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Evidence-Based Oncology October 2015
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Tips for Caring for Patients Who Have Been Treated for Childhood Cancer
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Tips for Caring for Patients Who Have Been Treated for Childhood Cancer

Lisa Diller, MD
Suggestions on how to approach a childhood cancer survivor in your practice, several useful resources, and information on what referrals and tests may be indicated.
Although recent research shows improvement in long-term survival rates for childhood cancer patients,1 it also highlights the challenges that remain2 for many of the almost 400,000 survivors in the United States. Other research3 illustrates that most primary care physicians do not feel comfortable treating survivors of pediatric cancer. As the number of survivors continues to increase, many internists, pediatricians, and obstetrician/gynecologists (OB-GYNs) with busy practices will have at least a few patients who had pediatric cancer under their care. Here I provide suggestions on how to approach a childhood cancer survivor in your practice, several useful resources, and information on what referrals and tests may be indicated.
 
Patients Should Have or Obtain a Cancer Treatment Summary and Survivorship Plan

Children transitioning back to their primary care pediatrician will most likely return with a treatment summary from their cancer centers, along with guidance on surveillance for disease recurrence in the immediate post-therapy period. Longer term follow-up care plans, with screening for late sequelae, should be developed with the help of the treating oncologist.
 
Adult survivors of childhood cancer should provide their internist or OB-GYN with treatment summaries and survivorship plans; however, many survivors do not have a summary. If a patient does not have a treatment summary, encourage him or her to obtain one, as well as a survivorship plan, from the treating oncology center. If this is not possible, most major cancer centers and hospitals that treat pediatric cancer have clinics where survivors can be seen well into adulthood. Refer your patient for a one-time consultation, during which a treatment summary and survivorship care plan can be created based on a careful review of the patient’s records and discussion with the patient and, sometimes, the parent. For adults who were treated as children and may know very little about their cancer history, this process gives them important information.
 
For Pediatricians Caring for a Child Who Is Being Treated or Has Finished Treatment for Cancer

As the pediatrician, the information you receive from a child’s oncology team will include recommendations for ongoing routine care, such as a re-immunization schedule and management of fevers; a treatment summary; and guidance on surveillance for disease recurrence. This communication can help specify the respective roles for the pediatrician and the oncologist, which will differ from patient to patient based on the treatments received. A child who received hematopoietic stem cell transplants or is otherwise immunosuppressed, for instance, may need to see the oncologist for routine symptoms for an extended period of time versus a patient who received less intensive therapy.
 
Between 3 and 5 years following completion of therapy, survivors often have a follow-up visit with their oncologist that focuses less on disease recurrence and more on organ toxicity from treatment, assessment of growth and development in the face of prior therapy, and treatment-related risks that should be evaluated. At that visit, a new survivorship care plan can be created to lay out which survivorship screenings should be conducted and when, and which subspecialists should be included in the child’s care going forward.
 
Transition Is Often a Time of Anxiety for Children and Families
When a child finishes cancer therapy, it is often cause for both celebration and anxiety for the family. Parents may be particularly anxious about the end of therapy, the knowledge that their child will not be seen as frequently in the oncology setting, and the risk of cancer recurrence. If you have concerns about an increase in anxiety around this time, the oncology psychosocial provider at your patient’s cancer center can work with you to arrange for your patient and his/her family to be seen by a community provider.
 
Keep Watch for Signs of Early and Late Treatment Effects, and Be Aware of Screening Recommendations

Issues around treatment-related toxicities can emerge both during treatment and shortly after transition. For instance, patients who received platinum-containing drugs might experience hearing loss. Effects of treatment that can develop in the pediatric years also include heart disease in survivors treated with anthracycline compounds and neurocognitive and neuroendocrine dysfunction in patients who received radiation for a brain tumor. A child who received radiation to the brain might have difficulties with cognition that affect school performance. If problems arise, consider referring her for neurocognitive testing. Similarly, signs of growth delay, hypothyroidism, or early or late puberty could be a sign of treatment-related endocrine dysfunction that warrants referral to an endocrinologist. The Children’s Oncology Group provides detailed, peer-reviewed guidelines4 for screening and treating survivors of pediatric cancer.
 
For Internists Caring for Adult Survivors of Childhood Cancer
 
The Use of Radiation to Treat Childhood Cancer Is Associated With Significant Morbidities in Adulthood

Between two-thirds and three-quarters of children treated during between 1970 and 1990 received radiation. In addition to the risk of radiation-induced secondary cancers, radiation also increases a patient’s risk of chronic disease. For instance,
 
·         patients who received chest radiation may develop pulmonary fibrosis, heart valve disease, or early coronary artery disease;
·         patients who received brain radiation during childhood may have chronic issues with learning, vocational success, and organizational skills, as well as neuro-endocrine dysfunction;
·         patients who received neck radiation have a higher risk of thyroid failure; and
·         female patients who received radiation to the pelvis are at risk for ovarian failure, as well as pregnancy complications should they become pregnant.

Recommendations on how to monitor patients for these risks vary based on the site of radiation. Patients who received neck radiation, for example, should be screened for hypothyroidism, and those who received abdominal radiation should be screened early for colon cancer (see peer-reviewed guidelines4).
 
Two Commonly Used Classes of Chemotherapy Drugs, Anthracyclines and Alkylators, Are Associated with Serious Late Effects

Anthracyclines (eg, doxorubicin, daunorubicin, and epirubicin) and alkylating agents (eg, cyclophosphamide, melphalan, and procarbazine) have been linked respectively to late-onset heart disease and infertility. When administered to adults in high doses, doxorubicin, the most commonly used anthracycline, carries a well-known risk of acute congestive heart failure (CHF). In children, however, high doses of doxorubicin can lead to asymptomatic left ventricular dysfunction many years after exposure and is associated with progression to heart failure. Pharmacologic intervention with beta-blockers and/or ACE inhibitors at early signs of asymptomatic left ventricular dysfunction may delay the onset of overt CHF, which makes it important to implement a cardiac screening plan for these patients.

Alkylating agents have been linked to low or no sperm count in men and early menopause or primary ovarian failure in women. Encourage male patients who are ready to become fathers to obtain a semen analysis and, if indicated, explore assisted reproductive technology. Female patients should see a fertility specialist if they have not conceived within 6 months of starting to try to get pregnant, and those young women who are not ready to be mothers but are at risk for premature ovarian failure might consider freezing ovarian tissue, eggs, or embryos.
 
For OB-GYNs Caring for Adult Women Who Had Childhood Cancers

Women Treated With High-Dose Alkylating Agents Are at Risk of Primary Ovarian Failure, Early Menopause, and/or Infertility

Women at risk for early menopause, who were previously exposed to alkylating agents, may be menstruating regularly; however, taking into consideration their risk for early menopause will contribute to their management, both in counseling regarding timing of pregnancy and in consideration of egg preservation. Research that my colleagues and I published in Lancet Oncology5 found that many survivors of childhood cancer who eventually became pregnant took longer to conceive than other women of the same age, supporting the concept that menstruating survivors may have ovarian damage. Survivors of childhood cancer should be referred to a fertility specialist after no more than 6 months of trying unsuccessfully to get pregnant. Earlier referral is indicated when the patient has a history of pelvic radiation or high cumulative doses of alkylating agents.
 
Female Survivors Are at Risk of Cardiotoxicity if Their Treatment Included Anthracyclines

This risk may increase during pregnancy. Risk factors for late CHF include a history of CHF during cancer treatment, young age at exposure, radiation to the chest, and total dose of anthracyclines. Exposure to anthracyclines has been associated with development of CHF during pregnancy or in the peri-partum period. Consideration of heart disease risk based on exposure might include administering an echocardiography prior to pregnancy, as well as evaluation by a cardiologist or in a high-risk obstetric practice with expertise in cancer patients and survivors.
 
Women With a History of Chest Radiation in Childhood or Early Adolescence Are at Very High Risk of Developing Breast Cancer, Similar to the Risk Seen in BRCA1 and BRCA2 Carriers

These patients should start mammography and breast MRI screening at age 25 years, or 8 years after exposure, whichever is later. An ongoing study is looking at tamoxifen to prevent radiation-induced breast cancer,6 but this is not yet standard-of-care. Because the risk is so high, consultation with a breast cancer prevention program might be warranted.
 
Women Who Were Treated for Childhood Cancer May Have Had Poor Bone Mineralization During Adolescence

Reasons for this might include inadequate calcium intake, insufficient estrogen production, and lack of exercise and sun exposure during their cancer. illness. They may be at risk for osteopenia and osteoporosis even if they are menstruating or receiving estrogen-replacement therapy. These patients should have an early assessment of bone health.
 
Whether you are an internist, pediatrician, or OB-GYN, you should provide patients who are survivors of childhood cancer with the same advice about healthy living that you urge for all your patients: do not smoke, eat healthy, and exercise. My pediatric colleagues and I are constantly seeking ways to reduce the toxicity of treatment while maintaining or improving cure rates. However, the day has not yet arrived when surviving childhood cancer is consequence-free. Together we can work to ensure our patients live as long and as healthily as possible. EBO
Lisa Diller, MD, is chief medical officer of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and director of the David B. Perini Jr. Quality of Life Clinic for survivors of childhood cancer.
References
  1. Armstrong GT, Yasui Y, Chen Y, et al; St. Jude Children's Research Hospital, University of Alberta, Fred Hutchinson Cancer Research Center, et al. Reduction in late mortality among 5-year survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS). J Clin Oncol. 2015;33(suppl;abstract LBA2).
  2. Phillips SM, Padgett LS, Leisenring WM, et al. Survivors of childhood cancer in the United States: prevalence and burden of morbidity. Cancer Epidemiol Biomarkers Prev. 2015;24(4):653-663.
  3. Suh E, Daugherty CK, Wroblewski K, et al. General internists’ preferences and knowledge about the care of adult survivors of childhood cancer: a cross-sectional survey. Ann Intern Med. 2014;160(1):11-17.
  4. Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. Children’s Oncology Group website. www.survivorshipguidelines.org/. Published 2014. Accessed August 25, 2015.
  5. Barton SE, Najita JS, Ginsburg ES, et al. Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol. 2013;14(9):873-881.
  6. Low-dose tamoxifen citrate in reducing breast cancer risk in radiation-induced cancer survivors (LDTam). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT01196936?term=NCT01196936&rank=1. Accessed September 3, 2015.
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