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Care of the Cancer Survivor Management of Late Effects 12th Annual Mid-South Cancer Symposium Baptist Cancer Center November 14, 2014 Linda A. Jacobs, PhD, RN Director Survivorship Center of Excellence, Abramson Cancer Center University of Pennsylvania Clinical Associate Professor of Nursing Who is at Risk? • Risk depends upon a number of things: • Age – Now & when treated – Older vs. younger • • • • General health & lifestyle Family history Chance Treatment – More courses of treatment may increase risk – Type of drug/dose – Radiation • Dose & body location Immediate & Late Effects of Treatment Chemotherapy Radiation Surgery Possible Complications of Cancer Treatment • Long Term Effects of Treatment – Develop during active treatment – Persist for years • Neuropathies • Fatigue • Cognitive & sexual difficulties • Late Effects of Treatment – Not present or identified until after treatment • Develop as a result of treatment – Organ systems » Endocrine, cardiovascular (CV), pulmonary, CNS, etc. – Psychological process Hewitt M, Greenfield S, Stovall E. (2006). From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, D.C.: The National Academies Press. Survivorship care: What is the state of the science? • Prevention & detection of new cancers & recurrent cancer • Intervention for consequences of cancer & its treatment • Coordination between specialty & primary care – Fragmented care, poor communication – Confusion about role & responsibility – PCPs lack information to support optimal care • Disease & treatments received • Secondary consequences (surveillance, intervention) – Workforce trends will likely exacerbate problems Institute of Medicine & National Research Council, 2006; Grunfeld & Earle, 2010. Cancer Screening in Cancer Survivors • Background – Second cancers - 6th leading cause of cancer deaths – 10% of all new cancers are diagnosed in survivors • Adherence to cancer screening – Cancer survivors adhere to recommendations as well as or better than individuals without cancer – Factors influencing adherence • • • • • Sociodemographic factors Perceived vulnerability to cancer Perceived utility of screening Access to health care Provider recommendation of screening Mayer et al. (2007). Screening practices in cancer survivors. Journal of Cancer Survivorship 1: 17-26. Disease surveillance & follow up care Goals: 1. Ensure recovery from treatment 2. Detect late complications 3. Monitor ongoing therapy - i.e., endocrine therapy for breast cancer 4. Detect local & distant recurrence 5. Detect other cancers • • • Contralateral (if applicable) Secondary Other cancer screening Kramer, R. & Osborne, C.K. (2004). Evaluation of patients after primary therapy. Overview • NCCN Guideline Version 2:2014 Survivorship – Focused on survivors after completion of cancer treatment & in clinical remission – May also be appropriate for survivors living with metastatic disease as clinically appropriate – Screening, evaluation, & treatment recommendations for common consequences of cancer treatment and cancer – Provide a framework • General survivorship care/management of potential long-term &/or late effects of cancer & its treatment • coordination of care between health care providers NCCN Practice Guidelines Version 2. 2014: Survivorship http://www.nccn.org/professionals/physician_gls/f_guidelines.asp Long Term Survivors & Symptoms 1. Fatigue 2. Pain • Peripheral neuropathy 3. Cognitive function 4. Sleep disturbances 5. Appetite loss 6. Dyspnea 7. Nausea/Vomiting 8. Constipation/Diarrhea Journal of Pain & Symptom Management 2012 • N=863 long-term survivors of multiple cancer types • Principal component –factor analysis N=591 –All 8 symptoms significantly correlated with one another Karabulu, Erci, Ozer, et al. Journal of Advanced Nurs. 2010; Brearley., Stamataki, Addington-Hall, et al. European Journal of Oncology Nursing. 2011; Schmidt, Chang-Claude, Vrieling, et al. J Cancer Surviv. 2012; Yang, Cheville, Wampfler, et al. Journal of Thoracic Oncology. 2012; Zucca, Boyes, Linden, et al: Journal of Pain & Symptom Management, 2012. Long Term Survivors & Their Symptoms N=591 (5-6 years post diagnosis) • 71.2% no symptoms • 17.6% multiple symptoms • Reported 2 or more symptoms – – – – breast prostate colorectal melanoma 21.1% 20.2% 19.0% 4% • No cancer specific symptom clusters • Individual symptoms moderately discriminated specific cancer sites – – – – diarrhea pain constipation insomnia Zucca, Boyes, Linden, et al: Journal of Pain & Symptom Management, 2012. Survivorship care is many things • Patients completing treatment for different cancers have very different needs & concerns • Patients of different ages have very different needs & concerns A 70 yo man completing surgery, chemotherapy & radiation for head & neck cancer A 37 yo woman completing adjuvant chemotherapy & initiating hormone therapy for breast cancer A 17 yo woman completing combined modality therapy (ABVD & mediastinal radiation) for Hodgkin’s lymphoma Survivorship care is many things A 70 yo man completing surgery, chemotherapy & radiation for head & neck cancer • Speech & swallowing issues, nutrition, aspiration pneumonia A 37 yo woman completing adjuvant chemotherapy & initiating hormone therapy for breast cancer • Fertility, bone health, long-term cardiac issues A 17 yo woman completing combined modality therapy (ABVD & mediastinal radiation) for Hodgkin’s lymphoma • Breast cancer, cardiac & pulmonary disease, other second cancers Female Hodgkin’s Lymphoma Survivor Late Effects of Treatment occurring over 30 years • 1983, age 21 – Hodgkin Lymphoma, Stage IIA, splenectomy MOPP x 6, mantle & para-aortic radiation • 1987, age 25 – thyroid failure, & oral replacement • 1994, age 32 – breast cancer – T1c, N0, bilateral mastectomies, CMF chemotherapy • 2006, age 44 – fibroblastic proliferation left posterior back (in radiation field), most consistent with extra-abdominal desmoid tumor – resected with poorly healing wound • 2009, age 47 – > 40 colon sessile serrated polyps • 2010, age 48 – Barrett’s esophagus • 2013, age 51 – coronary artery disease, tachy-arrhythmias, intermittent complete heart block, permanent pacemaker placement, continued exertional dyspnea Medical Late Effects • • • • Cardiovascular Pulmonary Endocrine Central Nervous System (CNS) • Neurological • Renal • • • • • • Genitourinary Gastrointestional Musculoskeletal Integumentary Lymphatic Other • Systems approach can guide clinical practice Hewitt M, Greenfield S, Stovall E. (2006). From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, D.C.: The National Academies Press. Ganz, P. (2006) … Medical Issues Resulting from Cancer Treatment • Examples – – – – – Poor dental health Eye problems Lung fibrosis Reduced thyroid function Heart disease & stroke • Risk factors – – – – – – Smoking High blood pressure Diabetes Family history Obesity High cholesterol Screening for All Patients • Careful History & Physical exam – Exercise-induced symptoms – Other symptoms (dyspnea, chest pain, etc). – CV exam, BP, carotid bruits • Monitor risk factors – FH, HTN, tobacco, diabetes, obesity – Lipid profiles • Consider cardiac referral – Cardiac risk factors – Abnormal exam findings Carver et al. (2008). Cardiovascular late effects and the ongoing care of adult cancer survivors. Disease Management 11(1), 1 – 6. Chemotherapy Related Cardiac Issues • Anthracyclines & trastuzumab – Asymptomatic ventricular dysfunction – Cardiomyopathy & CHF • Alkylating agents, esp. cisplatin – Direct, chronic endothelial damage – Increased risk of cardiovascular disease in germ cell tumor survivors vs. controls • Atherosclerosis - Raynaud’s symptoms • Lipid abnormalities - Hypertension Yeh E et al. (2004). Cardiovascular complications of cancer therapy. Circulation 109:3122-3131. Carver et al. (2008). Cardiovascular late effects and the ongoing care of adult cancer survivors. Disease Management 11(1), 1 – 6. Radiation Therapy Related Cardiac Issues • Incidence of cardiac disease – Peaks at 4 -6 years post-exposure – 10 to 30% by 5 to 10 years post-treatment – Up to 88% with asymptomatic abnormality • Best studied in survivors of Hodgkin’s postmediastinal radiation – Increased risk (2.2 to 7.2 RR) for fatal cardiovascular disease – Manifests 5 – 10 years post radiation – 25% of non-Hodgkin’s related deaths Carver J, Shapiro C, Ng A, Jacobs L, Schwartz C, Virgo K, Hagerty K, Somerfield M, Vaughn D. (2007). Journal of Clinical Oncology, ASCO Special Article, 25, 25:3391-4008 Radiation Therapy Related Cardiac Issues • Specific radiation-related effects – Pericardial damage & fibrosis • pericardial effusion (early), pericardial constriction (late) – Vascular injury • premature coronary artery disease (CAD) • MI and sudden death • carotid disease (incl. stenosis), stroke – Valvular heart disease, fibrosis • Aortic regurgitation most common (60%) – Cardiomyopathy • restrictive, diastolic dysfunction – Conduction abnormalities/arrhythmias Carver J, Shapiro C, Ng A, Jacobs L, Schwartz C, Virgo K, Hagerty K, Somerfield M, Vaughn D. (2007). American Society of Clinical Oncology Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late Effects. Journal of Clinical Oncology, ASCO Special Article, 25, 25:3391-4008 Yeh E et al. (2004). Cardiovascular complications of cancer therapy.Circulation 109:3122-3131. Combination Anthracycline & Mediastinal Radiation (High Risk Population) • Patient characteristics – – – – – Age <18 or > 65 years at treatment initiation Pregnant or contemplating pregnancy Extreme athletics > 10 years from treatment Pre-existing cardiac risk (CAD, HTN, LVD) • Treatment factors – – – – – >300 mg/m2 doxorubicin, >600 mg/m2 epirubicin Mediastinal XRT + anthracycline Radiation prior to 1970 > 35Gy to heart +/- >2 Gy/day Absence of subcarinal blocking Carver et al. (2008). Cardiovascular late effects and the ongoing care of adult cancer survivors. Disease Management 11(1), 1 – 6. Cardiac Screening after Chest Radiation • Cardiac screening 5 years post-treatment if any cardiac abnormality or high risk – 10 years post-treatment if not high risk • Cardiovascular screening repeated every 5-10 years – Presence of cardiac abnormalities & the level of risk • All patients who had chest radiation – Cardiac examination starting with ECHO – Stress imaging, CT or cardiac MRI – No established role in asymptomatic survivors • Routine Holter, stress tests, or ECHOs Lancellotti P. Eur Heart J Cardiovasc Imaging. 2013;14:721-740. Breast Screening following Chest Radiation Under age 40 • Mantle radiation • Chest/chest region radiation • Cranio-spinal/spinal radiation • Annual breast MRI in women beginning at age 25 or at least 8 years after radiation treatment – Treated with any dose of radiation prior to age 40 NOTE: in addition to annual mammography Oeffinger KC, Ford JS, Moskowitz CS. (2009). Breast Cancer Surveillance Practices Among Women Previously Treated With Chest Radiation for a Childhood Cancer. JAMA, 301:4; 404-414. Mulder RL, Kremer LC, Hudson MM. (2013) Recommendations for breast cancer surveillance for female survivors of childhood, adolescent, and young adult cancer given chest radiation: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.www.thlancet.com/oncology Vol 14, 621-629. ACS 2014 Guidelines for Breast MRI • 20% to 25% or greater lifetime risk of breast cancer based mainly on family history • Known BRCA1 or BRCA2 gene mutation • First-degree relative with a BRCA1 or BRCA2 gene mutation – have not had genetic testing themselves • Radiation therapy to chest between the ages of 10-30 years • Li-Fraumeni, Cowden, or Bannayan-Riley-Ruvalcaba syndrome – have first-degree relatives with one of these syndromes http://www.cancer.org/cancer/breastcancer/moreinformation/breastcancerearlydetection/breast-cancer-early-detection-acs-recs 2014 Screening for Bone Health • NCCN Guidelines, 2011 – Screen all women at high risk • All postmenopausal women receiving AI’s • Therapy-associated premature menopause – Monitor BMD with DEXA scan every 2 years – Calcium (1200mg/day) & Vitamin D (400-600 IU/day supplementation for all women – Pharmacologic treatment when T-score < -2.5 • Lack of consensus between organizations on appropriate threshold for initiation of treatment Gralow J, Biermann JS, Farooki A, et al. (2011). NCCN Task Force Report: Bone Health in Cancer Care J Natl Compr Canc Netw. Author manuscript; available in PMC Mar 2, 2011. edited form J Natl Compr Canc Netw. Jun 2009; 7(Suppl 3): S1–S35. Pulmonary Late Effects • Reduced pulmonary function • Pneumonitis – Bleomycin-induced (BIP) – Radiation-induced (acute, chronic) • Fibrosis • Bronchiolitis obliterans • Idiopathic pneumonia • Interstitial pneumonitis Kattlove & Winn (2003). CA: Ca Jnl Clinicians 53(3), 172-196. Carver J, Shapiro C, Ng A, Jacobs L, Schwartz C, Virgo K, Hagerty K, Somerfield M, Vaughn D. (2007). ASCO Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors: Cardiac and Pulmonary Late Effects. JCO, ASCO Special Article, 25, 25:3391-4008 Gospodarowicz M. (2008). Hematol Oncol Clin North Am.(2):245-55. Pulmonary Late Effects • Screening & Management – Exercise endurance – PFTs as indicated – Radiation • Risk of lung cancer – Bleomycin • Scuba diving warning • Refer to Pulmonary – Management as needed Endocrine Late Effects • Radiation – Cranio-spinal radiation • Pituitary/testicular/thyroid gland dysfunction – Pelvic • Ovaries/testicles/adrenals/GU/bowel dysfunction • Chemotherapy – Cyclophosphamide, Procarbazine, BCNU/CCNU, Ifosfamide – Risk of premature ovarian/testicular failure • • • • bone density libido fertility Symptoms – hot flashes – fatigue Stricker and Jacobs (2008); Stein, Syrjala, & Andrykowski, 2008. Endocrine Late Effects • Screening & Management – TFTs – Exam – Assess symptoms – Fatigue – Sexual function – Mood – Males-testosterone/LH • Hormone replacement as needed – Females • Assess for ovarian failure • LH, FSH, Estradiol – Assess for psychosocial effects, refer as needed – Bone Mineral Density-DEXA Fertility & Sexual Function Issues • Males • Erectile dysfunction • Low/no sperm count • Psychological effects • Females • • • • • Hot flashes Vaginal dryness Pain Premature ovarian failure Psychological effects • Management – Refer to gynecology/urology/psychology/sex therapist as needed – Acupuncture/pain management Dorey G. (2007). A clinical overview of the treatment of post-prostatectomy incontinence. Br J Nurs. Oct 25-Nov 7;16(19):1194-9. Robinson et al. (2002). (meta-analysis of rates of erectile dysfunction) Central Nervous System (CNS) Late Effects • Causes/risk factors – Chemotherapy induced • Age < 3 years at treatment • Cytarabine, Methotrexate • Intrathecal chemotherapy – Radiation induced • dose related; combination w/chemo • age related CNS Late Effects Radiation & Chemotherapy • • • • Meningiomas Cavernomas Neurocognitive deficit Leukencephalopathy – Seizures – Radiation therapy, cytarabine, methotrexate, fludarabine Cognitive Dysfunction “Chemobrain” • Deficits in memory, concentration, & executive functioning • Examples of populations at risk – Breast CA: some impairment at “baseline” • 35% of women with breast cancer in one study – Prostate CA: androgen deprivation therapy • Psychological distress may be related • Genetic predisposition is under investigation Green et al., 2002; Koupparis et al., 2004, Wefel et al., 2004 Hede K, J Natl Cancer Inst. 2008 Feb 6;100(3):162-3, 169. Epub 2008 Jan 29. Renal Late Effects • Screening – blood pressure (yearly) – Urinalysis (yearly) • U/S if micro heme + – Baseline labs (repeat as clinically indicated) • • • • • BUN, creatinine creatinine clearance mag, phosphorus protein, albumin CBC, retic count Stricker and Jacobs (2008) • Treatment – Renal referral • hematuria • HTN, proteinuria • progressive renal insuff – Treatments as indicated • • • • renal diet diuretics Mg/Phos supplements AVOID nephrotoxins Dermatologic Late Effects • Radiation therapy – Benign dermatologic changes • Telangiectasias • Fibrosis • Hair loss, altered skin pigmentation – – – – Dysplastic nevi Basal cell carcinoma Squamous cell carcinoma Melanoma • Screening • annual skin exam • Refer to derm as indicated Stricker and Jacobs (2008); Ganz, 2006. Factors Predisposing to Second Malignancies • Genetic Conditions – – – – Genetic retinoblastoma (bilateral, familial) Neurofibromatosis Li-Fraumeni Syndrome BRCA-1, BRCA-2 • Treatment – Radiation • Sarcomas • Site-specific cancers – e.g., rectal CA with prostate radiation – Breast cancer with chest radiation age <30yo (15 year latency) – Chemotherapy • continued….. Grady & Russell (2005). Gastroenterology 128(4):1114-1117. Hancock et al. (1993). JNCI 85(1), 25-31. Chemotherapy & Second Malignancies • Alkylators – Myeloid leukemia & MDS • chromosomes 5 & 7 abnormalities • latent period 3 to 7 years • dose relationship • Epipodophyllotoxin – Monocytic leukemia • chromosome 11q23 abnormality • dose & schedule dependent • short latent period …Examples of Secondary Malignancies • Malignancies related to a number of factors – Breast – Lung – Skin – Chest & neck – Abdomen – Leukemia & other blood disorders Summary • Cancer treatments increase the risk for myriad late effects in survivors – Age & dose are key risk factors – Combination therapies are often synergistic • Clinical evaluation should be guided by – Treatments received – Body systems approach • Referral to specialists a critical component of care Other Late Effects of Treatment Common Symptoms & Management Von Ah DM, Kang DH, Carpenter JS. (2008). Predictors of Cancer-Related Fatigue in Women With Breast Cancer Before, During, and After Adjuvant Therapy. Cancer Nurs. (2):134-144. Patridge, Burstein, & Winer (2001). J Natl Cancer Inst Monogr 30:305-313 Halbert CH, Weathers B, Esteve R, Audrain-McGovern J, Kumanyika S, DeMichele A, Barg F. (2008). Experiences with weight change in African-American breast cancer survivors. Breast J. (2):182-7. Fatigue, Pain, & Sleep Issues • Among the most troublesome symptoms experienced by cancer survivors – Definition/description/associated factors – Management Pachman, Barton, Swetz, Loprinzi, JCO, October 20, 2012; Given, Given. Seminars in Oncology 2013. Treatment of Fatigue • Energy conservation • Physical activity • Psychosocial interventions • Treat contributing factors – Cognitive behavioral therapy – Psychoeducational therapies – Emotional distress NCCN Practice Guidelines Version 2. 2014: Survivorship; Brearley, Stamataki, Addington-Hall et al. European Journal of Oncology Nursing. 2011. Karabulu, Erci, Ozer, et al. Journal of Advanced Nursing. 2010. Bower, Bak, Berger, et al. JCO, 2014; NCCN Clinical Practice Guidelines in Oncology: Cancer related Fatigue Version 1.2013. – Medication effects – Pain * – Anemia • Iron, B12, folate deficiency, referral – Sleep issues * – Nutritional deficits – Co-morbidities • Hepatic, renal, cardiac, pulmonary, neuro, endocrine Medication Management for Fatigue • • • • Remains investigational More evidence for methylphenidate (ritalin) Less for modafinil (provigil) Psycho stimulants – Dosing & schedule have not been established • Small pilots – Ginseng, vitamin D, other supplements • No consistent evidence to date Chronic Pain • Reported by 33% post treatment cancer survivors • Often leads to psychological distress & poor quality of life • Categories of cancer pain syndromes – – – – – – Neuropathic Post-operative Myalgias/arthralgias Skeletal Myofacial GI/urinary/pelvic Pachman, Barton, Swetz, Loprinzi, JCO, October 20, 2012. Pain Management… • Multidisciplinary approach – Pharmacologic treatments (examples) • • • • • • Opiates (narcotics) NSAIDS (Motrin, Aleve) Vitamin D Muscle relaxants (Baclifen) Topical treatments Adjuvant analgesics – – – – Antidepressants (elavil) Anticonvulsants (gabapentin) Corticosteroids (prednisone) Topical agents Paice JA, Ferrell B. CA CancerJ Clin, 2011; NCCN Practice Guidelines Version 2. Survivorship: 2014. …Pain Management… • Multidisciplinary approach – Non-pharmacologic • • • • • • Exercise Heat Cold Physical therapy Aquatic therapy Ultrasound stimulation Syrjala, Jensen, Mendoza, et al. JCO, 2014. …Pain Management • Multidisciplinary approach – Psychosocial/behavioral interventions • Relaxation training • Cognitive-behavioral therapy – Proper hydration, bowel regimen, pelvic floor exercises – Exercise therapy – Interventional procedures • Trans electrical nerve stimulation (TENS) • Intercostal nerve blocks • Dorsal column stimulation • Referral to pain management Sleep Disorders • Affect 30-50% of patients with cancer & survivors – Often in combination with fatigue, anxiety, &/or depression – Successful treatment can improve fatigue, mood, QOL • Insomnia • Excessive sleepiness • Sleep related movement/breathing disorders – Parasomnias • Talking/walking/grinding teeth/eating/etc. • Restless leg syndrome – Ferritin level <45-50 ng per ml NCCN Practice Guidelines Version 2. 2014: Survivorship; Berger AM, Mitchell S. J Natl Compre Canc Netw , 2008. National Heart, Lung, and Blood Institute Working Group on Insomnia.NIH Publication, 1998; NCCN Practice Guidelines Version 2. 2014: . Survivorship; Nakamura, Lipschitz, Kuhn, et al. J Ca Survivorship, 2013 Treatment for Sleep Disorders… • General sleep hygiene • Physical activity • Pharmacologic treatments – Hypnotics • Zolpidem (ambien) • Ramalteon (rozerem ambien-like) – Psycho-stimulants including those for narcolepsy • Modafinil (provigil) • Methylphenidate (ritalin) Savard J, Simard S, Ivers H, et al. Journal of Clinical Oncology, 2005; NCCN Practice Guidelines Version 1. 2013: Survivorship. …Treatment for Sleep Disorders… • Pharmacologic treatments (cont.) – Dopomine agonists (examples) • Adderall & Adderall XR • Dexadrine • Ritalin – Benzodiazepines • Ativan • Xanax • Valium – Garapentin enacarbil (for restless leg syndrome) – Opiods (for restless leg syndrome) • Examples: – Hydrocodone, Vicodin, Oxycodone, Oxycontin, Percodan, Tramadol Ryzolt, Ultram • Refer to a sleep specialist …Treatment for Sleep Disorders • Psychosocial interventions – Cognitive-behavioral therapy – Psycho-educational therapy – Supportive expressive therapy (group or individual) – Exercise – Weight loss if indicated • Sleep apnea – CPAP Oral appliance NCCN Practice Guidelines Version 1. 2014: Survivorship; Bennett MI, Rayment C, Hjermstad M, et al. PAIN, 2011; Nakamura, Lipschitz, Kuhn, et al. J Ca Survivorship, 2013. Who should provide survivorship care? • Multiple disciplines • A designated individual should be responsible for coordinating survivorship care • Care is a shared responsibility Hewitt, Greenfield, & Stovall (2005). From Cancer Patient to Cancer Survivor: Lost in Transition. Care of the Cancer Survivor • Improve quality of life through early detection & intervention • Offer support, guidance, & education