Transcript HIV/AIDS Kaposi`s Sarcoma A Practical Approach

HIV/AIDS Kaposi’s Sarcoma
A Practical Approach
Anisa Mosam
MB ChB( Natal), FC Derm(SA), MMed( Derm)
NRMSOM, UKZN
AWACC
1-2 October 2009
ICC
Epidemiologic Types
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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
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>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 Syphilis
PPE
Pyogenic Granuloma
Purpura
Lichen Planus
Bacillary Angiomatosis
Haemangiomas
Basal Cell Carcinoma
Dermatofibroma
Naevi
Squamous Cell Carcinoma
Investigations
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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
Biopsy: Skin, endoscopic or transbronchial
• Proliferation of
abnormal vascular
spaces,
lymphaplasmacytic
infiltrates
• Endothelial cells
contain HHV 8
• Spindle cells
predominant cell
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
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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
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1988 ACTG: Good risk and Poor risk
T
tumour extent
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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”
Good Risk (All)
Poor Risk (Any)
T
(Tumor)
T0: 27 mo survival
Skin, minimal oral mucosa,
lymph node only
T1: 15 mo
Edema or ulceration
Extensive oral mucosa
Visceral KS
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(Immune System)
I0: 40 mo
I1: 13 mo
CD4>150
CD4<150
S
(Systemic Illness)
S0: 22 mo
No OI’s or thrush
No B symptoms
Karnofosky >70%
S1: 16 mo
Hx of OI’s or thrush
B symptoms present
Karnofosky<70%
Other HIV related disease
Krown, SE J Clin Oncol 1989; 7:120
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
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53%
T0S0
88%
T1S0
80%
T0S1
81%
(p= .0001)
poor risk
good risk
HAART and KS
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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
Adjusted incidence ratio
16
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2
0
1992
1997
Int Collaboration of HIV and Cancer,
J Nat Cancer Inst, 92(22) :1823-30 : 2000
HAART and KS
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Decreased HIV Tat and cytokines
Indirectly by CD4 restoration
Restored immunity to HHV 8
PI’s antiangiogenic
PI’s vs NNRTI’s
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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
KS IRIS
Before
4 Weeks HAART
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;19:20-25
Bower 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
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Radiation therapy
Cryotherapy : 80% RR regardless of CD4
Laser surgery
Excisional surgery
Electrocauterization
Intralesional chemotherapy
Topical retinoids
Systemic cytotoxic therapy
Important factors :
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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
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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
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HIV
CD4
FBC
Histology
On HAART
Public Sector Policy
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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
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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
ALGORITHMIC APPROACH TO HIV KS
Kaposi’s sarcoma
Biopsy
HIV
CD4
HAART
Localized disease
Limited to skin
Intralesional drugs
Cryotherapy
Systemic disease
Lymphoedema
Fungating tumour
Bleeding
Radiotherapy
Disseminated
Cutaneous
Lymphedoema
Etoposide
Visceral disease
IRIS
Large oral lesions
ABV/BV/V
Thank You
Assessing response
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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
Response
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