlling disease. IORT also has a role in cases in which previous external beam radiotherapy (EBRT) has been delivered and critical structures have already reached tolerance doses. There are advantages to irradiating in the intraoperative setting, among them the ability to directly visualize the tumor bed and the ability to directly shield or move sensitive structures out of the treatment field. Further clinical background can be found in the textbook Intraoperative Irradiation .

Support for the use of IORT comes mainly from single-institution studies; large randomized trials have been difficult to conduct. In the 1990s, for example, the Radiation Therapy Oncology Group (RTOG) began a phase III trial of IORT for pancreas and colorectal cancer but could not complete enrollment, and the IORT committee was subsequently disbanded. Nevertheless, there are numerous institutional studies and also pooled retrospective studies from Europe that support IORT. Some applications include colorectal cancer (locally advanced or unresectable for curative intent), pancreas and gastric cancer (where there is residual disease after resection), sarcomas of the abdomen or pelvis, breast cancers, and gynecological cancers that are locally recurrent.

An important disease site for IORT is breast cancer. IORT is one way of providing accelerated partial breast irradiation (APBI). The rationale for this treatment is to provide local control following breast conserving surgery since the site of recurrence is often the lumpectomy cavity. Recently, 5-year outcomes data were reported from the TARGIT-A trial, a large international randomized control trial that compares adjuvant whole breast EBRT to IORT. The 5-year local recurrence rates in the IORT-only arm were not statistically different from the EBRT arm, and there were fewer non-cancer deaths (e.g., related to cardiovascular disease). The authors conclude that IORT has a role in select breast cancer patients. IORT has also been used in breast cancer as a replacement for the boost portion of the course of treatment. One theory used to explain the positive results is that the sterilization of the wound fluid during surgery with radiation helps to prevent residual tumor cell growth.

In many situations outside of breast cancer IORT is used in combination with EBRT, with EBRT often being delivered prior to surgery. In this setting, typical IORT doses are:

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  7.5 to 10 Gy for negative or close margins

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  10 to 12.5 Gy for positive margins

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  15 to 20 Gy for gross residual disease or tumor that is unresectable

The margin status can be determined intraoperatively via frozen tissue pathology. In patients with recurrent disease who have received previous irradiation, it may not be safe to deliver high doses of EBRT, and so higher doses of IORT (15 to 20 Gy) may be delivered in order to compensate. The dose limiting structures depend on the site. In the pelvis, for example, the dose of IORT that can be safely delivered is limited by peripheral neuropathy and urethral stenosis. Surgical anastomoses are another at-risk structure. In many cases (roughly a half to a third of cases at some institutions), surgeries that begin as possible IORT candidates end up not being candidates for IORT because of the operative results.

23.2