Dataset Information

Early ultrasound evaluation identifies excellent responders to neoadjuvant systemic therapy among patients with triple-negative breast cancer.

ABSTRACT:

Background

Heterogeneity exists in the response of triple-negative breast cancer (TNBC) to standard anthracycline (AC)/taxane-based neoadjuvant systemic therapy (NAST), with 40% to 50% of patients having a pathologic complete response (pCR) to therapy. Early assessment of the imaging response during NAST may identify a subset of TNBCs that are likely to have a pCR upon completion of treatment. The authors aimed to evaluate the performance of early ultrasound (US) after 2 cycles of neoadjuvant NAST in identifying excellent responders to NAST among patients with TNBC.

Methods

Two hundred fifteen patients with TNBC were enrolled in the ongoing ARTEMIS (A Robust TNBC Evaluation Framework to Improve Survival) clinical trial. The patients were divided into a discovery cohort (n = 107) and a validation cohort (n = 108). A receiver operating characteristic analysis with 95% confidence intervals (CIs) and a multivariate logistic regression analysis were performed to model the probability of a pCR on the basis of the tumor volume reduction (TVR) percentage by US from the baseline to after 2 cycles of AC.

Results

Overall, 39.3% of the patients (42 of 107) achieved a pCR. A positive predictive value (PPV) analysis identified a cutoff point of 80% TVR after 2 cycles; the pCR rate was 77% (17 of 22) in patients with a TVR ≥ 80%, and the area under the curve (AUC) was 0.84 (95% CI, 0.77-0.92; P < .0001). In the validation cohort, the pCR rate was 44%. The PPV for pCR with a TVR ≥ 80% after 2 cycles was 76% (95% CI, 55%-91%), and the AUC was 0.79 (95% CI, 0.70-0.87; P < .0001).

Conclusions

The TVR percentage by US evaluation after 2 cycles of NAST may be a cost-effective early imaging biomarker for a pCR to AC/taxane-based NAST.

SUBMITTER: Adrada BE

PROVIDER: S-EPMC8319084 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

Early ultrasound evaluation identifies excellent responders to neoadjuvant systemic therapy among patients with triple-negative breast cancer.

Adrada Beatriz E BE Candelaria Rosalind R Moulder Stacy S Thompson Alastair A Wei Peng P Whitman Gary J GJ Valero Vicente V Litton Jennifer K JK Santiago Lumarie L Scoggins Marion E ME Moseley Tanya W TW White Jason B JB Ravenberg Elizabeth E EE Yang Wei T WT Rauch Gaiane M GM

Cancer 20210420 16

<h4>Background</h4>Heterogeneity exists in the response of triple-negative breast cancer (TNBC) to standard anthracycline (AC)/taxane-based neoadjuvant systemic therapy (NAST), with 40% to 50% of patients having a pathologic complete response (pCR) to therapy. Early assessment of the imaging response during NAST may identify a subset of TNBCs that are likely to have a pCR upon completion of treatment. The authors aimed to evaluate the performance of early ultrasound (US) after 2 cycles of neoadj ...[more]

PMID: 33878210

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Project description:BackgroundPathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) in triple-negative breast cancer (TNBC) is a strong predictor of patient survival. Edema in the peritumoral region (PTR) has been reported to be a negative prognostic factor in TNBC.PurposeTo determine whether quantitative apparent diffusion coefficient (ADC) features from PTRs on reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) predict the response to NAST in TNBC.Study typeProspective.Population/subjectsA total of 108 patients with biopsy-proven TNBC who underwent NAST and definitive surgery during 2015-2020.Field strength/sequenceA 3.0 T/rFOV single-shot diffusion-weighted echo-planar imaging sequence (DWI).AssessmentThree scans were acquired longitudinally (pretreatment, after two cycles of NAST, and after four cycles of NAST). For each scan, 11 ADC histogram features (minimum, maximum, mean, median, standard deviation, kurtosis, skewness and 10th, 25th, 75th, and 90th percentiles) were extracted from tumors and from PTRs of 5 mm, 10 mm, 15 mm, and 20 mm in thickness with inclusion and exclusion of fat-dominant pixels.Statistical testsADC features were tested for prediction of pCR, both individually using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC), and in combination in multivariable models with k-fold cross-validation. A P value < 0.05 was considered statistically significant.ResultsFifty-one patients (47%) had pCR. Maximum ADC from PTR, measured after two and four cycles of NAST, was significantly higher in pCR patients (2.8 ± 0.69 vs 3.5 ± 0.94 mm2 /sec). The top-performing feature for prediction of pCR was the maximum ADC from the 5-mm fat-inclusive PTR after cycle 4 of NAST (AUC: 0.74; 95% confidence interval: 0.64, 0.84). Multivariable models of ADC features performed similarly for fat-inclusive and fat-exclusive PTRs, with AUCs ranging from 0.68 to 0.72 for the cycle 2 and cycle 4 scans.Data conclusionQuantitative ADC features from PTRs may serve as early predictors of the response to NAST in TNBC.Evidence level1 TECHNICAL EFFICACY: Stage 4.

Project description:BackgroundHigher cytotoxic T lymphocyte (CTL) numbers in the tumor microenvironment (TME) predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and positive long-term outcomes in triple-negative breast cancer (TNBC). pCR to NAC is achieved only in 30-40% of patients. The combination of NAC with pembrolizumab increases the pCR rate but at the cost of immune-related adverse events (irAEs). Based on these considerations, we tested if systemic infusion of the chemokine modulatory regimen (CKM; selective toll-like receptor 3 (TLR3) agonist rintatolimod, interferon (IFN)-α2b, and cyclooxygenase-2 (COX-2) inhibitor celecoxib) regimen can be safely combined with NAC to enhance intratumoral CTL numbers and NAC effectiveness.MethodsPhase I study NCT04081389 evaluated nine patients with early-stage TNBC who received 3 weeks of paclitaxel with CKM (dose-escalation of IFN-α2b), followed by 9 weeks of paclitaxel alone, dose-dense doxorubicin and cyclophosphamide, and surgery. Primary and secondary endpoints were safety and clinical efficacy, respectively.ResultsThe combination treatment was well-tolerated with no dose-limiting toxicities or irAEs. 5/9 patients achieved pCR and one patient had microinvasive disease (ypTmic). We observed elevated IFN signature and uniform decreases in CTL numbers (average 8.3-fold) in the blood of all treated patients. This was accompanied by reciprocal uniform increases in CD8β (overall 5.9-fold), CD8α/FoxP3 (2.11-fold), and CCL5 (4.73-fold) transcripts in TME, particularly pronounced in patients with pCR. Multiplex immunohistochemistry revealed selectively increased numbers of CTL (but not regulatory T cells) in both the epithelial and stromal tumor compartments and early decreases in the numbers of αSMA+ vascular/stromal cells in the tumors of all pCR patients.ConclusionsCombined paclitaxel/CKM regimen was safe, with desirable TME changes and preliminary indications of promising pCR+ypTmic of 66%, comparable to the combination of NAC with pembrolizumab.

Dataset Information

Early ultrasound evaluation identifies excellent responders to neoadjuvant systemic therapy among patients with triple-negative breast cancer.

Background

Methods

Results

Conclusions

Publications

Early ultrasound evaluation identifies excellent responders to neoadjuvant systemic therapy among patients with triple-negative breast cancer.

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