18 F FDG PET/CT versus 99m Tc MDP Bone scintigraphy in imaging of metastatic osseous disease in breast cancer patients; Solving the discrepancies in light of serum markers.

To assess the performance of 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) versus 99m Tc MDP bone scan in assessment of metastatic osseous disease in breast cancer patients in relation to serum markers. We reviewed PET/CT studies and bone scans for 37 patients (mean age of 55.38 ± 13.08 years) with metastatic breast cancer to bone. To assess metastatic osseous burden, we used semiquantitative scores derived from PET/CT (PMS) and bone scans (BMS). We used McNemar test to compare lesion detection between both modalities and receiver operator characteristic analysis to define the cutoff value of serum CA 15-3 that best predicts additional value for PET/CT over bone scan. In 13 patients (35.1%), more lesions or higher-intensity lesions were detected on PET/CT, while only 4 patients (10.8%) had more prominent lesions on bone scans ( P = 0.049). Additional lesions seen on PET/CT are predominantly osteolytic or medullary (early phase). Most lesions with higher uptake on bone scans appear sclerotic (late phase). CA 15-3 was positively correlated to PMS ( r = 0.386; P = 0.018) but not to BMS ( r = -0.027; P = 0.874). However, serum alkaline phosphatase was positively correlated to both PMS ( r = 0.389; P = 0.017) and BMS ( r = 0.363; P = 0.027). CA 15-3 value of >47 U/ml best predicted additional findings on PET/CT compared to bone scans (area under the curve = 0.708; P = 0.0261). FDG PET/CT detects metastatic osseous lesions during an earlier phase. A higher CA 15-3 predicts a higher metastatic burden on PET/CT but not on bone scan. Bone scans are less specific, likely by missing early lesions and detecting persistent uptake in healing sclerotic lesions.

Nasr H ，Alnajashi N ，Farghaly H ，Alqarni A ... -  《-》

Diagnosing Bone Metastases in Breast Cancer: A Systematic Review and Network Meta-Analysis on Diagnostic Test Accuracy Studies of 2-[(18)F]FDG-PET/CT, (18)F-NaF-PET/CT, MRI, Contrast-Enhanced CT, and Bone Scintigraphy.

This systematic review and network meta-analysis aimed to compare the diagnostic accuracy of 2-[18F]FDG-PET/CT, 18F-NaF-PET/CT, MRI, contrast-enhanced CT, and bone scintigraphy for diagnosing bone metastases in patients with breast cancer. Following PRISMA-DTA guidelines, we reviewed studies assessing 2-[18F]FDG-PET/CT, 18F-NaF-PET/CT, MRI, contrast-enhanced CT, and bone scintigraphy for diagnosing bone metastases in high-stage primary breast cancer (stage III or IV) or known primary breast cancer with suspicion of recurrence (staging or re-staging). A comprehensive search of MEDLINE/PubMed, Scopus, and Embase was conducted until February 2024. Inclusion criteria were original studies using these imaging methods, excluding those focused on AI/machine learning, primary breast cancer without metastases, mixed cancer types, preclinical studies, and lesion-based accuracy. Preference was given to studies using biopsy or follow-up as the reference standard. Risk of bias was assessed using QUADAS-2. Screening, bias assessment, and data extraction were independently performed by two researchers, with discrepancies resolved by a third. We applied bivariate random-effects models in meta-analysis and network meta-analyzed differences in sensitivity and specificity between the modalities. Forty studies were included, with 29 contributing to the meta-analyses. Of these, 13 studies investigated one single modality only. Both 2-[18F]FDG-PET/CT (sensitivity: 0.94, 95% CI: 0.89-0.97; specificity: 0.98, 95% CI: 0.96-0.99), MRI (0.94, 0.82-0.98; 0.93, 0.87-0.96), and 18F-NaF-PET/CT (0.95, 0.85-0.98; 1, 0.93-1) outperformed the less sensitive modalities CE-CT (0.70, 0.62-0.77; 0.98, 0.97-0.99) and bone scintigraphy (0.83, 0.75-0.88; 0.96, 0.87-0.99). The network meta-analysis of multi-modality studies supports the comparable performance of 2-[18F]FDG-PET/CT and MRI in diagnosing bone metastases (estimated differences in sensitivity and specificity, respectively: 0.01, -0.16 - 0.18; -0.02, -0.15 - 0.12). The results from bivariate random effects modelling and network meta-analysis were consistent for all modalities apart from 18F-NaF-PET/CT. We concluded that 2-[18F]FDG-PET/CT and MRI have high and comparable accuracy for diagnosing bone metastases in breast cancer patients. Both outperformed CE-CT and bone scintigraphy regarding sensitivity. Future multimodality studies based on consented thresholds are warranted for further exploration, especially in terms of the potential role of 18F-NaF-PET/CT in bone metastasis diagnosis in breast cancer.

Gerke O ，Naghavi-Behzad M ，Nygaard ST ，Sigaroudi VR ，Vogsen M ，Vach W ，Hildebrandt MG ... -  《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》

Multi-level tuberculosis of the spine identified by 18 F-FDG-PET/CT and concomitant urogenital tuberculosis: a case report from the spinal TB X cohort.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and typically infects the lungs. However, extrapulmonary forms of TB can be found in approximately 20% of cases. It is suggested, that up to 10% of extrapulmonary TB affects the musculoskeletal system, in which spinal elements (spinal tuberculosis, STB) are involved in approximately 50% of the cases. STB is a debilitating disease with nonspecific symptoms and diagnosis is often delayed for months to years. In our Spinal TB X Cohort, we aim to describe the clinical phenotype of STB using whole-body 18 F-fluorodeoxyglucose positron emission tomography computed tomography (PET/CT) and to identify a specific gene expression profile for the different stages of dissemination on PET/CT. Here we report on the first patient recruited into our cohort who underwent PET/CT before treatment initiation, at 6-months and at 12-months - time of TB treatment completion. A 27-year-old immunocompetent male presented with severe thoracolumbar back pain for 9 months with severe antalgic gait and night sweats. Magnetic resonance imaging (MRI) of the whole spine revealed multilevel spinal disease (T5/6, T11/12, L3/4) in keeping with STB. After informed consent and recruitment into the Spinal TB X Cohort, the patient underwent PET/CT as per protocol, which revealed isolated multilevel STB (T4-7, T11/12, L3/4) with no concomitant lung or urogenital lesion. However, sputum and urine were Xpert MTB/RIF Ultra positive and Mtb was cultured from the urine sample. CT-guided biopsy of the T11/12 lesion confirmed drug-sensitive Mtb on Xpert MTB/RIF Ultra and the patient was started on TB treatment according to local guidelines for 12 months. The 6-month follow-up PET/CT revealed new and existing spinal lesions with increased FDG-uptake despite significant improvement of clinical features and laboratory markers. After 9 months of treatment, the patient developed an acute urethral stricture, most likely due to urogenital TB, and a suprapubic catheter was inserted. The 12-month PET/CT showed significantly decreased PET/CT values of all lesions, however, significant persistent spinal inflammation was present at the end of TB treatment. Clinically, the patient was considered cured by the TB control program and currently awaits urethroplasty. In our case, PET/CT emerged as a valuable imaging modality for the initial assessment, surpassing MRI by revealing more comprehensive extensive disease. Subsequent PET/CT scans at 6-month uncovered new lesions and increased inflammation in existing ones, while by the end of TB treatment, all lesions exhibited improvement. However, the interpretation of FDG avidity remains ambiguous, whether it correlates with active infection and viable Mtb. or fibro- and osteoblast activity indicative of the healing process. Additionally, the absence of extraspinal TB lesions on PET/CT despite positive microbiology from sputum and urine maybe explained by paucibacillary, subclinical infection of extraspinal organs. The Spinal TB X Cohort endeavours to shed light on whole-body imaging patterns at diagnosis, their evolution midway through TB treatment, and upon treatment completion. Ultimately, this study aims to advance our understanding of the biology of this complex disease.

Scherer J ，Mukasa SL ，Wolmarans K ，Guler R ，Kotze T ，Song T ，Dunn R ，Laubscher M ，Pape HC ，Held M ，Thienemann F ... -  《-》

Diagnostic ability of [(18)F]FDG PET/CT for distinguishing benign from malignant spleen lesions.

[18F]Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is a non-invasive imaging modality used in the differential diagnosis of splenic lesions, although ideal parameters and thresholds remain unclear. The present study evaluated the ability of [18F]FDG PET/CT, including its visual and quantitative parameters, to differentiate between benign and malignant splenic lesions. Patients who underwent [18F]FDG PET/CT following the detection of splenic lesions on contrast-enhanced CT were retrospectively analysed. Visual parameters assessed on [18F]FDG PET/CT included whole spleen uptake intensity, lesion multiplicity, and lesion uptake, and quantitative parameters included maximum standardised uptake value (SUVmax), lesion-to-background ratio (LBR), metabolic tumour volume (MTV), total lesion glycolysis (TLG), and lesion size. Parameters differentiating between benign and malignant lesions were evaluated by Pearson's chi-square test, Mann-Whitney U-test, and receiver operating characteristics (ROC) curve analysis. Splenic lesion uptake (p = 0.001) was the only visual parameter significantly distinguishing between benign and malignant lesions. ROC curve analysis demonstrated that SUVmax had the largest area under the ROC, 0.91 (p < 0.001), with an optimal cut-off > 5.3 having a sensitivity of 90.3% and a specificity of 80.6%. Subgroup analysis of malignant lesions showed that SUVmax (p = 0.013), LBR (p = 0.012), and TLG (p  = 0.034) were significantly higher in splenic lymphomas than in splenic metastases. Of the [18F]FDG PET/CT parameters investigated, SUVmax had the highest accuracy in diagnosing malignant splenic lesions and was significantly higher in splenic lymphomas than in splenic metastases. Visual determination of [18F]FDG uptake by splenic lesions may be an easily evaluated parameter. SUVmax and visual grade of [18F]FDG PET/CT help to differentiate spleen lesions. [18F]FDG PET/CT is useful for discriminating between benign and malignant spleen lesions. Many splenic lesions are difficult to diagnose on anatomical imaging, with histopathologic analyses are required. SUVmax of PET/CT provided the diagnostic ability to differentiate between benign and malignant splenic lesions. More than normal spleen uptake can be a convenient parameter to diagnose malignant spleen lesions.

Lee DY ，Kim YI ，Ryu JS 《-》