Mostafa Atri

Image Guided Photothermal Focal Therapy for Localized Prostate Cancer: Phase I Trial

PURPOSE We ascertained the feasibility and safety of image guided targeted photothermal focal therapy for localized prostate cancer. MATERIALS AND METHODS Twelve patients with biopsy proven low risk prostate cancer underwent interstitial photothermal ablation of the cancer. The area of interest was confirmed and targeted using magnetic resonance imaging. Three-dimensional ultrasound was used to guide a laser to the magnetic resonance to ultrasound fused area of interest. Target ablation was monitored using thermal sensors and real-time Definity contrast enhanced ultrasound. Followup was performed with a combination of magnetic resonance imaging and prostate biopsy. Validated quality of life questionnaires were used to assess the effect on voiding symptoms and erectile function, and adverse events were solicited and recorded. RESULTS Interstitial photothermal focal therapy was technically feasible to perform. Of the patients 75% were discharged home free from catheter the same day with the remainder discharged home the following day. The treatment created an identifiable hypovascular defect which coincided with the targeted prostatic lesion. There were no perioperative complications and minimal morbidity. All patients who were potent before the procedure maintained potency after the procedure. Continence levels were not compromised. Based on multicore total prostate biopsy at 6 months 67% of patients were free of tumor in the targeted area and 50% were free of disease. CONCLUSIONS Image guided focal photothermal ablation of low risk and low volume prostate cancer is feasible. Early clinical, histological and magnetic resonance imaging responses suggest that the targeted region can be ablated with minimal adverse effects. It may represent an alternate treatment approach to observation or delayed standard therapy in carefully selected patients. Further trials are required to demonstrate the effectiveness of this treatment concept.

Dynamic Microbubble Contrast-enhanced US to Measure Tumor Response to Targeted Therapy: A Proposed Clinical Protocol with Results from Renal Cell Carcinoma Patients Receiving Antiangiogenic Therapy

PURPOSE To develop and implement an evidence-based protocol for characterizing vascular response of renal cell carcinoma (RCC) to targeted therapy by using dynamic contrast material-enhanced (DCE) ultrasonography (US). MATERIALS AND METHODS The study was approved by the institutional research ethics board; written informed consent was obtained from all patients. Seventeen patients (four women; median age, 58 years; range, 42-72 years; 13 men, median age, 62 years; range, 45-81 years) with metastatic RCC were examined by using DCE US before and after 2 weeks of treatment with sunitinib (May 2007 to October 2009). Two contrast agent techniques--bolus injection and disruption-replenishment infusion of microbubbles--were compared. Changes in tumor blood velocity and fractional blood volume were measured with both methods, together with reproducibility and effect of compensation for respiratory motion. Tumor changes were assessed with computed tomography, by using the best response with the Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free survival (PFS). Follow-up RECIST measurements were performed at 6-week intervals until progressive disease was detected. RESULTS In response to treatment, median tumor fractional blood volume measured with the disruption-replenishment infusion method decreased by 73.2% (interquartile range, 46%-87%) (P < .002), with repeated-measure reproducibility of 9%-15%. Significant decreases were also seen with the bolus method, but with poor correlation of changes in bolus peak (r = 0.46, P = .066) and area under the curve (r = 0.47, P = .058), compared with infusion measurements. Changes in DCE US parameters over 2 weeks did not correlate with PFS and could not be used to predict long-term assessment of best response by using RECIST. Follow-up times ranged 28-501 days; the median was 164 days. CONCLUSION DCE US provides reproducible and sensitive assessment of vascular changes in response to antiangiogenic therapy. The disruption-replenishment infusion protocol is a flexible method suitable for many tumor types, but further studies are needed to assess whether this protocol may be predictive of patient outcome.

Surgically Important Bowel and/or Mesenteric Injury in Blunt Trauma: Accuracy of Multidetector CT for Evaluation

PURPOSE To determine the accuracy of multidetector computed tomography (CT) in the detection of surgically important blunt bowel and/or mesenteric injury, to identify and describe the most reliable CT features of bowel and/or mesenteric injury, and to evaluate the performance of readers with different levels of expertise. MATERIALS AND METHODS Institutional review board approval was obtained for this retrospective case-control study of 96 subjects with laparotomy-confirmed findings: 54 consecutive patients with bowel and/or mesenteric injury (surgically important and unimportant) (32 male patients, 22 female patients; mean age, 40.4 years +/- 17.6 [standard deviation]; range, 16-86 years) and 42 matched patients without bowel and/or mesenteric injury (22 male patients, 20 female patients; mean age, 36.8 years +/- 20.1; range, 14-84 years) who underwent four-detector CT prior to surgery. A second-year radiology resident, an abdominal imaging fellow, and a staff abdominal radiologist, blinded to patient outcome, independently reviewed CT studies and recorded the probability of bowel and/or mesenteric injury on a five-point scale. Sensitivity and specificity were calculated for each reviewer, and areas under the receiver operating characteristic curve (AUCs) were compared. RESULTS Thirty-eight (40%) of 96 patients had surgically important bowel and/or mesenteric injury, and 58 (60%) of 96 patients had either no or surgically unimportant bowel and/or mesenteric injury. Sensitivities of the three reviewers in the diagnosis of surgically important bowel and/or mesenteric injury ranged from 87% (33 of 38) to 95% (36 of 38); specificities ranged from 48% (28 of 58) to 84% (49 of 58). The only significantly better AUC belonged to the staff radiologist for surgically important mesenteric injury (P = .01). Bowel wall defect, extraluminal contrast material, thick large bowel, mesenteric vessel beading, abrupt termination of mesenteric vessels, and mesenteric vessel extravasation showed the best positive likelihood ratios for surgically important bowel and/or mesenteric injury; absence of peritoneal fluid showed the best negative likelihood ratio. CONCLUSION Multidetector CT findings accurately reveal surgically important bowel and/or mesenteric injury and have a high negative predictive value.

New Technologies and Directed Agents for Applications of Cancer Imaging

Molecular imaging represents tissue-specific imaging and quantification of physiologic (functional) and molecular events in tumors utilizing new noninvasive imaging modalities, radioligands, and contrast agents. It combines anatomic, physiologic, and metabolic information in a single imaging session. Molecular imaging relies on the ability to target genes and proteins that are linked directly or indirectly to human disease. New imaging biomarkers are being developed. In addition, functional and molecular imaging can potentially replace anatomic longitudinal studies by assessing treatment response earlier. Vascular targeting agents can be evaluated by imaging of tumor angiogenesis using magnetic resonance imaging (MRI), computed tomography and ultrasound, and positron emission tomography (PET). Targeted contrast agents can accomplish site-directed imaging or therapy by a variety of active and passive mechanisms. Furthermore, there is the possibility of combining different modalities such as ultrasonic imaging and MRI or MRI and PET to increase the flexibility unachievable with either modality alone. However, there is a need to standardize these techniques so that longitudinal evaluation of tumor response to treatment is feasible.

Imaging Features of Sclerosed Hemangioma

OBJECTIVE The purpose of this study was to review the imaging features of sclerosed hemangioma. CONCLUSION In our series, suggestive features of sclerosed hemangiomas include geographic outline, capsular retraction, decrease in size over time, and loss of previously seen regions of enhancement. Additional features include presence of transient hepatic attenuation difference (THAD), rim enhancement, and nodular regions of intense enhancement as seen in typical hemangiomas. Although not pathognomonic, some features of sclerosed hemangioma can suggest it as a diagnostic possibility and lead to biopsy rather than more extensive intervention.

Imaging-Based Diagnosis of Autosomal Dominant Polycystic Kidney Disease

The clinical use of conventional ultrasonography (US) in autosomal dominant polycystic kidney disease (ADPKD) is currently limited by reduced diagnostic sensitivity, especially in at-risk subjects younger than 30 years of age. In this single-center prospective study, we compared the diagnostic performance of MRI with that of high-resolution (HR) US in 126 subjects ages 16-40 years born with a 50% risk of ADPKD who underwent both these renal imaging studies and comprehensive PKD1 and PKD2 mutation screening. Concurrently, 45 healthy control subjects without a family history of ADPKD completed the same imaging protocol. We analyzed 110 at-risk subjects whose disease status was unequivocally defined by molecular testing and 45 unaffected healthy control subjects. Using a total of >10 cysts as a test criterion in subjects younger than 30 years of age, we found that MRI provided both a sensitivity and specificity of 100%. Comparison of our results from HR US with those from a previous study of conventional US using the test criterion of a total of three or more cysts found a higher diagnostic sensitivity (approximately 97% versus approximately 82%) with a slightly decreased specificity (approximately 98% versus 100%) in this study. Similar results were obtained in test subjects between the ages of 30 and 40 years old. These results suggest that MRI is highly sensitive and specific for diagnosis of ADPKD. HR US has the potential to rival the diagnostic performance of MRI but is both center- and operator-dependent.

Enhancing Component on CT to Predict Malignancy in Cystic Renal Masses and Interobserver Agreement of Different CT Features

OBJECTIVE The objective of our study was to determine the CT features of complex cystic renal masses that are the most predictive of malignancy and to assess interobserver variability when interpreting these features. MATERIALS AND METHODS Two radiologists blinded to pathology results retrospectively reviewed CT scans of 36 consecutive cystic renal masses in 30 patients (19 men and 11 women; age range, 28-76 years; mean age, 59 +/- 13 years) who had undergone surgery. The study population included only masses with a cystic component on gross pathology and imaging. All patients underwent contrast-enhanced CT. The reviewers recorded the CT features of each cystic mass, including the presence of enhancing components. Accuracy values and odds ratio to predict malignancy were calculated for each CT feature. Weighted kappa was used to measure interobserver agreement. RESULTS There were 21 cystic renal cell cancers and 11 benign cystic lesions. All cystic renal cell carcinomas showed an enhancing septal or nodular component. The mean sensitivity and specificity of the two reviewers in predicting malignancy for the presence of septal enhancement were 83% (95% confidence interval [CI], 65-93%) and 82% (95% CI, 56-94%); for nodular enhancement, 67% (95% CI, 49-81%) and 96% (95% CI, 75-99%); and for either septal or nodular enhancement, 100% (95% CI, 86-100%) and 86% (95% CI, 67-95%), respectively. The interobserver agreements for septal and nodular enhancement were good (kappa = 0.67) and moderate (kappa = 0.57), respectively. CONCLUSION The presence of either nodular or septal enhancement shows the highest sensitivity for predicting malignancy with moderate to good interobserver agreement.

Ectopic pregnancy versus corpus luteum cyst revisited: best Doppler predictors.

Objective. To determine the best Doppler values for differentiating ectopic pregnancy from a corpus luteum cyst of pregnancy. Methods. This was a prospective study of 80 consecutive patients with the diagnosis of ectopic pregnancy. All ectopic pregnancies were diagnosed on the basis of the presence of an extra‐ovarian adnexal mass on sonography and were confirmed surgically. The last menstrual period ranged from 4 to 11 weeks (mean, 6.3 weeks), and the maximal ectopic pregnancy diameter ranged from 0.7 to 5.5 cm (mean, 2.5 cm). Seventy‐six ectopic pregnancies showed color vascularity, and 40 showed corpus luteum cysts with vascular walls. The highest peak systolic velocity and the lowest resistive index of the vascular ectopic pregnancies were compared with the corresponding values in the vascular corpus luteum cysts. Results. The mean peak systolic velocity of the ectopic pregnancies was 35.4 cm/s compared with 28.4 cm/s in corpus luteum cysts, with no significant statistical difference (P = .1). The resistive index of the ectopic pregnancies ranged from 0.15 to 1.6 (mean ± SD, 0.61 ± 0.24) compared with 0.39 to 0.7 (mean, 0.52 ± 0.10) in corpus luteum cysts, with a significant statistical difference (P = .003). In this cohort, a resistive index of less than 0.39 had a specificity of 100% and a positive predictive value of 100% for diagnosing ectopic pregnancy but was present in only 15% (confidence interval, 7%–23%) of ectopic pregnancies. A resistive index of greater than 0.7 had a specificity of 100% and a positive predictive value of 100% for diagnosing ectopic pregnancy and was present in 31% (confidence interval, 21%–41%) of ectopic pregnancies. Conclusions. Both low and high resistive indices discriminate ectopic pregnancy from a corpus luteum cyst.

Early invasive cervical cancer: MRI and CT predictors of lymphatic metastases in the ACRIN 6651/GOG 183 intergroup study

PURPOSE To compare MRI, CT, clinical exam and histopathological analysis for predicting lymph node involvement in women with cervical carcinoma, verified by lymphadenectomy. METHODS A 25-center ACRIN/GOG study enrolled 208 patients with biopsy-proven invasive cervical cancer for MRI and CT prior to attempted curative radical hysterectomy. Each imaging study was interpreted prospectively by one onsite radiologist, and retrospectively by 4 independent offsite radiologists, all blinded to surgical, histopathological and other imaging findings. Likelihood of parametrial and uterine body involvement was rated on a 5-point scale. Tumor size measurements were attempted in 3 axes. Association with histologic lymph node involvement, scored as absent, pelvic only and common iliac or paraaortic, was evaluated using Cochran-Mantel Haenszel statistics, univariate and multivariate logistic regression, generalized estimating equations, accuracy statistics and ROC analysis. RESULTS Lymphatic metastases were found in 34% of women; 13% had common iliac nodal metastases, and 9% had paraortic nodal metastases. Based on the retrospective multi-observer re-reads, the average AUC for predicting histologic lymph node involvement based on tumor size was higher for MRI versus CT, although formal statistic comparisons could not be conducted. Multivariate analysis showed improved model fit incorporating predictors from MRI, but not from CT, over and above the initial clinical and biopsy predictors, although the increase in discriminatory ability was not statistically significant. CONCLUSION MRI findings may help predict the presence of histologic lymph node involvement in women with early invasive cervical carcinoma, thus providing important prognostic information.

Reprint of: Outcomes in patients with metastatic renal cell cancer treated with individualized sunitinib therapy: Correlation with dynamic microbubble ultrasound data and review of the literature.

BACKGROUND Increased sunitinib exposure (area under the curve) is associated with better outcome in metastatic renal cell cancer. Recommendations for dose modification do not take this into account. A treatment strategy, based on individual patient toxicity, was developed to maximize dose and minimize time without therapy for patients who could not tolerate the standard sunitinib schedule of 50mg given for 28 days with a 14-day break (50mg, 28/14). METHODS A single-center retrospective review was conducted on patients with metastatic renal cell cancer treated from October 2005 to March 2010. Dose/schedule modifications (DSM) were done to keep toxicity (hematological, fatigue, skin, and gastrointestinal) at ≤ grade 2. DSM-1 was 50mg, 14 days on/7 days off with individualized increases in days on treatment. DSM-2 was 50mg, 7 days on/7 days off with individualized increase in days on treatment. DSM-3 was 37.5mg with individualized 7-day breaks. DSM-4 was 25mg with individualized 7-day breaks. Multivariable analysis was performed for outcome as a function of patient and treatment variables. RESULTS Overall, 172 patients were included in the analysis. Most patients had clear cell histology (79.1%) with sunitinib given as a first-line therapy in 59%. The DSM-1 and 2 and DSM-3 and 4 groups had a progression-free survival (PFS) (10.9-11.9 mo) and overall survival (OS) (23.4-24.5 mo) that was significantly better than the PFS (5.3 mo; P<0.001) and OS (14.4 mo; P = 0.03 and 0.003) for the standard schedule (50mg, 28/14). DCE-US in a subset of patients showed that maximum antiangiogenic activity was achieved after 14 days on therapy. CONCLUSIONS Individualized sunitinib scheduling based on toxicity may improve PFS and OS. This hypothesis is supported by several other respective data that are reviewed. A confirmatory prospective trial is ongoing.