Preoperative Metastatic Brain Tumor-Associated Intracerebral Hemorrhage Is Associated With Dismal Prognosis.

OBJECT: Intra-tumoral hemorrhage is considered an imaging characteristic of advanced cancer disease. However, data on the influence of intra-tumoral hemorrhage in patients with brain metastases (BM) remains scarce. We aimed at investigating patients with BM who underwent neurosurgical resection of the metastatic lesion for a potential impact of preoperative hemorrhagic transformation on overall survival (OS). METHODS: Between 2013 and 2018, 357 patients with BM were surgically treated at the authors' neuro-oncological center. Preoperative magnetic resonance imaging (MRI) examinations were assessed for the occurrence of malignant hemorrhagic transformation. RESULTS: 122 of 375 patients (34%) with BM revealed preoperative intra-tumoral hemorrhage. Patients with hemorrhagic transformed BM exhibited a median OS of 5 months compared to 12 months for patients without intra-tumoral hemorrhage. Multivariate analysis revealed preoperative hemorrhagic transformation as an independent and significant predictor for worsened OS. CONCLUSIONS: The present study identifies preoperative intra-tumoral hemorrhage as an indicator variable for poor prognosis in patients with BM undergoing neurosurgical treatment.

The Surgical Management of Brain Metastases in Non-Small Cell Lung Cancer (NSCLC): Identification of the Early Laboratory and Clinical Determinants of Survival.

BACKGROUND: Brain metastases (BM) indicate advanced states of cancer disease and cranial surgery represents a common treatment modality. In the present study, we aimed to identify the risk factors for a reduced survival in patients receiving a surgical treatment of BM derived from non-small cell lung cancer (NSCLC). METHODS: A total of 154 patients with NSCLC that had been surgically treated for BM at the authors' institution between 2013 and 2018 were included for a further analysis. A multivariate analysis was performed to identify the predictors of a poor overall survival (OS). RESULTS: The median overall survival (mOS) was 11 months (95% CI 8.2-13.8). An age > 65 years, the infratentorial location of BM, elevated preoperative C-reactive protein levels, a perioperative red blood cell transfusion, postoperative prolonged mechanical ventilation (>48 h) and the occurrence of postoperative adverse events were identified as independent factors of a poor OS. CONCLUSIONS: The present study identified several predictors for a worsened OS in patients that underwent surgery for BM of NSCLC. These findings might guide a better risk/benefit assessment in the course of metastatic NSCLC therapy and might help to more sufficiently cope with the challenges of cancer therapy in these advanced stages of disease.

Outcome of Elderly Patients With Surgically Treated Brain Metastases.

OBJECT: In the light of an aging population and ongoing advances in cancer control, the optimal management in geriatric patients with brain metastases (BM) poses an increasing challenge, especially due to the scarce data available. We therefore analyzed our institutional data with regard to factors influencing overall survival (OS) in geriatric patients with BM. METHODS: Between 2013 and 2018, patients aged ≥ 65 years with surgically treated BM were included in this retrospective analysis. In search of preoperatively identifiable risk factors for poor OS, in addition to the underlying cancer, the preoperative frailty of patients was analyzed using the modified Frailty Index (mFI). RESULTS: A total of 180 geriatric patients with surgically treated BM were identified. Geriatric patients categorized as least-frail achieved a median OS of 18 months, whereas frailest patients achieved an OS of only 3 months (p<0.0001). Multivariable cox regression analysis detected "multiple intracranial metastases" (p=0.001), "infratentorial localization" (p=0.011), "preoperative CRP >5 mg/l" (p=0.01) and "frailest patients (mFI ≥ 0.27)" (p=0.002) as predictors for reduced OS in older patients undergoing surgical treatment for BM. CONCLUSIONS: In this retrospective series, pre-operative frailty was associated with poor survival in elderly patients with BM requiring surgery. Our analyses warrant thorough counselling and support of affected elderly patients and their families.

The Impact of Prolonged Mechanical Ventilation on Overall Survival in Patients With Surgically Treated Brain Metastases.

OBJECTIVE: Surgical resection represents a common treatment modality in patients with brain metastasis (BM). Postoperative prolonged mechanical ventilation (PMV) might have an enormous impact on the overall survival (OS) of these patients suffering from advanced cancer disease. We therefore have analyzed our institutional database with regard to a potential impact of PMV on OS of patients who had undergone surgery for brain metastases. METHODS: 360 patients with surgically treated brain metastases were included. The definition of PMV consisted of postoperative mechanical ventilation lasting for more than 48 hours. Analysis of survival incorporating established prognostic factors such as age, location of BM, and preoperative physical status was performed. RESULTS: 14 of 360 patients with BM (4%) suffered from postoperative PMV after surgical treatment of BM. Patients with PMV presented in a significantly more impaired neurological condition preoperatively than patients without (p<0.0001). Multivariate analysis determined PMV to be a significant prognostic factor for OS after surgical treatment in patients with BM, independent of other predictive factors (p<0.0001). CONCLUSIONS: The present study demonstrates postoperative PMV as significantly related to poor OS in patients with surgically treated BM. Postoperative PMV is a so far underestimated prognostic predictor, but might be utilized for optimized patient management early in the postoperative phase. For this purpose, the results of the present study should encourage the initiation of further scientific efforts.

Prognostic Value of Preoperative Inflammatory Markers in Melanoma Patients with Brain Metastases.

BACKGROUND: Metastatic melanoma disease is accompanied by highly systemic inflammatory responses. The prognostic value of preoperative laboratory inflammation markers in brain metastatic melanoma patients has not been adequately investigated so far. METHODS: Preoperative inflammatory blood parameters were correlated to overall survival (OS) rates in melanoma patients that underwent surgery for brain metastasis (BM) between 2013 and 2019 at the authors' institution. Receiver operating characteristic (ROC) analyses were used for cutoff determination of routine laboratory parameters. RESULTS: Median OS in the present cohort of 30 melanoma patients with surgically treated BM was 7 months (95% confidence interval (CI) 5.7-8.3). Initial elevated C-reactive protein (CRP) levels (>10 mg/L), neutrophil-to-lymphocyte ratio (NLR) ≥ 4, platelet-to-lymphocyte ratio (PLR) ≥ 145, and lymphocyte-to-monocyte ratio (LMR) < 2 were associated with significantly reduced OS rates. CONCLUSIONS: The present study identifies several preoperative peripheral inflammatory markers as indicators for poor prognosis in melanoma patients with BM undergoing neurosurgical treatment. Elevated initial CRP values, higher NLR and PLR, and lower LMR were associated with reduced OS and, thus, might be incorporated into preoperative interdisciplinary treatment planning and counseling for affected patients.

Comorbidity Burden and Presence of Multiple Intracranial Lesions Are Associated with Adverse Events after Surgical Treatment of Patients with Brain Metastases.

Surgical resection is a key treatment modality for brain metastasis (BM). However, peri- and postoperative adverse events (PAEs) might be associated with a detrimental impact on postoperative outcome. We retrospectively analyzed our institutional database with regard to patient safety indicators (PSIs), hospital-acquired conditions (HACs) and specific cranial surgery-related complications (CSCs) as high-quality metric profiles for PAEs in patients who had undergone surgery for BM in our department between 2013 and 2018. The comorbidity burden was assessed by means of the Charlson comorbidity index (CCI). A multivariate analysis was performed to identify independent predictors for the development of PAEs after surgical resection of BM. In total, 33 patients (8.5%) suffered from PAEs after surgery for BM. Of those, 17 PSI, 5 HAC and 11 CSC events were identified. Multiple brain metastases (p = 0.02) and a higher comorbidity burden (CCI > 10; p = 0.003) were associated with PAEs. In-hospital mortality of patients suffering from a PAE was significantly higher than that of patients without a PAE (24% vs. 0.6%; p < 0.0001). Awareness of risk factors for postoperative complications enables future prevention and optimal response, particularly in vulnerable oncological patients. The present study identified the presence of multiple brain metastases and increased comorbidity burden associated with PAEs in patients suffering from BM.

Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab.

Treatment options for patients with platinum-refractory, recurrent, metastatic head and neck squamous cell carcinoma (HNSCC) are limited, and prognosis is poor. Nivolumab (Opdivo) has been approved by the US Food and Drug Administration (FDA) for the treatment of patients with recurrent or metastatic HNSCC who have disease progression on or after platinum-based therapy. Recently, in patients with metastatic malignant melanoma a significant improvement of outcome and response was achieved with the combination of ipilimumab (CTLA4 antibody) and the programmed death (PD)-1 inhibitor nivolumab compared with monotherapy. Based on these results, the combination of nivolumab and ipilimumab has been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma. So far, there have been no data concerning the combination of nivolumab and ipilimumab in squamous cell head and neck cancer. We here present the case of a 46-year-old male with refractory squamous cell head and neck cancer, who was successfully treated with the PD-1 inhibitor nivolumab in combination with the anti-CTLA4 antibody ipilimumab.