Overuse of antianaerobic drug is associated with poor postchemotherapy prognosis of patients with hepatocellular carcinoma

Overuse of antibiotic drugs alters the composition of gut microbiota and has detrimental effects on the host. In our study, we investigated association of gut flora and antibiotics in the prognosis of patients with liver cancer who have undergone chemotherapy by analyzing two independent clinical studies. We retrospectively subanalyzed a previously reported randomized controlled trial (RCT) on hepatic arterial infusion chemotherapy in patients with hepatocellular carcinoma (HCC) to investigate the association between use of antibiotics and prognosis. In the other study, we prospectively determined the abundance of specific bacterial genus in patients with HCC by sequencing 16S ribosomal RNA and assessed its association with survival. Subanalysis of the RCT data showed that, of 26 types of antibiotics used, administration of carbapenem before or during chemotherapy was associated with poor progression-free survival (PFS) and overall survival (OS) of patients with HCC (carbapenem + vs. −; median PFS, 78 days vs. 154 days, p = 0.0053; median OS, 177 days vs. 475 days, p = 0.0003). Multivariate analysis revealed that antianaerobic drug use is an independent predictor of poor prognosis. In the prospective study, the abundance of Blautia in fecal microbiota correlated positively with both PFS and OS of patients with HCC who underwent chemotherapy. Use of antibiotics targeting anaerobes is associated with a poor prognosis in patients with HCC who have undergone chemotherapy, whereas the intestinal anaerobic bacteria, Blautia is associated with a good prognosis. These findings might indicate the need for caution regarding overuse of broad-spectrum antibiotics targeting anaerobes in patients with HCC.     

Proton beam radiotherapy versus transarterial chemoembolization for hepatocellular carcinoma: Results of a randomized clinical trial

Background

This study compares survival rates, recurrence patterns, toxicity, and treatment cost in patients with hepatocellular carcinoma (HCC) treated with either transarterial chemoembolization (TACE) or proton beam radiotherapy (PBT).

Methods

Subjects with untreated HCC meeting Milan or San Francisco transplant criteria were recruited. Subjects were randomized to receive PBT (n = 36) or TACE (n = 40). Proton therapy was administered in 15 fractions over 3 weeks to a total dose of 70.2 Gy. TACE was repeated until complete or maximal response. The primary outcome measure was overall survival (OS). Secondary end points were progression-free survival (PFS), local control (LC), toxicity, and cost.

Results

Of the 76 randomized patients, 74 were assessed for outcome measures. The 2-year OS for PBT versus TACE was similar at 68%, 95% confidence interval (CI), 0.54–0.86, and 65%, 95% CI, 0.52–0.83 (p = .80), however, median PFS was improved for PBT versus TACE (not reached vs. 12 months, p = .002). LC was improved with PBT versus TACE (hazard ratio, 5.64; 95% CI, 1.78–17.9, p = .003). Days of posttreatment hospitalization were 24 for PBT and 166 for TACE (p < .001). Total mean cost per patient for treatment and posttreatment care revealed a 28% cost savings for PBT.

Conclusions

PBT and TACE yielded similar OS for treatment of HCC, but PFS and LC were improved with PBT compared to TACE. Patients treated with PBT required fewer courses of treatment, fewer posttreatment hospitalization days, and reduced cost of treatment compared to TACE. These data support the use of PBT as a viable treatment alternative to TACE for patients with HCC within transplant criteria.     

Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort

Copper and zinc are essential micronutrients, whose imbalance may be involved in the development and progression of cancer. However, the role of copper and/or zinc imbalance in the prognosis of hepatocellular carcinoma (HCC) is currently unclear. Our objective was to investigate the association between serum levels of copper, zinc and their ratio (copper/zinc) at diagnosis with HCC survival. We included 989 patients with incident HCC in this prospective cohort study, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study within 30 days of diagnosis between September 2013 and February 2017. Serum copper and zinc were measured using inductively coupled plasma mass spectrometry. Primary outcomes were liver cancer-specific survival (LCSS) and overall survival (OS). Cox proportional hazards models were used to calculate the multivariable hazard ratios (HRs) and 95% confidence interval (CI). Higher serum copper levels were strongly associated with worse LCSS (Q4 vs. Q1: HR = 1.87, 95% CI: 1.22–2.86; p < 0.01 for trend) and OS (Q4 vs. Q1: HR = 2.06, 95% CI: 1.36–3.11; p < 0.01 for trend). The calculated copper/zinc ratio was positively associated with LCSS (Q4 vs. Q1: HR = 1.31, 95% CI: 0.89–1.92; P = 0.04 for trend) and OS (Q4 vs. Q1: HR = 1.43, 95% CI: 0.99–2.08; P = 0.01 for trend). No overall associations were observed between serum zinc levels and LCSS or OS in the entire cohort. The results suggest that higher serum copper and copper in relation to zinc levels (i.e., higher copper/zinc ratio) may be associated with worse HCC survival, but serum zinc levels may be not associated with HCC survival.     

Percutaneous microwave ablation of 5-6 cm unresectable hepatocellular carcinoma: local efficacy and long-term outcomes

Objective: This study aims to evaluate the local efficacy and long-term outcomes of microwave ablation (MWA) for treating large unresectable hepatocellular carcinomas (HCCs).

Methods: A total of 82 patients with 5-6?cm unresectable HCCs, who underwent a single MWA procedure during the period of January 2007 to July 2011, were retrospectively enrolled into this study. Percentages of technical success and complications of MWA and HCC local recurrence (LR) after MWA were determined. In addition, prognostic factors were screened and overall survival (OS) and recurrence-free survival (RFS) rates were estimated.

Results: One-, three- and five-year OS rates in this MWA-treated cohort were 92.7, 63.4 and 41.1%, respectively; and the corresponding RFS rates were 65.9, 31.7 and 23.0%, respectively. Primary technical efficacy was 89.0% after the first round of ablation, three (3.7%) patients developed major complications, and LR rate was 20.7%. Child-Pugh classification (p?p?=?.049) and LR (p?=?.002) were independent factors associated with OS, as determined by multivariate analysis.

Conclusions: MWA is safe and effective for the treatment of selected large HCCs, and provides an alternative treatment option for patients with unresectable HCCs. Furthermore, the favourable local efficacy of MWA could potentially improve long-term survival.     

Transarterial chemoembolization for the treatment of hepatocellular carcinoma: A single center experience including 221 patients

BackgroundHepatocelluar carcinoma (HCC) is a major health problem in Egypt as well as in many countries. Transarterial chemoemoblization (TACE) is a treatment modality applicable to locally advanced HCC beyond surgery or ablative therapies and is associated with survival improvements. The aim of this study was to assess the outcomes of TACE in our center over the past four years.MethodsThis is a retrospective cohort study that included 221 patients with locally advanced HCC treated with TACE in a single center between the years 2007 and 2010. The median age was 57 years with male predominance. Liver cirrhosis, viral hepatitis and Bilharziasis were encountered in 64%, 31% and 8% of patients, respectively. Abdominal pain was the most common presenting symptom (67%). Most cases were diagnosed based on radiology (57%) with a TNM stage I or II (73%) and a median AFP value of 150 ng/mL.Results221 patients received 440 cycles of TACE with a median of 2 cycles per patient. Cisplatin and doxorubicin (50 mg per cycle, each) were the most commonly used drugs. Impaired liver function was the most common toxicity. Liver cell failure occurred in 17% of patients. An objective tumor response was achieved in 44% of cases. The median overall survival (OS) was 16 months (95% CI, 13–19 months) and the median progression free survival (PFS) was 6 months (95% CI, 4.3–7.8 months). Responding patients, Child-Pugh class A and patients receiving standard doses of chemotherapy had a significantly better OS than their counterparts. Only Child-Pugh class A was associated with significantly longer PFS (p < 0.001).ConclusionTACE produces reasonable responses and fair survival rates in locally advanced HCC but with noticeable toxicities. Proper patients’ selection and prompt liver support are mandates for improving TACE outcomes.     

Aggressive intrahepatic therapies for synchronous hepatocellular carcinoma with pulmonary metastasis

Purpose

Prognosis of synchronous hepatocellular carcinoma (HCC) patients with pulmonary metastasis (PM) was poor, while aggressive intrahepatic therapies remained controversial. This study aimed to investigate the significance of aggressive intrahepatic therapies for synchronous PM–HCC.

Methods

Synchronous PM–HCC patients were retrospectively enrolled from Sun Yat-sen Memorial Hospital of Sun Yat-sen University during January 2000 and December 2015. Univariate and multivariate analysis were performed to investigate the prognostic factors. Patients were grouped according to different HCC treatment modalities including liver resection (LR), ablation, transarterial chemoembolization (TACE), systemic therapy (ST, systemic chemotherapy or sorafenib) and supportive care (SC). Case control studies were achieved using propensity score matching (PSM) analysis to further investigate the significance of LR, ablation and TACE.

Results

Eighty-one patients were enrolled, and the median overall survival (OS) was 4.5 months. Serum alpha fetal protein (AFP) ≥ 400 ng/ml, multiple HCC lesions and no intrahepatic therapies (LR/Ablation/TACE) were inferior independent prognostic factors. Patients were divided into LR group (n = 9), Ablation/TACE group (n = 24) and ST/SC group (n = 48). After PSM analysis, survival outcome was superior in LR group compared to Ablation/TACE group (19.6 vs. 6.9 months) (p = 0.023) or ST/SC group (19.6 vs. 2.8 months) (p = 0.034), while no significant difference was found between -Ablation/TACE and ST/SC group (5.1 vs. 3.2 months) (p = 0.338).

Conclusions

Prognosis of synchronous PM–HCC patients was poor. Serum AFP ≥ 400 ng/ml, multiple HCC lesions and no aggressive intrahepatic therapies were inferior prognostic factors. LR might provide survival benefits in well-selected patients, while the significance of ablation or TACE remained to be further investigated.

     

EGFR-TKIs plus local therapy demonstrated survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases

To investigate whether addition of local therapy to EGFR-TKIs could provide survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases (LM). Patients with EGFR-mutant NSCLC and oligometastatic or oligoprogressive LM who met inclusion criteria were retrospectively identified. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and patterns of failure. Addition of local therapy was associated with a significantly longer PFS (13.8 vs. 8.6 m, p <0.001) and OS (31.2 vs. 18.5 m, p <0.001) in whole group. In oligometastatic cohort, 20 patients received EGFR-TKIs and 23 received EGFR-TKIs plus local therapy as first-line treatment. Addition of local therapy showed a significantly longer PFS (12.9 vs. 7.9 m, p = 0.041) and OS (36.8 vs. 21.3 m, p = 0.034) than EGFR-TKIs alone. In oligoprogressive cohort, 24 patients received continuation of EGFR-TKIs plus local therapy and 25 received switching chemotherapy. Median PFS2 (13.9 vs. 9.2 m, p = 0.007) and OS (28.3 vs. 17.1 m, p = 0.011) was significantly longer in combined group than in switching chemotherapy group. Distant metastatic sites progression was the major pattern of failure in combined group while locoregional recurrence was the major reason in monotherapy or switching chemotherapy group. Our study suggested that EGFR-TKIs plus local therapy showed prolonged survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive LM, indicating addition of local therapy would be alternative choice in this clinical scenario.     

Different Types of <i>ROS1</i> Fusion Partners Yield Comparable Efficacy to Crizotinib

ROS1 rearrangements define a distinct molecular subset of non-small-cell lung cancer (NSCLC), which can be treated effectively with crizotinib, a tyrosine kinase inhibitor (TKI) targeting ROS1/MET/ALK rearrangements. Diverse efficacy was observed in ROS1-rearranged NSCLC patients. Because of its rareness, very limited studies have investigated the correlation between different fusion partners and response to crizotinib. In this study, we retrospectively screened 6,235 advanced NSCLC patients (stage IIIB to IV) from five hospitals and identified 106 patients with ROS1 rearrangements based on either plasma or tumor tissue testing using capturebased targeted sequencing. The most frequently occurring fusion partners included cluster of differentiation 74 (CD74), ezrin (EZR), syndecan 4 (SDC4), and tropomyosin 3 (TPM3), occurring in 49.1%, 17%, 14.2%, and 4.7% of patients, respectively. Among them, 38 patients were treated with crizotinib. Seventeen patients were treatment naive, and the remaining were previously treated with pemetrexed-based chemotherapy. Collectively, there was no significant difference among patients with various types of ROS1 fusion partners in overall survival (OS) and progression-free survival (PFS). Patients who were treated with crizotinib as first-line therapy showed comparable PFS (p=0.26) to patients who were previously treated with pemetrexed-based chemotherapy. For treatment-naive patients, patients with low baseline ROS1 allelic fraction (AF) had a statistically significant longer OS than those with high ROS1 AF (184 vs. 110 days, p=0.048). Collectively, our study demonstrates that ROS1⁺ patients with various fusion partners show comparable efficacy to crizotinib.     

Survival benefit of patients with inoperable hepatocellular carcinoma treated by a combination of transarterial chemoembolization and percutaneous ethanol injection—a single-center analysis including 132 patients

Hepatocellular carcinoma (HCC) is one of the most severe sequelae of chronic liver disease. The only potentially curative therapeutic options are surgical resection and orthotopic liver transplantation. In most HCC patients, however, at clinical presentation the tumors are unresectable because of multicentricity or poor hepatic functional reserve due to pre-existing cirrhosis or not transplantable because of too advanced tumor stage or severe co-morbidity. In clinical practice, therefore, percutaneous ethanol injection (PEI) and transarterial chemoembolization (TACE) are widely used non-surgical therapeutic strategies. We prospectively analyzed the clinical factors determining the prognosis of 132 inoperable HCC patients and assessed the feasibility, therapeutic efficacy and safety of PEI, TACE and a combination thereof. Mean age of patients was 64 years; 95% of patients had liver cirrhosis and 39% were Okuda stage I, 48% stage II and 13% stage III. Fifteen patients were treated by PEI (group 1), 33 by TACE (group 2), 39 by TACE and PEI (group 3) and 45 received best supportive care (group 4). Survival correlated with the Child-Pugh class of liver cirrhosis and the Okuda stage of HCC. Favorable prognostic parameters were alpha-fetoprotein (AFP) levels <100 ng/ml and absence of portal vein thrombosis. Median survival time was 18 months in group 1 [interquartile range (IQR) 10–19], 8 months in group 2 (IQR 5–15), 25 months in group 3 (IQR 13–36) and 2 months in group 4 (IQR 1–9). Multivariate analysis revealed that patients treated with a combination of TACE and PEI have a significantly better survival than patients receiving either PEI or TACE only (p = 0.001). Patients with inoperable HCCs treated by the combination of TACE and PEI have a clear survival benefit. A favorable outcome can be expected in patients with compensated cirrhosis, a low Okuda stage, a baseline AFP level <100 ng/ml and absence of portal vein thrombosis. Int. J. Cancer (Pred. Oncol.) 79:601–605, 1998. © 1998 Wiley-Liss, Inc.     

Donor miR‐196a‐2 polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation in a Han Chinese population

Recurrence of hepatocellular carcinoma (HCC) is one of the leading causes of death after liver transplantation (LT). We aim to evaluate the association of donor and recipient single nucleotide polymorphisms (SNPs) with the risk of HCC recurrence after LT. A total of 155 adult patients who underwent primary LT for HCC were enrolled. Ten SNPs associated with HCC susceptibility were genotyped. Patients who received donor livers with the rs11614913 homozygous CC variant presented significantly higher recurrence rates of HCC (41.7 vs. 15.3%, p = 0.009) and lower cumulative tumor‐free survival (p = 0.005) than those who received TT wild‐type donor livers. The donor rs11614913 genetic variant was an independent risk factor for HCC recurrence (odds ratio = 2 per each C allele, p < 0.05) and could significantly improve the predictive abilities of clinical models (Milan, UCSF and Hangzhou criteria). Donor livers homozygous for rs11614913 CC were associated with a higher miR‐196a expression than TT (p = 0.002). In a lentiviral infection of mouse liver and orthotopic mouse model of HCC, the liver miR‐196a overexpression group showed a significantly larger tumor size than the control group (p = 0.001). There is a close association between the tumor size and expression of miR‐196a in the liver (r = 0.693, p = 0.001). In conclusion, the donor miR‐196a‐2 rs11614913 polymorphism is associated with HCC recurrence after LT and improves the predictive value of clinical models. The overexpression of miR‐196a in the liver might provide a tumor‐favorable environment for the development of HCC.     

Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: Long-term results of phase 3 randomized controlled trial

To report long-term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III–IVB (except T3–4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m² d1), cisplatin (60 mg/m² d1), and fluorouracil (600 mg/m²/d civ d1–5) every 3 weeks. Patients from both groups received intensity-modulated radiotherapy concurrently with three cycles of 100 mg/m² cisplatin every 3 weeks. After a median follow-up of 71.5 months, the IC plus CCRT group showed significantly better 5-year failure-free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure-free survival (88% vs. 79.8%, p = 0.030), and locoregional failure-free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein–Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long-term follow-up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.     

Real-life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program

Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real-life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression-free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti-HER2 targeted therapies use, we thus performed a subanalysis in HER2− patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to “Other chemotherapies” patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth-line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p < 0.0001, third and fourth-line). No significant difference was reported in second-line (PFS: 5.06 vs. 4.14 months, p = 0.1171; OS: 13.99 vs. 11.66 months, p = 0.151). Among HER2− patients, a significant difference was seen for all lines, including 2nd-line (PFS: 4.57 vs. 3.91 months, p = 0.0379; OS: 14.98 vs. 10.51 months, p = 0.0113). In this large real-world database, HER2-negative MBC patients receiving EM in second or later CT line presented significantly better PFS and OS. This difference disappeared in second line in the overall population, probably because of the imbalance in HER2-targeted treatments use. Our results mirror those of the published randomized trials. The effect of anti-HER2 therapies addition in this setting still needs to be defined.     

Adjuvant chemotherapy for patients with primary hepatocellular carcinoma: A meta‐analysis

Numerous studies have investigated the effects of adjuvant chemotherapy for primary hepatocellular carcinoma (HCC) patients. We conducted this analysis to evaluate the efficacy of adjuvant chemotherapy in HCC patients after hepatectomy. PubMed/MEDLINE, EMBASE, Cochrane, and other databases were searched for eligible studies. The major endpoints were overall survival (OS) and disease‐free survival (DFS). The pooled odds ratio (OR) was calculated using a random‐effects model to summarize the results. In the meta‐analysis of 13 randomized control trials (RCTs) and 35 observational studies with 4747 patients, hepatectomy plus adjuvant chemotherapy showed superiority over hepatectomy alone in 1‐year DFS (OR = 1.86, 1.38–2.51, p < 0.001), 3‐year DFS (OR = 2.37, 1.73–3.24, p < 0.001) and 5‐year DFS (OR = 1.99, 1.55–2.55, p < 0.001), as well as 1‐year OS (OR = 2.16, 95% confidence interval 1.75–2.68, p < 0.001), 3‐year OS (OR = 1.77, 1.48–2.13, p < 0.001) and 5‐year OS (OR = 1.92, 1.44–2.56, p < 0.001). Subgroup and sensitivity analysis revealed that only adjuvant TACE had significant survival benefits. The meta‐analysis of studies involving patients with portal vein tumor thrombus (PVTT), but not other factors related to recurrence risk, revealed favorable outcomes of the Treatment arm over the Control arm. The present study shows that adjuvant chemotherapy can improve outcomes for HCC patients. The benefits of adjuvant TACE have been confirmed whereas the effects of other adjuvant chemotherapy modalities remain uncertain. Adjuvant chemotherapy is likely to be more applicable to certain patient populations for instance those with PVTT, but further research in identifying these patient factors is of importance for tailoring adjuvant therapies to individual patients in the future.     

Antiviral therapy improves overall survival in hepatitis C virus‐infected patients who develop diffuse large B‐cell lymphoma

Chronic Hepatitis C virus (HCV) infection is associated with increased incidence of non‐Hodgkin lymphoma. Several studies have demonstrated regression of indolent lymphoma with antiviral therapy (AVT) alone. However, the role of AVT in HCV‐infected patients with diffuse large B‐cell lymphoma (DLBCL) is unclear. We therefore analyzed AVT's impact on oncologic outcomes of HCV‐infected patients (cases) who developed DLBCL. Cases seen at our institution (June 2004–May 2014) were matched with uninfected counterparts (controls) and then divided according to prior AVT consisting of interferon‐based regimens. We studied 304 patients (76 cases and 228 controls). More cases than controls had extranodal (79% vs. 72%; p = 0.07) and upper gastrointestinal (GI; 42% vs. 24%; p = 0.004) involvement. Cases never given AVT had DLBCL more refractory to first‐line chemotherapy than that in the controls (33% vs. 17%; p = 0.05) and exhibited a trend toward more progressive lymphoma at last examination compared to controls (50% vs. 32%; p = 0.09) or cases given AVT (50% vs. 27%; p = 0.06). Cases never given AVT had worse 5‐year overall survival (OS) rates than did the controls (HR, 2.3 [95% CI, 1.01–5.3]; p = 0.04). Furthermore, AVT improved 5‐year OS rates among cases in both univariate (median [Interquartile range]: 39 [26–56] vs. 16 [6–41] months, p = 0.02) and multivariate analyses (HR = 0.21 [95% CI, 0.06–0.69]; p = 0.01). This study highlights the negative impact of chronic HCV on survival of DLBCL patients and shows that treatment of HCV infection is associated with a better cancer response to chemotherapy and improves 5‐year OS.     

Influence of mRNA expression of epiregulin and amphiregulin on outcome of patients with metastatic colorectal cancer treated with 5‐FU/LV plus irinotecan or irinotecan plus oxaliplatin as first‐line treatment (FIRE 1‐trial)

Our aim was to investigate the impact of EREG and AREG mRNA expression (by RT‐qPCR) in patients with metastatic colorectal cancer (mCRC). In addition, epidermal growth factor receptor (EGFR) expression (by immunohistochemistry) as well as RAS‐and PIK3CA‐mutations (by pyrosequencing) were assessed. Tumors of 208 mCRC patients receiving 5‐fluorouracil/leucovorin plus irinotecan (FUFIRI) or irinotecan plus oxaliplatin (mIROX) within the FIRE‐1 trial were analyzed for mutations. Molecular characteristics were correlated with response, progression‐free survival (PFS), overall survival (OS). mRNA expression was evaluated using ROC‐analysis in 192 tumors (AREG high n = 31 vs. low n = 161; EREG high n = 89 vs. low n = 103). High versus low AREG expression was associated with PFS of 10.0 versus 8.0 months (HR = 0.62, 95% CI: 0.402–0.940, p = 0.03) and OS of 24.6 versus 18.7 months (HR = 0.72, 95% CI: 0.476–1.078, p = 0.11). High versus low EREG expression correlated with prolonged PFS (9.4 vs. 6.8 months, HR = 0.62, 95% CI: 0.460–0.846, p = 0.002) and OS (25.8 vs. 15.5 months, HR = 0.48, 95% CI: 0.351–0.657, p < 0.001). The positive prognostic effect of high EREG expression was confirmed in a multivariate analysis and was neither affected by EGFR expression nor by mutations of RAS‐ and PIK3CA‐genes. EREG expression appears as an independent prognostic marker in patients with mCRC receiving first‐line irinotecan‐based chemotherapy.     

Plasma circular RNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma: A large-scale,multicenter study

To explore whether plasma circular RNAs (circRNAs) can diagnose hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), microarray and qPCR were used to identify plasma circRNAs that were increased in HBV-related HCC patients compared to controls (including healthy controls, chronic hepatitis B and HBV-related liver cirrhosis). A logistic regression model was constructed using a training set (n = 313) and then validated using another two independent sets (n = 306 and 526, respectively). Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. We identified a plasma circRNA panel (CircPanel) containing three circRNAs (hsa_circ_0000976, hsa_circ_0007750 and hsa_circ_0139897) that could detect HCC. CircPanel showed a higher accuracy than AFP (alpha-fetoprotein) to distinguish individuals with HCC from controls in all three sets (AUC, 0.863 [95% confidence interval, CI: 0.819–0.907] vs. 0.790 [0.738–0.842], p = 0.036 in training set; 0.843 [0.796–0.890] vs. 0.747 [0.691–0.804], p = 0.011 in validation set 1 and 0.864 [0.830–0.898] vs. 0.769 [0.728–0.810], p < 0.001 in validation set 2). CircPanel also performed well in detecting Small-HCC (solitary, ≤3 cm), AFP-negative HCC and AFP-negative Small-HCC.     

Microwave ablation with chemoembolization for large hepatocellular carcinoma in patients with cirrhosis

Objective: To evaluate the safety and long-term outcomes of microwave ablation (MWA) combined with transarterial chemoembolization (TACE) in a single stage for the treatment of hepatocellular carcinoma (HCC) with a maximum diameter of 5.0–10.0?cm.

Methods: From January 2013 to December 2016, 84 consecutive HCC patients with cirrhosis from two medical centers who underwent MWA-TACE as a first-line treatment for up to three HCCs with maximum diameters of 5.0–10.0?cm were included. Feasibility, safety and effectiveness were evaluated. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. Cox regression models were used to identify the prognostic factors.

Results: The technique was successfully performed in all the patients. Grade 3 complications consisted of two cases of hemoperitoneum requiring blood transfusions and embolization. The cumulative incidence of local tumor progression was 25.8% at 3?years, with tumor size found to be the only significant predictive factor (p?=?.007). The cumulative incidence of OS was 81%, 68% and 49% at 1, 2 and 3?years, respectively. According to the Cox proportional hazards model analysis, serum AFP level, Child-Pugh class and tumor number were significant prognostic factors for OS.

Conclusion: MWA-TACE is a safe, feasible and effective therapy for the treatment of 5.0- to 10.0-cm HCC lesions in patients with cirrhosis.     

Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma

We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin–gemcitabine (GC) regimen (800 mg/m² gemcitabine on Days 1 and 8 and 20 mg/m² cisplatin on Days 1–5, every 4 weeks) (sGC‐RT); sequential chemoradiotherapy with a cisplatin–fluorouracil (PF) regimen (20 mg/m² DDP and 500 mg/m² 5‐FU on Days 1–5, every 4 weeks) (sPF‐RT) and cisplatin‐based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con‐RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3‐year overall survival (OS), disease‐free survival (DFS) and distant metastasis‐free survival (DMFS) rates in the sGC‐RT group were significantly higher than those observed in the Con‐RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3‐year OS, DFS and MFS rates between the Con‐RT and the sPF‐RT groups. The GC‐RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC‐RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.     

Presence of EpCAM‐positive circulating tumor cells as biomarker for systemic disease strongly correlates to survival in patients with hepatocellular carcinoma

Current imaging technologies do not sufficiently detect micrometastasis and therefore do not allow adequate stratification of patients with hepatocellular carcinoma (HCC) for curative or systemic therapy. In HCC, presence of stem cell‐like, epithelial cell adhesion molecule (EpCAM)‐positive cells correlates with tumor aggressiveness and formation of metastasis. Therefore, we investigated the prognostic relevance of EpCAM‐positive circulating tumor cells (CTCs) in patients with HCC. Blood from 78 patients (19 patients in the control cohort and 59 patients with HCC) was tested for CTCs with the CellSearch? system. Correlation analysis to overall survival (OS), the Barcelona Clinic Liver Cancer (BCLC) staging system, macroscopic and microscopic vascular invasion and alpha‐fetoprotein (AFP) levels were performed. We detected ≥1 CTC in 18/59 HCC patients and in 1/19 patients with cirrhosis or benign hepatic tumor (p = 0.026). OS was significantly shorter (460 vs. 746 days) in the CTC‐positive cohort (p = 0.017). Comparing BCLC stages, significant differences in CTC detection rates were also observed: BCLC stages A 1/9, B 6/31 and C 11/19 (p = 0.006). Ten of 18 patients with macroscopic and 10/16 patients with microscopic vascular invasion exhibited positive findings in CTC testing (p = 0.004 and p = 0.006). Furthermore, CTC results correlated to AFP (cutoff > 400 ng/mL) levels (p = 0.050). Our study demonstrates frequent presence of EpCAM‐positive CTC in patients with intermediate or advanced HCC and its prognostic value for OS with possible implications for future treatment stratification.     

Efficacy and Safety of Drug-Eluting Beads Transarterial Chemoembolization by CalliSpheres^® in 275 Hepatocellular Carcinoma Patients: Results From the Chinese CalliSpheres^® Transarterial Chemoembolization in Liver Cancer (CTILC) Study

The purpose of this study was to investigate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) treatment in Chinese hepatocellular carcinoma (HCC) patients and the prognostic factors for treatment response as well as survival. A total of 275 HCC patients were included in this prospective study. Treatment response was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST), and progression-free survival (PFS) as well as overall survival (OS) were determined. Liver function and adverse events (AEs) were assessed before and after DEB-TACE operation. Complete response (CR), partial response (PR), and objective response rate (ORR) were 22.9%, 60.7%, and 83.6%, respectively. The mean PFS was 362 (95% CI: 34.9–375) days, the 6-month PFS rate was 89.4±2.1%, while the mean OS was 380 (95% CI: 370–389) days, and the 6-month OS rate was 94.4±1.7%. Multivariate logistic regression revealed that portal vein invasion (p=0.011) was an independent predictor of worse clinical response. Portal vein invasion (p=0.040), previous cTACE treatment (p=0.030), as well as abnormal serum creatinine level (BCr) (p=0.017) were independent factors that predicted worse ORR. In terms of survival, higher Barcelona Clinic Liver Cancer (BCLC) stage (p=0.029) predicted for worse PFS, and abnormal albumin (ALB) (p=0.011) and total serum bilirubin (TBIL) (p=0.009) predicted for worse OS. The number of patients with abnormal albumin, total protein (TP), TBIL, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were augmented at 1 week posttreatment and were similar at 1–3 months compared with baseline. The most common AEs were pain, fever, nausea, and vomiting, and no severe AEs were observed in this study. DEB-TACE was effective and tolerable in treating Chinese HCC patients, and portal vein invasion, previous cTACE treatment, abnormal BCr, ALB, and TBIL appear to be important factors that predict worse clinical outcome.