Sacral-Nerve-Sparing Planning Strategy in Pelvic Sarcomas/Chordomas Treated with Carbon-Ion Radiotherapy.

Nachankar A ，Schafasand M ，Hug E ，Martino G ，Góra J ，Carlino A ，Stock M ，Fossati P ... -  《Cancers》

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 ... -  《-》

Interventions for supporting pregnant women's decision-making about mode of birth after a caesarean.

Pregnant women who have previously had a caesarean birth and who have no contraindication for vaginal birth after caesarean (VBAC) may need to decide whether to choose between a repeat caesarean birth or to commence labour with the intention of achieving a VBAC. Women need information about their options and interventions designed to support decision-making may be helpful. Decision support interventions can be implemented independently, or shared with health professionals during clinical encounters or used in mediated social encounters with others, such as telephone decision coaching services. Decision support interventions can include decision aids, one-on-one counselling, group information or support sessions and decision protocols or algorithms. This review considers any decision support intervention for pregnant women making birth choices after a previous caesarean birth. To examine the effectiveness of interventions to support decision-making about vaginal birth after a caesarean birth.Secondary objectives are to identify issues related to the acceptability of any interventions to parents and the feasibility of their implementation. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013), Current Controlled Trials (22 July 2013), the WHO International Clinical Trials Registry Platform Search Portal (ICTRP) (22 July 2013) and reference lists of retrieved articles. We also conducted citation searches of included studies to identify possible concurrent qualitative studies. All published, unpublished, and ongoing randomised controlled trials (RCTs) and quasi-randomised trials with reported data of any intervention designed to support pregnant women who have previously had a caesarean birth make decisions about their options for birth. Studies using a cluster-randomised design were eligible for inclusion but none were identified. Studies using a cross-over design were not eligible for inclusion. Studies published in abstract form only would have been eligible for inclusion if data were able to be extracted. Two review authors independently applied the selection criteria and carried out data extraction and quality assessment of studies. Data were checked for accuracy. We contacted authors of included trials for additional information. All included interventions were classified as independent, shared or mediated decision supports. Consensus was obtained for classifications. Verification of the final list of included studies was undertaken by three review authors. Three randomised controlled trials involving 2270 women from high-income countries were eligible for inclusion in the review. Outcomes were reported for 1280 infants in one study. The interventions assessed in the trials were designed to be used either independently by women or mediated through the involvement of independent support. No studies looked at shared decision supports, that is, interventions designed to facilitate shared decision-making with health professionals during clinical encounters.We found no difference in planned mode of birth: VBAC (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.97 to 1.10; I² = 0%) or caesarean birth (RR 0.96, 95% CI 0.84 to 1.10; I² = 0%). The proportion of women unsure about preference did not change (RR 0.87, 95% CI 0.62 to 1.20; I² = 0%).There was no difference in adverse outcomes reported between intervention and control groups (one trial, 1275 women/1280 babies): permanent (RR 0.66, 95% CI 0.32 to 1.36); severe (RR 1.02, 95% CI 0.77 to 1.36); unclear (0.66, 95% CI 0.27, 1.61). Overall, 64.8% of those indicating preference for VBAC achieved it, while 97.1% of those planning caesarean birth achieved this mode of birth. We found no difference in the proportion of women achieving congruence between preferred and actual mode of birth (RR 1.02, 95% CI 0.96 to 1.07) (three trials, 1921 women).More women had caesarean births (57.3%), including 535 women where it was unplanned (42.6% all caesarean deliveries and 24.4% all births). We found no difference in actual mode of birth between groups, (average RR 0.97, 95% CI 0.89 to 1.06) (three trials, 2190 women).Decisional conflict about preferred mode of birth was lower (less uncertainty) for women with decisional support (standardised mean difference (SMD) -0.25, 95% CI -0.47 to -0.02; two trials, 787 women; I² = 48%). There was also a significant increase in knowledge among women with decision support compared with those in the control group (SMD 0.74, 95% CI 0.46 to 1.03; two trials, 787 women; I² = 65%). However, there was considerable heterogeneity between the two studies contributing to this outcome ( I² = 65%) and attrition was greater than 15 per cent and the evidence for this outcome is considered to be moderate quality only. There was no difference in satisfaction between women with decision support and those without it (SMD 0.06, 95% CI -0.09 to 0.20; two trials, 797 women; I² = 0%). No study assessed decisional regret or whether women's information needs were met.Qualitative data gathered in interviews with women and health professionals provided information about acceptability of the decision support and its feasibility of implementation. While women liked the decision support there was concern among health professionals about their impact on their time and workload. Evidence is limited to independent and mediated decision supports. Research is needed on shared decision support interventions for women considering mode of birth in a pregnancy after a caesarean birth to use with their care providers.

Horey D ，Kealy M ，Davey MA ，Small R ，Crowther CA ... -  《Cochrane Database of Systematic Reviews》

Stereotactic vs Hypofractionated Radiotherapy for Inoperable Stage I Non-Small Cell Lung Cancer: The LUSTRE Phase 3 Randomized Clinical Trial.

Swaminath A ，Parpia S ，Wierzbicki M ，Kundapur V ，Faria S ，Okawara GS ，Tsakiridis TK ，Ahmed N ，Bujold A ，Hirmiz K ，Owen T ，Leong N ，Ramchandar K ，Filion E ，Lau H ，Gabos Z ，Thompson R ，Yaremko B ，Mehiri S ，Louie AV ，Quan K ，Levine MN ，Wright JR ，Whelan TJ ... -  《-》

Fenoldopam for preventing and treating acute kidney injury.

Fenoldopam is a short-acting benzazepine selective dopaminergic A1 (DA1) receptor agonist with increased activity at the D1 receptor compared with dopamine. Activation of the DA1 receptors increases kidney blood flow because of dilatation of the afferent and efferent arterioles. Previous reviews have been published on the efficacy and safety of fenoldopam for acute kidney injury (AKI); however, they either combined data on its effect on both prevention and treatment of AKI, focused on only those undergoing cardiac surgery and/or excluded children. This review aimed to assess the benefits and harms of fenoldopam for the prevention or treatment of AKI in children and adults. We searched the Cochrane Kidney and Transplant Register of Studies up to 12 November 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. We included randomised controlled trials (RCTs) evaluating fenoldopam for the prevention or treatment of AKI in children and adults following surgery, radiocontrast exposure or sepsis. Two authors independently assessed studies for eligibility, assessed the studies for risk of bias and extracted data from the studies. Dichotomous outcomes were presented as relative risk (RR) with 95% confidence intervals (CI). For continuous outcomes, the mean difference (MD) with 95% CI was used. Statistical analysis was performed using the random-effects model. We assessed the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We identified 25 RCTs, including 3339 randomised participants. Twenty-three studies used fenoldopam for preventing AKI and two for the treatment of AKI. Nine studies included participants undergoing cardiac surgery, and one included children. The risks of bias for sequence generation and concealment were low in 11 and 13 studies, respectively. Only 13 and 18 studies were at low risk of performance bias and detection bias, respectively. The risk of attrition bias and selective reporting were judged to be at low risk of bias in 17 and 10 studies, respectively. We included data in the meta-analyses from eight of the 14 studies comparing fenoldopam with placebo or saline, all six studies comparing fenoldopam with dopamine, all five studies comparing fenoldopam with N-acetylcysteine (NAC) for the prevention of AKI and from the two studies comparing fenoldopam with placebo or saline for the treatment of AKI. Compared with placebo or saline fenoldopam probably results in fewer participants developing AKI (RR 0.72, 95% CI 0.53 to 0.98; 8 studies, 1147 participants; I2 = 48%; moderate certainty) but may make little or no difference to the number requiring kidney replacement therapy (KRT) (RR 0.81, 95% CI 0.31 to 2.15; 7 studies, 835 participants; I2 = 17%), risk of death (RR 0.76, 95% CI: 0.58 to 1.00; 7 studies, 944 participants; I2 = 0%) or change in urine output (SMD 0.20, 95% CI -0.44 to 0.84; 2 studies, 58 participants; I2 = 34%; all low certainty). Fenoldopam may result in a shorter stay in the ICU (MD -1.81 days; 95% CI -2.41 to -1.21; 4 studies, 403 participants; I2 = 0%). It is uncertain whether adverse events (hypotension, myocardial infarction, drug intolerance, cardiac arrhythmias) differed between the treatment groups as the certainty of the evidence was very low. In patients undergoing cardiac surgery, fenoldopam, compared to placebo or saline, may make little or no difference to the prevention of AKI, the need for KRT or death. Compared with dopamine, fenoldopam may make little or no difference to the prevention of AKI (RR 0.62, 95% CI 0.23 to 1.68; 4 studies, 398 participants; I2 = 78%), the number requiring KRT (RR 0.74, 95% CI 0.29 to 1.87; 4 studies, 434 participants; I2 = 0%) or the risk of death (RR 1.27, 95% CI 0.36 to 4.50; 2 studies, 174 participants; I2 = 0%) (all low certainty). It is uncertain whether participants receiving fenoldopam were more likely to develop hypotension compared with those receiving dopamine (RR 3.00, 95% CI 1.06 to 8.52; 1 study, 80 participants; very low certainty). Change in urine output was not reported. It is uncertain whether fenoldopam compared with NAC prevents AKI (RR 1.68, 95% CI 0.79 to 3.56; 3 studies, 359 participants; I2 = 38%), reduces the need for KRT (RR 0.96, 95% CI 0.15 to 6.26; 2 studies, 137 participants; I2 = 0%), or the risk of death (RR 1.05, 95% CI 0.07 to 15.66; 1 study, 39 participants) (all very low certainty). It is uncertain whether hypotension was more frequent with fenoldopam (RR 5.10, 95% CI 0.25, 104.94; 1 study, 192 participants; very low certainty). Change in urine output was not reported. In participants with established AKI, it is uncertain whether fenoldopam compared to placebo or half saline reduces the numbers needing KRT (RR: 0.91, 95% CI 0.54 to 1.54; 2 studies, 822 participants; I2 = 58%; very low certainty) or the risk of death (RR 0.81, 95% CI 0.44 to 1.48; 2 studies, 822 participants; I2 = 66%; very low certainty), or if it increases the risk of hypotension (RR 1.65, 95% CI 1.22 to 2.22; 2 studies, 822 participants; I2 = 0%; very low certainty). Fenoldopam administration in patients at risk of AKI is probably associated with a lower risk of developing AKI and shorter ICU stay when compared with placebo or saline, but has little or no effect on the need for KRT or the risk of death. In those undergoing cardiac surgery, fenoldopam may not confer any benefits compared with placebo or saline. Furthermore, it remains unclear whether fenoldopam is more or less effective than either dopamine or NAC in reducing the risk for AKI or the need for KRT. Further well-designed and adequately powered studies are required to evaluate the efficacy and safety of fenoldopam in preventing or treating AKI.

Esezobor CI ，Bhatt GC ，Effa EE ，Hodson EM ... -  《Cochrane Database of Systematic Reviews》