Is Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging Cost-effective in Prostate Cancer: An Analysis Informed by the proPSMA Trial.

BACKGROUND: Before integrating prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) into routine care, it is important to assess if the benefits justify the differences in resource use. OBJECTIVE: To determine the cost-effectiveness of PSMA-PET/CT when compared with conventional imaging. DESIGN, SETTING, AND PARTICIPANTS: A cost-effectiveness analysis was developed using data from the proPSMA study. proPSMA included patients with high-risk prostate cancer assigned to conventional imaging or 68Ga-PSMA-11 PET/CT with planned health economics data collected. The cost-effectiveness analysis was conducted from an Australian societal perspective. INTERVENTION: 68Ga-PSMA-11 PET/CT compared with conventional imaging (CT and bone scan). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome from proPSMA was diagnostic accuracy (nodal and distant metastases). This informed a decision tree analysis of the cost per accurate diagnosis. RESULTS AND LIMITATIONS: The estimated cost per scan for PSMA PET/CT was AUD$1203, which was less than the conventional imaging cost at AUD$1412. PSMA PET/CT was thus dominant, having both better accuracy and a lower cost. This resulted in a cost of AUD$959 saved per additional accurate detection of nodal disease, and AUD$1412 saved for additional accurate detection of distant metastases. The results were most sensitive to variations in the number of men scanned for each 68Ga-PSMA-11 production run. Subsequent research is required to assess the long-term costs and benefits of PSMA PET/CT-directed care. CONCLUSIONS: PSMA PET/CT has lower direct comparative costs and greater accuracy compared to conventional imaging for initial staging of men with high-risk prostate cancer. This provides a compelling case for adopting PSMA PET/CT into clinical practice. PATIENT SUMMARY: The proPSMA study demonstrated that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) better detects disease that has spread beyond the prostate compared with conventional imaging. Our analysis shows that PSMA PET/CT is also less costly than conventional imaging for the detection of disease spread. This research was presented at the European Association of Nuclear Medicine Scientific Meeting in October 2020.

Comparison between gallium-68 citrate positron emission tomography-computed tomography and gallium-67 citrate scintigraphy for infection imaging.

BACKGROUND: Preliminary studies have reported promising results for the utility of gallium-68 (Ga-68) citrate positron emission tomography-computed tomography (PET-CT) for infection imaging. This technique offers reduced radiation dose to patients, shorter time between injection and imaging and reduced time for image acquisition compared to the 'gold standard' nuclear imaging technique: gallium-67 (Ga-67) citrate scintigraphy. AIMS: To compare the two imaging modalities to ascertain whether Ga-68 citrate PET-CT is of equivalent diagnostic efficacy for bone and joint infection or pyrexia of unknown origin (PUO) and to assess image quality and reporter confidence. METHODS: Patients with PUO and suspected bone or joint infection underwent Ga-67 citrate scintigraphy and Ga-68 citrate PET-CT. Participants were followed up for 3 months to record subsequent treatment, investigations and outcome. RESULTS: 60 patients were recruited to this multicentre prospective study: 32 for bone and joint infection, 28 for PUO. The results show a sensitivity of 81% for Ga-67 citrate scintigraphy and 69% for Ga-68 citrate PET-CT, a specificity of 79% for Ga-67 citrate and 67% for Ga-68 citrate and were concordant for 76% of the participants. The reporting physician confidence was significantly lower for Ga-68 citrate (P < 0.05), frequently due to prominent physiologic blood pool activity adjacent to the site of infection. CONCLUSION: The sensitivity and specificity of Ga-68 citrate PET-CT were found to be consistently lower than Ga-67 citrate scintigraphy. Additionally, due to the insufficient level of confidence of the reporting physicians for the Ga-68 citrate PET-CT, this modality could not currently be recommended to replace Ga-67 citrate scintigraphy for routine clinical use.

68 Ga-somatostatin analogue PET-CT: Analysis of costs and benefits in a public hospital setting.

INTRODUCTION: Between 2009 and 2012, 68 Ga-somatostatin analogue PET-CT progressively replaced 111 In-octreotide scintigraphy for imaging neuroendocrine tumours in WA public hospitals due to published literature demonstrating improved diagnostic accuracy and increased availability. Despite significantly improved sensitivity and specificity, 68 Ga-somatostatin analogue PET is currently unfunded in Australia. This study sought to undertake cost analysis of the two modalities in a public hospital setting and to compare them with regard to patient factors such as imaging time and radiation dose. METHODS: This analysis was based on retrospective clinical data from 95 111 In-octreotide scintigraphies performed in 2007 and 2008 at Sir Charles Gairdner (SCGH) and Royal Perth (RPH) hospitals and 219 68 Ga-somatostatin analogue PET-CT studies performed in 2013 at SCGH. Whole body effective radiation dose was derived from the radiopharmaceutical and low-dose CT scan. The cost analysis included radiopharmaceutical and imaging costs. RESULTS: The median imaging time for an 111 In-octreotide scintigraphy was 152 min at SCGH, 100 min at RPH and 20 min for a 68 Ga-somatostatin analogue PET-CT scan. The mean effective radiation dose for 111 In-octreotide scintigraphy was 18.1 mSv at SCGH and 13.8 mSv at RPH. The effective dose for 68 Ga-somatostatin analogue PET-CT was 8.7-10.8 mSv. The average cost of 68 Ga-somatostatin analogue PET-CT was four times less than 111 In-octreotide scintigraphy. CONCLUSION: 68 Ga-somatostatin analogue PET-CT is not only more accurate than 111 In-octreotide scintigraphy, this study has also shown that it is significantly less expensive, delivers a lower radiation dose to patients and requires less imaging time for patients and staff. 68 Ga-somatostatin PET-CT provides an important combination of both reduced cost and improved clinical care for patients.

A pilot study of the utility of choline PET-CT in prostate cancer biochemical relapse following radical prostatectomy.

INTRODUCTION: To evaluate the detection rate of positive choline PET-CT and its clinical role in assisting with management decisions and the correlation between positive choline PET-CT and clinical/pathological parameters in prostate cancer patients with biochemical relapse following radical prostatectomy. METHODS: This was a longitudinal observational pilot study of 34 patients who received choline PET-CT scans with biochemical relapse after radical prostatectomy. Variables including peak PSA, PSA doubling time (DT), Gleason score, age, initial PSA at diagnosis, use of ADT prior to PET and initial clinical staging were statistically analysed to assess for independent predictive factors for positive PET findings. RESULTS: Choline PET-CT was positive in 38.2% of patients (13/34). The only statistically significant predictor for positive PET-CT was the use of ADT prior to PET-CT, with OR 18.7 (95% CI, 2.87-122.45), P < 0.01. Mean peak PSA for patients with positive PET-CT was 5.5 ± 4.8 ng/mL. Patients with positive PET-CT had a mean PSA DT of 5.1 ± 3.8 months and mean total Gleason of 7.6 ± 0.8. Although these variables were not statistically significant, they showed a tendency towards significance. At Receiver Operator Characteristics (ROC) analysis, a peak PSA value of 1.65 ng/mL and PSA DT of 4.4 months were determined to be the optimal cut-off values predicting positive PET-CT. CONCLUSION: Choline PET-CT has its potential as a diagnostic modality enabling the detection of occult prostate cancer recurrence and to differentiate localised disease from systemic disease thus guiding management. Use of ADT prior to PET-CT is a significant predictor of positive PET-CT. Patients with a short PSA DT, high-peak PSA and high Gleason score should also be considered for choline PET-CT.

Characterization of hypoxia in malignant pleural mesothelioma with FMISO PET-CT.

OBJECTIVES: Malignant pleural mesothelioma (MPM) is a chemotherapy resistant tumor with a poor prognosis. Hypoxia is increasingly recognized as an important factor in tumor aggressiveness and cellular resistance to chemotherapy and radiation treatment. This prospective pilot study was performed with [F-18] fluoromisonidazole (FMISO) PET-CT to characterize hypoxia in patients with MPM. MATERIALS AND METHODS: Twenty prospectively recruited patients with histologically or cytologically confirmed MPM not currently receiving systemic or local treatment underwent both FMISO and fluorodeoxyglucose (FDG) PET-CT scans within 2 weeks. FMISO and FDG PET-CT scans were independently analyzed visually and semi-quantitatively using SUVmax and tumor to background ratio (TBR) in order to assess tumor hypoxia and metabolic activity. Lesion by lesion analysis was performed in sites of measurable pleural masses. RESULTS: Visual analysis demonstrated tumor FMISO activity in 17 of 20 patients, and tumor FDG activity in 19 of 20 patients. Focal areas of bulky tumor were most likely to demonstrate hypoxia. In 19 patients suitable for semi-quantitative analysis the median FDG SUVmax was 6.4 (range 1.9-19.1), median FMISO SUVmax was 2.5 (range 1.4-3.7) and median FMISO TBR was 1.8 (1.1-2.5). There was a positive correlation between intensity of metabolic activity and hypoxia (r=0.72, p=0.001). Lesion by lesion analysis demonstrated a positive correlation between tumor thickness and FMISO activity (r=0.77, p<0.001). CONCLUSION: This pilot study confirms that MPM is a tumor with significant areas of hypoxia, particularly in dominant tumor masses. The relationship of tumor hypoxia to effectiveness of chemotherapy and/or radiation therapy warrants prospective assessment.

Imaging of hypoxia with 18F-FAZA PET in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy.

INTRODUCTION: For many cancers, tumour hypoxia is an adverse prognostic factor, and increases chemoradiation resistance; its importance in non-small cell lung cancer (NSCLC) is unproven. This study evaluated tumoural hypoxia using fluoroazomycin arabinoside ((18) F-FAZA) positron emission tomography (PET) scans among patients with locoregionally advanced NSCLC treated with definitive chemoradiation. METHODS: Patients with stage IIIA-IIIB NSCLC underwent (18) F-FAZA PET scans and (18) F-2-deoxyglucose (FDG)-PET scans within 4 weeks of commencing and 8 weeks following conventionally-fractionated concurrent platinum-based chemoradiation (60 Gy). Intra-lesional hypoxic volumes of the primary and nodal masses were compared with FDG-PET metabolic volumes. Baseline tumoural hypoxia was correlated with disease free survival (DFS). RESULTS: Seventeen patients underwent pre-treatment (18) F-FAZA PET and FDG-PET scans. Intra-lesional hypoxia was identified on 11 scans (65%). Baseline lesional hypoxic volumes were consistently smaller than FDG-PET volumes (P = 0.012). There was no statistical difference between the mean FDG-PET volumes in patients with or without baseline hypoxia (P = 0.38). Eight patients with baseline hypoxia had post treatment (18) F-FAZA scans and 6 of these (75%) had resolution of imageable hypoxia following chemoradiation. The DFS was not significantly different between the hypoxic or non-hypoxic groups (median 0.8 years and 1.3 years respectively, P = 0.42). CONCLUSIONS: Intra-lesional hypoxia, as detected by (18) F-FAZA PET, was present in 65% of patients with locally-advanced NSCLC and resolved in the majority of patients following chemoradiation. Larger studies are required to evaluate the prognostic significance of the presence and resolution of hypoxia assessed by PET in NSCLC.

Changing trends in venous thromboembolism-related imaging in Western Australian teaching hospitals, 2002-2010.

OBJECTIVE: To determine trends in referral for venous thromboembolism (VTE) imaging in Western Australian teaching hospitals. DESIGN AND SETTING: Retrospective audit of the WA picture archiving and communication system, PathWest Laboratory Medicine records, the hospital morbidity database at the four adult teaching hospitals in Perth, WA, and the WA death registry. PATIENTS: All patients referred for VTE-related imaging, and all hospital separations for pulmonary embolism (PE) during 2002-2010. MAIN OUTCOME MEASURES: Number of referrals for computed tomography pulmonary angiography (CTPA), ventilation-perfusion lung scintigraphy, leg ultrasound and plasma D-dimer assay; hospital separations for PE and deaths from PE. RESULTS: Referrals for VTE-related imaging increased by 34%, while PE-related imaging increased by 65% during the study period, owing entirely to referrals for CTPA, which increased by more than 500%. The number of hospital separations for PE increased by 45% over the same period and the prevalence of PE among referred patients fell from 22.1% in 2002 to 19.5% in 2010. There was no fall in the death rate from PE in WA during the study period (P = 0.19). The number of D-dimer tests performed in the same hospitals increased by 42% over the study period. CONCLUSIONS: The increased number of referrals for PE-related imaging resulted in more diagnoses but no reduction in deaths from PE in WA. Widespread D-dimer testing did not reduce referrals for imaging and is likely to have resulted in increased referrals. Increased imaging leads to overdiagnosis of clinically insignificant PE, and alternative strategies are required to reduce PE death rates.

Detection of hypoxia with 18F-fluoromisonidazole (18F-FMISO) PET/CT in suspected or proven pancreatic cancer.

PURPOSE OF THE REPORT: Pancreatic carcinoma is known to demonstrate molecular features of hypoxia. The aim of this prospective pilot study is to analyze the hypoxia agent fluoromisonidazole (FMISO) using PET/CT in pancreatic carcinoma and to compare FMISO activity with glucose metabolism reflected by FDG. PATIENTS AND METHODS: Ten patients with pancreatic carcinoma underwent FMISO and FDG PET scans. FMISO and FDG PET/CT scans were analyzed by 2 PET physicians. Regions of interest drawn on the FDG images were transposed to the FMISO images after study coregistration. The FDG SUVmax was used to quantify metabolic activity and FMISO SUVmax and tumor-to-background (muscle) ratio to quantify hypoxia. RESULTS: Seven patients were diagnosed with pancreatic adenocarcinoma. The remaining patients had a neuroendocrine tumor, poorly differentiated/sarcomatoid carcinoma, and mucinous neoplasm. Visual analysis demonstrated increased FMISO activity in 2 pancreatic adenocarcinomas. All patients, however, had increased FDG activity at the tumor site. Mean FDG SUVmax was 6 (range: 3.8 to 9.5) compared to 2.3 for FMISO (range: 1 to 3.4). The 2 positive studies on visual analysis of FMISO did not correspond to the largest tumors, the studies with the highest FMISO or FDG SUVmax. There was no significant correlation between FMISO and FDG SUVmax values. CONCLUSIONS: The hypoxia imaging agent, FMISO, demonstrates minimal activity in pancreatic tumors. If FMISO PET/CT is to be included in clinical trial protocols of hypoxia in pancreatic cancer, it would require correlation with other imaging modalities to localize the tumor and allow semiquantitative analysis.

Novel molecular imaging in lung and pleural diseases.

Molecular imaging provides an opportunity to study biological processes in vivo. Specific molecular 'probes' are labelled with radioactive tracers, and imaging is carried out using either PET or gamma-cameras. The imaging is quantitative, and therefore the activity of a specific biological process (e.g. metabolism or proliferation) can be numerically assessed, which may be important for prognosis or therapy monitoring. The use of molecular imaging may lead to the development of a 'molecular profile' of a disease, therefore facilitating individualization of therapy and rational treatment approaches. This review article summarizes the most commonly used molecular imaging agents and their role in lung and pleural diseases. This is a rapidly developing field as new targets and imaging probes are being developed and as their clinical roles are being established.