Entire Breast Volume Research Articles

Pilot study: A simple CAD-based tool to detect breast cancer on MRI of the breast

PurposeThis pilot-study aims to assess, whether quantitatively assessed enhancing breast tissue as a percentage of the entire breast volume can serve as an indicator of breast cancer at breast MRI and whether the contrast-agent employed affects diagnostic efficacy. MaterialsThis retrospective IRB-approved study, included 39 consecutive patients, that underwent two subsequent breast MRI exams for suspicious findings at conventional imaging with 0.1 mmol/kg gadobenic and gadoteric acid. Two independent readers, blinded to the histopathological outcome, assessed unenhanced and early post-contrast images using computer-assisted software (Brevis, Siemens Healthcare). Diagnostic performance was statistically determined for percentage of ipsilateral voxel volume enhancement and for percentage of contralateral enhancing voxel volume subtracted from ipsilateral enhancing voxel volume after crosstabulation with the dichotomized histological outcome (benign/malignant). ResultsIpsilateral enhancing voxel volume versus histopathological outcome resulted in an AUC of 0.707 and 0.687 for gadobenic acid, reader 1 and 2, respectively and in an AUC of 0.778 and 0.773 for gadoteric acid, reader 1 and 2, respectively. Accounting for background parenchymal enhancement by subtracting contralateral enhancing volume from ipsilateral enhancing voxel volume versus histolopathological outcome resulted in an AUC of 0.793 and 0.843 for gadobenic acid, reader 1 and 2, respectively and in an AUC of 0.692 and 0.662 for gadoteric acid, reader 1 and 2, respectively. Pairwise testing yielded no statistically significant difference both between readers and between contrast agents employed (p > 0.05). ConclusionOur proposed CAD algorithm, which quantitatively assesses enhancing breast tissue as a percentage of the entire breast volume, allows indicating the presence of breast cancer.

Experimental characterisation and modelling of breast Cooper's ligaments.

The aim of this study was to characterise the mechanical behaviour of Cooper’s ligaments. Such ligaments are collagenous breast tissue that create a three-dimensional structure over the entire breast volume. Ten ligaments were extracted from a human cadaver, from which 28 samples were cut and used to perform uniaxial tensile tests. Histological analysis showed that the main direction of the fibres visible to the naked eye corresponds to the orientation of the fibres on a microscopic scale. The specimens were cut according to this orientation, which allowed the sample to be stretched in the main fibre direction. From these experimental stretch/stress curves, an original anisotropic hyperelastic constitutive law is proposed to model the behaviour of Cooper’s ligaments and the material parameter validity is discussed.

Abstract PD9-05: Lack of background parenchymal enhancement suppression in breast MRI during neoadjuvant chemotherapy may be associated with inferior treatment response in hormone receptor positive breast cancer

Abstract Purpose In breast MRI, contrast enhancement of normal fibroglandular tissue is referred to as background parenchymal enhancement (BPE). Hormonal status significantly affects the degree of BPE, potentially due to the association with mammary vascularity and activity1-5. Studies have shown that BPE may be associated with breast cancer survival6, treatment response to neoadjuvant chemotherapy (NAC)7,8 and future breast cancer risk9. In most patients undergoing NAC, BPE is suppressed by the nonspecific anti-proliferative effects of chemotherapy on normal breast and/or ovary5,10. However, some patients exhibit equivalent or even stronger BPE post-NAC compared to pre-NAC. We hypothesized that non-suppressed BPE in post-NAC MRI may be associated with inferior treatment response. This study aimed to investigate the association between BPE suppression and treatment response as defined by pathologic complete response (pCR). Methods This study included patients with stage II/III breast cancer enrolled in the I-SPY 2 TRIAL being treated with standard NAC with or without investigational agents. The whole cohort was split into two subgroups based on hormone receptor status (HR+, n= 536; HR-, n=452). Patients underwent dynamic contrast enhanced MRIs at four time points during NAC: baseline (T0), after 3 weeks of the first regimen (T1), inter-regimen (T2), and pre-surgery (T3). Using in-house software, the contralateral breast parenchyma was automatically segmented for the entire breast volume. Quantitative BPE (qBPE) was calculated as the mean early (~150s post-contrast injection) percent enhancement of the central 50% of the axial slices. A breast radiologist reviewed all exams and excluded those where automated segmentation failed to accurately define tissue. For T1, T2 and T3, BPE was categorized based on the change from T0 as suppressed (qBPE < qBPE[T0]) or non-suppressed (qBPE ≥ qBPE[T0]). Chi-squared test was used to examine the association between BPE suppression and pCR, with p<0.05 considered statistically significant. Results HR+ cohort: pCR rates were lower for patients with non-suppressed BPE than those with suppressed BPE at every visit (T1-T3) (Table 1). The difference was statistically significant at T2 (p=0.04) and T3 (p=0.01). Table 1: HR+ cohortpCR rate (%)No. of pCR patientsNo. of non-pCR patientsTotal number of patientsP valueOverall22.8122414536BPE at T1suppressed23.6822663480.45non-suppressed20.532124156BPE at T2suppressed25.7972803770.04*non-suppressed16.01789106BPE at T3suppressed25.7982833810.01*non-suppressed12.5128496 HR- cohort: pCR rates were slightly lower for the non-suppressed BPE group, but no statistically significant association was found (Table 2). Table 2: HR- cohortpCR rate (%)No. of pCR patientsNo. of non-pCR patientsTotal number of patientsP valueOverall44.7202250452BPE at T1suppressed46.81411603010.66non-suppressed44.45265117BPE at T2suppressed48.81441512950.79non-suppressed47.3434891BPE at T3suppressed49.31461502960.94non-suppressed48.9434588 Conclusion In HR+ breast cancer, lack of BPE suppression may indicate inferior treatment response. The contrasting results in HR+ and HR- cohorts are noteworthy in terms of the possible relationship between suppression of normal mammary and ovarian activity and treatment response in HR+ cancer. Reference Radiographics 2014; 34: 234-47. Radiology 1997; 203: 137-44. Radiology 1997; 203: 145-9. Breast J 2005; 11: 236-41. AJR Am J Roentgenol 2015; 204: 669-73. Eur Radiol 2018; 28: 4705-16. Eur Radiol 2016; 26: 1590-6. Transl Oncol 2015; 8: 204-9. J Clin Oncol 2019; : JCO1800378. Radiology 2015; 277: 687-96. Citation Format: Natsuko Onishi, Wen Li, David C. Newitt, Roy Harnish, Jessica Gibbs, Ella F. Jones, Alex Nguyen, Lisa Wilmes, Bonnie N. Joe, Michael J. Campbell, Amrita Basu, Laura J. van’t Veer, Angela DiMichele, Douglas Yee, Donald A. Berry, Kathy S. Albain, Judy C. Boughey, A. Jo Chien, Amy S. Clark, Kirsten K. Edmiston, Anthony D. Elias, Erin D. Ellis, David M. Euhus, Heather S. Han, Claudine Isaacs, Qamar J. Khan, Julie E. Lang, Janice Lu, Jane L. Meisel, Zaha Mitri, Rita Nanda, Donald W. Northfelt, Tara Sanft, Erica Stringer-Reasor, Rebecca K. Viscusi, Anne M. Wallace, Rachel Yung, Michelle E. Melisko, Jane Perlmutter, Hope S. Rugo, Richard Schwab, W. Fraser Symmans, Smita M. Asare, Julie E. Yau, Christina Yau, Laura J. Esserman, Nola M. Hylton. Lack of background parenchymal enhancement suppression in breast MRI during neoadjuvant chemotherapy may be associated with inferior treatment response in hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD9-05.

Abstract P1-15-07: Simultaneous integrated boost incorporated into a hypofractionated regimen using tomoDirect: Acute toxicity assessment

Abstract Aim: We report on acute toxicity, which is the secondary endpoint of a phase II clinical trial specifically addressed to assess the chronic toxicity of a hypofractionated scheme including a simultaneous integrated boost, with intensity modulated radiotherapy. Materials and methods: From 2/2012 to 12/2013 194 patients with early breast cancer entered a phase II study on hypofractionated radiotherapy including a boost dose to the tumor bed. All patients were operated on conservatively. The whole breast and the tumor bed are planned to receive a dose of 45 Gy and 50 Gy, respectively, in 20 fractions, over 4 weeks. Treatment plans are generated using the TomoDirect modality,which is available on Tomotherapy Hi-Art System (Madison,WI). Acute toxicity was evaluated according to the RTOG acute toxicity scale, up to 6 months after the treatment. Afterwards, chronic toxicity is evaluated using LENT/SOMA scale. Results: 95% of the volume of the breast and boost PTVs received 99% and 100% of the planned dose, as median values, respectively and 0.1% (median value) of the entire breast volume received 100% of the boost dose. The median maximum dose to the breast and to the boost PTVs was 113% and 103.3 %, respectively. At the end of treatment, the acute toxicity, was distributed as follows. As far as erythema was concerned, at the end of treatment, 58% of the patients experienced grade 1 erythema, which dropped to 23% one month later. Grade 2 erythema affected 37% of the cases, and after one month, it decreased to 2%.Only 1 patient (0.5%) complained of Grade 3 erythema at the end of the treatment, which rapidly disappeared afterwards. With regard to breast oedema, at the end of treatment grade 1 was observed in 16% of the cases, for whom it tended to remain stable after one month, while grade 2 oedema was noted in 4% of the cases, decreasing to 1.5% on the first month- follow-up visit. Regarding desquamation, dry desquamation ( grade 1) was observed in less than 10% of cases at the end of treatment, but it tended to increase to 17% one month later. Patchy moist desquamation (grade 2) was present in 1.9% of the patients at the end of radiotherapy, and in 1% of them, one month afterwards. Confluent desquamation (grade 3) was noted only in 1 patient (0.5%), who was receiving concomitant chemotherapy with cyclophospamide, methotrexate and fluoruracil: it was still present 1 month after the radiotherapy completion, as the patient continued to be on chemotherapy. No significantly different side effects were observed between the whole breast and the boost area. No patients experienced any lung and cardiac symptoms. Conclusion: The clinical results of this SIB hypofractionated scheme showed low acute toxicity. In spite of the high dose per fraction, with the tumor bed receiving an even higher dose /per fraction, acute toxicity was within the limit acknowledged by literature for conventional fractionation. This non-rotational treatment option allows us to deliver treatment with a traditional tangent-like dose, without spreading low doses to the adjacent structures. Chronic toxicity will be assessed after 2 years. Therefore, a longer follow-up is needed to assess the effective tolerance to the SIB schedule. Citation Format: Maria Cristina Leonardi, Anna Morra, Federica Cattani, Luigi Santoro, Samantha Dicuonzo, Raffaella Cambria, Rosa Luraschi, Alessia Bazani, Roberta Lazzari, Veronica Dell'Acqua, Roberto Orecchia. Simultaneous integrated boost incorporated into a hypofractionated regimen using tomoDirect: Acute toxicity assessment [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-07.

Development of a patient-specific two-compartment anthropomorphic breast phantom

The purpose of this paper is to develop a technique for the construction of a two-compartment anthropomorphic breast phantom specific to an individual patient's pendant breast anatomy. Three-dimensional breast images were acquired on a prototype dedicated breast computed tomography (bCT) scanner as part of an ongoing IRB-approved clinical trial of bCT. The images from the breast of a patient were segmented into adipose and glandular tissue regions and divided into 1.59 mm thick breast sections to correspond to the thickness of polyethylene stock. A computer-controlled water-jet cutting machine was used to cut the outer breast edge and the internal regions corresponding to glandular tissue from the polyethylene. The stack of polyethylene breast segments was encased in a thermoplastic ‘skin’ and filled with water. Water-filled spaces modeled glandular tissue structures and the surrounding polyethylene modeled the adipose tissue compartment. Utility of the phantom was demonstrated by inserting 200 µm microcalcifications as well as by measuring point dose deposition during bCT scanning. Affine registration of the original patient images with bCT images of the phantom showed similar tissue distribution. Linear profiles through the registered images demonstrated a mean coefficient of determination (r2) between grayscale profiles of 0.881. The exponent of the power law describing the anatomical noise power spectrum was identical in the coronal images of the patient's breast and the phantom. Microcalcifications were visualized in the phantom at bCT scanning. The real-time air kerma rate was measured during bCT scanning and fluctuated with breast anatomy. On average, point dose deposition was 7.1% greater than the mean glandular dose. A technique to generate a two-compartment anthropomorphic breast phantom from bCT images has been demonstrated. The phantom is the first, to our knowledge, to accurately model the uncompressed pendant breast and the glandular tissue distribution for a specific patient. The modular design of the phantom allows for studies of a single breast segment and the entire breast volume. Insertion of other devices, materials and tissues of interest into the phantom provide a robust platform for future breast imaging and dosimetry studies.

TH-E-L100J-07: Comparison of Mammographic Percent Density and Volumetric Percent Density Determined From Ultrasound Tomography Images

Purpose: Previous ultrasound tomography work conducted by our group showed a direct correlation between measured sound speed and physical density in vitro, and increased in vivo sound speed with increasing mammographic density, a known risk factor for breast cancer. Building on these empirical results, we investigated the use of volumetric ultrasound percent density (USPD) for breast density estimation. Method and Materials: A breast phantom comprised of fat inclusions embedded in fibroglandular tissue was scanned four times with both ultrasound tomography and CT. The coronal transmission tomograms and corresponding CT images were analyzed using a semi-automatic segmentation routine. Next, a cohort of ∼100 patients was imaged encompassing the entire breast volume (50–75 tomograms/patient). USPD was determined by segmenting high sound speed areas from each slice using a k-means clustering routine, integrating these results over the entire breast, and dividing by total breast area. USPD was evaluated using two mammographic density measures: (1) qualitative, as determined by a radiologist's visual assessment using BI-RADS Criteria and (2) quantitative, via digitization and semi-automatic segmentation of craniocaudal and medio-lateral oblique mammograms. Results: The integrated areas of the phantom's fat inclusions were compared using both transmission ultrasound and CT for four repeated scans. The average variability for inclusion segmentation was ∼2% and ∼10%, respectively, and a close correlation was observed in the integrated areas between the two modalities. A strong positive association between BI-RADS category and USPD was demonstrated. Furthermore, comparing USPD to calculated mammographic density yielded moderate to strong positive associations (Pearson r = 0.76–0.84) for MLO and CC views, respectively. Conclusion: These results support the hypothesis that utilizing USPD as an analogue to mammographic breast density is feasible. USPD has the potential to provide a non-ionizing, whole-breast analysis of breast density, which may better elucidate the relationship between breast density and breast cancer risk.

TU‐E‐T‐6C‐01: Intensity Modulated Radiation Therapy for the Treatment of Breast Cancer

Intensity modulated radiation therapy for the treatment of Stage 0, I and II breast cancer has been in clinical use at William Beaumont Hospital since March 1999. The goals of IMRT for breast cancer delivered through static, multileaf collimator segments include optimizing dose homogeneity, avoiding unnecessary normal tissue irradiation and standardizing target volume coverage without significantly increasing the time required to plan and treat patients. The IMRT process can be divided into four different phases, simulation, treatment planning, treatment delivery and quality assurance. During the initial simulation procedure an immobilization device is constructed, level marks are tattooed and the treatment borders are defined. A CT is done in the treatment position in order to define the treatment area as well as delineate normal tissues. In addition to the CT scan the use of MR is becoming a useful tool to define nodal regions of interest. The treatment plan is generated to deliver a homogeneous dose throughout the breast volume and minimize dose to the lungs and in the case of left sided breast patients the heart. The beam arrangement of two tangential fields is adjusted for depth, gantry angle and collimator angle in order to provide full coverage to the breast and lumpectomy cavity with sufficient margin and avoid unnecessary irradiation of normal tissue. The IMRT segments are created based on 5% increments of isodose surfaces; these forward planned segments are then optimized in order to deliver a homogeneous dose throughout the breast volume. The plan is evaluated with respect to percent of breast volume receiving doses in excess of 105% and 110% of the prescribed dose. The treatment process includes patient positioning and setup, electronic portal imaging and treatment delivery. This is accomplished in a conventional treatment time slot of 12 minutes. As part of the overall patient quality assurance patients are imaged everyday for every port during their treatment. On weekly review the physicians have ten images, five medial and five lateral, with which to make clinical treatment decisions as to patient setup and treatment port placement. In addition to patient quality assurance plan quality assurance is assessed by completion of an independent calculation check as well as analysis of treatment delivered to the MapCheck device as compared to the planned treatment. Both the fluence and absolute dose measurements can be analyzed with this system. Using intensity modulated radiation therapy to deliver whole breast irradiation has proven to be an efficient method to deliver uniform dose throughout the entire breast volume which can be seen to reduce the acute and chronic toxicity's associated with radiation therapy for the treatment of breast cancer. Research supported by Philips Medical Systems and Elekta Corporation.Educational Objectives:1. To understand the goals and use of IMRT in the treatment of breast cancer.2. To understand the IMRT process for simulation, planning, treatment and quality assurance in the treatment of breast cancer.

Incorporating simultaneous in-field boost (SIB) with inverse-planned IMRT using dynamic multi-leaf collimation (DMLC) to the intact breast after lumpectomy

Patients with early stage breast cancer after lumpectomy have received inverse planned IMRT with dMLC and SIB in our Clinic since May of 2003. This abstract describes our technique, dosimetric parameters, and acute toxicity for the first 42 patients so treated. Patients are planned with CT simulation, and volumes contoured by the treating physician. Our current technique involves (1) setting opposed tangent beams in the usual fashion, minimizing lung dose and dose to the contralateral breast; (2) delivering the simultaneous cavity boost with two additional orthogonal beams; and (3) completing a three fraction (fx) tumor bed boost with two orthogonal cranio-caudal beams. A dose prescription of 45 Gy in 25 fx is prescribed to the entire breast volume, with a simultaneous boost of 0.34 Gy/fx delivered to the tumor cavity, such that it accumulates at 2.14 Gy/fx to a total dose of 53.5 Gy. Normal tissue constraints preclude a larger daily boost dose, therefore the tumor cavity is subsequently boosted with an additional three fractions of 2.14 Gy. This provides a resection bed prescription dose of 59.92 Gy in 28 fx and a whole breast dose of 45 Gy in 25 fx. All 42 patients were treated between May, 2003, and March, 2004. The average volume of breast tissue was 778 cc, with the average cavity boost volume 28 cc. The median D90 (dose received by 90% of the breast volume) was 46 Gy (mean 45.9 Gy, range 40–51 Gy). The median D90 of the resection cavity was 61 Gy (mean 61 Gy, range 58–64 Gy). The median V20 (volume of ipsilateral lung receiving at least 20 Gy) was 12% (mean 11.4 %, range 2–21 %). Of the 42 patients, toxicity data are available on 27 who have completed therapy, with RTOG toxicity scores of 0 (1 patient), 1 (15 patients), and 2 (11 patients). Another 5 patients are at greater than 50 Gy, with toxicity scores of 0 (1 patient), 1 (3 patients), and 2 (1 patient). No patient has experienced RTOG Grade 3 or 4 toxicity. Simultaneous in-field boost IMRT to the breast allows the radiobiologic advantage of higher dose per fraction to the tumor cavity--the site of highest risk of recurrence--while using conventional fractionation for the remaining breast tissue. This technique is extremely well tolerated

A simplified intensity modulated radiation therapy technique for the breast.

A simplified intensity modulated radiation therapy (sIMRT) technique for the breast is presented. The technique aims to produce a uniform dose distribution in the entire breast volume. Using the standard tangential beam arrangement, we first determine for each pencil beam the midpoint of the segment that intersects the treatment volume. The dose to the midpoint from the open field is then calculated. The intensity of the pencil beam is determined as proportional to the inverse of the open field dose. With this intensity modulated beam, the dose delivered to the midpoint of each pencil beam segment that intersects the treatment volume is now equalized. The dose distribution in the entire treatment volume is nearly as uniform as can be achieved under the given beam arrangement. Fifteen left breast patients were planned with the sIMRT technique. For comparison, the same group of patients was also planned with the standard wedged pair technique and the full-fledged volume-based IMRT (vIMRT) technique. Both the sIMRT and the vIMRT techniques achieved more homogeneous dose in the treatment volume than the standard plan. Doses to the heart, the ipsilateral lung, and the contralateral breast were also reduced. The planning time and the treatment time for the sIMRT technique were comparable to that of the standard technique, and significantly less than that required by the vIMRT technique. The sIMRT technique is practical for large-scale implementation in a busy clinic without requiring significant increase of resources.

Combined therapy in carcinomas of the female breast.

Of 606 female breast cancers treated, 364 of them in stage I, II and III, only 7 cases were in stage I. All stage II and III cases in good general condition received radical preoperative irradiation to the entire breast volume and the regional lymphatic areas over a period of 4 wk, followed 4 wk later by a radical mastectomy. No postoperative irradiation was administered. The biological basis of this therapeutic policy is explained in detail and the 5-yr disease-free survival of patients in relation to stage of disease, treatment method, histology of the primary tumor, histologic nodal metastatic status, postradiational status of the breast primary, the menstrual status of the patient, and the general metabolic status is discussed. It is explicitly shown by meticulous histological study of the breasts and the axillary lymph nodes removed at surgery that radical irradiation per se is inadequate to sterilize the breasts and that subsequent radical surgery is essential. Furthermore, two-thirds of the stage III cancers, which would have been considered inoperable by conventional criteria, were rendered operable by preoperative irradiation, with a near 50% 5-yr disease-free survival.