Researchers at Washington University School of Medicine in St. Louis have shown that highly targeted radiation therapy improves survival and lessens treatment-related complications in cervical cancer patients.
The technique, called intensity-modulated radiation therapy (IMRT), is widely accepted for treating many cancers of the pelvic region, head and neck, and central nervous system, but the use of IMRT for cervical cancer is not as common. This is the first large study to show its effectiveness as a primary therapy for cervical cancer.
"Previous studies of IMRT for cervical cancer have been small with limited follow-up and some used IMRT as a post-operative treatment instead of as primary therapy, but this evidence did suggest that IMRT could be an effective treatment choice," says lead author Elizabeth Kidd, M.D., a Barnes-Jewish Hospital resident in Washington University's Department of Radiation Oncology. "So we undertook a larger study involving IMRT treatment of advanced cervical cancer, and the positive results we saw will likely encourage more medical facilities to use IMRT for these patients."
Kidd and her colleagues, including researchers with the Siteman Cancer Center at Washington University and Barnes-Jewish Hospital, report their findings in an upcoming issue of the International Journal of Radiation Oncology, Biology, Physics.
In the United States, cervical cancer is the third leading cause of cancer death among women aged 15 to 34 and the fifth leading cause of cancer death among women aged 35 to 54. The American Cancer Society estimates that in 2009, about 11,000 women will be diagnosed with cervical cancer and about 4,000 will die.
IMRT is an advanced mode of radiotherapy that allows the radiation dose to conform more precisely to the three-dimensional shape of the tumor. IMRT minimizes the dose to surrounding normal tissues and organs, reducing possible damage to the bowels, bladder, rectum, vagina and pelvic bones.
The study included 452 patients with newly diagnosed cervical cancer who were treated with external-beam radiation therapy at Washington University in St. Louis. More than 80 percent of the patients received concurrent cisplatin, a chemotherapy drug commonly used for cervical cancer. The patients also received brachytherapy, in which a radioactive source is placed close to the cervical tumor.
From June 1997 to March 2005, 317 patients were treated with traditional whole-pelvic external-beam radiation. The central pelvic area was shielded during part of the external beam radiation to compensate for the dose delivered by brachytherapy. After March 2005, the department changed its treatment policies so that all cervical cancer patients received radiation using IMRT, and 135 patients were treated in the time period running until September 2008, when the study ended.
"Our IMRT protocol was designed to replicate the traditional approach in terms of the amount of radiation going to the tumor and pelvic lymph nodes, which is the first area where the cancer spreads," Kidd says. "In the IMRT group, we expected to see a reduction of radiation-induced side effects in adjacent normal tissues, but we expected that both approaches would result in equivalent control of the cancer. We did see fewer treatment-related complications in the IMRT group, but we were surprised that the IMRT group also had better overall survival."
After treatment ended, patients returned for follow-up examinations approximately every two months for the first six months, every three months for the next two years and then every six months. Because non-IMRT patients were treated only during the earlier phase of the study, their most recent follow-up averaged 72 months from the end of treatment, while the average time for the most recent follow-up in IMRT patients was 22 months. Even though the time between treatment and the last follow-up was shorter in the IMRT group, the improvement in survival for this group was discernable and was found to be statistically significant.
At the time of most recent follow-up, 67 percent of IMRT patients were alive with no evidence of disease compared to 49 percent of non-IMRT patients. Within the same time period, less than 4 percent of IMRT patients had died of cervical cancer, while 37 percent of non-IMRT patients had died of cervical cancer.
The rate of cancer recurrence between the two groups was similar. At the time of most recent follow-up, 28 percent of patients treated with IMRT had a recurrence of cancer while 44 percent of traditionally treated patients had a recurrence. Although those numbers seem to suggest an improvement in recurrence with IMRT, the difference in recurrence between the two groups was not statistically significant.
Positron emission tomography (PET) imaging at three months also showed that recurrence in both groups was similar, and previous studies by this research group has firmly established that three-month PET scan results are highly predictive of long-term outcome.
Complications of radiation exposure in the pelvis include opening of passages between pelvic organs, inflammation of pelvic organs and bowel obstruction. In this study, no patients in the IMRT group died from such radiation-related complications while three non-IMRT patients died of bowel complications. At time of last follow-up, 6 percent of patients in the IMRT group had developed serious bowel or bladder complications; this was significantly fewer than the 17 percent observed in the non-IMRT group.
Kidd says that one reason IMRT has not been more widely adopted for cervical cancer treatment is that cervical tumors are hard to distinguish from surrounding normal tissue with standard computed tomography (CT) scans, which are used to create a detailed three-dimensional simulation of patients' anatomy during treatment planning. The uncertainty concerning tumor location made a whole-pelvic approach more appropriate.
The Washington University researchers used PET imaging that allowed them to clearly delineate the extent and position of the cervical tumors as well as whether the cancer had spread to any lymph nodes. PET is particularly useful for imaging cervical cancer because the commonly used glucose tracer is highly absorbed by both the primary tumor and those that have spread, making them easy to locate. The use of PET and CT helped ensure that the IMRT fields were precisely contoured for each patient.
Kidd notes that the size of the study and strength of the data will likely make it easier for patients to receive insurance coverage for IMRT for cervical cancer, which will also encourage more medical facilities to adopt the technique.
Kidd EA, Siegel BA, Dehdashti F, Rader JS, Mutic S, Mutch DG, Powell MA, Grigsby PW. Clinical outcomes of definitive IMRT with FDG-PET simulation in patients with locally advanced cervical cancer. International Journal of Radiation Oncology, Biology, Physics (advance online publication Oct. 30, 2009).
This research received no external funding.
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Siteman Cancer Center is the only federally designated Comprehensive Cancer Center within a 240-mile radius of St. Louis. Siteman Cancer Center is composed of the combined cancer research and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine. Siteman has satellite locations in West County and St. Peters, in addition to its full-service facility at Washington University Medical Center on South Kingshighway.