December 10, 2012
Radiofrequency ablation (RFA) delivered in three pulses to 180 degrees of the anal mucosa is safe and tolerable when administered to HIV-infected patients with anal dysplasia, according to a poster presented at IDWeek 2012. Twelve participants took part in the study, which was the first attempt to formally and comprehensively define safety and tolerability of the treatment, according to study presenter A. George Smulian, M.D., an associate professor of medicine and chief of the infectious diseases division at the University of Cincinnati.
In the general population, anal carcinoma has a reported incidence of less than one case per 100,000 persons, but rates in HIV-positive individuals are as high as 70 to 100 in 100,000, according to the poster. RFA, which has been successfully used to eradicate Barrett's esophagus or squamous dysplasia of the esophagus, can also be used to treat anal cancer. "However, the rate of recurrence is as high as 50 to 80% in HIV-positive men who have sex with men [MSM], although most recurrences are not at the same area where you treat the patient," Smulian explained.
"These are precancerous lesions. If had an early intervention, that would be the way to go, because once they present with cancer, they have significant mortality, pain and disfigurement," he continued. "We have very good ways of screening for this condition, although we don't have very good ways of treating it. We know how to treat the cancer, but we don't know how to treat dysplasia before it gets to cancer."
In the phase 1 study, Smulian and colleagues conducted a two-stage, dose-escalation experiment to determine whether treatment of pre-cancerous anal mucosa with three rapid pulses of energy, conducting 12 Joules per square centimeter to 180° of the anal mucosa, was safe and tolerable.
In the first stage, 9 HIV-positive patients with anal dysplasia were treated with one to three RFA pulses to a single, 2 cm. by 1.3 cm. area during anoscopy. Patients were divided into three groups: The first received one pulse, the second received two pulses and the third received three pulses.
The patients completed a survey assessing their symptoms after the procedure, as well as a daily symptom survey for 28 days thereafter. They also underwent high-resolution anoscopy two, four and 12 weeks later to evaluate healing. Researchers evaluated changes to their bowel habits, bleeding and how many days they took off work, Smulian said.
The 9 patients experienced a mean procedural pain of four on a scale of one to 10, which was unaffected by the number of blasts they received.
In the second stage, six patients received RFA blasts at the two highest doses to one 180° of the anal mucosa while they were under moderate sedation. Most patients reported no recall of significant procedural pain, and procedural pain and post-procedure symptoms resulted in minimal disruption of daily activities.
In addition, complete healing was demonstrated within four weeks, the poster said. Eleven of the 12 participants enrolled in the study demonstrated mucosal healing within 14 days. While one participant experienced significant pain and developed ulceration extending to the anal verge, the ulcer had healed within 28 days.
The findings of this study may be particularly relevant given the increasing amount of attention being paid to anal health in HIV-infected people. In high-risk individuals, the rates of anal cancer are higher than the general population, Smulian said. "For example, among HIV-positive MSM, the rates are increased 200-fold. Among MSM who are HIV-negative, as well as those who are HIV-positive but who do not engage in anal sex, the rates are between 35 and 50 per 100,000. Among people who receive a renal transplant, the rates are 15 to 20 per 100,000, and rates are also elevated among women with cervical disease," he added.
These sobering facts speak to the need for more effective, tolerable treatments to prevent anal dysplasia from developing. "Anal dysplasia is a field disease; as you chop off the tallest weed, the next one grows up to take its place," Smulian explained. "We were able to use RFA to treat the whole lining without causing strictures, disfigurement, or local problems. Increasing the amounts of energy allows for the deeper destruction of the mucosa; you've got to get to the deeper levels to get rid of the infection."
Smulian and colleagues are now planning a study to more reliably evaluate the efficacy of the procedure. Although the researchers have identified academic centers to participate, they are still waiting for study sponsors and have not yet enrolled patients.