1. Integrative Oncology
Comprehensive Care of the Patient with
Cancer
Philip Trabulsy M.D.
Assistant Professor UVM COM
UVM Program In Integrative Health
Hematology Oncology Rounds UVM
September 18, 2012
2. Integrative Medicine and Health
“It is more important to know what sort of person has
a disease than to know what sort of disease a person
has.”
Hippocrates/Sir William Osler
“The good physician treats the disease; the great
physician treats the patient who has the disease.”
Sir William Osler, To his students
3. Integrative Medicine
What It’s Not
Alternative Medicine
• Typically promoted as a substitute for conventional
care
• Not been scientifically proven
• Scientific foundation lacking
• Some therapies disproved by scientific analysis
• Generally not taught in Medical Schools
• Not covered by third-party payors
NIH, NCCAM 2002
4. Integrative Medicine
What it is
Integrative medicine combines biomedical care with
appropriate complementary therapies, to heal and
preserve the health of the patient’s body, mind, and
spirit.
It emphasizes the individual’s capacity for self-healing
and offers an approach to care that is
personalized, collaborative, and comprehensive. This
approach is interdisciplinary and utilizes the skills of
other health care disciplines and professionals through
referral and consultation.
Consortium of Academic Health Centers for Integrative Medicine
5. Relationships
Research suggests that our presence as medical
or mental health clinicians, the way we bring
ourselves fully into connection with those for
whom we care, is one of the most crucial factors
supporting how people heal- how they respond
to our therapeutic efforts.
Dan Siegel: The Mindful Therapist, 2010
“ Care more for the individual patient than for the
special features of the disease… The kindly
word, the cheerful greeting, the sympathetic look
– these the patient understands”
Sir William Osler
6. Integrative Therapies
( Complementary and Alternative Medicine)
“ a group of diverse medical and health care systems, practices, and products
that are not presently considered part of conventional medicine”
• Biologically based :
dietary, nutreuceutical, herbal, homeopathy
• Mind-body : Hypnosis, guided
imagery, meditation, expressive arts: ie music
therapy
• Manual therapy :
Massage, chiropractic, osteopathic, physical therapy
• Energy therapies : Reiki, Healing/Therapeutic
Touch, QiGong, Reflexology
• Traditional medical systems : TCM, Ayurvedic
National Center for Complementary and Alternative Medicine( NCCAM)
7. Why Integrative Oncology?
• CAM use in adult oncology patients: 25-90%
• CAM use in pediatric oncology patients: 31-84%
• High risk women in genetic testing program: rate of 53% CAM use
• Hospitalized cancer patients supplement use of 73% in previous 30
days
• High rates of 68% in oncology pts, with 80% dietary use during
radiation therapy
Yates et al, Support Care Cancer 2005
Kelley KM, Eur. J Cancer 2004
Vapiwala et al, Cancer J 2006
8. Why Integrative Oncology?
Predictors of CAM use
n= 676, 302 non-ca volunteer, 219 ca pt., 156 professionals
-prevalence CAM use: 29%, 31%, and 39%
- female gender, 30-50yo (p <0.001)
- High school or higher education, private insurance, higher income
(p<0.001)
- No assoc. with ca. stage
Reasons for use: Non-Users
- 51% family , friends - 50% lack info
- 31% own choice, 9% media - 21% no interest
- 4% MD recommend - 12% no belief
- 61% immune support - 4.7% never needed it
- 27% well-being - 1.7% too expensive
- 6% prevent ca - 1.3% happy conventional
Chang et al. BMC Cancer 2011, 11:196
9. Why Integrative Oncology?
Communication Gaps
– CAM users : 30 % openly reported to MD
– 8/149 MD’s asked about CAM use
Provider perspective
• 17% encourage continue, 4% stop use, 60% neither
Patient perspective
• 37% encouraged continue, 16% stop use, 47% neither
• 35% MD did not ask, 4% not understand, 6% disapprove
Knowledge
• 59% faculty report lack knowledge base
• 78% faculty report not up to date on recent evidence
• > 50% would welcome further education
10. Why Integrative Oncology?
Patient Perspectives
– Locus of control - CAM is”safe,non-toxic”
– Empowerment - Loss faith in traditional
– Immune support
– Symptom management
– Fear
– Decrease stress
– Shouldering the hope
Richardson MA, et al., 2000 J Clin Oncol, 18: 2505
11. Disclosure of CAM use to the Oncologist
• 57% disclosure by cancer patients
• Majority of disclosures are incomplete (1 CAM)
• Prayer and relaxation most commonly reported
• Dietary supplement use reported 20-30%
• 85% Oncologists felt lack knowledge to recommend CAM
• 84% Oncologists concern for drug-interactions
Barriers
– Physicians indifference or opposition
– Did not think it important or that it was CAM
– Providers rarely asked
– Patient’s anticipation of a negative response from their physician
– Just asking directed question about CAM increased disclosure from 7%-43%
Hyodo et al, Cancer, 2003;97(11):2861-85
12. Pathways Study
• 1000 women AJCC stage I/II BC, prospective cohort
– 98% CAM use prior to Dx.
– >20% weekly green tea, omega-3fa , prayer, religion
– 86% use CAM post-diagnosis
• 47% botanicals
• 47% other”natural’ products
• 28% special diets
• 64% mind-body healing
• 27% manual, energy treatments
“CAM use before and after Dx is common. Emphasis on need to
discuss CAM use with all BC patients”
Greenlee et al., Breast Cancer Res Treat. 2009 Oct;117(3)
13. Don’t Ask, Don’t Tell
Optimizing Chemotherapy: Concomitant Medication Lists
M H Hanigan B Ldela Cruz SS Shord P J Medina J Fazili and D M Thompson
Clinical Pharmacology & Therapeutics (2011) 89 1, 114–119.
14.
15. Lifestyle and Cancer
• For the 12 common cancers about 35% of the
cases in the U.S. are preventable through a
healthy diet, being physically active and
maintaining a healthy weight. 37% for the
UK., 30% for Brazil and 27% for China.
• This translates to 340,000 preventable cases of
cancer in the USA
– AICR 2009 Policy Report, GLOBOCAN 2008
16. Weight Guidelines
Weight Guidelines
•Balance caloric intake with physical
activity
•Avoid excessive weight gain
throughout lifecycle
•Achieve and maintain a healthy
weight if currently overweight
19. Obesity-Associated Malignancies
% Annual U.S. Ca Excess Body Fat
TYPE % Cases
• Breast 17 33,000
• Esophagus 35 5,800
• Pancreas 28 11,900
• Gallbladder 21 2000
• Colorectal 9 13,200
• Endometrial 49 20,700
• Kidney 24 13,900
AICR/WCRF “Policy and Action for Cancer Prevention” report 2009
20. September: National Gynecologic
Cancer Awareness Month
• Endometrial Cancer
– 47,000 cases/yr. in U.S. 8000 deaths
– 33,000 preventable
• Stay lean
• Avoid abdominal fat
• Active every day
» Ferav Jet al., GLOBOCAN 2008, Cancer Incidence and
Mortality: AIRC
21. Insulin Like Growth Factor-I
• Evidence implicates IGF-I signaling in development
and progression of many cancers, including breast
– High IGF-I levels predict increased risk
– Antiestrogens reduce IGF-I levels
– IGF-IR hyperactive and overexpressed
– IGF-IR targeted in therapies
• IGF-I caused gene expression changes in breast ca.
assoc. cell proliferation, metabolism and DNA repair
Creighton et al., JCO, 2008
22. Exercise and Cancer Survival
• 50% decreased risk cancer-specific mortality with 9-15 MET
hrs./wk. Nurses Health Study
(Holmes et al. 2005)
• 49% risk reduction of recurrence/death at 3 years. Study: 832
pts. Stage III colon ca. Adjuvant chemo + physical therapy
• 61% reduction death. 573 nurses, stage I-III colorectal ca,
18 METs/wk
Meyerhardt JCO August 2006
23.
24. Supplement Debate
“ There is strong evidence that a diet rich in
vegetables, fruit, and other plant-based foods may
reduce the risk of cancer, but there is no evidence
that supplements can reduce cancer risk… and some
evidence that indicates that high-dose supplements
can increase cancer risk “
Selenium and Vitamin E(SELECT) Study, Alpha-
Tocopherol, B-Carotene Study (ATBC), Women’s
Antioxidant Cardiovascular (WACS)
25. Supplement Research Difficulties
• Concentrated intake of a single form vs. combined forms
natural foods
• Higher exposure than through normal food
• Lack of other healthy dietary components ( poor habits)
• Recommendations
– Use in those with micronutrient deficiencies
– Observe appropriate doses
– If high dose mimic natural form of supplement: ie. Vit E as mixed
tocopherols, Vitamin A in mixed caratenoids vs. B-caraotene or Vit A
palmitate
– Aim to meet needs through diet alone
WCRF/AICR
26. The Antioxidant Debate
Disadvantages Advantages
• Antioxidants interfere with • Oxidation supports
mechanism of cytotoxic malignant proliferation
chemo or radiotherapy • Oxidation may diminish
• Use of antioxidants causes therapeutic benefit of
diminished treatment effect chemo/radiation
and protection of tumor • Antioxidants improve Rx
efficacy and protect from
toxicity of treatments
27. Antioxidant Advice
• Depends on goal of treatment
If Cure, proceed with caution
• Delay antioxidants until end of Rx
• Discontinue day before, of, after chemo
• Avoid during radiotherapy unless for specific toxicity ameliroation
If Palliation, encourage use for protection of normal
tissue, optimization of QOL
Abrams D. Integrative Oncology 2006
→ Antioxidant radiation and chemoprotectants
(mesna, amifostine) reportedly do not interfere with
anti-tumor effects of Rx
28. Vitamin D3 ( Cholecalciferol)
• Long recognized as involved in bone
health, now felt to be linked to:
– Depression/Schizophrenia
– Pain syndromes
– Insulin resistance
– Infections (URI/Tb)
– Impaired immunity
– Macular degeneration
– Pre-eclampsia
29. Vitamin D3 ( Cholecalciferol)
• Cancer Modulation
– Promotes apoptosis
– Suppresses malignant cell proliferation
– Inhibits effects prostaglandins
– Suppresses production cytokines
– Decrease expression aromatase > reduces estrogen
– Inhibits new tumor vascular growth and inhibits
metastases
– Krishnan AV,Feldman D. Mechanisms of Anti-cancer and
Anti-Inflammatory Actions of Vitamin D. Annual review of
pharmacology and toxicology Jan. 2010
30. Vitamin D3 ( Cholecalciferol)
• Epidemiologic studies have shown that low Vit D levels are
assoc. with increased prevalence of
breast, colorectal, prostate, and pancreas.
• A recent meta-analysis of 35 studies showed that a 10ng/ml
increase in25(OH)D was assoc. with 15% risk reduction in
colorectal ca, but not for prostate or breast.
• Breast cancer research showed inverse assoc. of Vit D level
when checked post-diagnosis but not in prospective studies
• One study actually found adverse effects of Vit D for certain
cancers ( > 80nmol) stressing need to examine the health
status, life stage, adiposity, estrogen exposure, and nutritional
status of the population in question
Toner et al.; The Vitamin D and Cancer Conundrum:Aiming at a Moving
Target, J Amer Dietic Assoc, NCI, NIH
31. VITamin D and OmegA-3 TriaL
VITAL Study
• Randomized, double-blind, placebo controlled
multi-center trial in 20,000 participants, 5 year
study, began 2010
• Women > 65, men> 60 w/o hx cancer, CVD,
CVD
• One or both, or placebo
• Endpoints cancer, cardiovascular events,
cognitive function, diabetes, fractures
34. Potential Benefits of Dietary Supplement Use
During Conventional Therapy
• Immune Modulators
Medicinal mushroom ( PSK)
– Solid tumors, mostly animal studies, some human
– RCT 207 pt., Stage II,III colorectal ca. 3gm/day PSK
• 5yr disease free survival and regional metastases significantly
reduced in treatment group.
– 8 RCT’s 8009 gastric ca. pt’s: PSK 3gms/day
• pt’s> increased survival p<.018, increase disease free survival
– Study 30 advanced lung ca. pt’s. > no change survival
Ohwada S. et al.,Br J Cancer 2004;90(5
Oba K. et al., Cancer Immunol Immunother 2007;56(6)
Gao Y. et al.,J Med Food 2005;8(2)
35. Potential Benefits of Dietary Supplement Use
During Conventional Therapy
• Immune Modulation
Avemar
– Methoxy-substituted benzoquinone shown immunomodulatory and
anti-tumor activity in animal and human clinical trials
– Triggers apoptosis by regulating Poly( ADP-ribose) polymerase without
harm normal cellc
– Non-random advanced adult colorectal ca.pt’s (n=104) +conventional
Rx
– After 6mos. Fewer recurrences (3% vs 17%), new mets (8% vs
23%), death (12% vs 32%) all p< .01
• RCT Stage III melanoma (n=42) receive decarbazine chemo
– increase time-to-relapse (9 vs 4 mos.), without change in relapse
rate, and with increase no. free of disease at 1 yr (55% vs 38%)
Boros LG et al., Ann NY Acad Science 2005;1051:529-42
Jakob F et al.,Br J Cancer 2003;89(3)
Demidov L et al., 18th UICC Inter CA Congress.Oslo, 2002
36. Potential Benefits of Dietary Supplement Use
During Conventional Therapy
Stomatitis/Mucositis
Glutamine
– Positive results reported in a number of adult and pediatric
studies with oral glutmamine as swish and swallow. Both
chemotherapy and radiation induced mucositis. No
untoward chemo effects
• One large phase III trial using 5-FU chemo did not show
benefit
Cerchietti LC et al., Int J Radiat Oncol Biol Phys 2006
Okuno SH et al., et al., Am J Clin Oncol 1999
37. Potential Benefits of Dietary Supplement Use
During Conventional Therapy
Peripheral Neuropathy
• Glutamine
– Wang et al. small RCT (n=86) 15gm 2x/day
– Significantly lower incidence Grade 3-4 neuropathy after 4 cycles (5%
vs 18% p=0.05)
– After 6 cycles (12% vs 32%; p=0.04)
– Need for oxaliplatin dose reduction lower in treatment arm
– No between-group difference in response to chemo or survival
• Results promising, but need for larger RCT
Wang WS et al., Oral glutamine is effective for preventing oxaliplatin
induced neuropathy in colorectal cancer patients. Oncologist 2007;12(3)
38. Potential Benefits of Dietary Supplement Use
During Conventional Therapy
Melatonin
• Recent meta-analysis of 8 RCT’s ( n=761) Solid tumor
cancers
– Melatonin sig. improved complete and partial remission
(16.5% vs 32.6%; p< 0.00001)
– ↑1-year survival (28.4% vs 52.2%;p=0.001)
– Dramatic ↓radio-chemo side-effects ( p< 0.001)
– Consistent across all cancers.
– No serious adverse events
– Dosage studied: 20mg/day, target dose slowly over 1-3
weeks
Wang YM et al., Cancer Chemother Pharmacol. 2012
May:69(5)
39. Complementary Cancer Care
Massage Therapy
• Numerous observational studies demonstrate reduction anxiety,
pain, fatigue, and stress
• Most common forms used in oncology include Swedish massage,
therapeutic massage, acupressure, and reflexology
• East Carolina School of Nursing (2000)
– 23 inpatients with breast/lung ca
– foot reflexology 15 min. vs usual care
– Significant reduction anxiety scores and 1 in 3 of pain measures
Cochrane review meta-analysis prior 2002. 8 RCT, n=357 Anxiety
decrease 8, pain 1/3, nausea 2/3
40. Massage Therapy
Mechanism of Action Theories
• Gate theory of pain
• Parasympathetic activity
• Endorphins, serotonin,?enkephalins
• Blood flow
• Lymphatic flow
• Interpersonal attention
41. Complementary Cancer Care
Massage Therapy
• 87 hospitalized cancer patients randomized to foot
massage or an appropriate control
– VAS scale: treatment > control for” immediate” pain
and anxiety ( p<0.03)
Grealish L et al. Cancer Nurs 2000:23
• RCT comparing acupuncture + massage for post-
operative cancer patients
– N=94 Ac+massage, n=48 usual care
– Intervention 1.4 pts. 0-10 scale vs 0.6 control
(p=.038) Depressive mood: intervention 0.4 (1-5
scale), control =/-0 (p=0.003)
Mehling et al. J Pain Symptom Manag 2007:33
42. Complementary Cancer Care
Massage Therapy
• Largest uncontrolled study at Sloan Kettering Cancer
Center. 1290 cancer pts. Symptom score decreased 50%.
– Both in/outpatients, self-reported pre/post survey 48hrs
RC multi-center trial - Massage vs simple touch
– N=380 (90% hospice, mod/severe pain)
– 30 min massage or ST over two weeks
– Both improved pain and mood
– Massage superior immediate pain and mood
– Effects not sustained for pain, QoL, analgesic use
• Kutner JS et al. Ann Intern Med 2008
43. Massage Therapy
• Systematic review of all RCT’s of non-cancer
subacute and chronic back pain
– Massage therapy demonstrated significant
improvements in pain, Qol, function, and possibly
a reduction in cost of care
Evidence-Based Practice Guidelines for Integrative Oncology
• Recommend use for anxiety, pain by oncology- trained
massage therapist. Grade 1C
44. Supportive Cancer Care
Energy Therapies
• eg. Healing Touch, Therapeutic Touch, Reiki, Qi
gong
• Prospective study massage, healing touch, or
“caring presence” during chemotherapy
– N=230, 44% stage III, 4/wk x 45 min
– Credentialed nurses
– MT,HT significant decrease HR( 7bm), SBP, pain
– HT significantly reduced distress, fatigue ( Profile of Mood )
– MT significant decrease NSAID use
– Drawback of high drop out 29%
Post-White J et al. 2003 Integrative Cancer Therapies, 2(4)
45. Supportive Cancer Care
Energy Therapies
• Single-blind randomized trial, HT vs. Mock
– Gyn / breast ca. pts. undergoing Radiation Rx
– N=78, 62 completed
– Pts. Separated by screen from practitioner
• Results
– HT higher overall scores for QoL( SF-36), mental health, emotional
functioning, health transition
– Mock Rx did show similar increases in physical functioning and health
transition, not QoL
– Drawback: statistical analysis was different between groups
Cook CAL et al., 2004 Alternative Therapies, 10 (3)
46. Supportive Cancer Care
Acupuncture
• Strong evidence supports the use of acupuncture for
post-op pain, chronic pain, OA knee, and headache
Berman BM et al. 2004 Ann Intern Med
• Acupuncture also shown to suppress N/V related to
surgery, pregnancy, and motion sickness
Ming JL et al., J Adv Nurs 2002 (39)
Strietberger K et al. Anaesthesia 2004 (59)
47. Supportive Cancer Care
Acupuncture
Cancer related pain:
• Randomized, blinded, controlled trial auricular
acupuncture
– N=90, true acup., sham acup., acupressure
– Pain intensity decrease true >sham, pressure by
36% at two months ( p<0.001)
– Majority >60% with neuropathic pain
Alimi D et al., J Clin Oncol 2003(21)
48. Supportive Cancer Care
Acupuncture
Cancer related pain
- Pilot study acupuncture treatment for arthralgias
related to aromatase inhibitor therapy
– N=21 post-menopausal women with breast ca.
– Randomized to acupuncture 2x/wk x 6wks
– Full body + auricular acupuncture+ local points
– Results: worst pain (5.3 to 3.3,p=0.01), pain severity ( 3.7 to 2.5
p=0.02),functional interference (3.1 to 1.7, p=0.02), phys.well-being
FACT-G ( 19.9 to 23.4 p=0.03)and WOMAC (80.9 to 47.4, p=0.04)
Crew KD et al., J Cancer Surviv 2007(1)
49. Supportive Cancer Care
Acupuncture
Chemotherapy-induced N/V
• Randomized controlled trial true electroacupuncture,
minimal needling w/ mock electroacupuncture or
antiemetics alone
– N=104 breast cancer patients receive high emetogenic
chemotherapy. Acup Rx 1x/day x 5 days
– Results: significant decrease # episodes emesis in
electroacupuncture group sig. less than the other 2 groups ( #
episodes 5, 10, 15 respectively ; p<0.001) minimal needling<
pharm alone
– Differences among groups not significant at 9 days
Shen J et al., JAMA 2000 (284)
50. Supportive Cancer Care
Acupuncture
Other reported benefits:
Equal to venlafaxine in relief hot flashes ( RCT)
Walker EM et al J Clin Oncol 2010 (4)
• 30% improvement in radiation-induced xerostomia ( case
series)
Johnstone et al., Cancer 2002 (26)
• Effective in hot flashes in men undergoing ADT for prostate
cancer ( case control study)
Beer et al., Urology 2010
• Safe in children with cancer related thrombocytopenia
(retrospective study)
Ladas et al., Support Care Cancer
51. Supportive Cancer Care
Mind-Body Medicine
• Guided imagery
• Hypnosis
• Breath work
• Mindfulness therapies
• Biofeedback
• Music therapy, expressive arts
• Cognitive therapies
• Yoga, Tai Chi, movement therapies
52. Mind-Body Approach
Hypnosis Before Breast Cancer Surgery
• N=200 pts. randomized to a)15 min hypnosis before
surgery or b) empathic listening (attention control).
Staff blind ( surgeon, anesthesia, nursing, research)
• Hypnosis group
– Less anesthesia; same post-op meds
– Less pain intensity, pain
unpleasantness, nausea, discomfort, fatigue, emot
ional upset
– Cost savings: $770 per pt. ( 10.5 min less in
surgery)
• 100 cases annual $77,271 savings ? Hire hypnotherapist
Montgomery GH et al., J Nat Canc Inst 2007 ( 99)
53. Recommended Web-Sites
• NCI/CAM www.cancer.gov/cam/health
• Memorial Sloan Kettering Cancer Center www.mskcc.org
• U of T MD. Anderson Cancer Center www.mdanderson.org
• Cochrane Review Organization www.cochrane.org
• Natural Standard www.naturalstandard.com
• Natural Medicines Database www.naturaldatabase.com
• American Botanical Council www.herbalgram.org
54. Insights
• Integrative practitioner can assist oncology teams
navigation across the bridge between conventional
and complementary worlds.
• Non- judgemental communication needs to exist
between practitioner-patient to enhance
honesty, openness, and trust.
• A number of complementary therapies have a
reasonable evidence-base.
• Education (faculty and resident) and use of reputable
resources will help in supporting the clinical-decision
making process.
55. Evidenced-Based Clinical Practice Guidelines for
Integrative Oncology: Complementary Therapies
and Botanicals
• Practice recommendations based on strength of the
evidence and the risks/benefits ratio
• Grading system modeled from the American College
of Chest Physicians Task Force on Grading
– Recommendations: strong ( grade 1),weak (grade 2)
Quality of evidence high (grade A), moderate ( grade B
), low( grade C )
Journal of the Society for Integrative Oncology Vol 7, No. 3, 2009
56. “Two roads diverged in a wood, and I—
I took the one less traveled by,
And that has made all the difference”
Robert Frost, New England Wisdom
57. “ The role of the physician is to
Cure sometimes,
Heal often,
Support always “
Ambroise Pare
