Future directions in intraoperative radiation therapy

It is difficult to establish the degree of effectiveness of IORT as a component of treatment in some of the malignancies currently being treated by IORT. Locally advanced pancreatic cancer is a typical example of a neoplasm for which it has been challenging to find effective advances in treatment. The survival time of patients who have this disease is limited to 9 to 12 months (median), with a 2-year survival rate of 10% to 20% following even the most effective chemoradiation. It is perhaps overly optimistic to expect that IORT will significantly enhance survival, because currently available systemic treatment options have not meaningfully affected either overall patient survival times or the rate of distant metastasis in either the adjuvant setting or for metastatic disease. It is encouraging, however, that Willett has reported five patients with 5-year survival times in the Massachusetts General Hospital IOERT series for unresectable pancreatic cancer (C.G. Willett, personal communication, 2002). Also encouraging is the report from the Medical College of Ohio of a 5-year rate of 33% in a small group of patients with resectable pancreatic cancers treated with single IORT doses (without EBRT or chemotherapy) as the sole adjuvant to surgical resection. At the same institution, during the same time period, the same group of surgeons observed that no patient with resectable pancreatic cancer survived longer than 13 months following surgical resection alone [7]. Exciting possibilities involve the use of IORT when treating early-stage malignant disease, as is detailed in the chapter on breast cancer. The use of [table: see text] IORT as adjuvant therapy seems to be associated with an extremely low incidence of in-breast local recurrence. Whether this is because of early stage of the disease or the adjuvant EBRT is not entirely clear at the time of this writing. (The results of ongoing randomized studies may not be powered sufficiently to resolve the question.) Because the local recurrence rate currently is extremely low (only one reported recurrence), however, this finding is promising. Also exciting is the use of IORT as the sole radiation [table: see text] treatment following limited excision of breast cancer. The results of the Lanciano and Milano trials (see chapter 12) are awaited with great interest. Equally exciting is the finding of meaningful survival of 20% to 40% of patients who have local or regionally recurrent cancers when IORT is used as a component of treatment together with EBRT, maximal resection, and chemotherapy, as indicated. Many of these patients still have excessive rates of both local and distant relapse, however, necessitating the rationale for well-controlled multi-institutional studies that involve alternate systemic therapies, radiation sensitizers, among other criteria.