The purpose of this article is to review imaging modalities used in local staging of bladder urothelial carcinoma.
Urothelial carcinoma is the most common histologic subtype of bladder cancer, and ...accurate local staging of this tumor is crucial for management. Traditionally, local staging relied on biopsy. With increasing accuracy of imaging modalities and techniques, imaging also plays an important role in the multidisciplinary care of patients with this disease.
The Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT) pathway plays an important role in the pathogenesis of hematologic malignancies. We conducted a phase I dose-finding ...and pharmacokinetic/pharmacodynamic study of SB1518, a potent JAK2 inhibitor, in patients with relapsed lymphoma.
Patients with relapsed or refractory Hodgkin or non-Hodgkin lymphoma of any type except Burkitt's or CNS lymphoma were enrolled. Patient cohorts received escalating doses of SB1518 orally once daily for 28-day cycles. Response was evaluated after 8 weeks.
Thirty-four patients received doses of 100 to 600 mg/d. The maximum tolerated dose was not reached. Treatment was well tolerated, with mostly grade 1 and 2 toxicities. Gastrointestinal toxicities were the most common treatment-related events. Cytopenias were infrequent and modest. Pharmacologically active concentrations were achieved at all doses. Dose-related linear increases in area under the concentration-time curve were seen on day 1, with no significant accumulation on day 15. Mean terminal half-life was 1 to 4 days, and mean time to peak concentration ranged from 5 to 9 hours. SB1518 inhibited JAK2 signaling at 4 hours postdose at all levels. Increases in fms-like tyrosine kinase-3 (FLT-3) ligand, reflecting FLT-3 inhibition, were seen in most patients. There were three partial responses (≥300 mg/d) and 15 patients with stable disease (SD), with most responses lasting longer than 2 months. Seven of 13 SDs had tumor reductions of 4% to 46%.
SB1518 has encouraging activity in relapsed lymphoma, providing the first proof-of-principle of the potential therapeutic value of targeting the JAK/STAT pathway in lymphoma in the clinical setting.
To evaluate the safety and efficacy of panobinostat plus everolimus in patients with relapsed Hodgkin and non-Hodgkin lymphoma. The concept was supported by the single-agent clinical activity of ...histone deacetylase inhibitors and mTOR inhibitors, and on the in vitro mechanism-based synergistic antiproliferative activity.
This was a phase I study in patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma using panobinostat orally on Monday/Wednesday/Friday and everolimus orally daily. Toxicity and responses were assessed in dose-escalation cohort followed by expansion cohort at maximum-tolerated dose. Exploratory analysis of serum cytokine levels was performed.
Thirty patients were enrolled onto four dose levels. The dose-limiting toxicity was thrombocytopenia. The maximal tolerated dose was panobinostat 20 mg and everolimus 10 mg. Grade 3/4 toxicity included thrombocytopenia (64%), neutropenia (47%), anemia (20%), infection (10%), fatigue (7%), and dyspnea (7%). A total of 10 patients (33%; indolent lymphoma, T-cell lymphoma, mantle cell lymphoma, and Hodgkin lymphoma) achieved objective responses. In patients with Hodgkin lymphoma (n = 14), the overall response rate was 43% with complete response rate of 15%. In patients with Hodgkin lymphoma, multiple serum cytokine levels decreased significantly after treatment with this combination therapy. Of note, clinical responses were associated with a decrease in serum interleukin-5 levels (day 8, P = 0.013, and day 15, P = 0.021).
Our data suggest that the combination therapy is active but with significant thrombocytopenia. Future studies should explore alternate scheduling and different compounds that target the same pathways to improve the tolerability of this novel combination.
The purpose of this article is to review the use of dual-energy CT (DECT) in the assessment of gynecologic cancer.
DECT has the potential to improve diagnostic performance, may improve the ability to ...differentiate between simple cystic lesions and primary ovarian cancer, and may also improve the detection of musculoskeletal and liver metastases. Additional studies will be needed to determine the direction of future developments and the degree to which DECT will affect the imaging and management of gynecologic cancer.
We correlated changes in tumor density on CT with changes in glucose metabolism, or the maximum standardized uptake value (SUV(max)), on FDG PET and sought to develop CT imaging criteria that can be ...used to objectively evaluate tumor response in patients with metastatic gastrointestinal stromal tumors (GISTs) who undergo treatment with imatinib mesylate.
Using the criteria established by the Response Evaluation Criteria in Solid Tumors (RECIST) group, we selected 173 tumors (in 36 patients) for study. Tumor size and density were determined objectively, and overall tumor response (OTR) was evaluated subjectively on CT images. The changes in these parameters before and after treatment were correlated with changes in SUV(max).
Significant decreases were seen in both tumor density (mean, 12.3 H 16.5%; p < 0.0001) and SUV(max) (mean, 3.43 64.9%; p < 0.0001). OTR evaluated subjectively, correlated well with changes in SUV(max) (p < 0.0001). No statistically significant association was found between changes in tumor density and changes in SUV(max) (p = 0.3088), but 70% (14/20) of the patients with tumors that showed response on FDG PET exhibited at least a partial response by a change in tumor density. Tumor size was found to have decreased significantly 2 months after treatment (p = 0.0070). However, in 75% of the patients, the disease was stable according to the traditional tumor response criteria of RECIST.
FDG PET is sensitive and specific for evaluating tumor response but cannot be used in patients whose baseline FDG PET results are negative for tumors. Although subjective evaluation was a better indicator of treatment response than was tumor density alone, the tumor density measurement is a good indicator and provides a reliable quantitative means of monitoring the tumor. RECIST, using only tumor size, was unreliable for monitoring GISTs during the early stage of imatinib mesylate treatment.
Leiomyomas can develop in any organ containing smooth muscles. They most commonly occur in the gastrointestinal and the female genital tracts. Leiomyoma of the prostate is a rare, benign tumor. We ...report 3 cases of rare prostatic leiomyomas. The paucity of literature describing prostatic leiomyoma increases the chance for misdiagnosis. Fewer than 30 cases in the English literature, with none including magnetic resonance imaging, computed tomography (CT), ultrasound, positron emission tomography-CT, and pathological findings together were found. Over the past decade, there has been a shift in the management of prostatic leiomyomas. Prostatectomy was once considered a standard approach for treatment, but now nonsurgical treatment options such as embolization are preferred. Conservative management including surveillance is an option for asymptomatic patients.
The aim of this study was to assess the diagnostic performance of
F-fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) for gynecological cancers of the pelvis ...based on a systematic review and meta-analysis of published data.
A systematic literature search for original diagnostic studies was performed using PubMed/MEDLINE, the Cochrane Library, Embase and Web of Science. The methodological quality of each study was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Data necessary for entry in 2 × 2 contingency tables were obtained, and patients, study, and imaging characteristics were extracted from the selected articles. Statistical analysis included data pooling, heterogeneity testing, sensitivity analyses, forest plotting, and summary receiver operating characteristic curve construction.
Twelve studies met our predefined inclusion criteria and were included in this study. Patient-based analysis, the pooled sensitivity rate, specificity rate, diagnostic odds ratio, and area under the receiver operating characteristic curve for
F-FDG PET/MRI in diagnosis of gynecological malignancies were 74.2% (95% confidence interval, 66.2-80.8%), 89.8% (95% CI, 82.2-94.3%), 26 (95% CI, 10-67), and 0.834, respectively. On lesion-based analysis, the pooled sensitivity rate, specificity rate, diagnostic odds ratio, and area under the curve were 87.5% (95% CI, 75.8-94.0%), 88.2% (95% CI, 84.2-91.3%), 50 (95% CI, 23-111), and 0.922, respectively.
Our meta-analysis demonstrated that
F-FDG PET/MRI is a promising diagnostic method for primary tumors, nodal staging, and recurrence in patients with gynecological malignancies of the pelvis.
Computed tomography (CT) is increasingly being utilized for patient care, with a subsequent increase in the detection of incidental adrenal masses. It is important for physicians to be familiar with ...the various current and investigational CT techniques used to image and characterize adrenal masses, including noncontrast CT, dual-energy CT, post-contrast imaging with percentage washout calculations, and investigational techniques including histogram, perfusion, and biphasic CT analyses. Once an incidental adrenal mass is detected, it is important to utilize current CT adrenal imaging techniques to characterize adrenal masses and differentiate the indolent adrenal masses that may be left alone from malignant and symptomatic masses that need timely medical or surgical management. Current CT imaging techniques can be utilized to differentiate benign adrenal masses from malignant counterparts. In this article, we describe the common CT features of benign adrenal masses, including hyperplasia, adenoma, pheochromocytoma, and myelolipoma. We also describe the common CT features of malignant adrenal masses, including metastases, and adrenal cortical carcinoma.
Abstract 3718
Based on preclinical experiments that demonstrated in vitro synergism between pan-deacetylase (DAC) inhibitor Panobinostat (LBH589) with mTOR inhibitor Everolimus (RAD001) in Hodgkin ...and non-Hodgkin lymphoma cell lines, we conducted a phase I/II study to determine the safety and efficacy of this novel regimen. Patients were eligible if they had relapsed or refractory Hodgkin or non-Hodgkin lymphoma regardless of the number of prior regimens, including autologous and allogeneic transplantation. Everolimus was self administered orally daily and Panobinostat three times weekly on 4 dose escalation levels Table 1. To date, a total of 30 patients have been treated. The histologic subtypes include small lymphocytic (n=1), follicular (n=2), mantle cell (n=3), hodgkin (n=12), diffuse large B-cell (n=7), T-cell (n=3), one discordant Hodgkin/marginal zone lymphoma and one discordant Hodgkin/large cell lymphoma. The median number of prior therapies is 3 with 11 patients receiving prior autologous transplantation. 30 patients received at least 1 dose and are evaluable for safety and 28 are evaluable for response. The DLT was thrombocytopenia observed in the 4th cohort with a dose of 30mg Panobinostat and 10mg of Everolimus. Therefore, 6 patients were treated at the lower dose level of 20mg Panobinostat and 10mg Everolimus which was determined to be the maximum tolerated dose (MTD) and starting dose in the phase II portion of the study. To date, 16 patients have been treated in the phase II portion of the study. Treatment side effects are manageable with the following grade 3/4 adverse events most commonly observed: thrombocytopenia 48%, neutropenia 48% and anemia 20%. One death occurred on study, possibly related to pulmonary embolus. 20 out of 28 evaluable patients (71%) had tumor reduction ranging from -12% to -72% of whom 50% had PR or CR. Our data demonstrate safety and promising clinical activity of this novel combination in a variety of lymphomas. The phase II portion continues to enroll patients to determine the efficacy of this novel regimen.
Dose LevelEverolimusPanobinostatN15mg10mg325mg20mg33 (MTD)10mg20mg6410mg30mg2Phase II10mg20mg16
Neelapu:celgene: Research Funding. Pro:Celgene: Consultancy, Honoraria.
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