Prediction of Lung Shunt Fraction for Yttrium-90 Treatment of Hepatic Tumors Using Dynamic Contrast Enhanced MRI with Quantitative Perfusion Processing

There is no noninvasive method to estimate lung shunting fraction (LSF) in patients with liver tumors undergoing Yttrium-90 (Y90) therapy. We propose to predict LSF from noninvasive dynamic contrast enhanced (DCE) MRI using perfusion quantification. Two perfusion quantification methods were used to process DCE MRI in 25 liver tumor patients: Kety’s tracer kinetic modeling with a delay-fitted global arterial input function (AIF) and quantitative transport mapping (QTM) based on the inversion of transport equation using spatial deconvolution without AIF. LSF was measured on SPECT following Tc-99m macroaggregated albumin (MAA) administration via hepatic arterial catheter. The patient cohort was partitioned into a low-risk group (LSF ≤ 10%) and a high-risk group (LSF > 10%). Results: In this patient cohort, LSF was positively correlated with QTM velocity |u| (r = 0.61, F = 14.0363, p = 0.0021), and no significant correlation was observed with Kety’s parameters, tumor volume, patient age and gender. Between the low LSF and high LSF groups, there was a significant difference for QTM |u| (0.0760 ± 0.0440 vs. 0.1822 ± 0.1225 mm/s, p = 0.0011), and Kety’s Ktrans (0.0401 ± 0.0360 vs 0.1198 ± 0.3048, p = 0.0471) and Ve (0.0900 ± 0.0307 vs. 0.1495 ± 0.0485, p = 0.0114). The area under the curve (AUC) for distinguishing between low LSF and high LSF was 0.87 for |u|, 0.80 for Ve and 0.74 for Ktrans. Noninvasive prediction of LSF is feasible from DCE MRI with QTM velocity postprocessing

Bone biopsy protocol for advanced prostate cancer in the era of precision medicine.

BACKGROUND Metastatic biopsies are increasingly being performed in patients with advanced prostate cancer to search for actionable targets and/or to identify emerging resistance mechanisms. Due to a predominance of bone metastases and their sclerotic nature, obtaining sufficient tissue for clinical and genomic studies is challenging. METHODS Patients with prostate cancer bone metastases were enrolled between February 2013 and March 2017 on an institutional review board-approved protocol for prospective image-guided bone biopsy. Bone biopsies and blood clots were collected fresh. Compact bone was subjected to formalin with a decalcifying agent for diagnosis; bone marrow and blood clots were frozen in optimum cutting temperature formulation for next-generation sequencing. Frozen slides were cut from optimum cutting temperature cryomolds and evaluated for tumor histology and purity. Tissue was macrodissected for DNA and RNA extraction, and whole-exome sequencing and RNA sequencing were performed. RESULTS Seventy bone biopsies from 64 patients were performed. Diagnostic material confirming prostate cancer was successful in 60 of 70 cases (85.7%). The median DNA/RNA yield was 25.5 ng/μL and 16.2 ng/μL, respectively. Whole-exome sequencing was performed successfully in 49 of 60 cases (81.7%), with additional RNA sequencing performed in 20 of 60 cases (33.3%). Recurrent alterations were as expected, including those involving the AR, PTEN, TP53, BRCA2, and SPOP genes. CONCLUSIONS This prostate cancer bone biopsy protocol ensures a valuable source for high-quality DNA and RNA for tumor sequencing and may be used to detect actionable alterations and resistance mechanisms in patients with bone metastases. Cancer 2017. © 2017 American Cancer Society