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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

2

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

••

•

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