Independent Predictor Of Treatment Response Research Articles

Peripheral Blood CD8+ CD28+ T Cells as an Independent Predictor of Treatment Response and Survival After Concurrent Chemoradiotherapy in Pediatric High-Grade Glioma Patients.

The tumor immune microenvironment influences the efficiency of concurrent chemoradiotherapy (CCRT) in high-grade glioma (HGG). This study investigated peripheral blood T lymphocyte subsets as clinical indicators of therapeutic response and prognosis in pediatric high-grade glioma (pHGG). This retrospective study included 77 patients with postoperative pHGG who were treated concurrently with temozolomide and external beam radiotherapy between January 1, 2012, and December 31, 2018. The median follow-up was 26 (range: 5-106) months. Peripheral venous blood samples were collected before and after CCRT. The proportions of peripheral blood T lymphocytes and their association with treatment outcome and survival were determined. Sixty-four (83.1%) patients achieved complete remission, partial remission, and stable disease, and 13 (16.9%) patients had progressive disease. Higher CD3+ T cell, CD4+ T cell, and CD8+ CD28+ T cell ratios were predictive of better response, while a higher CD8+ CD28- T cell ratio was predictive of poorer response. Binary logistic regression analysis showed that the CD8+ CD28+ T cell ratio was a significant independent predictor of CCRT response (odds ratio [OR] = 53.521, 95% confidence interval [CI] = 4.294-667.119, P = .002). Univariate and multivariate analysis of prognostic factors associated with survival showed that the CD8+ CD28+ T lymphocyte ratio was a significant independent predictor of progression-free survival (hazard ratio [HR] = 1.80, 95% CI = 1.06-3.08, P = .03), but none of the subsets were significantly associated with overall survival. Peripheral blood T lymphocytes have potential as predictors of CCRT response and prognosis in pHGG.

Salivary pepsin as an independent predictor of treatment response for laryngopharyngeal reflux: prospective cohort study with multivariate analysis

To analyze the predictive value of salivary pepsin for treatment outcomes in laryngopharyngeal reflux (LPR) using multivariate analysis that includes various associated factors. This prospective cohort study was conducted between August 2020 and August 2022. Patients with LPR who had symptoms lasting more than 1 month and a reflux symptom index (RSI) of 14 or higher were enrolled. The participants received a 2-month regimen of proton pump inhibitors (PPIs) treatment and lifestyle modification. Salivary pepsin was checked using fasting saliva before treatment. Salivary pepsin was detected more frequently in the good treatment response group (61.1%), compared to 14.3% in the poor response group. Similarly, patients with higher compliance to lifestyle modifications (> 90%) had a higher chance of a good response (91.7%) compared to those with lower compliance, who had a 53.8% chance of a good response. Other clinical factors have no significant association with treatment response. In multivariate analysis, both pretreatment salivary pepsin and higher compliance with lifestyle modification were found to be independent factors for treatment response (OR 14.457, CI 1.075 ~ 194.37 for both). This study found that positive salivary pepsin and strict lifestyle modification are independent predictors of treatment outcomes in LPR.

Psychiatric and Substance Use Disorders Are Independent Predictors of Treatment Response and Outcomes in United States Veterans with Newly Diagnosed Acute Myeloid Leukemia Treated with Venetoclax Combinations

BACKGROUND: Venetoclax (VEN) combinations have become the standard frontline therapy for patients with newly diagnosed acute myeloid leukemia (AML) who are deemed unable to tolerate intensive induction chemotherapy, either due to age or comorbidities. However, outcomes in the real-world setting have been inferior to those observed in clinical trials. Preexisting psychiatric diagnoses and substance use disorders (SUDs) have previously been associated with increased mortality in patients with cancer, but their prognostic influence in veterans with AML is unclear. The aim of this study was to measure the prevalence of psychiatric and SUDs in veterans with AML treated with VEN combinations, determining the impact of these conditions on treatment response and outcomes. METHODS: This was a retrospective cohort study of veterans with newly diagnosed AML who received frontline therapy with VEN combinations within the national Veterans Affairs (VA) Healthcare System. To measure the prevalence of psychiatric and SUDs, we used the Centers for Medicare and Medicaid Services (CMS) Chronic Conditions Data Warehouse algorithm, which tracks health conditions by administrative claims data with International Classification of Diseases (ICD) diagnostic and procedural codes. Our endpoints were rates of complete remission or complete remission with incomplete marrow recovery (CR/CRi), early mortality (EM, or death within 60 days of treatment initiation), intensive care unit (ICU) admissions, and overall survival (OS). We evaluated the relationship between comorbid medical conditions and outcomes using Kaplan-Meier analysis and Cox proportional hazards regression models, first unadjusted, and then adjusted for all covariates. Patients who underwent allogeneic stem cell transplantation (HSCT) were excluded from statistical analyses. RESULTS: We identified 452 veterans treated with VEN up to April 1, 2022 (Table 1). In combination with VEN, 60% (n=270) received azacitadine, 37% (n=168) received decitabine, and 3% (n=14) received low-dose cytarabine. Median age was 74.3 years (IQR: 71.2-78.5) with 52% ≥75 years. By European LeukemiaNet (ELN) 2017 risk classification, 61% (n=274) were classified as adverse risk. Forty-six percent (n=206) of veterans had a preexisting psychiatric diagnosis, and 19% (n=84) had SUDs; 11% (n=49) had both comorbidities. Psychiatric disorders were significantly more prevalent in younger veterans (68% in <65 years vs 50% in 65-74 years vs 39% in ≥75 years, p<0.003); same was true for SUDs (38% in <65 years vs 26% in 65-74 years vs 9% in ≥75 years, p<0.001). For the entire cohort, CR/CRi was achieved by 57% (n=257), and only 3% (n=12) received HSCT. Zero veterans with SUDs and 8 with psychiatric diagnoses were transplanted. At the end of study period, 69% (n=310) had died. Median OS was 216 days (95% CI: 195-254). The 60-day mortality rate was 20% (n=87), of which 8 veterans had primary refractory AML. ICU admissions after treatment initiation was significantly higher in veterans with SUDs compared to those without history of SUDs (5.0 versus 2.2 per 5 person-years, p<0.001). On multivariable analyses (Table 2), both psychiatric and SUDs were independently associated with decreased odds of CR/CRi. Veterans with psychiatric disturbances had a 1.97 times higher hazard of EM (95% CI: 1.16-3.39, p=0.01) and a 1.28 times higher hazard of death (95% CI: 1.00-1.64, p=0.05) compared to veterans without concurrent psychiatric disorders. CONCLUSION: Psychiatric diagnoses and SUDs were not only prevalent among veterans with AML, but they also negatively impacted treatment response, EM, and OS-independently of age, sociodemographic variables, markers of disease risk, and VEN combination. Veterans with SUDs also had significantly higher ICU admissions after treatment initiation for AML. Compared to published clinical trials data, veterans experienced inferior outcomes. Veterans with psychiatric and SUDs may have difficulty adhering to regimens, reemergence of their mental instability and illness that is triggered by AML diagnosis and its treatment, or biologic mechanisms associated with these comorbidities. Better understanding of these factors contributing to health disparities and targeting these comorbidities with supportive care interventions alongside AML-specific therapy may improve outcomes and warrant further study.

Analysis of neutropenia as a predictive factor of the efficacy of trifluridine-tipiracil treatment.

Trifluridine-tipiracil (TAS-102), an oral cytotoxic agent used in adult patients with refractory metastatic colorectal cancer (mCRC), has been associated with neutropenia (chemotherapy-induced neutropenia) (CIN)). We evaluated the efficacy and safety of TAS-102 in a group of 45 mCRC patients (median age 66 years) in Huelva province, Spain, in a retrospective, multicenter observational study. We showed that the association between TAS-102 and CIN can be used as a predictor of efficacy. 20% (9/45) of patients with an Eastern Cooperative Oncology Group (ECOG) score of 2 had received at least one previous chemotherapy treatment. Overall, 75.5% (34/45) and 28.9% (13/45) had received anti-VEGF and anti-EGFR monoclonal antibodies, respectively. Additionally, 80% (36/45) of patients had received third-line treatment. The mean treatment period, duration of overall survival (OS), and duration of progression-free survival (PFS) were 3.4, 12, and 4 months, respectively. A partial response was seen in 2 patients (4.3%), and disease stabilization was observed in 10 patients (21.3%). Neutropenia was the most frequent grade 3 - 4 toxicity (46.7%; 21/45). Other findings were anemia (77.8%; 35/45), all grades of neutropenia (73.3%; 33/45), and gastrointestinal toxicity (53.3%; 24/45). The dose of TAS-102 needed to be reduced in 68.9% (31/45) of patients, whereas treatment needed to be interrupted in 80% (36/45) of patients. Grade 3 - 4 neutropenia was a positive prognostic factor for OS (p = 0.023). A retrospective evaluation shows that grade 3 - 4 neutropenia is an independent predictor of treatment response and survival in patients undergoing routine treatment for mCRC, but this finding needs confirmation in a prospective study.

Nomogram Based on Inflammatory Factor to Predict Therapeutic Response of Thrombocytopenia in Patients with Primary Sjögren's Syndrome.

Thrombocytopenia is a common manifestation of blood system involvement in primary Sjögren's syndrome (pSS) patients, and the treatment approach involves glucocorticoids and immune agents. However, a proportion of patients do not respond well to this therapy and failed to achieve remission. Accurate prediction of therapeutic response in pSS patients with thrombocytopenia is of great significance for improving the prognosis. This study aims to analyze the influencing factors of no remission to treatment in pSS patients with thrombocytopenia and establish an individualized nomogram to predict the treatment response of patients. The demographic data, clinical manifestations and laboratory examinations of 119 patients with thrombocytopenia pSS in our hospital were retrospectively analyzed. According to the 30-day treatment response, patients were divided into remission group and non-remission group. Logistic regression was used to analyze the influencing factors related to the treatment response of patients, and then a nomogram was further established. The discriminative ability and clinical benefit of the nomogram were evaluated by receiver operating characteristic (ROC) curve, calibration chart and decision curve analysis (DCA). After treatment, there were 80 patients in the remission group and 39 in the non-remission group. Comparative analysis and multivariate logistic regression analysis identified hemoglobin (P=0.023), C3 level (P=0.027), IgG level (P=0.040), and bone marrow megakaryocyte counts (P=0.001) as independent predictors of treatment response. The nomogram was constructed based on the above four factors, and the C-index of the model was 0.882 (95% CI 0.810-0.934). The calibration curve and DCA proved that the model has better performance. The nomogram incorporating hemoglobin, C3 level, IgG level, and bone marrow megakaryocyte counts could be used as an auxiliary tool to predict the risk of treatment non-remission in pSS patients with thrombocytopenia.

Baseline FeNO Independently Predicts the Dupilumab Response in Patients With Moderate-to-Severe Asthma

FeNO may have a role as both a prognostic and predictive biomarker in combination with eosinophils for assessing responsiveness to some biological therapies. We evaluated the value of baseline FeNO, adjusted for baseline blood eosinophil levels and other clinical characteristics, as an independent predictor of treatment response to dupilumab in patients with uncontrolled moderate-to-severe asthma. We performed a post hoc analysis of LIBERTY ASTHMA QUEST (NCT02414854), a phase 3, double-blind study in patients aged 12 years and older with uncontrolled moderate-to-severe asthma, who received dupilumab 200 or 300 mg, or placebo every 2 weeks up to 52 weeks. We assessed the annualized event rate of severe exacerbations and least-squares mean change from baseline in prebronchodilator FEV1 at weeks 12 and 52 in relationship to baseline FeNO, adjusted for eosinophils and other clinical characteristics. The annualized event rate increased with increasing baseline FeNO in placebo and decreased in dupilumab groups. The relative risk of severe exacerbations was 22·7%, 58·3%, and 69·3% lower for dupilumab versus placebo for the FeNO less than 25, 25 to less than 50, and 50 and greater parts per billion subgroups. The magnitude of FEV1 improvement increased with higher baseline FeNO for dupilumab and was consistent across the continuum of FeNO levels in placebo. Both findings were independent of blood eosinophil levels. Significant differences were observed between FeNO subgroups. Increased baseline FeNO was associated with greater clinical effects in dupilumab versus placebo independently of eosinophil levels and other clinical characteristics.

The role of serum sphingolipids as potential biomarkers of non-response to direct acting antiviral therapy in chronic hepatitis C virus infection.

Elimination strategies of chronic hepatitis C virus (HCV) infection aim to optimize the high antiviral potency of direct-acting antivirals (DAAs). Sphingolipids (SLs) constitute bioactive lipid compounds with a remarkable second messenger potential. SL levels associate with responsiveness to interferon treatment in HCV-patients, thus prompting the question whether failure to DAAs can be predicted by the serologic sphingolipidomic profile. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to retrospectively quantify various sphingolipid metabolites in baseline serum samples of 97 chronic HCV patients with DAA failure compared with an age-matched cohort of 95 HCV-patients with sustained virological response (SVR). Sphingosine, sphinganine, sphingosine-1-phosphate (S1P) and sphinganine-1-phosphate (SA1P) serum concentrations were significantly upregulated at baseline in patients with DAA failure compared to patients with SVR. Similarly, GluC24:1Cer baseline levels were significantly upregulated in patients with DAA failure compared to the patients with SVR. However, GluC18Cer serum levels showed decreased baseline levels for patients with DAA failure compared to patients with SVR. In multivariate analysis sphinganine (OR 0.08494, CI 0.07393-0.9759, p= .021223), SA1P (OR 0.9818, CI 0.9653-0.9987, p= .034801), GluCerC18 (OR 1.0683, CI 1.0297-1.1104, p= .000786) and GluCer24:1 (OR 0.9961, CI 0.994-0.998, p= .000294) constituted independent predictors of treatment response. In conclusion, serum sphingolipid concentrations, in particular sphingosine, sphinganine and their derivatives S1P and SA1P as well as glucosylceramides may identify at baseline the minority of HCV patients with DAA failure. Serum sphingolipids could constitute additional biomarkers for national treatment strategies aiming to eliminate HCV infection.

Application of circulating tumour cells to predict response to treatment in head and neck cancer

BackgroundLocal recurrence and metastasis remain the major causes of death in head and neck cancer (HNC) patients. Circulating tumour cells (CTCs) are shed from primary and metastatic sites into the circulation system and have been reported to play critical roles in the metastasis and recurrence of HNC. Here, we explored the use of CTCs to predict the response to treatment and disease progression in HNC patients.MethodsBlood samples were collected at diagnosis from HNC patients (n = 119). CTCs were isolated using a spiral microfluidic device and were identified using immunofluorescence staining. Correlation of baseline CTC numbers to 13-week PET-CT data and multidisciplinary team consensus data were conducted.ResultsCTCs were detected in 60/119 (50.4%) of treatment naïve HNC patients at diagnosis. Baseline CTC numbers were higher in stage III vs. stage I-II p16-positive oropharyngeal cancers (OPCs) and other HNCs (p = 0.0143 and 0.032, respectively). In addition, we found that baseline CTC numbers may serve as independent predictors of treatment response, even after adjusting for other conventional prognostic factors. CTCs were detected in 10 out of 11 patients exhibiting incomplete treatment responses.ConclusionsWe found that baseline CTC numbers are correlated with treatment response in patients with HNC. The expression level of cell-surface vimentin (CSV) on CTCs was significantly higher in patients with persistent or progressive disease, thus providing additional prognostic information for stratifying the risk at diagnosis in HNC patients. The ability to detect CTCs at diagnosis allows more accurate risk stratification, which in the future may be translated into better patient selection for treatment intensification and/or de-intensification strategies.

The Impact of Laboratory Findings and Optical Coherence Tomography Biomarkers on Response to Intravitreal Anti-VEGF Treatment in Patients with Diabetic Macular Edema

ABSTRACT Purpose To investigate potential laboratory and imaging biomarkers as treatment response predictors to intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in patients with diabetic macular edema (DME). Methods The study included 36 treatment naïve patients with DME, treated with intravitreal anti-VEGF agents and followed-up for 12 months. At baseline, all participants underwent best-corrected visual acuity (BCVA) measurement, dilated fundoscopy, optical coherence tomography, color fundus photography and fluorescein angiography, while full blood count and biochemical analysis of various parameters was also performed. At month 12, treatment response was examined and classified as “favorable” or “non-response”. Potential associations between laboratory/imaging biomarkers and treatment response were assessed. Results Univariate analysis showed that favorable response at month 12 after initiation of anti-VEGF treatment was correlated with baseline central subfield thickness (CST)≤405 μm (p < .001), absence of subretinal fluid (p = .034), absence of exudates (p = .041), absence of disorganization of the inner retinal layers (p = .037), intact ellipsoid zone (EZ) and external limiting membrane (ELM) (p < .001 and p = .002, respectively), absence of epiretinal membrane (ERM) (p = .040) and absence of macular ischemia (p = .042), while increased lipoprotein(a) was associated with no treatment response (p = .025). At the multivariate analysis, CST was found to be independent predictor of treatment response, while EZ, ELM and ERM were found to predict treatment response perfectly and they could not be entered in the model. Conclusion Intact EZ and ELM, absence of ERM and CST≤405 μm at baseline can predict favorable treatment response in patients with treatment naïve DME, while no correlation with baseline laboratory parameters was found.

The impact of laboratory findings and optical coherence tomography biomarkers on response to intravitreal anti-VEGF treatment in patients with retinal vein occlusion.

To investigate potential laboratory and imaging biomarkers as treatment response predictors to intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in patients with retinal vein occlusion (RVO). Participants in this prospective study were 53 patients with treatment naïve macular edema secondary to RVO, treated with intravitreal anti-VEGF agents and followed-up for 12months. At baseline, all participants underwent best-corrected visual acuity measurement, dilated fundoscopy, optical coherence tomography and fluorescein angiography (FFA), while full blood count and biochemical analysis of various parameters was also performed. At month 12, treatment response was examined and classified as "favorable" or "non-response". Potential associations between laboratory/imaging biomarkers and treatment response were assessed. Univariate analysis showed that "favorable" response at month 12 after initiation of anti-VEGF treatment was correlated with baseline central subfield thickness (CST) < 464μm (p < 0.001), absence of subretinal fluid (p = 0.004), absence of hyperreflective foci (HF) (p = 0.004), intact ellipsoid zone (EZ) and external limiting membrane (ELM) (p < 0.001 and p = 0.001, respectively), absence of epiretinal membrane (ERM) (p = 0.020) and absence of macular ischemia on FFA (p < 0.001), while increased monocytes-to-lymphocytes ratio was also associated with "favorable" treatment response (p = 0.010). All other laboratory parameters did not reach statistical significance. However, at the multivariate analysis, EZ and ELM status, HF, macular ischemia and monocytes-to-lymphocytes ratio were found to be independent predictors of treatment response. Intact EZ and ELM, absence of HF, absence of macular ischemia and increased monocytes-to-lymphocytes ratio at baseline can predict "favorable" treatment response in patients with treatment naïve macular edema secondary to RVO.

Neoadjuvant Chemoradiotherapy Changes the Landscape of Soluble Immune Checkpoint Molecules in Patients With Locally Advanced Rectal Cancer.

BackgroundWe aimed to investigate clinical implications of specific soluble immune checkpoint molecules (sICMs) in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (nCRT).MethodsWe prospectively enrolled 30 LARC patients treated with nCRT and collected blood samples from them before, during, and after nCRT for prospective studies. Immune checkpoints often refer to T cell surface molecules influencing the immune response. Immune checkpoints, in the form of a soluble monomeric form, is widely present in blood. In the study, eight immune checkpoint-related plasma proteins, including programmed death-ligand 1 (PD-L1), CD80, CD86, CD28, CD27, glucocorticoid-induced tumor necrosis factor receptor (GITR), GITR ligand (GITRL), and inducible T-cell costimulator (ICOS), were measured using the Luminex platform. Two independent pathologists categorized patients as the good responders and the poor responders according to Dworak tumor regression grade (TRG).ResultsOf the 30 patients, the levels of sPD-L1, sCD80, sCD86, sCD28, sGITR, sGITRL, sCD27, and sICOS decreased during nCRT (Pre-nCRT vs. During-nCRT, all p<0.05) but were restored after nCRT treatment (Pre-nCRT vs. Post-nCRT, all p>0.05). In the 14 good responders, the levels of sICMs, other than sGITR (p=0.081) and sGITRL (p=0.071), decreased significantly during nCRT (Pre-nCRT vs. During-nCRT, p<0.05), but they were all significantly increased after nCRT (During-nCRT vs. Post-nCRT, all p<0.05). In the 16 poor responders, only sCD80 was significantly reduced during nCRT (Pre-nCRT vs. During-nCRT, p<0.05), and none was significantly increased after nCRT (During-nCRT vs. Post-nCRT, all p<0.05). High levels of sICMs before nCRT were associated with poor response (all OR≥1). The Pre-model that incorporated the 8 sICMs before nCRT yielded a good predictive value (AUC, 0.848) and was identified as an independent predictor of treatment response (OR, 2.62; 95% CI, 1.11-6.18; p=0.027).ConclusionOur results suggest chemoradiotherapy could influence the change of sPD-L1, sCD80, sCD86, sCD28, sGITR, sGITRL, sCD27, and sICOS in patients with LARC. The levels of the majority of soluble immune checkpoint molecules were reduced during nCRT and then restored at the end of nCRT, particularly in patients who responded well to nCRT. Combined baseline sICMs can be developed to predict treatment response.

T2 Mapping with and without Fat-Suppression to Predict Treatment Response to Intravenous Glucocorticoid Therapy for Thyroid-Associated Ophthalmopathy.

ObjectiveTo evaluate the performance of baseline clinical characteristics and pretherapeutic histogram parameters derived from T2 mapping of the extraocular muscles (EOMs) in the prediction of treatment response to intravenous glucocorticoid (IVGC) therapy for active and moderate-to-severe thyroid-associated ophthalmopathy (TAO) and to investigate the effect of fat-suppression (FS) in T2 mapping in this prediction.Materials and MethodsA total of 79 patients clinically diagnosed with active, moderate-to-severe TAO (47 female, 32 male; mean age ± standard deviation, 46.1 ± 10 years), including 43 patients with a total of 86 orbits in the responsive group and 36 patients with a total of 72 orbits in the unresponsive group, were enrolled. Baseline clinical characteristics and pretherapeutic histogram parameters derived from T2 mapping with FS (i.e., FS T2 mapping) or without FS (i.e., conventional T2 mapping) of EOMs were compared between the two groups. Independent predictors of treatment response to IVGC were identified using multivariable analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the prediction models. Differences between the models were examined using the DeLong test.ResultsCompared to the unresponsive group, the responsive group had a shorter disease duration, lower kurtosis (FS-kurtosis), lower standard deviation, larger 75th, 90th, and 95th (FS-95th) T2 relaxation times in FS mapping and lower kurtosis in conventional T2 mapping. Multivariable analysis revealed that disease duration, FS-95th percentile, and FS-kurtosis were independent predictors of treatment response. The combined model, integrating all identified predictors, had an optimized area under the ROC curve of 0.797, 88.4% sensitivity, and 62.5% specificity, which were significantly superior to those of the imaging model (p = 0.013).ConclusionAn integrated combination of disease duration, FS-95th percentile, and FS-kurtosis was a potential predictor of treatment response to IVGC in patients with active and moderate-to-severe TAO. FS T2 mapping was superior to conventional T2 mapping in terms of prediction.

A Pooled Analysis Reporting the Efficacy and Safety of Secukinumab in Male and Female Patients with Ankylosing Spondylitis.

IntroductionDespite of higher disease burden, lower efficacy to biologics has been reported in female compared to male patients with ankylosing spondylitis (AS). The aim of this study was to evaluate the efficacy and safety of secukinumab by sex in patients with active AS from five phase 3 studies (MEASURE 1–5) through 52 weeks.MethodsBaseline demographics, disease characteristics and efficacy outcomes at Weeks 16 and 52 were summarized for males versus females. Baseline predictor analysis used multivariable logistic regression for binary outcome measures or generalized linear model for continuous outcome measures to assess the impact of sex as one of the independent variables on selected efficacy outcomes at Week 52.ResultsOverall, 1031 males and 396 females were included in this analysis. Smoking status, hs-CRP, prior exposure to TNF inhibitors, BASMI occiput-to-wall and tragus-to-wall distance (cm) were higher in males, whereas MASES was higher in females. Efficacy outcomes i.e., ASAS40 responses and BASDAI change from baseline at Weeks 16 and 52 were generally comparable between males and females. Response rates were found to be significantly higher in male patients when compared with female patients only for ASDAS-CRP inactive disease (ID) at Week 52.ConclusionComparable efficacy and safety outcomes were observed between male and female patients with active AS treated with secukinumab over 52 weeks. Further, sex was not an independent predictor of treatment response to secukinumab as assessed by ASAS40 responder rates and BASDAI change from baseline; association of ASDAS-CRP ID responder rates with sex warrants further exploration.Trial registrationClinicalTrials.gov; NCT01358175, NCT01649375, NCT02008916, NCT02159053, and NCT02896127.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00380-2.

Prediction of Treatment Response and Survival with Chemotherapy for Metastatic Penile Cancer by the Modified Glasgow Prognostic Score

Purpose: There is increasing evidence that a persistent systemic inflammatory response predicts lower survival in patients with malignant disease. The modified Glasgow Prognostic Score (mGPS) is defined by a combination of elevated C-reactive protein (CRP) (>10 mg/L) and hypoalbuminemia (<35 g/L). It is considered as an independent prognostic marker in several organ malignancies. The aim of this study was to investigate the value of mGPS in metastatic penile carcinoma in predicting treatment response and survival. Methods: One hundred and fifty-six patients with penile carcinoma treated with chemotherapy were included in this retrospective study. The mGPS before chemotherapy was classified into 3 groups (mGPS 0 [CRP <10, any albumin], mGPS 1 [CRP >10 mg/L, albumin >35 g/L], and mGPS 2 [CRP >10 mg/L, albumin <35 g/L]). Overall survival and disease-free survival were calculated by Kaplan-Meier analysis and chemotherapy toxicity by CTC criteria. Univariate Cox proportional hazards models were calculated to estimate the effect of each predictor on OS and DFS. Results: Survival was significantly different in the 3 mGPS classes, with mGPS 0 patients showing the best treatment response and survival. Univariate analysis showed that mGPS (p < 0.0001), tumor stage (p = 0.004), and venous and lymphatic invasion (p = 0.011) were factors independently associated with prognosis. The response to chemotherapy differed significantly between mGPS groups (mGPS 0, 36/51 [71%]; mGPS 1, 24/70 [34%]; mGPS 2, 9/35 [26%], p = 0.03 and p = 0.37, respectively). mGPS was significantly associated with chemotherapy-associated toxicity, with treatment adaptation (p < 0.01) and toxicity-related deaths (p = 0.028). Conclusions: Systemic inflammatory response and nutritional status as expressed by the mGPS are independent predictors of treatment response, chemotherapy-associated toxicity, and survival in metastatic penile carcinoma. In addition to other known pathological markers of tumor aggressiveness, the mGPS can be used as a clinical predictor of prognosis.

Low- vs. high-dose radiotherapy in Graves\u2019 ophthalmopathy: a\xa0retrospective comparison of long-term results

PurposeRadiotherapy represents an effective treatment option in Graves’ ophthalmopathy (GO), leading to palliation of clinical symptoms. However, there are only a limited number of trials comparing the effectiveness of low- vs. high-dose radiotherapy.MethodsWe analyzed 127 patients treated with radiotherapy for stage 3/4 GO (NOSPECS classification). Patients were treated with single doses of 2.0 Gy (cumulative dose 20 Gy) until 2007, afterwards a single dose of 0.8 Gy (cumulative dose 4.8 Gy) was applied. With a median follow-up-time of 9.0 years, the treatment efficacy (overall improvement, sense of eye pressure, lid edema, ocular motility, exophthalmos, subjective vision, and diplopia) and adverse effects were analyzed by a standardized survey.ResultsOverall, 63.8% described improvement of symptoms after radiotherapy. No significant differences in overall treatment response and improvement of main outcome measures between low- or high-dose radiotherapy treatments are detectable, while low-dose radiotherapy leads significantly more often to retreatment (13.1% vs. 1.7%, p = 0.016). The main independent predictor of treatment response is the presence of lid edema (odds ratio, OR, 3.53; p = 0.006).ConclusionAt long-term follow-up, the majority of patients reported palliation of symptoms with limited adverse effects, suggesting clinical effectiveness of radiotherapy for amelioration of GO symptoms independent of low- or high-dose radiotherapy.

Metabolic Parameters as Biomarkers of Response to Immunotherapy and Prognosis in Non-Small Cell Lung Cancer (NSCLC): A Real World Experience.

Simple SummaryThe advent of immune-checkpoint inhibitors (ICIs) has significantly changed the management of patients with non-small cell lung cancer (NSCLC). Although the assessment of PD-L1 expression remains the gold standard for the selection of cases for immunotherapy, previous experiments have investigated whether metabolic parameters from positron emission tomography (PET) scans could have a similar predictive role. In our retrospective study, we assessed if baseline fluorodeoxyglucose PET (FDG PET) can represent a further tool for selecting patients who are eligible for ICI therapy. Among the parameters tested, a surrogate of the entire tumor burden (metabolic tumor volume, MTV) demonstrated better performance in selecting patients with adequate disease control, as well as those with better overall and progression-free survival. These promising findings from a real-world experiment stress once again the pivotal role of PET scanning in the management of patients with NSCLC, requiring further validation on larger and prospective cohorts before its implementation in the stratification of patients for immunotherapy.Immune-checkpoint inhibitors (ICIs) have been proven to have great efficacy in non-small cell lung cancer (NSCLC) as single agents or in combination therapy, being capable to induce deep and durable remission. However, severe adverse events may occur and about 40% of patients do not benefit from the treatment. Predictive factors of response to ICIs are needed in order to customize treatment. The aim of this study is to evaluate the correlation between quantitative positron emission tomography (PET) parameters defined before starting ICI therapy and responses to treatment and patient outcome. We retrospectively analyzed 92 NSCLC patients treated with nivolumab, pembrolizumab or atezolizumab. Basal PET/computed tomography (CT) scan parameters (whole-body metabolic tumor volume—wMTV, total lesion glycolysis—wTLG, higher standardized uptake volume maximum and mean—SUVmax and SUVmean) were calculated for each patient and correlated with outcomes. Patients who achieved disease control (complete response + partial response + stable disease) had significantly lower MTV median values than patients who had not (progressive disease) (77 vs. 160.2, p = 0.039). Furthermore, patients with MTV and TLG values lower than the median values had improved OS compared to patients with higher MTV and TLG (p = 0.03 and 0.05, respectively). No relation was found between the other parameters and outcome. In conclusion, baseline metabolic tumor burden, measured with MTV, might be an independent predictor of treatment response to ICI and a prognostic biomarker in NSCLC patients.

A predictive model for treatment response in patients with locally advanced esophageal squamous cell carcinoma after concurrent chemoradiotherapy: based on SUVmean and NLR

BackgroundWe conducted this study to combine the mean standardized uptake value (SUVmean) and neutrophil to lymphocyte ratio (NLR) to establish a strong predictive model for patients with esophageal squamous cell carcinoma (ESCC) after concurrent chemoradiotherapy (CCRT).MethodsWe retrospectively analyzed 163 newly diagnosed ESCC patients treated with CCRT. Eighty patients (training set) were randomly selected to generate cut-off SUVmean and NLR values by receiver operating characteristic (ROC) curve analysis and to establish a predictive model by using the independent predictors of treatment outcomes. Then, we evaluated the performance of the prediction model regarding treatment outcomes in the testing set (n = 83) and in all sets.ResultsA high SUVmean (> 5.81) and high NLR (> 2.42) at diagnosis were associated with unfavorable treatment outcomes in patients with ESCC. The prediction model had a better performance than the simple parameters (p < 0.05). With a cut-off value of 0.77, the prediction model significantly improved the specificity and positive predictive value for treatment response (88.9 and 92.1% in the training set, 95.8 and 97.1% in the testing set, and 92.2 and 91.8% in all sets, respectively).ConclusionsThe pretreatment SUVmean and NLR were independent predictors of treatment response in ESCC patients treated with CCRT. The predictive model was constructed based on these two parameters and provides a highly accurate tool for predicting patient outcomes.

Predicting treatment response to neoadjuvant chemoradiotherapy in local advanced rectal cancer by biopsy digital pathology image features.

Quantitative features extracted from biopsy digital pathology images can provide predictive information for neoadjuvant chemoradiotherapy (nCRT) in local advanced rectal cancer (LARC) Machine learning technologies are applied to build the digital-pathology-based pathology signature The pathology signature is an independent predictor of treatment response to nCRT in LARC.

Effects of life events and emotional stress on short-term curative efficacy in adolescents with sudden hearing loss

Objective:To investigate the effects of life events and emotional stress on short-term curative efficacy in adolescents with low-tone sudden deafness （LTSD）. Method:Various psychological stress measures were conducted on adolescent patients with recently diagnosed LTSD before initiating treatment, and the follow-up hearing condition were also obtained after 3 months of treatment. Using logistic regression analysis, we identified the predictors of life stress and emotion symptoms of treatment response in these adolescent patients. Result:Treatment were effective in 103 cases and ineffective in 41 cases. The stress, depression and anxiety symptoms of the high-life events in the ineffective group were significantly higher than those in the effective group. The logistics regression analysis showed that life stress [OR（95%CI）=1.16（1.07-2.42） ] and depressive symptoms [OR（95%CI）=1.65（1.26-2.71） ] were significantly correlated with patients' prognosis after controlling for the duration of LTSD and the level of hearing loss before the treatment. Conclusion:We found life stress and depressive symptoms were the independent predictors of treatment response in adolescent patients with LTSD. Our results also highlighted that psychological intervention may be part of the primary treatment for LTSD in adolescents.

Predictors of treatment response in type-2 diabetes patients initiating basal-supported oral therapy with insulin glargine 100 U/mL: A sub-analysis of the Titration and OPtimisation (TOP) registry.

The aim of this study was to identify predictors of long-term response to the initiation of basal-supported oral therapy (BOT) with insulin glargine (IGlar-100). Patients from the observational TOP registry were grouped based on those who had achieved (responders) and those who had not achieved (non-responders) their HBA1c target and/or FBG ≤110 mg/dL 12 months after IGlar-100 initiation. Independent predictors of treatment response were identified by regression analysis. Data for 2444 patients were analysed (responders, n = 1610; non-responders, n = 834). Although the IGlar-100 dose increase over 12 months was larger for non-responders (+12.83 vs +9.46 U/d; P < 0.0001), the corresponding decrease in HbA1c was smaller (-0.88% vs -1.57%). Independent predictors of response included lower BMI (OR, 0.97; 95% CI, 0.95-1.00), lower FBG (OR, 0.98; 95% CI, 0.97-0.98) and HbA1c values at baseline (OR, 0.24; 95% CI, 0.18-0.31), a less ambitious HbA1c target (OR, 5.07; 95% CI, 3.37-7.63) and bedtime administration of IGlar-100 (OR, 1.55; 95% CI, 1.12-2.14). In conclusion, HbA1c was the clinically most significant baseline characteristic predictive of response to BOT. This may suggest an advantage of IGlar-100 initiation prior to excessive hyperglycaemia escalation.