Kaposi sarcoma

Background

• A tumour associated with HHV-8
• Closely associated with advanced HIV, but may also present as classic, endemic, or transplant-related KS
• This page is focussed on HIV-related KS

ACTG Staging

• Based on extent of tumour (T), immune status (I), and severity of systemic illness (S)

Criterion	Lower Risk (0)	Higher risk (1)
Tumour (T)	Confined to skin and/or lymph nodes and/or minimal oral disease (non-nodular KS confined to palate)	Tumor-associated edema or ulceration; extensive oral KS; gastrointestinal KS; or KS in other non-nodal viscera
Immune status (I)	CD4 cell count >200/µL	CD4 cell count <200/µL
Systemic illness (S)	No history of OI or thrush; no "B" symptoms; and Karnofsky performance status >70	History of OI or thrush; "B" symptoms present; Karnofsky performance status <70; or other HIV-related illness (eg, neurologic disease, lymphoma)

• However, staging only distinguishes between good risk (T0I0S0) and poor risk (literally all others), used for predicting mortality in the pre-ART era
  • The 3-year survival rate of patients post-ART with T1S1 is about 50%, whereas for T0S0, T1S0, and T0S1 was all 80-90%; immune status does not appear to be predictive1

Clinical Manifestations

• Non-tender, hyperpigmented skin lesions
• May be macular or nodular
• Oral lesions in about a third
• May involve lymphatics, causing severe edema
• May involve the viscera, which may be asymptomatic or cause dyspnea (lungs), hematochezia or melena (GI tract), or other signs and symptoms

IRIS

• Treatment of HIV-associated KS may cause IRIS, either associated with new lesions or with worsening of existing lesions
• May be "unmasking" (first presentation) or paradoxical worsening of pre-existing lesions
• Risk factors for IRIS include T1 tumour stage, pre-treatment HIV viral load > 5 logs, detectable HHV-8 viremia, and initiation of ART without concurrent chemotherapy

Management

• Treatment goals are symptom alleviation, prevention of disease progression, and shrinkage of tumour to alleviate edema, organ compromise, and psychological stress

HIV Patients

• Combination antiretroviral therapy is the mainstay of treatment for all patients with HIV
• Disease may worsen for 3 to 6 weeks following initiation of ART, due to immune reconstitution inflammatory syndrome
• Try to decrease or stop any corticosteroids, if possible, since it appears to worsen KS

Transplant Patients

• Try to include mTOR inhibitors, such as rapamycin and sirolimus, in the immunosuppression regimens

Local Treatments

• Intralesional vinblastine 0.2 to 0.3 mg/mL solution with a volume of 0.1 mL per 0.5 cm2 of lesion
  • May be repeated at 3 to 4 weeks
• Radiation therapy
• Topical alitretinoin

Systemic Chemotherapy

• Used in cases of advanced or rapidly-progressive disease
• Indications include:
  • Symptomatic visceral involvement
  • Widespread skin involvement (eg, more than 25 lesions)
  • Extensive cutaneous KS that is unresponsive to local treatment
  • Extensive edema
  • Immune reconstitution inflammatory syndrome
  • Progression of KS on ART alone

• Options include pegylated liposomal doxorubicin or liposomal daunorubicin, paclitaxel, bleomycin, vinblastine, vincristine, or etoposide
  • First-line: liposomal doxorubicin 20 mg/m² every three weeks
  • Second-line: paclitaxel

Direct Antivirals

• In vitro activity of ganciclovir, foscarnet, and cidofovir has not translated into clinical efficacy
• Not recommended

IRIS

• Supportive care
• Chemotherapy
• Avoid steroids

Prognosis

Prognostic Index

• Predicts survival following the development of HAART2

Criteria

Criterion	Score
KS as first AIDS-defining illness	-3
Age ≥50 years	+2
CD4 count	-1 for every 100 cells
S1 stage	3

Interpretation

Score	6 months	1 year	2 years	5 years
0	99.8%	99.3%	99.0%	98.4%
5	98.7%	96.7%	94.6%	91.8%
10	93.3%	83.4%	74.1%	63.1%
15	69.2%	37.8%	19.9%	8.4%

Further Reading

• Human Herpesvirus-8 Disease. In: Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. NIH, CDC, HIVMA, and IDSA. Available at [1]
• Diagnosis and treatment of Kaposi's sarcoma: European consensus-based interdisciplinary guideline (EDF/EADO/EORTC). Eur J Cancer. 2019;114:117-127. doi: 10.1016/j.ejca.2018.12.036