Assessment of Response to Neoadjuvant Systemic Treatment in Triple-Negative Breast Cancer Using Functional Tumor Volumes from Longitudinal Dynamic Contrast-Enhanced MRI.

Early assessment of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) is critical for patient care in order to avoid the unnecessary toxicity of an ineffective treatment. We assessed functional tumor volumes (FTVs) from dynamic contrast-enhanced (DCE) MRI after 2 cycles (C2) and 4 cycles (C4) of NAST as predictors of response in TNBC. A group of 100 patients with stage I-III TNBC who underwent DCE MRI at baseline, C2, and C4 were included in this study. Tumors were segmented on DCE images of 1 min and 2.5 min post-injection. FTVs were measured using the optimized percentage enhancement (PE) and signal enhancement ratio (SER) thresholds. The Mann-Whitney test was used to compare the performance of the FTVs at C2 and C4. Of the 100 patients, 49 (49%) had a pathologic complete response (pCR) and 51 (51%) had a non-pCR. The maximum area under the receiving operating characteristic curve (AUC) for predicting the treatment response was 0.84 (p < 0.001) for FTV at C4 followed by FTV at C2 (AUC = 0.82, p < 0.001). The FTV measured at baseline was not able to discriminate pCR from non-pCR. FTVs measured on DCE MRI at C2, as well as at C4, of NAST can potentially predict pCR and non-pCR in TNBC patients.

Functional tumor diameter measurement with molecular breast imaging: development and clinical application.

Purpose: Molecular breast imaging (MBI) is used clinically to visualize the uptake of99mTc-sestamibi in breast cancers. Here, we use Monte Carlo simulations to develop a methodology to estimate tumor diameter in focal lesions and explore a semi-automatic implementation for clinical data.Methods: A validated Monte Carlo simulation of the GE Discovery NM 750b was used to simulate >75,000 unique spherical/ellipsoidal tumor, normal breast, and image acquisition conditions. Subsets of this data were used to 1) characterize the dependence of the full-width at half-maximum (FWHM) of a tumor profile on tumor, normal breast, and acquisition conditions, 2) develop a methodology to estimate tumor diameters, and 3) quantify the diameter accuracy in a broad range of clinical conditions. Finally, the methodology was implemented in patient images and compared to diameter estimates from physician contours on MBI, mammography, and ultrasound imaging.Results: Tumor profile FWHM was determined be linearly dependent on tumor diameter but independent of other factors such as tumor shape, uptake, and distance from the detector. A linear regression was used to calculate tumor diameter from the FWHM estimated from a background-corrected profile across a tumor extracted from a median-filtered single-detector MBI image, i.e., diameter = 1.2 mm + 1.2 × FWHM, for FWHM ≥ 13 mm. Across a variety of simulated clinical conditions, the mean error of the methodology was 0.2 mm (accuracy), with >50% of cases estimated within 1-pixel width of the truth (precision). In patient images, the semi-automatic methodology provided the longest diameter in 94% (60/64) of cases. The estimated true diameters, for oval lesions with homogeneous uptake, differed by ± 5 mm from physician measurements.Conclusion: This work demonstrates the feasibility of accurately quantifying tumor diameter in clinical MBI, and to our knowledge, is the first to explore its implementation and application in patient data.

Assessment of Early Response to Neoadjuvant Systemic Therapy in Triple-Negative Breast Cancer Using Amide Proton Transfer-weighted Chemical Exchange Saturation Transfer MRI: A Pilot Study.

Purpose To determine if amide proton transfer-weighted chemical exchange saturation transfer (APTW CEST) MRI is useful in the early assessment of treatment response in persons with triple-negative breast cancer (TNBC). Materials and Methods In this prospective study, a total of 51 participants (mean age, 51 years [range, 26-79 years]) with TNBC were included who underwent APTW CEST MRI with 0.9- and 2.0-µT saturation power performed at baseline, after two cycles (C2), and after four cycles (C4) of neoadjuvant systemic therapy (NAST). Imaging was performed between January 31, 2019, and November 11, 2019, and was a part of a clinical trial (registry number NCT02744053). CEST MR images were analyzed using two methods-magnetic transfer ratio asymmetry (MTRasym) and Lorentzian line shape fitting. The APTW CEST signals at baseline, C2, and C4 were compared for 51 participants to evaluate the saturation power levels and analysis methods. The APTW CEST signals and their changes during NAST were then compared for the 26 participants with pathology reports for treatment response assessment. Results A significant APTW CEST signal decrease was observed during NAST when acquisition at 0.9-µT saturation power was paired with Lorentzian line shape fitting analysis and when the acquisition at 2.0 µT was paired with MTRasym analysis. Using 0.9-µT saturation power and Lorentzian line shape fitting, the APTW CEST signal at C2 was significantly different from baseline in participants with pathologic complete response (pCR) (3.19% vs 2.43%; P = .03) but not with non-pCR (2.76% vs 2.50%; P > .05). The APTW CEST signal change was not significant between pCR and non-pCR at all time points. Conclusion Quantitative APTW CEST MRI depended on optimizing acquisition saturation powers and analysis methods. APTW CEST MRI monitored treatment effects but did not differentiate participants with TNBC who had pCR from those with non-pCR. © RSNA, 2021 Clinical trial registration no. NCT02744053 Supplemental material is available for this article.Keywords Molecular Imaging-Cancer, Molecular Imaging-Clinical Translation, MR-Imaging, Breast, Technical Aspects, Tumor Response, Technology Assessment.

Monte Carlo simulation of pixelated CZT detector with Geant4: validation of clinical molecular breast imaging system.

Purpose. Molecular breast imaging (MBI) of99mTc-sestamibi with dual-headed, pixelated, cadmium-zinc-telluride (CZT) detectors is increasingly used in breast cancer care for screening/detecting lesions, monitoring response to therapy, and predicting risk of cancer. MBI as a truly quantitative tool in these applications, however, is limited due the lack of absolute99mTc-sestamibi uptake quantification. To help advance the field of quantitative MBI, we have developed a Monte Carlo simulation application of the GE Discovery NM 750b system.Methods. Our simulation consists of a two-step process using the Geant4 toolkit to model the detector and source geometry and to track photon interactions and a MATLAB script to model the charge transport within the pixelated CZT detector. Simulated detector and detector response model parameters were selected to match measured and simulated standard performance characteristics using various99mTc point-, line-, and film-sources in air. The final model parameters were verified by comparing the count profiles, energy spectra, and region of interest counts between simulated and measured images of a breast phantom with two spherical lesions in 5 cm thick medium of air or water.Results. Final performance characteristics with99mTc sources in air were: (1) energy resolution: 6.1% measured versus 5.9% simulated photopeak full-width at half-maximum (FWHM), (2) spatial resolution: mean error between measured and simulated FWHM of 0.08 mm across 4.4-14.0 mm FWHM range, and (3) sensitivity: 572 cpm/µCi measured versus 567 cpm/µCi simulated (<1% error). Good agreement was observed in the breast phantom line profiles through the spherical lesions and overall energy spectra, with <5% difference in sphere counts between simulated and measured data.Conclusion. A pixelated CZT charge transport and induction model was successfully implemented and validated to simulate imaging with the GE Discovery NM 750b system. This work will enable investigations improving MBI image quality and developing algorithms for uptake quantification.

Developing an intraoperative 3T MRI-guided brachytherapy program within a diagnostic imaging suite: Methods, process workflow, and value-based analysis.

PURPOSE: We integrated a brachytherapy procedural workflow within an existing diagnostic 3.0-T (3T) MRI suite. This setup facilitates intraoperative MRI guidance for optimal applicator positioning, particularly for interstitial needle placements in gynecologic cases with extensive parametrial involvement. METHODS AND MATERIALS: Here we summarize the multidisciplinary collaboration, equipment, and supplies necessary to implement an intraoperative MRI-guided brachytherapy program; outline the operational workflow via process maps; and address safety precautions. We evaluate internal resource utilization associated with this progressive approach via time-driven activity-based costing methodology, comparing institutional costs to that of a traditional workflow (within a CT suite, followed by separate postprocedure MRI) over a single brachytherapy procedural episode. RESULTS: Resource utilization was only 15% higher for the intraoperative MRI-based workflow, attributable to use of the MRI suite and increased radiologist effort. Personnel expenses were the greatest cost drivers for either workflow, accounting for 76-77% of total resource utilization. However, use of the MRI suite allows for potential cost-shifting opportunities from other resources, such as CT, during the procedural episode. Improvements in process speed can also decrease costs: for each 10% decrease in case duration from baseline procedure time, total costs could decrease by roughly 8%. CONCLUSIONS: This analysis supports the feasibility of an intraoperative MRI-guided brachytherapy program within a diagnostic MRI suite and defines many of the resources required for this procedural workflow. Longer followup will define the full utility of this approach in optimizing the therapeutic ratio for gynecologic cancers, which may translate into lower costs and higher value with time, over a full cycle of care.

Digital Breast Tomosynthesis for Intraoperative Margin Assessment during Breast-Conserving Surgery.

BACKGROUND: Intraoperative margin assessment for breast cancer patients undergoing segmental mastectomy (SM) enables identification of positive margins, with immediate excision of additional tissue to obtain negative margins. OBJECTIVE: The aim of this study was to determine the ability of digital breast tomosynthesis (DBT) to detect positive margins compared with an institution's standard extensive processing (SEP). METHODS: SM specimens underwent intraoperative SEP with two-dimensional (2D) imaging of the intact and sliced specimen, with review by a breast radiologist and gross assessment by a breast pathologist. Findings guided the surgeon to excise additional tissue. DBT images of intact specimens were prospectively obtained and retrospectively reviewed by a breast radiologist. A positive margin was defined as tumor at ink. RESULTS: Ninety-eight patients underwent 99 SMs. With SEP, 14 (14%) SM specimens had 19 positive margins. SEP did not detect 3 of the 19 positive margins, for a sensitivity of 84%, specificity of 78%, positive predictive value (PPV) of 11%, and negative predictive value (NPV) of 99%. Moreover, DBT did not detect 5 of the 19 positive margins, for a sensitivity of 74% (p > 0.05), specificity of 91% (p < 0.05), PPV of 21.5%, and NPV of 99%. With SEP guidance to excise additional tissue, six cases had final positive margins, with SEP not identifying three of these cases and DBT not identifying two. Pathology from the second surgery of these patients showed either no additional malignancy or only focal ductal carcinoma in situ. CONCLUSIONS: DBT is an accurate method for detecting positive margins in breast cancer patients undergoing SM, performing similar to institutional labor-intensive, intraoperative standard processing.

Biopsy Feasibility Trial for Breast Cancer Pathologic Complete Response Detection after Neoadjuvant Chemotherapy: Imaging Assessment and Correlation Endpoints.

PURPOSE: This study was designed to present the secondary imaging endpoints of the trial for evaluating mammogram (MMG), ultrasound (US) and image guided biopsy (IGBx) assessment of pathologic complete response (pCR) in breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC). METHODS: Patients with T1-3, N0-3, M0 triple-negative or HER2-positive BC who received NAC were enrolled in an Institutional Review Board-approved prospective, clinical trial. Patients underwent US and MMG at baseline and after NAC. Images were evaluated for residual abnormality and to determine modality for IGBx [US-guided (USG) or stereotactic guided (SG)]. Fine-needle aspiration and 9-G, vacuum-assisted core biopsy (VACBx) of tumor bed was performed after NAC and was compared with histopathology at surgery. RESULTS: Forty patients were enrolled. Median age was 50.5 (range 26-76) years; median baseline tumor size was 2.4 cm (range 0.8-6.3) and 1 cm (range 0-5.5) after NAC. Nineteen patients had pCR: 6 (32%) had residual Ca2+ presurgery, 5 (26%) residual mass, 1 (5%) mass with calcifications, and 7 (37%) no residual imaging abnormality. Sensitivity, specificity, and accuracy of US, MMG, and IGBx for pCR were 47/95/73%, 53/90/73%, and 100/95/98%, respectively. Twenty-five (63%) patients had SGBx and 15 (37%) had US-guided biopsy (USGBx). Median number of cores was higher with SGBx (12, range 6-14) than with USGBx (8, range 4-12), p < 0.002. Positive predictive value for pCR was significantly higher for SG VACBx than for USG VACBx (100 vs. 60%, p < 0.05). CONCLUSIONS: SG VACBx is the preferred IGBx modality for identifying patients with pCR for trials testing the safety of eliminating surgery.