Post on 26-Feb-2021
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2020 Master Class CourseOptimizing Outcomes for Survivors of Cancer
Ann H. Partridge, MD, MPH
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Faculty Disclosure
• UpToDate- royalties as co-author of Breast Cancer Survivorship section
Faculty of this CE activity may include discussions of products or devices that are not currently labeled for use by the FDA. The faculty have been informed of their responsibility to disclose to the audience if they will be discussing off label or investigational uses (any uses not approved by the FDA) of products or devices.
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• An individual is considered a cancer survivor from the time of diagnosis, through the balance of his or her life. There are many types of survivors, including those living with cancer and those free of cancer
• This term is meant to capture a population of those with a history of cancer rather than to provide a label that may or may not resonate with individuals
Who is a “Cancer Survivor”?
National Cancer Institute, 2019
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Survivorship Spans the Cancer Journey
Adapted from NCI, 2005
Pre-Diagnosis Diagnosis & Treatment
Palliative Care;
End of Life
• Needs vary between individuals• Needs vary within individuals along the continuum
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• As of January 2019, it is estimated that there are 16.9 million cancer survivors in the United States alone
• ~5.0% of the population
Bluethmann, Mariotto, & Rowland, 2016; Homer et al, 2019
US Cancer Survivors: Growing Numbers
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Estimated Number of Cancer Survivors in US by Current Age
7Based on data from Surveillance Epidemiology and End Results.
Estimated Number of Cancer Survivors in US by Cancer Site
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• She had stage 3 disease diagnosed when she presented with a mass in her L breast: IDC, grade 3, ER+,PR+, HER2+
• Underwent pre-operative THP chemotherapy with pCRfollowed by lumpectomy, completion of a year of HP and is on ovarian suppression and tamoxifen
• She comes to see you in follow-up and is concerned about how you will follow her and know treatment is working
Hensley et al., 2005
AB is a 42 year old women with early stage breast cancer
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• Follow-up can detect problems that can be:prevented, cured, or controlled
• Overuse and underuse of medical resources for follow-up appears common in long-term survivors
Hensley et al., 2005
Why does survivorship care matter?
10Slide courtesy of Antonio Wolfe, adapted from Tran et al, Taxonomy of the burden of treatment,
a multi-country web-based qualitative study of patients with chronic conditions.BMC Med 2015 PMID 25971838
The Web of Cancer Survivorship
Economic Comorbidities
Personal
Secondary cancers
Structural factors
Employment
Mortality
Quality of life
Follow-up care/maintenance Lifestyle
changes
Situational factors
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4 Major Areas of Focus in Cancer Survivorship
Recurrence and new cancers
Long-term and late effects
Modifiable health behaviors Coordination of care
provider-providerpatient-provider
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• Detection of asymptomatic disease would improve morbidity or mortality
• Lead to earlier additional testing and potential early intervention
• Is cost-effective and safe in a population• Makes sense for that individual patient
Rationale for screening for recurrent cancer
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Summary of Screening for Recurrence - H & P- Mammography if
BCT/contralateral breast remains
- No imaging or bloodwork otherwise
- H & P- CEA q3-6 mos x 5 yrs- CT q12 mos x 3 yrs
- H & P- PSA q 6 mos x 5,
then q yr- DRE annually
- H & P- Chest scans q3-6 mos x
2yrs, then annually
- H & P- Scans and
bloodwork
- H & P- scans and
bloodwork
- H & P, pelvic
- Scans and bloodwork
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New primary disease risk: Update family history and re-visit genetics
Ruddy et. al. J Clin Oncol 2016
• Survivorship care should entail updating family history and revisiting genetic issues
• (re-) testing as needed• Why?
• Barriers to testing at diagnosis may have diminished• Testing is evolving• Patient and systems level indications for testing are
evolving
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Due to Either/All• menopausal
symptoms, infertility, sexual dysfunction
• osteoporosis • weight gain• cognitive impairment• fatigue• metabolic syndrome
Chemotherapy And Biologics
• neuropathy• secondary leukemia• cardiac dysfunction• Autoimmune problems• GVHD
Hormonal Therapy• menopausal
symptoms• sexual dysfunction• myalgias,arthralgia• cataracts• hyperlipidemia• uterine malignancies• vascular events
Local Therapy (Surgery and Radiation)
• Pain, numbness, lymphedema, restricted motion or weakness
• cosmetic breast or reconstruction changes• cellulitis, nerve damage, rib fracture,
pneumonitis• heart disease, sarcomas, skin and other
second cancers, lung fibrosis• Site-specific problems (hypothyroidism)
Adapted from Nekhlyudov and Partridge, 2013
Psychosocial distress
Long-term and Late Effects in Cancer Survivors
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• He was diagnosed after abnormality detected on digital rectal exam by his internist
• He underwent radiation and ADT which he will take for 2 years given he had localized high risk disease (Gleason 9)
• He comes to see you in follow-up and his wife is concerned about how she will know whether treatment is working, and about his smoking and drinking and lack of exercise
Hensley et al., 2005
BC is a 70 year old man with history of hypertension with early stage prostate cancer
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Preventable diseases:
• Heart disease• Second cancers• Suicide
Zaorsky et al, Annals of Oncology 2017
What do cancer survivors die of?
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Links Between Cancer and CV Disease
Slide courtesy of A. Nohria
• Increasing Age Biomarkers including Clonal Hematopoiesis of
Indeterminate Potential• Shared risk factors Tobacco, obesity, physical inactivity, menopause
• Cardiotoxicity of certain cancer treatments
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Oxybutynin Reduces Hot Flashes
Leon-Ferre et al. JNCI Cancer Spectrum 2019
• 150 women enrolled, mean age was 57 years; 65% on tam or AI• Randomized to 2.5 mg bid, 5mg bid or placebo• Both oxybutynin doses lead to:
greater reductions in the weekly HF score P < .005 HF frequency P < .003 improvement in most HF-related daily interference scale measures and in
overall quality of life more side effects (most grade 1 or 2): dry mouth, difficulty urinating, and
abdominal pain No differences in study discontinuation because of adverse effects 5mg bid a little more effective numerically
• Works for men on Androgen Deprivation Therapy too! (Smith et al case report NEJM 2018)
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Mean Hot Flash Score Percent ReductionRandomized Trials
0
20
40
60
80
100
0 1 2 3 4 5 6Week
% Ven (vs MPA) (n=94)Citalopram (n=57)
Placebo (n=759)Clonidine (n=75)
Venlafaxine (n=48)
Fluoxetine (n=36)
Pregabalin (n=63)
MPA 400 mg (n=94)
Megestrol (n=74)Oxybutynin (n=35)
Not superior to placebo:- Soy - Flaxseed - Black Cohosh - Mg oxide- Vitamin E
C Loprinzi, DL Barton, and colleagues. Mayo Clinic, Rochester, MN
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Randomized Blinded Sham- and Waitlist-Controlled Trial of Acupuncture for Joint Symptoms Related to Aromatase Inhibitors in Women with Early Stage Breast Cancer (SWOG 1200)
AI > 3/10 Worst Pain
N=226
True Acupuncture 2x week x 6 weeks
True Acupuncture 1x week x 6 weeks
No Acupuncture12 weeks
Sham Acupuncture 2x week x 6 weeks
Sham Acupuncture 1x week x 6 weeks
No Acupuncture12 weeks
Wait List Control6 weeks
Wait List Control6 weeks
Wait List Control12 weeks
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1
1
Assessment Week 0 6 12 24
Presented with permission, Hershman et al., SABCS 2017
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Significant Improvement in Pain from True AcupunctureLinear Mixed Model - Worst Pain (BPI)
Presented with permission, Hershman et al., SABCS 2017
• Sustained over tapered treatment, and for 12 weeks beyond
• Improvements also seen with true acupuncture on multiple additional measures of pain/stiffness
• Toxicity minimal
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Screening and Prevention of Late Effects• Many unanswered questions- cardiac, bone health recommendations
• Secondary malignancies- e.g., lung after lung cancer, bowel and bladder after prostate considered in follow-up recommendations
• HD or Lymphoma s/p chest irradiation- 148 women with HD s/p chest RT age < 35, at least 8 years prior Followed for 3 years with annual mammogram and MRI 63 biopsies in 45 patients (30%); 18 of 63 biopsies (29%) showed malignancy Sensitivity 63% for MRI; 68% for mammogram; Sensitivity for both: 95% All but 1 of the image detected malignancies were pre-invasive or sub cm and all were node
negative
• Many studies ongoing and reporting out- e.g.: ACE inhibitor etc. for prevention of cardiac complications after xrt, anthracyline
therapy Low dose tamoxifen for prevention of breast cancer after chest irradiation
(Ng et al, JCO 2013)
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Fertility Preservation for People with Cancer
Eligible for proven fertility preservation methodFemale:Embryo and oocyte cryopreservationSurgical “shielding”Ovarian suppression through chemotherapy (breast cancer)
Assessment of risk for infertilityCommunication with patient
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Patient at risk for treatment induced infertility
-Patient interested in fertility preservation options
Refer to specialist with expertise in fertility preservation
Investigational fertilitypreservation technique*
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*Clinical trial participation encouraged
Male:Sperm cryopreservation
••
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Cryopreservation of testicular orOvarian tissue
www.asco.org Modified and updated from Lee et al., J Clin Onc; 2006
25Krebber et al. (2014) – PsychoOncologyCella et al. (2001) – Journal of Clinical OncologyMinisini et al. (2004) – Lancet Oncology
14%
37%
32%
0%
5%
10%
15%
20%
25%
30%
35%
40%
Depression Fatigue Cognitive dysfunction
% of Patients
Psychosocial, Neurocognitive and Fatigue Problems are Prevalent in Cancer Survivors
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• Depression and anxiety in survivors Associated with symptom distress, maladaptive coping Depression associated with heightened risk for premature
mortality (RR 1.22-1.39) and cancer death (RR 1.18) Increased rates of suicide among populations of long-term
breast and testicular cancer survivors• Screen in your clinic• Reassure, treat or refer as appropriate• Guidelines from NCCN at www.nccn.org and from ASCO at
www.asco.orgAndersen et al, JCO 2014
Mental Health in Cancer Survivors
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Depressionand Anxiety
Cognitive-Behavioral Therapy
Pharmacotherapy
Third-Wave Psychotherapies (ACT, mindfulness meditation
etc.)
Fatigue
Exercise
Distraction (e.g., socialization)
Complementary Therapies (sleep, yoga, psychosocial
stress reduction etc.)
Stimulants ???
Cognitive Dysfunction
Neuropsychological (e.g., memory/attention
behavioral training)
Adaptive Computerized Training ?
Exercise ?
Medicinal (gingko biloba, methylphenidate) ???
Treatment Considerations
Guidelines from NCCN at www.nccn.org and from ASCO at www.asco.org
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Exercise, diet and energy balance matter for cancer survivors• Risk of weight gain, obesity and metabolic syndrome in breast,
colorectal, prostate, testicular, myeloma pediatric cancer survivors Effects cancer outcomes in breast, colorectal and prostate
survivors Effects cardiovascular and overall mortality
• Fortunately … Physical activity, diet and attention to diabetic and cardiovascular
risk factors likely helps Associated with lower risk of cancer recurrence and death
Ligibel and Meyerhardt, UpToDate, last accessed 3-30-15
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Habits to DROP or DECREASE
• Tobacco• Alcohol• High risk sexual behavior• Illicit drug use
Habits to MAINTAIN or INCREASE
• Physical activity• Prudent diet• Weight management
COMMON SENSE!
Promotion of improvements of modifiable health behaviors
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American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Survivors• Achieve and maintain a healthy weight If overweight or obese, limit consumption of high-calorie foods and beverages
and increase physical activity to promote weight loss
• Engage in regular physical activity Avoid inactivity and return to normal daily activities as soon as possible
following diagnosis Aim to exercise at least 150 minutes per week. Include strength training exercises at least 2 days per week.
• Achieve a dietary pattern that is high in vegetables, fruits, and whole grains Follow the American Cancer Society Guidelines on Nutrition and Physical
Activity for Cancer Prevention
Rock et al., CA Journal for Clin 2012
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Treatment Summaries & Survivorship Care Plans
• Can help to communicate standard and tailored needs
• New tools, apps– Patient facing portals/apps
How to best coordinate and communicate?
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Cancer Survivorship Care Guidelines: Clinician Mobile App
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• Putting it all together
Survivorship Programs
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• New Standard 4.8: Survivorship Program: Focuses on the development of a survivorship program to oversee and meet the needs of a cancer survivor
• The cancer program has a survivorship care program in place that includes the following elements documented in a written plan: Designed program director and team that is responsible for the
development of survivorship care delivery models and activities, and for evaluation of the program
A survivorship program that addresses the needs of cancer survivors, through care and consultative services provided either on-site or by referral
CoC Survivorship Requirements 2020
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• Services (may be available on-site or by referral):
Treatment summaries • Survivorship care plans • Screening programs for cancer recurrence, new cancers • Seminars for survivors • Rehabilitation services • Nutritional services • Psychological support & psychiatric services
Support groups and services • Formalized referrals to experts in cardiology, pulmonary services, sexual dysfunction, fertility counseling • Financial support services • Physical activity programs
• Treatment Summaries and Survivorship Care Plans (SCP): patients should receive a treatment summary and survivorship care plan (SCP), but delivery of such plans is not a required component of this standard
Components of Survivorship Program
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Conclusion: Survivorship Spans the Cancer Care Continuum
Modified from Levit et al Committee on Improving the Quality of Cancer Care 2013