Multicenter real world study on the efficacy and safety of eribulin for the treatment of advanced breast cancer / 中华肿瘤杂志

Objective: To explore the efficacy and safety of real-world eribulin in the treatment of metastatic breast cancer. Methods: From December 2019 to December 2020, patients with advanced breast cancer were selected from Beijing Chaoyang District Sanhuan Cancer Hospital, Shandong Cancer Hospital, Peking University Cancer Hospital, Baotou Cancer Hospital, Shengjing Hospital Affiliated to China Medical University, and Cancer Hospital of Chinese Academy of Medical Sciences. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: The median progression-free survival (PFS) of 77 patients was 5 months, the objective response rate (ORR) was 33.8%, and the disease control rate (DCR) was 71.4%. The ORR of patients with triple-negative breast cancer was 23.1%, and the DCR was 57.7%; the ORR of patients with Luminal breast cancer was 40.0%, and the DCR was 77.8%; the ORR of patients with HER-2 overexpression breast cancer was 33.3%, and the DCR was 83.3%. ORR of 50.0% and DCR of 66.7% for patients treated with eribulin as first to second line treatment, ORR of 29.4% and DCR of 76.5% for patients treated with third to fourth line and ORR of 28.6% and DCR of 71.4% for patients treated with five to eleven line. The ORR of patients in the eribulin monotherapy group was 40.0% and the DCR was 66.0%; the ORR of patients in the combination chemotherapy or targeted therapy group was 22.2% and the DCR was 81.5%. Patients with a history of treatment with paclitaxel, docetaxel, or albumin paclitaxel during the adjuvant phase or after recurrent metastasis had an ORR of 32.9% and a DCR of 69.9% when treated with eribulin. The treatment efficacy is an independent prognostic factor affecting patient survival (P<0.001). The main adverse reactions in the whole group of patients were Grade Ⅲ-Ⅳ neutrophil decline [29.9% (23/77)], and other adverse reactions were Grade Ⅲ-Ⅳ fatigue [5.2% (4/77)], Grade Ⅲ-Ⅳ peripheral nerve abnormality [2.6% (2/77)] and Grade Ⅲ-Ⅳ alopecia [2.6% (2/77)]. Conclusions: Eribulin still has good antitumor activity against various molecular subtypes of breast cancer and advanced breast cancer that has failed multiple lines of chemotherapy, and the adverse effects can be controlled, so it has a good clinical application value.

The prospects of DNA damage repair variants guiding platinum compounds in the treatment of triple negative breast cancer / 中华肿瘤杂志

Triple negative breast cancer (TNBC) is prone to recurrence and metastasis, which is the subtype of poorest prognosis. Chemotherapy is the main treatment, although there is lack of effective adjuvant chemotherapy regimens. The unsatisfactory efficacy of chemotherapy has been a bottleneck in improving the outcome of TNBC. Platinum compounds act directly on DNA to kill tumor cells, and they have a stronger killing effect on tumor cells carrying DNA damage repair (DDR) defects, which is an important entry point to improve the efficacy of TNBC. Biomarkers for predicting the efficacy of platinum drugs in TNBC treatment have always been a hot topic. The DDR pathway contains a large number of related genes, and recent studies have shown that deficiencies in the DDR pathway may be associated with the efficacy of platinum drugs, which is expected to be a biomarker for predicting the efficacy of platinum drugs in breast cancer treatment.

Study on the Medical Device Registration Submission Dossier Requirements in China / 中国医疗器械杂志

The evolution throughout the whole supervision history of Class II/III safety and effectiveness related NMPA submission dossier requirements was studied in this study, meanwhile elaborating the revolution progress of clinical evaluation domestically. The relationship between submission dossier requirements and Essential Principles of Safety and Performance of Medical Devices as well as IMDRF relevant documents was deeply analyzed and illustrated, in order to comprehensively understanding the background and future reform direction of NMPA submission dossier requirements under the background of the government's deepening reform of medical device evaluation and approval system strategy.

Research progress of conversion therapy in colorectal cancer liver metastases / 中华胃肠外科杂志

The probability of developing liver metastases in patients with colorectal cancer is 40%-50%. Liver metastases remain an important adverse factor affecting long-term prognosis of colorectal cancer patients. Surgical resection of liver metastases is the only potentially curative treatment option. After comprehensive treatment, initially unresectable liver metastases might be converted to resectable tumors. This concept is known as conversion therapy. In this review, research status of conversion therapy in colorectal cancer liver metastases was summarized, providing updated concept of resectability, discussions on the assessment of tumor response and timing of operation, debates on the influence on tumor sidedness, and latest advancement in the treatment strategy of conversion therapy. Through analyzing existing problems, we hope to offer insights into possible progress in the future and provide references for the development of clinical practice.

Clinical research progress on disappearing colorectal liver metastases / 中华胃肠外科杂志

Colorectal cancer is currently one of the most common digestive system tumors, and the liver is the most common metastatic site of colorectal cancer. In recent years, with the continuous development of the multidisciplinary treatment for colorectal cancer patients, there are quite a few cases of disappearing liver metastases (DLM) after receiving preoperative chemotherapy (or combined targeted drug therapy), and the diagnosis and treatment of DLM is currently still a very challenging and controversial topic. This article sorts out the related researches on DLM in recent years, mainly including the following 4 aspects: (1) The factors associated with DLM, including the size and number of liver metastases, chemotherapy regimens and cycles, targeted therapy drugs, and the pattern of liver metastases, Ras/Braf status and the location of the primary lesion. (2) The relationship between DLM and true complete response (pathological complete response and persistent clinical complete response), and the related predictive factors of pathological complete response. (3) Clinical evaluation of DLM: preoperative evaluation includes ultrasound, CT, MRI, and PET, while intraoperative evaluation includes intraoperative exploration, intraoperative ultrasound, and augmented reality. (4) DLM treatment strategies, including surgical treatment, local treatment, non-surgical treatment and individualized treatment.

Clinical analysis of 554 patients with colorectal diverticulosis / 中华胃肠外科杂志

Objective: Most patients with asymptomatic colorectal diverticulosis are easily overlooked. However, some of diverticulosis become diverticulitis, bleeding and even perforation, which cause extensive harm to patients. The purpose of this study is to analyze the incidence, clinical features, diagnosis and treatment of colorectal diverticulosis in order to improve the clinical understanding of diverticulosis and its related complications. Methods: A descriptive cohort study was carried out. Clinical data of 554 patients with colorectal diverticulosis confirmed by CT, colonoscopy, digestive tract radiography or operation in Peking University First Hospital from January 2009 to June 2019 were retrospectively analyzed. Patients with malignant tumors, autoimmune diseases, long term use of immunosuppressive drugs, chronic liver diseases and renal diseases, and mental disorders were excluded. The analysis parameters included gender, onset age, clinical symptoms, location of diverticulitis, treatment and prognosis. According to the criteria established by the World Society of Emergency Surgery (WSES), acute diverticulitis was divided into 5 stages based on the extension of the infectious process. Stage 0 was simple diverticulitis and stage 1-4 was complicated diverticulitis. Results: Among the 554 patients with colorectal diverticulosis, 358 (64.6%) were males, the median onset age was 63 years; 191 patients (34.5%) had various digestive symptoms, of whom 113 (20.4%) had chronic constipation and abdominal distension, 78 (14.1%) had chronic diarrhea and abdominal pain; the other 363 patients had no obvious abdominal symptoms. Four hundred and six patients were found by colonoscopy and 465 patients were found by CT. Twenty-five patients were diagnosed by lower gastrointestinal tract radiography and 3 were confirmed during operation. There were 339 patients with multiple diverticula (61.2%) and 215 patients with single diverticulum (38.8%). 76.5% (424/554) of diverticula were located in colon, 37.0% (205/554) in ascending colon, 21.3% (118/554) in multiple sites, and 2.2% (12/554) in rectum. The median diameter of diverticulum was 7 mm, and 78 cases (14.1%) was ≥30 mm. Forty-nine patients (8.8%) developed acute diverticulitis, including 13 patients with simple diverticulitis and 36 patients with complicated diverticulitis. Among 36 patients with complicated diverticulitis, 29 (80.6%) were males, 27 (75.0%) had recurrent abdominal pain and fever before onset; diverticula of 25 cases were located in sigmoid colon; 11 cases in ascending colon. Nine cases developed sigmoid colon perforation and 8 cases developed vesicocolonic fistula, and these 17 patients underwent surgical treatment. The other 19 cases with complicated diverticulitis developed gastrointestinal bleeding, of whom 18 cases were male, 11 cases were located in ascending colon; 13 cases were healed after conservative treatment, 4 cases received endoscopic hemostatic intervention, and 2 cases underwent surgery. Conclusions: Colorectal diverticulosis is more common in male patients, and CT and colonoscopy are main diagnostic methods. The symptoms of complicated colonic diverticulitis are related to the location of diverticulum. In addition to symptomatic treatment, surgical procedures are the most important treatments.

Meta-analysis of external fixator and open reduction and internal fixation for the treatment of distal radius fracture / 中国骨伤

OBJECTIVE@#To compare clinical efficacy and safety of plate internal fixation (ORIF) and external fixator (EF) in treating distal radius fractures by Meta-analysis.@*METHODS@#From establishment of database to August, 2019, randomized controlled trial (RCT) about open reduction and internal fixation (ORIF) and external fixation (EF) in treating distal radius fractures was conducted by using computer-based databases, including CNKI, VIP, Wanfang Data, Medline, Cochrane library databases. Data extraction and quality evaluation of included study according to inclusion and exclusion criteria, RevMan 5.3 software was used to perform Meta-analysis. Palm angle, ulnar deflection angle, radius height, grip strength, ulnar variation, disabilities of arm, shoulder and hand (DASH) score, total complication rate, infection rate and tendon rupture between two groups were compared.@*RESULTS@#Totally 19 RCT were included with 1 730 patients, 873 patients in ORIF group and 857 patients in EF group. Meta analysis result showed that after operation at 12 months, there were no significant difference in radial height [@*CONCLUSION@#Compared with EF in treating distal radius fracture, ORIF has better clinical effects in postoperative complications, palm angle, ulnar deviation angle, ulnar variation rate and infection rate. While there were no significant difference between in DASH score, radial height, tendon rupture and carpal tunnel syndrome better EF and ORIF. For the patient pursue rapid recovery of function, ORIF is better choice.

Progress of molecular typing and heterogeneity in hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer / 肿瘤研究与临床

Hormone receptor-positive and human epidermal growth factor receptor 2-positive (HR + HER2 +) breast cancer is a highly heterogeneous disease, accounting for about 10% of breast cancers. The molecular biological characteristics, therapeutic effect and prognosis of all subtypes have significant differences. This paper reviews the research progress of molecular biological characteristics, diagnosis and treatment condition and single-cell level in HR + HER2 + breast cancer from the perspective of heterogeneity.

Effects of vitrification and cryostorage duration on single-cell RNA-Seq profiling of vitrified-thawed human metaphase II oocytes / 医学前沿

Oocyte cryopreservation is widely used for clinical and social reasons. Previous studies have demonstrated that conventional slow-freezing cryopreservation procedures, but not storage time, can alter the gene expression profiles of frozen oocytes. Whether vitrification procedures and the related frozen storage durations have any effects on the transcriptomes of human metaphase II oocytes remain unknown. Four women (30-32 years old) who had undergone IVF treatment were recruited for this study. RNA-Seq profiles of 3 fresh oocytes and 13 surviving vitrified-thawed oocytes (3, 3, 4, and 3 oocytes were cryostored for 1,2, 3, and 12 months) were analyzed at a single-cell resolution. A total of 1987 genes were differentially expressed in the 13 vitrified-thawed oocytes. However, no differentially expressed genes were found between any two groups among the 1-, 2-, 3-, and 12-month storage groups. Further analysis revealed that the aberrant genes in the vitrified oocytes were closely related to oogenesis and development. Our findings indicated that the effects of vitrification on the transcriptomes of mature human oocytes are induced by the procedure itself, suggesting that long-term cryostorage of human oocytes is safe.

The effect of early rehabilitation on cardiopulmonary function after lung transplantation / 中华物理医学与康复杂志

Objective:To explore the effect on cardiopulmonary function of early rehabilitation after lung transplantation.Methods:Forty patients undergoing lung transplantation were randomly divided into an observation group and a control group, each of 20. Both groups received routine rehabilitation treatment, psychological counseling and health education about rehabilitation, medications and nutrition. The observation group was additionally given systematic early lung rehabilitation treatment as soon as their vital signs were stable after the operation. It included body position transfers, aerobic training, resistance training and breathing training 3 to 5 times a week for 4 weeks supervised by physical therapists. The control group were informed about methods of aerobic training, respiratory training and airway clearance but carried them out by themselves. The percentage of forced expiratory volume (FVC%), FVC in the first second (FEV1%, ) and FEV1%/ FVC% of the two groups were evaluated using a bedside lung function instrument before the lung transplantation and after 4 weeks of treatment. The six-minute walking distances (6MWDs) of the two groups were compared and their facility in the activities of daily living was evaluated using the modified Barthel index (MBI).Results:Before treatment, there was no significant difference in the average FEV1%, FVC%, FEV1%/FVC%, 6MWD or MBI ratings between the two groups. After the 4 weeks of treatment, both groups showed significant improvement in all of those measurements, on average. The observation group′s averages were, however, significantly better than those of the control group.Conclusion:Early rehabilitation after lung transplantation helps to improve cardiopulmonary function and promote a better quality of life.

Complex total knee arthroplasty assisted by a 3D printed patient-specific guider / 中华创伤骨科杂志

Objective:To explore the application of a 3D printed patient-specific guider (3D-PSG) in complex total knee arthroplasty (TKA).Methods:A retrospective analysis was performed of the data of 44 patients who had received complex artificial TKA for articular and extra-articular deformities of the knee from January 2016 to October 2019 at Department of Orthopaedic Surgery, Nanjing First Hospital. According to whether a 3D-PSG had been applied, the patients were divided into 2 groups. In the 3D-PSG group of 23 patients, there were 11 males and 12 females, with an age of 63.7 years ± 10.2 years (from 53 to 81 years); in the conventional group of 21 cases, there were 10 males and 11 females, with an age of 64.2 years ±12.1 years (from 51 to 79 years). In the 3D-PSG group, the preoperative CT data were 3D reconstructed for measurement of a full lower limb and design of a 3D-PSG and TKA was assisted by a 3D-PSG which had been manufactured by a 3D printer using the STL files of the 3D-PSG imported. In the conventional group TKA was performed in a standard manner. In the 3D-PSG group, the TKA surgical parameters in the preoperative plan were compared with actual surgical measurements. The 2 groups were compared in terms of operation time, intraoperative blood loss, postoperative drainage volume, length of hospital stay, visual analogue scale (VAS), Knee Society Score (KSS), hip knee ankle (HKA), frontal femoral component (FFC), frontal tibial component (FTC), lateral femoral flexion (LFF) and lateral tibial component (LTC).Results:There were no significant differences between the 2 groups in the preoperative general data, showing comparability ( P>0.05). In the 3D-PSG group, no significant differences were found between preoperative parameters designed and actual intraoperative measurements in the prosthetic type of femoral condyle (3.4±1.1 versus 3.5±0.9) or of tibial plateau (3.1±0.9 versus 3.3±1.2), or in the filler thickness (10.6 mm ± 3.2 mm versus 10.9 mm ± 4.7 mm) ( P>0.05). The 44 patients were followed up for an average of 10.8 months (from 7 to 13 months). The 3D-PSG group had significantly less operation time (65.7 min ± 10.5 min), intraoperative blood loss (19.8 mL ±7.3 mL), postoperative drainage volume (124.6 mL ± 27.9 mL) and hospital stay (7.3 d ± 2.5 d) than the conventional group (82.4 min ± 11.7 min, 86.5 mL ± 35.7 mL, 154.6 mL ± 21.3 mL and 10.6 d ± 3.1 d) ( P<0.05). The VAS and KSS scores at postoperative day 1, week 1 and week 2 in the 3D-PSG group were significantly better than those in the conventional group ( P<0.05). Significantly more patients in the 3D-PSG group achieved approximately ideal values in HKA, FFC, FTC, LFF and LTC than those in the conventional group ( P<0.05). Conclusion:A 3D printed patient-specific guider may improve surgical accuracy, reduce operation time and achieve better surgical outcomes in complex total knee arthroplasty.

Application of Near-Infrared Fluorescence Imaging with Indocyanine Green in Totally Laparoscopic Distal Gastrectomy

Purpose@#Recently, totally laparoscopic gastrectomy has been gradually accepted by surgeons worldwide for gastric cancer treatment. Complete dissection of the lymph nodes and the establishment of the surgical margin are the most important considerations for curative gastric cancer surgery. Previous studies have demonstrated that indocyanine green (ICG)-traced laparoscopic gastrectomy significantly improves the completeness of lymph node dissection. However, it remains difficult to identify the tumor location intraoperatively for gastric cancers that are staged ≤T3. Here, we investigated the feasibility of ICG fluorescence for lymph node mapping and tumor localization during totally laparoscopic distal gastrectomy. @*Materials and Methods@#Preoperative and perioperative data from consecutive patients with gastric cancer who underwent a totally laparoscopic distal gastrectomy were collected and analyzed. The patients were categorized into the ICG (n=61) or the non-ICG (n=75) group based on whether preoperative endoscopic mucosal ICG injection was performed. @*Results@#The ICG group had a shorter operation time and less intraoperative blood loss.Moreover, significantly more lymph nodes were harvested in the ICG group than the non-ICG group. No pathologically positive margin was found and there was no significant difference in either the proximal or distal surgical margins between the 2 groups. @*Conclusions@#Near-infrared fluorescence imaging with ICG can be successfully used in totally laparoscopic distal gastrectomy, and it contributes to both the completeness of D2 lymph node dissection and confirmation of the gastric transection line. Well-designed prospective randomized studies are needed in the future to fully validate our findings.

Primary study of chemoradiotherapy combined with radioactive iodine-125 implantation for locally advanced non-small cell lung cancer / 中华放射肿瘤学杂志

Objective To comparatively evaluate the clinical efficacy and adverse events of chemoradiotherapy combined with/without radioactive iodine-125 ( 125-I) implantation for locally advanced non-small cell lung cancer. Methods With locally advanced non-small cell lung cancer admitted to Department of Radiotherapy of Jianhu County People's Hospital and Yancheng Third People's Hospital from March 2014 to March 2015 of 38 patients were enrolled and randomly divided into the observation ( chemoradiotherapy+ radioactive 125-I implantation, n=20) and control groups ( chemoradiotherapy, n=18) . All patients underwent conventional three-dimensional conformal radiotherapy and TC chemotherapy. In the observation group, 125-I implantation was performed at 3 months after chemoradiotherapy. The short-term clinical efficacy, progression-free survival, overall survival and adverse events were statistically compared between two groups. Results The total effective rate in the observation group was 85%, significantly higher than 56% in the control group ( P=0.046) . Until May, 2018, the progression-free survival rates in the observation and control groups were 65% and 61% ( P=0.457) , the overall survival rates were 32% and 26%, and the median survival time was 22.8( 95%CI: 20.5-23.5) and 21.3( 95%CI: 15.9-26.0) months ( P=0.633) . The incidence rates of adverse events in the observation and control groups were 45% and 78% ( P>0.05) . Conclusions Concurrent chemoradiotherapy combined with radioactive 125-I implantation yields high short-term efficacy in the treatment of locally advanced non-small cell lung cancer. It can prolong the long-term survival to certain extent and yield a low incidence rate of severe adverse events, which deserves to be validated by large sample-size investigations.

Influence of ultrasound‐guided lauromacrogol foam sclerotherapy on peripheral blood levels of CEC , ET‐1 and NO in patients with saphenous vein varicosis／ / 心血管康复医学杂志

To explore influence of ultrasound‐guided lauromacrogol foam sclerotherapy on peripheral blood levels of counting of endothelial cells (CEC) , endothelin (ET)‐1 and nitric oxide (NO) in patients with sa‐phenous vein varicosis .Methods : A total of 90 patients with saphenous vein varicosis were randomly and equally di‐vided into lauromacrogol group (received ultrasound‐guided lauromacrogol foam sclerotherapy ) and routine treat‐ment group (received routine stripping ).Peripheral blood levels of CEC , ET‐1 and NO were observed and com‐pared between two groups before and after surgery , and therapeutic effect and incidence of complications were eval‐uated.Results : Compared with routine treatment group , there were significant reductions in surgery time [ (81. 79 ± 16.88) min vs .(40.55 ± 10. 19) min] , hospitalization time [(3.94 ± 1.36) d vs.(2. 17 ± 1.31) d] and hospital‐ization fee [ (7640. 15 ± 1025.11) RMB vs.(3998.89 ± 910. 67 ) RMB ] in lauromacrogol group , P＝ 0.001 all. Compared with routine treatment group after surgery , there were significant reductions in incidence rate of total complications (17.78% vs .4. 44%) , percentage of patient＇s condition class IV (17. 78% vs.4.44%) , peripheral blood levels of CEC [ (5562. 48 ± 1194. 73)／L vs.(4655.87 ± 1209. 88)／L] and ET‐1 [ (70. 32 ± 10.30) ng／L vs. (62.95 ± 13.78) ng／L] , and significant rise in percentage of patient’ s condition class I (6.67% vs.25. 00%) and peripheral blood NO level [(1.27 ± 0.42) μmol／L vs.(1. 59 ± 0.51) μmol／L] in lauromacrogol group , P＜0. 05 or＜0. 01. Conclusion : Ultrasound‐ guided lauromacrogol foam sclerotherapy can significantly increase therapeutic effect , improve vascular endothelial function in patients with saphenous vein varicosis .And its complications are few .

Correlation between gut microbiota and behavior symptoms in children with autism spectrum disorder / 中国当代儿科杂志

OBJECTIVE@#To investigate the composition of gut microbiota and its correlation with the severity of behavior symptoms in children with autism spectrum disorder (ASD).@*METHODS@#A total of 30 children with ASD were enrolled as the ASD group, and 20 healthy children matched for age and sex were enrolled as the healthy control group. Related clinical data were analyzed. The V3-V4 hypervariable regions of the bacterial 16S rRNA gene in fecal samples were sequenced. The severity of behavior symptoms in children with ASD was assessed using the autism behavior checklist. The Spearman's correlation analysis was used to investigate the correlation between gut microbiota and the severity of behavior symptoms in children with ASD.@*RESULTS@#There was a significant difference in the composition of gut microbiota between the two groups. Compared with the healthy control group, the ASD group had significant reductions in Shannon index and Shannoneven index (P<0.05), as well as a significant reduction in the percentage of Firmicutes and a significant increase in the percentage of Acidobacteria in feces (P<0.05). In the ASD group, the dominant bacteria were Megamonas, Megasphaera, and Barnesiella, while in the healthy control group, the dominant bacteria were Eubacterium_rectale_group, Ezakiella, and Streptococcus. In the children with ASD, the abundance of Megamonas was positively correlated with the scores of health/physical/behavior and language communication (P<0.05).@*CONCLUSIONS@#The development of ASD and the severity of behavior symptoms are closely associated with the composition of gut microbiota.

Association Between Organic Dust Exposure and Adult-Asthma: A Systematic Review and Meta-Analysis of Case-Control Studies

BACKGROUND: Exposure to organic dust has been widely investigated as a potential risk factor for asthma with different results. To clarify a potential relationship, we performed the present meta-analysis to integrate the results of studies examining the association of organic dust exposure with asthma. METHODS: A comprehensive literature search in the electronic databases including EMBASE, PubMed and Cochrane Library databases (up to August 2018) was conducted. The adjusted odds ratios (ORs) with corresponding 95% confidence interval (CI) for organic dust exposure and asthma were retrieved and pooled to generate summary effect estimates in Revman 5.2. RESULTS: Database searches retrieved 1,016 records. A total of 17 studies containing 3,619 cases and 6,585 controls were finally included in our meta-analysis. The summary estimates suggested that organic dust exposure was positively associated with asthma (OR, 1.48; 95% CI, 1.26–1.75; P < 0.00001), whether among population-based case-control studies (OR, 1.24; 95% CI, 1.13–1.35; P < 0.00001) or hospital-based case-control studies (OR, 2.79; 95% CI, 1.27–6.12; P = 0.01). Subgroup analysis showed that paper/wood (OR, 1.62; 95% CI, 1.38–1.90; P < 0.00001), flour/grain (OR, 1.48; 95% CI, 1.11–1.97; P = 0.008), and textile dust (OR, 1.50; 95% CI, 1.08–2.09; P = 0.02) exposure were significantly associated with asthma. CONCLUSIONS: Based on the studies evaluated, our meta-analysis results prompt that organic dust exposure is a risk factor inducing asthma, although precise analysis focus on specific organic dust materials is still warranted.

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 / 中华肿瘤杂志

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.

Genetic variation in DNA polymerase kappa gene is associated with the prognosis after platinum-based chemotherapy in small cell lung cancer patients / 中华肿瘤杂志

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.

Clinical value of heat shock protein-90α on diagnosis, prediction of treatment response, and monitoring of relapse in breast cancer / 中国肿瘤临床

To explore the prognostic value of heat shock protein-90α (HSP-90α) plasma levels on breast cancer and non-breast malignant tumors, monitoring the response of chemotherapy, and the predictive value of cancer recurrence and metastasis. Methods: A total of 615 female patients were enrolled between June 2016 and September 2016 in Cancer Hospital, Chinese Academy of Medical Sciences, who were divided into the examination (n=389) and control (n=216) groups. The former group consisted of static (n=289) and dynamic (n=110) groups, which were analyzed by stages, histological and molecular type, and so on. The latter group in-cluded healthy people (n=103), and those with breast benign tumors (n=51) and non-breast malignant tumors (n=62). In all the plasma samples, HSP-90α was detected using a double-antibody enzyme-linked immunosorbent assay. The receiving-operating characteristic curve was used to analyze the effectiveness of plasma HSP-90α in the diagnosis of breast cancer. Wilcoxon＇s rank test and the Kruskal-Wallis test were used to analyze the association between clinical characteristics and levels of plasma HSP-90α. Results: The levels of plasma HSP-90α were significantly higher in patients with breast cancer than in healthy controls (P<0.001). When the cut-off value was set as 59.7 ng/mL for the diagnosis of breast cancer and 43.22 ng/mL for disease recurrence, the areas under the curve were 0.834 and 0.877, sensitivities were 90.3% and 95.7%, and specificities were 78.6% and 74.5%, respectively. The levels of plasma HSP-90α sig-nificantly decreased after achieving a response to neoadjuvant chemotherapy or surgery (P<0.05). Conclusions: Plasma HSP-90α has good clinical value in the diagnosis and monitoring of response and recurrence in breast cancer.

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 / 癌症

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.