Commentary (Nori): High-Dose-Rate Intraoperative Radiation Therapy For Colorectal Cancer

In this comprehensive review of a pilot study, Dr. Harrison and colleagues at Memorial Sloan-Kettering Cancer Center (MSKCC) describe a new intraoperative radiation treatment, its technical details, early results, and complications. This new treatment, high-dose-rate intraoperative radiotherapy using a remote afterloading technique (HDR-IORT), is being explored in a number of major centers in the United States and abroad. My comments below will focus on Dr. Harrison's technique. In addition, data from the MSKCC pilot study as well as information from other centers are summarized in Tables 1 and 2.

Rationale for HDR-IORT

Despite current advances in multimodality treatment, more than one third of patients with locally advanced rectal cancer develop pelvic recurrences. A significant portion of these recurrences involve the presacral space or pelvic side walls. To improve our ability to deliver higher doses of radiation to the tumor or tumor bed without exposing the surrounding normal tissues to excessive radiation, radiation oncologists have developed several new strategies, such as intraoperative or percutaneous brachytherapy, intraoperative electron-beam radiation, radiosensitizers, radioprotectors, heavy-charged particle irradiation, and more recently, conformal three-dimensional radiation.

Intraoperative low-dose-rate brachytherapy has been extensively studied for more than two decades in various clinical sites, including the rectum. The HDR-IORT technique presented in this article by Harrison et al seems to overcome some of the limitations of intraoperative low-dose-rate brachytherapy in terms of its ability to minimize the dose to normal structures. Standard intraoperative electron-beam radiation requires accessibility of the treatment cone to the tumor bed, and hence it cannot be used to treat sloping surfaces, such as the presacral space and pelvic side walls. The technique described by Harrison et al overcomes these limitations as well by the use of flexible applicators to access the sites.

Disadvantages of HDR-IORT

The major disadvantage of HDR-IORT is the radiobiology of a large single dose. Administering radiation in one large dose defeats the general principle of fractionation in radiation treatments, which allows for the repair of sublethal damage to normal tissues and permits reoxygenation. The linear quadratic (L-Q) bioeffect dose mode with a/b for tumor set at a 10-Gy single dose of HDR-IORT is equivalent to a low-dose-rate brachytherapy dose of about 18.7 Gy; similarly, a 15-Gy single dose is equivalent to a brachytherapy dose of 35 Gy. The radiobiologic significance of single-fraction HDR-IORT clearly needs further study.

Another limitation of this technique is the inability to perform preplanning for HDR-IORT treatment, and the current brachytherapy planning is based on a standard treatment planning atlas.

The authors present a highly selected group of patients with locally advanced primary rectal cancer treated with HDR-IORT. It is unclear why one third of the patients explored were not considered for HDR-IORT. Also, the median follow-up in this group is rather short (8 months). However, it is encouraging that no grade 4 complications or treatment-related mortality was observed in this group.

Summary

The HDR-IORT technique described by the authors appears to be simple and reproducible, and the radiation dose distribution conforms to the extent and slope of the surgical bed. Normal tissue protection is greatly facilitated by physical displacement and shielding. In spite of the logistic advantages, cost effectiveness, and other favorable features of HDR-IORT, only a handful of major centers in the United States are able to launch HDR-IORT programs at present.

References:

1. Dale RG: The application of the linear-quadratic dose-effect equation to fractionated and protracted radiotherapy. Br J Radiol 58:515, 1985.

2. Dritschilo A, Harter KW, Thomas D, et al: Intraoperative radiation therapy of hepatic metastases: Technical aspects and report of a pilot study. Int J Radiat Oncol Biol Phys 14:1007-1011, 1988.

3. Hilaris BS, Nori D, Anderson LL (eds): Atlas of Brachytherapy, New York, MacMillan Publishing, 1987.

4. Lukas P, Stepan R, Ries G, et al: A new modality for intraoperative radiation therapy with a high-dose rate afterloading unit. Radiology 181:251, 1991.

5. Nori D, Williams H: Intraoperative brachytherapy: Rationale and future directions. Proceedings of an International Brachytherapy Symposium, pp 132-137. Nucletron International, Baltimore, 1992.

6. Nag S, Orton C: Development of intraoperative high dose rate brachytherapy for treatment of resected tumor beds in anesthetized patients. Endocurie/Hypertherm OncolIntl J 9:187-193, 1993.