Multiparametric Magnetic Resonance Imaging, Spectroscopy and Multinuclear (23Na) Imaging Monitoring of Preoperative Chemotherapy for Locally Advanced Breast Cancer

Abstract

Rationale and Objectives-We conducted a prospective study to investigate using multiparametric and multinuclear magnetic resonance imaging(MRI) during preoperative systemic treatment(PST) for locally advanced breast cancer.Methods-Women with operable stage II or III breast cancer who received PST were studied using dynamic-contrast-enhanced(DCE)-MRI, spectroscopy(MRS), and ( 23 Na)sodium MR. Quantitative metrics of choline peak signal-to-noise ratios(SNR), total sodium concentration(TSC;mM), tumor volumes and Response Evaluation Criteria In Solid Tumors (RECIST) were determined and compared to final pathological result with ROC analysis. Hormonal markers were investigated. Statistical significance was set at p<0.05.Results-Eighteen(n=18) eligible women were studied. Fifteen(n=15) responded to therapy, four(22%) with pathological-complete-response(pCR) and eleven(61%) with a pathologicalpartial-response(pPR). Three patients(17%) had no response(pNR). Among ER+, HER2+, and Triple Negative(TN) phenotypes, observed frequencies of pCR, pPR, and pNR were 2/5/0, 1/4/0, and 1/1/3, respectively. Responders(pCR and pPR) had the largest reduction in choline SNR (35%:7.2±2.3 to 4.6±2;p<0.01) compared to pNR(11%:8.4±2.7 to 7.5±3.6;p=0.13) after the first cycle. TSC significantly decreased in responders(27%:66±18 to 48.4±8mM;p=0.01), while there was little change in non-responders(51.7±7.6 to 56.5±1.6;p=0.50). Lesion volume decreased in responders(40%:78±78 to 46±51mm 3 ;p=0.01) and nonresponders(21%:100±104 to 79.2±87 mm 3 ;p=0.23) after the first cycle. The largest reduction in RECIST occurred after the first treatment in responders(18%:24.5±20 to 20.2±18mm;p=0.01) with a slight decrease in tumor diameter noted in nonresponders(17%;23±19 to 19.2±19.1mm;p=0.80). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusion-Multiparametric and Multinuclear imaging parameters were significantly reduced after the first cycle of PST in responders, specifically, Choline SNR and Sodium. These new surrogate radiological biomarkers maybe able to predict and provide a platform for potential adaptive therapy in patients. NIH Public Access

Multiparametric and Multimodality Functional Radiological Imaging for Breast Cancer Diagnosis and Early Treatment Response Assessment

“…Significant decreases (>40%) in choline within the tumor have been reported in several studies after the first or second cycle of treatment, with high sensitivities (86%-90%) and specificities (~91%) in detecting responders from nonresponders (35)(36)(37)(38)52). Some of these changes in choline levels were noted within 24 hours of treatment, and, in most cases, only the responders had large declines in choline (35).…”

“…Some of these changes in choline levels were noted within 24 hours of treatment, and, in most cases, only the responders had large declines in choline (35). Finally, a few studies have looked at the sodium concentration in patients undergoing PST, where the changes in sodium concentration after the first cycle of treatment was predictive of pathological response (38).…”

“…Moreover, changes in the concentration of Cho are increasingly being used as an intermediate radiological biomarker for the detection and monitoring of treatment response. Since Cho is involved in membrane turnover, treatment response can be seen within 24 hours to 1 week after the first cycle of chemotherapy (34)(35)(36)(37)(38).…”

“…These changes in tumor and the surrounding tissue result in an increased intracellular Na+ concentration, Na + /H + transporter, and Na + /K + -ATP-ase activity, and have been linked to tumor malignancy (39,40). These changes in the cellular level sodium concentration within different tissue types after treatment must be monitored by advanced MRI methods (38,41). Thus, sodium MRI methods will have immense potential value for the molecular assessment of tissue to determine treatment response in patients.…”

Bilaterale 23Na-MR-Bildgebung der Mamma und Quantifizierung der Natriumkonzentration

“…In [6] wurde bestätigt, dass die 23 Na-MR-Bildgebung Informationen über Verän-derungen der Vitalität von Lungenkarzinomen vor, während und nach einer Chemotherapie liefern kann. In [7] wurden Frauen mit operablem Brustkrebs in Stadium 2 und 3 während der PST untersucht und es konnte gezeigt werden, dass die TSC nach dem ersten Durchlauf der PST in Brust-Tumoren der "Responder" um 27% abnimmt, in denen der "NonResponder" jedoch gleich bleibt. Diese Studien deuten darauf hin, dass eine Veränderung der TSC in Tumorgewebe als Anhaltspunkt zur frühen Einschätzung des Therapie-Erfolgs verwendet werden könnte.…”