Detection of HIV-1 CXCR4 tropism and resistance in treatment experienced subjects receiving CCR5 antagonist-Vicriviroc.

BACKGROUND: Vicriviroc (VCV), a small-molecule antagonist of the C-C chemokine receptor 5 (CCR5), blocks HIV's entry into CD4+ cells. Small studies have suggested that resistance to CCR5 antagonists is slow to develop. OBJECTIVES: To examine resistance to VCV in isolates from treatment experienced patients who experienced virologic failure in two phase 3 trials. STUDY DESIGN: Genotypic and phenotypic susceptibility to VCV, and other antiretroviral drugs were evaluated at baseline and at defined intervals during the study. In a post hoc analysis, viral tropism at baseline was evaluated using the Trofile-ES assay. Only subjects with R5-tropic virus were included in the analysis. Viral envelope sequencing was performed on samples from subjects with emergent VCV resistance defined using a relative MPI cutoff. RESULTS: 71/486 subjects treated with VCV for 48 weeks met the protocol-defined virologic failure criteria. 7/71 (10%) had DM/X4 virus at the time of virologic failure; VCV resistance was identified in 4/486 treated subjects (1%). No control subject had detectable DM/X4 virus or VCV resistance at virologic failure. Clonal analysis of envelope sequences from VCV-resistant virus identified 2-5 amino acid substitutions at or near the crown of the V3 loop; however, no signature V3 mutations were identified. Changes outside the V3 loop were also observed in resistant clones; no consistent variant pattern was observed. CONCLUSIONS: In these trials, use of a sensitive tropism assay and potent antiretroviral drug combinations contributed to the infrequent detection of X4-tropic virus and VCV resistance. Substitutions in the V3 loop were associated with VCV resistance, however, no specific pattern of amino acid changes were sufficient to reliably predict VCV susceptibility.

Endorectal MR imaging before salvage prostatectomy: tumor localization and staging.

PURPOSE: To evaluate retrospectively the accuracy of endorectal magnetic resonance (MR) imaging for the depiction of tumor, extracapsular extension (ECE), and seminal vesicle invasion (SVI) before salvage prostatectomy in patients with locally recurrent prostate cancer after radiation therapy, by using pathologic analysis as the reference standard. MATERIALS AND METHODS: The Institutional Review Board granted exempt status for this HIPAA-compliant study, with a waiver of informed consent. Forty-five consecutive patients (age range, 43-76 years) were identified who underwent salvage radical prostatectomy for prostate cancer at Memorial Sloan-Kettering Cancer Center between December 1, 1998, and October 31, 2004, and who underwent endorectal MR imaging prior to surgery. Tumor localization and determination of local stage with MR imaging were performed independently by two radiologists. Interpretations were compared to pathologic findings from surgical specimens. Interrater variability was estimated with the kappa statistic. Areas under the receiver operating characteristic curve (AUCs) were used to assess the accuracy of endorectal MR imaging in tumor detection and determination of ECE and SVI. RESULTS: Findings of histologic examination showed that tumor was present in all patients. For tumor detection, the AUC value for reader 1 was 0.75 (95% confidence interval [CI]: 0.67, 0.84), whereas the AUC value for reader 2 was 0.61 (95% CI: 0.52, 0.71). The AUC values for prediction of ECE were 0.87 (95% CI: 0.80, 0.94) for reader 1 and 0.76 (95% CI: 0.67, 0.85) for reader 2. The AUC values for prediction of SVI were 0.76 (95% CI: 0.62, 0.90) for reader 1 and 0.70 (95% CI: 0.56, 0.85) for reader 2. For all variables, the kappa statistics used to assess interrater agreement between readers were fair (0.45, 0.52, and 0.47 for tumor location, ECE, and SVI, respectively). CONCLUSION: Endorectal MR imaging following radiation therapy can help identify tumor sites and depict ECE and SVI with reasonable accuracy in patients with recurrent prostate cancer.

The role of preoperative endorectal magnetic resonance imaging in the decision regarding whether to preserve or resect neurovascular bundles during radical retropubic prostatectomy.

BACKGROUND: Because the recovery of erectile function and the avoidance of positive surgical margins are important but competing outcomes, the decision to preserve or resect a neurovascular bundle (NVB) during radical prostatectomy (RP) should be based on the most accurate information concerning the location and extent of the tumor. In the current study, the authors determined the incremental value of endorectal magnetic resonance imaging (eMRI) in making this decision. METHODS: eMRI was performed in 135 patients preoperatively. For each NVB, tumor extension to the NVB and the need for NVB resection was judged by a surgeon on a scale from 1 (definite preservation) to 5 (definite resection) before and after reviewing eMRI with a radiologist. Histopathologic findings were used as the standard of reference. The value of eMRI was assessed using binormal receiver operating characteristic (ROC) analysis adjusted for multiple observations per patient, and a mixed effects ordinal regression model was used for risk stratification. RESULTS: Histopathologic examination determined that NVB resection was warranted in 44 of 270 NVBs (16%) because of posterolateral extracapsular extension (n = 29), positive surgical margins (n = 7), or both (n = 8). The areas under the ROC curves (AUC) were 0.741 for pre-MRI and 0.832 for post-MRI surgical planning (P < 0.01). MRI findings suggested altering the surgical plan in 39% of NVBs (106 of 270 NVBs). When the surgeon judged that the NVB resection was definitely not necessary (165 NVBs), MRI confirmed that decision in 138 NVBs (84%); the concordant decision was correct in 96% of the cases (133 of 138 NVBs). In 36 high-risk patients (> or = 75% probability of extracapsular extension), MRI findings changed the surgical plan for 28 NVBs (78%); the change was found to be appropriate in 26 cases (93%). CONCLUSIONS: MRI was found to significantly improve the surgeon's decision to preserve or resect the NVB during radical prostatectomy.

Suspected local recurrence after radical prostatectomy: endorectal coil MR imaging.

PURPOSE: To evaluate endorectal coil magnetic resonance (MR) imaging in the depiction of local recurrence after radical prostatectomy. MATERIALS AND METHODS: Endorectal MR images were reviewed retrospectively in 82 patients who underwent prostatectomy. The interval between prostatectomy and MR imaging ranged between 0.5 and 13.0 years (mean, 3.25 years). Local recurrence was considered present if there was no evidence of distant metastases and there was a positive biopsy result, subsequent reduction in prostate-specific antigen (PSA) level after radiation therapy of the pelvis, or serial MR imaging findings of increased tumor size. Local recurrence on MR images was assessed for location, size, signal intensity, and invasion of adjacent structures. All images were reviewed independently by two readers who were blinded to clinical information. RESULTS: Thirty-four of 82 patients did not meet inclusion criteria. Forty-one of 48 remaining patients had clinically documented local recurrence, which MR imaging depicted in 39 of 41 (95%) patients. Seven of 48 patients had no evidence of local or distant metastases, and none had positive MR imaging findings. Sensitivity of MR imaging was 95%, and specificity was 100%. Local recurrences were perianastomotic in 12 (29%) patients and retrovesical in 17 (40%), within retained seminal vesicles in nine (22%), and at anterior or lateral surgical margins in four (9%). All local recurrences were hyperintense to adjacent pelvic muscles on T2-weighted MR images. The mean diameter of tumors was 1.4 cm (range, 0.8-4.5 cm). PSA levels at MR imaging in patients with clinically proved recurrences ranged from undetectable to 10 ng/mL (mean, 2.18 ng/mL). CONCLUSION: MR imaging depicts a high proportion of local recurrence after prostatectomy. The authors propose incorporation of endorectal coil MR imaging in the diagnostic paradigm of patients who have undergone prostatectomy and are suspected of having local recurrence.

Advances in imaging in the postoperative patient with a rising prostate-specific antigen level.

Imaging prostate cancer continues to represent a clinical challenge for both primary and recurrent disease. In the evaluation of the persistent/recurrent/metastatic prostate cancer, knowledge of cancer location (local v distant), size, and extent are essential in order to design a treatment, tailored to each patient's needs. There are evidence-based guidelines for the use of imaging in assessing the presence of distant spread of prostate cancer. Radionuclide bone scans and computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) supplement clinical and biochemical evaluations (prostate-specific antigen [PSA]) for suspected metastatic disease to bones and lymph nodes. There is no consensus about the use of imaging in the evaluation of local tumor recurrence. The use of ultrasound has been limited to biopsy guidance of the prostatic bed, or percutaneous biopsy of enlarged lymph nodes detected on CT or MRI. The use of MRI is evolving. Recent studies indicate that the use of MRI provides valuable information in the evaluation of local tumor recurrence, and nodal and bony metastases. In a patient post-radiation therapy, the method of combining MRI anatomic information with MR spectroscopic metabolic information is evolving. Another modality offering information about anatomy and metabolism of the local disease is PET/CT. The value of PET/CT at present is controversial, but new studies exploring the role of PET/CT in aggressive prostate cancer are promising.

Utility of an informational intranet in a radiology department.

RATIONALE AND OBJECTIVES: The authors performed this study to assess the usefulness of the various features of their radiology department intranet and to quantify its effect in facilitating intradepartmental information flow. MATERIALS AND METHODS: The number, length, and nature of visits to each directory on the intranet were recorded by a commercially available intranet analysis software package. RESULTS: During the last 6 months of 2001, 89,411 page views (mean, 485 per day) occurred during 26,344 visits to the radiology department intranet. The most commonly accessed features were billing code lists (29% of total views); the intranet home page (27%); faculty telephone and pager numbers (2.6%); digital dictation access codes (1.6%); and magnetic resonance imaging protocols (1.5%). A total of 32,408 files, including daily clinical assignments, monthly fellow and resident schedules, and protocol forms, were downloaded as portable document files by intranet users. CONCLUSION: The intranet has proved an invaluable addition to the authors' departmental infrastructure, as evidenced by its extensive use by the staff. It has facilitated the rapid dissemination of information without hard copy.