Intraoperative Electron Radiation Therapy - History of IORT and IOERT

History of IORT and IOERT

As early as 1905 Spanish doctors and then 1915 German doctors used IORT (IntraOperative RadioTherapy ), in an attempt to eradicate residual tumor left behind after surgical resection. Radiation equipment of that era could only deliver low energy x-rays, which had relatively poor penetration. With equipment of that time, high doses of radiation could not be applied externally without doing unacceptable damage to normal tissues. IORT treatment with low energy or "orthovoltage" x-rays gained advocates throughout the 1930s and 40's, but the results were inconsistent. The x-rays penetrated beyond the tumor bed to the normal tissues beneath, had poor dose distributions and took a relatively long time to administer. The technique was largely abandoned in the late 1950s with the advent of megavoltage radiation equipment, which enabled the delivery of more penetrating external radiation.

The modern era of IOERT began in Japan at Kyoto University in 1965. These patients were treated with electrons generated by a betatron. Compared with other forms of IntraOperative Radiation Therapy (IORT) such as orthovoltage x-ray beams, electron beams improved IOERT dose distributions, limited penetration beyond the tumor and delivered the required dose much more rapidly. Normal tissue beneath the tumor bed can be protected as well as shielded if required and the treatment takes only a few minutes to deliver. These advantages make electrons the preferred radiation for IOERT. The technique gained favor in Japan. Other Japanese hospitals initiated IOERT using electron beams, principally, generated from linear accelerators. At most institutions, patients were operated on in the OR and transported to the radiation facility for treatment.

With the Japanese IOERT technique, relatively large single doses of radiation were administered during surgery, and most patients received no follow-up external radiation treatment. Even though this reduced the overall dose that could potentially be delivered to the tumor site, the early Japanese results were impressive, particularly for gastric cancer.

The Japanese experience was encouraging enough for several U.S. centers to institute IOERT programs. The first one began at Howard University in 1976 and followed the Japanese protocol of large, single dose. Howard built a standard radiation therapy facility with one room that could also be used as an OR as well as for conventional treatment. Because the radiation equipment was also used for conventional therapy, the competition for the machine limited the number of patients that could be scheduled for IOERT.

In 1978 Massachusetts General Hospital started an IORT program . The MGH doctors opted not to remodel a radiation therapy room for surgery. They scheduled one of their conventional therapy rooms for IOERT one afternoon a week, performed surgery in the OR and transported the patient to the radiation therapy room during surgery. This more "practical" approach used the radiation equipment more efficiently and required no additional capital outlay. However, about 30-50% of the patients planned for IOERT are found not be suitable candidates for IORT at the time of surgery, principally because the disease has spread to adjacent organs. Thus, if the radiation equipment can be used only occasionally, as is the case in busy radiotherapy departments, this method of IOERT, surgery followed by transport to the radiation therapy facility, severely limits the number of patients that can be treated. The risks and complexities of moving a patient during surgery remain as well.A particular method to facilitate surgery followed by transport to the radiotherapy treatment room, started in Italy in 1985 (first IOERT in Italy). Another French method was named Lyon intra-operative device... About the terms to describe the devices used in the time, to remember: : applicator; applicator guide; cones, cylinders,applicators with other complex geometrical shapes; metallic cones, beveled cones, cones of different sizes; perspex cylinders, beveled cylinders, cylinders of different sizes ;docking procedure and systems in process of docking ; hard-docking, soft docking, non-docking applicator systems; guide systems for alignment ; view systems of the treatment field;video monitoring of patients and his requested anesthetic parameters, from outside the Operating Room . In the MGH IOERT program, conventional fractionated external beam irradiation was added to the IOERT dose, either prior to or subsequent to the surgery.

In 1979 the National Cancer Institute (NCI) started an IOERT program... Their approach combined maximal surgical resection and IOERT, and in most cases did not include conventional external beam therapy as part of the treatment. Because the NCI protocol relied on IOERT radiation alone, the IOERT fields were often very large, sometimes requiring two or three adjacent and overlapping fields to cover the tumor site. While the NCI results for these very large tumors were not encouraging, they showed that even the combination of aggressive surgery and large IOERT fields had acceptable toxicity. Furthermore, they introduced several technical innovations to IOERT, including the use of television for simultaneous perioscopic viewing of the tumor by the surgical team.

In 1981 the Mayo Clinic tried yet another arrangement. They built an operating room (OR) adjacent to the radiation therapy department. Potential IOERT patients underwent surgery in the regular OR suite. If they were found to be candidates for IOERT, a second surgical procedure was scheduled in the OR adjacent to radiation facility. By scheduling only those patients known to be suitable for IOERT, they made more efficient use of their radiation therapy machine, but at the cost of subjecting patients to a second surgery. Subsequently, Mayo Clinic remodeled an OR and installed a conventional radiation therapy machine including its required massive shield walls, and the clinic now routinely treats over 100 IORT patients per year. After 1985 Siemens Medical Systems offered a specialized linac for IOERT. It was designed to be used in the OR, but it weighed more than 8 tons and required about 100 tons of shielding. This proved to be too expensive an approach for the medical community, and only seven of these specialized units were ever sold.

Dedicating an OR to IOERT increases the number of patients that can be treated and eliminates the risks of double surgeries and moving a patient during surgery. It also does away with the complex logistics involved in moving patients form OR to therapy room and back to OR. However this solution has its own disadvantages: Remodeling an OR and purchasing an accelerator is expensive. Moreover, IORT is restricted to that one, specialized OR. Even so, the Mayo Clinic model demonstrated that when therapy equipment is located within an OR, the number of IOERT procedures will increase.

In 1982 the Joint Center for Radiation Therapy (JCRT). at Harvard Medical School attempted to reduce the cost of performing IORT in an OR by using orthovoltage x-rays to provide the intraoperative dose, similar the approach used in Germany in 1915. But this is less than ideal. While the shielding costs and the cost and weight of the equipment compare favorably with conventional electron accelerators, dose distributions are inferior, treatment times are longer, and bones receive a higher radiation dose.For these reasons, the centers have rejected IO Orthovoltage (X-rays) RT. In addition, these orthovoltage machines (of 300 kvp) are not designed to be mobile. In 1998 was designed at the University College London a technique named TARGIT (TARGeted Intra-operative radioTherapy) for treatment of the tumour bed after wide local excision (lumpectomy) of breast cancer,using a miniature and mobile X-ray source which emits low energy X-ray radiation (max. 50 kV) in isotropic distribution. In breast cancer is also used (IO)-Brachytherapy with MammoSite. Despite the logistical and cost considerations involved in implementing IORT, interest in this treatment technique is growing ( also tanks to development of Linac for IOERT by Factories)..... Over 70 centers in Japan and the U.S. and more than 200 other centers in over 27 countries worldwide perform IORT.After 1987- 1997 IORT meetings . .., in 1998, a new professional society, the International Society of IORT (ISIORT) was formed to foster the scientific and clinical development of IORT including IOERT. The ISIORT has over 1000 members from more than 20 countries and meets every two years. The first meeting of the ISIORT was held in September 1998 in Pamplona Spain, at the University of Navarre, one of the world's most famous IOERT centers. The second meeting was held in October 2000 in Boston. Significantly, the Boston Meeting established an IOERT Protocol Study Group.The references above cited about clinical applications and results of IOERT have evidenced experiences and studies that have suggested a role of IOERT in management of solid tumors e.g. pancreatic cancer, locally advanced and recurrent rectal cancer, breast tumors, sarcomas, and selected gynaecologic and genitourinary malignancies,neuroblastoma and brain tumors. NB : October 14–16, 2010, 6th International Conference of the International Society of Intraoperative Radiation Therapy (ISIORT) in Scottsdale, Arizona .