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BACKGROUND 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. METHODS 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. RESULTS 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 (≤ 5 years) recurrence (P = 0.003). CONCLUSIONS 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. Cancer 2003;97:30–9. © 2003 American Cancer Society. DOI 10.1002/cncr.10981

The introduction and development of comprehensive two‐dimensional gas chromatography offers greatly enhanced resolution and identification of organic analytes in complex mixtures compared to any one‐dimensional separation technique. Initially promoted by the need to resolve highly complex petroleum samples, the technique’s enormous separation power and enhanced ability to gather information has rapidly attracted the attention of analysts from all scientific fields. In this Minireview, we highlight the fundamental theory, recent advances, and future trends in the instrumentation and application of comprehensive two‐dimensional column separation.

SUMMARY In order to assess the utility of margin width in relation to other histopathologic features as a determinant of local control in ductal carcinoma in situ (DCIS) of the breast, we retrospectively examined the treatment of 109 breasts treated with (n ‫؍‬ 54) or without adjuvant radiotherapy (n ‫؍‬ 55). Median follow-up was 49 and 54 months for patients treated with excision alone (E) or excision plus adjuvant radiotherapy (E؉XRT), respectively. Cases treated with E؉XRT were significantly larger and had a trend towards closer surgical margins than those treated with E alone. For all cases, margin width <1 mm and lesion diameter >15 mm were significantly associated with increased local recurrence. Lesion size <15 mm was associated with no cases of local failure regardless of treatment arm. For lesions >15 mm in diameter, there was a significant decrease in 5-year local failure with E؉XRT compared to E alone (21% vs. 36%, P ‫؍‬ 0.03). Tumor margin >1 mm was associated with a low rate of 5-year local failure for either E alone or E؉XRT (10.9% vs. 4.6%, P ‫؍‬ NS). Tumor margin <1 mm had a high rate of local failure that was not significantly decreased by the addition of adjuvant radiotherapy. These results show that large diameter (>15mm) and close surgical margins (<1 mm) are the dominant risk factors for local recurrence in DCIS. E؉XRT significantly decreased local failure risk compared to E alone for large lesions but not for those with close margins.

The findings support the concept that postlumpectomy radiotherapy can be tailored according to the degree of surgical resection. There is an easily identifiable subgroup of patients who can avoid a tumor bed boost, thus resulting in a reduced treatment time and improved cosmesis, while maintaining local control rates that approach 100%. The data suggest that in patients who undergo a negative re-excision, treatment with whole-breast radiotherapy to 50 Gy is a sufficient dose to maximally reduce the risk of local recurrence.

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