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Conventional frequency ultrasonic biomarkers of cancer treatment response in vivo.

ABSTRACT: BACKGROUND:Conventional frequency quantitative ultrasound in conjunction with textural analysis techniques was investigated to monitor noninvasively the effects of cancer therapies in an in vivo preclinical model. METHODS:Conventional low-frequency (?7 MHz) and high-frequency (?20 MHz) ultrasound was used with spectral analysis, coupled with textural analysis on spectral parametric maps, obtained from xenograft tumor-bearing animals (n = 20) treated with chemotherapy to extract noninvasive biomarkers of treatment response. RESULTS:Results indicated statistically significant differences in quantitative ultrasound-based biomarkers in both low- and high-frequency ranges between untreated and treated tumors 12 to 24 hours after treatment. Results of regression analysis indicated a high level of correlation between quantitative ultrasound-based biomarkers and tumor cell death estimates from histologic analysis. Applying textural characterization to the spectral parametric maps resulted in an even stronger correlation (r (2) = 0.97). CONCLUSION:The results obtained in this research demonstrate that quantitative ultrasound at a clinically relevant frequency can monitor tissue changes in vivo in response to cancer treatment administration. Using higher order textural information extracted from quantitative ultrasound spectral parametric maps provides more information at a high sensitivity related to tumor cell death.

SUBMITTER: Sadeghi-Naini A

PROVIDER: S-EPMC3678128 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Conventional frequency ultrasonic biomarkers of cancer treatment response in vivo.

Sadeghi-Naini Ali A Falou Omar O Tadayyon Hadi H Al-Mahrouki Azza A Tran William W Papanicolau Naum N Kolios Michael C MC Czarnota Gregory J GJ

Translational oncology 20130601 3

<h4>Background</h4>Conventional frequency quantitative ultrasound in conjunction with textural analysis techniques was investigated to monitor noninvasively the effects of cancer therapies in an in vivo preclinical model.<h4>Methods</h4>Conventional low-frequency (∼7 MHz) and high-frequency (∼20 MHz) ultrasound was used with spectral analysis, coupled with textural analysis on spectral parametric maps, obtained from xenograft tumor-bearing animals (n = 20) treated with chemotherapy to extract no ...[more]

PMID: 23761215

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Project description:ImportanceUnderstanding molecular mechanisms of response and resistance to anticancer therapies requires prospective patient follow-up and clinical and functional validation of both common and low-frequency mutations. We describe a whole-exome sequencing (WES) precision medicine trial focused on patients with advanced cancer.ObjectiveTo understand how WES data affect therapeutic decision making in patients with advanced cancer and to identify novel biomarkers of response.Design, setting, and patientsPatients with metastatic and treatment-resistant cancer were prospectively enrolled at a single academic center for paired metastatic tumor and normal tissue WES during a 19-month period (February 2013 through September 2014). A comprehensive computational pipeline was used to detect point mutations, indels, and copy number alterations. Mutations were categorized as category 1, 2, or 3 on the basis of actionability; clinical reports were generated and discussed in precision tumor board. Patients were observed for 7 to 25 months for correlation of molecular information with clinical response.Main outcomes and measuresFeasibility, use of WES for decision making, and identification of novel biomarkers.ResultsA total of 154 tumor-normal pairs from 97 patients with a range of metastatic cancers were sequenced, with a mean coverage of 95X and 16 somatic alterations detected per patient. In total, 16 mutations were category 1 (targeted therapy available), 98 were category 2 (biologically relevant), and 1474 were category 3 (unknown significance). Overall, WES provided informative results in 91 cases (94%), including alterations for which there is an approved drug, there are therapies in clinical or preclinical development, or they are considered drivers and potentially actionable (category 1-2); however, treatment was guided in only 5 patients (5%) on the basis of these recommendations because of access to clinical trials and/or off-label use of drugs. Among unexpected findings, a patient with prostate cancer with exceptional response to treatment was identified who harbored a somatic hemizygous deletion of the DNA repair gene FANCA and putative partial loss of function of the second allele through germline missense variant. Follow-up experiments established that loss of FANCA function was associated with platinum hypersensitivity both in vitro and in patient-derived xenografts, thus providing biologic rationale and functional evidence for his extreme clinical response.Conclusions and relevanceThe majority of advanced, treatment-resistant tumors across tumor types harbor biologically informative alterations. The establishment of a clinical trial for WES of metastatic tumors with prospective follow-up of patients can help identify candidate predictive biomarkers of response.

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Conventional frequency ultrasonic biomarkers of cancer treatment response in vivo.

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Conventional frequency ultrasonic biomarkers of cancer treatment response in vivo.

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