Evaluation Of Treatment Response Research Articles

Helping Patients to Predict and Confirm Ovulation with the Use of Combined Urinary Hormonal and Smartphone Technology: A Proof-of-Concept Retrospective Descriptive Case Series.

Smartphone-based fertility awareness methods with home-based urinary hormonal testing are gaining popularity for fertility tracking. In our university-affiliated family practice, we integrated a previously developed ovulation tracking application into a protocol for monitoring urinary sex hormones and cervical secretions. Serum progesterone was used to confirm the luteal phase, with levels ≥ 15.9 nmol/L ensuring confirmation. Data from 110 women seen for infertility treatment (n = 95) or family planning advice (n = 15) and using our ovulation prediction protocol showed that most opted for a combination of cervical mucus and luteinizing hormone testing (n = 86). Among those using it for family planning, the median usage among women spanned 56 cycles, and 13 cycles per woman required progesterone testing for confirmation. Thirteen patients are still using the method without unintended pregnancies. No unintended pregnancies occurred. Confidence in tests based on serum progesterone was high (93%). For infertility, the method helped in the identification of anovulation, evaluating treatment response, and in diagnosing subfertility causes. This proof-of-concept retrospective descriptive case series suggests the potential for smartphone-based monitoring in fertility management, urging further studies for application enhancements and prospective validation.

Integrative analysis of multiple cell death model for precise prognosis and drug response prediction in gastric cancer.

Gastric cancer (GC) is a common upper gastrointestinal tumor. However, the evaluation of prognosis and treatment response in patients with gastric cancer remains a challenge. Programmed cell death (PCD) is one of the important terminal paths for the cells of metazoans, and is involved in a variety of biological events that include morphogenesis, maintenance of tissue homeostasis, and elimination of harmful cells. The objective of this project is to investigate the predictive significance of cell death pathways and create prognostic signatures associated to cell death, with the purpose of forecasting prognosis and providing guidance for the treatment of gastric cancer. Gene transcription profiles and corresponding clinical data of gastric cancer patients were collected from The Cancer Genome Atlas (TCGA-STAD, n = 448) and the Gene Expression Comprehensive Database (GSE84437, n = 483). Thirteen types of cell death-related genes, including apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy, cuprotosis, parthanatos, entotic cell death, netotic cell death, lysosome-dependent cell death, alkaliptosis, oxeiptosis, and disulfidptosis, were analysed. Cell death-related genes associated with prognosis were identified in the TCGA-STAD training cohort using Lasso-Cox regression to generate a risk score. Patients were categorized into high and low-risk groups based on the median risk score for survival difference analysis. Cell death-related genes associated with prognosis were identified in the TCGA-STAD training cohort using Lasso-Cox regression to generate a risk score. Additionally, the response to immunotherapy in the high-risk and low-risk groups was calculated using the oncoPredict algorithm. Futhermore, the model genes were validated in the GEO validation set. A total of 324 differential programmed cell death (PCD)-related genes were identified, and 65 were selected through single-factor Cox analysis. Six PCD-related genes were ultimately identified by Lasso regression to construct a prognostic risk score model. The log-rank test revealed that patients in the high-risk group had inferior survival time compared with those in the low-risk group. The area under the ROC curve (AUC) for the training group at years 1, 3, and 5 were 0.684, 0.713, 0.743, respectively, while the AUC for the validation cohort at years 1, 3, and 5 were 0.695, 0.704, and 0.707, respectively. Unsupervised clustering identified potential subtypes included in the model, and a survival difference was also observed between the two subgroups. Multifactor Cox results, combined with clinical information, demonstrated that the prognostic risk score can serve as an independent prognostic factor, irrespective of other clinical features. By comprehensively analyzing multiple cell death patterns, we have established a novel model that accurately forecasts the clinical prognosis and drug sensitivity of gastric cancer. It was found that all 12 representative drugs may not be suitable for patients in high-risk groups.

Therapeutic efficacy and short-term durability of trans-urethral amniotic bladder injections for the treatment of refractory COVID-associated cystitis

Introduction: COVID-19-associated cystitis (CAC) may arise following a COVID-19 infection and is characterized by the development of novel or worsening overactive bladder (OAB). CAC is possibly associated with bladder mucosal damage and the release of pro-inflammatory cytokines, resulting in inflammation and fibrosis of the bladder wall. Amniotic membrane (AM) has been shown to possess anti-inflammatory and anti-fibrotic properties and might potentially be beneficial for CAC. This study investigated the safety and efficacy of bladder injections of AM in CAC patients with resistant OAB symptoms. Methods: Five CAC patients, with an average age of 73 ± 1.0 years and a median disease duration of 2.4 years, received intra-detrusor injections of 100 mg micronized AM under general anesthesia and were followed for 20 weeks. Key urodynamic measures (involuntary detrusor contraction and maximum cystometric capacity) were determined to evaluate treatment response. Quality of life (QOL) was assessed using the OAB assessment tool, and safety was analyzed. Results: All five patients showed improved urodynamic bladder function and significantly improved QOL improvements. The improvement was evident from 4 weeks post-treatment and sustained until 12 weeks. Symptoms re-surged at 20 weeks. No safety concerns arose during the study. Conclusion: The observed improvements in symptom scores and bladder volume parameters highlighted the promise of AM bladder injections as a viable intervention for CAC patients with refractory OAB symptoms. Comprehensive studies are needed to validate its therapeutic potential, and treatment protocol refinement is warranted to address the observed reduction in efficacy over time.

B-342 Teclistamab interference in serum protein electrophoresis and serum immunofixation electrophoresis in patients with recurrent or relapsed multiple myeloma

Abstract Background Serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (IFE) analyses are mainstays in the initial diagnosis, risk stratification, and evaluating treatment response in patients with multiple myeloma (MM) in accordance with the International Myeloma Working Group criteria. Published reports have demonstrated that therapeutic monoclonal antibodies (mAbs) used to treat MM (e.g. anti-CD38 IgG-kappa) are detectable by SPEP and IFE, which may interfere with accurate evaluation of complete response. Recently, Teclistamab (Tecvayli®; Janssen Biotech, Horsham Township, PA), a humanized bispecific IgG-lambda mAb targeting B-cell maturation antigen (BCMA) and CD3 on T cells was approved for treating patients with penta-refractory MM. In contrast with other IgG-kappa therapeutic mAbs, the degree to which Teclistamab may interfere with detection and quantification of monoclonal proteins is unknown. Therefore, we sought to assess the interference of Teclistamab therapy on routine SPEP and IFE analysis. Methods Patients treated with Teclistamab were identified by retrospective review of electronic medical records. Teclistamab (90 mg/mL) was spiked into a remnant patient sample with IgG lambda MM at a final concentration of 10 μg/mL, which corresponds to ½Cmax values in patients infused with Teclistamab. SPEP and IFE were performed using the Helena SPIFE Touch instrument. Computer-assisted densitometry was used to quantify monoclonal proteins in the gamma region of SPEP gels. Results In several patients with refractory MM treated with Teclistamab, IFE analysis revealed IgG lambda or lambda light chain monoclonal proteins, which were inconsistent with previously-identified monoclonal proteins (e.g. IgG kappa). In one patient diagnosed with IgG lambda MM, spiking 10 μg/mL Teclistamab increased M-spike abundance by approximately 0.15 g/dL when quantified by SPEP. Conclusions In patients with relapsed or refractory MM, treatment with Teclistamab may confound accurate clinical assessment of complete response by SPEP and IFE methods. Increased awareness of this preanalytical interference is necessary to guide clinical decision making.

B-337 Mass Spectrometry to evaluate treatment response in patients with Multiple Myeloma. A comparative study versus Immunofixation

Abstract Background The International Myeloma Working Group (IMWG) defines treatment response categories based on monoclonal protein (MP) changes by serum protein electrophoresis (SPE) and immunofixation (sIFE). Patients that after treatment remain positive by sIFE while SPE is negative, are categorized as very good partial response (VGPR) and, if sIFE becomes negative, patients would be considered in complete remission (CR). However, the interpretation of sIFE is qualitative and subjective. In this study we evaluate the discrepancies between sIFE and Mass Spectrometry (MS) to evaluate tumor burden and the accuracy of treatment response and it´s clinical impact in terms of progression free survival (PFS). Methods Patient samples were automatically prepared on the EXENT-iP®500 liquid handler, and sample spots were analysed using the EXENT-iX®500 MALDI-TOF mass spectrometer. Light chain spectral peaks were identified by EXENT-iQ® software and then quantified indirectly in combination with total immunoglobulins concentrations by immunoturbidimetry in the Optilite® platform (The Binding Site, part of Thermo Fisher Scientific). MPs were also identified and quantified by SPE and sIFE. Results From the 430 samples from the GEM12, GEM14 and GEM-CESAR clinical trials analyzed at pre-determined time points to evaluate treatment response (post-Induction, post-ASCT, post-cons, 1st and 2nd year after maintenance), MS identified the M protein in 45% of cases (193/430) and sIFE was positive in 32% (137/430). Combining the results of both methods, we found that MS and sIFE were concordant in 76% of cases (326/430), 26.28% IFE+/ MS+ and 49.53% IFE-/ MS-. Considering sIFE as a reference, the negative predictive value (NPV) of MS was 0.8987, with a sensitivity and a specificity of 0.8248 and 0.7270, respectively (p<0.0001). Nevertheless, the positive predictive value (PPV) was 0.5855 which could be explained by the discordances observed between IFE and MS techniques (5.58% of patients IFE+/MS- and 18.6% of patients IFE-/MS+). Indeed, when the 137 patients in VGPR (IFE+ patients) were analyzed according to MS status we found that patients IFE+/ MS+ had a trend to an inferior mPFS in comparison to IFE+/MS- (5.96 years vs not reached). These discordances were even more noticeable when comparing the 293 patients in CR (IFE- patients) with MS status, since IFE-/ MS+ patients had a mPFS of 4.65 years vs mPFS not reached for IFE-/ MS- patients (p=0.0001). Conclusions Our data confirms that IFE sensitivity limitations can affect the evaluation of treatment response in patients with MM, being more noticeable when the presence of MP band in sIFE is not clear because is very fuzzy or oligoclonal bands appear. Consequently, heterogeneity in interpretation practices across labs is a major cause of misattributed response categories, especially on those patients achieving treatment responses >VGPR. In an era of highly effective MM treatments that induce quick and deep responses, we believe IMWG response criteria should be updated with an MS response category.

PSMA PET/CT for treatment response evaluation at predefined time points is superior to PSA response for predicting survival in metastatic castration-resistant prostate cancer patients

BackgroundIn metastatic castration-resistant prostate cancer (mCRPC), using serum prostate-specific antigen (PSA) levels to evaluate treatment response is not always accurate. This study aimed to assess the efficacy of PSMA PET/CT at specific time points for evaluating treatment response and predicting survival in mCRPC patients, compared to PSA. MethodsSixty mCRPC patients underwent [18F]PSMA-1007 PET/CT at baseline and for treatment response evaluation of either androgen receptor-targeted agents (after 3 months) or chemotherapy (after completion), and were retrospectively analysed. Visual assessment categorised overall response and response of the worst responding lesion as partial response, stable disease, or progressive disease, using the EAU/EANM criteria. Additionally, percentage changes in SUVmax, total tumour volume and total lesion uptake (tumour volume * SUVmean) were calculated. PSA response was defined according to the PCWG3 criteria. Cox regression analysis identified predictors of overall survival. ResultsPSMA PET/CT and PSA response were discordant in 47 % of patients, and PSMA PET/CT response was worse in 89 % of these cases. Overall response on PSMA PET/CT independently predicted overall survival (progression versus non-progression: HR = 4.05, p < 0.001), outperforming PSA response (progression versus non-progression: HR = 2.53, p = 0.010) and other PSMA PET/CT parameters. Among patients with a PSA decline of > 50 %, 31 % showed progressive disease on PSMA PET/CT, correlating with higher mortality risk (progression versus non-progression: HR = 4.38, p = 0.008). No flare in PSMA uptake was observed in this cohort. ConclusionsPSMA PET/CT for assessing treatment response at predefined time points was superior to PSA-based response for predicting overall survival in mCRPC patients treated with androgen receptor-targeted agents and chemotherapy. PSMA PET/CT showed the ability to detect disease progression earlier than PSA levels, which can affect treatment decisions and has the potential to improve patient outcomes. We recommend further research to validate these findings in larger patient cohorts, to extend the number of treatments, and to evaluate cost-effectiveness and impact on patient outcomes.

The treatment response evaluation through the combination of contrast-enhanced ultrasound and squamous cell carcinoma antigen in cervical cancer

The treatment response evaluation through the combination of contrast-enhanced ultrasound and squamous cell carcinoma antigen in cervical cancer

18F]FDG PET/CT Integration in Evaluating Immunotherapy for Lung Cancer: A Clinician's Practical Approach.

The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment paradigm of lung cancer, resulting in notable enhancements in patient survival. Nevertheless, evaluating treatment response in patients undergoing immunotherapy poses distinct challenges due to unconventional response patterns like pseudoprogressive disease (PPD), dissociated response (DR), and hyperprogressive disease (HPD). Conventional response criteria such as the RECIST 1.1 may not adequately address these complexities. To tackle this issue, novel response criteria such as the iRECIST and imRECIST have been proposed, enabling a more comprehensive assessment of treatment response by incorporating additional scans and considering the best overall response even after radiologic progressive disease evaluation. Additionally, [18F]FDG PET/CT imaging has emerged as a valuable modality for evaluating treatment response, with various metabolic response criteria such as the PERCIMT, imPERCIST, and iPERCIST developed to overcome the limitations of traditional criteria, particularly in detecting pseudoprogression. A multidisciplinary approach involving oncologists, radiologists, and nuclear medicine specialists is crucial for effectively navigating these complexities and enhancing patient outcomes in the era of immunotherapy for lung cancer. In this review, we delineate the key components of these guidelines, summarizing essential aspects for radiologists and nuclear medicine physicians. Furthermore, we provide insights into how imaging can guide the management of individual lung cancer patients in real-world multidisciplinary settings.

Contribution of [18F]FET PET in the Management of Gliomas, from Diagnosis to Follow-Up: A Review.

Gliomas, the most common type of primary malignant brain tumors in adults, pose significant challenges in diagnosis and management due to their heterogeneity and potential aggressiveness. This review evaluates the utility of O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) positron emission tomography (PET), a promising imaging modality, to enhance the clinical management of gliomas. We reviewed 82 studies involving 4657 patients, focusing on the application of [18F]FET in several key areas: diagnosis, grading, identification of IDH status and presence of oligodendroglial component, guided resection or biopsy, detection of residual tumor, guided radiotherapy, detection of malignant transformation in low-grade glioma, differentiation of recurrence versus treatment-related changes and prognostic factors, and treatment response evaluation. Our findings confirm that [18F]FET helps delineate tumor tissue, improves diagnostic accuracy, and aids in therapeutic decision-making by providing crucial insights into tumor metabolism. This review underscores the need for standardized parameters and further multicentric studies to solidify the role of [18F]FET PET in routine clinical practice. By offering a comprehensive overview of current research and practical implications, this paper highlights the added value of [18F]FET PET in improving management of glioma patients from diagnosis to follow-up.

Real-world response assessment of immune checkpoint inhibition: comparing iRECIST and RECIST 1.1 in melanoma and non-small cell lung cancer patients.

To compare immune response evaluation criteria in solid tumors (iRECIST) and response evaluation criteria in solid tumors (RECIST) 1.1 for response assessment of immune checkpoint inhibitor (ICI) therapy in a real-world setting in patients with melanoma and non-small cell lung cancer (NSCLC). Two-hundred fifty-two patients with melanoma and NSCLC who received CTLA-4 inhibitor ipilimumab or PD-1 inhibitors nivolumab or pembrolizumab and who underwent staging CT of the chest and abdomen were retrospectively included. Treatment response evaluation according to the RECIST 1.1 and iRECIST guidelines was performed for all patients. Response patterns, as well as overall response rate (ORR), disease control rate (DCR), and time to progression (TTP), were compared between RECIST 1.1 and iRECIST. Out of 143 patients with progressive disease (PD) according to RECIST 1.1, 48 (33.6%) did not attain confirmation of progression (iCPD) as per iRECIST and six patients who were treated beyond RECIST 1.1 progression reached PD at a later point in time in iRECIST, resulting in a significant difference in TTP between iRECIST and RECIST 1.1 (618.3 ± 626.9 days vs. 538.1 ± 617.9 days, respectively (p < 0.05)). The number of non-responders as per RECIST 1.1 was 79, whereas it was 60 when using iRECIST. ORR was 28.5% for RECIST 1.1 and 34.1% for iRECIST, and corresponding DCR of 67.4% for RECIST 1.1 and 74.6% for iRECIST. iRECIST was more suitable than RECIST 1.1 for capturing atypical response patterns to ICI therapy in patients with melanoma and NSCLC, resulting in differences in the assessment of treatment response. Compared to RECIST 1.1, iRECIST may improve patient care and treatment decisions for patients with NSCLC or melanoma who are treated with immune checkpoint inhibitors in clinical routine. RECIST 1.1 may incorrectly assess atypical treatment patterns to immune checkpoint inhibitors. iRECIST better captured atypical response patterns compared to RECIST 1.1. iRECIST was more suitable for assessing response to immune checkpoint inhibitors in non-small cell lung carcinoma and melanoma.

EGFR-TKI combined with radiotherapy in 105 patients of lung adenocarcinoma with brain metastasis: a retrospective study of prognostic factors analysis.

This study aimed to retrospectively analyze the response and prognosis factors for patients of lung adenocarcinoma with brain metastasis and epidermal growth factor receptor (EGFR) mutation, who were treated by EGFR-tyrosine kinase inhibitor (TKI) combined with brain radiotherapy (RT). From Jan 2021 to Jan 2024, the clinicopathological data of lung adenocarcinoma patients were collected from the First Affiliated Hospital of Hebei North University. SPSS version 26.0 statistical software was used for statistical analysis. P &lt; 0.05 was determined to be statistically significant. 105 patients were included. The 1, 2, 3-year overall survival (OS) rate was 82.9%, 61.2%, and 33.7%, respectively. 1, 2 ,3-year progression-free survival 1 (PFS1) rate was 62.7%, 36.6%, 22.1%. 1,2,3-year PFS2 rate was 80.8%, 54.6%, and 31.4%. The median OS, PFS1 and PFS2 was 29.8, 18.0 and 28.1 months, respectively. The COX multivariate analysis showed that gene mutation status and brain radiation dose were independent prognostic factors for OS; Gene mutation status, brain radiation dose, and response evaluation to initial treatment (response evaluation) are independent prognostic factors for PFS1; Clinical stage, gene mutation status, brain radiation dose, and response evaluation are independent prognostic factors for PFS2. TKI combined with brain radiotherapy is effective on lung adenocarcinoma patients with EGFR mutation and brain metastasis. Patients with 19 Del or 21 L858R mutation and brain radiation doses ≥ 40 Gy have longer OS, PFS1, and PFS2, and complete remission (CR) + partial remission (PR) is associated with longer PFS1 and PFS2, Patients in stage IVA have longer PFS2.

Values of apparent diffusion coefficient in pancreatic cancer patients receiving neoadjuvant therapy

BackgroundTo investigate the values of apparent diffusion coefficient (ADC) for the treatment response evaluation in pancreatic cancer (PC) patients receiving neoadjuvant therapy (NAT).MethodsThis study included 103 NAT patients with histologically proven PC. ADC maps were generated using monoexponential diffusion-weighted imaging (b values: 50, 800 s/mm2). Tumors’ minimum, maximum, and mean ADCs were measured and compared pre- and post-NAT. Variations in ADC values measured between pre- and post-NAT completion for NAT methods (chemotherapy, chemoradiotherapy), tumor locations (head/neck, body/tail), tumor regression grade (TRG) levels (0–2, 3), N stages (N0, N1/N2) and tumor resection margin status (R0, R1), were further analyzed.ResultsThe minimum, maximum, and mean ADC values all increased dramatically after NAT, rising from 23.4 to 25.4% (all p < 0.001): mean (average: 1.626 × 10− 3 mm2/s vs. 1.315 × 10− 3 mm2/s), minimum (median: 1.274 × 10− 3 mm2/s vs. 1.034 × 10− 3 mm2/s), and maximum (average: 1.981 × 10− 3 mm2/s vs. 1.580 × 10− 3 mm2/s). The ADCs between the subgroups of all the criteria under investigation did not differ significantly for the minimum, maximum, or mean values pre- or post-NAT (P = 0.08 to 1.00). In the patients with borderline resectable PC (n = 47), the rate of tumor size changes after NAT was correlated with the pre-NAT mean ADC values (Spearman’s coefficient: 0.288, P = 0.049).ConclusionsThe ADC values of PC increased significantly following NAT; however, the percentage increases failed to provide any predictive value for the resection margin status or TRG levels.

Evaluation of HER2 immunohistochemistry-positive and immunohistochemistry-negative FISH amplification breast cancers using next-generation sequencing

Abstract Objectives In this study, we aimed to assess the concordance between HER2 positivity, defined as scores of 2+ or 3+ by immunohistochemistry (IHC), and HER2 gene amplification results obtained by fluorescence in situ hybridization (FISH) and gene panel testing (GPT). Methods A total of 45 breast cancer patients with sufficient biopsy, breast-conserving surgery, or mastectomy specimens collected between 2018 and 2024 at Hokuto Hospital were included in the study. HER2 status was defined as HER2+ in cases with scores of 3+ on IHC staining, HER2-FISHamp in cases with scores of 2+ on IHC staining plus FISH amplification. FISH amplification was defined as a ratio of HER2 to the amplification of the chromosome 17 centromere ≥2.0. Next-generation sequencing (NGS) for these genes was conducted using MiSeq. The criterion for ERBB2 amplification requires gene amplification of more than 2 standard deviations (SD) above the average of the panel genes and CN ≥4. Results HER2+ correlated with the presence of NGS amplification of ERBB2 (p&lt;0.001). NGS amplification was significantly more detectable in HER2+ than in HER2-FISHamp. HER2-FISHamp correlated with larger tumor size (p=0.009) and the presence of lymph node metastases (p&lt;0.001). No correlations were observed between the HER2 status and other parameters such as age, histological grade, stage histological type, recurrence, treatment response evaluation, and breast cancer mortality. Conclusions To achieve a comprehensive diagnosis, it is crucial to integrate GPT findings with other diagnostic approaches and to have a though understanding of the characteristics and limitations of each method.

Engineering two-in-one DNA nanohybrids to evaluate anti-cancer effects through activatable RNA imaging

The development of DNA-based imaging techniques provides a promising way for theranostic applications. However, the dramatic chemical difference between DNA probes and therapeutics significantly hinders the construction of an ideal theranostic system for evaluation of therapeutic effects via in situ molecular imaging. In this work, we report a simple approach for the construction of a two-in-one DNA nanohybrid via one-step assembly of DNA probes and small molecular drugs, enabling evaluation of therapeutic effects via sensitive imaging of apoptosis-related mRNA. The nanohybrid was self-assembled from a rationally designed molecular beacon (MB) probe, doxorubicin (DOX, a chemotherapeutic drug) and Fe (II) ions through coordination interactions, which possesses anti-cancer effects from chemotherapeutics and the capability of efficient co-delivery of DNA probes without transfection agents. By tracking pro-apoptotic Bax mRNA expression with the MB, this system allows real-time monitoring of cell apoptotic process in response to drug treatment, enabling assessment of therapeutic effects of small molecular drugs. In addition, the approach is extended to the imaging of target microRNA in the drug treatment based on flexible DNA probe design, demonstrating the universality of this strategy. Moreover, the modular design of this DNA nanohybrid allows the introduction of photosensitizers into this system for efficient photodynamic therapy and simultaneous mRNA monitoring. This strategy expands the theranostic toolbox for the in situ evaluation of treatment response and screening anticancer drugs.

Measurement of changes in serum-based inflammatory indicators to monitor response to nivolumab monotherapy in advanced gastric cancer: a multicenter retrospective study

BackgroundNonresectable gastric cancer develops rapidly; thus, monitoring disease progression especially in patients receiving nivolumab as late-line therapy is important. Biomarkers may facilitate the evaluation of nivolumab treatment response. Herein, we assessed the utility of serum-based inflammatory indicators for evaluating tumor response to nivolumab.MethodsThis multicenter retrospective cohort study included 111 patients treated with nivolumab monotherapy for nonresectable advanced or recurrent gastric cancer from October 2017 to October 2021. We measured changes in the C-reactive protein (CRP)-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) in serum from baseline to after the fourth administration of nivolumab. Furthermore, we calculated the area under the receiver operating characteristic curves (AUC ROCs) for CAR, PLR, and NLR to identify the optimal cutoff values for treatment response. We also investigated the relationship between clinicopathologic factors and disease control (complete response, partial response, and stable disease) using the chi-squared test.ResultsThe overall response rate (complete and partial response) was 11.7%, and the disease control rate was 44.1%. The median overall survival (OS) was 14.0 (95% CI 10.7‒19.2) months, and the median progression-free survival (PFS) was 4.1 (95% CI 3.0‒5.9) months. The AUC ROCs for CAR, PLR, and NLR before nivolumab monotherapy for patients with progressive disease (PD) were 0.574 (95% CI, 0.461‒0.687), 0.528 (95% CI, 0.418‒0.637), and 0.511 (95% CI, 0.401‒0.620), respectively. The values for changes in CAR, PLR, and NLR were 0.766 (95% CI, 0.666‒0.865), 0.707 (95% CI, 0.607‒0.807), and 0.660 (95% CI 0.556‒0.765), respectively. The cutoff values for the treatment response were 3.0, 1.3, and 1.4 for CAR, PLR, and NLR, respectively. The PFS and OS were significantly longer when the treatment response values for changes in CAR, PLR, and NLR were below these cutoff values (CAR: OS, p < 0.0001 and PFS, p < 0.0001; PLR: OS, p = 0.0289 and PFS, p = 0.0302; and NLR: OS, p = 0.0077 and PFS, p = 0.0044).ConclusionsMeasurement of the changes in CAR, PLR, and NLR could provide a simple, prompt, noninvasive method to evaluate response to nivolumab monotherapy.Trial registrationThis study is registered with number K2023006.

Assessing disease progression and treatment response in progressive multiple sclerosis.

Progressive multiple sclerosis poses a considerable challenge in the evaluation of disease progression and treatment response owing to its multifaceted pathophysiology. Traditional clinical measures such as the Expanded Disability Status Scale are limited in capturing the full scope of disease and treatment effects. Advanced imaging techniques, including MRI and PET scans, have emerged as valuable tools for the assessment of neurodegenerative processes, including the respective role of adaptive and innate immunity, detailed insights into brain and spinal cord atrophy, lesion dynamics and grey matter damage. The potential of cerebrospinal fluid and blood biomarkers is increasingly recognized, with neurofilament light chain levels being a notable indicator of neuro-axonal damage. Moreover, patient-reported outcomes are crucial for reflecting the subjective experience of disease progression and treatment efficacy, covering aspects such as fatigue, cognitive function and overall quality of life. The future incorporation of digital technologies and wearable devices in research and clinical practice promises to enhance our understanding of functional impairments and disease progression. This Review offers a comprehensive examination of these diverse evaluation tools, highlighting their combined use in accurately assessing disease progression and treatment efficacy in progressive multiple sclerosis, thereby guiding more effective therapeutic strategies.

High-Dose Furmonertinib in Patients With EGFR-Mutated NSCLC and Leptomeningeal Metastases: A Prospective Real-World Study

IntroductionLeptomeningeal metastasis (LM) is one of the most severe complications of NSCLC. Furmonertinib is a pan-EGFR tyrosine kinase inhibitor (TKI) with a high rate of brain penetration and a wide therapeutic window. Here, we evaluated the efficacy and safety of high-dose furmonertinib in patients with EGFR-mutated NSCLC and LM. MethodsThis prospective real-world study included patients with EGFR-mutated NSCLC and LM treated with a high-dose furmonertinib (240 mg once daily) as a monotherapy or in combination with other treatments. The primary end point was overall survival, and the secondary end points included time to treatment discontinuation and clinical response rate. Additional efficacy evaluations included changes in brain magnetic resonance imaging by the response assessment in neuro-oncology–LM radiologic criteria. We also introduced next-generation sequencing–based assays to evaluate genomic and epigenomic features of cell-free DNA (cfDNA) in patients’ cerebrospinal fluid (CSF) samples and to analyze their associations with patient outcomes. ResultsWe enrolled 48 patients, of whom 35 (72.9%) had received third-generation EGFR TKIs. The median overall survival was 8.43 months (95% confidence interval: 5.48–11.39 mo), while the median time to treatment discontinuation was 8.27 months (95% confidence interval: 5.40–11.14 mo), and the clinical response rate was 75%. The LM objective response rate and disease control rate assessed with response assessment in neuro-oncology-LM radiologic criteria were 50.0% and 92.1%, respectively. The adverse event profiles were consistent with previous reports of furmonertinib. Briefly, 22 (45.8%) had adverse events possibly related to furmonertinib and 3 (6.3%) had a grade 3-elevated aminotransaminase or nausea or leucopenia, leading to a dose reduction to 160 mg daily. Furthermore, methylation analysis of cfDNA in CSF revealed that there was a significant correlation between the changes of aberrant methylated fragments from lung cancer cells and the response of the patients. Meanwhile, the copy number burden scores derived from the low-pass whole genome sequencing assay may offer another objective and effective method for the diagnosis and evaluation of treatment efficacy in LM. ConclusionsIn the real world, the high-dose furmonertinib-based treatment may potentially have clinical efficacy and tolerable safety in patients of EGFR-mutated NSCLC with LM, even in patients previously treated with other third-generation EGFR TKIs. Methylation and copy number burden analysis of cfDNA in CSF may be considered objective indicators for the diagnosis of LM and evaluation of treatment response.

Multimodality imaging of urinary tract tuberculosis.

Imaging is a key component of diagnosis and treatment response evaluation of urinary tract tuberculosis (UT TB). Tuberculosis can have a long latency, but if found early, one may have the opportunity to prevent complications such as ureteral strictures, obstructive nephropathy, contracted (thimble) bladder, renal parenchymal destruction/calcification, and renal failure. Imaging can aid in diagnosis and differential diagnoses, evaluate the extent of disease and complications, and guide image-directed biopsy, surgical planning, and evaluation of treatment response. Imaging abnormalities in the renal parenchyma and urinary tract at different stages of the disease, lymphadenopathy, and extra-urinary tract organ involvement are suggestive of UT TB. Recent advances in imaging modalities aid in UT TB diagnosis, follow-up, and guiding treatment.

FAM136A as a Diagnostic Biomarker in Esophageal Cancer: Insights into Immune Infiltration, m6A Modification, Alternative Splicing, Cuproptosis, and the ceRNA Network.

FAM136A promotes the progression and metastasis of various tumors. However, there are few studies on the role of FAM136A in esophageal cancer (ESCA). The TCGA, GTEx, and GEO databases are employed to analyze the expression of FAM136A in ESCA, and qPCR and TMA experiments are performed for validation. Enrichment analyzes are performed to investigate the association of FAM136A expression with immune features, m6A modification, alternative splicing, cuproptosis, and the ceRNA network via bioinformatics analysis. FAM136A is highly expressed in ESCA and correlated with lymph node metastasis and overall survival (OS). Bioinformatics analysis suggested that FAM136A may participate in the following processes to promote ESCA development and progression: 1) Promotion of mast cells infiltration to influence the ESCA immune microenvironment, 2) HNRNPC upregulation to regulate m6A modification, 3) ALYREF upregulation to increase the occurrence of retained intron (RI) events, 4) CDK5RAP1 upregulation to achieve inhibition of tumor cell apoptosis, and 5) promotion of ESCA progression through the lncRNA SNHG15/hsa-miR-29c-3p/FAM136A ceRNA network. FAM136A is a potential biomarker for ESCA diagnosis and treatment response evaluation, and the underlying mechanisms may be associated with immune infiltration, m6A modification, alternative splicing, cuproptosis, and the ceRNA regulatory network.

Potential utility of ADNP in circulating tumor cells as biomarker for prognostics in non-muscle-invasive bladder cancer

This study aims to evaluate the prognostic utility of Activity-dependent neuroprotective protein (ADNP) expression in Circulating Tumor Cells (CTCs) inpatients with Non-muscle-invasive Bladder Cancer (NMIBC) undergoing Transurethral Resection of Bladder Tumor (TURBT). A prospective cohort of 74 bladder cancer patients and 22 non-cancer controls were enrolled. The expression of ADNP mRNA was detected by immunomagnetic beads-droplet digital PCR. The ADNP mRNA expression was evaluated in patients with high-risk NMIBC and those with indeterminate invasion depth post 2nd TURBT. Primary cultured bladder cancer cells and PBMCs from healthy donors were immunofluorescence stained. Our findings suggest that baseline ADNP mRNA level in CTCs shows potential as a prognostic marker for NMIBC with a sensitivity of 83.33% and a specificity of 73.58%. In comparison to baseline, ADNP mRNA expression increased post 2nd TURBT in 5 patients, where 2 experienced recurrence. Meanwhile, among the 12 patients with decreased levels, only one patient relapsed. A considerable limitation of this study entails the small sample size. The Immuno-magnetic beads-ddPCR technique provided a viable method for ADNP mRNA detection in CTCs from bladder cancer patients. The preoperative ADNP mRNA level in CTCs was identified as a prognostic indicator for NMIBC. Longitudinal monitoring of ADNP mRNA in CTCs of bladder cancer patients shows promise in evaluating treatment responses and predicting prognosis.