Arif Sheikh

Viscous topical is more effective than nebulized steroid therapy for patients with eosinophilic esophagitis

We performed a randomized trial to compare nebulized and viscous topical corticosteroid treatments for eosinophilic esophagitis (EoE). Subjects with incident EoE (n = 25) received budesonide 1 mg twice daily, either nebulized and then swallowed (NEB) or as an oral viscous slurry (OVB), for 8 weeks. Baseline eosinophil counts for the NEB and OVB groups were 101 and 83 (P = .62). Posttreatment counts were 89 and 11 (P = .02). The mucosal medication contact time, measured by scintigraphy, was higher for the OVB group than the NEB group (P < .005) and was inversely correlated with eosinophil count (R = -0.67; P = .001). OVB was more effective than NEB in reducing numbers of esophageal eosinophils in patients with EoE. OVB provided a significantly higher level of esophageal exposure to the therapeutic agent, which correlated with lower eosinophil counts.

Phase II Efficacy and Pharmacogenomic Study of Selumetinib (AZD6244; ARRY-142886) in Iodine-131 Refractory Papillary Thyroid Carcinoma with or without Follicular Elements

Purpose: A multicenter, open-label, phase II trial was conducted to evaluate the efficacy, safety, and tolerability of selumetinib in iodine-refractory papillary thyroid cancer (IRPTC). Experimental Design: Patients with advanced IRPTC with or without follicular elements and documented disease progression within the preceding 12 months were eligible to receive selumetinib at a dose of 100 mg twice daily. The primary endpoint was objective response rate using Response Evaluation Criteria in Solid Tumors. Secondary endpoints were safety, overall survival, and progression-free survival (PFS). Tumor genotype including mutations in BRAF, NRAS, and HRAS was assessed. Results: Best responses in 32 evaluable patients out of 39 enrolled were 1 partial response (3%), 21 stable disease (54%), and 11 progressive disease (28%). Disease stability maintenance occurred for 16 weeks in 49%, 24 weeks in 36%. Median PFS was 32 weeks. BRAF V600E mutants (12 of 26 evaluated, 46%) had a longer median PFS compared with patients with BRAF wild-type (WT) tumors (33 versus 11 weeks, respectively, HR = 0.6, not significant, P = 0.3). The most common adverse events and grades 3 to 4 toxicities included rash, fatigue, diarrhea, and peripheral edema. Two pulmonary deaths occurred in the study and were judged unlikely to be related to the study drug. Conclusions: Selumetinib was well tolerated but the study was negative with regard to the primary outcome. Secondary analyses suggest that future studies of selumetinib and other mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK; MEK) inhibitors in IRPTC should consider BRAF V600E mutation status in the trial design based on differential trends in outcome. Clin Cancer Res; 18(7); 2056–65. ©2012 AACR.

Fractionated radioimmunotherapy with 90Y-clivatuzumab tetraxetan and low-dose gemcitabine is active in advanced pancreatic cancer: A phase 1 trial

It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single‐dose yttrium‐90‐labeled hPAM4 (90Y‐hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low‐dose gemcitabine in this disease.

Initial experience in hybrid PET-MRI for evaluation of refractory focal onset epilepsy

PURPOSE We aim to evaluate the utility/improved accuracy of hybrid PET/MR compared to current practice separate 3T MRI and PET-CT imaging for localization of seizure foci. METHOD In a pilot study, twenty-nine patients undergoing epilepsy surgery evaluation were imaged using PET/MR. This subject group had 29 previous clinical 3T MRI as well as 12 PET-CT studies. Prior clinical PET and MR images were read sequentially while the hybrid PET/MR was concurrently read. RESULTS The median interval between hybrid PET/MR and prior imaging studies was 5 months (range 1-77 months). In 24 patients, there was no change in the read between the clinical exams and hybrid PET/MR while new anatomical or functional lesions were identified by hybrid PET/MR in 5 patients without significant clinical change. Four new anatomical MR lesions were seen with concordant PET findings. The remaining patient revealed a new abnormal PET lesion without an MR abnormality. All new PET/MR lesions were clinically significant with concordant EEG and/or SPECT results as potential epileptic foci. CONCLUSION Our initial hybrid PET-MRI experience increased diagnostic yields for detection of potential epileptic lesions. This may be due to the unique advantage of improved co-registration and simultaneous review of both structural and functional data.

Zika Virus–Associated Cognitive Impairment in Adolescent, 2016

Incidence of neurologic manifestations associated with Zika virus infection has been increasing. In 2016, neuropsychological and cognitive changes developed in an adolescent after travel to a Zika virus–endemic area. Single-photon emission computed tomography and neuropsychological testing raised the possibility that Zika virus infection may lead to neuropsychiatric and cognitive symptoms.

Quantitative Comparison of Misregistration in Abdominal and Pelvic Organs Between PET/MRI and PET/CT: Effect of Mode of Acquisition and Type of Sequence on Different Organs

OBJECTIVE The objective of our study was to quantitatively compare misregistration in selected abdominopelvic organs between PET/CT acquisitions and simultaneous and sequential PET/MRI acquisitions. SUBJECTS AND METHODS PET/MR images of 15 healthy volunteers and seven patients with bladder cancer were acquired. Ten clinical PET/CT studies acquired during the same time frame of body mass index-matched control subjects were chosen. PET/MRI and PET/CT registration of selected abdominopelvic organs was measured and compared. RESULTS The overall mean misregistration with PET/MRI was significantly higher than that with PET/CT (p < 0.001). Sequential PET/MRI acquisition was significantly inferior to PET/CT (p = 0.02), whereas there was no significant difference between simultaneous PET/MRI acquisition and PET/CT (p = 0.38). Simultaneous PET/MRI acquisition was significantly better than sequential PET/MRI acquisition (p < 0.001). The mean misregistration for all organs with the T1-weighted volumetric interpolated breath-hold examination (VIBE) sequence (2.39 cm) was significantly inferior to PET/CT (p < 0.001). Although the T2-weighted HASTE breath-hold sequence was significantly inferior to PET/CT (p = 0.04), the T2 HASTE non-breath-hold sequence and T2 STIR sequence (0.18 cm) were significantly superior to both PET/CT and the T1 VIBE sequence (p < 0.001). Within the same sequence (T1 VIBE breath-hold sequence), the mean misregistrations with sequential and simultaneous PET/MRI acquisitions were both significantly greater than with PET/CT (p < 0.001), whereas simultaneous PET/MRI acquisition was superior to sequential PET/MRI acquisition (p < 0.001). CONCLUSION In the abdominopelvic organs, sequentially obtained PET/MRI data have significantly higher misregistration than both PET/CT data and simultaneously acquired PET/MRI data. Simultaneously obtained PET/MRI data are statistically noninferior to PET/CT. Nonradial T1 VIBE has the highest misregistration, whereas T2 STIR and T2 HASTE non-breath-hold are significantly better than both PET/CT and T1 VIBE.

90Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies

BACKGROUND For patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering (90)Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine. METHODS Fifty-eight patients with three (2-7) median prior treatments were treated on Arm A (N=29, (90)Y-clivatuzumab tetraxetan, weekly 6.5 mCi/m(2)doses×3, plus gemcitabine, weekly 200 mg/m(2) doses×4 starting 1 week earlier) or Arm B (N=29, (90)Y-clivatuzumab tetraxetan alone, weekly 6.5 mCi/m(2)doses×3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated. RESULTS Cytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3-9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan-Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29-0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4 months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1 year. CONCLUSIONS Clinical studies of (90)Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting.

Nuclear Molecular and Theranostic Imaging for Differentiated Thyroid Cancer.

Traditional nuclear medicine is rapidly being transformed by the evolving concepts in molecular imaging and theranostics. The utility of new approaches in differentiated thyroid cancer (DTC) diagnostics and therapy has not been fully appreciated. The clinical information, relevant to disease management and patient care, obtained by scintigraphy is still being underestimated. There has been a trend towards moving away from the use of radioactive iodine (RAI) imaging in the management of the disease. This paradigm shift is supported by the 2015 American Thyroid Association Guidelines (1). A more systematic and comprehensive understanding of disease pathophysiology and imaging methodologies is needed for optimal utilization of different imaging modalities in the management of DTC. There have been significant developments in radiotracer and imaging technology, clinically proven to contribute to the understanding of tumor biology and the clinical assessment of patients with DTC. The research and development in the field continues to evolve, with expected emergence of many novel diagnostic and therapeutic techniques. The role for nuclear imaging applications will continue to evolve and be reconfigured in the changing paradigm. This article aims to review the clinical uses and controversies surrounding the use of scintigraphy, and the information it can provide in assisting in the management and treatment of DTC.

Multimodality Molecular Imaging Correlation of a GLUT1-Positive Myopericytic Lesion with a Typical Features-A Case Study

Myopericytomas represent about 1% of all vascular tumors. They are seen more commonly in middle-aged adults and may arise from a wide range of anatomic sites, typically in the subcutaneous tissue of the extremities, [2,3,5]. About 25% arise from the head and neck [6]. Though these are usually benign tumors, and the local recurrence rate in these tumors is considered to be about 17% [7]. In addition, rare cases of myopericytomas that demonstrate atypical features of high cellularity, frequent mitotic figures, pleomorphism and necrosis have been described, and have been termed as malignant myopericytomas [3]. The malignant variant of myopericytoma shares the same basic histological features with their benign counterpart, but is distinguished by features such as high cellularity, pleomorphism, atypical mitotic figures and necrosis [3]. Malignant myopericytoma invariably demonstrates myoid differentiation and therefore stains positively for smooth muscle actin in the nodular as well as in the areas of perivascular infiltration [3]. Very few reports of malignant myopericytomas have been reported since McMenamin and Fletcher’s original article in 2002 [3].

TU-G-BRA-01: Assessing Radiation-Induced Reductions in Regional Lung Perfusion Following Stereotactic Radiotherapy for Lung Cancer

Purpose: The dose-dependent nature of radiation therapy (RT)-induced lung injury following hypo-fractionated stereotactic RT is unclear. We herein report preliminary results of a prospective study assessing the magnitude of RT-induced reductions in regional lung perfusion following hypo-fractionated stereotactic RT. Methods: Four patients undergoing hypo-fractionated stereotactic lung RT (SBRT: 12 Gy x 4 fractions or 10 Gy x 5 fractions) had a pre-treatment SPECT (single-photon emission computed tomography) perfusion scan providing a 3D map of regional lung perfusion. Scans were repeated 3–6 months post-treatment. Pre- and post SPECT scans were registered to the planning CT scan (and hence the 3D dose data). Changes in regional perfusion (counts per cc on the pre-post scans) were computed in regions of the lung exposed to different doses of radiation (in 5 Gy intervals), thus defining a dose-response function. SPECT scans were internally normalized to the regions receiving <5 Gy. Results: At 3 months post-RT, the changes in perfusion are highly variable. At 6 months, there is a consistent dose-dependent reduction in regional perfusion. The average percent decline in regional perfusion was 10% at 15–20 Gy, 20% at 20–25 Gy, and 30% at 25–30 Gy representing a relatively linear dose response with an approximate 2% reduction per Gray for doses in excess of 10 Gy. There was a subtle increase in perfusion in the lung receiving <10 Gy. Conclusion: Hypo-fractionated stereotactic RT appears to cause a dose-dependent reduction in regional lung perfusion. There appears to be a threshold effect with no apparent perfusion loss at doses <10 Gy, though this might be in part due to the normalization technique used. Additional data is needed from a larger number of patients to better assess this issue. This sort of data can be used to assist optimizing RT treatment plans that minimize the risk of lung injury. Partly supported by the NIH (CA69579) and the Lance Armstrong Foundation