Androgen Deprivation therapy for Oligo-recurrent Prostate cancer in addition to radioTherapy (ADOPT): study protocol for a randomised phase III trial.

BACKGROUND: More than 60% of oligo-recurrent prostate cancer (PCa) patients treated with metastasis-directed radiotherapy (MDRT) develop biochemical recurrence within 2 years. This recurrence rate emphasises the need for improved treatment and patient selection. In line with the treatment of primary PCa, the efficacy of MDRT may be enhanced when combined with androgen-deprivation therapy (ADT). Furthermore, the availability of PSMA PET/CT offers an excellent tool for optimal patient selection for MDRT. This phase III randomised controlled trial will investigate the role of the addition of ADT to MDRT in oligo-recurrent PCa patients selected with PSMA PET/CT to enhance oncological outcome. METHODS: Two hundred and eighty patients will be randomised in a 1:1 ratio to the standard treatment arm (MDRT alone) or the experimental arm (MDRT + 6 months ADT). Patients with biochemical recurrence after primary treatment of PCa presenting with ≤ 4 metastases will be included. The primary endpoint is the 2.5-year metastases progression-free survival (MPFS). Secondary endpoints are acute and late toxicity, quality of life, biochemical progression-free survival, overall survival, and the sensitivity of the PSMA PET/CT for detecting oligometastases at low PSA-levels. So far, between March 2020 and December 2021, one hundred patients have been included. DISCUSSION: This phase III randomised controlled trial will assess the possible benefit of the addition of 6 months ADT to MDRT on metastases progression-free survival, toxicity, QoL and survival in PCa patients with 1-4 recurrent oligometastatic lesions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04302454 . Registered 10 March 2020.

Phase III randomised controlled trial on PSMA PET/CT guided hypofractionated salvage prostate bed radiotherapy of biochemical failure after radical prostatectomy for prostate cancer (PERYTON-trial): study protocol.

BACKGROUND: Salvage external beam radiotherapy (sEBRT) for patients with a biochemical recurrence (BCR) after radical prostatectomy provides a 5-year biochemical progression-free survival up to 60%. Multiple studies have shown that dose escalation to the primary prostate tumour improves treatment outcome. However, data is lacking on the role of dose escalation in the recurrent salvage setting. The main objective of the PERYTON-trial is to investigate whether treatment outcome of sEBRT for patients with a BCR after prostatectomy can be improved by increasing the biological effective radiation dose using hypofractionation. Moreover, patients will be staged using the PSMA PET/CT scan, which is superior to conventional imaging modalities in detecting oligometastases. METHODS: The PERYTON-study is a prospective multicentre open phase III randomised controlled trial. We aim to include 538 participants (269 participants per treatment arm) with a BCR after prostatectomy, a PSA-value of < 1.0 ng/mL and a recent negative PSMA PET/CT scan. Participants will be randomised in a 1:1 ratio between the conventional fractionated treatment arm (35 × 2 Gy) and the experimental hypofractionated treatment arm (20 × 3 Gy). The primary endpoint is the 5-year progression-free survival after treatment. The secondary endpoints include toxicity, quality of life and disease specific survival. DISCUSSION: Firstly, the high rate of BCR after sEBRT may be due to the presence of oligometastases, for which local sEBRT is inappropriate. With the use of the PSMA PET/CT before sEBRT, patients with oligometastases will be excluded from intensive local treatment to avoid unnecessary toxicity. Secondly, the currently applied radiation dose for sEBRT may be too low to achieve adequate local control, which may offer opportunity to enhance treatment outcome of sEBRT by increasing the biologically effective radiotherapy dose to the prostate bed. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (Identifier: NCT04642027 ). Registered on 24 November 2020 - Retrospectively registered. The study protocol was approved by the accredited Medical Ethical Committee (METc) of all participating hospitals (date METc review: 23-06-2020, METc registration number: 202000239). Written informed consent will be obtained from all participants.

[Not Available]. / PSMA-PET voor prostaatkanker en eventuele metastasen.

(68)Gallium (Ga)-PSMA PET/CT (PSMA stands for "prostate-specific membrane antigen") is a new diagnostic tool for patients with prostate cancer or with prostate cancer metastases. PET/CT is a combination scan which uses the physiological information of the PET scan and the anatomic information of the CT scan. The radioligand (68)Ga-PSMA is a radioactively labelled peptide that binds to the membrane protein PSMA. Prostate cancer cells in the primary tumour and in metastases express increased levels of PSMA in the plasma membrane. A number of studies have shown that (68)Ga-PSMA PET/CT is sensitive in detecting primary prostate cancer and metastases in lymph nodes and bone. In the same patient, (68)Ga-PSMA PET/CT detects more metastases in an earlier phase, i.e. at a lower PSA level, than fluorine-18 choline PET/CT. Furthermore, the (68)Ga-PSMA can be produced in the investigating hospital with a gallium generator. The expectation is that the use of (68)Ga-PSMA PET/CT will increase to a major extent over the coming years in patients with prostate cancer.

Patients with left bundle branch block pattern and high cardiac risk myocardial SPECT: does the current management suffice?

INTRODUCTION: Myocardial perfusion SPECT (MPS) is frequently used for cardiovascular risk stratification. The significance of MPS in patients with abnormal electrical ventricular activation is often questionable. This review assesses the value of MPS for risk stratification of patients with intrinsic left bundle branch block or that due to right ventricular apical pacing. METHODS: We reviewed the literature by a search of the MEDLINE database (January 1980 to September 2010). The terms prognosis or prognostic value were combined with SPECT and LBBB or pacing or pacemakers. MPS was categorised as low and high risk according to the original definitions. RESULTS: We identified 11 studies suitable for review. A low-risk MPS is associated with a low risk of cardiac events whereas high-risk MPS carries a 4.8-fold increased risk, 95% CI [3.2 - 7.2] (p < 0.0001). Despite secondary prevention and an improved medical and interventional care, these figures have hardly changed over time. CONCLUSION AND CLINICAL IMPLICATIONS: A low-risk MPS permits a policy of watchful waiting whereas a high-risk MPS requires further analysis and treatment. The persistent high cardiac death and acute myocardial infarction rate after a high-risk MPS suggest that the current management of these patients does not suffice and needs reconsideration.

No firm association between N-terminal pro-brain natriuretic peptide and percentage of pulmonary vascular obstruction in patients with acute pulmonary embolism.

INTRODUCTION: High concentrations of N-terminal-pro-brain natriuretic peptide (NT-proBNP) are found in patients with right ventricular overload. Right ventricular overload may be the result of large perfusion defects in patients with pulmonary embolism (PE). NT-proBNP levels are associated with poorer outcome in patients with acute PE. Likewise, the percentage of pulmonary vascular obstruction (PVO) has shown to be a prognostic parameter for outcome in PE-patients. We postulated that NT-proBNP is associated with the amount of perfusion defects, expressed as the PVO, on perfusion scintigraphy. METHODS: We included 85 consecutive patients in whom the diagnosis PE was confirmed by ventilation-perfusion scintigraphy. PVO was calculated in all patients. NT-proBNP concentrations were measured at presentation. We plotted the logarithm of NT-proBNP versus the PVO. The strength of the estimated association between NT-proBNP and the PVO was expressed by R2. RESULTS: Eighteen percent of the variation in PVO could be explained by NT-proBNP. A positive association becomes apparent for NT-proBNP values above 200 pg/mL, with an increase in PVO of 6.3% (95% Confidence Interval 2.0 to 10.6), with every doubling of NT-proBNP. CONCLUSION: There is an association between NT-proBNP concentrations and PVO, although this relation is quite weak. Some patients with low NT-proBNP values can have a high PVO, which might be relevant for outcome. Therefore, we advise caution in risk stratification and not to focus on NT-proBNP, without involving the clinical condition.

18F-FDG PET in sarcoidosis: an observational study in 12 patients treated with infliximab.

BACKGROUND: 18F-FDG PET is a promising technique in sarcoidosis imaging, although it is not incorporated in routine activity assessment. The purpose of this study was to correlate 18F-FDG PET with standard sarcoidosis activity parameters during infliximab treatment. METHODS: Twelve patients with refractory sarcoidosis were treated with 6 cycles of infliximab. Pre- and post-therapy 18F-FDG PET was visually evaluated and SUVmax was measured. In addition, the effect of infliximab was evaluated by changes in symptoms, angiotensin converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R), vital capacity (VC), diffusion capacity of the lung for carbon monoxide (DLCO) and chest radiography. SUVmax and conventional parameters were correlated. RESULTS: Clinical improvement as judged by conventional parameters was seen in all patients, though with a minor response in one. Symptoms improved in 11/12 patients while chest radiographic stages did not change. The decrease in ACE was 39% and in sIL-2R 47% (p<0.01). Improvement of VC and DLCO was 5.4% and 3.3% (p<0.05), respectively. 18F-FDG PET revealed either improvement or normalization in 11/12 (92%) clinically responding patients. The overall decrease in SUVmax was 55% (p<0.01); the patient with a limited response showed a 34% increase. A decrease in SUVmax of the lung parenchyma correlated with an improvement of VC (r=-0.75, p<0.01). No significant correlation between SUVmax and other parameters was found. CONCLUSION: Changes imaged by 18F-FDG PET during infliximab treatment in sarcoidosis patients correlate with signs of clinical improvement to a considerate extent, which supports the hypothesis that 18F-FDG uptake represents disease activity.

The intra-articular distribution of 90yttrium does not influence the clinical outcome of radiation synovectomy of the knee.

OBJECTIVES: To assess the impact of the intra-articular distribution of (90)yttrium-citrate ((90)Y) on the clinical effect of radiosynoviorthesis (RSO) of the knee and on (90)Y leakage from this joint. METHODS: Patients with arthritis of the knee received 185 MBq (90)Y combined with a glucocorticoid, followed by clinical bed rest. Intra-articular (90)Y distribution, measured with a dual-head gamma camera immediately or after 24 hours, was scored as mainly diffuse or mainly focal. Leakage to regional lymph nodes, the liver and spleen was assessed with a dual-head gamma camera after 24 hours. Clinical effect was scored after 6 months by a composite change index (CCI), range 0-12; responders were defined as having a CCI > or =6. RESULTS: Seventy-eight knees of 69 patients, mostly suffering from undifferentiated arthritis (42%) or RA (28%), were treated. (90)Y distribution was mainly diffuse in 54% and mainly focal in 46% with clinical response rates of 40% versus 56%, respectively, p = 0.3. CCI was not correlated with distribution. (90)Y leakage was found only to the liver and the spleen (mean leakage 0.4% and 1.1%, respectively). Leakage was significantly less in case of diffuse intra-articular (90)Y distribution, whereas leakage to the liver was correlated with distribution (r = 0.68, p<0.001). (90)Y leakage was not correlated with CCI. CONCLUSIONS: Intra-articular (90)Y distribution does not influence the clinical effect of RSO of the knee. Although (90)Y leakage from the joint is less if (90)Y distributes diffusely in the joint cavity, leakage does not seem to hamper the clinical effect.

Prognostic value and quality of life in patients with normal rest thallium-201/stress technetium 99m-tetrofosmin dual-isotope myocardial SPECT.

BACKGROUND: The prognostic value of normal dual-isotope single photon emission computed tomography (SPECT), with technetium 99m-tetrofosmin for the stress images, is not well known. Furthermore, thallium-201 cross talk in the Tc-99m window may reduce the defect severity of the Tc-99m images. METHODS AND RESULTS: In a consecutive series of 610 patients, 246 patients with normal rest and stress SPECT images by means of visual semiquantitative analysis were included. The patients' pre-test likelihood of coronary artery disease was determined, based on age, sex, symptoms, and the results of stress electrocardiography. Quality of life was assessed by using a mailed self-administered general quality-of-life questionnaire. We compared the mean scores (8 dimensions) of our study population with the scores of 1063 control subjects, sampled randomly out of the inhabitant register of a Dutch city. The mean follow-up period was 25+/-3 months. Compared with the control group, patients in our study scored lower (less perceived health) for all dimensions of the SF-36 (P<.05), suggesting a selection of symptomatic or otherwise diseased patients. The primary cardiac event rate was 0.4% per year. The cardiac events occurred in patients with an intermediate-to-high pre-test likelihood of disease and negative or nondiagnostic exercise electrocardiographic results. In a subset of patients with a high pre-test likelihood of coronary artery disease (more than 85%), the primary cardiac event rate was 0.7% per year. CONCLUSIONS: Patients with normal results on dual-isotope myocardial perfusion scintigraphy, performed with Tc-99m-tetrofosmin for the stress images, have an excellent prognosis. Furthermore, our results suggest that Tl-201 cross talk in the Tc-99m window may be low and functionally and clinically unimportant.

SPECT versus planar 99mTc-sestamibi myocardial scintigraphy: comparison of accuracy and impact on patient management in chronic ischemic heart disease.

A head-to-head comparison between 99mTc-sestamibi SPECT and planar myocardial imaging using dipyridamole low-level exercise stress was performed for the assessment of coronary artery disease (CAD) and for the impact on patient management in 78 patients (pts) who underwent coronary arteriography. Overall sensitivity and specificity for detection of CAD were 82% and 82% for SPECT, and 78% and 73% for planar imaging, respectively (both NS). Compared to planar imaging the sensitivity of SPECT imaging was significantly higher for detecting left anterior descending (p = 0.02) and left circumflex (p = 0.03) coronary artery disease. In predicting distally located stenoses, SPECT was significantly superior to planar imaging for the left circumflex artery (p = 0.025). Concordance analysis of perfusion status showed agreement in 308 of 390 (79%) of coronary flow regions both with respect to the presence or absence of perfusion and to the reversibility or irreversibility of defects (kappa = 0.60, SE 0.04). Stress-induced perfusion defects were significantly more detected by SPECT than by planar imaging (p < 0.001). Based on SPECT findings 31 pts were proposed for revascularization compared to 30 pts based on planar imaging (NS). Overall there was agreement in 65 (83%) pts regarding treatment strategy. We conclude that in a head-to-head comparison SPECT provided improved diagnostic value compared with planar imaging. However, with respect to patient treatment, the superiority of SPECT was not always translated into improved patient management.

Potential for imaging cerebral amyloid deposits using 123I-labelled serum amyloid P component and SPET.

The systemic and cerebral accumulation of 123I-labelled serum amyloid P component (123I-SAP) was studied in patients with hereditary cerebral amyloid angiopathy-Dutch type (HCHWA-D) to determine the usefulness of 123I-SAP imaging in cerebral amyloidosis. Whole-body and SPET scintigraphic imaging was performed in two patients with HCHWA-D and four controls after the intraveous injection of 123I-SAP. Venous 123I-SAP clearance was also determined. Accumulation of the tracer was observed in the cerebral cortex of both patients, whereas no accumulation was seen in the controls. Blood clearance of radioactivity was similar in the patients and controls, suggesting that the amount of uptake of 123I-SAP in the cerebral amyloid deposits is relatively small. We believe this to be the first demonstration of cerebral amyloid deposits in vivo. Our findings indicate that 123I-SAP scintigraphy has possibilities for the diagnosis of patients with cerebral amyloid diseases, in addition to its use in patients with systemic amyloid deposition.

Detection of coronary artery disease: comparison between technetium 99m-labeled sestamibi single-photon emission computed tomography and two-dimensional echocardiography with dipyridamole low-level exercise-stress.

BACKGROUND: Myocardial perfusion imaging in conjunction with dipyridamole low-level exercise stress has proved its value in the evaluation of patients with coronary artery disease (CAD). Simultaneous wall motion analysis by two-dimensional (2D) echocardiography may provide additional information beyond that obtained by myocardial perfusion imaging alone. The purpose of this study was to compare 99mTc-labeled sestamibi single-photon emission computed tomography (SPECT) and 2D echocardiography for the evaluation of CAD according to a dipyridamole low-level bicycle exercise stress protocol. METHODS AND RESULTS: We studied 35 consecutive patients referred for the evaluation of chest pain who had undergone coronary arteriography. 99mTc-labeled sestamibi SPECT and 2D echocardiography agreed in 27 patients (80%) studied for overall detection of CAD. On a segmental basis, agreement was found between SPECT and 2D echocardiography in 124 (73%) of 170 segments (Cohen's kappa = 0.43). The accuracy of the combined assessment of myocardial perfusion and echocardiographic wall motion in detecting CAD was 86%, which was not different from the accuracy of SPECT alone (80%; difference not significant) but significantly higher than for 2D echocardiography alone (71%; p = 0.03). In the detection of individual coronary artery stenoses, SPECT had a significantly higher accuracy for detecting left anterior descending coronary artery lesions than had 2D echocardiography (80% vs 60%; p < 0.01); combining the two method did not improve the accuracy (80%). The combined assessment slightly improved the accuracy for detecting left circumflex coronary artery stenoses from 71% to 83% (p = 0.05). CONCLUSION: The combined simultaneous assessment of myocardial perfusion by 99mTc-labeled sestamibi SPECT and wall motion by 2D echocardiography did not significantly improve overall accuracy over that obtained by 99mTc-labeled sestamibi SPECT alone. Therefore 99mTc-labeled sestamibi SPECT with dipyridamole low-level exercise stress appears the preferred imaging modality for the evaluation of patients with CAD.

Comparison of technetium-99m sestamibi left ventricular wall motion and perfusion studies with thallium-201 perfusion imaging: in search of the combination of variables with the highest accuracy in predicting coronary artery disease.

Measurements of myocardial perfusion and ventricular function are expected to provide additional information in the detection of coronary artery disease (CAD). The purpose of this study was threefold: (1) to determine to what extent technetium-99m sestamibi wall motion yields different information compared with 99mTc-sestamibi and thallium-201 perfusion; (2) to test which information unique to either study is of value in diagnosing CAD; and (3) to assess the combination of variables with the highest diagnostic accuracy. Perfusion and wall motion scores (at rest and during exercise) obtained from visual and quantitative planar 201Tl and 99mTc-sestamibi scintigraphy of 60 patients with suspected CAD were compared with the angiographic results by means of a polytomous logistic regression model and the diagnostic values were compared with one another. All univariate variables were significantly related to the probability of CAD and its extent. Comparative studies revealed a large degree of correlation between 201Tl stress and redistribution variables. The rest 99mTc-sestamibi and wall motion studies contained partially different information. Stepwise logistic regression analysis showed the strongest diagnostic power for the combination of 201Tl visual analysis of the stress images with quantitative redistribution images (sensitivity 93%, specificity 71%). The diagnostic power was similar for all combinations of visual and quantitative analyses of the exercise and redistribution images. The strongest diagnostic power of the 99mTc-sestamibi variables was the score of the diastolic stress image (sensitivity 91%, specificity 79%). Comparable sensitivity and specificity estimates were found when both optimal models were compared. Wall motion studies did not have additional diagnostic power. Although 99mTc-sestamibi wall motion studies, both at rest and during exercise, provide information in addition to the 99mTc-sestamibi or 201Tl myocardial perfusion variables, the information does not enhance the diagnostic power with regard to the prediction of CAD.