Miss Maggie Smith. Chelsea and Westminster Hospital, London THIRD JOINT CONFERENCE OF BHIVA AND BASHH 2014

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2 THIRD JOINT CONFERENCE OF BHIVA AND BASHH 2014 Miss Maggie Smith Chelsea and Westminster Hospital, London 1-4 April 2014, Arena and Convention Centre Liverpool

3 Second Malignancies in patients with Kaposi s Sarcoma: does systemic chemotherapy contribute to the risk? Maggie Smith Chelsea and Westminster Hospital NHS Foundation Trust

4 Background Second primary cancers are an increasingly important concern Cancer, both NADM and ADM is increasing in PLWA Risk of developing second cancers are increased by chemotherapy and radiotherapy (second primary cancers) Factors increasing risk of second malignancies include: People living with HIV (PLWH) Systemic chemotherapy/radiotherapy The contribution of systemic liposomal anthracycline chemotherapy (SLAC) to the development of second cancers in PLWH is unknown

5 Long term side effects of chemotherapy Type of agent, cumulative dose, exposure time, mode of administration and interaction with other treatments all seem to play a role in secondary cancer developments. Accumulating evidence to suggest topoisomerase inhibitors, including anthracyclines doxorubicin and daunorubicin cause second primary malignancies.

6 Anthracyclines Mechanism of action: Anthracyclines intercalate DNA and inhibit religation of DNA cleaved by topoisomerases causing apoptosis and oncogenesis of second cancers Characteristic translocation involving chromosome band 11q23 Short latency period (months- 2 years)

7 Liposomal Anthracyclines Successful treatment for KS used in conjunction with cart. Bound within a nano-scale liposome. Liposomes increase uptake by cancer cells. Slows drug binding to proteins of healthy cells, delivering chemotherapy over a longer period of time. Unknown whether the lipid capsule can protect against long term side effects of Liposomal Anthracyclines.

8 Study Objectives Aim Does Liposomal Anthracycline chemotherapy contribute to the risk of developing second malignancies in patients with KS? Objective Incidence of Cancer (ADM/NADM) after LA vs. no chemo Secondary Objectives Does incidence correlate to cumulative LA dose/m 2 What second malignancies occurred Correlation with other risk factors age, gender, T stage, CD4 count, HHV8 titre, ARV use, Hep B/C status

9 Research Methods Retrospective analysis of prospective collected cohort data Population - PLWH and KS treated with a stagestratified approach since 1998 (T1= chemo + cart : T0 = cart) Controls - PLWH and KS who have not received chemotherapy

10 Results Since 1998, 496 PLWH and KS have been treated with a stage-stratified approach including 157 who received SLAC More patients who received SLAC had T1 stage disease (p<0.0001) No significant differences in other variables between the two groups

11 Results

12 Results Median follow-up 4.3 years (maximum 15 years) from KS diagnosis 34 patients developed a second cancer (10 ADM & 24 NADM) 5 year cumulative risk of second cancer is 5.6% (95%CI: %) No significant difference in the rate between those treated with SLAC and those not (log rank p=0.69)

13 Results NADM cart alone (n=19) cart + LA (n=5) BCC (n=4) SCC Cholangiocarcinoma Myeloma (n=2) Hodgkin's Disease (n=3) Glomus Tumour Anal Cancer (n=3) NSCLC (n=2) CUP Head and Neck Cancer SCC (n=2) Rectal Hodgkin's Disease NSCLC ADM cart alone (n=5) cart + LA (n=5) DLBCL (n=3) Burkitts Lymphoma Microlymphoma DLBCL (n=2) Primary CNS Lymphoma Microlymphoma Primary Effusion Lymphoma

14 Results Most patients (n=117) were treated with daunoxome (liposomal daunorubicin) chemotherapy No significant correlation between risk of second cancer and cumulative dose of daunoxome (p=0.06) Percentage second cancer free No chemo n= 338 (24 cancers) Liposomal anthracycline chemo n=156 (9 cancers) Years

15 Limitations Paclitaxel chemotherapy and radiotherapy not accounted for No correction for second or subsequent lines of therapy (Paclitaxel/radiotherapy)

16 Conclusions Longevity of the HIV/AIDS population has allowed for the emergence of age-related diseases including NADMs. There is a rising incidence of NADM in PLWH. Prior Liposomal Anthracycline Chemotherapy for KS does not appear to be a major contributor to this. Can reassure patients no significant increase in the development of second primary malignancies after LAC was found.

17 Acknowledgements Professor Mark Bower Dr Mark Nelson Dr Kirsty Balachandran Ms Jessica Pealing Ms Shauna McCann Galen and St Stephen s AIDS Trust for financial support

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