Glioblastoma in the elderly

BACKGROUND:

Glioblastoma (GBM) is the most common malignant primary brain tumor, and approximately 50% of cases occur in patients aged ≥65 years. However, to the authors' knowledge, there is no accepted standard treatment for elderly GBM patients, and specific prognostic factors in the elderly GBM population have not been systematically studied to date.

METHODS:

The Memorial Sloan‐Kettering Cancer Center institutional database was used to identify patients with histologically confirmed GBM who were aged ≥65 years at the time of diagnosis.

RESULTS:

Three hundred ninety‐four GBM patients with a median age of 71.9 years (59% of whom were men) were included. Approximately 18% of patients underwent biopsy, whereas 82% underwent tumor resection; 81% received radiotherapy (RT), and 43% received adjuvant chemotherapy. The median overall survival was 8.6 months; at the time of last follow?up, 90% of patients had died, and the median follow‐up of the 39 surviving patients was 12 months. In a multivariate analysis, younger age, better Karnofsky performance status (KPS), single tumor, and surgical resection were found to be independent predictors of survival. Comparing 103 patients who received adjuvant chemotherapy with 48 who were only followed after RT, there was a 55% decrease in the risk of death (hazards ratio, 0.45; 95% confidence interval, 0.30‐0.66 [P < .0001]) after adjusting for age, KPS, extent of surgical resection, and number of lesions.

CONCLUSIONS:

Similar to studies in younger GBM patients, advancing age, KPS, and extent of tumor resection were found to be independent prognostic factors in the current study. Although survival is inferior in older GBM patients, age alone should not disqualify patients from aggressive therapy with surgical resection, RT, and chemotherapy. Cancer 2009. © 2009 American Cancer Society.     

Treating high grade gliomas in the elderly: the end of ageism?

Introduction Treating high grade gliomas in the elderly is a challenge for multidisciplinary teams. Most studies on this topic exclude patients aged >65 and a Karnofsky Performance Status (KPS) score of <70, a group most likely to have a poor outcome. We undertook this study to analyze the outcomes in a cohort of patients which included such patients. Methods Ours was a retrospective cohort study. About 71 consecutive patients with high grade gliomas, who were seen in the neurooncology clinic in 2004, were included. The case records of these patients were scrutinized for the demographic, clinical data, follow-up and survival. The cohort was divided into two groups; Age ≥65 and age <65 for analysis. The factors influencing survival were analyzed using the Cox’s proportional hazards model in each group. Results In the age group ≥65 years, patients treated with a radical resection ± adjuvant therapy had a lower risk of death (hazard ratio 0.14, 95%CI 0.04–0.51, P = 0.003) when compared to patients undergoing a biopsy ± adjuvant therapy and palliative treatment. In the group <65 years, the greater the age, greater was the risk of death (hazard ratio 2.05, 95%CI 1.13–3.73, P = 0.01). The median survival was 12 months in the group <65 years and 5 months in age ≥65 years (P = 0.001). In the group ≥65 years, those patients who had radical resection ± adjuvant treatment had a median survival of 7 months as compared to 3 months in the patients who had biopsy ± adjuvant treatment (P = 0.003). KPS, presence of co-morbidities, duration of symptoms, location of the lesion and sex were not found to be significant independent predictors of survival in our study. Conclusions Age is an important predictor of survival in younger patients, however in the elderly treatment matters most. Elderly patients undergoing radical surgery ± adjuvant treatment had a longer median survival as compared to the elderly patients undergoing a biopsy ± adjuvant treatment. KPS was not found to be a significant independent predictor of survival probably because of underrepresentation of patients with poor KPS. Radical treatment should not be denied to elderly patients who are deemed fit as the outcome is significantly better.     

Procarbazine, lomustine, and vincristine (PCV) chemotherapy for anaplastic astrocytoma: A retrospective review of radiation therapy oncology group protocols comparing survival with carmustine or PCV adjuvant chemotherapy.

PURPOSE: To determine any differences in outcome for patients with anaplastic astrocytoma (AA) treated with adjuvant carmustine (BCNU) versus procarbazine, lomustine, and vincristine (PCV) chemotherapy. MATERIALS AND METHODS: The Radiation Therapy Oncology Group (RTOG) database was reviewed for patients with newly diagnosed AA treated according to protocols that included either BCNU or PCV adjuvant chemotherapy. All patients were treated with radiation therapy. The outcome analysis included overall survival, taking into account patient age, extent of resection, Karnofsky performance status (KPS), and treatment group (BCNU v PCV). Stratified and nonstratified Cox proportional hazards models were used, as well as an analysis using matched cases between the groups. RESULTS: A total of 257 patients were treated with BCNU according to RTOG protocols 70-18, 83-02, and 90-06; 175 patients were treated with PCV according to RTOG protocol 94-04. All pretreatment characteristics except KPS were well balanced by treatment group; 61% of the BCNU group had a KPS of 90 to 100 compared with 73% of the PCV group (P =.0075). No statistically significant difference in survival was observed in any age group or by KPS or extent of surgery. The stratified analysis also showed no trends for improved survival by treatment group (P =. 40). The Cox model identified only age, KPS, and extent of surgery as important variables influencing survival, not treatment group. Matching cases between groups using age, KPS, and surgery resulted in 133 matched pairs. No difference in survival was observed (P =. 41). In a Cox model in which each matched pair is a strata, there was no difference between groups (P =.20). CONCLUSION: Using this retrospective analysis, there does not seem to be any survival benefit to PCV chemotherapy. Future phase III studies for patients with AA may need to consider whether BCNU or PCV is used in the control arm.     

Analysis of prognostic and survival factors related to treatment of low-grade astrocytomas in adults

Prognostic factors for low-grade astrocytomas have been proposed, but optimal treatment remains controversial. Eighty-eight consecutive adult patients with supratentorial low-grade astrocytomas were retrospectively reviewed to determine specific factors influencing outcome. All underwent craniotomy (43 radical resections, 45 nonradical resections). Sex, age at diagnosis, preoperative Karnofsky performance status (KPS), tumor location, estimated extent of resection, radiation, chemotherapy, histological type, p53 status, MIB-1 staining and the apoptotic index were assessed as parameters for prognostic significance. KPS (p = 0.03), tumor location (p < 0.001), extent of surgical resection (p < 0.001) and radiotherapy (p = 0.01) were significantly associated with longer survival rates by univariate analysis. Multivariate analysis also showed a significant correlation between radiation therapy after surgical removal and survival time (p < 0.001). p53 status was not of importance in determining the necessity for radiotherapy. Radical surgical removal is the most important factor in the management of low-grade astrocytomas. Radiation therapy appears to be effective in improving the prognosis regardless of the extent of surgical resection or the p53 status.     

Intense P53 Staining is a Valuable Prognostic Indicator for Poor Prognosis in Medulloblastoma/central Nervous System Primitive Neuroectodermal Tumors

Intense p53 immunostaining may predict for a poor prognosis in central nervous system primitive neuroectodermal tumor of childhood. Background: Medulloblastoma is a common childhood primary brain tumor. Potential prognostic indicators for patients with local disease are age, extent of resection, and gender. However, none of these are well established. Immunohistologic staining is a potentially useful means to identify high-risk patients. The purpose of this clinical pathologic study was to investigate the prognostic significance of GFAP, synaptophysin, Ki-67, and p53 immunostaining in medulloblastoma/central nervous system primitive neuroectodermal tumors (CNS PNETs.) Materials and methods: The records of 40 patients with CNS PNETs were reviewed. Their surgical specimens were immunostained for p53, glial fibrillary acidic protein (GFAP), synaptophysin, and Ki-67. The p53 specimens were scored blindly for the intensity of staining of nuclei (intense vs weak) and the quantity of cells stained. The Ki-67, GFAP, and synaptophysin specimens were analyzed for quantity of cells stained. Results: Ten patients' specimens stained intensely for the p53 protein. Eleven had weakly staining nuclei. Nineteen specimens had no staining. The patients with specimens that stained intensely had a statistically significant decreased disease free survival (P = 0.03). Mere presence or quantity of p53 nuclear staining did not correlate with disease free survival. Immunohistochemical staining for Ki-67, GFAP, and synaptophysin did not correlate with disease free survival. Clinical parameters of age, gender, and extent of resection also did not approach statistical break significance for disease free survival. Conclusion: Intense nuclear staining for p53 was the only variable in this clinical pathologic study that reached statistical significance for disease free survival. This suggests that intense staining for p53 may be the most important prognostic indicator for non-metastatic CNS PNETs. p53 Immunostaining with antibodies against p53 in CNS PNETs should be studied in a multi-institutional setting with larger numbers of patients.     

The impact of symptom interference using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) on prediction of recurrence in primary brain tumor patients

BACKGROUND:

Tumor grade, age, extent of resection, and performance status are established prognostic factors for survival in primary brain tumor (PBT) patients. Development of disease‐related symptoms is predictive of tumor recurrence in other cancers but has not been reported in the PBT population.

METHODS:

A cross‐sectional sample of 294 PBT patients participated. Progression was based on the radiologist report of the magnetic resonance imaging (MRI). The relation of clinical variables (age, extent of resection, tumor grade, and Karnofsky performance status [KPS]) and MD Anderson Symptom Inventory‐Brain Tumor Module (MDASI‐BT) mean symptom and interference subscales with progression was examined using logistic regression.

RESULTS:

The study enrolled more men (60%, n = 175); median age was 46 years. The majority had less than a gross total resection (n = 186, 64%), and a good KPS (KPS ≥ 90) (N = 208). The majority had a grade 3 or 4 tumor (n = 199) and 24% of patients had recurrence. Tumor grade and activity‐related interference were significantly related to progression. Patients with tumor grade 4 were 2.4 times more likely to have recurrence (95% CI, 1.2‐5.; P < .015). Patients with significant (ratings of ≥5) activity‐related interference were 3.8 times more likely to have recurrence (95% CI, 2.14‐6.80; P < .001). Mean activity‐related score was 4.8 for those with progression on MRI and 2.2 for those with stable disease.

CONCLUSIONS:

Significant activity‐related interference and tumor grade were associated with recurrence but not KPS, age, or extent of resection. These results provide preliminary support for the use of symptom interference in assessment of disease status. Because the authors used a cross‐sectional sample, future studies evaluating change over time are needed. Cancer 2011. © 2011 American Cancer Society.     

Prognostic implication of clinical,radiologic, and pathologic features in patients with anaplastic gliomas

BACKGROUND: The clinical evolution of anaplastic glioma (anaplastic astrocytoma, oligodendroglioma, and oligoastrocytoma) is variable. Previous studies merged patients with anaplastic glioma and the much more common glioblastoma multiforme. Therefore, the conclusions on prognostic factors reflected in part the consequences of an analysis in a heterogeneous population. METHODS: To identify clinical, neuroradiologic, pathologic, and molecular factors with prognostic significance, we analyzed 95 treated patients with a histologic diagnosis of anaplastic glioma. Variables included age, gender, clinical manifestations at diagnosis (seizures, focal neurologic deficit, and cognitive changes), computed tomographic (CT) scan characteristics (diffuse, ring, and no enhancement), tumor location, extent of resection, histopathology, postoperative Karnofsky performance status (KPS) score, adjuvant chemotherapy, tumor response, proliferation index (Ki-67 expression), and p53, p16, pRb, and epidermal growth factor receptor immunohistochemical expression. RESULTS: Ninety-five patients with a histologic diagnosis of anaplastic astrocytoma (73%), anaplastic oligoastrocytoma (16.6%), or anaplastic oligodendroglioma (10.4%) constituted the basis of this study. Median overall survival was 29 months. Multivariate analysis revealed that an age of 49 years or younger (P < 0.03), postoperative KPS score of 80 or higher (P < 0.007), absence of ring enhancement (P = 0.03), and a proliferation index of 5.1% or lower (P = 0.044) were independently associated with longer survival. The presence of an oligodendroglial component was associated with better prognosis in the univariate analysis (P = 0.009), although this lost power in the multivariate analysis. CONCLUSIONS: In addition to previously recognized prognostic variables such as age and KPS score, CT ring enhancement and tumor proliferation index were identified as independent predictors of survival in a homogeneous series of patients with anaplastic gliomas.     

Prognostic Factors Influencing Clinical Outcomes of Malignant Glioblastoma Multiforme: Clinical,Immunophenotypic, and Fluorescence in Situ Hybridization Findings for 1p19q in 816 Chinese Cases

Malignant glioblastoma multiforme (GBM) is the most malignant brain tumor and despite recent advancesin diagnostics and treatment prognosis remains poor. In this retrospective study, we assessed the clinical andradiological parameters, as well as fluorescence in situ hybridization (FISH) of 1p19q deletion, in a series ofcases. A total of 816 patients with GBM who received surgery and radiation between January 2010 and May2014 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to findthe factors independently influencing patient progression free survival (PFS) and overall survival (OS). Age atdiagnosis, preoperative Karnofsky Performance Scale (KPS) score, KPS score change at 2 weeks after operation,neurological deficit symptoms, tumor resection extent, maximal tumor diameter, involvement of eloquent cortexor deep structure, involvement of brain lobe, Ki-67 and MMP9 expression level and adjuvant chemotherapywere statistically significant factors (p<0.05) for both PFS and OS in the univariate analysis. Cox proportionalhazards modeling revealed that age ≤50 years, preoperative KPS score ≥80, KPS score change after operation ≥0,involvement of single frontal lobe, deep structure involvement, low Ki-67 and MMP9 expression and adjuvantchemotherapy were independent favorable factors (p<0.05) for patient clinical outcomes.     

Adjuvant Chemotherapy Following Surgical Resection Improves Survival in Patients With Early Stage Small Cell Lung Cancer

The purpose of this study was to determine the effects of resection coupled with standard chemotherapy on the survival prognosis of patients with early stage small cell lung carcinoma (SCLC). Patients (n=110) with mediastinal lymph node-negative SCLC were enrolled in this study. The baseline clinical data of patients with surgery were retrospectively reviewed. Overall survival (OS) and progression-free survival (PFS) were measured by Kaplan–Meier and log-rank test analyses. Ninety-eight patients received mediastinoscopy biopsy, and pulmonary lobectomy or sublobar resection, and 67 patients underwent adjuvant chemotherapy after pulmonary lobectomy. Adjuvant chemotherapy after surgical intervention was associated with longer OS (median OS: 42.14 vs. 33.53 months, p=0.01) and PFS (median PFS: 25.20 vs. 13.48 months, p=0.000) compared to resection alone for all patients. Adjuvant chemotherapy was associated with improvement of survival for N1 patients with stage II (median OS: 36.42 vs. 26.68 months, p=0.021). The median PFS was 19.02 m (16.08, 21.96) and 13.25 m (10.19, 16.30) (p=0.031), respectively, for patients of N1 stage who received chemotherapy and those who did not. Cox regression analysis demonstrated that age, TNM stage (N stage, not T stage), and chemotherapy were independent risk factors that might affect overall survival in patients with mediastinal lymph node-negative SCLC. These findings suggest that the application of adjuvant chemotherapy following pulmonary lobectomy is associated with improvements of survival prognoses for patients with SCLC. The combination of surgical intervention with conventional therapy should be taken into consideration as a prospective multidisciplinary regimen for early stage SCLC.     

Management and survival rates in patients with glioma in China (2004–2010): a retrospective study from a single-institution

To analyze the clinical characteristics and prognostic factors in patients with glioma in an academic institute in China. From October 2004 to August 2010, total 1,285 patients were diagnosed as glioma at the Glioma Center of Beijing Tiantan Hospital. Clinical and molecular pathology features and survival rates were analyzed. The median overall survival (OS) times were 78.1, 37.6 and 14.4 months for low-grade glioma (WHO grade II), anaplastic glioma (WHO grade III) and glioblastoma (WHO grade IV), respectively. In patients with low-grade glioma, age, preoperative Karnofsky performance scale (KPS), pathological type, radiotherapy, O⁶-methylguanine-DNA methyltransferase (MGMT) expression and Ki-67 expression, were significantly associated with OS in multivariate analyses; and preoperative KPS and radiotherapy were significantly associated with progression-free survival (PFS). For anaplastic gliomas, age, preoperative KPS, pathological type, extent of resection, radiotherapy, p53 expression and phosphatase and tensin homolog (PTEN) expression were associated with OS. For glioblastomas, age, preoperative KPS, pathology type, extent of resection, radiotherapy and chemotherapy were associated with OS; and age, gender, preoperative KPS, extent of resection, radiotherapy and chemotherapy were associated with PFS. This is the largest survey for glioma management in China to date. We found significant differences in age, presenting symptoms and the expression of p53, MGMT, PTEN, and Ki-67 among patients with different types of glioma. Age, preoperative KPS, tumor grades, radiotherapy, chemotherapy and Ki-67 expression were significantly associated with clinical prognosis.     

Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme

Objectives The optimal treatment for elderly patients (age > 70 years) with glioblastoma remains controversial. We conducted a prospective trial in 32 consecutive elderly patients with glioblastoma who underwent surgery followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide. Patients and Methods 32 patients 70 years of age or older with a newly diagnosed glioblastoma and a Karnofsky performance status (KPS) ≥ 70 were treated with RT (daily fractions of 2 Gy for a total of 60 Gy) plus temozolomide at the dose of 75 mg/m² per day followed by six cycles of adjuvant temozolomide (150–200 mg/m² for 5 days during each 28-day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and toxicity. Results The median OS was 10.6 months and the median PFS was 7 months. The 6-month and 12-month survival rates were 91% and 37%, respectively. The 6-month and 12-month PFS rates were 56% and 16%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.01). Adverse effects were mainly represented by neurotoxicity (40%), which resolved in most cases with the use of steroids, and Grade 3–4 hematologic toxicity in 28% of patients. Chemotherapy was stopped in 2 patients, delayed in 9 patients and reduced in 4 patients. Conclusions Standard RT plus concomitant and adjuvant temozolomide is a feasible treatment for elderly patients with newly diagnosed glioblastoma who present with good prognostic factors.     

59例青少年及儿童骨肉瘤患儿远期预后影响因素分析

目的探讨59例青少年及儿童骨肉瘤患儿远期预后影响因素。方法选择59例青少年及儿童骨肉瘤患儿,所有患儿均给予手术及术后辅助化疗,采用Kplan-Meier法对患儿的术后总生存率进行计算,采用单因素分析法对随访资料进行分析,采用Cox比例风险回归模型行多因素分析。结果 59例患儿中,术后3年患儿生存41例,死亡18例,生存率为69. 5%(41/59)。单因素分析结果表明,KPS评分、Enneeking分期、辅助化疗次数与青少年和儿童骨肉瘤患儿的远期预后相关,而性别、年龄、肿瘤部位、肿瘤大小、病理性骨折、肿瘤类型、手术类型与青少年和儿童骨肉瘤的远期预后无关。多因素分析结果表明,KPS评分、Enneeking分期、辅助化疗次数是影响青少年和儿童骨肉瘤的远期预后的独立相关影响因素。结论规范的辅助化疗可提高患儿的生存率,KPS评分、Enneeking分期是影响青少年、儿童骨肉瘤预后的独立危险因素。     

The prognostic significance of midline shift at presentation on survival in patients with glioblastoma multiforme

Purpose: While patients with glioblastoma multiforme (GBM) who present with midline shift have a presumably worse prognosis, there is little literature evaluating the prognostic significance of this presentation in multivariate analysis in the context of other known prognostic factors.

Methods and Materials: From March 1981 to September 1993, 219 patients underwent irradiation for intracranial glioma at our institution. One hundred fourteen patients with a diagnosis of a primary GBM were analyzed for the influence of the presence of midline shift at diagnosis on survival with respect to other known prognostic factors, including age, Karnofsky performance status (KPS), and extent of surgery. Eighty-five patients (74%) presented with midline shift. Surgical treatment consisted of subtotal/total resection in 86 patients (75%). Among patients presenting with midline shift, 68 (80%) underwent subtotal/total resection before irradiation.

Results: Multivariate analysis of the entire cohort of patients found none of the potential prognostic factors analyzed to significantly influence survival. The overall median survival was 6 months. However, when multivariate analysis was limited to patients with a KPS of ≥ 70, only the presence of midline shift and age were found to significantly influence survival. Patients with a KPS ≥ 70 and with midline shift present at diagnosis had a median survival of 8 months, as compared to 14 months for those not having midline shift at presentation (p = 0.04). Patients with a KPS ≥ 70 and age > 50 years had a median survival of 5 months as compared to 11 months for those ≤ 50 (p = 0.02).

Conclusion: In this series, where 80% of patients who presented with a midline shift underwent decompressive resection of GBM before irradiation, the presence of midline shift at diagnosis remained an independent prognostic factor influencing survival among good performance status patients. While the role of decompressive surgery in this setting is likely of some benefit, the extent of this benefit remains to be defined.     

Prognosis for primary retroperitoneal sarcoma survivors: a conditional survival analysis

BACKGROUND:

The AJCC staging system and post‐operative nomograms use patient and tumor characteristics to provide prognostic estimates after resection of retroperitoneal sarcoma (RPS). While these variables help to predict survival at the time of diagnosis and resection, the applicability of these prognostic factors to survivors of RPS remains unknown. We hypothesized that the variables evaluated in the current staging system and post‐operative nomograms would have limited ability to predict conditional survival in patients surgically treated for RPS.

METHODS:

A retrospective study was conducted using National Cancer Institute‐sponsored tumor registries. We identified 1,199 patients who underwent surgical resection for non‐metastatic RPS from 1988 to 2007. Conditional survival was defined as time‐specific estimates conditioned on living a certain number of years post‐diagnosis. Cox proportional hazards regression was used to assess the impact of various factors on sarcoma‐specific survival (SSS) at baseline and up to 5 years after diagnosis.

RESULTS:

Older age, male gender, histologic subtype, and high tumor grade predicted worse SSS at the time of diagnosis. After 1 year of survival, older age, male gender, and histologic subtype were no longer significant predictors of conditional survival. Only high grade tumors remained a significant predictor of worse prognosis after 5 years of survival (HR 1.95).

CONCLUSIONS:

This population‐based study demonstrates that the factors which are predictive of survival at baseline lose significance after one year of survival. Conditional survival estimates allow clinicians to provide survivors with more meaningful prognostic estimates that may impact surveillance schedules and streamline adjuvant therapy decisions and design of future clinical trials. Cancer 2012. © 2012 American Cancer Society.     

Local control and overall survival in atypical meningioma: a retrospective study

PURPOSE: To evaluate local control and overall survival after primary surgery for patients with atypical meningiomas. METHODS AND MATERIALS: From the Department of Pathology database, we identified 491 cases of meningioma treated at the Cleveland Clinic Foundation from 1979 through 1995. Thirty-three were diagnosed with atypical meningioma. Eleven of the excluded patients had incomplete records, were lost to follow-up, or received treatment elsewhere. Of the 22 evaluable patients, 15 underwent gross total resection (GTR), 4 had a subtotal resection (STR), and 3 had a resection of unknown extent. Eight patients received radiation therapy (2 after initial resection and 6 after at least one recurrence). The median radiation dose was 5,400 cGy (range 3,500-5,940). The median age at presentation was 55.5 years, the male:female ratio was 14:8, and 19/22 patients had a Karnofsky performance score (KPS) > or =80. The independent variables analyzed for overall survival and local control were gender, KPS (> or =80 vs. < 80), extent of surgery (GTR vs. STR or unknown extent of surgery), and postoperative radiation therapy. RESULTS: Median survival was 10.6 years, with a median follow-up of 5.5 years (range 1.5-14.8). Eight of the 22 patients had local recurrence, including 2/15 with GTR, 3/4 with STR, and all 3 patients who underwent resection of unknown extent. At 10 years, patients with GTR had a higher local control rate than those who had either a STR or a resection of unknown extent (87% vs. 17%; p = 0.02). The 5- and 10-year overall survival rates for the entire group were 91% and 76%, respectively. Patients who had GTR had 5- and 10-year overall survival of 87% and 87%, respectively. Patients with STR or resection of unknown extent had 5- and 10-year overall survival rates of 100% and 75%, respectively. CONCLUSION: In patients with atypical meningiomas, gross total resection is associated with a lower recurrence rate than in subtotal resection.     

Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival

According to recent developments the best treatment options for glioblastoma (GBM) consist in maximum safe resection and additional adjuvant treatment with radiotherapy (RT) and alkylating chemotherapy (CHX). These options have been evaluated for populations with a median age of approximately 58 years. We therefore addressed the issue of whether elderly patients (>65years) could also benefit from cytoreductive surgery (CS) and adjuvant treatment using alkylating chemotherapy. One-hundred and three patients suffering from newly diagnosed, primary supratentorial glioblastoma multiforme >65 years (median 70.8 years) were identified in our single-center glioma database (2002–2007) and retrospectively divided into group A (n = 31) treated with surgery alone (biopsy, BY, n = 21, CS n = 10), group B (n = 37) surgery plus radiation (BY n = 18, CS n = 19), and group C (n = 35) surgery, RT and CHX (BY n = 4, CS n = 31). Progression-free survival (PFS) and overall survival (OAS) were determined in each group and correlated to age, Karnofsky performance score (KPS), and extent of resection (biopsy (BY), partial (PR), and complete resection (CR)). Progression was defined according the Macdonald criteria. For all patients PFS and OAS were 3.2 months and 5.1 months (m) respectively. PFS and OAS for groups A/B/C were 1.8/3.2/6.4 m (P = 0.000) and 2.2/4.4/15.0 m (P = 0.000), respectively. Median age for groups A/B/C was 74.4/70.6/68.5 years and median KPS was 60/70/80. Age (<75, ≥75) was inversely correlated with OAS (5.8/2.5 m, P = 0.01). KPS (<70, ≥70) was correlated with OAS 2.4/6.5 m (P = 0.000). Extent of resection (BY, PR, or CR) correlated with PFS (2.1/3.4/6.4 m, P = 0,000) and OS (2.2/7.0/13.9 m, P = 0,000), respectively. Our study shows that elderly GBM patients can benefit from maximum treatment procedures with cytoreductive microsurgery, radiation therapy, and chemotherapy. Treatment options are obviously affected by KPS and age. The most impressive outcome predictor in this population was the extent of microsurgical resection for patients treated with adjuvant radiotherapy and chemotherapy. To conclude, elderly GBM patients should not be per se excluded from intensive treatment procedures.     

Postoperative seizures in meningioma patients: improving patient selection for antiepileptic drug therapy

The diagnosis of glioblastoma (GBM) often carries a dismal prognosis, with a median survival of 14.6 months. A particular challenge is the diagnosis of GBM in the elderly population (age?>?75 years), who have significant comorbidities, present with worse functional status, and are at higher risk with surgical treatments. We sought to evaluate the impact of current GBM treatment, specifically in the elderly population. The authors undertook a retrospective review of all patients aged 75 or older who underwent treatment for GBM from 1997 to 2016. Patient outcomes were evaluated with regards to demographics, surgical variables, postoperative treatment, and complications. A total of 82 patients (mean age 80.5?±?3.8 years) were seen. Most patients presented with confusion (57.3%) and associated comorbidities, and prior anticoagulation use was common in this age group. Extent of resection (EOR) included no surgery (9.8%), biopsy (22.0%), subtotal resection (40.2%), and gross-total resection (23.2%). Postoperative adjuvant therapy included temozolomide (36.1%), radiation (52.5%), and bevacizumab (11.9%). A mean overall survival of 6.3?±?1.2 months was observed. There were 34 complications in 23 patients. Improved survival was seen with increased EOR only for patients without postoperative complications. A multivariate Cox proportional hazards model showed that complications (HR?=?5.43, 95% CI 1.73, 17.04, p?=?0.004) predicted poor outcome. Long-term survivors (>?12 months survival) and short-term survivors had similar median preoperative Karnofsky Performance Scale (KPS) score (80 vs. 80, p?=?0.43), but long-term survivors had unchanged postoperative KPS (80 vs. 60, p?=?0.02) and no complications (0/9 vs. 23/72, p?=?0.04). The benefit of glioblastoma treatment in our series was limited by the postoperative complications and KPS. Presence of a complication served as an independent risk factor for worsened overall survival in this age group. It is likely that decreased patient function limits postoperative adjuvant therapy and predisposes to higher morbidity especially in this age group.     

高分级脑胶质瘤术后精确放疗患者的预后影响因素

目的:分析高分级脑胶质瘤术后精确放疗患者预后的危险因素及干预对策。方法:回顾自2009年6月至2013年6月入我院的病理诊断为高分级脑胶质瘤术后精确放疗的患者资料。对患者的一般情况如性别、年龄、手术切除程度、病理分级、化疗、放疗量、KPS评分、术前癫痫发作、总生存期（随访2年）等数据进行分析,评价高分级脑胶质瘤术后精确放疗患者预后的危险因素。结果:在123例患者中,年龄16~86岁,平均发病年龄46.9岁,男性平均发病年龄42.0岁,女性平均发病年龄49.5岁。小于40岁患者68例,大于等于40岁患者55例。从发病到明确诊断平均时间9.8月,中位生存时间19个月,1年生存率69%,2年生存率37.4%。单因素分析显示,年龄、手术切除程度、病理分级、化疗与高分级脑胶质瘤术后精确放疗患者预后显著相关（P＜0.05）,性别、放疗、术前癫痫发作、KPS评分与高分级脑胶质瘤术后精确放疗患者预后无明显相关（P>0.05）。多因素COX回归分析显示,年龄<40岁（RR=1.844,95%CI:1.047~3.249）、肿瘤全切（RR=2.348,95%CI:1.389~3.968）、病理分级3级（RR=2.632,95%CI:1.479~4.684）、同步替莫唑胺化疗（RR=0.557,95%CI:0.329~0.944）能够显著延长患者的总生存时间。结论:年龄、手术切除程度、病理分级、化疗等是高分级脑胶质瘤术后精确放疗患者生存预后的危险因素。年龄<40岁、肿瘤全切、病理分级低、同步化疗患者生存预后较好。     

Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic astrocytoma: validation of Radiation Therapy Oncology Group-Recursive Partitioning Analysis in the IMRT and temozolomide era

Since the development of the Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) risk classes for high-grade glioma, radiation therapy in combination with temozolomide (TMZ) has become standard care. While this combination has improved survival, the prognosis remains poor in the majority of patients. Therefore, strong interest in high-grade gliomas from basic research to clinical trials persists. We sought to evaluate whether the current RTOG-RPA retains prognostic significance in the TMZ era or alternatively, if modifications better prognosticate the optimal selection of patients with similar baseline prognosis for future clinical protocols. The records of 159 patients with newly-diagnosed glioblastoma (GBM, WHO grade IV) or anaplastic astrocytoma (AA, WHO grade III) were reviewed. Patients were treated with intensity-modulated radiation therapy (IMRT) and concurrent followed by adjuvant TMZ (n = 154) or adjuvant TMZ only (n = 5). The primary endpoint was overall survival. Three separate analyses were performed: (1) application of RTOG-RPA to the study cohort and calculation of subsequent survival curves, (2) fit a new tree model with the same predictors in RTOG-RPA, and (3) fit a new tree model with an expanded predictor set. All analyses used a regression tree analysis with a survival outcome fit to formulate new risk classes. Overall median survival was 14.9 months. Using the RTOG-RPA, the six classes retained their relative prognostic significance and overall ordering, with the corresponding survival distributions significantly different from each other (P < 0.01, χ² statistic = 70). New recursive partitioning limited to the predictors in RTOG-RPA defined four risk groups based on Karnofsky Performance Status (KPS), histology, age, length of neurologic symptoms, and mental status. Analysis across the expanded predictors defined six risk classes, including the same five variables plus tumor location, tobacco use, and hospitalization during radiation therapy. Patients with excellent functional status, AA, and frontal lobe tumors had the best prognosis. For patients with newly-diagnosed high-grade gliomas, RTOG-RPA classes retained prognostic significance in patients treated with TMZ and IMRT. In contrast to RTOG-RPA, in our modified RPA model, KPS rather than age represented the initial split. New recursive partitioning identified potential modifications to RTOG-RPA that should be further explored with a larger data set.     

Significance of vascular endothelial growth factor,interleukin-18 and nitric oxide in patients with breast cancer: correlation with carbohydrate antigen 15.3

JAK/STAT pathway transmits signals from the cell membrane to the nucleus in response to extracellular growth factors and cytokines. Activation of this pathway has been found in certain types of human tumors. The goal of this study was to investigate the correlation between the JAK/STAT pathway in human gliomas and patients’ prognosis, which currently is unknown. Western blotting analysis and immunohistochemical staining were performed to detect JAK-1, phosphorylated JAK-1, and STAT-3 expression patterns in the biopsies from 96 patients with primary gliomas. Kaplan–Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Western blotting analysis and immunohistochemical staining both indicated that the expression levels of JAK-1, phosphorylated JAK-1, and STAT-3 in primary glioma tissues were significantly higher than those in normal brain tissues (P < 0.001). Especially, the positive expression rates of JAK-1, phosphorylated JAK-1, and STAT-3 were significantly higher in patients with higher grade (P = 0.001, 0.001, and 0.002, respectively) and lower KPS score (P = 0.01, 0.008, and 0.01, respectively). Statistical analysis showed that patients with gliomas expressing JAK-1 and STAT-3 have lower overall survival rates relative to those not expressing these proteins. Cox multi-factor analysis showed that KPS (P = 0.03), WHO grade (P = 0.008), JAK-1 (P = 0.005), and STAT-3 (P = 0.006) were independent prognosis factors for human gliomas. These results provide convincing evidence for the first time that the JAK/STAT pathway may play a role in the progression of human gliomas. Its activated state might be a potent tool for predicting the clinical prognosis of patients with glioma.