Aaron T. Gerds, MD, MS Hematology Oncology Fellow University of Washington School of Medicine

Transcription

1 Survivor: Hodgkin Aaron T. Gerds, MD, MS Hematology Oncology Fellow University of Washington School of Medicine Discussant: K Scott Baker MD MS K. Scott Baker, MD, MS Professor, Department of Pediatrics, UW Medical Director, Pediatric Blood and Marrow Transplant Program Seattle Cancer Care Alliance/Seattle Children s Hospital Member, CRD, Fred Hutchinson Cancer Research Center

2 Hodgkin lymphoma closing in on a cure for all 70 95% cured up front Response adapted (PET) approach may improve outcomes and reduce toxicity Auto transpalnt can cure ~40% Non ablative allo HCT may cure ~30% Novel agents Control relapsed disease Earlier use may yield more initial cures Slide courtesy of A. Gopal, MD

3 Progress in HL BEACOPP escalated ( ) BEACOPP baseline ( ) Pr robability COPP/ABVD ( ) 1993) Only alkylating agents (1965) Stanford V, CLVP/EVA ABVD? 0.2 No treatment (1940) Overall Survival (y) Figure courtesy of O. Press, MD, PhD

4 Age Specific Incidence and Death Rates, UK, Ic cidence pe er 100, Female Death Rate Male Death Rate Female Incidence Male Incidence 0.0 Age Cancer Research UK (2008). CancerStats report Hodgkin Lymphoma UK, Cancer Research UK.

5 Case

6 History of present illness A 21 year old male presented with a 3 hour history of substernal chest pain radiating to the left arm and jaw The pain began during strenuous exercise and was not relieved with rest. He had no dyspnea, lightheadedness, nausea, vomiting, or diaphoresis.

7 Past medical history Stage IIA Hodgkin s disease of the mediastinum diagnosed in cycles of COPP ABV 2,100 cgy mantle RT Recurrence in November cycles of ICE Autologous PBSCT in April cGy of mediastinal RT FVL heterozygote, h/o line thrombus

8 Meidcation, family, and social history Medications: None Family History Father: History of DVT Factor V Leiden Social History Athletic college student No alcohol or drugs

9 Examination Vitals: BP 138/80 HR 100 RR 18 99% RA 97kg Gen: Fit appearing male in mild distress HEENT: No JVD, no LAD CV: Tachycardic, regular rhythm, S1, S2, no murmur Lungs: Clear Abd: Soft, NABS, no organomegaly Ext: Warm, no edema

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11 Laboratory and imaging Troponin 91 (Normal <1.1) Echocardiogram Moderately hypokinetic anterolateral wall, EF 55% Angiogram Large filling df defect tin the proximal llad, small apical defect consistent with possible distal embolization

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13 Hospital course Admitted to ICU, thrombolytics Repeat angiogram 2 days later revealed decrease in thrombus Cardiac rehabilitation Discharged on hospital day 6 Discharge medications ASA, clopidogrel, warfarin, lisinopril, metoprolol, atorvastatin

14 Life after HL "Today, we have learned in the agony of war that great power involves great responsibility. FDR 1. Better understand the biological basis and clinical consequences of a cancer diagnosis and the associated therapeutic exposure 2 Propose develop and test strategies to avoid or 2. Propose, develop, and test strategies to avoid or minimize the adverse impact of cancer and its treatment

15 Common complications of HL therapy Secondary malignancies agaces Up to 20% in 20 yr (breast, lung, MDS/AML, NHL) Cardiovascular events Premature coronary artery disease Cardiomyopathy Valvular disorders Hypothyroidism (mantle RT) Bleomycin lung toxicity Sterility (esp. MOPP, escbeacopp)

16 Adverse events after chemo + RT Armatage, JO. N Engl J Med Aug 12;363(7):

17 JAMA Mar 17;303(11): Because many therapies used to treat patients with cancer have cardiotoxic effects, teamwork by oncologists and cardiologists is important in preventing treatment related heart problems.

18 Cardiotoxicity incidence CVD incidence in 1474 survivors of HL < 41 years at treatment ( ) Median follow up of 18.7 years As compared to general population lti SIR of MI and CHF was 3.6 and excess cases of MI and 25.6 excess cases of CHF per patients/year Anthracyclines further increase the elevated risks of CHF and valvular disorders from mediastinal radiotherapy HRs were 2.81 and 2.10 respectively Aleman et al. Blood 2007;109:

19 Aleman et al. Blood 2007;109:

20 Aleman et al. Blood 2007;109: Angina pectoris

21 Myocardial infarction Aleman et al. Blood 2007;109:

22 Cumulative incidence all CVD Aleman et al. Blood 2007;109:

23 Cardiotoxicity incidence Predisposing risk factors for cardiovascular disease can be detected at higher rates in pediatric cancer survivors compared with siblings Survivors were 19times 1.9 more likely to take medications for HTN 1.6 times more likely to take cholesterol medication 1.7 times more likely to take medications for diabetes Not more likely than their siblings to be obese Meacham LR et al. Cancer Epidemiol Biomarkers Prev. 2010;19:

24 How can we predict an increased risk for cardiovascular complication in HL patients up front before treatment? Dfii Defining populations at high risk h ikfor adverse outcomes is critical when beginning to contemplate targeted intervention i approaches.

25 Anthracycline induced induced cadiotoxicity

26 Traditional risk factors for anthracycline induced dcadiotoxicity Therapeutic risk factors Incidence is <10%, cumulative dose <500 mg/m 2 Approaches 36% for doses > 600 mg/m 2 Clinical risk factors Exposed at a younger age (<5 years) Females > males Preexisting heart disease Chest irradiation

27 Increasingly evident that the conventionally described clinical and therapeutic risk factors may not fully explain the wide interindividual variability in susceptibility to anthracyclinerelated cardiomyopathy. Cardiotoxicity has been reported at cumulative exposure of less than 250 to 300 mg/m 2 in some patients, doses exceeding 1,000 mg/m 2 have been tolerated well by others.

28 Anthracycline induced induced CHF MRP1 MRP2 CBR1 CBR3 NAD(P)H oxidase subunit NCF4 Bhatia. Cancer Epidemiol Biomarkers Prev 2011;20(10):

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30 2,977 SNPs in 220 key drug biotransformation genes Discoverycohort cohort of 156 anthracycline treated treated children from British Columbia Replication in a second cohort of 188 children from across Canada 2 nd replication of the top SNP in a third cohort of 96 patients from Amsterdam, the Netherlands Visscher et. al. J Clin Oncol Oct 11. [Epub ahead of print]

31 Visscher et. al. J Clin Oncol Oct 11. [Epub ahead of print]

32 Visscher et. al. J Clin Oncol Oct 11. [Epub ahead of print]

33 Visscher et. al. J Clin Oncol Oct 11. [Epub ahead of print]

34 Visscher et. al. J Clin Oncol Oct 11. [Epub ahead of print]

35 Visscher et. al. J Clin Oncol Oct 11. [Epub ahead of print]

36 HL survivor follow up NCCN guidelines recommend follow up with oncologist attune to the long term risks 2 4 months in the first 2 years Every 3 6 months for years 3 5 Annually after 5 years

37 Recommended follow up for CVD XRT induced cardiotoxicity occurs 5 10 years But cardiovascular symptoms can occur at any age NCCN guidelines Baseline stress test or echo at 10 years after tx Annual blood pressure monitoring Aggressive management of CV risk factors

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39 van Leeuwen Segarceanu et al. Cancer Treatment Rev 2011;37:

40 Robison and Demark Wahnefried. Cancer Epidemiol Biomarkers Prev 2011;20:

41 Thanks Dr. Baker Dr. Gopal Dr. Blau