Although promising preliminary results have been widely observed with bevacizumab for recurrent malignant gliomas, many unanswered questions remain to be resolved to achieve an optimal outcome. No predictive biomarkers of a survival benefit from bevacizumab have been established, and no consensus exists about the response or survival benefit regarding the prior recurrence pattern or tumor location. Here we retrospectively analyzed the clinical benefit from bevacizumab for recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location. Thirty-one consecutive patients with recurrent malignant gliomas who were treated with bevacizumab were investigated. The treatment response and survival benefit from bevacizumab were analyzed in association with age, sex, Karnofsky performance status, prior pathological diagnosis, prior recurrence pattern, primary location of tumor, recurrence status, and expression of angiogenic and hypoxic markers. The group with leptomeningeal dissemination had a significantly shorter median overall survival with bevacizumab (OSBev) (6.0 months, 95% confidence interval (CI) 1.4–10.7) compared to those in the local/distant group (11.8 months, 95% CI 6.1–17.4). The median OSBev of the infratentorial tumor group and supratentorial tumor group were 9.2 months (95% CI 5.0–13.4) and 10.4 months (95% CI 6.6–14.3), respectively. With multivariate analysis, the prior recurrence pattern was the only independent prognostic factor of OSBev. Patients with leptomeningeal dissemination of recurrent malignant glioma experienced minimal benefit from bevacizumab. Therefore, in the context of cost effectiveness, bevacizumab is not recommended for patients with leptomeningeal dissemination. 相似文献
Isocitrate dehydrogenase 1 (IDH1) mutation is a known prognostic factor in glioblastoma multiforme (GBM). It has been well documented that patients with IDH1 mutant (IDH1-mu) GBM have a better outcome compared to patients with IDH1 wild-type (IDH1-WT) GBM. IDH1-mu tumors have been shown to be more commonly located in the frontal lobe, and less likely to be in multiple lobes. It is unclear whether differential location is part of the prognostically favorable profile of these tumors. We performed a case-control study, matching IDH1-mu GBMs to IDH1-WT GBMs that are controlled for age, sex and tumor location. There were 21 IDH1-mu tumors and 21 matched IDH1-WT tumors. Age, sex and tumor location were matched between the two groups. After controlling for the factors described, the IDH1-mu tumors were more likely to be secondary GBM (61.9% secondary vs. 14.3%, p = 0.004). There was an insignificant trend towards smaller tumor volume in the IDH1-mu group (28.13 ± 6.56 vs. 41.8 ± 7.33 cm3, p = 0.173). Extent of surgical resection was similar in both groups (mean 84.49% vs. 89.89%, p = 0.419). There was no survival advantage for IDH1-mu tumors when controlled for location: 25.2 months overall survival for IDH1-mu patients and 23.6 for IDH1-WT patients, p = 0.794. IDH1 mutation may provide part of its prognostic significance by differential localization of tumor, both making IDH1-mu tumors more amenable to gross total resection and placing these tumors in less eloquent areas, thereby lowering neurological morbidity. 相似文献
The genotype–phenotype correlations of the specific BRCA1 and BRCA2 mutations in multi‐ethnic populations in USA have not yet been fully investigated. This study was designed to evaluate the effects of ethnicity at specific mutation locations and breast/ovarian cancer phenotypes. Our cohort included 445 women with different ethnic backgrounds who underwent BRCA genetic testing between 1997 and 2010. Known clinical and pathologic characteristics were compared with Chi‐Square Analysis or Fisher's Exact test as appropriate. The three most common mutation locations in BRCA1 (exons 2, 11, and 20) and BRCA2 (exons 10, 11, and 25) genes were chosen. Prevalence of BRCA1 exon 2 mutations were significantly higher in Ashkenazi Jewish (AJ) women compared to Caucasians (41% versus 15%; p = 0.001). Similarly, AJ women with breast cancer were more likely to have BRCA1 exon 2 mutation (47% positivity in AJ women versus 0–12.5% positivity in other ethnicities; p = 0.004). Women carrying the exon 20 BRCA1 mutation had the highest probability of having combined breast and ovarian cancers compared to women carrying other exon mutations (p = 0.05). The median age at initial cancer diagnosis, phenotypic features of breast cancer tumors, and overall survival did not vary significantly by ethnicity or mutation location. Our data suggest that ethnicity does not affect age of onset, overall survival or confer different risks of breast and ovarian cancer development in BRCA carriers. These results also suggest that women carrying the exon 20 BRCA1 mutation may warrant mutation‐specific counseling and be more aggressively managed for risk reduction. 相似文献