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).

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.

Objective:The 6th edition American Joint Committee on Cancer (AJCC) staging system for breast cancer classifies ipsilateral supraclavicular lymph node metastasis (ISLM) downing stage from M1 to N3, suggesting more patients might receive radical treatment. The aim of this study was to analyze the effect of ISLM on the prognosis of N3 breast cancer and verify the rationality of modified staging.Methods:A total of 321 breast cancer patients with N3 according to the 6th edition AJCC staging system were retrospectively analyzed. Propensity Score Matching (PSM) was used to pair the different subgroups of N3. The primary end point was disease-free survival (DFS), the secondary end point was overall survival (OS). Kaplan-Meier method was used to calculate the DFS and OS. The differences between two groups were analyzed by the Log-rank test.Results:After PSM pairing twice, 78 patients with none-ISLM and 78 patients with ISLM were enrolled in the first group; 51 patients with none-ISLM was compared patients with isolated ISLM in the second group. The results of the two groups showed that patients with none-ISLM have a prolonged DFS (the first group: 58.9 months vs 32.1 months, P=0.101; the second group: 59.0 months vs 44.0 months, P=0.533), while the OS was opposite (the first group: 87.4 months vs 140.4 months, P=0.289; the second group: 87.4 months vs 137.1 months, P=0.289). Conclusions:The prognosis of breast cancer patients with ISLM is similar to that of patients with none-ISLM in stage N3. It is reasonable to include ISLM in N3 in the 6th edition AJCC staging system. Yet, prospective studies with larger sample size are needed to further confirmation.

Objective:The 6th edition American Joint Committee on Cancer (AJCC) staging system for breast cancer classifies ipsilateral supraclavicular lymph node metastasis (ISLM) downing stage from M1 to N3, suggesting more patients might receive radical treatment. The aim of this study was to analyze the effect of ISLM on the prognosis of N3 breast cancer and verify the rationality of modified staging.Methods:A total of 321 breast cancer patients with N3 according to the 6th edition AJCC staging system were retrospectively analyzed. Propensity Score Matching (PSM) was used to pair the different subgroups of N3. The primary end point was disease-free survival (DFS), the secondary end point was overall survival (OS). Kaplan-Meier method was used to calculate the DFS and OS. The differences between two groups were analyzed by the Log-rank test.Results:After PSM pairing twice, 78 patients with none-ISLM and 78 patients with ISLM were enrolled in the first group; 51 patients with none-ISLM was compared patients with isolated ISLM in the second group. The results of the two groups showed that patients with none-ISLM have a prolonged DFS (the first group: 58.9 months vs 32.1 months, P=0.101; the second group: 59.0 months vs 44.0 months, P=0.533), while the OS was opposite (the first group: 87.4 months vs 140.4 months, P=0.289; the second group: 87.4 months vs 137.1 months, P=0.289). Conclusions:The prognosis of breast cancer patients with ISLM is similar to that of patients with none-ISLM in stage N3. It is reasonable to include ISLM in N3 in the 6th edition AJCC staging system. Yet, prospective studies with larger sample size are needed to further confirmation.

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 (ORs) and 95% confidence intervals (CIs) from logistic regression model. Cox regression was used for survival analysis between SNPs and overall survival by computing the hazard ratios (HRs) and 95% CIs. Results: Among 1 030 cases, 558 (54.2%) cases received cis-platinum and etoposide treatment while others treated with carboplatin and etoposide. Seven hundred and eighty eight patients were chemotherapy responders in the study with a response rate of 76.5%. The median follow-up time of these patients was 22.0 months. Patients were followed up to get their survival information. The median survival time of these patients was 22.5 months. Six hundred and seventy three patients (65.3%) had died by the last date of follow-up to get their survival information (Dec 21, 2017). Five htSNPs of POLK were not associated with the chemotherapy response of SCLC patients who received platinum-based chemotherapy (all P>0.05). Multivariate Cox proportional hazards regression model analysis showed that, rs73120833 of POLK was significantly associated with the overall survival (OS) of SCLC patients, compared with POLK rs73120833 T allele, C allele can prolong OS (adjusted HR=0.87, 95% CI=0.77-0.97, P=0.021). The remaining 4 SNPS, including rs10077427, rs3756558, rs4549504 and rs5744545, were not significantly associated with overall survival. Age≤56, KPS> 80, limited-stage, chemotherapy response and radiation therapy can remarkably prolong OS (all P<0.05). Conclusion These results suggest that POLK genetic polymorphism rs73120833 plays an important role on the prognosis of SCLC patients, which can be potential genetic biomarker for SCLC personalized treatment.

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 (OR=1.268, P=0.046; OR=1.244, P=0.036). With G-CSF support, the probability of grade 3-4 dose limiting toxicity, i. e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased(P>0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P=0.814) or dose reduction (P=0.282). Conclusions EC-T dose-dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen. With G-CSF support, epirubicin 85-90 mg/m² is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.

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.

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 ( OR＝1.268, P＝0.046; OR＝1.244, P＝0.036). With G?CSF support, the probability of grade 3?4 dose limiting toxicity, i.e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased ( P＞0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P＝0.814) or dose reduction (P＝0.282). Conclusions EC?T dose?dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen.With G?CSF support, epirubicin 85?90 mg／m2 is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.

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.

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 ( OR＝1.268, P＝0.046; OR＝1.244, P＝0.036). With G?CSF support, the probability of grade 3?4 dose limiting toxicity, i.e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased ( P＞0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P＝0.814) or dose reduction (P＝0.282). Conclusions EC?T dose?dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen.With G?CSF support, epirubicin 85?90 mg／m2 is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.