Systematic review and meta-analysis of monotherapy compared with combined androgen blockade for patients with advanced prostate carcinoma

BACKGROUND: The current systematic review and meta-analysis compared monotherapy and combined androgen blockade in the treatment of men with advanced prostate carcinoma. Outcomes of interest included overall, cancer specific, and progression-free survival; time to treatment failure; adverse events; and quality of life. METHODS: The literature search identified randomized trials comparing monotherapy (orchiectomy and luteinizing hormone-releasing hormone [LHRH] agonists) with combination therapy using orchiectomy or a LHRH agonist plus a nonsteroidal or steroidal antiandrogen. Dual independent review occurred. The meta-analysis used a random effects model. RESULTS: Twenty-one trials compared survival after monotherapy with survival after combined androgen blockade (n = 6871 patients). The meta-analysis found no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade and those treated with monotherapy (20 trials; hazard ratio [HR] = 0.970; 95% confidence interval [95% CI], 0.866-1.087). The authors determined a statistically significant difference in survival at 5 years that favored combined androgen blockade (10 trials; HR = 0.871; 95% CI, 0.805-0.942). For the subgroup of patients with a good prognosis, there was no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. To the authors' knowledge there is little evidence published to date comparing the effects of combined androgen blockade and monotherapy on quality of life, but the single randomized trial that adequately addressed this outcome reported an advantage for monotherapy over combined androgen blockade. CONCLUSIONS: A thorough examination of the usefulness of combined androgen blockade must balance the modest increase in expected survival observed at 5 years against the increased risk of adverse effects and the potential for adversely affecting the patient's overall quality of life.     

Adverse events risk associated with bevacizumab addition to breast cancer chemotherapy: a meta-analysis

BackgroundBevacizumab is a monoclonal antibody against vascular endothelial growth factor with the ability to increase progression-free survival in metastatic breast cancer (MBC). A systematic review and meta-analysis was conducted to determine the risk of the most clinically relevant adverse outcomes associated with the use of bevacizumab in the treatment of breast cancer.Patients and methodsWe included phase III clinical trials that used bevacizumab alone or in combination with chemotherapy as for MBC or locally recurrent. Statistical analyses were conducted to calculate summary odds ratio (OR) of the eight most relevant adverse outcomes related with bevacizumab.ResultsFive clinical trials were included in the meta-analysis. Summary odds ratios obtained showed a statistically significant bevacizumab-associated increased risk in four of the adverse outcomes studied: proteinuria (OR = 27.68), hypertension (OR = 12.76), left ventricular dysfunction (LVD) (OR = 2.25), and hemorrhagic events (OR = 4.07). No statistically significant differences were found for gastrointestinal (GI) perforation, vascular events, fatal events, or febrile neutropenia.ConclusionsBevacizumab did increase the risk of LVD and hemorrhagic events. The addition of bevacizumab to chemotherapy in patients with metastatic breast cancer was not associated with a significant increase in grade ≥3 arterial or venous thromboembolic events, GI perforation, or fatal events.     

Chemoradiotherapy for esophageal cancer: current status and perspectives

The optimal role of chemoradiotherapy in the multimodality treatment of esophageal cancer is still controversial. According to a series of clinical trials, definitive chemoradiotherapy is considered the standard of care for patients with medically inoperable or surgically unresectable esophageal cancer. This modality provides survivals comparable to those in Western series of surgery alone and is one of the standards of care even for resectable-stage disease. Recent reports of primary chemoradiotherapy from Japan suggest survival comparable to that of surgery in Japanese patients with stage I disease, but radical surgery is still the standard treatment for T2–3NanyM0 disease in Japan. However, it is clear that this approach has limitations in treatment outcomes. Trimodality therapy, i.e., preoperative chemoradiotherapy followed by surgery, is more favored than surgery alone in clinical practice, particularly in patients with adenocarcinoma, although current data from randomized trials are insufficient to support this approach. To improve the local control rate of chemoradiotherapy, intensification of the radiation dose has been attempted, but this has failed to demonstrate any superiority in terms of local control or survival. The addition of new agents, including molecular targeting agents, to the current standard chemoradiotherapy has shown more promising results and warrants further investigations in future studies. Salvage treatment for patients who do not achieve a complete response (CR) is necessary to improve the overall treatment results. Salvage surgery, as well as endoscopic resection, in selected patients, may provide an improvement in survival. Until high rates of local control can be consistently achieved with chemoradiotherapy alone, these salvage treatments will be an integral component of multimodality treatment for esophageal cancer, and should be active areas for clinical investigations.     

食管癌放化疗后复发再程放疗的Meta分析

目的 Meta分析食管癌放化疗后复发再程放疗与其他疗法疗效和不良反应。方法 通过计算机检索PubMed、Embase、Cochrane Library、CNKI、万方等数据库,搜集有关食管癌放化疗后复发再程放疗与其他治疗方法比较的临床对照研究。检索时间为建库至 2020年4月。采用RevMan 5.1软件进行分析,组间差异采用RR及 95%CI描述。结果 根据纳入排除标准最终纳入11篇文献,包括 842例患者。Meta分析结果显示再程放疗组与手术组相比总生存率略低(RR=0.40,95%CI为 0.27~0.61,P<0.001),与单纯化疗组相比则得到了提高(RR=2.91,95%CI为 1.43~5.95,P=0.003)。再程放疗组与手术组治疗相关死亡率相近(RR=0.53,95%CI为 0.14~1.98,P=0.350),但手术组发生率较高(1.7%~11.4%∶1.9%~2.8%)。结论 再程放疗是放化疗后复发食管癌的有效治疗手段,可作为临床患者的选择方案。     

Second-line treatments for advanced gastric cancer: Interpreting outcomes by network meta-analysis

AIM: To study the effectiveness of second-line treatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 treatments were evaluated: (1) irinotecan (camptothecins); (2) paclitaxel (taxanes class); (3) docetaxel (taxanes); (4) everolimus (mammalian target of rapamycin inhibitors); (5) ramucirumab (vascular endothelial growth factor receptor 2 inhibitors); (6) ramucirumab + paclitaxel. Our methodology was based on standard models of Bayesian network meta-analysis. The reference treatment was best supportive care (BSC). The end-point was overall survival. Median survival was the outcome measure along with 95% credible intervals.RESULTS: Our search identified a total of 7 randomized controlled trials. These trials included 2298 patients (in 15 treatment arms) in whom a total of 6 active treatments were evaluated as well as BSC. There were 21 head-to-head comparisons (6 direct, 15 indirect). The difference in survival between each of two active treatments (paclitaxel and ramucirumab + paclitaxel) vs BSC was statistically significant, while the other 4 showed no statistical difference. In the 6 head-to-head comparisons between active treatments, no significant survival difference was demonstrated.CONCLUSION: Our results indicate that both paclitaxel monotherapy and ramucirumab + paclitaxel determine a significant prolongation in survival as compared with BSC.     

Opioids for the management of dyspnea in cancer patients: a systematic review and meta-analysis

Dyspnea is a prevalent symptom that significantly reduces quality of life of cancer patients. Palliative treatment is necessary when the symptoms do not respond to treatment for their cause. Opioids are widely used as pharmacological therapy, but evidence for individual agents is inconsistent. The purpose of this study was to evaluate the efficacy and safety of opioids for dyspnea in cancer patients. We searched the CENTRAL, MEDLINE, EMBASE, and ICHUSHI for studies using opioids for dyspnea in adult cancer patients reported by September 2019. Screening of the retrieved literature and assessment of risk of bias and outcomes were performed by two independent authors. A meta-analysis was performed on the primary endpoint, relief of dyspnea, and secondary endpoints including quality of life, somnolence as a side effect, and serious adverse events. Twelve randomized controlled trials were evaluated regarding relief of dyspnea. Somnolence and serious adverse events were evaluated in seven and four randomized controlled trials, respectively, but no randomized controlled trials were evaluable for quality of life. Overall, opioids were more effective than placebo for dyspnea (standardized mean difference − 0.43, 95% confidence interval [CI] − 0.75 to – 0.12). Although significant difference was found between systemic morphine and placebo in the drug-specific analysis, no significant difference could be detected in the other analyses. Systemic administration of opioids is more effective than placebo in relieving dyspnea in cancer patients. Robust evidence on the efficacy and safety of opioids on dyspnea in cancer patients is lacking, and further studies are needed.

     

Bayesian network meta-comparison of maintenance treatments for stage IIIb/IV non-small-cell lung cancer (NSCLC) patients with good performance status not progressing after first-line induction chemotherapy: Results by performance status,EGFR mutation,histology and response to previous induction

BackgroundRecent trials have suggested that maintenance treatments improve outcomes for patients not progressing after first-line therapy for advanced non-small-cell lung cancer (NSCLC). However, physicians have little guidance on selecting which patients benefit the most and what drug or regimen is optimal. Here, we report a systematic review and network meta-analysis of maintenance treatments in subgroups determined by performance status (PS), epidermal growth factor receptor (EGFR) mutation, histology and response to induction.MethodsPubMed and conference proceedings were reviewed and individual study relative efficacy measures were meta-analysed in a Bayesian hierarchical model. The primary outcome, overall survival (OS), was evaluated in terms of (i) posterior surface under cumulative ranking curve (SUCRA), (ii) probability of being best treatment, (iii) probability of outperforming no maintenance, and (iv) posterior median hazard ratio (95% credible interval). Secondary outcomes were progression-free survival (PFS) and adverse events.FindingsTwelve trials evaluating eight maintenance treatments in 3850 patients were meta-analysed. Selected maintenance treatments showed clinically meaningful benefits of ⩾20% reduction in hazards of death with ⩾90% probability of outperforming no maintenance in terms of OS: (i) switch to or continue pemetrexed (nonsquamous), continue gemcitabine, or switch to EGFR tyrosine kinase inhibitors (TKIs) for PS 0 patients, (ii) switch to pemetrexed (nonsquamous) for PS 1 patients, (iii) switch to EGFR TKI for EGFR mutation positive patients, (iv) switch to or continue pemetrexed or switch to EGFR TKI for nonsquamous patients, (v) continue gemcitabine for squamous patients, (vi) switch to docetaxel or continue gemcitabine for responders to induction, or (vii) switch to or continue pemetrexed (nonsquamous) or switch to EGFR TKI for patients with stable disease post-induction.InterpretationMaintenance treatments show clinically meaningful survival benefits in good performance status patients with advanced NSCLC not progressing after first-line chemotherapy. Benefits are optimised by targeting specific maintenance to individual patients guided by PS, EGFR mutation status, histology and response to induction.     

可切除食管癌术前与术后放化疗对比Meta分析

目的 食管癌患者就诊时大多属中晚期,单纯手术疗效不佳,需结合放化疗提高疗效,但手术与放化疗治疗顺序备受争议.本研究通过对比中晚期可切除食管癌术前与术后放化疗2种治疗模式的疗效及安全性,探寻治疗食管癌的有效治疗模式,为指导临床实践提供理论依据.方法 计算机检索The Cochrane Library、Embase、PubMed、Web of Science、CBM和CNKI,同时辅佐其他检索途径,检索2016-10前所有关于对比食管癌术前放化疗与术后放化疗的临床研究.随机对照研究(randomized controlled trial,RCT)采用Cochrane质量评价标准评价文献质量,非随机对照研究采用纽斯卡尔-渥太华量表(newcastle-ottawa scale,NOS)质量评价标准评价文献质量,统计学分析采用Review Manager 5.3软件.本Meta分析遵循系统综述与荟萃分析优先报告条目(PRISMA)规范.结果 共纳入1个RCT和5个非随机对照研究,Meta分析结果显示,1年生存率(OR=1.24,95％CI:0.96～1.61,P=0.09)、3年生存率(OR=1.25,95％CI:1.00～1.55,P=0.05)、5年生存率(OR=1.39,95％CI:0.93～2.06,P=0.11)和术后并发症发生率(OR=1.45,95％CI:0.81～2.60,P=0.21)差异均无统计学意义.亚组分析显示,国内人群1年生存率(OR=1.30,95％CI:0.48～3.58,P=0.61)、国外人群1年生存率(OR=1.37,95％CI:0.79～2.38,P=0.26)、国内人群3年生存率(OR=1.16,95％CI:0.90～1.49,P=0.25)和国外人群3年生存率(OR=1.55,95％CI:1.00～2.41,P=0.05)差异均无统计学意义.结论 中晚期可切除食管癌术前放化疗与术后放化疗疗效及安全性相似.临床上可酌情考虑后决定手术与放化疗治疗顺序,但仍有待大量多中心、前瞻性随机对照临床实验证实.     

Comparative Efficacy of Second- and Subsequent-line Treatments for Metastatic NSCLC: A Fractional Polynomials Network Meta-analysis of Cancer Immunotherapies

BackgroundExtended onset of treatment effect and longer-term survival with anti–programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) immunotherapies, atezolizumab, nivolumab, and pembrolizumab, have changed the landscape of second- or subsequent-line (2L+) treatments for adults with non–small-cell lung cancer (NSCLC). This systematic literature review included phase I to IV randomized, controlled trials of 2L+ NSCLC therapies from MEDLINE, Embase, and secondary sources.Materials and MethodsStudies of treatments approved in the European Union or United States had to be in English with ≥ 10 patients per arm. A fractional polynomials network meta-analysis (NMA) was conducted because traditional NMA of hazard ratios does not account for delayed onset of clinical effect or long-term survival observed in PD-L1/PD-1 inhibitor trials. Adjusted analyses accounted for treatment switching in the atezolizumab OAK trial. Expected survival time reflected area under the curve over the time horizon. Expected overall survival (OS) was ranked by median ranking with 95% credible intervals and by surface under the cumulative ranking curve. Of 25,115 screened records, 28 studies were included in the quantitative analyses of OS and progression-free survival.ResultsPD-L1/PD-1 inhibitors had comparable expected 5-year OS; all performed better than other treatment options. In unadjusted analyses, surface under the cumulative ranking curve ranked nivolumab first (87.9%), followed by atezolizumab (85.8%) and pembrolizumab (82.8%). Analyses adjusted for patients switching from docetaxel to immunotherapy ranked atezolizumab first (89.6%), followed by nivolumab (86.5%) and pembrolizumab (81.9%).ConclusionThis NMA applied an appropriate approach for indirect comparisons, including cancer immunotherapies, and supported robustness of PD-L1/PD-1 immunotherapies for 2L+ treatment of NSCLC.     

吉西他滨固定剂量率输注联合奥沙利铂一线治疗晚期胰腺癌的Meta分析

背景与目的:有研究提示吉西他滨(Gemcitabine,GEM)固定剂量率(Fixed-dose rate,FDR)输注治疗晚期胰腺癌似有较好的疗效,Meta分析也显示含铂类联合化疗优于GEM单药化疗,本文试图通过Meta分析,探讨GEM FDR输注联合奥沙利铂(GEMOX)一线治疗晚期胰腺癌的地位和价值.方法:通过MEDLINE、EMBASE、ASCO等数据库及论文集检索国内外的相关文献.选择治疗组为GEMOX方案化疗,对照组为标准GEM单药化疗的晚期胰腺癌随机对照试验.由2位评价者分别按上述检索策略收集资料,按纳入标准入选,主要对总生存率及主要不良反应进行Meta分析.结果:从182篇文献中筛选出符合纳入标准的2个随机对照试验,共涉及869例患者.与GEM单药组比较,GEMOX组半年生存率提高9%(95%CI 0.03～0.16,P=0.005),1年生存率提高5%(95%CI-0.01～0.11,P=0.08),客观有效率提高6%(95%CI 0.02～0.10,P=0.006);WHO Ⅲ/Ⅳ度贫血发生率下降5%(95%CI-0.08～-0.01,P=0.01),恶心/呕吐提高13%(95%CI 0.08～0.18,P＜0.001),神经毒性增加14%(95%CI 0.04～0.24,P=0.009),粒细胞减少症、血小板减少症两组相似,差异无统计学意义.结论:现有的证据提示,GEM固定剂量率输注联合奥沙利铂组成的GEMOX方案一线治疗晚期胰腺癌可能有较好的应用前景,值得进行进一步的临床试验.     

食管癌患者同期放化疗顺铂加氟尿嘧啶方案Ⅱ期临床试验

背景与目的：国外已有研究表明,同期放化疗是局部晚期食管癌的标准治疗方案,但国内文献报道同期放化疗的疗效不尽相同,同期放化疗能否提高生存率尚无定论。本研究目的是评价PF方案同期放化疗对食管癌的疗效,并观察毒性。方法：44例食管鳞癌患者随机分为同期放化疗组（简称同期组）和后程加速超分割组（简称后超组）。同期组22例,全程常规分割照射,每天一次,每次2．0Gy,每周5次,25分割,总剂量50Gy。于放疗的第1天开始化疗：顺铂52．5mg／m^2 d1,氟尿嘧啶700mg／m^2 d1-d5,每28d重复,共4周期。后超组22例：总剂量60Gv,前半程30Gv同放化疗组,3周完成;后半程30Gv加速超分割照射,每日2次,间隔至少6h,每次1．5Gy,每周10次,2周完成。结果：同期组有效率高于后超组,分别为95．5％和86．4％,但差异无统计学意义（P=0．607）。同期组2年局控率和2年生存率分别为72．2％和56．7％,后超组分别为39．0％和31．6％。同期组获得了更高的局控率和生存率,但只有局控率差异有统计学意义（P=0．014）。两组的主要急性反应为放射性食管炎、放射性肺炎,晚期反应为食管和肺损伤。两组的急性和晚期反应均较轻。结论：同期放化疗与后程加速超分割相比,显著提高了食管癌局控率,有提高生存率的趋势,毒性可以耐受。     

Chemotherapy for carcinoma of the esophagus: A comparison of evidence from meta-analyses of randomized trials and of historical control studies

BACKGROUND:: Chemotherapy (CT) has been used as an adjunct to local treatment(surgery or radiotherapy) in esophageal carcinoma. A meta-analysisof all published randomized clinical trials and historical controlstudies which have used cisplatinum-based combination CT wascarried out to asses the effect of chemotherapy on survivalfor esophageal cancer. MATERIALS AND METHODS:: A computer-based literature search was performed for the periodfrom January 1988 to March 1995 using the index terms ‘Esophagealneoplasms’ and ‘Chemotherapy’. The frame ofreference was further narrowed to include only cisplatinum-basedcombination chemotherapy. Twelve randomized clinical trials(RCT) and eight historical control (HC) studies were includedin the meta-analysis. RESULTS:: In the overview of HC studies a highly significant reductionin odds of death with CT was observed (68% ±8% OR =0.32,95% CI 0.24–0.42). On the other hand, the over view ofRCTs showed a relative reduction in odds of death for the CTgroup of 4.2% ± 23.7% (OR = 0.96, 95% CI 0.75–1.22). CONCLUSIONS:: There was a gross overestimation of treatment effect in thestudies using HC as compared to RCTs, despite the use of cisplatinum-basedchemotherapy in both groups. The meta-analysis of RCTs revealno significant survival benefit from cisplatinum-based adjuvant/neoadjuvantchemotherapy in esophageal cancer. chemotherapy, historical controls, oesophageal neoplasms, randomized controlled trials     

Systematic review of systemic adjuvant therapy for patients at high risk for recurrent melanoma

The authors examined the role of systemic adjuvant therapy in patients with high-risk, resected, primary melanoma. Outcomes of interest included overall survival, disease-free survival, adverse effects, and quality of life. A systematic review of the literature was conducted to locate randomized controlled trials, practice guidelines, meta-analyses, and reviews published between 1980 and 2004. Thirty-seven randomized controlled trials, 2 meta-analyses, and 1 systematic review were identified that investigated interferon, levamisole, vaccine, or chemotherapy as adjuvant therapy. For high-dose interferon-alpha, the results from 3 randomized trials conducted by the Eastern Cooperative Oncology Group were pooled, and a meta-analysis of 2-year death rates yielded a risk ratio of 0.85 (95% confidence interval, 0.73-0.99; P = .03). Five randomized trials comparing low-dose interferon-alpha with observation only after surgery did not detect a statistically significant improvement in overall survival. A meta-analysis of 4 levamisole trials did not demonstrate a significant survival benefit for levamisole over control; similarly, no survival benefit was demonstrated by data from randomized controlled trials with vaccines (9 trials) or with chemotherapy (10 trials). In this review of the available literature, no systemic adjuvant therapy was identified that conferred a significant overall survival benefit in patients with high-risk, resected, primary melanoma. However, high-dose interferon should be considered in the treatment of these patients, because such therapy is associated with a significant improvement in disease-free survival and a reduction in 2-year mortality. Until the results of ongoing trials are available, the authors could not state with confidence whether such therapy benefits patients with microscopically detected, sentinel lymph node-positive disease.     

Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (oesophageal cancer collaborative group)

Purpose: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery.Methods and Materials: This quantitative meta-analysis included updated individual patient data from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials.Results: With a median follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78–1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p = 0.062). No clear differences in the size of the effect by sex, age, or tumor location were apparent.Conclusion: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients would be needed to reliably detect such an improvement (15→20%).     

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.     

Adjuvant chemotherapy in gastric cancer: a meta-analysis of randomized trials and a comparison with previous meta-analyses

AIMS AND BACKGROUND: Up to now adjuvant chemotherapy after curative resection for gastric cancer (GC) has been considered an experimental approach. The results of existing phase III randomized trials comparing chemotherapy with control after surgery are controversial. Three meta-analyses have been published in recent years. It is likely that each of them presents a theoretical bias, mainly as regards the inclusion criteria of the trials. In this article we re-examine this potential bias, highlighting the differences between the present and past meta-analyses on adjuvant chemotherapy for GC. METHODS: Only randomized controlled clinical trials comparing systemic adjuvant chemotherapy with control after radical resection of GC were eligible. Total mortality was assessed as outcome measure of the treatment effect and a pooled odds ratio was calculated using the Peto-Mantel-Haenszel method. RESULTS: After the selection process 17 papers (18 comparisons) proved eligible for inclusion in the meta-analysis with a total of 3118 patients, of whom 1546 randomized to the treatment arms and 1572 to the control arms; 762 and 871 deaths occurred in the treatment and control arms, respectively. Statistical analysis suggests an absence of significant heterogeneity between the trials and a significant advantage in survival for adjuvant chemotherapy (pooled odds ratio, 0.72, 95% Cl, 0.62-0.84). CONCLUSIONS: Our meta-analysis would seem to indicate that adjuvant chemotherapy results in a significant survival advantage in patients with GC. However, this observation undoubtedly requires confirmation in large randomized controlled trials including cisplatin before adjuvant chemotherapy after curative resection for GC can be proposed for use in clinical practice.     

食管癌扩大野与累及野3DRT的Meta分析

目的 比较食管癌3DRT选择性淋巴引流区(扩大野)照射与累及野照射的疗效、不良反应及治疗失败方式差异。方法 通过计算机检索万方、CNKI、维普、中国生物医学文献数据库、PubMed、Embase和Cochrane Library等数据库,搜集有关食管癌3DRT扩大野和累及野照射比较的临床对照研究资料,采用Stata 11.0软件进行分析。两组间差异采用OR及95%CI描述。结果 根据纳入和排除标准,最终纳入12个包括1095例患者的临床对照研究资料。Meta分析结果显示,与累及野照射比较,扩大野照射降低了食管癌3DRT患者野外失败率(OR=3.727,P=0.007),但≥3级放射性肺炎和放射性食管炎发生率更高(OR=0.348,P=0.001;OR=0.385,P=0.000)。两组1、2、3年LC率和OS率均相似(OR=0.966,P=0.837;OR=0.946,P=0.781;OR=0.732,P=0.098和OR=0.952,P=0.756;OR=1.149,P=0.422;OR=0.768,P=0.120),DM率也相似(OR=0.986,P=0.937)。结论 与累及野照射比较,食管癌3DRT扩大野照射可降低野外失败率,但LC和OS率未见明显优势,不良反应也相应增加。     

Efficacy and Safety of First-Line Immunotherapy Combinations for Advanced NSCLC: A Systematic Review and Network Meta-Analysis

IntroductionA series of randomized controlled trials have investigated different first-line immunotherapy combinations, but the optimal combination strategy is yet to be established.MethodsWe performed a systematic review and Bayesian network meta-analysis by retrieving relevant literature from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and major international conferences. We included published and gray sources of randomized clinical trials comparing immunotherapy combinations with other treatments as first-line treatments for patients with advanced NSCLC. This study was registered in the Prospective Register of Systematic Reviews (CRD42020210501) to ensure transparency.ResultsWe analyzed a total of 16 studies involving 8278 patients and including 10 immunotherapy combinations. For patients without programmed death-ligand 1 (PD-L1) selection, pembrolizumab plus chemotherapy was found to be comparable with sintilimab plus chemotherapy in providing the best overall survival (OS) benefit (hazard ratio = 0.96, 95% confidence interval [CI]: 0.72–1.29). Furthermore, atezolizumab plus bevacizumab plus chemotherapy seemed to provide the best progression-free survival (hazard ratio = 0.45, 95% CI: 0.36–0.55) and the best objective response rate (OR = 0.23, 95% CI: 0.12–0.42). Subgroup analysis by PD-L1 suggested that nivolumab plus ipilimumab plus chemotherapy was associated with the best OS in patients with PD-L1 less than 1% and that pembrolizumab plus chemotherapy was associated with the best OS in patients with PD-L1 greater than or equal to 1%. Pembrolizumab and sintilimab were associated with relatively fewer grade greater than or equal to 3 adverse events when compared with other immunotherapies combined with chemotherapy.ConclusionsOur results suggest that antiprogrammed death-1 combinations are associated with potentially higher survival outcomes than anti–PD-L1 combinations with comparable safety profiles. Moreover, pem-chemo and nivo-ipi-chemo seem to be superior first-line immunotherapy combinations for patients with advanced NSCLC with positive and negative PD-L1 expression, respectively. Although atezo-beva-chemo treatment provided the best progression-free survival and objective response rate, the addition of chemotherapy to immunotherapy would increase the toxicity, especially when antiangiogenesis drugs are simultaneously added.     

Managing side effects in adjuvant endocrine therapy for breast cancer

Introduction: Recent improvements in the survival of hormone-responsive breast cancer are strongly associated with therapeutic advances, particularly with the uptake of adjuvant endocrine therapy. Nevertheless, endocrine therapy is also linked with adverse effects that impact quality of life, social function, and adherence to treatment.

Areas covered: This review examines the spectrum and consequences of adverse effects of tamoxifen and aromatase inhibitors, and the pharmacological and non-pharmacological approaches to mitigate some of the most frequent and disturbing side effects of endocrine therapy (including vasomotor, musculoskeletal, and vulvovaginal symptoms). The authors performed a qualitative analysis of English papers indexed in PubMed through May 2017, including meta-analysis, randomized controlled trials, observational studies, and systematic reviews.

Expert commentary: Side effects of endocrine treatments are frequent and often underestimated in the care of breast cancer survivors, leading to a poor adherence to treatments that can compromise oncological outcomes. Many of the most common adverse events can be mitigated through pharmacological and non-pharmacological approaches that should be discussed and offered to patients in a dedicated setting of care.     

The role of thalidomide in multiple myeloma

Thalidomide has been demonstrated to be active as a first-line and salvage therapy in patients with multiple myeloma. Numerous studies over the past 8 years have shown it to induce high response rates and improve event-free survival in newly diagnosed patients as well as those with relapsed/refractory disease. Recent randomized clinical trials have demonstrated that thalidomide-based regimens are superior to conventional treatments in terms of response rates and event-free survival. However, few trials have demonstrated a survival benefit with thalidomide, indicating the need for further trials. This review will focus on recent trials of thalidomide in relapsed/refractory and newly diagnosed multiple myeloma and address some of the common adverse events associated with thalidomide treatment.