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Pathologic response prediction to neoadjuvant chemotherapy utilizing pretreatment near-infrared imaging parameters and tumor pathologic criteria.

ABSTRACT: The purpose of this study is to develop a prediction model utilizing tumor hemoglobin parameters measured by ultrasound-guided near-infrared optical tomography (US-NIR) in conjunction with standard pathologic tumor characteristics to predict pathologic response before neoadjuvant chemotherapy (NAC) is given.Thirty-four patients' data were retrospectively analyzed using a multiple logistic regression model to predict response. These patients were split into 30 groups of training (24 tumors) and testing (12 tumors) for cross validation. Tumor vascularity was assessed using US-NIR measurements of total hemoglobin (tHb), oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb) concentrations acquired before treatment. Tumor pathologic variables of tumor type, Nottingham score, mitotic index, the estrogen and progesterone receptors and human epidermal growth factor receptor 2 acquired before NAC in biopsy specimens were also used in the prediction model. The patients' pathologic response was graded based on the Miller-Payne system. The overall performance of the prediction models was evaluated using receiver operating characteristic (ROC) curves. The quantitative measures were sensitivity, specificity, positive and negative predictive values (PPV and NPV) and the area under the ROC curve (AUC).Utilizing tumor pathologic variables alone, average sensitivity of 56.8%, average specificity of 88.9%, average PPV of 84.8%, average NPV of 70.9% and average AUC of 84.0% were obtained from the testing data. Among the hemoglobin predictors with and without tumor pathological variables, the best predictor was tHb combined with tumor pathological variables, followed by oxyHb with pathological variables. When tHb was included with tumor pathological variables as an additional predictor, the corresponding measures improved to 79%, 94%, 90%, 86% and 92.4%, respectively. When oxyHb was included with tumor variables as an additional predictor, these measures improved to 77%, 85%, 83%, 83% and 90.6%, respectively. The addition of tHb or oxyHb significantly improved the prediction sensitivity, NPV and AUC compared with using tumor pathological variables alone.These initial findings indicate that combining widely used tumor pathologic variables with hemoglobin parameters determined by US-NIR may provide a powerful tool for predicting patient pathologic response to NAC before the start of treatment.ClincalTrials.gov ID: NCT00908609 (registered 22 May 2009).

SUBMITTER: Zhu Q

PROVIDER: S-EPMC4303135 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Pathologic response prediction to neoadjuvant chemotherapy utilizing pretreatment near-infrared imaging parameters and tumor pathologic criteria.

Zhu Quing Q Wang Liqun L Tannenbaum Susan S Ricci Andrew A DeFusco Patricia P Hegde Poornima P

Breast cancer research : BCR 20141028 5

<h4>Introduction</h4>The purpose of this study is to develop a prediction model utilizing tumor hemoglobin parameters measured by ultrasound-guided near-infrared optical tomography (US-NIR) in conjunction with standard pathologic tumor characteristics to predict pathologic response before neoadjuvant chemotherapy (NAC) is given.<h4>Methods</h4>Thirty-four patients' data were retrospectively analyzed using a multiple logistic regression model to predict response. These patients were split into 30 ...[more]

PMID: 25349073

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Project description:PurposeTo assess initial breast tumor hemoglobin (Hb) content before the initiation of neoadjuvant chemotherapy, monitor the Hb changes at the end of each treatment cycle, and correlate these findings with tumor pathologic response.Materials and methodsThe HIPAA-compliant study protocol was approved by the institutional review boards of both institutions. Written informed consent was obtained from all patients. Patients who were eligible for neoadjuvant chemotherapy were recruited between December 2007 and May 2011, and their tumor Hb content was assessed by using a near-infrared imager coupled with an ultrasonography (US) system. Thirty-two women (mean age, 48 years; range, 32-82 years) were imaged before treatment, at the end of every treatment cycle, and before definitive surgery. The patients were graded in terms of their final pathologic response on the basis of the Miller-Payne system as nonresponders and partial responders (grades 1-3) and near-complete and complete responders (grades 4 and 5). Tumor vascularity was assessed from total Hb (tHb), oxygenated Hb (oxyHb), and deoxygenated Hb (deoxyHb) concentrations. Tumor vascularity changes during treatment were assessed from percentage tHb normalized to the pretreatment level. A two-sample two-sided t test was used to calculate the P value and to evaluate statistical significance between groups. Bonferroni-Holm correction was applied to obtain the corrected P value for multiple comparisons.ResultsThere were 20 Miller-Payne grade 1-3 tumors and 14 grade 4 or 5 tumors. Mean maximum pretreatment tHb, oxyHb, and deoxyHb levels were significantly higher in grade 4 and 5 tumors than in grade 1-3 tumors (P = .005, P = .008, and P = .017, respectively). The mean percentage tHb changes were significantly higher in grade 4 or 5 tumors than in grade 1-3 tumors at the end of treatment cycles 1-3 (P = .009 and corrected P = .009, P = .002 and corrected P = .004, and P < .001 and corrected P < .001, respectively).DiscussionThese findings indicate that initial tumor Hb content is a strong predictor of final pathologic response. Additionally, the tHb changes during early treatment cycles can further predict final pathologic response.

Project description:The purpose of this study was to evaluate breast MRI radiomics in predicting, prior to any treatment, the response to neoadjuvant chemotherapy (NAC) in patients with invasive lymph node (LN)-positive breast cancer for two tasks: (1) prediction of pathologic complete response and (2) prediction of post-NAC LN status. Our study included 158 patients, with 19 showing post-NAC complete pathologic response (pathologic TNM stage T0,N0,MX) and 139 showing incomplete response. Forty-two patients were post-NAC LN-negative, and 116 were post-NAC LN-positive. We further analyzed prediction of response by hormone receptor subtype of the primary cancer (77 hormone receptor-positive, 39 HER2-enriched, 38 triple negative, and 4 cancers with unknown receptor status). Only pre-NAC MRIs underwent computer analysis, initialized by an expert breast radiologist indicating index cancers and metastatic axillary sentinel LNs on DCE-MRI images. Forty-nine computer-extracted radiomics features were obtained, both for the primary cancers and for the metastatic sentinel LNs. Since the dataset contained MRIs acquired at 1.5 T and at 3.0 T, we eliminated features affected by magnet strength using the Mann-Whitney U-test with the null-hypothesis that 1.5 T and 3.0 T samples were selected from populations having the same distribution. Bootstrapping and ROC analysis were used to assess performance of individual features in the two classification tasks. Eighteen features appeared unaffected by magnet strength. Pre-NAC tumor features generally appeared uninformative in predicting response to therapy. In contrast, some pre-NAC LN features were able to predict response: two pre-NAC LN features were able to predict pathologic complete response (area under the ROC curve (AUC) up to 0.82 [0.70; 0.88]), and another two were able to predict post-NAC LN-status (AUC up to 0.72 [0.62; 0.77]), respectively. In the analysis by a hormone receptor subtype, several potentially useful features were identified for predicting response to therapy in the hormone receptor-positive and HER2-enriched cancers.

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Pathologic response prediction to neoadjuvant chemotherapy utilizing pretreatment near-infrared imaging parameters and tumor pathologic criteria.

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Pathologic response prediction to neoadjuvant chemotherapy utilizing pretreatment near-infrared imaging parameters and tumor pathologic criteria.

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