Estrogen Receptor-targeted PET Imaging for Breast Cancer.

Two complementary patient cases are presented to highlight the importance of estrogen receptor (ER)-targeting imaging in treatment planning and selection for endocrine therapy in breast cancer patients. This article will discuss the radiopharmaceuticals and biology, imaging interpretation, and current clinical applications of ER-targeting imaging using fluorine 18 fluoroestradiol PET.

Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer.

PURPOSE: Lutetium-177 [177Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24 h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [177Lu]Lu-PSMA-617. METHODS: In this retrospective study, 68 men with progressive mCRPC treated with [177Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [177Lu]Lu-PSMA-617infusion (mean ± SD: 1.8 ± 0.6 h, range 1.1-4.9 h). Quantitative analysis of [177Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [177Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUVmax and SUVmean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates. RESULTS: 56 patients (means age 76.2 ± 8.1 years, range: 60-93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~ 12 min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [177Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0-15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had > 30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P = 0.008) and PSA-PFS (median 6 months vs. 1 months, P < 0.001). However, changes in SUVmax or SUVmean did not correlate with PSA-PFS or OS. CONCLUSION: We successfully implemented same-day post-therapy SPECT/CT after [177Lu]Lu-PSMA-617 infusions. Quantitation of 1-2 h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC.

Mask-Guided Convolutional Neural Network for Breast Tumor Prognostic Outcome Prediction on 3D DCE-MR Images.

In this proof-of-concept work, we have developed a 3D-CNN architecture that is guided by the tumor mask for classifying several patient-outcomes in breast cancer from the respective 3D dynamic contrast-enhanced MRI (DCE-MRI) images. The tumor masks on DCE-MRI images were generated using pre- and post-contrast images and validated by experienced radiologists. We show that our proposed mask-guided classification has a higher accuracy than that from either the full image without tumor masks (including background) or the masked voxels only. We have used two patient outcomes for this study: (1) recurrence of cancer after 5 years of imaging and (2) HER2 status, for comparing accuracies of different models. By looking at the activation maps, we conclude that an image-based prediction model using 3D-CNN could be improved by even a conservatively generated mask, rather than overly trusting an unguided, blind 3D-CNN. A blind CNN may classify accurately enough, while its attention may really be focused on a remote region within 3D images. On the other hand, only using a conservatively segmented region may not be as good for classification as using full images but forcing the model's attention toward the known regions of interest.

Positron Emission Tomography Imaging of Functional Transforming Growth Factor ß (TGFß) Activity and Benefit of TGFß Inhibition in Irradiated Intracranial Tumors.

PURPOSE: Transforming growth factor ß (TGFß) promotes cell survival by endorsing DNA damage repair and mediates an immunosuppressive tumor microenvironment. Thus, TGFß activation in response to radiation therapy is potentially targetable because it opposes therapeutic control. Strategies to assess this potential in the clinic are needed. METHODS AND MATERIALS: We evaluated positron emission tomography (PET) to image 89Zr -fresolimumab, a humanized TGFß neutralizing monoclonal antibody, as a means to detect TGFß activation in intracranial tumor models. Pathway activity of TGFß was validated by immunodetection of phosphorylated SMAD2 and the TGFß target, tenascin. The contribution of TGFß to radiation response was assessed by Kaplan-Meier survival analysis of mice bearing intracranial murine tumor models GL261 and SB28 glioblastoma and brain-adapted 4T1 breast cancer (4T1-BrA) treated with TGFß neutralizing monoclonal antibody, 1D11, and/or focal radiation (10 Gy). RESULTS: 89Zr-fresolimumab PET imaging detected engineered, physiological, and radiation-induced TGFß activation, which was confirmed by immunostaining of biological markers. GL261 glioblastoma tumors had a greater PET signal compared with similar-sized SB28 glioblastoma tumors, whereas the widespread PET signal of 4T1-BrA intracranial tumors was consistent with their highly dispersed histologic distribution. Survival of mice bearing intracranial tumors treated with 1D11 neutralizing antibody alone was similar to that of mice treated with control antibody, whereas 1D11 improved survival when given in combination with focal radiation. The extent of survival benefit of a combination of radiation and 1D11 was associated with the degree of TGFß activity detected by PET. CONCLUSIONS: This study demonstrates that 89Zr-fresolimumab PET imaging detects radiation-induced TGFß activation in tumors. Functional imaging indicated a range of TGFß activity in intracranial tumors, but TGFß blockade provided survival benefit only in the context of radiation treatment. This study provides further evidence that radiation-induced TGFß activity opposes therapeutic response to radiation.

Evaluation of primary breast cancers using dedicated breast PET and whole-body PET.

Metabolic imaging of the primary breast tumor with 18F-fluorodeoxyglucose ([18F]FDG) PET may assist in predicting treatment response in the neoadjuvant chemotherapy (NAC) setting. Dedicated breast PET (dbPET) is a high-resolution imaging modality with demonstrated ability in highlighting intratumoral heterogeneity and identifying small lesions in the breast volume. In this study, we characterized similarities and differences in the uptake of [18F]FDG in dbPET compared to whole-body PET (wbPET) in a cohort of ten patients with biopsy-confirmed, locally advanced breast cancer at the pre-treatment timepoint. Patients received bilateral dbPET and wbPET following administration of 186 MBq and 307 MBq [18F]FDG on separate days, respectively. [18F]FDG uptake measurements and 20 radiomic features based on morphology, tumor intensity, and texture were calculated and compared. There was a fivefold increase in SULpeak for dbPET (median difference (95% CI): 4.0 mL-1 (1.8-6.4 mL-1), p = 0.006). Additionally, spatial heterogeneity features showed statistically significant differences between dbPET and wbPET. The higher [18F]FDG uptake in dbPET highlighted the dynamic range of this breast-specific imaging modality. Combining with the higher spatial resolution, dbPET may be able to detect treatment response in the primary tumor during NAC, and future studies with larger cohorts are warranted.

Preclinical SPECT and SPECT-CT in Oncology.

Molecular imaging enables both spatial and temporal understanding of the complex biologic systems underlying carcinogenesis and malignant spread. Single-photon emission tomography (SPECT) is a versatile nuclear imaging-based technique with ideal properties to study these processes in vivo in small animal models, as well as to identify potential drug candidates and characterize their antitumor action and potential adverse effects. Small animal SPECT and SPECT-CT (single-photon emission tomography combined with computer tomography) systems continue to evolve, as do the numerous SPECT radiopharmaceutical agents, allowing unprecedented sensitivity and quantitative molecular imaging capabilities. Several of these advances, their specific applications in oncology as well as new areas of exploration are highlighted in this chapter.

Deep learning detection of prostate cancer recurrence with 18F-FACBC (fluciclovine, Axumin®) positron emission tomography.

PURPOSE: To evaluate the performance of deep learning (DL) classifiers in discriminating normal and abnormal 18F-FACBC (fluciclovine, Axumin®) PET scans based on the presence of tumor recurrence and/or metastases in patients with prostate cancer (PC) and biochemical recurrence (BCR). METHODS: A total of 251 consecutive 18F-fluciclovine PET scans were acquired between September 2017 and June 2019 in 233 PC patients with BCR (18 patients had 2 scans). PET images were labeled as normal or abnormal using clinical reports as the ground truth. Convolutional neural network (CNN) models were trained using two different architectures, a 2D-CNN (ResNet-50) using single slices (slice-based approach) and the same 2D-CNN and a 3D-CNN (ResNet-14) using a hundred slices per PET image (case-based approach). Models' performances were evaluated on independent test datasets. RESULTS: For the 2D-CNN slice-based approach, 6800 and 536 slices were used for training and test datasets, respectively. The sensitivity and specificity of this model were 90.7% and 95.1%, and the area under the curve (AUC) of receiver operating characteristic curve was 0.971 (p < 0.001). For the case-based approaches using both 2D-CNN and 3D-CNN architectures, a training dataset of 100 images and a test dataset of 28 images were randomly allocated. The sensitivity, specificity, and AUC to discriminate abnormal images by the 2D-CNN and 3D-CNN case-based approaches were 85.7%, 71.4%, and 0.750 (p = 0.013) and 71.4%, 71.4%, and 0.699 (p = 0.053), respectively. CONCLUSION: DL accurately classifies abnormal 18F-fluciclovine PET images of the pelvis in patients with BCR of PC. A DL classifier using single slice prediction had superior performance over case-based prediction.

Prospective Evaluation of 18F-DCFPyL PET/CT in Biochemically Recurrent Prostate Cancer in an Academic Center: A Focus on Disease Localization and Changes in Management.

18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoropyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) is a promising PET radiopharmaceutical targeting prostate-specific membrane antigen (PSMA). We present our experience with this single-academic-center prospective study evaluating the positivity rate of 18F-DCFPyL PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). Methods: We prospectively enrolled 72 men (52-91 y old; mean ± SD, 71.5 ± 7.2) with BCR after primary definitive treatment with prostatectomy (n = 42) or radiotherapy (n = 30). The presence of lesions compatible with PC was evaluated by 2 independent readers. Fifty-nine patients had scans concurrent with at least one other conventional scan: bone scanning (24), CT (21), MR (20), 18F-fluciclovine PET/CT (18), or 18F-NaF PET (14). Findings from 18F-DCFPyL PET/CT were compared with those from other modalities. Impact on patient management based on 18F-DCFPyL PET/CT was recorded from clinical chart review. Results:18F-DCFPyL PET/CT had an overall positivity rate of 85%, which increased with higher prostate-specific antigen (PSA) levels (ng/mL): 50% (PSA < 0.5), 69% (0.5 ≤ PSA < 1), 100% (1 ≤ PSA < 2), 91% (2 ≤ PSA < 5), and 96% (PSA ≥ 5). 18F-DCFPyL PET detected more lesions than conventional imaging. For anatomic imaging, 20 of 41 (49%) CT or MRI scans had findings congruent with 18F-DCFPyL, whereas 18F-DCFPyL PET was positive in 17 of 41 (41%) cases with negative CT or MRI findings. For bone imaging, 26 of 38 (68%) bone or 18F-NaF PET scans were congruent with 18F-DCFPyL PET, whereas 18F-DCFPyL PET localized bone lesions in 8 of 38 (21%) patients with negative results on bone or 18F-NaF PET scans. In 8 of 18 (44%) patients, 18F-fluciclovine PET had located the same lesions as did 18F-DCFPyL PET, whereas 5 of 18 (28%) patients with negative 18F-fluciclovine findings had positive 18F-DCFPyL PET findings and 1 of 18 (6%) patients with negative 18F-DCFPyL findings had uptake in the prostate bed on 18F-fluciclovine PET. In the remaining 4 of 18 (22%) patients, 18F-DCFPyL and 18F-fluciclovine scans showed different lesions. Lastly, 43 of 72 (60%) patients had treatment changes after 18F-DCFPyL PET and, most noticeably, 17 of these patients (24% total) had lesion localization only on 18F-DCFPyL PET, despite negative results on conventional imaging. Conclusion:18F-DCFPyL PET/CT is a promising diagnostic tool in the work-up of biochemically recurrent PC, given the high positivity rate as compared with Food and Drug Administration-approved currently available imaging modalities and its impact on clinical management in 60% of patients.

Performance Comparison of Individual and Ensemble CNN Models for the Classification of Brain 18F-FDG-PET Scans.

The high-background glucose metabolism of normal gray matter on [18F]-fluoro-2-D-deoxyglucose (FDG) positron emission tomography (PET) of the brain results in a low signal-to-background ratio, potentially increasing the possibility of missing important findings in patients with intracranial malignancies. To explore the strategy of using a deep learning classifier to aid in distinguishing normal versus abnormal findings on PET brain images, this study evaluated the performance of a two-dimensional convolutional neural network (2D-CNN) to classify FDG PET brain scans as normal (N) or abnormal (A). METHODS: Two hundred eighty-nine brain FDG-PET scans (N; n = 150, A; n = 139) resulting in a total of 68,260 images were included. Nine individual 2D-CNN models with three different window settings for axial, coronal, and sagittal axes were trained and validated. The performance of these individual and ensemble models was evaluated and compared using a test dataset. Odds ratio, Akaike's information criterion (AIC), and area under curve (AUC) on receiver-operative-characteristic curve, accuracy, and standard deviation (SD) were calculated. RESULTS: An optimal window setting to classify normal and abnormal scans was different for each axis of the individual models. An ensembled model using different axes with an optimized window setting (window-triad) showed better performance than ensembled models using the same axis and different windows settings (axis-triad). Increase in odds ratio and decrease in SD were observed in both axis-triad and window-triad models compared with individual models, whereas improvements of AUC and AIC were seen in window-triad models. An overall model averaging the probabilities of all individual models showed the best accuracy of 82.0%. CONCLUSIONS: Data ensemble using different window settings and axes was effective to improve 2D-CNN performance parameters for the classification of brain FDG-PET scans. If prospectively validated with a larger cohort of patients, similar models could provide decision support in a clinical setting.

Fungal endocarditis resembling primary cardiac malignancy in a patient with B-cell ALL with culture confirmation.

Fungal endocarditis is a rare subtype of infective endocarditis that often presents with nonspecific symptoms in patients with complex medical histories, making diagnosis challenging. Patients with a history of ALL may present with congestive heart failure, chemo-induced cardiomyopathy, acute coronary syndrome, cardiac lymphomatous metastasis, or infections. We present the case of a patient with a history of ALL who presented with acute coronary syndrome and imaging concerning for primary cardiac lymphoma, when in fact the patient ended up suffering from culture proven fungal endocarditis.

Identifying tests related to breast cancer care in claims data.

To develop a method for calculating rates of testing for breast cancer recurrence in patients who have already undergone initial treatment for breast cancer, we calculated rates in a cohort of Medicare breast cancer patients and an age-matched noncancer cohort. We first used only tests with claims including diagnosis codes indicating invasive breast cancer and then used all tests regardless of diagnosis code. For each method, we calculated testing rates in the breast cancer cohort above the background rate in the noncancer population. The two methods provided similar estimates of testing prevalence and frequency, with exception of prevalence of CT.

PET/CT Imaging of Human TNFα Using [89Zr]Certolizumab Pegol in a Transgenic Preclinical Model of Rheumatoid Arthritis.

PURPOSE: Tumor necrosis factor alpha (TNFα) drives inflammation and bone degradation in patients with rheumatoid arthritis (RA). Some RA patients experience a rapid clinical response to TNFα inhibitors such as certolizumab pegol (CZP) while other patients show limited to no response. Current methods for imaging RA have limited sensitivity and do not assist in the selection of patients most likely to respond to immune-mediated therapy. Herein, we developed a novel positron emission tomography (PET) radiotracer for immuno-PET imaging of TNFα in transgenic human TNFα-expressing mice. PROCEDURES: CZP was modified with p-isothiocyanatobenzyl-deferoxamine (DFO) and radiolabeled with Zr-89. The biological activity of [89Zr]DFO-CZP was evaluated by HPLC and binding assay using human recombinant TNFα (hTNFα). The feasibility of specific immuno-PET imaging of human TNFα was assessed in a transgenic mouse model of RA that expresses human TNFα. This model resembles the progression of RA in humans by maintaining lower levels of circulating hTNFα and exhibits chronic arthritis in the forepaw and hind paw joints. The dosimetry of [89Zr]DFO-CZP in humans was estimated using microPET/CT imaging in Sprague Dawley rats. RESULTS: [89Zr]DFO-CZP was isolated with radiolabeling yields of 85 ± 6 % (n = 5) and specific activities ranging from 74 to 185 MBq/mg (n = 5). Following size exclusion purification, the radiochemical purity of [89Zr]DFO-CZP was greater than 97 %. [89Zr]DFO-CZP retained high immunoreactivity with more than 95 % of the radioactivity shifted into higher molecular weight complexes. Images showed increasing uptake of the tracer in forepaw and hind paw joints with disease progression. No uptake was observed in the model previously administered with an excess amount of unmodified CZP and in normal control mice, demonstrating in vivo specific uptake of [89Zr]DFO-CZP. CONCLUSION: The feasibility of immuno-PET imaging of human TNFα with [89Zr]DFO-CZP has been demonstrated in a preclinical model of RA.

Initial experience of dedicated breast PET imaging of ER+ breast cancers using [F-18]fluoroestradiol.

Dedicated breast positron emission tomography (dbPET) is an emerging technology with high sensitivity and spatial resolution that enables detection of sub-centimeter lesions and depiction of intratumoral heterogeneity. In this study, we report our initial experience with dbPET using [F-18]fluoroestradiol (FES) in assessing ER+ primary breast cancers. Six patients with >90% ER+ and HER2- breast cancers were imaged with dbPET and breast MRI. Two patients had ILC, three had IDC, and one had an unknown primary tumor. One ILC patient was treated with letrozole, and another patient with IDC was treated with neoadjuvant chemotherapy without endocrine treatment. In this small cohort, we observed FES uptake in ER+ primary breast tumors with specificity to ER demonstrated in a case with tamoxifen blockade. FES uptake in ILC had a diffused pattern compared to the distinct circumscribed pattern in IDC. In evaluating treatment response, the reduction of SUVmax was observed with residual disease in an ILC patient treated with letrozole, and an IDC patient treated with chemotherapy. Future study is critical to understand the change in FES SUVmax after endocrine therapy and to consider other tracer uptake metrics with SUVmax to describe ER-rich breast cancer. Limitations include variations of FES uptake in different ER+ breast cancer diseases and exclusion of posterior tissues and axillary regions. However, FES-dbPET has a high potential for clinical utility, especially in measuring response to neoadjuvant endocrine treatment. Further development to improve the field of view and studies with a larger cohort of ER+ breast cancer patients are warranted.

Large Scale Semi-Automated Labeling of Routine Free-Text Clinical Records for Deep Learning.

Breast cancer is a leading cause of cancer death among women in the USA. Screening mammography is effective in reducing mortality, but has a high rate of unnecessary recalls and biopsies. While deep learning can be applied to mammography, large-scale labeled datasets, which are difficult to obtain, are required. We aim to remove many barriers of dataset development by automatically harvesting data from existing clinical records using a hybrid framework combining traditional NLP and IBM Watson. An expert reviewer manually annotated 3521 breast pathology reports with one of four outcomes: left positive, right positive, bilateral positive, negative. Traditional NLP techniques using seven different machine learning classifiers were compared to IBM Watson's automated natural language classifier. Techniques were evaluated using precision, recall, and F-measure. Logistic regression outperformed all other traditional machine learning classifiers and was used for subsequent comparisons. Both traditional NLP and Watson's NLC performed well for cases under 1024 characters with weighted average F-measures above 0.96 across all classes. Performance of traditional NLP was lower for cases over 1024 characters with an F-measure of 0.83. We demonstrate a hybrid framework using traditional NLP techniques combined with IBM Watson to annotate over 10,000 breast pathology reports for development of a large-scale database to be used for deep learning in mammography. Our work shows that traditional NLP and IBM Watson perform extremely well for cases under 1024 characters and can accelerate the rate of data annotation.

Delayed Fluorodeoxyglucose Positron Emission Tomography Imaging in the Differentiation of Tumor Recurrence and Radiation Necrosis in Pediatric Central Nervous System Tumors: Case Report and Review of the Literature.

Malignant central nervous system (CNS) tumors are often treated with radiation therapy, after which clinical and radiographic sequelae can lead to difficulties differentiating tumor recurrence from treatment effect. Magnetic resonance imaging (MRI) is often unable to distinguish between these two entities. The improved ability to delineate concerning foci could lead to earlier tumor detection with quicker access to new therapies and/or clinical trials; conversely, it could alleviate patient concerns in the case of radiation necrosis as the etiology. The utility of positron emission tomography with computed tomography (PET/CT) imaging with fluorodeoxyglucose (FDG) has been explored in CNS tumors in the past, as this imaging modality is widely used in oncologic practices. As there are concerns with false positive imaging in the case of cells with a high metabolic uptake due to causes other than malignancy (i.e. infection, inflammation), delayed FDG PET imaging has been proposed as a mechanism to reduce this confusion. Delayed FDG PET imaging has been explored in several adult and pediatric malignancies, including adult CNS tumors, though there are no current publications applying its use in pediatric CNS tumors. We present two cases of pediatric CNS tumors, where delayed FDG PET imaging helped in the early diagnosis of a recurrence through a distinguishing tumor from the treatment effect.

Exploration of PET and MRI radiomic features for decoding breast cancer phenotypes and prognosis.

Radiomics is an emerging technology for imaging biomarker discovery and disease-specific personalized treatment management. This paper aims to determine the benefit of using multi-modality radiomics data from PET and MR images in the characterization breast cancer phenotype and prognosis. Eighty-four features were extracted from PET and MR images of 113 breast cancer patients. Unsupervised clustering based on PET and MRI radiomic features created three subgroups. These derived subgroups were statistically significantly associated with tumor grade (p = 2.0 × 10-6), tumor overall stage (p = 0.037), breast cancer subtypes (p = 0.0085), and disease recurrence status (p = 0.0053). The PET-derived first-order statistics and gray level co-occurrence matrix (GLCM) textural features were discriminative of breast cancer tumor grade, which was confirmed by the results of L2-regularization logistic regression (with repeated nested cross-validation) with an estimated area under the receiver operating characteristic curve (AUC) of 0.76 (95% confidence interval (CI) = [0.62, 0.83]). The results of ElasticNet logistic regression indicated that PET and MR radiomics distinguished recurrence-free survival, with a mean AUC of 0.75 (95% CI = [0.62, 0.88]) and 0.68 (95% CI = [0.58, 0.81]) for 1 and 2 years, respectively. The MRI-derived GLCM inverse difference moment normalized (IDMN) and the PET-derived GLCM cluster prominence were among the key features in the predictive models for recurrence-free survival. In conclusion, radiomic features from PET and MR images could be helpful in deciphering breast cancer phenotypes and may have potential as imaging biomarkers for prediction of breast cancer recurrence-free survival.

Geographic Variation in Postoperative Imaging for Low-Risk Breast Cancer.

Background: The objective of this study was to examine the presence and magnitude of US geographic variation in use rates of both recommended and high-cost imaging in young patients with early-stage breast cancer during the 18 month period after surgical treatment of their primary tumor. Methods: Using the Truven Health MarketScan Commercial Database, a descriptive analysis was conducted of geographic variation in annual rates of dedicated breast imaging and high-cost body imaging of 36,045 women aged 18 to 64 years treated with surgery for invasive unilateral breast cancer between 2010 and 2012. Multivariate hierarchical analysis examined the relationship between likelihood of imaging and patient characteristics, with metropolitan statistical area (MSA) serving as a random effect. Patient characteristics included age group, BRCA1/2 carrier status, family history of breast cancer, combination of breast surgery type and radiation therapy, drug therapy, and payer type. All MSAs in the United States were included, with areas outside MSAs within a given state aggregated into a single area for analytic purposes. Results: Descriptive analysis of rates of imaging use and intensity within MSA regions revealed wide geographic variation, irrespective of treatment cohort or age group. Increased probability of recommended postoperative dedicated breast imaging was primarily associated with age and treatment including both surgery and radiation therapy, followed by MSA region (odds ratio, 1.42). Increased probability of PET use-a high-cost imaging modality for which postoperative routine use is not recommended in the absence of specific clinical findings-was primarily associated with surgery type followed by MSA region (odds ratio, 1.82). Conclusions: In patients with breast cancer treated for low-risk disease, geography has effects on the rates of posttreatment imaging, suggesting that some patients are not receiving beneficial dedicated breast imaging, and high-cost nonbreast imaging may not be targeted to those groups most likely to benefit.

Geographic and Patient Characteristics Associated With Election of Prophylactic Mastectomy in Young Breast Cancer Patients With Early Disease.

OBJECTIVES: To examine the association between geography and utilization rates of contralateral prophylactic mastectomy (CPM) relative to patient-level factors in patients with early stage breast cancer. MATERIALS AND METHODS: Using the Truven Health MarketScan Commercial Database, a descriptive analysis of geographic variation in genetic testing and CPM rates of 38,108 women ages 18 to 64 years treated with surgery for invasive unilateral breast cancer between 2010 and 2012 was conducted. Multivariate hierarchical analysis was used to examine the relationship between CPM likelihood and patient characteristics, with metropolitan statistical area (MSA) serving as a random effect. Patient characteristics included age group, BRCA1/2 carrier status, family history of breast cancer, breast surgery type, radiation therapy, drug therapy, and payer type. All MSAs in the United States were included, with areas outside MSAs within a given state aggregated into a single area for analytical purposes. RESULTS: Descriptive analysis demonstrated significant geographic variation in rates of CPM irrespective of risk inferred from primary malignancy treatment course (P<0.01 to <0.001). Odds of CPM were higher among BRCA1/2 carriers (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.52-2.06), followed by MSA (median OR among all MSAs was 1.61; 95% CI, 1.51-1.73) and family history of breast cancer (OR, 1.49; 95% CI, 1.28-1.53), respectively. Patients who were not tested for BRCA1/2 were less likely (OR, 0.66; 95% CI, 0.61-0.71) to undergo CPM than patients with a negative BRCA test. CONCLUSIONS: The large geographic variation we observed in CPM indicate a need to understand and optimize clinical decision-making.