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HIV Infection, Cancer Treatment Regimens, and Cancer Outcomes Among Elderly Adults in the United States......HIV+ Elevated Cancer Mortality-BREAST/PROSTATE/Colorectal
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In response to this paper:
Hi Jules, I thought if you when I read this manuscript, I do think drug -drug interactions can be a contributing factor. Here are my 3 cents in the manuscript:
In the manuscript published in JAMA Oncology on Aug 1, Coghill and colleagues evaluated cancer outcomes in people living with HIV by evaluating a large data base that links cancer diagnoses to Medicare claims. This important study was able to evaluate cancer outcomes in people > 65 years of age, which is a small but growing proportion of the population living with HIV. The study found that people living with HIV who had local or reginomal cancers NOT associated with HIV (breast, colorectal, and prostate cancer) had inferior survival, even after correcting for important demographic factors. It is critically important for the research community to understand why this may be the case, and the study raises several important questions.
1. The study accounted for reciept of cancer therapy, and other important factors such as time to treatment. However, cancer care is complex and it will be important to determine if there were other unmeasured provider and health care system related factors that may account for the findings such as polypharmacy, differences in administration of targeted therapies, decreased dosing of therapy in people with HIV, and importantly...lack of access to clinical trials.
2. Are there immune factors at play? The study design did not allow for evaluation of immune status (i.e CD4 count). There is a broad spectrum of immune suppression among people living with HIV that is related to how soon people start HIV therapy. The findings may not be generalizable to people who start HIV therapy early and have a normal CD4 count.
3. Why do women with HIV and stage 3 breast cancer relapse sooner? Is this due to treatment related factors, distribution of breast cancer biology (i.e. more triple negative breast cancer), or are there previously unrecognized factors related to underlying HIV or HIV related immune dysfuction?
4. Interestingly, the study did not find inferior outcomes for lung cancer, which is a cancer that is associated with HIV. This raises the possibility that HIV may affect cancer risk and cancer outcomes differently.
Cancer therapy has improved substantially in the last 20 years for both people living with HIV and the general population. Studies that aim to continue to reduce of cancer disparities in people living with HIV will be critical. This important manuscript highlights the need for greater attention to non-AIDS defining malignancies, and cancer care (and management of other co-morbidities) in people living with HIV over the age of 65.
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Elderly HIV-infected patients with cancer experience poorer cancer outcomes than HIV-uninfected patients receiving similar stage-appropriate cancer treatment. People living with HIV are expected to die at higher overall rates due to the contribution of AIDS-related comorbidities, but we report that HIV-infected patients with cancer who are 65 years or older are also at increased risk of cancer-specific death and relapse after initial therapy.
We previously reported that HIV-infected patients with cancer in the United States had elevated cancer-specific mortality for melanoma and cancers of the colorectum, pancreas, larynx, lung, breast, and prostate. 2 Recent findings in a study of data from the National Cancer Database suggest that this survival deficit persists for each of these cancers after adjustment for receipt of health insurance and the type of facility administering cancer care.5 However, those studies lacked detailed cancer treatment data, perhaps the most important determinant of prognosis. Our use of the SEER-Medicare linked database allowed us to adjust for the treatment effect of first-course cancer regimens on patient outcomes. This approach is important given the lower cancer treatment rates often observed in the HIV-infected patient population with cancer.6-8 Our observation of a persistent survival disparity after adjusting for available first-year cancer treatment data suggests that health care differences are not the sole driver of poor cancer outcomes in the HIV population.
We hypothesize that HIV-associated immunosuppression plays a direct role in affecting tumor behavior and patient outcomes. This is supported by the ever-growing body of evidence demonstrating the utility of immunotherapies for improving cancer outcomes,16-19 as well as data demonstrating impaired cancer survival in immunosuppressed transplant recipients.20 Of note, HIV is associated with worse outcomes across a range of cancers with different etiologies, implying a broad role for HIV-associated immunosuppression in controlling cancer after a tumor has been diagnosed.
• women diagnosed with regional-stage breast cancer, with HIV-infected women being nearly 3 times more likely than HIV-uninfected women to die from breast cancer (HR, 2.91
• HIV-infected patients experienced significant elevations in overall mortality compared with HIV-uninfected patients for cancers of the colorectum (hazard ratio [HR], 1.73; 95% CI, 1.11-2.68; P = .02), prostate (HR, 1.58; 95% CI, 1.23-2.03; P < .01), and breast (HR, 1.50; 95% CI, 1.01-2.24; P = .05) (Table 2). Cancer-specific mortality was also elevated in HIV-infected patients with cancer compared with their HIV-uninfected counterparts for cancers of the breast (HR, 1.85; 95% CI, 0.96-3.55; P = .07) and prostate (HR, 1.65; 95% CI, 0.98-2.79; P = .06)
JAMA Oncol.
Anna E. Coghill, PhD, MPH; Gita Suneja, MD; Anne F. Rositch, PhD; Meredith S. Shiels, PhD; Eric A. Engels, MD
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland (Coghill, Shiels, Engels); Cancer Epidemiology Program, H. Lee Moffitt Cancer Center &
Research Institute, Tampa, Florida (Coghill); Radiation Oncology, Duke University, Durham, North Carolina (Suneja); Department of
Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Rositch).
Mortality rates following a cancer diagnosis are higher in HIV-infected patients than in HIV-uninfected patients.1,2 Poorer survival is not limited to malignant neoplasms with a viral etiology,3,4 and worse outcomes persist after adjustment for differences in patient demographics and cancer stage. Recent findings from the National Cancer Database have indicated that elevated mortality rates in HIV-infected patients with cancer also remain after adjustment for receipt of health insurance and the type of facility administering cancer care.5 Together, these results suggest that HIV infection itself, likely because of associated immunosuppression, may contribute to elevated mortality in patients with cancer.
Question Can the elevated mortality rate in HIV-infected patients with cancer vs HIV-uninfected patients with cancer be explained by receipt of suboptimal cancer treatment?
Findings Data from the US Surveillance, Epidemiology, and End Results–Medicare linked database indicated that elevated cancer-specific mortality among HIV-infected patients diagnosed with cancer between 1996 and 2012 persisted after adjustment for administered first-course cancer treatments; evidence was strongest for prostate and breast cancers.
Meaning Elevated cancer-specific mortality in HIV-infected patients was not entirely explained by differences in cancer treatment and may instead reflect an association between immunosuppression and cancer control.
RESULTS: In this database study of 308 268 patients with nonadvanced cancer (168 998 men and 139 270 women; age, ≥65 years), HIV-infected patients (n = 288) had significant elevations in the overall mortality rate compared with HIV-uninfected patients for cancers of the colorectum (hazard ratio [HR], 1.73; 95% CI, 1.11-2.68; P = .02), prostate (HR, 1.58; 95% CI, 1.23-2.03; P < .01), and breast (HR, 1.50; 95% CI, 1.01-2.24; P = .05). Cancer-specific mortality was elevated for prostate (HR, 1.65; 95% CI, 0.98-2.79; P = .06) and breast cancer (HR, 1.85; 95% CI, 0.96-3.55; P = .07). Compared with their HIV-uninfected counterparts, HIV-infected men with prostate cancer also experienced significantly higher rates of relapse or death (HR, 1.32; 95% CI, 1.03-1.71; P = .03) as did HIV-infected women with breast cancer (HR, 1.63; 95% CI, 1.09-2.43; P = .02).
Conclusions and Relevance In the United States, elderly HIV-infected patients with cancer, particularly prostate and breast cancers, have worse outcomes than HIV-uninfected patients with cancer. This disparity persists even after adjustment for administered first-course cancer treatments and will become increasingly relevant as the HIV population in the United States continues to age.
As the HIV population continues to age, the association of HIV infection with poor breast and prostate cancer outcomes will become increasingly relevant, especially because prostate cancer is projected to become the most common malignant neoplasm in the HIV population in the United States by 2030.21 Research on clinical strategies to improve outcomes in HIV-infected patients with cancer is warranted
Elderly HIV-infected patients with cancer experience poorer cancer outcomes than HIV-uninfected patients receiving similar stage-appropriate cancer treatment. People living with HIV are expected to die at higher overall rates due to the contribution of AIDS-related comorbidities, but we report that HIV-infected patients with cancer who are 65 years or older are also at increased risk of cancer-specific death and relapse after initial therapy.
We previously reported that HIV-infected patients with cancer in the United States had elevated cancer-specific mortality for melanoma and cancers of the colorectum, pancreas, larynx, lung, breast, and prostate.2 Recent findings in a study of data from the National Cancer Database suggest that this survival deficit persists for each of these cancers after adjustment for receipt of health insurance and the type of facility administering cancer care.5 However, those studies lacked detailed cancer treatment data, perhaps the most important determinant of prognosis. Our use of the SEER-Medicare linked database allowed us to adjust for the treatment effect of first-course cancer regimens on patient outcomes. This approach is important given the lower cancer treatment rates often observed in the HIV-infected patient population with cancer.6-8 Our observation of a persistent survival disparity after adjusting for available first-year cancer treatment data suggests that health care differences are not the sole driver of poor cancer outcomes in the HIV population.
We hypothesize that HIV-associated immunosuppression plays a direct role in affecting tumor behavior and patient outcomes. This is supported by the ever-growing body of evidence demonstrating the utility of immunotherapies for improving cancer outcomes,16-19 as well as data demonstrating impaired cancer survival in immunosuppressed transplant recipients.20 Of note, HIV is associated with worse outcomes across a range of cancers with different etiologies, implying a broad role for HIV-associated immunosuppression in controlling cancer after a tumor has been diagnosed.
During the period starting 1 year after cancer diagnosis, HIV-infected patients experienced significant elevations in overall mortality compared with HIV-uninfected patients for cancers of the colorectum (hazard ratio [HR], 1.73; 95% CI, 1.11-2.68; P = .02), prostate (HR, 1.58; 95% CI, 1.23-2.03; P < .01), and breast (HR, 1.50; 95% CI, 1.01-2.24; P = .05) (Table 2). Cancer-specific mortality was also elevated in HIV-infected patients with cancer compared with their HIV-uninfected counterparts for cancers of the breast (HR, 1.85; 95% CI, 0.96-3.55; P = .07) and prostate (HR, 1.65; 95% CI, 0.98-2.79; P = .06). The association between HIV and elevated cancer-specific mortality was statistically significant for women diagnosed with regional-stage breast cancer, with HIV-infected women being nearly 3 times more likely than HIV-uninfected women to die from breast cancer (HR, 2.91; 95% CI, 1.31-6.46; P < .01). This distinction in cancer-specific mortality by stage could not be evaluated for prostate cancer because all men were classified in SEER as having nonadvanced disease without further categorization.
We examined the risk of the combined outcomes of relapse or death and relapse or cancer-specific death in patients who survived at least 15 months after diagnosis (Table 3). Compared with HIV-uninfected patients, HIV-infected men with prostate cancer were significantly more likely to experience relapse or death (HR, 1.32; 95% CI, 1.03-1.71; P = .03), and more likely to experience relapse or cancer-specific death (HR, 1.28; 95% CI, 0.92-1.78; P = .15). More than half (53%) of these events were claims for retreatment. The association of HIV with retreatment alone was 1.23 (95% CI, 0.87-1.75; P = .23). Among women, HIV-infected patients with breast cancer were significantly more likely than their HIV-uninfected counterparts to experience both relapse or death (HR, 1.63; 95% CI, 1.09-2.43; P = .02) and relapse or cancer-specific death (HR, 1.90; 95% CI, 1.10-3.28; P = .02). Retreatment for breast cancer comprised approximately one-third of these events, and the association of HIV with retreatment alone was 1.59 (95% CI, 0.83-3.07; P = .16).
Conclusions
In this nationally representative sample of the aging HIV population in the United States, HIV was associated with an elevated risk of overall and cancer-specific mortality. HIV-infected patients with prostate or breast cancer appeared to be at particularly increased risk of worse outcomes, even after adjustment for available data on first-year cancer treatments. As the HIV population continues to age, the association of HIV infection with poor breast and prostate cancer outcomes will become increasingly relevant, especially because prostate cancer is projected to become the most common malignant neoplasm in the HIV population in the United States by 2030.21 Research on clinical strategies to improve outcomes in HIV-infected patients with cancer is warranted
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