Second Malignancies?

by Nancy Keene and Kevin Oeffinger M.D
Source: Spring 2000 CCCF Newsletter

Some survivors of childhood cancer worry that they will get a second cancer. Others think that lightening won't strike twice. The chance of developing a second cancer depends on a number of factors including your original type of cancer, age at diagnosis, gender, types of therapy given, environmental exposures, genetic predisposition, and health decisions. Overall, for most survivors the chance of getting a second cancer is very small.

The information in this article is meant to make you aware, not concerned. There is no reason to be fearful about getting initial treatment that has the potential to cure the cancer, because of the very small chance that you may get a second cancer.

You can use the information presented here to spark discussion with your doctor about your individual risk (if any). That knowledge can help you make healthy choices and get appropriate follow-up care to give you the best chance for a long and healthy life.

Genetic risk

Cancers with known genetic causes sometimes carry a higher risk of second cancers. For instance, survivors of familial (inherited) cancers like bilateral retinoblastoma tumor should be evaluated regularly for the rest of their lives because they have a much higher chance of developing second tumors than do other survivors. In some cases, specific genes have been identified that increase the risk of second cancers.

Survivors of Hodgkin's disease, ovarian cancer, the inherited form of retinoblastoma, and the genetic form of Wilms tumor (extremely rare) are at increased risk for second cancers. Persons with genetic diseases such as von Recklinghausen's neurofibromatosis, xeroderma pigmentosum, Klinefelter's disease, Bloom's syndrome, and immunodeficiency syndromes also carry an increased risk of cancer.

If you are in one of the above groups, your follow-up care should be especially vigilant. This allows for earlier detection and treatment should you develop another cancer. It also gives you the opportunity to discuss ways to lower your risks by making healthy lifestyle and behavior choices.


Radiation kills cancer cells and also may cause changes in normal cells. In some cases, second cancers develop in the areas irradiated. For instance, Hodgkin's survivors who had mantle radiation have a higher risk of developing breast or lung cancer at a young age and leukemia survivors treated with cranial radiation have a small risk of developing brain tumors. In addition, some radiation (called "scatter") escapes into the areas surrounding the radiation field. Survivors who had radiation to the head or chest can develop late effects in the thyroid gland or salivary glands from scatter radiation. These areas as well as the radiation field should be routinely evaluated during follow-up appointments. In general, the higher the dose of radiation you received, the greater your risk of developing a second cancer.


Several chemotherapy drugs are associated with second cancers in some survivors. Examples of these are:

  • Alkylating agents-procarbazine, chlorambucil, BCNU, nitrogen mustard, (Cytoxan), ifosfamide. High doses of these drugs can cause malfunction of bone marrow causing abnormal cells (myelodysplastic syndrome) or acute myelocytic leukemia (AML).
  • Epipodophyllotoxins-VP-16 (etoposide), VM-26 (teniposide). These drugs cause acute myelocytic leukemia (AML) in a small number of survivors.
  • Platinum analogs-cisplatin, carboplatinum. The research is not clear concerning second cancers after treatment with these drugs. Most AML or myelodysplastic syndromes occur when the platinum drug is given in conjunction with alkylating agents or epipodophyllotoxins.

Secondary leukemias that occur in those treated with alkylating agents and/or epipodophyllotoxins are usually seen in the first ten years after treatment. Solid tumors tend to occur many years or decades after treatment ends.

Risks after treatment

After reading the above, you may be wondering what your actual risk of developing a second cancer is. It isn't possible to address your particular case because your risk depends on your age at treatment, the amount and location of radiation, the total doses of chemotherapy drugs, and perhaps your genetic predisposition to cancer. A physician who knows your medical history and is well informed about late effects can best help you estimate risk in your individual case.

Many of the treatment-related second cancers discussed earlier are attributed to treatments that are not considered standard of care today. Many current clinical trials are focusing on maintaining cure rates but using less toxic treatments. Thus, in the future, it is hoped that cures will continue to increase, while treatment-related second cancers decrease. All survivors, however, need life-long surveillance for second cancers to provide either reassurance that you are in the large majority of survivors who have no second cancer, or to diagnose any problem early.


Once you know what your risk might be, what can you do? Practical ways to deal with this information are to do everything you can to prevent a secondary cancer and get regular check-ups. While you cannot alter a genetic predisposition or damage done from radiation, you can modify risk factors by making healthy choices. Some of these are:

  • Don't smoke
  • Exercise regularly (at least three times a week)
  • Maintain a healthy body weight
  • Eat four to six fruits and vegetables a day
  • Learn how to do breast or testicular self-exams, and do them every month
  • Get regular check-ups
  • Drink alcohol only in moderation
  • Don't take illegal drugs or recreational inhalants
  • Avoid exposure to the sun and use sunscreen, particularly on irradiated skin

Taking control of your risk for second cancers includes regular check ups by a physician who knows your history and risks as well as making healthy lifestyle choices.

Nancy Keene is the author of Childhood Leukemia; Childhood Cancer: A Parent's Guide to Solid Tumor Cancers; (with co-author Honna Janes-Hodder); Your Child in the Hospital; Working with your Doctor; Childhood Cancer Survivors (co-authored with Wendy Hobbie RN and Kathy Ruccione) and Chemo, Craziness & Comfort: My book about childhood cancer. Nancy is the mother of a survivor of high risk ALL.

Kevin Oeffinger M.D. directs a multidisciplinary program for young adult survivors of childhood cancer at UT Southwestern at Dallas TX and is partially supported as a Robert Wood Johnson Foundation Generalist Physician Faculty Scholar.