What are examples of effects caused by treatment?

Long-term and late effects may be physical, emotional or practical. While physical and emotional issues are addressed about half the time, practical issues, such as employment, health insurance and medical debt, are addressed only about 20 percent of the time and can also contribute to s ignificant emotional and physical issues because of stress.

Survivors also face possible recurrence of the original cancer or the development of a new cancer that may or may not be related to their previous treatment. Long-term and late effects have garnered increasing attention as survival rates for cancer have climbed, new drug therapies have been introduced and survivors have lived long enough for late effects to begin appearing, sometimes 10, 15 or even 20 years after treatment ends.

For some survivors, the residual effects of treatment will be minor. For others, researchers are learning, the future may include health problems that could not have been foreseen. Researchers also know that in many cases the long-term effects of treatment can be identified and ameliorated. For those unknown potential late effects, a primary component of the survivorship care plan should be to educate survivors about the importance of good follow-up by the appropriate specialist, in collaboration with their oncologist.

Survivors can also be educated about lifestyle changes that have been shown to reduce their risk for some late effects. But the discussion of late effects challenges even the most competent healthcare provider because, except in a few situations, it is unclear which survivors will develop late effects from treatment.

Late effects that have become apparent in the past decade vary, and, depending on the treatment, may include:

> Cardiac effects: Myocardial dysfunction is associated with chemotherapy, most notably from the anthracyclines and tyrosine kinase inhibitors, but it can also be caused by some alkylating agents, antimetabolites, proteasome inhibitors and antimicrotubule agents. According to the American Cancer Society, “Some chemotherapy drugs may cause cardiotoxicity, a condition in which there is damage to the heart muscle that reduces heart functioning. If severe, this could lead to permanent heart damage (cardiomyopathy). Anthracycline chemotherapies, such as doxorubicin, can be particularly harmful to the heart.”

The most common cardiotoxic side effect of anthracyclines is a decline in ejection fraction, which is the heart’s ability to pump blood. Radiation therapy can also lead to cardiotoxicity if the heart or surrounding area was included in the radiation field. With imaging and adequate follow-up, cardiac conditions can often be diagnosed before symptoms begin, which can allow for early intervention.

> Pulmonary late effects: These can be caused by chemotherapy or radiation to the chest. Survivors who received combination chemotherapy and radiation may be at higher risk. Steroids can also impact lung function.

> Secondary cancers: The National Cancer Institute estimates that cancer survivors have a 14 percent higher risk of developing a new cancer as a result of being exposed to chemotherapy or radiation. An SCP discussion is an opportune time to talk about ways to lower the risk of a second cancer and also how follow-up will help with early detection.

> Hormone problems: Chemotherapy or hormone therapy can cause late effects related to changing hormone levels. Other treatments can damage the ovaries permanently, resulting not only in premature menopause but also hot flashes, sexual dysfunction and infertility. Moreover, the loss of estrogen for women is a risk factor for developing osteoporosis.

Osteoporosis is a common late effect among cancer survivors who receive agents such as aromatase inhibitors, a class of drug that blocks estrogen, a hormone that can contribute to cancer growth but is also crucial to bone health. Tamoxifen, a selective estrogen receptor modulator, affects women’s bones differently depending on their menopausal status. A 2008 study in the Journal of Clinical Oncology found that, in certain populations, current use of tamoxifen was associated with a reduction in fractures.

For men with prostate cancer, androgen deprivation therapy or bilateral orchiectomy increase the risk for osteoporosis, as well as infertility.

> Cognitive dysfunction: Often called chemo brain by survivors, cognitive dysfunction can be both a long-term and late effect that leaves survivors struggling to find words and regain mental ability. Some drugs have been linked directly to a greater possibility of chemo brain, but cognitive dysfunction is still being researched because it can be multifactorial and varies among survivors.

> Lymphedema: When lymph nodes are removed or damaged by radiation, survivors are at risk for developing lymphedema, a buildup of fluid that can lead to swollen, painful limbs. With the introduction of the sentinel node biopsy for women with breast cancer, fewer women have multiple nodes removed, but those who do are still at risk.

> Other late effects: Survivors who had radiation could also experience a separate set of late effects that include dental and oral cavity problems for those who received head and neck radiation, as well as the atrophy of tissue in the radiation field.

Late effects may be exacerbated by other conditions survivors may have, including comorbidities such as diabetes, high blood pressure or an existing heart condition. The list of possible late effects expands as more chronic health problems are connected to past cancer treatment. For example, survivors of Hodgkin lymphoma who received radiation to the stomach area have a dose-dependent increased risk for stomach cancer, researchers reported in a study published online in the Journal of Clinical Oncology in August 2013. Risk of stomach cancer also increased for Hodgkin lymphoma survivors who, in addition to radiation, received chemotherapy with highdose Matulane (procarbazine). Researchers studied 71 Hodgkin lymphoma survivors with stomach cancer who received their initial diagnosis of Hodgkin lymphoma between 1953 and 2003. They identified stomach cancer risk for those who had radiation to the stomach and specific alkylating agents. Those with highest radiation doses to the stomach area but lower doses of Matulane had a nearly threefold greater risk. The researchers recommended that survivors of Hodgkin lymphoma experiencing gastrointestinal symptoms be evaluated for possible stomach cancer. The risk for stomach cancer should also be included in SCP follow-up.

Perhaps the most important function of an SCP is to impress upon survivors the need for appropriate follow-up. As survivors move into the future, they should be followed by both their PCPs and their oncologists. Each survivor should have a set course of tests and visits to scan not only for recurrence of the cancer but also for late effects. Depending on a number of factors, these may be ordered by the survivor’s oncologist or PCP, which will be indicated by the SCP.