Single brain metastases - prognostic factors and impact of residual tumor burden on overall survival.

Background: Brain metastases (BM) are a common and challenging issue, with their incidence on the rise due to advancements in systemic therapies and increased patient survival. Most patients present with single BM, some of them without any further extracranial metastasis (i.e., solitary BM). The significance of postoperative intracranial tumor volume in the treatment of singular and solitary BM is still debated. Objective: This study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM. Methods: Patients with surgically treated single BM between 04/2007-01/2020 were retrospectively included. Residual tumor burden (RTB) was determined by manual segmentation of early postoperative brain MRI (72 h). Survival analyses were performed using Kaplan-Meier estimates for univariate analysis and Cox regression proportional hazards model for multivariate analysis, using preoperative Karnofsky performance status scale (KPSS), age, sex, RTB, incomplete resection and singular/solitary BM as covariates. Results: 340 patients were included, median age 64 years (54-71). 119 patients (35%) had solitary BM, 221 (65%) singular BM. Complete resection (RTB=0) was achieved in 73%, median preoperative tumor burden was 11.2 cm3 (5-25), and RTB 0 cm3 (0-0.2). Median OS of patients with singular BM was 13 months (4-33) vs 20 months (5-92) for solitary BM; p=0.062. Multivariate analysis revealed singular BM as independent risk factor for poorer OS: HR 1.840 (1.202-2.817), p=0.005. Complete vs. incomplete resection showed no significant OS difference (13 vs. 13 months, p=0.737). When focusing on solitary BM, complete resection led to a longer OS than incomplete resection (21 vs. 8 months), without statistical significance(p=0.250). Achieving RTB=0 resulted in higher OS for patients with solitary BM compared to singular BM (21 vs. 12 months, p=0.027). Patients who received postoperative radiotherapy (RT) had significantly longer OS compared to those without it (14 vs. 4 months, p<0.001), with favorable OS in those receiving stereotactic radiosurgery (SRS) (15 months (3-42), p<0.001) or hypofractionated stereotactic radiotherapy (HSRT). Conclusion: When complete intracranial tumor resection RTB=0 is achieved, patients with solitary BM have a favorable outcome compared to singular BM. Singular BM was confirmed as independent risk factor. There is a strong presumption that complete resection leads to an improved oncological prognosis. Patients with solitary BM tend to benefit with a favorable outcome following complete resection. Hence, surgical resection should be considered as a treatment option for patients presenting with either no or minimal extracranial disease. Furthermore, the highly favorable impact of postoperative RT on OS was demonstrated and confirmed, especially with SRS or HSRT.

Brain metastases in the elderly - Impact of residual tumor volume on overall survival.

Background: Due to demographic changes and an increased incidence of cancer with age, the number of patients with brain metastases (BMs) constantly increases, especially among the elderly. Novel systemic therapies, such as immunotherapy, have led to improved survival in recent years, but intracranial tumor progression may occur independently of a systemically effective therapy. Despite the growing number of geriatric patients, they are often overlooked in clinical trials, and there is no consensus on the impact of BM resection on survival. Objectives: The aim of this study was to analyze the impact of resection and residual tumor volume on clinical outcome and overall survival (OS) in elderly patients suffering from BM. Methods: Patients ≥ 75 years who had surgery for BM between April 2007 and January 2020 were retrospectively included. Residual tumor burden (RTB) was determined by segmentation of early postoperative brain MRI (72 h). Contrast-enhancing tumor subvolumes were segmented manually. "Postoperative tumor volume" refers to the targeted BMs. Impact of preoperative Karnofsky performance status scale (KPSS), age, sex and RTB on OS was analyzed. Survival analyses were performed using Kaplan-Meier estimates for the univariate analysis and the Cox regression proportional hazards model for the multivariate analysis. Results: One hundred and one patients were included. Median age at surgery was 78 years (IQR 76-81). Sixty-two patients (61%) had a single BM; 16 patients (16%) had two BMs; 13 patients (13%) had three BMs; and 10 patients (10%) had more than three BMs. Median preoperative tumor burden was 10.3 cm3 (IQR 5-25 cm3), and postoperative tumor burden was 0 cm3 (IQR 0-1.1 cm3). Complete cytoreduction (RTB = 0) was achieved in 52 patients (52%). Complete resection of the targeted metastases was achieved in 78 patients (78%). Median OS was 7 months (IQR 2-11). In univariate analysis, high preoperative KPSS (HR 0.986, 95% CI 0.973-0.998, p = 0.026) and small postoperative tumor burden (HR 1.025, 95% CI 1.002-1.047, p = 0.029) were significantly associated with prolonged OS. Patients with RTB = 0 survived significantly longer than those with residual tumor did (12 [IQR 5-19] vs. 5 [IQR 3-7] months, p = 0.007). Furthermore, prolongation of survival was significantly associated with surgery in patients with favorable KPSS, with an adjusted HR of 0.986 (p = 0.026). However, there were no significances regarding age. Conclusions: RTB is a strong predictor for prolonged OS, regardless of age or cancer type. Postoperative MRI should confirm the extent of resection, as intraoperative estimates do not warrant a complete resection. It is crucial to aim for maximal cytoreduction to achieve the best long-term outcomes for these patients, despite the fact the patients are advanced in age.

Association of immature platelets with perioperative complications in neurosurgery.

Immature platelets are newly formed platelets with an increased prothrombotic potential. This study evaluates whether immature platelets are associated with relevant complications in neurosurgical patients. Data were obtained in the frame of a prospectively conducted observational study exploring the association between immature platelets and major cardiovascular events after surgery. Immature platelet fraction (IPF) and H-IPF (highly fluorescent immature platelet fraction) were measured preoperatively and postoperatively at the neurosurgical ward (24-72 hours after surgery). Therapy-relevant complications after surgery were stratified using the Clavien-Dindo Grade (CDG >2) as primary outcome. Data were analyzed in 391 neurosurgical patients. While preoperatively there were no differences in IPF or H-IPF, patients with higher therapy-complication grades had higher values post-op compared to patients with lower grade complications (≤2 CDG). Cut-off values identified by receiver operating characteristic curve analysis revealed that there were significantly more patients with H-IPF ≥0.95% in the group with serious complications (CDG >2) [odds ratio OR (95% confidence interval CI) = 2.06 (1.09-3.9), p = .025], whereas this association was not present for the IPF cutoff value. In a multivariate model, H-IPF≥0.95% was independently associated with serious complications after surgery [OR (95% CI) = 1.97 (1.03-3.78), p = .041]. These findings suggest that H-IPF is associated with surgical complications and may improve risk stratification of neurosurgical patients (clinicaltrials.gov: NCT02097602, registration date: 27/03/2014).

What is the context?Immature platelets are newly formed platelets with a higher thrombotic potential and play an important role in atherothrombotic events.Higher levels of immature platelets were observed in patients with acute coronary syndrome or stroke.Lately, the focus in immature platelet research shifted from observation to outcomes. Immature platelets were identified as independent predictors of major cardiovascular events in cardiologic patients with coronary artery disease. Besides, an association between immature platelets and major cardiovascular events was described in surgical patients after non-cardiac surgery.What is new?This study builds on these findings and extends the focus to perioperative complications after neurosurgery.The data were obtained prospectively in the frame of an observational clinical trial exploring the association of immature platelets and major cardiovascular events in general. Data measured in the neurosurgical cohort of that study (391 neurosurgical patients) were analyzed in the present work.Within the limitations of our study, our analyses suggest that the postoperative IPF (immature platelet fraction) and H-IPF (highly fluorescent immature platelet fraction) values, which were measured at the neurosurgical ward after surgery are both associated with higher therapy-relevant complication grades (>2 according to Clavien-Dindo Grade), whereas preoperatively obtained values were not.What is the impact?This is the first study showing a relationship between immature platelets and therapy-relevant perioperative complications in neurosurgical patients. It could be a pilot trial for varied scientific questions including risk stratification of neurosurgical patients.

Immature platelets as a novel biomarker for adverse cardiovascular events in patients after non-cardiac surgery.

This study evaluates whether immature platelets (IPF) determined in the post anesthesia care unit (PACU) can predict major adverse cardiovascular events (MACE) or other thromboembolic events after intermediate and high-risk surgery. IPF are increased in patients with acute coronary syndrome and recently gained interest as novel biomarker for risk stratification. In this prospective observational trial 732 patients undergoing intermediate or high-risk non-cardiac surgery were enrolled (NCT02097602). IPF was measured preoperatively and postoperatively in the PACU. Primary outcome was a composite endpoint defined as MACE, deep vein thrombosis or pulmonary embolism during hospital stay (modMACE). A cut off for IPF identifying a threshold between a low and high risk for modMACE was calculated by log-rank optimization. A multivariate Cox regression was calculated in a forward stepwise manner to assess the relation between this IPF cut off and modMACE as well as other established risk factors (inclusion if p<0.05). Preoperatively, there were no differences in IPF between patients with and without modMACE (3.1 % [2.2 % - 4.7 %](median [interquartile range]) vs. 2.8 % [1.9 % - 4.3 %]. Patients with modMACE (28 of 730 patients; 3.8 %) had higher IPF values in the PACU compared to patients without modMACE (3.6 % [2.6-6 %] vs. 2.9 % [2-4.4 %]; p=0.011). The optimal cut off of IPF > 5.4 % was associated with an increased risk for modMACE after adjustment for covariates (hazard ratio: 2.528; 95 % confidence interval: 1.156 to 5.528, p=0.02). In conclusion, IPF is an independent predictor of modMACE after surgery and might improve risk stratification of surgical patients.

Algorithm-guided goal-directed haemodynamic therapy does not improve renal function after major abdominal surgery compared to good standard clinical care: a prospective randomised trial.

BACKGROUND: Acute kidney injury is a common complication after major surgery. In this study, we investigated whether an algorithm-guided goal-directed haemodynamic therapy (GDT) can improve renal outcome compared to good standard clinical care. METHODS: A total of 180 patients undergoing major abdominal surgery were prospectively and randomly assigned to one of two groups: in the GDT group, patients were treated with a GDT algorithm using transpulmonary thermodilution while standard care was applied to the control patients. Change in creatinine was studied as the primary end point, postoperative complications as well as 1-year mortality as secondary outcomes. Haemodynamics in GDT and control patients were compared calculating goal-achievement rates. RESULTS: Postoperative change in creatinine (18 ± 39 µmol/l (control) vs. 16 ± 42 µmol/l (GDT); mean difference (95 % confidence interval) 1.6 µmol/l (-10 to 13 µmol/l)) was comparable between the GDT and the control group. Postoperative complications and mortality during hospital stay and after 1 year were not influenced by the use of a GDT algorithm. Achievement rates of haemodynamic goals were not higher in the GDT group compared to the already high (>80 %) rates in the control group. Multivariate regression analysis revealed intraoperative hypotension (MAP < 70 mmHg) and postoperative hypovolaemia (GEDI < 640 ml/m(2)) as risk factors for postoperative renal impairment. CONCLUSIONS: In this study, GDT was not superior to standard clinical care in order to avoid renal failure after major abdominal surgery. The reason for this finding is most likely the high achievement rate of haemodynamic goals in the control group, which cannot be improved by the GDT algorithm. TRIAL REGISTRATION: Clinicaltrials.gov; NCT01035541; registered 17 December 2009.

Self-Reported, Structured Measures of Recovery to Detect Postoperative Morbidity.

Previous studies have focused on postoperative anaesthetic visit as a tool for measuring postoperative recovery or patient's satisfaction. Whether it could also improve timely recognition of complications has not been studied yet. Aim of our study was to assess pathological findings in physical examination requiring further intervention during postoperative visit and to explore whether a self-administered version of the Quality of Recovery (QoR)-9 score, compared to a detailed medical history, can act as a screening tool for identification of patients who show a low risk to develop postoperative complications. This observational study included 918 patients recovering from various types of non-cardiac surgery and anaesthesia. The postoperative visit implied three steps: measuring the QoR-9 score, a structured medical history and a physical examination. QoR-9-score showed a comparable negative predictive value (0.93 vs. 0.92) and a higher sensitivity of finding at least one pathological examination than a detailed medical history (0.92 vs. 0.81 respectively). At least one postoperative pathological examination finding was observed in 23.7% of the patients. Our approach presents a strategy on screening postoperative patients in order to identify patients whose examination and consequent treatment should be intensified. In further studies the question could be addressed whether the postoperative visit may help to reduce complications and mortality after surgery.