Publications by authors named "Roslyn J Francis"

34 Publications

The effect of vitamin K1 on arterial calcification activity in subjects with diabetes mellitus: a post hoc analysis of a double-blind, randomized, placebo-controlled trial.

Am J Clin Nutr 2021 Oct 12. Epub 2021 Oct 12.

Division of Internal Medicine, Medical School, University of Western Australia, Perth, Western Australia, Australia.

Background: Coronary and aortic artery calcifications are generally slow to develop, and their burden predicts cardiovascular disease events. In patients with diabetes mellitus, arterial calcification is accelerated and calcification activity can be detected using 18F-sodium fluoride positron emission tomography (18F-NaF PET).

Objectives: We aimed to determine whether vitamin K1 supplementation inhibits arterial calcification activity in individuals with diabetes mellitus.

Methods: This was a post hoc analysis of the ViKCoVaC (effect of Vitamin-K1 and Colchicine on Vascular Calcification activity in subjects with Diabetes Mellitus) double-blind randomized controlled trial conducted in Perth, Western Australia. Individuals with diabetes mellitus and established coronary calcification (coronary calcium score > 10), but without clinical coronary artery disease, underwent baseline 18F-NaF PET imaging, followed by oral vitamin K1 supplementation (10 mg/d) or placebo for 3 mo, after which 18F-NaF PET imaging was repeated. We tested whether individuals randomly assigned to vitamin K1 supplementation had reduced development of new 18F-NaF PET positive lesions within the coronary arteries and aorta.

Results: In total, 149 individuals completed baseline and follow-up imaging studies. Vitamin K1 supplementation independently decreased the odds of developing new 18F-NaF PET positive lesions in the coronary arteries (OR: 0.35; 95% CI: 0.16, 0.78; P = 0.010), aorta (OR: 0.27; 95% CI: 0.08, 0.94; P = 0.040), and in both aortic and coronary arteries (OR: 0.28; 95% CI: 0.13, 0.63; P = 0.002).

Conclusions: In individuals with diabetes mellitus, supplementation with 10 mg vitamin K1/d may prevent the development of newly calcifying lesions within the aorta and the coronary arteries as detected using 18F-NaF PET. Further long-term studies are needed to test this hypothesis.This trial was registered at anzctr.org.au as ACTRN12616000024448.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqab306DOI Listing
October 2021

Repeatability of image features extracted from FET PET in application to post-surgical glioblastoma assessment.

Phys Eng Sci Med 2021 Aug 26. Epub 2021 Aug 26.

School of Physics, Mathematics and Computing, The University of Western Australia, 35 Stirling Highway, Mailbag M013, Crawley, WA, 6009, Australia.

Positron emission tomography (PET) imaging using the amino acid tracer O-[2-(F)fluoroethyl]-L-tyrosine (FET) has gained increased popularity within the past decade in the management of glioblastoma (GBM). Radiomics features extracted from FET PET images may be sensitive to variations when imaging at multiple time points. It is therefore necessary to assess feature robustness to test-retest imaging. Eight patients with histologically confirmed GBM that had undergone post-surgical test-retest FET PET imaging were recruited. In total, 1578 radiomic features were extracted from biological tumour volumes (BTVs) delineated using a semi-automatic contouring method. Feature repeatability was assessed using the intraclass correlation coefficient (ICC). The effect of both bin width and filter choice on feature repeatability was also investigated. 59/106 (55.7%) features from the original image and 843/1472 (57.3%) features from filtered images had an ICC ≥ 0.85. Shape and first order features were most stable. Choice of bin width showed minimal impact on features defined as stable. The Laplacian of Gaussian (LoG, σ = 5 mm) and Wavelet filters (HLL and LHL) significantly improved feature repeatability (p ≪ 0.0001, p = 0.003, p = 0.002, respectively). Correlation of textural features with tumour volume was reported for transparency. FET PET radiomic features extracted from post-surgical images of GBM patients that are robust to test-retest imaging were identified. An investigation with a larger dataset is warranted to validate the findings in this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13246-021-01049-4DOI Listing
August 2021

Targeted radioactive therapy for prostate cancer - Authors' reply.

Lancet 2021 08;398(10299):488

St Vincent's Hospital, Sydney, NSW, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(21)01060-6DOI Listing
August 2021

The effect of Vitamin-K and Colchicine on Vascular Calcification Activity in subjects with Diabetes Mellitus (ViKCoVaC): A double-blind 2x2 factorial randomized controlled trial.

J Nucl Cardiol 2021 Apr 6. Epub 2021 Apr 6.

School of Medicine, Faculty of Health and Biomedical Science, University of Western Australia, Royal Perth Hospital Campus, M570, Po Box X2213, Perth, Western Australia, Australia.

Background: There is currently no treatment for attenuating progression of arterial calcification. F-sodium fluoride positron emission tomography (F-NaF PET) locates regions of calcification activity. We tested whether vitamin-K or colchicine affected arterial calcification activity.

Methods: 154 patients with diabetes mellitus and coronary calcification, as detected using computed tomography (CT), were randomized to one of four treatment groups (placebo/placebo, vitamin-K [10 mg/day]/placebo, colchicine [0.5 mg/day]/placebo, vitamin-K [10 mg/day]/ colchicine [0.5 mg/day]) in a double-blind, placebo-controlled 2x2 factorial trial of three months duration. Change in coronary calcification activity was estimated as a change in coronary maximum tissue-to-background ratio (TBRmax) on F-NaF PET.

Results: 149 subjects completed follow-up (vitamin-K: placebo = 73:76 and colchicine: placebo = 73:76). Neither vitamin-K nor colchicine had a statistically significant effect on the coronary TBRmax compared with placebo (mean difference for treatment groups 0·00 ± 0·16 and 0·01 ± 0·17, respectively, p > 0.05). There were no serious adverse effects reported with colchicine or vitamin-K.

Conclusions: In patients with type 2 diabetes, neither vitamin-K nor colchicine significantly decreases coronary calcification activity, as estimated by F-NaF PET, over a period of 3 months.

Clinical Trial Registration: ACTRN12616000024448.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12350-021-02589-8DOI Listing
April 2021

UpFrontPSMA: a randomized phase 2 study of sequential Lu-PSMA-617 and docetaxel vs docetaxel in metastatic hormone-naïve prostate cancer (clinical trial protocol).

BJU Int 2021 Sep 21;128(3):331-342. Epub 2021 Apr 21.

Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Objective: To assess the activity and safety of sequential lutetium-177 ( Lu)-PSMA-617 and docetaxel vs docetaxel on a background of androgen deprivation therapy (ADT) in men with de novo metastatic hormone-naïve prostate cancer (mHNPC).

Patients And Methods: UpFrontPSMA (NCT04343885) is an open-label, randomized, multicentre, phase 2 trial, recruiting 140 patients at 12 Australian centres. Key eligibility criteria include: prostate cancer with a histological diagnosis within 12 weeks of screening commencement; prostate-specific antigen (PSA) >10 ng/mL at diagnosis; ≤4 weeks on ADT; evidence of metastatic disease on computed tomography (CT) and/or bone scan; high-volume prostate-specific membrane antigen (PSMA)-avid disease with a maximum standardized uptake value >15; and absence of extensive discordant fluorodeoxyglcuose (FDG)-positive, PSMA-negative disease. Ga-PSMA-11 and F-FDG positron-emission tomography (PET)/CT undergo central review to determine eligibility. Patients are randomized 1:1 to experimental treatment, Arm A ( Lu-PSMA-617 7.5GBq q6w × 2 cycles followed by docetaxel 75 mg/m q3w × 6 cycles), or standard-of-care treatment, Arm B (docetaxel 75 mg/m q3w × 6 cycles). All patients receive continuous ADT. Patients are stratified based on disease volume on conventional imaging and duration of ADT at time of registration. The primary endpoint is the proportion of patients with undetectable PSA (≤0.2 ng/L) at 12 months after study treatment commencement. Secondary endpoints include safety, time to castration resistance, overall survival, PSA and radiographic progression-free survival, objective tumour response rate, early PSMA PET response, health-related quality of life, and frequency and severity of adverse events. Enrolment commenced in April 2020.

Results And Conclusions: The results of this trial will generate data on the activity and safety of Lu-PSMA-617 in men with de novo mHNPC in a randomized phase 2 design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bju.15384DOI Listing
September 2021

[Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial.

Lancet 2021 02 11;397(10276):797-804. Epub 2021 Feb 11.

Prostate Cancer Theranostics and Imaging Centre of Excellence, Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Background: Lutetium-177 [Lu]Lu-PSMA-617 is a radiolabelled small molecule that delivers β 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 [Lu]Lu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer.

Methods: 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 [Ga]Ga-PSMA-11 and 2-flourine-18[F]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 [Lu]Lu-PSMA-617 (6·0-8·5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m 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.

Findings: 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 [Lu]Lu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the [Lu]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 received; difference 23% [9-37]; p=0·0016). Grade 3-4 adverse events occurred in 32 (33%) of 98 men in the [Lu]Lu-PSMA-617 group versus 45 (53%) of 85 men in the cabazitaxel group. No deaths were attributed to [Lu]Lu-PSMA-617.

Interpretation: [Lu]Lu-PSMA-617 compared with cabazitaxel in men with metastatic castration-resistant prostate cancer led to a higher PSA response and fewer grade 3 or 4 adverse events. [Lu]Lu-PSMA-617 is a new effective class of therapy and a potential alternative to cabazitaxel.

Funding: Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, The Distinguished Gentleman's Ride, It's a Bloke Thing, and CAN4CANCER.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(21)00237-3DOI Listing
February 2021

The Australasian Radiopharmaceutical Trials Network: Clinical Trials, Evidence, and Opportunity.

J Nucl Med 2021 06 31;62(6):755-756. Epub 2020 Dec 31.

Department of Molecular Imaging and Therapy at Austin Health, Olivia Newton-John Cancer Research Institute and School of Cancer Medicine at La Trobe University, and Faculty of Medicine at University of Melbourne, Melbourne, Australia

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2967/jnumed.120.258152DOI Listing
June 2021

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

Eur Urol 2021 03 16;79(3):413-418. Epub 2020 Dec 16.

Centre for Health Economics Research and Evaluation, University of Technology Sydney, Sydney, Australia. Electronic address:

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 Ga-PSMA-11 PET/CT with planned health economics data collected. The cost-effectiveness analysis was conducted from an Australian societal perspective.

Intervention: Ga-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 Ga-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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2020.11.043DOI Listing
March 2021

F-Sodium Fluoride Positron Emission Tomography Activity Predicts the Development of New Coronary Artery Calcifications.

Arterioscler Thromb Vasc Biol 2021 01 3;41(1):534-541. Epub 2020 Dec 3.

School of Medicine (J.W.B., R.J.F., S.C.L., A.R., J.R.L., G.F.W., C.J.S.), University of Western Australia, Perth.

Objective: The coronary calcium score (CCS) predicts cardiovascular disease risk in individuals with diabetes, and rate of progression of CCS is an additional and incremental marker of risk. F-sodium fluoride positron emission tomography (F-NaF PET) detects early and active calcifications within the vasculature. We aimed to ascertain the relationship between F-NaF PET activity and CCS progression in patients with diabetes. Approach and Results: We identified individuals between 50 and 80 years with diabetes and no history of clinical coronary artery disease. Those with a CCS ≥10 were invited to undergo F-NaF PET scanning and then repeat CCS >2 years later. F-NaF PET and CCS analysis were performed on a per-coronary and a per-patient level. We compared the proportion of CCS progressors in F-NaF PET-positive versus F-NaF PET-negative coronary arteries. Forty-one participants with 163 coronary arteries underwent follow-up CCS 2.8±0.5 years later. F-NaF PET-positive coronary arteries (n=52) were more likely to be CCS progressors, compared with negative coronary arteries (n=111; 86.5% versus 52.3%, <0.001). Adjusting for baseline CCS, F-NaF PET-positive disease was an independent predictor of subsequent CCS progression (odds ratio, 2.92 [95% CI, 1.32-6.45], =0.008). All subjects (100%, 15/15) with ≥2 F-NaF-positive coronary arteries progressed in CCS.

Conclusions: In subjects with diabetes, F-NaF PET positivity at baseline, independently predicted the progression of calcifications within the coronary arteries 2.8 years later. These findings suggest F-NaF PET may be a promising technique for earlier identification of patients at higher risk of cardiovascular events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/ATVBAHA.120.315364DOI Listing
January 2021

Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study.

Lancet 2020 04 22;395(10231):1208-1216. Epub 2020 Mar 22.

Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.

Background: Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management.

Methods: In this multicentre, two-arm, randomised study, we recruited men with biopsy-proven prostate cancer and high-risk features at ten hospitals in Australia. Patients were randomly assigned to conventional imaging with CT and bone scanning or gallium-68 PSMA-11 PET-CT. First-line imaging was done within 21 days following randomisation. Patients crossed over unless three or more distant metastases were identified. The primary outcome was accuracy of first-line imaging for identifying either pelvic nodal or distant-metastatic disease defined by the receiver-operating curve using a predefined reference-standard including histopathology, imaging, and biochemistry at 6-month follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry, ANZCTR12617000005358.

Findings: From March 22, 2017 to Nov 02, 2018, 339 men were assessed for eligibility and 302 men were randomly assigned. 152 (50%) men were randomly assigned to conventional imaging and 150 (50%) to PSMA PET-CT. Of 295 (98%) men with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease. PSMA PET-CT had a 27% (95% CI 23-31) greater accuracy than that of conventional imaging (92% [88-95] vs 65% [60-69]; p<0·0001). We found a lower sensitivity (38% [24-52] vs 85% [74-96]) and specificity (91% [85-97] vs 98% [95-100]) for conventional imaging compared with PSMA PET-CT. Subgroup analyses also showed the superiority of PSMA PET-CT (area under the curve of the receiver operating characteristic curve 91% vs 59% [32% absolute difference; 28-35] for patients with pelvic nodal metastases, and 95% vs 74% [22% absolute difference; 18-26] for patients with distant metastases). First-line conventional imaging conferred management change less frequently (23 [15%] men [10-22] vs 41 [28%] men [21-36]; p=0·008) and had more equivocal findings (23% [17-31] vs 7% [4-13]) than PSMA PET-CT did. Radiation exposure was 10·9 mSv (95% CI 9·8-12·0) higher for conventional imaging than for PSMA PET-CT (19·2 mSv vs 8·4 mSv; p<0·001). We found high reporter agreement for PSMA PET-CT (κ=0·87 for nodal and κ=0·88 for distant metastases). In patients who underwent second-line image, management change occurred in seven (5%) of 136 patients following conventional imaging, and in 39 (27%) of 146 following PSMA PET-CT.

Interpretation: PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning.

Funding: Movember and Prostate Cancer Foundation of Australia. VIDEO ABSTRACT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(20)30314-7DOI Listing
April 2020

TheraP: a randomized phase 2 trial of Lu-PSMA-617 theranostic treatment vs cabazitaxel in progressive metastatic castration-resistant prostate cancer (Clinical Trial Protocol ANZUP 1603).

BJU Int 2019 11 22;124 Suppl 1:5-13. Epub 2019 Oct 22.

Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, NSW, Australia.

Objective: To assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with Lu-PSMA-617, a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), in men with metastatic castration-resistant prostate cancer (mCRPC) who have received prior docetaxel treatment.

Patients And Methods: The TheraP trial (ANZUP 1603) is an open-label, randomized, stratified, two-arm multicentre phase 2 trial comparing the activity and safety of cabazitaxel chemotherapy vs Lu-PSMA-617 therapy in the treatment of men with mCRPC. Key eligibility criteria include prior docetaxel chemotherapy, rising prostate-specific antigen (PSA) level, sufficient PSMA avidity, as defined by centrally reviewed Ga-PSMA-11 and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) with no discordant FDG-avid PSMA-negative sites of disease. Patients in the control group receive standard treatment with cabazitaxel (20 mg/m ) i.v. every 3 weeks with prednisolone 10 mg daily orally, for a maximum of 10 cycles. Patients in the experimental group receive Lu-PSMA-617 (8.5 GBq decreasing by 0.5 GBq per cycle) i.v. every 6 weeks, for up to a maximum of six cycles. In the event of an exceptional response as defined on centrally reviewed post-therapy single-photon emission CT imaging, treatment will be suspended but can recommence on progression. The trial aims to include 200 patients who will be centrally randomized to one of the two treatment groups, in a 1:1 ratio. The primary endpoint is PSA response. Secondary endpoints are overall survival, progression-free survival (PFS), radiographic PFS, PSA PFS, objective tumour response, pain response, pain PFS, health-related quality of life, and frequency and severity of adverse events. The treatment and outcomes of patients excluded on the basis of low PSMA avidity or discordant FDG-avid disease on screening Ga-PSMA-11 and Fluorine-18 ( F)-FDG-PET/CT scan will also be assessed. Enrolment in the study commenced on 29 January 2018.

Results And Conclusions: Lu-PSMA-617 offers a potential additional life-prolonging treatment option for men with mCRPC. The results of this trial will determine, for the first time in a randomized design, the activity and safety of Lu-PSMA-617, as compared with cabazitaxel chemotherapy in men with progressive mCRPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bju.14876DOI Listing
November 2019

Radiologic Considerations and Standardization of Malignant Pleural Mesothelioma Imaging Within Clinical Trials: Consensus Statement from the NCI Thoracic Malignancy Steering Committee - International Association for the Study of Lung Cancer - Mesothelioma Applied Research Foundation Clinical Trials Planning Meeting.

J Thorac Oncol 2019 10 27;14(10):1718-1731. Epub 2019 Aug 27.

Department of Medicine, Sir Charles Gairdner Hospital and Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia.

Detailed guidelines pertaining to radiological assessment of malignant pleural mesothelioma are currently lacking due to the rarity of the disease, complex morphology, propensity to invade multiple planes simultaneously, and lack of specific recommendations within the radiology community about assessment, reporting, and follow-up. In March 2017, a multidisciplinary meeting of mesothelioma experts was co-sponsored by the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and the Mesothelioma Applied Research Foundation. One of the outcomes of this conference was the foundation of detailed, multidisciplinary consensus imaging and management guidelines. Here, we present the recommendations for radiologic assessment of malignant pleural mesothelioma in the setting of clinical trial enrollment. We discuss optimization of imaging parameters across modalities, standardized reporting, and response assessment within clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2019.08.012DOI Listing
October 2019

Baseline and Post-treatment 18F-Fluorocholine PET/CT Predicts Outcomes in Hepatocellular Carcinoma Following Locoregional Therapy.

Dig Dis Sci 2020 02 22;65(2):647-657. Epub 2019 Aug 22.

Department of Hepatology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Perth, 6009, WA, Australia.

Background And Aims: F-fluorocholine positron emission tomography/computed tomography (F-FCH PET/CT) is an emerging functional imaging technique in the diagnosis and management of hepatocellular carcinoma (HCC). The aim of this study was to assess the ability of a pre- and post-treatment F-FCH PET/CT to predict prognosis and treatment response in early-stage HCC.

Methods: Patients with early- or intermediate-stage HCC planned for locoregional therapy were prospectively enrolled. Baseline demographic and tumor information was collected and baseline and post-treatment F-FCH PET/CT performed. Maximum standardized uptake values (SUVmax) were determined for each HCC lesion, and the difference between baseline and post-treatment SUVmax values were compared with progression-free survival outcomes.

Results: A total of 29 patients with 39 confirmed HCC lesions were enrolled from a single clinical center. Patients were mostly men (89.7%) with hepatitis C or alcohol-related cirrhosis (65.5%) and early-stage disease (89.7%). Per-patient and per-lesion sensitivity of F-FCH PET/CT was 72.4% and 59.0%, respectively. A baseline SUVmax < 13 was associated with a superior median progression-free survival compared with an SUVmax of > 13 (17.7 vs. 5.1 months; p = 0.006). A > 45% decrease in SUVmax between baseline and post-treatment F-FCH PET/CT ("responders") was associated with a superior mean progression-free survival than a percentage decrease of < 45% ("non-responders," 36.1 vs. 11.6 months; p = 0.034).

Conclusions: Baseline and post-treatment F-FCH PET/CT predicts outcomes in early-stage HCC undergoing locoregional therapy. This technique may identify patients with an objective response post-locoregional therapy who would benefit from further therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-019-05781-6DOI Listing
February 2020

Imaging in pleural mesothelioma: A review of the 14th International Conference of the International Mesothelioma Interest Group.

Lung Cancer 2019 04 28;130:108-114. Epub 2018 Nov 28.

Department of Radiology, The Ottawa Hospital, Ottawa, Ontario, Canada.

Mesothelioma patients rely on the information their clinical team obtains from medical imaging. Whether x-ray-based computed tomography (CT) or magnetic resonance imaging (MRI) based on local magnetic fields within a patient's tissues, different modalities generate images with uniquely different appearances and information content due to the physical differences of the image-acquisition process. Researchers are developing sophisticated ways to extract a greater amount of the information contained within these images. This paper summarizes the imaging-based research presented orally at the 2018 International Conference of the International Mesothelioma Interest Group (iMig) in Ottawa, Ontario, Canada, held May 2-5, 2018. Presented topics included advances in the imaging of preclinical mesothelioma models to inform clinical therapeutic strategies, optimization of the time delay between contrast administration and image acquisition for maximized enhancement of mesothelioma tumor on CT, an investigation of image-based criteria for clinical tumor and nodal staging of mesothelioma by contrast-enhanced CT, an investigation of methods for the extraction of mesothelioma tumor volume from MRI and the association of volume with patient survival, the use of deep learning for mesothelioma tumor segmentation in CT, and an evaluation of CT-based radiomics for the prognosis of mesothelioma patient survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2018.11.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548565PMC
April 2019

Coronary artery 18F-NaF PET analysis with the use of an elastic motion correction software.

J Nucl Cardiol 2020 06 25;27(3):952-961. Epub 2019 Jan 25.

Cardiology Department, Royal Perth Hospital, 197 Wellington St, Perth, WA, 6000, Australia.

Introduction: 18F-Sodium Fluoride Positron Emission Tomography (18F-NaF PET) is a novel molecular imaging modality with promise for use as a risk stratification tool in cardiovascular disease. There are limitations in the analysis of small and rapidly moving coronary arteries using traditional PET technology. We aimed to validate the use of a motion correction algorithm (eMoco) on coronary 18F-NaF PET outcome parameters.

Methods: Patients admitted with an acute coronary syndrome underwent 18F-NaF PET and computed tomography coronary angiography. 18F-NaF PET data were analyzed using a diastolic reconstruction, an ungated reconstruction and the eMoco reconstruction.

Results: Twenty patients underwent 18F-NaF PET imaging and 17 patients had at least one positive lesion that could be used to compare PET reconstruction datasets. eMoco improved noise (the coefficient of variation of the blood pool radiotracer activity) compared to the diastolic dataset (0.09 [0.07 to 0.12] vs 0.14[0.11 to 0.17], p < .001) and marginally improved coronary lesion maximum tissue-to-background ratios compared to the ungated dataset (1.33 [1.05 to 1.48]vs 1.29 [1.04 to 1.40], p = .011).

Conclusion: In this pilot dataset, the eMoco reconstruction algorithm for motion correction appears to have potential in improving coronary analysis of 18F-NaF PET by reducing noise and increasing maximum counts. Further testing in a larger patient dataset is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12350-018-01587-7DOI Listing
June 2020

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

Intern Med J 2019 08;49(8):1016-1022

Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imj.14231DOI Listing
August 2019

In search of the vulnerable patient or the vulnerable plaque: F-sodium fluoride positron emission tomography for cardiovascular risk stratification.

J Nucl Cardiol 2018 10 10;25(5):1774-1783. Epub 2018 Jul 10.

Department of Cardiology, Royal Perth Hospital, 197 Wellington St, Perth, WA, 6000, Australia.

Cardiovascular disease (CVD) remains a leading cause of death. Preventative therapies that reduce CVD are most effective when targeted to individuals at high risk. Current risk stratification tools have only modest prognostic capabilities, resulting in over-treatment of low-risk individuals and under-treatment of high-risk individuals. Improved methods of CVD risk stratification are required. Molecular imaging offers a novel approach to CVD risk stratification. In particular, F-sodium fluoride (F-NaF) positron emission tomography (PET) has shown promise in the detection of both high-risk atherosclerotic plaque features and vascular calcification activity, which predicts future development of new vascular calcium deposits. The rate of change of coronary calcium scores, measured by serial computed tomography scans over a 2-year period, is a strong predictor of CVD risk. Vascular calcification activity, as measured with F-NaF PET, has the potential to provide prognostic information similar to consecutive coronary calcium scoring, with a single-time-point convenience. However, owing to the rapid motion and small size of the coronary arteries, new solutions are required to address the traditional limitations of PET imaging. Two different methods of coronary PET analysis have been independently proposed and here we compare their respective strengths, weaknesses, and the potential for clinical translation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12350-018-1360-2DOI Listing
October 2018

A prospective randomized multicentre study of the impact of gallium-68 prostate-specific membrane antigen (PSMA) PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy (proPSMA study): clinical trial protocol.

BJU Int 2018 11 3;122(5):783-793. Epub 2018 Jun 3.

Genitourinary Oncology Tumour Multidisciplinary Team, Departments of Cancer Imaging, Cancer Surgery and Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.

Background: Accurate staging of patients with prostate cancer (PCa) is important for therapeutic decision-making. Relapse after surgery or radiotherapy of curative intent is not uncommon and, in part, represents a failure of staging with current diagnostic imaging techniques to detect disease spread. Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is a new whole-body scanning technique that enables visualization of PCa with high contrast. The hypotheses of this study are that: (i) PSMA-PET/CT has improved diagnostic performance compared with conventional imaging; (ii) PSMA-PET/CT should be used as a first-line diagnostic test for staging; (iii) the improved diagnostic performance of PSMA-PET/CT will result in significant management impact; and (iv) there are economic benefits if PSMA-PET/CT is incorporated into the management algorithm.

Objectives And Methods: The proPSMA trial is a prospective, multicentre study in which patients with untreated high-risk PCa will be randomized to gallium-68-PSMA-11 PET/CT or conventional imaging, consisting of CT of the abdomen/pelvis and bone scintigraphy with single-photon emission CT/CT. Patients eligible for inclusion are those with newly diagnosed PCa with select high-risk features, defined as International Society of Urological Pathology grade group ≥3 (primary Gleason grade 4, or any Gleason grade 5), prostate-specific antigen level ≥20 ng/mL or clinical stage ≥T3. Patients with negative, equivocal or oligometastatic disease on first line-imaging will cross over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT with that of conventional imaging for detecting nodal or distant metastatic disease. Histopathological, imaging and clinical follow-up at 6 months will define the primary endpoint according to a predefined scoring system. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross over, the cost of each imaging strategy, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer-term follow-up will also assess the prognostic value of a negative PSMA-PET/CT.

Outcome And Significance: This trial will provide data to establish whether PSMA-PET/CT should replace conventional imaging in the primary staging of select high-risk localized PCa, or whether it should be used to provide incremental diagnostic information in selected cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bju.14374DOI Listing
November 2018

Accuracy of Dose Calibrators for Ga PET Imaging: Unexpected Findings in a Multicenter Clinical Pretrial Assessment.

J Nucl Med 2018 04 11;59(4):636-638. Epub 2018 Jan 11.

Australasian Radiopharmaceutical Trials Network (ARTnet), Australia; and.

We report the discovery of a systematic miscalibration during the work-up process for site validation of a multicenter clinical PET imaging trial using Ga, which manifested as a consistent and reproducible underestimation in the quantitative accuracy (assessed by SUV) of a range of PET systems from different manufacturers at several different facilities around Australia. Sites were asked to follow a strict preparation protocol to create a radioactive phantom with Ga to be imaged using a standard clinical protocol before commencing imaging in the trial. All sites had routinely used Ga for clinical PET imaging for many years. The reconstructed image data were transferred to an imaging core laboratory for analysis, along with information about ancillary equipment such as the radionuclide dose calibrator. Fourteen PET systems were assessed from 10 nuclear medicine facilities in Australia, with the aim for each PET system being to produce images within 5% of the true SUV. At initial testing, 10 of the 14 PET systems underestimated the SUV by 15% on average (range, 13%-23%). Multiple PET systems at one site, from two different manufacturers, were all similarly affected, suggesting a common cause. We eventually identified an incorrect factory-shipped dose calibrator setting from a single manufacturer as being the cause. The calibrator setting for Ga was subsequently adjusted by the users so that the reconstructed images produced accurate values. PET imaging involves a chain of measurements and calibrations to produce accurate quantitative performance. Testing of the entire chain is simple, however, and should form part of any quality assurance program or prequalifying site assessment before commencing a quantitative imaging trial or clinical imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2967/jnumed.117.202861DOI Listing
April 2018

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

J Med Imaging Radiat Oncol 2018 Feb 17;62(1):57-63. Epub 2017 Jul 17.

Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

Introduction: Between 2009 and 2012, Ga-somatostatin analogue PET-CT progressively replaced 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, 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 In-octreotide scintigraphies performed in 2007 and 2008 at Sir Charles Gairdner (SCGH) and Royal Perth (RPH) hospitals and 219 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 In-octreotide scintigraphy was 152 min at SCGH, 100 min at RPH and 20 min for a Ga-somatostatin analogue PET-CT scan. The mean effective radiation dose for In-octreotide scintigraphy was 18.1 mSv at SCGH and 13.8 mSv at RPH. The effective dose for Ga-somatostatin analogue PET-CT was 8.7-10.8 mSv. The average cost of  Ga-somatostatin analogue PET-CT was four times less than In-octreotide scintigraphy.

Conclusion: Ga-somatostatin analogue PET-CT is not only more accurate than 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. Ga-somatostatin PET-CT provides an important combination of both reduced cost and improved clinical care for patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1754-9485.12638DOI Listing
February 2018

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

J Med Imaging Radiat Oncol 2016 Jun 20;60(3):374-81. Epub 2016 Apr 20.

Department of Nuclear Medicine/WA PET Service, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1754-9485.12455DOI Listing
June 2016

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

Lung Cancer 2015 Oct 30;90(1):55-60. Epub 2015 Jul 30.

School of Medicine and Pharmacology, University of Western Australia, Crawley 6009 & Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2015.07.015DOI Listing
October 2015

A gelatin liver phantom of suspended 90Y resin microspheres to simulate the physiologic microsphere biodistribution of a postradioembolization liver.

J Nucl Med Technol 2014 Dec 13;42(4):265-8. Epub 2014 Nov 13.

Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.

Unlabelled: For phantom studies involving (90)Y PET/CT, homogeneous solutions of (90)Y, for example, (90)Y citrate, are commonly used. However, the microsphere biodistribution of a postradioembolization liver is never homogeneous; therefore, such phantoms are physiologically unrealistic for simulating clinical scenarios. The aim of this work was to develop a safe and practical phantom capable of simulating the heterogeneous microsphere biodistribution of a postradioembolization liver.

Methods: Gelatin (5%) was used to suspend (90)Y resin microspheres, poured into plastic containers to simulate a liver with 2 tumors. Microspheres were added while the gelatin was maintained in a liquid state on a hot plate and continuously stirred with magnetic stir bars. The liquid microsphere mixture was then rapidly cooled in an ice bath while being stirred, resulting in a heterogeneous suspension of microspheres. The completed phantom was serially scanned by (90)Y PET/CT over 2 wk.

Results: All scans demonstrated a heterogeneous microsphere distribution throughout the liver and tumor inserts. Serendipitously, magnetic stir bars left inside the phantom produced CT artifacts similar to those caused by embolization coils, whereas pockets of air trapped within the gelatin during its preparation mimicked gas within hollow viscus. The microspheres and tumor inserts remained fixed and suspended within the gelatin, with no evidence of breakdown or leakage.

Conclusion: A gelatin phantom realistically simulating the physiologic microsphere biodistribution of a postradioembolization liver is feasible to construct in a radiopharmacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2967/jnmt.114.145292DOI Listing
December 2014

Observer variability in mesothelioma tumor thickness measurements: defining minimally measurable lesions.

J Thorac Oncol 2014 Aug;9(8):1187-94

Departments of *Radiology and ‖Health Studies, The University of Chicago, Chicago, Illinois; †School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia; and Departments of ‡Medical Oncology and §Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia.

Introduction: Single time-point unidimensional tumor thickness measurements define measurable disease for clinical trial inclusion and also constitute a field in the International Association for the Study of Lung Cancer prospective mesothelioma staging database. The modified Response Evaluation Criteria in Solid Tumors (RECIST) guidelines for mesothelioma did not alter the 10-mm minimum tumor measurement recommendation. However, as computed tomography technology has advanced, we sought to examine whether interobserver agreement was acceptable at smaller tumor thickness in mesothelioma.

Methods: The primary observer selected 170 discrete measurement sites from 105 thoracic computed tomography scans from 50 consenting patients with pleural mesothelioma. Sites represented a range of tumor thickness, lesion morphology, and location. The outer (parietal) tumor margin was marked at each site and presented to five additional observers, who then selected the visceral margin of the tumor to create a line segment that captured tumor thickness. Relative differences among the observer measurements were estimated using a random-effects analysis of variance model to identify the smallest tumor thickness at which linear measurements could be made reliably.

Results: Systematic bias was observed, with some observers consistently measuring larger or smaller thicknesses than the thickness measured by others. The mean range across all 170 sites was 15.1% of the mean per-site measurement (SD = 9.1%; median range, 13.1%). Measurements acquired at sites with mean tumor thickness less than 7.5 mm demonstrated interobserver variability with a 75th percentile included 20% of the tumor thickness. The 95% confidence interval for relative interobserver measurement differences obtained for mean measurement lengths in the range 5 to 7.5 mm does not exceed the RECIST thresholds.

Conclusions: This study has implications for the definition of minimally measurable tumor adopted by clinical trial and staging protocols. Although the statistical findings suggest that a reduction in "minimally measurable disease" from 10 mm to 5 or 7.5 mm might be warranted, clinical factors may ultimately dictate the most appropriate definition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JTO.0000000000000211DOI Listing
August 2014

Post-radioembolization yttrium-90 PET/CT - part 2: dose-response and tumor predictive dosimetry for resin microspheres.

EJNMMI Res 2013 Jul 25;3(1):57. Epub 2013 Jul 25.

Department of Nuclear Medicine and PET, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.

Background: Coincidence imaging of low-abundance yttrium-90 (90Y) internal pair production by positron emission tomography with integrated computed tomography (PET/CT) achieves high-resolution imaging of post-radioembolization microsphere biodistribution. Part 2 analyzes tumor and non-target tissue dose-response by 90Y PET quantification and evaluates the accuracy of tumor 99mTc macroaggregated albumin (MAA) single-photon emission computed tomography with integrated CT (SPECT/CT) predictive dosimetry.

Methods: Retrospective dose quantification of 90Y resin microspheres was performed on the same 23-patient data set in part 1. Phantom studies were performed to assure quantitative accuracy of our time-of-flight lutetium-yttrium-oxyorthosilicate system. Dose-responses were analyzed using 90Y dose-volume histograms (DVHs) by PET voxel dosimetry or mean absorbed doses by Medical Internal Radiation Dose macrodosimetry, correlated to follow-up imaging or clinical findings. Intended tumor mean doses by predictive dosimetry were compared to doses by 90Y PET.

Results: Phantom studies demonstrated near-perfect detector linearity and high tumor quantitative accuracy. For hepatocellular carcinomas, complete responses were generally achieved at D70 > 100 Gy (D70, minimum dose to 70% tumor volume), whereas incomplete responses were generally at D70 < 100 Gy; smaller tumors (<80 cm3) achieved D70 > 100 Gy more easily than larger tumors. There was complete response in a cholangiocarcinoma at D70 90 Gy and partial response in an adrenal gastrointestinal stromal tumor metastasis at D70 53 Gy. In two patients, a mean dose of 18 Gy to the stomach was asymptomatic, 49 Gy caused gastritis, 65 Gy caused ulceration, and 53 Gy caused duodenitis. In one patient, a bilateral kidney mean dose of 9 Gy (V20 8%) did not cause clinically relevant nephrotoxicity. Under near-ideal dosimetric conditions, there was excellent correlation between intended tumor mean doses by predictive dosimetry and those by 90Y PET, with a low median relative error of +3.8% (95% confidence interval, -1.2% to +13.2%).

Conclusions: Tumor and non-target tissue absorbed dose quantification by 90Y PET is accurate and yields radiobiologically meaningful dose-response information to guide adjuvant or mitigative action. Tumor 99mTc MAA SPECT/CT predictive dosimetry is feasible. 90Y DVHs may guide future techniques in predictive dosimetry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/2191-219X-3-57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733999PMC
July 2013

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

Clin Nucl Med 2013 Jan;38(1):1-6

Nuclear Medicine Department/WA PET Service, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, Australia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RLU.0b013e3182708777DOI Listing
January 2013

A phase II study of intermittent sunitinib malate as second-line therapy in progressive malignant pleural mesothelioma.

J Thorac Oncol 2012 Sep;7(9):1449-56

Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia.

Introduction: There is no accepted second-line therapy for patients with advanced malignant pleural mesothelioma (MPM), whose disease has progressed after first-line chemotherapy. The multitargeted tyrosine kinase inhibitor sunitinib malate targets several pathways overexpressed in mesothelioma. This phase II study assessed objective response to sunitinib and correlative biomarkers in patients with progressive pretreated MPM.

Methods: Eligible patients had confirmed MPM, radiological progression after chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 1, and measurable disease. Patients received oral sunitinib 50 mg daily for 28 of every 42 days. The primary endpoint was objective radiological response. Patients without prior pleurodesis had fluorodeoxyglucose positron emission tomographic response assessed by total glycolytic volume criteria. Correlative biomarkers included serum mesothelin, vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, sVEGFR-2, sVEGFR-3, and s-kit.

Results: Fifty-three patients received sunitinib between July 2006 and December 2009; 51 were assessable for response. Patients received a median of two cycles (range, 1-12); 40% required dose reduction. Fatigue was the most prominent toxicity. Six patients (12%) had a confirmed radiological partial response, 34 (65%) had stable disease, and 11 (22%) had progressive disease as best response. Six of 20 patients had a decrease in fluorodeoxyglucose positron emission tomographic total glycolytic volume of 15% or more. Median overall survival was 6.1 months, and median time to progression was 3.5 months. Correlative biomarkers did not predict treatment response.

Conclusions: Sunitinib has activity in a subset of patients with pretreated MPM. Consideration should be given to different treatment schedules and examination of other biomarkers for further study of sunitinib in MPM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JTO.0b013e31825f22eeDOI Listing
September 2012

A Multimodality Imaging Review of Malignant Pleural Mesothelioma Response Assessment.

PET Clin 2011 Jul;6(3):299-311

Division of Nuclear Medicine and Molecular Imaging, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.

Assessment of response is important to interpret early phase clinical trial results and to guide individual patient management. In malignant pleural mesothelioma (MPM), the circumferential growth pattern of the disease, the presence of pleural effusion and atelectasis, and the common use of pleurodesis make this a challenging task for imaging specialists and clinicians. This article reviews the current evidence for radiological and positron emission tomography (PET) response assessment in MPM, and the pitfalls and challenges in its application. Current research and future directions in radiological and PET response are discussed, including the use of novel radiotracers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cpet.2011.04.002DOI Listing
July 2011

Multimodality Imaging Review of Malignant Pleural Mesothelioma Diagnosis and Staging.

PET Clin 2011 Jul 14;6(3):275-97. Epub 2011 Jun 14.

Department of Medical Oncology, School of Medicine and Pharmacology, University of Western Australia, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands 6009, Western Australia, Australia; Department of Molecular Imaging, School of Medicine and Pharmacology, University of Western Australia, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands 6009, Western Australia, Australia.

Early diagnosis and accurate disease staging in patients with malignant pleural mesothelioma (MPM) are essential in classifying such patients into prognostic subgroups to allow delivery of stage-specific therapies. This review addresses the current status of multimodality imaging in the diagnosis and staging of MPM. Clinical, research, and future directions in computed tomography (CT), magnetic resonance imaging, and PET/CT diagnosis and staging of MPM are discussed, including the use of novel PET probes. The article concludes with important take-home messages summarized as the pearls and pitfalls of each diagnostic modality in the diagnosis and staging of patients with MPM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cpet.2011.04.001DOI Listing
July 2011

Serum soluble mesothelin concentrations in malignant pleural mesothelioma: relationship to tumor volume, clinical stage and changes in tumor burden.

Clin Cancer Res 2011 Mar 21;17(5):1181-9. Epub 2010 Dec 21.

National Research Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

Purpose: To examine the clinical utility of soluble mesothelin in patients with malignant pleural mesothelioma.

Experimental Design: A total of 97 patients (female: 11; male: 86) were prospectively enrolled, longitudinal serum samples collected, and mesothelin concentrations determined. Baseline mesothelin levels were analyzed relative to tumor stage, presence of metastatic disease, the positron emission tomography (PET) parameters maximum standardized uptake value, tumor volume, total glycolytic volume, and survival. Changes in mesothelin level were correlated to objective response to chemotherapy, as assessed radiologically and by PET imaging, and with patient survival.

Results: Baseline mesothelin levels greater than 5 nmol/L were a significant negative prognostic indicator (HR = 2.25; 95% CI, 1.20-4.21) and correlated with tumor stage and volume. In 55 patients who received chemotherapy, change in mesothelin correlated with radiological response (χ(2) = 11.32; P = 0.023) and change in metabolically active tumor volume (r = 0.58; P < 0.01). Median survival for patients with a reduction in mesothelin following chemotherapy (19 months) was significantly longer than for patients with increased mesothelin (5 months; P < 0.001).

Conclusion: These findings show the potential value of changes in mesothelin levels for prognostication and monitoring of treatment response in mesothelioma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-10-1929DOI Listing
March 2011
-->