cancer survivorship conference at jefferson university hospitals
DESCRIPTION
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.TRANSCRIPT
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Daniel A. Monti, M.D.
Professor and Director
Myrna Brind Center of Integrative Medicine
Thomas Jefferson University and Hospital
Cancer Survivorship and Integrative
Cancer Care
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Jefferson-Myrna Brind Center of Integrative Medicine: 925 Chestnut St.
STE 120
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• 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
Our Survivorship Model
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The Goals of Integrative Cancer
Survivorship Care
Reduction of Risk
Symptom Management
Quality of Life
Decrease Stress
Test Adjunctive therapies
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Trend Modification:
• Lifestyle
• Environment
• Nutrition
*Will account for up to 75% of health and
life expectancy after 40
Murray and Lopez (1997)
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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)
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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)
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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.
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Let your food be your medicine
And your medicine be your food Hippocrates
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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
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2000
Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
2010
1990
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
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Obesity Rates (OECD, 2012)
0%
5%
10%
15%
20%
25%
30%
35%
1970 1975 1980 1985 1990 1995 2000 2005 2010
Rat
e o
f o
bes
ity
Year
USA
England
Spain
France
Canada
Korea
Italy
Switzerland
Ireland
Hungary
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Insulin and IGF-1 and Cancer
Gallagher and LeRoith, Trends in Endo and Metab, 2010
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Obesity-Associated Malignancies
• Breast (post-
menopausal)
• 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
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WCRF/AICR Dietary Recommendations to
Reduce Cancer Risk 2007
• Limit consumption of red meats (beef, pork and
lamb) and avoid processed meats
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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
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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)
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Chronic Inflammation • Mood Disorders
• Autoimmune Disorders
• Cancer
• Cardiovascular Disease
• Psoriasis
• Alzheimer’s Disease
• Type I and II diabetes mellitus
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Nutrition and Inflammation
Foods that increase
inflammation
Foods that decrease
inflammation
Red meat, eggs 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
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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
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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
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Metabolic Pathways of Essential Fatty Acids
*Factors thought to impair delta-6-desaturase activity include Mg, Zn, and B1 deficiency; aging,
alcohol, trans fatty acids; and high cholesterol levels.
Omega-6 Fatty Acids (e.g. corn, safflower, sunflower oil)
Omega-3 Fatty Acids (e.g. canola, flaxseed oil, fish oils)
Linoleic acid (LA) Alpha-linoleic acid (LNA)
delta-6-desaturase delta-6-desaturase
Gamma-linolenic acid (GLA) (e.g. evening primrose, borage,
and black currant seed oils)
Steridonic acid
Dihomo-gamma-linolenic acid (DGLA)
Eicosapentaenoic acid
PGE1 (anti-inflammatory)
delta-5-desaturase
delta-5-desaturase
EPA (e.g. fish oils)
Arachidonic acid
DHA
cyclooxygenase lipoxigenase
PGE2 (pro-inflammatory)
LTB4 (pro-inflammatory)
cyclooxygenase lipoxigenase
PGE1 (anti-inflammatory)
(e.g. Mg, Zn)
LTB5 (anti-inflammatory)
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Butter Pork Beef Eggs
Ailhaud et al., Prog. Lip. Res., 2006
Omega-6
/Omega-3
x6
x10
x15
x20
Transformation of food chain
from 1960 to 2000
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“Fasting vs dietary restriction in cellular protection
and cancer treatment: from model organisms to patients”
Lee and Longo: Oncogene (2011) 30, 3305-3316
Traditional Dietary approaches such as
Fasting and Dietary Cleanses may have a
scientific basis
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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)
Multivitamins in the Prevention
of Cancer in Men:
The Physicians’ Health Study II JAMA, 2012
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Yellow Mouse Agouti Mouse
Cooney et al. J Nutr 132:2393S (2002); Dolinoy et al. Envir. Health Perspect 114: 567 (2006)
Maternal
Supplements
with
zinc, methionine
betaine, choline,
folate, B12
Or
Genistein
High risk cancer, diabetes,
obesity & reduced lifespan Lower risk of cancer, diabetes,
obesity and prolonged life
LTR Hypomethylated LTR Hypermethylated
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Rickets
Osteoporosis / Osteopenia
Cancer Skin
GI / Celiac Mood Disorders
Neurological: MS / PD / ALS
Cardiovascular
Vitamin D Research www.vitamindcouncil.com accessed July 6, 2009
TIGHT JUNCTIONS
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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
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Acupuncture
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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
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Endorphin Theory
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“It’s not the load that breaks you down, it’s the way you carry it.”
Lena Horne
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Anterior Pituitary
Adrenal Cortex
Cortisol
Blood sugar
Stress Response Pathways
Stimuli
Hypothalamus
Adrenal Medulla
Epinephrine
NorEpinephrine
HTN, High Chol
Sympathetic
Post-Ganglionic
Neurons
NorEpinephrine
Arrhythmia
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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
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Individual and group mind-
body interventions
• Classic examples include: mindfulness-
meditation, NET, Yoga, biofeedback,
qigong, tai chi, expressive arts therapies,
others
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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
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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
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MBAT Outcomes
Health Related Quality of Life 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, Psycho-
Oncology)
Figure 2. SF-36 General Health
p = 0.008
-5
0
5
10
15
Ad
juste
d M
ean
: W
k 8
- W
k 1
Treatment -0.59 7.97
Control MBAT
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MBAT Outcomes
Psychological Distress
Changes in the
SCL-90-R
Global Severity
Index in MBAT
participants as
compared to
controls (p <
0.001).
(Monti et al, 2006,
Psycho-Oncology)
Figure 1. SCL-90-R Global Severity Index
p < 0.001
-0.35
-0.25
-0.15
-0.05
0.05
Ad
jus
te
d M
ea
n: W
K 8
- W
k 1
Treatment -0.04 -0.20
Control MBAT
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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
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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)
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Stressor task post minus stressor pre-training program
Monti et al, Stress & Health (2012)
MBAT group (p<0.005) Control group (p<0.005)
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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!
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JeffQuit
- Three week program
- High success rate
- Study participation costs
less than a week’s
worth of cigarettes!
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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
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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
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Mastering Food Labels
2.5
Commercial Can of Soda
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Replacing Bad Fats with
Healthy Ones
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Sample Exercise- Week 3
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Ascorbic acid (Vitamin C)
and other nutrients are
being studied at Jefferson
for anti-cancer effects
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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.
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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