Jesper Mortensen

Does radioiodine therapy have an equal effect on substernal and cervical goiter volumes? Evaluation by magnetic resonance imaging.

Most often thyroidectomy is recommended in patients with large goiters. However, high-dose (131)I therapy may be used in case of contraindications to surgery. Large goiters are often partially located in the mediastinum. The aim of this study was to evaluate the impact of (131)I therapy on the cervical and the substernal goiter volume, separately. Fourteen patients (median age, 69 years; range, 52-86 years) with a large multinodular goiter (three hyperthyroid) and with a substernal extension greater than 15 mL were included. T1-weighted magnetic resonance (MR) estimates of the thyroid volume in the cervical and substernal compartments were obtained before and 1 year after high-dose (131)I therapy. The total goiter volumes ranged from 182 to 685 mL. The median substernal volume was 66 mL (fraction of total volume, 17.6%; range, 8.0%-78.9%). One year after treatment, the median substernal goiter volume was reduced by 29.2% (range, -6.1%-59.4%, mean: 26.1% +/- 6.0%), and the cervical goiter volume by 30.3% (range, 6.0%-75.4%, mean, 35.6 +/- 5.6%) compared to baseline values; p = 0.25 for difference in a regional effect. The volume reduction was unrelated to initial substernal goiter size. Likewise, deterioration of the inspiratory capacity did not correlate with the magnitude of the substernal goiter extension. In conclusion, high-dose (131)I therapy seems as effective in reducing the substernal as the cervical goiter volume. However, because the overall effect is modest, this therapy should primarily be considered for the patient with a high surgical risk.

Prospective Multicenter Study of Bone Scintigraphy in Consecutive Patients With Newly Diagnosed Prostate Cancer

Background International guidelines uniformly suggest no routine staging of bone metastasis in patients with bone scintigraphy (BS) in low-risk prostate cancer (PCa). These recommendations are based on retrospective investigations only. In addition, BS has most often been reported as a definitive investigation with no room for equivocal cases. Objective The objective of this study was to determine the diagnostic value of BS in a large cohort of consecutive patients with newly diagnosed PCa. Design, Setting, and Participants Over a period of 1.5 years in 2008 to 2009, consecutive patients with newly diagnosed PCa were enrolled in a noninterventional, multicenter, observational study. All patients had a whole-body, planar BS. Clinical history and clinical, pathological, and biochemical data were obtained from electronic patient files and questionnaires. Outcome Measurements and Statistical Analysis Bone scintigraphy was classified into 4 categories as nonmalignant, equivocal, likely malignant, or multiple metastasis. The primary end point was final imaging, which was a composite end point of BS and additional CT and MRI investigations. Results and Limitations A total of 635 eligible patients were recruited. Their median prostate-specific antigen (PSA) was 15 ng/mL, median Gleason was 7, and 80% of patients had local disease (T1 or T2). The proportion of nonmalignant BS was 61%, equivocal scans 26%, and likely or definitive metastasis 13%. A total of 154 patients had additional CT or MRI investigations. The final imaging diagnosis showed a prevalence of bone metastases in 87 (13.7%) of 635 patients. No bone metastases were observed in (1) patients with PSA of less than 10 ng/mL, independently of the clinical Tstage and Gleason score (n = 212) and (2) PSA of less than 20 ng/mL if Tstage is less than T3 and Gleason score is less than 8 (n = 97). Approximately 50% of the patients enrolled in this study met these criteria. Conclusion This is the first prospective trial to demonstrate that BS can be avoided in patients with low-risk PCa.

Observer agreement and accuracy in the evaluation of bone scans in newly diagnosed prostate cancer

ObjectiveThe aim of the study was to assess the agreement in the interpretation of bone scintigraphy (BS) in a newly diagnosed prostate cancer. Materials and methodsA total of 635 consecutive patients had their planar whole-body BS independently reviewed by three nuclear medicine physicians and classified by two grading systems: (a) a four-category scale (1: benign; 2: equivocal; 3: most likely malignant; and 4: multiple metastases) and (b) a dichotomous scale (bone metastasis present or absent). ResultsAgreement in the same category, or with one or two categories of differences, was found in 66, 34, and 1.3% of the readings, respectively. Average &kgr;-values were 0.59, 0.72, and 0.83 for unweighted, linear, and quadratic weighted variants, respectively. Very high agreement was observed (96% of the readings) with the dichotomous scale (average &kgr;=0.87); a comparison with a final imaging diagnosis with additional CT or MRI showed a sensitivity of 83% and a specificity of 98%. BS categories 1, 3, and 4 were consistent with the final imaging diagnosis in 96–99% of cases. The prevalence of metastasis was 10% in category 2. To optimize the diagnostic characteristics, category 2 should be regarded as a separate option. ConclusionClose agreement was found among trained observers for the evaluation of BS in prostate cancer. The high level of agreement with a dichotomous scale was hampered by diagnostic misclassification. A scale with equivocal findings on planar BS is considered important to allow for additional imaging and correct staging at the bone level of BS in a population with newly diagnosed prostate cancer.

Validation of contemporary guidelines for bone scintigraphy in prostate cancer staging: A prospective study in patients undergoing radical prostatectomy.

Abstract Objective: The aim of this study was to evaluate, using international urology and oncology guidelines, the criteria for performing bone scintigraphy (BS) in patients with newly diagnosed prostate cancer in a prospective setting with 2 years of follow-up after prostatectomy. Materials and methods: In a prospective setting, criteria from European and US urology and oncology guidelines were evaluated in 220 unselected patients with BS performed as a routine investigation before radical prostatectomy. A prostate-specific antigen level of 0.1 ng/ml or lower after surgery was considered successful and was used as a measure of true-negative BS. Results: Overall, 200 out of 220 patients (91%) experienced successful radical prostatectomy at 6 months, with a 2 year success rate of 83%. The proportion of redundant BS ranged from 56% to 89% among the guidelines, whereas the outcome after radical prostatectomy was 93% within 6 months after surgery and 86–89% after 2 years of follow-up, without significant differences among guideline recommendations. Conclusion: The guidelines from the American Urological Association and the criteria recently published by the present group proposed the largest proportion of redundant BS without compromising patient-related outcome.

Unexplained Bone Pain Is an Independent Risk Factor for Bone Metastases in Newly Diagnosed Prostate Cancer: A Prospective Study

OBJECTIVE To determine the relationship between bone pain and bone metastases in newly diagnosed prostate cancer. PATIENTS AND METHODS This prospective study of bone scintigraphy enrolled 567 consecutive patients with newly diagnosed prostate cancer. The presence of all-cause bone pain, known benign bone disease, and unexplained bone pain (ie, not related to known benign bone disease) was derived from a patient questionnaire. Univariate logistic regression models (LRMs) were used to assess the relationship between individual clinical variables (all-cause bone pain, unexplained bone pain, prostate-specific antigen, Gleason grade, T stage, and age) and bone metastases. A multivariate LRM was used to assess the relationship between bone metastases and all factors in combination. Agreement between the LRMs and bone metastases was estimated by accuracy and by Cohens κ. RESULTS All-cause bone pain predicted bone metastasis in univariate but not multivariate analysis. Unexplained bone pain remained an independent predictor of bone metastases in multivariate analysis (odds ratio: 4.5; P < .001). Prostate-specific antigen was the single most important predictor of bone metastases (P < .001). CONCLUSION Unexplained bone pain was a strong independent risk factor for bone metastasis. Guidelines should recommend staging bone scintigraphy in patients with unexplained bone pain, regardless of other risk factors.

Computer-assisted interpretation of planar whole-body bone scintigraphy in patients with newly diagnosed prostate cancer

PurposeThe aim of this study was to compare the diagnostic properties of EXINI BoneBSI in newly diagnosed prostate cancer in comparison with expert reading. Materials and methodsBone scintigraphy was performed in consecutive patients referred for staging at three clinics (342 patients with DICOM file format, 272 with Interfile format). Images were reported by three independent readers on a four-point scale (class 1–4) and by using a dichotomous outcome (M1 or M0). The software analyzed data in balanced mode, as well as using ‘patient-specific’ settings (based on tumor characteristics), and classified outcome as normal (N), probably normal (pN), probably abnormal (pA), and abnormal (A). ResultsClassification of bone metastasis using the software (pA+A) versus experts (class 3+4) showed a sensitivity of 93.3%, specificity of 89.3%, positive predictive value of 57.5%, and negative predictive value of 98.9% with DICOM files. The diagnostic properties of the software were notably different with Interfile format. For example, expert M1 versus software A showed a sensitivity of 90.0%, specificity of 98.9%, positive predictive value of 88.2%, and negative predictive value of 98.3% with DICOM files, versus 69.2, 88.2, 38.3, and 96.4% with Interfile format, respectively. Generally, patient-specific settings did not influence the diagnostic characteristics of the software versus balanced setting with expert reading as reference. ConclusionEXINI BoneBSI showed high sensitivity and specificity for bone metastasis in patients with newly diagnosed prostate cancer. The software ruled out metastasis with confidence, whereas the positive predictive value was modest. The diagnostic properties were different for DICOM and Interfile file formats.

Prospective evaluation of computer-assisted analysis of skeletal lesions for the staging of prostate cancer

BackgroundThe purpose of this study was to compare the agreement of the bone scan index (BSI) using EXINI BoneBSI versus experts’ readings in the initial staging for bone metastasis in prostate cancer. In addition, the diagnostic outcome was assessed in a large subset of patients where a true reference for metastases could be determined based on clinical and biochemical follow-up and/or supplementary imaging.MethodsA total of 342 patients had a bone scintigraphy as part of routine staging for prostate cancer. Supplementary imaging was obtained at the discretion of the referring urologist. After full recruitment, the BSI and the number of malignant lesions were calculated using EXINI BoneBSI, and three imaging experts independently classified bone status by a dichotomous outcome (M1 for bone metastasis, M0 for no bone metastasis). A true reference was available in a subset of the patients based on post-operative prostate-specific antigen responses after radical prostatectomy and/or supplementary imaging.ResultsSoftware analysis with a BSI > 0 as the cut-off for metastasis showed excellent agreement with expert classification for M1 disease (96% of the patients) but modest agreement for M0 disease (38%). With a BSI > 1, the agreement was 58% for M1 and 98% for M0. Software analyses based on individual European Association of Urology risk classification did not improve the diagnostic performance. Among patients with a true reference, the software showed metastasis in 64% of the M0 patients but correctly classified metastases in all M1 patients. The sensitivity was 100%, the specificity was 36%, the positive predictive value was 12.6% and the negative predictive value was 100% with a BSI >0 compared with 66.7%, 97.8%, 72.7%, and 97.0% with a BSI > 1.ConclusionThe diagnostic value of using EXINI Bone for the BSI in the staging of newly diagnosed prostate cancer is limited.

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.

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.

Prospective comparative study ofF-sodium fluoride PET/CT and planar bone scintigraphy for treatment response assessment of bone metastases in patients with prostate cancer

Abstract Aim: To compare 18F-sodium fluoride positron emission tomography/computed tomography (NaF PET/CT) and 99mTc-labelled diphosphonate bone scan (BS) for the monitoring of bone metastases in patients with prostate cancer undergoing anti-cancer treatment. Material and methods: Data from 64 patients with prostate cancer were included. The patients received androgen-deprivation therapy (ADT), next-generation hormonal therapy (NGH) or chemotherapy. The patients had a baseline scan and 1–3 subsequent scans during six months of treatment. Images were evaluated by experienced nuclear medicine physicians and classified for progressive disease (PD) or non-PD according to the Prostate Cancer Working Group 2 (PCWG-2) criteria. The patients were also classified as having PD/non-PD according to the clinical and prostate-specific antigen (PSA) responses. Results: There was no difference between NaF PET/CT and BS in the detection of PD and non-PD during treatment (McNemar’s test, p = .18). The agreement between BS and NaF PET/CT for PD/non-PD was moderate (Cohen’s kappa 0.53, 95% confidence interval 0.26–0.79). Crude agreement between BS and NaF PET/CT for the assessment of PD/non-PD was 86% (89% for ADT, n = 28; 88% for NGH, n = 16, and 80% for chemotherapy, n = 20). In most discordant cases, BS found PD when NaF PET/CT did not, or BS detected PD on an earlier scan than NaF PET/CT. Biochemical progression (27%) occurred more frequently than progression on functional imaging (BS, 22% and NaF PET/CT, 14%). Clinical progression was rare (11%), and almost exclusively seen in patients receiving chemotherapy. Conclusion: There was no difference between NaF PET/CT and BS in the detection of PD and non-PD; however, BS seemingly detects PD by the PCWG-2 criteria earlier than NaF-PET, which might be explained by the fact that NaF-PET is more sensitive at the baseline scan.

Bone Scan Index Is an Independent Predictor of Time to Castration-resistant Prostate Cancer in Newly Diagnosed Prostate Cancer: A Prospective Study

OBJECTIVE To prospectively determine the prognostic value of the bone scan index (BSI) for time to development of castration-resistant prostate cancer (CRPC) in consecutive, hormone-naïve patients with newly diagnosed prostate cancer. PATIENTS AND METHODS Eligible patients participated in a prospective, observational, multicenter study of the value of bone scintigraphy (BS) at staging. BSI was determined using the EXINI BoneBSI software in 208 consecutive patients undergoing androgen deprivation therapy. The presence or absence of bone metastases at staging was classified by BS with or without supplementary imaging. Follow-up was performed >5 years after including the last patient. RESULTS During follow-up, 149 of the 208 patients (72%) were diagnosed with CRPC. Median time to CRPC was 20 months. Median follow-up time was 4.4 years in patients without CRPC. In univariate analyses, presence of bone metastases (M1) (hazard ratio [HR] 3.00, 95% confidence interval [CI] 2.10-4.30), Gleason grade (HR 1.53, 95% CI 1.31-1.79), and BSI (HR 1.17, 95% CI 1.12-1.23) but not PSA significantly predicted time to CRPC (all, P < .001). The predictive values of M1 (HR 2.06), Gleason grade (HR 1.47), and BSI (HR 1.10) were confirmed in multivariate analyses. Log-rank test for equality of time to CRPC showed the significant predictive value of BSI (BSI = 0 vs 0 < BSI ≤ 1 vs BSI > 1, P < .001). In addition to routine assessment of M1 vs M0 status, BSI contributed to the predictive power. CONCLUSIONS BSI is an independent risk factor for the time from initiation of androgen deprivation therapy to CRPC in hormone-naïve patients. The significant prognostic factors, in rank order, were M1 status, Gleason grade, and BSI.