Impact of negative margin width on local recurrence in breast conserving therapy.

BACKGROUND AND PURPOSE: This study aims to explain the unexpected weak association between the width of the negative surgical margin and the risk of local recurrence in breast conserving therapy. MATERIALS AND METHODS: We utilized a classical tumor-control probability (TCP) model to estimate the risk of local recurrence, considering the heterogeneity of microscopic disease spread observed around the invasive index tumor in a pathology dataset (N=60). The estimated result was compared with the true risk observed in the EORTC boost-versus-no-boost trial (N=1616). RESULTS: The disease volume beyond any given distance from the edge of the index tumor varied considerably among patients. Adopting this disease volume variation in the TCP model accurately reproduced the local recurrence rate as function of surgical margin width in the boost-versus-no-boost trial (Pearson's correlation coefficients are 0.652 and 0.862, and significant at the 0.05 and 0.01 level for absence and presence of a radiation boost, respectively). CONCLUSIONS: The impact of a negative margin width on local recurrence is limited due to the large variation of microscopic disease that can reach large quantities beyond any given distance from the edge of the index tumor across the patient population of breast-conserving therapy.

Pre-treatment imaging and pathology characteristics of invasive breast cancers of limited extent: potential relevance for MRI-guided localized therapy.

BACKGROUND AND PURPOSE: Identifying breast cancers of limited extent (BCLE) is becoming increasingly important, especially for (image guided) minimally invasive therapy and partial breast irradiation. The purpose of this study is to establish characteristics at functional imaging and pathology associated with invasive BCLE. MATERIALS AND METHODS: Seventy-five patients (77 breasts) with invasive breast cancer were prospectively included. Excision specimens were processed using complete embedding. Microscopic findings were reconstructed and correlated with contrast-enhanced MRI. Tumors were stratified by absence or presence of occult disease ≥10 mm from the MRI-visible lesion: BCLE and non-BCLE, respectively. Imaging and pathology characteristics were evaluated for their ability to discriminate between BCLE and non-BCLE. Multivariate binary logistic regression was employed to create a prediction model for BCLE. RESULTS: At univariate analysis, imaging as well as pathology characteristics were indicative for BCLE (39/77=51%). At multivariate analysis, a mass on mammography, the absence of tumor washout, positive ER and low quantity of DCIS in the index tumor retained significance (area under ROC curve=0.87). CONCLUSIONS: Pre-treatment assessment of mammography findings, MRI washout kinetics, ER status and quantity of DCIS in the index tumor has the potential to accurately identify BCLE.

Precise correlation between MRI and histopathology - exploring treatment margins for MRI-guided localized breast cancer therapy.

BACKGROUND: Magnetic resonance imaging (MRI) is more often considered to guide, evaluate or select patients for partial breast irradiation (PBI) or minimally invasive therapy. Safe treatment margins around the MRI-visible lesion (MRI-GTV) are needed to account for surrounding subclinical occult disease. PURPOSE: To precisely compare MRI findings with histopathology, and to obtain detailed knowledge about type, rate, quantity and distance of occult disease around the MRI-GTV. METHODS AND MATERIALS: Patients undergoing MRI and breast-conserving therapy were prospectively included. The wide local excision specimens were subjected to detailed microscopic examination. The size of the invasive (index) tumor was compared with the MRI-GTV. The gross tumor volume (GTV) was defined as the pre-treatment visible lesion. Subclinical tumor foci were reconstructed at various distances to the MRI-GTV. RESULTS: Sixty-two patients (64 breasts) were included. The mean size difference between MRI-GTV and the index tumor was 1.3mm. Subclinical disease occurred in 52% and 25% of the specimens at distances ≥10mm and ≥20mm, respectively, from the MRI-GTV. CONCLUSIONS: For MRI-guided minimally invasive therapy, typical treatment margins of 10mm around the MRI-GTV may include occult disease in 52% of patients. When surgery achieves a 10mm tumor-free margin around the MRI-GTV, radiotherapy to the tumor bed may require clinical target volume margins >10mm in up to one-fourth of the patients.

3.0-T MR-guided focused ultrasound for preoperative localization of nonpalpable breast lesions: an initial experimental ex vivo study.

PURPOSE: To compare the accuracy of magnetic resonance-guided focused ultrasound (MRgFUS) with MR-guided needle-wire placement (MRgNW) for the preoperative localization of nonpalpable breast lesions. MATERIALS AND METHODS: In this experimental ex vivo study, 15 turkey breasts were used. In each breast phantom an artificial nonpalpable "tumor" was created by injecting an aqueous gel containing gadolinium. MRgFUS (n = 7) was performed with the ExAblate 2000 system (InSightec). With MRgFUS the ablated tissue changes in color and increases in stiffness. A rim of palpable and visible ablations was created around the tumor to localize the tumor and facilitate excision. MRgNW (n = 8) was performed by MR-guided placement of an MR-compatible needle-wire centrally in the tumor. After surgical excision of the tumor, MR images were used to evaluate tumor-free margins (negative/positive), minimum tumor-free margin (mm), and excised tissue volume (cm(3)). RESULTS: With MRgFUS localization no positive margins were found after excision (0%). With MRgNW two excision specimens (25%) had positive margins (P = 0.48). Mean minimum tumor-free margin (+/-SD) with MRgFUS was significantly larger (5.5 +/- 2.4 mm) than with MRgNW (0.9 +/- 1.4 mm) (P < 0.001). Mean volume +/- SD of excised tissue did not differ between MRgFUS and MRgNW localization, ie, 44.0 +/- 9.4 cm(3) and 39.5 +/- 10.7 cm(3) (P = 0.3). CONCLUSION: The results of this experimental ex vivo study indicate that MRgFUS can potentially be used to localize nonpalpable breast lesions in vivo.