Stable Disease Research Articles

Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series

Paediatric hepatocellular carcinomas (HCC) traditionally arise in the context of a normal structural and functional liver and carry a dismal prognosis. While chemotherapy is the frontline standard, there is emerging interest in the study of immunotherapies for paediatric patients with relapsed/refractory disease. There is limited data to support whether immunotherapies will be of utility in this patient population. Six paediatric patients (median age:16 years, range: 12-17at the time of treatment) with advanced hepatocellular neosplams, either conventional hepatocellular or fibrolamellar carcinoma, were treated with immunotherapy. Patients were consented to institutional genomic profiling and biobanking protocols. Baseline samples and serial tissue samples, when available, were evaluated for somatic mutation rate, actionable gene mutations, and pan-immune bulk RNA expression profiling. Results were correlated with clinical course. Three patients responded to checkpoint inhibition: one achieved a complete, durable response and the other two, prolonged stable disease. Three additional patients progressed. Diagnostic tissue from the complete responder demonstrated a higher relative mutational burden and robust immune infiltrate. Pre-treatment samples from the three responders demonstrated decreased expression of genes associated with T-cell dysfunction. A subset of patients with primary paediatric hepatocellular tumours will respond to immunotherapy. Immunotherapies are currently under prospective study for relapsed/refractory liver tumours in paediatric patients. Results from this report support the prospective collection of serial serum and tissue samples which may further identify genomic and immunophenotypic patterns predictive of response. This work was supported by Philanthropic funds (Pan Mass Challenge, Team Angus and Team Perspective).

Pulmonary manifestations, treatments and outcomes of IgG4-related disease-a systematic literature review.

Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. A consistent feature of many cases is pulmonary infiltrates, or respiratory failure. This systematic literature review aims to summarise the pulmonary manifestations of IgG4-RD, including clinical outcomes and treatment. This review was registered on PROSPERO (CRD42023416410). Medline, Embase and Cochrane databases were searched for articles discussing IgG4-RD syndrome. Information was extracted on demographics, type and prevalence of pulmonary manifestations, treatment and clinical outcomes. Initially, after deduplication, 3123 articles were retrieved with 18 ultimately included. A pooled total of 724 patients with IgG4-RD were included, 68.6% male, mean age 59.4 years (SD 5.8) at disease onset. The most frequently described pulmonary manifestation was mediastinal lymphadenopathy (n = 186, 48.8%), followed by pulmonary nodules (n = 151, 39.6%) and broncho-vascular thickening (n = 85, 22.3%). Where treatment was reported, the majority of patients received glucocorticoids (n = 211, 93.4%). Other immunosuppressive therapy included cyclophosphamide (n = 31), azathioprine (n = 18), with mycophenolate mofetil (n = 6), rituximab (n = 6), methotrexate (n = 5) and other unspecified immunomodulators (50). Clinical outcomes were reported in 263 patients, where 196 patients had remission of their disease, 20 had relapse, 35 had stable disease, four had progression and eight patients died from complications of IgG4-RD. This systematic review summarises pulmonary manifestations, treatments and outcomes in patients with IgG4-RD. Pulmonary involvement in IgG4-RD is relatively common, leading to high levels of morbidity and mortality. Glucocorticoids remain the mainstay of treatment, but further work is required to explore the management of patients with pulmonary manifestations in association with IgG4-RD.

Chronic coronary syndromes without standard modifiable cardiovascular risk factors and outcomes: the CLARIFY registry

Abstract Background and Aims It has been reported that patients without standard modifiable cardiovascular (CV) risk factors (SMuRFs—diabetes, dyslipidaemia, hypertension, and smoking) presenting with first myocardial infarction (MI), especially women, have a higher in-hospital mortality than patients with risk factors, and possibly a lower long-term risk provided they survive the post-infarct period. This study aims to explore the long-term outcomes of SMuRF-less patients with stable coronary artery disease (CAD). Methods CLARIFY is an observational cohort of 32 703 outpatients with stable CAD enrolled between 2009 and 2010 in 45 countries. The baseline characteristics and clinical outcomes of patients with and without SMuRFs were compared. The primary outcome was a composite of 5-year CV death or non-fatal MI. Secondary outcomes were 5-year all-cause mortality and major adverse cardiovascular events (MACE—CV death, non-fatal MI, or non-fatal stroke). Results Among 22 132 patients with complete risk factor and outcome information, 977 (4.4%) were SMuRF-less. Age, sex, and time since CAD diagnosis were similar across groups. SMuRF-less patients had a lower 5-year rate of CV death or non-fatal MI (5.43% [95% CI 4.08–7.19] vs. 7.68% [95% CI 7.30–8.08], P = 0.012), all-cause mortality, and MACE. Similar results were found after adjustments. Clinical event rates increased steadily with the number of SMuRFs. The benefit of SMuRF-less status was particularly pronounced in women. Conclusions SMuRF-less patients with stable CAD have a substantial but significantly lower 5-year rate of CV death or non-fatal MI than patients with risk factors. The risk of CV outcomes increases steadily with the number of risk factors.

Comparison of the sputum microbiome between patients with stable nontuberculous mycobacterial pulmonary disease and patients requiring treatment.

We evaluated whether the sputum bacterial microbiome differs between nontuberculous mycobacteria pulmonary disease (NTM-PD) patients with stable disease not requiring antibiotic treatment and those requiring antibiotics. We collected sputum samples from 21 clinically stable NTM-PD patients (stable group) and 14 NTM-PD patients needing antibiotic treatment (treatment group). We also obtained 13 follow-up samples from the stable group. We analyzed the 48 samples using 16S rRNA gene sequencing (V3-V4 region) and compared the groups. In the linear discriminant analysis effect size (LEfSe) analysis, the species Porphyromonas pasteri, Haemophilus parahaemolyticus, Prevotella nanceiensis, and Gemella haemolysans were significantly more prevalent in the sputum of the stable group compared to the treatment group. No taxa showed significant differences in alpha-/beta-diversity or LEfSe between the 21 baseline and 13 follow-up sputum samples in the stable group. In the stable group, the genus Bergeyella and species Prevotella oris were less common in patients who achieved spontaneous culture conversion (n = 9) compared to those with persistent NTM positivity (n = 12) (effect size 3.04, p = 0.039 for Bergeyella; effect size 3.64, p = 0.033 for P. oris). In the treatment group, H. parainfluenzae was more common in patients with treatment success (n = 7) than in treatment-refractory patients (n = 7) (effect size 4.74, p = 0.013). Our study identified distinct bacterial taxa in the sputum of NTM-PD patients based on disease status. These results suggest the presence of a microbial environment that helps maintain disease stability.

Molecularly matched targeted therapy: a promising approach for refractory metastatic melanoma.

Only a fraction of patients with metastatic melanoma derive durable benefit from approved treatments. The clinical impact of personalized medicine strategies for melanoma, apart from BRAF, NRAS, or CKIT targeting, has rarely been reported. By means of the Group of Cutaneous Oncology of the French Society of Dermatology, we retrospectively included all patients with advanced melanoma aged 18 years and older for whom molecular testing identified one or more actionable molecular alterations and who accordingly received molecularly matched therapy. We excluded patients with only BRAF, NRAS, or CKIT alterations and patients who received molecularly matched therapy for less than 15 days. We included 26 patients with a median follow-up of 8 months (1-54), a median age of 63 years (24-89), and a sex ratio of 2.7. These patients had been heavily pretreated, and 64% had elevated LDH levels. The disease control rate was 38%, with 4 cases of partial response (overall response rate: 15%) and 6 of stable disease for at least 6 months. The median duration of treatment was 3.1 months (0.9-13.5). Among patients with disease control, the median duration of control was 6.6 months (2.6-13.5) and 3 cases were ongoing at the end of the study. Patients with controlled disease had GNA11, MAP2K1, FYCO1-RAF1, HRAS, ATM, CCND1, MDM2/CDK4, and CDKN2A/NRAS alterations. High-throughput sequencing followed by matched targeted therapy is a promising approach for patients with advanced melanoma refractory to approved treatments.

Dual FDG/PSMA PET imaging to predict lesion-based progression of mCRPC during PSMA-RLT

Candidates for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) frequently have “mismatch” lesions with pronounced 18-fluorodeoxyglucose ([18F]FDG) but attenuated PSMA ligand uptake on positron emission tomography (PET). However, no quantitative criteria yet exist to identify mismatch lesions and predict their response to RLT. To define such criteria, we retrospectively analyzed 267 randomly-selected glucometabolic mCRPC metastases from 22 patients. On baseline PET, we determined [18F]FDG and [68Ga]Ga-PSMA-11 maximum standardized uptake value (SUVmax), and calculated the [18F]FDG SUVmax/[68Ga]Ga-PSMA-11 SUVmax quotient (FPQ). From follow-up [18F]FDG PET after two lutetium-177-PSMA-617 RLT cycles, we evaluated the treatment response and categorized the lesions into three subgroups (partial remission, stable disease, progression) based on change in [18F]FDG SUVmax. Lastly, we compared the baseline PET variables in progressing versus non-progressing lesions. Variables differing significantly, and a score incorporating them, were assessed via receiver operator characteristic (ROC) curve analysis, regarding ability to predict lesional progression, with area under the curve (AUC) as metric. Cut-offs with optimal sensitivity and specificity were determined using the maximum value of Youden's index. Fifty-one of 267 lesions (19.1%) progressed, 102/267 (38.2%) manifested stable disease, and 114/267 (42.7%) partially responded after two RLT cycles. At baseline, median [68Ga]Ga-PSMA-11 SUVmax was significantly lower (p < 0.001), median FPQ significantly higher (p < 0.001), and median [18F]FDG SUVmax similar in progressing versus non-progressing lesions. [68Ga]Ga-PSMA-11 SUVmax and FPQ showed predictive power regarding progression (AUCs: 0.89, 0.90). An introduced clinical score combining both further improved predictive performance (AUC: 0.94). Optimal cut-offs to foretell progression were: [68Ga]Ga-PSMA-11 SUVmax < 11.09 (88.2% sensitivity, 81.9% specificity), FPQ ≥ 0.92 (90.2% sensitivity, 78.7% specificity), clinical score ≥ 6/9 points (88.2% sensitivity, 87.5% specificity). At baseline, a low [68 Ga]Ga-PSMA-11 SUVmax and a high FPQ predict early lesional progression under RLT; [18F]FDG SUVmax does not. A score combining [68 Ga]Ga-PSMA-11 SUVmax and FPQ predicts early lesional progression even more effectively and might therefore be useful to quantitatively identify mismatch lesions.

Radiation enhancement using focussed ultrasound-stimulated microbubbles for breast cancer: A Phase 1 clinical trial.

Preclinical studies have demonstrated that tumour cell death can be enhanced 10- to 40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble (FUS-MB) treatment. The acoustic exposure of microbubbles (intravascular gas microspheres) within the target volume causes bubble cavitation, which induces perturbation of tumour vasculature and activates endothelial cell apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy. Subsequent irradiation of a microbubble-sensitised tumour causes rapid increased tumour death. The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a radioenhancement therapy for breast cancer. This prospective, single-center, single-arm Phase 1 clinical trial included patients with stages I-IV breast cancer with in situ tumours for whom breast or chest wall radiotherapy was deemed adequate by a multidisciplinary team (clinicaltrials.gov identifier: NCT04431674). Patients were excluded if they had contraindications for contrast-enhanced MR or microbubble administration. Patients underwent 2 to 3 MRgFUS-MB treatments throughout radiotherapy. An MR-coupled focussed ultrasound device operating at 800 kHz and 570 kPa peak negative pressure was used to sonicate intravenously administrated microbubbles within the MR-guided target volume. The primary outcome was acute toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Secondary outcomes were tumour response at 3 months and local control (LC). A total of 21 female patients presenting with 23 primary breast tumours were enrolled and allocated to intervention between August/2020 and November/2022. Three patients subsequently withdrew consent and, therefore, 18 patients with 20 tumours were included in the safety and LC analyses. Two patients died due to progressive metastatic disease before 3 months following treatment completion and were excluded from the tumour response analysis. The prescribed radiation doses were 20 Gy/5 fractions (40%, n = 8/20), 30 to 35 Gy/5 fractions (35%, n = 7/20), 30 to 40 Gy/10 fractions (15%, n = 3/20), and 66 Gy/33 fractions (10%, n = 2/20). The median follow-up was 9 months (range, 0.3 to 29). Radiation dermatitis was the most common acute toxicity (Grade 1 in 16/20, Grade 2 in 1/20, and Grade 3 in 2/20). One patient developed grade 1 allergic reaction possibly related to microbubbles administration. At 3 months, 18 tumours were evaluated for response: 9 exhibited complete response (50%, n = 9/18), 6 partial response (33%, n = 6/18), 2 stable disease (11%, n = 2/18), and 1 progressive disease (6%, n = 1/18). Further follow-up of responses indicated that the 6-, 12-, and 24-month LC rates were 94% (95% confidence interval [CI] [84%, 100%]), 88% (95% CI [75%, 100%]), and 76% (95% CI [54%, 100%]), respectively. The study's limitations include variable tumour sizes and dose fractionation regimens and the anticipated small sample size typical for a Phase 1 clinical trial. MRgFUS-MB is an innovative radioenhancement therapy associated with a safe profile, potentially promising responses, and durable LC. These results warrant validation in Phase 2 clinical trials. clinicaltrials.gov, identifier NCT04431674.

Assessment of safety and efficacy of transarterial chemoembolization combined with camrelizumab and donafenib in patients with hepatocellular carcinoma at BCLC stage C: A study of 20 cases.

Camrelizumab, donafenib, and transarterial chemoembolization (TACE) are recommended for advanced hepatocellular carcinoma (HCC), but their combined efficacy remains unclear. From July 2021 to January 2023, 20 Barcelona Clinic Liver Cancer stage C HCC patients were prospectively enrolled. Inclusion criteria were Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh Score ≤ 7, and Barcelona Clinic Liver Cancer B or C. Surgical candidates were excluded. The treatment included TACE, camrelizumab, and donafenib. Endpoints were median overall survival, progression-free survival, and adverse events (AEs) related to donafenib. Among 20 patients, 85% experienced AEs from targeted therapy and programmed cell death protein-1, with 40% having grade 3 AEs. No grade 4 or 5 AEs occurred. Median follow-up was 9 months, with 15% achieving complete response, 65% partial response, and 15% stable disease. Disease control rate was 90%. Median progression-free survival and overall survival were 9 and 14 months, respectively. TACE, camrelizumab, and donafenib combination therapy in Chinese advanced HCC patients show effectiveness in extending survival with low severe AEs incidence.

Prognostic factors in Kaposi sarcoma, single centre experience.

Kaposi sarcoma (KS) is a multicentric vascular and lymphatic neoplasm caused by human herpesvirus 8 (HHV-8). It generally concerns the elderly and immunosuppressed population. Four major clinical types of KS have been described. The most common subtype is Classical KS (CKS). Our retrospective study aimed to better define prognostic subgroups among patients with CKS, which is the most common in our country. Between 2014 and 2020, 43 patients with CKS were treated with local excision, radiotherapy and chemotherapy. Reviewed information included demographics, clinical features, laboratory findings, treatment responses and overall survival. During the follow-up, eight patients (18.6%) died of CKS. The complete response rate was 46.5%, partial response and stable disease 51.2%, and progressive disease 2.3% of all patients. Gender, haemoglobin level at diagnosis, and disseminated involvement were prognostic factors affecting survival in all patients. We confirmed that male gender, low haemoglobin levels, and disseminated involvement are associated with poor prognosis in CKS patients. It is the only Turkish study in which prognostic analysis was performed for this rare cancer.

Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials

Introduction: FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before.Methods: We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023.Results: Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h.Discussion: FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.

Impact of Direct Measurement of Small Dense Low-Density Lipoprotein Cholesterol for Long-Term Secondary Prevention in Patients with Stable Coronary Artery Disease.

This study investigated whether directly measured small dense low-density lipoprotein cholesterol (D-sdLDL-C) can predict long-term coronary artery disease (CAD) events compared with low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), and estimated small dense low-density lipoprotein cholesterol (E-sdLDL-C) determined by the Sampson equation in patients with stable CAD. D-sdLDL-C measured at Showa University between 2010 and 2022, and E-sdLDL-C were evaluated in 790 male and 244 female patients with stable CAD. CAD events, defined as sudden cardiac death, onset of acute coronary syndrome, and/or need for coronary revascularization, were monitored for 12 years. Cutoff lipid levels were determined by receiver operating characteristic curves. CAD events were observed in 238 male and 67 female patients. The Kaplan-Meier event-free survival curves showed that patients with D-sdLDL-C ≥32.1 mg/dL (0.83 mmol/L) had an increased risk for CAD events (P = 0.007), whereas risk in patients with E-sdLDL-C ≥36.2 mg/dL (0.94 mmol/L) was not increased. In the group with high D-sdLDL-C, the multivariable-adjusted hazard ratio (HR) was 1.47 (95% CI, 1.15-1.89), and it remained significant after adjustment for LDL-C, non-HDL-C, or apoB and in patients treated with statins. HRs for high LDL-C, non-HDL-C, or apoB were not statistically significant after adjustment for high D-sdLDL-C. Higher D-sdLDL-C was associated with enhanced risk of high LDL-C, non-HDL-C, and apoB (HR 1.73; 95% CI, 1.27-2.37). Higher D-sdLDL-C can predict long-term recurrence of CAD in stable CAD patients independently of apoB and non-HDL-C. D-sdLDL-C is an independent risk enhancer for secondary CAD prevention, whereas E-sdLDL-C is not. UMIN-CTR Clinical Trial Number: UMIN000027504.

Whole genome and transcriptome integrated analyses guide clinical care of pediatric poor prognosis cancers

The role for routine whole genome and transcriptome analysis (WGTA) for poor prognosis pediatric cancers remains undetermined. Here, we characterize somatic mutations, structural rearrangements, copy number variants, gene expression, immuno-profiles and germline cancer predisposition variants in children and adolescents with relapsed, refractory or poor prognosis malignancies who underwent somatic WGTA and matched germline sequencing. Seventy-nine participants with a median age at enrollment of 8.8 y (range 6 months to 21.2 y) are included. Germline pathogenic/likely pathogenic variants are identified in 12% of participants, of which 60% were not known prior. Therapeutically actionable variants are identified by targeted gene report and whole genome in 32% and 62% of participants, respectively, and increase to 96% after integrating transcriptome analyses. Thirty-two molecularly informed therapies are pursued in 28 participants with 54% achieving a clinical benefit rate; objective response or stable disease ≥6 months. Integrated WGTA identifies therapeutically actionable variants in almost all tumors and are directly translatable to clinical care of children with poor prognosis cancers.

Examining the Pre- and Post-percutaneous Coronary Intervention Blood Pressure Variability Using Ambulatory Blood Pressure Monitoring in Patients With Stable and Unstable Coronary Artery Disease

Examining the Pre- and Post-percutaneous Coronary Intervention Blood Pressure Variability Using Ambulatory Blood Pressure Monitoring in Patients With Stable and Unstable Coronary Artery Disease

Applicability of STOPP/START prescribing criteria in integrated Swedish administrative health registries and a Swedish population-based cohort.

The STOPP/START criteria are frequently applied in observational studies to assess potentially inappropriate prescribing in older adults. This study aimed to assess the applicability of the three available STOPP/START versions in two distinct data sources. To evaluate the applicability of the three versions of STOPP/START criteria, we used two observational data sources: (i) Integrated Swedish administrative health registries (ISHR) encompassing routinely collected health data and (ii) the population-based Swedish National study on Aging and Care in Kungsholmen (SNAC-K), based on health professional-led clinical assessments. The Anatomical Therapeutic Classification code (ATC) was used to categorise medications. Diseases were categorised using the international classification of diseases version 10 (ICD10). The first STOPP/START version demonstrated an applicability rate of 80% in ISHR and 84% in SNAC-K. The second version demonstrated an applicability of 64% in ISHR and 74% in SNAC-K. The third version showed an applicability of 66% in ISHR and 77% in SNAC-K. Challenges in applicability included broad definitions, vague terminology, and the lack of information on disease severity, symptomatic traits, and stability of certain conditions. The applicability of the STOPP/START criteria in observational studies seems to have decreased in more recent versions of the tool. Population-based studies with comprehensive clinical assessments may offer higher applicability compared to studies based on administrative data. Future versions of the STOPP/START criteria should prioritise clear and unambiguous definitions to improve their applicability in research and promote result generalisability and comparability.

TREATMENT OF OBESITY WITH SGLT–2: OUR RESULTS

Abstract SGLT–2 inhibitors were indicated to be able to reduce the weight of diabetic patients for around 4 kilograms. We investigated the possibility to reduce the weight of non–diabetic patients using SGLT–2. Materials and Methods A continuous series of 402 patients were enrolled in a prospective analysis. All patients started a therapy with SGLT–2 inhibitor for a cardiological (80%) or nephrological disease (20%). The 54% used dapagliflozin while the 46% used empagliflozin. In all patients affected by chronic heart failure the SGLT–2 – Inhibitor was added to optimal medical therapy without new symptoms in ambulatory. In nephrological patients the drug was added after a complete stabilization of disease. The recruitment period was long 6 months. After the recruitment the patient was follow for other 6 month. At the end of the follow–up, we evaluated the weight lost. The result was evaluated by an electrical balance, that was the same for all evaluations. The data was collected in excel and analysed by the Q–R–Calc program. Results The mean age of patients was 63 age, 54% female. None was diabetic patients. Hypertension was present in 73%, hypercholesterolemia in 43%. 11% was smokers. 94% were Caucasian patients. The mean of Weight was 75 kg at the first control. The mean height 174 cm. All patients performed a cardiological o nephrological control in which the medical doctor prescribed SGLT–2 inhibitor on top the optical medical therapy. All patients that presented during this control some causes of instability were excluded from the analysis. 90% of patients assumed RAAS inhibitors (ARNI 23%), 81% betablockers, 54% diuretics, 68% MRA. About the subtype of heart failure 60% was HFpEF and 40% HFrEF. The mean GFR of nephrological patients was 31 l/min. After 6 month the mean weight loss was 5,2 kgs with a standard deviation of 3,1 kgs. The reduction of weight was 6.6% of the initial weight. No statistical differences were evaluated comparing empagliflozin and dapagliflozin. Conclusion The SGLT–2 inhibitor in non–diabetic patients was. able to determinate a weight lost of 6.6% (mean 5,2).

Pertuzumab Plus Trastuzumab in Patients With Biliary Tract Cancer With ERBB2/3 Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study.

Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with biliary tract cancer (BTC) with ERBB2/3 amplification, overexpression, or mutation treated with pertuzumab plus trastuzumab are reported. Eligible patients had advanced BTC, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with ERBB2/3 alterations, and a lack of standard treatment options. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease of at least 16+ weeks duration (SD16+) according to RECIST v1.1. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of stable disease, and safety. Twenty-nine patients were enrolled from February 2017 to January 2022, and all had advanced BTC with an ERBB2/3 alteration. One patient was not evaluable for efficacy. One complete response, eight partial responses, and two SD16+ were observed for DC and OR rates of 40% (90% CI, 27 to 100) and 32% (95% CI, 16 to 52), respectively. The null hypothesis of 15% DC rate was rejected (P = .0015). Four patients had at least one grade 3 adverse event (AE) or serious AE at least possibly related to treatment: anemia, diarrhea, infusion-related reaction, and fatigue. Pertuzumab plus trastuzumab met prespecified criteria to declare a signal of activity in patients with BTC and ERBB2/3 amplification, overexpression, or mutation.

CD3, CD8, IFN-γ, tumor and stroma inflammatory cells as prognostic indicators for surgically resected SCLC: evidences from a 10-year retrospective study and immunohistochemical analysis

Current clinical guidelines limit surgical intervention to patients with cT1-2N0M0 small cell lung cancer (SCLC). Our objective was to reassess the role of surgery in SCLC management, and explore novel prognostic indicators for surgically resected SCLC. We reviewed all patients diagnosed with SCLC from January 2011 to April 2021 in our institution. Survival analysis was conducted using the Kaplan–Meier method, and independent prognostic factors were assessed through the Cox proportional hazard model. In addition, immunohistochemistry (IHC) staining was performed to evaluate the predictive value of selected indicators in the prognosis of surgically resected SCLC patients. In the study, 177 SCLC patients undergoing surgical resection were ultimately included. Both univariate and multivariate Cox analysis revealed that incomplete postoperative adjuvant therapy emerged as an independent risk factor for adverse prognosis (p < 0.001, HR 2.96). Survival analysis revealed significantly superior survival among pN0-1 patients compared to pN2 patients (p < 0.0001). No significant difference in postoperative survival was observed between pN1 and pN0 patients (p = 0.062). Patients with postoperative stable disease (SD) exhibited lower levels of tumor inflammatory cells (TIC) (p = 0.0047) and IFN-γ expression in both area and intensity (p < 0.0001 and 0.0091, respectively) compared to those with postoperative progressive disease (PD). Conversely, patients with postoperative SD showed elevated levels of stromal inflammatory cells (SIC) (p = 0.0453) and increased counts of CD3+ and CD8+ cells (p = 0.0262 and 0.0330, respectively). Survival analysis indicated that high levels of SIC, along with low levels of IFN-γ+ cell area within tumor tissue, may correlate positively with improved prognosis in surgically resected SCLC (p = 0.017 and 0.012, respectively). In conclusion, the present study revealed that the patients with pT1-2N1M0 staging were a potential subgroup of SCLC patients who may benefit from surgery. Complete postoperative adjuvant therapy remains an independent factor promoting a better prognosis for SCLC patients undergoing surgical resection. Moreover, CD3, CD8, IFN-γ, TIC, and SIC may serve as potential indicators for predicting the prognosis of surgically resected SCLC.

Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease: a randomized, double-blinded, placebo-controlled trial

Nattokinase (NK) and red yeast rice (RYR) are both indicated for their potential in cardiovascular disease prevention and management, but their combined effects especially in coronary artery disease (CAD) are scarcely examined. This 90-day randomized, double-blind trial aims to investigate the effect of NK and RYR supplementations on cardiometabolic parameters in patients with stable CAD. 178 CAD patients were randomized to four groups: NK + RYR, NK, RYR, and placebo. No adverse effects due to the interventions were reported. In comparisons across groups, NK + RYR showed the maximum effect in reducing triglyceride (−0.39 mmol), total cholesterol (−0.66 mmol/L), diastolic blood pressure (−7.39 mmHg), and increase in high-density lipoprotein cholesterol (0.195 mmol/L) than other groups (all p for multiple groups comparison&amp;lt;0.01). Both NK + RYR and NK groups had significantly better-improved lactate dehydrogenase than the others (−29.1 U/L and − 26.4 U/L). NK + RYR group also showed more potent reductions in thromboxane B2 and increases in antithrombin III compared to placebo (both p &amp;lt; 0.01). These improved markers suggest that combined NK and RYR may preferably alter antithrombin and COX-1 pathways, potentially reducing thrombosis risks in CAD patients. Overall, the combined NK and RYR supplementation is safe and more effective than separately in improving cardiometabolic markers among CAD patients with multiple heart medications use.

Clinical value of semi-quantitative parameters in 68Ga-DOTANOC PET/CT in treatment and diagnostics of cranial meningioma in a single-center retrospective analysis

BackgroundThe value of somatostatin-analogon PET tracers in theranostics in cranial meningioma has been demonstrated in several studies however, the value of semi-quantitative parameters for therapy and patient outcome is still unclear.MethodsA retrospective study was performed comparing measured semi-quantitative 68Ga-DOTANOC PET/CT parameters (maximum standardized uptake value = SUVmax, mean standardized uptake value = SUVmean, and metabolic tumor volume = MTV) and calculated ratios (SUVmax tumor/to pituitary gland, SUVmax tumor to superior sinus sagittalis), versus WHO grades and overall outcome. Patients with histological confirmed meningioma or high probability for meningioma in previous cranial MRI were eligible.ResultsThirty-two patients from January 2018 to February 2023 were retrospectively included. WHO grade I meningioma was confirmed in 17 patients, WHO grade II in five patients, WHO grade III in two patients, while in eight patients diagnosis was solely based on MRI and 68Ga-DOTANOC PET/CT findings. In 12 cases stable disease was present, in 15 cases radiation therapy was chosen, in three cases neurosurgery was preferred while in two cases palliative care was chosen. Median SUVmax values increased with WHO grade (15.84, 17.22, and 28.4, p = 0.134, Kruskal–Wallis-test) and no statistically significant difference was present for MTV, SUVmax, and calculated ratios, although the ratio for SUVmax tumor to superior sinus sagittalis had the lowest value of p = 0.067.ConclusionIncreased SUVmax values in the tumor in 68Ga-DOTANOC PET/CT are associated with higher WHO grade, although further studies including larger patient collectives are needed to solidify this hypothesis.

Immune checkpoint inhibitor score (IChIS) predicts survival benefit of immunotherapy in patients with non-small cell lung cancer.

The use of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer is increasing. Despite ongoing studies to predict the efficacy of ICIs, its use in clinical practice remains difficult. Thus, we aimed to discover a predictive marker by analyzing blood cell characteristics and developing a scoring system for patients treated with ICIs. This was a prospective multicenter study in patients with advanced non-small cell lung cancer (NSCLC) who received ICIs as second-line treatment from June 2021 to November 2022. Blood cell parameters in routine blood samples were evaluated using an automated hematology analyzer. Immune checkpoint inhibitor score (IChIS) was calculated as the sum of neutrophil count score and immature granulocyte score. A total of 143 patients from 4 institutions were included. The treatment response was as follows: partial response, 8.4%; stable disease, 37.1%; and progressive disease, 44.8%. Median progression-free survival and overall survival after ICI treatment was 3.0 and 8.3 months, respectively. Median progression-free survival in patients with an IChIS of 0 was 4.0 months, which was significantly longer than 1.9 months in patients with an IChIS of 1 and 1.0 month in those with an IChIS of 2 (p = 0.001). The median overall survival in patients with an IChIS of 0 was 10.2 months, which was significantly longer than 6.8 and 1.8 months in patients with an IChIS of 1 and 2, respectively (p < 0.001). Baseline IChIS could be a potential biomarker for predicting survival benefit of immunotherapy in NSCLC.