Predictive Factors Of Therapeutic Response Research Articles

ON/OFF non-motor evaluation: a new way to evaluate non-motor fluctuations in Parkinson’s disease

BackgroundNMF are currently poorly evaluated in therapeutic decisions. A quantification of their severity would facilitate their integration. The objective of this study was to validate an autoquestionnaire evaluating the severity...

Predictive factors of therapeutic response according to craniofacial skeletal biotype in patients with sleep apnea syndrome using mandibular advancement devices: a pilot study.

To evaluate the influence of facial biotype in the therapeutic effect of mandibular advancement devices (MADs) according to polysomnographic records in patients diagnosed with sleep apnea-hypopnea syndrome (SAHS). A total of 46 patients were recruited. Patients were classified according to facial biotype (mesofacial, brachyfacial, or dolichofacial). The quantitative variables were described as the arithmetic mean and standard deviation or the median and interquartile range. Hypothesis tests used were Pearson's chi-square, paired-sample Student's t- test, the Wilcoxon test, one-way analysis of variance, Kruskal-Wallis test, and Mann-Whitney U-test. P < .05 was considered statistically significant. A total of 46 patients were categorized into three facial biotype subgroups with no significant differences among them in age, body mass index, neck circumference, and sex. The respiratory disturbance index (RDI) results were as follows: brachyfacial patients had a reduction to 15 events/h (P < .001), the mesofacial patients had a reduction to 14 events/h (P < .001), and the dolichofacial patients did not show a significant reduction. The oxygen desaturation index (ODI) results were as follows: brachyfacial patients had a reduction in ODI episodes to 45 episodes/h (P = .001), mesofacial patients had a reduction to 18 episodes/h (P = .001). In the brachyfacial group, the number of awakenings with MAD therapy was reduced to 23 events/h (P = .003), while, in the mesofacial group, it was reduced to 37 episodes/h (P = .012). The facial biotype influences the effectiveness of MAD therapy and is considered a good predictive factor.

Impact of targeted pulmonary arterial hypertension therapies in severe pulmonary hypertension in chronic lung diseases.

Patients with severe pulmonary hypertension associated with chronic lung disease have a poor prognosis. Targeted pulmonary arterial hypertension therapies might improve exercise capacity and outcome, but there are no guidelines on treatments which are not recommended because of an unproven benefit, with discordant results from few studies in this context. The aim of our study was to evaluate targeted pulmonary arterial hypertension therapies for severe group 3 pulmonary hypertension patients. We conducted an observational retrospective monocentre study on patients with severe group 3 pulmonary hypertension diagnosed on right heart catheterisation treated with targeted therapies. Primary outcome was an improvement of the distance on 6-min walk test of ≥30 m. Secondary end-points included changes in haemodynamics (pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP)) and identification of potential predictive factors of therapeutic response. 139 patients were enrolled. Most patients had monotherapy with phosphodiesterase 5 inhibitors (n=128; 92%). Mean change in 6-min walk distance was +1.5 m after treatment (p=0.59). Forced expiratory volume in 1 s and forced vital capacity were not predictive factors for response. We found a significant improvement of PVR and mPAP of -1.0 Wood Units (p<0.001) and -4 mmHg (p<0.001), respectively, under treatment. 18% of patients had to withdraw treatment for intolerance. Treatment duration <3 months was associated with poor survival (hazard ratio 2.75, p=0.0005). Oral targeted pulmonary arterial hypertension therapies do not improve exercise capacity in patients with severe pulmonary hypertension associated with chronic lung disease, but could improve haemodynamic parameters.

A Systematic Review Assessing Patient-Related Predictors of Response to Transcranial Magnetic Stimulation in Major Depressive Disorder.

The safety and efficacy of transcranial magnetic stimulation (TMS) in the acute treatment of major depressive disorder (MDD) is well established. However, it is not well understood which patient-related factors are associated with a more robust antidepressant response. Identifying predictive factors for therapeutic response to TMS treatment in depression will guide clinicians in patient selection. By systematic review of clinical trial data, the current study aims to identify and analyze reported patient-specific predictors of response to an acute course of TMS treatment for MDD. PubMed was searched for randomized controlled trials of TMS for patients with depression. Studies were appraised for risk of bias using components recommended by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. TMS data were available from 375 studies, 18 of which were included in this review. Treatment response is inversely associated with treatment refractoriness and age. Inadequate sample size and large heterogeneity in study parameters among clinical trials limit any strong conclusions from being drawn; nonetheless, despite these limitations, there is mounting evidence, which points to age and treatment refractoriness as candidate variables for predicting clinical outcome. Implications of these findings for treatment of MDD are discussed.

Pretreatment Modified Albumin–Bilirubin Grade Is an Important Predictive Factor Associated with the Therapeutic Response and the Continuation of Atezolizumab plus Bevacizumab Combination Therapy for Patients with Unresectable Hepatocellular Carcinoma

Background: Atezolizumab plus bevacizumab (ATZ + BV) treatment is recommended as the first-line systemic therapy for patients with unresectable hepatocellular carcinoma (u-HCC). This study aimed to investigate the predictive factors of therapeutic response and the continuation of ATZ + BV treatment for u-HCC in a real-world setting. Methods: This retrospective study was conducted between January 2021 and April 2022. Twenty-eight patients with u-HCC, who were treated with ATZ + BV, were assessed for their treatment response, continuation, and adverse events (AEs). Results: Among the 28 patients, 24 were evaluated at the first imaging. The objective response rate (ORR) was 29.2% (n = 7), and 54.2% (n = 13) on the response evaluation criteria in solid tumors (RECIST 1.1) and in the modified RECIST (mRECIST) guidelines, respectively. Comparing the objective response (OR) group (n = 13) and the non-OR group (n = 11), the modified albumin–bilirubin (mALBI) grades 1 and 2a were found to be significant predictive factors for OR (p = 0.021) in the mRECIST guidelines. Among the 28 patients, 17 discontinued their treatment due to AEs. Comparing the treatment continuation (n = 11) and discontinuation groups (n = 17), a Child–Pugh score of five points (p = 0.009) and mALBI grades 1 and 2a (p = 0.020) were predictive factors with significant differences. Conclusions: Pretreatment mALBI grades 1 and 2a were the important predictive factors associated with the therapeutic response and the therapeutic continuation of ATZ + BV for patients with u-HCC.

Predictors of good visual outcomes in patients with neovascular age-related macular degeneration in daily practice

To report predictive factors for therapeutic response to anti-VEGF in patients with neovascular age-related macular degeneration (nAMD) in daily clinical practice in our patient population. Retrospective cohort study including 56 patients (69 eyes) with nAMD treated with anti-VEGF, followed for at least two years between February 2012 and April 2018. Patients received three intravitreal anti-VEGF (bevacizumab) injections (loading dose) and were monitored and treated according to a PRN regimen. We analysed whether a gain in visual acuity of 15 or more ETDRS letters at the final visit was associated with demographic characteristics, presence of systemic comorbidities, fundus lesions or measurable improvement on Cirrus optical coherence tomography (OCT) between the first and last visit. After a mean follow-up of 15.5 months (4.7-27.8 interquartile range), central retinal thickness (CRT) (RR: 1.004; IC 95%: 1.001-1.007; P=0.011) and macular hemorrhage (RR: 0.30; IC 95%: 0.10-0.90, P=0.032) at baseline were found to be useful predictive factors for visual acuity improvement (≥15 letters) in patients treated for nAMD by anti-VEGF in a real world clinical setting. In the present series of patients with nAMD receiving a loading dose of bevacizumab and followed according to a PRN regimen for 24 months, the only predictable factors for a ≥15 letter gain in visual acuity were anatomical response as measured by OCT and macular hemorrhage at baseline.

Impact of Hepatitis B Virus Genetic Variation, Integration, and Lymphotropism in Antiviral Treatment and Oncogenesis.

Chronic Hepatitis B Virus (HBV) infection poses a significant global health burden. Although, effective treatment and vaccinations against HBV are available, challenges still exist, particularly in the development of curative therapies. The dynamic nature and unique features of HBV such as viral variants, integration of HBV DNA into host chromosomes, and extrahepatic reservoirs are considerations towards understanding the virus biology and developing improved anti-HBV treatments. In this review, we highlight the importance of these viral characteristics in the context of treatment and oncogenesis. Viral genotype and genetic variants can serve as important predictive factors for therapeutic response and outcomes in addition to oncogenic risk. HBV integration, particularly in coding genes, is implicated in the development of hepatocellular carcinoma. Furthermore, we will discuss emerging research that has identified various HBV nucleic acids and infection markers within extrahepatic sites (lymphoid cells). Intriguingly, the presence of hepatocellular carcinoma (HCC)-associated HBV variants and viral integration within the lymphoid cells may contribute towards the development of extrahepatic malignancies. Improved understanding of these HBV characteristics will enhance the development of a cure for chronic HBV infection.

Abstract 4306: Retrospective analysis of docetaxel in combination with ramucirumab for previously treated non-small cell lung cancer patients

Abstract BACKGROUND: Current clinical trials demonstrated that combination regimens comprising chemotherapy and immunotherapy lead to better patient outcomes compared to chemotherapy alone as the first line of treatment for non-small cell lung cancer (NSCLC). In addition, the combination therapy of docetaxel (Doc) and ramucirumab (Ram) was considered one of the standard treatments for advanced or relapsed NSCLC patients. However, little is known about the therapeutic responders of this combination therapy among previously treated NSCLC patients. In the present study, we aimed to identify predictive factors for therapeutic response, including programmed death-ligand 1 (PD-L1) expression in tumors, for Doc treatment in combination with Ram. METHODS: We retrospectively analyzed a total of 135 advanced or relapsed NSCLC patients who were refractory to platinum-based chemotherapy at eleven institutions in Japan between July 2016 and November 2018. RESULTS: Our observations showed that PD-L1 expression in tumors is not associated with the efficacy of combined therapy of Doc and Ram in previously treated NSCLC patients. Analysis of the patient clinical profiles indicated that prior treatment with immune checkpoint inhibitors (ICIs) is a reliable predictor for the good progression-free survival (PFS) to this combination therapy (P=0.041). CONCLUSIONS: Our retrospective study indicated that combination regimens comprising chemotherapy and ICIs followed by Doc and Ram could be an optimal therapeutic option for NSCLC patients regardless of the PD-L1 status of tumors. Further investigations are required to strengthen clinical evidence demonstrating the effectiveness of the combination therapy of Doc plus Ram in previously treated NSCLC patients. Citation Format: Rui Kitadai, Akihiro Yoshimura, Tadaaki Yamada, Yusuke Okuma, Takayuki Takeda, Takanori Kanematsu, Junji Uchino, Yasuhiko Nishioka, Koichi Takayama. Retrospective analysis of docetaxel in combination with ramucirumab for previously treated non-small cell lung cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4306.

Retrospective analysis of docetaxel in combination with ramucirumab for previously treated non-small cell lung cancer patients.

Current clinical trials demonstrated that combination regimens comprising chemotherapy and immunotherapy lead to better patient outcomes compared to chemotherapy alone as the first line of treatment for non-small cell lung cancer (NSCLC). In addition, the combination therapy of docetaxel (Doc) and ramucirumab (Ram) was considered one of the standard treatments for advanced or relapsed NSCLC patients. However, little is known about the therapeutic responders of this combination therapy among previously treated NSCLC patients. In the present study, we aimed to identify predictive factors for therapeutic response, including programmed death-ligand 1 (PD-L1) expression in tumors, for Doc treatment in combination with Ram. We retrospectively analyzed a total of 135 advanced or relapsed NSCLC patients who were refractory to platinum-based chemotherapy at eleven institutions in Japan between July 2016 and November 2018. Our observations showed that PD-L1 expression in tumors is not associated with the efficacy of combined therapy of Doc and Ram in previously treated NSCLC patients. Analysis of the patient clinical profiles indicated that prior treatment with immune checkpoint inhibitors (ICIs) is a reliable predictor for the good progression-free survival (PFS) to this combination therapy (P=0.041). Our retrospective study indicated that combination regimens comprising chemotherapy and ICIs followed by Doc and Ram could be an optimal therapeutic option for NSCLC patients regardless of the PD-L1 status of tumors. Further investigations are required to strengthen clinical evidence demonstrating the effectiveness of the combination therapy of Doc plus Ram in previously treated NSCLC patients.

Predictive factors of therapeutic response in multiple myeloma in the Cameroonian subject: A multicentric study in Yaoundé

Predictive factors of therapeutic response in multiple myeloma in the Cameroonian subject: A multicentric study in Yaoundé

Switch to miriplatin for multinodular hepatocellular carcinoma unresponsive to transarterial chemoembolization with epirubicin: a prospective study

The aim of this prospective study was to evaluate the efficacy of transarterial chemoembolization using miriplatin, a platinum-based anticancer drug, as a retreatment regimen for hepatocellular carcinoma (HCC) unresponsive to chemoembolization using epirubicin. Between April 2013 and December 2014, we enrolled 57 consecutive chamoembolization-naïve patients with unresectable HCC, and performed chemoembolization with epirubicin. Treatment effect, necrotizing rate of the target nodules, was evaluated at 1-3 months after treatment using contrast-enhanced CT or MRI. We subsequently included retreatment chemoembolization with miriplatin for patients whose treatment effect was <50% after chemoembolization with epirubicin. The treatment effect after chemoembolization with miriplatin and the liver function before and after chemoembolization were evaluated. Eighteen patients of the 57 showed a treatment effect <50% after chemoembolization with epirubicin, and were switched to chemoembolization with miriplatin. The treatment effect after chemoembolization with miriplatin was ≥50% in four (22%) patients. Four of the remaining 14 (78%) patients who had <50% necrosis exhibited deterioration of the liver function after chemoembolization with miriplatin. Univariate analysis indicated that an alpha-fetprotein-L3 level <10% and a serum albumin level ≥3.6 g/dl were predictive factors of therapeutic response after chemoembolization with miriplatin (P < 0.05). However, there was no predictive factor regarding the deterioration of liver function after chemoembolization with miriplatin. In unresectable HCC patients who were unresponsive to chemoembolization with epirubicin, switching the chemotherapeutic regimen to a platinum-based anticancer drug in retreatment chemoembolization should be considered as a treatment option. Trial registration: UMIN 000015887.

Predictors of response to repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder

Repetitive transcranial magnetic stimulation (rTMS), based on the principle of electromagnetic induction, consists of applying series of magnetic impulses to the cerebral cortex so as to modulate neurone activity in a target zone. This technique, still experimental, could prove promising in the field of psychiatry, in particular for the treatment of major depressive disorder. It is important for the clinician to be able to assess the response potential of a given patient to rTMS, and this among other things requires relevant predictive factors to be available. This review of the literature aims to determine and analyse reported predictive factors for therapeutic response to rTMS treatment in major depressive disorder. Different parameters are studied, in particular age, the severity of the depressive episode, psychological dimensions, genetic factors, cerebral blood flows via cerebral imagery, and neuronavigation. The factors found to be associated with better therapeutic response were young age, low level of severity of the depressive episode, motor threshold intensity over 100%, more than 1000 stimulations per session, more than 10 days treatment, L/L genotype on the 5-HTTLPR transporter gene, C/C homozygosity on the promotor regions of the 5-HT1A receptor gene, Val/Val homozygosity on the BDNF gene, cordance analyses by EEG, and finally the accurate localisation provided by neuronavigation. The authors conclude that investigations in larger patient samples are required in the future, and that the work already achieved should provide lines of approach for the coming experimental studies.

THU0187 Memory B Cells Produce More TNF Than Other B Cell Subtypes and Their Percentage at Baseline Could Help to Predict Response to TNF-Inhibitors

BackgroundTumor necrosis factor (TNF) inhibitors are effective treatments for rheumatoid arthritis (RA). It is known that monoclonal antibodies and soluble receptors against TNF act slightly differently. Effects of TNFi on...

Predictive Factors for Therapeutic Response to Asthma Treatment with Montelukast or Fluticasone in a Randomized Controlled Trial with Asthmatic Smokers

We conducted an analysis to identify factors predictive of therapeutic response to montelukast or fluticasone (each vs. placebo) in a large, randomized controlled trial in a population of smoking asthmatics.

Amino acid substitutions in core and NS5A regions of the HCV genome can predict virological decrease with pegylated interferon plus ribavirin therapy

The current standard therapy for chronic hepatitis C is pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy. Recently, it has been reported that amino acid (aa) substitutions in the core region, as well as the IFN-sensitivity-determining region (ISDR), were predictive of non-virological response (NVR), sustained virological response (SVR) and early virological response. Despite the importance of these two predictive factors for combination therapy, their interaction is poorly understood. A total of 117 patients who were treated with PEG-IFN-α2b plus RBV combination therapy were selected for participation in this study. We determined the aa sequences in the core region and ISDR by direct sequencing and analysed them along with clinical data to identify predictive factors for therapeutic response. The aa sequences in the core region and γ-glutamyl transpeptidase (GTP) levels were associated with SVR and NVR, but aa sequences in the ISDR were not. However, substitutions at both aa 70 and aa 91 in the core region without substitutions in the ISDR and higher levels of γ-GTP were independent predictive factors for NVR. Wild-type aa 70 and aa 91 in the core region, higher platelet counts and lower levels of γ-GTP were independent predictive factors for SVR. These results indicate that analyses of aa substitutions in both the core region and the ISDR are useful for predicting the effectiveness of combination therapy, and could help to avoid therapy exposure for patients who have a low probability of SVR.

Concordance between epidermal growth factor receptor status in primary non-small-cell lung cancer and metastases: a post-mortem study☆

Epidermal growth factor receptor (EGFR)-targeted therapies are a valid therapeutic option for advanced non-small-cell lung cancer (NSCLC), but unequivocally recognised predictive factors for therapeutic response are lacking. However, intrinsic resistance might occur due to loss of EGFR expression during the course of the disease or its treatment. Paraffin-embedded tissue from cases with metastatic NSCLC obtained at autopsy was retrieved from our archive. Specimens of primary tumour (n=39; 64% adenocarcinoma) and of all corresponding metastases (n=70) were immunohistochemically stained for EGFR expression. Two observers independently scored staining intensity and evaluated the percentage of positively stained cells. Identical staining intensity and < or = 10% difference in number of stained cells were defined as perfect concordance; and one-increment difference in staining intensity and less than 30% difference in number of stained cells were defined as good concordance. Twenty-seven out of 39 primary tumours (69%) were EGFR-positive on immunohistochemistry (IHC), with 12/27 (44%) of positive tumours exhibiting intense or moderate EGFR expression. The median number of EGFR-expressing cells in primary tumours was 50% (range 0-100%). Overall Spearman's rank correlations for staining intensity and percentage of positively stained cells between primary tumours and paired metastases were 0.78 (p<0.001) and 0.60 (p<0.001), respectively. Perfect concordance was observed in 51% (20/39) and good concordance in 18% (7/39) of corresponding pairs, respectively, whereas 9/12 metastases showing discordant staining with their corresponding primary tumours had lacked EGFR expression. In most NSCLCs, EGFR status of primary tumours correlates with EGFR status of corresponding metastases. Hence, loss of EGFR expression is unlikely during disease progression, local or non-EGFR-targeting systemic treatment.

Clinical parameters predicting therapeutic response to surgical management in patients with chemotherapy-resistant gestational trophoblastic neoplasia

Objective Several studies have reported that surgical management of chemotherapy-resistant gestational trophoblastic neoplasia (GTN) is a useful adjunct to chemotherapy. We investigated the pretreatment predictive factors of therapeutic response in response to surgical management combined with chemotherapy. Methods The study involved 61 patients with chemotherapy-resistant GTN who underwent surgery between January 1996 and January 2007. Responses to the combination therapy with surgery and chemotherapy were assessed after the end of treatment. Statistical analyses were performed to identify preoperative clinical factors associated with response of chemotherapy-resistant GTN. Results After the end of combination therapy, 47 (77.0%), 4 (6.6%), 1 (1.6%), and 9 (14.8%) of 61 patients showed complete response (CR), partial remission (PR), stable disease (SD), and progressive disease (PD), respectively. Univariate analysis found that predictors of response were age ( p = 0.022), antecedent pregnancy ( p = 0.022), site of metastasis ( p = 0.026), and preoperative serum human chorionic gonadotropin-beta subunit (β-hCG) level ( p = 0.027). All patients with treatment failure had 2 or more of unfavorable factors, including age older than 35 years, antecedent non-molar pregnancy, distant metastasis outside of lungs and uterus, and preoperative serum β-hCG level greater than 10 IU/L. Conclusions The data suggest that age older than 35 years, antecedent non-molar pregnancy, distant metastasis outside of lungs and uterus, and a preoperative serum β-hCG level greater than 10 IU/L are important clinical predictors of treatment failure to surgery. They may benefit in the selection of salvage surgery as well as the assessment of individual prognosis.

P.3.a.005 Predictive factors for therapeutic response in first episode psychosis

P.3.a.005 Predictive factors for therapeutic response in first episode psychosis

A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment

BackgroundCetuximab, a monoclonal antibody targeting Epidermal Growth Factor Receptor (EGFR), is currently used in metastatic colorectal cancer (mCRC), but predictive factors for therapeutic response are lacking. Mutational status of KRAS and EGFR, and EGFR copy number are potential determinants of cetuximab activity.MethodsWe analyzed tumor tissues from 32 EGFR-positive mCRC patients receiving cetuximab/irinotecan combination and evaluable for treatment response. EGFR copy number was quantified by fluorescence in situ hybridization (FISH). KRAS exon 1 and EGFR exons coding for extracellular regions were sequenced.ResultsNine patients experienced an objective response (partial response) and 23 were considered as nonresponders (12 with stable disease and 11 with progressive disease). There was no EGFR amplification found, but high polysomy was noted in 2 patients, both of which were cetuximab responders. No EGFR mutations were found but a variant of exon 13 (R521K) was observed in 12 patients, 11 of which achieved objective response or stable disease. Progression-free and overall survivals were significantly better in patients with this EGFR exon 13 variant. KRAS mutations were found in 14 cases. While there was a trend for an increased KRAS mutation frequency in nonresponder patients (12 mutations out of 23, 52%) as compared to responder patients (2 out of 9, 22%), authentic tumor response or long-term disease stabilization was found in KRAS mutated patients.ConclusionThis preliminary study suggests that: an increase in EGFR copy number may be associated with cetuximab response but is a rare event in CRC, KRAS mutations are associated with low response rate but do not preclude any cetuximab-based combination efficacy and EGFR exon 13 variant (R521K) may predict for cetuximab benefit.

Symptom Pattern At Baseline Predicts Treatment Response in Erosive Esophagitis Patients

Purpose: Identification of reliable predictive factors for therapeutic response in GERD patients may influence treatment decisions, enhance effectiveness of individual therapy and reduce cost. The aim of this study was to analyze the influence of patients' baseline symptom pattern (using the validated GERD symptom assessment tool ReQuest™), the grade of erosive esophagitis (EE), and treatment group on the time to first symptom relief. Methods: 2,316 patients with EE (LA grade A-D) were randomized to once daily 40 mg pantoprazole or 40 mg esomeprazole over a period of 4 weeks using a randomized, double blind, multinational (11 countries), parallel group comparison trial.