Adults survivors of childhood cancer who were treated with radiation are at significantly greater risk of developing a second cancer, according to a study published in the journal Cancer. These cancer survivors are at five times greater risk to develop a second neoplasm at 30 years.

The probability of developing a second cancer does not appear to plateau even after 30 years, suggesting that the risk may continue to increase. Cancers were most commonly found within the original radiation field and were predominantly breast cancer, skin cancer, and brain cancer. Those at greater risk included women and those initially diagnosed with Hodgkin's Disease or Acute Lymphoblastic Leukemia (ALL).

The authors conclude, "Primary care physicians need to be aware of the elevated risk of secondary malignancy in childhood cancer survivors so that increased surveillance programs can be implemented, such as early mammograms for women who were treated with radiation for Hodgkin Disease."

Improvements in chemotherapy, radiation therapy and surgery protocols have increased 5-year survival rates for childhood cancers to over 80%. Survival into adulthood, however, brings complications related to chemotherapy and radiation treatment, including the development of a second cancer. In particular, radiation therapy, a known carcinogen, has been tentatively identified to be an independent risk factor for the development of a second cancer, such as bone cancer and breast cancer.

Radiation and chemotherapy agents have the therapeutic intention of causing DNA mutations that destroy rapidly dividing malignant cells. However, they can have an unwanted side effect of causing mutations in the DNA of healthy cells that can lead to malignancy - a malignancy not identified and destroyed by the immune system.

One hypothesis says children may be at particular risk to develop second cancers from cancer treatments because in the course of normal growth, their cells are undergoing rapid division and are more vulnerable to cancerous changes.

To understand the long-term risk for a second cancer and characterize the types of malignancies survivors of childhood cancers may face, Dusenbery et al reviewed data from 446 patients from initial treatment of first cancer to up to 40 years after treatment. All patients received treatment that included radiation therapy.

Patients who received radiation therapy had a cumulative probability of developing a second cancer of 13% at 30 years and an increased risk of developing a second cancer as measured by an overall standardized incidence ratio of 5.2. Survival also decreased from 91% at 10 years to 80% at 30 years. However, second cancers caused only a minority of deaths.

The most common second cancers were breast cancer, skin cancer and meningiomas. All eight breast cancer cases were subsequent to Hodgkin's Disease. At 30 years the cumulative risk of women developing breast cancer was 7%; the cumulative risk of developing brain cancer was 4%; the cumulative risk of developing skin cancer was 4%.

Further analysis identified female gender and two childhood cancers, Hodgkin's Disease and ALL, as risk factors for a second cancer. Contrary to other studies age and male gender were not risk factors.

The authors conclude that as the patients in this study age, "they will likely be at continued risk of developing second neoplasms, as the cumulative probability curve does not show evidence of plateau."

They recommend, "future studies aimed at evaluating preventive strategies in children treated for cancer who are at particularly high risk of developing second neoplasms and diligent surveillance of patients treated with chemotherapy and radiotherapy as children."

SOURCE:
Cancer, May 15, 2003