The prognostic value of MGMT promoter methylation in Glioblastoma multiforme: a meta-analysis

The prognostic significance of O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation on Glioblastoma multiforme (GBM) remains controversial. A meta-analysis of published studies investigating the effects of MGMT promoter methylation on both progression-free survival (PFS) and overall survival (OS) among GBM patients was performed. A total of 2,986 patients from 30 studies were included in the meta-analysis. In all, the frequency of MGMT promoter methylation was 44.27 %. Five studies undertook univariate analyses and nine undertook multivariate analyses of MGMT promoter methylation on PFS. The pooled hazard ratio (HR) estimate for PFS was 0.72 (95 % CI 0.55–0.95) by univariate analysis and 0.51 (95 % CI 0.38–0.69) by multivariate analysis. The effect of MGMT promoter methylation on OS was evaluated in 15 studies by univariate analysis and 14 studies by multivariate analysis. The combined HR was 0.67 (95 % CI 0.58–0.78) and 0.49 (95 % CI 0.38–0.64), respectively. For GBM patients treated with Alkylating agent, the meta-risk remained highly significant by both univariate (HR = 0.58; 95 % CI 0.42–0.79) and multivariate analysis (HR = 0.42; 95 % CI 0.29–0.60). This study showed that MGMT promoter methylation was associated with better PFS and OS in patients with GBM regardless of therapeutic intervention, and associated with longer OS in GBM patients treated with alkylating agents.     

Prognostic paradox: brain damage around the glioblastoma resection cavity

Hyperintense lesions around the resection cavity on magnetic resonance diffusion-weighted imaging (MR-DWI) frequently appear after brain tumor surgery due to the damage of surrounding brain. The putative connection between the lesion and the prognosis for patients with glioblastoma (GBM) was explored. This retrospective study reviewed consecutive sixty-one patients with newly diagnosed GBM. Postoperative MRI was performed within 2 weeks after the initial surgery. We classified the cases into two groups depending on whether DWI hyperintense lesions were observed or not [DWI(+) group and DWI(?) group]. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups. Forty-two patients were identified. The various extents of hyperintense lesions around the resection cavity were observed in 28/42 (66.7 %) cases. In the DWI(+) and DWI(?) groups, median PFS was 10.0 [95 % confidence interval (CI) 8.4–11.5] and 6.7 (95 % CI 4.9–8.5) months, respectively (p = 0.042), and median OS was 18.0 (95 % CI 12.2–23.8) and 17.0 (95 % CI 15.7–18.3) months, respectively (p = 0.254). On multivariate analysis, the presence of DWI hyperintense lesion was more likely to be an independent predictor for 6-month PFS (p = 0.019; HR, 0.038; 95 % CI 0.002–0.582). Tumor recurrence appeared outside the former DWI hyperintense lesion. Hyperintense lesions surrounding the resected GBM on MR-DWI might be a favorable prognostic factor in patients with GBM.     

Meta-analysis of Six Randomized Control Trials of Chemotherapy Plus Anti-HER Monoclonal Antibody for Advanced Gastric and Gastroesophageal Cancer

Background: A meta-analysis was performed to examine the benefit/risk ratio for the addition of anti-HER MoAbs to chemotherapy in patients with advanced gastric and gastroesophageal cancer from six andomized phase II/III trials. Materials and Methods: We searched relative trials from Pubmed, EMBASE, Cochrane library databases, China National Knowledge Infrastructure databases, Google Scholar and the NIH ClinicalTrials. Primary outcomes were overall response rate (ORR), progression-free survival (PFS), overall survival (OS). Secondary outcomes were toxicities. All analyses were performed using STATA 12.0. Results: This meta-analysis included six randomized controlled trials (RCTs) with 2, 297 patients and we demonstrated that the anti-HER MoAbs arm did have a positive effect on ORR in the anti-HER MoAbs arm (OR 1.28, 95% CI 1.00-1.64, p=0.01). There was an increasing benefit regarding OS (HR 0.74, 95% CI 0.60-0.88, p<0.05) and PFS (HR 0.72, 95% CI 0.60-0.84, p<0.05) in the anti-HER2 subgroup, but a reduction of OS (HR 1.11, 95% CI 0.87-1.36, p<0.05) and PFS (HR 1.13, 95% CI 0.98 -1.28, P<0.05) in anti-EGFR subgroup. Some grade 3-4 toxicity had a significantly higher incidence in the anti-HER MoAbs arm. There was no significant publicationbias for all endpoints. Conclusions: The addition of trstuzumab MoAb to chemotherapy for gastric and gastroesophageal cancer significantly improved outcome of OS and PFS endpoints, while other MoAbs led to no improvement in results. Some adverse events were increased in anti-HER MoAbs arm compared with the control.     

弥漫大B细胞淋巴瘤患者体质量指数对预后影响的Meta分析

目的:系统评价体质量指数（BMI）对弥漫大B细胞淋巴瘤（DLBCL）患者预后的影响。方法:计算机检索PubMed、Medline、Web of Science等数据库,按照纳入及排除标准筛选关于BMI与DLBCL患者预后关系的临床研究文献,采用RevMan 5.3软件对各研究的总生存（OS）、无进展生存（PFS）的风险比（ HR）及95%置信区间（95% CI）等数据进行分析,同时评估纳入文献质量、偏倚风险及异质性。 结果:共12篇文献纳入研究。Meta分析结果显示,与正常体质量（BMI 18.5~24.9 kg/m 2）患者相比,超重（BMI 25.0~29.9 kg/m 2）患者OS和PFS时间更长,但差异均无统计学意义（OS： HR=0.93,95% CI 0.78~1.11, P=0.42;PFS： HR=0.89,95% CI 0.67~1.20, P=0.45）;低体质量（BMI<18.5 kg/m 2）患者（OS： HR=1.97,95% CI 1.41~2.74, P<0.01;PFS： HR=1.89,95% CI 1.19~3.03, P<0.01）和肥胖（BMI≥30.0 kg/m 2）患者OS和PFS时间更短,但后者差异无统计学意义（OS： HR=1.15,95% CI 0.88~1.51, P=0.31;PFS： HR=1.32,95% CI 0.90~1.94, P=0.15）。漏斗图对称,纳入文献无发表偏倚。 结论:一定范围内BMI升高是DLBCL患者预后的保护性因素。     

Demonstration of DCE-MRI as an early pharmacodynamic biomarker of response to VEGF Trap in glioblastoma

The actin-binding protein fascin has been associated with clinically aggressive tumors and poor prognosis. The purpose of this study was to investigate possibility of fascin expression as a prognostic factor in a newly diagnosed primary glioblastoma (GBM). Between July 2007 and December 2013, 37 out of 126 patients diagnosed with GBM satisfied the following inclusion criteria: (1) the presence of immunohistochemically-available tissue, (2) a new primary GBM, (3) gross-total resection, and (4) standardized adjuvant treatment, known as the Stupp regimen. The median follow-up period was 18 months (range 5–95). According to the staining intensity of fascin, progression-free survival (PFS) in the low-intensity fascin group (median PFS 9.0 months; 95?% CI 6.0–12.0) was longer than PFS in the high-intensity fascin group (median PFS 7.0 months; 95?% CI 5.6–10.4; p?=?0.024). Overall survival (OS) in the low-intensity fascin group (median OS 20.0 months; 95?% CI 17.7–22.4) was longer than OS in the high-intensity fascin group (median OS 13.0 months; 95?% CI 8.2–17.8; p?=?0.031). And, the staining intensity of fascin was a statistically significant factor in PFS and OS according to univariate and multivariate analyses (univariate analysis p?=?0.043 and p?=?0.043; multivariate analysis p?=?0.041 and p?=?0.044). Our clinical study showed that fascin expression intensity may be correlated with clinical outcomes of a newly diagnosed primary GBM, especially with regard to PFS and OS.     

Correlation between sex and efficacy of immune checkpoint inhibitors (PD‐1 and CTLA‐4 inhibitors)

Immune checkpoint inhibitors (ICIs) exert the antitumor efficacy depending on immune response, which is affected by sex difference, where both biological and sociological factors are involved. The role of sex in ICI trials has been overlooked. How sex correlates with ICI efficacy is incompletely understood. Clinical trials evaluating ICI versus other therapies in male and female patients were included. The hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS) and progression‐free survival (PFS) were used. Six thousand and ninety‐six patients from 11 trials were included. More improvement of OS was observed in males (HR, 0.62; 95% CI, 0.53–0.71; p < 0.001) treated with ICI versus controls than females (HR, 0.74; 95% CI, 0.65–0.84; p < 0.001). ICIs improved PFS more in males (HR, 0.57; 95% CI, 0.43–0.71; p < 0.001) than females (HR, 0.71; 95% CI, 0.52–0.91; p < 0.001). The sex difference had more effect on the overall survival in melanoma patients versus NSCLC patients. Overall survival of patients treated with CTLA‐4 inhibitor was more influenced by sex variable compared with PD‐1 inhibitors. A significant sex‐related efficacy difference was observed between female and male melanoma patients. Although male patients had longer OS and PFS than females when treated with ICIs versus controls, the difference was not significant. Sex difference should be more considered in future clinical trials, guidelines and clinical practice.     

Use of metformin and outcome of patients with newly diagnosed glioblastoma: Pooled analysis

Metformin has been linked to improve survival of patients with various cancers. There is little information on survival of glioblastoma patients after use of metformin. We assessed the association between metformin use and survival in a pooled analysis of patient data from 1,731 individuals from the randomized AVAglio, CENTRIC and CORE trials. We performed multivariate Cox analyses for overall survival (OS) and progression-free survival (PFS) comparing patients' use of metformin at baseline and/or during concomitant radiochemotherapy (TMZ/RT). Further exploratory analyses investigated the effect of metformin with a history of diabetes and nonfasting glucose levels in relation to OS or PFS of glioblastoma patients. Metformin alone or in any combination was not significantly associated with OS or PFS (at baseline, hazard ratio [HR] for OS = 0.87; 95% confidence interval [CI] = 0.65–1.16; HR for PFS = 0.84; 95% CI = 0.64–1.10; during TMZ/RT HR for OS = 0.97; 95% CI = 0.68–1.38; HR for PFS = 1.02; 95% CI = 0.74–1.41). We found a statistically nonsignificant association of metformin monotherapy with glioblastoma survival at baseline (HR for OS = 0.68; 95% CI = 0.42–1.10; HR for PFS = 0.57; 95% CI = 0.36–0.91), but not during the TMZ/RT period (HR for OS = 0.90; 95% CI = 0.51–1.56; HR for PFS = 1.05; 95% CI = 0.64–1.73). Diabetes mellitus or increased nonfasting glucose levels were not associated with a difference in OS or PFS in our selected study population. Metformin did not prolong survival of patients with newly diagnosed glioblastoma in our analysis. Additional studies may identify patients with specific tumor characteristics that are associated with potential benefit from treatment with metformin, possibly due to metabolic vulnerabilities.     

Darbepoetin alfa for the treatment of chemotherapy-induced anemia: disease progression and survival analysis from four randomized, double-blind, placebo-controlled trials.

PURPOSE: To determine the effect of darbepoetin alfa (DA) on progression-free survival (PFS) and overall survival (OS) in patients with chemotherapy-induced anemia (CIA). PATIENTS AND METHODS: Two 16-week randomized, double-blind, placebo-controlled phase III studies of weekly DA in anemic patients with lung cancer (n = 314) or lymphoproliferative malignancies (LPMs; n = 344) undergoing chemotherapy were analyzed with prospectively defined long-term PFS and OS end points. Short-term effects of DA on PFS and OS were analyzed by including two additional 16-week dose-finding, double-blind, placebo-controlled studies in anemic patients with multiple tumor types (n = 405) and LPMs (n = 66). RESULTS: Median follow-up is 15.8 months (lung cancer) and 32.6 months (LPM). Median duration of PFS was comparable between DA and placebo: 5.1 months (95% CI, 4.1 to 6.9 months) versus 4.4 months (95% CI, 3.7 to 5.3 months) for lung cancer and 14.2 months (95% CI, 12.2 to 17.5 months) versus 15.9 months (95% CI, 13.1 to 19.0 months) for LPMs. The estimated hazard ratio (HR) of death related to DA use for lung cancer was 0.77 (95% CI, 0.59 to 1.01) and 1.26 (95% CI, 0.92 to 1.71) for LPMs. In the pooled analyses of all four studies (n = 1,129), no differences in PFS or OS were observed between DA and placebo (HR = 0.92; 95% CI, 0.78 to 1.07; and HR = 0.95; 95% CI, 0.78 to 1.16, respectively). CONCLUSION: Treatment with DA does not seem to influence PFS or OS in patients with CIA. Prospective, randomized clinical trials will provide additional insights into the effects of DA on PFS and OS in specific tumor types.     

血小板-淋巴细胞比值在鼻咽癌预后预测中的作用：Meta分析

背景与目的：已发现血小板-淋巴细胞比值（platelet-to-lymphocyte ratio,PLR）可预测鼻咽癌的临床结果。然而,先前关于PLR与鼻咽癌预后的报道不一致。根据Meta分析提供更准确的预后评估。方法：检索了PubMed、Web of Science和Scopus数据库确定评估治疗前PLR在鼻咽癌中的预后作用的研究。终点是总生存期（overall survival,OS）、无进展生存期（progression-free survival,PFS）、疾病特异性生存率（disease-specific survival,DSS）、无远处转移生存期（distant metastasis-free survival,DMFS）。提取风险比（hazard ratio,HR）和95%置信区间（confidence interval,CI）,并根据异质性检验选用固定效应模型或随机效应模型估计每个终点的合并HR。结果：共纳入10项研究,涉及4 655例鼻咽癌患者。Meta分析汇总结果显示,升高的治疗前PLR与鼻咽癌患者较差的OS（HR=1.92,95% CI：1.73~2.14,P＜0.01）、PFS（HR=1.56,95% CI：1.19~2.06,P=0.002）及DSS（HR=1.65,95% CI：1.19~2.27,P=0.002）相关,但与DMFS无显著相关性（HR=1.69,95% CI：0.97~2.96,P=0.06）。结论：升高的治疗前PLR可以预测鼻咽癌患者更差的OS、PFS和DSS,而对DMFS没有预测价值。     

Prognostic factors in young ovarian cancer patients: An analysis of four prospective phase III intergroup trials of the AGO Study Group,GINECO and NSGO

ObjectivesWe evaluated in a large study meta-database of prospectively randomised phase III trials the prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients < and >40 years of age with advanced epithelial ovarian cancer.MethodsA total of 5055 patients of the AGO, GINECO, NSGO intergroup studies AGO-OVAR 3, 5, 7 and 9 were merged to identify 294 patients <40 years and 4761 patients ≥40 years. We conducted survival analyses and Cox proportional hazard regression models and additionally analysed a very homogeneous subcohort of 405 patients with serous epithelial ovarian cancer, excellent performance status, who had received complete macroscopic upfront cytoreduction and ≥5 chemotherapy cycles.ResultsFor patients <40 years, the median PFS was 28.9 months and the median OS was 75.3 months, while the median PFS for patients ≥40 years was 18.1 months and the median OS was 45.7 months. Independent prognostic factors were similar in both age groups. In a multivariate analysis including prognostic factors potentially leading to confounding, young age appeared to improve PFS (hazard ratio [HR], 0.86; 95% confidence interval [CI]: 0.72–1.03) and OS (HR, 0.73; 95% CI: 0.59–0.91). The observed effect was even stronger in the subcohort of optimally treated patients with SEOC: PFS (HR, 0.34; 95% CI: 0.19–0.59) and OS (HR, 0.23; 95% CI: 0.09–0.56).DiscussionPrognostic factors were similar in both age groups. Young age appeared a strong independent protective prognostic factor for PFS and OS in the subcohort.     

Evaluation of potential circulating biomarkers for prediction of response to chemoradiation in patients with glioblastoma

Surgery followed by chemoradiation and adjuvant chemotherapy is standard of care for patients with a glioblastoma (GBM). Due to its limited benefit, an upfront method to predict dismal outcome would prevent unnecessary toxic treatment. We searched for a predictive blood derived biomarker in a cohort of 55 patients with GBM. Increasing age (HR 1.03, 95?% CI 1.01–1.06), and postoperative tumor residue (HR 1.07, 95?% CI 1.02–1.15) were independently associated with unfavourable progression free survival (PFS) in these patients. Corticosteroid use before start of chemoradiaton was strongly predictive for outcome (HR 3.26, 95?% CI 1.67–6.39) with a mean PFS and OS in patients using corticosteroids of 7.3 and 14.6 months, versus 16.1 and 21.6 months in patients not using corticosteroids (p?=?0.0005, p?相似文献   

Ki-67 is a Valuable Prognostic Factor in Gliomas: Evidence from a Systematic Review and Meta-analysis

Ki-67 has been widely used as an indicator of cell proliferation in gliomas. However, the role of Ki-67 as aprognostic marker is still undefined. Thus, we conducted a meta-analysis of the published literatures in order toclarify the impact of Ki-67 on survival in glioma cases. Eligible studies were identified in PubMed, EMBASE, ISIWeb of Science, Cochrane Central Register of Controlled Trials, Science Direct and Wiley Online Library withthe last search updated on August 31, 2014. The clinical characteristics, overall survival (OS) and progressionfreesurvival (PFS) together with Ki-67 expression at different time points were extracted. A total of 51 studies,covering 4,307 patients, were included in the current meta-analysis. The results showed that overexpression ofKi-67 can predict poor OS (HR=1.66, 95%CI: 1.53-1.80; Z=11.87; p=0.000) and poor PFS (HR=1.67, 95%CI:1.47-1.91; Z=7.67; p=0.000) in gliomas. Moreover, subgroup analyses also indicated that high level of Ki-67expression was related to poor OS and PFS in glioma patients regardless of region, pathology type, cut-offvalue and statistical method. In conclusion, the current meta-analysis revealed that Ki-67 expression might bea predicative factor for poor prognosis of glioma patients, emphasizing its importance as a predictor.     

Prognostic Value of Lactate Dehydrogenase in Metastatic Prostate Cancer: A Systematic Review and Meta-analysis

The purpose of this study was to assess the prognostic value of lactate dehydrogenase (LDH) in patients with metastatic prostate cancer (PC). A systematic review and meta-analysis was performed in March 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared patients with PC with high versus low LDH to determine the predictive value of LDH for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We performed a formal meta-analysis for both OS and PFS. A total of 59 articles with 14,851 patients were included in the systematic review and 45 studies with 12,224 patients for the qualitative assessment. High LDH was associated with both worse OS (pooled hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.75-2.44) and PFS (pooled HR, 1.08; 95% CI, 1.01-1.16). In subgroup analyses of both patients with castration-resistant prostate cancer (CRPC) and those with hormone-sensitive prostate cancer (HSPC), LDH was associated with OS (pooled HR, 2.02; 95% CI, 1.69-2.42 and pooled HR, 2.25; 95% CI, 1.78-2.84, respectively). In patients with CRPC, LDH was associated with OS in those treated with docetaxel systemic chemotherapy and androgen receptor–axis-targeting agents (pooled HR, 2.03; 95% CI, 1.37-3.00 and pooled HR, 1.79; 95% CI, 1.25-2.57, respectively). Elevated serum levels of LDH were associated with an increased risk of mortality and progression in patients with metastatic PC. LDH was independently associated with OS in both patients with CRPC and HSPC. LDH could be integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision-making process.     

The immunohistochemical expression of c-Met is an independent predictor of survival in patients with glioblastoma multiforme

Background and aims

Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols.

Methods

Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23–81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures.

Results

Compared with c-Met? subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2–1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1–2.3, p < 0.05).

Conclusions

Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care.     

MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy

Objective: To evaluate the impact of the multi-drug resistance 1(MDR1) C3435T polymorphism on clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. Methods: From January 2005 to December 2008, 102 patients with surgically resected gastric cancers were enrolled into this study in the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University. The polymorphism was tested using real time polymerase chain reaction (RT-PCR) cycling probes and the relationship with clinical outcomes after postoperative adjuvant chemotherapy was analyzed by SPSS 17.0. Results: The CT/TT genotype of C3435T was significantly associated with a shorter progression-free survival (PFS) and overall survival (OS) compared with the CC genotype [PFS: adjusted hazard ratio(HR)= 2.01, 95% confidence intervals(CI): 1.17-3.45, P = 0.012; OS: adjusted HR = 2.37, 95% CI: 1.31-4.28, P=0.004]. TNM stage was also associated with PFS (adjusted HR = 2.33, 95% CI: 1.34-4.05, P = 0.003) and OS (adjusted HR = 2.62, 95% CI: 1.44-4.76, P = 0.002) in gastric cancer patients treated with postoperative adjuvant chemotherapy. Conclusion: Our results suggest that the MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. This now needs to be confirmed by a randomized prospectively controlled study.     

Upfront Chemotherapy Followed by Stereotactic Body Radiation Therapy with or without Surgery in Older Patients with Localized Pancreatic Cancer: A Single Institution Experience and Review of the Literature

Objective: To report on clinical outcomes and toxicity in older (age ≥ 70 years) patients with localized pancreatic cancer treated with upfront chemotherapy followed by stereotactic body radiation therapy (SBRT) with or without surgery. Methods: Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and toxicity. Results: A total of 57 older patients were included in the study. Median OS was 19.6 months, with six-month, one-year, and two-year OS rates of 83.4, 66.5, and 42.4%. On MVA, resection status (HR: 0.30, 95% CI 0.12–0.91, p = 0.031) was associated with OS. Patients with surgically resected tumors had improved median OS (29.1 vs. 7.0 months, p < 0.001). On MVA, resection status (HR: 0.40, 95% CI 0.17–0.93, p = 0.034) was also associated with PFS. Patients with surgically resected tumors had improved median PFS (12.9 vs. 1.6 months, p < 0.001). There were 3/57 cases (5.3%) of late grade 3 radiation toxicity and 2/38 cases (5.3%) of Clavien-Dindo grade 3b toxicity in those who underwent resection. Conclusion: Multimodality therapy involving SBRT is safe and feasible in older patients with localized pancreatic cancer. Surgical resection was associated with improved clinical outcomes. As such, older patients who complete chemotherapy should not be excluded from aggressive local therapy when possible.     

Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR: A meta-analysis from six phase III randomized controlled trials

Gefiinib and erlotinib are two similar small molecules of selective and reversible epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which have been approved for second-line or third-line indication in previously treated advanced Non-small-cell lung cancer (NSCLC) patients. The results of comparing the EGFR-TKI with standard platinum-based doublet chemotherapy as the first-line treatment in advanced NSCLC patients with activated EGFR mutation were still controversial. A meta-analysis was performed to derive a more precise estimation of these regimens. Finally, six eligible trials involved 1,021 patients were identified. The patients receiving EGFR-TKI as front-line therapy had a significantly longer progression-free survival (PFS) than patients treated with chemotherapy [median PFS was 9.5 versus 5.9 months; hazard ratio (HR)=0.37; 95% confidence intervals (CI)=0.27-0.52; p<0.001]. The overall response rate (ORR) of EGFR-TKI was 66.60%, whereas the ORR of chemotherapy regimen was 30.62%, which was also a statistically significant favor for EGFR-TKI [relative risk (RR)=5.68; 95% CI=3.17-10.18; p<0.001]. The overall survival (OS) was numerically longer in the patients received EGFR-TKI than patients treated by chemotherapy, although the difference did not reach a statistical significance (median OS was 30.5 vs. 23.6 months; HR=0.94; 95% CI=0.77-1.15; p=0.57). Comparing with first-line chemotherapy, treatment of EGFR-TKI achieved a statistical significantly longer PFS, higher ORR and numerically longer OS in the advanced NSCLC patients harboring activated EGFR mutations, thus, it should be the first choice in the previously untreated NSCLC patients with activated EGFR mutation.     

Multi-institutional analysis of cervical esophageal carcinoma patients treated with definitive chemoradiotherapy: TROD 01-005 study

The aim of this study was to examine the prognostic factors and treatment outcomes of cervical esophageal carcinoma (CEC) patients who underwent definitive chemoradiotherapy (CRT). The clinical data of 175 biopsy-confirmed CEC patients treated with definitive CRT between April 2005 and September 2021 were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were assessed in uni- and multivariable analyses. The median age of the entire cohort was 56 years (range: 26–87 years). All patients received definitive radiotherapy with a median total dose of 60 Gy, and 52% of the patients received cisplatin-based concurrent chemotherapy. The 2-year OS, PFS, and LRFS rates were 58.8%, 46.9%, and 52.4%, respectively, with a median follow-up duration of 41.6 months. Patients’ performance status, clinical nodal stage, tumor size, and treatment response were significant prognostic factors for OS, PFS, and LRFS in univariate analysis. Non-complete treatment response was an independent predictor for poor OS (HR = 4.41, 95% CI, 2.78–7.00, p < 0.001) and PFS (HR = 4.28, 95% CI, 2.79–6.58, p < 0.001), whereas poor performance score was a predictor for worse LRFS (HR = 1.83, 95% CI, 1.12–2.98, p = 0.02) in multivariable analysis. Fifty-two patients (29.7%) experienced grade II or higher toxicity. In this multicenter study, we demonstrated that definitive CRT is a safe and effective treatment for patients with CEC. Higher radiation doses were found to have no effect on treatment outcomes, but a better response to treatment and a better patient performance status did.     

EGFR gene copy number as a predictive biomarker for resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer treatment:a meta-analysis简

Objective：The epidermal growth factor receptor （EGFR） inhibitors monoclonal antibodies （MoAbs） have already shown the therapeutic effectiveness in patients with metastatic colorectal cancer （mCRC）.But many patients resist to the treatment.The aim of this meta-analysis was to assess EGFR gene copy number （GCN） as a candidate predictive biomarker for resistance to anti-EGFR MoAbs in mCRC treatment.Methods：Systematic computerized searches of the PubMed,EMBase and Cochrane Library were performed.The primary endpoint was objective response rate （ORR）.The second endpoints included progression-free survival （PFS）,and overall survival （OS）.The pooled odd ratio （OR） and pooled sensitivity,specificity,and summary receiver operator characteristic （SROC） for ORR were estimated.The pooled hazard ratios （HR） for PFS and OS were also calculated.Results：Fourteen studies with 1,021 patients were included.Increased EGFR GCN was associated with increased ORR （OR=6.905; 95％ CI：4.489-10.620）.It was also found in wild-type KRAS mCRC patients,with the pooled OR of 8.133 （95 ％ CI：4.316-15.326）.GCN has medium value for predicting ORR,with the pooled sensitivity of 0.79 （95％ CI：0.73-0.84）,the pooled specificity of 0.59 （95％ CI：0.55-0.62）.In wildtype KRAS mCRC patients,the sensitivity and the specificity were 0.80 （95％ CI：0.70-0.87） and 0.60 （95％CI：0.53-0.66）,respectively.Increased EGFR GCN was associated with increased PFS （HR=0.557; 95％ CI：0.382-0.732） and OS （HR=0.579; 95％ CI：0.422-0.737）.Conclusions：This meta-analysis suggests that EGFR GCN represents a predictive biomarker for tumor response in mCRC patients treated with MoAbs regardless of KRAS mutation.mCRC patients with increased EGFR GCN are more likely to have a better response,PFS,and OS when treated with cetuximab or panitumumab.     

Panitumumab plus trifluridine/tipiracil as anti-EGFR rechallenge therapy in patients with refractory RAS wild-type metastatic colorectal cancer: Overall survival and subgroup analysis of the randomized phase II VELO trial

The randomized phase II VELO trial showed that the addition of panitumumab to trifluridine/tipiracil significantly improves progression-free survival (PFS) as compared to trifluridine/tipiracil in third-line therapy in patients with refractory RAS wild-type (WT) metastatic colorectal cancer (mCRC). With longer follow-up, final overall survival results and posttreatment subgroup analysis are presented. Sixty-two patients with refractory RAS WT mCRC were randomly assigned to receive, as third-line therapy, trifluridine/tipiracil alone (arm A) or in combination with panitumumab (arm B). Primary endpoint was PFS; secondary endpoints included overall survival (OS) and overall response rate (ORR). Median OS was 13.1 months (95% CI 9.5-16.7) in arm A compared to 11.6 months (95% CI 6.3-17.0) in arm B (HR: 0.96, 95% CI 0.54-1.71, P = .9). To evaluate the impact of subsequent lines of treatment, subgroup analysis was performed for the 24/30 patients in arm A, that received fourth-line therapy after disease progression. Median PFS was 4.1 months (95% CI 1.44-6.83) for 17 patients treated with anti-EGFR rechallenge as compared to 3.0 months (95% CI 1.61-4.31) for seven patients that received other therapies (HR: 0.29, 95% CI 0.10-0.85, P = .024). Median OS from the start of fourth-line treatment was 13.6 months (95% CI 7.2-20), and 5.1 months (95% CI 1.8-8.3) for patients treated with anti-EGFR rechallenge vs other therapies, respectively (HR: 0.30, 95% CI 0.11-0.81, P = .019). Final results of the VELO trial support the role of anti-EGFR rechallenge in the continuum of care of patients with RAS/BRAF WT mCRC.