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OBJECTIVE: PSMA PET/CT has demonstrated superior sensitivity over conventional imaging in the detection of local and distant recurrence in biochemically relapsed (BCR) prostate cancer. We prospectively investigated the management impact of 68 Ga-PSMA PET/CT imaging in men with BCR, with the aim of identifying baseline clinicopathological predictors for management change. PATIENTS AND METHODS: Men with BCR who met eligibility criteria underwent 68 Ga-PSMA-11 PET/CT at Monash Health (Melbourne, Australia). Intended management plans were prospectively documented before and after 68 Ga-PSMA PET/CT imaging. Binary logistic regression analysis was performed to identify potential clinicopathological predictors of management change. Descriptive statistics were used to characterize the nature of these changes. RESULTS: Seventy men underwent 68 Ga-PSMA-11 PET/CT imaging. Median age was 67 years (IQR 63-72) and median PSA was 0.48 ng/ml (IQR 0.21-1.9). PSMA-avid disease was observed in 56% (39/70) of patients. Pre-scan management plan was altered following scanning in 43% (30/70) of patients. Management changes were significantly more common in patients with higher baseline PSA levels (PSA≥2 ng/ml, p = 0.01). 18/36 (50%) of the patients initially planned for watchful waiting had their management changed, including the use of salvage pelvic radiotherapy (n = 7) and stereotactic ablative body radiotherapy to oligometastatic disease (n = 6). CONCLUSION: Management change after 68 Ga-PSMA PET/CT for BCR is common and typically resulted in treatment intensification strategies in those planned for a watchful waiting approach. This study adds to the growing pool of evidence supporting the clinical utility of PSMA PET/CT imaging in the care of patients with BCR after definitive therapy.

Aims: Prostate-specific membrane antigen (PSMA) PET/CT has emerged as the optimal imaging modality to detect recurrent prostate cancer in patients with biochemical relapse (BCR) following curative intent treatment. However, its impact on clinical decision making in the era of metastasis-directed therapy remains unclear. This study aims to explore the role of PSMA PET/CT on clinical decisionmaking in patients with BCR following definitive therapy. Method(s): We prospectively enrolled 40 patients with BCR to undergo 68Ga-PSMA PET/CT. Baseline clinicopathological factors were obtained and referring clinicians documented their proposed treatment plan both prior to and following imaging. Changes in clinical management were considered to have clinical impact. Result(s): 68Ga-PSMA PET/CT detected at least one suspicious lesion in 23/40 (58%) patients, with a median PSA level of 0.59 mug/L (IQR 0.21- 2.31). Positive scansweremore frequent at higher PSA levels (P<.001, Fischer's exact test). The most common sites of PSMA-avid disease were lymph nodes (61%) and bone (30%). Lymph node involvement was typically pelvic nodes (13/14, 93%). Bone involvement was mostly outside the axial skeleton (5/7, 71%). PSMA PET/CT altered management in 21/40 (53%) patients. Of those planned for watchful waiting, 14/24 (58%) proceeded to amore activemanagement strategy, including salvage radiotherapy (n = 6), stereotactic ablative body radiotherapy (SABR; n = 5), androgen deprivation therapy (n = 2) and salvage surgery (n = 1). Conclusion(s): 68Ga-PSMA PET/CT altered management strategy in a significant proportion of prostate cancer patients with BCR following definitive therapy. Our data demonstrate a shift from planned watchful waiting to more active treatment in over half patients with a positive 68Ga-PSMA PET/CT. Longer-term follow-up is required to assess the influence of such strategies on clinical outcomes.

Background: 68Gallium-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-11 PET) is a valuable staging tool, but its utility in characterising primary prostate cancer remains unclear. The maximum standardised uptake value (SUVmax) is a quantification measure of highest radiotracer uptake within PET-avid lesions. Objective(s): To assess the utility of SUVmax in detecting clinically significant prostate cancer (csPCa) on biopsy alone and in combination with multiparametric magnetic resonance imaging (mpMRI). Design, setting, and participants: This was a retrospective analysis of 200 men who underwent 68Ga-PSMA-11 PET/CT, mpMRI, and transperineal template prostate biopsy between 2016 and 2018. Outcome measurements and statistical analysis: The primary and secondary outcomes were detection of grade group (GG) 3-5 and GG 2-5 prostate cancer, respectively. We used the Mann-Whitney U test to compare SUVmax by GG, and calculated sensitivity and specificity for csPCa detection via 68Ga-PSMA-11 PET/CT, mpMRI, and both. Multivariable logistic regression analyses were used to identify predictors of csPCa on biopsy. Results and limitations: The median SUVmax was greater for GG 3-5 tumours (6.40, interquartile range [IQR] 4.47-11.0) than for benign and GG 1-2 tumours (3.14, IQR 2.55-3.91; p < 0.001). The median SUVmax was greater for GG 3 (5.70, IQR 3.68-8.67) than for GG 2 (3.47, IQR 2.70-4.74; p < 0.001). For GG 3-5 disease, sensitivity was 86.5%, 95.9%, and 98.6%, and the negative predictive value (NPV) was 88.4%, 88.5%, and 93.3% using SUVmax >=4, a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3-5, and both, respectively. This combined model detected more GG 3-5 disease than mpMRI alone (98.6% vs 95.9%; p = 0.04). SUVmax was an independent predictor of csPCa for GG 3-5 disease only (odds ratio 1.27 per unit, 95% confidence interval 1.13-1.45). Our results are limited by the retrospective study design. Conclusion(s): Greater SU

PURPOSE: Accurate risk stratification remains a barrier for the safety of active surveillance in patients with intermediate-risk prostate cancer. [68Ga]Ga-PSMA-11 Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography (68Ga-PSMA PET/CT) and the maximum Standardized Uptake Value (SUVmax) may improve risk stratification within this population. MATERIALS AND METHODS: We reviewed men with ISUP Grade Group 2-3 disease on transperineal template biopsy undergoing 68Ga-PSMA PET/CT from November 2015 to January 2021. Primary outcome was the presence of high percentage Gleason pattern 4 (GP4) disease per-segment at surgery, at three thresholds: >/<50% GP4, >/<20% GP4, and >/<10% GP4. SUVmax was compared by GP4, and multivariable logistic regression examined the relationship between SUVmax and GP4. Secondary outcome was association between SUVmax and pathologic upgrading (GG1/2 to GG >=3 from biopsy to surgery). RESULT(S): Of 220 men who underwent biopsy, 135 men underwent surgery. SUVmax was higher in high GP4 groups: 5.51 (IQR 4.19-8.49) vs 3.31 (2.64-4.41) >/<50% GP4 (p <0.001); 4.77 (3.31-7.00) vs 3.13 (2.64-4.41) >/<20% GP4 (p <0.001); and 4.54 (6.10-3.13) vs 3.03 (2.45-3.70) >/<10% GP4 (p <0.001). SUVmax remained an independent predictor of >50% (OR=1.39 [95%CI 1.18-1.65], p <0.001) and >20% (OR=1.24 [1.04-1.47], p=0.015) GP4 disease per-segment, and of pathologic upgrading (OR=1.22 [1.01-1.48], p=0.036). SUVmax threshold 4.5 predicted >20% GP4 with 58% specificity, 85% sensitivity, positive predictive value (PPV) 75% and negative predictive value (NPV) 72%. Threshold 5.4 predicted pathologic upgrading with 91% specificity and NPV 94%. CONCLUSION(S): SUVmax on 68Ga-PSMA PET/CT is associated with GP4. SUVmax may improve risk stratification for men with intermediate-risk prostate cancer.

Objective: PSMA PET/CT has demonstrated superior sensitivity over conventional imaging in the detection of local and distant recurrence in biochemically relapsed (BCR) prostate cancer. We prospectively investigated the management impact of 68Ga-PSMA PET/CT imaging in men with BCR, with the aim of identifying baseline clinicopathological predictors for management change. Patients and Methods: Men with BCR who met eligibility criteria underwent 68Ga-PSMA-11 PET/CT at Monash Health (Melbourne, Australia). Intended management plans were prospectively documented before and after 68Ga-PSMA PET/CT imaging. Binary logistic regression analysis was performed to identify potential clinicopathological predictors of management change. Descriptive statistics were used to characterize the nature of these changes. Result(s): Seventy men underwent 68Ga-PSMA-11 PET/CT imaging. Median age was 67 years (IQR 63-72) and median PSA was 0.48 ng/ml (IQR 0.21-1.9). PSMA-avid disease was observed in 56% (39/70) of patients. Pre-scan management plan was altered following scanning in 43% (30/70) of patients. Management changes were significantly more common in patients with higher baseline PSA levels (PSA>=2 ng/ml, p = 0.01). 18/36 (50%) of the patients initially planned for watchful waiting had their management changed, including the use of salvage pelvic radiotherapy (n = 7) and stereotactic ablative body radiotherapy to oligometastatic disease (n = 6). Conclusion(s): Management change after 68Ga-PSMA PET/CT for BCR is common and typically resulted in treatment intensification strategies in those planned for a watchful waiting approach. This study adds to the growing pool of evidence supporting the clinical utility of PSMA PET/CT imaging in the care of patients with BCR after definitive therapy.Copyright © 2021 John Wiley & Sons Australia, Ltd

Background: Lutetium-177 [177Lu]Lu-PSMA-617 is a radiolabelled small molecule that delivers beta radiation to cells expressing prostate-specific membrane antigen (PSMA), with activity and safety in patients with metastatic castration-resistant prostate cancer. We aimed to compare [177Lu]Lu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer. Method(s): We did this multicentre, unblinded, randomised phase 2 trial at 11 centres in Australia. We recruited men with metastatic castration-resistant prostate cancer for whom cabazitaxel was considered the next appropriate standard treatment. Participants were required to have adequate renal, haematological, and liver function, and an Eastern Cooperative Oncology Group performance status of 0-2. Previous treatment with androgen receptor-directed therapy was allowed. Men underwent gallium-68 [68Ga]Ga-PSMA-11 and 2-flourine-18[18F]fluoro-2-deoxy-D-glucose (FDG) PET-CT scans. PET eligibility criteria for the trial were PSMA-positive disease, and no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings. Men were randomly assigned (1:1) to [177Lu]Lu-PSMA-617 (6.0-8.5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m2 intravenously every 3 weeks for up to ten cycles). The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline. This trial is registered with ClinicalTrials.gov, NCT03392428. Finding(s): Between Feb 6, 2018, and Sept 3, 2019, we screened 291 men, of whom 200 were eligible on PET imaging. Study treatment was received by 98 (99%) of 99 men randomly assigned to [177Lu]Lu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the [177Lu]Lu-PSMA-617 group than in the cabazitaxel group (65 vs 37 PSA responses; 66% vs 37% by intention to treat; difference 29% (95% CI 16-42; p<0.0001; and 66% vs 44% by treatment rec

Objective: To compare the accuracy of 68gallium prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) with multiparametric MRI (mpMRI) in detecting and localising primary prostate cancer when compared with radical prostatectomy (RP) specimen pathology. Patients and Methods: Retrospective review of men who underwent 68Ga-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 68Ga-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 68Ga-PSMA PET/CT and mpMRI. Result(s): In all, 205 men were included in our analysis, including 133 with clinically significant disease. There was no significant difference between 68Ga-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 68Ga

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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

Introduction and Objectives: Prostate specific membrane antigen (PSMA) ligands in positron emission tomography (PET) imaging have shown superior results when compared to traditional imaging in prostate cancer. Simultaneous PSMA PET/MRI is an emerging modality yielding promising results in detection and staging, although scant published evidence is available. We compared the diagnostic accuracy of multiparametric MRI, PSMA PET/MRI and PSMA PET/CT to wholemount histopathology for the localisation of primary prostate cancer. Method(s): A local prospective database for patients who underwent MRI was used. 13 patients underwent multiparametric MRI, transperineal prostate biopsy, PSMA PET/ CT, PSMA PET/MRI and subsequent radical prostatectomy with whole-mount histopathology. Imaging was reported with Prostate Imaging Reporting and Data System sector maps. These were individually evaluated by dividing the prostate into 12 sectors; apex/mid/base in the transverse plane, left/right in the sagittal plane, and anterior/posterior in the coronal plane. Result(s): Whole-mount histopathology revealed significant cancer in 13 patients, present in 59 of 156 sectors, with significant cancer defined as greater than or equal to Gleason 3 + 4 = 7 (Grade Group 2). MRI detected true positives in 31 of 36 MRI positive sectors and true negatives in 92 of 120 MRI negatives sectors, conferring a sensitivity and specificity of 51% and 95% respectively. PET/CT detected true positives in 25 of 32 PSMA avid sectors and true negatives in 90 of 124 PSMA non-avid sectors, conferring a sensitivity (Table pesented) and specificity of 42% and 93% respectively. PET/MRI detected true positives in 32 of 36 PSMA avid sectors and true negatives in 93 of 120 PSMA non-avid sectors, conferring a sensitivity and specificity of 54% and 96% respectively. The overall accuracy of all 3 modalities respectively were 78%, 74% and 80%. Conclusion(s): In this case-series involving highly selected patients undergoing pro

Objective: Both 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and multiparametric MRI (mpMRI) are emerging imaging modalities in the diagnostic pathway of prostate cancer. We assessed the accuracy of 68Ga- PSMA PET/CT and mpMRI in localising primary prostate cancer compared with radical prostatectomy (RP) specimens. Method(s): Retrospective analysis of the records of 88 men who underwent both 68Ga-PSMA PET/CT and mpMRI prior to RP between 2016 and 2018. Index tumour was defined as the lesion with highest standardised uptake value (SUVmax) on 68Ga- PSMA PET/CT, highest PIRADS score on mpMRI, and highest ISUP grade group on RP histopathology. All other lesions found on imaging were defined as non-index lesions. Accurate tumour localisation included correctly identifying sextant location compared with RP specimen. Descriptive statistics and McNemar's test were used. Result(s): 68Ga-PSMA PET/CT accurately localised index tumour in 71 (80.7%) men. In a further 7 men (7.95%), index tumour on RP corresponded with non-index lesions on 68Ga-PSMA PET/CT. mpMRI accurately localised index tumour in 74 (84.1%) men. Correct side was identified in 81 (92.1%) men. There was no significant difference between overall localisation of index tumour using 68Ga-PSMA PET/ CT (80.7%) and mpMRI (84.1%) (p = 0.664). 6 (6.82%) men had no avidity on 68Ga-PSMA PET/CT and 3 (3.41%) men had no lesion on mpMRI despite tumour on RP pathology (p = 0.450). Conclusion(s): There is no significant difference in tumour localisation of primary prostate cancer between 68Ga-PSMA PET/ CT and mpMRI, despite a trend of greater accuracy using the latter. Further studies are required to assess the diagnostic accuracy of 68Ga-PSMA PET/CT and the value of a combined PET/MRI model.

Objective: 68Ga-prostate-specific membrane antigen (PSMA) PET/CT has emerged as a valuable tool in the diagnosis of prostate cancer. Maximum standardised uptake value (SUVmax) is used to identify tumour foci within the prostate. Our objective was to correlate SUVmax with tumour grade on prostate biopsy. Method(s): Retrospective analysis of the records of 151 men who underwent 68Ga- PSMA PET/CT prior to prostate biopsy between 2016 and 2018. SUVmax on PET/ CT and ISUP Grade Group (GG) on biopsy were collected. Clinically significant disease was defined as GG 3-5. Receiver operating characteristic (ROC) curve analysis was used to identify SUVmax thresholds optimising predictive value for GG 3-5 disease. Result(s): Mean age was 67.2 (+/-1.39) years and mean PSA 9.77 (+/-1.77) ng/mL. There was no significant difference between mean SUVmax of GG1 (3.49 +/- 0.71) compared to GG2 (4.01 +/- 0.96) tumours (p = 0.850), or between GG3 (7.92 +/- 1.72), GG4 (6.48 +/- 2.54) and GG5 (10.65 +/- 3.49) tumours (p = 0.491, 0.152). However, mean SUVmax of GG 3-5 tumours (8.34 +/- 1.37) was significantly greater than that of GG 1-2 tumours (4.46 +/- 0.54) (p < 0.001). SUVmax 4.35 was identified as an ideal threshold, with sensitivity of 82.8% and specificity of 69.0%. Positive predictive value at this threshold was 66.3% and negative predictive value 84.5%. Conclusion(s): High grade tumours are associated with significantly higher SUVmax on 68Ga-PSMA PET/CT than lower grade tumours. Using a SUVmax threshold of 4.35 gives a high sensitivity and high negative predictive value for clinically significant disease. 68Ga-PSMA PET/CT may prove useful in active surveillance, and further studies are required to assess its role alongside prostate MRI.

Introduction: A solid hypofunctioning (cold) nodule on scintigraphy is associated with an increased risk of malignancy while a functioning (hot) nodule is rarely malignant. This study aims to assess if the risk of malignancy in patients with cold nodules can be stratified according to the presence of sonographic features and therefore determine the need for invasive cytopathological correlation. Method(s): This study is a retrospective audit correlating the sonographic and cytological findings of solid hypofunctioning nodules on Tc-99m pertechnetate scintigraphy. The sonographic features and cytology for benign and malignant nodules were compared using Fisher's exact test and the unpaired T-test. A P value <0.05 was considered statistically significant. Result(s): In the sample of 53 nodules, 21 nodules demonstrated suspicious features on ultrasound and 32 nodules had no suspicious ultrasound findings. Absence of suspicious sonographic features on ultrasound has a high negative predictive value of 0.94 (95% CI 0.79 - 0.99), but presence of suspicious sonographic features has a poor positive predictive value of 0.14 (95% CI 0.03 - 0.36) for cold nodules. There was a strong correlation between nodule echogenicity and cytology (P=0.02). The absence of marked hypoechogencity had a high negative predictive value of 0.96 (95% CI 0.85 - 0.99), but poor positive predictive value of 0.38 (95% CI 0.085 - 0.76). Conclusion(s): There was a statistically significant association between absence of suspicious sonographic findings and benign cytology in our study. This suggests that ultrasound can be used to stratify a cold thyroid nodule before invasive procedures are performed.

Background: Radiation-induced liver disease (RILD), also known as radiation-induced hepatic injury, is a potential radiotherapy-related complication. Documented cases of RILD include radiation-induced hepatitis and radiation-induced hepatitis B virus reactivation. These presentations can make interpreting 18Fluorine-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scans for therapeutic response more difficult. Aim(s): 1.To report an incident of 18F-FDG avidity in acute focal radiationinduced hepatitis found on PET/CT; 2.To provide a literature overview on radiation-induced hepatitis in PET/CT. Method(s): Case report and literature review. Result(s): A 71 year old male was diagnosed with diffuse large B cell lymphoma with the largest mass adjacent to the inferior vena cava. The patient underwent chemotherapy. Mid-treatment assessment with PET/CT showed an overall good response with some residual activity in the retroperitoneal nodes which were smaller in size.A post treatment PET/CT study however showed small volume nodal recurrence in the right retroperitoneal region at the L2/3 level. The patient then commenced Involved-Field Radiation Therapy (IFRT). Subsequent PET/CT assessment demonstrated a poor response of nodal disease to the treatment with incidental increased metabolic activity in the caudate lobe of the liver. Contemporaneous CT did not reveal any abnormality to correlate with the noted liver uptake. After reviewing the IFRT treatment field the possibility of focal radiation-induced hepatitis was raised. Follow-up PET/CT at six months post-RT showed resolution of uptake in the caudate lobe of the liver, which would fit with the reported suspected acute focal radiationinduced hepatitis. Radiation-induced hepatitis in itself is uncommon; with a handful of well documented cases in the literature. There are very few reports of focal radiation induced hepatitis demonstrated on PET/CT. Conclusion(s):We present a case of foca

Background: Phenotypic and genomic heterogeneity may contribute to the pathogenesis of Malignant Mesothelioma (MM). We have implemented a novel clinical study in which multiple samples of tumor and normal pleura are obtained from individual patients undergoing surgery for the management of MM. Method(s): Patients undergoing routine video-assisted thoracoscopic surgery (VATS) undergo a baseline FDGPET scan. Extra samples are taken from both PET positive and PET negative areas of pleura, along with normal pleural samples. Corresponding fresh and formalin fixed tissue samples are obtained. Patients are subsequently treated as per standard of care practice, along with detailed clinical follow up and serial PET imaging. Standard H&E will be performed on formalin fixed samples to look for morphological heterogeneity in tumor cells and stroma and the findings will be correlated with PET imaging. Result(s): Six (6) patients (4 epithelioid, 1 sarcomatoid and 1 biphasic subtype) with median age of 70 (62-81) have been recruited into the project so far. All patients underwent an FGD-PET scan prior to VATS procedure. Multiple samples from PET avid and PET non-avid areas were collected and stored from 5 out of 6 patients. Preliminary results show that high quality samples were obtained. The H&E analysis shows that tumors from PET avid area are morphologically different to PET not avid areas (Figure 1). Further IHC analysis of various MM specific markers is underway. Conclusion(s): This preliminary data demonstrate the feasibility of our clinical approach. We therefore propose to create a unique research platform in which MM samples from multiple sites from each patient will be integrated with clinical, imaging and therapeutic response. Further proof-of-principle studies will explore: (i) regional heterogeneity and the response to therapies; (ii) variability in the detection of predictive biomarkers within the same patient; (iii) genomic heterogeneity within MM, and its relations

Background: Urinary activity on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has long been a pitfall in pelvic PET imaging. High concentration of radioactive tracer in the urinary system causes interpretive challenges in differentiating between normal physiological activity (urine) and pathology. The key to reducing urinary activity on FDG PET/CT imaging is to wash out the excreted 18F-FDG. Past methods have centred on the use of urinary catheters for retrograde irrigation of the urinary bladder, good hydration and delayed static imaging. The use of hydration and diuretic administration prior to whole body PET/CT has in the past been avoided due to acquisition times greater than 20 minutes. With the advent of newer scanning technologies such techniques should be reconsidered. Aim(s): To use patient case studies to demonstrate how hydration and diuretic administration can enhance adequate visualisation of abdominal and pelvic disease in a non-invasive way. Method(s): Prior to administration of 18F-FDG the patient is asked to void to limit the need for toileting immediately post injection. At the time of injection the patient is hydrated orally or through intravenous (IV) infusion. At approximately 30 minutes post administration, 20mg Frusemide (Lasix) is administered and the patient is free to void as required. Whole body scanning is delayed until at least 75 minutes post administration to ensure the peak effect of Lasix has passed. Result(s): With hydration (IV or oral) and diuretic administration, sufficient bladder and urinary tract washout can be achieved, allowing for differentiation of disease from urinary activity. Conclusion(s): The use of such a protocol has improved visualisation of pelvic disease, renal disease and even recurrent primary bladder tumours.

The dorsomedial prefrontal cortex (dmPFC) is a key hub of the 'social brain', but little is known about specific processes supported by this region. Using focal high-definition transcranial direct current stimulation (HD-tDCS) and a social cognitive battery with differing demands on self-other processing, we demonstrate specific involvement of the dmPFC in tasks placing high demands on self-other processing. Specifically, excitatory (anodal) HD-tDCS enhanced the integration of external information into the self for explicit higher-order socio-cognitive tasks across cognitive domains; i.e. visual perspective taking (VPT) and episodic memory. These effects were task specific, as no stimulation effects were found for attributing mental states from the eyes or implicit VPT. Inhibitory (cathodal) HD-tDCS had weaker effects in the opposite direction towards reduced integration of external information into the self. We thus demonstrate for the first time a specific and causal role of the dmPFC in integrating higher-order information from others/external source into that of the self across cognitive domains.

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.Copyright © 2016 International Anesthesia Research Society.

Background: The presence of cervical lymph node metastasis is an important prognostic factor for patients with head and neck squamous cell carcinomas (HNSCC). Accurate assessment of lymph node metastasis in these patients is essential for appropriate prognostic and management purposes. Here, we evaluated the effectiveness of the maximum standardized uptake value (SUVmax) on positron emission tomography (PET) in assessing lymph node metastasis in HNSCC prior to surgery. Method(s): A retrospective review of 74 patients with HNSCC who underwent PET/CT prior to neck dissection were examined. Pre-operative PET/CT scans were reviewed by two experienced nuclear medicine physicians and SUVmax of the largest node in each nodal basin documented. These were compared with the histology results of the neck dissection. Result(s): A total of 359 nodal basins including 86 basins with metastatic nodes were evaluated. A nodal SUVmax >=3.16 yielded a sensitivity of 74.4 % and specificity of 84.9 % in detecting metastatic nodes. The nodal SUVmax/Liver SUVmax ratio was found on receiver operating characteristic (ROC) to be effective in detecting metastatic nodes with an area under ROC curve of 0.90. A nodal SUVmax/Liver SUVmax ratio >=0.90 yielded a sensitivity of 74.1 % and specificity of 93.4 %. By comparison, visual inspection yielded sensitivities of 66.3 and 61.6 % in observers 1 and 2 respectively. The corresponding specificities were 77.7 and 86.5 %. Conclusion(s): Nodal SUVmax and nodal SUVmax/liver SUVmax are both useful in the pre-operative detection of metastatic nodes with the latter being superior to visual inspection. The ratio is likely to be more useful as it corrects for inter-scanner variability.Copyright © 2016 The Author(s).

A hypofunctioning (cold) nodule on scintigraphy is associated with an increased risk of malignancy. This study assesses if the risk of malignancy in cold nodules can be stratified according to the presence of sonographic features and therefore determine the need for cytopathological correlation. A retrospective audit correlating the sonographic and histological findings of hypofunctioning nodules on Tc-99m pertechnetate scintigraphy was performed. Patients with cold nodules on scintigraphy carried out at our institution between January 2005 and February 2015 were identified. The presence or absence of specific sonographic features (marked hypoechogenicity, irregular margins, microcalcifications, hypervascularity, taller than wide) was established for each nodule. These findings were correlated with fine needle aspirate cytology results. The sonographic features and histology for benign and malignant nodules were compared using Fischer's exact test. A total of 53 cold nodules were examined with 21 nodules with suspicious ultrasound findings and 32 nodules with no suspicious ultrasound findings. In the nodules with no suspicious ultrasound findings, two had malignant histology including papillary carcinoma and follicular with micropapillary carcinoma (2/32) and 30 nodules were benign (30/32). There is a significant association between no suspicious ultrasound features and benign histology (p < 0.0001) using an unpaired t-test, with a negative predictive value of 0.94 (0.79 - 0.99). In the nodules with suspicious ultrasound findings, 3 cancers were detected (3/21), one follicular and two papillary thyroid carcinomas. There was a strong association between marked hypoechogenicity and malignant histology (p = 0.02) but no statistically significant correlation between other sonographic features and malignant histology. The rate of malignancy in cold nodules is low in the absence of suspicious ultrasound features. There was a statistically significant association between n

OBJECTIVES: The 320-slice computed tomography (CT) provides three-dimensional and dynamic imaging resulting in the ability to assess motion analysis between two adjacent structures (the fourth dimension). Differential movements between two adjacent structures would indicate that there is no fixation between the two structures. METHOD(S): Eight patients with non-small-cell lung cancers located adjacent to vital structures (e.g. the great vessels) (n = 4), mediastinum (n = 1) or chest wall (n = 3) where conventional CT was unable to exclude local invasion underwent dynamic four-dimensional (4D) CT assessment. In 3 patients, the lung tumour was abutting the chest wall and 1 patient had tumour abutting the mediastinum. The remaining patients included a patient with a large 14-cm left lower lobe cancer abutting the descending thoracic aorta who had previous pleurodesis; a patient with an apical right upper lobe 6-cm cancer with static imaging appearances suggestive of tumour invasion into the apex, the mediastinal surface and superior vena cava (SVC); a patient with a 3.5-cm cancer which had a broad 2.5-cm base abutting the distal aortic arch and a patient with a 14-cm left upper lobe cancer abutting the aortic arch, descending thoracic aorta and chest wall. Differential movements between the tumour and adjacent structure on 4D CT were considered indicative of the absence of frank invasion. RESULT(S): Dynamic 4D imaging revealed differential movements between the tumour and the adjacent structures in 7 cases, suggesting the absence of overt malignant invasion. Intraoperative assessments confirmed the findings. In 1 case, a small area of fixation seen on dynamic CT corresponded intraoperatively to superficial invasion of the adventitia of the SVC. CONCLUSION(S): Dynamic 4D 320-slice CT is useful in the preoperative assessment of the direct invasion of lung cancer into adjacent structures and hence its resectability.Copyright © The Author 2014.

Aim To determine whether the malignancy risk in an 2-[18F]-fluoro-2-deoxy-d-glucose (FDG)-avid thyroid nodule can be stratified according to the presence or absence of suspicious ultrasound features and thereby identify which nodules require further cytological assessment. Materials and methods A retrospective review of FDG-positron-emission tomography (PET) combined with computed tomography (CT) studies with FDG-avid thyroid nodules (defined as FDG uptake greater than blood pool) that were further assessed with ultrasound and fine-needle aspiration cytology or surgery was performed. FDG-avid thyroid nodules were classified as having either suspicious ultrasound features (marked hypo-echogenicity, irregular margins, microcalcifications, marked hypervascularity, or nodules that were taller than they were wide) or no suspicious ultrasound features and these findings were correlated with the subsequent cytological results. Results Forty-eight FDG-avid thyroid nodules were assessed. On cytological assessment five nodules were malignant (10.4%), nine were indeterminate (18.75%), and 34 were benign (70.8%). On ultrasound, 24 (50%) had no suspicious features and 24 (50%) had one or more suspicious features. Of the nodules with no suspicious features, 22 (91.6%) were benign, two (8.3%) were indeterminate, and none were malignant. Of the nodules with suspicious features, five (20.8%) were malignant, seven (29.1%) were indeterminate, and 12 (50%) were benign. The absence of suspicious ultrasound features demonstrated a strong association with benign cytology (p=0.009). Out of the suspicious sonographic features, marked hypoechoic appearance (p=0.02), irregular margins (p=0.009), and taller than wide morphology (p=0.04) were statistically most significantly associated with malignancy. Conclusion The rate of malignancy in FDG-avid thyroid nodules is low in the absence of specific suspicious ultrasound features. The SUV values are non-discriminatory to differentiate between beni

Purpose: To determine if the malignancy risk in an FDG-avid thyroid nodule can be stratified according to the presence or absence of suspicious ultrasound features and thereby identify which nodules require further histological assessment. Material(s) and Method(s): A retrospective audit of FDG-PET/CT studies with incidental FDG-avid thyroid nodules (defined as FDG uptake greater than blood pool) that were further assessed with ultrasound and fine needle aspiration or surgery was performed. FDG-avid thyroid nodules were classified as having either suspicious ultrasound features (marked hypoechogenicity, irregular margins, microcalcifications, marked hypervascularity or nodules taller than wide) or no suspicious ultrasound features and these findings were correlated with the subsequent pathological results. Result(s): 47 FDG-avid thyroid nodules were assessed. On pathological assessment 5 nodules were malignant (10.6%), 7 were indeterminate (14.9%) and 35 were benign (74.5%). On ultrasound 25 (53.2%) had no suspicious features and 22 (46.8%) had one or more suspicious features. Of the nodules with no suspicious features, 23 (92%) were benign, 2 (8%) were indeterminate and none were malignant. Of the nodules with suspicious features, 5 (22.7%) were malignant, 5 (22.7%) were indeterminate and 12 (54.6%) were benign. The ultrasound features used give a sensitivity of 100%, specificity of 65.7%, PPV of 29.4% and NPV of 100%. Conclusion(s): The rate of malignancy in FDG-avid thyroid nodules is low in the absence of specific suspicious ultrasound features. This suggests that further invasive procedures to investigate the FDG-avid thyroid nodule may not be necessary if there are no suspicious ultrasound features.

Background: A common problem when interpreting PET/CT results is the misregistration that occurs from breathing artefact. Artefact occurs as a result of the tidal breathing patterns throughout the PET acquisition. New technology and techniques are constantly evolving to improve breathing artefact in order to allow better interpretation of scans. Aim(s): The respiratory gating system employed in our PET/CT is very time consuming and result in long scan times. In a busy department additional acquisitions create time management problems due to high patient throughput. Our aim was to find an alternative simple protocol to reduce breathing artefact. Method(s): A one bed static acquisition was acquired following a whole body PET/CT scan with significant misregistration in either a lung or liver lesion. The patient is placed on the bed supine, with a firm strap around their lower chest. Instructions are given to breathe using their upper chest wall in isolation, limiting diaphragmatic motion. The patient is put on 2 litre of oxygen to allow for better oxygenation, and to reduce any distress to the patient. A1 bed PET/CT is acquired over the region of interest at 2/mins per bed to allow for enough counts but reduced time for patient. Result(s): Our new breathing acquisition has vastly improved PET to CT data registration and in a majority of patients providing a more accurate localisation and SUVs of lung and liver lesions. Conclusion(s): Dedicated acquisitions to reduce breathing artefact can be an effective way of reducing misregistration in departments that are time poor or respiratory gating is unavailable.

Background: Increasing use of 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) has resulted in increased incidental findings of focal thyroidal FDG uptake. Previous studies performed overseas suggest a high risk of malignancy in these incidentally detected thyroid lesions. Aim(s): To determine (i) the proportion of patients undergoing PET-CT for assessment of nonthyroid cancer in an Australian metropolitan hospital setting who have focal thyroidal FDG uptake; (ii) the proportion of these patients who undergo fine needle aspiration biopsy (FNAB) of the thyroid lesion, hemithyroidectomy or total thyroidectomy; and (iii) the proportion of these patients with incidentally detected thyroid malignancy. Method(s): A retrospective audit of all PET-CT studies performed at Southern Health between February 2011 and January 2013 was performed. Patients undergoing PET-CT for assessment of nonthyroid cancer with an incidental finding of focal thyroidal FDG uptake were identified from our database. Patient medical records, Radiology and Pathology databases were reviewed to identify patients who had been further investigated with FNAB of the thyroid lesion, hemithyroidectomy or total thyroidectomy. Result(s): Of 4395 PET-CT studies performed at Southern Health, 2.5% (112/4395) demonstrated focal thyroidal FDG uptake. 42% (35/84) of patients undergoing PET-CT for assessment of nonthyroid cancer with focal thyroidal FDG uptake had been further investigated with FNAB, hemithyroidectomy or total thyroidectomy. 17% (6/35) had a malignant cause for their focal thyroidal FDG uptake. Causes included follicular thyroid carcinoma (n = 2), papillary thyroid carcinoma (n = 2), medullary thyroid carcinoma (n = 1), and metastatic lung carcinoma (n = 1). The remaining 83% (29/35) were benign. Causes included hyperplastic nodules, colloid nodules and follicular adenomas. The average SUVmax of malignant lesions (8.9) was not significantly different from that of

Introduction: Chronic cholecystitis is an elusive diagnosis, with a good outcome following treatment, making the availability of a reliable diagnostic test essential for patient management. The variable access to CCK has necessitated an alternative method for assessing gall bladder function and determining the gall bladder ejection fraction (GBEF). The purpose of our study was to determine if 600 ml of full cream milk (21.6 g of fat) was an adequate fat challenge in hepatobiliary scintigraphy for the assessment of gall bladder function and GBEF, and to determine the GBEF with the highest accuracy for prediction of chronic cholecystitis using GBEF of 23%, 35% and 50%. Method(s): Retrospective review of 151 patients who underwent milk augmented HBS with confi rmation of histological diagnosis and symptom evaluation post therapy in 58 patients. These 58 patients' results were then statistically evaluated. Result(s): Overall the best results were obtained using GBEF of 35%, with the results summarised in Table 1. (Table presented) Conclusion(s): Hepatobiliary scintigraphy using 600 ml of full cream milk is an adequate fat challenge, and is an easily reproducible test for diagnosis of chronic cholecystitis. Using this fat challenge, a GBEF of < 35% was considered the most useful GBEF for prediction of chronic cholecystitis and overall outcome prediction post-therapy with the best combination of sensitivity, specifi city and overall accuracy.

Introduction: Iterative reconstruction methods that incorporate accurate system modelling are beginning to see increased use in clinical PET imaging. For example, depth-of-interaction (DOI) effects are corrected in the Siemens Biograph PET scanner by incorporating a scanner specific point spread function (PSF) into the system matrix. This paper aims to show the introduction of a 'Gibbs-like overshoot' artefact in images reconstructed with the Siemens TrueX algorithm and the possible implications to clinical imaging. Method(s): A series of Jaszczak phantom measurements have been performed with varying foreground/background activity concentrations. Phantom images are reconstructed using both OSEM-3D and TrueX algorithms. Visual comparisons of the reconstructed images have been conducted to view the presents of the Gibbs artifact. Image quality was quantified by calculating the percentage contrast of each of the hot and cold spheres as well as the percentage background variability using the equations defined in the NEMA NU2 protocol. The recovery coefficients for the different sphere volumes have also been calculated. Result(s): Noticeable artefacts are seen in the TrueX reconstructed images and are demonstrated in Figure 1. Where Figure 1a is the Jaszczak phantom reconstructed with OSEM-3D, Figure 1b is the TrueX reconstruction. Figure 1c is the subtraction of TureX with OSEM-3D and shows this artefact in areas of high contrast change. It has been found that the TrueX reconstruction overestimates the activity concentration (and therefore SUV) compared to the true activity and that in general there are some improvements in image contrast and background variability compared to OSEM-3D. (Figure presented) Conclusion(s): It is recommended that particular care should be taken when using the TrueX algorithm for quantitative SUV measurements. Clinicians should also be aware of the possible presence of this artefact in algorithms that incorporate direct modelling of the syste

Objectives: 177Lu-PSMA-617 is a radiolabelled small molecule that delivers p-radiation to cells expressing prostate specific membrane antigen (PSMA), with promising activity and safety in metastatic castration-resistant prostate cancer (mCRPC). We compared 177Lu-PSMA-617 and cabazitaxel in a randomised phase 2 trial. Method(s): Men with mCRPC progressing after docetaxel with high PSMA tumour-expression were randomized to 177Lu-PSMA-617 (6-8.5 GBq intravenously 6 weekly up to 6 cycles) vs cabazitaxel (20 mg/m2 intravenously 3 weekly up to 10 cycles) at 11-sites in Australia. The primary endpoint was prostate specific antigen (PSA) response rate defined by >50% reduction (PSA50-RR). Secondary endpoints included progression-free survival (PFS) (PSA and radiographic PFS), objective response rate (ORR) (RECIST 1.1), adverse events (CTCAE v4.03), patientreported outcomes (PROs) (EORTC QLQ-C30, PDF), and overall survival (OS). This trial is registered in ClinicalTrials.gov, NCT03392428. Result(s): 200 of 291 men identified as eligible on PET imaging were randomised to 177Lu-PSMA-617 (N=99) or cabazitaxel (N=101). 91 % had received prior androgen receptor-directed therapy (ARDT). PSA50-RR was significantly higher in those assigned 177Lu-PSMA-617 versus cabazitaxel (66% [95%CI,56-75%] vs 37% [95%CI,27-46%]; P<0.001). PFS was significantly longer in those assigned 177Lu-PSMA-617 than cabazitaxel (rates at 1yr 19% [95%CI,12-27%] vs 3% [95%CI,1-9%], hazard ratio (HR) 0 63 [95%CI,0.46-0.86; P=0.003). ORR in 78 men with measurable disease was significantly higher with 177Lu-PSMA-617 than cabazitaxel (49% vs 24%, RR 2.12; P=0.026). Follow-up remains immature for OS. Grade 3-4 adverse events occurred in 32/98 (33%) with 177Lu - PSMA-617 vs 45/85 (55%) with cabazitaxel. Overall quality-of-life and health status were similar, with significantly better outcomes for multiple PRO domains including diarrhoea, fatigue, social functioning, insomnia, hair loss, skin rash and sore hands/feet

Objectives: 177Lu-PSMA-617 is a radiolabelled small molecule that delivers p-radiation to cells expressing prostate specific membrane antigen (PSMA), with promising activity and safety in metastatic castration-resistant prostate cancer (mCRPC). We compared 177Lu-PSMA-617 and cabazitaxel in a randomised phase 2 trial. Method(s): Men with mCRPC progressing after docetaxel with high PSMA tumour-expression were randomized to 177Lu-PSMA-617 (6-8.5 GBq intravenously 6 weekly up to 6 cycles) vs cabazitaxel (20 mg/m2 intravenously 3 weekly up to 10 cycles) at 11-sites in Australia. The primary endpoint was prostate specific antigen (PSA) response rate defined by >50% reduction (PSA50-RR). Secondary endpoints included progression-free survival (PFS) (PSA and radiographic PFS), objective response rate (ORR) (RECIST 1.1), adverse events (CTCAE v4.03), patientreported outcomes (PROs) (EORTC QLQ-C30, PDF), and overall survival (OS). This trial is registered in ClinicalTrials.gov, NCT03392428. Result(s): 200 of 291 men identified as eligible on PET imaging were randomised to 177Lu-PSMA-617 (N=99) or cabazitaxel (N=101). 91 % had received prior androgen receptor-directed therapy (ARDT). PSA50-RR was significantly higher in those assigned 177Lu-PSMA-617 versus cabazitaxel (66% [95%CI,56-75%] vs 37% [95%CI,27-46%]; P<0.001). PFS was significantly longer in those assigned 177Lu-PSMA-617 than cabazitaxel (rates at 1yr 19% [95%CI,12-27%] vs 3% [95%CI,1-9%], hazard ratio (HR) 0 63 [95%CI,0.46-0.86; P=0.003). ORR in 78 men with measurable disease was significantly higher with 177Lu-PSMA-617 than cabazitaxel (49% vs 24%, RR 2.12; P=0.026). Follow-up remains immature for OS. Grade 3-4 adverse events occurred in 32/98 (33%) with 177Lu - PSMA-617 vs 45/85 (55%) with cabazitaxel. Overall quality-of-life and health status were similar, with significantly better outcomes for multiple PRO domains including diarrhoea, fatigue, social functioning, insomnia, hair loss, skin rash and sore hands/feet