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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Standard- versus extended-duration anticoagulation for primary venous thromboembolism prophylaxis in acutely ill medical patients.
Venous thromboembolism (VTE) includes two interrelated conditions, deep vein thrombosis (DVT) and pulmonary embolism (PE). Risk factors include dehydration, prolonged immobilization, acute medical illness, trauma, clotting disorders, previous thrombosis, varicose veins with superficial vein thrombosis, exogenous hormones, malignancy, chemotherapy, infection, inflammation, pregnancy, obesity, smoking, and advancing age. It is estimated that hospitalized patients are 100 times more likely to develop VTE and, compared with surgical patients, medical patients often have more severe forms of VTE. VTE carries a significant risk of morbidity and mortality. Prophylactic strategies, including mechanical and pharmacological methods, are recommended for patients at risk of VTE. Pharmacological prophylaxis is considered the standard practice for acutely ill medical patients at risk of developing VTE in the absence of contraindications. For hospitalized patients, the risk of VTE extends beyond hospital stay and up to 90 days, with most events occurring within 45 days of discharge. Despite that, it remains unclear whether extended-duration anticoagulation for primary VTE prophylaxis would provide benefits without added risks or harm.
To assess the benefits and risks of standard- versus extended-duration anticoagulation for primary VTE prophylaxis in acutely ill medical patients.
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialized Register, CENTRAL, MEDLINE, Embase, CINAHL and Web of Science databases, as well as the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers up to 27 March 2023. We also searched reference lists of all included studies for additional references and searched the last five years of the American Society of Hematology conference proceedings.
We included randomized controlled trials (RCTs) comparing standard-duration versus extended-duration anticoagulation for primary VTE prophylaxis in acutely ill medical patients (adults being treated in a medical inpatient setting).
We used the standard methodological procedures set by Cochrane. At least two authors independently screened titles and abstracts for inclusion and performed data extraction. Two authors independently assessed the risk of bias (RoB) using the Cochrane RoB 2 tool. We analyzed outcomes data using the risk ratio (RR) with 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence for each outcome. Our outcomes of interest were assessed in the short term (during the treatment period and within 45 days of hospitalization) and long term (assessed beyond 45 days of hospitalization). Primary outcomes were symptomatic VTE, major bleeding, and all-cause mortality. Secondary outcomes were total VTE, a composite of fatal and irreversible vascular events (including myocardial infarction, non-fatal PE, cardiopulmonary death, stroke), fatal bleeding, and VTE-related mortality.
A total of seven RCTs fulfilled our inclusion criteria, comprising 40,846 participants. All studies contributing data to our outcomes were at low risk of bias in all domains. Most studies reported the outcomes in the short term. Extended-duration anticoagulation, compared with standard-duration anticoagulation, for primary VTE prophylaxis in acutely ill medical patients reduced the risk of short-term symptomatic VTE (RR 0.60, 95% CI 0.46 to 0.78; standard-duration 12 per 1000, extended-duration 7 per 1000, 95% CI 6 to 10; number needed to treat for an additional beneficial outcome [NNTB] 204, 95% CI 136 to 409; 4 studies, 24,773 participants; high-certainty evidence). This benefit, however, was offset by an increased risk of short-term major bleeding (RR 2.05, 95% CI 1.51 to 2.79; standard-duration 3 per 1000, extended duration 6 per 1000, 95% CI 5 to 8; number needed to treat for an additional harmful outcome [NNTH] 314, 95% CI 538 to 222; 7 studies, 40,374 participants; high-certainty evidence). Extended-duration anticoagulation, compared with standard-duration, results in little to no difference in short-term all-cause mortality (RR 0.97, 95% CI 0.87 to 1.08; standard-duration 34 per 1000, extended-duration 33 per 1000, 95% CI 30 to 37; 5 studies, 38,080 participants; high-certainty evidence), reduced short-term total VTE (RR 0.75, 95% CI 0.67 to 0.85; standard-duration 37 per 1000, extended duration 28 per 1000, 95% CI 25 to 32; NNTB 107, 95% CI 76 to 178; 5 studies, 33,819 participants; high-certainty evidence), and short-term composite of fatal and irreversible vascular events (RR 0.71, 95% CI 0.56 to 0.91; standard-duration 41 per 1000, extended-duration 29 per 1000, 95% CI 23 to 37; NNTB 85, 95% CI 50 to 288; 1 study, 7513 participants; high-certainty evidence). Extended-duration anticoagulation may result in little to no difference in short-term fatal bleeding (RR 2.28, 95% CI 0.84 to 6.22; standard-duration 0 per 1000, extended-duration 0 per 1000, 95% CI 0 to 1; 7 studies, 40,374 participants; low-certainty evidence), and likely results in little to no difference in short-term VTE-related mortality (RR 0.78, 95% CI 0.58 to 1.05; standard-duration 5 per 1000, extended-duration 4 per 1000 95% CI 3 to 6; 6 studies, 36,170 participants; moderate-certainty evidence).
In the short term, extended- versus standard-duration anticoagulation for primary VTE prophylaxis in acutely ill medical patients reduced the risk of symptomatic VTE at the expense of an increased risk of major bleeding. Extended-duration anticoagulation resulted in little to no difference in all-cause mortality. Extended-duration anticoagulation reduced the risk of total VTE and the composite of fatal and irreversible vascular events, but may show little to no difference in fatal bleeding and VTE-related mortality. Further data, with longer follow-up, are needed to determine the optimal agent and duration for primary VTE prophylaxis in acutely ill medical patients.
Kolkailah AA
，Abdelghaffar B
，Elshafeey F
，Magdy R
，Kamel M
，Abuelnaga Y
，Nabhan AF
，Piazza G
... -
《Cochrane Database of Systematic Reviews》
ResearchGate
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