“HIV status alone should not be used for cancer treatment decision-making,” emphasized Gita Suneja, MD, MSHP, Associate Professor of Radiation Oncology and Global Health, Duke University School of Medicine, and Co-Chair of the NCCN Guidelines Panel for Cancer in People Living With HIV. According to the NCCN Guidelines, this patient population, for whom cancer is now a leading cause of death, should receive cancer treatment per standard guidelines, although modifications in antiretroviral therapy (ART) may be needed. Although Dr. Suneja admitted that HIV management during cancer therapy poses many clinical challenges, “Appropriate cancer treatment can successfully be delivered especially when oncologists and HIV specialists work together to optimize care for both diseases.”
Dr. Suneja acknowledged a knowledge deficit surrounding the treatment of cancer in patients with HIV, with 70% of surveyed oncologists stating that sufficient guidelines were not currently available for treating this population.1 Consequently, guidance for practicing clinicians on how to manage patients with both cancer and HIV infection was sorely needed, thus the inaugural NCCN Guidelines were developed.
Treating patients with cancer who are HIV-positive is complex and requires input from multiple clinicians. Dr. Suneja referenced a survey of 500 medical and radiation oncologists across the United States,1 which found that “20% to 25% said they would not offer standard cancer therapy to people living with HIV,…[yet] 45% said they rarely or never discussed a management plan with an HIV specialist.”
Intersection of HIV and Cancer
People living with HIV have a higher incidence of many cancers compared with the general population,2 with multiple contributing factors, including a higher chance of coinfection with oncogenic viruses, such as human papillomavirus (HPV) and human herpesvirus 8 (HHV-8), and a higher prevalence of smoking.3
“People living with HIV are less likely to receive cancer treatment compared with uninfected people,”4 said Dr. Suneja, shedding further light on cancer care disparities for those with HIV. Dr. Suneja also noted that “People living with HIV were previously excluded from clinical trials just by virtue of having HIV infection, and that's in part why this knowledge deficit exists.”5,6 For instance, in a 2017 report which examined >75 studies, 65 had a specific HIV exclusion, which has undoubtedly driven disparities in treatment for this unique patient population.5,6
AIDS-Defining and Non–AIDS-Defining Malignancies
Dr. Suneja briefly discussed 2 AIDS-defining cancers (Kaposi sarcoma [KS] and cervical cancer), as well as several non–AIDS-defining malignancies (anal cancer, non–small cell lung cancer, and Hodgkin lymphoma [HL]).
Kaposi Sarcoma
As one of the first cancers shown to be linked to HIV infection, KS has its own set of newly developed NCCN Guidelines (AIDS-Related KS) separate from the NCCN Guidelines for Cancer in People Living With HIV. Although the risk of developing KS has declined significantly (90%) with the use of ART, those living with HIV infection are still far more likely to develop KS than uninfected people, revealed Dr. Suneja. HHV-8 is the etiologic infection that underlies KS, and individual lesions may be distinct clones that arise from persistent immunosuppression and HHV-8 infection, which makes treatment of the existing disease tricky because it may not prevent the development of future lesions. Based on the algorithm, ART therapy is among the appropriate first-line options for those with symptomatic disease. “ART therapy is really the backbone of treatment for KS,” noted Dr. Suneja. She also mentioned the importance of watching for immune reconstitution inflammatory syndrome, which can be a life-threatening condition.
Cervical Cancer
The risk of cervical cancer is approximately 3 to 5 times higher in people living with HIV than in the general population, and persistent HPV infection is deemed the etiologic agent. “It is more of a problem in developing countries, because in the United States, we screen for cervical cancer and the US HIV population is largely male,” Dr. Suneja explained. The guidelines recommend that women living with HIV and cervical cancer be treated according to the NCCN Guidelines for Cervical Cancer, including the use of concurrent chemotherapy for those receiving definitive radiation treatment.
Anal Cancer
The risk of developing anal cancer in those with HIV infection is significantly higher than for other types of AIDS-related cancers. The guidelines recommend that those living with HIV infection and anal cancer be treated in concordance with the NCCN Guidelines for Anal Carcinoma. Dr. Suneja pointed out there should be more frequent posttreatment surveillance in the HIV population, with anoscopy every 3 to 6 months for 3 years.
Lung Cancer
Lung cancer is the most common non–AIDS-defining cancer in people living with HIV infection, with an estimated prevalence 2 to 5 times higher than in the HIV-negative population. At this time, there are no different screening guidelines for lung cancer in HIV populations, but Dr. Suneja suggested that ongoing studies may elucidate alternate screening recommendations for people with HIV in the future. Currently, patients with HIV infection at risk for lung cancer should be screened according to the NCCN Guidelines for Lung Cancer Screening. Lung cancer treatment for those with HIV should parallel the recommendations in the NCCN Guidelines for Non–Small Cell Lung Cancer. Dr. Suneja also noted the importance of smoking cessation in this patient population.
Hodgkin Lymphoma
HL is a common type of cancer found in HIV populations, with a 5 to 14 times higher risk of development than the general population. One major distinction for people with HL and an HIV infection, according to Dr. Suneja, is that nearly 90% of cases are Epstein-Barr virus–associated and that those with HIV infection often are found to have more advanced disease, including B symptoms and bone marrow involvement. Dr. Suneja emphasized that B symptoms should prompt a workup for opportunistic infection, especially if CD4-positive T-cell counts are low.
The ABVD regimen (doxorubicin, bleomycin, vinblastine, and dacarbazine) is recommended for treating HL in people with HIV infection. However, dose reductions may be required for prolonged severe neutropenia.7 In this population, growth factors may be required for those with a low CD4-positive T-cell count and prolonged neutropenia, according to Dr. Suneja. Although it is recommended, PET/CT-guided therapy may be challenging in HIV-positive populations due to potential confounders, such as enlarged or metabolically active nodes due to infection,
Principles of systemic therapy and drug–drug interactions table from the NCCN Guidelines for Cancer in People Living with HIV.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 5S; 10.6004/jnccn.2018.0033
HIV Management in Patients Receiving Cancer Therapy
“All people with HIV and cancer should be comanaged by an oncologist and an HIV specialist,” emphasized Dr. Suneja. HIV therapy should be continued during cancer treatment because it results in better tolerance of cancer treatment, higher response rates, and improved survival. However, modifications to HIV therapy may be required to avoid drug–drug interactions or overlapping toxicities. More frequent CD4-positive T-cell counts and viral load testing should be performed during cancer treatment (once a month for the first 3 months then every 3 months thereafter) due to potential drug interactions that may make ART less effective.
For this patient population, there are unique considerations when selecting drugs for treatment. Dr. Suneja noted the possibility of drug–drug interactions and potential overlapping toxicities, suggesting that cancer therapy, supportive care medications, and ART should be reviewed by an oncologist, an HIV specialist, and a pharmacist. The NCCN Guidelines provide a useful table outlining drug–drug interactions by ART drug class, as well as potential clinically significant pharmacokinetic interactions (Figure 1).
In the guidelines, sections on Principles of Imaging, Principles of Radiation Therapy, and Principles of Surgery are included to guide treatment decisions. In addition, the NCCN Guidelines also offer a section on Principles of Supportive Care, “to ensure that treatment toxicity is minimized,” said Dr. Suneja.
References
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Suneja G, Boyer M, Yehia BR et al.. Cancer treatment in patients with HIV infection and non-AIDS-defining cancers: a survey of US oncologists. J Oncol Pract 2015;11:e380–387.
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Engels EA, Pfeiffer RM, Goedert JJ et al.. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS 2006;20:1645–1654.
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Robbins HA, Pfeiffer RM, Shiels MS et al.. Excess cancers among HIV-infected people in the United States. J Natl Cancer Inst 2015;107:pii: dju503.
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Suneja G, Shiels MS, Melville SK et al.. Disparities in the treatment and outcomes of lung cancer among HIV-infected individuals. AIDS 2013;27:459–468.
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Persad GC, Little RF, Grady C. Including persons with HIV infection in cancer clinical trials. J Clin Oncol 2008;26:1027–1032.
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Uldrick TS, Ison G, Rudek MA et al.. Modernizing clinical trial eligibility criteria: recommendations of the American Society of Clinical Oncology-Friends of Cancer Research HIV Working Group. J Clin Oncol 2017;35:3774–3780.
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Spitzer TR, Ambinder RF, Lee JY et al.. Dose-reduced busulfan, cyclophosphamide, and autologous stem cell transplantation for human immunodeficiency virus-associated lymphoma: AIDS Malignancy Consortium study 020. Biol Blood Marrow Transplant 2008;14:59–66.
