New Hope: AIDS Malignancy Consortium Offers New Hope to People with AIDS-related Cancer

Following is Part I of a two-part interview with Dr. David Aboulafia, a leading Northwest oncologist in the field of AIDS-related cancer. Dr. Aboulafia, who heads the AIDS Malignancy Consortium, presented a two-hour community meeting on AIDS-related cancers titled "The Trouble With Tumors" on April 13 at Volney Auditorium in Seattle. Dr. Aboulafia was interviewed by Brian Coppedge and Richard March, treatment specialists from the Seattle Treatment Education Project.

STEP: Dr. Aboulafia, can you tell us about the new clinic you have started and what services it offers to people with AIDS-related cancer?

Dr. David Aboulafia: Let me first say this is not a clinic per se. Virginia Mason has always had a large number of HIV-infected patients who receive care for lymphoma. But what we received a grant for -- and this is really a grant for the city of Seattle -- is for the AIDS Malignancy Consortium (or AMC). The AMC is made up of about 15 academic centers across the country that are typically associated with large AIDS Clinical Trial Units (or ACTUs) and that banded together around AIDS-related cancers. They were asked by the National Cancer Institute to come up with protocols to be done nationally. The AMC was formed in 1994 or 1995, and last year it was felt that this group needed to be broadened, and that there needed to be new ways of tackling the problem, particularly when KS [Kaposi's sarcoma] and lymphoma rates seem to be declining rather dramatically across the United States. We applied for a grant, and got a lot of support with the emphasis that this wasn't supposed to be a Virginia Mason thing but something for the city of Seattle to take advantage of.

This grant allows us to provide state-of-the-art care for patients with HIV-related cancers. And not in an individual or haphazard way, but with the goal of answering specific questions. Many of the studies are not available outside of the AMC. So, for example, we have a therapy of angiogenesis inhibitors for Kaposi's sarcoma. It's not a pill or an injection and it doesn't appear to have any side effects, but it's not available outside the AMC. The grant is designed so that we also will have a clinical site at Harborview. The grant will pay for a part-time nurse who will see the patients, record the data, etc.

STEP: So people could be referred through their primary care provider to see you?

DA: Yes, they can be referred through whatever their usual pattern of referral is. If they are referred to Harborview or Swedish we already have dedicated people who are familiar with the protocols. If they are referred to someone else, at least initially, we will need to send someone to that office to get the information and work directly with the patient. Recently I had a meeting with a Group Health oncologist and they bought in to this. They don't see a lot of AIDS-related cancer or lymphoma, but when they do, now they know how to get it going. Often times the patient does not want to leave their caregiver or support group, or their insurance doesn't allow them to move. This has become a real challenge for these kinds of protocols. Hopefully this [structure] is the answer; that Cheryl (research nurse) will go to Swedish or to Providence or anywhere she needs to and we'll work by fax and by talking to the doctors. One of our goals is to get this out into the oncology community so they are more aware of it.

STEP: You have mentioned Kaposi's sarcoma, and clearly that is the most commonly known AIDS-related cancer. Are there other HIV-related cancers people need to be aware of and any symptoms to look for?

DA: Each one is a little different. In 1984, Kaposi's sarcoma was one of the AIDS-defining illnesses that the CDC put in their inclusion criteria. If you're HIV-positive and you have KS, by definition you have AIDS. Shortly after, lymphoma was brought into that group and in particular, peripheral or lymph-node-bearing non-Hodgkin's lymphoma. It turns out that primary CNS [central nervous system] lymphoma, which is a lymphoma that develops within the brain itself, is distinct from the lymphomas we are used to seeing. It is also considered an AIDS-defining illness. So, three types of cancers are AIDS-defining when a person is HIV-positive: Kaposi's sarcoma; peripheral, intermediate, or high-grade non-Hodgkin's lymphoma; and primary CNS lymphoma.

A couple of other cancers, probably in higher incidence in people with HIV, have not been recognized yet by the CDC as AIDS-defining illnesses. One is Hodgkin's disease, which is a variation on lymphoma. Typically, patients will present with painless swelling, usually in a lymph-node-bearing region, often associated with what are called "B" symptoms: night sweats, weight loss. A biopsy or CAT scan will show an abnormal growth of lymph tissue that, after biopsy, shows either the non-Hodgkin's or Hodgkin's. Hodgkin's is a disease of young people; 18 to 40 is considered one "hump" in the curve, and then there is increased incidents in very old people. So HIV, which has generally been a disease of young people, may have an over-representation of one type of cancer. It does seem that Hodgkin's is more aggressive and more difficult to cure in the setting of HIV. And I suspect that when the CDC does develop new case definitions of AIDS, they will include Hodgkin's.

The cancer that is emerging, and that we are still learning about, is anal cancer, in particular pre-anal cancer, or something called anal intraepithelial neoplasia. Harborview has a clinic, as part of the ACTU, to follow HIV-infected patients with rectal pap smears every three months, including rectal exams and immune surveillance. These studies are trying to find out how common these pre-cancerous lesions in the rectum are and how often might they evolve into a true cancer. Fortunately, although HPV (human papilloma virus) infection is common in the rectum, true cancer is very rare. What we really don't know is, now that people are living for decades with HIV, will there be a higher incidence of anal or rectal cancer?

One of the things the AMC is involved in is the new HPV work group. Once a month we meet on a conference call to develop the protocols for patients with rectal and anal cancer, as well as to define what is going to be the best care for patients with pre-cancerous lesions. A lot of people get those lesions surgically removed. Sometimes drugs like interferon or aldera are used to reduce the likelihood that they will grow.

Maybe we should be doing antiviral agents, like we are trying with the new treatments for Kaposi's.

There are also vaccine studies for HPV, and the first one is just starting in San Francisco. If it looks promising, it will probably be broadened to the rest of the AMC group. You'd get a couple of shots over a period of time, develop an immune response against that virus, and hopefully that immune response would be able to cause a regression of the rest of the cancerous lesions.

STEP: So it's a therapeutic vaccine?

DA: Yes. The other thing I think worth noting is that 15 years ago no one lived for 15 years with HIV. People who had histories of smoking or alcohol abuse and who would have been at high risk for pancreatic cancer or stomach cancer or lung cancer never survived; they were dying at 25 or 26.

Last year we took care of a fellow who was 65 when he came down with pneumocystis, and at that point had an HIV test and found out he had advanced disease. He was put on HAART and had what we think of now as a rather typical response. His T-cells went from under 50 to over 200 over a two-year period and his viral load remained non-detectable. One day he came in with a large abdomen, and he actually thought he had a "crix belly." In fact he had fluid collection (not fat) and it turned out he had pancreatic cancer. When he was 30 he had been a heavy drinker and a heavy smoker, but he hadn't done either for 15 years. When he died, he had a non-detectable viral load and a T-cell count of about 300!

So just like we are recognizing there are cardiovascular implications for patients who have high triglycerides -- many may have problems down the line with their cardiac status -- personal histories can influence disease progression many years into the future. People need to be aware of this when symptoms present.

STEP: You mentioned that many people are living years longer than was initially expected with HIV infection. Is there a relationship between length of infection and the probability of developing any of the cancers you have mentioned?

DA: We're not sure. The incidence of KS has fallen dramatically. A study done a year ago showed how rapidly the incidence of KS had declined since 1990, particularly since 1995. Lymphoma is a little bit different. In many parts of the country, lymphoma rates have increased or stayed the same. In King County, lymphoma rates decreased between 1995 and 1997, but that has not been the norm. In August, an article in the British Medical Journal showed that the incidence of lymphomas was rising in Scandinavian countries during the HAART era. And although it hasn't been reported well yet, New York is seeing a resurgence of lymphomas, at least in clinics with a large number of HIV patients. We don't understand totally what causes lymphomas, but if it's immune activation, people who have HIV infection (even though on HAART therapies) have very stimulated immune systems. The dividing of cells with mitogenic stimulation is never really taken away. It is conceivable that lymphoma rates can take a swing up.

STEP: Has the decline in KS rates affected the ability to perform good clinical trials for new KS treatments?

DA: That is one of the ironies of the progress we have made -- KS has become a relatively rare disease. Back in 1984 about 50% of people who were HIV-infected were going to get KS sometime during the course of their disease, and about 20% of the newly diagnosed had KS at the time of their diagnosis. That number now is less than 10%. Over the last six months most of the KS patients I have seen have had KS for a while. They are not presenting "de novo" or if they are, they have also been off therapies, or refused therapies, or didn't know they were HIV infected, and in fact came to medical attention because of a skin lesion like KS. It does make it much harder because there just aren't enough patients. That is why it's important for people to make themselves available for these studies.

KS is a disease, we say, that is not going to kill you. But it is going to impact on your quality of life. And if we can't find better therapies than we're using now, we are going to diminish quality of life when we treat. The treatments we use now are chemotherapy drugs, radiation therapy, and for small disease, liquid nitrogen or intra-dermal injections of chemotherapy. As an oncologist, most patients I see already have disease in one or two locations. And for that group, quality of life becomes crucial.

AIDS oncology shouldn't be handed out to all oncologists. Ideally, if you are going to recommend a lymphoma treatment to someone with HIV, you should know what antiretroviral drugs they are taking, how those drugs will interact with the chemotherapy drugs, and what kind of immunosuppression you are going to induce. I think you can expect generally better outcomes in people who have more experience treating those things.

In Part II of the interview in the next issue of the Perspective, Dr. Aboulafia discusses how patients can advocate for their own healthcare when facing AIDS-related cancer, answers questions about Burkitt's lymphoma, and summarizes his hopes for the future of the AIDS Malignancy Consortium in Seattle.