Response evaluation of bone metastasis in prostate cancer: Preliminary comparison of computerized bone scan index versus standardized clinical criteria.

OBJECTIVE: The correlation between the computer-assisted bone scan index (BSI) responses versus clinical response classification if bone metastases in prostate cancer patients are not clear. We compared changes in BSI with Prostate Cancer Working Group-3 (PCWG3) and MD Anderson (MDA) criteria. MATERIALS AND METHODS: Fifty-six consecutive patients with at least two bone scans (BS) within 12 months were included, who had BS before and after treatment with the same anticancer agent. RESULTS: Progressive disease (PD) by PCWG3 criteria was seen in 28% of the cases (median BSI increased by 1.69 units) versus non-PD in 72% (BSI change -0.13). MDAnderson showed PD in 34% (BSI increase 0.49), 45% stable disease (BSI change 0.00), and 20% partial responses (BSI decrease 1.44). Absolute BSI changes differed significantly among response categories by PCWG3 and MDA criteria (both P<0.0001). Response classification using dichotomized BSI data (>0/≤0 and >0.3/≤0.3 BSI units) showed a significant correlation with PCWG3 and MDA criteria (all P<0.001). Absolute BSI changes and dichotomized BSI correlated to prostate-specific antigen responses (both P<0.001) but not to clinical responses. CONCLUSION: Absolute changes in BSI and BSI response classification correlated significantly with standardized clinical response criteria for the assessment of treatment responses of skeletal metastases in prostate cancer.

A comparison of the diagnostic value of 2D strain stress echocardiography, myocardial perfusion scintigraphy, and Duke treadmill score in patients suspected of coronary artery disease.

BACKGROUND: Preinvasive risk stratification is recommended in patients suspected of coronary artery disease (CAD). Stress echocardiography (SE), myocardial perfusion scintigraphy (MPS), and exercise test are the dominant methods of choice. Vasodilator SE is fast and induces only minor increase in heart rate. The diagnostic value of the absolute stress-rest difference in endocardial global longitudinal strain (ΔeGLS) and wall motion (ΔWMI) from adenosine SE was compared to summed stress score (SSS) from MPS and Duke treadmill score (DTS) from exercise test, using quantitative invasive coronary angiography (ICA) as the reference. METHODS AND RESULTS: A total of 128 patients (69% male, 62.7 (8.8) years) underwent adenosine SE, MPS, exercise test, and ICA. Forty-five patients (35%) had CAD. All stress outcomes differed significantly (P<.001) between patients with and without CAD: ΔeGLS: -1.3 (3.6)% vs -5.0 (3.3)%; WMI: 1.20 (0.34) vs 1.06 (0.13); SSS: 12.5 (8.2) vs 1.7 (3.6); and DTS: -3.4 (9.0) vs 3.9 (5.5). The cutoff values yielding the best sensitivity/specificity/accuracy were as follows: ΔeGLS: -2.3% or ΔWMI: 0 (69%/84%/79%), SSS: 4 (82%/94%/90%), and DTS: 1 (73%/78%/77%). The sensitivity of ΔeGLS + ΔWMI was similar to SSS (P=.11) and DTS (P=.59). The specificity of ΔeGLS + ΔWMI was inferior to SSS (P=.03) and similar to DTS (P=.28). CONCLUSION: Alterations in eGLS and wall motion during adenosine SE were closely associated with the presence of CAD and the combined sensitivity similar to that of MPS. If nuclear medical facilities are unavailable or radiation issues important, vasodilator ΔeGLS could be an acceptable alternative for patients unable to exercise.

Observer experience and accuracy of 18F-sodium-fluoride PET/CT for the diagnosis of bone metastases in prostate cancer.

OBJECTIVE: To evaluate the diagnostic accuracy of observers with different levels of experience in reading 18F-sodium fluoride (NaF) PET/CT images for the diagnosis of bone metastases in prostate cancer (PCa) patients. METHODS: Nine observers with varying NaF PET/CT experience, ranging from no experience to 2000+ examinations, evaluated 211 NaF PET/CT scans from PCa patients participating in one of four prospective trials. Each observer evaluated each NaF PET/CT on a patient level using a trichotomous scale: M0 (no bone metastases), Me (equivocal for bone metastases) and M1 (bone metastases). Subsequently, a dichotomous evaluation was conducted (M0/M1). The final diagnosis was retrieved from the original study. For each observer, ROC curves and the diagnostic accuracy were calculated based on dichotomous and trichotomous scales; in the latter case, Me was first regarded as M1 and then M0. RESULTS: Across all experience levels, the sensitivity, specificity and accuracy using the dichotomous scale ranged from 0.81 to 0.89, 0.93 to 1.00 and 0.91 to 0.94, respectively. Employing the trichotomous scale, novice and experienced observers chose Me in up to 20 vs. 10% of cases, respectively. Considering Me as M0, the sensitivity, specificity and accuracy ranged from 0.78 to 0.89, 0.95 to 1.00 and 0.91 to 0.95, respectively. Considering Me as M1, the sensitivity, specificity and accuracy ranged from 0.86 to 0.92, 0.71 to 0.96 and 0.77 to 0.94, respectively. CONCLUSION: Novice observers used the equivocal option more frequently than observers with NaF PET/CT experience. However, on the dichotomous scale, all observers exhibited high and satisfactory accuracy for the detection of bone metastases, making NaF PET/CT an effective imaging modality even in unexperienced hands.

Technetium-99m-MAG3 and technetium-99m-DTPA: Renal clearance measured by the constant infusion technique - Old news?

BACKGROUND: Accurate, precise and straightforward methods for measuring glomerular filtration rate (GFR) and/or renal plasma flow (RPF) are still in demand today. The time-consuming constant infusion technique (CIT) is the gold standard and preferred for research, whereas the simple, but less precise, single injection technique (SIT) is used in clinical settings. This study investigated the use of 99m Tc-DTPA and 99m Tc-MAG3 by CIT as a measure of renal function. We developed and evaluated a model to balance the primer dose and infusion rate in an attempt to obtain plasma steady state as quickly as possible. METHODS: 14 healthy subjects received 99m Tc-DTPA and 6 hypertensive patients received 99m Tc-MAG3 in a standardized protocol. All participants had an eGFR above 60 ml/min and none had fluid retention. An intravenous primer injection of the relevant tracer was followed by a sustained infusion over 4.5 h with the same radiopharmaceutical. Blood and urine samples were collected at fixed intervals. RESULTS: 99m Tc-DTPA clearance reached steady state after 210 min (plasma clearance 78 ± 18 ml/min, urine clearance 110 ± 28 ml/min), whereas 99m Tc-MAG3  clearance achieved steady state after 150 min (plasma clearance 212 ± 56 ml/min, urine clearance 233 ± 59 ml/min). CONCLUSION: Constant infusion technique with fixed primer and infusion rate using 99m Tc-MAG3 is feasible for research purposes. The longer time for reaching plasma steady state using 99m Tc-DTPA makes CIT with this tracer less optimal. If the primer/sustained balance can be optimized, for example using a priori SIT information, 99m Tc-DTPA as tracer for CIT may also be feasible.

Inter- and intraobserver agreement in standard and ultra-fast single-photon emission computed tomography/computed tomography for the assessment of bone metastases.

OBJECTIVE: To investigate inter- and intraobserver agreement using standard (std)-single-photon emission computed tomography/computed tomography (SPECT/CT) or ultra-fast acquisition (UF)-SPECT/CT as an add-on to planar whole-body bone scintigraphy (WB-BS) for the detection of bone metastases in patients with known cancer. METHODS: Images from patients (n = 104) participating in a prospective trial comparing SPECT/CT as an add-on to WB-BS with two different acquisition methods (std-SPECT/CT; 20 s per view, 32 views and UF-SPECT/CT; 16 views of 10 s per view) were included. The combinations of WB-BS with the two different SPECT/CT acquisition methods were independently evaluated by two experienced observers using a three-point scale (M0: no metastases, Me: equivocal for bone metastases and M1: bone metastases). The observers re-evaluated the scans 6 months later. Inter- and intraobserver agreement was calculated using linear weighted kappa. RESULTS: The linear weighted kappa for the interobserver agreement was 0.78 [95% confidence interval (CI) 0.61-0.94] for WB-BS with std-SPECT/CT and 0.84 (95% CI 0.67-1.00) for WB-BS with UF-SPECT/CT. Similar values were observed for the intraobserver agreement, in which the linear weighted kappa was 0.76 (95% CI 0.60-0.92) and 0.73 (95% CI 0.57-0.90) for std-SPECT/CT and UF-SPECT/CT, respectively. CONCLUSION: Satisfactory inter- and intraobserver agreement was seen for both acquisition methods, emphasizing that the use of SPECT/CT as an add-on to WB-BS is a robust method for the detection of bone metastases even when conducted with a very short acquisition time.

Added value of 68Ga-PSMA PET/CT for the detection of bone metastases in patients with newly diagnosed prostate cancer and a previous 99mTc bone scintigraphy.

PURPOSE: To investigate the added value and diagnostic accuracy of 68Ga-PSMA PET/CT versus bone scintigraphy (BS) for bone metastasis detection at the primary staging of prostate cancer (PCa). METHODS: Inclusion criteria involved consecutive patients with newly diagnosed intermediate- to high-risk PCa, who had undergone BS, mostly with supplementary SPECT/low-dose CT, and 68Ga-PSMA-11 PET/CT within less than 3 months without therapy initiation between the two investigations. BS was evaluated according to clinical routine and reported as no bone metastases (M0), bone metastases (M1), or equivocal (Me). The 68Ga-PSMA-11 PET/CT was blindly evaluated by three specialists as M0, M1, or Me at the patient level. Sensitivity analyses were conducted using a "best valuable comparator" using all available imaging and clinical follow-up as a reference. RESULTS: In total, 112 patients were included; 68Ga-PSMA-11 PET/CT showed a sensitivity of 1.00, specificity of 0.93-0.96, positive predictive value of 0.74-0.81, and negative predictive value of 1.00. 68Ga-PSMA-11 PET/CT revealed bone metastases in 8 of 81 patients with M0 disease according to BS. 68Ga-PSMA-11 PET/CT confirmed the presence of bone metastases in all patients (n = 9) with M1 disease according to BS. In patients with Me by BS, 68Ga-PSMA PET/CT provided a definite result in 20 of 22 patients. 68Ga-PSMA-11 PET/CT resulted in a false-positive answer in four patients with solitary rib lesions. CONCLUSION: 68Ga-PSMA-11 PET/CT revealed bone metastases in 10% of patients without bone metastases on BS and in 36% patients with indeterminate BS. However, solitary PSMA-avid lesions in the ribs should be interpreted cautiously as they may represent false-positive findings.

An unusual case of sudden unexpected death: postmortem investigation and biomechanical analysis of the cervical spine.

A naked man died under peculiar circumstances and the postmortem examination revealed unexpected lesions in the cervical spine. Investigations of the cervical spine (computed tomography, magnetic resonance imaging, and histological examination) showed that a piece of bone was torn of the anterior part of vertebra C6 and that there was fresh bleeding in the surrounding tissue. The cause of death remained unclear but was most likely cardiac arrhythmia initiated by beta-2 agonist inhalation due to an acute asthmatic attack. Data from biomechanical investigation using finite element analysis supported the conclusion that the cervical spine injury was secondary to impact during falling as a consequence of the cardiac arrhythmia.

Diagnostic value of layer-specific global longitudinal strain during adenosine stress in patients suspected of coronary artery disease.

Speckle tracking global longitudinal strain (GLS) from dobutamine stress echocardiography (SE) predicts coronary artery disease (CAD). The diagnostic value of GLS from vasodilator SE and the additional value of layer-specific speckle tracking analysis are unclear. We explored the usefulness of layer-specific GLS and non-layer-specific strain (automated functional imaging, AFI) from adenosine SE. The included 132 patients (67% male, 62.6 (9.0) years), of which 46 (35%) had CAD defined as ≥1 stenosis ≥70% (≥50% in the left main), underwent adenosine SE and invasive coronary angiography. Resting AFI and layer-specific GLS were similar in patients with or without CAD (p > 0.05). The stress-rest difference (Δvalue = stress-value - rest-value) in patients with CAD was less pronounced compared to patients without proved CAD (Δendocardial GLS: -1.2 (3.5)% vs. -5.0 (3.2)%; Δmidventricular GLS: -0.95 (3.0)% vs. -4.2 (2.7)%; Δepicardial GLS: -0.7 (2.5)% vs. -3.4 (2.3)%; ΔAFI: -0.8 (2.9)% vs. -3.6 (3.1)%, p < 0.00001 for all comparisons). The diagnostic value of the three layer-specific GLS values and AFI were statistically similar (p = 0.19). The four Δvalues provided independent predictive value to the risk assessment given by gender, age, wall motion and ΔEF (p = 0.002, AFI and p < 0.0001, layer-specific GLS). The accuracies were acceptable (71-80%) with modest sensitivities (54-65%) and high specificities (80-91%). The deformation response to vasodilator infusion was associated with the presence of CAD. Endocardial, midventricular and epicardial GLS and AFI from adenosine SE had similar diagnostic values. The specificities were high, but the modest sensitivities are a limitation to the clinical application.

Stress-only myocardial perfusion scintigraphy: a prospective study on the accuracy and observer agreement with quantitative coronary angiography as the gold standard.

OBJECTIVE: Patients with normal stress perfusion have an excellent prognosis. Prospective studies on the diagnostic accuracy of stress-only scans with contemporary, independent examinations as gold standards are lacking. PATIENTS AND METHODS: A total of 109 patients with typical angina and no previous coronary artery disease underwent a 2-day stress (exercise)/rest, gated, and attenuation-corrected (AC), 99m-technetium-sestamibi perfusion study, followed by invasive coronary angiography. The stress datasets were evaluated twice by four physicians with two different training levels (expert and novice): familiar and unfamiliar with AC. The two experts also made a consensus reading of the integrated stress-rest datasets. The consensus reading and quantitative data from the invasive coronary angiography were applied as reference methods. RESULTS: The sensitivity/specificity were 0.92-1.00/0.73-0.90 (reference: expert consensus reading), 0.93-0.96/0.63-0.82 (reference: ≥1 stenosis>70%), and 0.75-0.88/0.70-0.88 (reference: ≥1 stenosis>50%). The four readers showed a high and fairly equal sensitivity independent of their familiarity with AC. The expert familiar with AC had the highest specificity independent of the reference method. The intraobserver and interobserver agreements on the stress-only readings were good (readers without AC experience) to excellent (readers with AC experience). CONCLUSION: AC stress-only images yielded a high sensitivity independent of the training level and experience with AC of the nuclear physician, whereas the specificity correlated positively with both. Interobserver and intraobserver agreements tended to be the best for physicians with AC experience.

Observer agreement of treatment responses on planar bone scintigraphy in prostate cancer patients: importance of the lesion assessment method.

PURPOSE: The aim of this study was to assess observer agreement on the evaluation of treatment responses of bone metastases by bone scintigraphy (BS) using different scoring methods in prostate cancer patients. PATIENTS AND METHODS: Sixty-three paired BS from 55 patients were included. BS was performed before and after more than 12 weeks of anticancer treatment. A panel of experienced nuclear medicine physicians from several institutions evaluated treatment response using three different methods: (a) standard clinical assessment, (b) MD Anderson criteria, and (c) Prostate Cancer Working Group 2 (PCWG-2) criteria. All methods were based on the evaluation of paired before-after bone scans. RESULTS: Readers were able to classify the presence of bone metastases at baseline with a high level of agreement [Cohen's κ=0.94, 95% confidence interval (CI) 0.82-1.00]. Observer agreement on bone response by PCWG-2 criteria showed considerable agreement (Cohen's κ=0.84, 95% CI: 0.69-0.99). Evaluation using standard clinical assessment and MD Anderson criteria showed moderate agreement (0.52, 95% CI: 0.36-0.69 and 0.64, 95% CI: 0.48-0.79, respectively). There was considerable variation among readers for regional lesion count on individual scans, with limits of agreement of -10 to 10 lesions or more for the majority of anatomical regions, including the thorax, spine, and pelvis. CONCLUSION: Observer agreement on treatment response by BS varied notably across methods. Optimal agreement was achieved by the PCWG-2 criteria. Variation in the classification of treatment response of bone metastases may have a significant impact on clinical decision-making, emphasizing the need for a uniform approach, including during clinical practice. Response assessment by lesion counting on repeated BS without access to previous scans cannot be recommended.

Three-minute SPECT/CT is sufficient for the assessment of bone metastasis as add-on to planar bone scintigraphy: prospective head-to-head comparison to 11-min SPECT/CT.

BACKGROUND: The aim of this study is to assess whether ultra-fast acquisition SPECT/CT (UF-SPECT/CT) can replace standard SPECT/CT (std-SPECT/CT) as "add-on" to whole-body bone scintigraphy (WB-BS) for the investigation of bone metastases. Consecutive cancer patients referred for WB-BS who underwent SPECT/CT in addition to WB-BS were included. Std-SPECT, UF-SPECT, and low-dose CT were performed (std-SPECT: matrix 128 × 128, zoom factor 1, 20 s/view, 32 views; UF-SPECT: identical parameters except for 10 s/view and 16 views, reducing the acquisition time from 11 to 3 min). A consensus diagnosis was reached by two observers for each set of images (WB-BS + standard SPECT/CT or WB-BS + UF-SPECT/CT) using a three-category evaluation scale: M0: no bone metastases; M1: bone metastases; and Me: equivocal findings. RESULTS: Among the 104 included patients, most presented with prostate cancer (n = 71) or breast cancer (n = 28). Using WB-BS + std-SPECT/CT, 71 (68%) patients were classified as M0, 19 (18%) as M1, and 14 (14%) as Me. Excellent agreement was observed between WB-BS + std-SPECT/CT and WB-BS + UF-SPECT/CT using the three-category scale: kappa = 0.91 (95% CI 0.84-0.97). No difference in observer agreement between cancer types was detected. SPECT/CT provided a definitive classification in 90 of 104 cases in which WB-BS was not entirely diagnostic. CONCLUSIONS: To investigate potential bone metastases, UF-SPECT/CT can be conducted as add-on to WB-BS to notably reduce the SPECT acquisition time without compromising diagnostic confidence.

Diagnostic test accuracy study of 18F-sodium fluoride PET/CT, 99mTc-labelled diphosphonate SPECT/CT, and planar bone scintigraphy for diagnosis of bone metastases in newly diagnosed, high-risk prostate cancer.

The aim of this study was to prospectively compare planar, bone scan (BS) versus SPECT/CT and NaF PET/CT in detecting bone metastases in prostate cancer. Thirty-seven consecutive, newly diagnosed, prostate cancer patients with prostate specific antigen (PSA) levels ≥ 50 ng/mL and who were considered eligible for androgen-deprivation therapy (ADT) were included in this study. BS, SPECT/CT, and NaF PET/CT, were performed prior to treatment and were repeated after six months of ADT. Baseline images from each index test were independently read by two experienced readers. The reference standard was based on a consensus decision made by a multidisciplinary team on the basis of baseline and follow-up images of the index tests, the findings of the baseline index tests by the experienced readers, and any available imaging, biochemical, and clinical data, including the response to ADT. Twenty-seven (73%) of the 37 patients had bone metastases according to the reference standard. The sensitivities for BS, SPECT/CT and NaF PET/CT were 78%, 89%, and 89%, respectively, and the specificities were 90%, 100%, and 90%, respectively. The positive predictive values of BS, SPECT/CT and NaF PET/CT were 96%, 100%, and 96%, respectively, and the negative predictive values were 60%, 77% and 75%, respectively. No statistically significant difference among the three imaging modalities was observed. All three imaging modalities showed high sensitivity and specificity. NaF PET/CT and SPECT/CT showed numerically improved, but not statistically superior, sensitivity compared with BS in this limited and selected patient cohort.

Impairment of Lung Function During Adjuvant Oxaliplatin Treatment in Patients with Colorectal Cancer: A Prospective Trial.

BACKGROUND: Forty-seven cases (38 men and 9 women) of pulmonary toxicity caused by oxaliplatin have previously been published, but the issue has not been investigated in a prospective setting. Our purpose was to assess how oxaliplatin affects the pulmonary function in colorectal cancer patients during adjuvant treatment. MATERIAL AND METHODS: Forty patients (median age 57.5 years, range 33-74) radically resected for colorectal cancer, underwent three pulmonary function tests during post-surgery adjuvant treatment with oxaliplatin. RESULTS: Mean±sd haemoglobin corrected diffusion capacity (DLCOc) in the entire patient cohort were 7.65±2.24 at baseline, 7.11±2.11 during and 7.12±1.99 three months after oxaliplatin treatment (p=0.0002). The decrease was similar in men (n=22, p=0.02) and women (n=18, p=0.01), but most prominent in smokers (n=23, p=0.0005) and in patients exposed to occupational dust (n=21, p=0.0009). Besides a small decrease in the FEV1/FVC ratio (p=0.03), all other pulmonary parameters remained constant and no clinical signs of pulmonary failure were observed during the study period. CONCLUSION: A decline in DLCOc was detected in a majority of the examined patients, but none reported any clinical symptoms of pulmonary distress. The subtle decrease in DLCOc does not appear to be an isolated predictor of PT. Our data suggest that smoking and dust exposure might aggravate the effect of oxaliplatin on DLCOc. Routine pulmonary function test in patients treated with oxaliplatin is not recommended, but it is important to be aware of the early signs of pulmonary toxicity.