The Clinical Utility of Gallium-68-DOTATATE Positron Emission Tomography Scanning in Medullary Thyroid Cancer.

OBJECTIVE: Somatostatin receptor (SST) functional imaging with positron emission tomography (PET)/computed tomography (CT) has broadened the diagnostic and staging capabilities for medullary thyroid cancer (MTC). Gallium-68 (68Ga)-DOTA-conjugated peptide (Tyr3)-octreotate (DOTATATE) is a radiotracer with a high affinity for type 2 SSTs expressed in several, but not all, MTCs. The utility of 68Ga-DOTATATE PET/CT and 18fluorine-labeled fluoro-2-deoxy-D-glucose (18F-FDG)-PET/CT imaging in predicting MTC prognosis is also unknown. METHODS: In this single-center retrospective study, 103 of patients with MTC underwent assessment of SST2 and SST5 immunohistochemistry (IHC). A subgroup of 37 patients received 68Ga-DOTATATE PET/CT imaging, and 13 received contemporaneous 18F-FDG-PET/CT imaging. The maximum standardized uptake value (SUV), mean SUV, metabolic tumor volume, and total lesion activity (TLA) were assessed. RESULTS: Forty-two patients (41%) demonstrated positive expression of SST2, and 45 (44%) had a positive SST5 IHC result. Seventeen patients (17%) expressed both SST2 and SST5. No survival advantage was identified with SST2 or SST5 IHC positivity. No correlation was noted between the maximum SUV, mean SUV, metabolic tumor volume, or TLA and SST2 and/or SST5 expression by IHC. Shorter survival was associated with a TLA of >20 (P = .04). A RET-negative status also appeared to have shorter survival, although this may be because the small numbers did not reach statistical significance (P = .12). CONCLUSION: Assessment of TLA from 68Ga-DOTATATE PET/CT may predict survival. SST2 IHC was not correlated with 68Ga-DOTATATE avidity. Metastatic disease may be optimally assessed by concurrent 18F-FDG and 68Ga-DOTATATE imaging.

Dual [68Ga]DOTATATE and [18F]FDG PET/CT in patients with metastatic gastroenteropancreatic neuroendocrine neoplasms: a multicentre validation of the NETPET score.

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) are heterogeneous in clinical course, biology, and outcomes. The NETPET score predicts survival by scoring uptake on dual [68Ga]DOTATATE and [18F]FDG PET/CT scans. We aimed to validate previous single-centre findings in a multicentre, international study. METHODS: Dual scans were assigned a NETPET score of P1 (DOTATATE positive/FDG negative), P2-4 (DOTATATE positive/FDG positive), or P5 (DOTATATE negative/FDG positive). NETPET score, histological grade, age at diagnosis, and presence/absence of extrahepatic disease were compared to overall survival/time to progression on univariate and multivariate analysis. RESULTS: 319 metastatic/unresectable GEPNEN patients were included. The NETPET score was significantly associated with overall survival and time to progression on univariate and multivariate analysis (all p < 0.01). Median overall survival/time to progression was 101.8/25.5 months for P1, 46.5/16.7 months for P2-4, and 11.5/6.6 months for P5. Histological grade correlated with overall survival and time to progression on univariate and multivariate analysis (all p < 0.01), while presence/absence of extrahepatic disease did not. Age at diagnosis correlated with overall survival on univariate and multivariate analysis (p < 0.01). The NETPET score also correlated with histological grade (p < 0.001). CONCLUSION: This study validates the NETPET score as a prognostic biomarker in metastatic GEPNENs, capturing the complexity of dual PET imaging.

I-PET score: Combining whole body iodine and 18 F-FDG PET/CT imaging to predict progression in structurally or biochemically incomplete thyroid cancer.

OBJECTIVE: We propose a new scoring system (I-PET) combining whole body scan (WBS) and FDG findings to identify patients who have or are likely to become refractory to radioactive iodine. DESIGN: Retrospective analysis of 142 patients age >18 with differentiated thyroid cancer who had a F-18 labelled fluoro-2-deoxyglucose (18 F-FDG) positron emission tomography (PET) and WBS within a 6-month period between 2010 and 2020. Pairs of 18 F-FDG PET and WBS were reviewed by three independent nuclear medicine physicians and an I-PET score was assigned: I-PET [0]: Iodine -ve/FDG -ve, I-PET [1]: Iodine +ve/FDG -ve, I-PET [2]: Iodine +ve/FDG +ve and I-PET [3]: Iodine -ve/FDG +ve. Patients with FDG +ve lesions (I-PET [2] and I-PET [3]) were further classified into groups A and B if SUVmax was ≤5 or >5, respectively. Follow-up data were obtained by chart review. Progression was defined as structural progression as per RECIST 1.1 or further surgical intervention; or biochemical progression as unstimulated thyroglobulin increasing >20% from baseline. RESULTS: Of 142 patients included in the study 121 patients had follow-up data available for review. At baseline, 49 patients were classified as I-PET [0], 10 as I-PET [1], 16 as I-PET [2] and 46 as I-PET [3]. Progression was seen in 11/49 (22%) of I-PET [0], 4/10 (40%) of I-PET [1], 10/16 (63%) of I-PET [2] and 34/46 (74%) of I-PET [3] (p < 0.001). I-PET [2B] and I-PET [3B] had a progression rate of 88% (7/8) and 78% (25/32), respectively. I-PET [3B] were 9.6 times more likely to commence multikinase inhibitor therapy (p = 0.001) and had 8 times greater mortality (p = 0.003) than patients in other I-PET groups combined. CONCLUSION: I-PET is a simple readily acquired imaging biomarker that potentially enhances the dynamic risk stratification and guide treatment in thyroid cancer.

Delineation and agreement of FET PET biological volumes in glioblastoma: results of the nuclear medicine credentialing program from the prospective, multi-centre trial evaluating FET PET In Glioblastoma (FIG) study-TROG 18.06.

PURPOSE: The O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation. METHODS: Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBRmax), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBRmax/TBRmean) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD]). RESULTS: Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBRmax, and TBRmean were 21.53% (12.00-30.10%), 5.89% (5.01-6.68%), and 5.01% (3.37-6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63-0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement. CONCLUSION: The FIG study credentialing program has increased expertise across study sites. TBRmax and TBRmean were robust, with considerable variability in BTV delineation and image interpretation observed.

The Clinical Significance of Small Vessel Vasculitis on Temporal Artery Biopsies.

BACKGROUND: Giant cell arteritis (GCA) is the most common type of systemic vasculitis in the elderly. Untreated, it can lead to irreversible blindness. Its diagnosis relies on a temporal artery biopsy (TAB). However, a proportion of patients have small vessel vasculitis (SVV) on biopsy; the prognosis of which remains unclear. The aim of this study is to compare the clinical presentation and long-term outcomes of those with SVV with negative and positive biopsies to determine whether long-term corticosteroid therapy can be avoided in these patients. METHODS: Post hoc analysis of patients with suspected GCA who underwent TAB and fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan as part of a prospective GCA and PET cohort. Patients were divided in to 3 groups based on TAB result: positive (inflammation in the main artery wall), negative (no inflammation), and SVV (isolated vasa vasorum or periadventitial SVV). Clinical, serological, and PET/CT data of patients with SVV were compared with those with positive and those with negative biopsies. RESULTS: For the 58 eligible patients recruited between May 2016 and December 2017, 11 had SVV, 12 had positive, and 35 had negative biopsies. Patients with SVV had similar clinical, serological, and PET/CT findings to those with negative biopsies. Compared with those with positive biopsies, patients with SVV had lower erythrocyte sedimentation rate (25 vs 78 mm/hour; P = 0.02), platelet count (296 vs 385 ×109/L; P = 0.03), and a lower median total vascular score on PET/CT scan (1.0 vs 13.5; P = 0.01). Median prednisone dose was lower (4.8 vs 11.7 mg; P = 0.015) and fewer were on steroid-sparing agents (20% vs 67%; P = 0.043) at 6 months. The percentage of patients with a clinical diagnosis of GCA was similar between those with SVV (3/11, 27.3%) and those with negative biopsies (5/35, 14.3%; P = 0.374). CONCLUSIONS: Patients with SVV on TAB had similar clinical features, PET/CT findings, and 6-month outcomes to those with negative biopsies. Small vessel vasculitis can be treated as equivalent to a negative biopsy when being considered for diagnosis and treatment of GCA.

Quantifying the effects of absorbed dose from radioembolisation on healthy liver function with [99mTc]TcMebrofenin.

PURPOSE: To quantify the effects of absorbed radiation dose on healthy liver parenchyma following radioembolisation (RE) using [99mTc]TcMebrofenin to analyse both global and regional liver function. METHODS: Patients having RE to treat hepatic disease underwent a [99mTc]TcMebrofenin hepatobilliary scintigraphy (HBS) study at both baseline and 8 weeks following treatment. Changes in global liver uptake rate were compared with healthy liver absorbed dose measures derived from the post-treatment 90Y PET/CT, including average dose, minimum dose to 70% of the volume (D70) and volume receiving at least 50 Gy (V50). Changes in functional burden associated with treatment and spared liver volumes in patients receiving lobar RE were also assessed, as were changes experienced by regional volumes corresponding to various dose ranges. Standard liver function pathology tests (LFTs) (bilirubin, albumin, ALP, AST, ALT and GGT) were examined for changes between baseline and post-treatment. RESULTS: Thirty-five patients were included in the study, of which, 9 had lobar treatment. A significant linear correlation was found between both baseline global liver uptake rate (negative) and D70 with change in global liver uptake rate. Patients undergoing lobar treatments demonstrated a shift in functional burden, and a significant difference was seen between the mean dose corresponding to liver volumes that increased their functional burden (9 Gy) and those that decreased their functional burden (35 Gy). No baseline LFTs predicted a decrease in global liver function; however, D70 demonstrated a linear correlation with changes in bilirubin and GGT. CONCLUSIONS: Given the significant negative relationship between baseline and change in global liver uptake rate, baseline HBS studies should not be used alone to disqualify patients considered for RE. In terms of treatment planning and evaluation, D70 may be the most appropriate metric of dose, with values greater than 15 Gy indicative of a likely drop in global liver function. The evidence of increasing functional burden in spared liver volumes suggests that patients at risk of complications could benefit from a lobar approach to treatment.

High Metabolic Tumour Volume on 18-Fluorodeoxyglucose Positron Emission Tomography Predicts Poor Survival from Neuroendocrine Neoplasms.

INTRODUCTION: 18-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) avidity in neuroendocrine neoplasms (NENs) has been associated with higher-grade disease. 18F-FDG avidity and high SUVmax have been demonstrated to predict poor outcome. Quantitative metrics of 18F-FDG PET, specifically metabolic tumour volume (MTV) and total lesion glycolysis (TLG), have been shown to be prognostic factors in other malignancies, but these have not been investigated to date in NENs. METHODS: Patients with NEN undergoing 18F-FDG at Royal North Shore Hospital from 2012 to 2018 were included. Images were analysed with automated segmentation (SUV cut-off of 4) followed by contour verification by a nuclear medicine physician and manual segmentation where required. Variables collected included patient age, histological grade, MTV, TLG, and SUVmax/SUVmean. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Univariate (UV) and multivariate (MV) analyses were performed for OS and PFS for MTV and TLG separately. For UV analysis, the median MTV and TLG were used to dichotomise the cohort. MTV/TLG for NENs of different histological grade were compared using ANOVA. RESULTS: One hundred and ninety patients were included (median age 63.5, 49% female). Primary site: 42% small bowel, 32% pancreas, 15% other gastrointestinal, 6% lung, 6% other. Grade for gastroenteropancreatic NENs and bronchial NEN: G1/typical carcinoid 37%, G2/atypical carcinoid 40%, G3/large-cell/small-cell neuroendocrine carcinoma 16%, unknown 8%. Median MTV was 4.83 mL (range 0-3,161 mL) and median TLG was 29.22. Patients with high MTV had worse median OS compared to those with low MTV (29.7 months vs. not reached, HR 4.1, 95% CI 2.25-7.49, p < 0.00001). Considered as a continuous variable, MTV predicted for poorer OS on UV (p < 0.00001) and MV (p = 0.003) analyses. Whilst histological grade was significant on both UV and MV, SUVmax was significant on UV (p < 0.00001) but not MV (p = 0.76). Tumours of higher grade had higher MTV (mean MTV - G1: 39.6 mL, G2: 107 mL, G3: 337 mL; p = 0.0001 by ANOVA). CONCLUSIONS: Quantitative analysis of 18F-FDG PET in NEN is feasible. High MTV/TLG are predictors of poor prognosis in NEN. Further analyses are underway to investigate a larger cohort of NEN patients.

[18F]FDG PET/CT-Avid Discordant Volume as a Biomarker in Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Multicenter Study.

[18F]FDG PET/CT and [68Ga]Ga-DOTATATE PET/CT are both used to predict tumor biology in neuroendocrine neoplasms. Although the presence of discordant ([18F]FDG-avid/non-[68Ga]Ga-DOTATATE-avid) disease predicts poor prognosis, the significance of the volume of such discordant disease remains undetermined. The aim of this study is to investigate discordant tumor volume as a potential biomarker in patients with advanced gastroenteropancreatic neuroendocrine neoplasms (GEPNENs). Methods: A multicenter retrospective study in patients with advanced GEPNENs and paired [18F]FDG and [68Ga]Ga-DOTATATE PET/CT no more than 85 d apart was conducted. Patients with discordant disease were identified by the NETPET score, and discordant lesions were contoured with a flat [18F]FDG SUV cutoff of 4. The primary variable of interest was the total discordant volume (TDV), which was the sum of the volumes of discordant lesions. Patients were dichotomized into high- and low-TDV cohorts by the median value. The primary endpoint was overall survival. Results: In total, 44 patients were included (50% men; median age, 60 y), with primary cancers in the pancreas (45%), small bowel (23%), colon (20%), and other (12%). Of the patients, 5% had grade 1 disease, 48% had grade 2 disease, and 48% had grade 3 disease (24% well differentiated, 67% poorly differentiated, 10% unknown within the grade 3 cohort). The overall median survival was 14.1 mo. Overall survival was longer in the low-TDV cohort than in the high-TDV cohort (median volume, 43.7 cm3; survival time, 23.8 mo vs. 9.4 mo; hazard ratio, 0.466 [95% CI, 0.229-0.948]; P = 0.0221). Patients with no more than 2 discordant intrahepatic lesions survived longer than those with 2 or more lesions (31.8 mo vs. 10.2 mo, respectively; hazard ratio, 0.389 [95% CI, 0.194-0.779]; P = 0.0049). Conclusion: TDV is a potential prognostic biomarker in GEPNENs and should be investigated in future neuroendocrine neoplasm trials.

Development of a novel clinical support tool for active surveillance of low risk papillary thyroid cancer.

Background: Active surveillance (AS) is an alternative to surgery in select patients with very low risk papillary thyroid cancer (PTC). Many clinicians feel ill-equipped in selecting appropriate patients. We aimed to 1) Develop an evidence-based web delivered decision support tool to assist clinicians in identifying patients appropriate for AS; and 2) Evaluate the prevalence of patients suitable for AS in a tertiary high volume thyroid cancer centre. Method: A REDCap web based clinical support tool was developed utilising evidence-based characteristics for AS suitability available to clinicals during initial assessment. A retrospective database was interrogated for patients who underwent hemithyroidectomy between 2012 - 2021 with final histopathology demonstrating PTC. Patients with PTCs>2cm, missing data, benign disease on surgical histopathology or incidental PTC were excluded. Results: Between 2012 - 2021, 763 patients underwent hemithyroidectomy with final histopathology confirming PTC. Of these, 316 patients were excluded (missing data, incidental PTC, concomitant hyperparathyroidism were most common reasons for exclusion) and 114/447 remaining patients had a pre-operative fine needle aspirate (FNA) of Bethesda V or VI (high likelihood of malignancy). Using the tool, 59/114 (52%) met criteria for AS. The majority of patients were female (85% vs 15% male); median age 36 years (range 19 - 78). Following initial surgery, 10/59 patients had a completion thyroidectomy, with 4/10 demonstrating malignancy in contralateral lobe and eight of those patients undergoing I131 ablation. During a median follow up of over 3 years, 49/59 (83%) did not require further surgery or intervention with no patients developing recurrence. A subgroup analysis with second radiology assessment excluded 4/59 patients as meeting criteria for AS based on presence of ETE on preoperative ultrasound. None of these 4 patients had completion thyroidectomy. Conclusion: Our clinical support tool identifies patients with PTC potentially suitable for AS which could be utilised during initial patient assessment. In a retrospective cohort of patients who had hemithyroidectomy for PTC with a pre-operative FNA diagnosis of Bethesda V or VI, 55/114 (48%) patients may have been suitable for AS. Prospective validation studies are required for implementation of the tool in clinical practice.

64Cu Treatment Planning and 67Cu Therapy with Radiolabeled [64Cu/67Cu]MeCOSar-Octreotate in Subjects with Unresectable Multifocal Meningioma: Initial Results for Human Imaging, Safety, Biodistribution, and Radiation Dosimetry.

Our aim was to report the use of 64Cu and 67Cu as a theranostic pair of radionuclides in human subjects. An additional aim was to measure whole-organ dosimetry of 64Cu and 67Cu attached to the somatostatin analog octreotate using the sarcophagine MeCOSar chelator (SARTATE) in subjects with somatostatin receptor-expressing lesions confined to the cranium, thereby permitting normal-organ dosimetry for the remainder of the body. Methods: Pretreatment PET imaging studies were performed up to 24 h after injection of [64Cu]Cu-SARTATE, and normal-organ dosimetry was estimated using OLINDA/EXM. Subsequently, the trial subjects with multifocal meningiomas were given therapeutic doses of [67Cu]Cu-SARTATE and imaged over several days using SPECT/CT. Results: Five subjects were initially recruited and imaged using PET/CT before treatment. Three of the subjects were subsequently administered 4 cycles each of [67Cu]Cu-SARTATE followed by multiple SPECT/CT imaging time points. No serious adverse events were observed, and no adverse events led to withdrawal from the study or discontinuation from treatment. The estimated mean effective dose was 3.95 × 10-2 mSv/MBq for [64Cu]Cu-SARTATE and 7.62 × 10-2 mSv/MBq for [67Cu]Cu-SARTATE. The highest estimated organ dose was in spleen, followed by kidneys, liver, adrenals, and small intestine. The matched pairing was shown by PET and SPECT intrasubject imaging to have nearly identical targeting to tumors for guiding therapy, demonstrating a potentially accurate and precise theranostic product. Conclusion: 64Cu and 67Cu show great promise as a theranostic pair of radionuclides. Further clinical studies will be required to examine the therapeutic dose required for [67Cu]Cu-SARTATE for various indications. In addition, the ability to use predictive 64Cu-based dosimetry for treatment planning with 67Cu should be further explored.

A Retrospective Cohort Study with Validation of Predictors of Differentiated Thyroid Cancer Outcomes.

Background: The goal of radioactive iodine (RAI) in differentiated thyroid cancer (DTC) is to treat metastasis and reduce recurrence risk. International guidelines provide broad risk stratification to aid treatment decisions, but a more nuanced approach to individualize care is warranted. We developed a predictive risk model for DTC. Methods: We performed a retrospective multivariable analysis of 899 patients who received RAI after thyroidectomy at a quaternary center in Australia between 2008 and 2016. Collected data included age, gender, histology, stimulated thyroglobulin (sTg), and 8th American Joint Committee Cancer (AJCC) staging. The ATA Modified Initial Risk (ATA) was calculated retrospectively. Recurrence was defined as clinically significant progression requiring either surgical intervention or administration of a second activity of RAI. Synchronous metastasis was defined as distant metastasis (i.e., outside of the neck) that was present at the time of diagnosis on structural imaging or initial post-iodine treatment scan. The features significantly associated with synchronous metastasis or recurrence were employed in the generation of a predictive risk model. A separate cohort of 393 patients who received RAI in 2017-2021 was used for validation. Results: On multivariate analysis, sTg ≥10 µg/L, extrathyroidal extension (ETE) and lymph node involvement predicted recurrence. Independent of ATA, patients with sTg ≥10 µg/L had a shorter disease-free survival (DFS) than those with sTg <10 µg/L (p < 0.001). The ETE stratified by four histological categories was significantly associated with worse DFS (p < 0.001). In a subset of patients, the presence of thyroglobulin antibody (TgAb) did not influence recurrence in patients with sTg <10 µg/L. On multivariate analysis, widespread ETE, sTg ≥10 µg/L, multifocal papillary thyroid cancer and follicular thyroid cancer were positively associated with synchronous metastasis. A predictive risk model was developed to estimate synchronous metastasis/recurrence risk and validated successfully in the second cohort. Conclusions: Our novel predictive risk model modifies and extends ATA stratification by including sTg and ETE, which we found to be independent predictors of both recurrence and synchronous metastasis in DTC.

Is 67gallium dead? A retrospective review of 67gallium imaging in a single tertiary referral centre.

BACKGROUND: [67Ga]Ga-citrate scanning has been used to investigate patients with known or suspected infection for over 50 years, continuing to maintain a clinical niche in many centres. The introduction of single photon emission tomography/computed tomography (SPECT/CT) in addition to planar imaging has improved the specificity of diagnosis. AIM: To examine the experience of modern [67Ga]Ga-citrate scanning in a single tertiary referral centre, considering the diagnostic yield of the study. METHODS: A retrospective audit was undertaken of 100 consecutive [67Ga]Ga-citrate scans at Royal North Shore Hospital, Sydney. Recorded information included patient demographics, clinical information/history, and primary and secondary diagnoses. Subgroup analyses included patients with a confirmed diagnosis of infection or a suspected diagnosis of infection. RESULTS: The median age of patients was 68.5 years. Totally, 39/100 patients undergoing [67Ga]Ga-citrate scanning presented with a confirmed site of infection, with 2/6 patients with infective endocarditis and 5/12 patients with bacteraemia diagnosed with an additional, previously unknown, site of active infection (compared to 1/21 patients without documented bacteraemia). 61/100 patients did not have a confirmed site of infection before [67Ga]Ga-citrate scan (as per clinical history). 34/61 of these patients had a positive scan result for active infection/inflammation. Of 20 patients with a positive blood culture but no suspected site of infection, the source was identified in 9. CONCLUSION: [67Ga]Ga-citrate has diagnostic value in the evaluation of complex patients with high-risk infection. High diagnostic yield is demonstrated in patients with bacteraemia with or without a confirmed site of infection, particularly when combined with SPECT/CT.

Case Report of 18F-FDG PET/CT Features of Polyacrylamide Hydrogel Mammoplasty.

ABSTRACT: A 57-year-old woman with a history of previous bilateral breast polyacrylamide hydrogel injection presented for 18F-FDG PET/CT imaging to investigate recurrent retroperitoneal liposarcoma. Incidental symmetrical FDG-positive accumulation was noted in the bilateral axillae tracking between the interpectoral planes. The finding is consistent with a chronic inflammatory process secondary to the migration of the polyacrylamide hydrogel injections.

Change in Practice of Radioactive Iodine Administration in Differentiated Thyroid Cancer: A Single-Centre Experience.

OBJECTIVE: Our study aimed to analyse temporal trends in radioactive iodine (RAI) treatment for thyroid cancer over the past decade; to analyse key factors associated with clinical decisions in RAI dosing; and to confirm lower activities of RAI for low-risk patients were not associated with an increased risk of recurrence. METHODS: Retrospective analysis of 1,323 patients who received RAI at a quaternary centre in Australia between 2008 and 2018 was performed. Prospectively collected data included age, gender, histology, and American Joint Committee on Cancer stage (7th ed). American Thyroid Association risk was calculated retrospectively. RESULTS: The median activities of RAI administered to low-risk patients decreased from 3.85 GBq (104 mCi) in 2008-2016 to 2.0 GBq (54 mCi) in 2017-2018. The principal driver of this change was an increased use of 1 GBq (27 mCi) from 1.3% of prescriptions in 2008-2011 to 18.5% in 2017-2018. In patients assigned as low risk per ATA stratification, lower activities of 1 GBq or 2 GBq (27 mCi or 54 mCi) were not associated with an increased risk of recurrence. In patients assigned to intermediate- or high-risk categories who received RAI as adjuvant therapy, there was no difference in risk of recurrence between 4 GBq (108 mCi) and 6 GBq (162 mCi). CONCLUSIONS: Our data demonstrate an evolution of RAI activities consistent with translation of ATA guidelines into clinical practice. Use of lower RAI activities was not associated with an increase in recurrence in low-risk thyroid cancer patients. Our data also suggest lower RAI activities may be as efficacious for adjuvant therapy in intermediate- and high-risk patients.

Cranial and large vessel activity on positron emission tomography scan at diagnosis and 6 months in giant cell arteritis.

AIM: Positron emission tomography/computed tomography (PET/CT) can detect cranial and large vessel inflammation in giant cell arteritis (GCA). We aimed to determine the change and significance of vascular activity at diagnosis and 6 months. METHOD: Newly diagnosed GCA patients underwent time-of-flight fluorine-18-fluoro-2-deoxyglucose PET/CT from vertex to diaphragm within 72 hours of commencing corticosteroids and were followed for 12 months. A 6 months scan was performed in patients with inflammatory features on biopsy or CT aortitis. Vascular uptake was visually graded by 2 blinded readers across 18 artery segments from 0 (no increased uptake) to 3 (very marked uptake). Scores were summed to give a total vascular score (TVS). RESULTS: We enrolled 21 GCA patients and 15 underwent the serial scan. Twelve (57%) patients experienced a relapse and 5 of these had ischemic features of vision disturbance, jaw or limb claudication. The median TVS fell from 14 (interquartile range [IQR] 4-24) at baseline to 5 (IQR 0-10) at 6 months (P < .01) with reduction in both cranial and large artery scores. While the overall relapse rate was similar between patients with a high (≥10) and low baseline TVS, patients with high scores were numerically more likely to experience an ischemic relapse (33% vs 11%, P = .34). Five out of 15 patients had persistent uptake in at least 1 vessel on the serial PET/CT but none experienced a subsequent relapse. CONCLUSION: Vascular activity decreased in cranial and large arteries between diagnosis and 6 months. Persistent activity did not predict subsequent relapse.

Interim Results of a Prospective Prostate-Specific Membrane Antigen-Directed Focal Stereotactic Reirradiation Trial for Locally Recurrent Prostate Cancer.

PURPOSE: To report the feasibility, toxicity, and preliminary outcomes (metabolic and biochemical) of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-directed focal prostate reirradiation using linear accelerator (LINAC)-based stereotactic body radiation treatment (SBRT). METHODS AND MATERIALS: From March 2016 to March 2019, 25 patients were enrolled in a prospective single institution trial (ACTRN12617000035325). Eligibility criteria included patients with biopsy proven isolated prostate recurrence after definitive irradiation, with concordant multiparametric MRI and 68Ga-PSMA PET/CT findings, and a prostate-specific antigen of less than 15 ng/mL at the time of recurrence. The study included a sequential dose escalation component with the first 18 patients receiving 36 Gy in 6 fractions on alternate days with subsequent patients receiving 38 Gy in 6 fractions assuming acceptable toxicity. RESULTS: Median age was 72 years (range, 62-83) with a median time between first radiation treatment and salvage SBRT of 8.3 years (range, 4.5- 13.6). Median prostate-specific antigen at reirradiation was 4.1 (range, 1.1-16.6). The median follow-up was 25 months (range, 13-46). Acute grade 1 and 2 genitourinary (GU) toxicity occurred in 6 (24%) and 1 (4%) men, respectively. Acute grade 1 gastrointestinal (GI) toxicity occurred in 8% with one acute grade 3 GI toxicity (4%) due to a rectal ulcer overlying the hydrogel. Late grade 1 and 2 GU toxicity occurred in 28% and 4%. Late grade 1 GI toxicity occurred in 8% with no grade 2 or greater toxicity. Twenty-four patients have undergone per-protocol 12-month 68Ga-PSMA PET/CT, of which 23 (92%) demonstrated a complete metabolic response. Biochemical freedom from failure was 80% at 2 years with 3 out of 4 of the biochemical failures exhibiting recurrent local disease. CONCLUSIONS: PSMA-directed salvage focal reirradiation to the prostate using linear accelerator-based SBRT is feasible and safe. Toxicity was low, with very favorable short term local and biochemical control in a carefully selected cohort of patients.

Evaluation of Fluorodeoxyglucose Positron Emission Tomography Scanning in the Neoadjuvant Therapy Paradigm in Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Little data exist on the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) in operable pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant (NA) therapy. METHODS: Consecutively treated patients with potentially operable PDAC were recruited from a quaternary referral center between 2015 and 2018. Data were collated on demographic, clinical, radiological, treatment, and disease-free and overall survival (OS) outcome measures, correlated with FDG-PET findings. RESULTS: Of 115 patients recruited, 61% were deemed upfront operable (n = 70), 33% borderline (n = 38), and 6% (n = 7) locally advanced. Ninety-five (83%) received NA chemotherapy with 23 (24%) sequential radiotherapy. Sixty-nine (73%) treated with NA were resected, 37 (54%) attained an R0 resection, 43 (62%) had N1 disease with median tumor viability of 50%. The median OS in the entire cohort was 30.48 months and in those who received NA chemotherapy followed by resection 37.98 months. Twelve percent (n = 13) were upstaged during NA therapy by PET. Preoperative standardized uptake value maximum of less than 5 versus 5 or greater after NA predicted for improved OS, 42.95 months versus 26.05 months, P = 0.02. CONCLUSIONS: In this real-world cohort study of PDAC, the utility of FDG-PET in informing the patient treatment pathway was meaningfully demonstrated.

Diffuse Large B-Cell Lymphoma Recurring as Neurolymphomatosis on FDG PET/CT.

Two patients with diffuse large B-cell lymphoma relapsing as neurolymphomatosis diagnosed on FDG PET/CT are presented. Both patients were treated initially with chemotherapy and had a complete metabolic response. Patient 1 represented with lower-limb pain. An FDG PET/CT demonstrated intense uptake throughout the sciatic nerves bilaterally extending distally with relapse confirmed on biopsy. Patient 2 represented to hospital with worsening mobility, neuropathic pain, and facial asymmetry. An FDG PET/CT demonstrated relapse within the spinal cord, left sciatic nerve, and facial nerve branches. Neurolymphomatosis is an uncommon finding on FDG PET/CT and can be the only site of relapse.