DNA defect predicts RT outcome for endometrial cancer

Radiation therapy (RT) may not be an effective treatment for women diagnosed with endometrioid endometrial cancer whose tumors have a DNA deficiency, according to preliminary research from the Canary Institute for Cancer Research in Las Palmas, Spain.

The study, designed to determine whether the presence of microsatellite instability in endometrioid endometrial cancer can predict radiation therapy response, has confirmed that patients who have this condition have poorer outcomes. Study results were published in the January issue of the International Journal of Radiation Oncology, Biology, Physics (2010, Vol. 76:1, pp. 9-13).

Microsatellite instability, a defect in the DNA mismatch repair system, is associated with endometrioid histology and is present in 20% to 30% of tumors, according to principal investigator Cristina Bilbao, Ph.D., of the department of radiation oncology at the Hospital Universitario de Gran Canaria Dr. Negrín, and colleagues.

The researchers identified microsatellite instability tumor determination and classification in 20 of 93 consecutive patients who received radiation therapy for localized endometrioid endometrial cancer between 1990 and 1999 at the hospital. More than half (62%) of the women had stage I disease, 23% had stage II disease, and 15% had stage III disease.

All of the women had undergone exploratory laparotomy, extrafascial hysterectomy, and bilateral salpingo-oophorectomy. The patients received 1.8-2.0 Gy fractions for a mean radiation dose of 50.44 Gy, and 88 patients received brachytherapy.

The women were followed through June 2009, during which time 23 died from their disease. Local recurrence for the entire patient cohort was 15%, and disease recurrence was 29%. Older age, advanced cancer stage, higher tumor grade, and vascular invasion were significantly associated with poor disease-free survival and cancer-specific survival.

The presence of microsatellite instability in the tumors was associated with significantly worse 10-year outcomes, the researchers reported. Patients with microsatellite stability had a 91.1% local disease-free survival outcome, compared with 62.9% for patients with microsatellite instability. Overall disease-free survival was 75.9% and 53.8%, respectively, and cancer-specific survival was 82.8% and 58.7%.

Absence of the MLH1 protein through promoter hypermethylation, the main cause of microsatellite instability in sporadic endometrial cancer, could drive the accumulation of DNA aberrations, increasing tumor cell malignancy after irradiation, the researchers suggested. Because of the small size of the patient cohort, they recommended that further studies be conducted to confirm their findings.

By Cynthia E. Keen
AuntMinnie.com staff writer
January 6, 2010

Related Reading

Molecular imaging holds promise for uterine cancer, October 1, 2009

Endometrial cancer radiation treatment increases second cancer risk, April 24, 2009

Survival odds better with RT for endometrial cancer, April 2, 2009

Lymphadenectomy and radiotherapy not useful for early endometrial cancer, December 15, 2008

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