Positron Emission Tomography Avidity Research Articles

Preoperative predictors of successful tumour localization by intraoperative molecular imaging with pafolacianine in lung cancer to create predictive nomogram.

Intraoperative molecular imaging (IMI) uses cancer-targeted fluorescent probe to locate nodules. Pafolacianine is a Food and Drug Administration-approved fluorescent probe for lung cancer. However, it has a 8-12% false negative rate for localization. Our goal is to define preoperative predictors of tumour localization by IMI. We performed a retrospective review of patients who underwent IMI using pafolacianine for lung lesions from June 2015 to August 2019. Candidate predictors including sex, age, body mass index, smoking history, tumour size, distance of tumour from surface, use of neoadjuvant therapy and positron emission tomography avidity were included. The outcome was fluorescence in vivo and comprehensively included those who were true or false positives negatives. Multiple imputation was used to handle the missing data. The final model was evaluated using the area under the receiver operating characteristic curve. Three hundred nine patients were included in our study. The mean age was 64 (standard deviation 13) and 68% had a smoking history. The mean distance of the tumours from the pleural surface was 0.4 cm (standard deviation 0.6). Smoking in pack-years and distance from pleura had an odds ratio of 0.99 [95% confidence interval: 0.98-0.99; P = 0.03] and 0.46 [95% confidence interval: 0.27-0.78; P = 0.004], respectively. The final model had an area under the receiver operating characteristic curve of 0.68 and was used to create a nomogram that gives a probability of fluorescence in vivo. Primary tumours that are deeper from the pleural surface, especially in patients with a higher pack-years, are associated with a decreased likelihood of intraoperative localization. We identified a nomogram to predict the likelihood of tumour localization with IMI with pafolacianine.

Clinical significance of incidental 18 FDG PET uptake in the gastrointestinal tract: a retrospective cohort study.

Incidental gastrointestinal tract (GIT) uptake is found in up to 6.3% of patients undergoing positron emission tomography (PET). This may be physiologic or pathologic and requires endoscopic assessment. To determine the diagnostic yield of endoscopy in this setting and characterise PET avidity as a predictor of clinically significant findings. We retrospectively reviewed all consecutive patients undergoing upper endoscopy or colonoscopy for incidental 18 FDG PET positivity in the GIT. A total of 255 patients (62% male, median age 67 years) underwent colonoscopy or sigmoidoscopy for 276 separate areas of PET avidity in the colon. Malignancy was found in 44 cases (16%), and a significant polyp was found in an additional 103 cases (37%). Neoplastic change was found more often in the case of intense compared with non-intense PET avidity (odds ratio (OR) 3.40, 95% confidence interval (CI) 1.95-5.93, P < 0.001), and in focal compared with diffuse uptake (OR 5.97, 95% CI 2.9-12.2, P < 0.001). Upper GIT endoscopy was performed in 75 patients (46 male, median age 63 years) for 77 isolated areas with PET avidity. Malignancy was found in 16 cases (21%), and all were new primary lesions. Numerically, malignant findings were more common in intense (29.7%) than non-intense (12.5%) PET avidity (OR 2.96, 95%, CI 0.92-9.57, P = 0.069). Both focal and intense colonic 18 FDG uptake correlate strongly with a high-risk polyp or malignant lesion. Up to 21% of all gastroscopies performed for evaluation of incidental PET uptake diagnosed a new primary malignancy. These referrals need appropriate triaging and timely endoscopic assessment.

Pharyngeal Inflammation on Positron Emission Tomography/Magnetic Resonance Imaging Before and After Obstructive Sleep Apnea Treatment.

Rationale: There is upper airway inflammation in patients with obstructive sleep apnea (OSA), which reduces with continuous positive airway pressure (CPAP) therapy. Objectives: Validate the use of positron emission tomography (PET)/magnetic resonance imaging (MRI) to quantify metabolic activity within the pharyngeal mucosa of patients with OSA against nasal lavage proteomics and assess the impact of CPAP therapy. Methods: Adults with OSA underwent [18F]-Fluoro-2-deoxy-D-glucose PET/MRI of the neck before and 3 months after initiating CPAP. Nasal lavage samples were collected. Inflammatory protein expression from samples was analyzed using the Olink platform. Upper airway imaging segmentation was performed. Target-to-background ratio (TBRmax) was calculated from target pharyngeal maximum standard uptake values (SUV) and personalized background mean SUV. Most-diseased segment TBRmax was identified per participant at locations with the highest PET avidity. Correlation analysis was performed between baseline TBRmax and nasal lavage proteomics. TBRmax was compared before and after CPAP using linear mixed-effect models. Results: Among 38 participants, the baseline mean age was 46.3 years (standard deviation [SD], 12.5), 21% were female, the mean body mass index was 30.9 kg/m2 (SD, 4.6), and the mean respiratory disturbance index measured by peripheral arterial tonometry was 31 events/h (SD, 16.4). There was a significant positive correlation between pharyngeal mucosa most-diseased segment TBRmax and nasal lavage proteomic inflammation (r = 0.41 [P < 0.001, false discovery rate = 0.002]). Primary analysis revealed a reduction in the most-diseased segment TBRmax after a median of 2.91 months of CPAP therapy (-0.86 [standard error (SE) ± 0.30; P = 0.007]). Stratified analysis by smoking status revealed a significantly decreased most-diseased segment TBRmax after CPAP therapy among never-smokers but not among ever-smokers (-1.01 [SE ± 0.39; P = 0.015] vs. -0.64 [SE ± 0.49; P = 0.201]). Conclusions: CPAP therapy reduces metabolic activity measured by PET/MRI within the upper airway of adults with OSA. Furthermore, PET/MRI measures of upper airway metabolic activity correlate with a noninvasive marker of inflammation (i.e., nasal lavage inflammatory protein expression).

Robustness of Biology-Guided Radiotherapy Delivery to PET Biodistribution Changes within Target

<h3>Purpose/Objective(s)</h3> Biology-guided radiotherapy (BgRT) is a novel tracked dose delivery modality that uses positron emission tomography (PET) emissions to deliver hypofractionated planned fluence to the target. This study evaluated PET biodistribution changes within target during BgRT delivery. <h3>Materials/Methods</h3> Two phantom experiments were designed to evaluate the FDG signal variations and dosimetric effects under stationary target and moving target on a non-clinical investigational radiotherapy system. For the stationary case, a custom built cylindrical 4-D detector phantom insert with a spherical target of 22 mm in diameter containing 4 quadrants that can be filled independently was used to mimic homogenous and non-homogenous FDG uptake conditions. A C-shape insert was used as a PET avid OAR. For simulating PET signal loss within tumor: BgRT plan was created for the spherical target with all quadrants filled and the plan was delivered when ¾ volume of the target was PET-avid. For the PET signal gain within tumor scenario: BgRT plan was created for the same spherical CTV structure where ¾ volume of the target was filled with FDG, mimicking non-homogeneous uptake, and delivered to a full volume PET-avid target. The dosimetric accuracy of BgRT delivery was evaluated using 3%/3 mm Gamma criterion using 4-D detector measurements. Target biodistribution changes under motion was evaluated by creating a BgRT plan with an FDG filled 26 mm diameter spherical target as a CTV and C-shape OAR moving independently (target:3D respiratory, OAR: sinusoidal motions) within a large water filled phantom. During BgRT delivery the PET avid target insert was switched to a smaller 22 mm spherical insert, simulating 40% uniform PET distribution reduction within 26mm CTV. For the moving target experiment, BgRT delivered dose was evaluated using the radiographic film under the condition of CTV coverage ≥97% and maximum dose ≤130%. For all the experiments, the target and the C-shaped OAR were filled with FDG at a ratio of 8:1 with respect to the water background mimicking normal tissue uptake, and a 5 mm CTV to PTV expansion to be targeted with a prescription of 50Gy in 5 fractions. <h3>Results</h3> For the stationary scenarios, BgRT delivery at remissive and progressive conditions achieved gamma pass-rate of 93.2 and 97.7%, respectively. The CTV coverage goals for the motion experiment were met where the minimum CTV dose was 103.3% and the maximum dose was 123.8%. <h3>Conclusion</h3> This study evaluated the biodistribution changes within CTV from planning to delivery suggesting the BgRT delivery is robust with respect to daily variations of PET signal within the PTV under these experimental conditions. Clinical feasibility of BgRT needs further evaluation.

MP51-13 FLUORINE-18 (18F) PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) POSITRON EMISSION TOMOGRAPHY (PET) AND THE DIAGNOSIS AND STAGING OF PRIMARY PROSTATE CANCER (PCA)

MP51-13 FLUORINE-18 (18F) PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) POSITRON EMISSION TOMOGRAPHY (PET) AND THE DIAGNOSIS AND STAGING OF PRIMARY PROSTATE CANCER (PCA)

SARCOID MASQUERADING AS MALIGNANCY ON IMAGING

TOPIC: Imaging TYPE: Medical Student/Resident Case Reports INTRODUCTION: Sarcoidosis is a multi-system inflammatory disease that predominantly affects the lungs and histopathologically characterized by non-caseating granulomas. A comprehensive evaluation must be pursued to diagnose Sarcoidosis as some findings can overlap with other compatible conditions. CASE PRESENTATION: A-44-year-old woman presented with chronic fatigue, shortness of breath, left sided chest pain, and cough. CT chest revealed left hilar, anterior mediastinal, right paratracheal, and subcarinal lymphadenopathy. An 18-F-fluorodeoxyglucose (FDG) positron emission tomography (PET) CT showed extensive mediastinal and hilar PET avid adenopathy. Notable lymph nodes include a 25mm subcarinal node with a Standardized Uptake Value (SUV) of 32.6 and 11mm left hilar node with a SUV of 27.7. The PET CT findings were highly concerning for lymphoma. Patient subsequently underwent an Endobronchial Ultrasound-guided transbronchial needle aspiration of lymph nodes, and forceps biopsy of station 7. Pathology of the lymph nodes was significant for non-caseating granulomas. Ziehl–Neelsen and silver stains were negative for acid fast bacilli and fungi, respectively. Patient was diagnosed with Sarcoidosis and treatment with Methotrexate and folic acid was initiated. Steroids were avoided in the setting of morbid obesity (BMI >40), prediabetes and history of psychiatric disease. DISCUSSION: This case illustrates the potential for misdiagnosis based on high Standardized Uptake Values on FDG PET-CT scan and the value of a comprehensive evaluation involving tissue biopsy. A SUV of >2.5 is suggestive of malignancy however, false positives due to 18-FDG uptake by inflammatory cells in infectious and granulomatous diseases have been reported in a few case series. Sarcoidosis is characterized by non-caseating granulomas that are formed by the recruitment of multiple inflammatory cells such as activated macrophages and lymphocytes which can lead to increased radiotracer uptake. Other causes of granulomatous disease such as fungal and mycobacterial infections, foreign bodies, pneumoconiosis and vasculitis should be explored. Newer nuclear imaging modalities using alternate radio-tracers have been developed to improve specificity however, low accessibility has rendered a paucity of available data. CONCLUSIONS: FDG PET-CT can aid in the detection and monitoring of various pathologies including Sarcoid. Due to the lack of specificity of any one diagnostic evaluation currently, it is important to obtain pathological confirmation in addition to imaging, and rule out other causes of non-caseating granulomas, prior to starting treatment. REFERENCE #1: Anjali Shetty, M., and John D Carter, MD, Sarcoidosis mimicking lymphoma on FDG-PET imaging. Radiology Case Reports 2011. REFERENCE #2: Paul E. Kinahan, P.a.J.W.F., MD, PET/CT Standardized Uptake Values (SUVs) in Clinical Practice and Assessing Response to Therapy. Semin Ultrasound CT MR., 2010. REFERENCE #3: Miyakubo M, Oriuchi N, Tsushima Y, Higuchi T, Koyama K, Arai K, et al. Diagnosis of maxillofacial tumor with L-3-[F-18]-fluoro-alpha-methyltyrosine (FMT) PET: a comparative study with FDG-PET. Ann Nucl Med. 2007. DISCLOSURES: No relevant relationships by Hamna Ahmad, source=Web Response No relevant relationships by Sarah Dubin, source=Web Response No relevant relationships by Ashraf Gohar, source=Web Response No relevant relationships by Sindhuja Palle, source=Web Response

Utilization of High-pressure Suction for EBUS-TBNA Sampling in Suspected Lung Cancer.

Background:Sample adequacy for immediate molecular testing is paramount in lung cancer. To date, several endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) sampling setups have been evaluated, however, the utilization of high-pressure suction (HPS) has not yet been reported.The aim of this study was to evaluate the utilization of HPS onto the needle and its effect on sample volume and adequacy for molecular testing in patients with suspected lung cancer.Methods:We retrospectively analyzed 128 consecutive EBUS-TBNA performed for suspected lung cancer. This was confirmed in 109 patients. Other diagnoses confirmed in 12, and 7 referred for surgery. Sixty-three patients (89 targets) had HPS (May to September 2020), and compared with 46 (72 targets) who had standard vacuum syringe suction (October 2019 to March 2020). Several parameters and outcomes evaluated, such as number of needle passes, needle strokes, needle size, target size, positron emission tomography avidity, procedure time, blood content score, sample volume, adequacy for molecular testing, as well as baseline patient characteristics and complication rate.Results:There was no difference between the 2 groups in all baseline parameters and characteristics. In multivariable analysis, HPS was associated with significantly higher sample volume (11.2 vs. 9.1 mm3, P=0.036) and less additional procedures to achieve full molecular profiling (2/52 vs. 7/40, P=0.042), in necrotic targets of non−small cell lung cancer. Diagnostic yields were comparable.Conclusion:HPS appears to be simple, no-cost, and safe, promising higher sample volume compared with vacuum syringe suction, and also appears to be associated with higher success of full molecular testing with less additional procedures, in non−small cell lung cancer necrotic targets.

Dose escalated simultaneous integrated boost of gross nodal disease in gynecologic cancers: a multi-institutional retrospective analysis and review of the literature.

PurposeTypical doses of 45–50.4 Gy used to treat regional nodes have demonstrated inadequate control of gross nodal disease (GND) in gynecologic cancer, and accelerated repopulation may limit the efficacy of a sequential boost. We reviewed outcomes of patients treated with a simultaneous integrated boost (SIB) at 2.25 Gy per fraction to positron emission tomography (PET) avid GND to evaluate toxicity and tumor control using this dose-escalated regimen.Materials and MethodsA total of 83 patients with gynecologic cancer and PET avid inguinal, pelvic, or para-aortic lymphadenopathy were treated using intensity-modulated radiation therapy (IMRT) with SIB. Primary cancers were mostly cervical (51%) and endometrial (34%), and included patients who received concurrent chemotherapy (59%) and/or brachytherapy boost (78%).ResultsMedian follow-up from radiation completion was 12.6 months (range, 2.7 to 92.9 months). Median dose to elective lymphatics was 50.4 Gy (range, 45 to 50.4 Gy) at 1.8 Gy/fraction. Median SIB dose and volume were 63 Gy (range, 56.3 to 63 Gy) and 72.8 mL (range, 6.8 to 1,134 mL) at 2–2.25 Gy/fraction. Nodal control was 97.6% in the SIB area while 90.4% in the low dose area (p = 0.013). SIB radiotherapy (RT) field failure-free, non-SIB RT field failure-free, and out of RT field failure-free survival at 4 years were 98%, 86%, and 51%, respectively. Acute and late grade ≥3 genitourinary toxicity rates were 0%. Acute and late grade ≥3 gastrointestinal toxicity rates were 7.2% and 12.0%, respectively.ConclusionDose escalated SIB to PET avid adenopathy results in excellent local control with acceptable toxicity.

A cost-utility analysis comparing CT surveillance, PET-CT surveillance, and planned postradiation neck dissection for advanced nodal HPV-positive oropharyngeal cancer.

The cost utility of image-guided surveillance using computed tomography (CT) and positron emission tomography (PET)-CT to planned postradiation neck dissection (PRND) was compared for the management of advanced nodal human papillomavirus-positive oropharyngeal cancer following chemoradiation. A universal payer perspective was adopted. A Markov model was designed to simulate four treatment approaches with 3-month cycles over a lifetime horizon: 1) CT surveillance, 2) standard PET-CT surveillance, 3) a novel PET-CT approach with repeat PET at 6 months postchemoradiation for equivocal responders, and 4) PRND. Parameters including probabilities of CT nodal progression/resolution, PET avidity, recurrence, and survival were obtained from the literature. Costs were reported in 2019 Canadian dollars and utilities were expressed in quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty. PET-CT surveillance dominated CT surveillance and PRND in the base case scenario, and the novel PET-CT approach was the most cost-effective strategy across a wide range of variables tested in one-way sensitivity analysis. On probabilistic sensitivity analysis, novel PET-CT surveillance was the most cost-effective strategy in 78.1% of model iterations at a willingness-to-pay of $50,000/QALYs. Novel PET-CT surveillance resulted in a 49% lower rate of neck dissection compared with traditional PET-CT, and yielded an incremental benefit of 0.14 QALYs with average cost savings of $1309. Image-guided surveillance including PET-CT and CT are more cost effective than PRND. The novel PET-CT approach with repeat PET for equivocal responders was the dominant strategy and yielded both higher benefit and lower costs compared with standard PET-CT surveillance.

Modern Management of High-risk Soft Tissue Sarcoma With Neoadjuvant Chemoradiation: A Single-center Experience.

Neoadjuvant chemoradiation (NA-CRT), followed by resection of high-risk soft tissue sarcoma (STS), may offer good disease control and toxicity outcomes. We report on a single institution's modern NA-CRT experience. Delay to surgical resection, resection margin status, extent of necrosis, tumor cell viability, presence of hyalinization, positron emission tomography (PET)/computed tomography data, and treatment toxicities were collected. Using the Kaplan-Meier survival analysis, 5-year overall survival, disease-free survival, distant metastasis-free survival, and local control (LC) were estimated. Clinicopathologic features and PET/computed tomography avidity changes were assessed for their potential predictive impact using the log-rank test. From 2011 to 2018, 37 consecutive cases of localized high-risk STS were identified. Twenty-nine patients underwent ifosfamide-based NA-CRT to a median dose of 50 Gy before en bloc resection. At a median follow-up of 40.3 months, estimated 5-year overall survival was 86.1%, disease-free survival 70.2%, distant metastasis-free survival 75.2%, and LC 86.7%. Following NA-CRT, a median reduction of 54.7% was observed in tumor PET avidity; once resected, median tumor necrosis of 60.0% with no viable tumor cells was detected in 13.8% of the cases. Posttreatment resection margins were negative in all patients, with 27.6% having a margin of ≤1 mm. Delays of over 6 weeks following the end of radiation treatment to surgical resection occurred in 20.7% cases and was suggestive of inferior LC (92.8% vs. 68.6%, P=0.025). This single-institution series of NA-CRT demonstrates favorable disease control. Delay in surgical resection was associated with inferior LC, a finding that deserves further evaluation in a larger cohort. Level III-retrospective cohort study.

BRONCHOCENTRIC GRANULOMATOSIS: THE MALIGNANCY MIMICKER

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Bronchocentric Granulomatosis (BG) is a rare disorder with a wide variety of clinical presentations. It can be subdivided into two epidemiological categories: asthmatic and non-asthmatic. Here, we describe a non-asthmatic with BG whose presentation was concerning for malignancy. CASE PRESENTATION: A 46 year-old male never smoker with a history of bronchiectasis and seizures was referred for abnormal computed tomography (CT) scans of the chest, performed in the context of a 2 year history of dry cough. He had no associated symptoms including wheezing, dyspnea, nasal congestion, acid reflux, and weight loss. Serial CT scans revealed a spiculated nodule in the left upper lobe that had decreased in size but persisted across 2 years. Notably, he had a biological sister who passed away from a biopsy proven small cell lung carcinoma at age 27. Physical examination was unremarkable, as well as pulmonary function testing and serological testing, including a normal eosinophil count. A positron emission tomography (PET) scan showed that the nodule was PET avid with an SUV of 5.74 g/mL. The patient ultimately underwent a left upper lobe trisegmentectomy for the nodule. Pathology revealed necrotizing granulomatous inflammation with destruction of adjacent bronchiolar walls, consistent with BG. Surgical specimen bacterial and fungal cultures were negative. Serum aspergillus antibodies, galactomannan, antineutrophil cytoplasmic antibodies, and rheumatoid factor were also negative. His cough improved after his surgery, and a CT scan done 2 months postoperatively showed no abnormalities other than post-surgical changes. DISCUSSION: Patients with BG commonly present with constitutional symptoms such as fatigue and fever. Respiratory symptoms are reportedly rare, but tend to be seen more commonly in the asthmatic type. A chronic indolent presentation is more common for non-asthmatic patients. Associated etiologies include allergic bronchopulmonary aspergillosis, rheumatoid arthritis, vasculitides, and mycobacterial infections. In the context of such associated diseases, treatment of the underlying cause is imperative. In idiopathic disease, most patients recover without therapy but steroids can also be used. Radiographically BG can present as pulmonary nodules or consolidation, often in the upper lobes. Diagnosis of BG is made based on histopathology of a surgical lung biopsy specimen. It is characterized by peribronchiolar necrotizing granulomatous inflammation, limited to the airway and parenchyma without vascular involvement. CONCLUSIONS: In our case, the pulmonary nodule decreased in size prior to resection, which could represent the spontaneous resolution previously described in idiopathic non-asthmatic patients. This case illustrates that BG should be in the differential diagnosis for patients with a suspected malignant nodule in the absence of clinical symptoms or comorbidities concerning for malignancy. Reference #1: Ohshimo, S., et al. (2017). “Differential diagnosis of granulomatous lung disease: clues and pitfalls: Number 4 in the Series “Pathology for the clinician” Eur Respir Rev 26(145). Reference #2: Mimur, K., et al. (2011). “A case of bronchocentric granulomatosis resembling lung cancer on diagnostic imaging.” Nihon Kokyuki Gakkai Zasshi 49(12): 970-975 Reference #3: Granada, M. and A. C. Theodore (2010). A Case Of Bronchocentric Granulomatosis Following Treatment For Non Hodgkin Lymphoma. C43. Case Reports In Interstitial Lung Disease and More II, American Thoracic Society: A4505-A4505. DISCLOSURES: No relevant relationships by Johanna Ben-Ami, source=Web Response No relevant relationships by Oki Ishikawa, source=Web Response No relevant relationships by Bushra Mina, source=Web Response No relevant relationships by Doaa Morrar, source=Web Response

Clear Cell Sugar Tumour

A 56-year-old female smoker with a history of right breast cancer (T1N0M0) had an incidental finding of an 8-mm right lower lobe solitary pulmonary nodule on computed tomography scan. The lesion was not positron emission tomography avid; however, it slowly progressed in size on surveillance computed tomography to 11 mm. She proceeded to thoracotomy and right lower lobectomy with lymph node sampling. Histology confirmed a clear cell sugar tumour. Clear cell sugar tumour of the lung is a remarkably rare benign pulmonary neoplasm of perivascular epithelioid origin, and a member of the PEComatous group of tumours. PEComas of the lung are divided into lymphangioleiomyomatosis, benign PEComas (including clear cell sugar tumour), and malignant PEComas. PEComas can be found in other sites, including the female genital and gastrointestinal tracts. The tumours characteristically contain a large amount of glycogen; therefore, leading differentials to consider are metastatic renal cell carcinoma and clear cell pulmonary carcinomas. Diagnosis is established by demonstrating immunoreactivity for human melanoma black (HMB-45) and S-100 protein, with no reactivity for cytokeratin 7 or epithelial membrane antigen. The general recommendation is for surgical resection without adjuvant chemotherapy.

Induction of Thioredoxin-Interacting Protein by a Histone Deacetylase Inhibitor, Entinostat, Is Associated with DNA Damage and Apoptosis in Esophageal Adenocarcinoma.

In 2017, an estimated 17,000 individuals were diagnosed with esophageal adenocarcinoma (EAC), and less than 20% will survive 5 years. Positron emission tomography avidity is indicative of high glucose utilization and is nearly universal in EAC. TXNIP blocks glucose uptake and exhibits proapoptotic functions. Higher expression in EAC has been associated with improved disease-specific survival, lack of lymph node involvement, reduced perineural invasion, and increased tumor differentiation. We hypothesized that TXNIP may act as a tumor suppressor that sensitizes EAC cells to standard chemotherapeutics. EAC cell lines and a Barrett epithelial cell line were used. qRT-PCR, immunoblot, and immunofluorescence techniques evaluated gene expression. TXNIP was stably overexpressed or knocked down using lentiviral RNA transduction techniques. Murine xenograft methods examined growth following overexpression of TXNIP. Apoptosis and DNA damage were measured by annexin V and γH2AX assays. Activation of the intrinsic apoptosis was quantitated with green fluorescence protein-caspase 3 reporter assay. In cultured cells and an esophageal tissue array, TXNIP expression was higher in Barrett epithelia and normal tissue compared with EAC. Constitutive overexpression of TXNIP decreased proliferation, clonogenicity, and tumor xenograft growth. TXNIP overexpression increased, whereas knockdown abrogated, DNA damage and apoptosis following cisplatin treatment. An HDAC inhibitor, entinostat (currently in clinical trials), upregulated TXNIP and synergistically increased cisplatin-mediated DNA damage and apoptosis. TXNIP is a tumor suppressor that is downregulated in EACC. Its reexpression dramatically sensitizes these cells to cisplatin. Our findings support phase I/II evaluation of "priming" strategies to enhance the efficacy of conventional chemotherapeutics in EAC. Mol Cancer Ther; 17(9); 2013-23. ©2018 AACR.

Significance of pleural effusion at diagnosis in pediatric Hodgkin lymphoma: a report from Children\u2019s Oncology Group protocol AHOD0031

BackgroundPleural effusion at presentation in Hodgkin lymphoma has been associated with inferior outcome but has not been systematically evaluated.ObjectiveTo determine whether pleural effusion at presentation in children with Hodgkin lymphoma is a primary indicator of poor prognosis or secondary to associated factors.Materials and methodsChildren’s Oncology Group (COG) AHOD0031, a randomized, response-based, centrally reviewed protocol, enrolled 1,712 eligible patients <22 years of age with initial presentation of intermediate risk, biopsy-proven Hodgkin lymphoma; 1,423 had available imaging for retrospective review. We coded effusions as fluid-only or with associated pleural nodule or adjacent lung or bone involvement and correlated this with disease stage, tumor response, large mediastinal adenopathy, and mass effect on the superior vena cava (SVC) and left innominate vein. We recorded change in size and character of effusions post-chemotherapy.ResultsPleural effusions were present in 217, with 204 having fluid-only and 13 having associated solid components. Patients with effusions were more likely to have large mediastinal adenopathy (P<0.0001), be slow early responders (P<0.0001) and have higher relapse rate (P<0.0001). Vascular compression was not significantly correlated with pleural effusion. Of 121 patients with adequate [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT imaging, no FDG PET avidity was seen in any pleural effusion but was present in solid components. The side of the pleural effusion in those with moderate or large effusions was highly associated with the side of large mediastinal adenopathy (P<0.0001). Statistical analysis indicates that pleural effusion is an independent risk factor for poorer response and relapse.ConclusionPleural effusion in Hodgkin lymphoma is an important independent poor prognostic indicator for response and relapse.

Uptake of [18F]fluorodeoxyglucose in initial positron-emission tomography predicts survival in MALT lymphoma

AbstractThe role of [18F]fluorodeoxyglucose (FDG) positron-emission tomography (PET) in mucosa-associated lymphoid tissue (MALT) of marginal zone lymphoma remains poorly defined. We correlated initial PET with pathology, clinical factors, and outcome. From January 2001 to July 2012, 173 MALT lymphoma patients with a biopsied lesion identified on PET within 90 days of tissue biopsy were analyzed. PET positivity and intensity of FDG uptake were correlated with clinical factors and patient outcome. Among 173 accrued cases, biopsied site was PET avid in 123 patients (71%); median standardized uptake value (SUV) was 6.0 (range: 0.7-28.0), and SUV >10.0 in 20 patients (16%). PET avidity varied by organ sites. PET positivity correlated with higher International Prognostic Index, but not with 5-year overall survival (OS; 96% vs 88%, PET negative vs positive, P = .229) or 5-year progression-free survival (67% vs 56%, P = .493). SUV was an independent prognostic factor of OS, and an increased SUV was associated with a decreasing 5-year OS. Patients who presented with SUV ≥10 had a higher rate of subsequent large cell transformation (20% vs 5%, P = .035) and inferior OS (78% vs 92%, P = .008). The exact role of FDG PET in the management of MALT lymphoma, beyond initial staging, remains to be defined.

MP18-11 EXPLORING THE CLINICAL UPTAKE AND USE OF PSMA PET MRI HYBRID IMAGING IN PROSTATE CANCER PATIENTS AT AN ACADEMIC CENTER IN AUSTRALIA

You have accessJournal of UrologyImaging/Radiology: Uroradiology III1 Apr 2017MP18-11 EXPLORING THE CLINICAL UPTAKE AND USE OF PSMA PET MRI HYBRID IMAGING IN PROSTATE CANCER PATIENTS AT AN ACADEMIC CENTER IN AUSTRALIA Andre Joshi, Cheryl Nicholson, Handoo Rhee, Ian McKenzie, Janelle Munns, Greg Malone, Eric Chung, Malcolm Lawson, Peter Heathcote, John Preston, Simon Wood, Sonja Gustafson, Ken Miles, and Ian Vela Andre JoshiAndre Joshi More articles by this author , Cheryl NicholsonCheryl Nicholson More articles by this author , Handoo RheeHandoo Rhee More articles by this author , Ian McKenzieIan McKenzie More articles by this author , Janelle MunnsJanelle Munns More articles by this author , Greg MaloneGreg Malone More articles by this author , Eric ChungEric Chung More articles by this author , Malcolm LawsonMalcolm Lawson More articles by this author , Peter HeathcotePeter Heathcote More articles by this author , John PrestonJohn Preston More articles by this author , Simon WoodSimon Wood More articles by this author , Sonja GustafsonSonja Gustafson More articles by this author , Ken MilesKen Miles More articles by this author , and Ian VelaIan Vela More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.621AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Positron emission tomography (PET) using prostate specific membrane antigen (PSMA) detects prostate cancer lesions with a higher sensitivity and specificity when compared to standard imaging. Hybrid PET Magnetic Resonance Imaging (MRI) has now been introduced to provide potentially improved characterization of lesions with added PET avidity. We evaluate the utilization of this novel imaging modality at the Princess Alexandra Hospital (PAH) and assess our initial outcomes. METHODS A retrospective review of all PSMA PET MRI scans undertaken at the PAH since the introduction of the technology was performed. Imaging data was collected alongside baseline clinical data, PSA, previous histology, previous treatments, indication of scans, requesting clinicians and clinical outcomes. RESULTS A total of 187 PSMA PET MRI scans were performed at the PAH from April 2015 to October 2016. The median age of imaged patients was 68, with a median PSA of 6ng/ml and Gleason score of 7 at the time of scan. 153 scans were positive for PSMA avid disease (81.8%). Scans were requested in the setting of biochemical recurrence (n=94), preoperative staging (n=77), evaluation of treatment response (n=11) and diagnostic purposes (n=5). Urologists requested PSMA PET MRI most frequently with 111 scans, of which 58.6% requested for preoperative staging. Radiation oncologists requested 69 scans with 75.4% of these in the biochemical recurrence setting. Only 7 scans were requested by medical oncologists. Amongst patients with biochemical recurrence the lowest PSA of a positive scan was 0.02 ng/ml. In this group 43 patients had prior surgery with 19 positive scans (44%). 51 patients were treated with ADT and or EBRT and 46 had positive scans (90.2%). 29 patients had tissue samples to validate PSMA PET MRI. 26 patients (89.7%) had adenocarcinoma on histology correlating with avid lesions on PSMA PET. CONCLUSIONS PSMA PET MRI has had rapid uptake in use since introduction at the PAH. Urologists and radiation oncologists appear to utilize this imaging modality most; Urologists for a preoperative “one stop shop” staging study and radiation oncologists in biochemical recurrence. From this data is also appears that a positive PSMA PET/MRI is highly suggestive of prostate cancer, with a specificity of 89.7%. Hybrid PET/MRI may be used to stage men locally and systemically with one scan, with lower radiation and at PSA ≤1 ng/ml. This modality has the potential to significantly improve prostate cancer staging and allow early identification of recurrent disease. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e224 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Andre Joshi More articles by this author Cheryl Nicholson More articles by this author Handoo Rhee More articles by this author Ian McKenzie More articles by this author Janelle Munns More articles by this author Greg Malone More articles by this author Eric Chung More articles by this author Malcolm Lawson More articles by this author Peter Heathcote More articles by this author John Preston More articles by this author Simon Wood More articles by this author Sonja Gustafson More articles by this author Ken Miles More articles by this author Ian Vela More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Imaging Hepatocellular Carcinoma With 68Ga-Citrate PET: First Clinical Experience.

While cross-sectional imaging with computed tomography (CT) and magnetic resonance imaging is the primary method for diagnosing hepatocellular carcinoma (HCC), they provide little biological insight into this molecularly heterogeneous disease. Nuclear imaging tools that can detect molecular subsets of tumors could greatly improve diagnosis and management of HCC. To this end, we conducted a patient study to determine whether HCC can be resolved using 68Ga-citrate positron emission tomography (PET). One patient with recurrent HCC was injected with 300 MBq of 68Ga-citrate and imaged with PET/CT 249 minutes post injection. Four (28%) of 14 hepatic lesions were avid for 68Ga-citrate. One extrahepatic lesion was not PET avid. The average maximum standardized uptake value (SUVmax) for the lesions was 7.2 (range: 6.2-8.4), while the SUVmax of the normal liver parenchyma was 4.7 and blood pool was 5.7. The avid lesions were not significantly larger than the quiescent lesions, and a prior contrast CT showed uniform enhancement among the lesions, suggesting that tumor signals are due to specific binding of the radiotracer to the transferrin receptor, rather than enhanced vascularity in the tumor microenvironment. Further studies are required in a larger patient cohort to verify the molecular basis of radiotracer uptake and the clinical utility of this tool.

P2.04-008 Diagnostic Performance of PET-CT for Anterior Mediastinal Lesions - The DECiMaL Study: Topic: Thymic Malignancies Clinical and Translational

The diagnostic performance of 18-FDG positron emission tomography (PET) on the ability to differentiate malignant from benign lesions in the anterior mediastinum is not defined and therefore the clinical utility is unknown. The aim of this study is to collate multi-institutional data to determine the value by defining diagnostic performance of FDG PET/CT for malignancy in patients undergoing surgery with an anterior mediastinal mass. DECiMaL Study is a multicenter, retrospective, collaborative cohort study in seven UK sites. We included all patients undergoing surgery (diagnostic or therapeutic) who presented with an anterior mediastinal mass and underwent PET/CT as part of their diagnostic work-up. PET/CT was considered positive for any reported PET avidity as stated in the official report and the reference was the resected specimen reported by histopathology using WHO criteria. Diagnostic test performance was expressed as sensitivity, specificity, positive and negative predicted values with corresponding 95% confidence intervals. Between January 2002 and June 2015 a total of 134 patients were submitted with a mean age (SD) of 55 years (16) of which 69 (51%) were men. All patients had pre-operative PET CT and the histology was thymic hyperplasia in 10 patients (8%), thymic cyst in 8 (6%) and no malignancy in 15 (11%) and these were classified as “benign”. Histology was thymoma in 55 patients (41%), other malignancies in 38 (28%) and thymic carcinoma in 8 (6%), and these were classified as “malignant.” The sensitivity and specificity of PET/CT to correctly classify malignant disease were 83% (95% CI 74 to 89) and 58% (37 to 78). The positive and negative predictive values were 90% (83 to 95) and 42% (26 to 61%). The results of our study suggests reasonable sensitivity but no specificity implying that a negative PET/CT is useful to rule out the diagnosis of malignant disease whereas a positive result has no value in the discrimination between malignant and benign disease of the anterior mediastinum.

Impact of pre-operative positron emission tomography in gallbladder cancer

BackgroundCurrent pre-operative staging methods for gallbladder cancer (GBC) are suboptimal in detecting metastatic disease. Positron emission tomography (PET) may have a role but data are lacking. MethodsPatients with GBC and PET assessed by a hepatobiliary surgeon in clinic between January 2001 and June 2013 were retrospectively reviewed. Computed tomography (CT)/magnetic resonace imaging (MRI) were correlated with PET scans and analysed for evidence of metastatic or locally unresectable disease. Medical records were reviewed to determine if PET scanning was helpful by preventing non-therapeutic surgery or enabling resection in patients initially deemed unresectable. ResultsThere were 100 patients including 63 incidental GBC. Thirty-eight patients did not proceed to surgery, 35 were resected and 27 patients were explored but had unresectable disease. PET was positive for metastatic disease in 39 patients (sensitivity 56%, specificity 94%). Five patients definitively benefitted from PET: in 3 patients PET found disease not seen on CT, and 2 patients with suspicious CT findings had negative PET and successful resections. In a further 12 patients PET confirmed equivocal CT findings. Three patients had additional invasive procedures performed owing to PET avidity in other sites. Utility of PET was higher in patients with suspicious nodal disease on CT [odds ratio (OR) 7.1 versus no nodal disease, P = 0.0004], and in patients without a prior cholecystectomy (OR 3.1 versus post-cholecystectomy, P = 0.04). ConclusionAddition of PET to conventional cross-sectional imaging has a modest impact on management pre-operatively particularly in patients without a prior cholecystectomy and to confirm suspicious nodal disease on CT.

Positron Emission Tomography-avid Adrenal Mass and Incidental Renal Mass in a 70-Year-Old Woman With Newly Diagnosed Breast Cancer

Positron Emission Tomography-avid Adrenal Mass and Incidental Renal Mass in a 70-Year-Old Woman With Newly Diagnosed Breast Cancer