2013 Cancer Survivorship Conference at Jefferson University Hospitals


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Jefferson's Cancer Survivorship Program will help you understand what it means to be a cancer survivor and what to expect from your cancer diagnosis, treatment and follow-up care. This Program is for current patients, cancer survivors and loved ones who have lived with a cancer diagnosis or have undergone cancer treatment at Jefferson.

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2013 Cancer Survivorship Conference at Jefferson University Hospitals

  1. 1. Cancer Survivorship and Integrative Cancer Care Daniel A. Monti, M.D. Professor and Director Myrna Brind Center of Integrative Medicine Thomas Jefferson University and Hospital
  2. 2. Jefferson-Myrna Brind Center of Integrative Medicine: 925 Chestnut St. STE 120
  3. 3. Our Survivorship Model • You and your primary KCC specialists (medical, radiation and surgical oncology) are at the helm • Focus on Proactive Lifestyle Management (diet, activity level and stress management) to support and enhance care plan • Phenotype = Genotype + Life
  4. 4. The Goals of Integrative Cancer Survivorship Care Reduction of Risk Symptom Management Quality of Life Decrease Stress Test Adjunctive therapies
  5. 5. Trend Modification: • Lifestyle • Environment • Nutrition *Will account for up to 75% of health and life expectancy after 40 Murray and Lopez (1997)
  6. 6. Highest male healthy life expectancy Lancet, 2012 • • • • • • • • • • Rank (95% uncertainty intervals) Japan 1 (1–2) Singapore 2 (1–6) Switzerland 3 (2–10) Spain 4 (2–8) Italy 5 (3–14) Australia 6 (4–15) Canada 7 (4–18) Andorra 8 (2–28) Israel 9 (3–18) South Korea 10 (4–18)
  7. 7. Highest female healthy life expectancy Lancet, 2012 • • • • • • • • • • Rank (95% uncertainty intervals) Japan 1 (1–1) South Korea 2 (2–7) Spain 3 (2–6) Singapore 4 (2–17) Taiwan 5 (2–16) Switzerland 6 (2–22) Andorra 7 (2–33) Italy 8 (5–18) Australia 9 (6–19) France 10 (7–26)
  8. 8. Nutrition is a key element of Integrative Oncology -Food is an important factor in gene expression. -Food is emphasized over supplements. -Food affects cancer risk. -Food affects cancer outcomes.
  9. 9. Let your food be your medicine And your medicine be your food Hippocrates
  10. 10. Body Fat Increases CA Risk • Body fat secretes cytokines that promote inflammation • Too much body fit triggers insulin resistance, raising levels of insulin and growth factors that promote cancer • Fat increases estrogen production • Increase in body fat may impair immunity
  11. 11. Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010 (*BMI 30, or about 30 lbs. overweight for 5’4” person) 2000 1990 2010 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
  12. 12. Obesity Rates (OECD, 2012) 35% 30% Rate of obesity 25% 20% Hungary Ireland England 15% Canada USA 10% Spain Italy France 5% Switzerland Korea 0% 1970 1975 1980 1985 1990 Year 1995 2000 2005 2010
  13. 13. Insulin and IGF-1 and Cancer Gallagher and LeRoith, Trends in Endo and Metab, 2010
  14. 14. Obesity-Associated Malignancies • Breast (postmenopausal) • Endometrium • Prostate • Kidney • Colon • Esophagus • Pancreas • Gallbladder AICR report estimates that obesity-related excesses of these 7 cancers account for approx 105,000 preventable deaths a year in the US
  15. 15. WCRF/AICR Dietary Recommendations to Reduce Cancer Risk 2007 • Limit consumption of red meats (beef, pork and lamb) and avoid processed meats
  16. 16. Nutritional Risk Reduction Strategies Eat More: • Phytoestrogens – Soy foods • • • • • • – Flaxseed Cruciferous vegetables Garlic and onions Turmeric and ginger Green tea Omega 3 fatty acids Vitamin D
  17. 17. Estrogen Adducts,Cancer, Dietary Effects *Compelling evidence supports the hypothesis that specific estrogen metabolites, predominantly catechol estrogen-3,4 quinones, react with DNA to form depurinating estrogen-DNA adducts (review: Pruthi et al, 2012) *I3C and DIM (found in cruciferous veggies) are potent inducers of steroid-metabolizing enzymes such as 2-hydroxylating cytochrome (cyp1A1) that converts circulating estradiol, a mitogenic estrogen, to a 2-hydroxy metabolite that correlates with lower risk of breast and gynecological cancers and may enhance chemo in pancreatic cancer (Banerjee et al 2009)
  18. 18. Chronic Inflammation • Mood Disorders • • • • • • Autoimmune Disorders Cancer Cardiovascular Disease Psoriasis Alzheimer’s Disease Type I and II diabetes mellitus
  19. 19. Nutrition and Inflammation Foods that increase inflammation Red meat, eggs Foods that decrease inflammation Omega-3 fats Sugar Spices and herbs turmeric,,rosemary,ginger, Hot peppers alcohol Green tea High-Glycemic Foods like Soda Pop Low-Glycemic Foods like Green Veggies
  20. 20. Chronic Inflammation The Gut is an important variable • GALT > Nitric Oxide > intestinal permeability > liver alarm system : Kuppfer Cells > message to whole body : red alert, man your battle stations! • Anti-inflammatory Armor: FOOD, pro-biotics/ supplements, Sleep, Stress Reduction
  21. 21. Omega-3 fat • Highly promising for supporting: – Physical health – Mental health – Disease prevention *Sources of Omega-3 fats include cold water fish, flax seeds, raw walnuts, and others
  22. 22. Metabolic Pathways of Essential Fatty Acids Omega-6 Fatty Acids Omega-3 Fatty Acids (e.g. corn, safflower, sunflower oil) (e.g. canola, flaxseed oil, fish oils) Linoleic acid (LA) Alpha-linoleic acid (LNA) delta-6-desaturase delta-6-desaturase Gamma-linolenic acid (GLA) Steridonic acid (e.g. evening primrose, borage, and black currant seed oils) Eicosapentaenoic acid Dihomo-gamma-linolenic acid (DGLA) delta-5-desaturase PGE1 (e.g. fish oils) delta-5-desaturase Arachidonic acid cyclooxygenase PGE2 DHA EPA (anti-inflammatory) lipoxigenase LTB4 cyclooxygenase PGE1 (anti-inflammatory) (e.g. Mg, Zn) lipoxigenase LTB5 (anti-inflammatory) (pro-inflammatory) (pro-inflammatory) *Factors thought to impair delta-6-desaturase activity include Mg, Zn, and B1 deficiency; aging, alcohol, trans fatty acids; and high cholesterol levels.
  23. 23. Transformation of food chain from 1960 to 2000 x20 Omega-6 /Omega-3 x15 x10 x6 Butter Pork Beef Eggs Ailhaud et al., Prog. Lip. Res., 2006
  24. 24. Traditional Dietary approaches such as Fasting and Dietary Cleanses may have a scientific basis “Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients” Lee and Longo: Oncogene (2011) 30, 3305-3316
  25. 25. Multivitamins in the Prevention of Cancer in Men: The Physicians’ Health Study II JAMA, 2012 Conclusion: In this large prevention trial of male physicians, daily multivitamin supplementation modestly but significantly reduced the risk of total cancer. - Adds to evidence that low-dose vitamins (versus high dose) can have a protective effect - Underscores need to study long-term effects, which also was seen in the WHI Vit D and calcium study showing total reduction in cancer (J Bone Miner Research, 2012)
  26. 26. LTR Hypomethylated LTR Hypermethylated Maternal Supplements with zinc, methionine betaine, choline, folate, B12 Or Genistein Yellow Mouse High risk cancer, diabetes, obesity & reduced lifespan Agouti Mouse Lower risk of cancer, diabetes, obesity and prolonged life Cooney et al. J Nutr 132:2393S (2002); Dolinoy et al. Envir. Health Perspect 114: 567 (2006)
  27. 27. Rickets Osteoporosis / Osteopenia Cancer Skin GI / Celiac Mood Disorders Neurological: MS / PD / ALS Cardiovascular TIGHT JUNCTIONS Vitamin D Research www.vitamindcouncil.com accessed July 6, 2009
  28. 28. Herb-Drug Interactions: CYP3A4 • • • • • • Anticancer Agents Camptothecins Cyclophosphamide EGFR-TK inhibitors Epipodophyllotoxins Taxanes Vinca alkaloids Herbal Products • CYP3A induction – – – – – SJW Echinacea Grape seed Kava ?Garlic • CYP3A inhibition – Gingko
  29. 29. Acupuncture
  30. 30. Acupuncture for Symptom Management • Acupuncture Prevents Radiation-induced Xerostomia in Head and Neck Cancer patients (Meng et al 2011, Cancer) • Acupuncture Treats Xerostomia • Acupuncture relieves chemo-induced nausea • Acupuncture may reduce cancer-related pain and improve sleep
  31. 31. Endorphin Theory
  32. 32. “It’s not the load that breaks you down, it’s the way you carry it.” Lena Horne
  33. 33. Stress Response Pathways Stimuli Hypothalamus Anterior Pituitary Adrenal Cortex Cortisol Blood sugar Epinephrine Sympathetic Post-Ganglionic Neurons NorEpinephrine NorEpinephrine HTN, High Chol Arrhythmia Adrenal Medulla
  34. 34. Biology of Stress: Immune/inflammatory Variables • Cytokines and Chemokines (such as IL-1 and -, IL-2, TNF-, IL-8, IL-10, and others) • Nuclear Factors, such as NF-B • Functional activities of leukocytes, such as NK cell activity and receptor changes
  35. 35. Individual and group mindbody interventions • Classic examples include: mindfulnessmeditation, NET, Yoga, biofeedback, qigong, tai chi, expressive arts therapies, others
  36. 36. Mindfulness-based Stress Reduction (MBSR) • MBSR is a well-researched, standardized eight-week program that utilizes mindfulness meditation techniques and gentle Hatha Yoga to teach participants the skills to better cope with life stressors. • Learn to be present, in the moment, non-judgmentally. Learn how to breath, learn how to relax. • Use mindfulness to facilitate connection to that which has personal meaning
  37. 37. Mindfulness-Based Art Therapy (MBAT) for Cancer Patients • Uses standard 8-week mindfulness-based stress reduction (MBSR) curriculum • Incorporates playful art tasks that allow for nonverbal expression of stressful experiences • Group format allows for camaraderie and sharing
  38. 38. MBAT Outcomes Health Related Quality of Life Figure 2. SF-36 General Health p = 0.008 Adjusted Mean: Wk 8 - Wk 1 Changes in the General Health Subscale, on the SF-36, in MBAT participants as compared to wait-list controls. Adjusted mean differences for each group pre and post intervention are shown (p = 0.008). (Monti et al, 2006, PsychoOncology) 15 10 5 0 -5 Treatment Control MBAT -0.59 7.97
  39. 39. MBAT Outcomes Psychological Distress (Monti et al, 2006, Psycho-Oncology) Figure 1. SCL-90-R Global Severity Index p < 0.001 Adjusted Mean: WK 8 - Wk 1 Changes in the SCL-90-R Global Severity Index in MBAT participants as compared to controls (p < 0.001). 0.05 -0.05 -0.15 -0.25 -0.35 Treatment Control MBAT -0.04 -0.20
  40. 40. Desensitizing Distressing Cancer-related Events • Objective To assess treatment effects of Neuro-Emotional Technique (NET), a 3-5 session, individualized program for reducing traumatic stress symptoms. Specific endpoints include: - Distress and QOL measures, - Autonomic reactivity - fMRI imaging in response to stressful cue - Genomics testing
  41. 41. Differences between Post-training and Pre-training resting scans Monti et al, Stress & Health (2012) MBAT group (p<0.001) Control group (p<0.005)
  42. 42. Stressor task post minus stressor pre-training program Monti et al, Stress & Health (2012) MBAT group (p<0.005) Control group (p<0.005)
  43. 43. NET for Distressing Events – Distressing cancer-related recollection lasting at least 6 months – NET is a mind-body technique that quickly addresses distress in a few short sessions – Distressing memory causes autonomic reactivity – Our preliminary data shows highly encouraging results!
  44. 44. JeffQuit - Three week program - High success rate - Study participation costs less than a week’s worth of cigarettes!
  45. 45. JEFFQuit Smoking Cessation Study • Inclusion criteria – History of cancer diagnosis – Current tobacco use – No medical or psychiatric issue that would interfere with program participation – 18 years or older
  46. 46. Healthy Living, Healthy You • Overview – 8 week program (one hour per week) – Each session has a nutrition module and fitness training – Participants keep daily food journals and are encouraged to practice exercises – Evaluate QOL measures and basic health measures (e.g., weight, BMI) pre and post program
  47. 47. Mastering Food Labels Commercial Can of Soda 2.5
  48. 48. Replacing Bad Fats with Healthy Ones
  49. 49. Sample Exercise- Week 3
  50. 50. Ascorbic acid (Vitamin C) and other nutrients are being studied at Jefferson for anti-cancer effects
  51. 51. Vit C plus Standard Chemo for Pancreatic Cancer (Monti et al, 2013) • • • • • • • • • Ascorbate concentrations were reached safely Minimal adverse events attributed to ascorbate 8 of 9 patients with decreased size of primary tumor Metastases stable or improved in 7 subjects, including all 3 at highest dose 7 of 9 patients had stable disease by RECIST criteria Target concentrations of 30 mM ascorbate achieved Deaths due to advancing underling disease Ascorbate effects appear more gradual than cytotoxic chemo Next study step: phase II, longer duration disease progression, more patients.
  52. 52. Thrive throughout Survivorship • An Integrative plan that focuses on improved lifestyle can have a significant positive impact on survivorship • Today we have a scientific basis to modify gene expression through lifestyle interventions • Complementary therapies integrated within a medical treatment plan can may have a role • The Jefferson Kimmel Cancer Center in partnership with the Jefferson Myrna Brind Center provides a comprehensive range of survivorship tools
  53. 53. Thank you! No industry support, conflicts of interest or disclosures to report daniel.monti@jefferson.edu