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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Postoperative nutritional support after pancreaticoduodenectomy in adults.
Resection of the head of the pancreas is most commonly done by a pancreaticoduodenectomy, known as a Whipple procedure. The most common indication for pancreaticoduodenectomy is malignancy, but can include benign tumours and chronic pancreatitis. Complete surgical resection, with negative margins, provides the best prospect of long-term survival. Pancreaticoduodenectomy involves specific and unique alterations to the digestive system and maintaining nutritional status (optimising outcomes and achieving resumption of a normal diet) in patients with cancer after major surgery is a challenge. Malnutrition is a risk factor following pancreaticoduodenectomy, due to the magnitude of the operation and the frequency of complications. Postoperatively, patients are fed either orally, enterally or parenterally. Oral intake may start with fluids and then progress to solid food, or may be ad libitum. Enteral feeding may be via a nasojejunal tube or feeding tube jejunostomy. Parenteral nutrition can be delivered via a central or peripheral intravenous line, and may provide full nutrition (TPN) or partial nutrition (supplemental PN).
To assess the effects of postoperative nutritional support strategies on complications and recovery in adults after pancreaticoduodenectomy.
We searched CENTRAL, MEDLINE, Embase, LILACS and CINAHL (from inception to October 2022), ongoing trials registers and other internet databases. We searched previous systematic reviews, relevant publications on the same topic and the references of included studies.
Randomised controlled trials of postoperative nutritional interventions in an inpatient setting for patients undergoing pancreaticoduodenectomy. We specifically looked for studies comparing route or timing rather than nutritional content.
Two review authors independently assessed studies for inclusion, judged the risk of bias and extracted data. Studies requiring translation were assessed for inclusion, risk of bias and data extraction by an external translator and another author. We used GRADE to evaluate the certainty of the evidence.
We included 17 studies (1897 participants). Of these, eight studies could be included in a meta-analysis. The route, timing and target of nutritional support varied widely between studies. Enteral feeding (jejunostomy, nasojejunal or gastrojejunostomy) was used in at least 13 studies (one study did not specify the method of enteral route), parenteral nutrition (PN) was used in at least 10 studies (two studies had a control of 'surgeon's preference' and no further details were given) and oral intake was used in seven studies. Overall, the evidence presented in this review is of low to very low certainty. Four studies compared jejunostomy feeding with total parenteral nutrition. When we pooled these four studies, the evidence demonstrated that jejunostomy likely results in a reduced length of hospital stay (mean difference (MD) -1.61 days, 95% confidence interval (CI) -2.31 to -0.92; 3 studies, 316 participants; moderate-certainty evidence). The evidence suggested that there may be no difference in postoperative pancreatic fistula (risk ratio (RR) 0.77, 95% CI 0.41 to 1.47; 4 studies, 346 participants; low-certainty evidence) and that there may be no difference in delayed gastric emptying (RR 0.38, 95% CI 0.04 to 3.50; 2 studies, 270 participants; very low-certainty evidence) or post pancreatectomy haemorrhage (RR 0.36, 95% CI 0.06 to 2.29; 2 studies, 270 participants; very low-certainty evidence), but the evidence is uncertain. There were no data for major and minor complications defined by the Clavien-Dindo classification. Two studies compared nasojejunal feeding with total parenteral nutrition. When the two studies were pooled, the evidence suggested that there may be little to no difference between nasojejunal feeding and TPN in the length of hospital stay (MD 1.07 days, 95% CI -2.64 to 4.79; 2 studies, 242 participants; low-certainty evidence), delayed gastric emptying (RR 1.26, 95% CI 0.83 to 1.91; 2 studies, 242 participants; low-certainty evidence) or post pancreatectomy haemorrhage (RR 1.00, 95% CI 0.62 to 1.62; 2 studies, 242 participants; low-certainty evidence). TPN may slightly improve rates of clinically relevant postoperative pancreatic fistula (RR 2.13, 95% CI 1.21 to 3.74; 2 studies, 242 participants; low-certainty evidence). One study reported on major complications (RR 1.27, 95% CI 0.83 to 1.94; very low-certainty evidence) and minor complications (RR 1.01, 95% CI 0.68 to 1.50; 204 participants; very low-certainty evidence) defined by the Clavien-Dindo classification and there may be little to no difference in effect, but the evidence is uncertain. Two studies compared jejunostomy feeding with oral intake. Of note, one of the studies used a modified surgical technique as part of the intervention. We pooled these studies and found that there may be little to no difference in the length of hospital stay (MD -1.99 days, 95% CI -4.90 to 0.91; 2 studies, 301 participants; very low-certainty evidence) or delayed gastric emptying (RR 0.98, 95% CI 0.33 to 2.88; 2 studies, 307 participants; very low-certainty evidence). One study reported on major complications (RR 1.01, 95% CI 0.44 to 2.34; 247 participants; very low-certainty evidence) and minor complications (RR 0.83, 95% CI 0.59 to 1.15; 247 participants; very low-certainty evidence) defined by the Clavien-Dindo classification, postoperative pancreatic fistula (RR 0.86, 95% CI 0.30 to 2.50; 247 participants; very low-certainty evidence) and post pancreatectomy haemorrhage (RR 2.02, 95% CI 0.52 to 7.88; 247 participants; very low-certainty evidence) and there may be little to no difference in effect on these outcomes, but the evidence is uncertain. No difference in mortality was detected in any of the analyses (Clavien-Dindo Grade V) (very low-certainty evidence).
When compared with parenteral nutrition, enteral nutrition by jejunostomy likely results in a decreased length of hospital stay and may lead to no difference in the incidence of postoperative complications. When compared with parenteral nutrition, enteral feeding by nasojejunal tube may result in no difference in the incidence of postoperative complications or length of hospital stay. When compared with oral nutrition, enteral nutrition by jejunostomy feeding may result in no difference in the incidence of postoperative complications or length of hospital stay, but the evidence is very uncertain. Further high-quality research is required and there are several ongoing studies. Given the number of different nutritional interventions available in the postoperative setting, a network meta-analysis would be more appropriate in future.
Robertson RH
，Russell K
，Jordan V
，Pandanaboyana S
，Wu D
，Windsor J
... -
《Cochrane Database of Systematic Reviews》
ResearchGate
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