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Cancer Survivorship Challenges and Opportunities
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  • 1. Learning Objectives1. Define cancer survivorship goals.2. Learn the general biomarkers cancer patients should havemonitored3. How do cancer survivors become active participants inmaintaining wellness?4. What are the major nutritional goals for survivors of cancer?
  • 2. CANCER SURVIVORSHIP-CHALLENGES ANDOPPORTUNITIESMitchell L Gaynor , M.D.Founder and President, GaynorIntegrative Oncology
  • 3. Cancer Survivor Facts• 60% of survivors are currently over the age 65years.• Breast, Prostate, and colorectal, are the 3 mostprevalent cancer sites.• Approximately 14% of the 11.1 millionestimated cancer survivors were diagnosed over20 years ago.• Average age of male and female cancersurvivors is 69 and 64 respectively.
  • 4. Trends in Five-year Related Survival (%)* Rates, US, 1975-2003Site 1975-1977 1984-1986 1996-2003All sites 50 54 66Breast (female) 75 79 89Colon 51 59 65Leukemia 35 42 50Lung and bronchus 13 13 16Melanoma 82 87 92Non-Hodgkin lymphoma 48 53 64Ovary 37 40 45Pancreas 2 3 5Prostate 69 76 99Rectum 49 57 66Urinary Bladder 74 58 81*5-year relative survival rates based on follow up of patients through 2004.Source: Surveillance, Epidemiology, and End Results Program, 1975-2004, Division of Cancer Control andPopulation Sciences, National Cancer Institute, 2007
  • 5. CURE VS. HEALING• Cure: (curarae) – To set right on a physical level• Healing: (haelen) – To restore to wholeness“I will keep pure and holy both my life and myart.”—Hippocratic oath
  • 6. IOM Study:Survivorship Care• Survivorship care is a neglected phase ofcancer care• Cancer recurrence, second cancers, andtreatment late effects concern survivors• Few guidelines on follow-up care• Primary care M.D.s lack survivorshipeducation and training
  • 7. GAYNOR INTEGRATIVE ONCOLOGY:Treatment + Healing=Care• Patients given cancer therapeutic options as well aslate effects of cancer treatments, with expected timecourse• Plan for what needs to be done in the future(screening, delayed Rx effects)• Comprehensive plan for healthy lifestyle to preventrecurrence and reduce the risk of other comorbidconditions. Includes nutrition, exercise andpsychospiritual support
  • 8. Burden of Illness in Cancer Survivors: Findings From a Population-Based National SampleK Robin Yabroff, William F. Lawrence, Steven Clauser, William W. Davis,Martin L. Brown• Comparison of cancer survivors and age-matchedindividuals from the national Health Interview Survey(NHIS) in 2000• Health status significantly poorer in cancer survivors• Required more help with activities of daily living.JNCI 96:1322,2004
  • 9. Stress and CancerProstate Cancer and Distress- 3 U.S. cancer centers- 263 patient/spouse dyads- Functional Assessment of Cancer Therapy (FACT)- More advanced cancer – more distress- Patients and spouses equally affected- Recurrence = worse emotional QOLNorthouse,2007Journal of Clinical Oncology, Vol 25, No 27 (September 20), 2007: pp.4171-4177
  • 10. Meditation and Cancer PatientsMeta-analysis- 3RC trials, 7 uncontrolled trials- Positive results- Mood, sleep quality, subjective stress reduction- Dose-response effect observedSmith 2005Smith, Joanna E. and Richardson, Janet and Hoffman, Caroline and Pilkington, Karen (2005)Mindfulness-based stress reduction as supportive therapy in cancer care: systematic review.Journal of Advanced Nursing, 52 (3). pp. 315-327.
  • 11. Yoga and StressStudy Evaluated:- N = 39 lymphoma patients- Tibetan yoga (TY) (7 wkly sessions)- Wait list control- Patients in TY group- Better subjective sleep quality (P<0.02)- Longer sleep duration (P<0.03)- Less use of sleep medications (P<0.02)Cohen 2004Alternative and Complementary Therapies. August 2004, 10(4): 235-236.
  • 12. Imagery• A technique of using the imagine to visualize asoothing, pleasant image.• Benefits include: decreased physical tension,anxiety, and the adverse effects ofchemotherapy.
  • 13. Exercise• Currently nearly 10 million cancersurvivors in the U.S.• Numerous studies suggest that exercisehas a positive effect on quality of lifefollowing a cancer disgnosis.(Courneya & Friedenriech, 1999: Dimeo et al., 1999)
  • 14. • Suffering occurs when there is aresistance reaction to a perceivedthreat to the integrity or existence ofthe person.• Pain is part of the human life.SUFFERING VS. PAIN
  • 15. ONCOLOGY AND MUSIC• First visit• Chemotherapy• Surgery
  • 16. Music in Oncology Patients• Music alleviates anxiety in patients receivingRT (Smith,et.al. Nurs Forum 28:855-862. 2001)• Reduces anxiety mood disorders in pediatricpatients (Barrera<M. et.al. Psychooncology11:379-388, 2002)• QOL indices improved in terminal cancerpatients (Hilliard,R. J.Music Ther 40:113-137,2003)
  • 17. Sound TherapySound therapy is the systematic, scientific, and creativeapplication of sound and chanting to achieve a sense ofharmony and inner peace. Sound therapy is an integrativewellness practice similar to yoga and meditation. As a holistictreatment approach, sound therapy focuses on the well beingof the entire person, not just the part which is diseased.
  • 18. SPIRITUALITY AND DEPRESSION• Most studies show that there is an inverserelationship between religious observance andseverity of depression (85% of studies)• Intrinsic religious faith is associated with lowerlevels of depressive symptoms.• Private religious behaviors (prayer and meditation)inversely associated with depression. (Koenig, 1997)
  • 19. K-ras, Oncotype DX, CYP2D6By increasing efficacy and screening outpatients who likely will not respond to aparticular drug, biomarkers improve patientcare and the treatment of cancer, whilereducing costs associated with unnecessaryless effective therapies.
  • 20. OncotypeDx Predictive BiomarkerTherapeutically Relevant Gene ExpressionSignature• <10% of node negative ER+ breast cancerpatients require or benefit from the cytotoxicchemotherapy that they receive• Identify patients with node negative ER+breast cancer who have low risk of recurrenceon tamoxifen alone
  • 21. B-14 Results—Relapse-Free Survival338 pts149 pts181 ptsp<0.0001Paik et al, SABCS 2003
  • 22. • Thiopurines – TPMT• Irinotecan – UGT1A1• Warfarin – CYP2C9 and VKORC1• Tamoxifen – CYP2D6Biomarkers of Drug Metabolism may also bepredictive of responders
  • 23. Cytochrome P450Genetic Polymorphisms•CYP2C9•CYP2C19•CYP2D6
  • 24. Jin et al., J. Natl. Cancer Inst. 97:20-39, 2005.Tamoxifen Biotransformation
  • 25. Relapse–Free Survival, % Disease–Free SurvivalTamoxifen PharmacogenomicsGoetz et al., Breast Cancer Res. Treat. 101:113-121, 2007.Breast Cancer (190 Patients)
  • 26. Relapse-Free (RF) Probabilityby CYP2D6 GenotypeSchroth et al., JCO 25:5187-93, 2007No Tamoxifen TamoxifenTamoxifen
  • 27. Fasting Insulin and Outcome in Early-Stage BreastCancer: Results of a Prospective Cohort StudyPurpose: Insulin, a member of a family of growthfactors that includes insulin-like growth factor (IGF)-I andIGF-II, exerts mitogenic effects on normal and malignantbreast epithelial cells, acting via insulin and IGF-I receptors.Because of this and because of its recognized associationwith obesity, an adverse prognostic factor in breast cancer,we examined the prognostic associations of insulin in early-stage breast cancer.J Clin Oncol 20(1):42-51, January 1, 2002
  • 28. Fasting Insulin and Outcome in Early-Stage BreastCancer: Results of a Prospective Cohort StudyHigh levels of fasting insulin identify womenwith poor outcomes in whom more effectivetreatment strategies should be explored.J Clin Oncol 20(1);42-51, January 1, 2002
  • 29. I G F-1 Biomarkers• similar in structure to insulin.• regulated by growth hormone.• Levels of growth hormone and IGF-1 decline as men and women age.• this decrease is believed to be linked to health problems associated withold age.• 633 men, aged 50 and older.• IGF-1 levels were measured between 1988 and 1991.• 18 years of follow-up, men whose IGF-1levels were above 100 nanogramsper milliliter at the start of the study twice a likely to die of cancer asthose with lower levels.• The increased risk of cancer death for older men with highlevels of IGF-1 was not explained by differences in age, body size,lifestyle or cancer history.March 2010, Journal of Clinical Endocrinology & Metabolism
  • 30. FRENCH LILACGallega officianalis• Metformin—A new targeted therapy forcancer treatment and prevention?• Diabetics on metformin-40% less canceroverall, 56% less breast cancer, 62% lesspancreatic cancer• Suppresses EGFR 2 (her2neu)• 3 fold increased path CR rate in neoadjuvantchemo• Induces apoptosis in pancreatic cancer
  • 31. DETOXIFYING ENZYMES and BREASTCANCER• JOHNS HOPKINS UNIVERSITY STUDY– Compared genetic detoxifying enzyme ability of110 patients with breast cancer vs. 113 controls– Abnormal glutathione-S-transferase genes causingdecreased enzyme activity resulted in a fourfoldincreased risk of breast cancer(Helzlsouer, K. et al., J. Nat. Can. Inst. 1998)
  • 32. VITAMIN D AND BREAST CANCERGarland,Cedric et al.(UCSD) AACR 2006Meta-analysis 1,760 women- 25-OH Vit. D levelsMultiple regression analysis: D3 level>52ng/ml assocwith 50% lower risk breast CA compared withlevels<12 ng/ml.Previous study (Prev Med 1990:19:614-22):Demonstrated women living closer to the equator,had significantly lower risk of breast cancer death
  • 33. Deficiency of Vitamin D, a Membrane BoundAntioxidant, Linked to Poorer outcome in BreastCancer• Vitamin D receptors found in breast cancer cell nuclei• Effects: slow cell growth, induces apoptosois anddifferentiation• 37.5% had levels < 50 (deficient), 38% 50-72(insufficient), 24%>72(sufficient)• Median f/u 512 women 11.6 years-Deficient patents94% >chance mets and 73%.chance of death thanpatients with levels over 50.• Goodwin,P. et. al ASCO 2008 abst. 511
  • 34. Post- treatment Biomarkers• Infectious Agents (HPV, H.pylori, D-arabinitol foryeast overgrowth)• Inflammation (CRP,ESR, fatty acid metabolism)• Metabolic syndrome (IGF-1,A1C, beta-hydroxybutyrate, insulin)• Hormones• Immunologic (NK cell number/activity)• Inherited Susceptibility Polymorphisms, BRCA• Micronutrients (selenium,zinc)
  • 35. Inherited Breast / Ovarian CancerBRCA1 or 2 MutationFuture of Predictive Genomics• Women have an 82% lifetime risk of breast or ovarian cancer• Risk has increased since 1940• Risk of breast cancer 24% if born before 1940 but67% if born after 1940• Risk of ovarian cancer was twice as high for BRCA1carriers and 23% higher for BRCA2 carriers if bornafter 1940King et.al Science 24 October 2003 Vol.302 P 643-646
  • 36. Soy and Breast Cancer•Soy Food Intake and Breast Cancer Survival Xiao Ou Shu, MD, PhD; Ying Zheng, MD, MSc; HuiCai, MD, PhD; Kai Gu, MD; Zhi Chen, MD, PhD; Wei Zheng, MD, PhD; Wei Lu, MD, PhD• JAMA. 2009;302(22):2437-2443.• Context Soy foods are rich in isoflavones, a major group of phytoestrogens that have been hypothesized to reduce the risk ofbreast cancer. However, the estrogen-like effect of isoflavones and the potential interaction between isoflavones and tamoxifen have led to concernabout soy food consumption among breast cancer patients.• Objective To evaluate the association of soy food intake after diagnosis of breast cancer with total mortality and cancer recurrence.• Design, Setting, and Participants The Shanghai Breast Cancer Survival Study, a large, population-based cohort study of 5042 female breast cancersurvivors in China. Women aged 20 to 75 years with diagnoses between March 2002 and April 2006 were recruited and followed up through June2009. Information on cancer diagnosis and treatment, lifestyle exposures after cancer diagnosis, and disease progression was collected atapproximately 6 months after cancer diagnosis and was reassessed at 3 follow-up interviews conducted at 18, 36, and 60 months after diagnosis.Annual record linkage with the Shanghai Vital Statistics Registry database was carried out to obtain survival information for participants who werelost to follow-up. Medical charts were reviewed to verify disease and treatment information.• Results During the median follow-up of 3.9 years (range, 0.5-6.2 years), 444 deaths and 534 recurrences or breast cancer–related deaths weredocumented in 5033 surgically treated breast cancer patients. Soy food intake, as measured by either soy protein or soy isoflavone intake, wasinversely associated with mortality and recurrence. The hazard ratio associated with the highest quartile of soy protein intake was 0.71 (95%confidence interval [CI], 0.54-0.92) for total mortality and 0.68 (95% CI, 0.54-0.87) for recurrence compared with the lowest quartile of intake. Themultivariate-adjusted 4-year mortality rates were 10.3% and 7.4%, and the 4-year recurrence rates were 11.2% and 8.0%, respectively, for women inthe lowest and highest quartiles of soy protein intake. The inverse association was evident among women with either estrogen receptor–positive or –negative breast cancer and was present in both users and nonusers of tamoxifen.• Conclusion Among women with breast cancer, soy food consumption wassignificantly associated with decreased risk of death and recurrence
  • 37. Nurses Health Study• Women who take Aspirin regularly following a breastcancer diagnosis cut their risk of death and metastasisby nearly 50%.• “aspirin has relatively benign adverse effects comparedwith cancer chemotherapeutic drugs and may alsoprevent colon cancer, cardiovascular disease, andstroke”• Appears to affect estrogen receptor–positive and –negative tumors.• (J. Clin. Oncol. October 2010)
  • 38. SOY ISOFLAVONES AND BREASTPROLIFERATION• Palomares,M San Antonio Breast Cancer Symposium(2005)(Poster)• 23 postmenopausal breast cancer (Stage I, II, DCIS) patients atCity of Hope National Medical Center• Randomized:Isoflavone tab 100mg/d vs.placebo for 1 year• Bx contralat. breast at 0, 6, and 12 mo:Ki67 index decreasedfrom baseline in Rx group by 3.1% vs.0.9% control (6 mo.) and4.9% vs.4.1% (12 mo.) “Our findings suggest no negativeeffects of soy and perhaps even a beneficial effect”
  • 39. Obesity /Survival /Ovarian Cancer-Pavelka et al., Cancer (Published Online): 28 August 2006●Evaluated association of of excess body weight onovarian cancer survival●For patients with advanced stage disease, obesity wasindependently associated with both shorter time torecurrence and shorter overall survival. Findings suggestadverse effect of excess body weight on tumor biology.
  • 40. HE4 for Recurrence of Ovarian Cancer• FDA approved 2010• Slightly higher sensitivity and specificity thanCA 125• 75% PTS. W/NO CHANGE— CORRELATEDW/NO PROGRESSION OF DISEASE• 60% W/+ CHANGE—CORRELATED WITHDISEASE PROGRESSION
  • 41. Green Tea and Prostate Cancer• Bertuzzi,S AACR 2005(abstract)• 30 men with high grade PIN• Randomized Control vs 600 mg/d green tea catechins• Bx done at 0 and 12 mo• 9 cases prostate CA control and 1 in Rx group at 1year• The 30% incidence at 1 year is c/w literature• No adverse effects in Rx group
  • 42. INTEGRATIVE ONCOLOGY PATIENT TOOLS• Acupuncture• Biofeedback• Healing Touch• Guided Imagery• Writing/Journal workshops• Massage• Nutrition Consultation• Stress Mastery (Yoga/Meditation)• Vitamin & Herbal Consultations• Fitness Consultations
  • 43. The Art of Medicine• Understanding with the heart• “I will keep pure and holy both my life andmy art” Hippocratic Oath
  • 44. Gaynor’s Four Principles ofHarmonious Survivorship
  • 45. The new definition ofsuccess is having eachday more peaceful thanthe one before.
  • 46. The Subtle HarmonyOvercomes AllDisharmony
  • 47. You Are Not That Which You WereNor Are You That Which YouImagineYou Are That Which You AreBecoming
  • 48. You Are Not That Which You WereNor Are You That Which YouImagineYou Are That Which You AreBecoming