Precise correlation between MRI and histopathology – Exploring treatment margins for MRI-guided localized breast cancer therapy

Schmitz, Annemarie C.; Bosch, Maurice A.A.J. van den; Loo, Claudette E.; Mali, Willem P.Th.M.; Bartelink, Harry; Gertenbach, M.; Holland, Roland; Peterse, Johannes L.; Rutgers, Emiel J.; Gilhuijs, Kenneth G. A.

doi:10.1016/j.radonc.2010.07.025

Cited by 48 publications

(37 citation statements)

References 59 publications

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“…Overestimation remains common (33%) but the most worrisome finding for a preoperative technique, underestimation of tumors, was noted in only 15% 12 . In another study, 93% of patients had no invasive disease more than 10mm's beyond that identified on MRI 25 . We used a generous margin in this series, but at present, the optimal margin has not been established.…”

Section: Discussionmentioning

confidence: 89%

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

Horton

Blitzblau

Yoo

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

119

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Summary This phase I dose-escalation trial evaluates the feasibility of single-dose preoperative partial breast irradiation delivered with external beam techniques in early stage breast cancer patients. No acute dose-limiting toxicity was observed at 15, 18, or 21Gy. Paired pre- and post-radiation imaging and tumor biopsies offer unique insight into the biology of breast cancer radiation response. Purpose Women with biologically favorable early stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large post-operative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase I trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods Women 55 or older with clinically node negative, ER+ and/or PR+, HER2-, T1 invasive carcinomas or low-intermediate grade in situ disease ≤2cm were enrolled (n=32). Intensity-modulated radiotherapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21Gy (n=16) to the tumor with a 1.5cm margin. Lumpectomy was performed within 10 days. Paired pre- and post-radiation MRI images and patient tumor samples were analyzed. Results No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent and chronic toxicities were grade 1-2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions Preoperative single-dose radiotherapy to intact breast tumors is well-tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first-step towards a novel PBI approach. Preoperative radiation should be tested in future clinical trials as it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.

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Section: Discussionmentioning

confidence: 89%

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

Horton

Blitzblau

Yoo

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

119

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“…More than 1800 microscopic slides of invasive breast cancers in 60 patients (48 patients with age > 50 and 12 with age 6 50) were examined by two experienced breast cancer pathologists [12,13]. MSD was observed on the microscopic slides.…”

Section: Pathology Datasetmentioning

confidence: 99%

The effect of age in breast conserving therapy: A retrospective analysis on pathology and clinical outcome data

Chen

Sonke

Stroom

et al. 2015

Radiotherapy and Oncology

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“…This enables differentiation between the tumor and benign lesions like post-biopsy hematomas or cysts. Furthermore, MRI has a high sensitivity for detection of invasive breast cancer and a good correlation with histopathology findings [24,25]. However, standard diagnostic MRI is performed in prone position, while patients in most departments are irradiated in supine position.…”

Section: Introductionmentioning

confidence: 99%

MRI and CT imaging for preoperative target volume delineation in breast-conserving therapy

et al. 2014

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BackgroundAccurate tumor bed delineation after breast-conserving surgery is important. However, consistency among observers on standard postoperative radiotherapy planning CT is low and volumes can be large due to seroma formation. A preoperative delineation of the tumor might be more consistent. Therefore, the purpose of this study was to determine the consistency of preoperative target volume delineation on CT and MRI for breast-conserving radiotherapy.MethodsTumors were delineated on preoperative contrast-enhanced (CE) CT and newly developed 3D CE-MR images, by four breast radiation oncologists. Clinical target volumes (CTVs) were created by addition of a 1.5 cm margin around the tumor, excluding skin and chest wall. Consistency in target volume delineation was expressed by the interobserver variability. Therefore, the conformity index (CI), center of mass distance (dCOM) and volumes were calculated. Tumor characteristics on CT and MRI were scored by an experienced breast radiologist.ResultsPreoperative tumor delineation resulted in a high interobserver agreement with a high median CI for the CTV, for both CT (0.80) and MRI (0.84). The tumor was missed on CT in 2/14 patients (14%). Leaving these 2 patients out of the analysis, CI was higher on MRI compared to CT for the GTV (p < 0.001) while not for the CTV (CT (0.82) versus MRI (0.84), p = 0.123). The dCOM did not differ between CT and MRI. The median CTV was 48 cm3 (range 28–137 cm3) on CT and 59 cm3 (range 30–153 cm3) on MRI (p < 0.001). Tumor shapes and margins were rated as more irregular and spiculated on CE-MRI.ConclusionsThis study showed that preoperative target volume delineation resulted in small target volumes with a high consistency among observers. MRI appeared to be necessary for tumor detection and the visualization of irregularities and spiculations. Regarding the tumor delineation itself, no clinically relevant differences in interobserver variability were observed. These results will be used to study the potential for future MRI-guided and neoadjuvant radiotherapy.Trial registrationInternational Clinical Trials Registry Platform NTR3198.

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Precise correlation between MRI and histopathology – Exploring treatment margins for MRI-guided localized breast cancer therapy

Cited by 48 publications

References 59 publications

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

The effect of age in breast conserving therapy: A retrospective analysis on pathology and clinical outcome data

MRI and CT imaging for preoperative target volume delineation in breast-conserving therapy

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