HIV/AIDS Kaposi’s Sarcoma

A Practical Approach

Anisa MosamMB ChB( Natal), FC Derm(SA), MMed( Derm)

NRMSOM, UKZN

AWACC1-2 October 2009

ICC

Epidemiologic Types

• Classic• Endemic• Iatrogenic• Epidemic

Introduction

• Multicentric tumour originating from vascular and lymphatic endothelial cells

• Sites: – Skin– Lymphatics– Mucosal– Visceral: GIT & Pulmonary

Cutaneous Features

• Asymptomatic pink to purple or brown

• Patches, papules, plaques, nodules or tumours

• Round, oval, elongated, fusiform• Undiagnosed or overlooked

Cutaneous Sites

Head and neck, earlobes, occiput

Cutaneous Sites• upper torso, extremities• Widespread, symmetric, Langers lines

Mucosal Involvement

• Oral cavity in 20% at diagnosis

• Tongue, hard & soft palate• Associated with GIT KS

Visceral Involvement: GIT

• >50% clinically• 80% at autopsy• May be asymptomatic• Symptoms: Abd pain, bloody stools,

LOW

Visceral Involvement: Pulmonary

• 30% clinically• 50% at autopsy• Symptoms: dyspnoea,

cough, effusions• Survival poor

Lymphatic Involvement

• Lymphadenopathy

• Lymphoedema• Woody hard

induration• Non-pitting

oedema

KS mimickers

Patch Papules Nodules

Bruises Secondary SyphilisPPE

Pyogenic Granuloma

Purpura Lichen Planus Bacillary Angiomatosis

Haemangiomas Basal Cell Carcinoma Dermatofibroma

Naevi Squamous Cell Carcinoma

Investigations

• biopsy• CD4 and HIV-1 viral load • CXR• Stool occult blood• Sputa MCS and AFB• If GIT symptoms, endoscopy• If abnormal CXR or symptoms,

bronchoscopy

Diagnosis

• Proliferation of abnormal vascular spaces, lymphaplasmacytic infiltrates

• Endothelial cells contain HHV 8

• Spindle cells predominant cell

Biopsy: Skin, endoscopic or transbronchial

Aetiopathogenesis

• HIV Tat protein, angiogenic• Inhalant nitrites and exposure of lymphatic and

vascular endothelium to nitrites in semen• Saliva• HHV 8

HHV 8 and KS

• Genes homologous to cellular oncogenes

• Alter cell cycle• Inhibit apoptosis• Evade immune mechanisms• Promote angiogenesis

Direct role of HIV-1 in KS

• Production of the HIV-1 Tat protein– Indirectly increases B-FGF Angiogenesis– Activates HHV 8

•Increases viral loads•Expression of viral oncogenes

–v-GPCR–V-Bcl-2

• Promoting cytokine production– Tumour initiation– Progression

Staging

• 1988 ACTG: Good risk and Poor risk• T tumour extent• I immune status CD4• S systemic symptoms• Validated by Krown et al• TIS system effectively predicted survival Prior

to HAART• Data from 281 patients from 34 ACTG sites

Staging Classification- “TIS”

Krown, SE J Clin Oncol 1989; 7:120

Good Risk (All) Poor Risk (Any)

T (Tumor)

T0: 27 mo survivalSkin, minimal oral mucosa, lymph node only

T1: 15 mo Edema or ulcerationExtensive oral mucosaVisceral KS

I (Immune System)

I0: 40 mo

CD4>150

I1: 13 mo

CD4<150

S (Systemic Illness)

S0: 22 mo No OI’s or thrushNo B symptomsKarnofosky >70%

S1: 16 mo Hx of OI’s or thrushB symptoms presentKarnofosky<70%Other HIV related disease

Staging in HAART era

• Nasti et al, 2003• 211 patients from 2 prospective

Italian cohort studies• 3yr survival:• 85% T0 69% T1 (p=0007)• 83% S0 63% S1 (p=.003)• 83% I0 71% I1 (p=.06)

3 year survival

• T1S1 53% poor risk

• T0S0 88%• T1S0 80%• T0S1 81% good risk• (p= .0001)

HAART and KS

• Profoundly influenced natural history of KS• Incidence declined• Lengthened time to rx failure• Improved survival in pulmonary KS with CXT• KS regression

Krown JCO vol 22 no 3 2004:399-402

HAART and KS

Int Collaboration of HIV and Cancer, Int Collaboration of HIV and Cancer,

J Nat Cancer Inst, 92(22) :1823-30 : J Nat Cancer Inst, 92(22) :1823-30 : 20002000

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HAART and KS

• Decreased HIV Tat and cytokines• Indirectly by CD4 restoration• Restored immunity to HHV 8• PI’s antiangiogenic

PI’s vs NNRTI’s

• PI’s have anti-angiogenic activity• both PI and NNRTI’s similarly improved • HHV 8 immunity to and clearance of

viraemia• No evidence that PI’s regimen of choice• HAART durable HIV VL suppression and CD4

restoration is key

Bourboulia AIDS 18,485-493 2004

Baseline 8 weeks 12 weeks

16 weeks HAART 20 weeks HAART 48 weeks HAART

IRIS related oedema

Baseline 2 weeks HAART

Before 4 Weeks HAART

KS IRIS

8 weeks post HAART

KS IRIS• Worsening of existing KS or development

of new lesions on HAART• Associated with rapid decline in HIV VL

and increase in CD4 • Close monitoring required• pulmonary involvement fatal• HAART continued but CXT required• British cohort of 150 KS 6.6% developed

IRIS KS• Higher CD4, KS oedema, PI + NNRTI

regimen

Lipman Curr Opinion Inf Dis 2006;19:20-25Bower J Clin Oncol 2005 Aug 1;23(22):5224-8

Corticosteroids and KS

• Corticosteroids have been associated with the induction or exacerbation of KS in HIV patients

• Generally, should be avoided • Use only in:

– acute respiratory distress syndrome accompanying HIV-related opportunistic pulmonary infection

– tuberculosis meningitis or pericarditis– immune thrombocytopenic purpura, if necessary

Treatment

• HAART• Local therapy• Systemic therapy

Local treatment of KS

• Radiation therapy• Cryotherapy : 80% RR regardless of CD4• Laser surgery • Excisional surgery• Electrocauterization• Intralesional chemotherapy• Topical retinoids

Systemic cytotoxic therapy

Important factors :

– Extent of KS – performance status– organ function (especially liver and bone

marrow)– Degree of immunosuppression (CD4 count), – Concomitant medications

Systemic cytotoxic therapy

Indications : • palliation of tumour-related symptoms (pedal or

scrotal oedema)• treatment of pulmonary KS,• progressive mucocutaneous lesions (> 25 lesions)• extensive Kaposi’s sarcoma of the oral cavity• Symptomatic visceral involvement• IRIS

Combination chemotherapy

• ABV / ABVb • Oral Etoposide• most widely used in poor resource settings • Standard of care in the past• Been replaced by newer drugs• More toxic and less effective than • Liposomal anthracyclines • Paclitaxel• Should only be reserved where Liposomal

anthracyclines and paclitaxel aren't available

Local Policy

• HIV• CD4• FBC• Histology• On HAART

Public Sector Policy

• If CD4 >150• Oral Etoposide 50-100 mg for 3

weeks• Repeated for at least 3-6 months• If tumour progression• IVI CXT with AVB• If T progression and good HIV control

and performance….3rd line CXT

Public Sector Policy

• If CD4 count <150• Continue HAART• Review in 6 months• If local control required/palliation• 8Gy RXT single dose• Max 20-30 Gy esp for oral disease

Kaposi’s sarcomaBiopsy

HIVCD4

HAART

Localized disease Systemic disease

Etoposide ABV/BV/VRadiotherapyIntralesional drugsCryotherapy

Limited to skin LymphoedemaFungating tumour

BleedingDisseminated

CutaneousLymphedoema

Visceral diseaseIRIS

Large oral lesions

ALGORITHMIC APPROACH TO HIV KS

Thank You

Assessing response

• numerous cutaneous lesions• reproducible lesion counts difficult• Estimates of <10;10-50 and >50 used• Photographs of all body areas• 3-5 marker lesions selected • photos and body diagrams• Tumour-assd oedema documented• Checklist of anatomical area

Complete response (CR) resolution of any detectable disease for 4 weeks.

Partial response (PR) is a 50% or > decrease in number and/or size of all existing lesions for at least 4 weeks, without the appearance of new lesions. A response may be assigned to a diminution in the diameter of all lesions, or to flattening of at least 50% of the lesions. The size of each lesion will be the product of the longest dimension and the maximum dimension perpendicular to it.

Stable disease (SD) response not meeting the criteria for progression or PR

Progression is defined as at least a 25% increase in the size of any lesion or the appearance of any new lesions. Krown J Clin Oncol 1989

ResponseResponse