Predictive Factor For Poor Response Research Articles

Predictors of poor response to oral propranolol in infantile hemangiomas

BackgroundPropranolol is the first-line treatment for infantile hemangiomas (IH). Cases of propranolol-resistant infantile hemangiomas are rarely reported. The purpose of our study was to investigate the predictive factors for poor response to propranolol. MethodsA prospective analytical study was conducted between January 2014 and January 2022 including all patients with IH who received oral propranolol therapy at a dose of 2–3 mg/kg/day maintained for at least 6 months. ResultsA total of 135 patients with IH were treated with oral propranolol. Poor response was reported in 18 (13.4%) of the patients: 72% were girls and 28% were boys. Overall, 84% of the IH were mixed, and hemangiomas were multiple in three cases (16%), nasal tip hemangiomas accounted for four cases (22%), and 15 patients (83%) had segmental hemangiomas. There was no significant association between the age or sex of the children and type of response to treatment (p > 0.05). No significant association was found between the type of hemangioma and the therapeutic outcome as well as the recurrence after treatment discontinuation (p > 0.05). Multivariate logistic regression analysis revealed that nasal tip hemangiomas, multiple hemangiomas, and segmental hemangiomas were at greater risk of poor response to beta-blockers (p < 0.05). ConclusionPoor response to propranolol therapy has rarely been reported in the literature. In our series, it was approximately 13.4%. To our knowledge, no previous publications have focused on the predictive factors of poor response to beta-blockers. However, the reported risk factors for recurrence are discontinuation of treatment before 12 months of age, mixed or deep type IH, and female gender. In our study, the predictive factors for poor response were multiple type IH, segmental type IH, and location on the nasal tip.

Docetaxel-Cisplatin-Fluorouracil Induction Chemotherapy for Larynx Preservation in Patients with Locally Advanced Hypopharyngeal Cancer: Predictive Factors of Oncologic and Functional Outcomes.

The aims of this study were to evaluate the clinical outcomes and their predictive factors in locally advanced hypopharyngeal cancer (HC) patients included in a docetaxel-cisplatin-fluorouracil induction chemotherapy (ICT)-based larynx preservation (LP) program. Between 2005 and 2021, 82 patients with a locally advanced resectable HC who received ICT in an LP program were included in this retrospective study. The predictors of oncologic and swallowing outcomes were determined in univariate and multivariate analyses. The three- and five-year overall survival (OS) rates were 67 and 54%, respectively. The T4 tumor stage was the only predictive factor of poor response to ICT (p = 0.03). In multivariate analysis, a T stage = 4 (p = 0.02), an ICT cycle number < 3 (p = 0.003) and the absence of a response to ICT (p = 0.03) were significantly associated with worse OS. A low body mass index before therapy (p = 0.003) and enteral nutrition during therapy (p = 0.005) were significantly associated with severity of dysphagia 6 months after treatment. The T stage, number of ICT cycles performed and response to ICT are the main predictors of oncologic outcomes. Patients with T4 HC are poor candidates for LP and should be referred to immediate radical surgery.

Factors affecting the course of Graves’ Orbitopathy and poor response to glucocorticoid treatment followed by orbital radiotherapy.

Graves’ orbitopathy is a rare autoimmune disorder characterized by the inflammation of orbital tissues. The course of disease can be described in terms of its activity and severity.&#x0D; Aim: The aim of our study was to determine the factors affecting the activity and severity of Graves’ orbitopathy, as well as to identify the predictive factors of poor response to glucocorticoid treatment followed by orbital irradiation.&#x0D; Methods: We performed a prospective observational study of 214 patients with Graves’ orbitopathy who were divided into two groups depending on the treatment they had previously obtained for their Graves’ disease. They received i.v. methylprednisolone pulses followed by orbital radiotherapy. They were examined and had their TSH, TRAb and FT4 levels evaluated prior to treatment and after 1, 6 and 12 months.&#x0D; Results: A pre-treatment TRAb concentration higher by one unit (U/L) implied a mean increase in the relative risk of active orbitopathy by 4.7% (p = 0.0362). A TRAb concentration higher by one U/L 1 month after treatment implied a mean increase in the relative risk of moderate-to-severe and severe GO by 8.7% (p = 0.0167) 6 months after treatment. As regards poor response to treatment, patients with moderate-to-severe and severe Graves’ orbitopathy on admission carried a higher risk of being non-responders. Each point scored on the NOSPECS scale prior to treatment increased the relative risk of the patient being a non-responder by 30%.&#x0D; Conclusions: Patients with higher TRAb levels have a higher risk of active Graves’ orbitopathy and moderate-to-severe and severe Graves’ orbitopathy. Monitoring TRAb serum concentration in those patients is of great importance. Patients with more severe Graves’ orbitopathy carry a higher risk of being poor responders to immunosuppressive treatment. Therefore, careful monitoring of patients with Graves’ orbitopathy and their early referral to specialized centers is essential.

Grade group system and plasma androgen receptor status in the first line treatment for metastatic castration resistant prostate cancer.

In localized prostate cancer (PCa), Grade Group (GG) and Gleason Score (GS) have a well-established prognostic role. In metastatic castration resistant prostate cancer (mCRPC), the prognostic role of GS and GG is less defined. In first-line treatment of mCRPC, androgen receptor (AR)-directed drugs (abiraterone acetate, enzalutamide) and docetaxel represent the referring options. There is no evidence that the GS/GG systems can add information to guide the choice between AR-directed drugs and docetaxel in the first-line setting of mCRPC. Nowadays there are no validated biomarkers, which define patients who may benefit or not from hormonal treatments or chemotherapy. Androgen receptor (AR) copy number variations (CNV) are predictive factors of poor response to abiraterone and enzalutamide. There are no available data about the association between AR CNV and GG. In this retrospective study, we analysed the association of the highest GG score with AR CNV and their impact on the clinical outcome of AR-directed drugs and docetaxel as first-line therapy for mCRPC patients. Patients benefit from docetaxel, abiraterone or enzalutamide regardless the GG. However, the presence of GG5 and AR CNV gain identifies a subgroup of patients with poor prognosis, which could benefit from front-line docetaxel instead of AR-directed drugs.

Association between P-Selectin Autoantibody Positive and Response to Steroid Treatment in Newly Diagnosed Immune Thrombocytopenia Patients

Objective: This study aimed to detect the association between P-selectin autoantibody positive and response to steroid treatment in newly diagnosed immune thrombocytopenia (ITP) patients. Methods: The data from 105 newly diagnosed adult ITP patients administered with first-line of steroid treatment from October 2016 to May 2021 were retrospectively analyzed. Treatment responses were evaluated within 3 months after the onset of treatment. Results: Among the 105 patients, 80.00% (84/105) of patients presented with platelet glycoprotein-specific antibody positive; 44.76% (47/105) patients were anti-P-selectin positive, while 35.24% (37/105) were anti-P-selectin negative. No significant difference in overall response was observed between patients who were anti-P-selectin positive and those who were anti-P-selectin negative (74.47% vs. 89.19, χ² = 2.910, p = 0.088). But patients who were anti-P-selectin negative had significantly higher complete response rate, compared to those who were anti-P-selectin positive (72.97% vs. 48.94%, χ² = 4,965, p = 0.026). Logistic regression analysis revealed that anti-GP IIb/IIIa positive (OR = 3.114, p = 0.010, 95% CI: 1.313–7.388) and anti-P-selectin positive (OR = 0.309, p = 0.036, 95% CI: 0.127–0.753) were two factors that could affect patients’ response. Conclusions: Our study found that ITP patients with anti-GP IIb/IIIa may have a higher response to steroid treatment, but anti-P-selectin-mediated-ITP might be less responsive to steroid treatment. In adults with ITP, the presence of anti-P-selectin autoantibodies is a predictive factor for poor response to steroid treatment.

Prognostic Impact of An Integrative Landscape of Clinical, Immune, and Molecular Features in Non-Metastatic Rectal Cancer.

Rectal Cancer (RC) is a complex disease that involves highly variable treatment responses. Currently, there is a lack of reliable markers beyond TNM to deliver a personalized treatment in a cancer setting where the goal is a curative treatment. Here, we performed an integrated characterization of the predictive and prognostic role of clinical features, mismatch-repair deficiency markers, HER2, CDX2, PD-L1 expression, and CD3−CD8+ tumor-infiltrating lymphocytes (TILs) coupled with targeted DNA sequencing of 76 non-metastatic RC patients assigned to total mesorectal excision upfront (TME; n = 15) or neoadjuvant chemo-radiotherapy treatment (nCRT; n = 61) followed by TME. Eighty-two percent of RC cases displayed mutations affecting cancer driver genes such as TP53, APC, KRAS, ATM, and PIK3CA. Good response to nCRT treatment was observed in approximately 40% of the RC cases, and poor pathological tumor regression was significantly associated with worse disease-free survival (DFS, HR = 3.45; 95%CI = 1.14–10.4; p = 0.028). High neutrophils-platelets score (NPS) (OR = 10.52; 95%CI=1.34–82.6; p = 0.025) and KRAS mutated cases (OR = 5.49; 95%CI = 1.06–28.4; p = 0.042) were identified as independent predictive factors of poor response to nCRT treatment in a multivariate analysis. Furthermore, a Cox proportional-hazard model showed that the KRAS mutational status was an independent prognostic factor associated with higher risk of local recurrence (HR = 9.68; 95%CI = 1.01–93.2; p <0.05) and shorter DFS (HR = 2.55; 95%CI = 1.05–6.21; p <0.05), while high CEA serum levels were associated with poor DFS (HR = 2.63; 95%CI = 1.01–6.85; p <0.05). Integrated clinical and molecular-based unsupervised analysis allowed us to identify two RC prognostic groups (cluster 1 and cluster 2) associated with disease-specific OS (HR = 20.64; 95%CI = 2.63–162.2; p <0.0001), metastasis-free survival (HR = 3.67; 95%CI = 1.22–11; p = 0.012), local recurrence-free survival (HR = 3.34; 95%CI = 0.96–11.6; p = 0.043) and worse DFS (HR = 2.68; 95%CI = 1.18–6.06; p = 0.012). The worst prognosis cluster 2 was enriched by stage III high-risk clinical tumors, poor responders to nCRT, with low TILs density and high frequency of KRAS and TP53 mutated cases compared with the best prognosis cluster 1 (p <0.05). Overall, this study provides a comprehensive and integrated characterization of non-metastatic RC cases as a new insight to deliver a personalized therapeutic approach.

Platelet autoantibody specificity and response to rhTPO treatment in patients with primary immune thrombocytopenia.

This retrospective study aimed to evaluate the relationship between plasma autoantibody species and rhTPO response in adult ITP patients who failed the first-line treatments. Plasma anti-glycoprotein (GP) IIb/IIIa and anti-GPIb/IX autoantibodies were detected in 47·2% and 40·6% of the 123 patients, respectively. Overall response rate to rhTPO treatment in patients without anti-GPIb/IX autoantibodies was significantly higher than patients with anti-GPIb/IX autoantibodies (82·2% vs. 60·0%, P=0·006). By contrast, no statistical difference in response rate was observed between patients with or without anti-GPIIb/IIIa autoantibodies (74·1% vs. 72·3%, P=0·819). Therefore, the presence of anti-GPIb/IX autoantibodies might serve as a predictive factor for poor response to rhTPO treatment in ITP.

Introducing the POPVESL Score for Intrarenal Vascular Complications of Percutaneous Nephrolithotomy: Experience from a Single high-volume Referral Center.

Percutaneous-nephrolithotomy (PCNL), is the current modality of choice for large renal stones. Delayed post-op bleeding may herald pseudo aneurysm (PA) or arteriovenous fistula (AVF) necessitating costly and inconsistently available angioembolization, or prolonged hospitalization. The goal of this study is to identify criteria that may predict response to conservative therapy, for delayed bleeding from post PCNL intrarenal vascular lesions. We reviewed all data on patients re-admitted for post PCNL gross hematuria at our high volume center between 2011 and 2016. Perioperative findings, factors related to the stone and management details, were subjected to multifactorial analysis. Logistic regression for multivariable analysis and ROC curves to find thresholds predicting mandatory angioembolization. Of 4403 PCNLs, 83 (1.9%) with delayed bleeding were diagnosed with intrarenal vascular lesions: Arteriovenous fistulas in 54 (AVF, 65%) and pseudoaneurysm in 29 (PA, 35%). Overall 49 (59%) responded to conservative management but 34 (41%) eventually required angioembolization. On multivariable analysis, predictive factors for poor response to conservative treatment were requiring transfusion beyond initial stabilization, pseudoaneurysm, history of open renal surgery, longer interval-to-second-admission, and size of vascular lesion. The proposed POPVESL score (short for Post PNL Vascular Embolization selection) when below 11, correctly predicts success of conservative management with 81.6% sensitivity and 100% specificity. Our findings including the proposed POPVESL score have the potential for clinical application and enhancing practical guidelines on the management of post-PCNL bleeding.

Increased tumor-associated macrophages in the prostate cancer microenvironment predicted patients' survival and responses to androgen deprivation therapies in Indonesian patients cohort.

BackgroundTumor-associated macrophages (TAMs) and microvessel density (MVD) play an essential role for tumor progression in prostate cancer (PCa). In this study, we evaluated the association between TAMs, the infiltration with tumor angiogenesis and the response to androgen deprivation therapies (ADTs) in PCa to evaluate TAM infiltration as a predictive factor for PCa survival.Materials and methodsFifty-four specimens were collected and stained with CD 68 antibody to investigated TAM infiltration in tumor. Von Willebrand factor was stained to evaluate MVD around the cancer foci. We assessed the association between patient's age, preoperative serum prostate-specific antigen, pathologic Gleason sum (GS), TAM infiltration, MVD, and the response to ADT for 5 years after PCa diagnosis.ResultsThe median TAM was observed in 28 (6-76)/high power field (x400). Increasing TAM correlated with increasing tumor angiogenesis (P < 0.001, r = 0.61), and the response to ADT was significantly better in patients with fewer TAMs (<28) than in patients with higher TAMs (>28) (P = 0.003). TAM infiltration was significantly higher in those with higher serum prostate-specific antigen, higher GS, and metastasis. Multivariate analysis showed that GS, ADT type, and MVD number were significant prognostic factors for response to ADT in PCa (P < 0.0001). An increased infiltration of TAM [hazards ratio (HR) = 4.47; 95% confidence interval (CI): 1.97–10.15], MVD (HR = 2.66; 95% CI: 1.27–5.61), metastatic status (HR = 2.29; 95% CI: 0.14-0.60), and prostate volume (HR = 2.19; 95% CI: 1.27–3.12) significantly correlated with shorter survival in PCa patients by univariate analysis (P < 0.05). Multivariate analyses revealed that TAM and metastatic status significantly correlated with poor overall survival.ConclusionsTAM infiltration is associated with response to ADT and increased tumor angiogenesis in PCa. GS, ADT type, and MVD in PCa specimens are useful predictive factors for poor response to ADT. Increasing TAM and positive metastatic status were prognostic factors for a poorer survival in PCa patients.

Anti-CD(25) monoclonal antibody as a salvage therapy for steroid-refractory acute graft-versus-host disease in 80 patients receiving allogeneic hematopoietic stem cell transplantation

Objective: To investigate the efficacy of anti-CD(25) monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 80 patients with SR-aGVHD from January 1st 2012 to December 31st 20l6 were enrolled in this study. Acute GVHD were classified as classic aGVHD (n=72) and late-onset aGVHD (n=8). Anti-CD(25) monoclonal antibodys (mAb) were administrated on days 1, 4, 8, 15, and 22. The efficacy of anti-CD(25) mAb was evaluated at day 28 after the initial treatment. The associated factors of clinical outcome were analyzed. Results: The overall response (OR) rate of anti-CD(25) mAb was 75% (60/80), with complete response (CR) rate, partial response (PR) rate and no response(NR) rate 52.5% (42/80), 22.5% (18/80), and 25% (20/80), respectively. GVHD-relapse was not observed with a median follow-up time of 394.5 days (range, 12-1 761 days). The 6-month overall survival (OS) rate was 68.4%(95%CI 63.2%-73.6%). The 1-year OS rate was 63.1% (95%CI 57.6%-68.6%), and 2-years OS rate was 50.7% (95%CI 44.3%-57.1%). Non-relapse mortality (NRM) rate of 1 and 3 years was 32.6% (95%CI 27.2%-38%) and 41.7% (95%CI 35.3%-48.1%), respectively. The 1 and 2 years cumulative incidence of chronic graft versus host disease (cGVHD) was 32.9% (95%CI 26.4%-39.4%) and 38.9% (95%CI 31.8%-46.0%). By univariate and multivariate analysis, liver involvement was an independent poor risk factor of SR-aGVHD (OR=4.66, 95%CI 1.145-18.962, P=0.032). Conclusion: Anti-CD(25) mAb serves as an alternative and effective salvage therapy for SR-aGVHD at present. Liver involvement is a predictive factor of poor response in patients with SR-aGVHD.

New predictive factors of poor response to therapy in autoimmune hepatitis: role of mean platelet volume.

The response to immunosuppressive therapy in autoimmune hepatitis (AIH) is a matter of debate. The aim of this work is to identify the histological, biochemical, and clinical predictive factors of incomplete response/treatment failure to the standard treatment (prednisone with or without azathioprine) in a well-characterized series of AIH Egyptian patients. Of 49 AIH patients, only 36 patients completed this retrospective cohort study. The immunological, biochemical, histopathological, and clinical characteristics of patients were evaluated at diagnosis and during follow-up. Patients were classified into two groups; group A showed a complete response to therapy (n=22; 61%) and group B showed partial response/treatment failure (n=14; 39%). In a multivariate analysis, we observed that age at diagnosis up to 22 years [odds ratio (OR): 23.22; confidence interval (CI): 3.978-135.549; P<0.001], serum albumin up to 3.2 g/dl (OR: 5.36; CI: 1.237-23.209; P=0.025), mean platelet volume (MPV) of at least 10.75 fl (OR: 16.5; CI: 3.093-88.037; P<0.001), and presence of cirrhosis at diagnosis (OR: 8.44; CI: 1.682-42.392; P=0.001) were independent variables that can predict partial response/treatment failure. MPV correlated positively with stages of fibrosis/cirrhosis and grades of activity in liver biopsy at diagnosis and correlated inversely with serum albumin and age at presentation. During therapy, group B showed a fluctuation in MPV levels, however, group A showed a progressive decline until the end point. Our study confirmed that younger age, hypoalbuminemia, increased MPV, and cirrhosis at diagnosis were all independent predictors of incomplete response/treatment failure in AIH patients. MPV may reflect the response to therapy.

Progression from Injection to Surgery for Trigger Finger: A Statistical Analysis.

The purpose of this study was to identify predictive factors of poor response to intra-flexoral sheath corticosteroid injection, as well as to identify factors associated with patients' decisions to undergo surgical treatment. Data from 112 patients who received steroid injection treatment for trigger finger were reviewed retrospectively. Logistic regression was used to assess the prognostic value of factors assumed to affect prognosis (age, sex, underlying disease, history of illness, presence of carpal tunnel syndrome, multiple digit involvement, and pre- and post-operative disability scores). Multiple digits were affected in 42 patients. Associated and underlying conditions were carpal tunnel syndrome (n = 36), hypertension (n = 23), hyperlipidemia (n = 14), and history of malignant tumor (n = 10). Logistic regression analysis showed that multiple digit involvement and Froimson clinical severity score were factors significantly associated with surgical treatment after intra-flexoral sheath corticosteroid injection treatment. These two factors were also found to be associated with the patients' decisions to undergo surgical treatment. Although local corticosteroid injection is useful in most cases, providers need to counsel patients with multiple digit involvement and/or severe cases about the possibility of requiring additional surgical treatment.

Predictive factors of poor response to therapy in Autoimmune Hepatitis

AimTo evaluate “ex ante” the predictive factors of incomplete/absent response to the standard therapy in a well characterized series of Autoimmune Hepatitis (AIH) patients from Italy. MethodsOf 282 AIH patients screened from our database 166 (59%) had a sustained response and 116 (41%) had an incomplete/absent response to the therapy; all patients were analyzed for the clinical, serological and histological parameters at diagnosis. ResultsThe patients with incomplete/absent response were characterized by significantly younger age (30 aa vs 42 aa p=0.001) and a significantly higher frequency of cirrhosis at diagnosis than patients who had a complete response to therapy (26% vs 3% p<0.0001); furthermore, patients with incomplete/absent response were distinguished from those with a complete response for significantly lower serum levels of both AST (7.9×upper normal limit [unl] vs 13×unl p<0.005) and ALT (10.9×unl vs 18×unl p=0.002) at diagnosis, and by an increase in IgG serum levels (1.43×unl vs 1.27×unl p=0.009). After stepwise logistic regression, cirrhosis at diagnosis (p=0.003, OR 0.12, 95% CI 0.03–0.49) and younger age (p=0.001, OR 1.03, 95% CI 1.01–1.05) represent two independent variables of incomplete/absent response. ConclusionsYounger age and cirrhosis are predictive of lack of response to the standard therapy in AIH patients.

Increased expression of interleukin-6 predicts poor response to chemoradiotherapy and unfavorable prognosis in oral squamous cell carcinoma.

Recent studies have revealed that cancer cells are exacerbated by chronic inflammation. The present study examined the immunohistochemical expression for interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, in oral squamous cell carcinoma (OSCC) to elucidate the association of IL-6 expression with tumor progression, chemoresistance and prognosis. Seventy-eight patients with primary OSCC were analyzed by immunohistochemical staining for IL-6. These labeling indexes (LIs) were calculated and evaluated in association with the clinicopathologic characteristics and prognosis in the OSCC patients. The patients were divided into three groups as follows: negative group = LI <5%; low IL-6 group = 5% ≤ LI <30%; high IL-6 group = LI ≥30%. The patient numbers of the negative, low and high expression groups were 24, 22 and 32, respectively. In the high IL-6 expression group, IL-6 receptor (IL-6R), phospho-signal tranducer and activator of transcription 3 (p-STAT3) were also detected in almost all the cancer cells. The prevalence of the cervical lymph node or the distant metastasis in the high expression group was significantly higher than those in the negative and low expression groups. Furthermore, the high expression group had a significantly poorer tumor response to the preoperative chemoradiotherapy and a more unfavourable prognosis than the negative and the low expression groups. Interestingly, IL-6, IL-6R and p-STAT3 were expressed in the residual cancer cells of all the patients in the high expression group with poor response to chemoradiotherapy. These results suggested that IL-6 signaling possibly is involved in the progression and treatment-resistance of OSCC and IL-6 expression in cancer cells could be a useful predictive factor of poor response to chemoradiotherapy and unfavorable prognosis.

Abstract 2927: Rapamycin decreases expression of thymidylate synthase and enhances the response to pemetrexed in preclinical studies and a Phase I/II clinical study of subjects with non-small cell lung cancer

Abstract Non-small-cell lung cancer (NSCLC) accounts for 80-85% of lung cancers and almost half of patients with newly diagnosed NSCLC have metastatic disease. Platinum-based chemotherapy regimens given as first-line treatment for advanced NSCLC patients with metastasis are standard but have modest response rates. Pemetrexed is well tolerated and inhibits several folate-dependent enzymes including thymidylate synthase, TS. Increased expression of TS confers resistance to pemetrexed in vitro and is a predictive factor for poor response to pemetrexed. Rapamycin is a mTOR inhibitor and suppresses protein synthesis. Here, we show that rapamycin decreases endogenous expression of TS in NSCLC cells. The combination of rapamycin and pemetrexed synergistically inhibits NSCLC cell proliferation and enhances the inhibition of 4E-binding protein 1 (4E-BP1) activation that is regulated by mTOR. Although pemetrexed as a single agent upregulated expression of TS, pretreatment with rapamycin suppressed pemetrexed-upregulated TS expression. In vivo, the combination of rapamycin and pemetrexed inhibited the growth of NSCLC xenografts, which correlated with decreased mTOR activity and inhibition of pemetrexed-induced upregulated expression of TS. Based on these preclinical data, we have conducted a Phase I/II clinical trial combining rapamycin and pemetrexed in subjects with relapsed NSCLC. This regimen was well tolerated, and resulted in a 22% partial response rate that is above what is expected for response to single agent pemetrexed (9%). In biomarker analyses, pretreatment with rapamycin decreased the expression of TS in peripheral blood mononuclear cells, which correlated with increased progression free survival. Collectively, these studies identify rapamycin and pemetrexed as an effective combination in NSCLC, and suggest that rapamycin enhances the efficacy of pemetrexed by suppressing TS expression. Citation Format: Shigeru Kawabata, Chun-Te Chiang, Regan M. Memmott, Takefumi Komiya, Joell J. Gills, Phillip A. Dennis. Rapamycin decreases expression of thymidylate synthase and enhances the response to pemetrexed in preclinical studies and a Phase I/II clinical study of subjects with non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2927. doi:10.1158/1538-7445.AM2014-2927

Association of autoantibody specificity and response to intravenous immunoglobulin G therapy in immune thrombocytopenia: a multicenter cohort study

Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder, in which platelet glycoprotein (GP)IIb-IIIa and GPIb-IX are the two most frequently targeted autoantigens. Our previous studies in animal models of ITP demonstrated that intravenous immunoglobulinG (IVIG) could protect against anti-GPIIb-IIIa autoantibody-mediated thrombocytopenia but failed to ameliorate ITP induced by most anti-GPIb-IX autoantibodies. The objective of this human study was to evaluate the association between the specificity of antiplatelet autoantibodies and response to IVIG treatment. In this retrospective study, a cohort of 156 previously untreated adults with severe ITP who underwent IVIG therapy (0.4gkg(-1) day(-1) for 5days) was analyzed. The primary outcome was response defined as platelet counts of ≥30×10(9) L(-1) and a doubling of baseline counts within 7days of dosing, and an absence of bleeding. Among the 66 patients with anti-GPIb-IX autoantibodies, only 24 (36.4%) achieved a response, as compared with 72 of 90 patients (80.0%) who were negative for anti-GPIb-IX autoantibodies (relative risk 2.2; 95% confidence interval 1.6-3.1). This study found no difference in response between patients with anti-GPIIb-IIIa autoantibodies (61.7%) and those without anti-GPIIb-IIIa autoantibodies (61.3%). Logistic regressions, including main effects and the interaction between these two autoantibodies, showed no influence of anti-GPIIb-IIIa autoantibodies on the effects of anti-GPIb-IX autoantibodies with regard to their association with IVIG response. Thus, in adults with ITP, the presence of anti-GPIb-IX autoantibodies is a predictive factor for poor response to IVIG treatment. ClinicalTrials.gov NCT01666795.

PReS-FINAL-2095: Older age predicts poor response to 6-months methotrexate therapy in a juvenile idiopathic arthritis cohort of patients

The identification of predictive factors of poor response to methotrexate (MTX) in juvenile idiopathic arthritis (JIA) patients could contribute to optimize the treatment strategy, namely by the earlier introduction of biological treatments.

AB0696 Predictors of poor response to 6-months methotrexate therapy in a juvenile idiopathic arthritis cohort of patients

BackgroundThe identification of predictive factors of poor response to methotrexate (MTX) in juvenile idiopathic arthritis (JIA) patients could contribute to optimize the treatment strategy, namely by the earlier introduction of...

Identification of an AKT-dependent signalling pathway that mediates tamoxifen-dependent induction of the pro-metastatic protein anterior gradient-2

The pro-metastatic protein anterior gradient-2 (AGR2) was previously demonstrated as a predictive factor of poor response to tamoxifen treatment. In this study we aimed to delineate the key signalling pathway that may contribute to regulation of AGR2 protein induction in order to identify novel targets to overcome tamoxifen resistance in tumour cells. Together, our data identify PDPK1-AKT as a pro-oncogenic signalling pathway that triggers AGR2 protein induction in response to tamoxifen and suggest that AKT inhibitors could be used as part of a therapeutic strategy to treat tamoxifen resistant, AGR2 over-expressing cancers.

P.4.e.006 Is body dysmorphic disorder a predictive factor for poor response to sequential pharmacological treatment strategies in OCD patients?

P.4.e.006 Is body dysmorphic disorder a predictive factor for poor response to sequential pharmacological treatment strategies in OCD patients?