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Purpose To evaluate heterogeneity within tumor subregions or “habitats” via textural kinetic analysis on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the classification of two clinical prognostic features; 1) estrogen receptor (ER)-positive from ER-negative tumors, and 2) tumors with four or more viable lymph node metastases after neoadjuvant chemotherapy from tumors without nodal metastases. Materials and Methods Two separate volumetric DCE-MRI datasets were obtained at 1.5T, comprised of bilateral axial dynamic 3D T1-weighted fat suppressed gradient recalled echo-pulse sequences obtained before and after gadolinium-based contrast administration. Representative image slices of breast tumors from 38 and 34 patients were used for ER status and lymph node classification, respectively. Four tumor habitats were defined based on their kinetic contrast enhancement characteristics. The heterogeneity within each habitat was quantified using textural kinetic features, which were evaluated using two feature selectors and three classifiers. Results Textural kinetic features from the habitat with rapid delayed washout yielded classification accuracies of 84.44% (area under the curve [AUC] 0.83) for ER and 88.89% (AUC 0.88) for lymph node status. The texture feature, information measure of correlation, most often chosen in cross-validations, measures heterogeneity and provides accuracy approximately the same as with the best feature set. Conclusion Heterogeneity within habitats with rapid washout is highly predictive of molecular tumor characteristics and clinical behavior.

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Purpose: Talimogene laherparepvec (TVEC) is an oncolytic herpes simplex 1 virus approved for treatment of melanoma. We hypothesized intratumoral TVEC may enhance response to neoadjuvant chemotherapy (NAC). This article reports the results of a trial combining NAC with TVEC for triple-negative breast cancer (TNBC). Patients and Methods: Patients with stage II–III TNBC enrolled in a 3+3 phase I trial (NCT02779855) of two TVEC dose levels [DL; DL 1 = 106 plaque-forming units (PFU) × 5 doses; DL 2 = 106 PFUs first dose, then 108 PFUs × 4 doses] on weeks 1, 4, 6, 8, and 10 plus weekly paclitaxel (80 mg/m2) for 12 weeks, followed by doxorubicin/cyclophosphamide (60/600 mg/m2) every 2 weeks for 8 weeks. Postoperative response assessment using residual cancer burden (RCB) was performed. Primary endpoints were safety and MTD. Secondary endpoints were RCB0 rate and immune correlates. Dose-limiting toxicity (DLT) rule was grade 3–5 adverse events due to TVEC during first 5 weeks. Results: Nine patients [DL 1 (n = 3); DL 2 (n = 6)] were enrolled. Six had stage II disease, and 3 had stage III (6 clinically N+). No DLTs occurred, and MTD was DL 2. Most common toxicities with TVEC were fever (n = 8), chills (n = 3), hematomas (n = 3), and injection site pain (n = 3). Thromboembolic events (n = 2) and bradycardia (n = 1) occurred during or after NAC. Five patients (55%) achieved RCB0, 2 had RCB1 (22%), and 2 had RCB2 (22%). Conclusions: The addition of TVEC to NAC was feasible at the approved dose, with manageable toxicity. The complete response rate was 55%.

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