Low Karnofsky Performance Score Research Articles

Epidemiological Analysis of Cancer Patients Diagnosed With Cranial Metastasis at Initial Presentation

Introduction: Metastatic lesions are the most common brain tumors, comprising 52% of all cases. Early diagnosis is crucial to improve patient outcomes, but many cases remain undiagnosed until advanced stages. This study aimed to investigate the characteristics of patients diagnosed with brain metastasis concurrently with their primary malignancy, examine prognostic factors, and compare these findings with brain metastases of known primary origins. Method: A retrospective analysis was conducted on 184 patients between 18-80 years diagnosed with brain tumors between January 2018 and January 2019. Patient data were collected from clinical records, and statistical analyses were performed using SPSS 26.0. Results: Out of the total patients, 43% were diagnosed brain metastases. Among these, 33% had no known primary malignancy at diagnosis. In this group, 92.3% were over 50 years old, and 77% were male. The most frequent primary cancer was lung cancer (81%). Males had an average time to metastasis diagnosis approximately twice as long as females. A higher incidence of metastasis correlated with a lower Karnofsky Performance Score, indicating reduced operability and quality of life. Conclusion: Early diagnosis is critical to improving outcomes. Routine cranial imaging for patients over 50 may aid in early intervention.

Microsurgical Management of Pineal Region Tumors

BackgroundPineal tumours are rare and the pineal region is a challenging surgical location for neurosurgeons. The present study aimed to investigate the effects of microsurgical management in patients with pineal region tumours and explore probable factors associated with preoperative hydrocephalus, postoperative hydrocephalus remission, and prolonged length of hospital stay (LoS). MethodsA retrospective study of patients with pineal region tumours, who underwent microsurgical management at the First Affiliated Hospital of Soochow University(Jiangsu, China) between 1 January 2010 and 31 October, 2022, was conducted. ResultsData from 36 patients were included in this study. The top five common symptoms included headache (58%), dizziness (44%), double vision (22%), vomiting (19%), and nausea (14%). Patients with a lower Karnofsky Performance Score (KPS), younger age, and larger maximum tumour diameters were more vulnerable to preoperative hydrocephalus. Preoperative hydrocephalus also led to a prolonged postoperative LoS (P=0.021). Patients with a lower KPS score (P=0.020) or larger maximum tumour diameters (P=0.045) were more likely to achieve postoperative remission of hydrocephalus. Most postoperative complications led to increased hospital LoS. ConclusionMicrosurgical resection of pineal tumours yielded favourable long-term outcomes. Patients with a lower KPS score, younger age, and larger maximum tumour diameters were more vulnerable to preoperative hydrocephalus and prolonged LoS. Patients with a lower KPS score or larger tumour diameter were likely to achieve significant remission of hydrocephalus after tumour resection.

Risk of Tumor Progression after Microsurgery for Parasellar Meningioma Invading the Cavernous Sinus.

Parasellar meningiomas, which may invade the cavernous sinus, pose a significant challenge to neurosurgeons due to the high risk of postoperative neurological deficits associated with aggressive resection of the intracavernous part of the tumour. Therefore, subtotal tumour removal followed by observation or radiotherapy for the residual meningioma in the cavernous sinus is recommended. This retrospective study aimed to identify prognostic factors influencing recurrence and progression-free survival (PFS) in parasellar meningiomas invading the cavernous sinus after incomplete surgical treatment. This study included adult patients diagnosed with benign parasellar meningioma (WHO Grade I) invading the cavernous sinus, treated at our institution between 2006 and 2020, and with a postsurgical follow-up of at least 3 years. Surgical treatment involved near-total resection (NTR) with an intracavernous residual tumour or subtotal resection (STR) with additional extracavernous tumour left in place. Kaplan-Meier analysis estimated PFS rates, and Cox regression tested survival time differences between groups. Among the 32 patients, the estimated median PFS was 11 years. Radiotherapy improved 5-year PFS only in patients with STR (p = 0.003). The univariate analysis identified preoperative tumour size, low preoperative Karnofsky Performance Score (KPS), and marked brain oedema as significant factors affecting meningioma progression after surgery. The multivariate analysis confirmed tumour size as an independent factor for progression (p = 0.012). For patients with parasellar meningioma invading the cavernous sinus, extracavernous tumour removal followed by close radiological surveillance of the residual intracavernous meningioma is a safe and appropriate strategy. When an extracavernous tumour component is left, adjuvant stereotactic radiotherapy or radiosurgery is recommended to control tumour growth.

Enhancing outcomes: neurosurgical resection in brain metastasis patients with poor Karnofsky performance score - a comprehensive survival analysis.

A reduced Karnofsky performance score (KPS) often leads to the discontinuation of surgical and adjuvant therapy, owing to a lack of evidence of survival and quality of life benefits. This study aimed to examine the clinical and treatment outcomes of patients with KPS < 70 after neurosurgical resection and identify prognostic factors associated with better survival. Patients with a preoperative KPS < 70 who underwent surgical resection for newly diagnosed brain metastases (BM) between 2007 and 2020 were retrospectively analyzed. The KPS, age, sex, tumor localization, cumulative tumor volume, number of lesions, extent of resection, prognostic assessment scores, adjuvant radiotherapy and systemic therapy, and presence of disease progression were analyzed. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with better survival. Survival > 3 months was considered favorable and ≤ 3 months as poor. A total of 140 patients were identified. Median overall survival was 5.6 months (range 0-58). There was no difference in the preoperative KPS between the groups of > 3 and ≤ 3 months (50; range, 20-60 vs. 50; range, 10-60, p = 0.077). There was a significant improvement in KPS after surgery in patients with a preoperative KPS of 20% (20 vs 40 ± 20, p = 0.048). In the other groups, no significant changes in KPS were observed. Adjuvant radiotherapy was associated with better survival (44 [84.6%] vs. 32 [36.4%]; hazard ratio [HR], 0.0363; confidence interval [CI], 0.197-0.670, p = 0.00199). Adjuvant chemotherapy and immunotherapy resulted in prolonged survival (24 [46.2%] vs. 12 [13.6%]; HR 0.474, CI 0.263-0.854, p = 0.013]. Systemic disease progression was associated with poor survival (36 [50%] vs. 71 [80.7%]; HR 5.975, CI 2.610-13.677, p < 0.001]. Neurosurgical resection is an appropriate treatment modality for patients with low KPS. Surgery may improve functional status and facilitate further tumor-specific treatment. Combined treatment with adjuvant radiotherapy and systemic therapy was associated with improved survival in this cohort of patients. Systemic tumor progression has been identified as an independent factor for a poor prognosis. There is almost no information regarding surgical and adjuvant treatment in patients with low KPS. Our paper provides novel data on clinical outcome and survival analysis of patients with BM who underwent surgical treatment.

Prognostic Significance of the Cachexia Index in Patients with Non-Small-Cell Lung Cancer and Brain Metastases after Stereotactic Radiotherapy.

The cachexia index (CXI) has been proposed as a novel biomarker of cancer cachexia. We aimed to investigate the association between CXI and survival outcomes after stereotactic radiotherapy (SRT) in patients with non-small cell lung cancer (NSCLC) and brain metastases. Data from 145 patients with NSCLC, who underwent SRT for brain metastases between April 2016 and August 2020, were retrospectively analyzed. Cachexia index was calculated as skeletal muscle index (SMI) × serum albumin level/neutrophil-to-lymphocyte ratio, whereas SMI was calculated from computed tomography images captured at the L1 level. Kaplan-Meier curves and Cox proportional hazards models were used to assess progression-free survival (PFS) and overall survival (OS). The prognostic values of CXI and other cachexia biomarkers were assessed using receiver operating characteristic (ROC) curve analysis. Lower pretreatment CXI (<30.8) was significantly associated with older age (P = .039), lower Karnofsky performance score (P = .009), and a high likelihood of extracranial metastases (P = .001). Patients with a lower pretreatment CXI had a significantly shorter PFS and OS than those with a higher CXI (P < .001). Multivariate analysis revealed that pretreatment CXI was an independent risk factor for both PFS, hazard ratio (HR) = 2.375; 95% confidence interval (CI) = 1.610-3.504; P < .001, and OS, HR = 2.340; 95% CI = 1.562-3.505; P < .001. Compared with other biomarkers, pretreatment CXI had the highest area under the ROC curve value for prognostic assessment, reaching 0.734. Moreover, the loss of CXI was a strong risk factor for survival independent of pretreatment CXI (P = .011). Cachexia index may serve as a clinically useful tool for predicting survival outcomes of patients with NSCLC and brain metastases who undergo SRT.

SURVIVAL OUTCOMES AMONG PATIENTS WITH HIGH-GRADE GLIOMA: A SINGLE INSTITUTION RETROSPECTIVE STUDY

BackgroundThe prognosis for glioma patients is poor, despite recent advances in diagnosis and treatment. Understanding Glioma’s clinical characteristics and predictive factors is crucial for patient treatment and management.&#x0D; ObjectivesTo assess the survival duration of HGG patients at a single facility and to discover clinical determinants of treatment outcome in HGG treated with a combined modality approach in Zhianawa Cancer Center.&#x0D; Patients and MethodsThis study included 133 patients with high-grade gliomas diagnosed between January 2015 and January 2020; these patients were referred to the Zhianawa Cancer Center. A retrospective analysis of the clinical data included survival outcomes, tumour characteristics, and demographic information. While the Cox regression model was used for the evaluation of multivariate data to look at the risk factors for mortality, on the other hand, survival data were analyzed using Kaplan-Meier curves with a log-rank test.&#x0D; ResultsIn this particular patient cohort, grade IV glioma (83.9%), grade III glioma (16.1), and glioblastoma (81.4%) were the most common pathological types. A poor prognosis was associated with not using temozolomide, having a Karnofsky Performance Score (KPS) of less than 70%, and not receiving radiotherapy. Univariate analysis showed low KPS (70) to increase the risk of mortality. Patients who had radiotherapy with normal fractionation, concurrent chemotherapy, and radiotherapy adjuvant chemotherapy had the highest overall survival rates.&#x0D; ConclusionMortality was significantly related to aging, absence of seizures, presence of motor alteration, pathological grade IV gliosarcoma, glioblastoma multiform, and non-standard radiation dose.

Caspase-3 in glioma indicates an unfavorable prognosis by involving surrounding angiogenesis and tumor cell repopulation.

Effective biomarkers for estimating glioma prognosis are deficient. Canonically, caspase-3 acts as an "apoptosis executioner". However, its prognostic role in glioma and mechanistic effects on prognosis remain unclear. With glioma tissue microarrays, the prognostic roles of cleaved caspase-3 and its association with angiogenesis were explored. Next, by analyzing the mRNA microarray data from the CGGA, the prognostic role of CASP3 expression and correlations between CASP3 and markers of glioma angiogenesis and proliferation were investigated. To biologically interpret the prognostic role of caspase-3 in glioma, the influence of caspase-3 on surrounding angiogenesis and glioma cell repopulation was investigated with an in vitro cell co-culture model, which comprises irradiated U87 cells and un-irradiated firefly luciferase (Fluc)-labeled HUVEC (HUVEC-Fluc) or U87 (U87-Fluc) cells. The over-expressed dominant-negative caspase-3 was used to suppress normal caspase-3 activity. High levels of cleaved caspase-3 expression were associated with poor survival outcomes in glioma patients. Higher microvessel density was observed in patients with high levels of cleaved caspase-3 expression. By mining the microarray data in CGGA, it was revealed that higher CASP3 expression was found in glioma patients with lower Karnofsky Performance score, higher WHO grade, malignant histological subtype, wild-type IDH. Higher CASP3 expression indicated a worse survival rate in glioma patients. Patients with high CASP3 expression and negative IDH mutation showed the worst survival rate. Positive correlations were found between CASP3 and markers of tumor angiogenesis and proliferation. Subsequent data based on an in vitro cell co-culture model revealed that caspase-3 in irradiated glioma cells mediated pro-angiogenic and repopulation-promoting effects via regulating COX-2 signaling. With glioma tissue microarrays, high levels of COX-2 expression showed inferior survival outcomes in glioma patients. Glioma patients with high levels of cleaved caspase-3 and COX-2 expression showed the worst survival outcomes. This study innovatively identified an unfavorable prognostic role of caspase-3 in glioma. The pro-angiogenic and repopulation-prompting effects of caspase-3/COX-2 signaling may explain its unfavorable prognostic role and offer novel insights into therapy sensitization and curative effect prediction of glioma.

The impact of neurological performance and volumetrics on overall survival in brain metastasis in colorectal cancer: a retrospective single-center case series

BackgroundBrain metastasis (BM) of colorectal cancer is a disease with a poor prognosis of only a few months survival. However, it is difficult to estimate the individual prognosis of each patient due to the lack of definitive prognosis parameters. The number of metastases and the Karnofsky performance score are known predictors for survival. We investigated whether or not the neurological performance score and the tumor volumetrics are equally suitable predictors for survival.DesignAll patients with histologically diagnosed BM linked to colorectal cancer between 2012 and March 2020 were reviewed. The Medical Research Council Neurological Performance Score was used to quantify neurological performance. Univariate analysis with Kaplan-Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression.ResultsTwenty-five patients were included in our analysis with an overall survival of 4.9 months after surgery of the BM. Survival decreased in the univariate analysis with increasing postoperative neurological performance score, low Karnofsky performance score, absence of radiation therapy and radiation therapy modality. The neurological performance score is a reliable scoring parameter for estimating the prognostic course analogous to the Karnofsky performance score. Neither preoperative nor post resection residual tumor volume had any impact on overall survival in our small cohort.ConclusionOur data suggest that the postoperative neurological performance is a valuable prognostic factor for colorectal cancer patients with BM. Tumor volumetrics show no correlation to survival. Further investigations with a larger number of cases are mandatory.

Racial and Socioeconomic Disparities in Patients With Meningioma: A Retrospective Cohort Study.

Meningiomas are the most common intracranial neoplasms. Although genomic analysis has helped elucidate differences in survival, there is evidence that racial disparities may influence outcomes. African Americans have a higher incidence of meningiomas and poorer survival outcomes. The etiology of these disparities remains unclear, but may include a combination of pathophysiology and other factors. To determine factors that contribute to different clinical outcomes in racial populations. We retrospectively reviewed 305 patients who underwent resection for meningiomas at a single tertiary care facility. We used descriptive statistics and univariate, multivariable, and Kaplan-Meier analyses to study clinical, radiographical, and histopathological differences. Minority patients were more likely to present through the emergency department than an outpatient clinic (P < .0001). They were more likely to present with more advanced clinical symptoms with lower Karnofsky Performance scores, more frequently had peritumoral edema (P = .0031), and experienced longer postoperative stays in the hospital (P = .0053), and African-American patients had higher hospitalization costs (P = .046) and were more likely to be publicly insured. Extent of resection was an independent predictor of recurrence freedom (P = .039). Presentation in clinic setting trended toward an association with recurrence-free survival (P = .055). We observed no significant difference in gross total resection rates, postoperative recurrence, or recurrence-free survival. Minority patients are more likely to present with severe symptoms, require longer perioperative hospitalization, and generate higher hospitalization costs. This may be due to socioeconomic factors that affect access to health care. Targeting barriers to access, especially to subspecialty care, may facilitate more appropriate and timely diagnosis, thereby improving patient care and outcomes.

Predictors of Long-Term Survival Among Patients With Brain Metastases

The prognosis for patients with brain metastases (BrM) remains guarded, with population-based data indicating a median survival of 3-12 months. However, a subset of patients with BrM display prolonged survival. We sought to characterize the likelihood and predictors associated with survival ≥ 5 years after BrM diagnosis.We identified 1,370 patients diagnosed with BrM at a tertiary cancer center between 2008 and 2015 who either died or survived ≥ 5 years. Patients censored before 5 years were excluded from the analysis (N = 66). Multivariable logistic regression was used to characterize predictors of long-term (i.e., ≥ 5 years) survival after BrM diagnosis (odds ratios > 1 indicated a greater odds of long-term survival). Median survival for subgroups was calculated with the Kaplan-Meier method; comparisons were made with the log-rank test.Among all 1,304 patients, median survival after BrM diagnosis was 10.8 months. In total, 123 patients (9.4%) survived ≥ 5 years. On multivariable logistic regression, significant predictors of survival ≥ 5 years included: breast as the primary tumor site vs. the reference of non-small cell lung cancer (NSCLC) (OR: 2.44 [95% CI, 1.23-4.83], P = 0.01), high Karnofsky performance score (KPS) (90-100) vs. low KPS (< 90) (OR: 2.32 [95% CI, 1.48-3.62], P < 0.001), and lack of progressive extracranial disease at time of BrM diagnosis (OR: 2.33 [95% CI, 1.47-3.70], P < 0.001). Factors significantly associated with not surviving ≥ 5 years included: receipt of whole brain radiation therapy vs. the reference of SRT as initial management (OR: 0.30 [95% CI, 0.13-0.70], P = 0.005), presence of 2-4 BrM vs. 1 BrM (OR: 0.63 [95% CI, 0.40-1.00], P = 0.05), an increasing number of extracranial sites of disease (OR: 0.73 per additional site [95% CI, 0.59-0.90], P = 0.003), and an increasing number of systemic therapy regimens for metastatic disease prior to diagnosis of BrM (OR: 0.64 per additional regimen [95% CI, 0.50-0.84], P = 0.001). When limiting to patients with NSCLC for whom EGFR and ALK status were known, there were significant differences in survival among patients with an ALK rearrangement, EGFR mutation, or neither (median survival of 30.9, 15.0, and 12.7 months, respectively, P = 0.04). Subsetting patients with breast cancer based on receptor subtype, there were significant differences in survival among patients with HER2-positive, hormone receptor-positive/HER2-negative, or triple-negative breast cancer (median survival of 26.0, 11.2, and 6.5 months, respectively, P < 0.001).Although patients with BrM generally have a poor prognosis, select patients live for ≥ 5 years. Multidisciplinary teams caring for favorable sub-populations should consider the long-term impact of oncologic therapy when formulating treatment recommendations.N. Lamba: None. D.N. Cagney: Research Grant; NhTheraguix, Viewray. P.J. Catalano: None. P. Wen: None. D. Haas-Kogan: Research Grant; Novartis; Cellworks. A.A. Aizer: Research Grant; Varian. Consultant; Novartis. Advisory Board; Seattle Genetics.

Surgical strategies for older patients with glioblastoma

ObjectiveWhile adjuvant treatment regimens have been modified for older patients with glioblastoma (GBM), surgical strategies have not been tailored.MethodsClinical data of 48 consecutive patients aged 70 years or older, who underwent surgical resection for GBM with intraoperative ultrasonography (IoUS) alone or combination with intraoperative MRI (IoMRI) at Yale New Haven Hospital were retrospectively reviewed. Variables were analyzed, and comparative analyses were performed.ResultsThe addition of IoMRI was not superior to IoUS alone in terms of overall survival (OS) (P = 0.306), Karnofsky Performance Score (KPS) at postoperative 6 weeks (P = 0.704) or extent of resection (P = 0.263). Length of surgery (LOSx), however, was significantly longer (P = 0.0002) in the IoMRI group. LOSx (P = 0.015) and hospital stay (P = 0.025) were predictors of postoperative complications. Increased EOR (GTR or NTR) (P = 0.030), postoperative adjuvant treatment (P < 0.0001) and postoperative complications (P = 0.006) were predictive for OS. Patients with relatively lower preoperative KPS scores (<70) showed significant improvement at postoperative 6 weeks (P<0.0001). Patients with complications (P = 0.038) were more likely to have lower KPS at postoperative 6 weeks.ConclusionsAggressive management with surgical resection should be considered in older patients with GBM, even those with relatively poor KPS. The use of ioMRI in this population does not appear to confer any measurable benefit over ioUS in experienced hands, but prolongs the length of surgery significantly, which is a preventable prognostic factor for impeding care.

Stereotactic Radiosurgery for Differentiated Thyroid Cancer Brain Metastases: An International, Multicenter Study.

Background: Brain metastases (BM) from differentiated thyroid cancer are rare. Stereotactic radiosurgery (SRS) is commonly used for the treatment of BMs; however, the experience with SRS for thyroid cancer BMs remains limited. The goal of this international, multi-centered study was to evaluate the efficacy and safety of SRS for thyroid cancer BMs. Methods: From 10 institutions participating in the International Radiosurgery Research Foundation, we pooled patients with established papillary or follicular thyroid cancer diagnosis who underwent SRS for histologically confirmed or radiologically suspected BMs. We investigated patient overall survival (OS), local tumor control, and adverse radiation events (AREs). Results: We studied 42 (52% men) patients who underwent SRS for 122 papillary (83%) or follicular (17%) thyroid cancer BMs. The mean age at SRS was 59.86 ± 12.69 years. The mean latency from thyroid cancer diagnosis to SRS for BMs was 89.05 ± 105.49 months. The median number of BMs per patient was 2 (range: 1-10 BMs). The median SRS treatment volume was 0.79 cm3 (range: 0.003-38.18 cm3), and the median SRS prescription dose was 20 Gy (range: 8-24 Gy). The median survival after SRS for BMs was 14 months (range: 3-58 months). The OS was significantly shorter in patients harboring ≥2 BMs, when compared with patients with one BM (Log-rank = 5.452, p = 0.02). Two or more BMs (odds ratio [OR] = 3.688; confidence interval [CI]: 1.143-11.904; p = 0.03) and lower Karnofsky performance score at the time of SRS (OR = 0.807; CI: 0.689-0.945; p = 0.008) were associated with shorter OS. During post-SRS imaging follow-up of 25.21 ± 30.49 months, local failure (progression and/or radiation necrosis) of BMs treated with SRS was documented in five (4%) BMs at 7.2 ± 7.3 months after the SRS. At the last imaging follow-up, the majority of patients with available imaging data had stable intracranial disease (33%) or achieved complete (26%) or partial (24%) response. There were no clinical AREs. Post-SRS peritumoral T2/fluid attenuated inversion recovery signal hyperintensity was noted in 7% BMs. Conclusion: The SRS allows durable local control of papillary and follicular thyroid cancer BMs in the vast majority of patients. Higher number of BMs and worse functional status at the time of SRS are associated with shorter OS in patients with thyroid cancer BMs. The SRS is safe and is associated with a low risk of AREs.

Large German Multicenter Experience on the Treatment Outcome of 207 Patients With Adenoid Cystic Carcinoma of the Major Salivary Glands.

IntrodutionWe aimed to evaluate treatment outcome of combined radiotherapy (RT) including photon intensity modulated radiotherapy (IMRT) and carbon ion boost for adenoid cystic carcinomas (ACCs) of the major salivary glands, the currently available largest German collective for this cohort.Materials and MethodsOverall, 207 patients who were irradiated with combined RT between 2009 and 2019 at Heidelberg University Hospital were analyzed retrospectively for local control (LC), progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier estimates. The majority of patients received postoperative RT (n=176/207, 85%) after previous surgery in large German hospitals mainly Mainz, Freiburg, Mannheim and Heidelberg University Hospitals and 15% received primary RT (n=31/207).ResultsAfter a median follow-up time of 50 months, 84% of the patients were still alive (n=174/207). Disease progression occurred in 32% of the patients (n=66/207) while local recurrence was diagnosed in 12% (n=25/207), and distant relapse in 27% (n=56/207). Estimated 5-year LC, PFS and OS rates were 84%, 56% and 83% for OS, respectively. In multivariate analysis, we could identify two prognostic subgroups: one subgroup resulting in decreased LC, PFS and OS rates and another subgroup having an additional survival disadvantage in PFS and OS. Patients with a macroscopic tumor disease (yes vs. no; p<0.001 for LC, p=0.010 for PFS and p=0.040 for OS) treated in a definitive setting (vs. postoperative setting; p=0.001 for LC, p=0.006 for PFS, p=0.049 for OS) and tumors of upper T stage (T1-4; p=0.004 for LC, p<0.001 for PFS, p<0.001 for OS) showed significantly more local relapses and a decreased PFS and OS. Upper Age (p<0.001 for both PFS and OS), lower Karnofsky Performance Score (<80% vs. ≥80%; p<0.001 for both PFS and OS) and solid histology (vs. non-solid; p=0.049 for PFS and p=0.003 for OS) were in addition associated with worse survival outcome. Toxicity was moderate with 18% late grade 2 and 3 toxicity.ConclusionsCombined RT results in superior LC rates compared to photon data with moderate toxicity. In multivariate analysis, upper T stage, the existence of a macroscopic tumor before RT and definitive RT setting were identified as major prognostic factors affecting LC negatively.

Prognostic factors of patients with Gliomas \u2013 an analysis on 335 patients with Glioblastoma and other forms of Gliomas

BackgroundThe prognosis of glioma is poor, despite recent advances in diagnosis and treatment of the disease. It is important to investigate the clinical characteristics and prognostic factors of glioma so as to provide basis for treatment and management of patients.MethodA total of 335 patients with glioma were included in this study. These patients were admitted to the medical center between November 2015 and December 2018. The clinical data, including demographic data, tumor characteristics, treatment strategy, expression pattern of tumor markers, and survival data, were retrospectively reviewed. Survival data were analyzed using Kaplan-Meier curves with log-rank test, while multivariate analysis Cox regression model was used to investigate risk factors for mortality.ResultsIn this patient cohort, glioblastoma (40%), diffuse glioma (14.6%) and oligodendroglioma (9.6%) were the most common pathological types. The expression of Ki-67 was associated with several clinicopathological parameters (e.g. tumor type, grade, and number of lesions). In addition, Ki-67 correlated with the mortality within the first year of the post-treatment follow-up (P < 0.001). Kaplan-Maier analysis revealed that older patients (≥ 45 years) displayed worse prognosis than those aged under 45 years (P = 0.038). Dismal prognosis was also associated with clinical parameters, including high tumor grade, multiple lesions, and Karnofsky performance score (KPS). Multivariate analysis showed that low KPS (< 85) increased the risk of mortality by 2.3 folds with a 95% CI of 1.141 to 4.776 (P = 0.020). Low tumor grade (grade 1–2) oppositely reduced the mortality risk by 0.22 folds (95% CI, 0.065 to 0.763, P = 0.0168).ConclusionKPS and tumor grade were independent prognostic factors in patients with gliomas.

Characteristics and survival of ovarian cancer patients treated with neoadjuvant chemotherapy but not undergoing interval debulking surgery.

ObjectiveNeoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) confers similar outcomes as primary debulking surgery and chemotherapy. Little is known about patients who receive NACT but do not undergo debulking surgery. Our aim was to characterize these patients.MethodsWe prospectively identified patients with newly diagnosed stage III/IV ovarian cancer treated with NACT from 7/1/15–12/1/17. Fisher exact and Wilcoxon rank-sum tests were used to compare clinical characteristics by surgical status. The Kaplan-Meier method was used to estimate survival outcomes. Log-rank test and Cox proportional hazards model were applied to assess the relationship of covariates to outcome, and time-dependent covariates were applied to variables collected after diagnosis.ResultsOf 224 women who received NACT, 162 (72%) underwent IDS and 62 (28%) did not undergo surgery. The non-surgical group was older (p<0.001), had higher Charlson comorbidity index (CCI; p<0.001), lower albumin levels (p=0.007), lower Karnofsky performance scores (p<0.001), and were more likely to have dose reductions in NACT (p<0.001). Reasons for no surgery included poor response to NACT (39%), death (15%), comorbidities (24%), patient preference (16%), and loss to follow-up (6%). The no surgery group had significantly worse overall survival (OS) than the surgery group (hazard ratio=3.34; 95% confidence interval=1.66–6.72; p<0.001), after adjustment for age, CCI, and dose reductions.ConclusionsA significant proportion of women treated with NACT do not undergo IDS, and these women are older, frailer, and have worse OS. More studies are needed to find optimal therapies to maximize outcomes in this high-risk, elderly population.

Decreased expression of miR-410-3p correlates with poor prognosis and tumorigenesis in human glioma.

BackgroundGliomas are the most common type of primary tumors in the central nervous system. This study aimed to investigate the biological role of miR-410-3p in glioma and elucidate the potential molecular mechanisms involved.MethodsThe expression levels of miR-410-3p in clinical tissue samples and glioma cell lines were determined using qRT-PCR analysis. The clinical significance of miR-410-3p in glioma was evaluated using Kaplan-Meier survival analysis and Fisher’s exact test. The effects of miR-410-3p on glioma cell proliferation, apoptosis, migration and invasion were investigated using MTT assays, flow cytometry, transwell migration and invasion assays. Besides, corresponding mechanistic studies were carried out.ResultsmiR-410-3p was significantly down-regulated in glioma tissues. Besides, Kaplan-Meier analysis demonstrated that patients with low miR-410-3p expression had a shorter overall survival. Decreased miR-410-3p expression was associated with larger tumor size, lower Karnofsky performance score (KPS), and higher World Health Organization (WHO) grade. Over-expression of miR-410-3p suppressed cell proliferation, migration, and invasion, and accelerated apoptosis; whereas depletion of miR-410-3p facilitated cell proliferation, migration, and invasion, and inhibited apoptosis. Mechanistic investigations demonstrated that Ras-related protein 1A (RAP1A) was a direct target of miR-410-3p, and that rescue of RAP1A expression reversed miR-410-3p over-expression-induced inhibitory effects on cell proliferation, migration, and invasion. Notably, miR-410-3p over-expression repressed tumor growth in mouse xenograft models.ConclusionOur findings indicate that miR-410-3p functions as a tumor suppressor in glioma by directly targeting RAP1A. Thus, this study may provide some new insights into gliomagenesis and progression.

380P - Ventricular–Subventricular zone involvement: A predictive factor for survival in glioblastoma

BackgroundMRI imaging is an essential tool in diagnosing glioblastoma and it can give various anatomical details related to disease. It gives an assessment of involvement of disease with ventricular – subventricular zone (VSVZ), subgranular (SGZ) and corpus callosum (CC). This study aims at assessment of survival outcomes in diseases involving neurogenic zones and corpus callosum and the associated prognostic factors. MethodsWe retrospectively analyzed 376 adult patients treated for histologically proven Glioblastoma. MRI studies were assessed for the tumor volume and its association with the neurogenic zones and corpus callosum. Age of patient, comorbidities associated, performance status, extent of resection and radiation doses received by these structures were evaluated. Overall (OS) and progression free (PFS) survivals were calculated and analyzed with multivariate Cox analyses. ResultsOf the 376 patients, 121 had VSVZ involved, 62 had CC involved and 43 had SGZ involved and remaining 150 had cortical involvement and the latter served as controls. Overall median age was 60.4 years, median Karnofsky performance score (KPS) was 80 and median tumor volume was 34.7 cm3. Gross total resection (GTR) was seen in 50.6% and subtotal resection in 38.1% and rest were unresectable. On multivariate cox analyses, VSVZ was found to be an independent factor for poor OS and PFS. Besides, increasing age, lower KPS, less than GTR status were associated independent factors for reduced survival. ConclusionsPatients with GBMs contacting the VSVZ and SGZ neurogenic zones exhibit divergent clinical patterns of tumor recurrence and survival and VSVZ involvement are associated with early recurrences and lower survival. VSVZ has a rich stem cell and growth factor microenvironment and these structures can be considered as organs at risk in uninvolved disease for probably better outcomes. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Long non-coding RNA LINC00473 promotes glioma cells proliferation and invasion by impairing miR-637/CDK6 axis

LINC00473 has been reported to be aberrantly expressed in diverse kinds of human malignancy. However, the function and underlying mechanisms of LINC00473 in glioma still remain unclear. In the present study, LINC00473 was notably elevated in glioma tissues and cell lines. High LINC00473 expression was associated with advanced WHO grade (III–IV), low Karnofsky performance score (KPS), and poor prognosis. Loss function assays showed that LINC00473 knockdown decreased glioma cell proliferation, invasion and epithelial–mesenchymal transition (EMT) processes in vitro, and reduced tumor growth in vivo. Mechanistic analysis indicated that LINC00473 regulated CDK6 expression by competitively binding to miR-637. Moreover, rescue assays revealed that miR-637 inhibitors abolished the effects of LINC00473 suppression on glioma cells progression. Thus, we demonstrated that LINC00473 could act as a ceRNA of miR-637 to promote glioma progression through regulating CDK6 expression, which provided a potential therapeutic target for treatment of glioma patients.

Low microRNA-622 expression predicts poor prognosis and is associated with ZEB2 in glioma.

BackgroundMicroRNAs have been recently reported to play an important role in tumorigenesis and progression in several forms of tumors. Previous studies have shown that microRNA-622 (miR-622) was associated with glioma proliferation and invasion. However, the clinical significance of miR-622 in glioma has not been elucidated. The aim of our study was to investigate the clinical values of miR-622, as well as investigate the potential molecular mechanisms in glioma.Materials and methodsqRT-PCR and Western blot analysis were used to analyze the expression of miR-622 and ZEB2, respectively. Kaplan–Meier analysis and Cox’s proportional hazards model were used in survival analysis. MTT assay, wound healing assay, transwell assay and flow cytometry analysis were carried out to detect the impact of miR-622 on glioma cell proliferation, migration, invasion and apoptosis.ResultsOur result indicated that miR-622 expression was greatly decreased in glioma tissues and cell lines and the downregulation of miR-622 was significantly associated with the advanced pathological grade and low Karnofsky performance score of glioma. In addition, Kaplan–Meier curves with log-rank analysis revealed a close correlation between downregulation of miR-622 expression and low overall survival rate in glioma patients. Furthermore, Cox regression analysis demonstrated that downregulated miR-622 could be considered as an independent poor prognostic indicator in glioma patients. Finally, our findings demonstrated that miR-622 overexpression remarkably suppressed glioma cell proliferation, migration and invasion, while facilitated apoptosis by suppressing ZEB2 in vitro.ConclusionOur study suggested that miR-622 may be identified as a valuable prognostic biomarker and a promising therapeutic target for glioma patients.

Clinical, radiological, and histopathological predictors for long-term prognosis after surgery for atypical meningiomas.

Despite considerable rates of recurrence and mortality in atypical meningiomas, reliable predictors for estimating postoperative long-term prognosis remain elusive. Clinical, histopathological, and radiological variables from 138 patients, including 64 females and 74 males (46% and 54%, median age 62years), who underwent surgery for intracranial atypical meningioma were retrospectively analyzed. Associations between variables and recurrence and mortality were investigated using uni- and multivariate analyses. Gross total (GTR) and subtotal resection (STR) was achieved in 81% and 19% of cases, respectively. Within a median follow-up of 62months, recurrence occurred in 52 (38%) and mortality in 22 (16%) cases. In patients who did not receive adjuvant irradiation, recurrence rates were higher after STR than after GTR (32% vs 63%, p = 0.025). In univariate analyses, only intratumoral calcifications on preoperative MRI (p = 0.012) and the presence of brain invasion in the absence of other histological grading criteria (p = 0.010) were correlated with longer progression-free intervals (PFI). In multivariate analyses, patient age was positively (HR 1.03, 95%CI 1.04-1.05; p = 0.018) and the presence of brain invasion as the only grading criterion (HR 0.37, 95%CI 0.19-0.74; p = 0.005) was negatively related with progression, while rising age at the time of surgery (HR 1.07, 95%CI 1.03-1.12; p = 0.001) was prognostic for mortality. PFI was longer in brain invasive but otherwise histological benign meningiomas and in tumors displaying calcifications on preoperative MRI. Advancing patient age and lower Karnofsky Performance Score were associated with higher overall mortality.