Low Karnofsky Performance Scale Score Research Articles

Impact of Demographic Characteristics on Self-Reported Psychological Distress of Cancer Patients during the COVID-19 Pandemic

Purpose/Objective(s)To investigate how at-risk demographic features correlate with the perceived level of psychological distress in cancer patients actively receiving care during the COVID-19 pandemic.Materials/MethodsPatients treated with radiotherapy at a single academic cancer center were reviewed 3 months before (11/01/2019-03/16/2020) and during (03/17/2020- 2/01/2021) the COVID-19 pandemic. Patients who reported an NCCN distress score (range 0=no distress to 10=extreme distress) as a part of their radiation care were reviewed for inclusion. Variables of interest were extracted from the medical record including age, gender, ethnicity, and Karnofsky Performance Scale (KPS) score. Distress scores were recorded around the time of simulation or treatment start. The relationship between these variables and NCCN distress scores were assessed using univariate and multivariate linear regression.ResultsOf all the patients receiving active treatment during the study interval (n=3,129), a total of 2,012 patients reported distress scores and thus were included. Median pre-pandemic distress was 3 (Interquartile Range 0-5) compared to median score of 2 (IQR 0-4) during the pandemic. There was no change in pre- and during pandemic distress on subgroup analysis by age, gender, ethnicity, or KPS score. The following variables were significantly correlated with increased distress on univariate analysis: older age (beta-age = -0.0163 [95% CI: -0.0262 to -0.0063], female gender (OR = 2.43 [95% CI 1.88 to 3.03], race (“black” race OR = 2.77 [95% CI: 1.68 to 4.57] and “other” race OR 1.96 [95% CI: 1.34-2.83]) and lower KPS score (beta-KPS = -0.403 [95% CI: -0.509 to -0.298]. Multivariate analysis was used to test if these demographic features were correlated with psychological distress among all patients. The overall regression was statistically significant albeit with a small effect size (R2=0.0605, p < .0001). On multivariate analysis, the following variables remained significant: age (beta-age = -0.0145 [95% CI: -0.0266 to -0.00241]), KPS score (beta-KPS = -0.429 [95% CI: -0.561 to -0.297]), and female gender (OR = 1.88 [95% CI: 1.28-2.75]).ConclusionThe ongoing COVID-19 pandemic did not significantly affect patient-reported distress levels at the time of receiving cancer-directed therapy. Older age, female gender, and low KPS score were associated with higher psychological distress in cancer patients receiving radiotherapy. Current analysis reveals vulnerable populations of cancer patients may have higher risk of distress during radiotherapy. These populations would warrant additional surveillance during treatment and may benefit from additional psychosocial support.

Absorbable Artificial Dura Versus Nonabsorbable Artificial Dura in Decompressive Craniectomy for Severe Traumatic Brain Injury: A Retrospective Cohort Study in Two Centers.

BackgroundSevere traumatic brain injury (TBI) patients usually need decompressive craniectomy (DC) to decrease intracranial pressure. Duraplasty is an important step in DC with various dura substitute choices. This study aims to compare absorbable dura with nonabsorbable dura in duraplasty for severe TBI patients.MethodsOne hundred and three severe TBI patients who underwent DC and dura repair were included in this study. Thirty-nine cases used absorbable artificial dura (DuraMax) and 64 cases used nonabsorbable artificial dura (NormalGEN). Postoperative complications, mortality and Karnofsky Performance Scale (KPS) score in one year were compared in both groups.ResultsAbsorbable dura group had higher complication rates in transcalvarial cerebral herniation (TCH) (43.59% in absorbable dura group vs. 17.19% in nonabsorbable dura group, P = 0.003) and CSF leakage (15.38% in absorbable dura group vs. 1.56% in nonabsorbable dura group, P = 0.021). But severity of TCH described with hernial distance and herniation volume demonstrated no difference in both groups. There was no statistically significant difference in rates of postoperative intracranial infection, hematoma progression, secondary operation, hydrocephalus, subdural hygroma and seizure in both groups. KPS score in absorbable dura group (37.95 ± 28.58) was statistically higher than nonabsorbable dura group (49.05 ± 24.85) in one year after operation (P = 0.040), while no difference was found in the rate of functional independence (KPS ≥ 70). Besides, among all patients in this study, TCH patients had a higher mortality rate (P = 0.008), lower KPS scores (P < 0.001) and lower functionally independent rate (P = 0.049) in one year after surgery than patients without TCH.ConclusionsIn terms of artificial biological dura, nonabsorbable dura is superior to absorbable dura in treatment of severe TBI patients with DC. Suturable nonabsorbable dura has fewer complications of TCH and CFS leakage, and manifest lower mortality and better prognosis. Postoperative TCH is an important complication in severe TBI which usually leads to a poor prognosis.

Impact of race on nonroutine discharge, length of stay, and postoperative complications after surgery for spinal metastases.

Previous studies have suggested the possibility of racial disparities in surgical outcomes for patients undergoing spine surgery, although this has not been thoroughly investigated in those with spinal metastases. Given the increasing prevalence of spinal metastases requiring intervention, knowledge about potential discrepancies in outcomes would benefit overall patient care. The objective in the present study was to investigate whether race was an independent predictor of postoperative complications, nonroutine discharge, and prolonged length of stay (LOS) after surgery for spinal metastasis. The authors retrospectively examined patients at a single comprehensive cancer center who had undergone surgery for spinal metastasis between April 2013 and April 2020. Demographic information, primary pathology, preoperative clinical characteristics, and operative outcomes were collected. Factors achieving p values < 0.15 on univariate regression were entered into a stepwise multivariable logistic regression to generate predictive models. Nonroutine discharge was defined as a nonhome discharge destination and prolonged LOS was defined as LOS greater than the 75th percentile for the entire cohort. Three hundred twenty-eight patients who had undergone 348 operations were included: 240 (69.0%) White and 108 (31.0%) Black. On univariable analysis, cohorts significantly differed in age (p = 0.02), marital status (p < 0.001), insurance status (p = 0.03), income quartile (p = 0.02), primary tumor type (p = 0.04), and preoperative Karnofsky Performance Scale (KPS) score (p < 0.001). On multivariable analysis, race was an independent predictor for nonroutine discharge: Black patients had significantly higher odds of nonroutine discharge than White patients (adjusted odds ratio [AOR] 2.24, 95% confidence interval [CI] 1.28-3.92, p = 0.005). Older age (AOR 1.06 per year, 95% CI 1.03-1.09, p < 0.001), preoperative KPS score ≤ 70 (AOR 3.30, 95% CI 1.93-5.65, p < 0.001), preoperative Frankel grade A-C (AOR 3.48, 95% CI 1.17-10.3, p = 0.02), insurance status (p = 0.005), being unmarried (AOR 0.58, 95% CI 0.35-0.97, p = 0.04), number of levels (AOR 1.17 per level, 95% CI 1.05-1.31, p = 0.004), and thoracic involvement (AOR 1.71, 95% CI 1.02-2.88, p = 0.04) were also predictive of nonroutine discharge. However, race was not independently predictive of postoperative complications or prolonged LOS. Higher Charlson Comorbidity Index (AOR 1.22 per point, 95% CI 1.04-1.43, p = 0.01), low preoperative KPS score (AOR 1.84, 95% CI 1.16-2.92, p = 0.01), and number of levels (AOR 1.15 per level, 95% CI 1.05-1.27, p = 0.004) were predictive of complications, while insurance status (p = 0.05), income quartile (p = 0.01), low preoperative KPS score (AOR 1.64, 95% CI 1.03-2.72, p = 0.05), and number of levels (AOR 1.16 per level, 95% CI 1.05-1.30, p = 0.004) were predictive of prolonged LOS. Race, insurance status, age, baseline functional status, and marital status were all independently associated with nonroutine discharge. This suggests that a combination of socioeconomic factors and functional status, rather than medical comorbidities, may best predict postdischarge disposition in patients treated for spinal metastases. Further investigation in a prospective cohort is merited.

Morbidity in Patients with Nasopharyngeal Carcinoma and Radiation-Induced Skin Lesions: Cause, Risk Factors, and Dermatitis Evolution and Severity.

Radiation-induced skin injuries such as lesions (RSLs) and dermatitis are the most common complication during radiotherapy (RT) for nasopharyngeal carcinoma, but little is known about risk factors unique to oncology. This study sought a greater understanding of these risk factors to stratify patients based on risk and guide clinical decision-making. Investigators analyzed the data of 864 consecutive patients referred to the RT center of the Southern Theater General Hospital for a new RSL from 2013 to 2019. These patients were followed up for an average of approximately 16 months until their death or March 30, 2020, whichever came first. Multivariate logistic regression analysis and Cox proportional hazards model were used to identify predictors of grade 3 or 4 dermatitis. The main causes of treatment interruption included dermatitis and oral mucositis. Significant patient-specific risk factors for RSLs included current smoking, current drinking, and lower Karnofsky Performance Scale score and significant procedure-specific risk factors included receiving intensity-modulated radiation therapy (IMRT), hyperfractionated RT, induction chemotherapy, multicycle chemotherapy, and taxol- and cisplatin-based drugs. The three factors that independently predicted risk of RSL were IMRT, lower Karnofsky Performance Scale score, and multicycle chemotherapy. Comparing predictive factors among patients with severe RSL revealed that patients who received IMRT were more likely to develop grade 3 or 4 dermatitis. Oncology providers should note that IMRT is an aggressive technique with a trend toward increased RSL. Providers should pay special attention to adverse effects to skin in patients with nasopharyngeal carcinoma.

BIOM-29. ASSOCIATION OF PLASMA microRNA-21 EXPRESSION WITH KARNOFSKY PERFORMANCE SCALE SCORES IN GLIOMA PATIENTS

Abstract Gliomas are one of the most common primary brain tumors. MicroRNA-21 (miRNA-21) has been shown in previous studies to be associated with prognosis in glioma patients. However, similar studies in the Asian population, particularly in Indonesia, are very limited. This study aimed to find the association of plasma miRNA-21 expression with functional status measured by Karnofsky Performance Scale (KPS) in Indonesian glioma patients. The patients were enrolled from a neuro-oncology referral center in Yogyakarta, Indonesia. MiRNA-21 expression from plasma was measured by real-time quantitative PCR. Clinical data were obtained from medical records. KPS scores were classified as low (&amp;lt; 70) and high (&amp;gt; 70). In total, 50 patients were included in this study. Most patients were diagnosed with WHO grade IV gliomas (30.4%), followed by grade II (30.4%), grade III (21.4%), and grade I (5.4%). Most patients (64%) have low KPS scores (&amp;lt; 70). Patients in the low KPS scores group have significantly higher miRNA-21 expression compared to patients in the high KPS scores group (2-∆CT 4.26 vs. 0.68, p=0.002). In conclusion, higher expression of plasma miRNA-21 is associated with worse functional status in glioma patients as measured by KPS.

Clinical features and prognosis of patients with leptomeningeal metastases

Objective: To describe the clinical manifestations, neuroimaging, cerebrospinal fluid(CSF) cytology and prognosis of Leptomeningeal metastases(LM). Methods: The clinical manifestations, imaging features and CSF cytology of LM patients admitted to Henan Provincial People's Hospital from May 1, 2015 to May 31, 2020 were retrospectively analyzed. The overall survival (OS) was evaluated by the time from the diagnosis of LM to death. Results: A total of 88 patients with LM were enrolled in the study, and the median age was 59 years (range:28-78 years). There were 42 males (47.7%) and 46 females (52.3%). According to the pathological classification, it was lung cancer in 58 cases (65.9%), gastric cancer in 13 cases (14.8%), breast cancer in 7 cases (8.0%), melanoma in 1 case, esophageal cancer in 1 case, gallbladder cancer in 1 case, renal cell carcinoma in 1 case, double source cancer in 2 cases, and unknown source in 4 cases. The median Karnofsky Performance Scale (KPS) score was 50. LM was the initial manifestation of cancer in 34 patients. All patients had LM-related clinical symptoms, including headache in 73 cases (83.0%), nausea and vomiting in 63 cases (71.6%), abnormal physical and mental behaviors in 37 cases (42.0%), seizure in 41 cases (46.6%). Cranial nerve involvement was observed in 23 patients (39.0%) and spinal nerve involvement in 20(33.9%). There were 61 patients (83.6%) who showed neuroimaging features of LM. Tumor cells or atypical cells were found in 90.8% of patients for the first time, and activated monocytes in 47 cases (54.7%). The median OS was 13.0 weeks (95%CI:2.9-23.1) with the 1-year survival rate of 19.1%. Univariate analysis of survival indicated that lung cancer, lower KPS score, tyrosine kinase inhibitors (TKIs) and whole brain radiotherapy were favorable predictors of survival (P<0.05). Conclusions: The overall prognosis of LM is poor. Good physical condition, TKIs treatment and whole brain radiotherapy might improve clinical outcomes of LM patients.

Clinical significance of interleukin-10 concentration in the cerebrospinal fluid of patients with primary central nervous system lymphoma.

The diagnostic and prognostic evaluation of primary central nervous system lymphoma (PCNSL) is challenging due to the lack of sensitive biomarkers. The present study aimed to evaluate the value of interleukin (IL)-10 in this context. Between October 2016 and December 2018, 91 patients with suspected intracranial neoplasms were recruited, and the concentrations of IL-10 or IL-6 in both the cerebrospinal fluid (CSF) and blood were measured and analyzed by the Kruskal-Wallis test. The correlation between CSF IL-6 or IL-10 levels and tumor size was determined by Spearman's coefficient analysis. The receiver operating characteristic curve was used to evaluate the diagnostic value of CSF IL-6 and IL-10 levels. Median progression-free survival (PFS) and overall survival time were calculated using Kaplan-Meier survival analysis. Among the 91 patients, 3 were diagnosed with PCNSL on the basis of neuroimaging data and CSF IL-10 levels. A total of 35 cases were verified to show diffuse large B-cell lymphoma on histological assessment, 17 of which were diagnosed as PCNSL by MRI. The median PFS and OS were 8.00 months [95% confidence interval (CI), 3.94–12.06) and 17.5 months (95% CI, 11.55–23.45) respectively in the 12 PNCSL cases with regular follow up. The diagnostic efficiency of serum IL-6 levels was lower than that of serum IL-10 levels (P=0.030), which, in turn, was lower than that of CSF IL-10 levels (P<0.001). The decline and increase in CSF IL-10 levels was concurrent with improvement and deterioration in manifestation, respectively, which predated the MRI variation. High CSF IL-10 levels indicated low Karnofsky performance scale scores and shortened PFS times. CSF IL-10 levels higher than 1,000 pg/ml signified disease progression. CSF IL-10 levels could be a sensitive biomarker guiding the differential diagnosis, early recurrence detection, prognostic evaluation and therapeutic strategy establishment in cases of PCNSL.

The prognostic value of prognostic nutritional index (PNI) and neutrophil to lymphocyte ratio (NLR) for advanced non-small cell lung cancer treated with platinum-based chemotherapeutics

The present study aimed to investigate the relationship between prognostic nutritional index (PNI) and peripheral blood neutrophil to lymphocyte ratio (NLR), and the prognosis of patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based therapeutics. The data of 99 advanced NSCLC patients treated with platinum chemotherapeutics between January 2011 and June 2019 were retrospectively analyzed. The association between PNI and NLR and the clinicopathological characteristics of the patients was examined. The patients were randomized into high or low groups according to PNI and NLR. The predictive value of PNI and NLR for overall survival (OS) was evaluated by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate Cox proportional hazards regression analyses were performed to investigate the prognostic factors of advanced NSCLC patients treated with platinum-based chemotherapeutics. The association between PNI and NLR and progression-free survival (PFS) or OS was determined using the Kaplan-Meier method and compared between groups using the log-rank test. The ROC curve analysis determined the optimal cut-off values of PNI and NLR for predicting OS to be 52.525 and 3.525, respectively. Univariate analysis indicated that low Karnofsky performance scale (KPS) score (P=0.005), poor tumor differentiation (P=0.022), brain metastasis (P<0.001), and low PNI (P=0.001) were independent risk factors for PFS in patients with advanced NSCLC; however, there was no significant correlation observed between NLR (P=0.082) and PFS in patients with advanced NSCLC. Low KPS score (P=0.003), poor tumor differentiation (P=0.001), brain metastasis (P<0.001), low PNI (P<0.001), and high NLR (P=0.046) were significantly associated with shorter OS. Furthermore, Cox multivariate analysis revealed that brain metastasis (P=0.005) and low PNI (P=0.008) were significant independent prognostic factors for PFS, while brain metastasis (P=0.003) and low PNI (P=0.028) were also found to be significant independent risk factors for poor OS. PNI is a reliable, simple, easily available, and inexpensive biomarker for predicting the prognosis of advanced NSCLC patients treated with platinum-based chemotherapeutics in routine clinical practice. Furthermore, PNI is superior to NLR in as a prognostic indicator for advanced NSCLC patients treated with platinum-based chemotherapeutics.

Impact of preoperative Karnofsky Performance Scale (KPS) and American Society of Anesthesiologists (ASA) scores on perioperative complications in patients with recurrent glioma undergoing repeated operation

Objective:The objective of this study was to document the impact of the preoperative Karnofsky Performance Scale (KPS) and American Society of Anesthesiologists (ASA) scores on perioperative complications in patients with recurrent glioma who underwent tumor resection via craniotomy.Methods:A total of 96 patients were retrospectively reviewed. Based on KPS and ASA scores, patients were categorized into high KPS (&gt; 70) or low KPS (≤ 70) and high ASA (3~4) or low ASA (1~2) groups. Differences in intraoperative risk factors and perioperative complications among the groups were analyzed. Multivariate analysis was performed to identify risk factors for perioperative complications.Results:The most frequent perioperative complications were cerebrospinal fluid leakage (31.8%) and intracranial infection (27.0%); 30-day mortality was 5.2%. The incidence rates of severe complications, central nervous system complications, and total complications were comparable in the low and high KPS groups and in the low and high ASA groups (all p &gt; 0.05). Multivariate analysis showed that low KPS and high ASA scores were not the independent risk factors for perioperative complications.Conclusion:Low KPS and high ASA scores are not associated with increased postoperative complications in patients with recurrent glioma who undergo tumor resection via craniotomy.

Risk Score for the Development of Veno-Occlusive Disease after Allogeneic Hematopoietic Cell Transplant

A risk score identifying patients at high risk for veno-occlusive disease (VOD) may aid efforts to study preventive strategies for this uncommon complication of hematopoietic cell transplantation (HCT). Patients receiving a first allogeneic HCT between 2008 and 2013 as reported to the Center for International Blood and Marrow Transplant Research (N = 13,097) were randomly divided into training and validation sets. Independent prognostic factors for development of VOD by day +100 after HCT were identified with a multivariate logistic regression model. A risk score was constructed in the training set using the significant factors and confirmed in the validation set. Baseline characteristics of the training and validation sets were balanced. In total, 637 patients (4.9%) developed VOD by day +100. Younger age, positive hepatitis B/C serology, lower Karnofsky performance scale score, use of sirolimus, disease, disease status at transplant, and conditioning regimen were independent prognostic factors. Myeloablative conditioning regimens were associated with higher risk of VOD. Busulfan-based myeloablative conditioning regimens guided by pharmacokinetic monitoring were associated with higher risk than those without pharmacokinetic monitoring. Patients were stratified into 4 distinct, statistically significantly different groups by their risk score percentile. This pretransplant risk score successfully stratified allogeneic HCT patients by risk of developing VOD, was validated in an independent set, and demonstrated strong discriminatory ability to identify a high-risk cohort.

Reduced circulating microRNA-203 predicts poor prognosis for glioblastoma.

MicroRNAs (miRNAs) have been demonstrated to play an important role in the development and progression of various types of cancer including glioblastoma (GBM). The aim of this study was to investigate the expression pattern and prognostic significance of serum miR-203 in patients with GBM. miR-203 extracted from cell culture medium and serum samples was detected by real-time PCR. The correlation between serum miR-203 expression as well as clinicopathological characteristics and patient survival was determined. The expression level of miR-203 was remarkably reduced in the GBM cells and their culture medium. Serum miR-203 expression was significantly decreased in GBM patients compared with low grade glioma (LGG) patients and healthy controls. In addition, serum miR-203 discriminated GBM patients from LGG patients and healthy subjects. Chi-squared analysis showed that a significant correlation was found between low serum miR-203 expression and larger tumor size as well as lower Karnofsky Performance Scale scores. Patients with lower serum miR-203 suffered poorer overall survival (OS) and progression free survival (PFS). Multivariate analysis indicated that low miR-203 expression is an independent prognostic factor for poor OS in GBM patients. These data demonstrate that serum miR-203 expression might serve as a potential prognostic indicator of GBM.

No news, bad news? A deeper examination of the correlation between patient functional status and level of postoperative telephone communication with the surgical team.

102 Background: In attempts to improve outcomes for and survival of geriatric oncology patients, studies have demonstrated the utility of phone communication as a tool for post-operative care. However, very little data is available to determine if this method of care is reaching the most vulnerable patients. The purpose of this study is to compare patient-surgical team phone communication for geriatric cancer patients of higher and lower preoperative functional status. Methods: This is a retrospective review of data from an internal geriatric assessment questionnaire and phone log data as recorded in the EHR at a single institution. Patients were stratified into two groups: those who had at least one recorded postoperative care phone call (PC) and those with no postoperative care phone call (NPC). Quantitative analysis of the data was performed, assessing the correlation between preoperative functional status and patient-surgical service communication in the first 30 postoperative days. Results: NPC group patients were more likely to be amongst the more frail patients, with lower preoperative functional status and a higher level of distress. Specifically, patients in the NPC group were more likely to be dependent for ADLs (61.0% vs. 50.8%, P = 0.013) and IADLs (59.6% VS. 44.7%, P = 0.001), and have a lower Karnofsky Performance Scale score (46.2% vs. 39.1%, P = 0.048) and also reported a higher level of distress (4.5 vs. 4.00, P = 0.001). There was a trend toward more cognitive impairment among the NPC group compared to the PC group (18.2% vs. 12.1%, P = 0.058). Conclusions: Our study highlights a disparity in the utilization of patient-surgical team phone calls as a method for postoperative care for more frail patients. Despite significant number of phone calls initiated during the postoperative period, mainly by surgical nurses, frail and distressed patients are more likely not to participate in a call. Future studies of postoperative phone communication with geriatric oncology patients should assess the utility of this tool for more frail patients and seek measures that will increase access and participation among this population.

Downregulation of serum microRNA-205 as a potential diagnostic and prognostic biomarker for human glioma.

OBJECT Circulating microRNAs (miRNAs) are a new class of highly promising cancer biomarkers. Malignant glioma is one of the most devastating and lethal forms of intrinsic CNS tumor. Here, the authors evaluated serum miRNA 205 (miR-205) levels in patients with glioma. METHODS Sixty-four patients in whom glioma was diagnosed and 45 healthy controls were recruited between October 2011 and March 2012 and randomly assigned to the screening cohort or the validation cohort. Cohorts of patients with other brain tumors, including meningioma (n = 8), primary diffuse large B-cell lymphoma of the CNS (n = 6), and pituitary adenoma (n = 5), were investigated and compared. miR-205 extraction from serum was detected by real-time quantitative reverse-transcription polymerase chain reaction. The Kaplan-Meier method was applied to perform survival analysis, the risk factors were analyzed by using a Cox regression model, and the receiver operating characteristic working curve was used to analyze the value of miR-205 in the prognostic evaluation of the patients. RESULTS The authors first demonstrated that serum miR-205 expression was significantly lower in patients with glioma than in healthy controls (p < 0.001). It is important to note that serum miR-205 expression demonstrated a stepwise decrease with ascending pathological grades. The serum miR-205 biomarker had high sensitivity, specificity, and accuracy in patients with glioma. Serum levels of miR-205 were identified as an individual diagnostic marker and were significantly lower in the glioma cohort than in the other brain tumor cohorts. Serum miR-205 levels were significantly increased in postoperative samples over those in the preoperative samples and were reduced again during glioblastoma recurrences. Statistical analysis revealed a significant correlation between low serum miR-205 expression and both ascending pathological grades (p = 0.002) and low Karnofsky Performance Scale scores (p = 0.01). Patients with glioma at an advanced pathological grade (Grade III or IV) and a higher miR-205 serum level showed longer overall survival than those with a lower miR-205 serum concentration (p < 0.01). Furthermore, Cox regression analysis revealed that miR-205 serum levels were independently associated with overall survival. CONCLUSIONS These data indicate that serum miR-205 expression is a novel and valuable biomarker for the diagnosis of glioma and a prognostic factor for those with a tumor at an advanced pathological grade.

Intracranial meningioma surgery in the elderly (over 65 years): prognostic factors and outcome.

Meningiomas are more prevalent in elderly individuals; however, the surgical outcome and prognostic factors in this age group are unclear. This retrospective study aimed to identify the prognostic factors of elderly patients with intracranial meningiomas who underwent surgical resection. Eighty-six patients (aged ≥ 65) diagnosed with an intracranial meningioma were surgically treated at our department. The clinical, radiological, and follow-up data were retrospectively reviewed. Univariate and multivariate logistic analyses were performed to identify relationships between factors [age, sex, neurological condition, concomitant disease, American Society of Anesthesiology (ASA) classification, preoperative Karnofsky Performance Scale (KPS) score, tumor location and size, peritumoral edema, and Simpson resection grade] and outcome. One patient (1.2 %) died within 30 days of surgery. The morbidity rate was 37.2 %. Postoperative morbidities occurred more frequently in the patients with preoperative neurological deficits than in those without (p = 0.049). Univariate analysis identified significant relationships between a low KPS score (≤ 70) at discharge and preoperative neurological deficits, low preoperative KPS score (≤ 70), and critical tumor location (p < 0.001, p < 0.001, and p = 0.04, respectively). In the multivariate logistic analysis, only the preoperative KPS score remained significant for the KPS score at discharge (p = 0.005); there was no significant association with the most recent KPS score. The outcome of intracranial meningioma resection in elderly individuals is favorable if the preoperative KPS score is >70 and no neurological deficits are present. Treatment decisions should be patient-specific, and additional factors should be considered when operations are performed in patients with a low preoperative KPS score or neurological deficits.

Nucleophosmin overexpression is associated with poor survival in astrocytoma.

The multiple functions of the protein nucleophosmin (NPM) include the regulation and balance of cell growth, proliferation, and apoptosis. Many cancers have suspected associations with overexpression of NPM or with mutation of the NPM gene. Although NPM and anaplastic lymphoma kinase fusion proteins are known to be related to the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) signaling pathway, the relationships of NPM, JAK2, and STAT5 to astrocytoma remain unclear. Therefore, this study performed histochemical analyses of expressions of NPM, p-JAK2, and STAT5B proteins in patients with astrocytoma. The results showed that high NPM expression was significantly associated with high tumor grade (p = 0.000), old age (p = 0.000), low Karnofsky Performance Scale (KPS) score (p = 0.000), and tumor recurrence (p = 0.045). High p-JAK2 expression was significantly associated with old age (p = 0.000), high tumor grade (p = 0.000), low KPS score (p = 0.000), and tumor recurrence (p = 0.036). Expression of STAT5B was significantly correlated with tumor grade (p = 0.018) and KPS score (p = 0.002). High expressions of NPM, p-JAK2, and STAT5B were associated with a short survival time (p = 0.035, 0.003 and 0.002, respectively). In multivariable analysis, STAT5B expression was a significant predictor of survival time (p = 0.003). In conclusion, NPM and p-JAK2/STAT5B may have important roles in tumor progression, and STAT5B is an independent prognostic marker of astrocytoma.

External validation of the number of risk factors score in a palliative care outpatient clinic at a comprehensive cancer center.

Prognostic tools are available to predict if terminally ill cancer patients have days or weeks to live. Tools for predicting the prognosis in ambulatory patients at an earlier stage are lacking. The Number of Risk Factors (NRF) score developed in ambulatory cancer patients receiving palliative radiation therapy may be suitable for this purpose but has not been tested in a palliative care setting. Our aim was to evaluate the prognostic accuracy of the NRF score in patients referred to a palliative care outpatient clinic at a comprehensive cancer center. We conducted a retrospective chart review of NRF scores and survival in 300 consecutive, newly referred patients. Measurements included primary cancer type, extent of disease, Karnofsky Performance Scale (KPS) score, and survival duration after first visit. One point was allocated each for cancer other than breast cancer, metastases other than bone, and low KPS score. Of 300 patients, 236 (79%) had advanced disease. Of those 236, 212 (90%) had a cancer other than breast cancer, 180 (76%) had metastatic disease in sites other than bone, and 64 (27%) had a KPS score <70%. During the 2-year follow-up, 221 (94%) patients died, with overall median survival of 4.9 months (95% confidence interval, 3.9-6.1 months). NRF scores of 0 to 1, 2, and 3 split the sample into subgroups with highly significantly different survival among the groups, with medians 9.0, 4.6, and 2.1 months, respectively (Wilcoxon test χ(2)=43.9, degrees of freedom [df] 2, p<0.0001). A simple parametric model was fit to determine the probability of subgroup members surviving to a certain number of months. In cancer patients referred to palliative care earlier in their disease trajectory, the NRF score may be a useful prognostic tool. Further validation in other palliative care populations is needed.

Downregulation of chromatin remodeling factor CHD5 is associated with a poor prognosis in human glioma

Chromodomain helicase DNA-binding protein 5 (CHD5), a member of the CHD family, is involved in key cellular processes including chromatin remodeling, cell cycle regulation, and cellular adhesion. Recent studies have demonstrated that CHD5 is the product of a novel tumor suppressor gene and is implicated in certain tumor types. However, the clinicopathological significance of CHD5 expression in human malignant gliomas remains unclear. To address this problem, CHD5 expression in human gliomas and non-neoplastic brain tissues was measured using real-time quantitative polymerase chain reaction (RT–PCR) assay, Western blot, and immunohistochemistry. The association of CHD5 immunostaining with clinicopathological factors or prognosis of glioma patients was statistically analyzed. Genetic and protein expression of CHD5 were downregulated in glioma tissues compared to corresponding non-neoplastic brain tissues (both p<0.001). Additionally, decreased expression of CHD5 in glioma was significantly associated with pathological grade (p=0.007); high pathological grade was associated with low CHD5 expression. Loss of CHD5 protein expression was also significantly correlated with a low Karnofsky performance scale score (p=0.01). Moreover, overall survival of patients with low CHD5 protein expression was dramatically shorter than those of patients with high CHD5 protein expression (p=0.003). Multivariate Cox regression analysis indicated that CHD5 expression was an independent prognostic factor for patients with gliomas (p=0.01). In conclusion, these data offer convincing evidence for the first time that CHD5 might act as a tumor suppressor in glioma, may act as a regulator of aggressive development, and is a candidate prognostic marker for this malignancy.

Forkhead-box A1 transcription factor is a novel adverse prognosis marker in human glioma

Forkhead-box A1 (FOXA1), a member of the FOX family of transcription factors, has been implicated in certain tumor types including breast, prostate, lung, thyroid and esophageal squamous cell carcinomas. The aim of this study was to investigate the clinicopathological significance of FOXA1 expression in human malignant glioma. FOXA1 expression in human glioma and non-neoplastic brain tissue was measured by quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry. The association of FOXA1 immunostaining with clinicopathological factors and prognosis in patients with glioma was also investigated. The expression levels of FOXA1 messenger RNA (mRNA) and protein in glioma tissues were significantly higher than those in corresponding non-neoplastic brain tissue (both p<0.001). In addition, the expression of FOXA1 was upregulated in high-grade glioma tissue compared with that in low-grade tissues, and increased with ascending World Health Organization (WHO) tumor grade (p=0.001). The increased expression of FOXA1 protein was also significantly correlated with low Karnofsky performance scale score (p=0.02). Moreover, the overall survival rate for patients with high FOXA1 protein expression was clearly lower than that for patients with low FOXA1 protein expression (p=0.01). Multivariate analysis showed that high FOXA1 protein expression was an independent prognostic factor for overall survival (p=0.02) in patients with glioma. In conclusion, our results suggest, for the first time, that FOXA1 might be a potential regulator of progression of human glioma and its upregulation might be closely associated with a poor clinical outcome for patients with this serious disease.

Role of Gamma Knife surgery in patients with 5 or more brain metastases

The authors evaluated overall survival and factors predicting outcome in patients with ≥ 5 brain metastases who were treated with Gamma Knife surgery (GKS). Medical records from patients with ≥ 5 brain metastases treated with GKS between 1997 and 2010 at the Cleveland Clinic Gamma Knife Center were retrospectively reviewed. Patient demographics, tumor characteristics, treatment-related factors, and outcome data were evaluated. One hundred seventy patients were identified, with a median age of 58 years. The female/male ratio was 1.2:1. Gamma Knife surgery was used as an upfront treatment in 35% of patients and as salvage treatment in 65% of patients with multiple brain metastases. The median overall survival after GKS was 6.7 months (95% CI 5.5-8.1). At the time of GKS, 128 patients (75%) had concurrent extracranial metastases, and in 69 patients (41%) multiple extracranial sites were involved. Ninety-two patients (54%) had a history of whole-brain radiation therapy, and 158 patients (93%) had a Karnofsky Performance Scale (KPS) score ≥ 70. The median total intracranial disease volume was 3.2 cm(3) (range 0.2-37.2 cm(3)). A total intracranial tumor volume ≥ 10 cm(3) was observed in 32 patients (19%). Lower KPS score at the time of treatment (p < 0.0001), patient age > 60 years (p = 0.004), multiple extracranial metastases (p = 0.0001), and greater intracranial burden of disease (p = 0.03) were prognostic factors for poor outcome in the univariate and multivariate analyses. In this study, GKS was safe and effective for upfront and salvage treatment in patients with ≥ 5 brain metastases. Gamma Knife surgery should be considered as an additional treatment modality for these patients, especially in the subset of patients with favorable prognostic factors.

Prognosis of patients with multifocal glioblastoma: a case-control study

The prognosis of patients with glioblastoma who present with multifocal disease is not well documented. The objective of this study was to determine whether multifocal disease on initial presentation is associated with worse survival. The authors retrospectively reviewed records of 368 patients with newly diagnosed glioblastoma and identified 47 patients with multifocal tumors. Each patient with a multifocal tumor was then matched with a patient with a solitary glioblastoma on the basis of age, Karnofsky Performance Scale (KPS) score, and extent of resection, using a propensity score matching methodology. Radiation and temozolomide treatments were also well matched between the 2 cohorts. Kaplan-Meier estimates and log-rank tests were used to compare patient survival. The incidence of multifocal tumors was 12.8% (47/368). The median age of patients with multifocal tumors was 61 years, 76.6% had KPS scores ≥ 70, and 87.2% underwent either a biopsy or partial resection of their tumors. The 47 patients with multifocal tumors were almost perfectly matched on the basis of age (p = 0.97), extent of resection (p = 1.0), and KPS score (p = 0.80) compared with 47 patients with a solitary glioblastoma. Age (>65 years), partial resection or biopsy, and low KPS score (<70) were associated with worse median survival within the multifocal group. In the multifocal group, 19 patients experienced tumor progression on postradiation therapy MRI, compared with 11 patients (26.8%) with tumor progression in the unifocal group (p = 0.08). Patients with multifocal tumors experienced a significantly shorter median overall survival of 6 months (95% CI 4-10 months), compared with the 11-month median survival (95% CI 10-19 months) of the matched solitary glioblastoma group (p = 0.02, log-rank test). Two-year survival rates were 4.3% for patients with multifocal tumors and 29.0% for the unifocal cohort. Patients with newly diagnosed multifocal tumors were found to have an almost 2-fold increase in the hazard of death compared with patients with solitary glioblastoma (hazard ratio 1.8, 95% CI 1.1-3.1; p = 0.02). Tumor samples were analyzed for expression of phosphorylated mitogen-activated protein kinase, phosphatase and tensin homolog, O(6)-methylguanine-DNA methyltransferase, laminin β1 and β2, as well as epidermal growth factor receptor amplification, and no significant differences in expression profile between the multifocal and solitary glioblastoma groups was found. Patients with newly diagnosed multifocal glioblastoma on presentation experience significantly worse survival than patients with solitary glioblastoma. Patients with multifocal tumors continue to pose a therapeutic challenge in the temozolomide era and magnify the challenges faced while treating patients with malignant gliomas.