新辅助化疗与放疗间断对鼻咽癌总生存的影响*

目的:探讨较强烈的新辅助化疗和放疗间断对鼻咽癌患者长期生存的影响。方法:选取1995年1 月至1998年12月福建省肿瘤医院1 706 例鼻咽癌患者接受或不接受新辅助化疗,1 081 例患者单纯放疗,而625 例接受1 个疗程较强烈的新辅助化疗。化疗方案以DDP 为基础,每14天为1 个周期,多为2～3 个周期,放疗在最后一次化疗结束后2～5 天开始。化疗包括:DDP80mg/m2分3 天（d1～d3）静脉推注;5-FU 750mg/（m2·d）,连续5 天（d1～d5）静脉滴注。1 706 例患者中有177 例患者由于各种原因造成放疗间断1 周以上。分析患者、肿瘤和治疗等因素对长期生存的影响,尤其是新辅助化疗和放疗间断对生存的影响。结果:中位随访时间75个月（6～126 个月）,失访162 例,随访率为90.50% 。3 年和5 年生存率分别为79.2% 和67.6% 。多因素分析显示性别、年龄、治疗前贫血、肿瘤分期、是否采用新辅助化疗以及放疗是否间断等是影响长期生存的独立预后因素。Ⅰ、Ⅱ、Ⅲ和Ⅳ期的5 年生存率分别为100.0% 、75.9% 、66.5% 和49.3%（P<0.05）。 Ⅲ/Ⅳ期患者中接受与不接受辅助化疗的5 年总生存率分别为65.3%（95%CI:0.796～0.869）和60.5%（95% CI:0.755～0.824）（P=0.041）。 放疗间断与放疗不间断的5 年总生存率分别为51.69%（95% CI:0.449～0.584）和69.45%（95% CI:0.672～0.717）（P<0.001）。 结论:较强烈的新辅助化疗和放疗过程的不间断是鼻咽癌患者长期生存的有利因素。      

Combined chemoradiation vs radiation therapy alone in stage-II nasopharyngeal carcinoma: A meta-analysis of the published literature

The aim of this meta-analysis was to evaluate the efficacy and toxicity of adding chemotherapy to radiotherapy (RT) in the treatment of stage-II nasopharyngeal carcinoma (NPC). We searched Pubmed, Cochrane Library, Embase, China National Knowledge Internet, China Biology Medicine, VIP, and Wanfang database for studies of the RT with or without chemotherapy in patients with stage-II NPC that were published in any language. Analyses were carried out using RevMan 5.3 software. The relative risk was used to evaluate the data, the I² test was used to compare heterogeneity, sensitivity analysis was used to evaluate the stability and reliability of the results. There were 16 studies with 3038 patients that were included in this analysis. Risk ratios (RR) of 1.04 (95% CI: 1.01-1.06), 1.05 (95% CI: 1.00-1.10), 1.05 (95% CI: 1.02-1.07), and 1.00 (95% CI: 0.97-1.03) were observed for overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFS), and distant metastasis-free survival (DMFS). Subgroup analysis showed that compared with conventional RT alone, chemoradiation (CRT) could significantly improve OS (RR = 1.09, 95% CI: 1.03-1.15), PFS (RR = 1.20, 95% CI: 1.08-1.35), and LRFS (RR = 1.09, 95% CI: 1.04-1.14), but did not significantly improve the rate of DMFS (RR = 1.03, 95% CI: 0.94-1.12). However, compared with intensity modulated radiation therapy alone, CRT did not significantly improve the rate of OS (RR = 1.01, 95% CI: 0.99-1.03), PFS (RR = 0.99, 95% CI: 0.95-1.03), LRFS (RR = 1.02, 95% CI: 0.99-1.05), and DMFS (RR = 0.99, 95% CI: 0.96-1.01). Compared with conventional RT alone, CRT could significantly improve patients’ prognoses in terms of OS, PFS, and LRFS for stage-II NPC, but not DMFS, and CRT can provide greater benefits from concurrent chemotherapy than neoadjuvant chemotherapy. With intensity modulated radiation therapy, the stage-II NPC patients did not benefit from the addition of chemotherapy.     

Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety.

PURPOSE: The Intergroup 00-99 Trial for nasopharyngeal cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy. However, there were controversies regarding the applicability of the results to patients in endemic regions. This study aims to confirm the findings of the 00-99 Trial and its applicability to patients with endemic NPC. PATIENTS AND METHODS: Between September 1997 and May 2003, 221 patients were randomly assigned to receive radiotherapy (RT) alone (n = 110) or chemoradiotherapy (CRT; n = 111). Patients in both arms received 70 Gy in 7 weeks using standard RT portals and techniques. Patients on CRT received concurrent cisplatin (25 mg/m2 on days 1 to 4) on weeks 1, 4, and 7 of RT and adjuvant cisplatin (20 mg/m2 on days 1 to 4) and fluorouracil (1,000 mg/m2 on days 1 to 4) every 4 weeks (weeks 11, 15, and 19) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The median follow-up time was 3.2 years. RESULTS: Distant metastasis occurred in 38 patients on RT alone and 18 patients on CRT. The difference in 2-year cumulative incidence was 17% (95% CI, 14% to 20%; P = .0029). The hazard ratio (HR) for disease-free survival was 0.57 (95% CI, 0.38 to 0.87; P = .0093). The 2- and 3-year overall survival (OS) rates were 78% and 85% and 65% and 80% for RT alone and CRT, respectively. The HR for OS was 0.51 (95% CI, 0.31 to 0.81; P = .0061). CONCLUSION: This report confirms the findings of the Intergroup 00-99 Trial and demonstrates its applicability to endemic NPC. This study also confirms that chemotherapy improves the distant metastasis control rate in NPC.     

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。     

Benefit of taxanes as adjuvant chemotherapy for early breast cancer: pooled analysis of 15,500 patients

BACKGROUND: The magnitude of the survival benefit of taxanes as adjuvant chemotherapy for early breast cancer is still unclear. A pooled analysis of Phase III trials was performed to assess the advantages that adjuvant taxane chemotherapy has over standard chemotherapy. METHODS: All Phase III trials were considered eligible. A pooled analysis was accomplished and event-based relative risk ratios (RR) with 95% confidence intervals (95% CI) were derived. The significant differences in disease-free survival (DFS) and overall survival (OS) were explored. Magnitude outcome measures were absolute benefits and the number of patients needed to treat. A heterogeneity test was applied as well. A sensitivity analysis in 6 subpopulations was also performed. RESULTS: Nine trials designed to assess if paclitaxel or docetaxel improve survival (15,598 patients) were gathered. One of the 9 trials did not report OS results. Significant differences in favor of taxanes were seen in DFS in the overall (RR: 0.86; 95% CI, 0.81-0.90 [P<.00001]) and lymph node-positive population (RR: 0.84; 95% CI, 0.79-0.89 [P<.0001]), and in OS in the overall (RR: 0.87; 95% CI, 0.81-0.83 [P<.0001]) and lymph node-positive population (RR: 0.84; 95% CI, 0.77-0.92 [P<.0001]). The absolute benefits in DFS and OS in favor of taxanes ranged from 3.3% to 4.6% and from 2.0% to 2.8%, respectively. CONCLUSIONS: Considering all the available Phase III trials, taxane-based adjuvant chemotherapy for early breast cancer seems to add a significant benefit in both DFS and OS over standard chemotherapy. The lack of significant heterogeneity in the sensitivity analysis underscores the homogeneous effect across all trials.     

Timing of adjuvant chemotherapy and tamoxifen in women with breast cancer: findings from two consecutive trials of Gruppo Oncologico Nord-Ovest-Mammella Intergruppo (GONO-MIG) Group.

BACKGROUND: The timing of adjuvant chemotherapy and tamoxifen (TAM) has been investigated only in postmenopausal women with breast cancer. We analyzed the outcome of both pre- and postmenopausal women who entered two randomized trials (Gruppo Oncologico Nord-Ovest-Mammella Intergruppo studies) on adjuvant chemotherapy and received either concomitant or sequential TAM. PATIENTS AND METHODS: Patients who received anthracycline-based regimens and either concomitant or sequential TAM were eligible. The primary end point was overall survival (OS). Hazard ratios (HRs) of death or recurrence for treatment comparisons were estimated by Cox proportional hazards regression models. RESULTS: Among the 1096 eligible patients, 507 (46.3%) and 589 (53.7%) received concomitant and sequential TAM, respectively. The median follow-up time was 6.6 years. Ten-year OS was 83% [95% confidence interval (CI) 78-88%] and 80% (95% CI 74-86%) in the concomitant and sequential groups, respectively. Multivariate analyses confirmed no significant difference in the hazard of death (HR = 1.13; 95% CI 0.78-1.64; P = 0.534) and recurrence (HR = 1.03; 95% CI 0.80-1.33; P = 0.88) between the two groups. A decreasing trend (P = 0.015) in HR of death with increasing age was observed indicating, that concomitant therapy might be more effective than sequential therapy in young patients. CONCLUSIONS: We observed no outcome difference between sequential and concomitant chemo-endocrine therapy. The potential advantage of concomitant TAM in young patients needs to be further addressed in prospective trials.     

Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: A prospective randomized controlled multi-center trial

Background and purpose: Triple-negative breast cancer (TNBC) presents a high risk breast cancer that lacks the benefit from hormone treatment, chemotherapy is the main strategy even though it exists in poor prognosis. Use of adjuvant radiation therapy, which significantly decreases breast cancer mortality, has not been well described among poor TNBC women. The aim of this study was to evaluate whether the combination of chemotherapy and radiotherapy could significantly increase survival outcomes in TNBC women after mastectomy. Patients and methods: A prospective randomized controlled multi-center study was performed between February 2001 and February 2006 and comprised 681 women with triple-negative stage I–II breast cancer received mastectomy, of them, 315 cases received systemic chemotherapy alone, 366 patients received radiation after the course of chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were estimated. Simultaneously local and systemic toxicity were observed. Results: After a median follow-up of 86.5 months, five-year RFS rates were 88.3% and 74.6% for adjuvant chemotherapy plus radiation and adjuvant chemotherapy alone, respectively, with significant difference between the two groups (HR 0.77 [95% CI 0.72, 0.98]; P = 0.02). Five-year OS significantly improved in adjuvant chemotherapy plus radiation group compared with chemotherapy alone (90.4% and 78.7%) (HR 0.79 [95% CI 0.74, 0.97]; P = 0.03). No severe toxicity was reported. Conclusions: Patients received standard adjuvant chemotherapy plus radiation therapy was more effective than chemotherapy alone in women with triple-negative early-stage breast cancer after mastectomy.     

Adjuvant ovarian function suppression and tamoxifen in premenopausal breast cancer patients: A meta-analysis

Background: The benefit of adding ovarian function suppression (OFS) to tamoxifen in the adjuvant treatment of premenopausal women with breast cancer is uncertain. We conducted a meta-analysis of randomized controlled trials that addressed this question. Methods: Systematic search of PubMed, the web of science, and the meeting library of ASCO, ESMO, and SABCS was conducted using the following keywords: tamoxifen, ovarian suppression, and breast cancer. Eligible studies were those recruiting patients with breast cancer randomized to receive adjuvant tamoxifen and OFS versus tamoxifen alone. Pooled hazard ratio [HR]) for disease-free (DFS) and overall survival (OS) with 95% confidence interval (CI) were calculated using the fixed effect model. Results: We searched a total of 845 records, of which 5 clinical trials, including 7557 patients, were eligible for our analysis. Adding OFS to tamoxifen improved DFS with pooled HR: 0.88 (95% CI: 0.80-0.96, P= 0.004) and OS (pooled HR: 0.87 {95% CI: 0.77-0.98, P= 0.02}) compared to tamoxifen alone. The benefit of the addition of OFS to tamoxifen was mostly observed in patients younger than 40 years where the pooled HRs of DFS was 0.76 (95% CI: 0.63-0.91; P= 0.004), and in those who received adjuvant chemotherapy with pooled HRs of DFS 0.80 (95% CI: 0.65-0.99, P= 0.042). There was an increase in the incidence of all grade musculoskeletal symptoms and high-grade hot flushes with the addition of OFS with risk ratios of 1.12 (95% CI: 1.07-1.17, P< 0.001) and 2.14 (95% CI: 1.01-4.51, P= 0.047) respectively. Conclusion: Our analysis indicates that the addition of OFS to tamoxifen improves DFS and OS. This strategy could be considered in patients in which tamoxifen alone is not deemed sufficient or in case of poor tolerance to OFS with aromatase inhibitors.     

Prognostic and predictive value of epigenetic silencing of MGMT in patients with high grade gliomas: a systematic review and meta-analysis

Epigenetic silencing of the O⁶-methylguanine-DNA methyltransferase (MGMT) gene is associated with improved survival in patients with high-grade gliomas (HGG), with varying estimates of magnitude. The objective of this meta-analysis is to determine the prognostic value of MGMT silencing, and assess its predictive value by treatment type. MEDLINE and EMBASE databases were searched for studies relating to gliomas and MGMT. Studies reporting overall survival (OS) by MGMT status in patients with HGG were considered potentially eligible. We excluded studies that did not control for potential confounding variables. A meta-analysis of studies was performed via random-effects modelling. Subgroup meta-analyses by treatment were performed according to a priori hypotheses. Twenty studies were ultimately eligible, including 2,018 patients. In the pooled analysis, MGMT silencing was associated with improved OS (HR = 0.436; 95% CI: 0.333–0.571; P < 0.001). The prognostic utility of MGMT status varies significantly by treatment type (P = 0.001): the HR for OS for MGMT silenced tumors is 0.190 (0.047–0.770), 0.403 (0.282–0.576), 0.743 (0.579–0.954), and 1.070 (0.722–1.585) for studies using surgery plus the addition of either: chemotherapy (CT), chemoradiotherapy (CRT), radiotherapy (RT), and nothing (surgery alone), respectively. Epigenetic silencing of MGMT is associated with markedly improved survival in patients with HGG who receive adjuvant therapy. MGMT silencing serves as a predictive marker, with the largest benefit seen in patients receiving CT as a component of adjuvant treatment, an intermediate benefit in patients receiving adjuvant RT, and no evidence to support benefit in those receiving surgery alone.     

Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: A propensity score matched analysis

BackgroundChemotherapy is frequently used in cholangiocarcinoma as an adjunct to surgical resection, but the appropriate sequence of chemotherapy with surgery is unclear.Patients and methodsUsing the National Cancer Database, we identified patients who underwent surgery and chemotherapy for stage I-III cholangiocarcinoma between 2006 and 2014. The propensity score reflecting the probability of receiving neoadjuvant chemotherapy was estimated by multivariate logistic regression method. Patients in the neoadjuvant and adjuvant chemotherapy study arms were then propensity-matched in 1:3 ratios using the nearest neighbor method. Overall Survival (OS) in the matched data set was estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using Cox proportional hazard regression model.ResultsOf the 1450 patients who met our inclusion criteria, 299 (20.6%) received neoadjuvant chemotherapy while 1151 (79.3%) received adjuvant chemotherapy. The median age at diagnosis was 63 years. 278 patients in the neoadjuvant group were matched to 700 patients in the adjuvant group. In the matched cohort, patients who received neoadjuvant chemotherapy had a superior OS compared to those who received adjuvant chemotherapy (Median OS: 40.3 vs. 32.8 months; HR: 0.78; 95% CI: 0.64–0.94, p = 0.01). The 1- and 5-year OS rates for the neoadjuvant chemotherapy group were 85.8% and 42.5% respectively compared to 84.6% and 31.7% for the adjuvant chemotherapy group.ConclusionIn this large national database study, neoadjuvant chemotherapy was associated with a longer OS in a select group of patients with cholangiocarcinoma compared to those who underwent upfront surgical resection followed by adjuvant chemotherapy.     

78例乳腺癌改良根治术后pT3N0M0期患者放疗价值探讨

目的 探讨乳腺癌改良根治术后病理分期为T₃N₀期患者的术后放疗价值。方法 回顾分析1997-2014年收治的乳腺癌改良根治术后患者资料,筛选标准为女性、术后病理提示浸润性癌、肿瘤最大径>5 cm且腋窝淋巴结未见转移、未接受新辅助化疗及内分泌治疗,且无远处转移及其他第二原发癌。78例符合条件。40例(51%)接受术后放疗,67例(86%)接受辅助化疗。Kaplan-Meier法计算DFS、OS及LRR率,组间差异用Logrank法检验。结果 中位随访时间79个月(6~232个月),5年OS、DFS和LRR分别为89%、87%和2%。放疗组与未放疗组患者5年DFS分别为84%与91%(P=0.641),5年OS分别为84%与96%(P=0.126),5年LRR分别为0%和5%。仅ER/PR状态、分子分型影响患者DFS (P=0.002、0.031)。未放疗组有1例患者出现胸壁复发。结论 乳腺癌改良根治术后T₃N₀M₀期患者LRR率较低,仅ER/PR状态及分子分型影响患者DFS。在有效系统全身治疗基础上术后病理T₃N₀患者可能不需全部接受胸壁+锁骨上野放疗,但仍需大样本病例证实。     

High-risk Surgically Resected Renal Cell Carcinoma: Is There a Role for Adjuvant VEGF-TKI Inhibitors?

The indications for adjuvant vascular endothelial growth factor–tyrosine kinase inhibitor (VEGF-TKI) agents after curative intent nephrectomy for renal cell carcinoma are still a matter of debate. The ASSURE, PROTECT and ATLAS trials have failed to meet their primary end-points. Conversely, S-TRAC has shown a disease free survival (DFS) benefit. To date, meta-analyses have repeatedly proved the absence of a clinical benefit, in term of DFS and overall survival (OS). Nevertheless, the results of the SORCE trial have been recently released and might add valuable information. We pooled the results of all five reported trials testing for any potential DFS and OS benefits associated with VEGF-TKI use. Interestingly, for pooled DFS we found a marginal positive hazard ratio (HR) of 0.92 (95% confidence interval [CI] 0.85-1.00; P-value = 0.049) in favor of adjuvant VEGF-TKI agents. This benefit was more pronounced for DFS in the sub-groups of only high-risk patients (HR: 0.89, 95% CI 0.80-0.99; P-value = 0.026), but less pronounced in clear-cell only subgroup (HR 0.92, 95% CI: 0.85-1.00; P-value = 0.044). Overall survival benefit was instead not reached. However, pooled relative risk for high-grade (grade ≥3 according to CTCAE classification) adverse events was irremediably high, 2.56 (95% CI: 2.15-3.04; P-value < 0.001). Given the marginal benefit in terms of DFS and the drawback of high-grade adverse events, even after the SORCE trial publication, adjuvant VEGF-TKIs therapy cannot be considered in the whole group of patients with non-metastatic high-risk renal cell carcinoma after surgery.     

Chemoradiotherapy regimens for locoregionally advanced nasopharyngeal carcinoma: A Bayesian network meta-analysis

BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-A) is often the regimen of choice in locoregionally advanced nasopharyngeal carcinoma (NPC). Many alternative regimens have been reported in the literature, however, it is unknown how effective these regimens are compared to each other due to the lack of direct comparisons. Our objective was to perform a network meta-analysis (NMA) to determine the relative survival benefits of these treatments for locoregionally advanced NPC.MethodsWe performed a systematic review following the Cochrane methodology, using MEDLINE, EMBASE and CENTRAL to identify all randomised controlled trials (RCTs) that compared different chemoradiotherapy regimens for locoregionally advanced NPC. Overall survival (OS) was the primary outcome of interest, and hazard ratios (HRs) were extracted using the Parmar method. Bayesian NMAs with random effects were conducted using WinBUGS.ResultsTwenty-five RCTs (5576 patients) were included in this review. All together, these trials compared seven different regimens: radiotherapy (RT), concurrent chemoradiotherapy (CRT), neoadjuvant followed by CRT (N-CRT), CRT-A, RT-A, N-RT and N-RT-A. All regimens that contained CRT performed significantly better than RT. CRT-A did not improve survival compared to CRT alone (0.98; 95% credible regions: 0.71–1.34). For N-CRT versus CRT, the HR was 1.03 (0.69–1.47). When CRT-A was compared against N-CRT, the resulting HR was 0.96 (0.64–1.48).ConclusionsAdjuvant chemotherapy does not appear to improve survival following CRT. The efficacies of CRT, CRT-A and N-CRT all appeared to be similar. Further studies are warranted to determine the value of additional chemotherapy phases in specific patient subgroups.     

Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer

The aim of this study was to investigate the worldwide evidence of the roles of adjuvant chemoradiation and adjuvant chemotherapy on survival in potentially curative resected pancreatic cancer. Five randomised controlled trials of adjuvant treatment in patients with histologically proven pancreatic ductal adenocarcinoma were identified, of which the four most recent trials provided individual patient data (875 patients). This meta-analysis includes previously unpublished follow-up data on 261 patients. The pooled estimate of the hazard ratio (HR) indicated a 25% significant reduction in the risk of death with chemotherapy (H = 0.75, 95% confidence interval (CI): 0.64, 0.90, P-values(stratified) (Pstrat) = 0.001) with median survival estimated at 19.0 (95% CI: 16.4, 21.1) months with chemotherapy and 13.5 (95% CI: 12.2, 15.8) without. The 2- and 5-year survival rates were estimated at 38 and 19%, respectively, with chemotherapy and 28 and 12% without. The pooled estimate of the HR indicated no significant difference in the risk of death with chemoradiation (HR = 1.09, 95% CI: 0.89, 1.32, Pstrat = 0.43) with median survivals estimated at 15.8 (95% CI: 13.9, 18.1) months with chemoradiation and 15.2 (95% CI: 13.1, 18.2) without. The 2- and 5-year survival rates were estimated at 30 and 12%, respectively, with chemoradiation and 34 and 17% without. Subgroup analyses estimated that chemoradiation was more effective and chemotherapy less effective in patients with positive resection margins. These results show that chemotherapy is effective adjuvant treatment in pancreatic cancer but not chemoradiation. Further studies with chemoradiation are warranted in patients with positive resection margins, as chemotherapy appeared relatively ineffective in this patient subgroup.     

Systematic review of microsatellite instability and colorectal cancer prognosis.

PURPOSE: A number of studies have investigated the relationship between microsatellite instability (MSI) and colorectal cancer (CRC) prognosis. Although many have reported a better survival with MSI, estimates of the hazard ratio (HR) among studies differ. To derive a more precise estimate of the prognostic significance of MSI, we have reviewed and pooled data from published studies. METHODS: Studies stratifying survival in CRC patients by MSI status were eligible for analysis. The principal outcome measure was the HR. Data from eligible studies were pooled using standard techniques. RESULTS: Thirty-two eligible studies reported survival in a total of 7,642 cases, including 1,277 with MSI. There was no evidence of publication bias. The combined HR estimate for overall survival associated with MSI was 0.65 (95% CI, 0.59 to 0.71; heterogeneity P = .16; I(2) = 20%). This benefit was maintained restricting analyses to clinical trial patients (HR = 0.69; 95% CI, 0.56 to 0.85) and patients with locally advanced CRC (HR = 0.67; 95% CI, 0.58 to 0.78). In patients treated with adjuvant fluorouracil (FU) CRCs with MSI had a better prognosis (HR = 0.72; 95% CI, 0.61 to 0.84). However, while data are limited, tumors with MSI derived no benefit from adjuvant FU (HR = 1.24; 95% CI, 0.72 to 2.14). CONCLUSION: CRCs with MSI have a significantly better prognosis compared to those with intact mismatch repair. Additional studies are needed to further define the benefit of adjuvant chemotherapy in locally advanced tumors with MSI.     

早期小细胞肺癌术后胸内放射治疗预后价值的Meta分析

目的:通过Meta分析探究术后辅助化疗联合胸内照射对于早期小细胞肺癌（small cell lung cancer,SCLC）的预后价值。方法:采用主题词和关键词相结合的检索方法,检索Pubmed、Embase、Cochrane Library、Web of Science、中国生物医学文献数据库、万方数据库和中国知网数据库从建库至2020年08月20日发表的比较SCLC术后辅助胸内放疗的文献。主要研究终点为总生存时间（overall survival,OS）,次要研究终点为无病生存时间（disease-free survival,DFS）;是否术后胸内照射同OS、DFS的相关性通过风险比(hazard ratio,HR)表达。文献质量评估采用纽卡斯尔-渥太华量表（Newcastle-Ottawa scale,NOS)文献质量评分;异质性检验采用Q检验和I2统计量,并通过亚组分析、敏感性分析以及Meta回归分析用来探讨异质性来源。发表偏倚评价采用剪补漏斗图。软件采用R语言 4.0.0版本meta包。结果:共纳入5篇文献,3 907例患者。Meta分析结果显示,早期SCLC患者术后接受辅助化疗联合术后胸内照射同单纯辅助化疗相比,在OS上差异无统计学意义（HR=0.99,95%CI:0.88~1.11）;但亚组分析中术后淋巴结阳性的患者OS可能获益,N1患者为（HR=0.73,95%CI:0.59~0.91）,N2患者为（HR=0.60,95%CI:0.49~0.74）。此外,DFS存在获益（HR=0.277,95%CI:0.160~0.480）。结论:术后胸内照射治疗不能改善早期SCLC患者的OS,但亚组分析中可以延长术后淋巴结阳性患者的OS;而且无论术后淋巴结状态,胸内照射都可以延长DFS。     

Mucinous histology is associated with poor prognosis in locally advanced colorectal adenocarcinoma treated with postoperative first-line adjuvant chemotherapy: A systematic review and meta-analysis

PurposePostoperative adjuvant chemotherapy followed surgery is the standard management for localized advanced colorectal carcinoma (CRC). Mucinous adenocarcinoma (MAC) is a peculiar histological subtype of CRC, but the prognosis of MAC patients is controversial. The objective of this study is to assess the implication of MAC in survival of patients treated with surgery and firs-line adjuvant chemotherapy.MethodsStudies describing outcomes for advanced MAC and non-specific adenocarcinoma (AC) of CRC patients treated with first-line postoperative adjuvant chemotherapy followed surgery were searched in PubMed, Embase, Medline, EBSCO, Wiley, and Cochrane Library (January 1963–August 2021). Hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) for MAC to AC were extracted. Random-effects model was used for calculating the pooled HRs and 95% confidence interval (CI).ResultsThis meta-analysis is comprised of 8 studies involving a total of 124,303 CRC patients treated with first-line adjuvant chemotherapy followed surgery. The pooled HR for MAC was 1.23 (95% CI, 1.07–1.41, p < 0.01, I² = 80%), and the DFS (HR, 2.95, 95% CI, 1.22–7.14) of MAC patients were significantly poorer than AC patients. Similar results were also observed in stage III and FOLFOX regimen subgroups.ConclusionMAC was a risk factor for prognosis of localized advanced CRC patients treated with postoperative first-line adjuvant chemotherapy. Thus, the role of first-line adjuvant chemotherapy regimens should be further studied in these MAC patients.     

Prognostic Impact of Radiation Therapy in Pure Mucinous Breast Carcinoma

PurposePure Mucinous breast carcinoma (PMBC) is an invasive breast cancer with favorable prognosis. While pathology-specific guidelines exist for PMBC regarding adjuvant chemotherapy and endocrine therapy, no recommendations exist regarding locoregional treatment based on tumor histology. Prognostic impact of radiotherapy for patients with PMBC remains unclear.Materials and MethodsThe National Cancer Database was queried (2004-2017) for patients with pN0M0 PMBC who underwent lumpectomy. Chi-square testing compared categorical frequencies between patients who received radiotherapy versus those who did not. Propensity score matching created a 1:1 matched cohort of patients who received radiotherapy and patients who didn't. Kaplan-Meier analysis evaluated overall survival (OS). Cox proportional hazard analyses identified clinical and treatment factors prognostic for OS.Results17,259 patients met selection criteria; 11,087 (74%) received radiotherapy while 3852 (26%) did not. After PSM, radiotherapy (HR 0.629; 95% CI 0.531-0.746), endocrine therapy (HR 0.676; 95% CI 0.567-0.805), black race (HR 0.703; 95% CI 0.498-0.991), and private insurance (HR 0.184; 95% CI 0.078-0.432) were favorable prognostic factors on multivariate Cox regression analysis while age ≥ 70 years (HR 2.668; 95% CI 1.903-3.740), tumor size > 20 mm (HR 1.964; 95% CI 1.613-2.391), and CDCC score > 0 (HR 1.770; 95% CI 1.474-2.126) were unfavorable prognostic factors. After PSM, 5-year OS was 86% for those who received radiotherapy and 81% for those who did not (P < .001).ConclusionThis is the largest study to date on PMBC and the prognostic impact of adjuvant radiotherapy. Radiotherapy is associated with a survival advantage, suggesting omission of radiotherapy is not warranted.