Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme

Glioblastoma multiforme (GBM) frequently involves amplification and alteration of the epidermal growth factor receptor (EGFR) gene, resulting in overexpression of varied mutations, including the most common mutation, EGFRvIII, as well as wild-type EGFR (EGFRwt). To test the prognostic value of EGFR, we retrospectively analyzed the relationship between treatment outcomes and the EGFR gene in 87 newly diagnosed adult patients with supratentorial GBM enrolled in clinical trials. The EGFR gene status was assessed by Southern blots and EGFR expression by immunohistochemistry using three monoclonal antibodies (EGFR.25 for EGFR, EGFR.113 for EGFRwt, and DH8.3 for EGFRvIII). EGFR amplification was detected in 40 (46%) of the 87 GBM patients; in 39 (97.5%) of these, EGFR was overexpressed. On the other hand, in 46 of 47 patients without EGFR amplification (97.9%), no EGFR overexpression was present. There was a close correlation between EGFR amplification and EGFR overexpression (P < 0.0001). EGFRwt was overexpressed in 27 of the 40 (67.5%) patients with, and in none without, EGFR amplification (P < 0.0001). Similarly, EGFRvIII was overexpressed in 18 (45.0%) of 40 patients with and in 4 (8.5%) of 47 patients without EGFR amplification (P < 0.0001). The finding that 8 (20%) of the patients with EGFR amplification/EGFR overexpression manifested overexpression of neither EGFRwt nor EGFRvIII indicates that they overexpressed other types of EGFR. Multivariate analysis demonstrated that EGFR amplification was an independent, significant, unfavorable predictor for overall survival (OS) in all patients (P = 0.038, HR = 1.67). With respect to the relationship of age to EGFR prognostication, the EGFR gene status was a more significant prognosticator in younger patients, particularly in those <60 years (P = 0.0003, HR = 3.15), whereas not so in older patients. EGFRvIII overexpression, on the other hand, was not predictive for OS. However, in patients with EGFR amplification, multivariate analysis revealed that EGFRvIII overexpression was an independent, significant, poor prognostic factor for OS (P = 0.0044, HR = 2.71). This finding indicates that EGFRvIII overexpression in the presence of EGFR amplification is the strongest indicator of a poor survival prognosis. In GBM patients, EGFR is of significant prognostic value for predicting survival, and the overexpression of EGFRvIII with amplification plays an important role in enhanced tumorigenicity.     

Tinzaparin prophylaxis against venous thromboembolic complications in brain tumor patients

Not all Glioblastoma multiforme (GBM, grade IV WHO) manifest the same clinical course. Different prognostic classes may arise from different morphologic and genetic profiles. The observation of oligodendroglial foci within GBM samples and their correlation with genetic alterations may predict a better prognosis. 450 patients affected by histologically proven supratentorial cerebral GBM were treated at our institutions from January 2000 to December 2006: all patients received at least subtotal surgical removal, followed by the same standard radio-chemotherapy adjuvant treatment. In a subgroup of 36 patients (8.0%) an oligodendroglial component was observed. Molecular assessment of these cases was performed and LOH for 1p, 19q and 10q, EGFR amplification and TP53 gene expression was determined. Median age of this subgroup was 52.1 years (range: 29–78 years) vs 62.4 years in the entire GBM population. Chromosome analysis resulted as follows: LOH 1p and/or 19q in 27 cases (75.0%), LOH of 10q in 21 cases (58.1%), EGFR amplification in 14 cases (39%) and TP53 mutation in eight patients (22.2%). OS was of 20.9 months while it was 13.6 months in the entire GBM population. Progression free survival (PFS) was 10.3 months and 7.6 months the entire group. Two-year survival was of 55%. The presence of an oligodendroglial component in GBM appears to be an important prognostic factor to which better prognosis can be related. LOH 1p and 19q was significantly associated with GBM with oligodendroglial component.     

Results of whole brain radiotherapy and recursive partitioning analysis in patients with brain metastases from renal cell carcinoma: a retrospective study

PURPOSE: To determine the benefit of whole brain radiotherapy (WBRT) and the use of the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classification system in patients with brain metastases from renal cell carcinoma. METHODS AND MATERIALS: We identified 46 consecutive patients with brain metastases from renal cell carcinoma who were treated with WBRT at the Cleveland Clinic Foundation between 1983 and 2000. We reviewed their charts for patient and tumor characteristics and categorized them according to the RTOG RPA classes. RESULTS: The median follow-up and survival time for all 46 patients (15 women and 31 men) was 3.0 months. The median radiation dose was 3000 cGy in 10 fractions. Patients who received higher radiation doses (>3000 cGy) survived longer than those who received 3000 cGy or less than 3000 cGy (8.5 months vs. 2.7 months vs. 0.4 months, p = 0.0289). However, the Karnofsky performance status and RPA class were confounding factors in these data. The median survival for patients by RTOG RPA class was 8.5 months for Class I (n = 2), 3 months for Class II (n = 37), and 0.6 months for Class III (n = 7, p = 0.0834). CONCLUSION: Despite the relatively poor prognosis of patients who receive WBRT alone, it appears that they benefit from this palliative treatment. The RTOG RPA classification system may be a useful tool in assessing prognosis in this patient population.     

Recurrence-free survival rates after external-beam radiotherapy for patients with clinical T1-T3 prostate carcinoma in the prostate-specific antigen era: what should we expect?

BACKGROUND: The objective of the current study was to report biochemical recurrence-free survival (bRFS) rates among men with T1-T3 prostate carcinoma who were treated with external-beam radiotherapy (RT) at the Cleveland Clinic Foundation (Cleveland, OH). METHODS: In total, 1352 patients were identified between 1987 and 2000 with a minimum follow-up of 1 year (median follow-up, 55 months; range, 12-189 months). The median radiation dose was 74.0 grays (Gy) (range, 63.0-83.0 Gy). The median radiation doses for patients who received < 68.0 Gy (n = 201), 68.0-72.0 Gy (n = 373), and > or = 72.0 Gy (n = 778) were 66.6 Gy, 70.0 Gy, and 78.0 Gy, respectively. The RT techniques used were standard RT in 41% of patients, 3-dimensional conformal RT in 34% of patients, and intensity-modulated RT in 25% of patients. Androgen-deprivation (AD) therapy lasting < or = 6 months was administered to 34% of patients. RESULTS: The 5-year and 7-year bRFS rates were 63% and 59%, respectively. On multivariate analysis, T classification (P < 0.001), pretreatment prostate-specific antigen level (P < 0.001), biopsy Gleason score (P = 0.001), radiation dose (P < 0.001), and year of therapy (P < 0.001) were independent predictors of biochemical failure. Age, race, AD therapy, and RT technique did not predict for biochemical failure. For patients with low-risk tumors, the 5-year bRFS rates for those who received RT doses of < or = 68.0 Gy, 68.0-72.0 Gy, and > or = 72.0 Gy were 52%, 82%, and 93%, respectively (P < 0.001); for patients with intermediate-risk tumors, the respective 5-year bRFS rates were 27%, 51%, and 83% (P < 0.001); and for patients with high-risk tumors, the respective 5-year bRFS rates were 21%, 29%, and 71%, respectively (P < 0.001). CONCLUSIONS: The most significant therapeutic factor affecting bRFS rates after RT was radiation dose, rather than AD therapy use or radiation technique.     

Efficacy of High Dose Radiotherapy in Post-operative Treatment of Glioblastoma Multiform - A Single Institution Report

Background: Glioblastoma multiform (GBM) is a highly aggressive tumor with median survival ofapproximately 14 months. Management consists of maximal surgical resection followed by post-operativechemoradiation with concurrent then adjuvant temozolamide. The standard radiotherapy dose is 60Gy in 2-Gyfractions recommended by the radiation therapy oncology group (RTOG). With the vast majority of tumorrecurrences occurring within the previous irradiation field and the poor outcome associated with standardtherapy, regimens designed to deliver higher radiation doses to improve local control and enhance survival areneeded. In this study, we report a single institutional experience in treatment of 68 consecutive patients withGBM, treated with resection, and given post-operative radiotherapy followed by concurrent and/or adjuvantchemotherapy. Results: Of the 80 patients who entered this study, 68 completed the treatment course; 45 (66.2%)males and 23 (33.8%) females with a mean age at diagnosis of 49.0±12.9 (21-75) years. At a median follow up of19 months, 39 (57.3%) patients had evidence of tumor progression and 36 (52.9%) had died. The median overall survival for all patients was 16 months and progression free survival for all patients was 6.02 months. Allpotential prognostic factors were analyzed to evaluate their effects on overall survival. Age ≤50 year, concurrentand adjuvant chemotherapy and extent of surgery had significant p values. We found lower progression rateamong patients who received higher doses of radiotherapy (>60Gy). Higher radiation doses improved progressionfree survival (p=0.03). Despite increasing overall survival, this elevation was not significant. Conclusions: Thisstudy emphasize that higher radiation doses of (>60Gy) can improve local control and potentially survival, sowe strongly advise prospective multi centric studies to evaluate the role of higher doses of radiotherapy on GBMpatient outcome.     

Prolonged temozolomide for treatment of glioblastoma: preliminary clinical results and prognostic value of p53 overexpression

We report retrospective data on the feasibility and efficacy of prolonging adjuvant temozolomide (TMZ) more than 6?months after chemoradiotherapy completion in patients with glioblastoma (GBM). Molecular prognostic factors were assessed. Data from 46 patients were reviewed. Patients received postoperative irradiation, 60?Gy in 30 fractions, combined with concurrent TMZ, 75?mg/m². Four weeks later, adjuvant TMZ was prescribed, 150?C200?mg/m² for a total of 24 cycles unless there was progression or toxicity. Tumor samples were tested for the following prognostic factors: EGFR overexpression, 1p19q deletion, p53 overexpression and proliferation index. Overall survival (OS) was 84.8% at 6?months, 54.3% at 12?months, 26.1% at 18?months, and 21.7% at 24?months. Progression-free survival (PFS) was 73.9% at 6?months, 34.8% at 12?months, 15.2% at 18?months and 10.4% at 24?months. In the adjuvant phase, no treatment disruption for toxicity was necessary but eight patients required dose adaptation because of side effects. No significant molecular prognostic factor was evidenced for OS. We found that p53 overexpression was the only significant prognostic factor for PFS, with a median PFS of 9.3?months versus 7?months for patients without p53 overexpression (P?=?0.031). This study suggests that delivering adjuvant TMZ therapy for more than 6?months is feasible in patients with GBM. Efficacy data warrant further prospective assessment with the focus on molecular prognostic factors, such as p53 overexpression, which was found to be the only significant molecular prognostic factor for outcome.     

A phase II trial of accelerated radiotherapy using weekly stereotactic conformal boost for supratentorial glioblastoma multiforme: RTOG 0023

PURPOSE: This phase II trial was performed to assess the feasibility, toxicity, and efficacy of dose-intense accelerated radiation therapy using weekly fractionated stereotactic radiotherapy (FSRT) boost for patients with glioblastoma multiforme (GBM). METHODS AND MATERIALS: Patients with histologically confirmed GBM with postoperative enhancing tumor plus tumor cavity diameter <60 mm were enrolled. A 50-Gy dose of standard radiation therapy (RT) was given in daily 2-Gy fractions. In addition, patients received four FSRT treatments, once weekly, during Weeks 3 to 6. FSRT dosing of either 5 Gy or 7 Gy per fraction was given for a cumulative dose of 70 or 78 Gy in 29 (25 standard RT + 4 FSRT) treatments over 6 weeks. After the RT course, carmustine (BCNU) at 80 mg/m(2) was given for 3 days, every 8 weeks, for 6 cycles. RESULTS: A total of 76 patients were analyzed. Toxicity included: 3 Grade 4 chemotherapy, 3 acute Grade 4 radiotherapy, and 1 Grade 3 late. The median survival time was 12.5 months. No survival difference is seen when compared with the RTOG historical database. Patients with gross total resection (41%) had a median survival time of 16.6 months vs. 12.0 months for historic controls with gross total resection (p = 0.14). CONCLUSION: This first, multi-institutional FSRT boost trial for GBM was feasible and well tolerated. There is no significant survival benefit using this dose-intense RT regimen. Subset analysis revealed a trend toward improved outcome for GTR patients suggesting that patients with minimal disease burden may benefit from this form of accelerated RT.     

Postoperative radiotherapy in thymic carcinoma: treatment results and prognostic factors

PURPOSE: To analyze the treatment results and prognostic factors of patients with primary thymic carcinoma treated by total or subtotal tumor resection followed by radiotherapy alone. METHODS AND MATERIALS: Between October 1987 and October 1997, 26 patients with thymic carcinoma were treated with complete or incomplete surgical resection and postoperative adjuvant irradiation without chemotherapy. The radiation was delivered with 10-MV X-ray given 5 days per week at 1.8 to 2 Gy per fraction. Total doses ranged from 40 to 70 Gy. All patients had at least 40 months of follow-up. RESULTS: The 5-year overall survival rate, local control rate, and distant metastasis-free rate were 77%, 91%, and 57%, respectively. Several prognostic factors, including sex, age, extent of resection (total resection vs. subtotal resection), Masaoka staging (early Stage I + II vs. advanced Stage III + IV), pathology (low-grade vs. high-grade), and postoperative radiation dose (> or =60 Gy vs. <60 Gy), were evaluated in univariate analysis. The Masaoka staging system was the only statistically significant predictor in overall survival rate (p = 0.0482) and distant metastasis-free rate (p = 0.0193). CONCLUSIONS: The Masaoka staging system is the most important prognostic factor in primary thymic carcinoma patients receiving postoperative radiotherapy alone. For resectable tumors, surgery and postoperative radiotherapy can achieve good local control, but the distant metastatic rate is still high. Further investigation of more effective chemotherapy is needed.     

RPA classification has prognostic significance for surgically resected single brain metastasis

PURPOSE: To retrospectively evaluate prognostic factors that correlate with overall survival among patients with a surgically resected single brain metastasis. METHODS AND MATERIALS: An Institutional Review Board-approved database of the Cleveland Clinic Brain Tumor Institute was queried for patients with a single brain metastasis treated by surgical resection between February 1984 and January 2004. The primary endpoint was overall survival from the date of surgery by the Kaplan-Meier method. RESULTS: A total of 271 patients were included. Statistically significant variables for improved survival on multivariate analysis included age <65 years, lack of extracranial metastases, control of primary tumor, histology (non-small-cell lung carcinoma), and use of stereotactic radiosurgery. The median survival for all patients was 10.2 months. Survival of patients in recursive partitioning analysis (RPA) class 1 was better (21.4 months) than those in RPA class 2 (9.0 months, p < 0.001), RPA class 3 (8.9 months, p = 0.15), or the combined group of RPA classes 2 and 3 (9.0 months, p < 0.001). Patients had a median survival of 10.6 months after documented gross total resection and 8.7 months after subtotal resection, which approached statistical significance (p = 0.07). Those who were treated with stereotactic radiosurgery had a median survival of 17.1 months, which was greater than patients who were not treated with stereotactic radiosurgery (8.9 months, p = 0.006). CONCLUSIONS: This analysis supports the prognostic significance of the RPA classification in patients with a single brain metastasis who undergo surgical resection and adjuvant therapy. RPA class 1 patients have a very favorable prognosis with a median survival of 21.4 months.     

Re-irradiation with radiosurgery for recurrent glioblastoma multiforme

Local tumor control remains a significant challenge in patients with glioblastoma multiforme (GBM). Despite aggressive radiation therapy approaches, most recurrences are within the high-dose field, limiting the ability to safely re-irradiate recurrence using conventional techniques. Fractionated stereotactic radiosurgery (fSRS) is a technique whose properties make it useful for re-irradiation. We retrospectively reviewed the charts of 14 patients with recurrent GBM treated with salvage radiosurgery. Seven patients were male and seven were female with a median age of 58 (range: 39-76). All patients had prior cranial radiation therapy to a median dose of 60 Gy (58-69). There were 18 lesions treated with a median tumor volume of 6.97 cm3 (0.54-50.0 cm3). fSRS was delivered in 1-3 fractions to a median dose of 24 Gy (18-30 Gy). Median follow-up for the cohort was 8 months (3-22 months). On follow-up MRI, 8 of 18 lesions had a radiographic response. The median time-to-progression following primary irradiation was 8 months (1-28 months) while the median time-to-progression (TTP) following fSRS was 5 months (1-16 months). Median local control following re-irradiation was 5 months and actuarial local control was 21% at 1-year. Overall survival following primary irradiation was 79% at 12 months and 46% at 2 years. Overall survival following re-irradiation was 79% at 6 months and 30% at 1 year. No significant treatment-related toxicity was seen in follow-up. These results indicate that re-irradiation for recurrent GBM using fSRS is well-tolerated and can offer a benefit in terms of progression-free survival (PFS).     

Primary glioblastoma multiforme in younger patients: a single-institution experience

AIMS AND BACKGROUND: To report our experience of patients with primary glioblastoma multiforme of young age by evaluating the characteristics, prognostic factors, and treatment outcomes. PATIENTS AND METHODS: Seventy patients with primary glioblastoma multiforme (GBM) treated at our department between 1996 and 2004 were studied. The male-female ratio was 2.6:1. The median age was 53 (16-74). Sixty-eight patients (97%) were operated on before radiotherapy and 2 patients (3%) underwent only stereotactic biopsy. All patients received radiotherapy. Postoperative chemotherapy as an adjuvant to radiotherapy was given to 9 patients (12%). The patients were divided into 2 groups according to their age (group A < or = 35 years, n = 21 vs group B > 35 years, n = 49). Survival was determined with the Kaplan-Meier method and differences were compared using the log-rank test. Cox regression analysis was performed to identify the independent prognostic factors. Karnofsky performance status (> or = 70 vs < 70), age (< or = 35 vs > 35 years), gender, tumor size (< or = 4 vs > 4 cm), number of involved brain lobes (1 vs more than 1), type of surgery (total vs subtotal), preoperative seizure history (present vs absent), radiotherapy field (total cranium vs partial), total radiotherapy dose (60 vs 66 Gy), and adjuvant chemotherapy (present vs absent) were evaluated in univariate analysis. RESULTS: The median survival was 10.3 months in the whole group, 19.5 months in the younger age group and 5.7 months in the older age group. During follow-up re-craniotomy was performed in 2 patients (3%), and 1 patient (1%) developed spinal seeding metastases and was given spinal radiotherapy. In univariate analysis younger age vs older age: median 19.5 months vs 5.27 months (P = 0.0012); Karnofsky performance status > or = 70 vs < 70: median 15.3 months vs 2.67 months (P < 0.0001), and external radiotherapy dose 60 Gy vs 66 Gy: median 11.6 months vs 3 months (P = 0.02) were found as significant prognostic factors for survival. In regression analysis a worse performance status (KPS <70) was found to be the only independent factor for survival (P = 0.014, 95% CI HR = 0.0043 [0.0001-0.15]). CONCLUSIONS: Younger patients with primary glioblastoma multiforme had a relatively long survival (median, 19.5 months, with a 2-year survival rate of 30%) compared to older patients. This was due particularly to their better performance status.     

Supratentorial malignant glioma: an analysis of radiation therapy in 178 cases

To analyze treatment results of supratentorial malignant gliomas in the megavoltage era, all the histologic specimens were reviewed and glioblastoma multiforme (GBM) was distinguished from anaplastic astrocytoma (AA) by the presence of necrosis. Among those who had completed radiotherapy and who had been followed for at least one year, 135 GBM and 43 AA patients were found. The median survival time (MST) after operation was 12 months for GBM and 18 months for AA. The 5-year survival rate was 0.9% for GBM and 18% for AA. The size of radiation field had little influence on survival time; MST was 12 months for GBM patients treated with a local field covering tumor plus less than 2 cm margin, 12 months for those treated with a generous field (2 cm or more margin), and 13 months for those treated to whole brain. Also for AA, whole brain radiation did not prolong survival. Initial relapse of GBM and AA developed within the irradiated volume in 86% of the cases treated with a generous field. Whole brain radiation seemed useless for the treatment of malignant gliomas. Survival time appeared to be dose-dependent; MST was 10, 13, and 16 months for GBM patients who received 45-57, 57-63, and 63-72 Gy, respectively. Extensive surgical resection was associated with a better prognosis in GBM. AA patients 60 years old or older had a poorer prognosis than younger patients, but age was not a significant prognostic factor for GBM. Chemotherapy appeared to prolong survival slightly without improving long-term survival.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation of EGFR, IDH1 and PTEN status with the outcome of patients with recurrent glioblastoma treated in a phase II clinical trial with the EGFR-blocking monoclonal antibody cetuximab

Mutation and gene amplification of the epithelial growth factor receptor (EGFR) is one of the most common genetic alterations in glioblastoma (GB). EGFR is, therefore, an attractive molecular target for the treatment of GB. EGFR-targeted therapies however have been largely ineffective in clinical trials. In this study, we investigated the correlation between the EGFR gene amplification status, expression of the EGFR variant III (EGFRvIII) and EGFR variant IV (EGFRvIV) mutations, expression of the phosphatase and tensin homologue gene on chromosome 10 (PTEN) and mutation of the isocitrate dehydrogenase 1 (IDH1) gene and the survival of patients suffering from recurrent glioblastoma who were treated with the EGFR-targeted monoclonal antibody cetuximab in a prospective phase II clinical trial. EGFR amplification was detected in 19 out of 35 GB (54%), EGFRvIII expression in 11 (31.4%) and EGFRvIV expression in 7 (20%). The EGFRvIII and EGFRvIV mutations were exclusively found in GB with EGFR amplification and were almost mutually exclusive with IDH1 mutation (EGFRvIII mutation was found in 1 out of 11 GB with an IDH1 mutation). Patients with an EGFR amplification lacking EGFRvIII expression had a significantly superior progression free survival (PFS) and a numerical better overall survival (OS) following treatment with cetuximab [median PFS 3.03 vs. 1.63 months (p=0.006); median OS 5.57 vs. 3.97 months (p=0.12)]. Within the subgroup of patients with EGFR amplification, patients with EGFRvIII positive glioblastoma had a worse survival [median PFS 1.63 vs. 3.03 months (p=0.01); median OS 3.27 vs. 5.57 months (p=0.08)]. Our observations indicate that the type of EGFR mutation may determine the outcome of GB patients treated with cetuximab. Prospective investigation of both the EGFR amplification and mutation status in clinical trials with EGFR-targeted therapies for GB is indicated.     

Salvage reirradiation for recurrent glioblastoma with radiosurgery: radiographic response and improved survival

Purpose To determine the radiographic and clinical efficacy of stereotactic single dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) as salvage therapy for glioblastoma (GBM) at recurrence. Methods Thirty-six patients with pathologically proven recurrent GBM were treated with salvage reirradiation by either SRS or FSRT between March of 2001 and August of 2006. Thirty-one patients had an initial diagnosis of GBM. Five patients had a malignant transformation. All patients had received radiotherapy with a dose of 50–60 Gy, a median 13.6 months prior to reirradiation (range: 0.8–119 months). At the time of recurrence, 26 patients were treated with SRS with a median dose of 18 Gy (range: 12–20 Gy). FSRT was performed in ten patients with a dose of 36 Gy in six fractions, twice weekly. Follow-up included MRI and clinical examination every 2 months. Results Median survival time after SRS was 8.5 months, compared to 7.4 months after FSRT (P = 0.81). Of 26 patients treated with SRS, radiographic tumor response or stable disease was observed in eight (35%) patients and tumor progression was seen in 18 (65%) patients. Of 10 patients treated by FSRT, radiographic tumor response or stable disease was observed in four (40%) patients and tumor progression was observed in four (40%) patients (two lost to follow-up). Patients who responded to treatment had statistically improved survival compared to non-responders, with median survival of 15.8 vs. 7.3 months (P < 0.05). Conclusion Salvage reirradiation with SRS or FSRT for recurrent GBM results in radiographic response in a proportion of patients. Survival was significantly improved among patients who either responded or had stable disease after salvage reirradiation, compared to non-responders. Further study is warranted to investigate the method and time of reirradiation for recurrent GBM.     

食管鳞癌三维放疗或同期放化疗优选照射剂量分析

目的 分析不同治疗模式及照射剂量下食管鳞癌患者的OS状况,探讨优选照射剂量及获益亚组人群。方法 选取2003-2014年本院接受3DRT的1387例食管鳞癌患者,分别对单纯放疗(780例)和同期放化疗(302例)不同照射剂量患者进行分析,采用Logrank检验和Cox多因素分析筛选优选照射剂量及获益亚组人群。结果 单纯放疗中照射剂量<60 Gy (91例)、60 Gy (429例)、>60 Gy组(260例)的中位OS期分别为9、20、23个月(P=0.000);60 Gy与>60 Gy组OS曲线相近(P=0.362),且均优于<60 Gy组(P=0.000、0.000)。同期放化疗中照射剂量<60 Gy (18例)、60 Gy (224例)和>60 Gy组(60例)的中位OS期分别为22、34、15个月(P=0.004);<60 Gy与>60 Gy组OS曲线相近(P=0.952),60 Gy组OS优于>60 Gy组(P=0.002)。多因素预后分析结果显示不同治疗模式食管鳞癌预后不同,但GTV与照射剂量为2种治疗模式共同的预后因素(P=0.045、0.001);单纯放疗时照射剂量为≥60 Gy为生存获益因素(P=0.000);同期放化疗时仅照射剂量为60 Gy是生存获益因素(P=0.050)。结论 单纯放疗时食管鳞癌患者照射剂量≥60 Gy为优选剂量,同期放化疗时建议照射剂量尽量控制为60 Gy。     

Incompletely resected rectum, recto-sigmoid, or sigmoid carcinoma: results of postoperative radiotherapy and prognostic factors

Postoperative radiotherapy was given in 40 patients with gross or microscopic pathologically proven residual disease after surgical resection of rectum, recto-sigmoid, or sigmoid carcinoma. The radiotherapy target volume included the pelvis with (9 patients) or without (31 patients) the perineum. Median total dose of radiation was 50 Gy (range 30-60). One patient received 30 Gy, 10 received greater than 30 to 40 Gy, 13 received greater than 40 to 50 Gy, and 16 patients received greater than 50 to 60 Gy. The median follow-up in the survivors (16 patients) was 53 months (range: 16-85). Probability of survival with censoring for death due to intercurrent disease was 36% at 5 years. Survival for patients with microscopic residual disease (21 patients) was 40% at 5 years compared to 12% for those with gross residual disease (19 patients) (p = 0.09). Twenty-five patients relapsed. All but one relapse occurred earlier than 50 months after radiotherapy. Approximately half (12/25) of the relapses were observed within 6 months after radiotherapy. Local relapse inside the radiotherapy portals was observed in 9/40 (22%) patients. Therapy-related urogenital complications occurred in no patient and gastro-intestinal complications in three patients (7%). In one patient they were scored WHO grade 4 and in two patients WHO grade 3. Prognostic factors were analyzed using the Cox proportional hazards model. For survival differentiation, grade (p less than 0.001), stage (p = 0.04), and perineal irradiation (p = 0.03) were independent prognostic factors. With relapse-free survival as the endpoint, only stage (p = 0.003) was a statistically significant prognostic factor. There was a trend toward a better relapse-free survival when the perineum was included in the radiation portals (p = 0.09).     

不同EGFR突变肺腺癌脑转移患者WBRT分析

目的 探讨肺腺癌脑转移患者不同EGFR突变状态WBRT疗效差别。方法 回顾分析2010—2015年在本院诊治的89例肺腺癌脑转移患者,所有患者均行EGFR检测。脑转移一线6 MV X线外照射:WBRT30 Gy分10次或40 Gy分20次(≤3个脑转移灶IMRT同步加量40~45 Gy分10次或50~60 Gy分20次)。比较EGFR突变和野生型患者的有效率、IPFS、OS。Kaplan-Meier法计算IPFS、OS并Logrank检验和单因素分析,Cox模型多因素分析。结果 89例患者总有效率为62%,中位IPFS为7.0个月(95%CI为6.060~7.940),中位OS为12.0个月(95%CI为9.539~14.465)。单因素和多因素分析结果显示脑转移患者有效率与KPS评分、EGFR突变状态相关(P=0.009、0.035),KPS评分、EGFR突变状态是IPFS的影响因素(P=0.048、0.000),KPS评分、原发灶控制是OS的影响因素(P=0.000、0.031)。结论 肺腺癌脑转移患者WBRT后,EGFR突变较野生型有效率高,IPFS时间长,OS无差别。     

Prognostic stratification of patients with anaplastic gliomas according to genetic profile

BACKGROUND: There is a need to improve the current, controversial, and poorly reproducible classification of anaplastic gliomas, which represent a highly heterogeneous entity in terms of survival. METHODS: The impact of the most common genetic alterations on survival was investigated based on 156 anaplastic gliomas: Among the patients who were included, the gender ratio was 1.32, the median age was 45.5 years (range, 20-83 years), and the median Karnofsky performance status was 70 (range, 40-100). Genetic analysis included a search for loss of heterozygosity (LOH) on chromosomes 1p and 19q; amplification of chromosomes 9p and 10q and of the epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4) and mouse double-minute (MDM2) genes; and p53 expression. RESULTS: The median survival was 33.5 months, and the median progression-free survival was 15.8 months. In a univariate analysis, LOH on 1p and 19q was correlated with longer survival, whereas p53 expression, LOH on 9p, LOH on 10q, amplified EGFR, and deleted CDKN2A were correlated with shorter survival. LOH on 1p and 19q were associated with oligodendrogliomas, LOH on 10q was related to EGFR amplification, and LOH on 1p and 19q was mutually exclusive with EGFR amplification and LOH on 10q. In a multivariate analysis, the significant prognostic factors were age, histology, LOH on 1p and 19q, and P16/CDKN2A deletion. Recursive partitioning analysis (RPA) divided the whole group hierarchically into 3 distinct prognostic subgroups: Group A with 1p19q codeletion (median survival, 98 months), Group B with EGFR amplification (median survival, 17 months), and Group CC (median survival, 31 months), providing a basis for a genetically based prognostic subclassification for patients with Grade III gliomas. CONCLUSIONS: The search for 1p19q codeletion and EGFR receptor amplification provides a simple, clinically relevant prognostic subclassification of grade III gliomas.     

High-grade gliomas in patients with prior systemic malignancies

BACKGROUND: The current study was conducted to characterize the impact of a prior malignancy on the diagnosis, treatment, and outcome of high-grade glioma. METHODS: A retrospective study of 21 patients with a histologic diagnosis of glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), or anaplastic oligodendroglioma (AO) after a prior diagnosis of solid tumor or hematologic malignancy was conducted. Glioma histology (GBM vs. AA/AO), patient age ( 60 years), and extent of resection (biopsy vs. subtotal vs. complete) were evaluated for their prognostic influence. RESULTS: Of the 21 patients studied, 17 had GBM, 3 had AA, and 1 patient had high-grade AO. There were 25 systemic carcinomas diagnosed in 21 patients (18 solid tumors including breast carcinoma, prostate carcinoma, and melanoma and 7 hematologic malignancies). The glioma occurred within a previous radiation field in only three patients, two of whom had solid tumors and one of whom had a childhood hematologic malignancy. Surgical resection was the initial treatment for the brain tumor in 17 patients, and the majority of patients received radiation therapy and adjuvant chemotherapy. Four patients who initially were misdiagnosed as having brain metastases received whole brain radiation therapy as their initial treatment, thereby compromising optimal care. The overall median survival for all the patients in the current study was 14 months (range, 1-44 months) from the time of brain tumor diagnosis. The extent of resection was found to be the only prognostic variable that was associated with survival (P = 0.03). CONCLUSIONS: Secondary glioma may occur in patients as a consequence of therapy for a prior malignancy, but most often represents a sporadic event. The outcome and recommended treatment are identical to those for patients with primary gliomas. Accurate diagnosis is essential; neuroimaging often is suggestive of a primary brain tumor and should initiate surgical intervention so that histopathology can be obtained early and appropriate treatment instituted.