Long-term follow-up of a prospective policy of margin-directed radiation dose escalation in breast-conserving therapy.
A prospectively applied treatment policy for breast-conserving therapy used margin assessment as the exclusive guide to the intensity of radiation therapy directed at the tumor bed.
From 1982 to 1994, 498 women with 509 Stage I/II breast carcinomas with a median follow-up of 121 months were treated. Final margin status (FMS) categories were defined as greater than 5 mm, greater than 2-5 mm, greater than 0-2 mm, and positive. For margins less than or equal to 2 mm or indeterminate, reexcisions were performed if feasible. All patients received whole breast irradiation to 50.0-50.4 Gy. Final tumor bed boosts as a function of FMS were as follows: no residual on reexcision, no boost performed; FMS greater than 5 mm, boost of 10 Gy; FMS greater than 2-5 mm, boost of 14 Gy; FMS greater than 0-2 mm or positive, boost of 20 Gy. Cases were analyzed for local failure with respect to histology, age, tumor size, excision volume, reexcision, and total dose.
FMS was positive, greater than 0-2 mm, greater than 2-5 mm, and greater than 5 mm, and no residual tumor on reexcision in 21%, 20%, 17%, 14%, and 28% of cases, respectively. At 12 years, Kaplan-Meier local failure rates were 17% for FMS positive, 9% for FMS greater than 0-2 mm, 5% for FMS greater than 2-5 mm, 0% for FMS greater than 5 mm, and 6% for specimens without evidence of residuum on reexcision (P = 0.009). Patients 45 years old and younger had a 12-year local failure rate of 15% whereas patients older than 45 years had a 12-year local failure rate of 6% (P = 0.01). On multivariate analysis, young age (P = 0.03) predicted increased local failure rate, whereas margins that were less than or equal to 2 mm or positive predicted late (> 5 years) but not early (< or = 5 years) recurrence (P = 0.003).
Graded tumor bed dose escalation in response to FMS results in very low rates of local failure over the first 5 years for all FMS categories. However, tumors with close/positive margins have significantly increased local failure rates after 5 years of follow-up even with increased radiation boost dose. In addition, graded tumor bed dose escalation does not fully overcome the adverse influence of young age.
Neuschatz AC
,DiPetrillo T
,Safaii H
,Price LL
,Schmidt-Ullrich RK
,Wazer DE
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《CANCER》
Effect of margins on ipsilateral breast tumor recurrence after breast conservation therapy for lymph node-negative breast carcinoma.
Breast conservative surgery (CS) with radiotherapy (RT) is the most commonly used treatment for early-stage breast carcinoma. However, there is controversy regarding the importance of the pathologic margin status on the risk of ipsilateral breast tumor recurrence (IBTR). The current study evaluated the effect of the pathologic margin status on IBTR rates in a cohort of women with lymph node-negative breast carcinoma treated with CS and RT.
Between August 1980 and December 1994, 452 women with pathologically lymph node-negative breast carcinoma were treated with CS and RT at Westmead Hospital (Westmead, Australia). Central pathology review was performed for all women. The final margins were negative for 352 women (77.9%), positive (invasive and/or in situ) for 42 women (9.3%), and indeterminate for 58 women (12.8%). Information regarding an extensive intraductal component (EIC), lymphovascular invasion, pathologic tumor size, histologic grade, and nuclear grade was available for most women. After macroscopic total excision of the tumor, all women received whole-breast irradiation (usually 45-50.4 grays [Gy]) and the majority of women also received a local tumor bed boost (range, 8-30 Gy).
After a median follow-up of 80 months, 34 women (7.5%) developed an IBTR. The crude 5-year rates of IBTR for women with negative margins, positive margins, and indeterminate margins were 3.1%, 11.9%, and 6.9%, respectively. For women with negative margins, the 5-year and 10-year actuarial rates of freedom from IBTR were 96% and 92%, respectively, compared with 88% and 75%, respectively, for women with positive margins (P = 0.003). Univariate analysis demonstrated that the only factors associated with a significantly higher risk of IBTR were age at diagnosis (P < 0.050) and margin status (P = 0.005). Multivariate analysis showed that both age and margin status were independent predictors of IBTR. None of 24 patients with an EIC and negative margins were found to have developed an IBTR.
The results of the current study were comparable to other published reports and supported the association of higher IBTR rates with positive or indeterminate margins compared with negative, pathologic margins. Furthermore, young age (age < 35 years at diagnosis) was associated with the highest risk of IBTR regardless of margin status.
Leong C
,Boyages J
,Jayasinghe UW
,Bilous M
,Ung O
,Chua B
,Salisbury E
,Wong AY
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《CANCER》