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Objective To evaluate the diagnostic accuracy of observers with different levels of experience in reading F-18-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.

BACKGROUND: Melanoma-related limb lymphoedema is a well-known late effect following sentinel node biopsy (SNB), and lymph node dissection (LND) in patients treated of melanoma. However, data on associated risk factors are sparse. This study aimed to investigate factors associated with melanoma-related limb lymphoedema.METHODS: The present cross-sectional single-center clinical study included patients between 18 and 75 years with American Joint Committee on Cancer Stages I-III melanoma treated with wide local excision (WLE) and unilateral axillary or inguinal SNB and/or completion LND (CLND) or therapeutic LND (TLND). The diagnosis of secondary unilateral limb lymphoedema was based on the history, symptoms, and physical examination and staged according to the International Society of Lymphology (ISL). Data on factors associated with lymphoedema were analysed with binary logistic regression models.RESULTS: In total, 642 patients were eligible, of which 435 (68%) patients participated in the study. Among these 431 patients, 109 (25%) had lymphoedema of which 48 (44%), and 61 (56%) were classified with ISL Stages I and II-III, respectively. Multivariate analyses identified primary tumour on the limb (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.17-4.56; p value .017), inguinal surgery (OR, 6.91; 95% CI, 3.49-14.11; p value <.0001), LND (OR, 6.45; 95% CI, 3.18-13.57; p value <.0001), and persistent pain at the site of lymph node surgery as factors associated with lymphoedema (OR, 3.52; 95% CI, 1.54-8.19; p value .003). Multivariable analysis of ISL Stage II-III lymphoedema further identified limb cellulitis to be associated with lymphoedema (OR 5.74; 95% CI, 2.11-15.99; p value .0006).CONCLUSIONS: Melanoma-related limb lymphoedema is associated with inguinal surgery, LND, primary tumour on the limb, persistent pain at the site of lymph node surgery, and cellulitis of the limb. This study highlights the importance of increasing awar

The aim of this study was to determine if additional 18F-sodium fluoride PET/CT (NaF PET/CT) improves the prognostic accuracy in the initial staging of prostate cancer patients with normal bone scintigraphy undergoing prostatectomy. Methods: A prospective cohort study examined NaF PET/CT in intermediate- or high-risk prostate cancer with negative bone scintigraphy who were scheduled for prostatectomy. Biochemical response: PSA levels > 0.2 ng/mL at 6 wk and 6 mo postoperatively, PSA level < 0.2 ng/mL was biochemical failure. Results: Eighty-one patients were included in the study; 75 patients (93%) achieved biochemical responses, 6 patients had biochemical failure. NaF PET/CT indicated bone metastasis in 1 patient (1.2%), was equivocal in 7 patients (8.6%), without bone metastases in 73 patients (90.1%). Eight patients with bone metastases or equivocal results on NaF PET/CT exhibited biochemical responses. All patients with biochemical failure had negative NaF PET/CT and bone scintigraphy for bone metastases. Conclusion: NaF PET/CT has no added value for bone staging in intermediate- and high-risk prostate cancer patients with normal bone scintigraphy results undergoing prostatectomy.

Objectives: To determine the diagnostic accuracy of 68 gallium prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in comparison with 18 F-fluoride-based PET/CT (NaF-PET/CT) and whole-body magnetic resonance imaging (WB-MRI) for the detection of bone metastases in patients with prostate cancer. Methods: Sixty patients with prostate cancer were included in the period May 2016 to June 2017. The participants underwent three scans (index tests) within 30 days: a NaF-PET/CT, a WB-MRI and a PSMA-PET/CT. Experienced specialists assessed the scans. In the absence of a histological reference standard, the final diagnosis was determined as a panel diagnosis. Measures of the diagnostic performances of the index tests were calculated from patient-based dichotomous outcomes (0 or ≥ 1 bone metastasis) and pairwise compared (McNemar test). For each index test, the agreement with the final diagnosis with regard to the number of bone metastases detected (0, 1–5, > 5) and the inter-reader agreement was calculated (kappa coefficients). Results: Fifty-five patients constituted the final study population; 20 patients (36%) were classified as having bone metastatic disease as their final diagnosis. The patient-based diagnostic performances were (sensitivity, specificity, overall accuracy) PSMA-PET/CT (100%, 100%, 100%), NaF-PET/CT (95%, 97%, 96%) and WB-MRI (80%, 83%, 82%). The overall accuracy of PSMA-PET/CT was significantly more favourable compared to WB-MRI (p = 0.004), but not to NaF-PET/CT (p = 0.48). PSMA-PET/CT classified the number of bone metastases reliably compared to the final diagnosis (kappa coefficient 0.97) and with an “almost perfect” inter-reader agreement (kappa coefficient 0.93). Conclusions: The overall accuracy of PSMA-PET/CT was significantly more advantageous compared to WB-MRI, but not to NaF-PET/CT. Key Points: • PSMA-PET/CT assessed the presence of bone metastases correctly in a

INTRODUCTION: The clinical assessment of unilateral limb lymphedema is commonly based on measurements of interlimb volume differences. Reference values for interlimb percentage differences of the volume, fat mass, and lean mass measured with dual-energy X-ray absorptiometry (DXA) scan are, however, not established. The aim of the study was to establish and categorize these reference values in normal limbs.METHODS AND RESULTS: DXA scans of the normal arms of 167 and normal legs of 196 melanoma patients (aged 18-75 years, body mass index <40), respectively, were performed. The interlimb percentage difference is calculated as follows: ("Limb-of-interest"-contralateral)/contralateral × 100. The interlimb percentage differences for the limb-of-interest were stratified to upper (according to handedness) and lower limbs and categorized as none/mild, moderate, or severe, respectively, based on whether the value is below, in between, or above the two prediction limits. The prediction limits for interlimb total volume percentage difference were 6% and 10%, 0% and 4%, and 3% and 6% for the dominant arm, nondominant arm, and leg, respectively. Further data are given for interlimb percentage differences of regional (upper arm, lower arm, hand, thigh, lower leg, and foot) and total volume, fat mass, and lean mass, respectively.CONCLUSIONS: The provided clinical reference values allow for identifying and categorizing pathophysiological differences of limbs-of-interest and evaluating tissue composition.

Background Patient acceptance is an important factor when implementing imaging methods in clinical practice in line with availability, diagnostic accuracy, and cost-effectiveness. Purpose To investigate patient experience and acceptance regarding18F-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT), 11 C-choline-PET/CT, whole-body magnetic resonance imaging (WB-MRI), and 99mTc-hydroxymethane diphosphonate (HDP) single photon emission/computed tomography (SPECT/CT). Material and Methods One hundred and forty-nine patients with prostate cancer filled in a questionnaire regarding their experience of the imaging procedures they had been undergoing as part of a diagnostic accuracy study. Each patient had been undergoing a NaF-PET/CT, a WB-MRI, and either a SPECT/CT (group A) or a choline-PET/CT (group B). Results All four imaging methods received overall experience ratings at the favorable end of a 5-point Likert scale with the two PET/CT scans receiving marginally better average ratings (2.0) compared to SPECT/CT (2.2) and WB-MRI (2.3). The arm positioning above the head was the most uncomfortable part of the three nuclear medicine scans, whereas the acoustic noise was the most unpleasant part of the WB-MRI. The experience of staff instruction was relatively strongly correlated to the overall scanning experience of all four imaging modalities. Overall, the patients were willing to repeat the four imaging methods and NaF-PET/CT was the method most preferred in both groups. Conclusion Four imaging procedures were evaluated from the perspective of a selected group of prostate cancer patients. NaF-PET/CT, choline-PET/CT, WB-MRI, and bone SPECT/CT are well accepted imaging methods, and most patients prefer NaF-PET/CT.

Background: For decades, the most widely used imaging technique for myeloma bone lesions has been a whole-body skeletal X-ray survey (WBXR), but newer promising imaging techniques are evolving.Purpose: To compare WBXR with the advanced imaging techniques 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), 18F-sodium fluoride (NaF) PET/CT and whole-body magnetic resonance imaging (WB-MRI) in the detection of myeloma bone lesions.Material and Methods: Fourteen patients with newly diagnosed multiple myeloma were prospectively enrolled. In addition to WBXR, all patients underwent FDG-PET/CT, NaF-PET/CT, and WB-MRI. Experienced specialists performed blinded readings based on predefined anatomical regions and diagnostic criteria.Results: In a region-based analysis, a two-sided ANOVA test showed that the extent of detected skeletal disease depends on the scanning technique (P < 0.0001). Tukey's multiple comparison test revealed that WB-MRI on average detects significantly more affected regions than WBXR (P < 0.005), FDG-PET/CT (P < 0.0001), and NaF-PET/CT (P < 0.05). In a patient-based analysis, a Cochran's Q test showed that there are no significant differences in the proportion of patients with bone disease detected by the different scanning techniques (P = 0.23). Determination of intrareader variability resulted in Kappa coefficients corresponding to moderate (FDG-PET/CT) and substantial agreement (WB-MRI, WBXR, NaF-PET/CT).Conclusion: WB-MRI detects on average significantly more body regions indicative of myeloma bone disease compared to WBXR, FDG-PET/CT, and NaF-PET/CT. The lack of significance in the patient-based analysis is most likely due to the small number of study participants.

Abstracts Background: The aim of this cross-sectional study was to investigate the volume, fat mass, and lean mass in both upper and lower limbs measured with dual-energy X-ray absorptiometry (DXA) in melanoma patients with melanoma-related limb lymphedema.METHODS AND RESULTS: Four hundred thirty-one patients who had undergone surgical treatment with wide local excision and unilateral axillary or inguinal sentinel lymph node biopsy and/or complete lymph node dissection participated in a survey, and they underwent clinical examination and measurements of their upper or lower limbs with DXA. Limb lymphedema was diagnosed on the basis of history and characteristic physical findings on the clinical examination. The inter-limb differences in volume, fat mass, and lean mass measured with DXA were categorized as none/mild, moderate, or severe according to reference values (taking handedness into account for the upper limbs). Of the 431 patients, 109 (25%) had clinical melanoma-related limb lymphedema corresponding to 23 (10%) who had undergone axillary nodal surgery and 86 (45%) who had undergone inguinal nodal surgery. The majority of patients developed lymphedema within the first year (90%) after surgery, and the majority of lymphedemas were categorized as mild. The increase in the volume of limbs with lymphedema was primarily due to an increase in fat mass.CONCLUSION: There is a high prevalence of melanoma-related limb lymphedema. The increase in volume in the limb with lymphedema is primarily due to an increase in fat mass. This increase in fat mass in limbs with lymphedema is important for the understanding of the pathophysiology and may be important in the treatment of lymphedema.

Immune checkpoint inhibitor therapy (ICT) is a new treatment strategy developed for the treatment of cancer. ICT inhibits pathways known to downregulate the innate immune response to cancer cells. These drugs have been shown to be effective in the treatment of a variety of cancers, including metastatic melanoma and lung cancer. Challenges in response evaluation of patients in ICT have risen as immune related side effects and immune cell infiltration may be confused with progressive disease. Furthermore, the timing of the evaluation scan may be challenged by relatively slow responses. To overcome this, new response criteria for evaluating these patients with morphologic imaging have been proposed. The aim of this paper is to review and discuss the current evidence for the use of molecular imaging, e.g., PET/CT (Positron Emission Tomography/Computer Tomography) with18F-Fluorodeoxyglucoes (FDG) as an alternative imaging method for monitoring patients undergoing ICT. Following the currently available evidence, this review will primarily focus on patients with malignant melanoma.

AIM: To explore health-related quality of life (HRQoL) in recurrence-free melanoma patients, with a focus on the association between melanoma-related limb lymphoedema and HRQoL.METHODS: HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the breast cancer module (EORTC QLQ-BR23) subscales body image and future perspective, the Functional Assessment for Cancer Therapy-General subscale social/family well-being and the Hospital Anxiety and Depression Scale. Data were analysed using linear and ordinal logistic regression adjusting for age and gender.RESULTS: A total of 431 melanoma patients who had undergone wide local excision and axillary or inguinal sentinel lymph node biopsy (SLNB) and/or complete lymph node dissection (CLND) participated. No patients had had recurrence of the disease or had received adjuvant radiotherapy. The HRQoL scores improved with time after surgery. Melanoma-related limb lymphoedema was present in 109 patients (25%). Patients with lymphoedema had significantly worse HRQoL scores in the EORTC QLQ-C30 subscales global health status/quality of life, role and social functioning, fatigue, pain and financial difficulties, as well as in the QLQ-BR23 body image subscale. No associations were found between the limb affected (upper or lower limb), clinical stage of lymphoedema, duration of lymphoedema or type of surgery (SLNB or CLND) and HRQoL. We found an interaction with age and gender in the associations between lymphoedema and HRQoL: younger patients and women with lymphoedema had worse social functioning and women had significantly more impaired body image.CONCLUSIONS: The negative impact of melanoma-related limb lymphoedema on HRQoL emphasises the importance of developing strategies for increasing awareness and improving prevention and treatment of lymphoedema.

Lower limb lymphedema is a dynamic condition in which tissue composition and volume measurements are affected. Various definitions of lower limb lymphedema exist but volume differences between the limbs are widely used. It is therefore necessary to have a readily available noninvasive measurement technique allowing multiple measurements of the lower limbs. This study investigated the repeatability of duplicate volume and regional body composition measurements of the lower limb using the GE Lunar Prodigy dual-energy X-ray absorptiometry (DXA) scanner Prodigy (GE Medical Systems, Madison, WI). Twenty-seven participants (54 limbs), 14 women and 13 men aged 33-71 years with body mass index ranging from 14 to 32 kg/m(2) were recruited. Duplicate whole-body DXA scans were performed with repositioning between examinations. Regions of interest were manually drawn for the thigh, lower leg, and foot, and total volume was calculated using the density of bone mineral content, fat, and lean mass. The repeatability of the volume of the lower limb and regional thigh and lower leg tissue composition (bone mineral content, fat, and lean mass) was good with intraclass correlation coefficient values of 0.97 to 0.99, and narrow limits of agreement on the Bland-Altman plots. These results confirm DXA to be a highly repeatable method for volume and tissue composition measurements of the lower limb. In a population at risk of lymphedema, DXA offers a clinically readily available noninvasive method allowing multiple measurements of volume and tissue composition on a routine basis, important for diagnosing, monitoring, managing, and researching lymphedema.

Many studies have found that positron emission tomography-computed tomography (PET-CT) has a high sensitivity and specificity in the identification of metastasis in cervical cancer. Herlev Hospital, Denmark, has been performing PET-CTs in stage I-IV cervical cancer since 1 May 2006. The present study investigates the positive (PPV) and negative predictive value (NPV) of PET-CT in stage I disease and the clinical impact of the scan results in all disease stages.

To investigate the skeletal muscle mitochondrial function in HIV-infected patients with lipodystrophy or elevated p-lactate levels.

Udgivelsesdato: 2002-Sep, PURPOSE: The current study was designed to evaluate the role of planar bone scintigraphy in the diagnosis of sarcomatous change in osteochondromas (cartilaginous exostoses). MATERIALS AND METHODS: Histologically verified cases of chondrosarcoma and osteochondroma, in which Tc-99m bone scintigraphy was performed, were reviewed in a retrospective study. RESULTS: Twenty-two cases were evaluated. Of 11 cases with chondrosarcomas, 8 (73%) had clearly increased tracer uptake, whereas the remaining cases had normal or decreased tracer uptake. Of the 11 cases with osteochondromas, 8 (73%) had clearly increased tracer uptake, whereas the remaining cases had normal or decreased tracer uptake. No significant difference in the distribution of scintigraphic results was noted between the two pathoanatomic groups (p = 1). CONCLUSION: In conclusion, single standing planar bone scintigraphy has no value in distinguishing benign osteochondromas from malignant chondrosarcomas.