Purpose:To determine if oxidative and nitrative stress and/or apoptosis contribute to increased coagulation when combining radiofrequency (RF) ablation with liposomal doxorubicin. Materials and Methods:Animal care committee approval was obtained. R3230 mammary adenocarcinomas in Fischer rats were treated with either RF ablation ( n = 43), 1 mg of intravenously injected liposomal doxorubicin ( n = 26), or combined therapy ( n = 30) and were compared with control subjects ( n = 11). A subset of animals receiving combination therapy ( n = 24) were treated in the presence or absence of N -acetylcysteine (NAC) administered 24 hours and 1 hour before RF ablation. Tumors were analyzed 2 minutes to 72 hours after treatment to determine the temporal range of response by using immunohistochemical staining of the apoptosis marker cleaved caspase-3, phosphorylated g H2AX , and Results:By 4 hours after RF ablation alone, a 0.48-mm 6 0.13 (standard deviation ) peripheral band with 57.0% 6 7.3 cleaved caspase-3 positive cells was noted at the ablation margin, whereas a 0.73-mm 6 0.18 band with 77.7% 6 6.3 positivity was seen for combination therapy ( P , .03 for both comparisons). Combination therapy caused increased and earlier staining for 4-HNE-modifi ed proteins, 8-OHdG, NT, and g H2AX with colocalization to cleaved caspase-3 staining. A rim of increased HSP70 was identifi ed peripheral to the area of cleaved caspase-3. Parameters of oxidative and nitrative stress were signifi cantly inhibited by NAC 1 hour following RF ablation, resulting in decreased cleaved caspase-3 positivity (0.28-mm 6 0.09 band of 25.9% 6 7.4 positivity vs 0.59-mm 6 0.11 band of 62.9% 6 6.0 positivity, P , .001 for both comparisons). Conclusion:Combining RF ablation with liposomal doxorubicin increases cell injury and apoptosis in the zone of increased coagulation by using a mechanism that involves oxidative and nitrative stress that leads to accelerated apoptosis.q RSNA, 2010

Purpose:To determine whether arterial spin-labeling (ASL) magnetic resonance (MR) imaging findings at baseline and early during antiangiogenic therapy can predict later resistance to therapy. Materials and Methods:Protocol was approved by an institutional animal care and use committee. Caki-1, A498, and 786-0 human renal cell carcinoma (RCC) xenografts were implanted in 39 nude mice. Animals received 80 mg sorafenib per kilogram of body weight once daily once tumors measured 12 mm. ASL imaging was performed at baseline and day 14, with additional imaging performed for 786-0 and A498 (3 days to 12 weeks). Mean blood flow values and qualitative differences in spatial distribution of blood flow were analyzed and compared with histopathologic findings for viability and microvascular density. t Tests were used to compare differences in mean tumor blood flow. Bonferroni-adjusted P values less than .05 denoted significant differences. Results:Baseline blood flow was 80.1 mL/100 g/min Ϯ 23.3 (standard deviation) for A498, 75.1 mL/100 g/min Ϯ 28.6 for 786-0, and 10.2 mL/100 g/min Ϯ 9.0 for Caki-1. Treated Caki-1 showed no significant change (14.9 mL/100 g/min Ϯ 7.6) in flow, whereas flow decreased in all treated A498 on day 14 (47.9 mL/100 g/min Ϯ 21.1) and in 786-0 on day 3 (20.3 mL/100 g/min Ϯ 8.7) (P ϭ .003 and .03, respectively). For A498, lowest values were measured at 28 -42 days of receiving sorafenib. Regions of increased flow occurred on days 35-49, 17-32 days before documented tumor growth and before significant increases in mean flow (day 77). Although 786-0 showed new, progressive regions with signal intensity detected as early as day 5 that correlated to viable tumor at histopathologic examination, no significant changes in mean flow were noted when day 3 was compared with all subsequent days (P Ͼ .99). Conclusion:ASL imaging provides clinically relevant information regarding tumor viability in RCC lines that respond to sorafenib.

PurposeResistance to antiangiogenic therapy is an important clinical problem. We examined whether resistance occurs at least in part via reversible, physiologic changes in the tumor, or results solely from stable genetic changes in resistant tumor cells.Experimental DesignMice bearing two human RCC xenografts were treated with sorafenib until they acquired resistance. Resistant 786-O cells were harvested and reimplanted into naïve mice. Mice bearing resistant A498 cells were subjected to a 1 week treatment break. Sorafenib was then again administered to both sets of mice. Tumor growth patterns, gene expression, viability, blood vessel density, and perfusion were serially assessed in treated vs control mice.ResultsDespite prior resistance, reimplanted 786-O tumors maintained their ability to stabilize on sorafenib in sequential reimplantation steps. A transcriptome profile of the tumors revealed that the gene expression profile of tumors upon reimplantation reapproximated that of the untreated tumors and was distinct from tumors exhibiting resistance to sorafenib. In A498 tumors, revascularization was noted with resistance and cessation of sorafenib therapy and tumor perfusion was reduced and tumor cell necrosis enhanced with re-exposure to sorafenib.ConclusionsIn two RCC cell lines, resistance to sorafenib appears to be reversible. These results support the hypothesis that resistance to VEGF pathway therapy is not solely the result of a permanent genetic change in the tumor or selection of resistant clones, but rather is due to a great extent to reversible changes that likely occur in the tumor and/or its microenvironment.

Perfusion MDCT can detect focal blood flow changes even when the tumor is shrinking, possibly indicating early reversal of tumor responsiveness to antiangiogenic therapy. Given that changes in tumor volume after antiangiogenic therapy do not necessarily correlate with true treatment response, physiologic imaging of tumor perfusion may be necessary.

Purpose bone lesions on prostate MRI often raise concern about metastases. This study aimed to evaluate the prevalence of bone metastases on staging prostate MRI and evaluate associations between their MRI features and clinical/pathologic characteristics. Methods Retrospective, IRB-approved study of 3765 patients undergoing prostate MRI for newly-diagnosed PCa between 2000-2014. The reference standard to calculate the prevalence of bone metastases was bone biopsy and/or ≥1-year follow-up after MRI. In a subsample of 228 patients, the MRI characteristics of bone lesions were recorded by two radiologists independently. Associations between MRI and clinical/pathologic findings, including National Comprehensive Cancer Network (NCCN) risk categories, were calculated. Results 57/3765 patients (1.5%, 95%CI:1.2-2.0%) had bone metastases. No patient with NCCN low-risk PCa (Gleason <7, PSA<10 ng/mL, cT1-2a) had bone metastases. In the subsample, ≥1 bone lesion was present on MRI in 74% (95%CI:0.67-0.79) and 72% (95%CI:0.66-0.78) of patients (R1 and R2). Larger lesion diameter (OR:1.33/1.19; p<0.001 for both readers) and absence of intralesional fat (OR:0.07/0.11; p=0.004/0.002 for R1/R2) were significantly associated with bone metastases. Conclusion Bone lesions are common in prostate MRI, but only rarely represent metastases. MRI should be interpreted in the context of clinical features that influence the likelihood of metastatic disease.

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To reduce radiation dose in tumor perfusion with CT, TST can be reduced without causing significant changes in BF calculation in an animal model. Scanning the aortic reference with peak contrast enhancement reduces variability sufficiently to allow for longer ISDs.

Objective To describe the CT features of organizing pneumonia (OP) in an oncologic patient population and to also identify features associated with lung cancer and patients undergoing haemopoietic stem cell transplant (HSCT). Methods In retrospective CTs from 151 patients with pathologically confirmed OP between 01/09 and 12/14, number of lesions, location, size, margin type, and consistency, as well as volume of lymphadenopathy and the presence and size of pleural effusions, were recorded. Associated malignancy was noted. Results OP most commonly presented as a diffuse process (n = 62, 41%); frequently occupied both a central and peripheral location (n = 79, 53%); and commonly presented with a solid appearance (n = 67, 44%) or with ground glass opacity (n = 80, 53%). Pleural effusions were seen in 68 patients (45%). OP less frequently contained air bronchograms, cavitation, necrosis, surrounding GGO, or adjacent bronchiectasis. In lung cancer patients (n = 25, 17%), OP more likely presented as discrete lesions and occupied a peripheral location as compared to patients with other malignancies (p = 0.025, 0.002). In HSCT patients, (n = 29, 19%), a diffuse process was more commonly seen than non-HSCT patients (p = 0.038). Conclusion OP more commonly presents as discrete lesions with a peripheral location in lung cancer patients, and as a diffuse process in patients who had undergone HSCT.