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Abstract Background A recent randomised trial demonstrated [18F]fluorodeoxyglucose positron-emission tomography in combination with low-dose CT (FDG-PET/CT), compared to standard of care computed tomography (CT) imaging, positively impacted antimicrobial management and outcomes of acute leukaemia and haematopoietic stem cell transplant recipients with persistent and recurrent neutropenic fever. We conducted an economic evaluation from a healthcare perspective alongside the clinical trial. Methods Unit costs in Australian dollars were applied to all resources used (antimicrobials, diagnostic tests, ICU and hospital bed days). Effectiveness was measured as number of patients with antimicrobial rationalisation, 6-month mortality and quality-adjusted life years (QALYs) derived from patient-reported trial-based health-related quality-of-life. Generalised linear models were used to analyse costs and outcomes. Incremental cost-effectiveness ratios (ICERs) for all outcomes and net monetary benefit (NMB) for QALYs were calculated. We performed bootstrapping with 1000 replications using the recycled predictions method. Results The adjusted healthcare costs were lower for FDG-PET/CT (mean $49,563; 95%CI 36,867, 65,133) compared to CT (mean $57,574; 95% CI 44,837, 73,347). The difference in QALYs between the two groups was small (0.001; 95% CI -0.001, 0.004). When simulated 1000 times, FDG-PET/CT was the dominant strategy as it was cheaper with better outcomes than the standard CT group in 74% of simulations. The estimated NMBs at willingness-to-pay thresholds of $50,000 and $100,000 per QALY were positive, thus FDG-PET/CT remained cost-effective at these thresholds. Conclusions FDG-PET/CT is cost effective when compared to CT for investigation of persistent/recurrent neutropenic fever in high-risk patients, providing further support for incorporation of FDG-PET/CT into clinical guidelines and funding. Trial registration This trial is registered with ClinicalTrials.gov, NCT03429387.

IntroductionHypophysitis is reported in 8.5%–14% of patients receiving combination immune checkpoint inhibition (cICI) but can be a diagnostic challenge. This study aimed to assess the role of routine diagnostic imaging performed during therapeutic monitoring of combination anti-CTLA-4/anti-PD-1 treatment in the identification of hypophysitis and the relationship of imaging findings to clinical diagnostic criteria.MethodsThis retrospective cohort study identified patients treated with cICI between January 2016 and January 2019 at a quaternary melanoma service. Medical records were reviewed to identify patients with a documented diagnosis of hypophysitis based on clinical criteria. Available structural brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT) of the brain and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography (FDG-PET/CT) were assessed retrospectively. The main radiological outcome measures were a relative change in pituitary size or FDG uptake temporally attributed to cICI.ResultsThere were 162 patients (median age 60 years, 30% female) included. A total of 100 and 134 had serial CT/MRI of the brain and FDG-PET/CT, respectively. There were 31 patients who had a documented diagnosis of hypophysitis and an additional 20 who had isolated pituitary imaging findings. The pituitary gland enlargement was mild, and the largest absolute gland size was 13 mm, with a relative increase of 7 mm from baseline. There were no cases of optic chiasm compression. Pituitary enlargement and increased FDG uptake were universally transient. High-dose glucocorticoid treatment for concurrent irAEs prevented assessment of the pituitary–adrenal axis in 90% of patients with isolated imaging findings.ConclusionCareful review of changes in pituitary characteristics on imaging performed for assessment of therapeutic response to iICI may lead to increased identification and more prompt management of cICI-induced hypophysitis.

Abstract Background Prostate-Specific Membrane Antigen (PSMA) PET/CT and multiparametric MRI (mpMRI) are well-established modalities for identifying intra-prostatic lesions (IPLs) in localised prostate cancer. This study aimed to investigate the use of PSMA PET/CT and mpMRI for biologically targeted radiation therapy treatment planning by: (1) analysing the relationship between imaging parameters at a voxel-wise level and (2) assessing the performance of radiomic-based machine learning models to predict tumour location and grade. Methods PSMA PET/CT and mpMRI data from 19 prostate cancer patients were co-registered with whole-mount histopathology using an established registration framework. Apparent Diffusion Coefficient (ADC) maps were computed from DWI and semi-quantitative and quantitative parameters from DCE MRI. Voxel-wise correlation analysis was conducted between mpMRI parameters and PET Standardised Uptake Value (SUV) for all tumour voxels. Classification models were built using radiomic and clinical features to predict IPLs at a voxel level and then classified further into high-grade or low-grade voxels. Results Perfusion parameters from DCE MRI were more highly correlated with PET SUV than ADC or T2w. IPLs were best detected with a Random Forest Classifier using radiomic features from PET and mpMRI rather than either modality alone (sensitivity, specificity and area under the curve of 0.842, 0.804 and 0.890, respectively). The tumour grading model had an overall accuracy ranging from 0.671 to 0.992. Conclusions Machine learning classifiers using radiomic features from PSMA PET and mpMRI show promise for predicting IPLs and differentiating between high-grade and low-grade disease, which could be used to inform biologically targeted radiation therapy planning.

Abstract “Total-body” and ultra-extended field-of-view PET/CT scanners are now available commercially with great enthusiasm for their potential in both streamlining clinical practice and providing unique research opportunities. Accordingly, many groups are rushing to implement this technology. For early adopters, the challenges of these systems compared with more standard PET/CT systems have been significant. In this guide, aspects that need to be considered in planning installation of one of these scanners are discussed. These include financing, space, structural engineering, power supply, chilled water and environmental controls to manage heat loads, IT infrastructure and data storage, radiation safety and radiopharmaceutical procurement, staffing levels, patient handling logistics and imaging protocol redesign to leverage the superior sensitivity of these scanners, and marketing. It is a daunting but worthwhile endeavor in the author’s opinion but needs a great team and the ability to bring in the appropriate expertise at the appropriate time.

Pheochromocytomas and paragangliomas (PCPG) are rare neuroendocrine tumours. Here, the authors use single-nuclei and bulk-tissue RNA-seq to characterise PCPG tumours and their microenvironments and reveal molecular subtypes as well as expression patterns associated with metastasis.

Background: FDG-PET/CT used for immune checkpoint inhibitor (ICI) response assessment can incidentally identify immune-related adverse events (irAEs), including thyroiditis. This study aimed to correlate the time course of FDG-PET/CT evidence of thyroiditis with clinical and biochemical evolution of thyroid dysfunction. Methods: A retrospective review was performed by two independent blinded nuclear medicine physicians (NMPs) of thyroidal FDG uptake in 127 patients who underwent PET/CT between January 2016 and January 2019 at baseline and during treatment monitoring of combination ICI therapy for advanced melanoma. Interobserver agreement was assessed and FDG-PET/CT performance defined by a receiver-operating characteristic (ROC) curve using thyroid function tests (TFTs) as the standard of truth. Thyroid maximum standardized uptake value (SUVmax) and its temporal changes with respect to the longitudinal biochemistry were serially recorded. Results: At a median of 3 weeks after commencing ICI, 43/127 (34%) had a diagnosis of thyroiditis established by abnormal TFTs. FDG-PET/CT was performed at baseline and at a median of 11 weeks (range 3–32) following the start of therapy. ROC analysis showed an area under the curve of 0.87 (95% CI 0.80, 0.94) for FDG-PET/CT for detection of thyroiditis with a positive predictive value of 93%. Among patients with biochemical evidence of thyroiditis, those with a positive FDG-PET/CT were more likely to develop overt hypothyroidism (77% versus 35%, p < 0.01). In the evaluation of the index test, there was an almost perfect interobserver agreement between NMPs of 93.7% (95% CI 89.4–98.0), kappa 0.83. Conclusion: Increased metabolic activity of the thyroid on routine FDG-PET/CT performed for tumoral response of patients undergoing ICI therapy is generally detected well after routine biochemical diagnosis. Elevation of FDG uptake in the thyroid is predictive of overt clinical hypothyroidism and suggests that an ongoing robust inflammatory response beyond the initial thyrotoxic phase may be indicative of thyroid destruction.

Abstract Neuroendocrine neoplasia (NEN) is an umbrella term that includes a widely heterogeneous disease group including well-differentiated neuroendocrine tumours (NETs), and aggressive neuroendocrine carcinomas (NECs). The site of origin of the NENs is linked to the intrinsic tumour biology and is predictive of the disease course. It is understood that NENs demonstrate significant biologic heterogeneity which ultimately translates to widely varying clinical presentations, disease course and prognosis. Thus, significant emphasis is laid on the pre-therapy evaluation of markers that can help predict tumour behavior and dynamically monitors the response during and after treatment. Most well-differentiated NENs express somatostatin receptors (SSTRs) which make them appropriate for peptide receptor radionuclide therapy (PRRT). However, the treatment outcomes of PRRT depend heavily on the adequacy of patient selection by molecular imaging phenotyping not only utilizing pre-treatment SSTR PET but 18F-Fluorodeoxyglucose (18F-FDG) PET to provide insights into the intra- or inter-tumoural heterogeneity of the metastatic disease. Molecular imaging phenotyping may go beyond patient selection and provide useful information during and post-treatment for monitoring of temporal heterogeneity of the disease and dynamically risk-stratify patients. In addition, advances in the understanding of genomic-phenotypic classifications of pheochromocytomas and paragangliomas led to an archetypical example in precision medicine by utilizing molecular imaging phenotyping to guide radioligand therapy. Novel non-SSTR based peptide receptors have also been explored diagnostically and therapeutically to overcome the tumour heterogeneity. In this paper, we review the current molecular imaging modalities that are being utilized for the characterization of the NENs with special emphasis on their role in patient selection for radioligand therapy.

Abstract Immune checkpoint inhibitors and related molecules can achieve tumour regression, and even prolonged survival, for a subset of cancer patients with an otherwise dire prognosis. However, it remains unclear why some patients respond to immunotherapy and others do not. PET imaging has the potential to characterise the spatial and temporal heterogeneity of both immunotherapy target molecules and the tumor immune microenvironment, suggesting a tantalising vision of personally-adapted immunomodulatory treatment regimens. Personalised combinations of immunotherapy with local therapies and other systemic therapies, would be informed by immune imaging and subsequently modified in accordance with therapeutically induced immune environmental changes. An ideal PET imaging biomarker would facilitate the choice of initial therapy and would permit sequential imaging in time-frames that could provide actionable information to guide subsequent therapy. Such imaging should provide either prognostic or predictive measures of responsiveness relevant to key immunotherapy types but, most importantly, guide key decisions on initiation, continuation, change or cessation of treatment to reduce the cost and morbidity of treatment while enhancing survival outcomes. We survey the current literature, focusing on clinically relevant immune checkpoint immunotherapies, for which novel PET tracers are being developed, and discuss what steps are needed to make this vision a reality.

Different adaptive mechanisms have been reported to reduce the efficacy of mutant BRAF inhibition in melanoma. Here, the authors show BRAF inhibition induces the translational regulation of metabolic genes leading to acquired therapy resistance.

Abstract 18F-FDG PET/CT plays an increasingly pivotal role in the staging and post-treatment monitoring of high-risk melanoma patients, augmented by the introduction of therapies, including tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICIs), that have novel modes of action that challenge conventional response assessment. Simultaneously, technological advances have been regularly released, including advanced reconstruction algorithms, digital PET and motion correction, which have allowed the PET community to detect ever-smaller cancer lesions, improving diagnostic performance in the context of indications previously viewed as limitations, such as detection of in-transit disease and confirmation of the nature of small pulmonary metastases apparent on CT. This review will provide advice regarding melanoma-related PET protocols and will focus on variants encountered during the imaging of melanoma patients. Emphasis will be made on pitfalls related to non-malignant diseases and treatment-related findings that may confound accurate interpretation unless recognized. The latter include signs of immune activation and immune-related adverse events (irAEs). Technology-related pitfalls are also discussed, since while new PET technologies improve detection of small lesions, these may also induce false-positive cases and require a learning curve to be observed. In these times of the COVID 19 pandemic, cases illustrating lessons learned from COVID 19 or vaccination-related pitfalls will also be described.

Abstract Background The role of FDG-PET/CT imaging in assessing response to immunotherapy in advanced cutaneous squamous cell carcinoma (CSCC) is unknown. This study compared complete metabolic response (CMR) rates by FDG-PET and RECIST1.1 via CT or MRI in patients on cemiplimab for > 10 months. Methods This was a single-centre retrospective study of 15 patients treated with cemiplimab for advanced CSCC who had CT/MRI and FDG-PET/CT at > 10 months to assess metabolic treatment response. The median age was 73 years (range 55–84) and 93% were male. RECIST1.1 and PERCIST1.0 tumor responses were evaluated by blinded readers. Results Seventy-three percent (11/15) (95%CI 44.9, 92.2%) achieved a CMR on PET. Of these 11, on RECIST1.1 there was one complete response, 9 partial responses and one stable disease. Conclusions In patients on cemiplimab for > 10 months, there was discordance between CR rates on FDG-PET versus RECIST1.1. FDG-PET/CT may have utility for clarifying depth of response in patients treated with immunotherapy for CSCC.

The prognosis of castration-resistant prostate cancers remains dismal, but accurate preclinical models can lead to effective therapies. Here the Melbourne Urological Research Alliance establish prostate cancer patient-derived xenografts, use the tumors for organoids and single-cell RNA-seq, and show the efficacy of PARP inhibitor combination treatments.

Abstract Background Recent studies reported metabolic uptake in at least one of the evaluated ganglia in 98.5% of patients undergoing 68Ga -PSMA-11 and in 96.9% of patients undergoing 18F-DCFPyL PET/CT examination. We have observed different patterns of ganglion visualization with 18F-DCFPyL compared to 68Ga-PSMA-11. This includes more frequent visualization of cervical and sacral ganglia, which may be attributable to better imaging characteristics with 18F PET imaging. Case presentation This pictorial essay is to illustrate and compare, in the same patient, various representative cases of 68Ga-PSMA-11 and 18F-DCFPyL PET/CT uptake in ganglia at different anatomic locations, with different patterns and distribution of metabolic activity. Conclusion Reading physicians should be aware of the frequently encountered and occasionally different physiologic uptake of 68Ga-PSMA-11 and 18F DCFPyL in different ganglia.

Abstract Background Positron Emission Tomography with Computed Tomography (PET/CT) is widely used in the assessment of many diseases, particularly including cancer. However, many factors can affect image quality and diagnostic performance of PET scans using FDG or other PET probes. Main body The aim of this pictorial essay is to review PET/CT protocols that can be useful to overcome these confounding factors in routine clinical situations, with a particular focus on pharmacological interventions and problem-oriented CT acquisition protocols. Conclusion Imaging protocols and representative cases will be discussed, in addition to potential contraindications and precautions to be taken.

Abstract Background Immune checkpoint blockade such as ipilimumab and anti-PD1 monoclonal antibodies have significantly improved survival in advanced melanoma. Biomarkers are urgently needed as a majority of patients do not respond, despite treatment-related toxicities. We analysed pre-treatment 18F-fluorodeoxyglucose positron emission tomography/computerised tomography (FDG PET/CT) parameters to assess its correlation with patient outcome. Methods This retrospective study evaluated pre-treatment FDG PET/CT scans in a discovery cohort of patients with advanced melanoma treated with ipilimumab or anti-PD1. Pre-treatment scans were assessed for maximum tumoral standardised uptake value (SUVmax), metabolic tumour volume (MTV) and spleen to liver ratio (SLR). Progression-free survival (PFS) and overall survival (OS) were characterised and modelled using univariable and multivariable analyses. Correlation of SLR and OS was validated in an independent cohort. Blood parameters and stored sera of patients from the discovery cohort was analysed to investigate biological correlates with SLR. Results Of the 90 evaluable patients in the discovery cohort: 50 received ipilimumab monotherapy, 20 received anti-PD1 monotherapy, and 20 patients received ipilimumab followed by anti-PD1 upon disease progression. High SLR > 1.1 was associated with poor PFS (median 1 vs 3 months; HR 3.14, p = 0.008) for patients treated with ipilimumab. High SLR was associated with poor OS after ipilimumab (median 1 vs 21 months; HR 5.83, p = 0.0001); as well as poor OS after first line immunotherapy of either ipilimumab or anti-PD1 (median 1 vs 14 months; HR 3.92, p = 0.003). The association of high SLR and poor OS after ipilimumab was validated in an independent cohort of 110 patients (median 2.3 months versus 11.9 months, HR 3.74). SLR was associated with poor OS in a multi-variable model independent of stage, LDH, absolute lymphocyte count and MTV. Conclusions Pre-treatment Spleen to liver ratio (SLR) > 1.1 was associated with poor outcome after ipilimumab in advanced melanoma. This parameter warrants prospective evaluation.

Prostate-specific membrane antigen (PSMA) is highly expressed on the membrane of most prostate cancer cells and to a lesser extent in normal tissues. Many vectors targeting this protein have been created over the past decade and numerous clinical studies have positively demonstrated the tolerance and efficacy of radiolabeled prostate-specific membrane antigen ligands for PSMA radioligand therapy (PRLT). Preliminary results are encouraging that PRLT will become an important addition to the current therapeutic options in a number of settings. Improvement in radiopharmaceutical targeting and combination with other oncological agents are under investigation to further improve its therapeutic efficacy. These encouraging results have led to the development of other therapies using PSMA as a target, such as PSMA–targeted chimeric antigen receptor T-cells, PSMA–targeted antibody drug conjugates, and PSMA–targeted bi-specific T-cell-directed therapy. This narrative review details the current state and advancements in prostate-specific membrane antigen targeting in prostate cancer treatment.

Abstract Technical advances in imaging are well demonstrated by MRI (Magnetic Resonance Imaging) and PET (Positron Emission Tomography). Excellent anatomical detail and a lack of ionising radiation make MRI the standard of care for most neuroimaging indications, and advanced sequences are providing an ever-growing ability for lesion characterisation. PET utilising the tracer fluorine-18 fluorodeoxyglucose is widely used in oncology, while newer PET tracers are able to target a growing number of metabolic pathways and cell membrane receptors. The sequential use of these modalities harnesses the strengths of both, providing complementary diagnostic and therapeutic information. Here we outline the ways in which we use MRI and PET in a complementary manner to improve lesion characterisation in neuro-oncology. Most commonly, an abnormality is detected on either PET or MRI, and the addition of the other modality allows a more confident diagnosis and/or demonstrates additional lesions, guiding treatment decisions and, in some cases, obviating the need for biopsy. These modalities may also be combined to guide the treatment of intracranial masses for which the diagnosis is known, such as neuro-endocrine tumour metastases or meningiomas refractory to conventional therapies.

Abstract Background Gallium-68 ([68Ga]Ga) labelled radiopharmaceuticals have become a valuable tool in clinical practice using Positron Emission Tomography (PET). These agents are typically produced on-site owing to the short half-life of [68Ga]Ga (68 min), which hinders distant transportation and often cannot comply with Good Manufacturing Practice (GMP) in hospital environments due to limited resources or infrastructure constraints. Moreover, full blown GMP production of radiopharmaceuticals under development can be prohibitively expensive. [68Ga]Ga-DOTA-CP04 is a promising peptide for imaging neuroendocrine tumors overexpressing the cholecyctokinin-2 receptor. Automation is an integral process in ensuring the radiopharmaceuticals produced under non-GMP conditions are of a uniform quality for routine clinical use. Herein, we describe the development of an automation platform, the iPHASE MultiSyn radiosynthesizer, to produce 68Ga-labelled DOTA-CP04 for routine clinical provision. Results The use of the MultiSyn module for 68Ga-labelling of DOTA-CP04 was investigated. [68Ga]Ga-DOTA-CP04, was reproducibly prepared in high (> 70%) decay-corrected yields. [68Ga]Ga-DOTA-CP04 passed all predetermined acceptance criteria for human injection. Conclusions [68Ga]Ga-DOTA-CP04 was produced effectively using the MultiSyn module in a consistent and reproducible manner suitable for human injection.

Abstract Purpose Detailed data comparing the biodistribution of PSMA radioligands is still scarce, raising concerns regarding the comparability of different compounds. We investigated differences in normal-organ biodistribution and uptake variability between the two most commonly PSMA tracers in clinical use, 68Ga-PSMA-11 and 18F-DCFPyL. Methods This retrospective analysis included 34 patients with low tumor burden referred for PET/CT imaging with 68Ga-PSMA-11 and subsequently 18F-DCFPyL. Images were acquired with 4 cross-calibrated PET/CT systems. Volumes of interest were placed on major salivary and lacrimal glands, liver, spleen, duodenum, kidneys, bladder, blood-pool and muscle. Normal-organ biodistribution of both tracers was then quantified as SUVpeak and compared using paired tests, linear regression and Bland-Altman analysis. Between-patient variability was also assessed. Clinical and protocol variables were investigated for possible interference. Results For both tracers the highest uptake was found in the kidneys and bladder and low background activity was noted across all scans. In the quantitative analysis there was significantly higher uptake of 68Ga-PSMA-11 in the kidneys, spleen and major salivary glands (p

Abstract Background Testicular germ cell tumour is the commonest malignancy affecting males aged between 15 and 35, with an increased relative risk amongst those with a history of cryptorchidism. In patients presenting with locoregional metastatic disease, retroperitoneal and pelvic soft tissue masses are common findings on ultrasound and computed tomography, which has several differential diagnoses within this demographic cohort. On staging 18F-FDG-PET/CT, understanding the typical testicular lymphatic drainage pathway facilitates prompt recognition of the pathognomonic constellation of unilateral absence of testicular scrotal activity, and FDG-avid nodal masses along the drainage pathway. We describe the cases of three young males presenting with abdominopelvic masses, in whom FDG-PET/CT was helpful in formulating a unifying diagnosis of metastatic seminoma, retrospectively corroborated by a history of testicular maldescent. Case presentations In all three cases, the patients were males aged in their 30s and 40s who were brought to medical attention for back and lower abdominal pain of varying duration. Initial imaging evaluation with computed tomography and/or ultrasound revealed large abdominopelvic soft tissue masses, with lymphoproliferative disorders or soft tissue sarcomas being high on the list of differential diagnoses. As such, they were referred for staging FDG-PET/CT, all of whom demonstrated the pathognomonic constellation of, 1) unilateral absence of scrotal testicular activity, and 2) FDG-avid nodal masses along the typical testicular lymphatic drainage pathway. These characteristic patterns were corroborated by a targeted clinical history and examination which revealed a history of cryptorchidism, and elevated β-hCG in two of three patients. All were subsequently confirmed as metastatic seminoma on biopsy and open resection. Conclusion These cases highlight the importance of clinical history and examination for the clinician, as well as a sound knowledge of the typical testicular lymphatic drainage pathway for the PET physician, which would assist with prompt recognition of the characteristic imaging patterns on FDG-PET/CT. It further anecdotally supports the utility of FDG-PET/CT in evaluating undiagnosed abdominopelvic masses, as well as a potential role in the initial staging of germ cell tumours in appropriately selected patients.

Abstract Background Hyperglycaemia can influence 18F-fluorodeoxyglucose (FDG) uptake due to competition for glucose transport and phosphorylation by hexokinase. Major international nuclear medicine societies recommend blood glucose level (BGL) 10 mmol/L) prior to FDG PET/CT at the Peter MacCallum Cancer Centre over a 2-year period. Cohort 1 comprised a 12-month period (April 1, 2014–March 31, 2015) using the department’s established empiric-dose insulin protocol, and Cohort 2 the 12 months (April 1, 2015–March 31, 2016) following introduction of a personalised insulin calculator protocol. Variables including body mass index, insulin-dose calculated and/or administered, BGL at baseline and nadir, and time to FDG injection were analysed. There were 115 and 136 patients treated with insulin in Cohorts 1 and 2 respectively, with similar baseline variables including mean BGL (14.5 vs 14.4 mmol/L) and range (10.5–22.7 vs 10.4–24.3 mmol/L). Use of the new personalised insulin calculator resulted in significantly fewer hypoglycaemic events (0.7% vs 5.2%; P

Abstract Background Both constrast-enhanced computed tomography (ceCT) and 18F-Fluorodeoxyglucose positron emission tomography (PET) are widely used for evaluation of colorectal cancer. Not infrequently patients undergo both tests, increasing cost and radiation burden. Whether this combination provides useful incremental diagnostic information remains unclear. Our purpose was to determine whether the addition of ceCT to PET/CT results in an appropriate change in the N or M stage in patients with colorectal cancer. Methods This was a single centre, retrospective study in a tertiary referral hospital. Over 9 months, 74 consecutive patients with colorectal carcinoma were referred for PET with a recent ceCT scan and adequate follow-up were analysed. The N and M stage of each modality was compared. Management was determined according to institutional guidelines with incremental impact of ceCT results on management categorised as appropriate, inappropriate or unchanged, based on pathological results, clinical or imaging follow-up of discrepant findings. Results Of 74 patients, PET/CT and ceCT N and M stages were concordant in 56 patients (76%) but PET/CT and ceCT identified additional abnormalities in 9 cases each respectively. Of the 18 discordant cases, accepting the ceCT result would have appropriately changed management in only 2 patients and inappropriately in 1 with most management plans unchanged. When comparing PET/CT and ceCT, kappa agreement (95% confidence interval) for N and M stage was 0.58 (0.20–0.95) and 0.60(0.41–0.79) respectively reflecting moderate agreement. Conclusions Whole-body ceCT probably has limited management impact in colorectal cancer patients who are also undergoing PET/CT and therefore may possibly be omitted from routine use. Targeted regional MRI or ceCT should, however, be considered based on clinical suspicion or when high-resolution anatomical information is required for treatment planning.

Non-melanoma skin cancers are one of the most common cancers diagnosed worldwide, with the highest incidence in Australia and New Zealand. Systemic treatment of locally advanced and metastatic cutaneous squamous cell carcinomas has been revolutionized by immune checkpoint inhibition with PD-1 blockade. We highlight treatment issues distinct to the management of the disease including expansion of the traditional concept of pseudoprogression and describe delayed responses after immune-specific response criteria confirmed progressive disease with and without clinical deterioration. We term this phenomenon “delayed response after confirmed progression (DR)”. We also discuss the common development of second primary tumors, heterogeneous disease responses, and expanding clinical boundaries for immunotherapy use.

Objectives:68Ga Ventilation/Perfusion V/Q PET-CT is a promising imaging tool for pulmonary embolism diagnosis. However, no study has verified whether the interpretation is reproducible between different observers. The aim of this study was to assess the interobserver agreement in the interpretation of V/Q PET-CT for the diagnosis of acute PE, and to compare it to the interobserver agreement of CTPA interpretation.Methods: Twenty-four cancer patients with suspected acute PE underwent V/Q PET-CT and CTPA within 24 h as part of a prospective pilot study evaluating V/Q PET-CT for the management of patients with suspected PE. V/Q PET-CT and CTPA scans were reassessed independently by four nuclear medicine physicians and four radiologists, respectively. Physicians had different levels of expertise in reading V/Q scintigraphy and CTPA. Interpretation was blinded to the initial interpretation and any clinical information or imaging test result. For each modality, results were reported on a binary fashion. V/Q PET/CT scans were read as positive if there was at least one segmental or two subsegmental mismatched perfusion defects. CTPA scans were interpreted as positive if there was a constant intraluminal filling defect. Interobserver agreement was assessed by calculating kappa (κ) coefficients.Results: Out of the 24 V/Q PET-CT scans, the diagnostic conclusion was concordantly negative in 22 patients and concordantly positive in one patient. The remaining scan was interpreted as positive by one reader and negative by three readers. Out of the 24 CTPA scans, the diagnostic conclusion was concordantly negative in 16 and concordantly positive in one. Out of the seven remaining scans, PE was reported by one reader in four cases, by two readers in two cases, by three readers in one case. Most of discordant results on CTPA were related to clots reported on subsegmental arteries. Mean kappa coefficient was 0.79 for V/Q PET-CT interpretation and 0.39 for CTPA interpretation.Conclusions: Interobserver agreement in the interpretation of V/Q PET-CT for PE diagnosis was substantial (kappa 0.79) in a population with a low prevalence of significant PE. Agreement was lower with CTPA, mainly as a result of discrepancies at the level of the subsegmental arteries.

Abstract Background To evaluate the effects of long-acting somatostatin analogue (SSA) therapy on 68Ga-DOTA-octreotate (GaTate) uptake at physiological and metastatic sites in neuroendocrine tumour (NET) patients. Methods Twenty-one patients who underwent GaTate PET/CT before and after commencement of SSA therapy were reviewed. Maximum standardized uptake values (SUVmax) were measured in normal organs. Changes in uptake of 49 metastatic lesions in 12 patients with stable disease were also compared. Serum chromogranin-A (CgA) levels were available for correlation between scans in 17/21 patients. Results Mean thyroid, spleen and liver SUVmax decreased significantly following SSA therapy from a baseline of 5.9 to 3.5, 30.3 to 23.1 and 10.3 to 8.0, respectively (p =

Abstract Background 68Ga-labelled prostate specific membrane antigen (PSMA) ligand PET/CT is a promising modality in primary staging (PS) and biochemical relapse (BCR) of prostate cancer (PC). However, pelvic nodes or local recurrences can be difficult to differentiate from radioactive urine. CT urography (CT-U) is an established method, which allows assessment of urological malignancies. The study presents a novel protocol of 68Ga-PSMA-11 PET/CT-U in PS and BCR of PC. Methods A retrospective review of PSMA PET/CT-U preformed on 57 consecutive patients with prostate cancer. Fifty mL of IV contrast was administered 10 min (range 8–15) before the CT component of a combined PET/CT study, acquired approximately 60 min (range 40–85) after administration of 166 MBq (range 91–246) of 68Ga-PSMA-11. PET and PET/CT-U were reviewed by two nuclear medicine physicians and CT-U by a radiologist. First, PET images were reviewed independently followed by PET/CT-U images. Foci of activity which could not unequivocally be assessed as disease or urinary activity were recorded. PET/CT-U was considered of potential benefit in final interpretation when the equivocal focal activity in PET images corresponded to opacified ureter, bladder, prostate bed, seminal vesicles, or urethra. Student’s T test and Pearson’s correlation coefficient was used for assessment of variables including lymph node size and standardized uptake value. Results Overall 50 PSMA PET/CT-U studies were performed for BCR and 7 for PS. Median PSA with BCR and PS were 2.0 ± 11.4 ng/ml (0.06–57.3 ng/ml) and 18 ± 35.3 ng/ml (6.8–100 ng/ml), respectively. The median Gleason-score for both groups was 7 (range 6–10). In BCR group, PSMA PET was reported positive in 36 (72%) patients, CT-U in 11(22%) patients and PET/CT-U in 33 (66%) patients. In PS group, PSMA PET detected the primary site in all seven patients, of which one patient with metastatic nodal disease had negative CT finding. Of 40 equivocal foci (27/57 patients) on PET, 11 foci (10/57 patients, 17.5%) were localized to enhanced urine on PET/CT-U, hence considered of potential benefit in interpretation. Of those, 3 foci (3 patients) were solitary sites of activity on PSMA imaging including two local and one nodal site and 4 foci (3 patients) were in different nodal fields. Conclusions PET/CT-U protocol is a practical approach and may assist in interpretation of 68Ga-PSMA-11 imaging by delineation of the contrast opacified genitourinary system and matching focal PSMA activity with urinary contrast.

Abstract Background Functional volumes computed from 68Ga-ventilation/perfusion (V/Q) PET/CT, which we have shown to correlate with pulmonary function test parameters (PFTs), have potential diagnostic utility in a variety of clinical applications, including radiotherapy planning. An automatic segmentation method would facilitate delineation of such volumes. The aim of this study was to develop an automated threshold-based approach to delineate functional volumes that best correlates with manual delineation. Thirty lung cancer patients undergoing both V/Q PET/CT and PFTs were analyzed. Images were acquired following inhalation of Galligas and, subsequently, intravenous administration of 68Ga-macroaggreted-albumin (MAA). Using visually defined manual contours as the reference standard, various cutoff values, expressed as a percentage of the maximal pixel value, were applied. The average volume difference and Dice similarity coefficient (DSC) were calculated, measuring the similarity of the automatic segmentation and the reference standard. Pearson’s correlation was also calculated to compare automated volumes with manual volumes, and automated volumes optimized to PFT indices. Results For ventilation volumes, mean volume difference was lowest (− 0.4%) using a 15%max threshold with Pearson’s coefficient of 0.71. Applying this cutoff, median DSC was 0.93 (0.87–0.95). Nevertheless, limits of agreement in volume differences were large (− 31.0 and 30.2%) with differences ranging from − 40.4 to + 33.0%. For perfusion volumes, mean volume difference was lowest and Pearson’s coefficient was highest using a 15%max threshold (3.3% and 0.81, respectively). Applying this cutoff, median DSC was 0.93 (0.88–0.93). Nevertheless, limits of agreement were again large (− 21.1 and 27.8%) with volume differences ranging from − 18.6 to + 35.5%. Using the 15%max threshold, moderate correlation was demonstrated with FEV1/FVC (r = 0.48 and r = 0.46 for ventilation and perfusion images, respectively). No correlation was found between other PFT indices. Conclusions To automatically delineate functional volumes with 68Ga-V/Q PET/CT, the most appropriate cutoff was 15%max for both ventilation and perfusion images. However, using this unique threshold systematically provided unacceptable variability compared to the reference volume and relatively poor correlation with PFT parameters. Accordingly, a visually adapted semi-automatic method is favored, enabling rapid and quantitative delineation of lung functional volumes with 68Ga-V/Q PET/CT.

Abstract Background This study evaluates the consistency of PET evaluation response criteria in solid tumours (PERCIST) and European Organisation for Research and Treatment of Cancer (EORTC) classification across different reconstruction algorithms and whether aligning standardized uptake values (SUVs) to the European Association of Nuclear Medicine acquisition (EANM)/EARL standards provides more consistent response classification. Materials and methods Baseline (PET1) and response assessment (PET2) scans in 61 patients with non-small cell lung cancer were acquired in protocols compliant with the EANM guidelines and were reconstructed with point-spread function (PSF) or PSF + time-of-flight (TOF) reconstruction for optimal tumour detection and with a standardized ordered subset expectation maximization (OSEM) reconstruction known to fulfil EANM harmonizing standards. Patients were recruited in three centres. Following reconstruction, EQ.PET, a proprietary software solution was applied to the PSF ± TOF data (PSF ± TOF.EQ) to harmonize SUVs to the EANM standards. The impact of differing reconstructions on PERCIST and EORTC classification was evaluated using standardized uptake values corrected for lean body mass (SUL). Results Using OSEMPET1/OSEMPET2 (standard scenario), responders displayed a reduction of −57.5% ± 23.4 and −63.9% ± 22.4 for SULmax and SULpeak, respectively, while progressing tumours had an increase of +63.4% ± 26.5 and +60.7% ± 19.6 for SULmax and SULpeak respectively. The use of PSF ± TOF reconstruction impacted the classification of tumour response. For example, taking the OSEMPET1/PSF ± TOFPET2 scenario reduced the apparent reduction in SUL in responding tumours (−39.7% ± 31.3 and −55.5% ± 26.3 for SULmax and SULpeak, respectively) but increased the apparent increase in SUL in progressing tumours (+130.0% ± 50.7 and +91.1% ± 39.6 for SULmax and SULpeak, respectively). Consequently, variation in reconstruction methodology (PSF ± TOFPET1/OSEMPET2 or OSEM PET1/PSF ± TOFPET2) led, respectively, to 11/61 (18.0%) and 10/61 (16.4%) PERCIST classification discordances and to 17/61 (28.9%) and 19/61 (31.1%) EORTC classification discordances. An agreement was better for these scenarios with application of the propriety filter, with kappa values of 1.00 and 0.95 compared to 0.75 and 0.77 for PERCIST and kappa values of 0.93 and 0.95 compared to 0.61 and 0.55 for EORTC, respectively. Conclusion PERCIST classification is less sensitive to reconstruction algorithm-dependent variability than EORTC classification but harmonizing SULs within the EARL program is equally effective with either.

Background: This prospective study aims to determine the impact of PET/CT on radiotherapy planning and outcomes in patients with oesophageal cancer. Methods: All patients underwent PET/CT scanning in the radiotherapy treatment position, and received treatment planned using the PET/CT dataset. GTV was defined separately on PET/CT (GTV-PET) and CT (GTV-CT) datasets. A corresponding PTV was generated for each patient. Volumetric and spatial analysis quantified the proportion of FDG-avid disease not included in CT-based volumes. Clinical data was collected to determine locoregional control and overall survival rates. Results: 13 (24.1%) of 57 accrued patients had metastatic disease detected on PET. Median follow up was 4 years. FDG-avid disease would have been excluded from GTV-CT in 29 of 38 patients (76%). In 5 patients, FDG-avid disease would have been completely excluded from the PTV-CT. GTV-CT underestimated the cranial and caudal extent of FDG-avid tumour in 14 (36%) and 10 (26%) patients. 4-Year overall survival and locoregional failure free survival were 37% and 65%. Conclusions: PET/CT altered the delineation of tumour volumes when compared to CT alone, and should be considered standard for treatment planning. Although clinical outcomes were not improved with PET/CT planning, it did allow the use of smaller radiotherapy volumes.

Serous carcinomas of the testis or para-testis are extremely rare tumors of Mullerian type. We report a case of high-grade serous papillary carcinoma of the tunica vaginalis, treated with radical orchiectomy and hemi-scrotectomy after being referred for a rapidly growing painless scrotal mass. In addition to negative testicular tumor markers, scrotal ultrasound, and conventional computerized tomography (CT) scanning, this patient's workup included a positron emission tomography (PET) scan using F-18-fluoro-deoxyglucose (FDG), demonstrating metabolically avid uptake of the disease. This patient is completing ongoing close follow up and is currently disease free at nine months post definitive treatment. Keywords: Tunica vaginalis, Serous carcinoma, FDG-PET, Testicular cancer

Advanced-stage follicular lymphoma (FL) is generally considered incurable with conventional systemic therapies, but historic series describe long-term disease-free survival in stage III disease treated with wide-field radiation therapy (WFRT), encompassing all known disease sites. We report outcomes for patients staged with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and treated with CT-planned WFRT, given as either comprehensive lymphatic irradiation (CLI) or total nodal irradiation (TNI). This analysis of a prospective cohort includes PET-staged patients given curative-intent WFRT as a component of initial therapy, or as sole treatment for stage III FL. Thirty-three PET-staged patients with stage III FL received WFRT to 24–30Gy between 1999 and 2017. Fifteen patients also received planned systemic therapy (containing rituximab in 11 cases) as part of their primary treatment. At 10 years, overall survival and freedom from progression (FFP) were 100% and 75%, respectively. None of the 11 rituximab-treated patients have relapsed. Nine relapses occurred; seven patients required treatment, and all responded to salvage therapies. A single death occurred at 16 years. The principal acute toxicity was transient hematologic; one patient had residual grade two toxicity at one year. With FDG-PET staging, most patients with stage III FL experience prolonged FFP after WFRT, especially when combined with rituximab.

BackgroundConvolutional neural networks (CNNs) have been shown to be powerful tools to assist with object detection and—like a human observer—may be trained based on a relatively small cohort of reference subjects. Rapid, accurate organ recognition in medical imaging permits a variety of new quantitative diagnostic techniques. In the case of therapy with targeted radionuclides, it may permit comprehensive radiation dose analysis in a manner that would often be prohibitively time-consuming using conventional methods.MethodsAn automated image segmentation tool was developed based on three-dimensional CNNs to detect right and left kidney contours on non-contrast CT images. Model was trained based on 89 manually contoured cases and tested on a cohort of patients receiving therapy with 177Lu-prostate-specific membrane antigen-617 for metastatic prostate cancer. Automatically generated contours were compared with those drawn by an expert and assessed for similarity based on dice score, mean distance-to-agreement, and total segmented volume. Further, the contours were applied to voxel dose maps computed from post-treatment quantitative SPECT imaging to estimate renal radiation dose from therapy.ResultsNeural network segmentation was able to identify right and left kidneys in all patients with a high degree of accuracy. The system was integrated into the hospital image database, returning contours for a selected study in approximately 90 s. Mean dice score was 0.91 and 0.86 for right and left kidneys, respectively. Poor performance was observed in three patients with cystic kidneys of which only few were included in the training data. No significant difference in mean radiation absorbed dose was observed between the manual and automated algorithms.ConclusionAutomated contouring using CNNs shows promise in providing quantitative assessment of functional SPECT and possibly PET images; in this case demonstrating comparable accuracy for radiation dose interpretation in unsealed source therapy relative to a human observer.

In the treatment of diffuse large B-cell lymphoma, a persistently positive [18F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan–BEAM (BCNU, etoposide, cytarabine, and melphalan) for high-risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone) can improve 2-year progression-free survival from a historically unfavorable rate of 40% to a rate of 65%. Patients received 4 cycles of R-CHOP-14, followed by a centrally-reviewed PET performed at day 17–20 of cycle 4 and assessed according to International Harmonisation Project criteria. Median age of the 151 evaluable patients was 57 years, with 79% stages 3–4, 54% bulk, and 54% International Prognostic Index 3–5. Among the 143 patients undergoing interim PET, 101 (71%) were PET-negative (96 of whom completed R-CHOP), 42 (29%) were PET-positive (32 of whom completed R-ICE and 90Y-ibritumomab tiuxetan-BEAM). At a median follow up of 35 months, the 2-year progression-free survival for PET-positive patients was 67%, a rate similar to that for PET-negative patients treated with R-CHOP-14 (74%, P=0.11); overall survival was 78% and 88% (P=0.11), respectively. In an exploratory analysis, progression-free and overall survival were markedly superior for PET-positive Deauville score 4 versus score 5 (P=0.0002 and P=0.001, respectively). Therefore, diffuse large B-cell lymphoma patients who are PET-positive after 4 cycles of R-CHOP-14 and who switched to R-ICE and 90Y-ibritumomab tiuxetan-BEAM achieved favorable survival outcomes similar to those for PET-negative R-CHOP-14-treated patients. Further studies are warranted to confirm these promising results. (Registered at: ACTRN12609001077257).

Alterations in hippocampal GABAA/central benzodiazepine receptor (GABAA/cBZR) expression and mossy fibre sprouting (MFS) may have aetiological significance in temporal lobe epileptogenesis. Their relationship with each other is also unknown. We utilised [3H]-flumazenil autoradiography to quantify changes in GABAA/cBZR density and affinity in all hippocampal laminae, and Timm's staining for MFS at different stages of epileptogenesis in the amygdala kindling rat model (after 24 stimulations, 48 stimulations and two weeks post-kindling). During kindling, receptor density was significantly elevated within the dentate stratum moleculare and granulosum, but decreased within the stratum radiatum of CA3 and CA2. Two weeks post-kindling, receptor density remained upregulated in the dentate stratum moleculare and was also upregulated in CA3 stratum oriens and CA1 stratum moleculare. MFS was significantly increased in the dentate stratum moleculare at two weeks post-kindling, with a strong inverse correlation between MFS and GABAA/cBZR density in this region. No changes in GABAA/cBZR binding affinity were detected for any hippocampal subregion at any time point. Our results demonstrate that changes in hippocampal GABAA/cBZR expression are lamina- and time-specific. Within the dentate gyrus, receptor density is upregulated throughout epileptogenesis, whilst within the hippocampus proper, receptor density is downregulated early in epileptogenesis but upregulated at the chronic phase. A novel association between MFS and GABAA/cBZR density has been demonstrated by this study, which could represent an important compensatory or pathological mechanism associated with epileptogenesis.