The vision that oncology professionals have for their patients after treatment is that they enjoy long, healthy lives both mentally and physically. For the vast majority of cancer survivors, this is their future.

Unfortunately, that is not the case for a percentage of survivors who will have some degree of long-term or late effects as a result of their cancer treatment—effects that could impact the quality or length of their remaining life.

A survivor who develops a side effect during treatment that does not resolve when treatment ends is experiencing a long-term effect. For example, a number of drugs can cause peripheral neuropathy, although it is often the result of drugs in the platinum or taxane classes, as well as certain immunomodulating drugs. As with many side effects, neuropathy is dose-dependent, meaning it worsens as more of the drug is given to the patient. Chronic pain, such as neuropathy, can greatly impact a survivor’s quality of life and possibly lead to depression and fatigue.

Both chemotherapy and radiation can cause fatigue, diminished cognitive function and insomnia. Survivors may also experience changes in hormone levels that result in mood swings, alterations in behavior, premature menopause or infertility. During a survivorship care plan discussion, each aspect of treatment should be looked at in detail, including surgery, radiation and chemotherapy. Survivors should be encouraged to ask questions about the longterm effects connected to every aspect of their treatment.

For survivors with ongoing, long-term side effects, the discussion aspect of the SCP becomes increasingly important because they might not mention a side effect to their oncologist, thinking it is a normal part of their healing process or something they have to endure.

If a side effect appears for the first time months or years after a patient has finished treatment, it is considered a late effect. For example, the survivor who moves on after treatment to live well and healthily only to develop a treatment-related cardiac problem 15 years after therapy is experiencing a late effect of cancer treatment.

During the SCP discussion, it can be difficult to get the survivor to focus on something that may or may not happen 10 or 15 years in the future; survivors may be more concerned about recurrence or coping with ongoing pain or financial issues. And yet, building an awareness of potential late effects is important so that survivors understand the need for follow-up with their primary care physician (PCP) or oncologist.

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The vision that oncology professionals have for their patients after treatment is that they enjoy long, healthy lives both mentally and physically.

What are long-term and late effects?

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:

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.

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.

 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.

 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.

 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.

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.

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 

 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.

Long-term and late effects of cancer may be physical, emotional or practical.

What are examples of effects caused by treatment?

The numbers of those who will be affected by long-term and late effects are difficult to determine because, in many cases, each cancer or treatment is accompanied by its own list of issues, which survivors may or may not experience. The primary research on late effects has occurred in the pediatric cancer community. According to a study by researchers at St. Jude Children’s Research Hospital in Memphis, Tennessee, and Memorial Sloan Kettering Cancer Center in New York, 98.2 percent of 1,713 adult survivors of childhood cancer included in the study had at least one chronic health condition. Of those survivors, 67.6 percent had health issues that could be classified as serious, disabling or life-threatening.

Information about long-term and late effects for adult patients can be difficult to ascertain, but a study published in 2003 in The Journals of Gerontology: Series A found that cancer survivors without other chronic diseases were “significantly more likely to report being in fair or poor health.” Among those respondents, survivors under the age of 65 were more likely to be unable to work because of their health, compared with people who didn’t have a history of cancer or other chronic illnesses.

The numbers of those who will be affected by long-term and late effects are difficult to determine because, in many cases, each cancer or treatment is accompanied by its own list of issues, which survivors may or may not experience.

How prevalent are long-term and late effects in survivors?

 The SCP discussion also allows time to determine if the survivor needs rehabilitation to regain strength and conditioning. Rehabilitation may offer an opportunity for another healthcare professional to interact with the survivor concerning unresolved physical issues that may not be apparent in a single discussion.

For example, women may be reluctant to use the arm on the side of their mastectomy because of nerve pain they have not mentioned. Men may be reluctant to walk very far after having undergone prostate surgery for reasons that range from fear of lingering pain to depression. These issues may be addressed by a physiatrist (a physical medicine and rehabilitation specialist), a physical therapist or an occupational therapist.

A few visits to one of these specialists may also help a survivor resume his or her exercise regimen, receive an assessment related to cancer recurrence and monitor for signs of late effects. Exercise is highly recommended to minimize fatigue, depression and anxiety; decrease constipation; and improve appetite as well as strength, balance and other normal bodily functions.

Research shows that 14 to 96 percent of patients in treatment experience fatigue as do 19 to 82 percent of patients posttreatment. To their own detriment, survivors often do not mention fatigue to their healthcare provider, assuming it is a normal side effect of their treatment. When fatigue is discussed as part of the SCP, survivors have an opportunity to learn that there are ways to resolve this long-term side effect.

One model of survivorship care places rehabilitation at its core: rehabilitation specialists evaluate survivors for both long-term and late effects and then refer them to the appropriate clinician for followup. The importance of rehabilitation for cancer survivors is reflected in the CoC’s accreditation standards, which require that rehabilitation services be made available to cancer patients and survivors.

 The CoC has also included distress screening as an accreditation criterion to be phased in by 2015. Distress management is also recommended by the National Comprehensive Cancer Network.

Studies show that up to one-quarter of people with cancer have clinical depression, the symptoms of which include anger, irritability, difficulty concentrating, feelings of helplessness or despair, an inability to experience joy, loss of interest in usual activities, restlessness, difficulty sleeping and even suicidal thoughts. Research has also identified fear of recurrence as one of the most common emotional issues survivors experience as treatment ends. In addition to depression and anxiety, survivors may face a host of other issues related to the cancer experience: financial and employment concerns, changes in family relationships, emotional isolation or sexual dysfunction.

Unfortunately, studies indicate distress assessment is rarely a part of routine care by oncologists, and survivors, in turn, rarely volunteer information about their emotional condition.

The SCP discussion also allows time to determine if the survivor needs rehabilitation to regain strength and conditioning.

November 2014

What are long-term and late effects?

What are examples of effects caused by treatment?

How prevalent are long-term and late effects in survivors?

What are ways to ease long-term and late effects?