SPOP-Mutated/CHD1-Deleted Lethal Prostate Cancer and Abiraterone Sensitivity.

Purpose: CHD1 deletions and SPOP mutations frequently cooccur in prostate cancer with lower frequencies reported in castration-resistant prostate cancer (CRPC). We monitored CHD1 expression during disease progression and assessed the molecular and clinical characteristics of CHD1-deleted/SPOP-mutated metastatic CRPC (mCRPC).Experimental Design: We identified 89 patients with mCRPC who had hormone-naive and castration-resistant tumor samples available: These were analyzed for CHD1, PTEN, and ERG expression by IHC. SPOP status was determined by targeted next-generation sequencing (NGS). We studied the correlations between these biomarkers and (i) overall survival from diagnosis; (ii) overall survival from CRPC; (iii) duration of abiraterone treatment; and (iv) response to abiraterone. Relationship with outcome was analyzed using Cox regression and log-rank analyses.Results: CHD1 protein loss was detected in 11 (15%) and 13 (17%) of hormone-sensitive prostate cancer (HSPC) and CRPC biopsies, respectively. Comparison of CHD1 expression was feasible in 56 matched, same patient HSPC and CRPC biopsies. CHD1 protein status in HSPC and CRPC correlated in 55 of 56 cases (98%). We identified 22 patients with somatic SPOP mutations, with six of these mutations not reported previously in prostate cancer. SPOP mutations and/or CHD1 loss was associated with a higher response rate to abiraterone (SPOP: OR, 14.50 P = 0.001; CHD1: OR, 7.30, P = 0.08) and a longer time on abiraterone (SPOP: HR, 0.37, P = 0.002, CHD1: HR, 0.50, P = 0.06).Conclusions: SPOP-mutated mCRPCs are strongly enriched for CHD1 loss. These tumors appear highly sensitive to abiraterone treatment. Clin Cancer Res; 24(22); 5585-93. ©2018 AACR.

Single-Cell Analyses of Prostate Cancer Liquid Biopsies Acquired by Apheresis.

Purpose: Circulating tumor cells (CTCs) have clinical relevance, but their study has been limited by their low frequency.Experimental Design: We evaluated liquid biopsies by apheresis to increase CTC yield from patients suffering from metastatic prostate cancer, allow precise gene copy-number calls, and study disease heterogeneity.Results: Apheresis was well tolerated and allowed the separation of large numbers of CTCs; the average CTC yield from 7.5 mL of peripheral blood was 167 CTCs, whereas the average CTC yield per apheresis (mean volume: 59.5 mL) was 12,546 CTCs. Purified single CTCs could be isolated from apheresis product by FACS sorting; copy-number aberration (CNA) profiles of 185 single CTCs from 14 patients revealed the genomic landscape of lethal prostate cancer and identified complex intrapatient, intercell, genomic heterogeneity missed on bulk biopsy analyses.Conclusions: Apheresis facilitated the capture of large numbers of CTCs noninvasively with minimal morbidity and allowed the deconvolution of intrapatient heterogeneity and clonal evolution. Clin Cancer Res; 24(22); 5635-44. ©2018 AACR.

Monitoring neurointerventional radiation doses using dose-tracking software: implications for the establishment of local diagnostic reference levels.

OBJECTIVES: There is potential for high radiation exposure during neurointerventional procedures. Increasing regulatory requirements mandate dose monitoring of patients and staff, and justification of high levels of radiation exposure. This paper demonstrates the potential to use radiation dose-tracking software to establish local diagnostic reference levels. METHODS: Consecutive neurointerventional procedures, performed in a single institution within a one-year period, were retrospectively studied. Dose area product (DAP) data were collected using dose-tracking software and clinical data obtained from a prospectively generated patient treatment database. RESULTS: Two hundred and sixty-four procedures met the selection criteria. Median DAP was 100 Gy.cm2 for aneurysm coiling procedures, 259 Gy.cm2 for arteriovenous malformation (AVM) embolisation procedures, 87 Gy.cm2 for stroke thrombolysis/thrombectomy, and 74 Gy.cm2 for four-vessel angiography. One hundred and nine aneurysm coiling procedures were further studied. Six significant variables were assessed using stepwise regression analysis to determine effect on DAP. Aneurysm location (anterior vs posterior circulation) had the single biggest effect (p = 0.004). CONCLUSIONS: This paper confirms variable radiation exposures during neurointerventional procedures. The 75th percentile (used to define diagnostic reference levels) of DAP measurements represents a reasonable guidance metric for monitoring purposes. Results indicate that aneurysm location has the greatest impact on dose during coiling procedures and that anterior and posterior circulation coiling procedures should have separate diagnostic reference levels. KEY POINTS: • Dose-tracking software is useful for monitoring patient radiation dose during neurointerventional procedures • This paper provides a template for methodology applicable to any interventional suite • Local diagnostic reference levels were defined by using the 75th percentile of DAP as per International Commission on Radiological Protection recommendations • Aneurysm location is the biggest determinant of radiation dose during coiling procedures. • Anterior and posterior circulation coiling procedures should have separate diagnostic reference levels.