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Effect of MR Imaging Contrast Thresholds on Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes: A Subgroup Analysis of the ACRIN 6657/I-SPY 1 TRIAL.

ABSTRACT: Functional tumor volume (FTV) measurements by dynamic contrast-enhanced magnetic resonance imaging can predict treatment outcomes for women receiving neoadjuvant chemotherapy for breast cancer. Here, we explore whether the contrast thresholds used to define FTV could be adjusted by breast cancer subtype to improve predictive performance. Absolute FTV and percent change in FTV (ΔFTV) at sequential time-points during treatment were calculated and investigated as predictors of pathologic complete response at surgery. Early percent enhancement threshold (PEt) and signal enhancement ratio threshold (SER_t) were varied. The predictive performance of resulting FTV predictors was evaluated using the area under the receiver operating characteristic curve. A total number of 116 patients were studied both as a full cohort and in the following groups defined by hormone receptor (HR) and HER2 receptor subtype: 45 HR+/HER2-, 39 HER2+, and 30 triple negatives. High AUCs were found at different ranges of PE_t and SER_t levels in different subtypes. Findings from this study suggest that the predictive performance to treatment response by MRI varies by contrast thresholds, and that pathologic complete response prediction may be improved through subtype-specific contrast enhancement thresholds. A validation study is underway with a larger patient population.

SUBMITTER: Li W

PROVIDER: S-EPMC5214452 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To compare magnetic resonance (MR) imaging findings and clinical assessment for prediction of pathologic response to neoadjuvant chemotherapy (NACT) in patients with stage II or III breast cancer.The HIPAA-compliant protocol and the informed consent process were approved by the American College of Radiology Institutional Review Board and local-site institutional review boards. Women with invasive breast cancer of 3 cm or greater undergoing NACT with an anthracycline-based regimen, with or without a taxane, were enrolled between May 2002 and March 2006. MR imaging was performed before NACT (first examination), after one cycle of anthracyline-based treatment (second examination), between the anthracycline-based regimen and taxane (third examination), and after all chemotherapy and prior to surgery (fourth examination). MR imaging assessment included measurements of tumor longest diameter and volume and peak signal enhancement ratio. Clinical size was also recorded at each time point. Change in clinical and MR imaging predictor variables were compared for the ability to predict pathologic complete response (pCR) and residual cancer burden (RCB). Univariate and multivariate random-effects logistic regression models were used to characterize the ability of tumor response measurements to predict pathologic outcome, with area under the receiver operating characteristic curve (AUC) used as a summary statistic.Data in 216 women (age range, 26-68 years) with two or more imaging time points were analyzed. For prediction of both pCR and RCB, MR imaging size measurements were superior to clinical examination at all time points, with tumor volume change showing the greatest relative benefit at the second MR imaging examination. AUC differences between MR imaging volume and clinical size predictors at the early, mid-, and posttreatment time points, respectively, were 0.14, 0.09, and 0.02 for prediction of pCR and 0.09, 0.07, and 0.05 for prediction of RCB. In multivariate analysis, the AUC for predicting pCR at the second imaging examination increased from 0.70 for volume alone to 0.73 when all four predictor variables were used. Additional predictive value was gained with adjustments for age and race.MR imaging findings are a stronger predictor of pathologic response to NACT than clinical assessment, with the greatest advantage observed with the use of volumetric measurement of tumor response early in treatment.

Project description:PurposeTo evaluate volumetric magnetic resonance (MR) imaging for predicting recurrence-free survival (RFS) after neoadjuvant chemotherapy (NACT) of breast cancer and to consider its predictive performance relative to pathologic complete response (PCR).Materials and methodsThis HIPAA-compliant prospective multicenter study was approved by institutional review boards with written informed consent. Women with breast tumors 3 cm or larger scheduled for NACT underwent dynamic contrast-enhanced MR imaging before treatment (examination 1), after one cycle (examination 2), midtherapy (examination 3), and before surgery (examination 4). Functional tumor volume (FTV), computed from MR images by using enhancement thresholds, and change from baseline (ΔFTV) were measured after one cycle and before surgery. Association of RFS with FTV was assessed by Cox regression and compared with association of RFS with PCR and residual cancer burden (RCB), while controlling for age, race, and hormone receptor (HR)/ human epidermal growth factor receptor type 2 (HER2) status. Predictive performance of models was evaluated by C statistics.ResultsFemale patients (n = 162) with FTV and RFS were included. At univariate analysis, FTV2, FTV4, and ΔFTV4 had significant association with RFS, as did HR/HER2 status and RCB class. PCR approached significance at univariate analysis and was not significant at multivariate analysis. At univariate analysis, FTV2 and RCB class had the strongest predictive performance (C statistic = 0.67; 95% confidence interval [CI]: 0.58, 0.76), greater than for FTV4 (0.64; 95% CI: 0.53, 0.74) and PCR (0.57; 95% CI: 0.39, 0.74). At multivariate analysis, a model with FTV2, ΔFTV2, RCB class, HR/HER2 status, age, and race had the highest C statistic (0.72; 95% CI: 0.60, 0.84).ConclusionBreast tumor FTV measured by MR imaging is a strong predictor of RFS, even in the presence of PCR and RCB class. Models combining MR imaging, histopathology, and breast cancer subtype demonstrated the strongest predictive performance in this study.

Project description:PurposeNeoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers.Patients and methodsEligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets.ResultsIn 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets.ConclusionIn this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology.

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Effect of MR Imaging Contrast Thresholds on Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes: A Subgroup Analysis of the ACRIN 6657/I-SPY 1 TRIAL.

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