18F-FDG Dedicated Breast PET Complementary to Breast MRI for Evaluating Early Response to Neoadjuvant Chemotherapy.

Purpose To compare quantitative measures of tumor metabolism and perfusion using fluorine 18 (18F) fluorodeoxyglucose (FDG) dedicated breast PET (dbPET) and breast dynamic contrast-enhanced (DCE) MRI during early treatment with neoadjuvant chemotherapy (NAC). Materials and Methods Prospectively collected DCE MRI and 18F-FDG dbPET examinations were analyzed at baseline (T0) and after 3 weeks (T1) of NAC in 20 participants with 22 invasive breast cancers. FDG dbPET-derived standardized uptake value (SUV), metabolic tumor volume, and total lesion glycolysis (TLG) and MRI-derived percent enhancement (PE), signal enhancement ratio (SER), and functional tumor volume (FTV) were calculated at both time points. Differences between FDG dbPET and MRI parameters were evaluated after stratifying by receptor status, Ki-67 index, and residual cancer burden. Parameters were compared using Wilcoxon signed rank and Mann-Whitney U tests. Results High Ki-67 tumors had higher baseline SUVmean (difference, 5.1; P = .01) and SUVpeak (difference, 5.5; P = .04). At T1, decreases were observed in FDG dbPET measures (pseudo-median difference T0 minus T1 value [95% CI]) of SUVmax (-6.2 [-10.2, -2.6]; P < .001), SUVmean (-2.6 [-4.9, -1.3]; P < .001), SUVpeak (-4.2 [-6.9, -2.3]; P < .001), and TLG (-29.1 mL3 [-71.4, -6.8]; P = .005) and MRI measures of SERpeak (-1.0 [-1.3, -0.2]; P = .02) and FTV (-11.6 mL3 [-22.2, -1.7]; P = .009). Relative to nonresponsive tumors, responsive tumors showed a difference (95% CI) in percent change in SUVmax of -34.3% (-55.9%, 1.5%; P = .06) and in PEpeak of -42.4% (95% CI: -110.5%, 8.5%; P = .08). Conclusion 18F-FDG dbPET was sensitive to early changes during NAC and provided complementary information to DCE MRI that may be useful for treatment response evaluation. Keywords: Breast, PET, Dynamic Contrast-enhanced MRI Clinical trial registration no. NCT01042379 Supplemental material is available for this article. © RSNA, 2024.

The role of digital mammographic surveillance for detection of asymptomatic recurrence in autologous flap reconstructions.

OBJECTIVE: To evaluate the utility of digital mammography in detecting asymptomatic malignancy in autologous flap reconstructions after mastectomy. METHODS: A retrospective database review identified all mammograms performed on asymptomatic patients with flap reconstructions over a 9-year period (1/1/2009 to 12/31/2017). A negative examination was defined as BI-RADS 1 or 2 and a positive examination was defined as BI-RADS 0, 4, or 5 assigned to the mastectomy side. Malignant outcomes were determined by pathology results. Interval cancers, or false negatives, were defined as locoregional malignant diagnosis within one year of a negative mammogram. Sensitivity, specificity, predictive values, abnormal interpretation rate, and cancer detection rate were calculated. RESULTS: 626 mammograms of asymptomatic flap reconstructions were performed in 183 patients. The most common flap type was TRAM (83.5 %, 523/626) and DIEP (13.4 %, 84/626). Most exams (98.2 %, 615/626) were negative, assessed as BI-RADS 1 or 2, with no interval cancers at follow-up. Eleven exams (1.8 %, 11/626) were positive, assessed as BI-RADS 0, 4, or 5. After diagnostic work-up of all BI-RADS 0 exams, 9 cases had a final recommendation for biopsy of which 3 were malignant. Mammography yielded a cancer detection rate of 0.5 % (3/626), abnormal interpretation rate of 1.8 % (11/626), NPV of 100 % (615/615), overall PPV of 27.3 % (3/11), PPV2 (positive predictive value of a biopsy recommendation) of 33.3 % (3/9), sensitivity of 100 % (3/3), and specificity of 98.7 % (615/623). CONCLUSION: Digital mammography of asymptomatic autologous flap reconstructions after mastectomy demonstrated high sensitivity and low abnormal interpretation rate. Cancer detection rate was comparable to current national benchmarks for mammographic screening in the general U.S. population without mastectomy.

Effect of Longitudinal Variation in Tumor Volume Estimation for MRI-guided Personalization of Breast Cancer Neoadjuvant Treatment.

Purpose To investigate the impact of longitudinal variation in functional tumor volume (FTV) underestimation and overestimation in predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). Materials and Methods Women with breast cancer who were enrolled in the prospective I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2) from May 2010 to November 2016 were eligible for this retrospective analysis. Participants underwent four MRI examinations during NAC treatment. FTV was calculated based on automated segmentation. Baseline FTV before treatment (FTV0) and the percentage of FTV change at early treatment and inter-regimen time points relative to baseline (∆FTV1 and ∆FTV2, respectively) were classified into high-standard or standard groups based on visual assessment of FTV under- and overestimation. Logistic regression models predicting pCR using single predictors (FTV0, ∆FTV1, and ∆FTV2) and multiple predictors (all three) were developed using bootstrap resampling with out-of-sample data evaluation with the area under the receiver operating characteristic curve (AUC) independently in each group. Results This study included 432 women (mean age, 49.0 years ± 10.6 [SD]). In the FTV0 model, the high-standard and standard groups showed similar AUCs (0.61 vs 0.62). The high-standard group had a higher estimated AUC compared with the standard group in the ∆FTV1 (0.74 vs 0.63), ∆FTV2 (0.79 vs 0.62), and multiple predictor models (0.85 vs 0.64), with a statistically significant difference for the latter two models (P = .03 and P = .01, respectively). Conclusion The findings in this study suggest that longitudinal variation in FTV estimation needs to be considered when using early FTV change as an MRI-based criterion for breast cancer treatment personalization. Keywords: Breast, Cancer, Dynamic Contrast-enhanced, MRI, Tumor Response ClinicalTrials.gov registration no. NCT01042379 Supplemental material is available for this article. © RSNA, 2023 See also the commentary by Ram in this issue.

Deep Learning to Simulate Contrast-enhanced Breast MRI of Invasive Breast Cancer.

Background There is increasing interest in noncontrast breast MRI alternatives for tumor visualization to increase the accessibility of breast MRI. Purpose To evaluate the feasibility and accuracy of generating simulated contrast-enhanced T1-weighted breast MRI scans from precontrast MRI sequences in biopsy-proven invasive breast cancer with use of deep learning. Materials and Methods Women with invasive breast cancer and a contrast-enhanced breast MRI examination that was performed for initial evaluation of the extent of disease between January 2015 and December 2019 at a single academic institution were retrospectively identified. A three-dimensional, fully convolutional deep neural network simulated contrast-enhanced T1-weighted breast MRI scans from five precontrast sequences (T1-weighted non-fat-suppressed [FS], T1-weighted FS, T2-weighted FS, apparent diffusion coefficient, and diffusion-weighted imaging). For qualitative assessment, four breast radiologists (with 3-15 years of experience) blinded to whether the method of contrast was real or simulated assessed image quality (excellent, acceptable, good, poor, or unacceptable), presence of tumor enhancement, and maximum index mass size by using 22 pairs of real and simulated contrast-enhanced MRI scans. Quantitative comparison was performed using whole-breast similarity and error metrics and Dice coefficient analysis of enhancing tumor overlap. Results Ninety-six MRI examinations in 96 women (mean age, 52 years ± 12 [SD]) were evaluated. The readers assessed all simulated MRI scans as having the appearance of a real MRI scan with tumor enhancement. Index mass sizes on real and simulated MRI scans demonstrated good to excellent agreement (intraclass correlation coefficient, 0.73-0.86; P < .001) without significant differences (mean differences, -0.8 to 0.8 mm; P = .36-.80). Almost all simulated MRI scans (84 of 88 [95%]) were considered of diagnostic quality (ratings of excellent, acceptable, or good). Quantitative analysis demonstrated strong similarity (structural similarity index, 0.88 ± 0.05), low voxel-wise error (symmetric mean absolute percent error, 3.26%), and Dice coefficient of enhancing tumor overlap of 0.75 ± 0.25. Conclusion It is feasible to generate simulated contrast-enhanced breast MRI scans with use of deep learning. Simulated and real contrast-enhanced MRI scans demonstrated comparable tumor sizes, areas of tumor enhancement, and image quality without significant qualitative or quantitative differences. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Slanetz in this issue. An earlier incorrect version appeared online. This article was corrected on January 17, 2023.

Safety and efficacy of HSP90 inhibitor ganetespib for neoadjuvant treatment of stage II/III breast cancer.

HSP90 inhibitors destabilize oncoproteins associated with cell cycle, angiogenesis, RAS-MAPK activity, histone modification, kinases and growth factors. We evaluated the HSP90-inhibitor ganetespib in combination with standard chemotherapy in patients with high-risk early-stage breast cancer. I-SPY2 is a multicenter, phase II adaptively randomized neoadjuvant (NAC) clinical trial enrolling patients with stage II-III breast cancer with tumors 2.5 cm or larger on the basis of hormone receptors (HR), HER2 and Mammaprint status. Multiple novel investigational agents plus standard chemotherapy are evaluated in parallel for the primary endpoint of pathologic complete response (pCR). Patients with HER2-negative breast cancer were eligible for randomization to ganetespib from October 2014 to October 2015. Of 233 women included in the final analysis, 140 were randomized to the standard NAC control; 93 were randomized to receive 150 mg/m2 ganetespib every 3 weeks with weekly paclitaxel over 12 weeks, followed by AC. Arms were balanced for hormone receptor status (51-52% HR-positive). Ganetespib did not graduate in any of the biomarker signatures studied before reaching maximum enrollment. Final estimated pCR rates were 26% vs. 18% HER2-negative, 38% vs. 22% HR-negative/HER2-negative, and 15% vs. 14% HR-positive/HER2-negative for ganetespib vs control, respectively. The predicted probability of success in phase 3 testing was 47% HER2-negative, 72% HR-negative/HER2-negative, and 19% HR-positive/HER2-negative. Ganetespib added to standard therapy is unlikely to yield substantially higher pCR rates in HER2-negative breast cancer compared to standard NAC, and neither HSP90 pathway nor replicative stress expression markers predicted response. HSP90 inhibitors remain of limited clinical interest in breast cancer, potentially in other clinical settings such as HER2-positive disease or in combination with anti-PD1 neoadjuvant chemotherapy in triple negative breast cancer.Trial registration: www.clinicaltrials.gov/ct2/show/NCT01042379.

Diffusion-Weighted MRI for Predicting Pathologic Complete Response in Neoadjuvant Immunotherapy.

This study tested the hypothesis that a change in the apparent diffusion coefficient (ADC) measured in diffusion-weighted MRI (DWI) is an independent imaging marker, and ADC performs better than functional tumor volume (FTV) for assessing treatment response in patients with locally advanced breast cancer receiving neoadjuvant immunotherapy. A total of 249 patients were randomized to standard neoadjuvant chemotherapy with pembrolizumab (pembro) or without pembrolizumab (control). DCE-MRI and DWI, performed prior to and 3 weeks after the start of treatment, were analyzed. Percent changes of tumor ADC metrics (mean, 5th to 95th percentiles of ADC histogram) and FTV were evaluated for the prediction of pathologic complete response (pCR) using a logistic regression model. The area under the ROC curve (AUC) estimated for the percent change in mean ADC was higher in the pembro cohort (0.73, 95% confidence interval [CI]: 0.52 to 0.93) than in the control cohort (0.63, 95% CI: 0.43 to 0.83). In the control cohort, the percent change of the 95th percentile ADC achieved the highest AUC, 0.69 (95% CI: 0.52 to 0.85). In the pembro cohort, the percent change of the 25th percentile ADC achieved the highest AUC, 0.75 (95% CI: 0.55 to 0.95). AUCs estimated for percent change of FTV were 0.61 (95% CI: 0.39 to 0.83) and 0.66 (95% CI: 0.47 to 0.85) for the pembro and control cohorts, respectively. Tumor ADC may perform better than FTV to predict pCR at an early treatment time-point during neoadjuvant immunotherapy.

Effect of Inter-Reader Variability on Diffusion-Weighted MRI Apparent Diffusion Coefficient Measurements and Prediction of Pathologic Complete Response for Breast Cancer.

This study evaluated the inter-reader agreement of tumor apparent diffusion coefficient (ADC) measurements performed on breast diffusion-weighted imaging (DWI) for assessing treatment response in a multi-center clinical trial of neoadjuvant chemotherapy (NAC) for breast cancer. DWIs from 103 breast cancer patients (mean age: 46 ± 11 years) acquired at baseline and after 3 weeks of treatment were evaluated independently by two readers. Three types of tumor regions of interests (ROIs) were delineated: multiple-slice restricted, single-slice restricted and single-slice tumor ROIs. Compared to tumor ROIs, restricted ROIs were limited to low ADC areas of enhancing tumor only. We found excellent agreement (intraclass correlation coefficient [ICC] ranged from 0.94 to 0.98) for mean ADC. Higher ICCs were observed in multiple-slice restricted ROIs (range: 0.97 to 0.98) than in other two ROI types (both in the range of 0.94 to 0.98). Among the three ROI types, the highest area under the receiver operating characteristic curves (AUCs) were observed for mean ADC of multiple-slice restricted ROIs (0.65, 95% confidence interval [CI]: 0.52-0.79 and 0.67, 95% CI: 0.53-0.81 for Reader 1 and Reader 2, respectively). In conclusion, mean ADC values of multiple-slice restricted ROI showed excellent agreement and similar predictive performance for pathologic complete response between the two readers.

Utility and Outcomes of Preoperative Screening Breast MRI for Planned Bilateral Prophylactic Mastectomy in High-Risk Patients.

BACKGROUND. There is a paucity of data and consensus guidelines on the utility of preoperative MRI for planned bilateral prophylactic mastectomy. OBJECTIVE. The purpose of this study was to evaluate the utility of breast MRI performed in high-risk patients for the indication of planned bilateral prophylactic mastectomy, with attention given to the diagnostic performance for breast cancer detection. A secondary aim was to assess the potential impact of breast MRI findings on the decision to perform sentinel lymph node biopsy at the time of prophylactic mastectomy. METHODS. A retrospective database review identified MRI examinations performed at an academic medical center from August 2003 to January 2020 for the indication of planned bilateral prophylactic mastectomy. Patient demographics, imaging findings, operative details, and pathology were recorded. BI-RADS category 1 and 2 assessments were considered negative examinations, and BI-RADS category 3, 4, and 5 assessments were considered positive examinations. Descriptive statistics and performance metrics were calculated. RESULTS. The final cohort included 53 patients (mean age, 45 years). Most (35/53; 66.0%) studies were baseline examinations. Of the 53 patients, 31 (58.5%) had negative MRI examinations and 22 (41.5%) had positive MRI examinations. MRI detected two malignancies (one invasive lobular carcinoma and one high-grade ductal carcinoma in situ), both of which were assessed as BI-RADS category 4. The patient with invasive lobular cancer underwent sentinel lymph node biopsy at the time of mastectomy, which showed metastasis. Breast MRI had sensitivity of 100.0% and specificity of 60.8% for overall breast cancer detection and sensitivity of 100.0% and specificity of 59.6% for invasive cancer detection. CONCLUSION. Preoperative MRI for planned bilateral prophylactic mastectomy detected all cancers, indicating a potential role for MRI in impacting surgical decision making. CLINICAL IMPACT. Given the high NPV for cancer, our results suggest that lymph node biopsy may be safely avoided in patients with a negative MRI examination. This is clinically relevant because sentinel nodes cannot be identified after mastectomy.