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

Jefferson-Myrna Brind Center of Integrative Medicine: 925 Chestnut St.

STE 120

• 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

The Goals of Integrative Cancer

Survivorship Care

Reduction of Risk

Symptom Management

Quality of Life

Decrease Stress

Test Adjunctive therapies

Trend Modification:

• Lifestyle

• Environment

• Nutrition

*Will account for up to 75% of health and

life expectancy after 40

Murray and Lopez (1997)

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)

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)

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.

Let your food be your medicine

And your medicine be your food Hippocrates

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

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%

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

Insulin and IGF-1 and Cancer

Gallagher and LeRoith, Trends in Endo and Metab, 2010

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

WCRF/AICR Dietary Recommendations to

Reduce Cancer Risk 2007

• Limit consumption of red meats (beef, pork and

lamb) and avoid processed meats

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

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)

Chronic Inflammation • Mood Disorders

• Autoimmune Disorders

• Cancer

• Cardiovascular Disease

• Psoriasis

• Alzheimer’s Disease

• Type I and II diabetes mellitus

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

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

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

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)

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

“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

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

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

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

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

Acupuncture

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

Endorphin Theory

“It’s not the load that breaks you down, it’s the way you carry it.”

Lena Horne

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

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

Individual and group mind-

body interventions

• Classic examples include: mindfulness-

meditation, NET, Yoga, biofeedback,

qigong, tai chi, expressive arts therapies,

others

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

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

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

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

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

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)

Stressor task post minus stressor pre-training program

Monti et al, Stress & Health (2012)

MBAT group (p<0.005) Control group (p<0.005)

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!

JeffQuit

- Three week program

- High success rate

- Study participation costs

less than a week’s

worth of cigarettes!

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

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

Mastering Food Labels

2.5

Commercial Can of Soda

Replacing Bad Fats with

Healthy Ones

Sample Exercise- Week 3

Ascorbic acid (Vitamin C)

and other nutrients are

being studied at Jefferson

for anti-cancer effects

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.

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

Thank you!

No industry support, conflicts of

interest or disclosures to report

daniel.monti@jefferson.edu