primary care after cancer: practical advice for lymphoma survivors

Ann M. Maguire, MD, MPHClinical Associate Professor

Department of Medicine

April 5, 2014

Educational ObjectivesWhat makes Cancer Survivors unique?

What information is needed when transitioning back to primary care?

What are some of the key concerns for lymphoma survivors during the first 5 years after treatment? 

Educational ObjectivesWhat are the most common late effects of

lymphoma therapies? 

Do screening/ preventive care services differ for adult lymphoma survivors?

What can a lymphoma survivor do to stay healthy?

[Estimations and modeling provided by Angela Mariotto, PhD, based on: Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States: 2010-2020. J Natl Cancer Inst. 2011 Jan 19;103(2):117-28. Epub 2011 Jan 12

Estimated Number of Cancer Survivors in the US from Estimated Number of Cancer Survivors in the US from 1975 to 20121975 to 2012

Estimated Number of Cancer Survivors in the U.S. by Site Estimated Number of Cancer Survivors in the U.S. by Site January 1, 2012 by Site N=13.7 M Survivors)January 1, 2012 by Site N=13.7 M Survivors)

Estimations and modeling provided by Angela Mariotto, PhD, based on: Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States: 2010-2020. J Natl Cancer Inst. 2011 Jan 19;103(2):117-28. Epub

2011 Jan 12.

Estimated Number of Cancer Survivors by Current Age Estimated Number of Cancer Survivors by Current Age January 1, 2012 by Site N=13.7 M Survivors)January 1, 2012 by Site N=13.7 M Survivors)

Estimations and modeling provided by Angela Mariotto, PhD, based on: Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States: 2010-2020. J Natl Cancer Inst. 2011 Jan 19;103(2):117-28. Epub

2011 Jan 12.

What is Cancer Survivorship?Includes the physical, psychosocial, and

economic issues of cancer, from diagnosis until the end of life.

Involves issues related to follow-up, late effects of treatment, second cancers, and quality of life.

Survivorship experience is highly individual

and is impacted by short-term, long-term, and late effects of cancer therapy.

Adverse Effects of Therapy

Short-Short-TermTerm

Long-Long-TermTerm

Late-EffectsLate-Effects

Treatment Treatment PhasePhase

Post Treatment Post Treatment PhasePhase

Short-term side effects occur during treatment.

Examples: nausea, hair loss, pain, fatigue, and weight loss.

Resolve after active treatment ends.

Some symptoms are treatable using medications or complementary therapies.

Long-term side effects begin during treatment and continue after the end of treatment.

Examples: infertility, neuropathy, vascular complications related to surgery.

Symptoms may be treatable to varying degrees.

Late Effects of Cancer TreatmentLate effects are symptoms that first appear

months or years after treatment has ended.Examples: heart failure, osteoporosis,

cognitive problems and second cancers.Surveillance for late effects is challenging.

PCPs are less likely to associate such common conditions with a remote history of cancer therapy.

Unique needs for early screening in this population are not widely known.

Goals of Survivorship Care?The IOM indicates survivorship care should:

1. Prevent recurring and new cancers as well as other late effects.

2. Intervene for symptoms that result from cancer and its treatment.

3. Coordinate the work of specialists and PCPs to ensure that all of a Survivor’s health needs are met.

Barriers to Survivor Care

Oeffinger Peds Blood Canc 2006;46:135-142

Survivorship Care Models

Cancer Center Models

Primary oncology careSpecialized LTFU clinic

Shared care

Young Adult Transition Models

Formalized transition programs

Adult oncology-directed care

Community-Based Models

Community-based care

Need-Based Models

RISK-BASED CARE

What are the essential components of Survivor follow up care?• Prevent recurrent and new cancers and other late

effects

• Monitor for cancer spread, recurrence, or 2nd cancers

• Assess medical and psychosocial late effects

• Manage consequences of cancer and its treatment

• Coordinate with other doctors (Shared Care) so all health needs met

• Provide routine health promotion

What is Risk-Based Care?

Risk-based care involves a systematic plan of periodic screening, surveillance, and prevention that considers a survivor’s personal health risks predisposed by the previous cancer and its treatment, genetic and familial factors, comorbid health conditions, and lifestyle behaviors.

Follow up care for low risk patients• Shared care beginning 1-2 years post cancer

treatment. Early transition to PCP-led care.

• You are low risk if the following are true:

• Cancer was early-stage or low-risk for late effects and recurrence

• No treatment with alkylating agents, anthracyclines, bleomycin

• No radiation

• Mild or no persistent toxicity of therapy

• PCP can provide preventive care and other non-cancer care throughout treatment for ALL SURVIVORS

Follow up care for moderate risk patients• Shared Care beginning 5 years post cancer

treatment. Later transition to PCP led care - Increased need for oncologist to direct surveillance for recurrence.

• You are moderate risk if the following are true:

• Cancer was moderate risk based on staging and type.

• Treatment with low-moderate dose alkylating agents, anthracyclines, bleomycin, or autologous stem cell transplant

• Low to moderate dose radiation increasing risk for late effects

• Moderate persistent toxicity of therapy

Follow up care for high risk patients• Shared care starting 1-2 years post treatment .

Increased treatment related complications requires earlier involvement of PCP and other specialists. Delayed transition to PCP-led care

• You are high risk if the following are true:

• Cancer was high risk for recurrence based on staging and type

• Exposure to high dose alkylating agents, anthracyclines, bleomycin, or allogeneic stem cell transplant

• High dose radiation increasing risk for late effects

• Multi-organ persistent toxicity of therapy

What is a Survivor Care Plan?The IOM recommends these 7 elements be included for all patients:1.Personal treatment summary2.Identification of possible late and long term effects3.Signs of recurrence to watch for4.Guidelines for follow up care5.Identification of providers involved in follow up care6.Lifestyle recommendations7.Supportive resources

• Timing varies for transition from oncology-led care to PCP-led care

• Shared care model is optimal for most patients

• Outcomes are better with shared care model.

• Information needed for PCP to lead follow-up care:

• Treatment summary

• Survivorship care plan – your Oncology team can help with this if you do not have one.

Transition to PCP-Led Care

Follow up Care: First 5 Years• Examination by oncologist:

• Every 3-6 months for years 1-3• Every 6 months for years 4-5• Highest risk of recurrence in first 2 years

• Follow CBC: • Every 6-12 months for up to 10 years• Risk of therapy-related MDS/ Leukemia is 2-

3%• Chronic treatment related cytopenias can

occur.• Serial imaging/ CT scans as per

Oncology recommendations• Simultaneous Primary care follow-up

important

Late EffectsLate effects of cancer therapy affect the

majority of patients.Risk increases gradually over time.Cancer survivors are 10 times more likely than

their siblings to develop a serious chronic disease.

At 30 yrs from cancer diagnosis, 73% will develop at least 1 chronic condition.

Late effects depend on the type of cancer therapy.

Nathan, et al. J Clin Oncol 26: 4401-4409; 2008

Factors that contribute to late effects of cancer treatment

Linda A. Jacobs, David J. Vaughn; Care of the Adult Cancer Survivor. Annals of Internal Medicine. 2013 Jun;158(11):ITCS6:14(Used with permission from K. Scott Baker, MD)

Common Lymphoma Therapies - ABVD• ABVD (Adriamycin, Bleomycin, Vinblastine,

Dacarbazine)  - Hodgkin lymphoma• Toxicity includes:• Acute Myeloid Leukemia (most during the first

5 years)• Cardiomyopathy/ LV dysfunction, Arrhythmias,

and Valvular disease• Pulmonary Toxicity – especially Bleomycin +

Radiation• Peripheral Neuropathy• Infertility (uncommon)

Common Lymphoma Therapies – RCHOP and CHOP

RCHOP and CHOP – (Rituxan, Cytoxan, Adriamycin, Vincristine, Prednisone)

Toxicity includes:Acute Myeloid Leukemia (most during the first

5 years) Cardiomyopathy/ LV dysfunction, Arrhythmias,

and Valvular disease Peripheral Neuropathy Infertility (uncommon) Osteoporosis Metabolic Syndrome

Common High Grade Lymphoma Therapies: HyperCVAD and Autotransplantation• HyperCVAD (CHOP drugs alternating with high

dose methotrexate + cytarabine) • Toxicity is similar to CHOP• Cognitive impairment may be more common if

intrathecal therapy is used.OR

• High dose chemotherapy (such as BEAM) used with auto transplantation

• Transplant patients may have greater treatment related toxicity due to the higher doses of therapy needed to ablate the marrow.

• Chronic low white count predisposes to infection

Late Effects of Radiation TherapySecond cancersEndocrine diseases: Thyroid nodules/

cancer, Hypothyroidism, Gonadal Dysfunction, Osteoporosis

Heart disease: Coronary Artery Disease, Heart Failure, Valve disease

CataractsDental problemsLung disease: Restrictive, obstructive,

interstitialKidney disease: Chronic kidney disease,

HypertensionInfertility: Male and Female

Periodic Evaluation for Survivors Treated with Radiation TherapyYearly complete skin examYearly eye exam and dental examYearly UA, BMP, and Blood PressureYearly thyroid exam, TSH and T4 if neck

radiationOther evaluation depends upon exposure.

For chest radiation: PFT and Chest X-Ray plus ECG and Echocardiogram to screen for heart and lung disease.

Mammogram or Breast MRI for womenEvaluation should be done on entry into follow

up care Repeat as needed based on results and symptoms.

Screening for Cardiac Toxicity after Lymphoma Therapy

ECHO or MUGA plus ECG at baseline and periodically depending on results.

Evaluation should be done on entry into follow up care and repeated as needed based on results and symptoms

Cardiology consultation for patients with abnormal findings.

Cardiovascular Risk after Lymphoma TherapySurvivors have a 2-3 fold increased risk of CVD.

Risk factors include: Cardiotoxic therapies, HTN secondary to treatment related CKD or other factors, Obesity/ Metabolic Syndrome, Dyslipidemia, and Type 2 Diabetes.

Recommendations: Aggressive risk factor reduction. Control and treat lipids early with statins (Screen at age

20 and then every 3 yrs)Control Blood Pressure (< 140/90)Avoid SmokingScreen for Diabetes and treat aggressively (A1c< 7.0)Control WeightIncrease daily physical activity

Osteoporosis Steroids, Radiation, and Hypogonadism are

the primary risk factors. Radiation may increase risk for osteonecrosis. Recommendations:

Calcium and Vitamin D preferably from diet sources

Repeat Bone Density testing every 1-2 years When appropriate in female patients, consider

OCP or other hormonal therapy. In men, treat low testosterone.

Bisphosphonates should be used only when truly necessary.

Lack of fracture history and young age increase chance that bone mass can still be increased.

Infertility and Cancer Therapy

Risk of gonadal dysfunction/ low sex hormones increases with older age at time of alkylating agent exposure.

Radiation therapy exposure has increased toxicity at younger ages.

Recovery of fertility is highly variable. Some women regain ovarian function

years after therapy.

Evaluation and Management of Female Infertility and Gonadal DysfunctionSymptoms include:

Irregular menses or loss of menstruationHot flashes and other symptoms of early

menopauseRecommended Evaluation:

Hormone testing including estrogen annuallyTreatment: Oral contraceptives up to age of

natural menopause.Repeat hormone testing annually off OCP to assess

recovery of ovarian function for the first 10 years after treatment.

Reproductive Endocrinology referral as needed.

Evaluation and Management of Male Infertility or Gonadal DysfunctionSymptoms of Low testosteerone include:

Fatigue and decreased muscle massLow sperm count/ InfertilityLow libido/ sexual dysfunction

Recommended evaluation: Check hormones including testosterone.Semen analysis as indicated to assess fertility.Reproductive endocrinology referral as indicated.Bone Density testing for patients with low testosterone.

Treatment: Testosterone gel or shots.Sperm production can resume up to 10 years

after cancer therapy.

Risk Factors for Second CancersRadiotherapy

May increase risk of cancers in the field of radiation including sarcomas, thyroid cancer, stomach cancer, lung cancer

ChemotherapyMay increase risk of Leukemia or MDS

Hereditary Cancer syndromes/ Genetic risk: Lynch Syndrome/ HNPCC (hereditary nonpolyposis colorectal

cancer) increases risk for cancers of bladder, kidney, prostate, breast, ovary, uterus, stomach, small bowel, pancreas and liver

BRCA mutations increase risk for breast and ovarian cancerAmong older adults, tobacco and alcohol use surpass

cancer treatment as key risk factors for future cancers

Engles and Fraumemi, SEER New Malignancies among Cancer Survivors Ch 12

Nature Medicine 2011

Second Cancer Risk

Second Cancers after Lymphoma TherapyBreast Cancer

Highest risk: RT before age 30 (esp before age 20), axillary (mantle) RT, continued menses, strong family history of breast CA

For a woman who received chest XRT at age 20, lifetime risk approaches 50%, similar to BRCA + women

Lung Cancer:Highest risk: smokers who received XRT to chest

Other malignancies: Depends on total radiation (RT) dose and area treated.Sarcoma (in radiation site), melanoma, thyroid, GI

cancers, Leukemia/ MDSRadiation risk is dose dependent, increases

steadily over time and extends beyond 10 yrs

Cancer Screening and SurveillanceLymphoma survivors should adhere to USPSTF

recommended guidelines.Mammogram and Clinical Breast ExamColonoscopy or other Colorectal ScreeningPAP testing/ Cervical Cancer ScreeningPSA/ Prostate Screening?

All survivors should have an annual exam with a primary physician who is aware of your cancer history.This is the best way to allow early detection of

thyroid nodules, skin cancers, and other cancers for which there is no USPSTF screening recommendation.

Breast Cancer after LymphomaPrior lymphoma therapy limits treatment options

for women with breast cancer.Breast cancer after mantle radiation may have

poorer prognosis .More likely to be hormone receptor negative

Breast MRI in addition to Mammogram is appropriate for women with lymphoma treated with chest radiation at highest risk for Breast Cancer.

Specific recommendations about which Survivors benefit from Breast MRI are evolving.

Ask your Oncologist or Breast Radiologist

Breast Cancer ScreeningRoutine surveillance mammography starting age 40

may be insufficient for many lymphoma survivors.Mammogram may not be effective screening in

young females, especially those receiving mantel radiation for Hodgkins before age 30.

For women with mantel radiation before age 30: Recommend annual Mammogram and Breast

MRI starting 8 years after therapy or age 25 ,whichever is last.

For women with mantel radiation after age 30Recommend annual Mammogram starting 8

years after therapy or age 40, whichever is first .

Lung Cancer ScreeningChest radiation and alkylating agents have

only modest effect on lung cancer risk in non-smokers and light smokers.

Among heavy smokers, lymphoma therapy increases lung cancer risk by 20 fold.

Low dose Chest CT for lung cancer screening is now approved for all heavy smokers (> 30 pack years) and is covered by most insurersCT can be ordered by Primary Care physicians.

Optimal lung cancer screening strategy for non-smokers unknown

Interventions to Decrease Cancer Risk

Smoking cessation.Decrease alcohol intake.Reduce excess weight.Minimize UV exposure.Minimize exposure to other carcinogens.Increase physical activity.Increase intake of fruits and vegetables.

LTFU Guidelines, 2006.

Cognitive Impairment after Cancer Therapy“Chemo Brain” is commonly reported among

many cancer survivors.Impairment may be difficult to document in highly

educated people.It has been observed that this form of cognitive

dysfunction may be exacerbated by aging.There are few studies and little high quality

evidence to direct interventions.Some success has been reported with SSRI

antidepressants and stimulants including modafinil.

Neuropsych testing is the best way to diagnose impairment and rule out depression.

SummaryLife-long risk-based care is recommended for

all cancer survivors.Health systems will be challenged to develop

appropriate long-term follow up programs as the number of survivors continues to grow.

Use available tools to organize your cancer treatment history.

Ask your oncologist to identify most appropriate areas to target for follow up care.

Be your own advocate!

“Top 10 Tips for Cancer Patients”

in “No Such Thing as a Bad Day” by Hamilton Jordan

“Tip #10 Your attitude and your beliefs are your most powerful weapon against cancer.”

ResourcesJourney Forward

www.journeyforward.org

National Coalition for Cancer Survivorshipwww.canceradvocacy.org