The use of radiation in the treatment of rectal cancer dates back to the early 1900s. One of the initial approaches involved application of a radium source internally, within the rectum. This technique came to be called “brachytherapy” (from the Greek “brachy,” meaning “short distance”), and described utilization of a radioactive source to deliver therapeutic radiation directly to a tumor. Eventually, external beam radiotherapy replaced brachytherapy.
Today, radiation therapy plays a vital role in the management of this disease. For patients with locally advanced rectal cancer, preoperative chemoradiation followed by a total mesorectal excision is the standard of care.
While approximately 20 percent of patients have a pathologic complete response to preoperative chemoradiation, meaning that there is no tumor left at the time of surgery, 80 percent of patients may still harbor residual tumor cells and will benefit from surgical resection of the tumor.
However, surgery for low-lying rectal cancer can result in the need for a permanent or temporary colostomy, as well as the development of long-term urinary and sexual dysfunction. This can have a negative impact on health-related quality of life. Elderly patients and patients with multiple medical problems may not be good candidates for radical pelvic surgery. Furthermore, some patients refuse any treatment that will leave them with a stoma.
To improve response rates in patients who are medically unfit for surgery or who are unwilling to undergo an abdominoperineal resection (APR) requiring a permanent colostomy, other options are necessary. This brings us back to the concept of brachytherapy: delivering high-dose radiation directly to a rectal tumor, with the goal of improving complete response and avoiding radical resection. If patients with locally persistent or recurrent disease after chemoradiation decline to undergo an APR or are unfit for radical surgery, endorectal brachytherapy may represent an option for providing local disease control.
Many groups, especially in Europe, have reported on combination external beam radiotherapy followed by a “boost” to the tumor using brachytherapy in patients with locally advanced rectal cancer. This was first described by the French physician Jean Papillon (1914-1993), who pioneered the approach at the University of Lyon.
Contact x-ray therapy, using a low-energy x-ray endorectal tube to deliver a high dose of radiation to the tumor, has demonstrated efficacy in controlling small, early-stage rectal tumors without external beam radiation.
While this type of superficial radiotherapy does not utilize a radioactive source, the technique of applying high-dose radiotherapy directly to the tumor works in a way very similar to brachytherapy. The high radiation dose, close to the radioactive or contact x-ray source, is directed to the tumor, while rapid dose fall-off ensures that only lower doses are delivered to deeper tissues.
Another technique is high-dose-rate (HDR) brachytherapy using an Iridium-192 source. The source is introduced through catheters fitted into an endorectal applicator, which is then inserted into the rectum. This allows physicians to deliver high doses of radiation in a relatively short period of time, tailoring the dose to the particular tumor.
At Memorial Sloan Kettering, this procedure is performed in the operating room with the patient under general anesthesia. After identifying and marking the extent of the tumor, we work in collaboration with colorectal surgeons to insert the endorectal applicator. We use CT- and MRI-based planning to develop a conformal radiation dose specific to the rectal tumor, thus minimizing the dose to the bladder and small bowel.
First, our physicists calculate a plan for delivery of the appropriate dose. The treatment is then applied to the tumor utilizing the Iridium-192 source via a remote delivery system. The availability of a remote afterloading technique, whereby the Iridium-192 source exits the machine and delivers radiation to the tumor region (while the staff is outside of a shielded operating room), ensures that clinicians will have minimal exposure. Typically, this treatment is delivered once a week for a total of three weeks, with concurrent capecitabine (oral 5-FU) chemotherapy.
At Memorial Sloan Kettering, we are currently using HDR brachytherapy to treat selected patients with low-lying rectal cancers who have other medical comorbidities and/or have refused an APR. Additionally, since surgical resection is the salvage therapy for persistent or recurrent anal cancer after definitive chemoradiation, we offer HDR brachytherapy to patients with small, recurrent anal cancers.
New Clinical Trial
We are opening a new protocol to evaluate the dose per fraction of brachytherapy: determining the appropriate dose that can be delivered safely while minimizing side effects. This phase I dose-escalation study will evaluate the safety of endorectal brachytherapy with concurrent capecitabine or 5-FU in the management of locally recurrent/residual rectal or anal cancer in patients who have received pelvic external beam radiation with or without chemotherapy.
We will use MRI with dynamic contrast enhancement and diffusion weighted imaging series to enhance our assessment of tumor response.
The goal is to extend our use of brachytherapy to improve outcomes and individualize treatment of patients with rectal cancer. Given the morbidity of radical surgery, and its long-term impact on quality of life, selective nonoperative treatment may be an alternative in some cases. With appropriate use of endorectal brachytherapy, rectal surgery may be selectively omitted from the management of some rectal cancer patients. These include individuals for whom surgery poses a prohibitive risk, or who refuse to have an APR, or whose cancers respond dramatically to chemoradiation.
Brachytherapy also serves a palliative purpose in the management of patients with metastatic disease who may benefit from local therapy, but for whom radical resection is inappropriate. With advances in treatment options for rectal cancer and continued collaboration with our colleagues across disciplines, our ultimate goal is to tailor therapies based on patient risk factors and tumor characteristics, taking into account the impact of treatment on each patient’s quality of life.