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Background: The benefit of palliative gastrectomy for patients with metastatic gastric cancer (mGC) is controversial, and suitable candidates for surgery and treatment strategies remain unclear. The present study aimed to investigate the efficacy of palliative gastrectomy plus chemotherapy among patients with mGC and to identify the potential patients for such treatment using real-world data. Methods: A dataset of 236 patients with mGC diagnosed at the Sun Yat-Sen University Cancer Center from January 1, 2006 to December 31, 2012 were analyzed retrospectively. The cohort comprised 80 patients who had palliative gastrectomy plus chemotherapy (SC) and 156 patients who had chemotherapy only (CO). Propensity score matching (PSM) was employed to minimize the influence of confounders. Results: The median overall survival of the SC group was significantly better than that of the CO group (Before PSM: 17.0 months vs 12.0 months, P=0.038; after PSM: 17.0 months vs 13.0 months, P=0.017). In the multivariate analysis, SC (Before PSM: hazard ratio (HR) =0.68, P=0.023; after PSM: HR =0.64, P=0.021) was favored for better survival after adjustment for sex, age, year of diagnosis, primary tumor location, and tumor grade. Total gastrectomy (P=0.026) was associated with worse survival for the SC group. The significant survival advantage of SC over CO was retained in patients with single organ metastasis (P=0.016), peritoneal seedings (P=0.039), and those receiving taxane-based chemotherapy (P=0.011). Conclusion: SC could improve the overall survival of patients with mGC as compared with CO. The chemotherapy regimen and type of resection were proven to influence efficacy. Patients who received taxane-based regimens might be suitable for palliative gastrectomy. [ABSTRACT FROM AUTHOR]

Background: About 75% of newly diagnosed bladder cancer cases suffer from non-muscle invasive bladder cancer (NMIBC), which used to recur and progress despite transurethral resection of bladder tumor (TURBT). This meta-analysis was conducted to examine if combined application of intravesical bacille Calmette-Guérin (BCG) with chemotherapy is associated with better prognosis. Methods: Systematic searches of randomized controlled trials (RCTs) concerning NMIBC were performed in PubMed, EMbase, CENTRAL, CNKI, WanFang, VIP, CBM databases, and some specialized websites. Two researchers independently implemented study selection, quality assessment and data extraction. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for treatment effects on recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS) and disease-specific survival (DSS) were directly extracted, if available, or estimated using relevant data from included studies. Side effects, such as fever, gastrointestinal reaction, cystitis, irritative bladder symptoms and hematuria, were also extracted as outcome measurements, and associated relative risks (RRs) were calculated to assess treatment safety. RevMan 5.3 software was used to perform statistical analyses. Results: Thirteen RCTs containing 1,754 patients with NMIBC were included in this meta-analysis. Compared with BCG alone, the combination therapy significantly improved RFS (HR = 0.53, 95% CI: 0.43–0.66, P < 0.01), OS (HR = 0.66, 95%CI: 0.50–0.86, P = 0.002), and DSS (HR = 0.48, 95%CI: 0.29–0.80, P = 0.005). While PFS showed no obvious difference between combination therapy and BCG alone (HR = 0.65, 95%CI: 0.25–1.68, P = 0.38). The rate of fever (RR = 0.50, 95%CI: 0.27–0.91, P = 0.02), irritative bladder symptoms (RR = 0.69, 95%CI: 0.52–0.90, P = 0.007) and hematuria (RR = 0.50, 95%CI: 0.28–0.89, P = 0.02) were significantly decreased in patients treated with combination therapy compared to those with BCG alone. There were no statistically significant differences between combination therapy and BCG alone in toxicity (RR = 0.69, 95%CI: 0.34–1.40, P = 0.30), gastrointestinal reaction (RR = 2.54, 95%CI: 0.61–10.60, P = 0.20) or cystitis (RR = 0.67, 95%CI: 0.29–1.54, P = 0.34). Conclusions: Combined application of intravesical BCG and chemotherapy appears to be an effective treatment for patients with intermediate- to high-risk NMIBC, but not for those with tumor in situ alone or recurrent bladder cancer. [ABSTRACT FROM AUTHOR]

Crizotinib is an anti‑cancer drug with a substantial beneficial effect in advanced non‑small‑cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement. However, the real‑world data currently available on this drug are limited. Thus, the present study aimed to retrospectively examine the treatment patterns and survival outcome of 83 advanced NSCLC patients with ALK rearrangement in a single center in China. Of the 83 patients enrolled, 33 (39.8%) patients received crizotinib and the remaining 50 (60.2%) patients received chemotherapy as the initial therapy. The first‑line use of crizotinib prolonged the PFS1 (progression‑free survival to the first detection of subsequent disease progression) compared with chemotherapy (median, 18.5 vs. 4.9 months; P<0.001), however, it did not prolong the overall survival (OS; P=0.802). At the last follow up, 71 (85.5%) patients had received crizotinib and 12 (14.5%) patients were crizotinib‑naive. Patients who had received crizotinib exhibited a significantly longer OS as compared with those who were crizotinib‑naive [hazard ratio (HR) for mortality, 0.279; 95% confidence interval, 0.107‑0.727; P<0.05). Among the 71 patients who had received crizotinib, this was administered as a first‑line therapy in 33 (46.5%) cases, as a second‑line therapy in 22 (31.0%) cases and after the second‑line therapy in 16 (22.5%) cases. No significant difference in the OS among the three groups was observed (P=0.577). The Cox multivariate analysis identified the following independent negative prognostic factors for OS: Smoking history (HR=4.565), liver invasion at diagnosis (HR=4.294) and bone invasion at diagnosis (HR=2.587). In addition, the use of crizotinib (HR=0.319) was identified as a positive prognostic factor for OS. In conclusion, the present real‑world study revealed that the use of crizotinib improved the long‑term survival of patients with ALK‑positive advanced NSCLC. There was no difference in survival outcome between patients with initial use of crizotinib and those with subsequent use of crizotinib after first‑line therapy. [ABSTRACT FROM AUTHOR]

Intrinsic or acquired chemoresistance is a hurdle in oncology. Only 7%–16% of estrogen receptor α (ERα) positive breast cancer cases achieve a pathological complete response (pCR) after neo-adjuvant chemotherapy. Nogo-B receptor (NgBR) is a cell surface receptor that binds farnesylated Ras and promotes Ras translocation to the plasma membrane. Here, we demonstrate NgBR as a potential therapeutic target for ERα positive breast cancer patients to attenuate paclitaxel resistance. NgBR knockdown enhanced paclitaxel-induced cell apoptosis by modulating expression of p53 and survivin in ERα positive breast cancer cells via NgBR-mediated PI3K/Akt and MAPK/ERK signaling pathways. NgBR knockdown attenuated either 17β-estradiol or epidermal growth factor stimulated phosphorylation of ERα at Serine 118 residue. The ChIP-PCR assay further demonstrated that NgBR knockdown decreased ERα binding to the estrogen response element (ERE) of the ERα target gene and increased the binding of p53 to the promoter region of survivin to attenuate survivin transcription. In summary, our data suggest that NgBR expression is essential to promoting ERα positive breast cancer cell resistance to paclitaxel. Findings from this study implicate a novel therapeutic target for treating ERα positive breast cancer in neo-adjuvant/adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach.Patients and Methods: A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Peripheral blood was sampled prospectively for baseline expression of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS), CYP2A6 gene polymorphisms, and 5-FU pharmacokinetics.Results: The ORR and DCR were 41.0 and 76.9%. The median PFS, TTF, and OS were 4.13, 3.70, and 11.40 months. Grade 3-4 AEs occurred in only 13 patients, and grade 4 AEs occurred in only 1 of them. High OPRT/TS and peritoneal metastasis (vs. liver metastasis) independently predicted responding. High OPRT/DPD independently predicted grade 3-4 AEs. High AUC0-24h of 5-FU and metastatic/recurrent sites ≤2 (vs. >3) independently predicted prolonged PFS. Low baseline plasmic DPD independently predicted prolonged OS.Conclusions: Two-week, oral S-1/LV regimen demonstrated promising efficacy and safety as first-line chemotherapy for AGC. CLINICALTRIALS.Gov Identifier: NCT02090153. [ABSTRACT FROM AUTHOR]

Pediatric ovarian malignant tumors are an uncommon type of childhood cancer and account for only 1% of all malignancies in children. The main histopathologic type is germ cell tumor, which is different from adult ovarian tumor deriving mainly from epithelial tissue, including teratoma, gonadoblastoma, endodermal sinus tumor (also known as yolk sac tumor), polyembryony cancer, and embryonal carcinoma, choriocarcinoma. Non germ cell tumors include sex cord stromal tumor and epithelial tumors, sex cord stromal tumor including theca fibrous tumor, Sertoli-Leydig cell tumor and juvenile granulosa cell tumor. Most of adolescent patients are in early clinical stage at their first medical treatment and conservative operation is feasible. Effective treatment of tumors with fertility sparing are the aims of treatment for adolescent ovary tumors. [ABSTRACT FROM AUTHOR]

Background: Although general agreement exists on palliative surgery with intent of symptom palliation in advanced gastric cancer (AGC), the role of non-curative surgery for incurable, asymptomatic AGC is hotly debated. We aim to clarify the role of non-curative surgery in patients with incurable, asymptomatic AGC under the first-line chemotherapy. Methods: A total of 737 patients with incurable, asymptomatic advanced gastric adenocarcinoma between January 2008 and May 2012 at the Sun Yat-sen University Cancer Center were retrospectively analyzed, comprising 414 patients with non-curative surgery plus first-line chemotherapy, and 323 patients with first-line chemotherapy only. The clinicopathologic data, survival, and prognosis were evaluated, with propensity score adjustment for selection bias. Results: The median overall survival (OS) outcomes significantly favored non-curative surgery group over first-line chemotherapy only group in entire population (28.00 versus 10.37 months, P = 0.000), stage 4 patients (23.87 versus 10.37 months, P = 0.000), young patients (28.70 versus 10.37 months, P = 0.000) and elderly patients (23.07 versus 10.27 months, P = 0.031). The median OS advantages of non-curative surgery over first-line chemotherapy only were also maintained when the analyses were restricted to single organ metastasis (P = 0.001), distant lymph node metastasis (P = 0.002), peritoneal metastasis (P = 0.000), and multi-organ metastasis (P = 0.010). Significant OS advantages of non-curative surgery over chemotherapy only were confirmed solid by multivariate analyses before and after adjustment on propensity score (P = 0.000). Small subsets of patients with surgery of single metastatic lesion after previous curative gastrectomy, and with surgery of both primary and single metastatic sites showed sound median OS. Conclusions: There is a role for non-curative surgery plus first-line chemotherapy for incurable, asymptomatic AGC, in terms of survival. Randomized controlled trials are warranted to fill a gap in knowledge about the value of metastectomy and patient selection strategies. [ABSTRACT FROM AUTHOR]

Background and objective: No randomized trial has been reported comparing different chemotherapy regimens on disseminated nasopharyngeal carcinoma (NPC). This study aims to compare five cisplatin-based regimens including cisplatin + 5-fluororacil (PF), paclitaxel + cisplatin (TP), gemcitabine + cisplain (GP), paclitaxel + cisplatin + 5-fluororacil (TPF), and bleomycin + cisplatin + 5-fluororacil (BPF) regimen most frequently used as the first-line protocols for metastatic NPC retrospectively. Methods: Eight hundred and twenty-two patients with metastatic NPC were divided into five groups according to the regimen they received. Then, their response rate, toxicity, and long-term survival outcome as well as the prognostic factors were analyzed. Results: The higher response rates in GP and TPF regimens comparing to PF regimen were achieved ( Χ = 4.57, P = 0.033; Χ = 7.04, P = 0.008), as well as in TPF regimen comparing to TP regimen ( Χ = 5.579, P = 0.018). The occurrence rate of the major III-IV grade toxicity was significantly different between the five groups. However, no statistically significant difference was observed in progression-free survival (PFS; P = 0.247) and overall survival ( P = 0.127) among the five groups. Cox multivariate analysis identified the following independent prognostic factors: liver metastases, plasma Epstein Barr Virus (EBV)-DNA level, cycles of chemotherapy, and second-line chemotherapy. Conclusions: PF, TP, and GP are all effective regimens as the first-line chemotherapy for metastatic NPC, which can be well tolerated. Over four cycles of chemotherapy are recommended under no contraindication. Patients should transfer to the second-line regimen after the treatment failure of the first-line chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Bone is the most common site of metastases from nasopharyngeal carcinoma (NPC). Zoledronic acid (ZA) used to prevent skeletal-related events (SREs) of bone metastases has shown anti-tumor effects; yet, no report has been found on the survival benefit of ZA in NPC. This study aimed to evaluate whether ZA can bring survival benefits to patients with bone metastases from NPC. Methods: A total of 307 patients with of NPC who had bone metastases were analyzed retrospectively. The differences of survival between patients treated with chemotherapy combined with ZA and those with chemotherapy alone were evaluated by the log-rank test. The Cox multivariate analyses of clinical features and different treatment methods of the 307 patients were conducted. Results: The prevalence of SREs in the combined approach group was lower than that with chemotherapy alone (34% vs. 48%, X = 7.003, P = 0.008). The combined approach group had better progression-free survival (PFS) (11.5 vs. 5.5 months, P < 0.001) and overall survival (OS) (23.5 vs. 17.5 months, P < 0.001) than chemotherapy alone group. Cox multivariate analysis identified the following independent prognostic factors: ZA treatment, bone metastatic sites, baseline serum alkaline phosphatase (ALP) level, SREs and cycles of chemotherapy. Conclusions: ZA treatment combined with chemotherapy could reduce SREs and improve PFS and OS for NPC patients with bone metastases. [ABSTRACT FROM AUTHOR]

Although chemotherapy plus PD-1 blockade (chemo+anti-PD-1) has become the standard first-line therapy for advanced esophageal squamous cell carcinoma (ESCC), reliable biomarkers for this regimen are lacking. Here we perform whole-exome sequencing on tumor samples from 486 patients of the JUPITER-06 study and develop a copy number alteration-corrected tumor mutational burden that depicts immunogenicity more precisely and predicts chemo+anti-PD-1 efficacy. We identify several other favorable immunogenic features (e.g., HLA-I/II diversity) and risk oncogenic alterations (e.g., PIK3CA and TET2 mutation) associated with chemo+anti-PD-1 efficacy. An esophageal cancer genome-based immuno-oncology classification (EGIC) scheme incorporating these immunogenic features and oncogenic alterations is established. Chemo+anti-PD-1 achieves significant survival improvements in EGIC1 (immunogenic feature-favorable and oncogenic alteration-negative) and EGIC2 (either immunogenic feature-favorable or oncogenic alteration-negative) subgroups, but not the EGIC3 subgroup (immunogenic feature-unfavorable and oncogenic alteration-positive). Thus, EGIC may guide future individualized treatment strategies and inform mechanistic biomarker research for chemo+anti-PD-1 treatment in patients with advanced ESCC. [Display omitted] • Prospectively collected ESCC specimens from a phase 3 trial on immunochemotherapy • CNA-corrected TMB predicts benefit from chemotherapy plus anti-PD-1 • Identified resistance genomic events to immunochemotherapy in ESCC • Immuno-oncogenic classification sheds light on individualized treatment in ESCC Chen et al. perform genomic analyses on prospectively collected ESCC specimens from the JUPITER-06 trial and identify genomic immune-oncogenic characteristics associated with benefits from chemotherapy plus anti-PD-1 in ESCC. The esophageal cancer genome-based immuno-oncogenic classification scheme developed based on these characteristics sheds light on individualized treatment for ESCC patients. [ABSTRACT FROM AUTHOR]