Intraoperative electron radiation therapy is the application of electron radiation directly to the residual tumor or tumor bed during cancer surgery.Intraoperative Irradiation. Techniques and Results. by: L. L.Gunderson, C. G. Wilett, L. B. Harrison and F. A. Calvo.Springer-Verlag 1999.Calvo FA, et al, . Intraoperative radiation therapy. In: Perez CA, Brady LW, Halperin EC, Schmidt-Ullrich RK, eds. Principles and Practice of Radiation Oncology, Lippincott 2004; 4th Ed 428-56. Electron beams are useful for intraoperative radiation treatment because, depending on the electron energy, the dose falls off rapidly behind the target site, therefore sparing underlying healthy tissue.
IOERT has been called "precision radiotherapy," because the physician has direct visualization of the tumor and can exclude normal tissue from the field while protecting critical structures within the field and underlying the target volume. One advantage of IOERT is that it can be given at the time of surgery when microscopic residual tumor cells are most vulnerable to destruction. Also, IOERT is often used in combination with external beam radiotherapy (EBR) because it results in less integral doses and shorter treatment times.
Medical uses IOERT has a long history of clinical applications, with promising results, in the management of solid tumors (e.g., pancreatic cancer, locally advanced and recurrent rectal cancer, breast tumors, sarcomas, and selected gynaecologic and genitourinary malignancies, neuroblastomasSutton, Elizabeth J., Tong, Ricky T et al, "Decreased aortic growth and middle aortic syndrome in patients with neuroblastoma after radiation therapy." Pediatr Radiol;39(11):1194-1202.2009 and brain tumors.[October 14–16, 2010, 6th International Conference of the International Society of Intraoperative Radiation Therapy (ISIORT) in Scottsdale, Arizona (ISIORT) In virtually every tumor site, electron IORT improves local control, reducing the need for additional surgeries or interventions. The following is a list of disease sites currently treated by IOERT:
Breast cancer Since 1975, breast cancer rates have declined in the U.S., largely due to mammograms and the use of adjuvant treatments such as radiotherapy. Local recurrence rates are greatly reduced by postoperative radiotherapy, which translates into improved survival: Preventing four local recurrences can prevent one breast cancer death. In one of the largest published studies so far called (ELIOT),Veronesi U, Orecchia R, Patrick Maisonneuve p, et al. “Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial”.]“Lancet Oncol. “ 2013 Dec;14(13):1269-77. doi: 10.1016/S1470-2045(13)70497-2. Epub 2013 Nov 11. researchers found that after treating 574 patients with full-dose IOERT with 21 Gy, at a median follow-up of 20 months, there was an in-breast tumor recurrence rate of only 1.05%.Gunderson LL, Willett CG, Calvo FA, Harrison LB, eds. Intraoperative Irradiation: Techniques and Results. Second edition. New York: NY; Humana Press, 2011:189. Other studies show that IOERT provides acceptable results when treating breast cancer in low-risk patients. More research is needed for defining the optimal dose of IOERT, alone or in combination with EBRT, and for determining when it may be appropriate to use it as part of the treatment for higher risk patients.Maluta S1, Dall'Oglio S, Marciai N, et al. Accelerated partial breast irradiation using only intraoperative electron radiation therapy in early stage breast cancer. J Radiat Oncol Biol Phys. 2012 Oct 1;84(2):e145-52. doi: 10.1016/j.ijrobp.2012.03.013. Epub 2012 Apr 28.
Colorectal cancer Over the past 30 years, treatment of locally advanced colorectal cancer has evolved, particularly in the area of local control – stopping the spread of cancer from the tumor site. IOERT shows promising results. When combined with preoperative external beam irradiation plus chemotherapy and maximal surgical resection, it may be a successful component in the treatment of high-risk patients with locally advanced primary or locally recurrent cancers.Haddock MG1, Miller RC, Nelson H. Combined modality therapy including intraoperative electron irradiation for locally recurrent colorectal cancer. Int J Radiat Oncol Biol Phys. 2011 Jan 1;79(1):143-50. doi: 10.1016/j.ijrobp.2009.10.046. Epub 2010 Apr 13.
Gynecological cancer Studies suggest that electron IORT may play an important and useful role in the treatment of patients with locally advanced and recurrent gynecologic cancers, especially for patients with locally recurrent cancer after treatment for their primary lesion. Further research into radiation doses and how to best combine IOERT with other interventions will help to define the sequencing of treatment and the patients who would most benefit from receiving electron IORT, as part of the multimodality treatment of this disease.Barney BM, Petersen IA, Dowdy SC, Bakkum-Gamez JN, Klein KA, Haddock MG. “Intraoperative Electron Beam Radiotherapy (IOERT) in the management of locally advanced or recurrent cervical cancer. Radiat Oncol. 2013 Apr 8;8:80. doi: 10.1186/1748-717X-8-80.
Head and neck cancer Head and neck cancers are often difficult to treat and have a high rate of recurrence or metastasis. IOERT is an effective means of treating locally advanced or recurrent head and neck cancers. Furthermore, research shows that a boost given by IOERT reduces the ability for surviving tumor cells to replicate, creating extra time for healing of the surgical wound before EBRT is administered.Marucci L, Pichi B, Iaccarino G, et al. “Intraoperative radiation therapy as an “early boost” in locally advanced head and neck cancer: Preliminary results of a feasibility study” Head & Neck' 2008;30(6):701-708.Zeidan YH1, Shiue K, Weed D, Johnstone PA, et al, Intraoperative radiotherapy for parotid cancer: a single-institution experience. Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):1831-6. doi: 10.1016/j.ijrobp.2011.02.033. Epub 2011 Apr 20.
Pancreatic cancer In the U.S., pancreatic cancer is the fourth leading cause of cancer death, even though there has been a slight improvement in mortality rates in recent years. Although the optimal treatment plan remains debated, a combination of radiotherapy and chemotherapy is favored in the U.S.Gunderson LL, Willett CG, Calvo FA, Harrison LB, eds. Intraoperative Irradiation: Techniques and Results. Second edition. New York: NY; Humana Press, 2011:249. As part of a multimodality treatment, IOERT appears to reduce local recurrence when combined with EBRT, chemoradiation, and surgical resection.Cai S1, Hong TS, Goldberg SI, et al.Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010. Cancer. 2013 Dec 1;119(23):4196-204. doi: 10.1002/cncr.28329. Epub 2013 Sep 4.
Soft tissue sarcomas Soft tissue sarcomas can be effectively treated by electron IORT, which appears to be gaining acceptance as the current practice for sarcomas in combination with EBRT (preferably preoperative) and maximal resection. Used together, IOERT and EBRT appear to be improving local control, and this method is being refined so that it can effectively be used in combination with other interventions if indicated. In studies regarding the delivery of therapeutic radiation in the limb-sparing approach to extremity soft tissue sarcomas, electron IORT has been called ‘precision radiotherapy’ by some, because the treating physician has direct visualization of the tumor or surgical cavity and can manually exclude normal tissue from the field.Miller ED, Xu-Welliver M, Haglund KE. “The role of modern radiation therapy in the management of extremity sarcomas.” Journal of Surgical Oncology. 2015;111:599-603. . Accessed 2016-11-07.Tinkle CL, Weinberg V, Braunstein SE, et al. “Intraoperative Radiotherapy in the Management of Locally Recurrent Extremity Soft Tissue Sarcoma.” Sarcoma 2015 9;2015:913565. Epub 2015 Aug 9. . Accessed 2016-11-07.
History
SpanishComas C., Prio A. Irradiation roentgen intra-abdominale, après intervention chirurgicale dans un cas de cancer de l’uterus, Congres International d’Electrologie.Imprenta Francesca Badia, Barcelona, pp 5-14, 1907 and German doctors,Beck C.On external roentgen treatment of internal structures (eventration treatment). New York Medical Journal, Volumen LXXXIX No. 13: 621-622, 1909. in 1905 and 1915 respectively, used intraoperative radiation therapy (IORT) in an attempt to eradicate residual tumors left behind after surgical resection. However, radiation equipment in the early twentieth-century could only deliver low energy X-rays, which had relatively poor penetration; high doses of radiation could not be applied externally without doing unacceptable damage to normal tissues. IORT treatments with low energy or "orthovoltage" X-rays gained advocates throughout the 1930s and 1940s, 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.Abe M. History of Intraoperative radiation therapy. In:Debelbower RR, Abe M (eds) Intraoperative radiation therapy. CRC, Boca Raton; :1-10, 1989.
In 1965, the modern era of IOERT began in Japan at Kyoto University where patients were treated with electrons generated by a betatronGunderson LL, Willett CG, Calvo FA, Harrison LB, eds. Intraoperative Irradiation: Techniques and Results. Second edition. New York: NY; Humana Press, 2011:11. Compared with other forms of 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 could be protected and shielded, if required, and the treatment took only a few minutes to deliver. These advantages made electrons the preferred radiation for IOERT. The technique gained favor in Japan. Other Japanese hospitals initiated IOERT using electron beams, principally generated from linear particle accelerators. At most institutions, patients were operated on in the operating room (OR) and were 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.M.Abe, M.Takahashi, Intraoperative Radiotherapy: the Japanese Experience. Int.J. Radiat.Oncol.Biol. Phys. 7:863-868; 1981.
The Japanese experience was encouraging enough for several U.S. centers to institute IOERT programs. The first one began at Howard University in 1976Goldson A., Past, present and prospects of intraoperative radiotherapy (IOR). Semin Oncol 1981. and followed the Japanese protocol of a large, single dose. Howard built a standard radiation therapy facility with one room that could 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.