1.Analysis of Siewert classification, microsatellite instability and HER2 expression in 242 cases of adenocarcinoma of esophagogastric junction
Xinjun WU ; Qingzu GAO ; Yan LI ; Shuaichao LI ; Qiao ZHANG ; Binghe CHEN
International Journal of Surgery 2021;48(11):769-773,f4
Objective:To explore the characteristics of Siewert classification and microsatellite instability(MSI) and HER2 expression in adenocarcinoma of esophagogastric junction (AEG).Methods:The clinicopathological data of gastric adenocarcinoma from May 2019 to November 2020 were retrospectively analyzed. The patients were divided into two groups: AEG group and non AEG group. The composition ratio of Siewert type of AEG was counted, and the relationship between tumor size and Siewert type was analyzed. The MSI status and HER2 expression status of AEG and non AEG were statistically compared. The measurement data of normal distribution were expressed as mean ± standard deviation( Mean± SD), the comparison between groups were by t test, the comparison of count data between groups were by Chi-square test. Results:A total of 328 consecutive cases of gastric adenocarcinoma were collected, including 242 cases of AEG and 86 cases of non AEG. The Siewert classification of AEG was mainly type Ⅱ (151 cases, 62.40%), followed by type Ⅲ (86 cases, 35.54%) and type Ⅰ (5 cases, 2.07%). The analysis of the relationship between the size of the tumor length and the number of Siewert type showed that the number of Siewert type Ⅱ cases decreased and the number of Siewert type Ⅲ cases increased with the increase of the tumor size. MSI status was detected non selectively in 192 cases of gastric adenocarcinoma (140 cases of AEG and 52 cases of non AEG). There were 12 cases of MSI (6.25%), 2 cases of MSI-H (1.04%) and 10 cases of MSI-L (5.21%). There was no significant difference in MSI ratio between AEG group and non AEG group ( P>0.05). All MSI cases were negative or weakly positive for PMS2. The expression of HER2 was detected by immunohistochemistry in 313 cases of gastric adenocarcinoma, except 15 cases of PTIS/T1a. There were 30 cases (9.58%) with HER2 expression 3+ . Thirty-two cases (10.22%) expressed HER2 (2+ ), of which 7 cases were detected by fluorescence in situ hybridization (FISH), and 3 cases were positive. The proportion of HER2 (3+ ) in AEG was significantly higher than that in non AEG group ( P<0.05). Conclusions:The main type of AEG was Siewert type Ⅱ. AEG may mostly occur between 1 cm above the esophagogastric junction and 2 cm below the esophagogastric junction; For endoscopic screening of early AEG, more attention should be paid to this area of stomach. Siewert type Ⅲ may be derived from the development of Siewert type Ⅱ. The incidence of microsatellite instability in gastric cancer is low. Compared with other gastric adenocarcinoma, AEG has no specificity in MSI. The MSI of AEG was mainly the expression defect of PMS2. Compared with other gastric adenocarcinoma, there are more HER2 overexpression in AEG.
2.Results of combined therapy for 1260 patients with small cell lung cancer.
Dongfu CHEN ; Xiangru ZHANG ; Weibo YIN ; Yan SUN ; Yanjun MIAO ; Fengyi FENG ; Jinwan WANG ; Mei WANG ; Hongxing ZHANG ; Qinfu FENG ; Binghe XU ; Yuankai SHI
Chinese Journal of Oncology 2002;24(6):602-604
OBJECTIVETo evaluate the efficacy of combined modality treatment and determine the prognostic factors for small cell lung cancer (SCLC).
METHODSFrom January 1974 to December 1995, 1260 patients with SCLC treated were retrospectively evaluated, with limited lesions in 732 patients, extensive lesions in 500 and stage unrecorded in 28. 553 patients were alloted into chemotherapy + radiotherapy (C + R) group, 355 into C + R + C group, 97 into R + C group, 126 into C group, 64 into R group and 65 into surgery (S + C + R) group. Patients with limited lesions received 2 - 4 cycles of chemotherapy including COMC, COMP, COMVP and CE-CAP. Radiotherapy was given to a dose of 40 - 70 Gy/4 - 7 w. Radiation portals for patients with limited lesions encompassed the primary tumor, hilar lymphatic drainage areas, partial mediastinum and bilateral supraclavicular regions. Patients with extensive lesions mainly received chemotherapy with or without palliative irradiation.
RESULTSThe overall CR and PR rates were 26.7% and 52.3%. Local recurrence and distant metastasis rates were 58.8% and 61.5%. The 1-, 3- and 5-year survival rates were 50.2%, 14.7% and 11.7%, with median survival time of 12 months. The era, sex, age, tumor stage and treatment modality were all significant prognostic factors by both uni-variate and multi-variate analyses (P < 0.05). The result of S + C + R rated the best among these modalities and the result of C + R + C was superior to C + R, though the difference of which was not significant.
CONCLUSIONSurgical resection should be considered as one part of comprehensive therapy for small cell lung cancer patients with limited lesions whenever possible. On top of routine chemotherapy early administration of radiotherapy is advisable.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Carcinoma, Small Cell ; mortality ; therapy ; Combined Modality Therapy ; Female ; Humans ; Lung Neoplasms ; mortality ; therapy ; Male ; Middle Aged ; Radiotherapy ; Survival Rate ; Treatment Outcome
3. The clinical reports on adrenal insufficiency of patients with advanced solid tumors accepting anti-PD-1 antibody, SHR-1210 therapy
Jialin TANG ; Jing HUANG ; Xi WANG ; Xuelian CHEN ; Qun LI ; Hongnan MO ; Dawei WU ; Bo LAN ; Binghe XU
Chinese Journal of Oncology 2019;41(6):466-470
Objective:
To investigate the adrenocortical function changes of patients with advanced solid tumors who received the anti- programmed cell death protein-1 (PD-1) antibody, SHR-1210 therapy.
Methods:
The clinical data of 98 patients with advanced solid tumors who were enrolled in a prospective phase I trial of SHR-1210 therapy at our institution between April 27, 2016 and June 8, 2017 were collected. The levels of plasma adrenocorticotropic hormone (ACTH) and cortisol were evaluated in 96 patients. The clinical manifestations, laboratory tests and radiologic data were collected to define the immune-related adrenal insufficiency.
Results:
Until December 14th, 2018, no SHR-1210 related primary adrenal insufficiency occurred, and the incidence of immune-related secondary adrenal insufficiency was 1.0% among the 96 patients, which was identified as grade 2. No patient developed grade 3-4 adrenal insufficiency. The main clinical manifestations of the patient who was diagnosed as secondary adrenal insufficiency were grade 2 fatigue, anorexia and headache.The patient developed fatigue and anorexia at the 267th day after receiving the first dose of SHR-1210, the hypocortisolism occurred on the 279th day, and the headache emerged on the 291th day. The anorexia of patient who treated by physiological replacement doses of glucocorticoid since the 457th day was attenuated.The patient whose cortisol level was still below the normal limit continued to accept the hormone replacement therapy up to 776 days after the initial administration of SHR-1210.
Conclusions
The incidence of SHR-1210 related adrenal insufficiency of patients with advanced solid tumors is low, and the symptoms can be effectively ameliorated by hormone replacement therapy. The potential adverse outcome of adrenal insufficiency following immunotherapy should be noticed by clinicians to avoid the occurrence of adrenal crisis.
4. Feasibility and toxicity of EC-T dose-dense adjuvant chemotherapy: A real world study in Chinese early-stage breast cancer patients with high recurrence risk
Jiani WANG ; Yuxin MU ; Qing LI ; Ying FAN ; Jiayu WANG ; Fei MA ; Yang LUO ; Peng YUAN ; Shanshan CHEN ; Qiao LI ; Ruigang CAI ; Pin ZHANG ; Binghe XU
Chinese Journal of Oncology 2019;41(5):368-372
Objective:
We aimed to examine the feasibility and toxicity of EC-T dose-dense regimen and to demonstrate the suitable dose of epirubicin in a Chinese early-stage breast cancer population with high recurrence risk.
Methods:
370 patients with early-stage breast cancer at high risk of recurrence were treated with EC-T dose-dense adjuvant chemotherapy and prophylactic administration of recombinant human granulocyte stimulating factor (G-CSF). The incidence of delayed chemotherapy, drug reduction and adverse reactions were retrospectively analyzed.
Results:
370 patients completed the planned eight cycles of chemotherapy, 50 patients experienced chemotherapy delay, and 90 had chemotherapy dose reductions. Overall, 61.1% of the patients experienced grade 3 or 4 hematology toxicities, 4.1% of the patients experienced grade 3 gastrointestinal toxicity, 16.3% experienced grade 3 or 4 liver malfunction, and 1.9% experienced grade 3 alopecia. In the multivariate analysis, pretreatment epirubicin levels were associated with comprehensive and hematology toxicity risk (
5. Clinical observation of thyroid-related adverse events induced by anti-PD-1 antibody SHR-1210 in patients with advanced solid tumor
Ling QI ; Hongnan MO ; Xuelian CHEN ; Xi WANG ; Dawei WU ; Bo LAN ; Qun LI ; Xingyuan WANG ; Jianping XU ; Qing YANG ; Binghe XU ; Jing HUANG
Chinese Journal of Oncology 2018;40(10):772-775
Objective:
To assess the incidence and characteristics of thyroid dysfunction during anti-Programmed cell death 1 receptor (PD-1) antibody SHR-1210 therapy in patients with advanced solid tumor.
Methods:
The medical records of 98 patients who initiated SHR-1210 treatment between April 27, 2016 and June 8, 2017 in the phase 1 trial to evaluate the safety, efficacy, and pharmacokinetics of SHR-1210 in patients with advanced solid tumors were retrospectively reviewed. Serological tests of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at baseline and prior to each SHR-1210 administration.
Results:
A total of 86 patients had normal thyroid function before the first dose of SHR-1210 treatment. Nine out of 86 (10.5%) patients developed new onset hypothyroidism from euthyroid state. 12 patients presented thyroid dysfunction at baseline, 10 of whom were subclinical hypothyroid and 2 were hypothyroidism. Four out of 10 patients developed hypothyroidism from subclinical hypothyroid. Most patients with hypothyroidism were asymptomatic. Thyroid dysfunction occurred early (median, 55days) after the initiation of SHR-1210. The severity of hypothyroidism were all grade 1-2. No grade 3-4 hypothyroidism occurred. No patients discontinue the treatment of SHR-1210 due to clinical impact of the thyroid dysfunctions.
Conclusions:
Thyroid-related adverse events were common during anti-PD-1 antibody SHR-1210 treatment . The incidence of hypothyroidism is lower in patients with euthyroid state than in patients with thyroid dysfunction at baseline during SHR-1210 treatment . Thyroid function can be improved after thyroid hormone replacement. During SHR-1210 treatment, it is necessary to pay attention to monitor the thyroid function, especially in the patients with thyroid dysfunction at baseline.
Trial registration
Chinese Clinical Trial Registry, 2016L01455
6.A multicenter, randomized, controlled, phase Ⅲ clinical study of PEG-rhG-CSF for preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer.
Binghe XU ; Fuguo TIAN ; Jingrui YU ; Yanqiu SONG ; Jianhua SHI ; Baihong ZHANG ; Yanjun ZHANG ; Zhiping YUAN ; Qiong WU ; Qingyuan ZHANG ; Kejun NAN ; Qiang SUN ; Weilian LI ; Jianbing HU ; Jingwang BI ; Chun MENG ; Hong DAI ; Hongchuan JIANG ; Shun YUE ; Bangwei CAO ; Yuping SUN ; Shu WANG ; Zhongsheng TONG ; Peng SHEN ; Gang WU ; Lili TANG ; Yongchuan DENG ; Liqun JIA ; Kunwei SHEN ; Wu ZHUANG ; Xiaodong XIE ; Youhua WU ; Lin CHEN
Chinese Journal of Oncology 2016;38(1):23-27
OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.
METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.
RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).
CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.
Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects
7. Genetic variation in DNA polymerase kappa gene is associated with the prognosis after platinum-based chemotherapy in small cell lung cancer patients
Jinna CHEN ; Ting FENG ; Jie YANG ; Hongmin LI ; Peng YUAN ; Fei MA ; Luxi YIN ; Dongxin LIN ; Binghe XU ; Wen TAN
Chinese Journal of Oncology 2019;41(2):112-117
Objective:
To investigate the associations between genetic variations of DNA polymerase kappa (POLK) and treatment response to platinum-based chemotherapy of small cell lung cancer (SCLC), and to analyze the influencing factors on survival.
Methods:
Five haplotype-tagging single nucleotide polymorphisms (htSNPs) of POLK were genotyped by Sequenom MassARRAY methods in 1 030 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between SNPs and treatment response were analyzed by computing the odds ratios (
8.Genetic polymorphisms of autophagy-related gene 5 (ATG5) rs473543 predict different disease-free survivals of triple-negative breast cancer patients receiving anthracycline- and/or taxane-based adjuvant chemotherapy.
Meiying LI ; Fei MA ; Jiayu WANG ; Qing LI ; Pin ZHANG ; Peng YUAN ; Yang LUO ; Ruigang CAI ; Ying FAN ; Shanshan CHEN ; Qiao LI ; Binghe XU
Chinese Journal of Cancer 2018;37(1):4-4
BACKGROUND:
Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer (TNBC). Hence, autophagy-related gene 5 (ATG5), an essential molecule involved in autophagy regulation, is presumably associated with recurrence of TNBC. This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival (DFS) of early-stage TNBC patients treated with anthracycline- and/or taxane-based chemotherapy.
METHODS:
We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline- and/or taxane-based chemotherapy using the sequenom's MassARRAY system. Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.
RESULTS:
Three genotypes, AA, GA, and GG, were detected in the rs473543 of ATG5 gene. The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence (P = 0.024). Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543 (P = 0.034). In addition, after adjusting for clinical factors, multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS (hazard risk [HR], 1.73; 95% confidence interval [CI], 1.04-2.87; P = 0.034). In addition, DFS was shorter in node-negative patients with the presence of A allele (AA/GA) than in those with the absence of A allele (P = 0.027).
CONCLUSION
ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.
Adult
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Aged
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Anthracyclines
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administration & dosage
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adverse effects
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Autophagy-Related Protein 5
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genetics
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Bridged-Ring Compounds
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administration & dosage
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adverse effects
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Chemotherapy, Adjuvant
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Disease-Free Survival
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Female
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Genetic Association Studies
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Genetic Predisposition to Disease
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Humans
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Kaplan-Meier Estimate
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Middle Aged
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Neoplasm Recurrence, Local
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drug therapy
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genetics
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pathology
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Polymorphism, Single Nucleotide
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genetics
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Taxoids
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administration & dosage
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adverse effects
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Triple Negative Breast Neoplasms
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drug therapy
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genetics
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pathology
9.Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial.
Binghe XU ; Qingyuan ZHANG ; Xichun HU ; Qing LI ; Tao SUN ; Wei LI ; Quchang OUYANG ; Jingfen WANG ; Zhongsheng TONG ; Min YAN ; Huiping LI ; Xiaohua ZENG ; Changping SHAN ; Xian WANG ; Xi YAN ; Jian ZHANG ; Yue ZHANG ; Jiani WANG ; Liang ZHANG ; Ying LIN ; Jifeng FENG ; Qianjun CHEN ; Jian HUANG ; Lu ZHANG ; Lisong YANG ; Ying TIAN ; Hongyan SHANG
Acta Pharmaceutica Sinica B 2023;13(5):2250-2258
Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).