Search

Aim report primary results from the first multicentre randomised trial evaluating induction chemotherapy prior to trimodality therapy in patients with oesophageal or gastro-oesophageal junction adenocarcinoma. Notably, recent data from a single-institution randomised trial reported that induction chemotherapy prolonged overall survival (OS) in patients with well/moderately differentiated tumours. Methods In this phase 2 trial (28 centres in the U.S. NCI-sponsored North Central Cancer Treatment Group [Alliance]), trimodality-eligible patients (T3-4N0, TanyN+) were randomised to receive induction (docetaxel, oxaliplatin, capecitabine; Arm A) or no induction chemotherapy (Arm B) followed by oxaliplatin/5-fluorouracil/radiation and subsequent surgery. The primary endpoint was the rate of pathologic complete response (pathCR). Secondary/exploratory endpoints were OS and disease-free survival (DFS). Results Of 55 patients evaluable for the primary endpoint, the pathCR rate was 28.6% (8/28) in A versus 40.7% (11/27) in B (P = .34). Given interim results indicating futility, accrual was terminated, but patients were followed. After a median follow-up of 60.4 months, a longer median OS in Arm A versus B was unexpectedly observed (3-year rates 57.1% versus 41.7%, respectively) driven by longer DFS after margin-free surgery. In posthoc analysis, induction (versus no induction) chemotherapy was associated with significantly longer OS and DFS among patients with well/moderately differentiated tumours, but not among patients with poorly/undifferentiated tumours (Pinteraction = 0.037). Conclusions Adding induction chemotherapy prior to trimodality therapy did not improve the primary endpoint, pathCR. However, induction chemotherapy was associated with longer median OS, particularly among patients with well/moderately differentiated tumours. These findings may inform further development of curative-intent trials in this disease.

The advances in PET scanning for thoracic diseases that are deemed most likely to have clinical impact in the near-term future are highlighted in this article. We predict that the current practice of medicine will continue to embrace the power of molecular imaging and specifically PET scanning. 18F-fluorodeoxyglucose-PET scanning will continue to evolve and will expand into imaging of inflammatory disorders. New clinically available PET scan radiotracers, such as PET scan versions of octreotide and amyloid imaging agents, will expand PET imaging into different disease processes. Major improvements in thoracic PET/CT imaging technology will become available, including fully digital silicone photomultipliers and Bayesian penalized likelihood image reconstruction. These will result in significant improvements in image quality, improving the evaluation of smaller lung nodules and metastases and allowing better prediction of prognosis. The birth of clinical PET/MRI scan will add new imaging opportunities, such as better PET imaging of pleural diseases currently obscured by complex patient motion.

We examined the clinical impact of commercially available quantitation software using 3-dimensional stereotactic surface projection (3D-SSP) on the diagnostic accuracy of 18F fluorodeoxyglucose positron emission tomography (18F FDG PET) in mild cognitive impairment (MCI) and Alzheimer disease (AD).Enrollees underwent clinical evaluation to determine cognitive status and subsequent 18F FDG PET neuroimaging. Four blinded readers (2 novices and 2 experts) rated the images for degree of abnormality and interpretive confidence without and with 3D-SSP. Diagnostic accuracy was determined with area under the curve (area under the curve) of a receiver operating characteristic (receiver operating characteristic) curve analysis and change in confidence with model-based means (LSMeans).Twenty-three normal controls and 31 patients with cognitive impairment (18 MCI and 13 AD) were enrolled (28 female and 26 male; mean age 74 years). During follow-up (mean 3.6 years), all normal participants remained normal, 12 of 18 participants with MCI progressed to dementia, and all participants with baseline dementia progressed. The area under the curve with 3D-SSP (0.88; 95% CI: 0.76-0.95) was significantly higher than without it (0.72; 95% CI: 0.55-0.83). The specificity increased from 26% to 63% for novices and from 56% to 87% for experts with addition of 3D-SSP, whereas the sensitivity was essentially unchanged at 86% and 86% for the beginners and 81% and 79% for the experts. The interpretive confidence increased significantly from 3.3 to 4.0 (maximum value = 5, P = 0.048).The use of commercially available 3D-SSP quantitation improved diagnostic accuracy for evaluation of MCI and AD with 18F FDG PET.

The purpose of this study was to evaluate the clinical utility of 18F-FDG PET/CT in esthesioneuroblastoma staging and restaging and quantify the additional benefit of PET/CT to conventional imaging. Methods: A retrospective review was performed with institutional review board approval for patients with a diagnosis of esthesioneuroblastoma who underwent PET/CT from 2000 to 2010. PET/CT results were retrospectively reviewed by 2 radiologists who were unaware of the clinical and imaging data. Positive imaging findings were classified into 3 categories: local disease, cervical nodal spread, and distant metastasis. All conventional imaging performed in the 6 mo preceding PET/CT, and the medical records, were reviewed to determine the potential added value. Results: Twenty-eight patients (mean age, 52.3 ± 10 y; range, 23–81 y) were identified who underwent a total of 77 PET/CT examinations. Maximum standardized uptake value (SUVmax) was 8.68 ± 4.75 (range, 3.6–23.3) for the primary tumor and 8.57 ± 6.46 (range, 1.9–27.2) for the metastatic site. There was no clear association between primary tumor SUVmax and tumor grade (P = 0.30). Compared with conventional imaging, PET/CT changed disease stage or altered clinical management in 11 (39%) of 28 esthesioneuroblastoma patients. Of these, 10 (36%) of 28 were upstaged on the basis of their PET/CT studies. Cervical nodal metastases were found in 5 (18%) of 28, local recurrence in 2 (7%) of 28, cervical nodal and distant metastases in 2 (7%) of 28, and distant metastases in 1 (4%) of 28. One patient (4%) was downstaged after negative findings on PET/CT. Conclusion: PET/CT is a useful adjunct to conventional imaging in the initial staging and restaging of esthesioneuroblastoma by detecting nodal and distant metastatic disease not demonstrated by conventional imaging and identifying local recurrence hidden by treatment changes on conventional imaging.

Background The mammalian target of rapamycin (mTOR) functions within the PI3K/Akt signaling pathway as a critical modulator of cell survival. On the basis of promising preclinical data, the safety and tolerability of therapy with the mTOR inhibitor RAD001 in combination with radiation (RT) and temozolomide (TMZ) was evaluated in this Phase I study. Methods and Materials All patients received weekly oral RAD001 in combination with standard chemoradiotherapy, followed by RAD001 in combination with standard adjuvant temozolomide. RAD001 was dose escalated in cohorts of 6 patients. Dose-limiting toxicities were defined during RAD001 combination therapy with TMZ/RT. Results Eighteen patients were enrolled, with a median follow-up of 8.4 months. Combined therapy was well tolerated at all dose levels, with 1 patient on each dose level experiencing a dose-limiting toxicity: Grade 3 fatigue, Grade 4 hematologic toxicity, and Grade 4 liver dysfunction. Throughout therapy, there were no Grade 5 events, 3 patients experienced Grade 4 toxicities, and 6 patients had Grade 3 toxicities attributable to treatment. On the basis of these results, the recommended Phase II dosage currently being tested is RAD001 70 mg/week in combination with standard chemoradiotherapy. Fluorodeoxyglucose (FDG) positron emission tomography scans also were obtained at baseline and after the second RAD001 dose before the initiation of TMZ/RT; the change in FDG uptake between scans was calculated for each patient. Fourteen patients had stable metabolic disease, and 4 patients had a partial metabolic response. Conclusions RAD001 in combination with RT/TMZ and adjuvant TMZ was reasonably well tolerated. Changes in tumor metabolism can be detected by FDG positron emission tomography in a subset of patients within days of initiating RAD001 therapy.

Background Multiple Systems Atrophy (MSA) and Dementia with Lewy bodies (DLB) can present with both REM behavior disorder and severe autonomic dysfunction. In rare occasions, patients with MSA progress to cognitive impairment and even dementia. Positron emission topography (PET) imaging using both the amyloid ligand Pittsburgh Compound B (11C-PiB) and 18 flurodeoxyglucose (18F-FDG) was used to ascertain the presence of amyloid and pattern of glucose metabolic derangement in both disorders. Methods Patients diagnosed with probable DLB or MSA, with clinical symptoms of either REM Behavior Disorder (RBD), Parkinsonism, or dysautonomia were prospectively identified. All underwent both 11C-PiB and 18F-FDG PET imaging. Statistical comparison between DLB, MSA, and normal controls was performed. Results Six patients, 3 with DLB, 2 with Parkinson predominant MSA (MSA-P), and 1 with cerebellar predominant MSA (MSA-C) were identified. Increased level of PiB retention was noted in all patients diagnosed with DLB, but was absent in MSA. In those with DLB, glucose hypometabolism corresponded with regions of amyloid presence, and included prefrontal, parietotemporal, occipital and primary visual cortex regions. MSA patients were distinguished by cerebellar glucose hypometabolism. Conclusions These findings emphasize the distinguishing characteristics between the alpha-synuclein related disorders of DLB and MSA. The absence of amyloid in the cases of MSA is a possible distinguishing characteristic of the disorder.

Purpose To our knowledge, there are no published data pertinent to the use of [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in patients with natural killer (NK)/T—cell lymphoma. The purpose of this study was to assess the value of FDG PET/CT in this aggressive type of non-Hodgkin lymphoma. Patients and Methods All patients with NK/T-cell lymphoma referred for FDG PET/CT at our institution from July 2001 to July 2006 were retrospectively studied. PET/CT examinations were blindly reviewed by 2 experienced readers. The results were compared with the status of the disease, which was determined after evaluation of biopsy, laboratory, clinical and conventional imaging examination, and follow-up results. PET/CT results were thereby classified as true-positive, true-negative, false-positive, or false-negative. The degree of FDG uptake in the positive lesions was semiquantified using maximum standard uptake value (SUV max ). Results Twenty-one PET/CT examinations were performed in 10 patients with NK/T-cell lymphoma. For nasal disease, PET/CT was true-positive in 5 cases, true-negative in 15 cases, and positive but unconfirmed in 1 case. For extranasal disease, PET/CT was true-positive in 3 cases, true-negative in 16 cases, and false-negative in 2 cases. The mean SUV max in PET-positive lesions in nasal cavities or paranasal sinuses was 16 gm/mL (range, 5–25 gm/mL; median, 19.3 gm/mL). In extranasal disease, the mean SUV max was 10.9 gm/mL (range, 4.6–34.1 gm/mL; median, 5.6 gm/mL). Conclusion Viable NK/T-cell lymphoma is intensely FDG hypermetabolic. PET/CT appears to be sensitive for the detection of disease in the nasopharynx and, to a lesser extent, in extranasal sites.

Although an extremely useful technique for sentinel lymph node (SLN) identification in breast cancer, injections of 99mTc-sulfur colloid can be quite painful. The purpose of this study was to determine whether there is a correlation between perceived pain of injection and age, breast density, or timing of topical anesthetic cream administration. Methods: A retrospective review was conducted of women with breast cancer who received injections for sentinel lymphoscintigraphy from 2008 to 2010. After receiving 4 unilateral, intradermal, periareolar injections, women ranked their pain using a comparative scale (0 = no pain; 10 = unbearable pain). There were 3 categories based on length of time that topical anesthetic cream (2.5% lidocaine and 2.5% prilocaine) was applied before injection (1 h prior, 20 min prior, or no cream). In addition, other demographic information and breast density on mammography were analyzed for correlation with the comparative pain scale. Results: Among the 82 women (mean age, 58 y; range, 32–87 y), a wide spectrum on the comparative pain scale was recorded (mean, 4.0; SD, 2.6), with 35% attesting to significant pain, rated 5 or greater. The demographic information and breast density per the Breast Imaging Reporting and Data System were retrospectively reviewed (density: fatty, 14.6%; scattered fibroglandular, 36.6%; heterogeneous, 39.0%; extremely dense, 9.8%). Using bivariate linear regression, no correlation between the comparative pain scale and age (R2 = 0.0029, P = 0.63) or breast density (R2 = 0.00049, P = 0.84) was identified. Most patients had topical anesthetic cream applied 20 min before injection (n = 47, or 57.3%) with 24 (29.3%) having topical anesthetic cream applied 1 h beforehand. Eleven women (13.4%) had no topical anesthetic cream applied because of patient preference or concern about allergy. Again, no correlation was found between comparative pain scale and time of application or use of topical anesthetic cream (Kruskal–Wallis: χ22 = 1.0, P = 0.61). Conclusion: A wide range of pain is experienced with sentinel lymphoscintigraphy injections. In this study, the severity of perceived pain did not correlate with age or breast density. There was no correlation between the use or timing of anesthetic cream and perceived pain from injection. The use of topical anesthetic cream may need to be reexamined, and other means of pain control should be further investigated.

The kinetic pattern of a 11C-labeled histamine H1 receptor antagonist, [11C]pyrilamine, was investigated in the human brain by factor analysis of dynamic PET studies. Tissue time activity curves were also processed by compartment model curve fitting preceded by deconvolution analysis. Factor analysis revealed two statistically significant and physiologically meaningful kinetic patterns: one for specific and another for nonspecific binding of the radioligand. From these two factors a compartment model containing two tissue compartments (one for specific binding and another for nonspecific binding and free ligand) was constructed. The two-compartment model was also supported by the impulse response function, which was obtained by deconvolution and showed two components. The factor image constructed from factor two demonstrated a distribution pattern characteristic for brain regions rich (frontal, parietal, and temporal lobes) or poor (occipital lobe and cerebellum) in H1 receptors. Blockade of H1 receptors with unlabeled pyrilamine, diphenhydramine, or hydroxyzine caused a significant reduction of this factor. Blockade produced no significant changes in factor one representing nonspecific binding. We conclude that the kinetics of [11C]pyrilamine in the brain can be described by two tissue compartments, one related to the distribution of the H1 receptors. Factor analysis of dynamic studies can be used to locally separate these two compartments, for identification of regions rich and poor in H1 receptors and for noninvasive quantitative investigation of the effects of H1 receptor blockers such as pyrilamine, diphenhydramine, or hydroxyzine. © 1993 Wiley-Liss. Inc.

Summary This study prospectively evaluates whether a previously established adverse outcome score (the Geneva prognostic score) predicts 3 and 12-month overall mortality among the patients diagnosed with pulmonary embolism (PE) by a CT pulmonary angiogram (CTPA). Five hundred twenty-three consecutive patients who had CTPA for suspected PE were recruited prospectively from March 2003 to October 2004. The Geneva prognostic score was calculated for all patients. Twelve-month follow up was completed in all patients in December 2005. There were 105 patients diagnosed with PE. The mean score was 2.71 (standard deviation (SD) 1.25) for those patients who had died (n = 7) and 1.14 (SD 1.19) for those patients who were alive (n = 98) at 3-month follow up (P

Quality control of duplex imaging involves consistency in performance of grey scale and Doppler frequency shift or velocity measurements. Phantoms are used to measure the accuracy of Duplex scanners, and many phantoms used for grey scale imaging quality control are available commercially. However, simplistic and inexpensive phantoms for velocity measurements are not available. The authors designed and tested one such phantom—an in-house pump that recirculates fluid in a bottle with inlet and outlet tubes. Different pump settings control the speed of circulating fluid. Initially, the authors used discarded blood from the blood bank. However, because of the associated risks with blood, they searched for a substitute with good reflective properties for ultrasound. Small air bubbles in soda pop worked very effectively, because air is the strongest reflector for ultrasound. To the author's knowledge, use of soda pop for this purpose has not been described previously. Three scanners, an HP 2000, Quantum 2000, and ATL 3000, were evaluated for accuracy of velocity measurements. A similar MHz transducer, 45-degree Doppler angle, and same segment of tube with flowing soda pop were used each time. The Quantum scanner consistently measured velocities as lower than the other two scaners by approximately 10-20% at all velocity ranges (50-350 cm/sec). At the higher end of the spectrum, the Quantum scanner consistently displayed aliasing. Therefore, velocities could not be measured.

Clinical diagnosis of pulmonary embolus (PE) is difficult. Pulmonary angiography is still the gold standard for diagnosing PE, and ventilation perfusion (VQ) lung scans are used as a screening test. With normal VQ scans, PE can be ruled out. High probability VQ scans have high positive accuracy. The authors conducted a retrospective analysis of 45 patients who underwent intermediate VQ scans. Of the 45 patients who had intermediate VQ scans performed, 37 (82%) had venous duplex imaging (VDI) conducted, with 7 found to be positive for deep vein thrombosis. Of the 45 patients who had intermediate VQ scans performed, 12 (27%) had pulmonary angiograms performed, 7 (58%) of which were positive for PE. Six of these seven patients also had VDI conducted, all of which were negative. In total, of the 22 patients found to have a clinical discharge diagnosis of PE, 13 had either VDI studies or pulmonary angiographies positive for PE. These results indicate that a positive VDI study substantiates a diagnosis of PE. However, negative VDI study does not rule out pulmonary embolus.

A 60-year-old man with T-cell lymphoma post chemotherapy presented with progressive left greater than right lower extremity weakness and allodynia. Fluorodeoxyglucose-PET was consistent with neoplastic infiltration of multiple lumbosacral roots and sciatic nerves (figure). Spinal fluid cytology showed malignant T-cells, supporting the …