Prognostic Significance of Hypoxia-Inducible Factor Expression in Renal Cell Carcinoma: A PRISMA-compliant Systematic Review and Meta-Analysis

The prognostic value of hypoxia-inducible factor (HIF) in renal cell carcinoma (RCC) has been evaluated in a large number of studies, but the reports were inconsistent and remained inconclusive. Therefore, we conducted a systematic review and meta-analysis to clarify the significance of HIF expression in RCC prognosis.PubMed, Embase, Web of Science, Cochrane Library, EBSCO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Biological Abstracts were searched for eligible studies. Hazard ratio (HR) data for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) with 95% confidence interval (CI) related to the expression status of HIF-1α or HIF-2α detected by immunohistochemistry were all extracted. Data were combined using a random- or fixed-effects model based on the corresponding inter-study heterogeneity. Subgroup analyses were also performed.A total of 14 studies composed of 1258 patients for HIF-1α evaluation and 619 patients for HIF-2α evaluation were included for further analysis. When initially analyzed as a whole, the HIF-1α expression was not significantly correlated with OS (HR 1.637, 95% CI 0.898–2.985, P = 0.108), CSS (HR 1.110, 95% CI 0.595–2.069, P = 0.744), and PFS (HR 1.113, 95% CI 0.675–1.836, P = 0.674). Similarly, HIF-2α expression was not significantly correlated with CSS (HR 1.597, 95% CI 0.667–3.824, P = 0.293) and PFS (HR 0.847, 95% CI 0.566–1.266, P = 0.417). However, subgroup analyses concerning subcellular localization of HIFs revealed that the high nuclear expression of HIF-1α was significantly associated with poor OS (HR 2.014, 95% CI 1.206–3.363, P = 0.007) and the high cytoplasmic expression of HIF -2α was significantly associated with poor CSS (HR 2.356, 95% CI 1.629–3.407, P = 0.000).The increased nuclear expression of HIF-1α and cytoplasmic expression of HIF-2α indicate unfavorable prognosis in RCC patients, which may serve as biomarkers for disease management.     

Metaplastic Breast Carcinoma Versus Triple-Negative Breast Cancer: Survival and Response to Treatment

Metaplastic breast carcinoma (MBC) differs from classic invasive ductal carcinomas regarding incidence, pathogenesis, and prognosis. The purpose of this study was to compare patients with MBC with clinicopathologic and treatment-matched patients with triple-negative breast carcinoma (TNBC) in terms of response to treatment, progression, and survival.Fifty-four patients with MBC and 51 with TNBC, who were treated at Istanbul University, Institute of Oncology, between 1993 and 2014, were included in the study. After correctly matching the patients with 1 of the 2 groups, they were compared to determine differences in response to treatment, disease progression, clinical course, and survival.At a median follow-up of 28 months, 18 patients (17.1%) died and 27 (25.5%) had disease progression. Metaplastic histology was significantly correlated with worse 3-year progression-free survival (PFS) (51 ± 9% vs. 82 ± 6%, P = 0.013) and overall survival (OS) (68 ± 8% vs. 94 ± 4%, P = 0.009) compared with TNBC histology. Patients who received taxane-based chemotherapy (CT) regimens or adjuvant radiotherapy had significantly better PFS (P = 0.002 and P < 0.001) and OS (P < 0.001 and P < 0.001) compared with others. In the multivariate analysis, MBC (hazard ratio [HR]: 0.09, P < 0.001), presence of neoadjuvant chemotherapy (NACT) (HR: 12.8, P = 0.05), and metastasis development at any time during the clinical course (HR: 38.7, P < 0.001) were significant factors that decreased PFS, whereas metastasis development was the only independent prognostic factor of OS (HR: 23.8, P = 0.009).MBC is significantly correlated with worse PFS and OS compared with TNBC. Patients with MBC are resistant to conventional CT agents, and more efficient treatment regimens are required.     

Treatment and Prognoses in Patients With Primary Gastrointestinal Stromal Tumors ≥10?cm: A Single-Institution Experience in China

Data on treatments and specific outcomes of primary gastrointestinal stromal tumors (GISTs) ≥10 cm are limited. We here report the treatments and survival outcomes concerning a subgroup of primary giant GISTs.Data of 83 consecutive patients with primary GISTs ≥10 cm in a single institution were retrospectively collected. Fifty-eight patients underwent surgery before imatinib mesylate (IM) treatment (Group A), 10 underwent surgical resection following IM therapy (Group B), whereas 15 patients took IM as drug therapy alone (Group C).The baseline clinical characteristics were similar among the 3 groups. However, a lower proportion in Group A had metastatic disease at the time of diagnosis or surgery compared with Groups B and C (8.6% vs 40.0% vs 40.0%, P < 0.05). The median follow-up duration was 21.5 months. No statistically significant differences were observed on progression-free survival (PFS) among the groups. However, patients in Group B showed significantly better overall survival (OS) compared with those in Group C (P = 0.044). Multivariate analysis showed that patients treated with adjuvant IM were associated with better PFS (hazard ratio [HR] 3.01; 95% confidence interval [CI] 1.13–7.97; P = 0.027) and OS (HR 29.11; 95% CI 3.32–125.36; P = 0.004). The subgroup with mitotic count >10/50 high-power fields (HPF) showed worse PFS (HR 3.50; 95% CI 1.19–10.25; P = 0.022) and OS (HR 20.04; 95% CI 1.67–143.79; P = 0.018) than that of mitotic count ≤5/50 HPF.Clinical treatment patterns for primary giant GISTs are different, and the outcomes of different interventions vary. The optimal treatments for these subgroup of patients still require further long-term investigation. Moreover, mitotic count and adjuvant IM are closely associated with PFS and OS in giant GISTs.     

Third-Line Chemotherapy for Metastatic Urothelial Cancer: A Retrospective Observational Study

The prognosis of locally advanced (T3/T4 or N1) and metastatic disease urothelial carcinoma is poor. In this retrospective study, we reviewed data about patients receiving third-line chemotherapy for metastatic disease, in view of the lack of data in this setting.We retrospectively analyzed medical records of patients with a pathologic diagnosis of urothelial carcinoma treated with systemic chemotherapy for metastatic disease at 4 participating Institutions between January, 2010, and January, 2015. Cox proportional hazards regression was used to evaluate the association of the chemotherapy agent used versus others with overall survival, adjusted for 5 externally validated prognostic factors in advanced urothelial carcinoma.Of 182 patients that received first-line chemotherapy/adjuvant chemotherapy as defined above, 116 patients (63.73%) received second-line salvage treatment. Fifty-two patients were finally included in this analysis, whereas 9 were excluded due to missing data. Third-line chemotherapy was based on cyclophosphamide, platinum, vinflunine, taxanes, and gemcitabine in 16, 12, 11, 10, and 3 patients, respectively. Median PFS (progression-free survival) and OS (overall survival) of the population were 13 (10–17) and 31 (28–36) weeks. Single-agent cyclophosphamide was associated with a PFS of 18 (13–22) and an OS of 38 (33–41) weeks, whereas platinum-based combinations were associated with a PFS of 5 weeks and an OS of 8 weeks. Multivariate analysis showed improved survival in patients treated with cyclophosphamide (hazard ratio (HR) = 0.42; 95% CI: 0.20–0.89; P = 0.025) and a worse survival in those treated with platinum-based regimens (HR: 4.37; 95% CI = 1.95–9.77; P < 0.01).We observed a significantly longer overall survival in patients receiving single-agent cyclophosphamide, with few grade 3 to 4 toxicities. Further studies should assess the efficacy of metronomic single-agent cyclophosphamide in advanced lines of treatment, as it may yield a survival benefit with low costs and no detrimental effects on quality of life.     

A Meta-analysis Reveals S-1-based Chemotherapy Improves the Survival of Patients With Advanced Gastric Cancer

The aim of this study was to compare the efficacy and safety of S-1-based therapy versus non-S-1-based therapy in advanced gastric cancer (AGC) patients.Eligible studies stratifying objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in AGC patients were identified from Embase, Pubmed, Cochrane Library, and China National Knowledge Infrastructure databases. The STATA package (version 11.0) was used to pool the data from the eligible studies.Fifteen studies with 2973 AGC cases, of which 1497 (50.4%) received S-1-based therapy and 1476 (49.6%) received non-S-1-based therapy, were identified in the meta-analysis. AGC patients who had received S-1-based therapy had a higher median OS, median PFS, and ORR than those who had received 5-fluorouracil (FU)-based therapy (OS: hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80–0.98, P = 0.015; PFS: HR 0.88, 95% CI 0.80–0.98, P = 0.016; ORR: OR 1.25, 95% CI 1.08–1.45, P = 0.003, respectively). S-1-based therapy had similar efficacy to capecitabine-based therapy in terms of median OS (HR 1.14, 95% CI 0.91–1.41, P = 0.253), median PFS (HR 1.01, 95% CI 0.82–1.25, P = 0.927), and ORR (OR 0.84, 95% CI 0.63–1.12, P = 0.226). Subgroup analysis for grade 3 to 4 toxicity showed higher incidence of neutropenia (relative risk [RR] = 0.827, P = 0.006), nausea (RR = 0.808, P = 0.040), and lower diarrhea (RR = 1.716, P = 0.012) in 5-FU-based arm, and higher diarrhea (RR = 0.386, P = 0.007) in capecitabine-based arm.S-1-based chemotherapy is favorable to AGC patients with better clinical benefit than 5-FU-based chemotherapy and with equivalent antitumor compare with capecitabine-based therapy.     

Isocitrate Dehydrogenase (IDH)1/2 Mutations as Prognostic Markers in Patients With Glioblastomas

The purpose of this study was to perform a meta-analysis examining the association of isocitrate dehydrogenase (IDH)1/2 mutations with overall survival (OS) and progression-free survival (PFS) in patients with glioblastomas.Medline, Cochrane, EMBASE, and Google Scholar were searched from inception to January 28, 2015, using combinations of the following keywords: IDH mutation, brain tumor, glioma, glioblastoma, oligodendroglioma, prognosis. Randomized controlled trials, and prospective and retrospective studies of patients with glioblastomas that provided IDH mutation and survival data were included. OS and PFS were used to evaluate the association of IDH1 and IDH1/2 mutations and prognosis. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for OS and PFS were calculated and compared between patients with and without mutations.Of 165 studies that were identified, 136 nonrelevant studies were excluded. Twenty-nine full-text articles were assessed, and of these, 5 were excluded as they did not provide a quantitative outcome. Therefore, 24 studies were included in the qualitative synthesis. The pooled HR of 0.358 (95% CI 0.264–0.487, P < 0.001) indicated that IDH mutations were associated with better OS. Similarly, the pooled HR of 0.322 (95% CI 0.24200.455, P < 0.001) indicated that IDH mutations were associated with better PFS. When patients were stratified by surgery versus no surgery or IDH1 versus IDH1/2 mutations, the results also indicated that the presence of IDH mutations was associated with better OS and PFS.The IDH mutations are associated with improved survival in patients with glioblastomas.     

The prognostic value of inflammation markers in postoperative gliomas with or without adjuvant treatments

Recent studies have shown that some inflammatory markers are associated with the prognosis of solid tumors. This study aims to evaluate the prognosis of glioma patients with or without adjuvant treatment using the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR).All patients who were diagnosed with gliomas at the first and second affiliated hospital of Guangxi Medical University between 2011 and 2020 were included in this study. The optimal cutoff value of SII, NLR, and PLR was determined by X-tile software program. We stratified patients into several groups and evaluated the progression-free survival (PFS) and overall survival (OS) of SII, NLR, and PLR during the period of pre-surgical, con-chemoradiotherapy, and post-treatments. Multivariate Cox regression analyses were performed to detect the relationships between OS, PFS, and prognostic variables.A total of 67 gliomas patients were enrolled in the study. The cutoff values of SII, NLR, and PLR were 781.5 × 10⁹/L, 2.9 × 10⁹/L, and 123.2 × 10⁹/L, respectively. Patients who are pre-SII < 781.5 × 10⁹/L had better PFS (P = .027), but no difference in OS. In addition, patients who had low pre-NLR (<2.9 × 10⁹/L) meant better OS and PFS. PLR after adjuvant treatments (post-PLR) was significantly higher than pre-PLR (P = .035). Multivariate analyses revealed that pre-SII, pre-NLR were independent prognostic factors for OS (pre-SII: HR 1.002, 95% CI: 1.000–1.005, P = .030 and pre-PLR: HR 0.983, 95% CI: 0.973–0.994, P = .001), while pre-PLR was an independent factor for PFS (HR 0.989, 95% CI: 0.979–1.000, P = .041).High pre-SII or high pre-NLR could be prognostic markers to identify glioma patients who had a poor prognosis.     

Soluble Serum αKlotho Is a Potential Predictive Marker of Disease Progression in Clear Cell Renal Cell Carcinoma

Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies, and clear cell RCC (ccRCC), that has a high metastatic index and high relapse rate, is the most common histological subtype. The identification of new biomarkers in ccRCC is fundamental for stratifying patients into prognostic risk groups and to guide therapy. The renoprotective antiaging gene, αKlotho, has recently been found to work as a tumor suppressor in different human cancers. Here, we evaluated αKlotho expression in tissue and serum of ccRCC patients and correlated it with disease progression. Tissue αKlotho expression was studied by quantitative RT-PCR and immunohistochemistry. In addition, soluble serum αKlotho levels were preoperatively measured in 160 patients who underwent nephrectomy for RCC with ELISA. Estimates of cancer-specific (CSS) and progression-free survival (PFS) were calculated according to the Kaplan–Meier method. Multivariate analysis was performed to identify the most significant variables for predicting CSS and PFS. αKlotho protein levels were significantly decreased in RCC tissues compared with normal tissues (P < 0.01) and the more advanced the disease, the more evident the down-regulation. This trend was also observed in serum samples. Statistically significant differences resulted between serum αKlotho levels and tumor size (P = 0.003), Fuhrman grade (P = 0.007), and clinical stage (P = 0.0004). CSS and PFS were significantly shorter in patients with lower levels of αKlotho (P < 0.0001 and P = 0.0004, respectively). At multivariate analysis low serum levels of αKlotho were independent adverse prognostic factors for CSS (HR = 2.11; P = 0.03) and PFS (HR = 2.18; P = 0.03).These results indicate that a decreased αKlotho expression is correlated with RCC progression, and suggest a key role of declining αKlotho in the onset of cancer metastasis.     

Intensity-modulated radiotherapy with more than 60 Gy improved the survival of inoperable patients with locally advanced esophageal squamous cell carcinoma: A population-based real-world study

Intensity-modulated radiotherapy (IMRT) is widely applied during the treatment of esophageal squamous cell carcinoma (ESCC), but the optimal radiation dose still lacks a consensus. The aim of this study was to explore the optimal radiation dose for inoperable locally advanced ESCC patients treated with IMRT in a real-world clinical setting.A total of 90 inoperable ESCC patients with locally advanced stages of II-IVA treated with IMRT in our institute between February 1, 2014 and June 30, 2019 were included in this retrospective study. Sixty patients had received >60 Gy (high dose group) and 30 patients had received ≤60 Gy (low dose group). The median radiation dose was 66 Gy (range: 61–70 Gy) and 50.2 Gy (range: 40–60 Gy), respectively. Concurrent chemotherapies were platinum-based regimens.The median progression free survival (PFS) and overall survival (OS) of all patients were 7.6 and 14.1 months, respectively. Patients in the high dose group exhibited a significantly better PFS (1-year PFS 34.6% vs 22.8%; 2-year PFS 11.9% vs 0%, P = .008) and OS (1-year OS 57.5% vs 39.5%; 2-year OS 31.4% vs 15.8%, P = .007). The median PFS in the high and low dose groups were 8.1 and 6.1 months, and the median OS were 15.4 and 8.5 months, respectively. Multivariate Cox analysis showed that radiation dose (>60 Gy vs ≤60 Gy) was independently prognostic factor for OS (HR: 0.44; 95% CI: 0.22–0.89; P = .021), but not for PFS (HR: 0.56; 95% CI: 0.31–1.02; P = .058). There was no significant difference in treatment-related toxicities of grade ≥3 between the 2 groups (P = .402).This retrospective study confirmed that higher radiation dose (>60 Gy) resulted in better survival outcomes for inoperable patients with locally advanced ESCC treated with IMRT.     

Maintenance treatment of combination with bevacizumab vs single agent for advanced non-squamous non-small cell lung cancer: A systematic review and meta-analysis

Background:When the patients of advanced non-squamous non-small cell lung cancer (NSCLC) have achieved remission by induction therapy, it is controversial that combination with bevacizumab is used as maintenance therapy. Pemetrexed is a classic drug for maintenance therapy, is bevacizumab the superiority to pemetrexed is also unclear. This meta-analysis aims to evaluate the effectiveness and safety of advanced non-squamous NSCLC in the maintenance treatment.Method:From the establishment as of December 6, 2020, PubMed, Embase, and Cochrane electronic databases were searched and the American Society of Clinical Oncology, European Society of Medical Oncology, and National Comprehensive Cancer Network databases in the past 10 years. The application of combination with bevacizumab, pemetrexed was studied in clinical trials of maintenance treatment for advanced NSCLC. The extracted data include progression-free survival (PFS), overall survival (OS), and grade 3–4 adverse events (AE).Results:Seven clinical trials we screened, 6 were phase III RCTs, and a cohort trial, including 3298 patients. Compared with bevacizumab and pemetrexed, PFS of combination with bevacizumab was significantly improved (hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.65–0.77, P < .00001), but OS was not improved (HR = 0.93, 95% CI = 0.85–1.01, P = .10). Compared with bevacizumab and pemetrexed, no significant difference of PFS (HR = 0.87, 95% CI = 0.69–1.09, P = .21), and OS (HR = 0.87, 95% CI = 0.72–1.05, P = .15) was found. A higher incidence of grade 3–4 AE occurred in combination with bevacizumab (odds ratio = 1.63, 95% CI = 1.35–1.97, P < .00001).Conclusions:PFS was significantly improved in patients with advanced non-squamous NSCLC who use bevacizumab combination with single-agent as maintenance treatment, but it does not translate into the advantages of OS; compared with bevacizumab, no PFS and OS benefits were found. A higher incidence of grade 3–4 AE occurred in combination with bevacizumab than pemetrexed and bevacizumab.     

Apatinib combined with S-1 as second-line therapy in advanced gastric cancer

Advanced gastric cancer (AGC) patients are not tolerant to the toxicities of traditional chemotherapy and its second-line therapeutic regimens are limited. The aim of the present study is to evaluate the efficacy and safety of apatinib combined with S-1 as the second-line therapy for AGC patients.Patients with AGC were enrolled in this study. Patients received oral apatinib (250 mg to 500 mg once daily) and S-1(40 mg/m² twice daily) on days 1–14. Each cycle was 28 days and one course of treatment consisted of 2 cycles. Clinical efficacy and adverse events (AEs) were observed. Kaplan–Meier method was used for survival analysis.From November 2015 to December 2017, 58 AGC patients who failed first-line chemotherapy were enrolled and assessed retrospectively. According to the Response Evaluation Criteria in Solid Tumors (RECIST) standard, all patients were evaluable for response. None achieved CR, and 10 (17.2%) achieved PR (95% CI 7.2%–27.3%). SD was observed in 58.6% (34/58) of patients (95% CI 45.6%–71.7%) and NR in 24.1% (14/58) of patients (95% CI 12.8%–35.5%). The objective response rate (ORR) and the disease control rate (DCR) were 17.2% and 75.8% respectively. The median progression-free survival (PFS) and median overall survival (OS) were 143.1 days (95% CI 121.7–164.5) and 211.6 days (95% CI 162.9–219.7) respectively. The multivariate analysis showed that the ECOG PS was the independent factor of PFS and OS for AGC patients (PFS: HR = 3.565, 95% CI: 2.25–5.65, P < .001; OS: HR = 3.676, 95% CI: 2.29–5.89, P < .001). The main AEs were fatigue (72.4%), hypertension (46.6%), and leukopenia (48.3%).Apatinib combined with S-1 showed promising efficiency and was well tolerated as the second-line therapy for AGC patients. ECOG PS was the independent factor of PFS and OS for AGC patients. AEs were moderate and controllable, and leukopenia or hypertension was predictable factors for the PFS and OS of AGC patients.     

Pre-existing Type 2 Diabetes Mellitus Is an Independent Risk Factor for Mortality and Progression in Patients With Renal Cell Carcinoma

Malignancies are one of the main causes of mortality in diabetic patients; however, to date, very limited data have been reported on the specific influence of type 2 diabetes mellitus (T2DM) on the survival of patients with renal cell carcinoma (RCC). In the present long-term retrospective study, we investigated whether T2DM may influence the overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) in patients with surgically treated RCC.Medical records of 924 patients treated by radical or partial nephrectomy for sporadic, unilateral RCC were reviewed. Patients with type-1 DM and with T2 DM receiving insulin treatment were excluded. Survival estimates were calculated according to the Kaplan–Meier method and compared with the log-rank test. Univariate and multivariate analyses were performed using the Cox regression model.Of the 924 RCC patients, 152 (16.5%) had T2DM. Mean follow-up was 68.5 months. Mean OS was 41.3 and 96.3 months in T2DM and non-T2DM patients, respectively (P < 0.0001).The estimated CSS rates at 1, 3, and 5 years in T2DM versus non-T2DM patients were 63.4% versus 76.7%, 30.4% versus 56.6%, and 16.3% versus 48.6%, respectively (P = 0.001). Mean PFS was significantly lower (31.5 vs 96.3 months; P < 0.0001) in the T2DM group. At multivariate analysis, T2DM was an independent adverse prognostic factor for OS (hazard ratio [HR] = 3.44; 95% confidence interval [CI]:2.40–4.92), CSS (HR = 6.39; 95% CI: 3.78–10.79), and PFS (HR = 4.71; 95% CI: 3.11–7.15).In conclusion, our findings suggest that patients with RCC and pre-existing T2DM have a shorter OS, increased risk of recurrence, and higher risk for kidney cancer mortality than those without diabetes.     

Gemcitabine Compared With Gemcitabine and S-1 Combination Therapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis

Several reports suggest that gemcitabine (GEM) plus S-1 combination (GS) is associated to prolong the survival in patients with unresectable pancreatic cancer (PC). We conducted a systemic review and meta-analysis of studies comparing the safety and efficacy of GS versus GEM.Summary data from randomized trials and retrospective studies were searched in PubMed, EMBASE, Web of Science, and the Cochrane Library. Statistical analyses were conducted to calculate the hazard ratios (HRs) and relative risk (RR) with 95% confidence intervals (CIs) using random-effects models. Subgroup analyses based on the chemotherapy cycles were performed to explore the efficacy and toxicity for therapy. Sensitivity analyses were conducted by removing specific studies to assess the effects of study quality.Between January 2004 and August 2012, 4 RCTs and 2 retrospective studies including a total of 1025 cases were identified. The overall survival (OS) (HR: 0.82; 95% CI, 0.70–0.96; P = 0.01) and progression-free survival (PFS) (HR: 0.65; 95% CI, 0.55–0.77; P < 0.001) for the GS arm were significantly longer than the GEM arm. The differences in objective response rate (ORR) (RR: 1.24; 95% CI, 1.17–1.33; P < 0.001) and disease control rate (DCR) were also better in the GS arm (RR: 1.37; 95% CI, 1.19–1.59; P < 0.001). Grades 3 to 4 toxicities in both the groups were similar except neutropenia and diarrhea, which were more frequent in the GS arm (P < 0.001). In the subgroup analysis, the cycle for chemotherapy every 4 weeks has equivalent efficacy and less toxicity than regimens every 3 weeks in the GS arm.The current meta-analysis suggested that GEM significantly prolonged OS and PFS when added to S-1 combination in patients with unresectable PC. GS therapy also offers better ORR and DCR than GEM monotherapy and no unexpected toxicity was evident.     

The Highest Metabolic Activity on FDG PET Is Associated With Overall Survival in Limited-Stage Small-Cell Lung Cancer

We evaluated the prognostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET) parameters for limited-stage small-cell lung cancer (LS-SCLC).We retrospectively enrolled 59 LS-SCLC patients who underwent pretreatment FDG PET/CT. Various PET parameters were measured in all malignant lesions, and we recorded the highest maximum standardized uptake value (SUV_max), and sum of metabolic tumor volume (MTV_sum) and total lesion glycolysis (TLG_sum). The relationship between the highest SUV_max and volumetric PET parameters was evaluated. The prognostic significances of PET parameters and clinical variables were assessed using Cox''s proportional hazard regression analysis. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan–Meier method.The SUV_max of the highest metabolic lesion had a significant positive correlation with MTV_sum and TLG_sum (P < 0.001). Upon multivariate analysis, the highest SUV_max was an independent predictor of OS (1 unit increase, hazard ratio [HR]: 1.133, P = 0.003) and MTV_sum was a significant prognostic factor of PFS (10-cm³ increase, HR: 1.027, P = 0.034) after adjusting for age, sex, performance status, tumor stage, and treatment modality. The highest SUV_max was a prognostic factor for PFS with marginal significance (1 unit increase, HR: 1.078, P = 0.053). Patients with higher SUV_max (≥11) were also characterized by a significantly shorter median OS (P < 0.001) and PFS (P = 0.002) compared with patients with lower SUV_max.The highest SUV_max is an independent prognostic factor for survival in LS-SCLC patients. Therefore, the highest SUV_max might be a possible imaging biomarker for risk stratification in LS-SCLC. A further study in a large cohort is needed to validate the prognostic significance of the parameter.     

Determinants of Survival After Sorafenib Failure in Patients With BCLC-C Hepatocellular Carcinoma in Real-World Practice

Sorafenib may improve progression-free survival (PFS) and overall survival (OS) of advanced hepatocellular carcinoma (HCC). However, the survival benefit is short lived and survivals after progressive disease (PD) have not been well characterized. This study aimed to evaluate the survival predictors of OS and postprogression survival (PPS) in advanced HCC patients receiving sorafenib treatment.Consecutive 149 HCC patients receiving sorafenib under National Health Insurance were retrospectively enrolled. All patients fulfilled the reimbursement criteria: Barcelona Clinic Liver Cancer stage C HCC with macroscopic vascular invasion or extrahepatic metastasis (Mets), and Child–Pugh class A. Radiologic assessment was performed at a 2-month interval using modified Response Evaluation Criteria in Solid Tumors. Patients who maintained Eastern Cooperative Oncology Group ≤2 and Child–Pugh class A at PD were assumed to be candidates for second-line treatment.During the median follow-up period of 7.5 months (range, 1.1–18.5), PD developed in 120 (80.5%) patients and 96 (64.4%) deaths occurred. The median PFS, OS, and PPS were 2.5, 8.0, and 4.6 months, respectively. In general, patients with Mets only had better OS and PPS than those with portal vein invasion. Independent predictors of OS include baseline performance status (hazard ratio [HR] = 1.956), tumor size (HR = 1.597), alpha-fetoprotein (HR = 1.869), discontinuation of sorafenib due to liver function deterioration (LD) (HR = 6.142), or concurrent PD and LD (HR = 2.661) and PD within 4 months (HR = 5.164). Independent predictors of PPS include deteriorated performance status (HR = 7.680), deteriorated liver functions (HR = 5.603), bilirubin (HR = 2.114), early PD (HR = 6.109), and new extrahepatic lesion (HR = 1.804). In 46 candidates for second-line trials, development of new extrahepatic lesion independently predicts poorer PPS (HR = 3.669).In conclusion performance status, liver functions, early disease progression, and progression pattern are important determinants of survival after sorafenib failure. These factors should be considered in clinical practice and second-line trial designs for patients with sorafenib failure.     

The Relationship Between the Adverse Events and Efficacy of Sorafenib in Patients With Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Study from Northwest China

The aim of the study is to evaluate the relationship between the adverse events and efficacy of sorafenib in patients with metastatic renal cell carcinoma (mRCC), with a purpose to guide the judgment of efficacy in sorafenib treatment.Eighty-three mRCC patients who received sorafenib therapy at northwest China were studied retrospectively. Univariate and multivariate analyses were performed to correlate tumor response, progression-free survival (PFS), and overall survival (OS) with adverse event types and grades.Among 83 patients who underwent sorafenib therapy, 2 cases (2.4%) had completed response (CR), 14 cases (16.9%) had partial response (PR), 57 cases (68.7%) had stable disease (SD), and 10 cases (12.0%) developed progressive disease (PD). The median PFS and OS were 15.0 and 29.0 months, respectively. The most frequent grade 1 or 2 adverse events included hand-foot syndrome (68.7%), diarrhea (54.2%), and alopecia (51.8%). The most common grade 3 or 4 adverse events were hand-foot syndrome (6.0%), hypertension (4.8%), and diarrhea (3.6%). The frequency and severity of adverse events correlated with tumor response rate (both with P < 0.05). Multivariate analysis showed the independent predictors of better PFS included rash (OR 0.307, 95%CI 0.148–0.636, P = 0.001) and diarrhea (OR 0.391, 95%CI 0.169–0.783, P = 0.008). Elevated transaminase was the independent predictor of poor PFS (OR 2.606, 95%CI 1.299–5.532, P = 0.012). For OS, rash (OR 0.473, 95%CI 0.253–0.886, P = 0.019) and diarrhea (OR 0.321, 95%CI 0.171–0.605, P = 0.000) correlated with better OS.Sorafenib-related adverse events are associated with efficacy in patients with mRCC from northwest China. Rash and diarrhea are independent protective factors of both PFS and OS, and elevated transaminase is an independent risk factor of PFS. A large prospective study is warranted.     

Do Glioma Patients Derive Any Therapeutic Benefit From Taking a Higher Cumulative Dose of Temozolomide Regimens?: A Meta-Analysis

Temozolomide (TMZ) is an oral alkylating agent with established effects on the central nervous system of glioblastoma (GBM) patients. Clinical trials have demonstrated a significant impact on overall survival (OS) with TMZ. Ever since, several TMZ regimens have been designed to improve treatment efficacy by increasing the cumulative dose per cycle. We report a meta-analysis to systematically evaluate different treatment schedules of TMZ in GBM patients.All searches that were conducted in the Cochrane library, Science Direct, and PubMed Databases, and 3 randomized controlled trials (1141 patients) were included. OS and progression-free survival (PFS) were the primary outcomes to be pooled.Unexpectedly, this analysis did not reveal any OS or PFS advantage for the high cumulative dose (HCD) regimen compared with the normal cumulative dose regimen (1141 total patients; hazard ratio [HR] 1.07, 95% CI 0.94–1.22, P = 0.31). Then after analyzing the characteristics of the results from each trial, we found that the regimen with a higher peak concentration during a short-term period (daily doses ≥150 mg/m²/d within ≤7 days/cycle) always had a more superior clinical benefit. So we generated a new pooled HR of 1.10 with a 95% CI of 0.96–1.25 (P = 0.17), which prefers the high peak concentration schedule even without a significant difference. The adverse outcome also indicates a significant increased risk of leukopenia (risk ratio 1.59, 95% CI 1.03–2.46, P = 0.04) among the HCD group.Our study suggests that increasing the cumulative dose per cycle is not an ideal way to improve the efficacy of TMZ, and it will lead to increased risk for leukopenia. Future trials should be designed to examine schedules of higher peak concentration rather than the cumulative dose per cycle.     

Analysis of clinical characteristics and prognosis of patients with peripheral T-cell lymphoma

Background:This study aimed to explore the clinical characteristics, therapeutic efficacy and prognostic factors of peripheral T-cell lymphoma (PTCL).Methods:The clinical data of 119 PTCL patients who were admitted to the Xinjiang Medical University Affiliated Tumor Hospital from January 2010 to December 2017 were retrospectively analyzed, including the clinical characteristics, therapeutic efficacy, prognosis-related factors and treatments. Among the patients, 98 patients received antharcyclines-based therapeutic protocols, including Cyclophosphamide, Pirarubicin, Vincristine, Prednisone (CHOP) protocol and Cyclophosphamide, Pirarubicin, Vincristine, Prednisone, Etoposide (CHOPE) protocol, with median follow-up time of 32.5 months (2–166 months). The patients’ clinical characteristics were analyzed, and COX ratio risk regression model was adopted to analyze the prognostic factors related with the survival rate of PTCL patients.Results:The 5-year overall survival (OS) rate was 46.4% and progression-free survival (PFS) rate was 42.7% in the 98 patients, and there were insignificant differences between patients with CHOP protocol and those with CHOPE protocol in the 5-year OS and PFS rates (OS: P = 0.197, PFS: P = 0.663). The univariate analysis results showed that different pathological types, Ann Arbor stage, Eastern Cooperative Oncology Group (ECOG) score ≥ 2, the number of extranodal lymphomas involved, Lactic dehydrogenase (LDH) level, presence/absence of bone marrow involved, international prognostic index (IPI) score, β₂ microglobulin (β₂-MG) level and hemoglobin (Hb) level were poor prognosis factors influencing patients’ OS and PFS rates (P all < .05). Multivariate analysis demonstrated that different pathological types, Ann Arbor stage, presence/absence of bone marrow involved and Hb level were independent prognostic indicators influencing patients’ OS and PFS rates (P all < .05).Conclusion:PTCL is poor in therapeutic efficacy and prognosis, and different pathological types, Ann Arbor stage, presence/absence of bone marrow involved and Hb level are related with the prognosis of PTCL patients. Anemia occurring before the treatment is an important predictive indicator influencing the prognosis of PTCL patients and patients who experience anemia will be poor in prognosis.     

Comparative efficacy and safety for second-line treatment with ramucirumab,regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma progressed on sorafenib treatment: A network meta-analysis

Background:The present network meta-analysis was conducted to perform an indirect comparison among ramucirumab, regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma (HCC) progressed on sorafenib treatment.Methods:A systematic review through Medline, Embase, and Cochrane library was developed, with eligible randomized clinical trials been included. Hazard ratios (HRs) including progression-free survival (PFS), overall survival (OS), odds ratios of disease control rate (DCR), objective response rate (ORR), and adverse events were compared indirectly with network meta-analysis using random model in software STATA version 13.0.Results:A total of 4 randomized clinical trials including 2137 patients met the eligibility criteria and enrolled. Indirect comparisons showed that there was no statistical difference observed in the indirect comparison of PFS, OS, ORR, or DCR among agents of regorafenib, cabozantinib, and ramucirumab in advanced HCC patients with elevated α-fetoprotein (AFP) (400 ng/mL or higher). However, in patients with low-level AFP (lower than 400 ng/mL), regorafenib was the only agent associated with significant superiority in OS, compared with placebo (hazard ratio 0.67, 95% CI, 0.50–0.90).Conclusions:The present network meta-analysis revealed that there might be no statistical difference observed in the indirect comparison of PFS, OS, ORR, or DCR among regorafenib, cabozantinib, or ramucirumab in advanced HCC patients with elevated AFP (400 ng/mL or higher). However, in patients with low-level AFP (lower than 400 ng/mL), regorafenib might be associated with significant superiority in OS, compared to placebo, which need further investigation in clinical practice.     

Clinicopathologic Significance of HNF-1β, AIRD1A,and PIK3CA Expression in Ovarian Clear Cell Carcinoma: A Tissue Microarray Study of 130 Cases

Ovarian clear cell carcinoma (CCC) is a distinct histologic subtype with relatively poor survival. No prognostic or predictive molecular marker is currently available. Recent studies have shown that AT-rich interactive domain 1A (ARID1A) and phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) mutations are common genetic changes in ovarian CCC. Hepatocyte nuclear factor-1β (HNF-1β) expression has been proven to be highly sensitive and specific for clear cell histology. However, the correlations between these biomarkers and clinicopathologic variables and survival outcomes are controversial.The immunohistochemical analysis for HNF-1β, ARID1A, and PIK3CA was performed on a tissue microarray (TMA) consisting of 130 cases of ovarian CCC (237 tissue blocks) linked with clinical information. The immunostaining results were interpreted in a manner consistent with previous publications. The associations between biomarker expression and clinical and prognostic features were examined. All statistical analyses were conducted using 2-sided tests, and a value of P < 0.05 was considered significant.HNF-1β was expressed in 92.8% of all primary ovarian tumors, while the loss of ARID1A and PIK3CA was noted in 56.2% and 45.0%, respectively. Early-stage tumors tended to have high levels of HNF-1β immunoreactivity and expression of ARID1A (P = 0.02 and P = 0.03). Most patients (76.9%, 20/26) with concurrent endometriosis stained negative for ARID1A (P = 0.02). No relation was found between PIK3CA expression and clinical features. Low-level HNF-1β expression and loss of ARID1A were more commonly observed in patients with tumor recurrence (P = 0.02 and P < 0.001). Antibody expression was not associated with platinum-based chemotherapy response. Patients with negative ARID1A expression had worse survival outcome in terms of both overall survival (OS) and progression-free survival (PFS) (P = 0.03 and P = 0.01, respectively). On the contrary, patients with high-level HNF-1β were associated with good prognosis (P = 0.02 for OS and P = 0.01 for PFS). PIK3CA expression had no impact on survival. For univariate and multivariate analyses, only HNF-1β expression seemed to be a prognostic factor for favorable OS (P = 0.04).The loss of ARID1A was correlated with late-stage and endometriosis-associated tumors. The measurement of ARID1A expression might be a method to predict the risk of recurrence. Among the 3 biomarkers, only high-level HNF-1β expression proved to be a positive predictor for OS.