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

BackgroundDue 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.ObjectivesThe 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.MethodsPatients ≥ 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.ResultsOne 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.ConclusionsRTB 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

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

BackgroundBrain 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.ObjectiveThis study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM.MethodsPatients 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.Results340 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).ConclusionWhen 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

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

<div><p>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.</p></div

Quality of recovery-9 (QoR-9) questionnaire.

<p>^a: Percentages are of the total number of patients (N = 771)</p><p>Quality of recovery-9 (QoR-9) questionnaire.</p

Pathological medical history results.

<p>^a: Percentages are of the total number of patients (N = 771).</p><p>Pathological medical history results.</p

Pathological examination results in case of normal QoR-9/medical history results.

<p>^a: Percentages are of the total number of patients (N)</p><p>^b: Percentages are of the total number of patients for each pathological examination result</p><p>Pathological examination results in case of normal QoR-9/medical history results.</p

Medical history and pathological examinations.

<p>N = number of patients with a certain number of complaints in medical history; n = number of patients with at least one pathological examination for each number of complaints in medical history;</p><p>^a positive predictive value;</p><p>^b risk of a pathological finding in patients without any disorder</p><p>Medical history and pathological examinations.</p

Risk to overlook a patient with a pathological examination result using QoR-9 vs. medical history depending on the prevalence.

<p>Risk to overlook a patient with a pathological examination result using QoR-9 vs. medical history depending on the prevalence.</p

Consort diagram.

<p>Consort diagram.</p