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
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Intra-individual comparison of epicardial adipose tissue characteristics on coronary CT angiography between photon-counting detector and energy-integrating detector CT systems.
To explore the potential differences in epicardial adipose tissue (EAT) volume and attenuation measurements between photon-counting detector (PCD) and energy-integrating detector (EID)-CT systems.
Fifty patients (mean age 69 ± 8 years, 41 male [82 %]) were prospectively enrolled for a research coronary CT angiography (CCTA) on a PCD-CT within 30 days after clinical EID-based CCTA. EID-CT acquisitions were reconstructed using a Bv40 kernel at 0.6 mm slice thickness. The PCD-CT acquisition was reconstructed at a down-sampled resolution (0.6 mm, Bv40; [PCD-DS]) and at ultra-high resolutions (PCD-UHR) with a 0.2 mm slice thickness and Bv40, Bv48, and Bv64 kernels. EAT segmentation was performed semi-automatically at about 1 cm intervals and interpolated to cover the whole epicardium within a threshold of -190 to -30 HU. A subgroup analysis was performed based on quartile groups created from EID-CT data and PCD-UHRBv48 data. Differences were measured using repeated-measures ANOVA and the Friedman test. Correlations were tested using Pearson's and Spearman's rho, and agreement using Bland-Altman plots.
EAT volumes significantly differed between some reconstructions (e.g.
138 ml [IQR 100, 188]; PCD-DS: 147 ml [110, 206]; P<0.001). Overall, correlations between PCD-UHR and EID-CT EAT volumes were excellent, e.g. PCD-UHRBv48: r: 0.976 (95 % CI: 0.958, 0.987); P<0.001; with good agreement (mean bias: -9.5 ml; limits of agreement [LoA]: -40.6, 21.6). On the other hand, correlations regarding EAT attenuation was moderate, e.g. PCD-UHRBV48: r: 0.655 (95 % CI: 0.461, 0.790); P<0.001; mean bias: 6.5 HU; LoA: -2.0, 15.0.
EAT attenuation and volume measurements demonstrated different absolute values between PCD-UHR, PCD-DS as well as EID-CT reconstructions, but showed similar tendencies on an intra-individual level. New protocols and threshold ranges need to be developed to allow comparison between PCD-CT and EID-CT data.
Kravchenko D
,Vecsey-Nagy M
,Tremamunno G
,Schoepf UJ
,O'Doherty J
,Luetkens JA
,Kuetting D
,Isaak A
,Hagar MT
,Emrich T
,Varga-Szemes A
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Detection of myeloma-associated osteolytic bone lesions with energy-integrating and photon-counting detector CT.
A recent innovation in computed tomography (CT) imaging has been the introduction of photon-counting detector CT (PCD-CT) systems, which are able to register the number and the energy level of incoming x‑ray photons and have smaller detector elements compared with conventional CT scanners that operate with energy-integrating detectors (EID-CT).
The study aimed to evaluate the potential benefits of a novel, non-CE certified PCD-CT in detecting myeloma-associated osteolytic bone lesions (OL) compared with a state-of-the-art EID-CT.
Nine patients with multiple myeloma stage III (according to Durie and Salmon) underwent magnetic resonance imaging (MRI), EID-CT, and PCD-CT of the lower lumbar spine and pelvis. The PCD-CT and EID-CT images of all myeloma lesions that were visible in clinical MRI scans were reviewed by three radiologists for corresponding OL. Additionally, the visualization of destructions to cancellous or cortical bone, and trabecular structures, was compared between PCD-CT and EID-CT.
Readers detected 21% more OL in PCD-CT than in EID-CT images (138 vs. 109; p < 0.0001). The sensitivity advantage of PCD-CT in lesion detection increased with decreasing lesion size. The visualization quality of cancellous and cortical destructions as well as of trabecular structures was rated higher by all three readers in PCD-CT images (mean image quality improvements for PCD-CT over EID-CT were +0.45 for cancellous and +0.13 for cortical destructions).
For myeloma-associated OL, PCD-CT demonstrated significantly higher sensitivity, especially with small size. Visualization of bone tissue and lesions was considered significantly better in PCD-CT than in EID-CT. This implies that PCD-CT scanners could potentially be used in the early detection of myeloma-associated bone lesions.
Grözinger M
,Wennmann M
,Sawall S
,Wehrse E
,Sedaghat S
,Neelsen C
,Bauer F
,Goldschmidt H
,Weru V
,Ziener CH
,Kopp-Schneider A
,Schlemmer HP
,Rotkopf LT
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