Non-response Group Research Articles

Predictive value of quantitative dynamic contrast-enhanced magnetic resonance imaging for the efficacy of neoadjuvant chemotherapy in locally advanced gastric cancer

Objective: To investigate the predictive value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) quantitative parameters for the efficacy of neoadjuvant chemotherapy in locally advanced gastric cancer. Methods: Sixty-five patients with locally advanced gastric cancer (LAGC) confirmed by gastroscopy and received neoadjuvant chemotherapy (NCT) were enrolled in this study. Quantitative DCE-MRI was performed before NCT, and the quantitative parameters were measured, including volume transfer constant (K(trans)), rate constant (K(ep)), volume fraction of extravascular extracellular space (V(e)) and volume fraction of plasma (V(p)). After NCT, all patients received radical gastrectomy. According to postoperative pathological tumor regression grade, patients were divided into response group and non-response group, and the differences of DCE quantitative parameters between the two groups were compared. ROC curve was utilized to analyze the predictive efficacy of DCE quantitative parameters for NCT response of LAGC, and multivariate logistic regression analysis was performed to analyze the predictive efficacy of combined parameters. Results: Thirty-seven patients were in response group and 28 patients were in non-response group. The pretreatment K(trans) in the response group were [0.216 min(-1) (0.130 min(-1), 0.252 min(-1))], significantly higher than [0.091 min(-1) (0.069 min(-1), 0.146 min(-1))] of non-response group (P<0.001), and V(e) in the response group were [0.354(0.228, 0.463)], significantly higher than [0.200(0.177, 0.253)]of non-response group (P<0.001). ROC analysis showed the AUCS of K(trans) and V(e) in predicting NCT efficacy were 0.881 and 0.756, respectively. Multiple logistic regression analysis showed that the combination of the two parameters could improve the AUC to 0.921, with the sensitivity and specificity of 86.5% and 89.3%, respectively. Conclusion: DCE-MRI quantitative parameters could help to predict the NCT response of LAGC, and the combination of parameters could improve the predictive efficacy.

Accuracy of aortic valve velocity time integral in assessing fluid responsiveness during general anesthesia in elderly patients

Objective To evaluate the accuracy of aortic valve velocity time integral (VTI) in assessing fluid responsiveness during general anesthesia in elderly patients. Methods Forty-four elderly patients of both sexes, aged 65-80 yr, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, with New York Heart Association classⅠ or Ⅱ, undergoing elective surgery with general anesthesia in our hospital from February 2018 to August 2018, were enrolled in this study.All the patients underwent tracheal intubation after general anesthesia induction, and then volume expansion was carried out (6% hydroxyethyl starch 250 ml was intravenously infused for 30 min). The heart rate (HR), mean arterial pressure (MAP), VTI and stroke volume (SV) were recorded before and after volume expansion, and ΔHR, ΔMAP, ΔVTI and ΔSV were calculated.Patients were divided into 2 groups according to ΔSV: response group (R group, ΔSV≥15%) and non-response group (NR group, ΔSV<15%). The receiver operating characteristic curve (with the area under the standard ΔSV curve was 1) was used to analyze the ΔHR, ΔMAP and ΔVTI, and the Youden index at its best was calculated.The Person test was used to analyze the correlation between ΔVTI and ΔSV. Results There were 25 cases in R group and 19 cases in NR group.Compared with group NR, ΔHR was significantly decreased, and ΔVTI and ΔSV were increased in group R (P<0.05). The area under the ROC curve of ΔHR, ΔMAP and ΔVTI in assessing fluid responsiveness was 0.509 (95% confidence interval 0.314-0.689, P=0.415), 0.558 (95% confidence interval 0.379-0.737, P=0.515) and 0.905 (95% confidence interval 0.812-0.999, P<0.01), respectively. When Youden index was at its best, ΔVTI was 15.28%, with the sensitivity 88.0% and specificity 94.7%.There was a positive correlation between ΔSV and ΔVTI (r=0.936, P<0.05). Conclusion ΔVTI can accurately assess the fluid responsiveness during general anesthesia in elderly patients. Key words: Aortic valve; Aged; Fluid therapy

In vitro and molecular chemosensitivity in human cholangiocarcinoma tissues.

Adjuvant chemotherapy is required for cholangiocarcinoma (CCA) patients after surgical treatment. Gemcitabine and gemcitabine plus cisplatin are considered the appropriate regimen; however, the response spectrum to chemotherapy differs between patients. Thus, the present study aims to evaluate the response pattern of individual CCA patients by using an in vitro method, histoculture drug response assay (HDRA), to predict the chemosensitivity of individual patients in a prospective study. Moreover, we also investigate the expression of gemcitabine and cisplatin sensitivity factors in CCA tissues in the same cases. Based on the dose response curve, 1000 and 1500 μg/ml of gemcitabine were used as the testing concentrations. For cisplatin, concentrations of 20 and 25 μg/ml were selected for testing and for the combination regimen, 1000 μg/ml of gemcitabine and 20 μg/ml of cisplatin were chosen. The median %IR of each drug was measured as the cut-off to categorize the response pattern into response and non-response groups. In addition, we compared the effectiveness of the chemotherapy regimens between gemcitabine alone and gemcitabine plus cisplatin. The %IR of the combination of gemcitabine and cisplatin was significantly higher than gemcitabine alone. The relationship between the expression level of gemcitabine and cisplatin sensitive factors and the individual response pattern as well as clinicopathological data of CCA patients were analyzed. The results indicated that a low expression of the gemcitabine sensitive factor hENT-1 was significantly associated with the non-response group in vitro (p = 0.002). Moreover, the low expression of hENT-1 was also significantly associated with advanced stages CCA in the patients (p = 0.025). A low expression of MT and ERCC1 was significantly correlated with the response group in the in vitro experiments (p = 0.015 and p = 0.037 for MT and ERCC1, respectively). Therefore, HDRA may serve as an aid to selecting chemotherapy, and the expression of hNET-1, MT and ERCC1 may serve as biomarkers for predicting chemotherapy success.

Venetoclax and hypomethylating agents in TP53‐mutated acute myeloid leukaemia

Venetoclax and hypomethylating agents in <i>TP53</i>‐mutated acute myeloid leukaemia

Urinary nerve growth factor can predict therapeutic efficacy in children with monosymptomatic nocturnal enuresis.

To determine the urinary levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in children with monosymptomatic nocturnal enuresis (MNE) and evaluate whether these factors can be used as biomarkers for the treatment outcome. NGF and BDNF levels were measured and compared in 38 children (28 boys and 10 girls) with MNE and 25 children (18 boys and 7 girls) with no urinary symptoms were assessed. The mean ages in the patient and control groups were 9 and 10 years, respectively (P = .49). The patients were treated with either alarm or desmopressin therapy. The urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in the patient group than in the control group (P = .0003 and P = .0095, respectively). NGF and BDNF levels showed a significant positive correlation (P = .0020, r = 0.40). With respect to the degree of response, 19 patients (50%) showed complete response (CR) or partial response (PR), and 19 patients (50%) showed nonresponse (NR). The urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in the NR group than in the CR and PR groups (P = .0003 and P = .0003, respectively). Urinary NGF/creatinine and BDNF/creatinine ratios were significantly higher in children with MNE than in healthy controls. Urinary NGF/creatinine can be predictive factors of a poor treatment outcome in children with MNE.

The predictive value of cardiopulmonary interaction monitoring technology on volume responsiveness in septic shock patients

Objective To assess the predictive value of cardiopulmonary interaction monitoring technology on volume responsiveness in septic shock patients. Methods A cohort of 45 septic shock patients treated with mechanical ventilation at First People’s Hospital of Nantong City from January 2016 to June 2017 were prospectively selected. The hemodynamic variables including heart rate (HR), systolic pressure (SBP), mean arterial pressure (MAP), central venous pressure (CVP), cardiac index (CI), stroke volume variability (SVV), and pulse pressure variability (PPV) were monitored. PEEP elevation test, end-expiratory occlusion test and volume expansion were sequential conducted. Volume responsiveness was defined as an increase in CI (ΔCI) of 15% or greater after volume expansion, namely the response group (ΔCI≥15%) and non-response group (ΔCI<15%). Receiver operating characteristic (ROC) curve was constructed to indicate the predictive value of cardiopulmonary interaction monitoring technology in septic shock patients. The best cut-off value was assessed by Youden Index, and sensitivity and specificity were calculated respectively. Results There were 24 patients in the response group and 21 patients in the non-response group. There were no significant differences in basic clinical data between the two groups. After PEEP elevation test, CVP increased significantly, while SBP and CI decreased significantly in both groups (P<0.05). The degrees of ΔSBP and ΔCI in the response group were much higher than those in the non-response group (P<0.05). After end-expiratory occlusion test, CVP decreased significantly, while SBP, MAP and CI increased significantly in both groups (P<0.05). The degrees of ΔMAP and ΔCI in the response group were much higher than those in the non-response group (P<0.05). SVV and PPV in the response group were higher than those in the non-response group (P<0.05). The area under the ROC curve (AUC) of the ΔSBP and ΔCI after PEEP elevation test and ΔMAP and ΔCI after end-expiratory occlusion test were 0.737 (95%CI:0.581-0.89; P<0.05), 0.803 (95%CI: 0.660-0.946; P<0.05), 0.763 (95%CI: 0.617-0.908; P<0.05), and 0.808 (95%CI: 0.673-0.942; P<0.05), respectively. These AUC values were higher than or similar to traditional indicators, such as SVV and PPV. The best cut-off value of ΔCI and ΔSBP after PEEP elevation test was 12% and 9.5%, yielding a sensitivity and specificity of 70.8% and 95.2%, 75% and 71.4%, respectively. The best cut-off value of ΔCI and ΔMAP after end-expiratory occlusion test was 8.5% and 5.5%, yielding a sensitivity and specificity of 79.2% and 76.2%, 75% and 76.2% respectively. Conclusion ΔSBP and ΔCI after PEEP elevation test and ΔMAP and ΔCI after end-expiratory occlusion test can accurately predict volume responsiveness in septic shock patients. Key words: Cardiopulmonary interactions; PEEP elevation; End-expiratory occlusion; Septic shock; Volume responsiveness

The predictive values of serum dickkopf-1 and circulating tumor cells in evaluating the efficacy of transcatheter arterial chemoembolization treatment on hepatocellular carcinoma.

In this study, we aim to explore the values of serum dickkopf-1 (DKK1) and circulating tumor cells (CTCs) in predicting the efficacy and prognosis of transcatheter arterial chemoembolization (TACE) treatment on patients with hepatocellular carcinoma (HCC). We did a retrospective analysis on 155 HCC patients who underwent TACE treatment. The patients were divided into response group (complete response and partial response) and nonresponse group (stable disease and progressive disease), and their changes in serum DKK1 and CTCs after TACE were recorded. Receiver operating characteristic curve and survival analysis were used to assess the predictive values of DKK1 and CTCs for TACE efficacy and long-term prognosis of HCC. We found that the levels of preoperative DKK1 and CTCs in patients with HCC had a moderate positive correlation (r = 0.54). After TACE treatment, the serum DKK1 and CTCs in the response group were significantly decreased compared to pretreatment levels (P < .05), whereas the nonresponse group showed significantly increased serum DKK1 and CTCs levels (P < .05). The largest area under the curve (AUC) was achieved when using >0.02 μg/L reduction in DKK1 level after 4 weeks of TACE to predict the efficacy of TACE treatment (AUC = 0.913, 95% confidence interval: 0.856–0.952, P < .001), with the sensitivity of 78.26% and the specificity of 88.07%. The overall survival, disease-free survival, and 5-year survival rates were all significantly lower in the patients with positive preoperative levels of serum DKK1 and CTCs. COX multivariate regression analysis showed that Eastern Cooperative Oncology Group score, and preoperative levels of serum DKK1 and CTCs are independent influencing factors for the prognosis of patients with HCC. Overall, our results demonstrated that serum DKK1 and CTCs levels were good biomarkers for predicting the efficacy and prognosis of TACE treatment in patients with HCC. Moreover, these parameters exhibited different characteristics, and might have different potential applications.

Non-mono-exponential diffusion models for assessing early response of liver metastases to chemotherapy in colorectal Cancer

BackgroundPreoperative chemotherapy is becoming standard therapy for liver metastasis from colorectal cancer, so early assessment of treatment response is crucial to make a reasonable therapeutic regimen and avoid overtreatment, especially for patients with severe side effects. The role of three non-mono-exponential diffusion models, such as the kurtosis model, the stretched exponential model and the statistical model, were explored in this study to early assess the response to chemotherapy in patients with liver metastasis from colorectal cancer.MethodsThirty-three patients diagnosed as colorectal liver metastasis were evaluated in this study. Diffusion-weighted images with b values (0, 200, 500, 1000, 1500, 2000 s/mm2) were acquired at 3.0 T. The parameters (ADCk, K, DDC,α, Dsand σ) were derived from three non-mono-exponential models (the kurtosis, stretched exponential and statistical models) as well as their corresponding percentage changes before and after chemotherapy. The difference in above parameters between the response and non-response groups were analyzed with independent-samples T-test (normality) and Mann–Whitney U-test (non-normality). Meanwhile, receiver operating characteristic curve (ROC) analyses were performed to assess the response to chemotherapy.ResultsSignificantly lower values of K (the kurtosis coefficient derived from the kurtosis model) and σ (the width of diffusion coefficient distribution in the statistical model) (P < 0.05) were observed in the respond group before treatment, as well as higher ΔK and Δσ values (P < 0.05) after the first cycle of chemotherapy were also found compared with the non-respond group. ROC analyses showed the K value acquired before treatment had the highest diagnostic performance (0.746) in distinguishing responders from non-responders. Furthermore, the high sensitivity (100%) and accuracy (76.3%) from the K value before treatment was found in assessing the response of colorectal liver metastasis to chemotherapy.ConclusionsThe non-mono-exponential diffusion models may be able to predict early response to chemotherapy in patients with colorectal liver metastasis.

The dynamic characteristics and predictive value of hepatitis B core antibody titers in chronic hepatitis B patients treated with interferon

Objective To observe the dynamic characteristics of hepatitis B core antibody (anti-HBc) titers in chronic hepatitis B (CHB) patients treated with interferon and to explore the predictive value of anti-HBc for response to interferon. Methods The clinical information of the patients diagnosed with CHB in Department of Infectious Diseases, the First Affiliated Hospital of Xi′an Jiaotong University from October 2011 to October 2014 were collected. HBV DNA, liver function and HBV serological markers of CHB patients were tested dynamically during and after interferon treatment. The dynamic characteristics of anti-HBc titers in patients with different virological responses were analyzed. The predictive values of anti-HBc titer for the efficacy of interferon treatment of CHB patients were analyzed by binary logistic regression. Results Of the 42 CHB patients aging(30.8±10.1) years old, 34 patients were hepatitis B e antigen (HBeAg) positive and 8 were negative. All patients completed 48-week interferon treatment and 24-week follow-up after the end of treatment. Among them, 28.6% (12/42), 26.2% (11/42) and 45.2% (19/42) of patients achieved sustained virological response (SVR), virological relapse (VR) and non-response (NR), respectively. Patients with different virological response presented various characteristics of anti-HBc titers. Compared with NR group, the anti-HBc titers at baseline and week 12 were significantly higher in SVR group (at baseline: [4.93 ± 0.30] vs [4.70 ± 0.33] lg IU/mL, t=2.147, P=0.013; at week 12: [4.83 ± 0.23] vs [4.44 ± 0.41] lg IU/mL, t=3.032, P=0.007). The anti-HBc titers in SVR group at week 12 and week 24 were significantly higher than those in VR group (at week 12: [4.83 ± 0.23] vs [4.67 ± 0.51] lg IU/mL, t=2.400, P=0.039; at week 24: [4.73 ± 0.21] vs [4.55 ± 0.50] lg IU/mL, t=2.542, P=0.039). By multivariate logistic regression analysis, the anti-HBc titer at baseline was the independent predictive factor for SVR in CHB patients treated with interferon (OR=6.000, 95%CI: 1.118 - 20.486, P=0.037). The area under receiver operating characteristics curve was 0.753 and the optimal cutoff value of anti-HBc titer for the response to interferons in CHB patients was 5.03 lg IU/mL, with positive predictive value of 64.3% and negative predictive value of 89.3%. Conclusions Dynamic pattern of anti-HBc titers is correlated with different virological responses in CHB patients treated with interferon, and the baseline anti-HBc titer is the independent predictive factor for SVR. Key words: Interferon; Hepatitis B, chronic; Anti-HBc titer

The abnormal function of CD39+ regulatory T cells could be corrected by high-dose dexamethasone in patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia is an autoimmune disease, characterized with decreased platelet and increased risk of bleeding. Recent studies have shown the reduction and dysfunction of regulatory T (Treg) cells in ITP patients. CD39 is highly expressed on the surface of Treg cells. It degrades ATP to AMP and CD73 dephosphorylates AMP into adenosine. Then adenosine binds with adenosine receptor and suppresses immune response by activating Treg cells and inhibiting the release of inflammatory cytokines from effector T (Teff) cells. Adenosine receptor has several subtypes and adenosine A2A receptor (A2AR) plays a crucial role especially within lymphocytes. The CD39+ Treg cells and the expression of A2AR showed abnormality in some autoimmune disease. But knowledge of CD39+ Treg cells and A2AR which are crucial in the adenosine immunosuppressive pathway is still limited in ITP. Thirty-one adult patients with newly diagnosed ITP were enrolled in this study. CD39 and A2AR expression was measured by flow cytometry and RT-PCR. The function of CD39 was reflected by the change of ATP concentration detected by CellTiter-Glo Luminescent Cell Viability Assay. CD39 expression within CD4+CD25+ Treg cells in ITP patients was decreased compared to normal controls. After high-dose dexamethasone therapy, response (R) group showed increased CD39 expression within Treg cells while non-response (NR) group did not show any difference in contrast to those before treatment. The expression of A2AR in CD4+CD25- Teff and CD4+CD25+ Treg cells was both lower in ITP patients than that of normal controls. After therapy, CD4+CD25- Teff cells had higher A2AR expression while CD4+CD25+ Treg cells did not show any difference in comparison to that before treatment. The enzymatic activity of CD39 was damaged in ITP patients and improved after high-dose dexamethasone therapy. In ITP, there was not only numerical decrease but also impaired enzymatic activity in CD39+ Treg cells. After high-dose dexamethasone treatment, these two defects could be reversed. Our results also suggested that ITP patients had reduced A2AR expression in both CD4+CD25+ Treg cells and CD4+CD25- Teff cells. CD4+CD25- Teff cells had increased A2AR expression after treatment.

Scalp EEG high frequency oscillations as a biomarker of treatment response in epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS)

PurposeWe investigated whether the presence of interictal scalp EEG high frequency oscillations (HFOs) in children with epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS) can predict seizure and cognitive outcome after steroid therapy. MethodsTwenty-two children with CSWS were prospectively enrolled and received methylprednisolone therapy. Interictal scalp HFOs, spike wave index (SWI) and intelligence quotient (IQ) were assessed before and after the treatment. The children were divided into two groups based on the early seizure reduction ratio at 2 weeks (≥50%, “response group”; otherwise “non-response group”). The “response group” was further divided into two subgroups (“relapse” and “non-relapse” subgroups) according to the late seizure outcome (after 3 months). ResultsInterictal HFOs and electrical status epilepticus in sleep (ESES) (defined as SWI ≥ 85%) were detected in all children at the baseline. In the response with relapse group (n = 11), the detection ratio of HFOs was significantly higher than that of ESES at 2 weeks (81.2 vs. 27.3%), 3 months (90.9 vs. 36.4%), and 6 months (100 vs. 54.5%) post-therapy. In the non-response group (n = 4), both HFOs and ESES persisted in all children. The average IQ improved significantly only in the response with non-relapse group. The persistence of HFOs negatively correlated with both the average IQ, yet the persistence of ESES did not. ConclusionInterictal scalp HFOs may be a favorable non-invasive biomarker of predicting seizure and cognitive outcome in CSWS.

Biomarkers identified by serum metabolomic analysis to predict biologic treatment response in rheumatoid arthritis patients.

Biologic treatment has recently revolutionized the management of RA. Despite this success, ∼30-40% of the patients undergoing biologic treatment respond insufficiently. The aim of this study was to identify several specific reliable metabolites for predicting the response of RA patients to TNF-α inhibitors (TNFi) and abatacept (ABT), using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). We collected serum from RA patients with moderate or high disease activity prior to biologic treatment, and obtained the serum metabolomic profiles of these samples using CE-TOFMS. The patients' response was determined 12 weeks after starting biologic treatment, according to the EULAR response criteria. We compared the metabolites between the response and non-response patient groups and analysed their discriminative ability. Among 43 total patients, 14 of 26 patients in the TNFi group and 6 of 17 patients in the ABT group responded to the biologic treatment. Of the metabolites separated by CE-TOFMS, 196 were identified as known substances. Using an orthogonal partial least-squares discriminant analysis, we identified five metabolites as potential predictors of TNFi responders and three as predictors of ABT responders. Receiver operating characteristic analyses for multiple biomarkers revealed an area under the curve (AUC) of 0.941, with a sensitivity of 85.7% and specificity of 100% for TNFi, and an AUC of 0.985, with a sensitivity of 100% and specificity of 90.9% for ABT. By metabolomic analysis, we identified serum biomarkers that have a high ability to predict the response of RA patients to TNFi or ABT treatment.

The mutational profile analysis of different response to neoadjuvant chemoradiation therapy in local advanced esophageal squamous cell cancer patients.

e15560 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant diseases in the world and especially in China. The combined modality therapy neoadjuvant chemoradiation therapy (nCRT) has become the new standard of care. This study was aimed to investigate the molecular features in cell-free DNA (cfDNA) that is related with the response to nCRT in the local advanced ESCC. Methods: 24 eligible ESCC patients with received nCRT were included and baseline blood were collected from Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. 14 patients had response and the other 10 patients had no response to nCRT, respectively. Both cfDNA fragments and fragmented genomic DNA were extracted for enrichment of a 0.96M size panel covering exon regions of 1,408 genes. Gene alterations were analyzed to explore the relationship between genetic characterizations of cfDNA and response to nCRT. Results: The most common mutated genes were NOTCH1, IRS1, TP53. The somatic alternation of NOTCH1, IRS1, ZFHX4 occurred more frequently in response group than in non-response group. On the contrary, patients with response to nCRT had significantly less mutations of PDE11A, STK11. Moreover, the tumor mutation burden (TMB) of cfDNA in response group was significantly higher than non-response group(p = 0.024). Conclusions: The molecular features in cfDNA of patients with response to nCRT were different from those without response. Five genes’ mutational profile could identify the response and non-response patients with local advanced ESCC. However, prospective studies are needed to validate our findings.

Investigating the effect of chemotherapy combined with ketogenic diet on stage IV colon cancer.

e15182 Background: The effectiveness of carbohydrate restriction to limiting cancer growth has often been observed in in vitro and in vivo experiments; however, few cases of clinical efficacy have been reported. We examined the clinical effectiveness of chemotherapy with ketogenic diet for advanced cancer treatment. Methods: We administered chemotherapy with a modified medium-chain triglyceride (MCT) ketogenic diet at a ratio of 1.4:1 in 10 patients with stage IV recurrent colon cancer for one year and performed a conversion surgery in five of the cases. We followed-up for the next 3 years, compared the overall survival (OS) of the chemotherapy-only group of the stage IV colon cancer patients, and investigated the factors contributing to an improved OS. Results: Evaluations in the first year revealed a response rate of 21% and disease control rate of 64% for patients in the chemotherapy-only group. Patients in the ketogenic diet-chemotherapy combination group exhibited a response rate of 60%, disease control rate of 70%, and complete response rate of 50% for the five conversion surgeries. The time to conversion surgery was 4.0±0.9 months and the time to postoperative recurrence was 6.2±2.6 months. Regarding the duration of overall survival, there was no significant difference ( p value = 0.98) upon comparing the ketogenic diet group with the chemotherapy-only group (32.5 months and 37.9 months, respectively). However, overall survivals were 50 months, 23.0 months, and 32.5 months for the ketogenic diet-chemotherapy combination response group, ketogenic diet-chemotherapy combination non-response group, and chemotherapy-only group, respectively ( p value = 0.07). The ketogenic diet-chemotherapy combination response group tended to have a longer OS than the chemotherapy-only group. In addition, in the ketogenic diet-chemotherapy combination response group, introduction time was earlier than the ketogenic diet-chemotherapy combination non-response group for 5.7 months, with high serum ketone body levels and low blood sugar levels. Conclusions: Chemotherapy with ketogenic diet resulted in higher response and disease control rates than chemotherapy alone. Additionally, the conversion surgery rate was high and an improved OS could be expected. Therefore, ketogenic diet may be a supportive therapy to chemotherapy. Clinical trial information: 000029527.

Atezolizumab and Bevacizumab Attenuate Cisplatin Resistant Ovarian Cancer Cells Progression Synergistically via Suppressing Epithelial-Mesenchymal Transition.

The AURELIA trial demonstrated that adding Bevacizumab to chemotherapy significantly improved progression-free survival (PFS) for platinum resistant recurrent ovarian cancer. Recently, immunotherapy also presented potential anti-tumor effects in several malignant solid tumors. This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing <6 months after completing platinum-based therapy. Based on responding to at least 2 cycles of Bevacizumab-containing chemotherapy (BC), these Patients were divided into BC response group and BC non-response group. Immunohistochemistry was used to detect that PD-L1 expression and tumor angiogenesis-related proteins (VEGF and Semaphorin4D) in tissues from 124 patients with CREOC. The positive expressions of PD-L1, VEGF, and Semaphorin4D (SEMA4D) were found in 58.73, 50.79, and 71.43% of the 63 cases CREOC tissues with BC response, respectively, which were significantly higher than that in the 61 cases BC non-response group (P < 0.05). PD-L1 expression correlated with SEMA4D and VEGF positively (r = 0.344 and 0.363, P < 0.001). Over-expressions of PD-L1, VEGF and SEMA4D are associated with more malignant clinicopathologic characteristics of CREOC Patients. In survival analysis, patients' response to BC was the independent factor for evaluation of PFS and overall survival (OS). Cell functional assays showed that Atezolizumab in combination with Bevacizumab inhibited the proliferation, migration, and invasion of cisplatin resistant ovarian cancer cell line A2780cis in vitro synergistically, which maybe associate with Bevacizumab suppressing the epithelial-mesenchymal transition (EMT) and PD-L1 expression by targeting STAT3. Furthermore, Bevacizumab and Atezolizumab induced synergistic anti-tumor effect in vivo. These findings suggest a novel therapeutic strategy for cisplatin resistant recurrent EOC and its mechanism warrants further study.

Analysis of interleukin-17 and interleukin-23 for estimating disease activity and predicting the response to treatment in active lupus nephritis patients

Renal biopsy is a “gold standard” for establishing the diagnosis and assessing prognosis and monitoring therapy in lupus nephritis (LN) patients, but it is an invasive and inconvenient procedure. Evidences showed that interleukin-17(IL-17) and interleukin-23(IL-23) may be as alternative biomarkers for diagnosing LN, monitoring LN activity and predicting the response to treatment of LN. To analyze the roles of IL-17 and IL-23 in evaluation activity of LN and predicting active LN response to immunosuppressive treatment, by comparison between IL-17, IL-23 and clinical data of LN. Eighty patients with LN and 20 healthy volunteers were enrolled in this study. Plasma levels of IL-17 and IL-23 were detected by ELISA and clinical data were collected in patients with LN. Thirty-seven patients with active LN accepted immunosuppressive therapy and followed up to 6 months. The roles of IL-17 and IL-23 in evaluation the activity of LN and the predictability for active LN response to immunosuppressive treatment were analyzed. The ages or gender rations between LN patients and healthy controls were not significant difference at baseline. Baseline levels of IL-17 and IL-23 were higher in patients with active LN compare to them in patients with inactive LN or controls (P<0.001) and IL-23 in patients with inactive LN was higher than its in controls (P=0.004). IL-17 and IL-23 decreased significantly in active LN patients after 6 months therapy (P<0.001). The baseline level of IL-23 was significantly different in subgroups response to the immunosuppressive treatment in patients with active LN (P=0.0014). Baseline level of IL-23 in complete response group was lower than its in partial response group (P=0.0015) or nonresponse group (P=0.013). IL-17 was negative correlation with C3 (r=-0.44, P<0.001). IL-17 and IL-23 correlated with systemic lupus erythematosus (SLE) disease activity index (P<0.001). The correlation between IL-17 and LN pathological acute index (AI) was higher than the correlation between IL-23 and AI. (r=0.52, P<0.001 vs. r=0.41, P<0.001). Receiver Operation Characteristics (ROC) showed that IL-17 and IL-23 could be used to evaluate SLE disease activity index. IL-17 could be used as biomarker to evaluate pathological AI. IL-23 could be used as a predictor for predicting response to immunosuppressive treatment in patients with active LN. IL-17 and IL-23 may involve and contribute to LN. IL-17 could be used as a biomarker for LN clinical and pathological AI. IL-23 could be used as a predictor for predicting response to immunosuppressive treatment in patients with active LN.

Analysis of factors relevant to primary non-response to infliximab treatment in patients with Crohn's disease

Objective: To evaluate factors relevant to primary non-response in patients with Crohn's disease undergoing infliximab (IFX) treatment at week 14. Methods: Patients with Crohn's disease in the Third Hospital of Peking University who were subject to IFX treatment more than 3 times and followed-up for more than 14 weeks from October 2015 to October 2018 were reviewed. The response was defined by a decrease of ≥100 points from baseline in the Crohn's Disease Activity Index. The clinical data and laboratory examinations of the two groups were compared, and the treatment outcomes of non-responders were also followed up. Results: A total of 41 patients were enrolled, among which 27(65.9%) were male. The median age at treatment was 25 years, and 8 patients lost primary response (19.5%). There was no significant difference in the sex, age at diagnosis or treatment, Montreal disease type and laboratory examinations [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin, albumin] in the response group and non-response group at baseline phase (P>0.05). Baseline CRP decreased from 17.7 (26.2) mg/L to 2.2 (3.6) mg/L in the response group, but increased from 11.7 (9.5) mg/L to 31.6 (28.4) mg/L in the non-response group at week 14 (P=0.024). The trend of ESR change in the response group [from 23.0 (28.5) mm/h to 7.0 (8.5) mm/h] and the non-response group [from 24.5 (22.5) mm/h to 35.0 (26.5) mm/h] was similar with that of CRP (P=0.036). Hemoglobin and albumin were significantly elevated in the response group, but not in the non-response group at week 14 (P=0.593, P=0.255). Among the non-response patients, 5 were converted to responsive after the treatment protocols had been adjusted. The combined immunosuppressant treatment all obtained clinical response. Conclusions: The elevated CRP and/or ESR may serve as indicators of primary non-response (at week 14) to IFX treatment among Crohn's disease patients, and the combination of immunosuppressive agents may be one of the effective treatments after excluding infection and other causes.

Evaluation of the response of breast cancer patients to neoadjuvant chemotherapy by combined contrast-enhanced ultrasonography and ultrasound elastography.

The purpose of the present study was to investigate whether contrast-enhanced ultrasonography (CEUS) in combination with ultrasound elastography (UE) is able to accurately predict the efficacy of neoadjuvant chemotherapy (NAC) in breast cancer patients. A total of 65 breast cancer patients who received NAC at the First Affiliated Hospital of Zhejiang University (Hangzhou, China) between February 2016 and August 2017 and were recruited for the present study. Prior to and after NAC, examination by CEUS, UE or their combination was performed. Pathological results were obtained at the end of each chemotherapy cycle, based on which 41 cases were assigned to the response group and 24 to the non-response group. Kappa values were 0.710, 0.434 and 0.836 for CEUS, UE and CEUS+UE, respectively. The area under the receiver operating characteristic curves for CEUS, UE and CEUS+UE for determining the response to NAC was 0.864 [95% confidence interval (CI), 0.765–0.964], 0.715 (95% CI, 0.579–0.850) and 0.910 (95% CI, 0.826–0.993), respectively. It was identified that the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of CEUS+UE were higher than those of CEUS and US individually. The prediction accuracy was 89.2, 90.8 and 100% for CEUS, UE and their combination, respectively. CEUS and UE have their own advantages in evaluating the clinical efficacy of NAC in breast cancer, and a higher accuracy was achieved when the two techniques were applied in combination. Therefore, a combination of CEUS and UE may be a preferred method for the clinical assessment of the efficacy of NAC in breast cancer patients.

GSK-3β and BDNF genes may not be associated with venlafaxine treatment response in Chinese of Han ethnicity.

PurposeVenlafaxine is one of the commonly prescribed antidepressants for major depressive disorder (MDD). Accumulated evidence revealed the involvement of glutamatergic system in the pathophysiology of MDD and antidepressant treatment.MethodsWe recruited 193 MDD patients who have been taking venlafaxine for 6 weeks, and investigated whether single nucleotide polymorphisms (SNPs) in GSK-3β and BDNF were associated with treatment response. Nine SNPs were selected randomly depending on association studies. Efficacy of treatment was determined by 17-item Hamilton Rating Scale. Allele and genotype frequencies were compared between responders and nonresponders.ResultsAfter adjusting the false discovery rate, no significant difference was observed between response and nonresponse groups in allele or genotype distributions after venlafaxine treatment for 6 weeks.ConclusionOur results indicated that genetic variants in the GSK-3β and BDNF may not be associated with treatment response in MDD patients treated with venlafaxine.

Abstract P5-12-17: Prognostic and predictive value of serum level of vascular endothelial growth factor-A in metastatic breast cancer patients treated with bevacizumab plus paclitaxel

Abstract Background Several studies showed that first-line bevacizumab plus chemotherapy for HER2-negative metastatic breast cancer improves progression-free survival and tumor response rate but not overall survival. MERiDiAN trial evaluated plasma vascular endothelial growth factor-A (VEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer. However, results of this trial do not support using baseline plasma VEGF-A to identify patients benefitting most from bevacizumab. We measured baseline serum VEGF-A level from stored blood samples of metastatic breast cancer patient with treated bevacizumab plus paclitaxel as fist-line and later line therapy, and evaluated a correlation between serum VEGF-A level and efficacy of bevacizumab and prognosis of breast cancer patients tread with bevacizumab, retrospectively. Patients and methods We examined blood samples from 57 metastatic breast cancer patients treated with bevacizumab and paclitaxel, after obtaining written informed consent. And, we evaluated a correlation between baseline serum VEGF-A level and time to treatment failure (TTF) and overall survival (OS). We also compared the serum VEGF-A level of response group (CR and PR) and that of non-response group (SD and PD). Results Baseline serum level of VEGF-A ranged from 80 to 2079 pg/ml. Cases of treatment line were as follows: first-line, 22 cases (38.6%); second line, 11 cases (19.3%) and third-line and the later line, 24 cases (42.1%). The cutoff identified by ROC curve analysis that was able to differentiate response group and non-response group in first-line setting was 360pg/ml for serum VEGF-A. And, we separated high serum VGEF-A group and low serum VEGF-A group of patients treated with bevacizumab plus paclitaxel. In patients treated as first line therapy, median TTF was 4.0 months with high serum VGEF-A group versus 5.0 months with low serum VEGF-A group, and median OS was 12 months with high serum VGEF-A group versus 11months with low serum VEGF-A group. There were no significant differences in both TTF and OS in first line setting. In patients treated as second line and later line therapy, median TTF was 2.8 months with high serum VGEF-A group versus 7.1 months with low serum VEGF-A group, and median OS was 6.4 months with high serum VGEF-A group versus 12.7 months with low serum VEGF-A group. The prognosis of high serum VEGF-A group was significantly worse than that of low serum group in both TTF and OS. The serum VEGF-A level of response group was tend to be higher than that of non-response group in first line setting, and was lower in second and later line setting. However, there were no significant differences. Conclusion In this study, serum VEGF-A cannot be a predictor for efficacy of bevacizumab plus paclitaxel as first line therapy for metastatic breast cancer patients. On the other hand, there was a possibility that high serum level of VEGF-A can be a poor prognostic factor in late line therapy setting of bevacizumab. Citation Format: Tozuka K, Nagai SE, Matsumoto H, Hayashi Y, Kubo K, Tsuboi M, Sato A, Takai K, Wang X, Yamada Y, Inoue K. Prognostic and predictive value of serum level of vascular endothelial growth factor-A in metastatic breast cancer patients treated with bevacizumab plus paclitaxel [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-12-17.