ORCID Profile
0000-0001-8622-159X
Current Organisation
Peter MacCallum Cancer Centre
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2020
Publisher: Wiley
Date: 22-10-2019
DOI: 10.1111/BJU.14876
Abstract: To assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with The TheraP trial (ANZUP 1603) is an open-label, randomized, stratified, two-arm multicentre phase 2 trial comparing the activity and safety of cabazitaxel chemotherapy vs
Publisher: Society of Nuclear Medicine
Date: 06-2017
DOI: 10.2967/JNUMED.117.190215
Abstract: We evaluated the incidence of synchronous primary malignancies in patients undergoing
Publisher: Wiley
Date: 28-07-2021
Abstract: This study aims to investigate whether nodal metabolic tumour volume (nMTV) and nodal total lesion glycolysis (nTLG) on Fluorine‐18 fluoro‐deoxy‐glucose positron emission tomography–computed tomography ( 18 F‐FDG PET/CT) in inoperable node‐positive stage II and III non‐small cell lung cancer (NSCLC) are independent predictors of overall survival (OS) in patients undergoing curative‐intent chemoradiotherapy/radiotherapy (CRT/RT). Data from two prospective trials between 2004 and 2016 were analysed retrospectively. Primary, nodal and total metabolic tumour volume and total lesion glycolysis (pMTV, nMTV, tMTV, pTLG, nTLG and tTLG, respectively) were derived from baseline 18 F‐FDG PET/CT. Cox regressions were used to model OS by 18 F‐FDG PET/CT parameters adjusting for overall stage. 89 patients with stage II (8%) and stage III (92%) were included. The median age at diagnosis was 67 years 62% were male. The median follow‐up was 6.9 years the median OS was 2.2 years (95% CI 1.7–3.1). The median pMTV, nMTV and tMTV were 14 mL (range 0–360), 8 mL (range 0–250) and 34 mL (range 3–384), respectively. In 3 patients, the primary lesion could not be delineated from the central hilar mass. There was no association between nMTV (adjusted HR 1.04, 95% CI 0.95–1.15, P ‐value 0.43), pMTV (adjusted HR 1.0, 95% CI 0.96–1.04, P ‐value 0.92), tMTV (adjusted HR 1.0, 95% CI 0.97–1.04, P ‐value 0.88), nTLG, pTLG or tTLG and OS. Consistent results were noted when patients with central hilar lesions were excluded from analysis. In node‐positive stage II and III NSCLC patients who underwent 18 F‐FDG PET/CT‐guided target delineation curative‐intent concurrent CRT/RT, metabolic parameters did not appear to provide independent prognostication.
Publisher: Wiley
Date: 12-02-2020
DOI: 10.1111/BJU.14999
Abstract: Primary objectives: To determine the additive value of gallium‐68 prostate‐specific membrane antigen (PSMA) positron emission topography (PET)/computed tomography (CT) when combined with multiparametric magnetic resonance imaging (mpMRI) detecting clinically significant prostate cancer (csPCa) in men undergoing initial biopsy for suspicion of PCa, and to determine the proportion of men who could have avoided prostate biopsy with positive mpMRI (PI‐RADS ≥3) but negative PSMA‐PET/CT. Secondary objectives: To determine the proportion of men who had csPCa detected only by PSMA‐PET/CT or only by systematic prostate biopsy to compare index lesions by template biopsies vs targeted lesions identified on mpMRI or PSMA‐PET/CT to assess whether there may be health economic benefit or harm if PSMA‐PET/CT is incorporated into the diagnostic algorithm and to develop a nomogram which combines clinical, imaging and biomarker data to predict the likelihood of csPCa. The PRIMARY trial is a multicentre, prospective, cross‐sectional study that meets the criteria for level 1 evidence in diagnostic test evaluation. PRIMARY will investigate if a limited (pelvic‐only) PSMA‐PET/CT in combination with routine mpMRI can reliably discriminate men with csPCa from those without csPCa. We conducted a power calculation based on pilot data and will recruit up to 600 men who will undergo PSMA‐PET/CT (the index test), mpMRI (standard test) and transperineal template + targeted (PSMA‐PET/CT and/or mpMRI) biopsies (reference test). The conduct and reporting of the mpMRI and PSMA‐PET/CT will be blinded to each other. The PRIMARY trial will measure and compare sensitivity, specificity, positive predictive value and negative predictive value of both mpMRI and PSMA‐PET/CT vs targeted prostrate biopsy. The results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of csPCa. Furthermore, we will assess whether there is a health economic benefit in incorporating PSMA‐PET/CT into the diagnostic algorithm. This trial will provide robust prospective data to determine the diagnostic ability of PSMA‐PET/CT used in addition to mpMRI. It will establish if certain patients can avoid biopsy in the investigation of PCa.
Publisher: Springer Science and Business Media LLC
Date: 29-10-2018
DOI: 10.1007/S00345-018-2524-Z
Abstract: The heterogeneity of prostate cancer has made imaging modalities of crucial importance in this disease. Accurate diagnosis and staging of the volume and extent of disease, especially in advanced and metastatic prostate cancer, can help to tailor the timing and modalities of treatment. While MRI has been effective in the detection of significant prostate cancer, its use in the identification and quantification of extraprostatic disease is limited. This gap is now being filled by PSMA PET. PSMA PET scans have now been shown to have a role in all stages in the prostate cancer journey. Emerging evidence has shown its promise in primary staging, restaging and theranostics. In this paper, we review the evidence for the use of PSMA PET in the various stages of prostate cancer, from initial diagnosis to advanced metastatic disease where other systemic treatments have failed.
Publisher: Wiley
Date: 17-12-2016
DOI: 10.1118/1.4937599
Abstract: Computed tomography ventilation imaging (CTVI) aims to visualize air-volume changes in the lung by quantifying respiratory motion in 4DCT using deformable image registration (DIR). A problem is that DIR-based CTVI is sensitive both to 4DCT image artifacts and DIR parameters, hindering clinical validation of the technique. To address this, the authors present a streamlined CTVI approach that estimates blood-gas exchange in terms of time-averaged 4DCT Hounsfield unit (HU) values without relying on DIR. The purpose of this study is to quantify the accuracy of the HU-based CTVI method using high-resolution (68)Ga positron emission tomography ("Galligas PET") scans in lung cancer patients. The authors analyzed Galligas 4D-PET/CT scans acquired for 25 lung cancer patients at up to three imaging timepoints during lung cancer radiation therapy. For each 4DCT scan, the authors produced three types of CTVIs: (i) the new method (CTV IHU¯), which takes the 4D time-averaged product of regional air and tissue densities at each voxel, and compared this to DIR-based estimates of (ii) breathing-induced density changes (CTV IDIR-HU), and (iii) breathing-induced volume changes (CTV IDIR-Jac) between the exhale/inhale phase images. The authors quantified the accuracy of CTV IHU¯, CTV IDIR-HU and CTV IDIR-Jac versus Galligas PET in terms of voxel-wise Spearman correlation (r) and the separation of mean voxel values between clinically defined defect/nondefect regions. Averaged over 62 scans, CTV IHU¯ showed better accuracy than CTV IDIR-HU and CTV IDIR-Jac in terms of Spearman correlation with Galligas PET, with (mean ± SD) r values of (0.50 ± 0.17), (0.42 ± 0.20), and (0.19 ± 0.23), respectively. A two-s le Kolmogorov-Smirnov test indicates that CTV IHU¯ shows statistically significant separation of mean ventilation values between clinical defect/nondefect regions. Qualitatively, CTV IHU¯ appears concordant with Galligas PET for emphysema related defects, but differences arise in tumor-obstructed regions (where aeration is overestimated due to motion blur) and for other abnormal morphology (e.g., fluid-filled or peritumoral lung with HU ≳ - 600) where the assumptions of the HU model may break down. The HU-based CTVI method can improve voxel-wise correlations with Galligas PET compared to DIR-based methods and may be a useful approximation for voxels with HU values in the range (-1000, - 600). With further clinical verification, HU-based CTVI could provide a straightforward and reproducible means to estimate lung ventilation using free-breathing 4DCT.
Publisher: Springer Science and Business Media LLC
Date: 12-01-2016
Publisher: Society of Nuclear Medicine
Date: 18-01-2013
Publisher: Springer Science and Business Media LLC
Date: 25-06-2018
DOI: 10.1007/S00259-018-4070-8
Abstract: Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.CPET.2016.12.004
Abstract: The role of gallium-68 (
Publisher: Wiley
Date: 10-10-2013
DOI: 10.1118/1.4824318
Abstract: To create an accurate map of the distribution of radiation dose deposition in healthy and target tissues during radionuclide therapy. Serial quantitative SPECT∕CT images were acquired at 4, 24, and 72 h for 28 (177)Lu-octreotate peptide receptor radionuclide therapy (PRRT) administrations in 17 patients with advanced neuroendocrine tumors. Deformable image registration was combined with an in-house programming algorithm to interpolate pharmacokinetic uptake and clearance at a voxel level. The resultant cumulated activity image series are comprised of values representing the total number of decays within each voxel's volume. For PRRT, cumulated activity was translated to absorbed dose based on Monte Carlo-determined voxel S-values at a combination of long and short ranges. These dosimetric image sets were compared for mean radiation absorbed dose to at-risk organs using a conventional MIRD protocol (OLINDA 1.1). Absorbed dose values to solid organs (liver, kidneys, and spleen) were within 10% using both techniques. Dose estimates to marrow were greater using the voxelized protocol, attributed to the software incorporating crossfire effect from nearby tumor volumes. The technique presented offers an efficient, automated tool for PRRT dosimetry based on serial post-therapy imaging. Following retrospective analysis, this method of high-resolution dosimetry may allow physicians to prescribe activity based on required dose to tumor volume or radiation limits to healthy tissue in in idual patients.
Publisher: Springer Science and Business Media LLC
Date: 30-07-2015
Publisher: Springer Science and Business Media LLC
Date: 05-03-2014
DOI: 10.1007/S00277-014-2040-1
Abstract: The optimum follow-up of patients with transformed indolent lymphoma (TrIL) is not well defined. We sought to determine the utility of surveillance positron emission tomography-computed tomography (PET-CT) in patients with TrIL achieving complete metabolic remission (CMR) after primary therapy. We performed a retrospective analysis of patients with TrIL treated at Peter MacCallum Cancer Centre between 2002 and 2012 who achieved CMR after primary therapy who had ≥1 subsequent surveillance PET-CT. Of 55 patients with TrIL, 37 (67 %) received autologous stem cell transplantation as consolidation following chemoimmunotherapy. After a median follow-up of 34 (range 3-101) months, the actuarial 3-year progression-free (PFS) and overall survival (OS) were 77 % (95 %CI 62-86 %) and 88 % (75-94 %), respectively. Of 180 surveillance PET-CT scans, there were 153 true negatives, 4 false positives, 1 false negative, 7 indeterminate and 15 true positives. Considering indeterminate scans as false positives, the specificity of PET-CT for detecting relapse was 94 %, sensitivity was 83 %, positive predictive value was 63 % and negative predictive value was 98 %. All seven subclinical (PET detected) relapses were of low-grade histology in contrast, all nine relapses with diffuse large B cell lymphoma (DLBCL) were symptomatic. In our cohort of patients with TrIL achieving CMR, PET-CT detected subclinical low-grade relapses but all DLBCL relapses were accompanied by clinical symptoms. Thus, surveillance imaging of patients with TrIL achieving CMR is of limited clinical benefit. PET-CT should be reserved for evaluation of clinically suspected relapse.
Publisher: Springer Science and Business Media LLC
Date: 05-09-2019
Publisher: MDPI AG
Date: 04-09-2020
Abstract: Thoracic radiotherapy (RT) is required for the curative management of inoperable lung cancer, however, treatment delivery is limited by normal tissue toxicity. Prior studies suggest that using radiation-induced DNA damage response (DDR) in peripheral blood mononuclear cells (PBMC) has potential to predict RT-associated toxicities. We collected PBMC from 38 patients enrolled on a prospective clinical trial who received definitive fractionated RT for non-small cell lung cancer. DDR was measured by automated counting of nuclear γ-H2AX foci in immunofluorescence images. Analysis of s les collected before, during and after RT demonstrated the induction of DNA damage in PBMC collected shortly after RT commenced, however, this damage repaired later. Radiation dose to the tumour and lung contributed to the in vivo induction of γ-H2AX foci. Aliquots of PBMC collected before treatment were also irradiated ex vivo, and γ-H2AX kinetics were analyzed. A trend for increasing of fraction of irreparable DNA damage in patients with higher toxicity grades was revealed. Slow DNA repair in three patients was associated with a combined dysphagia/cough toxicity and was confirmed by elevated in vivo RT-generated irreparable DNA damage. These results warrant inclusion of an assessment of DDR in PBMC in a panel of predictive biomarkers that would identify patients at a higher risk of toxicity.
Publisher: Wiley
Date: 20-04-2022
DOI: 10.1111/BJU.15736
Publisher: Springer Science and Business Media LLC
Date: 20-09-2012
DOI: 10.1007/S00259-011-1937-3
Abstract: Tumour sequestration of radiotracer may lead to decreased bioavailability in healthy tissue resulting in lower absorbed radiation dose to critical organs. This study aims to assess the impact of disease burden, body habitus and urinary excretion on the biodistribution of (68)Ga-DOTA-octreotate. Ten patients with highly varied burden of somatostatin receptor-positive neuroendocrine tumour on (68)Ga-DOTA-octreotate positron emission tomography (PET)/CT were selected. Volumes of interest were drawn to derive the average uptake of renal parenchyma, spleen and body background, as well as to compute the fraction of injected activity sequestered in tumour and excreted in urine. Uptake values were assessed for correlation with tumour sequestration, weight, lean body weight, body surface area and urinary excretion. There was a trend for tumour sequestration, body habitus and urinary excretion to inversely influence all healthy tissue uptake values. In particular, renal uptake, splenic intensity and background soft tissue activity were all significantly correlated to composite factors combining tumour sequestration with body habitus and renal excretion. When combined with body habitus index or a body habitus index and renal excretion, tumour sequestration was strongly and significantly correlated inversely with renal uptake. Our results suggest that tumour sequestration of (68)Ga-DOTA-octreotate is a major factor leading to a sink effect that decreases activity concentration in healthy organs such as the kidney. However, body habitus and renal function also influence tissue biodistribution, in a synergistic fashion. Compared with a fixed-dose peptide receptor radionuclide therapy protocol, an adjusted-dose regimen tailored to tumour burden, body habitus and renal function may allow greater radiation dose to in idual lesions without substantially adding to toxicity in normal tissues.
Publisher: Wiley
Date: 28-01-2019
DOI: 10.1111/BJU.14648
Abstract: To develop a registration framework for correlating positron emission tomography/computed tomography (PET/CT) images with multiparametric magnetic resonance imaging (mpMRI) and histology of the prostate, thereby enabling voxel-wise analysis of imaging parameters. In this prospective proof-of-concept study, nine patients scheduled for radical prostatectomy underwent mpMRI and PET/CT imaging before surgery. One had PET imaging using PET/CT data from all nine patients were successfully registered with mpMRI and histology data. SUV We have developed a novel framework for registering and correlating PET/CT data at a voxel-level with mpMRI and histology. Despite registration uncertainties, perfusion and oxygenation parameters from DCE MRI and BOLD imaging showed correlations with PET SUV. Further analysis will be performed on a larger patient cohort to quantify these proof-of-concept findings. Improved understanding of the correlation between mpMRI and PET will provide supportive information for focal therapy planning of the prostate.
Publisher: Society of Nuclear Medicine
Date: 21-06-2017
Publisher: Elsevier BV
Date: 06-2018
Publisher: Society of Nuclear Medicine
Date: 17-03-2022
Publisher: Wiley
Date: 14-09-2023
DOI: 10.1111/BJU.16158
Abstract: Salvage radiation therapy and surveillance for low risk PSA recurrence have competing risks and benefits. The efficacy of early salvage radiation therapy to the prostate bed with or without pelvic lymph nodes compared to surveillance in patients with prostate specific antigen (PSA) recurrence following radical prostatectomy and no identifiable recurrent disease evident on prostate specific membrane antigen‐positron emission tomography/computerised tomography (PSMA‐PET/CT) is unknown. Dedicated Imaging Post‐Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) is an open‐label, multi‐centre, randomised phase 2 trial. The primary endpoint is 3‐year event‐free survival, with events comprising one of PSA recurrence (PSA ≥0.2ng/mL higher than baseline), radiologic evidence of metastatic disease or initiation of systemic or other salvage treatments. Secondary endpoints include patient reported outcomes, treatment patterns, participant perceptions and cost‐effectiveness. Eligible participants have PSA recurrence of prostate cancer following radical prostatectomy, defined by serum PSA 0.2‐0.5ng/mL, deemed low risk according to modified European Association of Urology (EAU) biochemical recurrence risk criteria (ISUP Grade Group ≤2, PSA doubling time more than 12 months), with no definite robable recurrent prostate cancer on PSMA‐PET/CT.
Publisher: Society of Nuclear Medicine
Date: 05-10-2019
Publisher: Elsevier BV
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 05-2019
DOI: 10.1007/S00259-019-04338-Z
Abstract: This pilot study assessed the independent and incremental value of All 24 cancer patients with suspected acute PE prospectively recruited underwent both The diagnostic conclusion was concordantly negative in 18 patients (75%). Of the six discordant diagnoses on independent reading, combined interpretation of V/Q PET/CTPA enabled a consensus conclusion in two patients, excluding PE in one and confirming PE in the other, similar to the initial diagnostic conclusion of the V/Q PET/CT. Of the remaining four patients, three had a single subsegmental thrombus on CTPA but a negative V/Q PET/CT scan, and two of these did not receive long-term anticoagulation and did not have a venous thromboembolic event during a 3-year follow-up period. The third patient, along with a patient with a positive V/Q PET/CT scan but a negative CTPA scan, presented with acute complications preventing any conclusions with regard to the appropriateness of the V/Q PET/CT results in the management of PE. Overall, V/Q PET had an impact on management in four patients (17%). In this pilot study, we demonstrated the feasibility and potential utility of V/Q PET/CT for the management of patients with suspected PE. V/Q PET/CT may be of particular relevance in patients with equivocal findings or isolated subsegmental findings on CTPA, adding further discriminatory information to allow important decision-making regarding the use or withholding of anticoagulation. Given the other advantages of V/Q PET/CT (reduced acquisition time, low radiation dose), and with the increasing availability of
Publisher: Wiley
Date: 31-08-2020
DOI: 10.1002/PROS.24056
Publisher: Springer Science and Business Media LLC
Date: 14-01-2020
DOI: 10.1038/S41585-019-0272-5
Abstract: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is rapidly being established as arguably the leading contemporary imaging modality in the management of prostate cancer. Outside of its conventional use in the de novo staging of localized disease and detection of biochemical recurrence, additional applications for the use of PSMA PET are emerging. Uptake of PSMA tracers in other genitourinary malignancies, particularly renal cell carcinoma, has led to new fields of investigation. Therapeutic delivery of radiolabelled PSMA small molecules has shown considerable promise in advanced prostate cancer. The ability to use the same molecule for imaging and therapy - theranostics - enables a highly personalized approach. PSMA PET can also have a considerable influence in the selection and guidance of radiotherapy fields for high-risk and recurrent disease. Intriguingly, changes in intensity of PSMA uptake during systemic therapy might provide early response assessment or novel insight into the biological responses of genitourinary malignancies to treatment. An evolving range of radiolabelled PSMA radiopharmaceuticals is emerging in the multiple facets of modern clinical practice.
Publisher: Society of Nuclear Medicine
Date: 12-10-2018
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.IJROBP.2015.04.027
Abstract: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)-positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Fifty-one patients were studied: 67% male median age 68 (range, 31-87) years 8% never smokers 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interin idual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow in such cases, in idual FLT-PET scans may be required.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2006
Publisher: Informa UK Limited
Date: 16-06-2015
DOI: 10.3109/10428194.2014.910656
Abstract: There are limited data regarding the role of (18)F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET-CT) scanning in primary mediastinal B-cell lymphoma (PMBL). We analyzed 28 patients with PMBL treated with chemotherapy, of whom 25 (89%) also received rituximab and 17 (61%) radiotherapy. PET-CT scans were interpreted using visual analysis and a 5-point scale. After a median follow-up of 2.6 years, four patients relapsed and two died. The 2-year progression-free survival and overall survival were 86% and 94%. PET-CT has excellent negative predictive value (interim, 86-87% end of treatment, 95%) but limited positive predictive value due to the high frequency of positive scans. Several patients with persistent metabolically active masses underwent biopsies, which showed necrosis but no lymphoma. Thus a negative PET-CT is an excellent predictor of subsequent outcome. However, residual metabolically active masses after treatment should be biopsied to confirm viable lymphoma prior to salvage therapy.
Publisher: Radiological Society of North America (RSNA)
Date: 05-2021
DOI: 10.1148/RADIOL.2021202771
Abstract: Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals are playing a large role at the time of initial staging and biochemical recurrence for localizing prostate cancer, as well as in other emerging clinical settings. PSMA PET has demonstrated increased detection rate compared with conventional imaging and has been shown to change management plans in a substantial percentage of cases. The aims of this narrative review are to highlight the development and clinical impact of PSMA PET radiopharmaceuticals, to compare PSMA to other agents such as fluorine 18 fluciclovine and carbon 11 choline, and to highlight some of the in idual PSMA PET agents that have contributed to the advancement of prostate cancer imaging.
Publisher: Massachusetts Medical Society
Date: 06-04-2017
DOI: 10.1056/NEJMC1701616
Publisher: Springer Science and Business Media LLC
Date: 10-2009
DOI: 10.1007/S00259-008-0946-3
Abstract: Error and variation in reporting remains one of the weakest features of clinical imaging despite enormous technological advances in nuclear medicine and radiology. The aim of this study was to evaluate agreement amongst experienced readers in staging non-small-cell lung cancer (NSCLC) with PET-CT. A series of (18)F-FDG PET-CT scans from 100 consecutive patients were reviewed independently by three experienced readers, with two readers reviewing each scan series a second time. In idual mediastinal lymph node stations were assessed as benign/inflammatory, equivocal or malignant, and AJCC N and M stage were also assigned. Kappa (kappa) was used to compare ratings from two categories and weighted kappa (kappa(w)) for three or more categories, and kappa values were interpreted according to the Landis-Koch benchmarks. Both intra- and interobserver agreement for N and M staging were high. For M staging there was almost perfect intra- and interobserver agreement (kappa = 0.90-0.93). For N staging, agreement was either almost perfect or substantial (intraobserver kappa(w) = 0.79, 0.91 interobserver kappa(w) = 0.75-0.81). Importantly, there was almost perfect agreement for N0/1 vs N2/3 disease (kappa = 0.80-0.97). Agreement for inferior and superior mediastinal nodes (stations 1, 2, 3, 7, 8, 9) was either almost perfect or substantial (kappa(w) = 0.71-0.88), but lower for hilar nodes (10 kappa(w) = 0.56-0.71). Interreporter variability was greatest for aortopulmonary nodes (5, 6 kappa(w) = 0.48-0.55). Amongst experienced reporters in a single centre, there was a very high level of agreement for both mediastinal nodal stage and detection of distant metastases with PET-CT. This supports the use of PET-CT as a robust imaging modality for staging NSCLC.
Publisher: Wiley
Date: 10-08-2017
DOI: 10.1002/RCR2.253
Publisher: Frontiers Media SA
Date: 14-06-2018
Publisher: Elsevier BV
Date: 10-2016
Publisher: Society of Nuclear Medicine
Date: 15-11-2019
Publisher: Society of Nuclear Medicine
Date: 03-10-2012
Publisher: Springer Science and Business Media LLC
Date: 13-11-2014
Publisher: Society of Nuclear Medicine
Date: 09-09-2011
DOI: 10.2967/JNUMED.111.093344
Abstract: Ventilation-perfusion (V/Q) scintigraphy is established for regional assessment of lung function in a variety of diseases, including pulmonary embolism (PE). PET/CT may further improve the accuracy and utility of V/Q imaging because of its superior technical characteristics. This pilot study assessed the feasibility of performing V/Q PET/CT and compared diagnostic utility with conventional V/Q imaging in patients with clinical suspicion of PE. Ten patients undergoing conventional V/Q imaging were prospectively recruited. PET/CT V/Q imaging was performed after inhalation of (68)Ga-carbon nanoparticles ("Galligas") and administration of (68)Ga-macroaggregated albumin. Blinded to the results of the other study, SPECT/CT (n = 9) or SPECT (n = 1) images and PET/CT images were graded by a predefined scoring system for scan quality. The number of matched or unmatched defects and diagnosis were also measured and compared with a final diagnosis. PET image quality was equivalent or superior to SPECT in all patients, with more homogeneous radiotracer distribution for both ventilation and perfusion studies (P < 0.01). Based on conventional V/Q imaging, the diagnosis was acute PE in 2 patients and no PE in 7 patients, and the imaging results were nondiagnostic in 1 patient. The PET/CT diagnosis was concordant in 8 patients, and these studies demonstrated a similar number and distribution of matched and unmatched defects. In 1 discordant case, a patient with a SPECT/CT study that was nondiagnostic because of severe airway disease showed no PE on PET/CT. In another, the diagnosis of PE established on SPECT/CT was not reported on PET/CT 2 d later, possibly because of interval clot lysis or migration. This intrain idual comparative study demonstrated that V/Q PET/CT with (68)Ga-labeled radiotracers can be performed in clinical practice. Compared with conventional V/Q imaging, advantages include higher-resolution, fully tomographic images with potentially better regional quantitation of lung function. The short half-life of (68)Ga also enables more flexible acquisition protocols with the option of performing ventilation studies selectively on patients with abnormal perfusion. On the basis of our results, further studies are indicated to assess whether V/Q PET/CT can improve diagnostic algorithms for patients with suspected PE.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2016
Publisher: SAGE Publications
Date: 2023
DOI: 10.1177/17588359231179309
Abstract: [ 177 Lu]Lu-PSMA has recently been approved for use in the post-taxane, post-novel hormonal-agent setting in patients with metastatic castration-resistant prostate cancer. As a beta-emitting radioligand targeting prostate-specific membrane antigen (PSMA), it delivers radiation to cells expressing PSMA on their surface. In pivotal clinical trials, patients were selected for this treatment based on positron emission tomography (PET)/CT imaging, requiring PSMA-avid disease with no evidence of discordant disease on 2-[ 18 F]fluoro-2-deoxy-D-glucose PET/CT or contrast CT scan. Despite exhibiting an optimal imaging phenotype, the response for many patients is not durable, and a minority do not respond to [ 177 Lu]Lu-PSMA at all. Disease progression is inevitable even for those who achieve an exceptional initial response. Reasons for both primary and acquired resistance are largely unknown however, they are likely due to the presence of underlying PSMA-negative disease not identified on imaging, molecular factors conferring radioresistance, and inadequate delivery of lethal radiation, particularly to sites of micrometastatic disease. Biomarkers are urgently needed to optimize patient selection for treatment with [ 177 Lu]Lu-PSMA by identifying those who are most and least likely to respond. Retrospective data support using several prognostic and predictive baseline patient- and disease-related parameters however, robust prospective data is required before these can be translated into widespread use. Further, early on-treatment clinical parameters (in addition to serial prostate-specific antigen [PSA] levels and conventional restaging imaging) may serve as surrogates for predicting treatment response. With little known about the efficacy of treatments given after [ 177 Lu]Lu-PSMA, optimal treatment sequencing is paramount, and biomarker-driven patient selection will hopefully improve treatment and survival outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2007
Publisher: Society of Nuclear Medicine
Date: 31-12-2020
Publisher: Wiley
Date: 31-12-2014
DOI: 10.1118/1.4856055
Abstract: CT ventilation imaging is a novel functional lung imaging modality based on deformable image registration. The authors present the first validation study of CT ventilation using positron emission tomography with (68)Ga-labeled nanoparticles (PET-Galligas). The authors quantify this agreement for different CT ventilation metrics and PET reconstruction parameters. PET-Galligas ventilation scans were acquired for 12 lung cancer patients using a four-dimensional (4D) PET/CT scanner. CT ventilation images were then produced by applying B-spline deformable image registration between the respiratory correlated phases of the 4D-CT. The authors test four ventilation metrics, two existing and two modified. The two existing metrics model mechanical ventilation (alveolar air-flow) based on Hounsfield unit (HU) change (VHU) or Jacobian determinant of deformation (VJac). The two modified metrics incorporate a voxel-wise tissue-density scaling (ρVHU and ρVJac) and were hypothesized to better model the physiological ventilation. In order to assess the impact of PET image quality, comparisons were performed using both standard and respiratory-gated PET images with the former exhibiting better signal. Different median filtering kernels (σm = 0 or 3 mm) were also applied to all images. As in previous studies, similarity metrics included the Spearman correlation coefficient r within the segmented lung volumes, and Dice coefficient d20 for the (0 - 20)th functional percentile volumes. The best agreement between CT and PET ventilation was obtained comparing standard PET images to the density-scaled HU metric (ρVHU) with σm = 3 mm. This leads to correlation values in the ranges 0.22 ≤ r ≤ 0.76 and 0.38 ≤ d20 ≤ 0.68, with r = 0.42 ± 0.16 and d20 = 0.52 ± 0.09 averaged over the 12 patients. Compared to Jacobian-based metrics, HU-based metrics lead to statistically significant improvements in r and d20 (p < 0.05), with density scaled metrics also showing higher r than for unscaled versions (p < 0.02). r and d20 were also sensitive to image quality, with statistically significant improvements using standard (as opposed to gated) PET images and with application of median filtering. The use of modified CT ventilation metrics, in conjunction with PET-Galligas and careful application of image filtering has resulted in improved correlation compared to earlier studies using nuclear medicine ventilation. However, CT ventilation and PET-Galligas do not always provide the same functional information. The authors have demonstrated that the agreement can improve for CT ventilation metrics incorporating a tissue density scaling, and also with increasing PET image quality. CT ventilation imaging has clear potential for imaging regional air volume change in the lung, and further development is warranted.
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.EJSO.2011.08.129
Abstract: To assess the clinical utility of peptide receptor chemoradionuclide therapy (PRCRT) using (177)Lu-octreotate (LuTate) with concurrent 5FU chemotherapy in patients with inoperable primary pancreatic and duodenal neuroendocrine tumours (NETs). Between December 2006 and October 2009, five patients with progressive inoperable pancreatic and duodenal NETs without distant metastatic disease or with a potentially resectable solitary distant metastasis were treated with PRCRT in combination with external beam radiotherapy in one case. Patients were followed up three months post-treatment with somatostatin receptor scintigraphy, radiology, biochemical markers and clinical assessment. Radiological response classification was defined by Response Evaluation Criteria in Solid Tumours (RECIST) with the addition of a minor response (MR 10-30% size reduction) classification. Long-term follow up was performed until July 2011. At three months post-treatment, all five patients had a scintigraphic response, four had a radiological response and three of the four symptomatic patients responded clinically. All five patients had an ongoing treatment response beyond three months including one where further tumour shrinkage facilitated curative surgery. All five patients are alive with 12-42 months of follow-up post-treatment. PRCRT can be effective in inoperable pancreatic and duodenal neuroendocrine tumours and may play a role as neoadjuvant therapy in this patient group.
Publisher: Wiley
Date: 16-02-2020
DOI: 10.1111/ANS.15723
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 21-03-2014
Publisher: Radiological Society of North America (RSNA)
Date: 05-2023
Publisher: Wiley
Date: 05-12-2022
DOI: 10.1111/BJU.15929
Abstract: To identify whether synchronous reading of multiparametric magnetic resonance imaging (mpMRI) and 68 Ga‐PSMA‐11 positron emission tomography (PET)/computed tomography (prostate‐specific membrane antigen [PSMA‐PET]) images can improve diagnostic performance and certainty compared with mpMRI/PSMA‐PET reported independently and synthesized, while also assessing concordance between imaging modalities and agreement with histopathology. This was a retrospective analysis of 100 patients randomly selected from the PRIMARY trial, a prospective Phase II multicentre imaging trial. Three dual‐trained radiologist/nuclear medicine physicians re‐reported the mpMRI and PSMA‐PET both independently and synchronously for the same patients in random order, blinded to previous results. Diagnostic performance was assessed for mpMRI/PSMA‐PET images read synchronously or independently and then synthesized. Agreement between imaging results and histopathology was examined. ‘Concordance’ between imaging modalities was defined as overlapping lesions. Reporting certainty was evaluated by the in idual reporters for each modality. International Society of Urological Pathology Grade Group ≥2 cancer was present in 60% of patients on biopsy. Synchronous reading of mpMRI/PSMA‐PET increased sensitivity compared to mpMRI or PSMA‐PET alone (93% vs 80% vs 88%, respectively), although specificity was not improved (63% vs 58% vs 78%, respectively). No significant difference in diagnostic performance was noted between mpMRI/PSMA‐PET read synchronously and mpMRI or PSMA‐PET reported independently and then synthesized. Most patients had concordant imaging (60%), while others had discordant lesions only (28%) or a mixture (concordant and discordant lesions 12%). When mpMRI/PSMA‐PET findings were concordant and positive, 95% of patients had clinically significant prostate cancer (csPCa). When PSMA‐PET alone was compared to synchronous PSMA‐PET/MRI reads, there was an improvement in reader certainty in 20% of scans. Synchronous mpMRI/PSMA‐PET reading improves reader certainty and sensitivity for csPCa compared to mpMRI or PSMA‐PET alone. However, synthesizing the results of independently read PSMA‐PET and mpMRI reports provided similar diagnostic performance to synchronous PSMA‐PET/MRI reads. This may provide greater flexibility for urologists in terms of referral patterns, reducing healthcare system costs and improving efficiencies in prostate cancer diagnosis.
Publisher: Society of Nuclear Medicine
Date: 07-04-2022
DOI: 10.2967/JNUMED.122.263996
Abstract: Theranostics is a burgeoning development in nuclear medicine which is being rapidly implemented worldwide. There is an increasing need to provide a multidisciplinary framework to the practice of theranostics, to ensure that patients receive this treatment in a safe manner and are provided with security in the knowledge that the health practitioners providing the service are adequately trained. Nuclear medicine experts in Australia have taken the initiative to produce a set of Theranostic guidelines relevant to Australian medical practice. These guidelines encompass specialist qualifications, patient care, radiopharmaceutical production, radiation safety and dosimetry. We propose these guidelines could be adapted for other countries, and promote standards of practice leading to optimal clinical outcomes for patients receiving theranostic treatments.
Publisher: Society of Nuclear Medicine
Date: 11-01-2018
DOI: 10.2967/JNUMED.117.202861
Abstract: We report the discovery of a systematic miscalibration during the work-up process for site validation of a multicenter clinical PET imaging trial using
Publisher: Wiley
Date: 02-05-2017
DOI: 10.1111/BJU.13871
Publisher: Informa UK Limited
Date: 05-12-2012
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-02-2013
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.IJROBP.2015.05.011
Abstract: Measuring changes in lung perfusion resulting from radiation therapy dose requires registration of the functional imaging to the radiation therapy treatment planning scan. This study investigates registration accuracy and utility for positron emission tomography (PET)/computed tomography (CT) perfusion imaging in radiation therapy for non-small cell lung cancer. (68)Ga 4-dimensional PET/CT ventilation-perfusion imaging was performed before, during, and after radiation therapy for 5 patients. Rigid registration and deformable image registration (DIR) using B-splines and Demons algorithms was performed with the CT data to obtain a deformation map between the functional images and planning CT. Contour propagation accuracy and correspondence of anatomic features were used to assess registration accuracy. Wilcoxon signed-rank test was used to determine statistical significance. Changes in lung perfusion resulting from radiation therapy dose were calculated for each registration method for each patient and averaged over all patients. With B-splines/Demons DIR, median distance to agreement between lung contours reduced modestly by 0.9/1.1 mm, 1.3/1.6 mm, and 1.3/1.6 mm for pretreatment, midtreatment, and posttreatment (P < .01 for all), and median Dice score between lung contours improved by 0.04/0.04, 0.05/0.05, and 0.05/0.05 for pretreatment, midtreatment, and posttreatment (P .2). Poorer posttreatment results were likely caused by posttreatment pneumonitis and tumor regression. Up to 80% standardized uptake value loss in perfusion scans was observed. There was limited change in the loss in lung perfusion between registration methods however, Demons resulted in larger interpatient variation compared with rigid and B-splines registration. DIR accuracy in the data sets studied was variable depending on anatomic changes resulting from radiation therapy caution must be exercised when using DIR in regions of low contrast or radiation pneumonitis. Lung perfusion reduces with increasing radiation therapy dose however, DIR did not translate into significant changes in dose-response assessment.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2016
Publisher: Wiley
Date: 02-07-2014
DOI: 10.1111/CEN.12519
Publisher: Springer Science and Business Media LLC
Date: 13-11-2012
DOI: 10.1038/NRCLINONC.2012.188
Abstract: For the evaluation of biological processes using radioisotopes, there are two competing technologies: single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Both are tomographic techniques that enable 3D localization and can be combined with CT for hybrid imaging. PET-CT has clear technical superiority including superior resolution, speed and quantitative capability. SPECT-CT currently has greater accessibility, lower cost and availability of a wider range of approved radiotracers. However, the past decade has seen dramatic growth in PET-CT with decreasing costs and development of an increasing array of PET tracers that can substitute existing SPECT applications. PET-CT is also changing the paradigm of imaging from lesion measurement to lesion characterization and target quantification, supporting a new era of personalized cancer therapy. The efficiency and cost savings associated with improved diagnosis and clinical decision-making provided by PET-CT make a cogent argument for it becoming the dominant molecular technique in oncology.
Publisher: Informa UK Limited
Date: 09-04-2012
Publisher: Springer Science and Business Media LLC
Date: 17-08-2016
Publisher: Wiley
Date: 06-07-2021
DOI: 10.1111/BJU.15491
Abstract: To determine the activity and safety of lutetium‐177 ( 177 Lu)‐prostate‐specific membrane antigen (PSMA)‐617 in men with metastatic castration‐resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression, and to identify potential prognostic and predictive biomarkers from imaging, blood and tissue. ENZA‐p (ANZUP 1901) is an open‐label, randomized, two‐arm, multicentre, phase 2 trial. Participants are randomly assigned (1:1) to treatment with enzalutamide 160 mg daily alone or enzalutamide plus 177 Lu‐PSMA‐617 7.5 GBq on Days 15 and 57. Two additional 177 Lu‐PSMA‐617 doses are allowed, informed by Day‐92 Gallium‐68 ( 68 Ga)‐PSMA positron emission tomography (PET up to four doses in total). The primary endpoint is prostate‐specific antigen (PSA) progression‐free survival (PFS). Other major endpoints include radiological PFS, PSA response rate, overall survival, health‐related quality of life, adverse events and cost‐effectiveness. Key eligibility criteria include: biochemical and/or clinical progression 68 Ga‐PSMA PET‐avid disease no prior androgen signalling inhibitor, excepting abiraterone no prior chemotherapy for mCRPC and ≥2 high‐risk features for early enzalutamide failure. Assessments are 4 weekly during study treatment, then 6 weekly until radiographic progression. Response Evaluation Criteria in Solid Tumours (RECIST) are used to assess imaging conducted every 12 weeks, 68 Ga‐PSMA PET at baseline, Days 15 and 92, and at progression, and 18 F‐fluorine deoxyglucose ( 18 F‐FDG) PET at baseline and progression. Translational s les include blood (and optional biopsies) at baseline, Day 92, and first progression. Correlative studies include identification of prognostic and predictive biomarkers from 68 Ga‐PSMA and 18 F‐FDG PET/CT, circulating tumour cells and circulating tumour DNA. The trial will enrol 160 participants, providing 80% power with a two‐sided type‐1 error rate of 5% to detect a hazard ratio of 0.625 assuming a median PSA‐PFS of 5 months with enzalutamide alone. The combination of 177 Lu‐PSMA‐617 and enzalutamide may be synergistic. ENZA‐p will determine the safety and efficacy of the combination in addition to developing predictive and prognostic biomarkers to better guide treatment decisions.
Publisher: Springer Science and Business Media LLC
Date: 10-10-2017
Publisher: Springer Science and Business Media LLC
Date: 06-11-2014
DOI: 10.1007/S00259-013-2607-4
Abstract: Our group has previously reported on the use of (68)Ga-ventilation erfusion (VQ) PET/CT scanning for the diagnosis of pulmonary embolism. We describe here the acquisition methodology for (68)Ga-VQ respiratory gated (4-D) PET/CT and the effects of respiratory motion on image coregistration in VQ scanning. A prospective study was performed in 15 patients with non-small-cell lung cancer. 4-D PET and 4-D CT images were acquired using an infrared marker on the patient's abdomen as a surrogate for breathing motion following inhalation of Galligas and intravenous administration of (68)Ga-macroaggregated albumin. Images were reconstructed with phase-matched attenuation correction. The lungs were contoured on CT and PET VQ images during free-breathing (FB) and at maximum inspiration (Insp) and expiration (Exp). The similarity between PET and CT volumes was measured using the Dice coefficient (DC) comparing the following groups (1) FB-PET/CT, (2) InspPET/InspCT, (3) ExpPET/Exp CT, and (4) FB-PET/AveCT. A repeated measures one-way ANOVA with multiple comparison Tukey tests were performed to evaluate any difference between the groups. Diaphragmatic motion in the superior-inferior direction on the 4-D CT scan was also measured. 4-D VQ scanning was successful in all patients without additional acquisition time compared to the nongated technique. The highest volume overlap was between ExpPET and ExpCT and between FB-PET and AveCT with a DC of 0.82 and 0.80 for ventilation and perfusion, respectively. This was significantly better than the DC comparing the other groups (0.78-0.79, p < 0.05). These values agreed with a visual inspection of the images with improved image coregistration around the lung bases. The diaphragmatic motion during the 4-D CT scan was highly variable with a range of 0.4-3.4 cm (SD 0.81 cm) in the right lung and 0-2.8 cm (SD 0.83 cm) in the left lung. Right-sided diaphragmatic nerve palsy was observed in 3 of 15 patients. (68)Ga-VQ 4-D PET/CT is feasible and the blurring caused by respiratory motion is well corrected with 4-D acquisition, which principally reduces artefact at the lung bases. The images with the highest spatial overlap were the combined expiration phase or FB PET and average CT. With higher resolution than SPECT/CT, the PET/CT technique has a broad range of potential clinical applications including diagnostic algorithms for patients with suspected pulmonary embolism, preoperative evaluation of regional lung function and improving assessment or understanding of pulmonary physiology in the vast range of pulmonary diseases.
Publisher: BMJ
Date: 06-01-2014
DOI: 10.1136/BMJ.F7705
Publisher: Elsevier BV
Date: 02-2017
Publisher: Springer International Publishing
Date: 27-12-2017
Publisher: Informa UK Limited
Date: 16-01-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2018
Publisher: Elsevier BV
Date: 08-2018
Publisher: Society of Nuclear Medicine
Date: 15-11-2010
Publisher: Informa UK Limited
Date: 17-12-2021
DOI: 10.1080/10428194.2021.2015345
Abstract: Salvage chemotherapy and autologous stem cell transplant remain a standard of care in the management of diffuse large B cell lymphoma (DLBCL) at first relapse. However, this paradigm is increasingly being challenged by novel immunotherapies, such as chimeric antigen receptor T-cells (CART-cells). Traditional positron emission tomography-based (PET) prognostication takes place after salvage and before autologous stem cell transplant (ASCT), and while useful, for many patients this information comes too late and at the expense of unnecessary toxicity. In this edition of Leukemia & Lymphoma, two groups present their findings on the use of early quantitative PET markers and the correlation with outcomes in patients embarking on second line salvage chemotherapy. These approaches have the potential to better identify patients who are destined for treatment failure and help guide appropriate sequencing of alternative therapies or the development of PET-adapted clinical trials.
Publisher: Springer Science and Business Media LLC
Date: 16-07-2015
Publisher: Elsevier BV
Date: 02-2018
Publisher: Wiley
Date: 29-04-2019
DOI: 10.1002/CASP.2406
Publisher: SAGE Publications
Date: 2023
DOI: 10.1177/17588359231177018
Abstract: Reported here is a case of rapidly progressive metastatic castration-resistant prostate cancer treated with [ 177 Lu]Lu-PSMA-617 in the setting of severe renal impairment and impending ureteric obstruction. PSMA is expressed on renal tubular cells, raising the possibility of radiation-induced nephrotoxicity, and this level of renal impairment would typically exclude the patient from [ 177 Lu]Lu-PSMA-617 therapy. Multidisciplinary input, in idualized dosimetry, and patient-specific dose reduction were used to ensure the cumulative dose to the kidneys remained within acceptable limits. He was initially planned for treatment with six cycles of [ 177 Lu]Lu-PSMA-617. However, he had an excellent response to therapy following four cycles of treatment and the last two cycles were omitted. He has been followed for 1-year posttherapy without evidence of disease recurrence. No acute or chronic nephrotoxicity was observed. This case report highlights the utility of [ 177 Lu]Lu-PSMA-617 therapy in severe renal impairment and provides evidence of relative safety in patients who would otherwise not be considered candidates for therapy.
Publisher: Elsevier BV
Date: 11-2019
Publisher: The Endocrine Society
Date: 02-2013
DOI: 10.1210/JC.2012-3642
Abstract: Tumor-induced osteomalacia (TIO) is a rarely diagnosed disorder presenting with bone pain, fractures, muscle weakness, and moderate-to-severe hypophosphatemia resulting from fibroblast growth factor 23-mediated renal phosphate wasting. Tumors secreting fibroblast growth factor 23 are often small and difficult to find with conventional imaging. We studied the utility of 68Ga-DOTA-octreotate (DOTATATE) somatostatin receptor positron emission tomography (PET)/computed tomography (CT) imaging in the diagnosis of TIO. A multicenter case series was conducted at tertiary referral hospitals. Six patients with TIO diagnosed between 2003 and 2012 in Australia were referred for DOTATATE PET imaging. We reviewed the clinical history, biochemistry, imaging characteristics, histopathology, and clinical outcome of each patient. Each case demonstrated delayed diagnosis despite severe symptoms. DOTATATE PET/CT imaging demonstrated high uptake and localized the tumor with confidence in each case. After surgical excision, there was resolution of clinical symptoms and serum phosphate, except in one patient who demonstrated residual disease on PET/CT. All tumors demonstrated high somatostatin receptor subtype 2 cell surface receptor expression using immunohistochemistry. In patients with TIO, DOTATATE PET/CT can successfully localize phosphaturic mesenchymal tumors and may be a practical first step in functional imaging for this disorder. Serum phosphate should be measured routinely in patients with unexplained muscle weakness, bone pain, or stress fractures to allow earlier diagnosis of TIO.
Publisher: Springer Science and Business Media LLC
Date: 08-10-2019
DOI: 10.1038/S41391-019-0174-X
Abstract: Theranostic principles utilize a molecular biomarker specific for a tumor target, initially for imaging to assess target expression and, if deemed suitable, for targeted therapy. This presents an exciting opportunity for a highly personalized treatment strategy in the era of precision medicine. Prostate-specific membrane antigen (PSMA) theranostics has attracted increasing attention as a promising targeted treatment in metastatic prostate cancer (PC).
Publisher: Wiley
Date: 21-04-2021
DOI: 10.1111/BJU.15384
Abstract: To assess the activity and safety of sequential lutetium‐177 ( 177 Lu)‐PSMA‐617 and docetaxel vs docetaxel on a background of androgen deprivation therapy (ADT) in men with de novo metastatic hormone‐naïve prostate cancer (mHNPC). UpFrontPSMA (NCT04343885) is an open‐label, randomized, multicentre, phase 2 trial, recruiting 140 patients at 12 Australian centres. Key eligibility criteria include: prostate cancer with a histological diagnosis within 12 weeks of screening commencement prostate‐specific antigen (PSA) ng/mL at diagnosis ≤4 weeks on ADT evidence of metastatic disease on computed tomography (CT) and/or bone scan high‐volume prostate‐specific membrane antigen (PSMA)‐avid disease with a maximum standardized uptake value and absence of extensive discordant fluorodeoxyglcuose (FDG)‐positive, PSMA‐negative disease. 68 Ga‐PSMA‐11 and 18 F‐FDG positron‐emission tomography (PET)/CT undergo central review to determine eligibility. Patients are randomized 1:1 to experimental treatment, Arm A ( 177 Lu‐PSMA‐617 7.5GBq q6w × 2 cycles followed by docetaxel 75 mg/m 2 q3w × 6 cycles), or standard‐of‐care treatment, Arm B (docetaxel 75 mg/m 2 q3w × 6 cycles). All patients receive continuous ADT. Patients are stratified based on disease volume on conventional imaging and duration of ADT at time of registration. The primary endpoint is the proportion of patients with undetectable PSA (≤0.2 ng/L) at 12 months after study treatment commencement. Secondary endpoints include safety, time to castration resistance, overall survival, PSA and radiographic progression‐free survival, objective tumour response rate, early PSMA PET response, health‐related quality of life, and frequency and severity of adverse events. Enrolment commenced in April 2020. The results of this trial will generate data on the activity and safety of 177 Lu‐PSMA‐617 in men with de novo mHNPC in a randomized phase 2 design.
Publisher: Springer Science and Business Media LLC
Date: 11-09-2015
DOI: 10.1007/S00259-014-2906-4
Abstract: Increased glycolytic activity on FDG PET/CT defines a subgroup of patients with metastatic gastroenteropancreatic neuroendocrine tumour (NET) with a poor prognosis. A limited range of systemic treatment options exist for more aggressive NET. The role of peptide receptor chemoradionuclide therapy (PRCRT) in such patients is, however, unclear. This retrospective study assessed the outcomes of patients with FDG-avid NET treated with PRCRT. Clinical, biochemical and imaging response was assessed after completion of induction treatment of PRCRT with 5-fluorouracil in 52 patients selected for treatment on the basis of somatostatin-receptor imaging without spatially discordant FDG-avid disease. Of the cohort, 67% had received prior chemotherapy. Overall survival (OS) and progression-free survival (PFS) were also analysed. PRCRT was well tolerated with negligible grade 3/4 toxicities. After a median follow-up period of 36 months, the median OS was not achieved with a median PFS of 48 months. At 3 months after completion of PRCRT 2% of patients showed a complete anatomical response, 28% a partial response, 68% stable disease, and only 2% progression. On FDG PET/CT, 27% achieved a complete metabolic response during the follow-up period. A biochemical response (>25% fall in chromogranin-A levels) was seen in 45%. PRCRT is an effective treatment in patients with FDG-avid NET, even in patients who have failed conventional therapies. Given apparently higher response rates than with alternative therapeutic options and low toxicity, further research is needed to establish whether PRCRT should be used as a first-line treatment modality in this patient population.
Publisher: Wiley
Date: 12-08-2020
DOI: 10.1111/BJU.15143
Publisher: Radiological Society of North America (RSNA)
Date: 2018
Abstract: Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed in prostate cancer. Radiolabeled small molecules that bind with high affinity to its active extracellular center have emerged as a potential new diagnostic standard of reference for prostate cancer, resulting in images with extraordinary tumor-to-background contrast. Currently, gallium 68 (
Publisher: Elsevier BV
Date: 10-2019
Publisher: Springer Science and Business Media LLC
Date: 20-11-2017
DOI: 10.1007/S00259-017-3886-Y
Abstract: On page 4 of the original version of this article, the text "Eight (29%) of the patients had significant FDG-avid disease (i.e. with intensity above liver parenchyma) prior to treatment" needs to be corrected.
Publisher: Society of Nuclear Medicine
Date: 07-2015
DOI: 10.2967/JNUMED.115.157743
Abstract: There are currently no data published regarding the proportion of nuclear medicine centers using SPECT or SPECT/CT rather than planar ventilation erfusion (V/Q) imaging in patients with suspected acute pulmonary embolism (PE). Furthermore, the reporting criteria used for interpretation of both planar and SPECT V/Q scans are variable and data are lacking regarding which criteria are commonly used in various centers. The aim of this study was to assess current practices regarding the performance and interpretation of lung scintigraphy across 3 different countries. A short online survey composed of simple multiple-choice questions was distributed to nuclear medicine departments in Australia, Canada, and France during the period April to December 2014. The survey covered image acquisition, interpretation criteria for SPECT and planar images, and use of pseudoplanar images and radiopharmaceuticals. Information was initially solicited by 2 sets of e-mails, which pointed to the survey internet link. Departments were subsequently contacted by telephone. A single response per department was consolidated. Three hundred thirty-one responses were collected (Australia, 74 Canada, 48 and France, 209). Twenty-eight percent of centers indicated use of V/Q planar imaging alone whereas 72% of centers included some form of SPECT in their acquisition protocol for evaluation of PE, specifically V/Q SPECT in 36%, V/Q SPECT/CT in 29%, Q SPECT/CT in 2%, and both V/Q planar and SPECT in 5%, with a strong variability among countries. The most commonly used criteria for SPECT interpretation were the those of the European Association of Nuclear Medicine (60%). Criteria used for planar interpretation were heterogeneous (European Association of Nuclear Medicine criteria, 35% Prospective Investigation of Pulmonary Embolism Diagnosis study, 29% no standardized criteria, 21%). Sixty-three percent of departments used pseudoplanar images in addition to SPECT images. In the 3 countries surveyed, SPECT has largely replaced planar imaging for evaluation of PE, with almost half of the SPECT studies incorporating a CT acquisition. Criteria used for interpretation are inconsistent, especially for planar imaging.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.RADONC.2018.07.014
Abstract: Advanced imaging techniques allow functional information to be derived and integrated into treatment planning. A systematic review was conducted with the primary objective to evaluate the ability of functional lung imaging to predict risk of radiation pneumonitis. Secondary objectives were to evaluate dose-response relationships on post treatment functional imaging and assess the utility in including functional lung information into treatment planning. A structured search for publications was performed following PRISMA guidelines and registered on PROSPERO. 814 articles were screened against review criteria and 114 publications met criteria. Methods of identifying functional lung included using CT, MRI, SPECT and PET to image ventilation or perfusion. Six studies compared differences between functional and anatomical lung imaging at predicting radiation pneumonitis. These found higher predictive values using functional lung imaging. Twenty-one studies identified a dose-response relationship on post-treatment functional lung imaging. Nineteen planning studies demonstrated the ability of functional lung optimised planning techniques to spare regions of functional lung. Meta-analysis of these studies found that mean (95% CI) functional volume receiving 20 Gy was reduced by 4.2% [95% CI: 2.3: 6.0] and mean lung dose by 2.2 Gy [95% CI: 1.2: 3.3] when plans were optimised to spare functional lung. There was significant variation between publications in the definition of functional lung. Functional lung imaging may have potential utility in radiation therapy planning and delivery, although significant heterogeneity was identified in approaches and reporting. Recommendations have been made based on the available evidence for future functional lung trials.
Publisher: Informa UK Limited
Date: 03-05-2013
Publisher: Elsevier BV
Date: 08-2021
Publisher: American Association for Cancer Research (AACR)
Date: 13-12-2019
DOI: 10.1158/1078-0432.CCR-19-1050
Abstract: Systemic androgen-signaling inhibition added to ongoing androgen-deprivation therapy (ADT) improved clinical outcomes in patients with nonmetastatic castration-resistant prostate cancer without detectable metastases by conventional imaging (nmCRPC). Prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET) detects prostate cancer with superior sensitivity to conventional imaging, but its performance in nmCRPC remains largely unknown. We characterized cancer burden in high-risk patients with nmCRPC using PSMA-PET. We retrospectively included 200 patients with nmCRPC, prostate-specific antigen (PSA) & ng/mL, and high risk for metastatic disease [PSA doubling time (PSADT) of ≤10 months and/or Gleason score of ≥8] from six high-volume PET centers. We centrally reviewed PSMA-PET detection rate for pelvic disease and distant metastases (M1). We further evaluated SPARTAN patients stratified by risk factors for PSMA-PET-detected M1 disease. PSMA-PET was positive in 196 of 200 patients. Overall, 44% had pelvic diseases, including 24% with local prostate bed recurrence, and 55% had M1 disease despite negative conventional imaging. Interobserver agreement was very high (κ: 0.81–0.91). PSA ≥ 5.5 ng/mL, locoregional nodal involvement determined by pathology (pN1), prior primary radiation, and prior salvage radiotherapy independently predicted M1 disease (all P & 0.05). PSMA-PET detected any disease in nearly all patients and M1 disease in 55% of patients previously diagnosed with nmCRPC, including subgroups with PSADT of ≤10 months and Gleason score of ≥8. The value of PSMA-PET imaging for treatment guidance should be tested in future studies.
Publisher: Wiley
Date: 07-2020
DOI: 10.1111/BJU.14858
Abstract: To compare the accuracy of 68 gallium prostate‐specific membrane antigen positron emission tomography/computed tomography ( 68 Ga‐PSMA PET/CT) with multiparametric MRI (mpMRI) in detecting and localising primary prostate cancer when compared with radical prostatectomy (RP) specimen pathology. Retrospective review of men who underwent 68 Ga‐PSMA PET/CT and mpMRI for primary prostate cancer before RP across four centres between 2015 and 2018. Patients undergoing imaging for recurrent disease or before non‐surgical treatment were excluded. We defined pathological index tumour as the lesion with highest International Society of Urological Pathology Grade Group (GG) on RP specimen pathology. Our primary outcomes were rates of accurate detection and localisation of RP specimen pathology index tumour using 68 Ga‐PSMA PET/CT or mpMRI. We defined tumour detection as imaging lesion corresponding with RP specimen tumour on any imaging plane, and localisation as imaging lesion matching RP specimen index tumour in all sagittal, axial, and coronal planes. Secondary outcomes included localisation of clinically significant and transition zone (TZ) index tumours. We defined clinically significant disease as GG 3–5. We used descriptive statistics and the Mann–Whitney U ‐test to define and compare demographic and pathological characteristics between detected, missed and localised tumours using either imaging modality. We used the McNemar test to compare detection and localisation rates using 68 Ga‐PSMA PET/CT and mpMRI. In all, 205 men were included in our analysis, including 133 with clinically significant disease. There was no significant difference between 68 Ga‐PSMA PET/CT and mpMRI in the detection of any tumour (94% vs 95%, P 0.9). There was also no significant difference between localisation of all index tumours (91% vs 89%, P = 0.47), clinically significant index tumours (96% vs 91%, P = 0.15) or TZ tumours (85% vs 80%, P 0.9) using 68 Ga‐PSMA PET/CT and mpMRI. Limitations include retrospective study design and non‐central review of imaging and pathology. We found no significant difference in the detection or localisation of primary prostate cancer between 68 Ga‐PSMA PET/CT and mpMRI. Further prospective studies are required to evaluate a combined PET/MRI model in minimising tumours missed by either modality.
Publisher: Wiley
Date: 02-2012
DOI: 10.1111/J.1754-9485.2011.02327.X
Abstract: Ga-68 DOTATATE (Ga-octreotate, GaTate) positron emission tomography (PET)/CT has multiple advantages compared with conventional and In-111 octreotide imaging for neuroendocrine tumours and other somatostatin-receptor expressing tumours. This study assesses the management impact of incremental diagnostic information obtained from this technique compared with conventional staging. Fifty-nine GaTate PET/CT studies were performed over an 18-month period (52 proven or suspected gastro-entero-pancreatic or bronchial neuroendocrine tumours and seven neural crest/mesenchymal tumours). A retrospective blinded review was performed on the number of abnormalities (1, 2-5 or >5) within defined regions with comparison to conventional imaging to assess incremental diagnostic information. Subsequent management impact (high, moderate or low) was determined by clinical review and follow up to assess pre-PET stage, treatment intent and post-PET management change. Eighty-eight percent of GaTate studies were abnormal. Compared with conventional and In-111 octreotide imaging, additional information was provided by GaTate PET/CT in 68 and 83% of patients, respectively. Management impact was high (inter-modality change) in 47%, moderate (intra-modality change) in 10% and low in 41% (not assessable in 2%). High management impact included directing patients to curative surgery by identifying a primary site and directing patients with multiple metastases to systemic therapy. GaTate PET/CT imaging provides additional diagnostic information in a high proportion of patients with consequent high management impact. GaTate PET/CT could replace (1)In-111 octreotide scintigraphy at centres where it is available given its superior accuracy, faster acquisition and lower radiation exposure. Rapid implementation could be achieved by allowing substitutional funding in the Medicare Benefit Schedule.
Publisher: Springer Science and Business Media LLC
Date: 27-06-2013
DOI: 10.1038/BJC.2013.338
Publisher: Wiley
Date: 04-08-2020
DOI: 10.1111/BJU.15151
Publisher: Radiological Society of North America (RSNA)
Date: 02-2023
Abstract: A 76-year-old man with metastatic castration-resistant prostate carcinoma progressing with antiandrogen and taxane therapy was treated with lutetium 177 prostate-specific membrane antigen (PSMA)-617 and showed marked biochemical and imaging response, with improvement in clinical status and osseous pain. A summary of nuclear medicine theranostics with emphasis on PSMA targeting agents is presented.
Publisher: Society of Nuclear Medicine
Date: 03-04-2020
Publisher: SAGE Publications
Date: 2019
Abstract: Radiolabelled small molecules for imaging prostate cancer have rapidly emerged over the last few years with gallium-68-labelled prostate-specific-membrane-antigen-11 ( 68 Ga-PSMA11), the most widely used. However, the current evidence-based guidelines for management of prostate cancer were established using computed tomography (CT), magnetic resonance imaging (MRI) and bone scan, despite their limitations. Prostate-specific-membrane antigen (PSMA) positron-emission tomography (PET)/CT, however, has higher sensitivity and specificity and can lead to both upstaging and downstaging and subsequent changes in management of prostate cancer. The literature for PSMA PET/CT is mostly in the setting of biochemical recurrence and primary staging of intermediate-to-high-risk prostate cancer. Preliminary studies also suggest that there may be a role in nonmetastatic castrate-resistant prostate cancer (nmCRPC) and possibly response to therapy. Despite high sensitivity and specificity, PSMA PET/CT as a single modality for staging advanced prostate cancer is suboptimal, given the low PSMA expression in this subgroup and the complementary role of fluorodeoxyglucose (FDG) PET/CT is required. This is also true in early-stage prostate adenocarcinoma with neuroendocrine differentiation or small-/large-cell neuroendocrine tumours of the prostate. Lack of a globally accepted standardized reporting system for PSMA PET/CT is a current limitation. This is essential to pave the way to incorporating this invaluable molecular imaging modality in clinical trials to assess its impact on outcome, particularly when upstaging or downstaging conventionally imaged disease. This would then lead to recognition by healthcare providers, incorporation into guidelines for management of prostate cancer and routine use in clinical practice.
Publisher: Springer Science and Business Media LLC
Date: 29-05-2023
DOI: 10.1007/S00259-023-06255-8
Abstract: Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [ 177 Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that 177 Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [ 177 Lu]Lu-PSMA-617 and [ 177 Lu]Lu-PSMA-I& T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from 177 Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [ 177 Lu]Lu-PSMA-617 or other emerging ligands on an in idual patient basis.
Publisher: Wiley
Date: 02-2019
DOI: 10.1002/MP.13346
Publisher: Wiley
Date: 03-2015
DOI: 10.1111/ANS.12935
Publisher: Springer Science and Business Media LLC
Date: 15-05-2019
Publisher: Elsevier BV
Date: 03-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2019
Publisher: Elsevier BV
Date: 06-2019
Publisher: Springer Science and Business Media LLC
Date: 27-09-2017
DOI: 10.1007/S00259-016-3527-X
Abstract: Bulky disease is an adverse prognostic factor for We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of Twenty-six pts (17 men aged 27-74 years) received a median cumulative activity of 6.5 GBq PRCRT with
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.RADONC.2015.04.013
Abstract: To assess the utility of functional lung avoidance using IMRT informed by four-dimensional (4D) ventilation erfusion (V/Q) PET/CT. In a prospective clinical trial, patients with non-small cell lung cancer (NSCLC) underwent 4D-V/Q PET/CT scanning before 60Gy of definitive chemoradiation. Both "highly perfused" (HPLung) and "highly ventilated" (HVLung) lung volumes were delineated using a 70th centile SUV threshold, and a "ventilated lung volume" (VLung) was created using a 50th centile SUV threshold. For each patient four IMRT plans were created, optimised to the anatomical lung, HPLung, HVLung and VLung volumes, respectively. Improvements in functional dose volumetrics when optimising to functional volumes were assessed using mean lung dose (MLD), V5, V10, V20, V30, V40, V50 and V60 parameters. The study cohort consisted of 20 patients with 80 IMRT plans. Plans optimised to HPLung resulted in a significant reduction of functional MLD by a mean of 13.0% (1.7Gy), p=0.02. Functional V5, V10 and V20 were improved by 13.2%, 7.3% and 3.8% respectively (p-values<0.04). There was no significant sparing of dose to functional lung when adapting to VLung or HVLung. Plan quality was highly consistent with a mean PTV D95 and D5 ranging from 60.8Gy to 61.0Gy and 63.4Gy to 64.5Gy, respectively, and mean conformity and heterogeneity index ranging from 1.11 to 1.17 and 0.94 to 0.95, respectively. IMRT plans adapted to perfused but not ventilated lung on 4D-V/Q PET/CT allowed for reduced dose to functional lung whilst maintaining consistent plan quality.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2013
DOI: 10.1007/S00259-013-2429-4
Abstract: PET/CT has a major role in lymphoma imaging, but glycolytic activity in inflammatory processes can reduce specificity. In this study we evaluated restaging PET/CT findings in patients with non-Hodgkin lymphoma (NHL) and fat necrosis. We identified 16 patients from 8,819 restaging FDG PET/CT scans with suspicion of or biopsy-proven fat necrosis on PET/CT. All patients had NHL and demonstrated focal FDG-avid nodular change on CT with density higher than that of fat but lower than that of soft tissue. Histological confirmation was obtained in eight patients, with high GLUT-1 staining between necrotic tissue and organizing fat necrosis evident. Uptake resolved in four patients, and surveillance was continuing in four without relapse. Although rare, identification of fat necrosis in patients with a solitary FDG-avid nodule after therapy is important and may lead to the avoidance of unnecessary interventions or treatment. Specific features on CT aid identification, whilst follow-up imaging can be helpful as the metabolic abnormality regresses with time.
Publisher: Springer Science and Business Media LLC
Date: 06-06-2013
Publisher: Society of Nuclear Medicine
Date: 06-10-2017
Publisher: Springer Science and Business Media LLC
Date: 23-10-2018
Publisher: Mary Ann Liebert Inc
Date: 11-2019
Publisher: Society of Nuclear Medicine
Date: 09-2017
DOI: 10.2967/JNUMED.116.186767
Abstract: The prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PC) cells. Therefore, the targeting of PSMA has become increasingly important over the last decade. Glu-urea-based PSMA ligands used for both imaging and radioligand therapy are the mainstays of the current success. For PET imaging, both
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: Springer Science and Business Media LLC
Date: 29-05-2019
Publisher: Springer Science and Business Media LLC
Date: 02-10-2014
Publisher: Springer Science and Business Media LLC
Date: 10-08-2013
Publisher: Elsevier BV
Date: 07-2023
Publisher: Informa UK Limited
Date: 07-02-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2007
Publisher: Radiological Society of North America (RSNA)
Date: 03-2015
DOI: 10.1148/RG.352140164
Abstract: Gallium 68 ((68)Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE, GaTate) positron emission tomography (PET)/computed tomography (CT) is an imaging technique for detecting and characterizing neuroendocrine tumors (NETs). GaTate, a somatostatin analog, has recently been accorded orphan drug status by the U.S. Food and Drug Administration, thereby increasing interest in and availability of this radiotracer. GaTate PET/CT allows whole-body imaging of cell surface expression of somatostatin receptors (SSTRs) and is rapidly evolving as the new imaging standard of reference for the detection and characterization of NETs. The authors discuss the normal appearance at GaTate PET/CT and the utility of this modality in a variety of these tumors, including gastrointestinal, pancreatic, and bronchial NETs as well as pheochromocytoma, paraganglioma, meningioma, and oncogenic osteomalacia. In addition, they discuss potential causes of false-positive findings, including pancreatic uncinate process activity, inflammation, osteoblastic activity, and splenosis. They also highlight the complementary role of 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) PET/CT, including the advantages of using both GaTate PET/CT and FDG PET/CT to evaluate sites of well- and poorly differentiated disease. The use of GaTate PET/CT together with FDG PET/CT allows identification of tumor heterogeneity, which provides prognostic information and can be pivotal in guiding biopsy. It also allows optimal patient management, including theranostic application of peptide receptor radionuclide therapy, and the restaging of patients following therapy.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.IJROBP.2015.06.005
Abstract: To investigate (68)Ga-ventilation erfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r(2)=0.99, P<.01), with ventilation strongly negatively linear (r(2)=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET/CT imaging. These findings may inform future studies of functional lung avoidance using V/Q PET/CT.
Publisher: Ivyspring International Publisher
Date: 2017
DOI: 10.7150/THNO.20855
Publisher: Wiley
Date: 24-01-2017
Abstract: Prostate specific membrane antigen (PSMA) positron emission tomography (PET) is an emerging imaging modality in prostate cancer. However, We present a retrospective series of eight patients in which comparative imaging modalities are evaluated against PSMA-PET scanning. FDG-PET and PSMA-PET scans were performed prior to definitive treatment (either surgery or SABR) of limited recurrent disease. Response assessment after SABR was performed with both PET imaging modalities at multiple time points in a subset of four patients. Prostate specific membrane antigen uptake is typically more intense than FDG in RCC. In all but two cases, one of which was papillary carcinoma, FDG-PET and PSMA-PET are concordant for detection of sites of disease. We demonstrate for the first time the differential kinetics of post-treatment response using PSMA and FDG-PET, with a more rapid metabolic response observed on FDG-PET. Both modalities demonstrate response earlier than morphological appearances on CT or MRI imaging. Our series suggests that PSMA shows early promise as a diagnostic and therapeutic response assessment tool in patients with metastatic RCC receiving definitive local therapies.
Publisher: Elsevier BV
Date: 02-2017
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.EURURO.2016.06.021
Abstract: Positron emission tomography (PET) of A systematic review and meta-analysis of reported predictors of positive We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Library, and Web of Science databases in April 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality was assessed using the Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analysis and meta-regression of proportions were performed using a random-effects model with pre-PET prostate-specific antigen (PSA) levels as the dependent variable. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models. Sixteen articles involving 1309 patients were analysed. The overall percentage of positive In the setting of BCR prostate cancer, pre-PET PSA predicts the risk of positive Positron emission tomography using
Publisher: Springer Science and Business Media LLC
Date: 23-05-2017
DOI: 10.1007/S00259-017-3725-1
Abstract: After primary treatment, biochemical relapse (BCR) occurs in a substantial number of patients with prostate cancer (PCa). PET/CT imaging with prostate-specific membrane antigen based tracers (68Ga-PSMA) has shown promising results for BCR patients. However, a standardized image interpretation methodology has yet to be properly agreed. The aim of this study, which was promoted and funded by European Association of Nuclear Medicine (EANM), is to define standardized image interpretation criteria for 68Ga-PSMA PET/CT to detect recurrent PCa lesions in patients treated with primary curative intent therapy (radical prostatectomy or radiotherapy) who presented a biochemical recurrence. In the first phase inter-rater agreement between seven readers from seven international centers was calculated on the reading of 68Ga-PSMA PET/CT images of 49 patients with BCR. Each reader evaluated findings in five different sites of recurrence (local, loco-regional lymph nodes, distant lymph nodes, bone, and other). In the second phase the re-analysis was limited to cases with poor, slight, fair, or moderate agreement [Krippendorff's (K) alpha<0.61]. Finally, on the basis of the consensus readings, we sought to define a list of revised consensus criteria for 68Ga-PSMA PET/CT interpretation. Between-reader agreement for the presence of anomalous findings in any of the five sites was only moderate (K's alpha: 0.47). The agreement improved and became substantial when readers had to judge whether the anomalous findings were suggestive for a pathologic, uncertain, or non-pathologic image (K's alpha: 0.64). K's alpha calculations for each of the five sites of recurrence were also performed and evaluated. First Delphi round was thus conducted. A more detailed definition of the criteria was proposed by the project coordinator, which was then discussed and finally agreed by the seven readers. After the second Delphi round only four cases of disagreement still remained. These were evaluated for a final round, allowing a final agreement table to be written. We hope that by developing these consensus guidelines on the interpretation of 68Ga-PSMA PET/CT, clinicians reporting these studies will be able to provide more consistent clinical reports and that within clinical trials, abnormality classifications will be harmonized, allowing more robust assessment of its diagnostic performance.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2008
Publisher: Wiley
Date: 03-06-2018
DOI: 10.1111/BJU.14374
Abstract: Accurate staging of patients with prostate cancer (PCa) is important for therapeutic decision-making. Relapse after surgery or radiotherapy of curative intent is not uncommon and, in part, represents a failure of staging with current diagnostic imaging techniques to detect disease spread. Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is a new whole-body scanning technique that enables visualization of PCa with high contrast. The hypotheses of this study are that: (i) PSMA-PET/CT has improved diagnostic performance compared with conventional imaging (ii) PSMA-PET/CT should be used as a first-line diagnostic test for staging (iii) the improved diagnostic performance of PSMA-PET/CT will result in significant management impact and (iv) there are economic benefits if PSMA-PET/CT is incorporated into the management algorithm. The proPSMA trial is a prospective, multicentre study in which patients with untreated high-risk PCa will be randomized to gallium-68-PSMA-11 PET/CT or conventional imaging, consisting of CT of the abdomen elvis and bone scintigraphy with single-photon emission CT/CT. Patients eligible for inclusion are those with newly diagnosed PCa with select high-risk features, defined as International Society of Urological Pathology grade group ≥3 (primary Gleason grade 4, or any Gleason grade 5), prostate-specific antigen level ≥20 ng/mL or clinical stage ≥T3. Patients with negative, equivocal or oligometastatic disease on first line-imaging will cross over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT with that of conventional imaging for detecting nodal or distant metastatic disease. Histopathological, imaging and clinical follow-up at 6 months will define the primary endpoint according to a predefined scoring system. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross over, the cost of each imaging strategy, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer-term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. This trial will provide data to establish whether PSMA-PET/CT should replace conventional imaging in the primary staging of select high-risk localized PCa, or whether it should be used to provide incremental diagnostic information in selected cases.
Publisher: The Endocrine Society
Date: 12-04-2019
Abstract: Germline succinate dehydrogenase (SDHx) mutation carriers, especially SDHB, are at increased risk for malignancy and require life-long surveillance. Current guidelines recommend periodic whole-body MRI imaging. We assessed the incremental value of 68Ga-DOTA-octreotate (GaTate) positron emission tomography (PET)/CT compared with conventional imaging in such patients. SDHx mutation carriers who had GaTate PET/CT were retrospectively reviewed. Detection of lesions were compared with MRI or CT on a per-patient and per-lesion basis. Proof of lesions were based on histopathology or clinical/imaging follow-up. Twenty consecutive patients (median age, 46 years 10 males) were reviewed. Fourteen patients had SDHB, four, SDHD, one SDHC, and one SDHA mutation. Fifteen had prior surgery and/or radiotherapy. Indications for PET/CT were as follows: 7 patients for surveillance for previously treated disease, 9 residual disease, 2 asymptomatic mutation carriers, and 2 for elevated catecholamines. Median time between modalities was 1.5 months. GaTate PET/CT had higher sensitivity and specificity than conventional imaging. On a per-patient basis: PET/CT sensitivity 100%, specificity 100% MRI/CT 85% and 50%. Per-lesion basis: PET/CT sensitivity 100%, specificity 75% MRI/CT 80% and 25%. PET/CT correctly identified additional small nodal and osseous lesions. MRI/CT had more false-positive findings. Change of management resulted in 40% (8/20 patients): 3 received localized treatment instead of observation, 1 changed to observation given extra disease detected, 4 with metastases had radionuclide therapy. GaTate PET/CT provided incremental diagnostic information with consequent management impact in SDHx-pheochromocytoma and paraganglioma. Incorporating this modality as part of a surveillance program seems prudent. Further research is needed to define the optimal surveillance strategy including use of MRI.
Publisher: Springer Science and Business Media LLC
Date: 30-05-2017
Publisher: Springer Science and Business Media LLC
Date: 07-09-2010
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.BEHA.2011.02.005
Abstract: Imaging contributes to management of follicular lymphoma (FL) through guiding biopsy, determining disease stage and assessing therapeutic response. Molecular imaging with positron emission tomography (PET), especially when combined with computer tomography (PET/CT), is more accurate than conventional imaging and extends the role of imaging to lesion characterisation, including non-invasive assessment of high-grade transformation. There is strong data to support the use of FDG PET/CT for primary staging, resulting in significant management change. In patients with early stage follicular lymphoma (stage I or II), there is a clear role for PET/CT to avoid futile involved-field radiotherapy in patients with widespread disease and to optimise the treatment field in patients with confirmed localised disease. For restaging, use of PET/CT allows discrimination between scar tissue and viable tumour in residual masses. Molecular imaging is likely to play an increasing role in selection of patients for specific treatments and in prognostic stratification.
Publisher: Society of Nuclear Medicine
Date: 20-03-2013
DOI: 10.2967/JNUMED.112.110890
Abstract: At present, there are no standard criteria that have been validated for interim PET reporting in lymphoma. In 2009, an international workshop attended by hematologists and nuclear medicine experts in Deauville, France, proposed to develop simple and reproducible rules for interim PET reporting in lymphoma. Accordingly, an international validation study was undertaken with the primary aim of validating the prognostic role of interim PET using the Deauville 5-point score to evaluate images and with the secondary aim of measuring concordance rates among reviewers using the same 5-point score. This paper focuses on the criteria for interpretation of interim PET and on concordance rates. A cohort of advanced-stage Hodgkin lymphoma patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were enrolled retrospectively from centers worldwide. Baseline and interim scans were reviewed by an international panel of 6 nuclear medicine experts using the 5-point score. Complete scan datasets of acceptable diagnostic quality were available for 260 of 440 (59%) enrolled patients. Independent agreement among reviewers was reached on 252 of 260 patients (97%), for whom at least 4 reviewers agreed the findings were negative (score of 1-3) or positive (score of 4-5). After discussion, consensus was reached in all cases. There were 45 of 260 patients (17%) with positive interim PET findings and 215 of 260 patients (83%) with negative interim PET findings. Thirty-three interim PET-positive scans were true-positive, and 12 were false-positive. Two hundred three interim PET-negative scans were true-negative, and 12 were false-negative. Sensitivity, specificity, and accuracy were 0.73, 0.94, and 0.91, respectively. Negative predictive value and positive predictive value were 0.94 and 0.73, respectively. The 3-y failure-free survival was 83%, 28%, and 95% for the entire population and for interim PET-positive and -negative patients, respectively (P < 0.0001). The agreement between pairs of reviewers was good or very good, ranging from 0.69 to 0.84 as measured with the Cohen kappa. Overall agreement was good at 0.76 as measured with the Krippendorf α. The 5-point score proposed at Deauville for reviewing interim PET scans in advanced Hodgkin lymphoma is accurate and reproducible enough to be accepted as a standard reporting criterion in clinical practice and for clinical trials.
Publisher: Springer Science and Business Media LLC
Date: 21-05-2014
Publisher: Wiley
Date: 16-01-2017
DOI: 10.1111/BJU.13600
Publisher: Wiley
Date: 16-07-2019
DOI: 10.1111/BJU.14814
Publisher: MDPI AG
Date: 20-01-2022
Abstract: Prostate cancer is the most commonly diagnosed solid-organ cancer amongst males worldwide. Metastatic castrate-resistant prostate cancer (mCRPC) is a rapidly fatal end-sequelae of prostate cancer. Therapeutic options for men with mCRPC are limited and are not curative in nature. The recent development of chimeric antigen receptor T-cell (CAR-T) therapy has revolutionised the treatment of treatment-resistant haematological malignancies, and several studies are underway investigating the utility of this technology in the treatment of solid tumours. In this review, we evaluate the current treatment options for men with mCRPC as well as the current landscape of preclinical and clinical trials of CAR-T cell therapy against prostate cancer. We also appraise the various prostate cancer-specific tumour-associated antigens that may be targeted by CAR-T cell technology. Finally, we examine the potential translational barriers of CAR-T cell therapy in solid tumours. Despite preclinical success, preliminary clinical trials in men with prostate cancer have had limited efficacy. Therefore, further clinically translatable preclinical models are required to enhance the understanding of the role of this investigational therapeutic in men with mCRPC. In the era of precision medicine, tailored immunotherapy administered to men in a tumour-agnostic approach provides hope to a group of men who otherwise have few treatment options available.
Publisher: Springer Berlin Heidelberg
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 18-07-2013
DOI: 10.1007/S00259-013-2504-X
Abstract: The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion. The whole-blood clearance of (177)Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion. LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline 95 % CI -6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion. The greatest renal exposure to circulating radiopeptide occurs in the first 1 - 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation.
Publisher: Springer Science and Business Media LLC
Date: 07-04-2017
DOI: 10.1007/S00259-017-3691-7
Abstract: The treatment of melanoma has been revolutionised in recent years by advances in the understanding of the genomic landscape of this disease, which has led to the development of new targeted therapeutic agents, and the ability to therapeutically manipulate the immune system through inhibition of cancer cell-T-cell interactions that prevent an adaptive immune response. While these therapeutic interventions have dramatically improved the prospects of survival for patients with advanced melanoma, they bring significant complexity to the interpretation of therapeutic response because their mechanisms and temporal profile of response vary considerably. In this review, we discuss the mode of action of these emerging therapies and their toxicities to provide a framework for the use of FDG PET/CT in therapeutic response assessment. We propose that the greatest utility of PET in assessment of response to agents that abrogate signalling related to BRAF mutation is for early assessment of resistance, while in anti-CTLA4 therapy, immunological flare can compromise early assessment of response but can identify potentially life-threatening autoimmune reactions. For anti-PD1/PDL1 therapy, the role of FDG PET/CT is more akin to its use in other solid malignancies undergoing treatment with conventional chemotherapy. However, further research is required to optimise the timing of scans and response criteria in this disease.
Publisher: Society of Nuclear Medicine
Date: 12-02-2015
DOI: 10.2967/JNUMED.114.147843
Abstract: Glomerular filtration rate (GFR) can accurately be determined using (51)Cr-ethylenediaminetetraacetic acid (EDTA) plasma clearance counting but is time-consuming and requires technical skills and equipment not always available in imaging departments. (68)Ga-EDTA can be readily available using an onsite generator, and PET/CT enables both imaging of renal function and accurate camera-based quantitation of clearance of activity from blood and its appearance in the urine. This study aimed to assess agreement between (68)Ga-EDTA GFR ((68)Ga-GFR) and (51)Cr-EDTA GFR ((51)Cr-GFR), using serial plasma s ling and PET imaging. (68)Ga-EDTA and (51)Cr-EDTA were injected concurrently in 31 patients. Dynamic PET/CT encompassing the kidneys was acquired for 10 min followed by 3 sequential 3-min multibed step acquisitions from kidneys to bladder. PET quantification was performed using renal activity at 1-2 min (PETinitial), renal excretion at 2-10 min (PETearly), and, subsequently, urinary excretion into the collecting system and bladder (PETlate). Plasma s ling at 2, 3, and 4 h was performed, with (68)Ga followed by (51)Cr counting after positron decay. The level of agreement for GFR determination was calculated using a Bland-Altman plot and Pearson correlation coefficient (PCC). (51)Cr-GFR ranged from 10 to 220 mL/min (mean, 85 mL/min). There was good agreement between (68)Ga-GFR and (51)Cr-GFR using serial plasma s ling, with a Bland-Altman bias of -14 ± 20 mL/min and a PCC of 0.94 (95% confidence interval, 0.88-0.97). Of the 3 methods used for camera-based quantification, the strongest correlation was for plasma s ling-derived GFR with PETlate (PCC of 0.90 95% confidence interval, 0.80-0.95). (68)Ga-GFR agreed well with (51)Cr-GFR for estimation of GFR using serial plasma counting. PET dynamic imaging provides a method to estimate GFR without plasma s ling, with the additional advantage of enabling renal imaging in a single study. Additional validation in a larger cohort is warranted to further assess utility.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.EUO.2018.11.007
Abstract: Prostate-specific membrane antigen (PSMA) is overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and represents a target for imaging and therapy. We undertook a prospective trial of To determine outcomes for men screened for the trial but not treated because of low PSMA expression. Patients screened with Subsequent treatments received were recorded. Kaplan-Meier analysis was used to determine overall survival from date of screening. Sixteen patients (24%) had low PSMA expression (n=8) or discordant FDG-avid disease (n=8). The median prostate-specific antigen doubling-time was 2.1mo. Eleven patients had Gleason ≥8 disease. All patients had previously progressed after docetaxel, 44% after cabazitaxel, and 94% after abiraterone and/or enzalutamide. Nine patients had subsequent systemic antitumour treatment. Fifteen patients died, with median OS of 2.5mo (95% confidence interval 1.7-5.0). Study limitations include uncertainty for imaging thresholds that define low PSMA expression. It is also possible that theranostic therapy could have improved survival in this cohort. Low PSMA expression or discordant FDG-avid disease in patients with mCRPC who progress after conventional therapies identifies a group with poor prognosis and short survival. The
Publisher: Wiley
Date: 06-2013
DOI: 10.1118/1.4815342
Publisher: Springer Science and Business Media LLC
Date: 20-10-2018
DOI: 10.1007/S00259-018-4196-8
Abstract: Rectal neuroendocrine neoplasia (NEN) is more common than other NEN origins, but is less commonly metastatic. However, when present, distant disease carries a particularly poor prognosis. Evidence guiding optimal treatment of such patients is lacking. We assessed PRRT outcomes in patients with somatostatin receptor (SSTR) positive metastatic rectal NEN from two referral centres. Patients treated with PRRT were retrospectively reviewed. Morphologic (RECIST 1.1), SSTR imaging responses and toxicity were assessed 3 months post-PRRT. Kaplan-Meier estimate was used to determine progression-free survival (PFS) and overall survival (OS) from start of PRRT. Twenty-seven consecutive patients (M = 20, age 31-81 years) were reviewed. The majority (70%) had ENETs grade 2 disease (19 patients), three had Grade 3, one Grade 1, and four not documented. Overall, 63% (10/16 patients with available FDG PET/CT) had FDG avid disease. Twenty-six patients were treated for disease progression. Most had Our results indicate high efficacy and morphologic responses with minimal toxicity and very encouraging survival from PRRT in patients with metastatic rectal NEN despite the adverse prognostic features of this cohort. Further prospective PRRT trials are warranted in this subgroup.
Publisher: Wiley
Date: 03-10-2018
DOI: 10.1111/ANAE.14447
Abstract: Cardiac events are a common cause of peri-operative morbidity. Cardiopulmonary exercise testing can objectively assess risk, but it does not quantify myocardial ischaemia. With appropriate dietary preparation to suppress basal myocardial glucose uptake, positron emission tomography with
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.EURURO.2018.06.004
Abstract: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option for oligometastatic prostate cancer. However, limited prospective evidence is available. To determine the safety and feasibility of single fraction SABR for patients with oligometastatic prostate cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen response. In a prospective clinical trial, patients were screened with computed tomography, bone scan, and sodium fluoride positron emission tomography scan and had one to three oligometastases. Kaplan-Meier methods were used to determine LPFS and DPFS. Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. QoL was assessed using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BM22 at 1, 3,12, and 24 mo. A single fraction of 20-Gy SABR to each lesion. Between 2013 and 2014, 33 consecutive patients received SABR to a total of 50 oligometastases and were followed for 2 yr. The median age was 70 yr. The Gleason score was ≥8 in 15 patients (45%). Twenty patients had bone only, 12 had node only, and one had mixed disease. SABR was feasible and delivered as planned in 97% of cases. There was one grade 3 adverse event (3.0%, vertebral fracture). No patient died. The 1 and 2-yr LPFS was 97% (95% confidence interval [CI]: 91-100) and 93% (95% CI: 84-100), and DPFS was 58% (95% CI: 43-77) and 39% (95% CI: 25-60), respectively. In those not on androgen deprivation therapy (ADT n=22), the 2-yr freedom from ADT was 48%. There was no significant difference from baseline QoL observed. Limitations include small s le size, limited duration of follow-up, and lack of a control arm. A single SABR session was feasible and associated with low morbidity in this cohort. Over one-third of patients did not progress and were free from ADT at 2-yr. QoL measures were maintained with this treatment strategy. This clinical trial investigated single treatment stereotactic radiotherapy for low volume advanced prostate cancer. The approach was found to be safe with avoidance of hormone therapy in almost half of the participants at 2 yr.
Publisher: American Medical Association (AMA)
Date: 24-09-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2016
DOI: 10.1213/ANE.0000000000001562
Abstract: Dilation of lymphatic vessels may contribute to iatrogenic dissemination of cancer cells during surgery. We sought to determine whether neuraxial anesthesia reduces regional lymphatic flow. Using nuclear lymphoscintigraphy, 5 participants receiving spinal anesthesia for brachytherapy had lower extremity lymph flow at rest compared with flow under conditions of spinal anesthesia. Six limbs were analyzed. Four limbs were excluded because of failure to demonstrate lymph flow (1 patient, 2 limbs), colloid injection error (1 limb), and undiagnosed deep vein thrombosis (1 limb). All analyzed limbs showed reduced lymph flow washout from the pedal injection site (range 62%–100%) due to neuraxial anesthesia. Lymph flow was abolished in 3 limbs. We report proof-of-concept that neuraxial anesthesia reduces lymphatic flow through a likely mechanism of sympathectomy.
Publisher: Society of Nuclear Medicine
Date: 09-06-2016
DOI: 10.2967/JNUMED.115.171983
Abstract: Pre- and posttreatment PET comparative scans should ideally be obtained with identical acquisition and processing, but this is often impractical. The degree to which differing protocols affect PERCIST classification is unclear. This study evaluates the consistency of PERCIST classification across different reconstruction algorithms and whether a proprietary software tool can harmonize SUV estimation sufficiently to provide consistent response classification. Eighty-six patients with non-small cell lung cancer, colorectal liver metastases, or metastatic melanoma who were scanned for therapy monitoring purposes were prospectively recruited in this multicenter trial. Pre- and posttreatment PET scans were acquired in protocols compliant with the Society of Nuclear Medicine and Molecular Imaging and the European Association of Nuclear Medicine (EANM) acquisition guidelines and were reconstructed with a point spread function (PSF) or PSF + time-of-flight (TOF) for optimal tumor detection and also with standardized ordered-subset expectation maximization (OSEM) known to fulfill EANM harmonizing standards. After reconstruction, a proprietary software solution was applied to the PSF ± TOF data (PSF ± TOF.EQ) to harmonize SUVs with the OSEM values. The impact of differing reconstructions on PERCIST classification was evaluated. For the OSEM Reconstruction algorithm-dependent variability in PERCIST classification is a significant issue but can be overcome by harmonizing SULs using a proprietary software tool.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.UCL.2018.03.016
Abstract: Radiolabeled prostate-specific membrane antigen PET (PSMA PET) is emerging as an important modality for imaging prostate cancer (PCa). Promising clinical experience has led to increasing number of studies exploring the role of PSMA PET in different aspects of PCa including primary detection, risk stratification, targeted biopsy, initial staging, restaging at biochemical recurrence, biologic characterization, treatment response assessment and prognostication. PSMA PET may prove an important disease biomarker, expand our understanding of the pathogenesis and pave the way for personalized management of PCa.
Publisher: Springer Science and Business Media LLC
Date: 12-06-2019
DOI: 10.1007/S00259-019-04388-3
Abstract: Inflammatory FDG uptake in the lung (PET-pneumonitis) following curative-intent radiotherapy (RT)/chemo-RT (CRT) in non-small cell lung cancer (NSCLC) can pose a challenge in FDG-PET/CT response assessment. The aim of this study is to describe different patterns of PET-pneumonitis to guide the interpretation of FDG-PET/CT and investigate its association with tumor response and overall survival (OS). Retrospective analysis was performed on 87 NSCLC patients in three prospective trials who were treated with radical RT (n = 7) or CRT (n = 80), with baseline and post-treatment FDG-PET/CT. Visual criteria were performed for post-treatment FDG-PET/CT response assessment. The grading of PET-pneumonitis was based on relative lung uptake intensity compared to organs of reference and classified as per Deauville score from grade 1-5. Distribution patterns of PET-pneumonitis were defined as follows: A) patchy/sub-pleural B) diffuse (involving more than a segment) and C) peripheral (diffusely surrounding a photopenic region). Follow-up FDG-PET/CT scans were performed approximately 3 months (median, 89 days interquartile range, 79-93) after RT. Overall, PET-pneumonitis was present in 62/87 (71%) of patients, with Deauville 2 or 3 in 12/62 (19%) and 4 or 5 in 50/62 (81%) of patients. The frequency of patterns A, B and C of PET-pneumonitis was 19/62 (31%), 20/62 (32%) and 23/62 (37%), respectively. No association was found between grade or pattern of PET-pneumonitis and overall response at follow-up PET/CT (p = 0.27 and p = 0.56, respectively). There was also no significant association between PET-pneumonitis and OS (hazard ratio [HR], 1.3 95% confidence interval [CI], 0.6-2.5 p = 0.45). Early FDG-PET/CT response assessment, however, was prognostic for OS (HR, 1.7 95% CI, 1.2-2.2 p < 0.001). PET-pneumonitis is common in early post-CRT/RT, but pattern recognition may assist in response assessment by FDG-PET/CT. While FDG-PET/CT is a powerful tool for response assessment and prognostication, PET-pneumonitis does not appear to confound early response assessment or to independently predict OS.
Publisher: Springer Science and Business Media LLC
Date: 18-10-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2018
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1053/J.SEMNUCLMED.2016.04.002
Abstract: Nuclear medicine renal imaging provides important functional data to assist in the diagnosis and management of patients with a variety of renal disorders. Physiologically stable metal chelates like ethylenediaminetetraacetic acid (EDTA) and diethylenetriamine penta-acetate (DTPA) are excreted by glomerular filtration and have been radiolabelled with a variety of isotopes for imaging glomerular filtration and quantitative assessment of glomerular filtration rate. Gallium-68 ((68)Ga) EDTA PET usage predates Technetium-99m ((99m)Tc) renal imaging, but virtually disappeared with the widespread adoption of gamma camera technology that was not optimal for imaging positron decay. There is now a reemergence of interest in (68)Ga owing to the greater availability of PET technology and use of (68)Ga to label other radiotracers. (68)Ga EDTA can be used a substitute for (99m)Tc DTPA for wide variety of clinical indications. A key advantage of PET for renal imaging over conventional scintigraphy is 3-dimensional dynamic imaging, which is particularly helpful in patients with complex anatomy in whom planar imaging may be nondiagnostic or difficult to interpret owing to overlying structures containing radioactive urine that cannot be differentiated. Other advantages include accurate and absolute (rather than relative) camera-based quantification, superior spatial and temporal resolution and integrated multislice CT providing anatomical correlation. Furthermore, the (68)Ga generator enables on-demand production at low cost, with no additional patient radiation exposure compared with conventional scintigraphy. Over the past decade, we have employed (68)Ga EDTA PET/CT primarily to answer difficult clinical questions in patients in whom other modalities have failed, particularly when it was envisaged that dynamic 3D imaging would be of assistance. We have also used it as a substitute for (99m)Tc DTPA if unavailable owing to supply issues, and have additionally examined the role of (68)Ga EDTA PET/CT for measuring glomerular filtration rate and split renal function.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2016
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.EURURO.2020.01.012
Abstract: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence. To present the results from the APCCC 2019. Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions. The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process. Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material. These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be in idualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials. The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.
Publisher: Wiley
Date: 12-07-2022
DOI: 10.1111/BJU.15773
Publisher: Springer Science and Business Media LLC
Date: 26-11-2014
Publisher: Springer Science and Business Media LLC
Date: 26-07-2018
Publisher: Springer Science and Business Media LLC
Date: 24-01-2018
Publisher: Society of Nuclear Medicine
Date: 12-08-2021
Publisher: Society of Nuclear Medicine
Date: 03-09-2015
DOI: 10.2967/JNUMED.115.162586
Abstract: Pulmonary function tests (PFTs) are routinely used to assess lung function, but they do not provide information about regional pulmonary dysfunction. We aimed to assess correlation of quantitative ventilation-perfusion (V/Q) PET/CT with PFT indices. Thirty patients underwent V/Q PET/CT and PFT. Respiration-gated images were acquired after inhalation of (68)Ga-carbon nanoparticles and administration of (68)Ga-macroaggregated albumin. Functional volumes were calculated by iding the volume of normal ventilated and perfused (%NVQ), unmatched and matched defects by the total lung volume. These functional volumes were correlated with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, and diffusing capacity for carbon monoxide (DLCO). All functional volumes were significantly different in patients with chronic obstructive pulmonary disease (P < 0.05). FEV1/FVC and %NVQ had the highest correlation (r = 0.82). FEV1 was also best correlated with %NVQ (r = 0.64). DLCO was best correlated with the volume of unmatched defects (r = -0.55). Considering %NVQ only, a cutoff value of 90% correctly categorized 28 of 30 patients with or without significant pulmonary function impairment. Our study demonstrates strong correlations between V/Q PET/CT functional volumes and PFT parameters. Because V/Q PET/CT is able to assess regional lung function, these data support the feasibility of its use in radiation therapy and preoperative planning and assessing pulmonary dysfunction in a variety of respiratory diseases.
Publisher: Informa UK Limited
Date: 06-06-2020
Publisher: Wiley
Date: 05-2007
Publisher: Society of Nuclear Medicine
Date: 12-08-2021
Publisher: Springer Science and Business Media LLC
Date: 05-03-2020
Publisher: The Endocrine Society
Date: 09-06-2017
Abstract: Treatment options for unresectable paraganglioma (PGL) heochromocytoma (PCC), especially with uncontrolled secondary hypertension (HTN), are limited. Preliminary studies with peptide receptor radionuclide therapy (PRRT) suggest efficacy, but data on HTN control and survival are lacking. We assessed PRRT outcomes in such patients from two referral centers. Twenty consecutive patients (13 men age range, 21 to 77 years) with high somatostatin receptor (SSTR) expression treated with 177Lu-DOTA-octreotate, nine with radiosensitizing chemotherapy, were retrospectively reviewed. Median cumulative activity was 22 GBq (median 4 cycles). Fourteen patients were treated for uncontrolled HTN and six for progressive or symptomatic metastatic disease or local recurrence. Three months after PRRT, 8 of 14 patients treated for HTN required reduced medication doses, 5 had no change in anti-HTN doses, and 1 was lost to follow-up. Eighty-six percent had serum chromogranin-A reduction. Of the entire cohort, 36% had disease regression (29% partial and 7% minor response) on computed tomography, with stable findings in 50%. Three other patients had bony disease evaluable only on SSTR imaging (2 partial response and 1 stable). Median progression-free survival was 39 months median overall survival was not reached (5 deaths median follow-up, 28 months). Four patients had grade 3 lymphopenia 2 had grade 3 thrombocytopenia. Renal impairment in 2 patients was attributed to underlying disease processes. PRRT achieves worthwhile clinical and biochemical responses with low toxicity and encouraging survival in PGL/PCC. Because PRRT has logistic and radiation-safety advantages compared to 131I-MIBG therapy, further prospective evaluation is warranted.
Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 06-2010
DOI: 10.1186/BCR2591
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.CPET.2015.05.005
Abstract: This review provides practical guidance for clinicians involved in the management of endocrine malignancies, including endocrinologists, medical oncologists, surgeons and nuclear medicine specialists regarding the indications and use of 2-fluoro-2-deoxy-d-glucose F-18 (FDG) PET/computed tomography (CT), particularly with respect to targeted radionuclide therapy. Key principles of FDG PET/CT for radionuclide therapy are explored in detail using gastroenteropancreatic neuroendocrine tumors as a prototype endocrine malignancy. The relevant literature is reviewed, and practical application in this new and emerging field is highlighted with the use of case ex les.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2013
Publisher: E-MED LTD
Date: 2011
Publisher: Springer Science and Business Media LLC
Date: 11-06-2019
DOI: 10.1007/S00259-019-04389-2
Abstract: Peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) is an effective therapy for metastatic neuroendocrine neoplasia (NEN), but therapy-related myeloid neoplasms (t-MN) remain of concern. The study reviewed the clinicopathological features and outcomes of patients who developed t-MN. Retrospective analysis of all patients diagnosed with t-MN by 2016 WHO classification, from a cohort of 521 patients who received PRRT/PRCRT over a 12-year period. Molecular next-generation sequencing using an in-house 26-gene panel was performed. Twenty-five of 521 (4.8%) patients were diagnosed with t-MN, including six acute myeloid leukaemia (AML) and 19 myelodysplastic syndrome (MDS). The median time from first cycle PRRT/PRCRT to diagnosis of t-MN was 26 months (range 4-91). Twenty-two of 25 (88%) patients had grade 1-2 pancreatic or small bowel NEN with moderate metastatic liver burden. Six patients (24%) had prior chemotherapy. Median number of PRRT cycles = 5 (22/25 (88%) with concomitant radiosensitising chemotherapy). All 25 patients achieved disease stabilisation (68%) or partial response (32%) on RECIST 1.1 at 3 months post-PRRT. At t-MN diagnosis, all patients presented with thrombocytopenia (median nadir 33 × 10 The diagnosis of t-MN after PRRT/PRCRT is an infrequent but serious complication with poor overall survival. Most patients present with thrombocytopenia unfavourable genetic mutations have a poor response to t-MN treatment. Prospective data are needed to explore potential pre-existing genetic factors and predictive biomarkers to minimise the risk of t-MN.
Publisher: Society of Nuclear Medicine
Date: 16-09-2009
DOI: 10.2967/JNUMED.109.064121
Abstract: Many studies demonstrate a high accuracy for PET in staging lymphoma, but few assess observer variation. This study quantified agreement for staging lymphoma with PET/CT. The PET/CT images of 100 patients with lymphoma who had been referred for staging were reviewed by 3 experienced observers, with 2 observers reviewing each series a second time. Ann Arbor stage and in idual nodal and extranodal regions were assessed. Weighted kappa (kappa(w)) and intraclass correlation coefficient were used to compare ratings. Intra- and interobserver agreement was high for Ann Arbor stage (kappa(w) = 0.79-0.91), number of nodal regions involved (intraclass correlation coefficient, 0.83-0.93), and presence of extranodal disease (kappa = 0.74-0.86). High agreement was also observed for all nodal regions (kappa(w) > 0.60) except hilar (kappa(w) = 0.56-0.82) and infraclavicular (kappa(w) = 0.14-0.55). Lower agreement was observed for bowel involvement (kappa(w) = 0.37-0.71). Experienced observers had a high level of agreement using PET/CT for lymphoma staging, supporting its use as a robust noninvasive staging tool. Further research is needed to evaluate observer variability for restaging during and after chemotherapy.
Publisher: American Association for Cancer Research (AACR)
Date: 31-08-2015
DOI: 10.1158/1078-0432.CCR-15-1073
Abstract: High somatostatin receptor expression on the cell membrane of succinate dehydrogenase mutation-related pheochromocytoma and paraganglioma provides a potential target for imaging and therapy. 68Ga-DOTATATE positron emission PET/CT may represent a new gold standard for staging pheochromocytoma araganglioma and have future therapeutic implications. Clin Cancer Res 21(17) 3815–7. ©2015 AACR. See related article by Janssen et al., p. 3888
Publisher: Informa UK Limited
Date: 28-12-2010
Publisher: SAGE Publications
Date: 09-01-2016
Abstract: Ga-68-macroaggregated albumin ( 68 Ga-perfusion) positron emission tomography/computed tomography (PET/CT) is a novel imaging technique for the assessment of functional lung volumes. The purpose of this study was to use this imaging technique for functional adaptation of definitive radiotherapy plans in patients with non-small cell lung cancer (NSCLC). This was a prospective clinical trial of patients with NSCLC who received definitive 3-dimensional (3D) conformal radiotherapy to 60 Gy in 30 fx and underwent pretreatment respiratory-gated (4-dimensional [4D]) perfusion PET/CT. The “perfused” lung volume was defined as all lung parenchyma taking up radiotracer, and the “well-perfused” lung volume was contoured using a visually adapted threshold of 30% maximum standardized uptake value (SUVmax). Alternate 3D conformal plans were subsequently created and optimized to avoid perfused and well-perfused lung volumes. Functional dose volumetrics were compared using mean lung dose (MLD), V5 (volume receiving 5 Gy or more), V10, V20, V30, V40, V50, and V60 parameters. Fourteen consecutive patients had alternate radiotherapy plans created based on functional lung volumes. When considering the original treatment plan, the dose to perfused and well-perfused functional lung volumes was similar to that of the conventional anatomical lung volumes with an average MLD of 12.15, 12.67, and 12.11 Gy, respectively. Plans optimized for well-perfused lung improved functional V30, V40, V50, and V60 metrics (all P values .05). The functional MLD of well-perfused lung was improved by a median of 0.86 Gy, P .01. However, plans optimized for perfused lung only showed significant improvement in the functional V60 dose parameter (median 1.00%, P = .04) but at a detriment of a worse functional V5 (median 3.33%, P = .05). This study demonstrates proof of principle that 4D-perfusion PET/CT may enable functional lung avoidance during treatment planning of patients with NSCLC. Radiotherapy plans adapted to well-perfused but not perfused functional lung volumes allow for reduction in dose to functional lung using 3D conformal radiotherapy.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1053/J.SEMNUCLMED.2018.10.013
Abstract: Ventilation/Perfusion (V/Q) positron emission tomography computed tomography (PET/CT) is now possible by substituting Technetium-99m (
Publisher: Wiley
Date: 20-07-2016
DOI: 10.1002/AJH.24469
Publisher: Springer Science and Business Media LLC
Date: 11-01-2016
Publisher: Elsevier BV
Date: 11-2018
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 10-11-2017
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.RADONC.2016.01.027
Abstract: To evaluate renal dysfunction after stereotactic ablative body radiotherapy (SABR) for inoperable primary renal cell carcinoma (RCC) using nuclear medicine assessments. In a prospective clinical trial, patients received single fraction renal SABR (26 Gy) for tumours 50% isodoses) may help reduce risk of functional loss.
Publisher: Society of Nuclear Medicine
Date: 29-03-2019
Publisher: No publisher found
Date: 2014
DOI: 10.1136/BMJ.G247
Publisher: Elsevier BV
Date: 09-2019
Publisher: The Endocrine Society
Date: 09-2014
DOI: 10.1210/JC.2013-4090
Publisher: Wiley
Date: 11-06-2023
DOI: 10.1111/BJU.16086
Publisher: Springer Science and Business Media LLC
Date: 20-08-2016
Publisher: American Society of Clinical Oncology (ASCO)
Date: 04-2019
DOI: 10.1200/JCO.18.01927
Publisher: Springer Science and Business Media LLC
Date: 12-09-2018
DOI: 10.1007/S00259-017-3821-2
Abstract: Grade 3 NENs are aggressive tumours with poor prognosis. PRRT+/- radiosensitising chemotherapy is a potential treatment for disease with high somatostatin receptor (SSTR) expression without spatially discordant FDG-avid disease. We retrospectively evaluated the efficacy of PRRT in G3 NEN. Kaplan-Meier estimation was used to determine progression-free survival (PFS) and overall survival (OS) defined from start of PRRT. Subgroup analysis was performed for patients with Ki-67 ≤ 55% and >55%. Anatomical response (RECIST 1.1) and toxicity 3 months after PRRT was determined. Disease control rate (DCR) was defined as complete response (CR), partial response (PR) and stable disease (SD) of those with prior progression. 28 patients (M = 17 age 16-78 years Ki-67 ≤ 55% = 22) were reviewed. 17 patients had pancreatic, 5 small bowel, 3 large bowel, 2 bronchial and 1 unknown primary disease. 25/28 had significant FDG-avid disease prior to treatment. Most had PRRT achieves clinically relevant disease control with acceptable toxicity in G3 NENs.
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.EURURO.2019.01.049
Abstract: Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer, typically in biochemically recurrent or advanced disease. Following our previous meta-analysis, a high-volume series has been reported highlighting the utility of To perform a systematic review and meta-analysis to update reported predictors of positive We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science databases in July 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analyses of proportions were performed using a random-effect model. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models. A total of 37 articles including 4790 patients were analysed. For patients with biochemical recurrence, positive Ga-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels of >0.2ng/ml (33%) and 0.2-0.5ng/ml (45%). Ga-68-PSMA-PET produces favourable sensitivity and specificity profiles on meta-analysis of pooled data. This analysis highlights different anatomic patterns of metastatic spread according to PSMA PET in the primary and biochemically recurrent settings. Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard of care imaging modalities to improve the detection of metastatic disease in prostate cancer, particularly in the setting of disease recurrence. To date, this imaging modality in the setting of primary staging is controversial, given the paucity of data. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.
Publisher: Society of Nuclear Medicine
Date: 26-03-2015
No related grants have been discovered for Michael Hofman.