Survival Analysis of Glioblastoma Multiforme

Introduction: To evaluate the survival of Glioblastoma Multiforme (GBM). Material and Methods: Patients witha pathological diagnosis of Glioblastoma Multiforme (GBM) between 1 January 1994 and 30 November 2013, wereretrospectively reviewed. Inclusion criteria: 1) GBM patients with confirmed pathology, 2) GBM patients were treatedby multimodality therapy. Exclusion criteria: 1) GBM patients with unconfirmed pathology, 2) GBM patients with spinalinvolvement, 3) GBM patients with incomplete data records. Seventy-seven patients were treated by multimodalitytherapy such as surgery plus post-operative radiotherapy (PORT), post-operative Temozolomide (TMZ) concurrent withradiotherapy (CCRT), post-operative CCRT with adjuvant TMZ. The overall survival was calculated by the Kaplan-Meiermethod and the log-rank test was used to compare the survival curves. A p-value of ≤ 0.05 was considered to bestatistically significant. Results: Seventy-seven patients with a median age of 53 years (range 4-76 years) showeda median survival time (MST) of 12 months. In subgroup analyses, the PORT patients revealed a MST of 11 monthsand 2 year overall survival (OS) rates were 17.2%, the patients with post-operative CCRT with or without adjuvantTMZ revealed a MST of 23 months and 2 year OS rates were 38.2%. The MST of patients by Recursive PartitioningAnalysis (RPA), classifications III, IV, V, VI were 26.8 months, 14.2 months, 9.9 months, and 4.0 months, (p <0.001).Conclusions: The MST of the patients who had post-operative CCRT with or without adjuvant TMZ was better thanthe PORT group. The RPA classification can be used to predict survival. Multimodality therapy demonstrated the mosteffective treatment outcome. Temozolomide might be beneficial for GBM patients in order to increase survival time.     

贝伐单抗结合化疗治疗晚期结肠癌的生存分析

目的:分析影响接受贝伐单抗结合化疗治疗晚期结肠癌患者生存情况的因素。方法:回顾性分析2008年5月至2012年5月期间接受贝伐单抗结合化疗治疗的60例晚期结肠癌患者的临床资料和随访记录,探讨治疗时间、心血管副反应、K-ras基因型、单器官转移部位及贝伐单抗维持治疗对生存期的影响。结果:接受治疗超过半年的患者中位无进展生存期(PFS)及总生存期(OS)长于治疗时间半年以内的患者,差异具有统计学意义(P=0.023;P=0.043)。出现心血管副反应的患者中位PFS及OS长于未出现心血管副反应的患者(P=0.014;P=0.032)。K-ras基因野生型和突变型患者的PFS及OS有统计学差异（P=0.024;P=0.039）。单器官转移至肝脏的患者与单器官转移到卵巢的患者,其PFS及OS无统计学差异（P=0.853;P=0.835）。行贝伐单抗维持治疗的患者,其OS长于未行维持治疗的患者(P=0.013)。结论:在贝伐单抗和化疗联合治疗的晚期结肠癌患者中,治疗时间和出现心血管副反应可能是患者的预后因素。行贝伐单抗维持治疗可使患者生存受益     

The efficacy and safety of extended adjuvant temozolomide following concurrent radio-chemotherapy among Egyptian patients with newly diagnosed glioblastoma multiforme

Although concurrent radio-chemotherapy and adjuvant temozolomide (TMZ) treatment for 6 cycles has been established as a standard of care for newly diagnosed glioblastoma multiforme (GBM) patients, the recommended duration of adjuvant TMZ remains a matter of debate. Hereby, we aimed to report for the first time our experience from Upper Egypt through comparing survival and toxicity profile between two treatment modalities of adjuvant TMZ (> six cycles versus six cycles) and delineating factors of prognostic significance in Egyptian patients with newly diagnosed GBM treated by radiation therapy with concomitant and adjuvant TMZ. Between June 2016 and February 2018, the medical records of 121 patients were eligible to be retrospectively reviewed to extract the study relevant data. All patients received concurrent radio-chemotherapy, followed by TMZ for 6 cycles in 29 patients (Group 1) and for >6 cycles in 26 patients (Group 2). Patients in Group 1 had a median PFS of 15 months (95% CI: 10.215-19.785), while those in Group 2 had a median PFS of 18 months (95% CI: 16.611-19.389). After a median follow up duration of 20 months (range: 12-41), the median OS was 18 months (95% CI: 13.420-22.580) in Group 1 and 22 months (95% CI: 18.777-25.223) in Group 2. There was no statistically significant correlation between the number of chemotherapy cycles and PFS (P=0.513) or OS (P=0.867). The extent of surgical resection was the only independent prognostic factor for both PFS (P=0.015) and OS (P=0.028) by multivariate analysis. Three grade ≥3 hematologic toxicity were encountered in 3 patients. One in the six-cycle group (neutropenia), and two in the extended cycles group (one had neutropenia and the other one developed thrombocytopenia). No statistically significant difference in the toxicity profile between both groups. The results of our study suggest that extended TMZ therapy is safe and tolerable, however it did not significantly improve PFS or OS as compared to the standard six-cycle course. Larger randomized studies are required to shed more light on this issue.     

Postprogression survival for first-line chemotherapy in patients with advanced gastric cancer

BackgroundWith the increasing availability of active agents, the importance of postprogression survival (PPS) has been recognised for several malignancies. However, little is known of PPS in advanced gastric cancer.Patients and methodsA literature search identified 43 randomised trials in chemotherapy-naive patients with advanced gastric cancer. We partitioned overall survival (OS) into progression-free survival (PFS) and PPS, and then examined the correlation between median OS and either median PFS or median PPS. The correlation between differences in OS (ΔOS) and those in PFS (ΔPFS) between trial arms was also investigated.ResultsThe average median OS was significantly longer in recent (2006 and later) trials than in older (2005 and earlier) trials (10.60 versus 8.64 months, P < 0.001), as was the average median PPS (5.34 versus 3.74 months, P = 0.001). Median PPS was correlated with median OS for all trials (r = 0.732), and this correlation was more pronounced in recent trials (r = 0.850). By contrast, the correlation between median PFS and median OS was less pronounced in recent trials (r = 0.282), as was that between ΔPFS and ΔOS (r = 0.365).ConclusionAn increase in median PPS was found in accordance with an increase in median OS in recent trials compared with older trials for patients with advanced gastric cancer.     

Lack of Sunlight Exposure Influence on Primary Glioblastoma Survival

Background: The prognosis of primary glioblastoma (GBM) is poor. Approximately 2/3 of primary braintumor diagnoses are GBM, of which 95% are primary lesions. In this study, we aimed to evaluate whether moresunlight exposure has an effect on survival of patients with primary GBM. Materials and Methods: A total of111 patients with primary GBM were enrolled from Kayseri in inner Anatolia which has a cold climate (n: 40)and Mersin in Mediterranean region with a warm climate and more sunlight exposure (n: 71). The patients withprimary GBM were divided into two groups as Kayseri and Mersin and compared for progression free survival(PFS) and overall survival (OS).Results: The PFS values were 7.0 and 4.7 months for Kayseri and Mersin groups,respectively (p=0.10) and the repsective OS values were 13.3 and 9.4 months (p=0.13). We did not found anysignificant difference regarding age, sex, comorbidity, smoking, surgery, resurgery, adjuvant chemoradiotherapyand palliative chemotherapy between the groups. Conclusions: We found that more sunlight exposure had noimpact on prognosis of patients with primary GBM, adding inconsistency to the literature about the relationshipbetween sunlight and GBM.     

Overexpression of c-Met is Associated with Poor Prognosis in Glioblastoma Multiforme: A Systematic Review and Meta-Analyses

Objective: The aim of this study is to evaluate the association of c-Met overexpression with survival of glioblastoma multiforme (GBM) patients. Methods: A systematic review with meta-analyses was conducted on related articles from PubMed, EBSCOhost, Scopus, and Cochrane databases with last updated search on October 31, 2020. A total of 7 studies regarding c-Met overexpression and overall survival (OS) and/or progression free survival (PFS) are included in this study. Results: All studies used immunohistochemistry to examine the expression of c-Met protein. The results showed that the positive rate of c-Met overexpression was detected in approximately 33,9% - 60,5% of GBM patients. c-Met overexpression was related to worse OS (HR: 1,74; 95% CI: 1,482-2,043; Z=6,756; p<0,001) and PFS (HR: 1,66; 95% CI: 1,327-2,066; Z=4,464; p<0,001) in GBM patients. Low heterogeneity of subjects was found in both OS and PFS analyses, I2 values were 7,8% and 0,0%, respectively. Conclusion: In conclusion, c-Met overexpression is significantly related to shorter OS and PFS in GBM patients, so c-Met can be considered as a potential prognostic indicator in GBM.     

Six-Month Progression-Free Survival as the Primary Endpoint to Evaluate the Activity of New Agents as Second-line Therapy for Advanced Urothelial Carcinoma

ObjectiveSecond-line systemic therapy for advanced urothelial carcinoma (UC) has substantial unmet needs, and current agents show dismal activity. Second-line trials of metastatic UC have used response rate (RR) and median progression-free survival (PFS) as primary endpoints, which may not reflect durable benefits. A more robust endpoint to identify signals of durable benefits when investigating new agents in second-line trials may expedite drug development. PFS at 6 months (PFS6) is a candidate endpoint, which may correlate with overall survival (OS) at 12 months (OS12) and may be applicable across cytostatic and cytotoxic agents.MethodsTen second-line phase II trials with individual patient outcomes data evaluating chemotherapy or biologics were combined for discovery, followed by external validation in a phase III trial. The relationship between PFS6/RR and OS12 was assessed at the trial level using Pearson correlation and weighted linear regression, and at the individual level using Pearson chi-square test with Yates continuity correction.ResultsIn the discovery dataset, a significant correlation was observed between PFS6 and OS12 at the trial (R² = 0.55, Pearson correlation = 0.66) and individual levels (82%, Қ = 0.45). Response correlated with OS12 at the individual level less robustly (78%, Қ = 0.36), and the trial level association was not statistically significant (R² = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%, Қ = 0.44) appeared stronger than the correlation of response (76%, Қ = 0.17) with OS12 in the external validation dataset.ConclusionsPFS6 is strongly associated with OS12 and appears more optimal than RR to identify active second-line agents for advanced UC.     

Effects of Genetic Polymorphisms in the ABCB1 Gene onClinical Outcomes in Patients with Gastric Cancer Treated bySecond-line Chemotherapy

Objective: Tumor cells that overexpress P-glycoprotein (Pgp) may be resistant to several anticancer agentsdue to altered pharmacokinetics and reduced intracellular concentrations of the anticancer agents. Pgp is encodedby the ATP binding cassette gene B1 (ABCB1). To our knowledge, only one previous report has evaluated theeffect of ABCB1 gene polymorphisms on clinical outcomes of gastric cancer. The purpose of this analysis was toevaluate the impact of genetic polymorphisms of the ABCB1 gene on clinical outcomes in patients with advancedgastric cancer (AGC) treated with second-line chemotherapy. Methods: We retrospectively analyzed the impactof ABCB1 gene polymorphisms (ABCB1 3435C>T) on clinical outcomes in 100 patients with AGC who receivedsecond-line chemotherapy. Results: Median overall survival (OS) since the initiation of second-line chemotherapywas 6.0 months (95% confidence interval [CI], 4.8 to 8.0 months), and median progression-free survival (PFS)was 2.7 months (95% CI, 2.1 to 3.4 months). In a multivariate analysis of PFS, a 3435 CC polymorphism (n =45) was significantly associated with longer PFS compared with the CT/TT type polymorphism (n = 55), withborderline significance (PFS of 3.2 months vs. 2.2 months, respectively; HR 1.50; 95% CI, 0.98-2.30; P = 0.061).ABCB1 3435 C>T polymorphisms were not associated with OS. No interaction was seen between ABCB1polymorphisms and treatment regimens. Conclusion: Genetic polymorphisms of ABCB1 3435C>T might havea possible impact on clinical outcomes of second-line chemotherapy in AGC. Further prospective evaluationusing a larger sample size is required.     

Progression-free survival as a predictor of overall survival in metastatic renal cell carcinoma treated with contemporary targeted therapy

BACKGROUND.

The majority of metastatic renal cell carcinoma (mRCC) clinical trials that examined targeted agents used progression‐free survival (PFS) as the primary endpoint. Whether PFS can be used as a predictor of overall survival (OS) is unknown.

METHODS.

Patients from 12 cancer centers who received targeted therapy for mRCC were identified. Landmark analyses for progression at 3 months and 6 months after drug initiation were performed to minimize lead‐time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS.

RESULTS.

In total, 1158 patients were included. The median follow‐up was 30.6 months, the median age was 60 years, and the median Karnofsky performance status was 80%. For the entire cohort, the median PFS was 7.6 months, and the median OS was 19.7 months. In the landmark analysis, the median OS for patients who progressed at 3 months was 7.8 months compared with 23.6 months for patients who did not progress (log‐rank test; P < .0001). Similarly, for patients who progressed at 6 months, the median OS was 8.6 months compared with 26 months for patients who did not progress (P < .0001). Compared with those who did not progress, for the patients who progressed at 3 months and at 6 months, the hazard ratios for death adjusted for adverse prognostic factors were 3.05 (95% confidence interval, 2.42‐3.84) and 2.96 (95% confidence interval, 2.39‐3.67), respectively. Similar results were demonstrated with landmark analyses at 9 months and at 12 months and in the bootstrap validation. Kendall tau rank correlation and a Fleischer model demonstrated a statistically significant dependent correlation.

CONCLUSIONS.

PFS at 3 months and at 6 months predicted OS, and the current results indicated that PFS may be a meaningful intermediate endpoint for OS in patients with mRCC who receive treatment with novel agents. Cancer 2011;. © 2010 American Cancer Society.     

Progression-Free Survival and Time to Progression as Real Surrogate End Points for Overall Survival in Advanced Breast Cancer: A Meta-Analysis of 37 Trials

Background

Progression-free survival (PFS) and time to progression (TTP) have been reported to correlate with overall survival (OS) in several cancer types. To our knowledge, however, the correlation between them is unclear.

Neurocognition in individuals with incidentally-identified meningioma

The ventricular-subventricular zone (V-SVZ), which lies in the walls of the lateral ventricles (LV), is the largest neurogenic niche within the adult brain. Whether radiographic contact with the LV influences survival in glioblastoma (GBM) patients remains unclear. We assimilated and analyzed published data comparing survival in GBM patients with (LV+GBM) and without (LV-GBM) radiographic LV contact. PubMed, EMBASE, and Cochrane electronic databases were searched. Fifteen studies with survival data on LV+GBM and LV-GBM patients were identified. Their Kaplan–Meier survival curves were digitized and pooled for generation of median overall (OS) and progression free (PFS) survivals and log-rank hazard ratios (HRs). The log-rank and reported multivariate HRs after accounting for the common predictors of GBM survival were analyzed separately by meta-analyses. The calculated median survivals (months) from pooled data were 12.95 and 16.58 (OS), and 4.54 and 6.25 (PFS) for LV+GBMs and LV-GBMs, respectively, with an overall log-rank HRs of 1.335 [1.204–1.513] (OS) and 1.387 [1.225–1.602] (PFS). Meta-analysis of log-rank HRs resulted in summary HRs of 1.58 [1.35–1.85] (OS, 10 studies) and 1.41 [1.22–1.64] (PFS, 5 studies). Meta-analysis of multivariate HRs resulted in summary HRs of 1.35 [1.14–1.58] (OS, 6 studies) and 1.64 [0.88–3.05] (PFS, 3 studies). Patients with GBM contacting the LV have lower survival. This effect may be independent of the common predictors of GBM survival, suggesting a clinical influence of V-SVZ contact on GBM biology.     

Overexpression of Golgi phosphoprotein-3 (GOLPH3) in glioblastoma multiforme is associated with worse prognosis

Golgi phosphoprotein-3 (GOLPH3), an important protein in mammalian target of rapamycin (mTOR) signaling, is overexpressed in and correlates with the pathological grade of glioma. However, the potential correlation between GOLPH3 and clinical outcome in patients with glioblastoma multiforme (GBM) remains unknown. In this study, we examined GOLPH3 expression in GBM by tissue microarray and correlated this measure to patient outcome. GOLPH3 expression in tumor tissue from 97 primary GBM patients was examined by tissue microarray and immunohistochemistry. Potential effects of GOLPH3 on tumor growth were also examined in representative cell lines (U251 and U87) by downregulating GOLPH3 with RNA interference. For this cohort, the median overall survival (OS) was 12?months [95?% confidence interval (CI): 10.31?C13.69?months], and the median progression-free survival (PFS) was 10?months (95?%?CI: 7.33?C12.67?months). Tissue microarray analysis revealed high GOLPH3 expression in 40 patients (40/97, 41.2?%) and low GOLPH3 expression in the remaining 57 patients (57/97, 58.8?%). Log-rank test showed that patients with low GOLPH3 expression had significantly longer median OS (15 versus 10?months in patients with high GOLPH3 expression, p?=?0.009) and median PFS (12 versus 7?months, p?=?0.015). Univariate and Cox analysis indicated that GOLPH3 was an independent prognostic factor for OS and PFS. In in?vitro experiments, GOLPH3 downregulation by small interfering RNA (siRNA) suppressed proliferation and clonogenic growth in cultured cell lines. These findings demonstrate that high GOLPH3 expression is associated with poor outcome of GBM patients.     

改良FOLFOXIRI方案一线治疗晚期结直肠癌的疗效及生存预后分析

目的:观察改良FOLFOXIRI方案一线治疗晚期结直肠癌的近期疗效、远期生存及不良反应.方法:采用前瞻性观察研究方法对47例晚期结直肠癌患者采用mFOLFOXIRI方案一线化疗.伊立替康(IRI)165mg/m2静脉滴注90min d 1,奥沙利铂(OXA)85mg/m2静脉滴注2h d 1,亚叶酸钙400mg/m2静脉滴注2h d 1,5-FU 2400~2800mg/m2持续静脉滴注48h,每2周为一周期.观察该方案的近期疗效及不良反应,并通过长期随访进行生存分析.结果:47例晚期结直肠癌患者治疗的总有效率(ORR)为51.1%,疾病控制率(DCR)为85.1%,中位无进展生存期(PFS)8.4个月(95%CI:6.6~10.2个月),中位总生存期(OS)20.7个月(95%CI:15.3~26.1个月).根据年龄及ECOG PS评分将患者分为体力状况较好组及体力状况中等组,两组近期疗效及PFS、OS均无显著统计学差异.亚组分析显示肿瘤早期缓解患者较非早期缓解患者的PFS及OS延长且具有统计学意义(PFS:11.0个月vs 7.1个月,P=0.044;OS:29.7个月vs 20.7个月,P=0.036);原发灶位于左半结肠/直肠者较右半结肠者的PFS及OS延长且具有统计学意义(PFS:10.6个月vs 3.7个月,P=0.002;OS:27.3个月vs 14.2个月,P=0.021).全组不良反应较轻,以I-II级为主,III-IV级不良反应主要为中性粒细胞减少及延迟性腹泻,但均为可控,无治疗相关死亡.结论:改良FOLFOXIRI三药联合方案作为晚期结直肠癌的一线治疗方案,其有效率高、不良反应可耐受,并可达到较长的生存时间,原发灶部位及是否达到早期缓解与患者预后生存可能有关,值得进一步临床研究.     

Progression-free survival and one-year milestone survival as surrogates for overall survival in previously treated advanced non-small cell lung cancer

The advent of immunotherapy leads to greater availability of effective subsequent treatments and extended survival in previously treated advanced non-small cell lung cancer (NSCLC), complicating the evaluation of overall survival (OS) in second-line NSCLC trials. Here, we aimed to assess the surrogacy of progression-free survival (PFS) and milestone survival for OS in second-line NSCLC trials investigating chemotherapy, targeted therapy and immunotherapy, respectively. We systemically searched for active-controlled, second-line NSCLC trials. The milestone time point was set at one-year based on pre-analysis. A two-stage meta-analytic validation model was adopted to assess associations between surrogate endpoint (SE) and OS and associations between treatment effects on SE and OS. Treatment effects on SE and OS were expressed as PFS hazard ratios (HR_PFS), 1 yr-milestone ratio (Ratio_1y-SUR) and HR_OS. Subgroup analyses stratified by treatment types and trial publication years evaluated the surrogacy in different clinical contexts. The study included 50 trials with 22,804 patients. One-year survival strongly correlated with OS (R²[95% confidence interval]: one-year survival -median OS = 0.707 [0.704–0.708]; Ratio_1y-SUR-HR_OS = 0.829 [0.828–0.831]). No correlation was established between PFS and OS (median PFS-median OS = 0.100 [0.098–0.101]; HR_PFS-HR_OS = 0.064 [0.059–0.069]), except in immunotherapy subgroup (HR_PFS-HR_OS = 0.835 [0.791–0.918]). In subgroup analyses, surrogacy of one-year survival persisted in different clinical contexts, and the disassociation between PFS and OS persisted in recent trials. One-year milestone survival showed strong surrogacy for OS in second-line NSCLC trials. Although no association was identified between PFS and OS, the strong HR_PFS-HR_OS correlation in immunotherapy trials indicates the potential of PFS as a SE in NSCLC trials involving immunotherapies.     

Phase II study of panobinostat in combination with bevacizumab for recurrent glioblastoma and anaplastic glioma

BackgroundPanobinostat is a histone deacetylase inhibitor with antineoplastic and antiangiogenic effects in glioma that may work synergistically with bevacizumab. We conducted a multicenter phase II trial of panobinostat combined with bevacizumab in patients with recurrent high-grade glioma (HGG).MethodsPatients with recurrent HGG were treated with oral panobinostat 30 mg 3 times per week, every other week, in combination with bevacizumab 10 mg/kg every other week. The primary endpoint was a 6-month progression-fee survival (PFS6) rate for participants with recurrent glioblastoma (GBM). Patients with recurrent anaplastic glioma (AG) were evaluated as an exploratory arm of the study.ResultsAt interim analysis, the GBM arm did not meet criteria for continued accrual, and the GBM arm was closed. A total of 24 patients with GBM were accrued prior to closure. The PFS6 rate was 30.4% (95%, CI 12.4%–50.7%), median PFS was 5 months (range, 3–9 months), and median overall survival (OS) was 9 months (range, 6–19 months). Accrual in the AG arm continued to completion, and a total of 15 patients were enrolled. The PFS6 rate was 46.7% (range, 21%–73%), median PFS was 7 months (range, 2–10 months), and median OS was 17 months (range, 5 months–27 months).ConclusionsThis phase II study of panobinostat and bevacizumab in participants with recurrent GBM did not meet criteria for continued accrual, and the GBM cohort of the study was closed. Although it was reasonably well tolerated, the addition of panobinostat to bevacizumab did not significantly improve PFS6 compared with historical controls of bevacizumab monotherapy in either cohort.     

Correlations of survival with progression-free survival,response rate,and disease control rate in advanced biliary tract cancer: a meta-analysis of randomised trials of first-line chemotherapy

Background:

The need to promote novel drug development for advanced biliary tract cancer (ABTC) has emphasised the importance of determining whether various efficacy end points can act as surrogates for overall survival (OS).

Methods:

We conducted a literature search of randomised trials of first-line chemotherapy for ABTC and investigated correlations between efficacy end points and OS using weighted linear regression analysis. The ratios of the median OS, median progression-free survival (PFS), response rate, and disease control rate in each trial were used to summarise treatment effects. The surrogate threshold effect (STE), which was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS, was calculated.

Results:

Seventeen randomised trials with 36 treatment arms were identified, and a sample size of 2148 patients with 19 paired arms was analysed. The strongest correlation between all evaluated efficacy end points was observed between median OS and median PFS ratios (r²=0.66). In trials with gemcitabine-containing therapies and targeted agents, the r²-values were 0.78. The STE was estimated at 0.83 for all trials and 0.81 for trials with gemcitabine-containing therapies, and was not calculated for trials with targeted agents.

Conclusions:

The median PFS ratio correlated well with the median OS ratio, and may be useful for planning a clinical trial for novel drug development.     

Surrogate End Points and Postprogression Survival in Renal Cell Carcinoma: An Analysis of First-Line Trials With Targeted Therapies

Our end point was to determine the correlations between progression-free survival (PFS), postprogression survival (PPS), response rate (RR), and disease control rate (DCR) (RR + stable disease) and overall survival (OS) in first-line trials of renal cell carcinoma (RCC) treated with targeted therapies and to identify a potential surrogate for OS. Data were collected from first-line phase III randomized trials in RCC. Linear regression was undertaken to evaluate the correlations between end points and a potential surrogate end point for OS. Six randomized trials were identified containing a total of 7 treatment arms. The nonparametric Spearman rank correlation coefficients (r_s) between PFS, PPS, and RR/DCR and OS are 0.869, and 1, 0.96/1 (all P < .0001), respectively. There is a strong relationship between differences (Δ) in DCR and ΔOS (r_s = 1). The slope of the regression line is 0.3963 ± 0.0019, indicating that a novel drug producing a 10% increase for DCR will yield an estimated absolute 3.9% increase in OS. In first-line trials including novel targeted agents for RCC, PFS is a relatively flawed surrogate end point because of PPS influence. Improvement in DCR is strongly associated with improvement in median OS. In this population, DCR may be an appropriate surrogate for OS.     

Survival outcomes of metastatic breast cancer patients by germline BRCA1/2 status in a large multicenter real-world database

The outcomes and best treatment strategies for germline BRCA1/2 mutation (gBRCAm) carriers with metastatic breast cancer (MBC) remain uncertain. We compared the overall survival and the first line progression free survival (PFS1) of patients with a gBRCAm identified at initiation of first-line treatment with those of BRCA wild-type (WT) and not-tested (NT) individuals in the ESME real-world database of MBC patients between 2008 and 2016 (NCT03275311). Among the 20 624 eligible patients, 325 had a gBRCAm, 1138 were WT and 19 161 NT. Compared with WT, gBRCAm carriers were younger, and had more aggressive diseases. At a median follow-up of 50.5 months, median OS was 30.6 (95%CI: 21.9-34.3), 35.8 (95%CI: 32.2-37.8) and 39.3 months (95% CI: 38.3-40.3) in the gBRCAm, WT and NT subgroups, respectively. Median PFS1 was 7.9 (95%CI: 6.6-9.3), 7.8 (95%CI: 7.3-8.5) and 9.7 months (95%CI, 9.5-10.0). In the multivariable analysis conducted in the whole cohort, gBRCAm status had however no independent prognostic impact on OS and PFS1. Though, in the triple-negative subgroup, gBRCAm patients had better OS and PFS1 (HR vs WT = 0.76; 95%CI: 0.60-0.97; P = .027 and 0.69; 95% CI: 0.55-0.86; P = .001, respectively). In contrast, in patients with HR+/HER2 negative cancers, PFS1 appeared significantly and OS non significantly lower for gBRCAm carriers (PFS1: HR vs WT = 1.23; 95%CI: 1.03-1.46; P = .024; OS:HR = 1.22, 95% CI: 0.97-1.52, P = .089). In conclusion, gBRCA1/2 status appears to have divergent survival effects in MBC according to IHC subtype.     

MGMT promoter methylation status as a prognostic factor for the outcome of gamma knife radiosurgery for recurrent glioblastoma

We conducted this study to determine whether the methylation status of the O⁶-methylguanine-DNA methyltransferase (MGMT) promoter was a prognostic marker for positive outcomes of gamma knife radiosurgery (GKS) for recurrent glioblastoma (GBM). We retrospectively examined 61 patients, who underwent GKS for local recurrent GBM between 2004 and 2015; in all patients, the methylation status of the MGMT promoter was identified via methylation-specific quantitative real-time polymerase chain reaction. All patients underwent surgical resection and were diagnosed histopathologically with GBM. Prognostic factors associated with progression-free survival (PFS) and overall survival (OS) were identified in univariate and multivariate analyses. Twenty-five (41%) had a methylated MGMT promoter, and 36 (59%) had an unmethylated MGMT promoter. The median age at GKS was 58 years. The median tumor volume at GKS was 7.0 cm³, and the median marginal dose was 16 Gy. The median follow-up period after GKS was 7.5 months. The median PFS time after GKS was 8.9 months (95% CI 4.3–13.5 months) in the methylated and 4.6 months (95% CI 3.7–5.5 months) in the unmethylated group (P?=?0.016). The median OS time after GKS was 14.0 months (95% CI 9.3–18.7 months) in the methylated group and 9.0 months (95% CI 6.5–11.5 months) in the unmethylated group (P?=?0.026). Methylation of the MGMT promoter correlated with better PFS and OS after GKS for recurrent GBM. Prospective comparative studies are required to determine whether MGMT methylation directly affects the efficiency of GKS.