Adding three cycles of induction chemotherapy with gemcitabine and cisplatin to concurrent chemoradiotherapy improved 3-year recurrence-free survival (85.3%, vs. 76.5% with concurrent ...chemoradiotherapy alone) and overall survival (94.6% vs. 90.3%). Patients receiving induction chemotherapy were more likely to have grade 3 or 4 myelosuppression, nausea, and vomiting.
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.
What's new?
Despite advances in the treatment of nasopharyngeal carcinoma, approximately 30% of high‐risk patients experience recurrence after treatment. Here the authors find that combining the conventional chemoradiotherapy with a triple induction chemotherapy (cisplatin/fluorouracil/docetaxel) prolonged survival of patients with locoregionally advanced cancer, even after more than 70 months of follow‐up. The combination treatment increased acute, but not late, toxicities, and the authors propose that it could present a new treatment option for this patient group.
There are no global screening recommendations for esophageal squamous cell carcinoma (ESCC). Endoscopic screening has been investigated in areas of high incidence in China since the 1970s. This study ...aimed to evaluate whether an endoscopic screening and intervention program could reduce mortality caused by ESCC.
Residents age 40 to 69 years were recruited from communities with high rates of ESCC. Fourteen villages were selected as the intervention communities. Ten villages not geographically adjacent to intervention villages were selected for comparison. Participants in the intervention group were screened once by endoscopy with Lugol's iodine staining, and those with dysplasia or occult cancer were treated. All intervention participants and a sample consisting of one tenth of the control group completed questionnaires. We compared cumulative ESCC incidence and mortality between the two groups.
Three thousand three hundred nineteen volunteers (48.62%) from an eligible population of 6,827 were screened in the intervention group. Seven hundred ninety-seven volunteers from an eligible population of 6,200 in the control group were interviewed. Six hundred fifty-two incident and 542 fatal ESCCs were identified during the 10-year follow-up. A reduction in cumulative mortality in the intervention group versus the control group was apparent (3.35% v 5.05%, respectively; P < .001). Furthermore, the intervention group had a significantly lower cumulative incidence of ESCC versus the control group (4.17% v 5.92%, respectively; P < .001).
We showed that endoscopic screening and intervention significantly reduced mortality caused by esophageal cancer. Detection and treatment of preneoplastic lesions also led to a reduction in the incidence of this highly fatal cancer.
Nitrogen‐doped carbon nanofiber webs (CNFWs) with high surface areas are successfully prepared by carbonization‐activation of polypyrrole nanofiber webs with KOH. The as‐obtained CNFWs exhibit a ...superhigh reversible capacity of 943 mAh g−1 at a current density of 2 A g−1 even after 600 cycles, which is ascribed to the novel porous nanostructure and high‐level nitrogen doping.
The diagnosis of biliary atresia (BA) remains a clinical challenge because affected infants have signs, symptoms, and serum liver biochemistry that are also seen in those with other causes of ...neonatal cholestasis (non‐BA). However, an early diagnosis and prompt surgical treatment are required to improve clinical outcome. Recently, the relative abundance of serum matrix metalloproteinase‐7 (MMP‐7) was suggested to have discriminatory features for infants with BA. To test the hypothesis that elevated serum concentration of MMP‐7 is highly diagnostic for BA, we determined the normal serum concentration of MMP‐7 in healthy control infants, and then in 135 consecutive infants being evaluated for cholestasis. The median concentration for MMP‐7 was 2.86 ng/mL (interquartile range, IQR: 1.32‐5.32) in normal controls, 11.47 ng/mL (IQR: 8.54‐24.55) for non‐BA, and 121.1 ng/mL (IQR: 85.42‐224.4) for BA (P < 0.0001). The area under the curve of MMP‐7 for the diagnosis of BA was 0.9900 with a cutoff value of 52.85 ng/mL; the diagnostic sensitivity and specificity were 98.67% and 95.00%, respectively, with a negative predictive value of 98.28%. Conclusion: Serum MMP‐7 assay has high sensitivity and specificity to differentiate BA from other neonatal cholestasis, and may be a reliable biomarker for BA.
Chiral luminescent lanthanide–organic cages have many potential applications in enantioselective recognition, sensing, and asymmetric catalysis. However, due to the paucity of structures and their ...limited cavities, host–guest chemistry with lanthanide–organic cages has remained elusive so far. Herein, we report a guest-driven self-assembly and chiral induction approach for the construction of otherwise inaccessible Ln4L4-type (Ln = lanthanide ions, i.e., EuIII, TbIII; L = ligand) tetrahedral hosts. Single crystal analyses on a series of host–guest complexes reveal remarkable guest-adaptive cavity breathing on the tetrahedral cages, reflecting the advantage of the variation tolerance on coordination geometry of the f-elements. Meanwhile, noncovalent confinement of pyrene within the lanthanide cage not only leads to diminishment of its excimer emission but also facilitates guest to host energy transfer, opening up a new sensitization window for the lanthanide luminescence on the cage. Moreover, stereoselective self-assembly of either Λ4- or Δ4- type Eu4L4 cages has been realized via chiral induction with R/S-BINOL or R/S-SPOL templates, as confirmed by NMR, circular dichroism (CD), and circularly polarized luminescence (CPL) with high dissymmetry factors (g lum) up to ±0.125.
Background
Since 2018, atrophy of the bursa has been found among vaccinated chickens with high antibody titres against infectious bursal disease virus (IBDV) in Fujian, China, suggesting poor vaccine ...efficacy against circulating IBDV strains.
Methods
Novel IBDV strains were isolated, and vp2 and vp1 genes were sequenced and used to carry out phylogenetic analysis. Pathogenicity was investigated using 21‐day‐old specific pathogen‐free (SPF) chickens. In addition, the effectiveness of current commercial vaccines used in China was evaluated against the isolated novel IBDV strains.
Results
Six IBDV isolates were successfully obtained, which formed an independent cluster and belonged to genotype A2dB1, based on phylogenetic analysis of the vp2 and vp1 genes. The pathogenicity of the novel IBDV FJ2019‐01 isolate in 21‐day‐old SPF chickens was characterised by severe atrophy of the bursa and a largely decreased number of lymphocytes, atrophy of the follicle and broadening of mesenchyme in the bursa 3–23 days after infection. Unfortunately, all vaccinated chickens with high antibody titres against IBDV also developed atrophy and largely decreased lymphocytes in the bursa, as in the unvaccinated birds challenged with FJ2019‐01. Furthermore, high viral loads of FJ2019‐01 were detected in the bursa of all vaccinated chickens.
Conclusions
These findings suggest that current commercial IBDV vaccines used in China did not provide protection against novel IBDV variants.
Summary Background The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is ...unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial. Methods We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III–IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18–59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m2 cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m2 on day 1), intravenous cisplatin (60 mg/m2 on day 1), and continuous intravenous fluorouracil (600 mg/m2 per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov , number NCT01245959. Findings Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38–49), 3-year failure-free survival was 80% (95% CI 75–85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66–78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48–0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 42% vs 17 7%), leucopenia (98 41% vs 41 17%), and stomatitis (98 41% vs 84 35%). Interpretation Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities. Funding Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000).
Enhancer of zeste homolog 2 (EZH2) is aberrantly expressed or mutated in multiple types of cancer cells and plays an oncogenic role in tumorigenesis and development in most cancers. Results from ...pilot clinical studies have implied that EZH2 inhibitors have therapeutic potential against some cancers. However, the exact mechanisms by which EZH2 plays oncogenic roles and EZH2 inhibition exerts anticancer effects are incompletely understood. To date, the findings of studies focusing on EZH2 and cancer cells have failed to fully explain the observations in preclinical and clinical studies. Therefore, recent studies about the roles of EZH2 in cancers have shifted from cancer cells to immune cells. The human immune system is a complex network comprising multiple subpopulations of immune cells. Immune cells communicate and interact with cancer cells during cancer development and treatment, dictating the fate of cancer cells. Elucidating the roles of EZH2 in immune cells, especially in cancer patients, promises the identification of novel immunotherapeutic strategies or priming of existing immunotherapies against cancer. Hence, we reviewed the studies focusing on the involvement of EZH2 in various immune cells, aiming to provide ideas for immunotherapies targeting EZH2 in immune cells.
Graphical
Review of EZH2 function in various immune cells to find ideas for cancer immunotherapies targeting EZH2 in immune cells.
Summary Background The effect of the addition of adjuvant chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to assess the ...contribution of adjuvant chemotherapy to concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone. Methods We did an open-label phase 3 multicentre randomised controlled trial at seven institutions in China. Randomisation was by a computer-generated random number code. Patients were stratified by treatment centre and randomly assigned in blocks of four. Treatment allocation was not masked. We randomly assigned patients with non-metastatic stage III or IV (except T3–4N0) nasopharyngeal carcinoma to receive concurrent chemoradiotherapy plus adjuvant chemotherapy or concurrent chemoradiotherapy alone. Patients in both groups received 40 mg/m2 cisplatin weekly up to 7 weeks, concurrently with radiotherapy. Radiotherapy was given as 2·0–2·27 Gy per fraction with five daily fractions per week for 6–7 weeks to a total dose of 66 Gy or greater to the primary tumour and 60–66 Gy to the involved neck area. The concurrent chemoradiotherapy plus adjuvant chemotherapy group subsequently received 80 mg/m2 adjuvant cisplatin and 800 mg/m2 per day fluorouracil for 120 h every 4 weeks for three cycles. Our primary endpoint was failure-free survival. We did efficacy analyses in our intention-to-treat population. Our trial is ongoing; in this report we present the 2 year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov , number NCT00677118. Findings 251 patients were assigned to the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 257 to the concurrent chemoradiotherapy alone group. After a median follow-up of 37·8 months (range 1·3–61·0), the estimated 2 year failure-free survival rate was 86% (95% CI 81–90) in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 84% (78–88) in concurrent chemoradiotherapy only group (hazard ratio 0·74, 95% CI 0·49–1·10; p=0·13). Stomatitis was the most commonly reported grade 3 or 4 adverse event during both radiotherapy (76 of 249 patients in the concurrent chemoradiotherapy plus adjuvant chemotherapy group and 82 of 254 in the concurrent chemoradiotherapy alone group) and adjuvant chemotherapy (43 21% of 205 patients treated with adjuvant chemotherapy). Interpretation Adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve failure-free survival after concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. Longer follow-up is needed to fully assess survival and late toxic effects, but such regimens should not, at present, be used outside well-designed clinical trials. Funding Sun Yat-sen University Clinical Research 5010 Programme (No 2007037), Science Foundation of Key Hospital Clinical Programme of Ministry of Health PR China (No 2010–178), and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2010).
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