What are "Late Effects?"
Late Effects: They Depend on a Number of Variables
Long-Term Survivors Are Encouraged to Work Closely with Their Providers
Many who receive a cancer diagnosis worry about the side effects of treatment--infections and hair loss caused by chemotherapy and fatigue after receiving radiation. Such side effects appear during or just after treatment.
Late effects are in a different category. These medical conditions may not appear for months, years or decades after cancer treatment has been completed. They can be serious, whether it is heart damage or another, completely different cancer--known as subsequent cancer. Long-term survivors of Hodgkin lymphoma are at greater risk than other cancer survivors of developing late effects. This is because the form of radiation and the types of chemotherapy--notably higher doses of anthracyclines and alkylating agents--that were used years ago maintain a presence in the body that, over time, may cause damage.
Also, the part of the body that most commonly receives treatment for Hodgkin lymphoma--the neck and chest area--is where vital organs are located. Radiation directed to this area can damage the heart, lungs, thyroid and breasts. If radiation is directed to the abdominal area, an individual may be at risk for colorectal cancer, diabetes and infertility.
“Radiation to wide areas of the body, particularly the chest, was how cures for Hodgkin’s were achieved all the way back to the 1960s,” notes Kevin Oeffinger, MD, founding Director of the Duke Cancer Institute Center for Oncology-Primary Care. “At the time, there was inadequate chemotherapy. Radiation worked, except that wide fields and high doses were used; this has caused problems for patients. Improved chemotherapy protocols became available in the 1970s and 1980s.”
There has been steady progress in refining treatment for Hodgkin’s. “Currently, among patients who were treated at age 15, about 40% will require radiation for a cure--60% will not--depending on the aggressiveness of the tumor and other risk factors,” he adds. Dr. Oeffinger served as lead investigator for a study of 3,000 individuals diagnosed with Hodgkin’s between 1970 and 1999.* A key finding from the study is the 20% reduction in the risk of developing a serious chronic condition with each decade interval from the 1970s to the 1990s. If no chest radiation was given, the risk was reduced by 70%.
There are two time periods in the course of one’s life when Hodgkin’s tends to be diagnosed. “We see an increased incidence in individuals age 10-29 and then another increased incidence around age 50. Life expectancy varies widely; it depends on the treatment someone received, their genetics, lifestyle--diet and exercise--and whether or not they have access to health care. Is their provider aware of their risks and following the national recommendations for monitoring? All of these things have an impact on life expectancy.
“In general, people with Hodgkin’s die from the same conditions as people who have other kinds of cancer where there is a high cure rate: heart attack, stroke or another cancer.” In Hodgkin’s survivors, these conditions occur at younger ages than in the general population.
The all-important goal is to then actively screen for certain conditions and reduce a person’s risk of developing late effects. “We can make a significant difference with breast cancer, which tends to develop in women who were treated for Hodgkin’s at a young age,” says Dr. Oeffinger. “We start screening at the age of 25 with an annual mammogram and a breast MRI so that, if breast cancer is detected, it is very early-stage and responds to treatment.”
The other area where careful follow-up can make a difference is with cardiovascular disease, where disease can be identified earlier and treated. “We can screen for it with some of our imaging studies, we can lower someone’s cholesterol level with statin medications, and we can counsel our patients to increase their activity level.”
Hodgkin’s survivors wrestle with a few other challenges. “Most people worry a lot about the late effects of treatment,” says Dr. Oeffinger, who acknowledges it is normal for cancer survivors to experience a certain level of uncertainty, even years after being told they are cured. “We need to provide good counseling or psychological services for patients who need help in managing those feelings.”
He has advice for Hodgkin’s survivors: “Find a primary care physician who shows interest in you. If they have only a few patients who had Hodgkin’s, they may not have much knowledge about the late effects. For many of us in the cancer survivorship field, the goal is to share the most current information, which our medical colleagues need in order to successfully manage your care. If you have a primary care physician who wants to work with you, that’s super.”
It is imperative that survivors locate clinicians who take the time to listen, understand what they need and connect them to the right services. Survivorship or late effects clinics are worth locating.
Those who are fortunate enough to have a survivorship or late effects clinic nearby will receive a holistic, comprehensive approach to their care, says Larissa Nekhlyudov, MD, MPH, Clinical Director, Internal Medicine for Cancer Survivors at Dana-Farber Cancer Institute in Boston. “We address everything, from surveillance and monitoring to general health, the patient’s psychosocial health and, of course, late effects--those they are experiencing and those for which they are at risk,” she explains.
Dr. Nekhlyudov agrees with Dr. Oeffinger about the importance of closely observing one’s primary care provider. “If your physician hears you had Hodgkin’s, and they move on without asking any questions related to it, you know you’re not going to receive the care you require from them.”
The following is Dr. Oeffinger’s overview of the late effects that are of most concern to individuals who were treated for Hodgkin lymphoma:
Cardiovascular disease: Radiation therapy can lead to radiation fibrosis--sclerosis or hardening of the affected tissue--and this makes the heart vulnerable. Hodgkin’s survivors need to be aware that they could develop coronary artery disease, which may produce angina or a heart attack. Arrhythmias (irregular heartbeat), such as ventricular fibrillation, which is a rapid, life-threatening heart rhythm, are also common, as is valvular heart disease, which might require heart valve replacement, and heart failure, which requires regular management and medication.
Pericardial disease (inflammation of the sac that surrounds the heart), blood clots and stroke are other late effects.
For more information, see Cardiovascular Disease.
Subsequent cancers: Female Hodgkin’s survivors, notably those who received radiation to the chest during 1970-1990 (although those treated later are also at risk), are at risk for breast cancer; ductal carcinoma in situ, a non-invasive form of breast cancer, is common.
Thyroid carcinoma is one of the more common subsequent cancers due to the thyroid gland’s location in the upper chest. Those who received radiation to the gastrointestinal tract are at risk for developing polyps, which can lead to colon cancer.
For more information, see Subsequent Cancers.
Pulmonary (lung) disease: In addition to emphysema, which requires medication, some Hodgkin’s survivors develop pulmonary fibrosis, which requires oxygen therapy. Primary pulmonary hypertension (high blood pressure in the lungs) is another concern. The symptoms include fatigue, shortness of breath and a dry cough.
Endocrine (hormonal) disorders: Radiation directed at or near the thyroid gland may produce thyroid nodules, which may require surgery. Some Hodgkin’s survivors experience premature menopause (earlier than age 40) and infertility, which is related to the type of chemotherapy they received, as well as the field of radiation. Males may experience testicular hypofunction where they do not produce sperm. Diabetes is another endocrine disorder for which Hodgkin’s survivors are at higher risk.
Gastrointestinal conditions: The gastrointestinal tract may develop late effects, such as intestinal obstruction related to prior abdominal surgery (such as exploratory laparotomy and splenectomy, often performed during the earlier decades of Hodgkin’s treatment), which may require additional surgery.
Renal (kidney) conditions: If the kidneys were affected by radiation treatment, Hodgkin’s survivors may develop urinary incontinence, nephrotic syndrome—where the body excretes too much protein in the urine—and even kidney failure.
Neurologic conditions: Radiation fibrosis may result in balance problems or difficulty in manipulating objects. In rare cases where the accessory nerve (this controls the muscles that tilt and rotate the head and move the shoulders) is affected, paralysis may develop. Dropped neck syndrome, a rare condition characterized by weakness in the cervical spine and adjacent muscles, is another concern, and another reason to monitor one’s musculoskeletal health.
Vision problems: In general, they are rather rare, but cataracts are more common in Hodgkin’s survivors. The good news is that today’s surgery is highly effective. Blindness in one eye has been known to develop.
For more information on late effects and appropriate screening/monitoring, visit our Survivorship Care Plan.
*Journal of Clinical Oncology, 2021