Subsequent Treatment Strategies Research Articles

Different treatments in chronic thromboembolic pulmonary hypertension: comparison of strategies in the Italian centre real-world experience

Abstract Rationale Pulmonary endarterectomy (PEA) has been the most effective therapy for chronic thromboembolic pulmonary hypertension (CTEPH). However, there is a substantial proportion of patients declared not operable in whom other treatment strategies are available: medical therapy and balloon pulmonary angioplasty (BPA). We aimed to compare different CTEPH treatment strategies effect in real-world setting. Methods All CTEPH referred to our Centre were included. We compare the short-term clinical, functional, exercise and haemodynamic effect of medical therapy (irrespective of subsequent treatment strategies), PEA and BPA (irrespective of previous/subsequent treatment strategies); we also describe the long-term outcome of the different patient groups. Results We included 467 patients (39% were treated only with medical therapy, 43% underwent PEA, 13% underwent BPA and 5% were not treated with any therapy). Patients treated only with medical therapy were the oldest; compared to patients undergoing PEA, they had a lower exercise capacity, a higher risk profile and gained a lower haemodynamic, functional and survival benefit from the treatment. Patients undergoing BPA had a lower haemodynamic improvement but a comparable functional, exercise and risk improvement and a similar survival compared to patients undergoing PEA; their survival is anyway better than patients undergoing only medical treatment. Untreated historical control patients had the worst survival. Conclusions We confirm the superiority of PEA compared to any alternative treatment in CTEPH and we observe that BPA, in patients declared not operable or with persistent/recurrent PH after PEA, leads to a better outcome than medical therapy alone.

ULTRASOUND IMAGING OF COMLICATIONS IN COMBAT CHEST TRAUMA

Abstract. Objective. The aim is to evaluate the effectiveness of ultrasound diagnostics in combat chest trauma at the stage of specialized surgical care. Materials and Methods: 53 cases of complications from combat chest trauma were analyzed during patient evacuation at the stage of specialized surgical care to assess the specificity, accuracy, and sensitivity of the ultrasound method for early detection of complications and to guide further treatment tactics. Results. The ultrasound diagnostic method has advantages in detecting complications of gunshot wounds to the chest, not only during the qualified medical care stages but also where continuous monitoring of these complications is required during further medical evacuation and treatment strategy selection. Conclusions.Therefore, the monitoring of chest trauma complications should be informative at all stages of medical care, accessible, and effective in determining the subsequent treatment strategy.

Prediction and validation of pathologic complete response for locally advanced rectal cancer under neoadjuvant chemoradiotherapy based on a novel predictor using interpretable machine learning

BackgroundPrecise evaluation of pathological complete response (pCR) is essential for determining the prognosis of patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (NCRT) and can offer clues for the selection of subsequent treatment strategies. Most current predictive models for pCR focus primarily on pre-treatment factors, neglecting the dynamic systemic changes that occur during neoadjuvant chemoradiotherapy, and are constrained by low accuracy and lack of integrity. PurposeThis study devised a novel predictor of pCR using dynamic alterations in systemic inflammation-nutritional marker indexes (SINI) during neoadjuvant therapy and developed a machine-learning model to predict pCR. MethodsTwo cohorts of patients with LARC from center one from 2012 to 2017 and from center two from 2020 to 2023 were integrated for analysis. This study compared dynamic changes in blood indexes before and after neoadjuvant therapy and surgical operation. A least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to mitigate collinearity and identify key indexes, constructing the SINI. Univariate and multiple logistic regression analyses were used to identify the independent risk factors associated with pCR. Additionally, 10 machine learning algorithms were employed to develop predictive models to assess risk. The hyperparameters of the machine learning models were optimized using a random search and 10-fold cross-validation. The models were assessed by examining various metrics, including the area under the receiver operating characteristic curves (AUC), the area under the precision-recall curve (AUPRC), decision curve analysis, calibration curves, and the precision and accuracy of the internal and external validation cohorts. Additionally, Shapley's additive explanations (SHAP) were employed to interpret the machine learning models. ResultsThe study cohort comprised 677 patients from the center one and 224 patients from the center two. Six key indexes were identified, and a predictive index, SINI, was constructed. Univariate and multiple logistic regression analyses revealed that SINI, clinical T-stage, clinical N-stage, tumor size, and the distance from the anal verge were independent risk factors for pCR in patients with LARC following NCRT. The mean AUC value of the extreme gradient boosting (XGB) model in the 10-fold cross-validation of the training set was 0.877. The XGB model demonstrated superior performance in the internal and external validation sets. Specifically, in the internal test set, the XGB model achieved an AUC of 0.86, AUPRC of 0.707, accuracy of 0.82, and precision of 0.80. In the external validation set, the XGB model exhibited an AUC of 0.83, AUPRC of 0.702, accuracy of 0.81, and precision of 0.81. Additionally, the predictions generated by the XGB model were analyzed using SHAP. ConclusionThis study involved developing and validating an XGB model using SINI to predict pCR in patients with LARC. Besides, a SINI-based machine learning model shows promise in accurately predicting pCR following NCRT in patients with resectable LARC, offering valuable insights for personalized treatment approaches.

A real world analysis of secondary BRAF variations after targeted therapy resistance in driver gene positive NSCLC

Secondary BRAF variations have been identified as a mechanism of resistance to tyrosine kinase inhibitors (TKIs) in patients with driver gene-positive NSCLC. Nevertheless, there is still a lack of consensus regarding the characteristics and subsequent treatment strategies for these patients. We retrospectively reviewed the medical records of patients with driver gene-positive NSCLC who received TKIs therapy at Zhejiang Cancer Hospital between May 2016 and December 2023. The clinical and genetic characteristics of these patients were assessed, along with the impact of various treatment strategies on survival. This study enrolled 27 patients with advanced NSCLC, in whom BRAF variations occurred at a median time of 28 months after the initiation of targeted therapy. The multivariate accelerated failure time (AFT) model revealed that, compared to chemotherapy-based regimens group, the combined targeted therapy group (p < 0.001) and the combined local treatment group for oligo-progression (p < 0.001) significantly extended patient survival. In contrast, continuing the original signaling pathway's targeted monotherapy was associated with shorter survival (p = 0.034). The median global OS for each treatment group was as follows: chemotherapy-based regimens group, 45 months; combined targeted therapy group, 59 months; combined local treatment group for patients with oligo-progression, 46 months; and targeted monotherapy group, 36 months. Study results indicate that the combination targeted therapy group (including TKIs, BRAF inhibitors, and/or MEK inhibitors) and the localized treatment group are more effective than traditional chemotherapy-based regimens in improving survival. Additionally, continuing targeted monotherapy along the original signaling pathway proves less effective than chemotherapy-based regimens.

Applications of Nanopore sequencing in precision cancer medicine.

Oxford Nanopore Technologies sequencing, also referred to as Nanopore sequencing, stands at the forefront of a revolution in clinical genetics, offering the potential for rapid, long read, and real-time DNA and RNA sequencing. This technology is currently making sequencing more accessible and affordable. In this comprehensive review, we explore its potential regarding precision cancer diagnostics and treatment. We encompass a critical analysis of clinical cases where Nanopore sequencing was successfully applied to identify point mutations, splice variants, gene fusions, epigenetic modifications, non-coding RNAs, and other pivotal biomarkers that defined subsequent treatment strategies. Additionally, we address the challenges of clinical applications of Nanopore sequencing and discuss the current efforts to overcome them.

Elemental Diet as a Therapeutic Modality: A Comprehensive Review

Elemental diets have been employed for the management of various diseases for over 50 years, with several mechanisms mediating their beneficial effects. Yet, they are underutilized due to poor palatability, access, cost, and lack of awareness regarding their clinical efficacy. Therefore, in this review, we aimed to systematically search and review the literature to summarize the formulation variability, mechanisms of action, clinical applications, and tolerability of the elemental diets in gastrointestinal diseases. While large prospective trials are lacking, elemental diets appear to exhibit objective and subjective clinical benefit in several diseases, including eosinophilic esophagitis, eosinophilic gastroenteritis, inflammatory bowel diseases, small intestinal bacterial overgrowth, intestinal methanogen overgrowth, chemoradiotherapy-associated mucositis, and celiac disease. Although some data support the long-term use of elemental diets as an add-on supplement for chronic pancreatitis and Crohn’s disease, most of the literature on exclusive elemental diets focuses on inducing remission. Therefore, subsequent treatment strategies for maintaining remission need to be adopted in chronic/relapsing diseases. Several mechanistic pathways were identified to mediate the effects of elemental diets, including food additive and allergen-free content, high passive absorption rate, and anti-inflammatory properties. High rates of intolerance up to 40% are seen in the trials where exclusive elemental diets were administered orally due to poor organoleptic acceptability; however, when tolerated, adverse events were rare. Other limitations of elemental diets are cost, access, and lifestyle/social restrictions. Moreover, judicious use is advised in presence of a concomitant restrictive food intake disorders. Elemental diets offer a potentially highly efficacious dietary intervention with minor side effects. Palatability, cost, access, and social restrictions are common barriers of use. Prospective clinical trials are needed to elucidate the role of elemental formulas in the management of individual diseases.

What are the benefits of therapeutic drug monitoring in the optimization of adalimumab therapy? a systematic review and meta-analysis up to 2022.

Persistent uncertainties exist surrounding the therapeutic drug monitoring (TDM) of adalimumab in clinical settings. To address these issues, we conducted a systematic review to assess the current evidence regarding the benefits of TDM for adalimumab. PubMed, EMBASE, and Cochrane Databases were searched from inception to October 2022. The trials regarding to the list three key questions were considered: 1) Could routine proactive TDM assist in improving outcomes in patients receiving adalimumab? 2) Could reactive TDM assist in guiding subsequent treatment strategies for patients with treatment failure to adalimumab? 3) Could TDM assist in informing dose reduction or discontinuation in patients with low disease activity or in remission treated with adalimumab? Two reviewers independently selected the studies and extracted the data. Meta-analysis was performed to calculate the relative risk (RR) and 95% confidence interval (CI). A total of 9 studies was included in this review. For proactive TDM, meta-analysis indicated that proactive TDM (n = 163/257, 63.42%) showed no significant superiority over reactive TDM and/or conventional management (n = 336/606, 55.44%) in achieving and/or maintaining clinical remission by random effects model (RR: 1.24, 95% CI 0.98-1.58, I 2 = 73%). There were three studies that supporting the reactive TDM, low drug levels in the absence of anti-drug antibodies (ADA) strongly indicate the need for dose intensification, and infliximab is a feasible choice for patients with low drug levels and ADA positivity. While swapping to another class should be considered in patients with adequate drug levels. In addition, TDM can help clinicians optimize dosing schedules and prevent overtreatment in patients who have achieved low disease activity and sufficient drug concentrations, with no predictive value for successful adalimumab discontinuation. Current evidence suggests that proactive TDM is numerically but not statistically significant superiority over reactive TDM and/or conventional management. Reactive TDM can aid in understanding treatment failure and developing subsequent therapy. For patients reaching low disease activity and remission, TDM can help successful dose reduction, while it cannot inform the successful drug discontinuation. However, existing trials are limited, and more well-designed trials are necessary to clarify the role of TDM in adalimumab treatment.

Real-World Outcomes of Subsequent Chemotherapy after Progression Following Chemoradiation and Consolidative Durvalumab Therapy in Locally Advanced Non-small Cell Lung Cancer: An Exploratory Analysis from the CRIMSON Study (HOPE-005)

BackgroundThe optimal subsequent treatment strategy for locally advanced non-small cell lung cancer (LA-NSCLC) after chemoradiotherapy (CRT) and consolidative durvalumab therapy remains unknown. We aimed to determine the optimal subsequent treatment strategy for this clinical population. Materials and MethodsWe retrospectively enrolled 523 consecutive patients with LA-NSCLC treated with CRT and analyzed the treatment outcomes of subsequent therapy after progression following CRT and consolidative durvalumab therapy. Patients who received tyrosine kinase inhibitors as subsequent therapy were excluded. ResultsOut of 122 patients who received subsequent chemotherapy, 55% underwent platinum-based, 25% non-platinum-based, and 20% immune checkpoint inhibitor (ICI)-containing therapies. In the platinum-based group, patients with a durvalumab-progression-free survival (Dur-PFS) ≥ 1 year had a significantly longer median subsequent therapy-PFS (SubTx-PFS) than those with Dur-PFS < 1 year (13.2 months vs. 4.7 months; hazard ratio, 0.45; 95% confidence interval, 0.21–0.97; P = .04). Furthermore, among patients receiving non-platinum-based chemotherapy, the median SubTx-PFS was longer in the combined with angiogenesis inhibitor group than in the without group, although the difference was not statistically significant. No significant difference of SubTx-PFS was observed between the reason for durvalumab discontinuation and the outcomes of ICI-containing therapy. ConclusionIn clinical practice, platinum-based chemotherapy rechallenge is frequently employed following progression subsequent to CRT and consolidative durvalumab therapy for LA-NSCLC. Optimal treatment strategies may consider Dur-PFS and angiogenesis inhibitor feasibility. Further research is warranted to identify clinical biomarkers that can help identify patients who would benefit from ICI rechallenge.

Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.

Gastric cancer is one of the most prevalent cancers worldwide, and human epidermal growth factor receptor 2 (HER2)-positive cases account for approximately 20% of the total cases. Currently, trastuzumab + chemotherapy is the recommended first-line treatment for patients with HER2-positive advanced gastric cancer, and the combination has exhibited definite efficacy in HER2-targeted therapy. However, the emergence of drug resistance during treatment considerably reduces its effectiveness; thus, it is imperative to investigate the potential mechanisms underlying resistance. In the present review article, we comprehensively introduce multiple mechanisms underlying resistance to trastuzumab in HER2-positive gastric cancer cases, aiming to provide insights for rectifying issues associated with resistance to trastuzumab and devising subsequent treatment strategies.

Tailoring advanced breast cancer treatment after cyclin-dependent kinase 4/6 inhibitors progression - real-world data analysis.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the gold standard of the hormone receptor positive human epidermal growth factor receptor 2 (HER-2) negative advanced breast cancer. However, optimal treatment after disease progression is a matter of debate. We aimed to assess predictive and prognostic factors associated with the treatment outcome following CDK4/6i progression. We retrospectively analyzed patients who progressed on CDK4/6i treatment between 2018 and 2024. Treatment based on molecular findings (PIK3CA mutation), genetic findings (BRCA1/2 germline mutation), or adapted to the change in the tumor phenotype in rebiopsy (anti-HER2 therapy in the transformation to HER-2-positive disease) was grouped into tailored treatment and compared to the endocrine-based therapy and chemotherapy alone. Five hundred twelve patients were treated with CDK4/6i. Two hundred patients with disease progression were enrolled in the study. Duration of response to CDK4/6i was not predictive of the response to subsequent treatment, whereas the progression in the central nervous system was the worst prognostic factor. Thirty patients were ineligible for subsequent treatment. Survival after CDK4/6i progression was significantly longer in patients eligible for tailored treatment. The median PFS in patients with tailored treatment (n=19) was 13.5 months vs. 4.9 months in patients with non-tailored therapy (n=151; p=0.045). 12-month PFS was 54.1% with tailored treatment [95% CI 24.1-76.7%] compared to 18.5% with non-tailored therapy [95% CI 11.6-26.6%]. The median OS for patients treated with a tailored approach was not reached compared to 11.5 months with non-tailored treatment (p=0.016). The 24-month OS for patients treated with a tailored approach was 80.2% [95% CI 40.3-94.8%] compared to 21.1% [95% CI 12.2-31.7%] for patients with non-tailored treatment. Tailoring of subsequent treatment strategy seems to be essential for achieving long-term benefit. Further studies are required, as the prognosis after CDK4/6i progression remains dismal, especially in cases affecting the central nervous system.

The treatment outcomes of patients who failed to be randomly assigned after atezo/bev induction therapy in the Chinese TALENTop study.

e16183 Background: Hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) are considered to be at an advanced stage of disease with limited treatment options. The combination therapy of atezolizumab (atezo) plus bevacizumab (bev) has become a global standard of care for those patients and made conversion resection possible. The Chinese TALENTop study (NCT04649489) is aiming to clarify whether hepatic resection may provide additional benefit in HCC patients with MVI responding to atezo/bev. For patients without opportunity to receive hepatic resection, subsequent treatment outcomes will be reported. Methods: Potentially resectable HCC patients with MVI and without extrahepatic metastasis are eligible for this study. Eligible patients receive 3 cycles of atezo/bev and 1 cycle of atezo as primary systemic therapy (induction phase). Patients assessed as partial response (PR) or stable disease (SD) per RECIST v1.1 and considered suitable for R0 hepatic resection are randomized in a 1:1 ratio to either Arm A, hepatic resection followed by atezo/bev for 1 year, or Arm B, continuing atezo/bev therapy. The primary endpoint is the time to treatment failure. Patients failed to be randomized will enter the survival follow-up phase. After 296 patients entered induction phase, the patient profile, subsequent treatments per local standard of care and survival of patients who failed to be randomized were analyzed. Results: From Apr 2021 to Jun 2023, 296 patients were enrolled and entered induction phase and 175 patients failed to be randomized and were followed up until Sept 2023. The main reasons for failure to be randomized were disease progression (64.6%), investigator assessment of unsuitability for R0 hepatic resection (14.3%), and others. The 175 patients were characterized with a median age of 52 (26-76), and 166 (95%) had HBV infection. Among them, 165 (94%) had combined PVTT, 24 (14%) had combined HVTT and 5 (3%) had combined IVCTT. At a median follow-up time of 10.9 months (9.7-13.1), the median overall survival (mOS) is 13.8 months (8.9-15.8), 6- and 12-month survival rate were 71% and 53%, respectively. As the result of best response during induction phase, 3 patients (1.7%) achieved PR, 92 patients (52.6%) achieved SD and 65 patients (37.1%) were PD. 123 patients (70%) received subsequent therapy. The mOS of patients received different subsequent therapies was showed below. Conclusions: This study provides data on HCC patients with MVI after receiving atezo/bev. The result shows favorable survival even in patients failed to randomization to receive conversion resection, and subsequent treatment strategy may differ survival outcomes. Clinical trial information: NCT04649489 . [Table: see text]

Severe Hyperhidrosis Secondary to Bupropion Use and Treatment. A case report.

IntroductionHyperhidrosis, the excessive and uncontrollable sweating, is a well-documented side effect of various medications. Among these, bupropion, a commonly prescribed antidepressant and smoking cessation aid, has been associated with the development of severe hyperhidrosis in a subset of patients. This clinical report aims to shed light on a compelling case of severe hyperhidrosis induced by bupropion use and the subsequent treatment strategies employedThe patient under discussion is a 42-year-old female with a history of recurrent major depressive disorder and a previous favorable response to selective serotonin reuptake inhibitors (SSRIs). Due to side effect concerns and a desire to quit smoking, she was transitioned to bupropion, a norepinephrine-dopamine reuptake inhibitor (NDRI), at a standard therapeutic dose of 150 mg daily.Approximately four weeks after initiating bupropion therapy, the patient began experiencing debilitating symptoms of excessive sweating, particularly affecting her palms, soles, and axillae. The profuse sweating episodes occurred throughout the day and night, significantly impairing her quality of life, social interactions, and occupational functioning. No previous history of hyperhidrosis was reported, and physical examinations revealed no underlying medical conditions or dermatological issues.ObjectivesTo aknowledge the importance of recognizing and addressing medication-induced side effects within the realm of psychiatry and an early implementation of patient-centered treatment.MethodsClinical case report and a brief literature review.ResultsThe treatment of hyperhidrosis secondary to bupropion use presents a challenging clinical scenario that requires a delicate balance between managing the distressing side effect and ensuring the continued efficacy of psychiatric therapy. Given the rarity of severe hyperhidrosis as a side effect of bupropion, there is a limited body of evidence guiding treatment strategies. Gradual withdrawal in the dose of bupropion was initiated, with careful monitoring of depressive symptoms to prevent relapse, switching to Duloxetine 90mg daily, with adecuate efectiveness.In this particular case, the combination of medication adjustment and psychological support led to a significant reduction in hyperhidrosis symptoms. The patient reported improved social interactions, enhanced self-esteem, and restored occupational functioning. Importantly, her depressive symptoms remained well-managed, underscoring the success of the treatment strategy.ConclusionsThis clinical report highlights the importance of a patient-centered approach when addressing rare medication-induced side effects within the field of psychiatry. Bupropion withdrawal and regular follow-up showed effective in the treatment of the simptoms. Future research may provide additional insights and treatment options for cases like this, further enhancing patient care and outcomes.Disclosure of InterestNone Declared

Development of a lateral flow immunochromatography assay for the detection of fluoroacetamide in blood samples

Fluoroacetamide (FAM) has been employed as a rodenticide for an extended duration, leading to a multitude of incidents involving human ingestion poisoning. Currently, FAMs have been prohibited by nations globally; however, there are still instances of their illegal usage. Conventional instrument methods are characterized by their time-consuming nature and complex operational procedures, rendering them inadequate for meeting urgent diagnostic needs in patients with acute FAM poisoning. Therefore, there is an immediate need to develop a prompt, user-friendly, and precise immunoassay method for the diagnosis of acute poisoning induced by FAM. A lateral flow immunochromatography assay (LFIA) was developed in this study for the visual detection of FAMs in blood samples, representing the first report of such an approach. The method exhibited a cut-off value of 0.5 mg/mL under the optimized conditions, enabling the entire FAM detection process in blood samples to be completed within a mere 8 min without any pretreatment requirements. Notably, the results were easily discernible by visual inspection alone. These results indicate that the developed LFIA holds great promise as a convenient and rapid diagnostic tool for FAM poisoning diagnosis, thereby offering valuable support for subsequent treatment strategies.

Incidental Prostate Cancer in Patients Treated for Benign Prostatic Hyperplasia: Analysis from a Contemporary National Dataset.

(1) Background: Prostate Cancer (PCa) may be incidentally diagnosed during the microscopic evaluation of resected tissue from BPH surgeries, characterizing the clinical condition known as incidental PCa (iPCa). This study aims to assess the prevalence of iPCa following BPH surgery to evaluate the associated surgical procedures and to scrutinize preoperative and postoperative management. (2) Methods: A retrospective analysis was conducted using the PearlDiver™ Mariner database, containing patient records compiled between 2011 and 2021. International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes were employed to identify the population and outcomes. Our primary objective was to assess the prevalence of iPCa, categorized by the type of procedures, and to evaluate the subsequent treatment strategies. The secondary aim was to assess the impact of prostate biopsy (PB) and prostate MRI on iPCa detection. (3) Results: The overall cohort, accounting for 231,626 patients who underwent BPH surgery, exhibited a 2.2% prevalence rate of iPCa. The highest rate was observed for TURP (2.32%), while the lowest was recorded for RASP (1.18%). Preoperative MRI and PB demonstrated opposing trends over the years. Of the 5090 patients identified with iPCa, nearly 68% did not receive active treatment. The most common treatments were RT and ADT; 34.6% underwent RT, 31.75% received ADT, and 21.75% were treated with RT+ADT. RP was administered to approximately 9% of patients undergoing endoscopic procedures. Multivariate logistic regression analysis revealed age and openSP as additional risk factors for iPCa. Conversely, PB and MRI before surgery were linked to a decreased risk. (4) Conclusions: The contemporary prevalence of iPCa after BPH surgery is <3%. The increase in the use of prostate MRI mirrors a decline in the PB biopsy prior to BPH surgery but without resulting in an increased detection rate of iPCa. In contemporary routine clinical practice, iPCa is mostly managed in a different way when compared to biopsy-detected PCa.

Chemotherapy versus personalized therapy for EGFR mutant lung adenocarcinoma resistance to EGFR-tyrosine kinase inhibitors: a retrospective dual-center study.

Advanced lung adenocarcinoma patients often develop resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), leaving uncertainties regarding subsequent treatment strategies. Although personalized therapy targeting individual acquired resistances (ARs) shows promise, its efficacy has not been systematically compared with platinum-containing doublet chemotherapy, a widely accepted treatment after EGFR-TKIs failure. A retrospective dual-center study was conducted involving patients with advanced lung adenocarcinoma and EGFR mutations who developed resistance to EGFR-TKIs between January 2017 and December 2022. Eligible patients were adults aged 18years or older with an Eastern Cooperative Oncology Group score of 0-1, normal organ function, and no prior chemotherapy. Patients were divided into the chemotherapy group (CG) or personalized therapy group (PG) based on the treatment received after disease progression. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). Of the 144 patients enrolled, there were 53 patients in the PG and 91 patients in the CG. The PG acquired resistance to EGFR-TKIs through the MET amplification (27, 50%) and small cell lung cancer transformation (16, 30%) and 18% of them reported multiple resistance mechanisms. The ORR of the PG was similar to that of the CG (34% vs. 33%, P = 1.0) and the PFS of the PG patients was not statistically different from that of their CG counterparts [4.2months (95% CI: 3.6-4.8months) vs. 5.3months (95% CI: 4.6-6.0months), P = 0.77]. These findings suggest that the therapeutic efficacy of chemotherapy approximates to that of personalized therapy, which signifies that chemotherapy is still a reliable choice for patients who develop resistance to EGFR-TKIs and that further research is awaited to explore the benefit of personalized treatment.

Chinese expert consensus on evaluation and treatment of advanced non-small cell lung cancer with negative driver genes after first-line immunotherapy resistance (2024 edition)

Immunotherapy has become the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with negative driver genes, which has significantly improved the prognosis of patients. However, there is still a lack of consistent guidelines or consensus on evaluation and treatment regimens after first-line immunotherapy resistance. The Committee of Non-Small Cell Lung Cancer of Chinese Society of Clinical Oncology organized multidisciplinary experts from medical oncology, respiratory medicine, thoracic surgery, radiotherapy, and imaging to conduct an in-depth discussion on the definition and classification of primary resistance and secondary resistance, evaluation criteria of immunotherapy, subsequent treatment strategies of oligo-progression or extensive progression after first-line immunotherapy, re-challenges of immunotherapy and clinical research of new drugs in advanced NSCLC patients with negative driver genes according to the existing evidence. After the consensus meeting, an expert consensus on evaluation and treatment strategy of advanced NSCLC with negative driver genes after first-line immunotherapy resistance was formed, aiming to provide standardized guidance for clinical practice of Chinese clinicians.

Reduction rate of anti‐acetylcholine receptor antibody titer levels is an early prognostic indicator for myasthenia gravis

AbstractBackgroundA realistic treatment goal for myasthenia gravis (MG) is achieving minimal manifestations or better status with prednisolone at ≤5 mg/day (MM‐or‐better‐5 mg), considering a patient's health‐related quality of life. Prognosis prediction during the early phases of immunotherapies might be critical for determining subsequent treatment strategies; however, the appropriate biomarkers remain unknown.AimThis study aimed to clarify whether the reduction rate of anti‐acetylcholine receptor antibody (RR‐AChR Ab) titer levels is a useful biomarker for predicting MM‐or‐better‐5 mg achievement.MethodsWe retrospectively investigated patients with MG and AChR Abs who received immunotherapy for the first time. The RR‐AChR Ab titer levels were calculated in the early (within 30 days), middle (31–60 days), and late (61–100 days) periods after starting immunotherapies. A receiver operating characteristic (ROC) curve was generated to determine an appropriate cutoff value for RR‐AChR Abs to achieve an MM‐or‐better‐5 mg.ResultsOf 53 patients, 24 (45%) achieved MM‐or‐better‐5 mg after 1 year. For the early period, the RR‐AChR Ab cutoff value to predict MM‐or‐better‐5 mg was 1.68%/day with an area under the curve (AUC) of 0.75 (sensitivity, 85%; specificity, 70%). However, the middle and late posttreatment AUC values did not predict MM‐or‐better‐5 mg achievement.ConclusionThe RR‐AChR Ab might be an appropriate prognostic biomarker during the early period of MM‐or‐better‐5 mg achievement. In the era of early fast‐acting treatment strategies, the RR‐AChR Ab trend after starting immunotherapies may guide the subsequent treatment choices.

Advances in the mechanism of CDK4/6 inhibitor resistance in HR+/HER2− breast cancer

Among women, breast cancer is the most prevalent form of a malignant tumour. Among the subtypes of breast cancer, hormone receptor (HR) positive and human epidermal growth factor receptor (HER2) negative kinds make up the biggest proportion. The advent of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, which are dependent on cell cycle proteins, has greatly enhanced the prognosis of patients with advanced HR+/HER2− breast cancer. This is a specific treatment that stops the growth of cancer cells by preventing them from dividing. Nevertheless, the drug resistance of the disease unavoidably impacts the effectiveness of treatment and the prognosis of patients. This report provides a thorough analysis of the current research advancements about the resistance mechanism of CDK4/6 inhibitors in HR+/HER2− breast cancer. It presents an in-depth discussion from numerous viewpoints, such as aberrant cell cycle regulation and changes in signalling pathways. In response to the drug resistance problem, subsequent treatment strategies are also being explored, including switching to other CDK4/6 inhibitor drugs, a combination of novel endocrine therapeutic agents, an optimal combination of targeted therapies and switching to chemotherapy. An in-depth study of the resistance mechanism can assist in identifying creative tactics that can overcome or postpone drug resistance, alleviate the problem of restricted treatment strategies following drug resistance and enhance the prognosis of patients.

Sex differences of neural connectivity in internet gaming disorder and its association with sleep quality: an exploratory fMRI study.

Sex-specific differences in internet gaming disorder (IGD) neurophysiology remain underexplored. Here we investigated sex-related variability in regional homogeneity (ReHo) and functional connectivity (FC) in IGD and their correlations with sleep quality. Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 52 subjects with IGD and 50 healthy controls (HCs). Two-way ANOVA was used to examine sex and diagnosis interactions in ReHo and FC, followed by post-hoc analyses to explore FC biomarkers for different sexes. In ReHo analysis, the four groups showed significant sex and diagnosis interactions in the right middle frontal gyrus (rMFG). FC analysis with rMFG as the seed region revealed a significant sex and diagnosis interaction effect in FC of the rMFG with the bilateral postcentral gyrus (PoCG). In male IGD group, FC between the rMFG and the bilateral PoCG correlates strongly with daytime dysfunction score and the Pittsburgh sleep quality inventory (PSQI) total score. These findings emphasize the importance of considering sexual dimorphism in the neurobiology of IGD, which might influence subsequent treatment strategies.

Advancing glioma diagnosis: Integrating custom U-Net and VGG-16 for improved grading in MR imaging.

In the realm of medical imaging, the precise segmentation and classification of gliomas represent fundamental challenges with profound clinical implications. Leveraging the BraTS 2018 dataset as a standard benchmark, this study delves into the potential of advanced deep learning models for addressing these challenges. We propose a novel approach that integrates a customized U-Net for segmentation and VGG-16 for classification. The U-Net, with its tailored encoder-decoder pathways, accurately identifies glioma regions, thus improving tumor localization. The fine-tuned VGG-16, featuring a customized output layer, precisely differentiates between low-grade and high-grade gliomas. To ensure consistency in data pre-processing, a standardized methodology involving gamma correction, data augmentation, and normalization is introduced. This novel integration surpasses existing methods, offering significantly improved glioma diagnosis, validated by high segmentation dice scores (WT: 0.96, TC: 0.92, ET: 0.89), and a remarkable overall classification accuracy of 97.89%. The experimental findings underscore the potential of integrating deep learning-based methodologies for tumor segmentation and classification in enhancing glioma diagnosis and formulating subsequent treatment strategies.