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PURPOSE Pembrolizumab or nivolumab plus chemotherapy was approved as a first-line treatment for high programmed cell death ligand 1 (PD-L1)–expressing esophageal squamous cell carcinoma (ESCC) by the European Medicines Agency, whereas the US Food and Drug Administration approved this regimen regardless of PD-L1 expression. The superiority of programmed death-1 (PD-1) antibody plus chemotherapy over chemotherapy alone in patients with low PD-L1–expressing ESCC remains debatable. METHODS Post hoc analysis of the Chinese JUPITER-06 study focusing on efficacy stratified by PD-L1 tumor proportion score (TPS; using JS311 antibody) was conducted. Electronic databases were searched to identify eligible randomized controlled trials for meta-analysis. Study-level pooled analyses of hazard ratios (HRs) for overall survival and progression-free survival and odds ratios for objective response rate according to PD-L1 expression were performed. RESULTS The post hoc analysis of JUPITER-06 showed more prominent clinical benefit with PD-1 antibody plus chemotherapy than with chemotherapy alone in both the high and low PD-L1–expressing subgroups. Five randomized controlled trials were included in the meta-analysis, and two PD-L1 expression scoring criteria, TPS (≥ 1%/< 1%) and combined positive score (CPS, ≥ 10/< 10), were analyzed. Significant overall survival benefit by adding PD-1 antibody to chemotherapy was observed in both the TPS < 1% (HR, 0.74; 95% CI, 0.56 to 0.97) and CPS < 10 (HR, 0.77; 95% CI, 0.66 to 0.89) subgroups. Similarly, significantly prolonged progression-free survival was observed in both the TPS < 1% (HR, 0.66; 95% CI, 0.50 to 0.86) and CPS < 10 (HR, 0.63; 95% CI, 0.47 to 0.84) subgroups. In addition, the objective response rate of the TPS < 1% subgroup was significantly improved (odds ratio, 1.71; 95% CI, 1.27 to 2.29). In all high PD-L1–expressing subgroups, the pooled benefit of PD-1 antibody plus chemotherapy was significantly better than that of chemotherapy. CONCLUSION This study provided novel evidence supporting the superiority of PD-1 antibody plus chemotherapy to chemotherapy alone in patients with advanced ESCC with low PD-L1 expression. Further studies of predictive biomarkers are warranted.

BackgroundThe clinical role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in gastric cancer (GC) is still controversial. We aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival.MethodsPatients who were diagnosed with GC at the three big cancer centers in China from 2015 to 2020 were evaluated retrospectively. MMR/MSI status was assessed using immunohistochemistry/PCR. Clinical and pathological data were collected from the medical record system.ResultsA total of 196 patients with dMMR/MSI-H status were enrolled for analysis. The prevalence of MSI-H/dMMR in GC was 6.6%. Another 694 proficient MMR (pMMR) GC patients were enrolled for comparison. Compared with pMMR patients, dMMR/MSI-H patients were associated with older age, female predominance, distal location in the stomach, earlier TNM stage, intestinal subtype, better differentiation, and more negative HER2 status. The median overall survival (OS) of the dMMR/MSI-H group was better than that of the pMMR/microsatellite stability (MSS) group (not reached vs. 53.9 months, p = 0.014). Adjuvant chemotherapy had no impact in both disease-free survival (DFS) and OS of dMMR/MSI-H patients (p = 0.135 and 0.818, respectively). dMMR/MSI-H patients had poorer response and progression-free survival (PFS) of first-line chemotherapy, though they were statistically significant (p = 0.361 and 0.124, respectively).ConclusionsdMMR/MSI-H GC patients have specific clinicopathological characteristics and better prognosis than pMMR patients.

Purpose: Several studies have reported controversial results about prognosis of gastric cancer in young age patients. The difference may partially result from variable definitions of young age. The aim of this study was to find out the relation between age and prognosis of gastric cancer patients, and to analyze the clinicopathological features and prognostic factors in young gastric cancer patients. Methods: Data queried for this analysis included GC patients from the Surveillance, Epidemiology, and End Results Program database from 1973 to 2014. Gastric cancer patients (N=79,505) diagnosed with an age≥18 were included. By combining patients with similar prognosis, we figured out 3 cutoff values of age, 35 years old, 65 years old and 75 years old. We divided patients into 4 groups: young age patients: 18-34 years; middle-age patients: 35-64 years; elderly patients: 65-74 years; extremely elderly patients: >74 years. GC patients from Sun Yat-sen University Cancer Center (SYSUCC) were used as external validation data. Results: The clinicopathological features of young age gastric cancer patients included: poor-differentiated, diffuse type of cancer, and advanced stage at diagnosis. The median survival of patients

Background World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). Methods AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. Results By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1–2) and 33.1% as serious (Grade 3–5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75–169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. Conclusions Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

Background: Pancreatic acinar cell carcinoma (PACC) is rare and its appropriate treatment remains unknown dued to limited and selection-biased dataMethods: The data on clinicopathologic characteristics, molecular alteration, treatment and survival of patients diagnosed as PACC in Sun Yat-sen university cancer center from 2005 to 2020 were collected. We explored the optimal treatment by co-analyzing our results and published literatures.Results: 22 PACC patients were enrolled. 8/17 non-metastatic patients received adjuvant chemotherapy. The patients receiving fluoropyrimidine-based regimen (n=3) had better mDFS than those with gemcitabine-based regimen (n=5) (unreached vs. 27 months). 8 metastatic patients received 1st-line chemotherapy. 4/5 patients with FOLFIRINOX regimen achieved partial response (PR) and 3 patients with AG (albumin paclitaxel+gemcitabine) regimen got progressive disease (PD). 4 patients received 2nd-line chemotherapy. 2 patients with FOLFIRINOX regimen achieved PR while 2 patients with AG regimen got PD. One patient who had responded to 1st-line FOLFIRINOX regimen received Olaparib as maintenance treatment for 5 months with good tolerance. 31 published literatures and a total of 86 cases were included in the co-analysis. Objective response rate of 1st-line fluoropyrimidine-based regimen (n=47) was higher than that of gemcitabine-based regimen (n=39) (59.6% vs.15.3%, PConclusions: The benefit of adjuvant chemotherapy remained unclear; however, fluoropyrimidine-based chemotherapy deserves attention. For metastatic patients, fluorouracil-based regimen such as FOLFIRINOX is preferred, and maintenance treatment of PARP inhibitors after effective platinum-containing treatment for BRAC mutation patients is worthy of exploration.

Background: Biomarkers that could predict the beneficial effects of immune checkpoint inhibitors (ICIs) in combination with chemotherapy in treatment-naive advanced or recurrent gastric or gastroesophageal junction (G/GEJ) adenocarcinoma patients are lacking. Methods: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with programmed death-1 (PD-1) inhibitor plus chemotherapy between October 2017 and July 2021. Comparative analysis of the objective response rate (ORR) was performed using the Chi-square or Fisher’s exact tests. Survival curves were plotted by the Kaplan-Meier analysis and compared for significance with a log-rank test. Univariate and multivariate Cox proportional hazard models were established for evaluating the prognostic value of clinicopathological factors. Results: Of the 172 enrolled patients, 142 showed measurable lesions. The ORR was 52.8%. Higher response rates were observed in patients with age greater than or equal to 60 (p = 0.013), non-diffuse type (p < 0.001), synchronous metastasis (p = 0.029), distant lymph node metastasis (p = 0.002), non-peritoneal metastasis (p= 0.002), HER2 positivity (p = 0.002), and PD-L1 CPS greater than or equal to 5 (p = 0.017). Through univariate analysis, age, histology, number of metastatic sites, and peritoneal metastasis were found to be associated with progression-free survival (PFS). Through multivariate analysis, peritoneal metastasis occurrence was the only identified independent indicator of poor PFS (HR 2.768, 95% CI 1.184-6.472, p = 0.019). Additionally, multi-factor combination results showed that patients with at least one of the following: mismatch repair-deficient (D-MMR)/microsatellite instability-high (MSI-H), HER2 (+), EBV (+), and/or PD-L1 CPS greater than or equal to 5, exhibited higher response rates and longer PFS as compared to those lacking these factors; this benefit was consistent after excluding PD-L1 expression. Among the clinical combinatorial factors, significantly poor ORRs and lower PFS were observed in patients with age < 60, diffuse type, and peritoneal metastasis as compared to those without any of these factors. Conclusions: Peritoneal metastasis was an independent biomarker of poor efficacy to immunotherapy combined with chemotherapy in G/GEJ cancer patients in first-line setting. Some combination factors could be beneficial for efficacy prediction. Citation Format: Yu-Ting Sun, Shi-Xun Lu, Ming-Yu Lai, Xia Yang, Wen-Long Guan, Li-Qiong Yang, Yu-Hong Li, Feng-Hua Wang, Rui-Hua Xu, Miao-Zhen Qiu. Predictive biomarkers for the efficacy of PD-1 inhibitors plus chemotherapy for gastric/gastroesophageal junction cancer in first-line setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5092.

e16063 Background: Both Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. However, the consistency of these two methods has not been determined. Therefore, we compared the prognostic value of TRG and RECIST 1.1 for gastric cancer (GC) patients and analyzed their consistency. Methods: Patients with gastric cancer who received preoperative chemotherapy or chemotherapy combined with immunotherapy and had record of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0-1 is considered as consistent with CR or PR in RECIST 1.1 and TRG 2-3 corresponds to SD or PD in RECIST 1.1. The primary endpoints were disease free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Kaplan-Meier method and Cox proportional hazards regression models were used for survival analysis. Results: We enrolled 157 GC patients, including 125 patients with preoperative chemotherapy, and 32 patients with preoperative chemotherapy combined with PD-1 inhibitors. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results of RECIST 1.1 and TRG. The pCR rate was 13.4% and the overall response rate (ORR) was 52.6% according to RECIST 1.1. Preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone, 34.4% vs 8.0%, P< 0.001. TRG was significantly correlated with both OS and DFS (P = 0.0162 and 0.0259, respectively) while response according to RECIST1.1 was not significantly related with OS and DFS ( P= 0.8598 and 0.2288, respectively). The median DFS had not reached in the TRG 0-1 group and was 16.13 months in TRG 2-3 group. Young patient, peritoneal metastasis or liver metastasis was correlated with TRG 2-3. Conclusions: Our results showed that TRG was in poor agreement with RECIST 1.1. TRG was better than RECIST 1.1 in predicting DFS and OS for GC patients who received neoadjuvant therapy.

Background The impact of HER2 somatic mutations in colorectal carcinoma (CRC) has not been well studied and its relationship with microsatellite instability‐high (MSI‐H) is yet to be fully elucidated. Materials and Methods From February 2017 to February 2020, the data of patients with CRC who underwent next‐generation sequencing and had detailed record of clinicopathological information were investigated. HER2 alteration and its relationship with MSI‐H were analyzed. Results Among 731 patients who underwent sequencing, 55 patients (7.5%) had HER2 alteration, including 29 (4.0%) with HER2 somatic mutations, 24 (3.3%) with HER2 gene amplification, and 2 patients (0.2%) with both HER2 mutations and amplification. R678Q was the most common mutated kinase domain, and no HER2 kinase domain in‐frame insertions/deletions were found in HER2 mutated cases. MSI‐H was found in 5.2% of our cohort and 36.8% of MSI‐H patients had HER2 mutation. For HER2 mutated cases, 48.3% were MSI‐H, whereas none of the HER2 amplification cases were MSI‐H. MSI‐H patients with HER2 mutation had significantly worse median progression‐free survival for programmed death‐1 (PD‐1) antibody than those without HER2 alteration (p = .036). Conclusion High MSI‐H rate was found in HER2 mutated cases, but no MSI‐H was found in HER2 amplification cases. MSI‐H patients with HER2 mutated had worse progression‐free survival for PD‐1 antibody than those without. Implications for Practice This study highlights the high microsatellite instability‐high (MSI‐H) rate in HER2 mutated cases but no MSI‐H in HER2 amplification cases. Moreover MSI‐H patients with HER2 mutated had worse progression‐free survival for programmed death‐1 antibody than those without. Further research to explore the internal relationship between HER2 alteration and MSI‐H is needed., The clinical significance of HER2 somatic mutations and its relationship with high microsatellite instability in colorectal cancer is not fully understood. This study investigated the relationship by analyzing data of patients with colorectal cancer who underwent next‐generation sequencing.

Background: Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This multicentre randomised controlled trial (RCT) aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. Methods: This superiority phase III trial was undertaken at 17 hospitals in 9 provinces of China. Patients with adenocarcinoma located between the cecum and the right third of the transverse colon, without evidence of distant metastases, were randomly assigned (in a 1:1 ratio) to receive either CME or D2 dissection during laparoscopic right colectomy. Morbidity and mortality in the first 30 days after surgery were compared between the two groups using a modified intention-to-treat (mITT) analysis. Findings: A total of 1072 patients were enrolled between January 11, 2016, and December 26, 2019. Of these patients, 995 (495 CME patients, 500 D2 patients) were included in the mITT analysis. The 30-day postoperative morbidity rate was 19·6% in the CME group vs. 21·8% in the D2 group (difference, -2·2% [95%CI, -0·07, - 0·03]; P = 0·34); no deaths occurred in either group. The CME procedures harvested significantly more lymph nodes (26·0 vs 23·0, difference, 3·4 [95%CI, 2·0, 4·9]; P

Background Gene mutations may play an important role in the development, response to treatment and prognosis of colorectal cancer (CRC). This retrospective study aimed to investigate the mutation profiling of Chinese patients with CRC, and its correlation with clinicopathological features and prognosis. Methods This study included 1190 Chinese CRC patients who were diagnosed between May 1998 and December 2018 and received clinical genetic testing. The OncoCarta Panel was used to test a total of 238 possible mutations in 19 common oncogenes. Results Five hundred and eighty‐two (48.9%) cases were detected with gene mutations. Of the 582 cases, there were 111 cases (19.7%) with two concurrent mutations, and six cases (1.0%) with three concurrent mutations. KRAS was the most common gene mutation that occurred in all cases (429, 36.1%), followed by PIK3CA (121, 10.2%), NRAS (47, 3.9%), BRAF (35, 2.9%), HRAS (11, 0.9%) and epidermal growth factor receptor (EGFR) (11, 0.9%). AKT1, KIT, FGFR1, FGFR3, FLT3, CDK, ERBB2, ABL1, MET, RET and PDGFRA mutations were also detected in several cases. When it came to prognosis, we found that KRAS/NRAS/PIK3CA/BRAF mutation was not associated with prognosis. But BRAF mutation was associated with poor prognosis in patients who accepted anti‐EGFR therapy. Conclusions The molecular testing offered the clinical data and mutation profile of Chinese CRC patients. The information of these mutated genes may help to find out the correlation between mutated genes and the development or prognosis of CRC., This is the largest sample size from Chinese colorectal cancer patients about gene mutation profiling. We found that KRAS was the most common mutated gene, followed by PIK3CA, NRAS and BRAF genes. BRAF mutation was associated with poor prognosis in patients who accepted anti‐epidermal growth factor receptor therapy.

e16014 Background: Programmed cell death 1 (PD-1) inhibitors have been approved as third line therapy for patients with metastatic gastric cancer (mGC). Epstein–Barr virus (EBV)-positive is a potential predictor to response of PD-1 inhibitors. The aim of this study was to assess the efficacy and safety of camrelizumab as salvage treatment in metastatic EBV positive GC patients and explored the potential biomarkers associated with response (NCT03755440). Methods: In this prospective single-arm, phase II study, stage IV EBV positive GC patients received 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR), which were based on RECIST V.1.1. Secondary endpoints were progression free survival (PFS), overall survival (OS), disease control rate (DCR), durationn of response (DoR), and toxicity. Exploratory analysis included association between response and tumor mutational burden (TMB) and cell death ligand-1 (PD-L1) expression. Results: According to Simon’s optimum two-stage design with α = 0.05 and β = 0.20. P0 = 15% (null hypothesis), the presence of at least 1 success in the 6 patients enrolled in the first stage allowed the trial to proceed to the second stage in which 13 more patients were needed to be enrolled for the minimum total of 20 patients (5% lost to follow-up calculated). Six eligible patients were enrolled at the first stage. All the patients were HER2 negative and pMMR. None of the patients had an objective response. The DCR was 66.7%. The median PFS was 2.2 months (95% CI: 1.5 months-not reached (NR)) and median OS was 6.8 months (95% CI: 1.7 months-NR). The most common treatment-related adverse event (TRAE) was reactive cutaneous capillary endothelial proliferation. No grade 3 or worse TRAEs were found. Only one patient had PD-L1 combined positive score (CPS) ≥1 but got disease progression. Three patients were TMB > 10Mb and two of them got stable disease while one got disease progression. Conclusions: EBV positive is not a good predictor for response to PD-1 inhibitors. Potential biomarkers are needed to identify EBVaGC patients who might respond to PD-1 inhibitors. Clinical trial information: NCT03755440.

Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) may account for 8-9% of all gastric cancer (GC) patients. All previous reports on EBVaGC were retrospective. Prospective study is warranted to evaluate the exact role of EBV status in predicting the prognosis of GC. It is of special interest to figure out whether dynamic detection of plasma EBV-DNA load could be a feasible biomarker for the monitor of EBVaGC. From October 2014 to September 2017, we consecutively collected GC patients (n = 2,760) from Sun Yat-sen University Cancer Center for EBER examination. We detected EBV-DNA load in plasma and tissue samples of EBVaGC patients at baseline. Subsequently, plasma EBV-DNA load was dynamically monitored in EBVaGC patients. The overall prevalence of EBVaGC is 5.1% (140/2,760). The incidence rate of EBVaGC decreased with advanced AJCC 7th TNM stage (p < 0.001), with the corresponding percentages of 9.3, 9.9, 6.7 and 1.4% for Stage I, II, III and IV patients. EBVaGC patients were predominately young males with better histologic differentiation and earlier TNM stage than EBV-negative GC (EBVnGC) patients. EBVaGC patients were confirmed to had a favorable 3-year survival rate (EBVaGC vs. EBVnGC: 76.8% vs. 58.2%, p = 0.0001). Though only 52.1% (73/140) EBVaGC patients gained detectable EBV-DNA and 43.6% (61/140) reached a positive cutoff of 100 copies/ml, we found the plasma EBV-DNA load in EBVaGC decreased when patients got response, while it increased when disease progressed. Our results suggested that plasma EBV-DNA is a good marker in predicting recurrence and chemotherapy response for EBVaGC patients.

The oxidation behavior of abietic acid was monitored by FT-IR and UV spectroscopy, using a novel, self-designed, gas–solid reactor, and the data was analyzed by 2D-IR. The hetero-spectral two-dimensional correlation of the FTIR data allowed the use of well-established band assignments to interpret less clearly assigned spectral features. Characteristic changes in the conjugated bond and the active methylene in abietic acid were revealed, and a mechanism was proposed. We concluded that the methylene at C7 was first transformed to a hydroxyl, thereby inducing the isomerization of the conjugated band. Meanwhile, the methylene at C12 was converted by an oxygen atom to a hydroxyl intermediate. Hydrogen continued to react with oxygen to form C O and water. Finally, the conjugated band was converted into a peroxide before transforming into an oxidant.

On the basis of current situations of urban underground transportation junctions and combining with on-site investigation of Beijing Xizhimen transportation junction station, this paper puts forward the disaster-prevention index system of urban underground transportation junctions. Specific analysis is on the disaster index in four aspects: informational sign, fire-fighting equipment, evacuation capability and refuge. 17 indexes are extracted reflecting the disaster evacuation performance, the weights of each disaster-prevention index are defined by Analytic Hierarchy Process (AHP), and fuzzy comprehensive evaluation method is adopted to conduct comprehensive evaluation of safety performance. The established disaster-prevention index system has practical value and significance to improve the disaster-prevention capability of urban underground transportation junctions.

The current treatment for multidrug-resistant tuberculosis (MDR-TB) takes a lengthy period of 18–24 months and has a poor cure rate of 50–60%. A multicenter, prospective cohort study was conducted to assess the role of testing for molecular susceptibility to pyrazinamide (PZA) in optimising treatment for MDR-TB. We assigned 76 patients to an optimised molecular susceptibility group and 159 patients to a regular treatment group where PZA susceptibility was not determined. Of these patients, 152 were matched after propensity score matching (76 in the optimised group and 76 in the regular group). Treatment success rate was measured in the propensity-matched cohort as the primary outcome. Patients in the optimised group achieved a higher treatment success rate than those in the regular group (76.3% versus 55.3%, p=0.006). Of 51 patients with isolates that were susceptible to PZA and who were receiving a 12-month regimen, 42 (82.4%) were treated successfully. The optimised group showed faster culture conversion than the regular group (p=0.024). After exclusion of pre-extensively drug-resistant TB (pre-XDR-TB), the treatment outcome in the optimised group was still better than the regular group (83.1% versus 62.1%, p=0.009). Introducing molecular susceptibility testing for PZA improved the treatment outcomes for MDR-TB without the use of new drugs. Introducing PZA for patients with PZA-susceptible (PZA-S) MDR-TB allows the current regimen to be shortened to 12 months with comparable success rates to the World Health Organization (WHO) recommended shorter regimen.