Studies of intraoperative radiotherapy in carcinoma of the pancreas

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Abstract
Intraoperative radiotherapy (IORT) involves the administration of therapeutic radiation to malignancies during surgical procedures. IORT permits high dose delivery to tumors with the simultaneous reduction of radiation exposure to normal tissues, which may be directly shielded or operatively mobilized from the treatment volume. IORT has been investigated in various intra-abdominal malignancies, including carcinoma of the pancreas. Techniques of IORT were initially developed in Japan during the 1970's. Reports of therapeutic benefit in some patients with unresectable pancreatic cancer encouraged further examinations by various institutions in the United States. Experiences at the Massachusetts General Hospital in the early 1980's suggested that IORT enhanced survival in selected patients with locally advanced but non-metastatic disease. However, subsequent investigations studies by a variety of institutions, including the Mayo Clinic, failed to establish any conclusive evidence that IORT significantly prolonged the survival enhancement of unresectable pancreatic cancer patients. A prospective multi-institutional study carried out by the Radiation Therapy Oncology Group (RTOG) showed an 8-month median survival, similar to conventional therapy and indicating that IORT failed to prolong survival. However, the RTOG did show that IORT rapidly and consistently palliated the severe visceral pain which often accompanied pancreatic cancer. By 1990, some institutions had explored IORT as an adjunct to pancreatectomy, in patients with resectable tumors. Studies typically involved highly selected uncontrolled patients but did suggest that IORT could enhance local disease control and, in some cases, overall survival, when performed in conjunction with pancreatic resection. IORT appeared to be most conspicuously beneficial when used with extended radical resections. A small prospectively randomized trial conducted at the National Cancer Institute showed significant improvement in local disease control in patients receiving IORT compared with patients receiving conventional external beam postoperative radiotherapy after resection. Current evidence suggests that IORT may have an important palliative role in patients with unresectable pancreatic cancers, ameliorating visceral pain and promoting local control of the primary tumor; however, IORT appears to have no significant effect on overall survival. For patients with resectable disease, especially patients with locally extensive tumor, IORT appears to have benefit in enhancing disease control and in some cases survival. It is reasonable to further explore the potential role of IORT in pancreatic cancer, especially as a component of multimodal therapy, since IORT's demonstrated enhancement of local control could be an important factor in eventual disease control.