Precision Medicine in Low- and Middle-Income Countries.

Most cancer cases occur in low- and middle-income countries (LMICs). The sophisticated technical and human infrastructure needed for optimal diagnosis, treatment, and monitoring of cancers is difficult enough in affluent countries; it is especially challenging in LMICs. In Western, educated, industrial, rich, democratic countries, there is a growing emphasis on and success with precision medicine, whereby targeted therapy is directed at cancers based on the specific genetic lesions in the cancer. Can such precision approaches be delivered in LMICs? We offer some examples of novel partnerships and creative solutions that suggest that precision medicine may be possible in LMICs given heavy doses of will, creativity, and persistence and a little luck.

Breast Cancer Clinical Trials: The Landscape at the Uganda Cancer Institute and Lessons Learned.

The Uganda Cancer Institute, the sole national comprehensive cancer center in Uganda, has a long and rich history of clinical investigation and locally relevant cancer research. Given the increasing burden of breast cancer in Uganda and elsewhere in sub-Saharan Africa (SSA) and driven by the limited availability of immunohistochemistry (IHC), we launched a clinical trial aimed at evaluating locally available diagnostics to detect the presence of hormone receptors (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2. Preliminary data from 32 women in the diagnostic component of the study reveal high sensitivity and specificity for estrogen receptor and progesterone receptor and high specificity for human epidermal growth factor receptor 2 when comparing reverse transcriptase polymerase chain reaction with the gold standard (IHC). Innovative diagnostic and treatment strategies are required to address the burden of breast cancer that is increasing throughout SSA. Given the costs, infrastructure, and trained personnel associated with IHC, alternative testing options (including reverse transcriptase polymerase chain reaction as tested in our study) may provide an expedited and cost-effective method to determine receptor testing in breast cancer. Clinical trials conducted in the local setting are critical to determining optimal strategies for effective breast cancer management in SSA.

AIDS-Related Kaposi Sarcoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin's lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.

Association Between HIV Infection and Cancer Stage at Presentation at the Uganda Cancer Institute.

PURPOSE: The HIV epidemic has contributed to the increasing incidence of cancer in sub-Saharan Africa, where most patients with cancer present at an advanced stage. However, improved access to HIV care and treatment centers in sub-Saharan Africa may facilitate earlier diagnosis of cancer among patients who are HIV positive. To test this hypothesis, we characterized the stage of cancer and evaluated the factors associated with advanced stage at presentation among patients in Uganda. METHODS: We conducted a retrospective analysis of adult patients with any of four specific cancers who presented for care in Kampala, Uganda, between 2003 and 2010. Demographic, clinical, and laboratory data were abstracted from the medical record, together with the outcome measure of advanced stage of disease (clinical stage III or IV). We identified measures for inclusion in a multivariate logistic regression model. RESULTS: We analyzed 731 patients with both AIDS-defining cancers (cervical [43.1%], and non-Hodgkin lymphoma [18.3%]), and non-AIDS-defining cancers (breast [30.0%] and Hodgkin lymphoma [8.6%]). Nearly 80% of all patients presented at an advanced stage and 37% had HIV infection. More than 90% of patients were symptomatic and the median duration of symptoms before presentation was 5 months. In the multivariate model, HIV-positive patients were less likely to present at an advanced stage as were patients with higher hemoglobin and fewer symptoms. CONCLUSION: Patients with limited access to primary care may present with advanced cancer because of a delay in diagnosis. However, patients with HIV now have better access to clinical care. Use of this growing infrastructure to increase cancer screening and referral is promising and deserves continued support, because the prognosis of HIV-positive patients with advanced cancer is characterized by poor survival globally.

Cancer in People Living With HIV, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

People living with HIV (PLWH) are diagnosed with cancer at an increased rate over the general population and generally have a higher mortality due to delayed diagnoses, advanced cancer stage, comorbidities, immunosuppression, and cancer treatment disparities. Lack of guidelines and provider education has led to substandard cancer care being offered to PLWH. To fill that gap, the NCCN Guidelines for Cancer in PLWH were developed; they provide treatment recommendations for PLWH who develop non-small cell lung cancer, anal cancer, Hodgkin lymphoma, and cervical cancer. In addition, the NCCN Guidelines outline advice regarding HIV management during cancer therapy; drug-drug interactions between antiretroviral treatments and cancer therapies; and workup, radiation therapy, surgical management, and supportive care in PLWH who have cancer.

Enzalutamide, a second generation androgen receptor antagonist: development and clinical applications in prostate cancer.

Enzalutamide, formerly known as MDV3100, is an oral second generation androgen receptor (AR) inhibitor that was chosen from a screen of agents and shown in preclinical studies to have greater affinity for the AR than its predecessors without any agonistic effects. The pre-clinical work that led to the interest in studying this agent and the history of the clinical development of enzalutamide from first in man phase 1 through phase 3 and regulatory approval are reviewed. Information about the toxicity profile and prescribing enzalutamide are discussed in detail. The availability of enzalutamide is put into context with the five other agents that modify survival outcomes in metastatic castration resistant prostate cancer. Some of the new challenges confronting the field regarding sequencing and combinations of these agents and the potential for a change in the natural history of the disease, are also discussed.