Primary tumor location and the prognosis of patients after local treatment of colorectal liver metastases: a systematic review and meta-analysis

BackgroundRecently numerous studies have reported primary tumor location as a potential prognostic factor after surgery for colorectal liver metastases (CRLM). The aim of this study was to comprehensively review and analyze all the available literature on the impact of primary tumor location in patients after local treatment of CRLM.MethodsStudies examining the association of right- and left-sided colorectal cancer and overall survival (OS) and recurrence free survival (RFS) after local treatment (resection and/or ablation) of CRLM were identified. Random-effects models were used for both clinicopathological and outcome variables. Pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were shown for both OS and RFS.ResultsTen studies (including 11 patient cohorts) were eligible for inclusion, representing 3962 patients. Right-sided tumors (i.e. proximal to the splenic flexure) were observed in 1340 patients (33.8%). Median follow-up ranged from 25 to 137 months. Patients with right-sided tumors had a significantly decreased OS (HR 1.60, 95% CI 1.30–1.98, p < 0.001) and RFS (HR 1.35, 95% CI 1.04–1.77, p = 0.03), when compared to patients with left-sided tumors.ConclusionThis meta-analysis suggests that patients with right-sided primaries suffer from a worse prognosis, compared to patients with left-sided primaries in patients after local treatment of CRLM.     

Prognostic impact of primary tumor location in Stage III colorectal cancer-right-sided colon versus left-sided colon versus rectum: a nationwide multicenter retrospective study

Background

Previous studies investigating the impact of tumor location on colorectal cancer prognosis only compared two groups by location, e.g., ‘right-sided colon vs. left-sided colon,’ ‘colon vs. rectum,’ and ‘right-sided (right-sided colon) vs. left-sided (left-sided colon and rectum).’ This nationwide multicenter retrospective study aimed to clarify the prognostic impact of tumor location in patients with stage III colorectal cancer by classifying tumors into three groups: right-sided colon, left-sided colon, and rectum.

Methods

Subjects were 9194 patients with stage III colorectal cancer who underwent curative surgery from 1997 to 2012. Relapse-free survival (RFS) after primary surgery and overall survival (OS) after recurrence were examined.

Results

Rectal cancer (n = 2922) was associated with worse RFS compared to right-sided colon cancer (n = 2362) (hazard ratio (HR) 0.65; 95% CI 0.59–0.72; p < 0.001) and left-sided colon cancer (n = 3910) (HR 0.72; 95% CI 0.66–0.78; p < 0.001) after adjusting for key clinical factors (i.e., sex, age, histological type, CEA, adjuvant therapy, T category, and N category). Among patients with recurrence (n = 2823), rectal cancer was associated with better OS compared to right-sided colon cancer (HR 1.23; 95% CI 1.08–1.40; p = 0.002) and worse OS compared to left-sided colon cancer (HR 0.88; 95% CI 0.79–0.99; p = 0.029). Twenty percent of right-sided colon cancer recurrences exhibited peritoneal dissemination, 42% of left-sided colon cancer recurrences were liver metastases, and 33% of rectal cancer recurrences were local recurrences.

Conclusions

The three tumor locations (right-sided colon, left-sided colon, rectum) had different prognostic implications for recurrence after curative resection and overall mortality, suggesting that tumor location serves as a prognostic biomarker in stage III colorectal cancer.

     

Better survival of right-sided than left-sided stage II colon cancer: a propensity scores matching analysis based on SEER database

Background/AimsMost studies have found that right-sided colon cancer (RCC) has worse prognosis than left-sided colon cancer (LCC), especially in stage III, but the reported prognosis of stage II colon cancer is variable. This study aimed to evaluate the impact of tumor location on survival outcomes in stage II colon cancer.Materials and MethodsPatients with stage II colon cancer were identified in the Surveillance, Epidemiology, and End Results database from 2004 to 2009. The effect of tumor location on overall survival and cancer-specific survival was analyzed using Cox proportional hazards regression models and propensity score matching.ResultsOf 16,519 patients, 69.6% had RCC and30.4% had LCC. In unadjusted analyses, RCC had a 13% increased overall mortality risk (hazards ratio [HR], 1.13; 95% confidence interval [CI], 1.07–1.19; p<0.001) but an18% reduction in cancer-specific mortality risk compared with LCC (HR, 0.82; 95% CI, 0.76–0.89; p<0.001). After propensity scores matching analyses, RCC had a 21% reduced overall mortality risk (HR, 0.79; 95% CI, 0.72–0.87; p<0.001) and a 49% reduction in cancer-specific mortality risk compared with LCC (HR, 0.51; 95% CI, 0.44–0.60; p<0.001).ConclusionWhen adjusted for multiple clinicopathological features, stage II RCC showed better prognosis than stage II LCC.     

Effect of prior cancer history on survival of patients with esophageal carcinoma: a propensity score matching,population-based study

BackgroundWhen conducting esophageal cancer clinical trials, prior cancer history is frequently considered an exclusion criterion due to the assumption that prior malignancy may exert significant interference with the prognosis in patients with esophageal carcinoma. This study aimed to evaluate the impact of prior cancer on survival of patients with esophageal cancer and provide valuable assistance for trial design.MethodsData regarding patients diagnosed with esophageal cancer between 2011 and 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and divided into two groups depending on the presence or absence of prior cancer history. Propensity score matching (PSM) was performed to minimize the confounding bias caused by covariates. Subsequently, Kaplan-Meier analysis and multivariate Cox proportional hazards models were used to compare all-cause and esophageal cancer-specific survival between patients with and without prior cancer.ResultsAmong 17,123 patients with esophageal carcinoma included in this study, 2,224 (13%) patients had prior cancer history. Before PSM, Kaplan-Meier curves between the two groups classified by prior cancer history showed no significant differences in all-cause (HR =1.047, 95% CI: 0.995–1.102, P=0.077) and esophageal cancer-specific survival (HR =0.986, 95% CI: 0.928–1.048, P=0.65). Similar results were obtained after PSM. In multivariate Cox analysis, prior malignancy was not significantly associated with all-cause (HR =1.002, 95% CI: 0.936–1.072, P=0.965) and esophageal cancer-specific survival (HR =0.964, 95% CI: 0.890–1.045, P=0.374). Subgroup analysis stratified by timing of prior cancer demonstrated that prior cancer had no significant effect on prognosis in the recent latency period subgroups (P>0.05). Furthermore, patients with a prior cancer of lung and bronchus (P=0.013) or head and neck (P=0.012) displayed significantly worse survival than patients without prior cancer, while other types of prior cancer showed no significant effect.ConclusionsThe findings suggest that prior cancer is likely not a definite factor that has an impact on all-cause and esophageal cancer-specific survival. Therefore, exclusion criteria of prior cancer history in esophageal cancer clinical trials should be seriously reconsidered.     

Real-World Outcomes of Gemcitabine,Cisplatin, and Nab-Paclitaxel Chemotherapy Regimen for Advanced Biliary Tract Cancer: A Propensity Score-Matched Analysis

Background/AimsAdvanced biliary tract cancer (BTC) is associated with poor survival. A recent phase II study of triplet combination chemotherapy, including gemcitabine, cisplatin, and nanoparticle albumin-bound (nab)-paclitaxel, has shown promising results. This study aimed to compare the efficacy of triplet and standard doublet chemotherapy in a real-world setting.MethodsPatients with advanced BTC treated with triplet and doublet chemotherapy regimens were recruited. The propensity-score nearest neighbor matching method with a ratio of one-to-one was used to create a matched cohort for comparison. Progression-free survival (PFS), overall survival (OS), and safety profiles were examined in both groups.ResultsA total of 68 patients (n=34 per group) were included in the matched cohort, and their baseline characteristics were well balanced. Survival outcomes in the triplet chemotherapy group were not better than those in the doublet chemotherapy group, with a median PFS of 7.5 months (95% confidence interval [CI], 4.1 to 10.9) versus 7.2 months (95% CI, 5.6 to 8.9) (hazard ratio [HR], 0.93; 95% CI, 0.53 to 1.62; p=0.793) and a median OS of 13.7 months (95% CI, 8.8 to 18.7) versus 12.2 months (95% CI, 8.4 to 16.0) (HR 0.73; 95% CI, 0.38 to 1.41; p=0.354), respectively. In addition, the treatment-related severe adverse events, such as neutropenia, were more common in the triplet chemotherapy group.ConclusionsGemcitabine, cisplatin, and nab-paclitaxel did not improve the PFS or OS compared to that achieved by standard chemotherapy in patients with advanced BTC. The benefits of triplet chemotherapy in advanced BTC require examination in large randomized controlled trials.Key Words Biliary tract cancer; Gemcitabine; Cisplatin; Albumin-bound paclitaxel     

Long-term results of percutaneous microwave ablation for colorectal liver metastases

BackgroundRadiofrequency ablation (RFA) has been used for therapy of colorectal liver metastases (CRLMs) several years, with considerable data confirming its safety and efficacy. However, there are few studies focusing on the long-term results of percrtaneous microwave ablation (PMWA) for CRLMs. The aim of this study was to evaluate the long-term survival and prognostic factors in patients with CRLMs undergoing PMWA.MethodsWe retrospectively analyzed treatment and survival parameters of 210 patients with CRLMs who had received PMWA in a single center from January 2010 to December 2017. Prognostic factors for survival were evaluated by means of univariate and multivariate analyses.ResultsThe median follow-up time after PMWA was 48 months. The median overall survival (OS) time were 40.0 months (95% CI, 31.4 to 48.5 months), with 1-, 2, 3-, 4, and 5-year cumulative survival rates of 98.6%, 73.3%, 53.3%, 42.2%, and 32.9%, respectively. Tumor number (P = 0.004; HR: 1.838; CI: 1.213– 2.784), main tumor size (P = 0.017; HR: 1.631; CI: 1.093– 2.436), and serum CEA level (P = 0.032; HR: 1.559; CI: 1.039–2.340) were found as independent predictors of OS. The median OS time for patients with resectable lesions was 60.91 months (95% CI, 51.36 to 70.47 months), with 5-year cumulative survival rates of 53.5%.ConclusionPMWA is a safe and effective treatment for CRLMs, with a favorable long-term outcome. Multiple lesions, main tumor diameter>3 cm, and serum CEA >30 ng/ml have a significant negative effect on OS.     

老年与非老年直肠黏液腺癌患者对不同放疗策略的受益可能不同：一项基于SEER数据库的回顾性研究

目的探讨老年与非老年直肠黏液腺癌患者对于新辅助放疗、辅助放疗的受益情况,并分析影响直肠黏液腺癌患者预后的因素。 方法应用美国国家癌症研究所的监测、流行病学和结果数据库（SEER）,收集2000~2016年,病理诊断为直肠黏液腺癌的患者共3 997例,根据年龄分为老年组（≥60岁）和非老年组（<60岁）,分析比较两组接受新辅助放疗联合手术、单纯手术和术后辅助放疗患者的预后情况,对两组患者的三种治疗方式分别进行倾向得分匹配,比较不同治疗方法对预后的影响,应用Kaplan-Meier法分别绘制生存曲线,应用Log-rank检验分析各组生存差异,应用COX比例风险模型分析影响直肠黏液腺癌患者预后的因素。 结果三种治疗方案的总生存率,新辅助放疗总生存率最高,其次为术后放疗,最后为单纯手术组,组间比较差异有统计学意义（χ²=13.117,22.541;P<0.05）。但三种治疗方案的肿瘤特异性生存,仅新辅助放疗显著高于术后放疗（χ²=4.023,P=0.045）。对各种治疗方案进行倾向得分匹配后,老年患者新辅助放疗的总体生存率显著高于单纯手术（χ²=4.874,P=0.027）,非老年患者单纯手术的总体生存率（χ²=5.530,P=0.019）和肿瘤特异性生存率（χ²=4.825,P=0.028）均显著高于术后放疗。高龄（≥60岁）、男性、未化疗和高TNM分期是直肠黏液腺癌患者总生存率较差的影响因素,其HR分别为1.689（95% CI=1.524~1.871）、1.110（95% CI=1.007~1.223）和1.549（95% CI=1.338~1.792）,Ⅱ期HR=2.675（95% CI=1.191~6.008）,Ⅲ期HR=3.617（95% CI=1.612~8.115）,Ⅳ期HR=10.835（95% CI=4.797~24.474）;高龄（≥60岁）、未化疗和高TNM分期是直肠黏液腺癌患者肿瘤特异性生存率较差的影响因素,其HR分别为1.297（95% CI=1.156~1.456）,1.344（95% CI=1.129~1.601）,Ⅲ期HR=6.365（95% CI=1.582~25.614）,Ⅳ期HR=20.957（95% CI=5.189~84.637）。 结论老年直肠黏液腺癌患者可能从新辅助放疗中获益,而对于非老年患者,放疗的预后并不优于单纯手术治疗。     

Survival after repeat hepatectomy for recurrent colorectal liver metastasis: A review and meta-analysis of prognostic factors

BackgroundFrequent recurrent hepatic metastasis after hepatic metastasectomy is a major obstacle in the treatment of colorectal liver metastasis (CRLM). We performed the present systematic review to evaluate the short- and long-term outcomes after repeat hepatectomy for recurrent CRLM and determine factors associated with survival in these patients.Data sourcesAn electronic search of PubMed database was undertaken to identify all relevant peer-reviewed papers published in English between January 2000 and July 2018. Hazard ratios (HR) with 95% confidence interval (95% CI) were calculated for prognostic factors of overall survival (OS).ResultsThe search yielded 34 studies comprising 3039 patients, with a median overall morbidity of 23% (range 8%–71%), mortality of 0 (range 0–6%), and 5-year OS of 42% (range 17%–73%). Pooled analysis showed that primary T3/T4 stage tumor (HR = 1.94; 95% CI: 1.04–3.63), multiple tumors (HR = 1.49; 95% CI: 1.10–2.01), largest liver lesion ≥5 cm (HR = 1.89; 95% CI: 1.11–3.23) and positive surgical margin (HR = 1.80; 95% CI: 1.09–2.97) at initial hepatectomy, and high serum level of carcinoembryonic antigen (HR = 1.87; 95% CI: 1.27–2.74), disease-free interval ≤12 months (HR = 1.34; 95% CI: 1.10–1.62), multiple tumors (HR = 1.64; 95% CI: 1.32–2.02), largest liver lesion ≥5 cm (HR = 1.85; 95% CI: 1.34–2.56), positive surgical margin (HR = 2.25; 95% CI: 1.39–3.65), presence of bilobar disease (HR = 1.62; 95% CI: 1.19–2.20), and extrahepatic metastases (HR = 1.60; 95% CI: 1.23–2.09) at repeat hepatectomy were significantly associated with poor OS.ConclusionsRepeat hepatectomy is a safe and effective therapy for recurrent CRLM. Long-term outcome is predicted mainly by factors related to repeat hepatectomy.     

Is lymph node dissection necessary for resectable intrahepatic cholangiocarcinoma? A systematic review and meta-analysis

BackgroundThe objective of this meta-analysis was to evaluate the effectiveness and safety of lymph node dissection (LND) in patients with intrahepatic cholangiocarcinoma (ICC).MethodsA literature search with a date range of January 2000 to January 2018 was performed to identify studies comparing lymph node dissection (LND+) with non-lymph node dissection (LND-) for patients with ICC. The LND + group was further divided into positive (LND + N+) and negative (LND + N-) lymph node status groups based on pathological analysis.Results13 studies including 1377 patients were eligible. There were no significant differences in overall survival (OS) (HR 1.13, 95% CI 0.94–1.36; P = 0.20), disease-free survival (DFS) (HR 1.23, 95% CI 0.94–1.60; P = 0.13), or recurrence (OR 1.39, 95% CI 0.90–2.15; P = 0.14) between LND + group and LND-group. Postoperative morbidity was significantly higher in the LND + group (OR 2.67, 95% CI 1.74–4.10; P < 0.001). A subset analysis showed that OS was similar between LND + N- and LND-groups (HR 1.13, 95% CI 0.82–1.56; P = 0.450). However when comparing, OS of the LND-group to the LND+N+ group there was a significant increase in OS for the LND-group (HR 3.26, 95% CI 1.85–5.76; P < 0.001).ConclusionsLND does not seem to positively affect overall survival and is associated with increased post-operative morbidity.     

免疫治疗相关性甲状腺功能异常与不可切除/晚期肝细胞癌患者预后改善相关

摘要 目的：探讨免疫治疗相关性甲状腺功能异常与不可切除/晚期肝细胞癌（HCC）患者预后改善的相关性。方法：回顾性分析45例接受免疫检查点抑制剂（ICIs）治疗的不可切除/晚期HCC患者。根据ICIs治疗过程中是否出现免疫相关性甲状腺功能异常分为甲状腺功能正常组（28例）和异常组（17例）,比较2组患者的预后和免疫应答情况,主要终点指标为中位总生存期（OS）、无进展生存期（PFS）,次要终点指标为疾病控制率（DCR）。结果：所有患者的中位OS、PFS分别为10.8个月（95% CI ：3.0~18.6）和5.0个月（95% CI ：3.0~12.2）。正常组中位OS为5.8个月（95% CI ：3.7~7.9）,异常组中位OS尚未达到（ P =0.026）。异常组中位PFS长于正常组（8.2个月 vs. 3.1个月, P =0.011）,DCR高于正常组（52.9% vs. 21.5%,P =0.030）。多因素Cox回归分析显示,甲状腺功能异常是达到6个月OS（ HR=0.213,95%CI ：0.048~0.944, P =0.042）和PFS（ HR=0.383,95%CI：0.151~0.967,P =0.042）的独立影响因素;甲状腺功能异常（ HR=0.403 ,95%CI：0.185~0.877,P =0.022）、基线无大血管侵犯（MVI）（ HR=2.848,95%CI：1.406~5.768,P =0.004）、Child-Pugh A级（ HR=2.404,95%：1.099~5.255,P =0.028）与12个月PFS相关。结论：免疫治疗相关性甲状腺功能异常的不可切除/晚期HCC患者预期生存和免疫应答效果更佳。治疗期间出现甲状腺功能异常、基线无MVI、Child-Pugh A级与患者预后改善相关。     

EGFR mutation types and abundance were associated with the overall survival of advanced lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors

BackgroundEpidermal growth factor receptor tyrosine kinases inhibitors (EGFR-TKIs) are currently recognized as the standard treatment for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations. Clinically found patients with different EGFR mutational status have different prognosis.MethodsA retrospective cohort study was performed to explore the relationship between EGFR mutations and abundance with patient survival by using patient data from the Affiliated Cancer Hospital of Zhengzhou University between January 2013 and November 2016. All patients involved in the present study had sensitive EGFR mutations [either exon 19 deletion (DEL) or exon 21 L858R] and treated by EGFR-TKIs. They were followed up every three months until lost or dead. Mutation abundance was calculated as the copies of EGFR mutation divided by copies of EGFR locus, and the cut-off values for 19DEL and L858R were 4.9% and 9.5%, respectively.ResultsTotal of 236 patients were included, comprising 116 (49.2%) patients with 19DEL mutation and 120 (50.8%) patients with L858R mutation. The median follow-up duration was 23.2 months (95% CI: 14.9–26.7 months). Overall survival (OS) was significantly longer in patients with 19DEL mutation (20.9 months, 95% CI: 17.7–24.1 months versus 17.0 months, 95% CI: 14.4–19.6 months in patients with L858R; P=0.008) and in patients with high mutation abundance (20.9 months, 95% CI: 18.3–23.5 months versus 13.0 months, 95% CI: 10.3–15.7 months in patients with low mutation abundance; P<0.001). Multivariate Cox regression including age, performance status and tumor stage revealed that longer OS was independently associated with 19DEL mutation (HR: 0.48, 95% CI: 0.39–0.67, P=0.033) and high mutation abundance (HR: 0.62, 95% CI: 0.50–0.79, P=0.027).ConclusionsEGFR mutation types and abundance was associated with the patients’ survival which might be used to predict the efficacy of targeted therapy by EGFR-TKIs.     

Intrahepatic cholangiocarcinoma: Introducing the preoperative prediction score based on preoperative imaging

Background: Intrahepatic cholangiocarcinoma(ICC) still has a poor long-term outcome, even after complete resection. We investigated different parameters gathered in preoperative imaging and analyzed their influence on resectability, recurrence, and survival. Methods: All patients who underwent exploration due to ICC between January 2008 and June 2018 were analyzed retrospectively. Kaplan-Meier model, log-rank test and Cox regression were used. Results: Out of 184 patients, 135(73.4%) underwent curative intended resection. Median overall survival(OS) was 22.2 months with a consecutive 1-, 3-and 5-year OS of 73%, 29%, and 17%. Median recurrencefree survival(RFS) was 9.3 months with a consecutive 1-, 3-and 5-year RFS of 36%, 15%, and 11%. Site of tumor, parenchymal localization, tumor configuration/dissemination, and estimated tumor volume had significant influence on resectability. Univariate analyses showed that site of tumor, tumor configuration/dissemination, number of nodules, and estimated tumor volume had predictive values for OS and RFS. Together with tumor size the preoperative prediction(POP) score was created showing significance for OS and RFS(all P 0.001). In multivariate analysis, POP score(HR = 1.779; 95% CI: 1.26 8-2.4 95; P = 0.001), T stage(HR = 1.255; 95% CI: 1.040-1.514; P = 0.018) and N stage(HR = 1.334; 95% CI: 1.081-1.645; P = 0.007) were the independent predictors for OS. For RFS, POP score(HR = 1.733; 95% CI: 1.30 0-2.311; P 0.0 01) and M stage(HR = 3.036; 95% CI: 1.376-6.697; P = 0.006) were the independent predictors. Conclusions: The POP score showed to have a highly significant influence on OS and RFS. The score is easy to assess through preoperative imaging. For patients in the high risk group at least staging laparoscopy or preoperative chemotherapy should be evaluated, because they showed equal outcome compared to the irresectable group.     

The impact of portal pedicle clamping on survival from colorectal liver metastases in the contemporary era of liver resection: a matched cohort study

IntroductionPortal pedicle clamping (PPC) may impact micro‐metastases’ growth. This study examined the association between PPC and survival after a hepatectomy for colorectal liver metastases (CRLM).MethodsA matched cohort study was conducted on hepatectomies for CRLM at a single institution (2003–2012). Cohorts were selected based on PPC use, with 1:1 matching for age, time period and the Clinical Risk Score. Outcomes were overall and recurrence‐free survival (OS and RFS). Cox regression was performed to assess the association between PPC and survival.ResultsOf 481 hepatectomies, 26.9% used PPC. One hundred and ten pairs of patients were matched in the cohorts. There was no significant difference in OS [hazard ratio (HR) 1.18; 95% confidence interval (CI): 0.76–1.83], with a 5‐year OS of 57.8% (95%CI: 52.4–63.2%) with PPC versus 62.3% (95%CI: 57.1–67.5%) without. Five‐year RFS did not differ (HR 0.98; 95%CI: 0.71–1.35) with 29.7% (95%CI: 24.9–34.5%) with PPC versus 28.0% (95%CI: 23.2–32.8%) without. When adjusting for extent of resection, transfusion, operative time and surgeon, there was no difference in OS (HR 0.91; 95%CI: 0.52–1.60) or RFS (HR: 0.86; 95%CI: 0.57–1.30).ConclusionsPPC was not associated with a significant difference in OS or RFS in a hepatectomy for CRLM. PPC remains a safe technique during hepatectomy.     

Does anemia affect outcome after lobectomy or pneumonectomy in early stage lung cancer patients who have not received neo-adjuvant treatment?

BACKGROUND: Preoperative anemia has been shown to be an ominous prognostic factor for survival in patients with early stage non small cell lung cancer. METHODS: Two hundred and fourteen patients underwent resection for early stage non small cell lung cancer between 2001 and 2006 without neo-adjuvant treatment. Patients were divided into four groups based on their admission hemoglobin (Hgb): group I: Hgb < or = 12 g/dl, group II: Hgb = 12.1 - 12.9 g/dl, group III: Hgb = 13.0 - 14.0 g/dl, and group IV: Hgb > 14 g/dl. Cox regression analysis was used to evaluate each variable's impact on midterm survival taking all causes and lung cancer-specific mortality into account. Kaplan-Meier survival plots were estimated. RESULTS: Preoperative hemoglobin (HR = 1.44, 95 % confidence intervals 1.08 - 1.94, P = 0.014) and pneumonectomy (HR = 3.58, 95 % confidence intervals 1.26 - 10.16, P = 0.017) were the only predictors of all-cause midterm mortality. Similarly, when only lung cancer-related mortality was considered, preoperative hemoglobin (HR = 1.81, 95 % confidence intervals 1.17 - 2.78, P = 0.007) and pneumonectomy (HR = 6.89, 95 % confidence intervals 2.29 - 20.73, P = 0.001,) were independent predictors. Age, gender, pulmonary function test results, tumor stage, and histology did not influence survival. CONCLUSIONS: Preoperative anemia and the type of resection in early stage non small cell lung cancer have an impact on midterm survival and lung cancer-specific mortality.     

Efficacy and safety comparison of PD-1 inhibitors vs. PD-L1 inhibitors in extensive-stage small-cell lung cancer: a retrospective comparative cohort study

BackgroundEvidence from clinical research and meta-analyses have suggested that programmed cell death 1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors plus chemotherapy could achieve a significant survival benefit for extensive-stage small-cell lung cancer (ES-SCLC) patients. However clinical researches concerned about the comparation between the PD-1 and PD-L1 inhibitors were relatively lacking.MethodsWe collected the data of ES-SCLC patients treated with PD-1 inhibitors or PD-L1 inhibitors. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint included adverse events (AEs).ResultsThe data of 221 ES-SCLC patients treated with PD-1 (n=146) or PD-L1 inhibitors (n=75) between February 2017 and June 2020 were retrospectively collected. The median OS (mOS) and median PFS (mPFS) were 19.07 and 8.27 months, respectively, in patients treated with PD-1 inhibitors. In the PD-L1 group, mOS has not been reached, and mPFS was 7.95 months. No significant differences were observed between the 2 groups in OS [hazard ratio (HR), 1.472; 95% confidence interval (CI), 0.847–2.220; P=0.198] and PFS (HR, 0.816; 95% CI, 0.577–1.155; P=0.251). The rates of patients showed AEs of any grade treated with PD-1 or PD-L1 were 67.12% and 64.00%, with no significant difference (P=0.642, χ²=0.216), ≥3 grade AEs occurred in 42 (28.76%) and 16 (21.33%) patients treated with PD-1 and PD-L1 inhibitors separately, also no significant difference (P=0.234, χ²=1.415) was observed. According to subgroup analysis, camrelizumab revealed a longer mPFS (15.17 months) compared with other immune-checkpoint inhibitors (ICIs). PD-1 and PD-L1 inhibitors revealed comparable efficacy in ES-SCLC patients with brain metastases, with no significant differences in OS (HR, 1.505; 95% CI, 0.684–3.311; P=0.309) and PFS (HR, 0.649; 95% CI, 0.356–1.182; P=0.157).ConclusionsPD-1 and PD-L1 inhibitors might achieved comparable survival benefit and safety in ES-SCLC patients. A longer PFS was observed in patients treated with PD-1 inhibitors in the first-line treatment, and the PD-1 inhibitor camrelizumab might have achieved a better PFS compared with other ICIs.     

The role of hepatic artery lymph node in pancreatic adenocarcinoma: prognostic factor or a selection criterion for surgery

BackgroundHepatic artery lymph node (HALN) metastasis in pancreatic adenocarcinoma reportedly confers a survival disadvantage. This has led some authors to propose it as an indicator against pancreaticoduodenectomy (PD).MethodsConsecutive patients who underwent PD during 2002–2012 were identified from the University of Louisville prospective hepatopancreaticobiliary database. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan–Meier analysis. The log-rank test and multivariate Cox proportional hazards regression were used in further analyses.ResultsA total of 420 patients underwent PD during the period of study, of whom 197 had lymph node (LN) metastasis. Among these, 41 (20.8%) patients had disease-positive HALNs. The HALN was the only site of LN metastasis in only three of the 247 patients (1.2%). Median follow-up was 18.5 months (interquartile range: 4.1–28.2 months). Median OS and DFS were 22.7 months [95% confidence interval (CI) 19.0–26.3] and 12.6 months (95% CI 10.2–15.2). There was no significant difference in median OS between HALN-positive patients (18.4 months, 95% CI 12.3–24.0) and HALN-negative patients (19.7 months, 95% CI 16.7–22.6) (P = 0.659). On multivariate analysis, the hazard ratio (HR) of death was highest among patients with an LN ratio of >0.2 (HR 1.2, 95% CI 1.1–1.29; P = 0.012) followed by those with poorly differentiated histology (HR 1.09, 95% CI 1.04–1.11; P = 0.029).ConclusionsIn pancreatic adenocarcinoma patients with LN disease, survival after PD is comparable regardless of HALN status. Therefore, HALN-positive disease should not preclude the performance of PD.     

Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized,phase III,Myeloma XI trial

The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n=2,042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalidomide, and dexamethasone (CRD). Additional intensification therapy with cyclophosphamide, bortezomib, and dexamethasone (CVD) was administered before autologous stem-cell transplantation to patients with a suboptimal response to induction therapy using a response-adapted approach. After receiving high-dose melphalan with autologous stem cell transplantation, eligible patients were further randomized to receive either lenalidomide alone or observation alone. Co-primary endpoints were progression-free survival (PFS) and overall survival (OS). The CRD regimen was associated with significantly longer PFS (median: 36 vs. 33 months; hazard ratio [HR], 0.85; 95% confidence interval [CI]: 0.75-0.96; P=0.0116) and OS (3-year OS: 82.9% vs. 77.0%; HR, 0.77; 95% CI: 0.63-0.93; P=0.0072) compared with CTD. The PFS and OS results favored CRD over CTD across all subgroups, including patients with International Staging System stage III disease (HR for PFS, 0.73; 95% CI: 0.58-0.93; HR for OS, 0.78; 95% CI: 0.56-1.09), high-risk cytogenetics (HR for PFS, 0.60; 95% CI: 0.43-0.84; HR for OS, 0.70; 95% CI: 0.42-1.15) and ultra-high-risk cytogenetics (HR for PFS, 0.67; 95% CI: 0.41-1.11; HR for OS, 0.65; 95% CI: 0.34-1.25). Among patients randomized to lenalidomide maintenance (n=451) or observation (n=377), maintenance therapy improved PFS (median: 50 vs. 28 months; HR, 0.47; 95% CI: 0.37-0.60; P<0.0001). Optimal results for PFS and OS were achieved in the patients who received CRD induction and lenalidomide maintenance. The trial was registered with the EU Clinical Trials Register (EudraCT 2009-010956-93) and ISRCTN49407852.     

Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia

The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that patients with DNMT3A(mutant) AML show significantly worse overall survival (OS; P = .022; hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.04-1.81), and relapse-free survival (RFS; P = .005; HR, 1.52; 95% CI, 1.13-2.05) than DNMT3A(wild-type) AMLs. In a multivariable analysis, DNMT3A mutations express independent unfavorable prognostic value for OS (P = .003; HR, 1.82; 95% CI, 1.2-2.7) and RFS (P < .001; HR, 2.2; 95% CI, 1.4-3.3). In a composite genotypic subset of cytogenetic intermediate-risk AML without FLT3-ITD and NPM1 mutations, this association is particularly evident (OS: P = .013; HR, 2.09; 95% CI, 1.16-3.77; RFS: P = .001; HR, 2.65; 95% CI, 1.48-4.89). The effect of DNMT3A mutations in human AML remains elusive, because DNMT3A(mutant) AMLs did not express a methylation or gene expression signature that discriminates them from patients with DNMT3A(wild-type) AML. We conclude that DNMT3A mutation status is an important factor to consider for risk stratification of patients with AML.     

Preoperative transarterial chemoembolization for barcelona clinic liver cancer stage A/B hepatocellular carcinoma beyond the milan criteria: a propensity score matching analysis

BackgroundDebate continues about the benefits of preoperative transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC). This study aimed to assess the impact of preoperative TACE on long-term outcomes after curative resection for HCC beyond the Milan criteria.MethodsPatients who underwent HCC resection exceeding the Milan criteria without macrovascular invasion between 2015 and 2018 were identified (n = 393). Short- and long-term outcomes were compared between patients who underwent preoperative TACE and patients who did not before and after propensity score matching (PSM). Factors associated with recurrence after resection were analyzed.Results100 patients (25.4%) underwent preoperative TACE. Recurrence-free survival (RFS) and overall survival (OS) were comparable with patients who underwent primary liver resection. 7 patients (7.0%) achieved total necrosis with better RFS compared with patients who had an incomplete response to TACE (P=0.041). PSM created 73 matched patient pairs. In the PSM cohort, preoperative TACE improved RFS (P=0.002) and OS (P=0.003). The maximum preoperatively diagnosed tumor diameter (HR 3.230, 95% CI: 1.116–9.353; P=0.031) and hepatitis B infection (HR 2.905, 95%CI: 1.281–6.589; P=0.011) were independently associated with favorable RFS after HCC resection.ConclusionPreoperative TACE made no significant difference to perioperative complications and was correlated with an improved prognosis after surgical resection for patients with HCC beyond the Milan criteria.     

Prognostic and Clinicopathological Value of PD-L1 in Melanoma: A Meta-Analysis

BackgroundThere is a growing interest in using programmed death ligand-1 (PD-L1) as a prognostic marker for melanoma. We conducted this meta-analysis to explore the prognostic and clinicopathological value of PD-L1 in melanoma.Materials and MethodsThe electronic databases PubMed, Web of Science and the Cochrane Library were searched for relevant studies. The major investigated parameters were PD-L1 expression levels in relation to patient gender, tumor-infiltrating lymphocytes (TILs), tumor stage, lymph node (LN) metastasis, histological type, progression-free survival (PFS) and overall survival (OS). Odds ratios (ORs) and hazard ratios (HRs) were computed using the fixed-effect or random-effects model according to data heterogeneity.ResultsPositive PD-L1 expression was significantly associated with high levels of TILs (OR = 7.56, 95% CI 2.04-28.02), metastatic melanoma (OR = 0.45, 95% CI 0.30-0.67) and LN-positive melanoma (OR = 2.56, 95% CI 1.31-4.99) but not gender or histological type. In addition, the pooled HRs showed no relation between PD-L1 expression and PFS (HR = 1.18, 95% CI 0.83-1.69) or OS (HR = 0.77, 95% CI 0.47-1.25). When restricted to metastatic melanoma, positive PD-L1 expression was significantly related to prolonged OS (HR = 0.57, 95% CI 0.46-0.70).ConclusionsPositive PD-L1 expression may be an important prognostic factor for longer OS in patients with metastatic melanoma.