Secondary Neoplasms in Childhood Cancer Survivors

TON - AUGUST 2012 VOL 5, NO 7 — August 23, 2012

There are a growing number of adults worldwide who are childhood cancer survivors. It is estimated that 80% of children diagnosed with cancer will be childhood cancer survivors and, as of 2005, there were 328,000 survivors of childhood cancer in the United States.As this population continues to grow in number and age, new challenges for these survivors emerge. Approximately two-thirds of childhood cancer survivors will have at least 1 chronic health condition as a consequence of their treatment, and one-third of those survivors will have multiple or severe long-term health conditions.2 As a healthcare community, it is our responsibility to care for these survivors now and in the future.

One of the consequences of treatment with chemotherapy and radiation therapy for childhood cancer is the development of secondary neoplasms, which can have a direct impact on the survivors’ morbidity and mortality and quality of life. In this article we will describe the incidence of secondary neoplasms in this population, the common secondary neoplasms that can occur, the risk factors that influence the development of secondary neoplasms, and current screening recommendations.

Much of what is known today comes from data obtained by the Childhood Cancer Survivor Study (CCSS). The CCSS is a multi-institutional (from both the United States and Canada), retrospective cohort study funded by a National Cancer Institute grant. The study population comprises childhood cancer survivors who have survived 5 or more years from the time of their original diagnosis. The enrollment population includes 20,346 survivors diagnosed between 1970 and 1996 and approximately 4000 siblings who serve as a comparison group.3 All participants have completed a baseline questionnaire, with information collected on demographics, medical history, family history, medical late effects, and diagnosis of new neoplasms. Therapeutic exposures are abstracted from a medical chart review.4 Other sources of data from this population come from international survivorship studies and single institutional studies.5-12

In recent studies published by the CCSS, the 20-year cumulative incidence for developing a secondary malignant neoplasm (SMN) is 3.2%,13 and the 30-year cumulative incidence is 7.9%.14 In 14,359 CCSS survivors, a total of 2703 subsequent neoplasms have been reported. Of those, there were 802 malignant neoplasms, 159 nonmalignant meningiomas, 168 other benign or in situ neoplasms, and 1574 nonmelanoma skin cancers. The median time to first occurrence was 17.8 years (range 5-35.2 years).14 Among childhood cancer survivors, SMNs are the most common cause of treatmentrelated death.4

As this population of survivors ages and there is a longer time interval for follow-up, other concerns begin to emerge. One of these concerns is that patients who have developed an initial secondary neoplasm are at greater risk for developing subsequent neoplasms. Armstrong and colleagues, in a study recently published by the CCSS, reported that among survivors with an initial subsequent neoplasm, the cumulative incidence of developing a second subsequent neoplasm, either malignant or benign, is 33.4% at 10 years, 38.8% at 15 years, and 46.9% at 20 years. At 15 years posttreatment, survivors exposed to radiation for their original cancer diagnosis had a cumulative incidence of 41.3% of developing 2 second subsequent neoplasms compared with those not exposed to radiation, whose cumulative incidence was 25.7%. Radiation-exposed survivors whose first secondary neoplasm was a nonmelanoma skin cancer were at higher risk for developing subsequent malignant neoplasms.4 Another concern that arises for this population is that treatments received for the primary cancer diagnosis may prohibit or limit the treatment modalities available for survivors who develop multiple subsequent neoplasms. Survivors may not be able to receive optimal treatment for subsequent neoplasms, which may ultimately affect their mortality.

Primary cancer therapy is a contributing factor in the risk of secondary neoplasm occurrence. The survivor’s initial diagnosis, the specific treatment received, and the time from last treatment are all risk factors. The CCSS and other studies have attempted to identify which patients are at highest risk for the development of secondary neoplasms. For example, survivors with a history of Hodgkin lymphoma, hereditary retinoblastoma, the genetic form of Wilms’ tumor, von Recklinghausen neurofibromatosis, xeroderma pigmentosum, and Klinefelter syndrome, as well as those who have immunodeficiency, are at the highest risk of secondary neoplasms.15,16 Age at time of initial diagnosis is also an important factor to consider: the younger the age at time of diagnosis, the greater the risk for secondary neoplasms.

Table 1
Host and Treatment Factors Increasing Risk of Selected Subsequent Neoplasms After Childhood Cancer.

The most common secondary neoplasms include breast cancer, skin cancer, thyroid cancer, treatment-related myelodysplasia or leukemia, lung cancer, central nervous system (CNS) tumors (including meningiomas), and bone cancers and soft tissue cancers. It appears that there are certain diagnoses, therapeutic exposures, and other characteristics that may increase the risk of secondary neoplasms in this population. Table 1 identifies host and treatment factors increasing the survivor’s risk of subsequent neoplasms.17-23 Survivors with genetic predispositions, including those with a family history of early-onset cancers, are more at risk than the general population. Survivors exposed to radiation to the head and neck are at increased risk for secondary malignant neoplasms. There is an increased risk of breast and lung cancer, particularly in female survivors who received mantle or chest radiation. Secondary skin cancer is commonly a basal cell carcinoma. The risk of thyroid cancer is greater in females and in those whose time from initial cancer therapy is greater than 10 years. Radiation-associated risks remain elevated for at least 20 years postradiation exposure and in doses ≥25 Gy.17 Secondary lung cancer occurs more often in survivors exposed to prior chest radiation. CNS tumors can also include relapsed CNS leukemia. Bone and soft tissue cancers occur more often in survivors of primary sarcomas. Survivors exposed to radiation and higher cumulative doses of anthracyclines and/or alkylating agents also appear to be at higher risk for the development of a secondary neoplasm. Prior exposure to alkylating agents (cyclophosphamide, ifosfamide, cisplatin, carboplatin, busulfan, melphalan, nitrogen mustard, and procarbazine), epipodophyllotoxins (etoposide), and anthracyclines (doxorubicin) increases the risk of secondary leukemia. The speculated latency period for secondary leukemia onset for alkylating agents is 4 to 7 years, whereas the latency period is much shorter for epipodophyllotoxins, at 1 to 3 years.15 In addition to primary cancer diagnosis and treatment, lifestyle and environmental factors may impact the development of secondary neoplasms in this population. These risk factors include exposure to smoking and chewing tobacco, alcohol consumption, lack of exercise, diet, and the use of reproductive hormones.

For most childhood cancer survivors, the thought of developing a second cancer can be discouraging and stressful. Anxiety may be reduced if the survivors understand their individual risk, recommended medical follow-up, and the importance of leading a healthy lifestyle. Childhood cancer survivors, who are aware of their bodies, may be able to detect problems early on. In 2006, the Children’s Oncology Group (COG) developed Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers (available at www.survivorshipguidelines.org).24 These guidelines are riskbased, exposure-related clinical practice guidelines for screening and management of late effects. The goal is to increase the quality of life for pediatric cancer survivors and to provide ongoing monitoring of health status.

The most important screening for childhood cancer survivors is to have a yearly comprehensive exam, either at the hospital or clinic where treated or with a primary care provider who knows the cancer treatment history and recommended follow-up. Many adult childhood cancer survivors were very young during their treatment and may not know the specifics of their therapy. Therefore, it is vital that survivors understand their cancer history, including surgeries, chemotherapies, and radiation exposure, in order to be aware of their individual risks and recommended screening. Late-effect clinics provide survivors with a cancer summary, or a survivor passport, which provides the details of individual treatment, including the protocol and total dosages of chemo therapy and radiation and follow-up recommendations. This summary can be a useful tool for the pediatric cancer survivor who transitions to adult care.

Figure 2
Children’s Oncology Group Cancer Screening Guidelines for Survivors at Highest Risk for Secondary Cancers.

There are specific guidelines for recommended screen ing to detect secondary malignancies in this population based on treatment exposures. If a hereditary predisposition for a secondary cancer is suspected (eg, genetic form of retinoblastoma, embryonal tumors, Wilms’ tumor, neuroblastoma), genetic counseling and testing may lead to interventions that could prevent future cancers.25 Table 2 provides a summary of a childhood cancer survivor’s potential exposure, risk of potential secondary neoplasms, and the current screening guidelines as recommended by the COG guidelines.24 Adherence to screening guidelines directed at the general population is of particular importance among averagerisk survivors.26 These screening guidelines are published by the US Preventive Services Task Force27 and Debra Schmidt, RN, the American Cancer Society.28

Nurses play a critical role in encouraging healthy lifestyles to lower a survivor’s risk of developing a secondary neoplasm. Survivors can take control of their health and reduce their cancer risks by avoiding tobacco; limiting alcohol consumption; protecting skin from sun exposure; maintaining a healthy weight; participating in regular physical activity; eating a healthy diet, including a minimum of 5 servings of fruits and vegetables per day; knowing their family history; knowing their personal risk factors; and, most importantly, having having regular checkups with the recommended cancer screening. In addition, education regarding symptoms to be aware of and to report is important in early detection of potential secondary neoplasms.

Education and communicating the risks to this population of survivors is crucial. Increasing compliance with medical follow-up and recommended medical surveillance may increase the longevity and enhance the quality of life for childhood cancer survivors. Encouraging these survivors to be advocates for their long-term healthcare is a vital role for oncology and cancer survivorship nurses worldwide.

References

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