Non-response Group Research Articles

CT-based radiomics for the identification of colorectal cancer liver metastases sensitive to first-line irinotecan-based chemotherapy.

Chemosensitivity prediction in colorectal cancer patients with liver metastases has remained a research hotspot. Radiomics can extract features from patient imaging, and deep learning or machine learning can be used to build models to predict patient outcomes prior to chemotherapy. In this study, the radiomics features and clinical data of colorectal cancer patients with liver metastases were used to predict their sensitivity to irinotecan-based chemotherapy. A total of 116 patients with unresectable colorectal cancer liver metastases who received first-line irinotecan-based chemotherapy from January 2015 to January 2020 in our institution were retrospectively collected. Overall, 116 liver metastases were randomly divided into training (n = 81) and validation (n = 35) cohorts in a 7:3 ratio. The effect of chemotherapy was determined based on Response Evaluation Criteria in Solid Tumors. The lesions were divided into response and nonresponse groups. Regions of interest (ROIs) were manually segmented, and sample sizes of 1×1×1, 3×3×3, 5×5×5 mm3 were used to extract radiomics features. The relevant features were identified through Pearson correlation analysis and the MRMR algorithm, and the clinical data were merged into the artificial neural network. Finally, the p-model was obtained after repeated learning and testing. The p-model could distinguish responders in the training (area under the curve [AUC] 0.754, 95% CI 0.650-0.858) and validation cohorts (AUC 0.752 95% CI 0.581-0.904). AUC values of the pure image group model are 0.720 (95% CI 0.609-0.827) and 0.684 (95% CI 0.529-0.890) for the training and validation cohorts respectively. As for the clinical data model, AUC values of the training and validation cohorts are 0.638 (95% CI 0.500-0.757) and 0.545 (95% CI 0.360-0.785), respectively. The performances of the latter two are less than that of the former. The p-model has the potential to discriminate colorectal cancer patients sensitive to chemotherapy. This model holds promise as a noninvasive tool to predict the response of colorectal liver metastases to chemotherapy, allowing for personalized treatment planning.

Extracellular volume fraction determined by dual-layer spectral detector CT: Possible role in predicting the efficacy of preoperative neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma

PurposeTo clarify the relationship between extracellular volume (ECV) measured by dual-energy CT (DECT) and efficacy of preoperative neoadjuvant chemotherapy (NAC) in patients with pancreatic ductal adenocarcinoma (PDAC), as compared with single-energy CT (SECT). MethodsWe enrolled 67 patients with PDAC who underwent dynamic contrast-enhanced CT with a dual-energy CT system prior to NAC. Attenuation values were measured on unenhanced and the equilibrium-phase 120-kVp equivalent CT images for PDAC and the aorta. ΔHU-tumor, ΔHU-tumor/ΔHU-aorta, and SECT-ECV were calculated. Iodine densities of the tumor and aorta were measured in the equilibrium phase, and DECT-ECV of the tumor was calculated. Response to NAC was evaluated and the correlation between imaging parameters and response to NAC was statistically assessed. ResultsTumor DECT-ECVs were significantly lower in the response group (n = 7) than in the non-response group (n = 60), with most significant difference (p = 0.0104). DECT-ECV showed highest diagnostic value with an Az value of 0.798. When using the optimal cut off value of DECT-ECV (<26.0 %), sensitivity, specificity, accuracy, positive predictive value, and negative value for predicting response group were 71.4 %, 85.0 %, 83.6 %, 35.7 % and 96.2 %, respectively. ConclusionPDAC with lower DECT-ECV can potentially show better response to NAC. DECT-ECV might be a useful biomarker for predicting response to NAC in patients with PDAC.

AFP Response to Locoregional Therapy Can Stratify the Risk of Tumor Recurrence in HCC Patients after Living Donor Liver Transplantation

(1) Background: Alpha-fetoprotein (AFP) has been incorporated into the selection criteria of liver transplantation and been used to predict the outcome of hepatocellular carcinoma (HCC) recurrence. Locoregional therapy (LRT) is recommended for bridging or downstaging in HCC patients listed for liver transplantation. The aim of this study was to evaluate the effect of the AFP response to LRT on the outcomes of hepatocellular carcinoma patients after living donor liver transplantation (LDLT). (2) Methods: This retrospective study included 370 HCC LDLT recipients with pretransplant LRT from 2000 to 2016. The patients were divided into four groups according to AFP response to LRT. (3) Results: The nonresponse group had the worst 5-year cumulative recurrence rates whereas the complete-response group (patients with abnormal AFP before LRT and with normal AFP after LRT) had the best 5-year cumulative recurrence rate among the four groups. The 5-year cumulative recurrence rate of the partial-response group (AFP response was over 15% lower) was comparable to the control group. (4) Conclusions: AFP response to LRT can be used to stratify the risk of HCC recurrence after LDLT. If a partial AFP response of over 15% declineis achieved, a comparable result to the control can be expected.

Tumor necrosis factor-related apoptosis-inducing ligand gene polymorphism and its plasma phenotype in relation to Crohn's disease

Objectives: To investigate the associations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene polymorphism and plasma soluble TRAIL level (sTRAIL) with Crohn's disease (CD) and to retrospectively analyze the effects of TRAIL gene variants and plasma sTRAIL levels on clinical response to infliximab (IFX). Methods: From January 2012 to January 2021, 312 CD patients [205 males, 107 females, average age (33.9±9.8) years] and 514 age-and gender-matched healthy controls [304 males, 210 females, average age (34.9±9.4) years] were recruited from the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University. Among them, 72 patients with active CD who were ineffective or intolerant to traditional drug therapy regularly received IFX (5 mg/kg) treatment. According to the changes in the Harvey-Bradshaw index (HBI) and the Simplified Endoscopic Score for Crohn's Disease (SES-CD) in the 14th week, these patients were classified into response group (a decrease in HBI≥3 or a decrease in SES-CD≥50%) and non-response group. TRAIL (rs1131568) gene polymorphism was analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry technique. The plasma sTRAIL level was examined by enzyme-linked immunosorbent assay (ELISA). Based on the Montreal CD classification criteria, all CD patients were divided into different subgroups. Finally, a comprehensive analysis was performed to investigate the relationship between TRAIL (rs1131568) gene polymorphism, the plasma sTRAIL level and the risk of CD, the clinicopathological characteristics of CD patients, and the clinical response to IFX. Results: The recessive model analysis showed that the homozygous variant genotype (CC) was more prevalent in patients with moderately to severely active CD than in those with mildly active CD (45.34% vs 29.23%, P=0.005). Both variant allele (C) and homozygous variant genotype (CC) in patients with stricturing and penetrating CD were more frequent than those in patients with non-stricturing and non-penetrating CD (65.48% vs 57.53%, P=0.046; 49.21% vs 31.18%, P=0.001). The dominant model analysis showed that variant allele (C) and variant genotype (TC+CC) was higher in CD patients with perianal lesions than in those without perianal lesions (66.83% vs 58.17%, P=0.037; 92.31% vs 78.37%, P=0.002). The average plasma sTRAIL level was higher in CD patients than in healthy controls [(243.04±42.74) ng/L vs (194.16±31.14) ng/L, P<0.001]. Compared with the patients with mildly active CD, the plasma sTRAIL level was increased in those with moderately to severely active CD [263.47(242.09, 281.91) ng/L vs 231.13(211.11, 247.11) ng/L, P<0.001]. The same conclusion was also drawn for the patients with stricturing and penetrating CD in contrast to those with non-stricturing and non-penetrating CD [266.18 (246.68, 289.91) ng/L vs 227.19 (204.57, 249.59) ng/L, P<0.001]. The plasma sTRAIL level was also higher in patients with perianal disease than in those without perianal disease [(261.40±41.51) ng/L vs (233.86±40.41) ng/L, P<0.001]. Multiple linear regression analysis further showed that disease activity (β=22.640, P<0.001) and homozygous variant genotype (CC) (β=16.814, P<0.001) may be positively related to the plasma sTRAIL level in CD patients independently. At the 14th week of IFX treatment, the plasma sTRAIL level in the response group was lower than that in the non-response group [205.98(190.72, 214.56) ng/L vs (238.33±29.38) ng/L, P<0.001]. Compared with week 0, the plasma sTRAIL level was decreased in the response group in the 14th week [(205.98 (190.72, 214.56) ng/L vs (239.89±42.43) ng/L, P<0.001]. Non-conditional logistic regression analysis showed that variant allele (C) and variant genotype (TC+CC) were less frequent in the response group than in the non-response group (53.33% vs 70.83%, P=0.037; 70.00% vs 91.67%, P=0.036). Conclusions: The increased plasma sTRAIL level may be a risk factor for CD. TRAIL (rs1131568) gene variation and the increase of plasma sTRAIL level may be associated with the increased disease activity of CD and may be the risk factors for stenosis, penetration, and perianal lesions in CD patients. In addition, TRAIL (rs1131568) gene variation or the increase of plasma sTRAIL level may be related to no response to IFX treatment in CD patients.

Relationship between efficacy and common metabolic parameters in first-treatment drug-naïve patients with early non-response schizophrenia: a retrospective study

BackgroundComorbid metabolic disorders in patients with schizophrenia are very common. Patients with schizophrenia who respond to therapy early are often strongly predictive of better treatment outcomes. However, the differences in short-term metabolic markers between early responders and early non-responders in schizophrenia are unclear.Methods143 first-treatment drug-naïve schizophrenia patients were included in this study and were given a single antipsychotic medication for 6 weeks after admission. After 2 weeks, the sample was divided into an early response group and an early non-response group based on psychopathological changes. For the study endpoints, we depicted the change curves of psychopathology in both subgroups and compared the differences between the two groups in terms of remission rates and multiple metabolic parameters.ResultsThe early non-response had 73 cases (51.05%) in the 2nd week. In the 6th week, the remission rate was significantly higher in the early response group than in the early non-response group (30,42.86% vs. 8,10.96%); the body weight, body mass index, blood creatinine, blood uric acid, total cholesterol, triglyceride, low-density lipoprotein, fasting blood glucose, and prolactin of the enrolled samples were significantly increased, and high-density lipoprotein was significantly decreased. ANOVAs revealed a significant effect of treatment time on abdominal circumference, blood uric acid, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, fasting blood glucose and prolactin, and a significant negative effect of early non-response to treatment on abdominal circumference, blood creatinine, triglyceride, fasting blood glucose.ConclusionsSchizophrenia patients with early non-response had lower rates of short-term remission and more extensive and severe abnormal metabolic indicators. In clinical practice, patients with early non-response should be given a targeted management strategy, antipsychotic drugs should be switched on time, and active and effective interventions for their metabolic disorders should be given.

The Value of Dynamic Contrast-Enhanced MRI in Predicting the Response of Idiopathic Granulomatous Mastitis to Steroid Therapy and Comparison of Clinical and Radiological Outcomes

Background: The aim of this study was to investigate the value of pre-treatment dynamic contrast-enhanced MRI (DCE-MRI) findings in predicting clinical and radiological response to treatment in patients with idiopathic granulomatous mastitis (IGM) receiving steroid therapy and to compare clinical and DCE-MRI results after treatment. Methods: Pre- and post-treatment MRI examinations of 86 patients (with a mean age of 33.8 years; range, 20–57 years) diagnosed with IGM between January 2014 and September 2022 were retrospectively evaluated. Lesion characteristics and longest diameter, number of involved quadrants, retroareolar involvement, and presence of fistula or lymphadenopathy were noted. Patients were categorized into clinical complete response (CCR), clinical non-response (CNR) groups based on clinical response and into radiological complete response (RCR) and radiological non-response (RNR) groups based on radiological response. Results: The analyses revealed no relationship between the lesion type (abscess, NME, abscess, and NME), presence of lymphadenopathy or fistula, number of involved quadrants, retroareolar involvement, and treatment response on pre-treatment MRI (p&gt;0.05). The longest lesion diameter was smaller in the CCR group than in the CNR group (p = 0.02). After treatment, 40.7% (35/86) of the patients achieved RCR + CCR, while 16.3% (14/86) achieved RNR + CNR. On the other hand, 43% (37/86) of the patients achieved CCR + RNR. Conclusion: CCR is more common in patients with smaller lesions. Other pre-treatment MRI findings were not correlated with radiological or clinical response. A significant proportion of patients with CCR had residual lesions radiologically.

P478 Platelet-related indicators for predicting vedolizumab response in patients with Ulcerative Colitis

Abstract Background Ulcerative Colitis (UC) combine both inflammation and coagulation in their pathogenesis and clinical manifestations. Although platelets (PLT) are well known for their role in hemostasis, there are a rising number of studies supporting their considerable role as inflammatory amplifiers in chronic inflammatory conditions. However, whether PLT are related to the efficacy of biologic agents is unknown. This study aimed to investigate whether platelet ratio before and after induction therapy can be predictive biomarkers for the therapeutic outcomes of vedolizumab therapy in UC. Methods Patients with moderate-to-severe UC receiving vedolizumab in our hospital between November 2020 and November 2022 were retrospectively evaluated. Patients with concomitant corticosteroid treatment≥20 mg, immunomodulators, or other conditions that could modify the platelet count were excluded. The primary endpoint was clinical response at the end of the induction period (at 14 weeks). We analyzed the association between platelet count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein (CRP), fecal calprotectin, and the clinical efficacy of vedolizumab. The above indicators between the response and nonresponse groups were compared via a univariate analysis. The independent risk factors of nonresponse were identified via a multivariate analysis. Results Seventy-one patients with moderate-to-severe active UC started treatment with vedolizumab and 20 patients (28.2%) experienced loss of response (LOR) after induction therapy. The platelet count, albumin, CRP, NLR, PLR, MLR, and Particul Mayo score between the LOR and response groups significantly differed. The Platelet ratio before and after induction therapy cut-off value of 1.077 was predictive of LOR, using receiver operating characteristic analysis (sensitivity:78.0%, specificity:81.8%). A univariate analysis revealed a significant relationship between LOR and the platelet ratio (P＜0.05). Multivariate analysis indicated the platelet ratio as an independent prognostic factor for LOR (OR=11.219, 95% CI:3.316-37.959, P＜0.05). Conclusion Platelet ratio before and after induction therapy is a useful prognostic marker in patients with moderate-to-severe active UC treated with vedolizumab, and may contribute to appropriate use of vedolizumab LOR. A large sample from multiple centers is needed to validate the association between platelet-related measures and the rate of vedolizumab response.

Computed Tomography-Based Radiomics Analysis for Prediction of Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.

Previous studies have pointed out that magnetic resonance- and fluorodeoxyglucose positron emission tomography-based radiomics had a high predictive value for the response of the neoadjuvant chemotherapy (NAC) in breast cancer by respectively characterizing tumor heterogeneity of the relaxation time and the glucose metabolism. However, it is unclear whether computed tomography (CT)-based radiomics based on density heterogeneity can predict the response of NAC. This study aimed to develop and validate a CT-based radiomics nomogram to predict the response of NAC in breast cancer. A total of 162 breast cancer patients (110 in the training cohort and 52 in the validation cohort) who underwent CT scans before receiving NAC and had pathological response results were retrospectively enrolled. Grades 4 to 5 cases were classified as response to NAC. According to the Miller-Payne grading system, grades 1 to 3 cases were classified as nonresponse to NAC. Radiomics features were extracted, and the optimal radiomics features were obtained to construct a radiomics signature. Multivariate logistic regression was used to develop the clinical prediction model and the radiomics nomogram that incorporated clinical characteristics and radiomics score. We assessed the performance of different models, including calibration and clinical usefulness. Eight optimal radiomics features were obtained. Human epidermal growth factor receptor 2 status and molecular subtype showed statistical differences between the response group and the nonresponse group. The radiomics nomogram had more favorable predictive efficacy than the clinical prediction model (areas under the curve, 0.82 vs 0.70 in the training cohort; 0.79 vs 0.71 in the validation cohort). The Delong test showed that there are statistical differences between the clinical prediction model and the radiomics nomogram ( z = 2.811, P = 0.005 in the training cohort). The decision curve analysis showed that the radiomics nomogram had higher overall net benefit than the clinical prediction model. The radiomics nomogram based on CT radiomics signature and clinical characteristics has favorable predictive efficacy for the response of NAC in breast cancer.

PD-1 blockade and lenalidomide combination therapy for chronic active Epstein-Barr virus infection

ObjectivesChronic active Epstein-Barr virus infection (CAEBV) is a prototype of EBV-associated T-or NK-cell lymphoproliferative diseases. It is a disease with poor outcome. Almost all current therapies are ineffective except of allogeneic hematopoietic stem cell transplantation. MethodsWe investigated the efficacy and safety of programmed death 1 (PD-1) blockade (Sintilimab), combined with lenalidomide, which is an immunomodulatory drug, in an open-label, single-center, prospective study involving CAEBV patients. PD1 blockade 2mg/kg was given every two weeks by intravenous infusion on day 1, and lenalidomide 5mg (age<18 years)/10mg (age ≥ 18 years) was given orally once a day on day 1-14. ResultsAs of Nov 15, 2020, 34 patients were enrolled. As of the Feb 1, 2021 analysis cut-off date, 24 cases completed at least 3 courses and were assessed for efficacy. The overall response rate is 54.2% (13/24, 45.8% complete response; 8.3% partial response). EBV-DNA copies in PBMC decreased significantly (p = 0.002). The proportion of CD8+T cells in lymphocytes increased (p = 0.007). The comparative analysis between response group and non-response group showed the proportion of Effector Memory CD8+ T cells and cytokines of CTLs activation (IFN-γ, CD27, CD30, MIG, IP-10) increased significantly in Response-group after treatment. Whole-exome sequencing generated from peripheral blood and saliva samples reveal that Non-Response group had a higher somatic mutational load of copy number variation in background. With a median follow-up time of 17.8 months, 22 of 24 patients were alive with an estimated survival probability of 91.3% at 1 year. All 34 patients were assessed for safety evaluation. The possible drug-related adverse events were reported in 17 (50%) patients. ConclusionsPD-1 blockade combined with lenalidomide was an effective and safe therapy for CAEBV patients. The significant therapeutic effect and the different characteristics between response and non-response group, provides a possible predictive value for CAEBV treatment option.

Machine Learning to Predict the Response to Lenvatinib Combined with Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma.

Lenvatinib and transarterial chemoembolization (TACE) are first-line treatments for unresectable hepatocellular carcinoma (HCC), but the objective response rate (ORR) is not satisfactory. We aimed to predict the response to lenvatinib combined with TACE before treatment for unresectable HCC using machine learning (ML) algorithms based on clinical data. Patients with unresectable HCC receiving the combination therapy of lenvatinib combined with TACE from two medical centers were retrospectively collected from January 2020 to December 2021. The response to the combination therapy was evaluated over the following 4-12 weeks. Five types of ML algorithms were applied to develop the predictive models, including classification and regression tree (CART), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost), random forest (RF), and support vector machine (SVM). The performance of the models was assessed by the receiver operating characteristic (ROC) curve and area under the receiver operating characteristic curve (AUC). The Shapley Additive exPlanation (SHAP) method was applied to explain the model. A total of 125 unresectable HCC patients were included in the analysis after the inclusion and exclusion criteria, among which 42 (33.6%) patients showed progression disease (PD), 49 (39.2%) showed stable disease (SD), and 34 (27.2%) achieved partial response (PR). The nonresponse group (PD + SD) included 91 patients, while the response group (PR) included 34 patients. The top 40 most important features from all 64 clinical features were selected using the recursive feature elimination (RFE) algorithm to develop the predictive models. The predictive power was satisfactory, with AUCs of 0.74 to 0.91. The SVM model and RF model showed the highest accuracy (86.5%), and the RF model showed the largest AUC (0.91, 95% confidence interval (CI): 0.61-0.95). The SHAP summary plot and decision plot illustrated the impact of the top 40 features on the efficacy of the combination therapy, and the SHAP force plot successfully predicted the efficacy at the individualized level. A new predictive model based on clinical data was developed using ML algorithms, which showed favorable performance in predicting the response to lenvatinib combined with TACE for unresectable HCC. Combining ML with SHAP could provide an explicit explanation of the efficacy prediction.

Abstract A023: Analysis of survival and prognostic factors for patients with non-small cell lung cancer and brain metastasis: 10-year experience in a single institution

Abstract The aims of the study were 1) to perform the review of non-small cell lung cancer (NSCLC) patients with brain metastasis in our institution, 2) to investigate the response and prognostic factor of brain metastasis after institution’s best treatment, and 3) to suggest the shift of treatment paradigms for brain metastasis. From Jan. 2007 to Oct. 2018, A total 214 NSCLC patients with brain metastasis were enrolled. Female to male ratio was 0.65 and median age at diagnosis of NSCLC was 64 years (range, 30-90). 54 patients had a solitary brain metastasis and 76 patients had more than 10 lesions. Supratentorial, infratentorial and both locations were 106, 17, and 91 patients, respectively. 116 patients (54%) had symptoms associated with brain metastasis at the diagnosis of brain metastasis. Radiation only, radiosurgery, craniotomy with whole brain radiotherapy (WBRT), and supportive care were given for brain metastasis in 111 (52%), 10 (5%), 13 (6%) and 61 (29%) patients, respectively. Overall survival (OS) was associated with age, treatment modality, histology, egfr mutation. Median OS of Radiation only, radiosurgery, craniotomy with WBRT, and supportive care was 13, 15, 15 and 9 months, respectively (P-value 0.044). Median OS of adenocarcinoma and squamous cell carcinoma was 15 and 4 months, respectively (P-value &amp;lt;0.05). Median OS of egfr mutation and wild type was 18 and 9 months, respectively (P-value 0.016). The number and location of brain metastasis, symptoms and sex were not associated with OS Serial brain imaging was performed in 99 patients. 61 out of them (62%) developed shrinkage of brain metastasis (response group). Median OS of response and non-response group were 23 and 17 months (p-value 0.618). Age is significantly associated with response of brain metastasis to the institution’s best treatment (p-value 0.047). Interestingly, 3 patients developed complete remission of brain metastasis following WBRT and chemotherapy. The response duration was 431, 390, 641 days, respectively. Our data show that the prognosis of brain metastasis primarily depends on the age of NSCLC patients rather than the number, location of brain metastasis, treatment modality. Survival of NSCLC patients with brain metastasis was about 15 months despite the institution’s best treatment. The authors suggest that we should update our institution’s treatment policy and provide the latest treatments for patients. Citation Format: Seung Ho Yang. Analysis of survival and prognostic factors for patients with non-small cell lung cancer and brain metastasis: 10-year experience in a single institution [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A023.

Tajectories of the self-efficacy of HIV testing among MSM based on latent class growth model

Objective: To analyze the trajectories of HIV testing self-efficacy among men who have sex with men (MSM) based on latent class growth model. Methods: From August 2019 to May 2021, 404 MSM were recruited in Shandong Province and subjected to a 1-year follow-up study with individual intervention (pushing intervention pictures and videos in WeChat and follow-up questionnaires) and community intervention (forwarding to friends and sharing and discussing HIV testing-related information in WeChat groups). The level of HIV testing self-efficacy among MSM was measured. The long-term trend of HIV testing self-efficacy was analyzed using the latent class growth model (LCGM), and the influencing factors of the trend were analyzed. Results: A total of 404 MSM were (28.25±8.95) years old, with the oldest being 58 and the youngest being 18. The scores of HIV testing self-efficacy M(Q1, Q3) at baseline and 4 follow-ups were 18.00 (17.00, 21.00), 19.00 (18.00, 22.00), 19.00 (18.00, 22.00), 19.00 (18.00, 22.00) and 19.00 (18.00, 22.00). The results of the freely estimated two-category LCGM model showed that the trend of HIV testing self-efficacy among MSM could be divided into two classes, "intervention response group" [255(63.1%)] and "intervention non-response group" [149(36.9%)]. The former had a higher level of HIV testing self-efficacy which tended to increase at first and then decrease over time, while the latter had a lower and more stable level. The results of the multifactorial logistic regression analysis showed that the OR values of MSM in business or service and jobless or unemployed were 0.261 (95%CI: 0.108-0.633) and 0.186 (95%CI: 0.057-0.610), respectively, using the students as the reference group. Conclusion: There is a group heterogeneity in the trend of HIV testing self-efficacy in the intervention conditions among MSM, and occupation may be an influencing factor.

Safety and effectiveness of neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in stage II–III NSCLC (LungMate 002): an open-label, single-arm, phase 2 trial

BackgroundThis trial aimed to analyse the safety, effectiveness and transcriptomic characteristics of neoadjuvant toripalimab plus chemotherapy in II–III non-small-cell lung cancer (NSCLC).MethodsPatient eligibility mainly involved treatment-naive, clinical stage II–III and wild-type EGFR/ALK NSCLC. The patients received 2–4 cycles of toripalimab (240 mg q3w) plus carboplatin-based chemotherapy. After the second treatment cycle, all patients were re-evaluated by a multidisciplinary team. Candidates eligible for surgery underwent surgery; otherwise, patients received the remaining treatment cycles. The primary endpoints were safety and major pathological response (MPR). Secondary endpoints were R0 resection rate, progression-free survival (PFS) and overall survival (OS). RNA sequencing of baseline and post-treatment samples was conducted to explore the transcriptomic characteristics of the therapeutic response.ResultsIn total, 50 eligible patients were enrolled, including 12 (24.0%) with resectable disease (RD) and 38 (76.0%) with potentially resectable disease (PRD). Treatment-related adverse events (TRAEs) were recorded in 48 cases (96.0%). Severe TRAEs occurred in 3 (6.0%) cases, including myelosuppression, drug-induced liver injury and death related to haemoptysis. The objective response rate (ORR) was 76.0%, with 8 (16.0%) patients having a complete response (CR), 30 (60.0%) partial response (PR), 10 (20.0%) stable disease (SD) and 2 (4.0%) progressive disease (PD). Surgery could be achieved in 12 (100%) patients with RD and 25 (65.8%) with PRD; 1 (2.0%) with PRD refused surgery. Therefore, R0 resection was performed for all 36 (100%) patients who underwent surgery; 20 (55.6%) achieved MPR, including 10 (27.8%) with a complete pathological response (pCR). The CHI3L1 (chitinase-3-like protein 1) immunohistochemistry (IHC) expression of baseline tumour samples could predict the therapeutic response (AUC=0.732), OS (P=0.017) and PFS (P=0.001). Increased PD-1 expression, T cell abundance and immune-related pathway enrichment were observed in post-treatment samples compared to baseline in the response group (CR+PR) but not in the non-response group (SD+PD).ConclusionsNeoadjuvant toripalimab plus chemotherapy was safe and effective, with a high MPR and manageable TRAEs for II–III NSCLC, even converting initially PRD to RD. Disparate transcriptomic characteristics of therapeutic efficiency were observed, and CHI3L1 expression predicted therapeutic response and survival.Trial registrationChiCTR1900024014, June 22, 2019.

Baseline Knee Pain Predicts Long-Term Response of Intra-Articular Steroid Injection in Symptomatic Knee Osteoarthritis: Data from OAI.

The current study aims to investigate the factors that could predict response to intra-articular corticosteroid injection (IACI) in patients with knee osteoarthritis (KOA). Data of participants were retrieved from the Osteoarthritis Initiative database. Participants with at least one IACI treatment on single or bilateral knees within the first 5 years of follow-up were retrospectively included. Demographic data, clinical and radiographic variables were collected at both baseline and the first follow-up after IACI treatment. Positive response to IACI treatment was defined as >20% reduction of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from V0 to V1. All the variables with P < 0.2 after the comparison between the response and non-response groups were included in a multivariable logistic regression model to identify independent response predictive patient-specific valuables. Receiver operating characteristic curves were performed to establish the cutoff values of independent predictors. The current study included a total of 385 participants (473 knees), with 155 and 318 knees classified into the response group and non-response group, respectively. Those with satisfied responses to IACI treatment had significantly higher WOMAC pain score (P < 0.001), disability score (P = 0.002), and stiffness score (P = 0.015) at the baseline. Baseline WOMAC pain score showed significant association with positive response to IACI treatment in multivariate logistic analysis and the best cutoff value was 5 points. The rate of analgesics utilization was lower (P = 0.014) in the response group than the non-response group after the IACI treatment. KOA patients with a baseline WOMAC pain score ≥5 are more likely to benefit from IACI treatment.

An efficient class of estimators for finite population mean in the presence of non-response under ranked set sampling (RSS).

In this study, we address the problem of estimating the finite population mean when the non-response occurs on the characteristics under study. We propose a class of Rao-regression type estimators when ranked set sampling (RSS) procedure is used to collect the data from non-response group only and from both, the response and non-response groups. The information provided on the auxiliary variable is used at both stages i.e., at designing stage and the estimation stage. Expressions for bias and mean square error of the estimators are obtained up to first order of approximation. A comprehensive simulation study is carried out to observe the performances of the estimators under non-response.

Serum proteomics analysis of biomarkers for evaluating clinical response to MTX/IGU therapy in early rheumatoid arthritis

Methotrexate (MTX) and iguratimod (IGU) are conventional synthetic disease modifying antirheumatic drugs widely used in the treatment of Rheumatoid arthritis (RA) in China. Although MTX combined with IGU can significantly inhibit the progression of RA, some patients do not respond to the treatment. The purpose of this study is to explore the difference of serum protein expression between RA patients with good and poor response to the combined therapy by label-free quantitative proteomic approach. From the proteomics data, a total of 782 proteins in the serum of RA patients were detected, and of which 9 were upregulated and 18 were downregulated in the good response group compared to poor response group. Among them, four significantly differentially expressed proteins (RELN, LDHA, MRC1 and TKT) were further validated by multiple reaction monitoring (MRM)-based quantification approach, and three of them (RELN, LDHA and MRC1) were confirmed to be correlated with the response to MTX/IGU therapy. Logistic regression and ROC analysis indicated that the combination of RELN, LDHA and MRC1 had good performance in evaluating the response. This result proved the different serum proteins signature fingerprint between response group and non-response group; and highlighted the potential of the label-free and mass spectrometry-based quantitative proteomic approach in screening biomarkers for evaluating clinical response to MTX/IGU therapy in RA.

Repetitive transcranial magnetic stimulation: Course and early prediction of response in depression

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, yet few studies have mapped the trajectories of symptom change over treatment. Tracking clinical response during early treatment may be helpful to predict outcome, particularly non-response. MethodsWe used naturalistic data (N = 117) to examine changes in the Daily Symptom Index (DI-5) scores of adult patients with unipolar or bipolar depression who underwent ≥16 treatment sessions of left dorsolateral prefrontal cortex rTMS at a private psychiatric facility in Western Australia, between 2016 and 2019. ResultsTwo response trajectories were charted: non-response (N = 71, 61%) and response (N = 46, 39%). Both trajectories diverged at 99% confidence interval at session 10, which was used as the point to predict treatment response at session 20. The response group showed a reduction of 4.21 in the mean DI-5 score from baseline at session 10. On this basis, a 4-point reduction in the DI-5 score at session 10 was defined as predictor of responder status at session 20. If the improvement is < 4 points at session 10, the probability of non-response at session 20 is 75%. If the improvement is ≥ 4 points, the probability of response at session 20 is 66%. LimitationsThe DI-5 scores were not examined beyond 20 treatment sessions, which may have shown delayed responders in the non-response group. ConclusionsIn this study of depression response trajectories with rTMS treatment, prediction of response at session 20 can be made at session 10 of treatment. Further research is required to generalise the current findings.

Integration of cancer stemness and neoantigen load to predict responsiveness to anti-PD1/PDL1 therapy.

Background: Anti-programmed cell death 1/programmed cell death ligand 1 (PD1/PDL1) therapy is an important part of comprehensive cancer therapy. However, many patients suffer from non-response to therapy. Tumor neoantigen burden (TNB) and cancer stemness play essential roles in the responsiveness to therapy. Therefore, the identification of drug candidates for anti-PD1/PDL1 therapy remains an unmet need. Methods: Three anti-PD1/PDL1 therapy cohorts were obtained from GEO database and published literatures. Cancer immune characteristics were analyzed using CIBERSORTX, GSVA, and ESTIMATE. WGCNA was employed to identify the gene modules correlated with cancer TNB and stemness. A machine-learning method was used to construct the immunotherapy resistance score (TSIRS). Pharmacogenomic analysis was conducted to explore the potential alternative drugs for anti-PD1/PDL1 therapy resistant patients. CCK-8 assay, EdU assay and wound healing assay were used to validate the effect of the predicted drug on cancer cells. Results: The therapy response and non-response cancer groups have different microenvironment features. TSIRS was developed based on tumor neoantigen and stemness. TSIRS can effectively predict the outcomes of patients with anti-PD1/PDL1 therapy in training, validation and meta cohorts. Meanwhile, TSIRS can reflect the characteristics of tumor microenvironment during anti-PD1/PDL1 therapy. PF-4708671 is identified as a potential alternative drug for patients with resistance to anti-PD1/PDL1 therapy. It possesses significant inhibitive effect on the proliferation and migration of BGC-823 cells. Conclusion: TSIRS is an effective tool in the identification of candidate patients who will be benefit from anti-PD1/PDL1 therapy. Small molecule drug PF-4708671 has the potential to be used in anti-PD1/PDL1 therapy resistant patients.

Pharmacodynamic mechanisms behind a refractory state in inflammatory bowel disease

Background and aimsBiological therapy for inflammatory bowel disease is efficient in many cases but not all. The underlying molecular mechanisms behind non-response to biological therapy in inflammatory bowel disease are poorly described. Therefore, we aimed to characterize the mucosal cytokine transcript profile in non-immunogenic, non-responder patients with adequate trough level.Material and methodsPatients with ulcerative colitis (UC) (n = 21) and Crohn’s disease (CD) (n = 12) with non-response to biological therapy (anti-tumor necrosis factor (TNF) or vedolizumab) were included. Reference groups were A: untreated patients with UC or CD at debut of disease who had severe 1-year outcome, B: patients with UC or CD treated to endoscopic remission with biological agents, and C: healthy normal controls. Mucosal transcripts of TNF, interleukin (IL)17 and IL23 were measured by reverse transcription real-time quantitative polymerase chain reaction.ResultsOf the non-responders, 2 out of 12 CD and 1 out of 21 UC patients needed surgery during follow-up. Of the remaining non-responding patients, 8 out of 10 CD and 12 out of 20 UC patients switched biologic treatment. The remaining 2 CD and 8 UC patients continued treatment with the same biological agent with the addition of steroids, immunomodulators (AZA/MTX) and /or local steroids/5ASA. Twelve (8 UC/4 CD) out of 20 IBD patients were still non-responders after changing biological therapy to either anti-TNF (2), vedolizumab (9) or ustekinumab (1).The transcripts of IL17, IL23 and TNF were significantly upregulated in the non-response group compared to normal controls and patients in remission. In UC, 24% of the non-responders had normal mucosal TNF transcript indicating a non-TNF mediated inflammation. No obvious differences in gene expression were observed between primary and secondary non-responders, nor between anti-TNF and vedolizumab non-responders.ConclusionsMucosal transcripts of IL17 and IL23 are highly associated with non-response to biological therapy, whereas some UC patients may also have a non-TNF mediated inflammatory pathway.

Electroconvulsive therapy for obsessive-compulsive disorder: A retrospective study.

Chronic mental diseases such as obsessive-compulsive disorder (OCD) are associated with a high disability rate. Some patients still do not improve their symptoms even with adequate cognitive-behavioral therapy and drug treatment. In the treatment of OCD, electroconvulsive therapy (ECT) is not considered a neuromodulation modality with sufficient evidence. This retrospective study aimed to determine the efficacy and associated risk factors of ECT in OCD patients. The study included 21 OCD patients who underwent ECT at a high-volume center in China between January 2009 and December 2020. The demographics and clinical characteristics of the patients were assessed using descriptive statistics. Based on Clinical Global Impressions-Improvement scale, patients were categorized into response and non-response groups. Clinical and demographic characteristics of two groups of patients were compared. An analysis of 21 patients was conducted. In total, 12 patients (57.1%) responded to ECT, 11 patients (52.4%) reported side effects, and an average of 7 ECT sessions were administered. In terms of demographic, there was no statistically significant difference between the two groups. It is noteworthy that the non-response group reported more depression and schizophrenia related disorders comorbidities than the response group (χ2 = 6.252, P = 0.041). The effectiveness of ECT in treating OCD is limited, especially in patients with refractory symptoms. Comorbidity with other mental disorders may affect the efficacy of ECT.