Initial Treatment Of Patients Research Articles

The efficacy of sclerotherapy as the initial treatment in patients with bleeding from Dieulafoy's lesion of the upper gastrointestinal tract.

Dieulafoy's lesion (DL) is a rare and important cause of acute nonvariceal upper gastrointestinal bleeding (ANVUGIB), however, there is a lack of clear guidelines focus on the endoscopic hemostasis treatment for DL. Sclerotherapy, as the ANVUGIB guideline recommended endoscopic hemostasis method, is widely used in clinical practice. The aim of this study is to investigate the efficacy of sclerotherapy as the initial treatment for Dieulafoy's lesion of the upper gastrointestinal tract (UDL). Patients with UDL who underwent the ANVUGIB standard endoscopic hemostasis between April 2007 and January 2023 were enrolled. The endoscopic therapy method was left to the discretion of the endoscopist. In total, 219 patients were finally obtained, with 74 (33.8%) receiving sclerotherapy and 145 (66.2%) receiving other standard endoscopic therapy. The rebleeding within 30days was significantly lower in the sclerotherapy group compared to the other standard group (5.8% vs. 16.8%, p = 0.047). There were no significant differences between the two groups in terms of successful hemostasis rate (93.2% vs. 94.5%, p = 0.713), median number of red blood cell transfusions (3.5 vs. 4.0 units, p = 0.257), median hospital stay (8.0 vs. 8.0days, p = 0.103), transferred to ICU rate (8.1% vs. 6.2%, p = 0.598), the need for embolization or surgery rate (12.2% vs. 9.7%, p = 0.567) and 30-day mortality (0 vs. 2.1%, p = 0.553). In addition, we found no difference in efficacy between sclerotherapy alone and combination (3.1% vs. 8.1%, p = 0.714). Further analysis revealed that thermocoagulation for hemostasis was associated with a higher rate of rebleeding (28.6% vs. 3.1%, p = 0.042) and longer hospital stay (11.5 vs. 7.5days, p = 0.005) compared to sclerotherapy alone. Sclerotherapy represents an effective endoscopic therapy for both alone and combined use in patients with upper gastrointestinal Dieulafoy's lesion. Therefore, sclerotherapy could be considered as initial treatment in patients with bleeding of UDL.

Neurosurgical and pharmacological management of dystonia.

Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements, often with repetitive or sustained contraction resulting in abnormal posturing. Different types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given intervention. For most patients afflicted with these disorders, an exact cause is rarely identified, so treatment mainly focuses on symptomatic alleviation. Pharmacological agents, such as oral anticholinergic administration and botulinum toxin injection, play a major role in the initial treatment of patients. In more severe and/or refractory cases, focal areas for neurosurgical intervention are identified and targeted to improve quality of life. Deep brain stimulation (DBS) targets these anatomical locations to minimize dystonia symptoms. Surgical ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to DBS. These management options grant providers and patients the ability to weigh the benefits and risks for each individual patient profile. This review article explores these pharmacological and neurosurgical management modalities for dystonia, providing a comprehensive assessment of each of their benefits and shortcomings.

Abstract PO1-19-04: Dalpiciclib and tucidinostat in patients with HR+/HER2- advanced breast cancer and resistance to CDK4/6 inhibitors: A phase Ib trial

Abstract Background: Hormone receptor (HR)-positive/epidermal growth factor receptor 2 (HER2)-negative breast cancer accounts for approximately 70% of all breast cancers and is associated with a better prognosis. Estrogen plays an important role in the growth of HR-positive breast cancer, thus patients with this type of tumor are sensitive to hormone inhibitors. However, a quarter of patients will inevitably relapse. Several large clinical trials have demonstrated that the combination of CDK4/6 inhibitors and endocrine therapy (ET) as first or second-line therapy could improve the progression-free survival (PFS) and overall survival for patients with breast cancer. In China, dalpiciclib (a CDK4/6 inhibitor) in combination with fulvestrant has been approved for patients with recurrent or metastatic HR-positive/HER2-negative breast cancer who have failed ET. Moreover, the combination of dalpiciclib and aromatase inhibitors (AI) as an initial treatment for patients with locally advanced or metastatic HR-positive/HER2-negative breast cancer has also been accepted. However, the standard treatment for patients who have failed CDK4/6 inhibitors has not been established. Histone deacetylase (HDAC) inhibitors cause alterations in gene expression in many signaling pathways associated with oncogenesis, leading to the arrest of tumor cell growth and differentiation, as well as promoting tumor apoptosis. Tucidinostat (an HDAC inhibitor) plus AI has been approved for the treatment of locally advanced HR-positive/HER2-negative postmenopausal breast cancer patients who have failed ET. Theoretically, synergistic effects may occur when HDAC inhibitors are combined with CDK4/6 inhibitors. Currently, the clinical data on combination therapy with CDK4/6 inhibitors and HDAC inhibitors have not been reported. Herein, our study aims to explore the efficacy and safety of dalpiciclib and tucidinostat in patients with late-stage HR+/HER2- breast cancer who have failed CDK4/6 inhibitors. Trial Design: The present study is a single-arm, open-label, phase I, dose escalation clinical trial (NCT 05586841). Patients were assigned to four groups to receive either dalpiciclib 125mg/d and tucidinostat 25mg/BIW (group A) or dalpiciclib 125mg/d and tucidinostat 20mg/BIW (group B) or dalpiciclib 100 mg/d and tucidinostat 25mg/BIW (group C) or dalpiciclib 100 mg/d and tucidinostat 20mg/BIW (group D). The Bayesian Optimal Interval (BOIN) design was performed to determine dose-escalation and de-escalation to find the maximum tolerated dose (MTD) of dalpiciclib plus tucidinostat. Key Eligibility Criteria: The study is enrolling female patients who are older than 18 years, with HR-positive/HER2-negative locally recurrent or metastatic breast cancer (MBC), with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2. Before entering this trial, all patients must have received ≤1 previous line of chemotherapy for recurrent or MBC, and have failed CDK4/6 inhibitor therapy. Aims: The BOIN design is employed to explore the optimal dose combination of dalpiciclib and tucidinostat and determine recommended doses for a phase II dose expansion clinical trial, based on prespecified dose-limiting toxicity (DLT). Statistical Methods: Safety will be evaluated in the safety set including all patients who received at least one dose of study treatment and underwent at least one safety assessment. Efficacy will be assessed in the full analysis set, defined as all patients who received at least one dose of study treatment. Present and Planned Accrual: Up to 30 participants were planned to be enrolled in the present study. The first participant was enrolled on 18 January 2023. The recruitment is ongoing. Citation Format: Tao Wang, Jinmei Zhou, Xuexue Wu, Zefei Jiang. Dalpiciclib and tucidinostat in patients with HR+/HER2- advanced breast cancer and resistance to CDK4/6 inhibitors: A phase Ib trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-04.

Abstract PO1-04-10: Body Mass Index and Treatment Efficacy in advanced Luminal Breast Cancer: Insights from the GEICAM/2013-02 (PEARL) trial

Abstract Background: Endocrine therapy (ET) and treatment directed against molecular targets (CDK 4/6, PI3K, mTOR) constitute the basis of initial treatments for patients with advanced luminal breast cancer. Most of these treatments are oral and have been developed at a fixed dose, without weight adjusted dosing. There is little evidence on the influence that patients’ weight might have on clinical outcomes of these oral drugs in the context of a randomized clinical trial. The present study analyzes the potential impact of the weight of patients treated in the two cohorts of the PEARL trial (NCT02028507) on Progression-Free Survival (PFS), Overall Survival (OS) and the incidence of side effects in each treatment arm. Methods: GEICAM/2013-02 (PEARL) is a multicenter, phase III randomized clinical trial that enrolled patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) who progressed to a prior aromatase inhibitor. Patients were randomized 1:1 to receive ET + palbociclib or capecitabine. Patient weight was assessed based on baseline body mass index (BMI) categories: normal (BMI ≤25 Kg/m2), overweight (BMI 25-29.9 Kg/m2) and obesity (BMI ≥30 Kg/m2). Cox's stratified proportional hazard model was used for survival analysis. Adverse events were assessed and graded according to National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 4.0. Results: A total of 600 patients were included in the study and all were evaluable for the weight-based analysis, including 301 in the ET +palbociclib arm and 299 in the capecitabine arm. The distribution of patient’s weights is shown in Table 1. For the Intention-to-treat (ITT) population, no significant difference in the median OS was found between the different weight categories (Normal: 32.8 months vs overweight: 31.9 months, [p=0.467]; obese: 32 months [p=0.407]). Specifically, for patients with normal weight, the median PFS was 9.3 months in the ET + palbociclib group compared to 9.0 months in the capecitabine group (hazard ratio (HR) 0.83, 95% confidence interval [CI]: 0.61-1.13; p=0.23). In the overweight group, the PFS was 7.5 months in the ET+palbociclib group and 11.1 months in the capecitabine group (HR 1.17, 95% CI: 0.87-1.58; p=0.30) while for the obese group, the PFS was 5.7 months vs 11.7 months (HR 1.14, 95% CI: 0.82-1.59; p=0.43), respectively. No substantial differences in the incidence of grade ≥ 3 events were observed when considering weight categories in the different treatment groups (capecitabine arm (Normal: 60%, Overweight: 70.4%, Obese: 61.6%) and ET+palbociclib arm (Normal: 74.5%, Overweight: 76.1%, Obese: 51.6%). Conclusions: Our findings, despite not finding statistically significant differences, suggest a potentially clinically relevant trend towards improved PFS with capecitabine in overweight and obese patients compared to those receiving palbociclib plus ET. The impact of weight on the outcomes with fixed-dose oral drugs warrants further investigation in future studies. Table 1. Citation Format: Manuel Alva, Sara López-Tarruella, Christoph Zielinski, Manuel Ruíz - Borrego, Nicholas Turner, Eva Ciruelos, Montserrat Muñoz, Begoña Bermejo, Mireia Margelí, Antonio Antón, Zsuzsanna Kahan, Tibor Csöszi, Maribel Casas, Laura Murillo, Serafin Morales Murillo, Emilio Alba, Einav Nili-Gal Yam, Angel Guerrero, Lourdes Calvo, Juan de la Haba-Rodríguez, Manuel Ramos, Isabel Álvarez, Andrés García-Palomo, María Koehler, José Ángel García-Sáenz, J. Ignacio Chacón, Claire Swift, Christiane Thallinger, Miguel Gil-Gil, Miguel Martín. Body Mass Index and Treatment Efficacy in advanced Luminal Breast Cancer: Insights from the GEICAM/2013-02 (PEARL) trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-10.

A low FODMAP diet plus traditional dietary advice versus a low-carbohydrate diet versus pharmacological treatment in irritable bowel syndrome (CARIBS): a single-centre, single-blind, randomised controlled trial

Dietary advice and medical treatments are recommended to patients with irritable bowel syndrome (IBS). Studies have not yet compared the efficacy of dietary treatment with pharmacological treatment targeting the predominant IBS symptom. We therefore aimed to compare the effects of two restrictive dietary treatment options versus optimised medical treatment in people with IBS. This single-centre, single-blind, randomised controlled trial was conducted in a specialised outpatient clinic at the Sahlgrenska University Hospital, Gothenburg, Sweden. Participants (aged ≥18 years) with moderate-to-severe IBS (Rome IV; IBS Severity Scoring System [IBS-SSS] ≥175) and no other serious diseases or food allergies were randomly assigned (1:1:1) by web-based randomisation to receive a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) plus traditional IBS dietary advice recommended by the UK National Institute for Health and Care Excellence (hereafter the LFTD diet), a fibre-optimised diet low in total carbohydrates and high in protein and fat (hereafter the low-carbohydrate diet), or optimised medical treatment based on predominant IBS symptom. Participants were masked to the names of the diets, but the pharmacological treatment was open-label. The intervention lasted 4 weeks, after which time participants in the dietary interventions were unmasked to their diets and encouraged to continue during 6 months' follow-up, participants in the LFTD group were instructed on how to reintroduce FODMAPs, and participants receiving pharmacological treatment were offered diet counselling and to continue with their medication. The primary endpoint was the proportion of participants who responded to the 4-week intervention, defined as a reduction of 50 or more in IBS-SSS relative to baseline, and was analysed per modified intention-to-treat (ie, all participants who started the intervention). Safety was analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02970591, and is complete. Between Jan 24, 2017, and Sept 2, 2021, 1104 participants were assessed for eligibility and 304 were randomly assigned. Ten participants did not receive their intervention after randomisation and thus 294 participants were included in the modified intention-to-treat population (96 assigned to the LFTD diet, 97 to the low-carbohydrate diet, and 101 to optimised medical treatment). 241 (82%) of 294 participants were women and 53 (18%) were men and the mean age was 38 (SD 13). After 4 weeks, 73 (76%) of 96 participants in the LFTD diet group, 69 (71%) of 97 participants in the low-carbohydrate diet group, and 59 (58%) of 101 participants in the optimised medical treatment group had a reduction of 50 or more in IBS-SSS compared with baseline, with a significant difference between the groups (p=0·023). 91 (95%) of 96 participants completed 4 weeks in the LFTD group, 92 (95%) of 97 completed 4 weeks in the low-carbohydrate group, and 91 (90%) of 101 completed 4 weeks in the optimised medical treatment group. Two individuals in each of the intervention groups stated that adverse events were the reason for discontinuing the 4-week intervention. Five (5%) of 91 participants in the optimised medical treatment group stopped treatment prematurely due to side-effects. No serious adverse events or treatment-related deaths occurred. Two 4-week dietary interventions and optimised medical treatment reduced the severity of IBS symptoms, with a larger effect size in the diet groups. Dietary interventions might be considered as an initial treatment for patients with IBS. Research is needed to enable personalised treatment strategies. The Healthcare Board Region Västra Götaland, the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, AFA Insurance, grants from the Swedish state, the Wilhelm and Martina Lundgren Science Foundation, Skandia, the Dietary Science Foundation, and the Nanna Swartz Foundation.

Patient characteristics, diagnostic testing, and initial treatment profiles of patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) using a Japanese claims database.

To investigate the diagnostic and therapeutic landscape for patients with connective tissue disease (CTD) and CTD-associated pulmonary arterial hypertension (CTD-PAH) in acute-care general hospitals in Japan. We conducted a retrospective cohort study by analysing the Medical Data Vision (MDV) database from April 2008 and September 2020. CTD patients who prescribed immunosuppressants were included in cohort 1, and CTD-PAH patients extracted from cohort 1 were included in cohort 2. Patient characteristics, diagnostic screening frequencies for PAH, and initial PAH-specific treatment patterns were assessed. Overall, 16648 patients with CTD and 81 patients with CTD-PAH were included in cohorts 1 and 2, respectively. The frequencies of screening tests for PAH, including brain natriuretic peptide (BNP), transthoracic echocardiogram (TTE), and diffusing capacity of the lungs for carbon monoxide (DLCO), among CTD patients were 0.7, 0.3, and 0.1 tests/person-year, respectively. The most common initial PAH-specific treatment therapy was monotherapy (87.7%), followed by dual therapy (7.4%), and triple therapy (2.5%). This is the first study to describe the patient flow from PAH diagnosis to initial PAH-specific treatment for real-world patients who were followed regularly due to CTD in Japanese clinical practice.

Prognostic factors for clinical outcomes after arthroscopic treatment of traumatic central tears of the triangular fibrocartilage complex.

The study aimed to assess the clinical outcomes of arthroscopic debridement and partial excision in patients with traumatic central tears of the triangular fibrocartilage complex (TFCC), and to identify prognostic factors associated with unfavourable clinical outcomes. A retrospective analysis was conducted on patients arthroscopically diagnosed with Palmer 1 A lesions who underwent arthroscopic debridement and partial excision from March 2009 to February 2021, with a minimum follow-up of 24 months. Patients were assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Mayo Wrist Score (MWS), and visual analogue scale (VAS) for pain. The poor outcome group was defined as patients whose preoperative and last follow-up clinical score difference was less than the minimal clinically important difference of the DASH score (10.83). Baseline characteristics, arthroscopic findings, and radiological factors (ulnar variance, MRI, or arthrography) were evaluated to predict poor clinical outcomes. A total of 114 patients were enrolled in this study, with a mean follow-up period of 29.8 months (SD 14.4). The mean DASH score improved from 36.5 (SD 21.5) to 16.7 (SD 14.3), the mean MWS from 59.7 (SD 17.9) to 79.3 (SD 14.3), and the mean VAS pain score improved from 5.9 (SD 1.8) to 2.2 (SD 2.0) at the last follow-up (all p < 0.001). Among the 114 patients, 16 (14%) experienced poor clinical outcomes and ten (8.8%) required secondary ulnar shortening osteotomy. Positive ulnar variance was the only factor significantly associated with poor clinical outcomes (p < 0.001). Positive ulnar variance was present in 38 patients (33%); among them, eight patients (21%) required additional operations. Arthroscopic debridement alone appears to be an effective and safe initial treatment for patients with traumatic central TFCC tears. The presence of positive ulnar variance was associated with poor clinical outcomes, but close observation after arthroscopic debridement is more likely to be recommended than ulnar shortening osteotomy as a primary treatment.

O57: Tailored risk assessment and forecasting in intermittent claudication using machine learning (TRAFIC-ML)

Abstract Introduction Guidelines recommend cardiovascular risk reduction and supervised exercise therapy as the initial treatment for patients with intermittent claudication(IC). However, implementation challenges and poor patient compliance lead to significant variation in management and therefore outcomes. We propose a precise machine learning derived decision support system that aims to provide personalised outcome predictions across different management strategies. Methods Feature selection was performed using the least absolute shrinkage and selection operator method. The model was developed using a bootstrapped sample of 10,000 patients based on 255 patients from our vascular centre. The model considered 27 baseline characteristics, compliance to best medical therapy/smoking cessation and treatment strategy. The model was validated using a separate dataset of 254 patients. This model was then used to build a prototype interactive decision support system which was evaluated using calibration curves, decision curve analyses and area under the receiver operator characteristic (AUROC) curves. Results The AUROC curves demonstrated excellent discrimination for the risk of progression to chronic limb threatening ischaemia at two years(0.892) and five years(0.866) and likelihood of major adverse cardiovascular events(0.836), major adverse limb events(0.891) and revascularisation(0.896)within 5 years, regardless of the treatment strategy. Calibration curves demonstrated good consistency between predicted and actual outcomes and decision curve analyses confirmed clinical utility. The tool maintained an accuracy of &amp;gt;80% and an effect size of &amp;gt;0.5. Conclusion Our decision support system successfully predicts outcomes in IC regardless of treatment strategy, offering potential for improved risk stratification and patient outcomes.

Targeting metabolic adaptive responses induced by glucose starvation inhibits cell proliferation and enhances cell death in osimertinib-resistant non-small cell lung cancer (NSCLC) cell lines

Osimertinib, a tyrosine kinase inhibitor targeting mutant EGFR, has received approval for initial treatment in patients with Non-Small Cell Lung Cancer (NSCLC). While effective in both first- and second-line treatments, patients eventually develop acquired resistance. Metabolic reprogramming represents a strategy through which cancer cells may resist and adapt to the selective pressure exerted by the drug. In the current study, we investigated the metabolic adaptations associated with osimertinib-resistance in NSCLC cells under low glucose culture conditions. We demonstrated that, unlike osimertinib-sensitive cells, osimertinib-resistant cells were able to survive under low glucose conditions by increasing the rate of glucose and glutamine uptake and by shifting towards mitochondrial metabolism. Inhibiting glucose/pyruvate contribution to mitochondrial respiration, glutamine deamination to glutamate, and oxidative phosphorylation decreased the proliferation and survival abilities of osimertinib-resistant cells to glucose starvation. Our findings underscore the remarkable adaptability of osimertinib-resistant NSCLC cells in a low glucose environment and highlight the pivotal role of mitochondrial metabolism in mediating this adaptation. Targeting the metabolic adaptive responses triggered by glucose shortage emerges as a promising strategy, effectively inhibiting cell proliferation and promoting cell death in osimertinib-resistant cells.

Pharmakokinetics of Mistletoe Lectins after Intravenous Application of a Mistletoe Product in Healthy Subjects.

Mistletoe lectins (ML) have cytotoxic and immunomodulating properties, and subcutaneously applied mistletoe products (MP) containing ML have approval for supportive cancer treatment. MP are also given off-label intravenously, but data about pharmacokinetics are widely lacking. Therefore, the aim of our phase I trial was to evaluate the pharmacokinetics and safety of intravenously applied natural ML. Initially, 12 healthy male volunteers were planned to receive a single infusion of 2000 mg Helixor® P. We had to terminate the study prematurely after the inclusion of eight subjects due to elevation of all subjects' liver enzymes. ML was detected in all subjects after infusion. The mean half-life of serum ML was 7.02 ± 2.01 h. Mean alanine transaminase increased from 23 ± 6 to a maximum of 445 ± 260 U/L, and mean aspartate aminotransferase increased from 24 ± 3 to a maximum of 318 ± 33 U/L 72 h after infusion. Severity grading for drug-induced liver injury was mild. Participants did not suffer from any liver-specific symptoms and recovered completely. As a conclusion, the dose of 2000 mg Helixor® P caused transient liver injury in healthy subjects and should, therefore, not be used for initial patient treatment. Liver enzymes should be monitored in patients receiving intravenous treatment with Helixor® P.

P1240 Systematic review with meta-analysis: faecal microbiota transplantation as treatment of chronic pouchitis

Abstract Background Pouchitis is inflammation of the ileal pouch-anal anastomosis after proctocolectomy in the surgical treatment of ulcerative colitis. Cohort studies have found evidence that allogenic faecal microbiota transplantation (FMT) can induce short term beneficial effects in patients with chronic pouchitis. Until recently results from randomized controlled trials (RCTs) have been missing. In this systematic review and meta-analysis, we investigated whether FMT treatment was superior to placebo in inducing remission in patients with chronic pouchitis. Methods We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to 15th of November 2023, for RCTs assessing the efficacy of allogenic FMT in the treatment of chronic pouchitis. Autologous FMT or placebo was accepted as control treatment. The primary outcome was the improvement of symptoms as defined by the authors following four weeks. Results The systematic literature search identified a total of three RCTs on the efficacy of FMT in chronic pouchitis comprising 62 patients with 32 patients treated with FMT. Both treatments (FMT and Placebo) and definition of treatment response varied between studies (Table 1). Meta-analysis revealed that FMT was not superior to placebo (risk ratio=0,68;95% CI=(0,47-0,99); p=0.35) in improvement of symptoms four weeks following treatment (Figure 1). Conclusion FMT was not superior to placebo in inducing short-term beneficial effects four weeks after initial treatment in patients with chronic pouchitis. Whether FMT may induce long-term beneficial effects remains to be established.

Comparison of diuretics and fluid expansion in the initial treatment of patients with normotensive acute pulmonary embolism: a systematic review and meta-analysis

BackgroundRight ventricular (RV) dysfunction is the main cause of death in patients with normotensive acute pulmonary embolism (PE). The optimal management for this subset of patients remains uncertain. This systematic...

The use of ribociclib in real clinical practice: results of a single-center observational retrospective study

Introduction. The standard initial treatment for patients with hormone receptor positive, HER2 negative, metastatic breast cancer (HR+/HER2– mBC) involves the use of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy. The combination therapy has proven effectiveness in numerous Phase II and III randomized controlled trials (RCTs). Nonetheless, RCTs may not fully represent real-world clinical situations due to their stringent inclusion criteria, resulting in a specific patient population.Aim. Analyze of ribociclib using for treating patients with HR+/HER2– advanced breast cancer (mBC) at the Republican Clinical Oncology Dispensary.Materials and methods. Patients diagnosed with HR+/HER2– mBC who were treated in clinical routine with ribociclib in combination with different endocrine agents between 2016 and 2020 were identified and enrolled in this retrospective study. Clinicopathological characteristics and clinical outcomes were recorded with particular emphasis on ribociclib therapy course (progression-free survival (PFS), toxicity, dose reduction).Results. Data from n = 101 patients were evaluated. The mean patient age was 61 years. The study included 67 (66.3%) patients with progression after radical treatment and 34 (33.7%) patients with primary disseminated breast cancer. Dose reduction due to adverse events was performed in n = 14 cases (13.9%). Presence of prior therapy lines and lower ECOG status were associated with shorter PFS, whereas estrogen positivity and the choice of fulvestrant over aromatase inhibitor were positively associated with PFS. Metastatic pattern, progesterone positivity and dose reduction due to toxicity did not significantly impact on PFS.Conclusion. Our real-world data analysis on ribociclib treatment in Russian regional hospital supports data from RCTs regarding both treatment efficacy and safety of CDK4/6i for treatment of patients with HR+/HER2– mBC. Currently, by expanding our experience with CDK4/6 inhibitors in different groups of patients with mBC, we will be able to provide patients with optimal treatment options.

Initial treatment with a single capsule containing half-dose quadruple therapy versus standard-dose dual therapy in hypertensive patients (QUADUAL): statistical analysis plan for a randomized, blinded, crossover trial

BackgroundCombined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown.Methods/designA randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140–179/90–109 mmHg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to two crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. Antihypertensive effects and related adverse effects of the two antihypertensive combination treatments will be compared. The primary outcome, i.e., mean 24-h systolic blood pressure in ambulatory blood pressure monitoring, will be assessed via linear mixed-effects model.DiscussionThis statistical analysis plan will be confirmed prior to blind review and data lock before un-blinding and is sought to increase the validity of the QUADUAL trial.Trial registrationClinicalTrials.gov, NCT05377203. Registered May 11, 2022, https://clinicaltrials.gov/study/NCT05377203.

Upfront or Deferred Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Triplet and Quadruplet Induction and Minimal Residual Disease/Risk-Adapted Therapy.

The standards of care for the initial treatment of patients with newly diagnosed multiple myeloma (NDMM) who are eligible for high-dose melphalan and autologous stem cell transplantation (HDM-ASCT) include highly active triplet and quadruplet regimens based on proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. These regimens are resulting in improved outcomes and increasingly high rates of minimal residual disease (MRD)-negative responses without HDM-ASCT as part of the upfront therapy. Furthermore, recent randomized studies have shown that, while transplant-based approaches as a frontline therapy result in significantly longer progression-free survival compared to non-transplant approaches, this has not translated into an overall survival benefit. Given these developments, and in the context of the treatment burden of undergoing HDM-ASCT, in addition to the acute toxicities and long-term sequelae of HDM, which are associated with the genotoxicity of melphalan, there is an increasing rationale for considering deferring upfront HDM-ASCT in select transplant-eligible patients and saving it as a treatment option for later salvage therapy. Here, we review the latest clinical trial data on upfront or deferred HDM-ASCT and on the activity of quadruplet induction regimens, including rates of MRD-negative responses, and summarize emerging treatment approaches in the upfront setting such as the use of MRD-directed therapy and alternatives to HDM-ASCT.

Abstract B032: Outcomes of patients with acute promyelocytic leukemia treated at John Peter Smith Hospital

Abstract Background: Acute Promyelocytic Leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML), accounting for about 10% of all AML cases. Historically, APL was considered to be the subtype of AML with the worst prognosis because most newly diagnosed patients died within a few weeks, and only 35% to 45% of patients achieved long-term survival. The discovery and application of all trans retinoic acid (ATRA) improved complete remission (CR) rate and overall survival (OS) to 70%. Combination of ATRA, a vitamin A derivative, and arsenic trioxide (ATO) as induction therapy for APL resulted in 90-95% CR and &amp;gt;90% 5-year OS. Even though CR and OS has improved, early death (5%-10%) remains the most challenging issue for the disease, especially in resource poor settings. Since APL is rare, oncologists in community may not be fully equipped to treat early complications. John Peter Smith hospital (JPS) is a safety-net hospital serving the needs of underserved population in north Texas. We report outcomes of patients with APL treated at JPS. Methods: Data was obtained from the JPS Oncology Registry. Patients were diagnosed with APL from 1/1/2017 to 12/31/2020 with partial or complete treatment at JPS. We collected non-identifiable patient demographics, diagnosis and initial treatment and complication details. Remission documentation by disappearance of the chromosome abnormality, time from diagnosis to date of death (if applicable) or last activity in medical chart (any phone call with patient, office visit) before 6/12/2023 were obtained. Time to CR and any use of consolidation or maintenance treatment was also collected. Results: 8 APL patients were included- 3 were high-risk patients and 5 were low-risk. Half were male. Age ranged from 22 to 64 years. 5 were under the age of 40 years, 2 were in their 40s and 1 was in 60s at diagnosis. Hispanic:4, Black:3, Asian:1. Induction treatment included ATRA+ATO in 6 patients, while 2 high risk patients received ATRA plus anthracycline-based chemotherapy. Bone marrow morphology post induction was negative in all patients indicating CR (median time to CR was 41.5 days). During induction, treatment complications occurred in all patients including bleeding (75%), clotting (63%), neutropenic fever (50%). Differentiation syndrome (50%) and DIC (50%). All patients underwent ATRA+ATO consolidation treatment for 8-10 months. No patients relapsed. All patients were alive at the time of last medical chart entry (6/12/2023) without active cancer. Conclusions: All patients were in CR post induction treatment. 4 had minimal residual disease post induction. All patients received consolidation with ATRA+ATO, eventually there was no disease detected at molecular level. No patients relapsed. All patients were alive with no active disease at their last follow-up. Excellent outcomes in APL are possible at safety-net setting but will need diligent care to prevent, predict and treat early complications; this may require communication with academic leukemia specialists when transfer to leukemia treatment centers is not possible. Citation Format: Kavya Athipatla, Kari Teigen, Kalyani Narra. Outcomes of patients with acute promyelocytic leukemia treated at John Peter Smith Hospital [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B032.

Effectiveness and Safety of a Cmop±R Regimen for the Initial Treatment of Patients with NHL

Introduction Non-Hodgkin's lymphoma (NHL) is a globally prevalent cancer with a high mortality rate. Although advances in treatment have improved patient survival, patients with high International Prognostic Index (IPI) scores continue to face challenges. The CMOP regimen (cyclophosphamide, mitoxantrone, vincristine, and prednisone) has shown promising efficacy in peripheral T-cell lymphomas with an overall response rate of 84%, but there is a lack of evidence in other NHL subtypes. In this study, we present preliminary results of a CMOP±R (CMOP±rituximab) regimen for the initial treatment of patients with NHL. The study is registered at ClinicalTrials.gov (NCT 2300074073). Aim This prospective, single-arm, open-label, multicenter phase 2 clinical trial was designed to evaluate the efficacy and safety of a CMOP±R regimen including mitoxantrone hydrochloride liposome in patients with newly diagnosed NHL. Method Adult patients with a confirmed diagnosis of NHL (predominantly DLBCL, MZL, FL, and AITL), ECOG performance status ≤1, normal organ and bone marrow function, and at least one measurable or evaluable lesion were enrolled in this study. Patients with significant cardiac dysfunction or uncontrolled cardiovascular disease were excluded. Treatment with the CMOP±R regimen was administered every 4 weeks for up to 6 cycles until disease progression or an intolerable toxic response. The primary endpoint was the objective response rate (ORR), which was assessed by the investigators. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Adverse events were graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) 5.0. The study was approved by the Institutional Ethics Committee (IRB number: 2022021). Results From November 26, 2022 through May 19, 2023, 17 Chinese patients with various NHL subtypes who were eligible for enrollment were treated with the CMOP±R regimen. Nine of these patients were eligible for efficacy evaluation. Results showed that 100% of evaluable patients achieved an objective response and 66.7% achieved a complete response. Hematological toxicity was the most common treatment-related adverse reaction, with leukopenia (100%) and neutropenia (100%) being the most common grade ≥3 toxic reactions. Conclusions The CMOP±R regimen using mitoxantrone hydrochloride liposome showed efficacy in the initial treatment of NHL with acceptable and manageable adverse effects. The role of this regimen in the treatment of NHL warrants further exploration.

Single patient learning for adaptive radiotherapy dose prediction.

Throughout a patient's course of radiation therapy, maintaining accuracy of their initial treatment plan over time is challenging due to anatomical changes-for example, stemming from patient weight loss or tumor shrinkage. Online adaptation of their RT plan to these changes is crucial, but hindered by manual and time-consuming processes. While deep learning (DL) based solutions have shown promise in streamlining adaptive radiation therapy (ART) workflows, they often require large and extensive datasets to train population-based models. This study extends our prior research by introducing a minimalist approach to patient-specific adaptive dose prediction. In contrast to our prior method, which involved fine-tuning a pre-trained population model, this new method trains a model from scratch using only a patient's initial treatment data. This patient-specific dose predictor aims to enhance clinical accessibility, thereby empowering physicians and treatment planners to make more informed, quantitative decisions in ART. We hypothesize that patient-specific DL models will provide more accurate adaptive dose predictions for their respective patients compared to a population-based DL model. We selected 33 patients to train an adaptive population-based (AP) model. Ten additional patients were selected, and their respective initial RT data served as single samples for training patient-specific (PS) models. These 10 patients contained an additional 26 ART plans that were withheld as the test dataset to evaluate AP versus PS model dose prediction performance. We assessed model performance using Mean Absolute Percent Error (MAPE) by comparing predicted doses to the originally delivered ground truth doses. We used the Wilcoxon signed-rank test to determine statistically significant differences in terms of MAPE between the AP and PS model results across the test dataset. Furthermore, we calculated differences between predicted and ground truth mean doses for segmented structures and determined statistical significance in the differences for each of them. The average MAPE across AP and PS model dose predictions was 5.759% and 4.069%, respectively. The Wilcoxon signed-rank test yielded two-tailed p-value= , indicating that the MAPE differences between the AP and PS model dose predictions are statistically significant, and 95% confidence interval=[-2.1610, -1.0130], indicating 95% confidence that the MAPE difference between the AP and PS models for a population lies in this range. Out of 24 total segmented structures, the comparison of mean dose differences for 12 structures indicated statistical significance with two-tailed p-values<0.05. Our study demonstrates the potential of patient-specific deep learning models in application to ART. Notably, our method streamlines the training process by minimizing the size of the required training dataset, as only a single patient's initial treatment data is required. External institutions considering the implementation of such a technology could package such a model so that it only requires the upload of a reference treatment plan for model training and deployment. Our single patient learning strategy demonstrates promise in ART due to its minimal dataset requirement and its utility in personalization of cancer treatment.

Comparison of clinical efficacy and safety of baloxavir marboxil versus oseltamivir as the treatment for influenza virus infections: A systematic review and meta-analysis

IntroductionBaloxavir marboxil (BXM), a newly developed cap-dependent endonuclease inhibitor, is widely used to treat influenza virus infections in inpatients and outpatients. A previous meta-analysis included only outpatients and patients suspected of having an influenza virus infection based on clinical symptoms. However, whether BXM or oseltamivir is safer and more effective for inpatients remains controversial. Therefore, we conducted a systematic review and meta-analysis validating the effectiveness and safety of BXM versus oseltamivir in inpatients with influenza virus. MethodsThe Scopus, EMBASE, PubMed, Ichushi, and CINAHL databases were systematically searched for articles published until January 2023. The outcomes were mortality, hospitalization period, incidence of BXM- or oseltamivir-related adverse events, illness duration, and changes of virus titers and viral RNA load in patients with influenza virus infections. ResultsTwo randomized controlled trials with 1624 outpatients and two retrospective studies with 874 inpatients were enrolled. No deaths occurred in outpatients treated with BXM or oseltamivir. Among inpatients, BXM reduced mortality (p = 0.06) and significantly shortened hospitalization period (p = 0.01) compared to oseltamivir. In outpatients, BXM had a significantly lower incidence of adverse events (p = 0.03), reductions in influenza virus titers (p < 0.001) and viral RNA loads (p < 0.001), and a tendency to be a shorter illness duration compared with that of oseltamivir (p = 0.27). ConclusionsOur meta-analysis showed that BXM was safer and more effective in patients than oseltamivir; thus, supporting the use of BXM for the initial treatment of patients with proven influenza virus infection.

The initial treatment in convulsive status epilepticus in China: A multi-center observational study

ObjectiveTo investigate the initial treatment of patients with convulsive status epilepticus (CSE) in a resource-limited region of China, and to discuss the difference of in-hospital outcomes and economic costs between those with guideline-recommended initial treatment and those without. MethodsIn this retrospective study, we screened adult patients discharged with the diagnosis of CSE in four centers in west China. Individuals with different exposure to the initial drug were divided into benzodiazepine (BDZ) and non-BDZ group for outcome comparison. The primary outcomes were seizure control, and the ratio of patients who developed refractory SE. The secondary outcomes included in-hospital mortality, the modified Rankin Scale (mRS) score at discharge, in-hospital respiratory support rate, length, and cost of the stay. ResultsThree-hundred and thirteen patients (127, 40.6% were women) with CSE were included. The median age was 43 (range 16–92). There were 152 (48.6%) patients initially treated with BDZ. Among the 36 who received midazolam as initial treatment, twenty-six received an insufficient dose. The other 116 (76.3%) patients in the BDZ group chose diazepam as initial treatment. Fifteen of them (12.9%) were treated underdose. In the non-BDZ group (161, 51.4%), antiseizure medications (ASMs) and/or coma-induced drugs were used as initial treatment. Among those initially administrated ASMs, intramuscular phenobarbital (38,37.6%) and valproate (46, 52.3%) were most frequently seen. There was a significant difference in the time latency to initial treatment and etiology between BDZ and non-BDZ group. The non-BDZ group reported a higher cessation rate after initial treatment compared to the BDZ group (P = 0.012). No significant difference in other primary and secondary outcomes. SignificanceNon-adherence and underdosing of the initial treatment of SE were common in China. However, the non-BDZ group showed a better seizure control rate. The effect came from early aggressive medication, that is, the combination of ASMs and anesthesia. Non-BDZ group was not inferior to BDZs in terms of seizure control, the occurrence of in-hospital death, and poor outcome at discharge. More robust evidence is needed in developing settings when choosing the initial treatment.