BOSTONHIV-positive patients often cannot tolerate treatment for anal squamous cell carcinoma and have a worse prognosis than other patients, according to two studies presented at the American Society of Colon and Rectal Surgeons (ASCRS) annual meeting.
Groups in Texas and Washington, DC, reported that review of recent charts of HIV-positive patients showed they were a distinct group that could not handle the toxicity of standard therapy. The trend was so strong that presenters from the University of Texas Southwestern Medical Center at Dallas said that anal squamous cell carcinoma should become an AIDS-defining illness, triggering intense antiretroviral treatment before cancer therapy is attempted.
They tend not to die from their cancer. Even if they die with cancer, they do not die from cancer; they die from AIDS. The cancer is a marker that AIDS is very severe, Clifford L. Simmang, MD, told ONI . He is associate professor of surgery and program director for Colon and Rectal Surgery at UT-Southwestern.
Bruce A. Orkin, MD, led the study at George Washington University Medical School. He told ONI, We have to reassess our treatment of HIV-positive patients with anal cancerlooking at methods for prevention and earlier detection as well as modification of the traditional treatment. Dr. Orkin is associate professor of surgery and director of the Division of Colon and Rectal Surgery, where he has already begun to experiment with a different regimen.
Although they acted separately, Drs. Orkin and Simmang both said they had noticed they were treating an unusual number of middle-aged HIV-positive men for a relatively rare disease that typically occurs in older women.
The Dallas Study
For the UT-Southwestern study, Ronald J. Place, MD, performed a retrospective chart review from 1980 to 1999 and identified 29 HIV-positive patients with anal cancer. Of these, 14 had invasive anal squamous cell carcinoma, 9 had in situ squamous cell carcinoma, and 6 had non-Hodgkins lymphoma. The mean age was 39.9 years, all but one was male, and 24 had AIDS.
Therapy was adjusted because of toxicity for nine of the patients with invasive anal squamous cell carcinoma and four of the lymphoma patients.
Five of the lymphoma patients died with a mean survival rate of 10 months; the only survivor was newly diagnosed. Eight of the invasive carcinoma patients died at a mean of 17 months; again, four of the six survivors had been newly diagnosed. Two of the patients with in situ carcinoma died. Both had CD4 counts of less than 20 cells/mm3. The rest are currently without anal disease.
CD4 counts showed a correlation with outcome. At diagnosis, the average counts were 93 for the lymphoma patients, 200 for those with the in situ carcinomas, and 210 for those with the invasive carcinomas. The mean CD4 cell count at diagnosis was 121 for those who died, compared with 248 for those surviving.
A CD4 count under 200 cells/mm³ predicts a poor prognosis for HIV-positive patients, according to the researchers, who attributed the deaths to HIV status rather than cancer. Patients with AIDS cannot tolerate the treatment because of their severe AIDS, Dr. Simmang said. We have to modify treatment, since it is the AIDS that kills them. We need to treat them first with antiviral therapy, so they can tolerate the cancer treatment.
Dr. Place, now chief of colorectal surgery, Madigan Army Medical Center, Fort Lewis, Washington, told ONI he believes that patients need to be identified before they develop invasive carcinoma. People who are HIV positive and who practice anal intercourse should have regular examinations, just like women have Pap smears, he said.
George Washington Study
The group at George Washington University treated 98 patients for anal neoplasms from 1985 to 1999. The researchers analyzed charts on a cohort of 73 patients who had invasive squamous cell carcinoma, including cloacogenic carcinoma. Of these patients, 13 were HIV positive and 60 were HIV negative.
The HIV-positive patients were younger, having a mean age of 42 vs 62 for the HIV-negative group. They were more likely to be male (92% vs 42%) and homosexual (54% vs 15%).
While stage and radiation dose did not differ between the groups, there were major differences in acute and late treatment toxicity: 62% of the HIV-positive patients vs 31% of HIV-negative patients had acute treatment toxicity, and 33% and 15%, respectively, had late toxicity.
After initial therapy, 62% of the HIV-positive patients were disease free vs 85% of the HIV-negative patients. Among those who died, the mean time to cancer-related death was 2.1 years for the HIV-positive patients vs 4.6 years for those who were HIV negative (P < .05).
The study concluded that the HIV-positive patients were a distinct population that had poor tolerance of combined chemotherapy and radiation, died in a shorter time, and demonstrated a strong trend toward poorer initial response.
In the 18 months since the study, Dr. Orkin told ONI that he has changed the regimen for HIV-positive patients from mitomycin(Drug information on mitomycin) C (Mutamycin) plus fluorouracil(Drug information on fluorouracil) to cisplatin(Drug information on cisplatin) (Platinol) plus fluorouracil, with promising results. He estimates that he has seen 20 more patients with anal cancer since the studyan unusually high number, he stressed, for a disease that was rare 10 years ago. The Washington group has solicited doctors at other centers for a larger study, he said.