No Adverse Effects With RT Delay After Surgery

VICTORIA, BC, Canada--Delaying radiation therapy for up to 5 months after surgery for breast cancer had no adverse effect on local recurrence or survival, a finding that may help lay to rest any controversy about delayed irradiation, Peter Froud, MD, reported at the San Antonio Breast Cancer Symposium.

In this retrospective study, 5-year in-breast recurrence averaged 3.8% in women with delays of 0 weeks to beyond 15 weeks, compared with 4.3% in women whose radiation therapy was delayed 15 or more weeks, which did not differ significantly from the overall recurrence rate, said Dr. Froud, a radiation oncologist at the Vancouver Island Cancer Centre.

The findings came from a review of data collected by the British Columbia Cancer Agency on 2,323 breast cancer patients who received radiation therapy between 1989 and 1994. During this period, the province had only two radiation therapy centers, and delays after surgery for breast cancer were common.

"There is conflicting evidence regarding the effect of the time interval between definitive surgery and the start of radiation therapy on in-breast recurrence of cancer," he said. "Some reports suggest that longer intervals are associated with an increased risk of recurrence, whereas others have found no increased risk."

He pointed out, however, that previous studies have been limited by small numbers of patients, different definitions of the time interval, and planned delays in radiation therapy for chemotherapy.

This review, he said, involved a large cohort of women, many of whom delayed initiation of radiation for more than 8 weeks after definitive surgery.

The patients were younger than 90 years of age at diagnosis (median, 63 years), and all survived more than 30 days after diagnosis. The study excluded patients who had T4N2M1 disease. He noted that this group had a relatively good prognosis in that no patient required or received adjuvant chemotherapy.

Dr. Froud and colleagues grouped the patients according to the delay between surgery and radiation therapy. The majority of patients fell into intervals of 6 to 8 weeks and 9 to 11 weeks (see table).

At a median follow-up of 41 months, 5-year actuarial incidence of in-breast recurrence was 3.8% for the entire cohort. Within the five time intervals, the incidence of in-breast recurrence ranged from 4.8% for the shortest delay (0 to 5 weeks) to a low of 2.4% associated with a delay of 12 to 14 weeks. No significant between-group differences were found.

Univariate analysis showed that the risk of in-breast recurrence increased with grade 3 lesions, absence of lymphatic or vascular invasion, negative estrogen-receptor status, no adjuvant use of tamoxifen (Nolvadex), younger age at diagnosis (35 years or younger), diagnosis in 1994, and treatment center. In a multivariate analysis, only histologic grade and absence of lymphatic or vascular invasion remained significant.

"According to our data, if you delay radiation by up to 5 months after surgery, it has no effect on the relapse rate," Dr. Froud said. "We were not able to define any critical time interval at which the risk increases. However, only seven patients had delays beyond 6 months, so we would not want to comment on the safety of delays beyond 20 weeks. Up to 20 weeks, there does not appear to be an adverse effect on the relapse rate."

Paradoxically, patients who had lymphatic or perivascular invasion actually had better outcomes. The finding probably reflected use of adjuvant tamoxifen in that patient subset. Overall, 27.5% of patients had lymphatic or perivascular invasion. About a third of the total study population received adjuvant tamoxifen.

The findings may also reflect treatment consistency throughout the province, Dr. Froud added, due to the use of provincial treatment guidelines with 95% adherence, according to data from the British Columbia Cancer Agency.