Older women who receive pelvic irradiation for cancer have increased risk for pelvic fracture

November 22, 2005

Older women who received radiation therapy for cervical, rectal or anal cancer have a substantially increased risk for pelvic fractures, according to a study in the November 23/30 issue of JAMA.

Pelvic fractures, including hip fractures, are common in older people and are a major source of illness and death, particularly in women, according to background information in the article. The lifetime risk of a hip fracture after 50 years of age for white women is estimated at 17 percent. Within the first year after a hip fracture, 10 percent to 20 percent more women die than expected for age. The number of deaths due to hip fractures is comparable with the number of deaths due to pancreatic cancer and is only slightly lower than the number of deaths due to breast cancer. It is well recognized that therapeutic radiation can result in bone damage and may increase fracture risks. However, the risks have not been well studied. Because of the high baseline incidence of fractures in older people and the significant illness and death associated with fractures, even a small increase in the fracture rate would be an important finding.

Nancy Baxter, M.D., Ph.D., of the University of Minnesota, Minneapolis, and colleagues conducted a study to determine if women who undergo pelvic irradiation for pelvic malignancies (anal, cervical, or rectal cancers) have a higher rate of pelvic fracture than women with pelvic malignancies who do not undergo irradiation. The researchers used Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked to Medicare claims data. A total of 6,428 women aged 65 years and older diagnosed with pelvic malignancies from 1986 through 1999 were included.

The researchers found that the cumulative incidence of pelvic fractures was greater in the irradiated group than in the nonirradiated group for all 3 types of cancer diagnoses. Within the first 5 years of the study period, the incidence of pelvic fractures was: for women with anal cancer, 14.0 percent in the irradiated group vs. 7.5 percent in the nonirradiated group; for women with cervical cancer, 8.2 percent in the irradiated group vs. 5.9 percent in the nonirradiated group; and for women with rectal cancer, 11.2 percent in the irradiated group vs. 8.7 percent in the nonirradiated group. The incidence of arm or spine fractures was similar in both groups.

"The observed hazard ratio for radiation therapy in women with anal cancer was 3.16. This value can be interpreted as a 3-fold increase in pelvic fracture risk for women with anal cancer who underwent radiation therapy (vs. women who did not) at any given time. The observed hazard ratio for radiation therapy in women with cervical cancer was 1.66; in women with rectal cancer, 1.65. These values indicate a lesser effect, but are still consistent with a substantial increase in fracture risk," the researchers write.

"Given the high baseline rate of fractures in women aged 65 years or older, the hazard ratio of 1.65 that we found in our study may represent an increased lifetime incidence of fractures from the baseline rate of 17 percent to 27 percent - a substantial and clinically significant absolute increase."

"The high risk of pelvic fracture after radiation therapy for anal cancer may reflect the radiation therapy technique used to treat this disease. In the treatment of anal cancer, it is usually appropriate to treat the inguinal [pertaining to the groin] nodes because of the risk of disease at this site. Because of the location of these nodes with respect to the femoral head and neck, it has been difficult to treat these nodes well without concomitant irradiation of the femur, and thus the femoral heads are exposed to a relatively high irradiation dose in the treatment of anal cancer patients," the authors write.

The researchers add that it is important to note that the study population (older, predominantly white women) was already at high risk for pelvic fractures. "Therefore, our results cannot be generalized to other populations (e.g., men, younger age groups). The risk of pelvic fractures after irradiation in other populations should be the focus of future studies."

"In conclusion, older women undergoing irradiation therapy for anal, cervical, or rectal cancer should be counseled with respect to fracture risks from irradiation. Potentially, these women could be targeted for preventive strategies, such as bone mineral densitometry screening, medical regimens aimed at preventing osteoporosis, and fall prevention. Such strategies should be evaluated in prospective studies. In addition, changes in irradiation techniques for high-risk individuals to minimize the irradiation dose received by bone should be investigated."
(JAMA.2005; 294:2587-2593. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: This research was supported by a Veterans of Foreign Wars Surgical Oncology research grant and by the University of Minnesota Comprehensive Cancer Center. Dr. Baxter is supported by a University of Minnesota Cancer Center Clinical Scholars Award and by an American Society of Clinical Oncology Career Development Award.

Editorial: Postradiotherapy Pelvic Fractures - Cause for Concern or Opportunity for Future Research?

In an accompanying editorial, William Small, Jr., M.D., of Northwestern University, Chicago, and Lisa Kachnic, M.D., of Boston University Medical Center, Boston, comment of the findings by Baxter and colleagues.

"How should clinicians use the knowledge of an increased risk of pelvic fractures associated with radiotherapy? This potential morbidity should be discussed with the patient at the time of radiation oncology consultation and factored into informed decision making and informed consent regarding the use of radiotherapy. More important, patients who have received prior pelvic radiation must receive long-term follow-up examinations, and must be carefully assessed when pelvic pain appears."

The authors add that besides improved targeting of radiotherapy, there may warrant consideration of agents that reduce toxicity or improve the osseous [of bone-like consistency or structure] environment after radiotherapy.

"In conclusion, Baxter et al have provided compelling evidence for a significant increase in pelvic fracture risk with the use of pelvic radiotherapy as a component of definitive cancer management. The morbidity associated with pelvic fractures and the widespread use of pelvic radiotherapy make research into reducing such osseous effects a high priority," the authors conclude.

(JAMA.2005; 294:2635-2637. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: Dr. Small is on the speakers bureau for MedImmune, the company that manufactures amifostine.

The JAMA Network Journals

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