At the 23rd National Comprehensive Cancer Network (NCCN) Annual Conference, held March 22-24 in Orlando, Florida, Gita Suneja, MD, Duke Cancer Institute, presented NCCN’s new guidelines on treating cancer in people living with HIV.
“The story of HIV in America began in June of 1981,” said Suneja, with the CDC's Morbidity and Mortality Weekly Report
that described 5 young men with biopsy-confirmed Pneumocystis carinii
pneumonia. While the CDC would not name AIDS-defining cancers (Kaposi sarcoma [KS], non-Hodgkin lymphoma, and cervical cancer) until 1993, Suneja said that “Cancer was a part of the story from the very beginning.” As early as July 1981, KS was described together with pneumonia among homosexual men.
Today, Suneja said, we understand that people with HIV have a higher incidence of many cancers—not only AIDS-defining cancers—compared with the general population. Some factors involved are coinfection with oncogenic viruses and a higher incidence of smoking within this population. Aging, too, is playing a role; antiretroviral therapy (ART) has increased survival of people living with HIV, and “HIV has really been converted over to a chronic disease … not only is the US HIV population growing over time, they’re also aging.”
While the incidence of AIDS-defining cancers is on the decline due to patients’ improved immune function with ART, the incidence of non–AIDS-defining cancer is rising among people with HIV. Some potential explanations include complications with AIDS, advanced cancer stage at diagnosis, decreased immune surveillance, and more biologically aggressive disease.
Concerningly, people living with HIV are also significantly less likely to receive cancer treatment compared with patients without HIV. Suneja pointed to a 2015 survey that she and her colleagues conducted among 500 US oncologists. Among the respondents, 20% to 25% said that they would not offer standard cancer therapy to a patient who had HIV, 70% said that sufficient guidelines for treating these patients were not available, and 45% said that they rarely or never discussed a management plan together with an HIV specialist.
Further compounding the problem is the fact that patients with HIV are routinely excluded from clinical trials, so there is a knowledge gap about how best to treat these patients. Suneja likens such a practice to excluding people with cardiovascular disease—something that wouldn't really be done.
“HIV status alone should not be used for cancer treatment decision-making,” said Suneja. Instead, clinicians should bear in mind unique considerations for patients who have HIV.
Because imaging may reveal lymphadenopathy with non-malignant etiology, clinicians should consider a lower threshold to perform a nodal biopsy to determine whether cancer is involved; lesions of the brain, bone, lung, spleen, liver, or gastrointestinal tract may be non-cancerous in nature, especially if a patient’s CD4+ T-cell count is low.
Poor performance status could be from HIV, cancer, or other causes, and drug-to-drug interactions among oncology and HIV therapies are possible. It is key to consult an HIV specialist and a pharmacist, said Suneja, before initiating therapy, and co-management between the oncologist and HIV specialist is critical.
While publications from the pre-ART era showed increased toxicity from cancer therapies in patients with HIV, modern data do not demonstrate the same results in patients who have CD4+ T-cell counts more than 200 cells/uL. Conformal radiotherapy techniques can be used to reduce the dose to bone marrow, skin, and mucosa, and there is no difference in clinical outcomes or complications for patients with HIV who undergo surgery compared with patients without HIV.
While the risk of KS has declined by 90% with better HIV management, patients with HIV are still at elevated risk for this cancer. It is important to understand that Individual lesions may be distinct clones that arise from persistent immunosuppression and human herpesvirus 8 infection, so treating existing disease may not prevent future lesions.
In AIDS-related KS, in patients who are asymptomatic and find their condition cosmetically acceptable, “sometimes we don’t need to do any cancer-related therapy … ART is really the backbone of treatment for KS," Suneja said.
Patients who are symptomatic or find their condition cosmetically unacceptable should receive ART with topical drugs, systemic therapy, radiation therapy, intralesional chemotherapy, local excision, or a clinical trial. Patients with advanced disease should receive ART together with treatment in a clinical trial if eligible.
Because reconstitution of immune function is important for the control of KS, the clinician should be aware of immune reconstitution inflammatory syndrome, during which glucocorticoids may become necessary (though they should be generally avoided, as they may promote KS). Potential lymphedema should also be closely monitored.
Cervical and anal cancers
NCCN recommends that patients who have cervical cancer or anal cancer be treated in line with existing NCCN guidelines for these conditions. In the case of anal cancer, patients should receive more frequent surveillance, with anoscopy every 3 to 6 months for 3 years.
The most common non–AIDS-defining cancer in people with HIV is lung cancer. Even after controlling for increased levels of smoking in the HIV population, people with HIV still have an increased risk for this disease. NCCN says that patients with HIV should receive treatment per NCCN’s guidelines for non–small cell lung cancer, and smoking cessation support should be offered.
Ninety percent of cases of Hodgkin lymphoma in people with HIV are related to Epstein-Barr virus, and many patients with HIV present with more advanced disease. The preferred treatment regimen in this population is doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine, but dose reductions may be required in cases of prolonged neutropenia; growth factors, which are generally avoided in this population, may be required. Autologous stem cell transplant has also been shown to be safe and effective for patients with HIV who have recurrent or relapsing Hodgkin lymphoma.
In general, steroids should be avoided because of the risk of opportunistic infections, and a high index of suspicion—together with early testing for opportunistic infection—is appropriate. Live vaccines should be avoided if CD4+ count is under 200 cells/uL, but patients over age 50 may receive the new recombinant zoster vaccine.
All patients with cancer should be screened for HIV. “Point of care testing [for HIV] is really in our domain” as oncologists, said Suneja, and together with an HIV specialist, the oncologist should undertake more frequent CD4+ T-cell count and viral load testing.
Drug-to-drug interactions should be reviewed by both specialists and a pharmacist; of greatest concern are pharmacologic boosters like ritonavir and cobicistat, as well as protease inhibitors. Overlapping toxicities may be present; both cancer drugs and HIV therapies may cause neuropathy and neutropenia, for example. If there is the potential for drug-to-drug interactions or overlapping toxicities, the oncologist may substitute ART, choose a different cancer therapy, or temporarily discontinue ART if cancer treatment is curative or palliative in nature.
In the future, said Suneja, NCCN plans to expand the number of cancers that it addresses in its guidelines, adapt guidelines for low-resource settings, generate an evidence base for the management of HIV-associated cancers, and increase clinical trial accrual.
CDC. Pneumocystis pneumonia—Los Angeles. MMWR Morb Mortal Wkly Rep