1. Lymphoma Survivors: Late and Long-Term Effects Carrie Thompson, MD NCCS Cancer Policy Advocate Training June 25, 2015

2. Outline What is lymphoma survivorship Medical survivorship issues Psychosocial survivorship issues Negative sequelae Positive sequelae

3. Lymphoma Survivors 14.5 million cancer survivors in the US 761,659 people living with or in remission from lymphoma in US SEER Cancer Statistics Review 2014 ACS Cancer Facts and Figures 2015

4. Non-Hodgkin Lymphoma in US 60% aggressive 40% indolent

5. Medical Sequelae of Treatment Thyroid Heart Secondary cancers

6. Thyroid Disease Caused by radiation therapy Radiation doses >15 Gy to the neck leads to hypothyroidism in ~50% Hyperthyroidism rare Thyroid nodules found in 30-40% of Hodgkins survivors who have received radiation Majority benign Metzger Ped Blood Ca 2006;46:314-9 Crom Med Pediatr Oncol 1997;28:15-21

7. Cardiovascular Disease Radiation therapy Causes fibrosis (scar tissue) Fibrosis can affect pericardium, myocardium, conduction system, coronary arteries, valves Chemotherapy (anthracyclines) Leads to myocyte loss and damage

8. Congestive heart failure Subclinical (asymptomatic, echo abnormal) 27.6% in lymphoma survivors 1 Do not know if this will lead to clinical CHF Clinical CHF 7.2% incidence with 6 year followup 2 May become evident during times of increased cardiac workload Pregnancy, anesthesia, BMT, illness 1 JCO 1998; 16:3502-8 2 Ryberg 1998

9. Coronary artery disease Prospective study in 294 asymptomatic survivors of Hodgkin lymphoma ≥35 Gy to mediastinum Excluded patients with known CVD Nuclear study and stress test 40 patients (14%) underwent coronary angiography Coronary artery stenosis >50% in 22 patients 7.4% of those screened JCO 2007; 25:43-9 Blood 2007; 109:1878-86

10. Other cardiac diseases Valvular disease Predominantly mitral and aortic valves affected Pericardial disease Historically most commonly affected cardiac structure Now <10% of patients Conduction system Arrhythmias and QT prolongation

11. Who is at risk? Incidence for all types of CVD: 1% incidence per year in NHL 1 CAD 10-20 years after treatment Treatment factors Radiation to chest, anthracycline chemo Patient factors Tobacco use, lack of exercise, family history, high blood pressure, high cholesterol, diabetes 1 Thompson Blood; 2011

12. Benefits of exercise JCO 2014; 32: 3643-50

13. Secondary Cancers Chemotherapy and radiation therapy are carcinogenic 16% of all new cancer cases are in patients who previously had a cancer Late sequelae of treatment Genetics Lifestyle factors Environmental exposures JNCI 2006;98:15-25

14. Types of secondary cancers Due to radiation Breast cancer In those treated for childhood HL, estimated incidence of breast cancer 20% at age 45 Thyroid cancer Lung cancer Risk significantly increases in those who smoke after radiation therapy JCO 2003; 21:4386-94

15. Types of secondary cancers, continued Due to radiation Gastric/colorectal cancers Sarcoma Skin cancers Due to chemotherapy AML/MDS Mostly due to chemotherapy (alkylators) NHL ~5% lifetime risk in those treated for HL

16. PSYCHOSOCIAL SURVIVORSHIP Quality of Life (QOL) Depression Anxiety PTSD

17. What is quality of life? QOL PhysicalFunctionalEmotionalSocial

18. Impact of Lymphoma on QOL and Functioning 76 CLL pts. vs. 152 HC 1 459 NHL pts. vs. Gen. Pop of Norway 2 93 NHL pts. vs. 186 HC France 3 46 HL pts. vs. 46 HC Spain 4 81 NHL 116 HC 5 Physicalxxxxx Rolexxx Cognitivexx Emotionalx Socialxxx General Health x Perceived Health x 1 Holzner et al.; Eur J Hematol;2004;72:381-389 2 Loge et al.; Annals of Onc; 10:71-77 3 Joly et al.; JCO; 1996:14(9):2444-2453 4 Gil-Fern et al.; Ann Hematol;2003;82:14-18 5 van Tulder et al.; Annals of Onc;1994;5:153-158

19. Depression and Anxiety in Cancer Survivors Depression higher than general population in 1 st 2 years after diagnosis, then no different Anxiety levels higher than general population and tend to persist Mitchell et al; Lancet Oncology 2013; 14:721-32

20. Anxiety 70 survivors of aggressive lymphoma 37% reported clinically significant anxiety Associations of higher anxiety levels with Worse doctor-patient relationship History of relapse Qualitative Fear of recurrence “Scan-itis” Anxiety worst in 1 st year after treatment Thompson et al.; Annals of Oncology; 2010

21. Anxiety in Lymphoma Survivors and Spouses Mitchell et al; Lancet Oncology 2013; 14:721-32

22. Post Traumatic Stress Disorder Cancer Feelings of loss and crisis PTSD symptoms 886 NHL survivors 1 8%- Full PTSD criteria 9.1%- Partial criteria 39%- Met at least one criteria 44 lymphoma survivors 2 vs. 44 other trauma 18%- Full PTSD 14%- Partial PTSD Prevalence of PTSD in general population- 2.4% 1 1 Smith et al., JCO; 2008; 26(6): 934-41 2 Geffen et al.; Leukemia and Lymphoma; 2003;44(11):1925-1929

23. Employment and Insurance Changing jobs, reducing hours, stopping work, interference with career 1 Insurance and loans 15% of 221 NHL survivor 2 31% of patients had trouble getting insurance because of cancer 3 1 Mols et al.; Cancer; 2007; 7(6):791-6 2 van Tudler et al.; Annals of Oncology; 1994: 5:153-158 3 Kornblith et al.; Cancer; 1992;70(10):2508-16

24. PSYCHOSOCIAL SURVIVORSHIP Positive Sequelae

25. Positive Sequelae Positive and negative may exist concurrently Study of 133 hem malignancy pts vs. 60 controls 3 Comparing life before/after cancer Hem pts had higher percentage of “better” responses Religion Relationships with family Outlook on life Friendships 1 Andrykowski et al.;JCO;23(3):599-608; 2 Fromm et al.;Journ of Beh Med;19(3):221-240; 3 Andrykowski et al.;Psycho-Oncology;1993;2:261-6; 4 Somerfield et al.;Journ of Beh Med;19(2):163-184

26. QOL in 3-year lymphoma survivors is better than the general population ASCO 2015

27. Survivorship Care Models Primary care providers not trained in care of long-term cancer survivors Communication and coordination of care is key Survivorship care plan Treatment summary Follow-up care plan JOP 2014; Epub 10/14/14 www.asco.org

28. Improvements in lymphoma survivors who attended clinic vs. those who did not: Receipt of SCP Education needs met -Late & long term effects, habits/lifestyle, decreasing risk of cancer, managing anxiety, staying fit, nutrition, sexuality, insurance Confidence in getting more information if needed Distress/PTSD (Impact of Events scale) Thompson Unpublished data

29. Summary Lymphoma diagnosis and treatment may have long-term effects Heart disease, secondary malignancies, fatigue, fertility, loss of immunity QOL, anxiety, psychosocial issues Positive effects Coordinated survivorship care is key

30. Thank you! Thompson.Carrie@mayo.edu