First-line Treatment Of Choice Research Articles

Real-world analysis of the impact of timing of biomarker testing on first-line treatment choice in patients with metastatic colorectal cancer in British Columbia.

253 Background: The treatment landscape for metastatic colorectal cancer (mCRC) has evolved significantly, shifting from chemotherapy alone to more personalized approaches that include immune checkpoint inhibitors and targeted therapies. Treatment decisions in mCRC are driven by molecular characteristics, and current guidelines recommend a minimum standard of biomarker testing, such as mismatch repair (MMR) status, and RAS and BRAF mutations, at the time of metastatic disease diagnosis to guide treatment selection. This study aimed to assess the real-world implementation of biomarker testing in a contemporary cohort of mCRC patients in British Columbia (BC) and its impact on treatment decisions by medical oncologists. Methods: We conducted a retrospective chart review of patients who received first-line systemic therapy for mCRC in BC between January 2022 and December 2023. Patient demographics, tumour characteristics, and treatment details were obtained from the BC Cancer provincial pharmacy database. Medical oncology documentation and pathology reports were reviewed to determine the availability of biomarkers, including MMR status, and RAS and BRAF mutations (OncoPanel), at the time of initial medical oncology consultation, and to assess how these results influenced treatment plan. Results: To date, 71 eligible patients have been identified, with data collection ongoing. Of these, 82% had proficient MMR status, 17% had deficient MMR status, and 1% had incomplete data. RAS mutations were present in 55% of cases, while BRAF mutations were found in 21% (Table). At the time of the initial medical oncology consultation, MMR status was unavailable in 14 patients (20%), two of whom were later found to have deficient MMR status. OncoPanel results were unavailable for 63 patients (88%) at the time of the initial consultation, and in 16 of these cases (25%), the systemic therapy plan was modified once the results were received. Conclusions: Even in contemporary practice with publicly funded biomarker testing, the results for RAS and BRAF mutations were not available at the time of initial medical oncology consultation for most patients. Biomarker testing is an essential tool for guiding therapeutic decisions in mCRC. This subsequently led to treatment plan changes in one-quarter of cases after results were received. These findings highlight the importance of timely biomarker testing to ensure optimal and efficient treatment decision-making for all mCRC patients. Metastatic colorectal cancer biomarker testing. Proficient/WT Deficient/Mutated Incomplete MMR 58 12 1 RAS 29 39 3 BRAF 53 15 3

First-Line (1L) Treatment Decision Patterns and Survival of Hormone Receptor (HR)-Positive/HER2-Negative Advanced Breast Cancer (ABC) Patients in a Latin American (LATAM) Public Institution.

Advanced breast cancer is an incurable disease, with a median overall survival of 3 years, including in countries without access problems. Although chemotherapy is reserved in some cases, it is still used in many countries as a first-line therapy. The aim of our study is to evaluate the first-line treatment choices and the factors that influence therapeutic decisions. A retrospective analysis was conducted of hormone receptor (+)/HER2 (-) advanced breast cancer patients classified into three groups according to the first-line and second-line treatment received: endocrine therapy-chemotherapy, endocrine therapy-endocrine therapy and chemotherapy-endocrine therapy. Additionally, we explored the overall survival of sequencing therapy groups. First-line chemotherapy was chosen in 34% of patients. Also, around 60% of our patients met the "aggressive disease" criteria from the RIGHT Choice trial, justifying the use of chemotherapy in a population with poor prognosis. Furthermore, de novo and progressive disease were prognostic factors that influenced the use of chemotherapy as a first-line treatment. Regarding overall survival, the sequencing treatment groups in this trial saw an increase in survival compared with patients of the MONALEESA trials (endocrine therapy alone arms). No significant differences in progression-free survival or overall survival were found in the treatment sequencing groups. There was a higher use of chemotherapy as a first-line therapy, with de novo and "aggressive disease" criteria being the main factors to influence the decision.

Treatment of elderly patients with acute myeloid leukemia: personal experience

Background. Acute myeloid leukemia (AML) is an aggressive malignancy of the hematopoietic system. Most patients with newly diagnosed AML are 65 years of age or older. Treatment of this cohort of patients is difficult due to the comorbidity of elderly patients and the genetic characteristics of hemoblastosis, which prevents the achievement of significant progress in treatment, in contrast to younger patients with AML. As domestic and foreign studies have shown, age is an independent universal prognosis factor for AML. In the era of targeted drugs, successful treatment of AML is becoming possible.Aim. To assess overall survival in elderly patients with AML, tolerability and effectiveness of various treatment regimens in patients with AML ≥65 years.Materials and methods. This paper presents our own experience in the treatment of elderly patients with AML in the hematology departments of the City Clinical Hospital No. 52. The study included patients over 65 years of age with AML from April 2022 to September 2023. A total of 40 patients were analyzed. To determine the risk factors for death, univariate and multivariate regression analyzes were performed using the logistic regression method. Variables that showed statistical significance on univariate analysis were included in the multivariate analysis. An analysis of 12‑month overall survival was also carried out using the Kaplan–Meier method with the construction of survival curves and calculation of median survival. A comparative analysis of two groups of patients treated with the AZA + EN and LdaraC regimens was carried out.Results. 63 % (n = 25) are men, 37 % (n = 15) are women. The median age was 75 years; all patients had complicated premorbid background. 53 % (n = 21) of patients were in the age range from 65 to 69 years, 47 % (n = 19) were over 70. Antitumor treatment was received by 88 % (n = 35) of patients. The remaining 5 underwent: best accompanying (n = 2), cytoreductive (early death at this stage) (n = 3) therapy. Complete remission after two cycles of therapy was achieved in 46 % (n = 16) of patients, and in 29 % (n = 10) it was maintained at the time of analysis. Early relapse occurred in 14 % (n = 5). Early mortality was recorded in 9 % (n = 3). Death was reported in 40 % (n = 16) of patients. 20 % (n = 7) of patients were refractory to first-line therapy, of which 36 % (n = 5) were treated with low doses of cytarabine (LdaraC), the rest to a combination of azacitidine (AZA) with venetoclax (EN). The number of relapses among patients on AZA + EN and LdaraC therapy was comparable.Conclusion. AZA + EN is the first-line treatment of choice in older patients with AML. The possibility of conducting this course in an outpatient setting makes it most convenient for both hematologists and patients. An important aspect in the treatment of AML in elderly patients is improving and maintaining quality of life.

Efficacy and safety of RET-TKI in advanced RET-rearranged non-small cell lung cancer in China: areal-worldretrospective chart review.

Selective RET inhibitors have been approved by the Chinese government for the treatment of RET-rearranged non-small cell lung cancer. This study aimed to illustrate the efficacy and safety of selective RET inhibitors in a real-world clinical context in China. Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring RET rearrangement and receiving RET tyrosine kinase inhibitors (RET-TKI) in the real world were enrolled in this retrospective study. Clinical data, including baseline clinicopathological information, efficacy parameters such as objective response rate (ORR) and progression-free survival (PFS), and adverse events (AEs), were collected from the electronic medical record system. The pattern of treatment failure of first-line RET-TKI was also described. Fifty-one patients were enrolled in this study. RET-TKI induced an ORR of 73.1% and a median PFS (mPFS) of 22.7months (95%CI, 11.7-33.7) in the first-line setting. The ORR and mPFS were 58.3% and 17.7months (95%CI, 9.1-26.2), 55.6% and 14.7months (95%CI, 12.6-16.8) in the second-line and later-line settings, respectively. No significant difference was observed among different application lines with respect to the ORR (P = 0.534) or PFS (P = 0.795). In the first-line setting, RET-TKI significantly prolonged PFS compared to other regimens including chemotherapy-based regimens, multikinase inhibitors and other systemic regimens without chemotherapy (P < 0.05). Poor ECOG performance status was related to shorter PFS (P = 0.018). The most common AEs of grade 3 or worse were a decreased neutrophil count (11.4%) and anemia (11.4%). No new AEs or grade 5 AEs were observed. Brain metastasis was one of the most common patterns of treatment failure. In patients with baseline brain metastasis, the intracranial ORR was 50%, and the DCR was 100%. RET-TKI had favorable efficacy and safety in real-world contexts in China and should be considered the preferred choice for first-line treatment in RET-rearranged NSCLC patients.

Cost-effectiveness analysis of lorlatinib and crizotinib in the first-line treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer

ABSTRACT Objectives To assess the economic value of lorlatinib and crizotinib in the first-line treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer at medical insurance negotiation prices from the viewpoint of China’s health system. Methods Based on data from the phase III clinical trial, a three-state partitioned survival model was established. In combination with parameters such as treatment costs, utility values, incidence of adverse reactions, and discount rates, the total incremental cost-effectiveness ratio (ICER) was simulated. Results The results of the fundamental analysis indicated that the patients in the lorlatinib group expended 709,671 yuan more than did the patients in the crizotinib group did but gained 3.09 quality-adjusted life years (QALYs). The ICER value was 229,782.6 yuan/QALY, which was lower than three times the per capita gross domestic product (GDP) of China. Conclusions Compared with crizotinib, lorlatinib may be a cost-effective first-line treatment choice for advanced ALK-positive NSCLC in China.

Diving into hot topics of salivary gland carcinoma management-an EORTC young and early career investigator survey.

Recently, the ASCO and ESMO guidelines on salivary gland carcinomas (SGCs) have been released. However, several crucial points lack strong recommendations due to low or intermediate quality of evidence. To better address these "grey zones" in the guidelines, we conducted a survey among the European Organization for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Group (HNCG) members on behalf of the EORTC young and early career investigators. The survey included 29 questions addressing diagnostic and therapeutic issues related to SGC patients and was shared among 539 members of the EORTC HNCG. Responses were collected from December 2022 to March 2023. The primary aim was to evaluate the decision-making criteria guiding physicians in areas with low evidence in SGC guidelines. With a response rate of 19%, the survey received input from 102 respondents, mainly medical oncologists (45%). Among those with pathological high-risk features, 35% and 30% of respondents opted for chemoradiotherapy (CRT) in the definitive and adjuvant settings, respectively. For patients with R0 resection of highly aggressive SGC at the pT1-2 stage, 37% proposed a close follow-up, while 38% proposed adjuvant lymph-node field RT. In cases of pT3-4 stage, 48% proposed adjuvant lymph-node field RT in all cases, and 44% proposed it based only on risk factors. The most important factors guiding the decision to give adjuvant RT after salvage surgery for locoregional relapse include previous radiotherapy, margin status, and the presence of extranodal extension. When faced with combined positivity to HER2 and AR, responses regarding the choice of first-line palliative treatment were heterogeneous. International guidelines lack strong recommendations in several fields of SGC diagnosis and treatment due to insufficient high-quality data, resulting in heterogeneity in physicians' treatment decision (e.g., adjuvant lymph-node field RT and their low concordance with guidelines, such as the use of concomitant CRT). The survey demonstrated the need for prospective clinical trial data to address these gaps in the future.

First-Line Treatment Choice and Risk of Other Malignancies in US Veterans Diagnosed with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

First-Line Treatment Choice and Risk of Other Malignancies in US Veterans Diagnosed with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Treatment patterns for advanced therapies in Canadians with moderate-to-severe inflammatory bowel disease: a retrospective cohort analysis

Abstract Many patients with inflammatory bowel disease (IBD) show an inadequate response or experience a loss of response to advanced therapies. Guidelines recommend dose optimization and switching among therapies until an optimal treatment response is attained. With several advanced treatments available, we aimed to evaluate the persistence of different therapeutic sequences in IBD. The RECORDED study was a retrospective cohort study of Canadians with moderate-to-severely active ulcerative colitis (UC) or Crohn’s disease (CD) who had been exposed to more than 1 advanced therapy between May 2015 and April 2021 for UC, and May 2016 and April 2021 for CD. The primary endpoint was time to permanent discontinuation of the first advanced treatment. Overall, 330 patients had CD and 344 had UC. The most common first-line treatments for CD and UC were adalimumab and infliximab, respectively. The median (95% CI) time to permanent discontinuation of first-line treatment was 12.3 (10.9, 13.6) months in patients with CD and 9.2 (8.2, 10.8) months for those with UC. The most common reason for treatment change across both diseases was lack of efficacy. First-line advanced treatments were optimized in 191 (58.1%) CD patients and 202 (59.1%) UC patients prior to permanent discontinuation. Second-line therapy was typically from a different class compared with the first-line treatment choice. The RECORDED study provides insights into the real-world sequencing and optimization patterns of advanced treatments in patients with moderate-to-severe IBD in Canada. Lack of efficacy was the most cited reason for switching to a different therapy.

Cost-effectiveness of first-line sintilimab plus chemotherapy versus chemotherapy for advanced esophageal carcinoma in China

ABSTRACT Background To evaluate the cost-effectiveness of first-line sintilimab plus chemotherapy versus chemotherapy for advanced esophageal squamous cell carcinoma (ESCC) from the perspective of the Chinese health service system. Methods A partitioned survival model was constructed to simulate quality-adjusted life years and incremental cost-effectiveness ratios over a patient’s lifetime based on a phase III clinical trial. Results Sintilimab plus chemotherapy increased by 0.316 QALY and 0.285 QALY with the additional cost of $5692 and $5269, which led to the ICER of $18000/QALY and $18519/QALY gained in the overall population and the patients with CPS ≥ 10, respectively. Conclusions Compared with chemotherapy alone, sintilimab may be a cost-effective first-line treatment choice for locally advanced or metastatic ESCC.

Le cancer thyroïdien différencié réfractaire à l’iode : quelle prise en charge en 2024 ?

TREATING RADIO-IODINE REFRACTORY DIFFERENTIATED THYROID CANCER IN 2024: About 5 to 10% of patients with differentiated thyroid cancer (DTC) have advanced tumors at presentation or recurrence, with invasive cervical disease and/or distant metastases that cannot be effectively treated by conventional treatment, i.e. thyroid surgery and radioactive iodine. These DTC cases are defined as refractory to radioiodine (RAIR) and require expert multidisciplinary management. In France, patients are referred to centers of the ENDOCAN-TUTHYREF Network. This review summarizes current management of RAIR DTC patients and therapeutic options available in 2024. We discuss following topics : epidemiological data, modalities of local ablative treatment for selected metastatic lesions, molecular tests to be performed, optimum timing for initiating systemic therapy, choice of first-line treatment among validated tyrosine kinase inhibitors (TKIs), alternative targeted treatments (including selective TKIs adapted to the molecular profile, some of which can redifferentiate and restore radioactive iodine uptake), proactive management of TKI side effects, and finally give an overview of systemic strategies. Management of RAIR DTC is still challenging but substantial progress has been made over the last decade that has significantly improved outcome for these more aggressive thyroid cancer.

Management Strategies for Children and Adolescents with Diabetes Mellitus

The principles of treatment for diabetes in children and adolescents cannot simply be derived from care routinely provided to adults with diabetes. The major consideration is that the epidemiology, pathophysiology, developmental considerations, and response to treatment of pediatric diabetes are often different from those of adult diabetes. Second, recommended treatments for children and adolescents with type 1 diabetes (T1DM), type 2 diabetes (T2DM), and other pediatric conditions such as monogenic diabetes (neonatal diabetes and MODY [maturity-onset diabetes of the young]) also differ. HbA1c goals in T1DM and T2DM must be individualized and reassessed over time. A HbA1c &lt; 7% is appropriate for many children and adolescents with T1DM. In a case with hypoglycemia, hypoglycemic unawareness, lack of access to analog insulins, advanced insulin delivery technology and/or continuous glucose monitoring, a less stringent HbA1c &lt; 7.5% will be required. A reasonable HbA1c goal for T2DM is &lt; 7%. If possible, a strict HbA1c target of &lt; 6.5% can be implemented. Metformin is the first-line treatment of choice in T2DM. In a case with ketosis or HbA1c &gt; 8.5%, insulin will be required with once daily basal insulin (0.25~0.5 IU/kg). If the glycemic goal is not attained, the addition of a second agent is considered in adult patients but might not be applicable or safe in pediatric cases. Therefore, the efficacy and safety of these drugs used in adult patients, including glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors, should be evaluated in pediatric patients worldwide.

Real-World Efficacy of Intravitreal Faricimab for Diabetic Macular Edema: A Systematic Review.

Diabetic macular edema (DME) is a prevalent exudative maculopathy, and anti-vascular endothelial growth factor (anti-VEGF) therapy is the first-line choice for treatment. Faricimab, a novel anti-VEGF and anti-angiopoietin-2 bispecific agent, has recently been approved for the treatment of DME. In this study, we systematically reviewed the real-world evidence of the efficacy of faricimab for the treatment of DME. We searched 11 databases for eligible studies. Study selection and data extraction were made independently by two authors in duplicate. Eligible studies were reviewed qualitatively. We identified 10 eligible studies that summarized data from a total of 6054 eyes with a mean follow-up of between 55 days and 12 months. Five studies reported outcomes in a population of both treatment-naïve and previously treated eyes, and five studies reported outcomes exclusively in relation to eyes that were previously treated. Faricimab improved the best-corrected visual acuity and macular thickness. The extension of the treatment interval was possible in 61-81% of treatment-naïve eyes and 36-78% of previously treated eyes. Faricimab for DME yields clinical outcomes similar to those known from previous anti-VEGF treatments but with extended treatment intervals, thus lowering the burden of therapy for patients. Long-term real-world studies are warranted.

Hypertension evaluation and management in new young patients: are we doing our female patients a disservice?

Purpose Cardiovascular disease (CVD) is one of the leading causes of death in women, largely underpinned by hypertension. Current guidelines recommend first-line therapy with a RAAS-blocking agent especially in young people. There are well documented sex disparities in CVD outcomes and management. We evaluate the management of patients with newly diagnosed hypertension in a tertiary care clinic to assess male–female differences in investigation and treatment. Methods Clinic letters of all new patients under the age of 51 attending the Glasgow Blood Pressure Clinic between January and December 2023 were reviewed. The primary outcomes measured were first-line treatment choices, deviations from guideline-recommended treatment, investigations for secondary hypertension, and documentation of female-specific risk factors and family planning advice. Secondary outcomes included clinical characteristics such as systolic and diastolic blood pressure at referral and at the new patient appointment, age at diagnosis, age at first appointment, and the number of antihypertensive drugs prescribed at referral. Results One hundred and five (59:46, M:F) new patient encounters were reviewed after sixteen exclusions for non-attendance and inappropriate clinic coding. Choice of first line antihypertensive agent did not vary between sexes with no deviation from guideline-recommended medical therapy. Men, however, had more biochemical investigations conducted for secondary causes across all ages. This was greatest in those under 40 years old. There was suboptimal documentation of female-specific risk factors (obstetric and gynaecological history), contraceptive drug history and family planning with 35%, 20%, and 15.6%, respectively. Conclusion In 2023, women under 51 years of age seen in a tertiary care hypertension clinic received similar first-line treatment to their male peers. However, relevant female-specific histories were suboptimally documented for these patients. Whilst therapeutic approaches in men and women appear to be similar in this clinic, there are opportunities to improve CVD prevention in women, even in a specialised clinic setting.

The treatment pattern of advanced HR-positive and HER2-negative breast cancer in central southern China: a hospital-based cross-sectional study

AimsThis investigation aims to elucidate the treatment status of advanced HR+/HER2- breast cancer patients in Hunan Province of Central Southern China from November 2021 to December 2022.MethodsData from 301 patients with advanced HR+/HER2- breast cancer were collected from the breast cancer investigation project in Hunan under the guidance of the Chinese Society of Clinical Oncolfogy (CSCO). The data included the clinical characteristics of patients and the status of first-line and second-line rescue treatment.ResultsFirst-line chemotherapy and endocrine therapy for mBC accounted for 40% (121/301) and 60% (180/301) of treatments, respectively. AI (21%), AI plus CDK4/6 inhibitor (28%), and fulvestrant (24%) or fulvestrant plus CDK4/6 inhibitor (18%) were the most common first-line endocrine therapies. Taxane-based chemotherapy was the most common first-line chemotherapy (59%). Second-line chemotherapy and endocrine therapy for mBC accounted for 43% (72/166) and 57% (94/166) of treatments, respectively. Fulvestrant (23%) or fulvestrant plus CDK4/6 inhibitor (29%) were the most common second-line endocrine therapies. The prevalences of AI and AI plus CDK4/6 inhibitor decreased to 19% and 11%, respectively. T (taxane)-based chemotherapy was still the most common chemotherapy regimen (46%). Third-line chemotherapy was more prevalent than endocrine therapy (57% vs. 41%). T (taxane)-based chemotherapy was still the most common chemotherapy regimen (46%). Fulvestrant plus CDK4/6 inhibitor was the most common endocrine therapy (33%). AI, AI plus CDK4/6 inhibitor, and fulvestrant accounted for 21%, 12% and 18% of third-line endocrine therapies, respectively.ConclusionsCompared to chemotherapy, endocrine therapy was a more favorable choice for first-line and second-line treatment for HR+/HER2- advanced breast cancer patients in Hunan Province.

Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed. A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70–145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient’s age, and patients’ origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders.What is Known:• Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness.What is New:• Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy.• PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.

Temporal trend of first-line drug choice and treatment continuity for hypertension among citizens 75 years or over - a register-based, cohort study

BackgroundLimited knowledge of antihypertensive treatment of the elderly potentially impedes effective strategies for hypertension management in this growing patient group. We aimed to investigate temporal trends for first-line drug choice for antihypertensive treatment and treatment continuity among patients ≥75 years from 2000 to 2021. MethodsUsing nationwide Danish registers, patients ≥75 years initiated for the first time on antihypertensive drugs: Angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), beta blockers (BB), calcium channel blockers (CCB), thiazides, or combinations, were identified. Patients with other indications than hypertension were excluded. Treatment continuity was described using claimed prescriptions the first 180 days following study entry. ResultsFrom 2000 to 2021, 170,769 patients (median age 80 years [interquartile range:77–84], 60.3% female) were included. From 2000 to 2003 to 2015–2021 the proportion of first-line drug choice increased for ACEi (8.7% to 14.9%), ARB (4.1% to 23.9%), and CCB (10.7% to 27.6%), decreased for thiazides (60.6% to 15.9%) and remained stable for BB (12.9% to 14.1%) and combinations (2.9% to 3.6%). For 157,457 patients alive after 180 days, discontinuation was highest among patients initiated on thiazides (28.3%) whereas most patients continued the same single drug regimen if they started on ACEi (55.2%), ARB (65.0%), BB (57.2%) or CCB (59.3%). ConclusionsFrom 2000 to 2021 thiazides have been replaced by ACEi, ARB and CCB. Thiazides had the lowest treatment continuity while ARB appeared preferred slightly over ACEi. Differences in adherence in relation to first-line drug choice may warrant scrutiny regarding recommendations for the elderly.

Abstract PO4-05-08: Primary endocrine therapy resistance in patients with de novo HR+/HER2- metastatic breast Cancer: a National Cancer Information Database Analysis in China

Abstract Background: Endocrine therapy resistance was classifed as primary and secondary, guiding the first-line (1L) treatment choices for hormone receptor positive, HER2-negative (HR+/Her2-) metastatic breast cancer (mBC). However, it is unknown whether it is primary ET resistance or not to the stage IV de novo patients. Therefore, We performed a retrospective study to predict primary resistance in advance in de novo patients and have a more appropriate treatment strategy. Methods: We identified newly diagnosed with stage IV de novo HR+/HER2- mBC patients received single-agent endocrine therapy (ET) or ET plus CDK4/6 inhibitors (CDK4/6i) in 1L setting from January 1, 2020 to Jun 30, 2022, using the National Cancer Information Database (NCID) in China. Primary ET resistance (PER) was defined as switching to second-line treatment within 6 months after receiving the 1L ET±CDK4/6i, whereas secondary ET resistance (SER) patients were those who received 1L ET±CDK4/6i treatment more than six months. The Chi-Square test was used to compare the baseline characteristics of PER and SER patients. Result: A total of 217 patients who met the inclusion criteria were included in the analysis, among which 161 patients received single-agent ET and 56 patients received ET plus CDK4/6i. 18.4% of the patients were classified as PER patients, whereas 81.6% showed SER patients. PER patients were younger (median age of 52 years vs. 58 years in SER patients, p=0.01). In terms of clinicopathological characteristics, patients with PER have a higher percentage of liver metastases (14/40 (35%) vs. 20/177 (11.3%) in SER, p&amp;lt; 0.01), distant lymph node metastases (19/40 (34%) vs. 45/177 (25.4%) in SER, p = 0.01), and bone metastases (30/40(75%) vs. 97/177(54.8%) in SER, p = 0.02). Furthermore, the PER rate was 21.7% (35/161) in patients received single-agent ET, compare with 8.9% (5/56) in ET plus CDK4/6i patients, p=0.04. Regarding the following treatment pattern in the PER patients, a high percentage of patients received chemotherapy, accounting for 50%, 30% still received another endocrine therapy, and the remaining 20% patients received CDK4/6i combined with endocrine therapy. Conclusions: There is still a significant proportion of de novo HR+/HER2- mBC patients with primary endocrine resistance, a relatively low proportion of PER in patients receiving endocrine in combination with CDK4/6i. Table. The proportion of primary endocrine resistance across treatment regimens in de novo HR+/HER2- metastatic breast Cancer Citation Format: Zhanhong Chen, Xiying Shao, Yabing Zheng, Wenming Cao, Junqing Chen, Weizhu Wu, Ting Wang, Xiaojia Wang. Primary endocrine therapy resistance in patients with de novo HR+/HER2- metastatic breast Cancer: a National Cancer Information Database Analysis in China [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 PO4-05-08.

Addressing Challenges in Standardizing Helicobacter pylori Treatment Protocols: Importance and Review.

Helicobacter pylori, one of the top carcinogens, is associated with most cases of gastric cancer-related deaths worldwide.Over the past two decades, the rising rates of antibiotic resistance in the bacterium have reduced the efficacy of conventional antibiotic-based treatments.This underscores the urgency for continued research and novel treatment approaches. Establishing a worldwide accepted physician guideline for antibiotic prescription is crucial to combat antibiotic resistance and improveH. pyloriinfection management. Therefore, it is important to address the challenges thatcomplicatethe establishment of a universally accepted treatment protocol to prescribe an antibiotic regimen to eradicateH. pylori. The answers to the questions of why conventional standard triple therapy remains a first-line treatment choice despite its low efficacy, and how different factors affect therapy choice, are needed to identify these challenges. Hence, this review addresses concerns related toH. pyloritreatment choice, role of antibiotic resistance and patient compliance in treatment outcomes, first-line vs. second-line therapy options, and methods for enhancing existing treatment methods. We also present a chart to aid antibiotic treatment prescription, which may support physician guidelines in this aspect. Eradication ofH. pyloriand patient adherence is paramount in overcoming antibiotic resistance in the bacterium, and our chart summarizes key considerations and suggests novel approaches to achieve this goal.

Principles in the Management of Glioblastoma.

Glioblastoma, the most aggressive and common malignant primary brain tumour, is characterized by infiltrative growth, abundant vascularization, and aggressive clinical evolution. Patients with glioblastoma often face poor prognoses, with a median survival of approximately 15 months. Technological progress and the subsequent improvement in understanding the pathophysiology of these tumours have not translated into significant achievements in therapies or survival outcomes for patients. Progress in molecular profiling has yielded new omics data for a more refined classification of glioblastoma. Several typical genetic and epigenetic alterations in glioblastoma include mutations in genes regulating receptor tyrosine kinase (RTK)/rat sarcoma (RAS)/phosphoinositide 3-kinase (PI3K), p53, and retinoblastoma protein (RB) signalling, as well as mutation of isocitrate dehydrogenase (IDH), methylation of O6-methylguanine-DNA methyltransferase (MGMT), amplification of epidermal growth factor receptor vIII, and codeletion of 1p/19q. Certain microRNAs, such as miR-10b and miR-21, have also been identified as prognostic biomarkers. Effective treatment options for glioblastoma are limited. Surgery, radiotherapy, and alkylating agent chemotherapy remain the primary pillars of treatment. Only promoter methylation of the gene MGMT predicts the benefit from alkylating chemotherapy with temozolomide and it guides the choice of first-line treatment in elderly patients. Several targeted strategies based on tumour-intrinsic dominant signalling pathways and antigenic tumour profiles are under investigation in clinical trials. This review explores the potential genetic and epigenetic biomarkers that could be deployed as analytical tools in the diagnosis and prognostication of glioblastoma. Recent clinical advancements in treating glioblastoma are also discussed, along with the potential of liquid biopsies to advance personalized medicine in the field of glioblastoma, highlighting the challenges and promises for the future.