Scoring tool predicts risk of KS progression

Swiss researchers have developed a scoring tool to help identify HIV-positive patients with Kaposi’s sarcoma (KS) who are most likely to experience KS disease progression. The tool, they write in a report in the May 31^st edition of AIDS, can help target treatment to patients who would benefit the most, while sparing lower-risk cases.

Effective HIV therapy has reduced incidence of Kaposi’s sarcoma among people with HIV, with dramatic decreases in the number of new cases seen following the introduction of effective antiretroviral therapy in the mid 1990s. Nonetheless, response of established KS to treatment is unpredictable; some cases regress, many progress, and 30% of patients with progression will die.

There is little information on predictors of KS disease progression, and clinicians have difficulty in directing treatment for KS to the patients who are mostly likely to have progression. A scoring method would help identify high-risk patients while sparing lower-risk patients the toxicity associated with anti-KS chemotherapy.

To better understand predictors of KS progression, investigators with the Swiss HIV Cohort Study performed a retrospective analysis of cases of KS pulled from the study’s extensive database. The records of patients with laboratory confirmed or clinically diagnosed KS were evaluated for a series of potential prognostic factors, including sociodemographic characteristics, KS disease stage, characteristics of HIV disease and treatment and virologic markers of infection by human herpesvirus 8 (HHV-8), the virus associated with KS.

KS tumours were staged as either T0: KS lesions confined to the skin, lymph nodes or with limited oral involvement; or T1: advanced KS of the skin and mouth, KS-associated oedema, or KS involving any visceral organ. Virologic markers of HHV8 were quantitative PCR of HHV-8 DNA and titres for antibodies against the virus.

Investigators recorded prognostic factors at baseline and then looked to see which cases resulted in chemotherapy or in death. Chemotherapy was started in 27% of cases, and the mortality rate, due to any cause, was 21%. These numbers, the investigators note, are in line with other published reports of KS survival.

In multivariate analysis the investigators identified three baseline factors associated with increased risk of poor outcome:

• Disease stage of T1 with a hazard ratio (HR) of 5.22 (p
• CD4 cell count below 200 cells/mm³, with a HR of 2.33 (p = 0.01)
• PCR assay positive for HHV8 DNA, with a HR of 2.14 (p = 0.01)

Factors not associated with a worse outcome included age, sex, sexual orientation, geographic origin or the use of antiretroviral therapy.

Based on the three factors and their associated risks, the investigators proposed a simple scoring system in which T1 disease stage counts for two points and CD4 cell count below 200 cells/mm³ and positive HHV8 DNA PCR both count for one point.

“Our score is simple to use at the patient’s bedside,” the investigators write. “Each point increase in the scale is associated with a two-fold increase in the risk of death or need for chemotherapy. We suggest that patients with an index of two or more have a poor risk and should be followed more closely and chemotherapy should be considered, whereas patients with a lower score could be treated with HAART alone.” A recent report by Italian researchers has suggested that antiretroviral therapy may be key to treating KS.

The investigators note that both KS disease stage and CD4 cell count have been previously associated with disease progression, but theirs is the first study to identify HHV-8 DNA quantification as a predictor. Results from the few, small studies completed have suggested that the absence of HHV8 in blood cells predicts a better clinical response.

The investigators also highlight that, in contrast with some reports that protease inhibitor-based antiretroviral regimens may be more effective at controlling KS than non-nucleoside reverse transcriptase inhibitor-based regimens, their results revealed no difference in outcomes between antiretroviral regimen types.