Risk of Second Cancer in Hodgkin Lymphoma Survivors

Since the introduction of high-energy radiotherapy and chemotherapy in the late 1960s, the 5-year survival rate for Hodgkin lymphoma patients has increased to more than 80%. Even if this disease is highly curable and treated patients have long survivorship, some studies indicate that Hodgkin lymphoma patients still have higher death rates than the general population. This may be attributed to various complications that may arise after treatment.

One of the most studied complications of Hodgkin lymphoma is the development of second cancers or cancers that are not recurrences of the first malignancy. This is because the excess mortality after the first 10 to 15 years after diagnosis is mainly due to second cancers, even if Hodgkin lymphoma itself is the major cause of death during the same period. Other late adverse Hodgkin lymphoma treatment effects are cardiac toxicity, thyroid dysfunction, subfertility, and infection.

According to 2015-published research that studied the risk of second malignancy in Hodgkin lymphoma survivors treated from 1965 to 2000, survivors were twice more likely to develop second cancer even beyond 35 years after the treatment. In the same study, the standardized incidence ratios were observed to be the highest for leukemia, connective tissue cancer, thyroid cancer, and non-Hodgkin’s lymphoma. Moreover, survivors have moderately increased risks for lung, breast, skin, and stomach cancers, among many others.

How second cancers develop in Hodgkin lymphoma survivors

About one in every six cancer patients develops a second malignancy years later after the first diagnosis. Different factors influence one’s risk—genetic susceptibility, lifestyle habits, and certain cancer treatments. The two most common cancer treatments linked to second cancer development are radiation therapy and chemotherapy, where the former accounts for only about 5% of the total second malignancies related to treatment.

According to the review made by Dracham, et al. in 2018, exposure to ionizing radiation during radiotherapy causes breaks in the single- and double-strand DNAs. Eventually, the double-strand DNA breaks (including the single-strand DNA breaks that are converted into double-strand DNA breaks during replication) may result in gene mutation and subsequent malignancy formation of the irradiated cell. The risk of developing malignancy depends on factors such as:

  • Age – Those treated at a young age have higher risks than adult patients. For a specific dose, children are ten folds more susceptible.
  • Gender – Several studies show that women are more prone to second cancer development than men due to increased radiation exposure at a young age, as breast and thyroid cancers have a high incidence among females.
  • Radiation dose – The risk increases as the dose of radiation increases.
  • Site of radiation – Malignancy tends to develop in or near the treated area. However, certain organs like the breast and thyroid are known to be more sensitive to radiation-induced malignancy than other organs.

Certain chemotherapy drugs have also been linked to second cancers, with blood-related cancers like myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) being the most linked. The risk depends on several factors, including high drug doses, long treatment time, and high dose intensity.

The same review article by Dracham, et al. in 2018 indicated that chemotherapy drugs containing alkylating agents (chlorambucil, cyclophosphamide, mechlorethamine, melphalan, etc.), topoisomerase II inhibitors, and antimetabolites are the ones with the greatest potential to cause MDS and AML

How to lower the risk of developing a second cancer after Hodgkin lymphoma treatment

Recent advancements in radiation therapy and chemotherapy technology make these treatments relatively safer now than in the past. For example, radiation beams can now target the tumor’s exact size, shape, and location, reducing exposure of the healthy tissues to radiation. In addition, the manner of administration of this treatment has also changed in terms of frequency. The traditional external beam radiation therapy required daily administration for several weeks and now only requires less frequent administration. Chemotherapy, on the other hand, now eliminates or reduces the use of leukemogenic agents like alkylating agents.

As the late adverse treatment effects of Hodkin lymphoma treatment result in reduced life expectancy and quality of life, patients and survivors must also take part in lowering their risk of developing a second malignancy. Here is a checklist:

  • Get cancer screening regularly

Depending on the patient’s level of risk, he might be asked to follow specific cancer screening guidelines to avoid recurrence and second cancer. For example, women who have undergone Hodgkin lymphoma radiation therapy and are at risk of breast cancer may benefit from a yearly breast MRI along with mammograms and clinical breast exams to detect second cancer earlier.

Since cancer screening detects cancer before any signs or symptoms show up, patients have a better chance of avoiding the adverse effects of cancer and its treatments.

  • Maintain follow-ups

Once treatment is completed, the doctor may require follow-up sessions. These allow patients to let their health care team know if they have developed new symptoms as a sign of cancer recurrence or second cancer so a confirmation test and new treatment can be done.

  • Make lifestyle changes

The primary lifestyle change a survivor might be advised to practice is abstinence from tobacco. Smoking tobacco produces carcinogenic substances that cause damage to the DNA, which can result in abnormal growth of the cells or cancer. Aside from this, smoking weakens the immune system, making it more difficult to fight cancer cells.

Maintaining a healthy weight through diet and exercise also plays a significant role. The American Cancer Society recommends a healthy diet consisting of a variety of dark green vegetables, fiber-rich legumes, whole fruits, and whole grains. It does not recommend red and processed meat, refined grain products, and sugar-sweetened beverages. In terms of physical activities, a 150 to 300-minute exercise of moderate intensity or 75 to 150-minute exercise of vigorous intensity each week for adults is recommended, while sedentary behavior like sitting and lying down for an extended period is discouraged.

Read more on Positive Lifestyle Changes to Help Manage Lymphoma for other tips.


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