Racial disparity lies at the intersection of HIV and Hodgkin lymphoma

A new study finds a significant racial disparity within a doubly troubled population of patients: those with HIV and Hodgkin lymphoma. In such cases, blacks are at significantly higher risk than whites of not receiving treatment for the cancer that in many cases would be effective.

Black patients have higher rates of not receiving treatment,” said lead author Dr. Adam Olszewski, associate professor of medicine in the Alpert Medical School of Brown University and a physician in the Cancer Center of Memorial Hospital in Pawtucket, R.I. “Hodgkin lymphoma is generally believed to be highly curable. We have an expectation to cure over 90 percent of early stage patients and even 70-80 percent of quite advanced cases.”

Olszewski’s study in the journal AIDS, conducted with Dr. Jorge Castillo of Dana-Farber Cancer Institute, identified the racial disparity in data from nearly 2,100 cases in the National Cancer Data Base between 2004 and 2012.

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​While the disparity is clear, Olsewski said, the root cause of it is not. Several closely entangled epidemiological, socioeconomic, and medical factors are at play.Heading into the study, researchers knew that people with HIV have a risk of Hodgkin lymphoma that is five to 20 times greater than people who do not have HIV. They also knew that HIV incidence has remained relatively high among blacks, while it has dropped significantly for whites. As a result, the new study found that between 2004 and 2012, blacks surpassed whites as the largest racial group with simultaneous HIV infection and Hodgkin lymphoma, making up 49 percent of such cases in 2012.

Meanwhile, doctors have had a muddy sense of whether HIV-positive people with Hodgkin lymphoma survive the cancer as well as people who are HIV-negative. Many HIV-positive patients didn’t tolerate an older treatment regime for the lymphoma, Olszewski said, but chemotherapy treatment has vastly improved in more recent years. While some small studies, particularly in Europe, have found that HIV status makes no difference to survival, observations in the U.S. population suggest that being HIV-positive makes survival less likely.

The new study, the largest to date, may reconcile that conflict. It shows that in the United States the reason people with HIV seem to fare worse with the cancer is because they are less likely to be treated for it.

Specifically, the study ostensibly showed that HIV-negative people had an 80 percent Hodgkin lymphoma survival rate five years after diagnosis, but HIV-positive people survived at a rate of only 66 percent over the same timeframe. But among HIV-positive patients, 16 percent went untreated. Among people in the study who did get lymphoma treatment, HIV-positive people were statistically just as likely to survive as HIV-negative people. The results apply to the majority of cases in which the subtype of Hodgkin lymphoma is determined.

Importantly, further statistical analysis showed that one of the main risk factors for an HIV-positive person going untreated was being black. Statistically adjusting for possibly confounding factors, HIV-positive blacks were 67 percent more likely than HIV-positive whites to go untreated for the lymphoma. Other risk factors, which are often related to race, were low income and lacking health insurance. Another was being over 60 years of age.

Olszewski acknowledged it’s not clear how the racial disparity arises. It could correlate with more advanced or poorly controlled HIV infection. It could also be a lingering assumption that HIV-positive patients (who are increasingly likely to be black) won’t tolerate the treatment well. Some patients may be declining treatment, either for HIV (thereby making them seem more vulnerable) or for the lymphoma itself. Another possibility is that the often-related socioeconomic status of being black and poor and uninsured makes it hard for patients to remain connected to care after diagnosis.

For patients who have HIV and Hodgkin lymphoma, treatment can be effective and tolerated, especially when the lymphoma subtype is known, Olszewski said, but doctors should understand that some patients many need extra assistance or attention to ensure they connect with that care.

To date, this study suggests, it’s apparent that some people who should get treatment aren’t getting it.

Olszewski et al., Outcomes of HIV-associated Hodgkin lymphoma in the era of antiretroviral therapy: analysis of the National Cancer Data Base. AIDS, 2016; doi: 10.1097/QAD.0000000000000986 [Abstract]

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Two studies examine long-term outcomes in childhood and young adult cancer survivors

JAMA Oncology published two studies and a related editorial focused on long-term outcomes in survivors of childhood or young adult cancer.

In the first study, Kathrine Rugbjerg, PhD, and Jørgen Olsen, MD, DMSc, of the Danish Cancer Society Research Center, Copenhagen, examined the risk for hospitalization up to 34 years after a diagnosis of adolescent and young adult cancer survivors. The study included 33,555 five-year cancer survivors diagnosed from 1943 through to 2004 with a comparison group from the general population. The authors identified 53,032 hospitalizations in cancer survivors for one or more of 97 disease categories.

Cancer survivors had an overall increased risk of hospitalization compared with those in the general population. Cancer survivors at highest risk for hospitalizations were leukemia, brain cancer and Hodgkin lymphoma survivors.

Survivors of adolescent and young adult cancers face persistent risks for a broad range of somatic diseases requiring hospitalization. The morbidity pattern, which is highly dependent on the type of cancer being treated, underscores the need for further implementation of strict evidence-based sex-, age- and cancer-specific follow-up plans for survivors, thereby increasing the likelihood for early detection and ultimately prevention of treatment-induced morbidities.

In the second study, Kevin Krull, PhD, of St. Jude Children’s Research Hospital, Memphis, and coauthors examined neurocognitive and patient-reported outcomes in adult survivors of childhood osteosarcoma, a type of bone cancer. The study included 80 survivors of osteosarcoma who were an average age of nearly 39 years and almost 25 years past diagnosis. The cancer survivors were compared with 39 community members unrelated to the cancer survivors. Long-term survivors had lower average scores in reading skills, attention, memory and processing speed. However, plasma concentration of methotrexate following high-dose intravenous administration during chemotherapy was not associated with neurocognitive outcomes at nearly 25 years after diagnosis.

Long-term survivors of osteosarcoma are at risk for neurocognitive impairment, which is related to current chronic health conditions and not to original treatment with high-dose methotrexate. … Our results demonstrate the need for increased attention in this diagnosis, with prospective studies to delineate the evolution of impairment over the course of therapy and long-term survival,” the authors conclude.

In a related editorial, Karen E. Effinger, MD, MS, and Michael P. Link, MD, of the Stanford University School of Medicine, California, write: “Advances in cancer therapy have led to increased survival; there are more than 9 million 5-year survivors of cancer in the United States. As this number continues to grow, focus on improved health and quality of life becomes a priority. … Going forward, we must apply our knowledge of late effects to improve monitoring and interventions for patients. While the progress made in the management of cancer in children and young adults has been gratifying, we must remember the words of Giulio D’Angio, who reminds us that ‘cure is not enough.'”Rugbjerg et al. Long-term Risk of Hospitalization for Somatic Diseases in Survivors of Adolescent or Young Adult Cancer. JAMA Oncol. Published online November 19, 2015. doi:10.1001/jamaoncol.2015.4393 [Article]Krull et al. Neurocognitive and Patient-Reported Outcomes in Adult Survivors of Childhood Osteosarcoma. JAMA Oncol. Published online November 19, 2015. doi:10.1001/jamaoncol.2015.4398 [Abstract]

Cancer scan could remove the need for radiotherapy in some patients

A UK National Cancer Research Institute trial led from The University of Manchester and the Christie NHS Foundation Trust has suggested that in patients with early stage Hodgkin lymphoma the late effects of radiotherapy could be reduced by using a scan to determine those who actually need it.

In a paper published in the New England Journal of Medicine, the researchers show that a positron-emission tomography (PET) scan immediately after treatment with chemotherapy can identify patients who have a very good outcome without additional radiotherapy.

Hodgkin lymphoma is a cancer that develops in the lymphatic system, which is a network of vessels and glands spread throughout the body. Around 1,900 people a year, many of whom are teenagers and young adults, are diagnosed in the UK.

The current standard treatment is for all Hodgkin lymphoma patients to receive chemotherapy, followed by radiotherapy. However, this radiotherapy comes with undesirable late effects, such as cardiovascular disease and other cancers – despite the fact that they have already been cured of Hodgkin lymphoma.

The 602 patients who agreed to take part in the ‘RAPID’ trial had a PET scan performed after their chemotherapy. Patients who tested positive received radiotherapy. Those who tested negative were divided into two groups – one group of 211 patients received no further treatment, while the other group of 209 had the standard radiotherapy.

After three years of regular check-ups, the proportion of patients who were alive and free of disease was 94.6% in the radiotherapy group, and 90.8% in the group which hadn’t received further treatment.

Lead researcher, Professor John Radford, is based at The University of Manchester’s Institute of Cancer Sciences and the Christie NHS Foundation Trust. He said: “This research is an important step forward. The results of RAPID show that in early stage Hodgkin lymphoma radiotherapy after initial chemotherapy marginally reduces the recurrence rate, but this is bought at the expense of exposing to radiation all patients with negative PET findings, most of whom are already cured.”

Despite the findings from this study the researchers stress that a longer follow-up period is needed in order to determine whether this approach will ultimately lead to fewer late side-effects and improved overall survival.

The research was funded by Leukaemia & Lymphoma Research. Dr Matt Kaiser, Head of Research at the charity, said: “This ground breaking clinical trial shows that, by using scans to predict an individual’s risk of relapse, many patients can remain disease-free with just chemotherapy alone. Radiotherapy can cause a range of long-term problems like heart disease and hard-to-treat second cancers. As many Hodgkin lymphoma patients are relatively young, it is particularly important to avoid using intensive treatment when it is unnecessary.”

Radford et al. Results of a Trial of PET-Directed Therapy for Early-Stage Hodgkin’s Lymphoma. N Engl J Med. 2015; 372:1598-1607, DOI:10.1056/NEJMoa1408648 [Article]