louis s. constine, md, fastro professor of radiation oncology and pediatrics

Curing Patients with Cancer,But At What Cost: The Double-

edged Sword of Cancer Therapy ---

May the best of what we have done in the past, be the worst of what we will do in the

future

Louis S. Constine, MD, FASTROProfessor of Radiation Oncology and Pediatrics

Cancer Incidence – Distribution by Site SEER Program, 2006

PercentTotal invasive cancers: 129,552

0.20%

0.50%

0.60%

0.60%

0.60%

1.20%

0.80%

0.70%

1.00%

1.20%

1.30%

2.20%

1.30%

2.10%

2.30%

2.50%

3.50%

3.70%

3.30%

9.80%

12.20%

14.60%

17.70%

7.90%

Multiple primary cancersProstate

BreastLung and bronchus

Colon /rectumUrinary bladder

Melanomas of the skinNon-Hodgkin lymphoma

Uterine corpusKidney

PancreasOvary

ThyroidStomach

Brain & CNSMultiple myeloma

CervixEsophagus

Liver Larynx

Hodgkin lymphomaTestis

Soft tissue including heartBone and joint

0 2 4 6 8 10 12 14 16 18

5-Year Survival of Patients with Cancer by Era, SEER, 1975-1998

Age at Diagnosis (Years)

40

50

60

70

80

0 10 20 30 40 50 60 70

Year of Diagnosis

1993-98

1987-92

1981-86

1975-80

Su

rviv

al (

%)

Peak to Valley Transformation

2004Projected

In patients diagnosed with cancer before age 15, the 5-year survival rate improved from

58% in 1975 to 80% in 1997

--- an average annual change of 1.68%

Less well known is the remarkable improvement in prolonging survival in adult patients, especially those between 50 and 80 years of age

Estimated Number of Cancer Survivors in the United States Over Time

12.1 Million Cancer SurvivorsUnited States: 2007

Source: http://dccps.nci.nih.gov/ocs/prevalence/prevalence.html. Last accessed Oct. 2009

Cancer Survivorship

U.S.: 12 million cancer survivors• 3.5% population• Impact on public health

Increases in cancer survival• Earlier diagnosis (screening)• More effective treatment• Prevention of secondary disease• Decreases in mortality from other causes

Caring for Cancer Survivors

Do you care for survivors in your practice?

Always 264 (31.4%)

Sometimes 408 (48.6%)

Rarely 126 (15.0%)

Not at all 36 (4.3%)

Do not care for survivors 6 (0.7%)

Are you comfortable providing this care?

Yes 512 (61.2%)

No 213 (25.5%)

Do not provide 111 (13.3%)

ASCO Prevention Survey, 2004

Essential Elements Of Survivorship Care

• Education of the cancer survivor, family, health care providers – Care plan based on future health risks

– Promotion of healthy lifestyles

– Possible genetic predispositions for counseling

• Surveillance for cancer spread, recurrence, or second cancers and for long-term adverse physical, psychosocial, socioeconomic effects

• Intervention to prevent or treat consequences of cancer or therapy

• Communication between specialists and primary care providers to ensure that the survivor’s health needs are met

• Research focused on understanding, preventing, treating adverse consequences of cancer or its therapy

• Patient advocacy to address problems related to employment, insurance, and disability

Components of Treatment Summary

• Contact information for key individual providers • Dates of treatment initiation and completion • Diagnostic tests and results• Tumor characteristics • Therapies provided, including specific agents, title of

clinical trials (if any), treatment response, and toxicities experienced

• Psychosocial and nutritional services provided • Identification of a coordinator of continuing care

Components of Care Plan

• Likely course of recovery from treatment • Recommended surveillance• Possible long-term effects of treatment and symptoms • Possible signs of recurrence and second tumors • Possible effects of cancer on daily life (personal

relationships, work, mental health) and available resources for support

• Potential insurance, employment, and financial consequences of cancer and referrals to counseling, legal aid, and financial assistance if needed

Treatment Summary Concordance with IOM

Concordance with IOM recommendations N=65 TSs/13 sites (for each domain)

No. of sites achieving adequate (≥75%) concordance

Descriptive statistics Mean SD Range N (%)

Diagnosis 0.46 0.31 0.00–1.00 2 (15.4)

Staging and tumor characteristics 0.65 0.35 0.00–1.00 9 (69.2)

Surgery 0.73 0.22 0.38–0.98 7 (53.8)

Treating physician contact information 0.33 0.30 0.00–0.75 1 (7.7)

Clinical trials 0.18 0.25 0.00–0.60 0 (0.0)

Chemotherapy 0.52 0.24 0.10–0.83 3 (23.1)

Radiotherapy 0.55 0.19 0.26–0.80 2 (15.4)

Hormonal therapy 0.79 0.20 0.40–1.00 7 (53.8)

Targeted therapy 0.34 0.38 0.00–1.00 3 (23.1)

Toxicity 0.52 0.48 0.00–1.00 7 (53.8)

Genetic testing 0.26 0.24 0.00–0.60 0 (0.0)

Supportive therapy 0.03 0.08 0.00–0.27 0 (0.0)

Follow-up care contacts 0.08 0.18 0.00–0.50 0 (0.0)

TS Total 0.46 0.19 0.14–0.70 0 (0.0)

Survivorship Care Plan concordance with IOM

Concordance with IOM recommendations N=65 TSs/13 sites (for each domain)

No. of sites achieving adequate (≥75%) concordance

Descriptive statistics Mean SD Range N (%)

Toxicities and late effects 0.98 0.07 0.75–1.00 13 (100)

Breast cancer surveillance 0.82 0.11 0.67–1.00 8 (61.5)

Cancer surveillance 0.43 0.35 0.00–1.00 3 (23.1)

Non-cancer surveillance 0.77 0.21 0.33–1.00 6 (46.2)

Signs of cancer (recurrent and second) 0.32 0.27 0.00–1.00 1 (7.7)

Psychosocial effects 0.52 0.35 0.00–0.86 6 (46.2)

Referrals and resources 0.62 0.35 0.00–1.00 8 (61.5)

Prevention/health promotion 0.46 0.14 0.00–0.50 0 (0.0)

Genetic testing recommendations 0.62 0.51 0.00–1.00 8 (61.5)

Relatives’ cancer risk 0.01 0.03 0.00–0.10 0 (0.0)

SCP total 0.59 0.16 0.37–0.83 2 (15.4)

Survivorship Program Components Across Four Health Care Organizations

Organization Type Survivorship Program Providers Partnerships

Academic medical center

In-person clinical evaluation with multidisciplinary team

Medical oncologist, nurse practitioner, psychologist, social worker

Faculty practice medical group

Community hospital

Nurse-led, telephone-based program; survivors also receive mailings and follow- up calls

Oncology-certified registered nurse

Local physician-owned oncology network

County hospital

Nurse-practitioner–led clinical program; survivors assessed, followed and primary care needs addressed

Nurse practitioner

In-house Navigation Program

Primary-care medical group

Social worker–led, telephone- based program; survivors also receive mailings and follow-up calls

Licensed clinical social worker

Oncology medical groups contracted to provide services to plan members

SCP Components Across Four Health Care Organizations

Organization Type SCP Completed ByTreatment History

Components Received By

Academic medical center

Multidisciplinary survivorship team: oncologist, nurse practitioner, psychologist

Detailed summary of radiation, chemotherapy, surgeries, hormonal treatment

Patient copy, provider copy (PCP, oncologist, ob/gyn, etc), paper chart, and EMR

Community hospital Patient, with telephone assistance from survivorship oncology nurse

General summary of radiation, chemotherapy, surgeries, hormonal treatment

Patient keeps own copy and distributes to oncology care team and primary care

County hospital Survivorship nurse practitioner


Patient copy, copy in paper chart, and copy scanned into EMR (electronic template in progress)

Primary-care medical group

Contracted oncology group physicians and staff, with assistance from survivorship social worker


Scanned into EMR (electronic template in progress) and in oncology group paper chartAbbreviations: SCP, survivorship care plan, EMR, electronic medical record; PCP, primary care provider; ob/gyn, obstetrician/gynecologist

Survivorship begins at diagnosis!

Health &Quality of

Life

Long-Term Survival

Cancer Diagnosis &Treatment

What are the physical What are the physical costs of survivorship?costs of survivorship?

General Considerations

• Risk of late effects depends on the tissue and age of patient at time of treatment

• Late effects are dose and modality specific (e.g., surgery, radiation, chemotherapy)

• Combined modality therapy can have additive risks

Tissues at Risk for Late Toxicity

• Bone/soft tissues

• Cardiovascular

• Dental

• Endocrine

• Gastrointestinal

• Hepatic

• Hematological

• Immune system

• Nervous system

• Neuropsychologic

• Ophthalmologic

• Pulmonary

• Renal

• Reproductive

Factors Contributing to Morbidity

Cancer-Related Morbidity

Premorbid Conditions

Treatment Events

Aging

Host Factors

AgeGenderRace

HistologySiteBiologyResponse

Tumor Factors

Treatment Factors

SurgeryChemotherapyRadiation therapy

Health Behaviors

TobaccoDietAlcoholExerciseSun

Genetic

BRCA, ATM, p53polymorphisms

Why, a four-year old child could understand this.

Someone get me a four-year old child!

-- Groucho Marx

Radiation therapy is getting complicatedRadiation therapy is getting complicated

Tables and data and lines, oh my...Tables and data and lines, oh my...

Know Your Cancer-Related Health Risks

• After removal of one of paired organs, the remaining organ usually maintains function:

– Enucleation (removal of eye)– Nephrectomy (removal of kidney)– Oophorectomy (removal of ovary)– Orchiectomy (removal of testes)

• It’s important to take precautions to preserve the health of the remaining organ

Surgery for Solid Tumors


• Surgery to remove tumors of bones or soft tissue may affect strength, function, mobility

• These surgeries may also cause chronic pain that limits activity

• Examples include:– Amputation– Limb-sparing surgery

Surgery for Solid Tumors

Bleomycin, BCNU, CCNU, and busulfan

can cause lung scarring

Anthracyclines (drugs like doxorubicin and daunorubicin) affect

heart muscle function

Prednisone and Methotrexate affect

bone strength


Chemotherapy for Cancer

Cisplatin, carboplatin and ifosfamide can

affect kidney function

Know Your Cancer-Related Health RisksChemotherapy for Cancer

Cyclophosphamide can cause injury to the bladder lining

Cisplatin and carboplatin can cause hearing loss


Vincristine and cisplatin can affect nerve function


Methotrexate and Cytarabine (Ara C) given by vein or into the spinal fluid can affect learning, concentration and memory


Alkylating agents chemotherapy affects testicular and ovarian function• Risk of injury is related to total dose of medication received• Alkylating agents most often used for childhood cancer:

cyclophosphamide, procarbazine, nitrogen mustard, ifosfamide

Know Your Cancer-Related Health RisksRadiation for Cancer

Brain radiation can affect learning & memory, motor

function and sensation

Endocrine gland radiation can affect growth, metabolism, and reproduction

Radiation for Cancer

Scarring from radiation can affect heart rhythms, heart

muscle and valve function and blood vessel flow

Lung scarring from radiation leads to stiff lungs that restrict air flow during

breathing



Radiation cause kidney damage and bladder scarring

Some of the signs of radiation injury of the urinary tract are:

• High blood pressure• Blood in urine• Incontinence • Problems voiding


• Decreased testosterone• Decreased, damaged or

absent sperm• Damage to duct system to

transport sperm• Sexual dysfunction from

damage to pelvic nerves


• Decreased estrogen• Damage or depletion of

eggs in ovaries• Scarring of lining of the

uterus (womb)• Scarring of blood supply

to uterus

Multiple Primary Cancers

Etiologic Factors

Cancer

#1

Cancer

#2

Treatment

Lifestyle

• Tobacco• Alcohol• Diet• Other

Environment

• Contaminants• Occupation• Viruses• Other

Host factors

• Age and gender• Genetics• Immune function• Hormonal, other

Interactions andother influences

• Gene-environment• Gene-gene

Modified from Travis LB. Acta Oncologica 2002; 323-333.

Subsequent Malignant NeoplasmsDCCPS and DCEG

Who is at risk? When to worry?

• Age at treatment• Sex/race of survivor• Type/strength of

therapy– Chemotherapy

– Radiation therapy

– Transplant

• Time from treatment• Type of cancer• History of relapse• Family history• Health habits

Age at Treatment Matters…

• Learning problems after brain radiation– Younger patients at higher risk compared

to older patients• Infertility after alkylating chemotherapy

– Older females at highest risk compared to younger females

Chemotherapy Dose Matters…

Heart muscle problems after anthracyclines

Risk Anthracycline dose

Low Less than 100 mg/m2

Medium Between 100 and 300 mg/m2

High More than 300 mg/m2

Combination of Treatments Matters…

• Chest radiation: scarring of heart lining, heart valves, or blood vessels

• Anthracycline chemotherapy: weakening of the heart muscle

Risk of heart problems is greater if cancer treatments have similar risks

for health problems.

Health habits matter…

• Lung scarring can occur after chest radiation and bleomycin

• Stiff lungs restrict air flow during breathing

• Thick scarred air sacs do not release oxygen to the tissues as well

• Smoking increases the risk of lung injury

Genes & Family History Matter…

• Heart disease• High cholesterol• High blood pressure• Diabetes

• Arthritis• Osteoporosis• Kidney problems• Cancer

Cancer treatment may result in an earlier onset of diseases that “run” in families, especially

those that usually present in adulthood

Important Facts About Late Effects

• The chances of having late effects after cancer is high• The chance of having serious or life-threatening late

effects after modern cancer therapy is low• Knowing your cancer history and possible health risks can

help you and your doctorwork together to prevent late effects or diagnose health problems early

• Regular check-ups are needed to diagnose and prevent late effects

What Doctors Can Do…

• Design cancer treatments to reduce the risk of late effects

• Develop therapies to protect normal tissues

• Monitor childhood cancer patients for late effects

• Prescribe corrective therapy

What Survivors Can Do…

• Have regular check-ups so late effects can be prevented or detected in earlier stages

• Follow doctor’s advice about medications and other interventions that can reduce the risk of late effects

• Practice health behaviors that reduce the risk of late effects

Habits that affect risk

• Smoking• Sun

exposure• Diet• Physical

activity• Alcohol

intake

Tobacco Use

• Don’t smoke. If you do smoke, QUIT!• Don’t use any tobacco products• Avoid smoke-filled rooms• Exercise regularly to keep your lungs fit• Check out:

1.877.4SJ.QUIT

Preventing Skin Cancer

• Do not tan.• When outdoors, stay

in the shade.• Limit sun exposure

from 10-4.• Practice sun

protection measures.– Sunscreen Apply frequently!– Wide brim hat– Long-sleeve shirt– Sun glasses with UV

absorption

A Healthy Diet

• Eat a variety of healthful foods, with an emphasis on plant sourcesEat > 5 vegetables and fruits servings each day.Choose whole, rather than processed, grains Limit consumption of red meatsChoose foods to maintain a healthful weight

• Check out:

Physical Activity and Weight

• Adopt a physically active lifestyleModerate activity for > 30 minutes on > 5 daysModerate-to-vigorous activity for > 45 minutes on

> 5 days may further reduce breast and colon cancer risks

Balance caloric intake with physical activity• Check out:

http://www.cdc.gov/healthyweight/http://www.mypyramidtracker.gov/

Maintain a Healthy Weight

• Body mass indexWeight (kg) divided by

height (cm)2

• Normal weight = BMI 18.5-25• Overweight = BMI 25-30• Obese = BMI > 30

Check out: http://www.cdc.gov/healthyweight

Alcohol and Health

• Alcohol increases risk of cancer of the mouth, throat, voice box, esophagus, liver, and breast

• Alcohol may also increase the risk of colon cancer

• Alcohol increases risk of liver injury in people with chronic hepatitis and other liver disease

• Alcohol may have some benefit in preventing cardiovascular disease

Guidelines for Alcohol Intake

• If you drink, limit alcohol drinks to less than two drinks a day for men and one for women

• A drink is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits

Just remember, only one

or two!

Good Health Habits…

• Lower cancer risk• Lower cardiovascular disease risk• Lower bone and muscle problems• Improve energy level and mood• Improve productivity• Lower late effects risks in

cancer survivors

Specific f/u recommendations for Hodgkin Lymphoma, part 1

• Annual visit to health care provider for prevention and age appropriates screening

• Annual physical exam including thyroid and breast exam for women

• Consider low dose CT in patients at high risk for lung cancer

• Thyroid function tests annually in pts after neck/chest RT

Specific f/u recommendations for Hodgkin Lymphoma part 2

• Vaccinations q 6 years in patients after splenectomy

• Lipid screening q 1-3 years (LDL <100)• CAD risk factor modification• Women after chest RT treated at age <35 y:

– Yearly mammogram 8 years after RT or age 40

– Consider breast MR

Specific f/u recommendations for Hodgkin Lymphoma - part 3

• Cardiac work up with EKG, echo, stress test; consider visit with a cardiologist at 10 years

• Skin check annually• Baseline vitamin D level• Consider a screening colonoscopy prior to

age 50 if prior abdominal radiation

We Are Working Hard:

»To cure patients with cancer

»To minimize late effects

And we are making progress!

louis s. constine, md, fastro professor of radiation oncology and pediatrics

Documents