Joint NCCTG and NABTC prognostic factors analysis for high-grade recurrent glioma

The purpose of this study is to determine prognostic factors in patients with high-grade recurrent glioma for 3 outcome variables (overall survival, progression-free survival [PFS], and PFS rate 6 months after study registration [PFS6]). Data from 15 North Central Cancer Treatment Group (NCCTG) trials (n = 469, 1980–2004) and 12 North American Brain Tumor Consortium (NABTC) trials (n = 596, 1998–2002) were included. Eighteen prognostic variables were considered including type of treatment center (community/academic) and initial low-grade histology (yes/no). Recursive partitioning analysis (RPA), Cox proportional hazards, and logistic regression models with bootstrap resampling were used to identify prognostic variables. Longer survival was associated with last known grade (Grade) of III, younger age, ECOG performance score (PS) of 0, shorter time from initial diagnosis (DxTime), and no baseline steroid use. Factors associated with longer PFS were Grade III and shorter DxTime. For patients without temozolomide as part of the treatment regimen, the only factor associated with better PFS6 was Grade III, although DxTime was important in RPA and PS was important in logistic regression. Grade was the most important prognostic factor for all three endpoints regardless of the statistical method used. Other important variables for one or more endpoints included age, PS, and DxTime. Neither type of treatment center nor initial low-grade histology was identified as a major predictor for any endpoint.     

A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population-based cohort study (CCLG CNS9702)

The purpose of this study was to identify risk factors for the progression of low-grade glioma in children from a large population-based cohort. Patient and tumor details of a national cohort of children with low-grade glioma, recruited into an international multidisciplinary clinical strategy, were subjected to univariate and multivariate analyses of progression-free survival and overall survival. From the cohort of 798 patients, 639 patients were eligible, with a median age 6.71 years (0.26–16.75 years); 49% were males; 15.9% had neurofibromatosis type 1, 63.7% pilocytic astrocytoma, 5.9% fibrillary astrocytoma, 4.2% mixed neuronal-glial tumors, and 3.6% others; 21.1% were diagnosed clinically. Anatomically implicated were 31.6% cerebellum, 24.6% chiasma/hypothalamus, 16.0% cerebral hemispheres, 9.9% brain stem, 6.1% other supratentorial midline structures, 5.9% optic nerve only, 4.5% spinal cord, and 1.4% others. The 5-year overall survival and progression-free survival in the whole cohort were 94.6% and 69.4%, respectively. There was a significant association between age and site (P < .001) and extent of tumor resection and site (P < .001). Multivariate analysis identified young age, fibrillary astrocytoma, and extent of surgical resection as significant independent risk factors for progression. Hypothalamic/chiasmatic tumors demonstrated the most sustained tendency to progress. In conclusion, the influence of age and anatomical site upon the risk of tumor progression suggests that these factors strongly influence tumor behavior for the majority of pilocytic tumors. Age <1 year and 1–5 years, fibrillary histology, completeness of resection, and chiasmatic location are candidates for stratification in future studies.     

The prognostic influence of bcl-2 in malignant glioma

The bcl-2 gene is one of a complex group of genes which control programmed cell death. Bcl-2 acts to extend cell survival by blocking apoptosis, and thereby may influence tumour prognosis. This study of 187 high grade gliomas reviews clinicopathological prognostic features and the relationship to bcl-2 expression. Bcl-2 immunostaining was assessed in 159 specimens from these patients, by scoring systems of 0 to 3 for intensity of scoring and proportion of cells staining. Age, histology, pre- and post-operative performance status were found to be strongly predictive of survival (log rank test P<0.0001). The type of surgery performed did not influence survival in this group of patients. The expression of bcl-2 had a significant relationship with survival (univariate Cox model P=0.0302, hazard ratio 0.8, 95% confidence interval 0.65-0.98), with increased staining associated with improved survival. Multivariate analysis showed performance status, histology and proportion of cells staining for bcl-2 to be independently predictive of survival. Bcl-2 staining was not related to histological grade of tumours.     

Pretreatment prognostic factors for survival in small-cell lung cancer: A new prognostic index and validation of three known prognostic indices on 341 patients

Aims: a) To identify which pretreatment clinical or blood parameters werepredictive of patient survival in small-cell lung cancer (SCLC) in aretrospective analysis. b) To validate three known prognostic indices: RoyalMarsden Model (index 1), London Group (index 2) and Manchester Score (index3).Patients and methods: From 1981 to 1993, 341 SCLC patients were treatedwith chemotherapy with or without surgery or radiotherapy. Univariate andmultiple regression analyses of survival were performed and the feasibilityof these models was explored, index 1: Karnofsky index, albumin, sodium andalkaline phosphatase; index 2: ECOG performance status (PS), albumin andalanine transaminase; and index 3: lactate dehydrogenase (LDH), diseaseextent, sodium, Karnofsky index, alkaline phosphatase and bicarbonate.Results: Significant prognostic factors for survival after univariate andmultiple regression analysis were: disease extent, PS, creatine kinase,neutrophilia, LDH, hypoalbuminemia, hyperglycemia and bicarbonate. A newprognostic index was performed that included LDH, hypoalbuminemia,neutrophilia, disease extent and PS. It defined three prognostic groups (PG).Median survival and two-year survival for these PG were 12.3, 8 and 3.4 monthsand 16.5%, 2.3% and 0%, respectively. The following PGwere identified after application of the three models proposed: Index 1identified two PG with 0% and 16.6% two-year survival (P <0.001); index 2 detected three PG with 0%, 5% and 15.7%two-year survival (P < 0.001) and index 3 detected three PG with 0%,2.5% and 16.2% two-year survivals, respectively (P < 0.001).Conclusion: A new prognostic index is proposed allowing identification ofthree different PG. The feasibility of three known prognostic models wasvalidated and demonstrated. Variables other than disease extent or PS (albuminor LDH) should be taken into account in designing future clinical trials.     

Prognostic factors in angiosarcoma: A multivariate analysis of 55 cases

Data for prognostic factors in angiosarcoma (AS) are limited, prompting a large-scale study of AS with multivariate analysis. To analyze prognostic factors in angiosarcoma (AS), clinical and histologic findings in 55 patients collected from hospitals in Japan were reviewed. Prognostic factors were evaluated by univariate and multivariate Cox's proportional hazards models. The study involved 32 males and 23 females, ages 18–93 (median, 69) years. The primary sites of tumors included head and neck (32 cases), trunk (10), extremities (3), spleen (3), breast (3), and other (4). The overall 2-year survival rate was 21%. Univariate analysis of clinical factors including age, sex, size and depth of tumor, tumor-related symptoms, interval between onset of symptoms and admission, surgical procedures, adjuvant chemotherapy, and adjuvant radiotherapy showed that age, tumor size, and mode of treatment were significant for survival. Histologic factors analyzed were mitotic counts, cellularity, cellular pleomorphism, extent of necrosis, vascular differentiation, and nonspecific diagnosis. Only mitotic counts were significant for prognosis. Multivariate analysis on these four factors revealed that tumor size, mode of treatment, and mitotic counts were independent prognostic factors. © 1996 Wiley-Liss, Inc.     

术前预后营养指数在脑胶质瘤患者术后预后评估中的应用

目的:探讨术前预后营养指数(prognostic nutrition index,PNI)在脑胶质瘤患者术后临床预后中的应用。方法:收集2011年1月至2017年6月四川省大邑县人民医院神经外科手术治疗且经术后病理确诊的131例初发脑胶质瘤患者的临床资料及术后生存资料,采用ROC曲线分析获得PNI的最佳临界值,依据该最佳临界值将患者分为高PNI值组及低PNI值组,采用卡方检验比较两组临床病理学特征,采用Cox比例风险回归模型分析PNI与胶质瘤患者术后临床预后的关系。结果:131例脑胶质瘤患者术后中位总生存时间（overall survival,OS）为23个月,95%CI:9.736~36.264个月,术后1年、2年、3年、5年生存率分别为76.3%、52.0%、43.0%、33.5%。ROC曲线分析,PNI的最佳临界值为48.5。低PNI值组中年龄≥45岁、行非全切手术和较低级别肿瘤分级所占的比例较高PNI值组更高(P＜0.05)。多因素Cox回归分析显示,肿瘤分级、PNI值是影响脑胶质瘤患者术后预后的独立影响因素。结论:PNI值为脑胶质瘤患者预后的独立危险因素,较低的PNI水平预示着较差的预后。PNI值可用于初步判断脑胶质瘤患者的预后。     

Prognostic indexes in follicular lymphoma: a comparison of different prognostic systems.

BACKGROUND: The International Prognostic Index (IPI), initially designed for aggressive lymphomas, is also used in follicular lymphoma (FL) and other indolent lymphomas. Two new prognostic indexes have recently been proposed for FL [the Italian Lymphoma Intergroup (ILI) Index and the Follicular Lymphoma International Prognostic Index (FLIPI)]. PATIENTS AND METHODS: Three indexes, IPI [age >60 years, extranodal involvement two or more sites, elevated lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group performance status > or =2, stage > or =3], ILI (age >60 years, extranodal involvement two or more sites, elevated LDH, male sex, B symptoms, erythrocyte sedimentation rate > or =30 mm first hour) and FLIPI (age >60 years, stage > or =3, elevated LDH, nodal involvement five or more, haemoglobin level < or =12 g/dl) were calculated in 411 patients with FL. RESULTS: Overall concordance between the three indexes was 54%. A total of 126 (31%) patients were included in the high-risk group according to IPI, 131 (32%) according to ILI and 157 (38%) after FLIPI application. Ten-year overall survival rates after applying the prognostic indexes (IPI, ILI and FLIPI) were, respectively: 72%, 71% and 72%, in the low-risk group; 51%, 60% and 49% in the intermediate-risk group; and 24%, 16% and 31% in the high-risk group. CONCLUSIONS: In this series, all three indexes, IPI, ILI and FLIPI, were useful to classify FL patients into differentiated risk groups, although the FLIPI identified a larger proportion of high-risk patients than the IPI and ILI.     

常规加IMRT推量放疗联合化疗治疗高分级胶质瘤的疗效和预后因素

Objective:The aim of the study was to retrospectively evaluate the outcomes and important prognostic factors for patients with high-grade gliomas(HGG)treated with conventionalradiotherapy(RT)followed by IMRT as a boost in com bination with chemotherapy.Methods:From November 2004 to November 2006,112 consecutive patients with high-grade gliomas were treated with radiotherapy,which included initial conventional radiotherapy and an IMRT boost to a total dose of 57.5-62.5 Gy,with 27-29 fractions delivered over 37-45 days.All cases received 3-6 cycles of chemotherapy,63 cases received temozolomide,and another 49 cases received methyl-CCNU and teniposide.The acute and late treatment toxicities and the patterns of treatment failure were recorded.The overall survival(OS)rate and progression-free survival(PFS)rate were calculated,and the prognostic factors were analyzed.Results:Most of the acute radiation reactions were grade 1 or 2.No grade 4 acute reactions were noted.Three cases developed radiation necrosis.Grades Ⅰ,Ⅱ,and Ⅲ myelosuppressions were observed in 5,32,and 12 cases of 49 patients treated with teniposide and methyl-CCNU,respectively.Grades Ⅰ and Ⅱmyelosuppressions were observed in 15 and 3 of the 63 patients who were treated with temozolomide,respectively.The 57 cases(50.9%)had recurred locally,and 13 cases(11.6%)had intracranial dissemination.The OS rates at 1,2,and 3 years were 78.9%,54.7%,and 30.8%,respectively.The PFS rates at 1,2,and 3 years were 63.8%,38.9%,and 10.5%,respectively.A multivariate analysis showed that only tumor location and KPS were prognostic factors of OS.These same two variables and histopathology were statistically significant predictive factors in a multivariate analysis for PFS.Conclusion:Radiation toxicities were not found to be increased in this retrospective study with 112 consecutive patients of combined modality therapy including an IMRT boost treatment for HGG.Higher rate of local regional dissemination within the brain was observed than before.Tumor location,histopathology and KPS were important prognostic factors.     

Analyzing prognostic factors in breast cancer using a multistate model

In breast cancer clinical research, an important goal is to analyze how factors are seen to affect the disease process. Meanwhile, the disease progression is not fully modelled using standard analysis since transitions between intermediate events such as local-regional recurrences (LRR) or metachronous contralateral breast cancer (MCBC) are not considered. In the present study, the progression of disease was modelled using a multistate model. By this approach, we assessed transitions during the course of the disease and studied prognostic factors for each transition. The model was applied to 6,185 patients with unilateral ductal invasive breast cancer, clinical stage I through III, treated between 1981 and 1988 at the Curie Institute.At first diagnosis, high clinical stage, high histological grade, positive lymph nodes, and age less than 40 years were associated with increased risks of LRR, metastases, or death. Except age, the same factors remained predictive for metastases or death following LRR. Chemotherapy for the first cancer was associated with a decreased risk for developing MCBC. As the time interval from diagnosis of the primary tumor to that of a local or contralateral recurrence increased, the risk of metastases or death decreased. Nodal status for the first tumor and clinical stage for the contralateral tumor increased the risk of metastases or death following MCBC. Conversely, the risk decreased for patients who received adjuvant hormone therapy following MCBC. In conclusion, the multistate model offers us a much more appropriate way to study prognostic factors for each transition in breast cancer disease.     

分子标志物在高级别胶质瘤患者预后评估中的价值

目的:探讨分子标志物在高级别胶质瘤患者预后评估中的价值。方法:收集2010年09月至2015年07月之间经我院收治的高级别胶质瘤患者31例,免疫组织化学染色检测患者肿瘤组织中Ki-67、6-氧-甲基鸟嘌呤-DNA甲基转移酶（MGMT）、表皮生长因子受体（EGFR）、p53和基质金属蛋白酶-9（MMP-9）的表达;电话及门诊随访患者生存状况,分析上述分子标志物在高级别胶质瘤患者预后评估中的价值。结果:Ki-67和MGMT高表达患者的PFS明显低于低表达患者（P＜0.05）,但MMP-9、EGFR和p53表达水平与PFS间未见明显相关性（P＞0.05）。多因素分析发现Ki-67是影响PFS的独立预后因素(RR=5.19,P＜0.05)。结论:Ki-67是影响高级别胶质瘤患者PFS的独立危险因素,在预后评估中可能具有潜在的应用价值。     

Prognostic factors: Rationale and methods of analysis and integration

Summary With the proliferation of potential prognostic factors for breast cancer, it is becoming increasingly more difficult for physicians and patients to integrate the information provided by these factors into a single accurate prediction of clinical outcome. Here we review Cox's proportional hazards model, recursive partitioning, correspondence analysis, and neural networks for their respective capabilities in analyzing censored survival data in the presence of multiple prognostic factors, and we present some clinical applications where these models have been used.     

Prognostic factors of esophageal carcinoma: univariate and multivariate analyses

The correlation of 5-year survival rate with various clinical and histopathological factors was studied using univariate and multiple analyses of 128 patients who had undergone resection for esophageal carcinoma between 1965 and 1978 in the Department of Surgery, Kyushu University Hospital. The depth of penetration, lymph node metastasis, lymphatic or vascular invasion, and INF had a significant correlation with 5-year survival in the univariate analysis; however, only depth of penetration and lymph node metastasis were prognostic factors with a significant difference, in the multivariate analysis. In 55 patients in whom the cell nuclear DNA content had been determined, the DNA pattern was the greatest prognostic factor (p less than 0.01), in multivariate analysis. We propose that the DNA distribution in the malignant cells should be examined as a most pertinent prognostic factor.     

Multivariate analysis of factors affecting postoperative survival in malignant astrocytoma

Summary Fifty-eight patients with supratentorial malignant astrocytoma were analyzed statistically to evaluate the actors most important for predicting postoperative survival. Clinical information such as age, sex, duration of preoperative symptom, Karnofsky score at admission and at discharge, location of tumor, amount of tumor removal, number of operations, and postoperative survival in months, together with data on radiation and chemotherapy were analyzed by chi square test, t-test, and multivariate analysis. Cytofluorometric DNA quantification using paraffin embedded specimens was also performed in 20 cases and these data were also evaluated.Multiple correlation coefficient, and therefore the total statistical accuracy, increased to 0.824 when data of DNA quantification, percentages of S phase cells and of polyploid cells, were included. Multivariate analysis revealed that 6 items were the major factors for predicting postoperative survival, i.e. the location of tumor, the Karnofsky score at discharge, the percentage of S phase cells, the number of operations, the percentage of polyploid cells, and the amount of tumor removed. Based on this analysis, the estimated survival time could be expressed as a formula.This work was partly supported by a Grant-in Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.     

Development and validation of a pretreatment prognostic index to predict death and lung metastases in extremity osteosarcoma

Background

To develop a prognostic index to predict the 5-year overall survival (OS) and 5-year lung metastasis-free survival (LMFS) of patients with extremity osteosarcoma at the time of diagnosis.

Methods

We retrospectively evaluated 454 patients with extremity osteosarcoma at our center from 2005 to 2013. The cohort was randomly divided into training and validation sets. The association of potential risk factors with OS and LMFS was assessed by Cox proportional hazards analysis in the training set, and a prognostic index was created according to scores that were proportional to a regression coefficient for each factor. This prognostic index was assessed in the validation set.

Results

For the 5-year OS, 5 independent prognostic factors were identified: tumor size, Enneking stage, pretreatment platelet, alkaline phosphatase(ALP), and neutrophils. The multivariate Cox model identified tumor size, pretreatment platelets, ALP, and neutrophils as associated with the 5-year LMFS. A prognostic index for death and lung metastases was calculated. Three risk groups were defined for each survival point: low, intermediate, and high risk for the 5-year OS; low, intermediate, and high risk for the 5-year LMFS. The C statistic for the 5-year OS was 0.723 in the training set and 0.710 in the validation set. The C statistic for the 5-year LMFS was 0.661 and 0.693 respectively.

Conclusion

This prognostic index is based on routine tests and characteristics of extremity osteosarcoma patients and is a useful predictor of OS and lung metastases. This index could be applied to clinical practice and trials for individualized risk-adapted therapies.     

Prognostic factors in chordoma: Role of postoperative radiotherapy

We have investigated prognostic factors for survival in a series of 26 patients with chordoma treated in Lyon, France, between 1979 and 1993. In this series, the median progression-free (PFS) and overall survival (OS) were 10 and 90 months, respectively. In univariate analysis, PFS, but not OS, was found significantly longer in males as compared to females (median: 19 versus 7 months, P = 0.05); and patients under 60 years of age had a longer PFS (median: 18 versus 6 months; P = 0.06) and OS (median: 108 versus 47+, P = 0.05) than older patients. A favourable prognostic subgroup including male patients under 60 years and a poor prognostic group including female patients and male over 60 years were thus defined (median PFS: 36 versus 6 months, P = 0.001; median OS: 108 versus 55+, P = 0.15). Primary treatment combining surgery and postoperative radiotherapy was associated with a longer PFS than surgery only (median: 36 versus 7 months, P = 0.002) in the whole series and in both prognostic subgroups.     

Prognostic significance of the immunohistochemical index of survivin in glioma: a comparative study with the MIB-1 index

Summary Objective: Survivin has been identified as a protein expressed in cancer cells and a member of the inhibitor-of-apoptosis protein family. Recent studies suggest that the expression of survivin increases during the G2/M phase of the cell cycle, and may be used in clinical prognosis. We examined whether survivin expression in human gliomas would be a correlative of prognosis. Methods: We prepared polyclonal anti-survivin serum to establish a survivin index for stained sections, using an immunohistochemical procedure, according to the method used for scoring MIB-1 index, and then stained 29 paraffin-embedded sections from surgical specimens of 29 patients who were classified into three grades of World Health Organization with the mean age of low grade astocytoma (grade II) being 34.7; anaplastic astrocytoma (grade III), 48.8; and glioblastoma multiform (grade IV), 58.4. Results: On staining with the anti-survivin antiserum, all specimens contained positive cells, but the survivin index was heterogeneous among grades. The mean percentage of immunoreactive cells in each specimen was 70.0 (SD 18.2) in grade II, 81.3 (16.5) in grade III, and 85.0 (13.6) in grade IV. Then we compared the survivin index to the MIB-1 index and found that in low-grade gliomas (grade II and III), the difference in survival times between the high and low survivin indexes was significant (P=0.007), whereas that between the high and low MIB-1 indexes was not significant (P=0.092).Conclusion: Survivin is more sensitive marker than MIB-1 for the evaluation of low-grade gliomas in that it helps to predict patient survival. Much larger glioma patient series are needed to validate the findings of our limited study.     

Increased tryptophan uptake on PET has strong independent prognostic value in patients with a previously treated high-grade glioma

Background

Previously, we demonstrated the high accuracy of alpha-[¹¹C]methyl-L-tryptophan (AMT) PET for differentiating recurrent gliomas from radiation injury. The present study evaluated the prognostic value of increased AMT uptake in patients with previously treated high-grade glioma.

Methods

AMT-PET was performed in 39 patients with suspected recurrence of World Health Organization grades III–IV glioma following surgical resection, radiation, and chemotherapy. Mean and maximum standardized uptake values (SUVs) and unidirectional AMT uptake (K) were measured in brain regions suspicious for tumor and compared with the contralateral cortex (ie, background). Optimal cutoff thresholds for 1-year survival prediction were determined for each AMT parameter and used for calculating the prognostic value of high (above threshold) versus low (below threshold) values for post-PET overall survival (OS).

Results

In univariate analyses, 1-year survival was strongly associated with 3 AMT parameters (SUV_max, SUV_mean, and tumor-to-background K-ratio; odds ratios: 21.3–25.6; P ≤ .001) and with recent change in MRI contrast enhancement (odds ratio: 14.7; P = .02). Median OS was 876 days in the low- versus 177 days in the high-AMT groups (log-rank P < .001). In multivariate analyses, all 3 AMT parameters remained strong predictors of survival: high AMT values were associated with unfavorable 1-year survival (binary regression P ≤ .003) and shorter overall survival in the whole group (Cox regression hazard ratios: 5.3–10.0) and in patients with recent enhancement change on MRI as well (hazard ratios: 7.0–9.3; P ≤ .001).

Conclusion

Increased AMT uptake on PET is highly prognostic for 1-year and overall survival, independent of MRI contrast enhancement and other prognostic factors in patients with a previously treated high-grade glioma.     

Prognostic factors of hepatic resection for hepatocellular carcinoma with cirrhosis: univariate and multivariate analysis

BACKGROUND AND OBJECTIVES: The objective of this investigation was to study the clinicopathological factors influencing long-term outcome of hepatocellular carcinoma (HCC) with liver cirrhosis in patients undergoing hepatectomy. Liver cirrhosis, especially the macronodular variety, has been found in up to 90% of patients with HCC. In Asia, the incidence of liver cirrhosis in patients with HCC who had undergone hepatic resection varies from 42.5% to 73.8%. However, the optimal surgical approach for HCC patients with cirrhosis is less clearly defined. Resection of the cirrhotic liver is challenging and remains controversial in the treatment of HCC. METHODS: This study retrospectively analyzed the surgical outcomes of HCC concomitant with liver cirrhosis in 218 patients who underwent hepatic resection between 1986 and 1998. Post-resection prognostic factors were assessed using a univariate log-rank test and a multivariate Cox proportional hazards model. RESULTS: The overall postoperative complication rate was 15.6%, while the surgical mortality rate was 8.8%. Meanwhile, the 1-, 3-, and 5-year disease-free survival rates were 50.9%, 33.98%, and 27.03%, respectively, and. the overall cumulative survival rates at 1, 3, and 5 years were 63.14%, 41.88%, and 31.83%, respectively. Applying Cox's multivariate proportional hazard model indicated that significant adverse prognostic indicators included elevated alkaline phosphatase value, tumor size >2 cm, presence of satellite lesions, and vascular invasion. CONCLUSIONS: This investigation found that overall survival for HCC patients concomitant with liver cirrhosis who underwent hepatic resection should be stratified on the basis of the high value of alkaline phosphatase, tumor size, satellite lesions, and vascular invasion.