Donald A. Goer

This past decade has seen an explosion in new technology for external beam radiation therapy treatment, including intensity modulated radiation therapy, tomotherapy, image guided radiation therapy, respiratory gating proton therapy and more.  The goal of all of these new technologies is to better direct radiation to a tumor or tissue at risk and to safely escalate the dose to affect better cures. Locally advanced cancers are typically hypoxic or oxygen deprived and require significantly higher does of radiation, hence the interest in pursuing dose escalation techniques.  These external beam radiation therapy technologies have been widely adopted, even though they are still new and evolving and have not to date demonstrated improvement in either local control or cure.  In some cases, they have reduced normal tissue toxicity. 

In contrast, a specialized radiation treatment exists that has had more than a quarter century of clinical results and has proven to be efficacious, but it is not yet widely available.  This treatment is called intraoperative electron radiation therapy. This therapy is the application of electron beam radiation directly to a tumor or tumor bed during surgery. In it, most of the tumor is removed through conventional surgical techniques. Radiation is then directly applied to the area immediately surrounding the tumor, while still exposed during surgery, with the surrounding normal tissue retracted out of the radiation beam. This direct application of radiation to the tumor site increases the effective dose to the tumor.

Intraoperative electron radiation therapy has already demonstrated improved local control and, in many cases, increased survival for a number of disease sites. It is safely used to escalate the dose for advanced disease because normal tissue is displaced from the path of the radiation beam. The therapy can also replace a portion of the adjuvant external beam radiation therapy by substituting a single dose at the time of surgery. When used as a ''boost dose,'' it replaces two to three weeks of conventional fractionated radiotherapy treatments, with the added benefit of avoiding radiation to normal tissue that would otherwise surround the treatment area if external beam radiation therapy alone were used. Finally, because the therapy is delivered at the time of surgery, when microscopic residual tumor cells are most vulnerable, any subsequent adjuvant therapy will benefit because even a modest intraoperative electron radiation therapy dose is likely to result in one or two log-cell kills.

The widespread adoption of intraoperative electron radiation therapy as a routine adjuvant therapy has been limited by the difficulty of delivering it using conventional electron accelerator technology. Patients were either transported from or to the radiation department in the middle of a surgical procedure to receive their intraoperative electron radiation therapy, or costly shielded bunkers in the operating theater were constructed to house a conventional linear accelerator. The complex logistics of patient transportation and the cost of constructing a shielded bunker in the operating theater have limited the availability of this therapy.

Now, however, new mobile electron linear accelerator technologies allow the medical device to be used in almost any unmodified hospital operating room, thereby facilitating the delivery of intraoperative electron radiation therapy. Mobile intraoperative electron radiation therapy technology has been embraced in many countries in Europe and is gradually gaining interest in the United States as more clinical results are published and the availability of mobile intraoperative electron radiation therapy technology becomes more widely known. Some of the recent results are encouraging in both the treatment of advanced and recurrent disease where hypoxia may be an issue, as well as in earlier stage disease where intraoperative electron radiation therapy can provide effective eradication of microscopic residual disease left in the surgical bed, making the subsequent adjuvant treatment that much more effective.

Intraoperative electron radiation therapy is generally most effective as a precision boost. Healthy tissue that might normally surround the target structure when delivering external beam boost or external beam dose escalation is displaced and/or protected during surgery, which significantly enhances the therapeutic ratio. Furthermore, the therapy boosts may have some biological advantages over external beam boosts or external beam dose escalations given many weeks post-surgery.  Since it is delivered at the time of surgery, when residual tumor cells from the surgery are most vulnerable, a tumorcidal dose is delivered to the tumor bed before tumor cells have the opportunity to reimplant, proliferate or migrate. This lowers the tumor burden for any adjuvant external beam radiation therapy radiation or chemotherapy treatment. 

The large single dose of intraoperative electron radiation therapy is equivalent to two to three weeks of conventionally fractionated external beam radiation therapy, and the large single dose may in addition overcome hypoxia of the residual tumor cells since the dose is two to three times greater than the equivalent external beam radiation therapy dose.  Because the intraoperative electron radiation therapy dose allows for a potential reduction in the adjuvant external beam radiation therapy dose, adding it is also consistent with the overall goal of reducing the treatment time to deliver the total dose needed for effective treatment.

Finally, intraoperative electron radiation therapy is given in conjunction with radiation sensitizers, which enhances the effect of the therapy on tumor cells.  In fact, single dose applications may be the best application for radiation sensitizers as the pharmcokinetics can be measured to ensure that the organ of interest has absorbed sufficient drug for the sensitization to be effective. As well, because the sensitizer is applied only once, the toxicity associated with these drugs is more manageable. 

Patients with locally advanced or recurrent cancers generally have a grim prognosis for survival even if they receive the best traditional treatment available. Mobile intraoperative electron radiation therapy offers new hope for cancer patients. As this advanced medical technology continues to gain worldwide acceptance patients are able to benefit from better local control, shorter treatment cycles and fewer side effects. Doctors and patients alike should educate themselves on intraoperative electron radiation therapy and the different ways in which in can be administered. New treatment applications are being developed every day, as radiation and surgical oncologists around the globe continue to uncover the benefits of this therapy.

Donald A. Goer is chief scientist and co-founder of Intraop Medical Inc., which develops, manufactures, markets the Mobetron, a mobile electron beam system designed for intraoperative electron radiation therapy treatment of cancer, coronary/vascular restenosis and other medical applications.