-
The International Journal of Oral &... Jun 2024As the population gets older, the prevalence of complete or partial tooth loss is increasing, significantly impacting people's quality of life. Scientific research...
PURPOSE
As the population gets older, the prevalence of complete or partial tooth loss is increasing, significantly impacting people's quality of life. Scientific research demonstrates that implant-fixed complete dentures offer high levels of satisfaction. In certain cases, tooth loss can lead to significant bone atrophy, necessitating pre-implant bone reconstruction. We conducted a retrospective cohort study involving 43 arches, including or not bone grafts, rehabilitated using a stackable guided approach, which included an immediate loading protocol. The primary outcome measure was the survival rate of the implant at 4 months.
MATERIAL AND METHODS
The digital workflow helps the design of the provisional prothesis before the implant surgery, which will be loaded immediately after the implant's placement. The stacked guides integrate both surgical and prosthetic considerations into a digital workflow.
RESULT
A total of 284 implants were placed. After a 4-month follow-up period, 10 implants (3.5%) exhibited no osseointegration and were subsequently replaced, resulting in an overall success rate of 96.5%. After 1 year of follow-up, a prosthetic success rate of 100% was observed, with all patients being able to progress to the stages for the permanent fixed dentures.
CONCLUSION
Our findings support the use of this protocol for all patients, whether they require bone grafts or not. However, a long-term follow-up is essential for a comprehensive evaluation of these treatment outcomes.
PubMed: 38941165
DOI: 10.11607/jomi.10998 -
Oncology and Therapy Jun 2024Breast cancer presents diverse molecular subtypes affecting treatment strategies. Human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+)...
BACKGROUND
Breast cancer presents diverse molecular subtypes affecting treatment strategies. Human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+) breast cancer poses a challenge due to limited targeted therapies. Current neoadjuvant treatment primarily utilizes chemotherapy, with conflicting results regarding efficacy in patients with HER2-low breast cancer. Trastuzumab deruxtecan (T-DXd) shows promise in HER2-low metastatic disease, and preliminary evidence suggests synergy with endocrine therapy.
OBJECTIVE
This editorial explores the hypothesis that neoadjuvant T-DXd with or without endocrine therapy offers efficacy in the clinical management of HR+/HER2-low breast cancer.
METHODS
We propose a phase II study with two treatment arms: T-DXd + letrozole and T-DXd alone. The primary endpoint is the radiological complete response rate. Secondary endpoints include pathological complete response rate, safety, event-free survival, and overall survival. Exploratory analyses will compare the arms to identify potential for optimizing treatment efficacy and minimizing side effects.
CONCLUSIONS
This study design allows for initial assessment of T-DXd with or without endocrine therapy in the treatment of HER2-low breast cancer. The findings may pave the way for personalized treatment strategies and inform future research, potentially leading to a chemotherapy-sparing approach.
PubMed: 38941050
DOI: 10.1007/s40487-024-00286-3 -
Discover Oncology Jun 2024Gastric cancer (GC) is a malignant digestive tract tumor with a high recurrence rate and poor prognosis. Fucosylation is important in tumor glycosylation, in which the...
BACKGROUND
Gastric cancer (GC) is a malignant digestive tract tumor with a high recurrence rate and poor prognosis. Fucosylation is important in tumor glycosylation, in which the key enzyme is fucosyltransferase (FUT). FUT11 is a member of the fucosyltransferase family and has been closely associated with the development of multiple cancers. However, the specific relationship between FUT11 and GC prognosis and its molecular mechanism has not been fully studied. This study explored FUT11 expression, clinical correlation, and its role in GC occurrence and development to deepen understanding of its function.
METHODS
FUT11 expression in 33 cancers was preliminarily analyzed using the Tumor Immunoassay Resource (TIMER2.0) database. FUT11 expression in GC was evaluated using The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) and Gene Expression Profiling Interactive Analysis (GEPIA2) data and verified using the Gene Expression Omnibus (GEO) GSE65801 dataset. Furthermore, we studied the survival prognosis of FUT11 in GC and analyzed its effect on the survival rate of patients with GC using the KM-plotter. We also performed COX regression analysis on TCGA GC clinical data and analyzed FUT11 expression in the pathway using the STRING and LinkedOmics databases. Moreover, the relationship between FUT11 and GC immune infiltration level was examined, and the Kaplan-Meier survival analysis diagram was constructed. The FUT11 genetic variation information was retrieved using cBioPortal, and its drug sensitivity was analyzed using CellMiner. Finally, differential FUT11 expression in GC tissues was verified using immunohistochemistry.
RESULTS
The data mining and analysis demonstrated that FUT11 expression was abnormally elevated in GC tissues and correlated with poor patient prognosis. The FUT11 expression level was an independent prognostic factor for GC. The difference in FUT11 expression level resulted in different degrees of immune cell infiltration in the patients with GC, which might regulate the tumor microenvironment. FUT11 affected GC development by participating in cancer pathways such as PI3K-AKT, neuroactive ligand-receptor, and MAPK. Immunohistochemical staining revealed that FUT11 was highly expressed in GC.
CONCLUSIONS
This study revealed that FUT11 expression is significantly increased in GC tissues. This increase is associated with poor prognosis and might affect immune regulation. FUT11 might have immunological and targeted therapeutic value, providing a new approach to GC treatment.
PubMed: 38941002
DOI: 10.1007/s12672-024-01120-y -
Journal of Nephrology Jun 2024Although the widespread use of long-acting erythropoiesis-stimulating agents (ESAs) has facilitated the improvement of anemia in patients with chronic kidney disease...
BACKGROUND
Although the widespread use of long-acting erythropoiesis-stimulating agents (ESAs) has facilitated the improvement of anemia in patients with chronic kidney disease (CKD), the improvement in prognosis has not been fully demonstrated. Iron deficiency is associated with the development of cardiovascular diseases (CVDs), and the relative iron deficiency induced by erythropoiesis-stimulating agents may prevent the improvement of prognosis. Therefore, we investigated the association between iron deficiency and cardiovascular events during long-acting erythropoiesis-stimulating agent therapy using transferrin saturation (TSAT), which is less susceptible to inflammation than ferritin.
METHODS
This study included 1040 patients with non-dialysis-dependent CKD, aged ≥ 20 years, with a glomerular filtration rate < 60 mL/min/1.73 m and hemoglobin < 11 g/dL, who were treated with darbepoetin alfa for 96 weeks. The patients were recruited in the BRIGHTEN Trial, a multicenter, prospective, observational study conducted to evaluate erythropoiesis-stimulating agent resistance to darbepoetin alfa in treating anemia in non-dialysis-dependent CKD in a clinical setting. The association between transferrin saturation and the cumulative incidence of cardiovascular events was evaluated using the Kaplan-Meier method. To calculate the hazard ratio (HR), 95% confidence intervals (CI) and the Cox proportional hazards model were used.
RESULTS
Survival curve analysis for cardiovascular events indicated that patients with transferrin saturation ≥ 30% had a significantly better prognosis, with an adjusted hazard ratio of 0.34 (95% confidence interval 0.22-0.52). Stratified analysis revealed that patients with transferrin saturation of 30-40% had a significantly lower risk of cardiovascular events than those with transferrin saturation of 20-30%, even after a multivariate-adjusted hazard ratio of 0.33 (95% confidence interval 0.21-0.54).
CONCLUSION
Patients with CKD and transferrin saturation of 30-40% had significantly fewer cardiovascular events than those with transferrin saturation of 20-30% among patients treated with long-acting erythropoiesis-stimulating agents. Therefore, it may be useful to maintain higher transferrin saturation from the viewpoint of erythropoiesis-stimulating agent responsiveness and the reduction of cardiovascular events.
PubMed: 38941000
DOI: 10.1007/s40620-024-02000-y -
Clinical and Experimental Medicine Jun 2024Both atezolizumab (a PD-L1 inhibitor) plus bevacizumab (A+B) and sintilimab (a PD-1 inhibitor) plus bevacizumab (S+B) are recommended as the first-line regimen for... (Comparative Study)
Comparative Study
Both atezolizumab (a PD-L1 inhibitor) plus bevacizumab (A+B) and sintilimab (a PD-1 inhibitor) plus bevacizumab (S+B) are recommended as the first-line regimen for advanced hepatocellular carcinoma (HCC) in China. Different efficacy between the two regimens combined with transvascular intervention for unresectable HCC (uHCC) remain unknown. We retrospectively analyzed uHCC patients treated in three centers by simultaneous combination of A+B or S+B with transarterial chemoembolization (TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (HAIC). Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs) were compared. Totally 188 patients were included, with 92 and 96 administered A+B+TACE-HAIC (ABTH) and S+B+TACE-HAIC (SBTH), respectively. ORRs (62.0 vs. 70.8%, respectively; P = 0.257) and disease control rates (88.0 vs. 93.8%, P = 0.267) were similar between groups by the mRECIST criteria. ABTH showed no survival advantage over SBTH, with median PFS times of 11.7 months and 13.0 months, respectively (HR = 0.81, 95% CI, 0.52-1.26, P = 0.35) and similar OS times (HR = 1.19, 95% CI, 0.32-4.39, P = 0.8). No significant differences were observed in grade 3-4 TRAEs between groups. Either PD-L1 or PD-1 inhibitor plus bevacizumab combined with TACE-HAIC have similarly excellent therapeutic efficacy with manageable adverse events, representing promising treatment options for uHCC.
Topics: Humans; Carcinoma, Hepatocellular; Male; Bevacizumab; Middle Aged; Female; Liver Neoplasms; Retrospective Studies; Aged; Antineoplastic Combined Chemotherapy Protocols; Adult; Antibodies, Monoclonal, Humanized; Treatment Outcome; Immune Checkpoint Inhibitors; China; Chemoembolization, Therapeutic; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Fluorouracil; Leucovorin
PubMed: 38940944
DOI: 10.1007/s10238-024-01415-y -
Radiology. Imaging Cancer Jul 2024In patients with head and neck cancer (HNC), surgical removal of cancerous tissue presents the best overall survival rate. However, failure to obtain negative margins... (Review)
Review
In patients with head and neck cancer (HNC), surgical removal of cancerous tissue presents the best overall survival rate. However, failure to obtain negative margins during resection has remained a steady concern over the past 3 decades. The need for improved tumor removal and margin assessment presents an ongoing concern for the field. While near-infrared agents have long been used in imaging, investigation of these agents for use in HNC imaging has dramatically expanded in the past decade. Targeted tracers for use in primary and metastatic lymph node detection are of particular interest, with panitumumab-IRDye800 as a major candidate in current studies. This review aims to provide an overview of intraoperative near-infrared fluorescence-guided surgery techniques used in the clinical detection of malignant tissue and sentinel lymph nodes in HNC, highlighting current applications, limitations, and future directions for use of this technology within the field. Molecular Imaging-Cancer, Fluorescence © RSNA, 2024.
Topics: Humans; Head and Neck Neoplasms; Lymphatic Metastasis; Surgery, Computer-Assisted; Lymph Nodes; Optical Imaging; Fluorescent Dyes; Spectroscopy, Near-Infrared; Fluorescence
PubMed: 38940689
DOI: 10.1148/rycan.230178 -
Clinical Transplantation and Research Jun 2024Renal impairment (RI) is a frequent complication of liver cirrhosis and is associated with increased mortality and morbidity. Liver transplantation (LT) serves as an...
BACKGROUND
Renal impairment (RI) is a frequent complication of liver cirrhosis and is associated with increased mortality and morbidity. Liver transplantation (LT) serves as an effective treatment method for patients with cirrhosis who have impaired renal function. However, renal function often declines after LT, influenced by various factors. This study aimed to investigate the factors contributing to RI following LT in our cases.
METHODS
We analyzed the demographic data, preoperative and perioperative parameters, and postoperative outcomes of patients who underwent LT at the First Central Hospital of Mongolia from September 2011 to December 2022. Renal function was assessed by measuring the glomerular filtration rate using the Cockcroft-Gault creatinine clearance formula pretransplantation and at 24 hours, 72 hours, 7 days, 14 days, and 28 days post-LT.
RESULTS
Several factors increased the risk of RI among recipients. These included female sex (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.58-5.91), Child-Turcotte-Pugh (CTP) scores of B and C (OR, 4.23; 95% CI, 0.92-19.41 and OR, 7.68; 95% CI, 1.67-35.30, respectively), preoperative continuous renal replacement therapy (CRRT; OR, 5.86; 95% CI, 1.1-31.21), and a high graft-to-recipient weight ratio (GRWR; OR, 3.45; 95% CI, 1.23-9.63). Additionally, the survival rates for recipients with RI post-LT were 93.4% at 1 year and 78.1% at 3 years.
CONCLUSIONS
Female sex, a high CTP score, preoperative CRRT, and high GRWR were identified as risk factors for RI after LT in Mongolia.
PubMed: 38940688
DOI: 10.4285/ctr.24.0017 -
Clinical Cancer Research : An Official... Jun 2024To assess efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive, unresectable or recurrent/metastatic salivary gland carcinoma (URM-SGC).
PURPOSE
To assess efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive, unresectable or recurrent/metastatic salivary gland carcinoma (URM-SGC).
PATIENTS AND METHODS
This was an open-label, single-arm, multicenter phase II study for patients with AR-positive URM-SGC. The primary endpoint was the overall response rate (ORR) by an independent central radiology review (ICRR) in the first 24 response evaluable patients who had been observed at least 24 weeks from study initiation (primary RE patients). The efficacy was to be declared when at least 8 of the 24 primary RE patients responded.
RESULTS
31 patients were enrolled. In the first 24 primary RE patients with a median follow-up of 7.4 months, confirmed ORR by ICRR was 25.0% (6/24 patients; 95%CI: 9.8%-46.7%; P =0.11 (one-sided)), which did not meet the predefined criteria of efficacy. Clinical benefit rate (ORR + rate of stable disease for at least 24 weeks) and median progression-free survival were 50.0% and 7.4 months, respectively. Both median duration of response and overall survival were not reached. Exploratory analyses showed a better ORR of 54.5% (6/11) in patients with AR-positivity ≥ 70% and no history of prior systemic therapy. Grade 3 or higher treatment-emergent adverse events were reported in 35.5% (11/31), which included skin rash, anemia, leukopenia, and cancer pain.
CONCLUSIONS
Although this study did not meet the predefined efficacy criteria, apalutamide plus goserelin showed clinically meaningful efficacy in a subset of patients with AR-positive SGC and safety consistent with prior experience in prostate cancer.
PubMed: 38940667
DOI: 10.1158/1078-0432.CCR-24-0455 -
Clinical Cancer Research : An Official... Jun 2024Recurrent small cell lung cancer (SCLC) has few effective treatments. The EZH2-SLFN11 pathway is a driver of acquired chemoresistance that may be targeted.
PURPOSE
Recurrent small cell lung cancer (SCLC) has few effective treatments. The EZH2-SLFN11 pathway is a driver of acquired chemoresistance that may be targeted.
PATIENTS AND METHODS
This phase I/II trial investigated valemetostat, an EZH1/2 inhibitor, with fixed-dose irinotecan in patients with recurrent SCLC. Phase I primary objectives were to assess safety and a recommended phase II dose (RP2D). The phase II primary objective was to determine overall response rate (ORR), with secondary objectives of duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Immunohistochemistry of pre- and on-treatment tumor biopsies and pharmacokinetics analysis were performed.
RESULTS
Twenty-two patients enrolled (phase I, n=12; phase II n=10); one withdrew consent prior to treatment. Three dose-limiting toxicities (DLTs) in dose-escalation resulted in valemetostat 100 mg orally daily selected as RP2D. Among 21 toxicity-evaluable patients, the most frequent (≥20%) treatment-related adverse events were diarrhea, fatigue, nausea, and rash; 3 patients discontinued treatment for toxicity. In phase II, 3/10 patients experienced DLTs triggering a stopping rule. The ORR was 4/19 (21%, 95% CI 6 to 46%). The median DoR, PFS and OS were 4.6 mo, 2.2 mo (95% CI 1.3 to 7.6 mo) and 6.6 mo (95% CI 4.3 to not reached). SLFN11, EZH2 and SCLC subtyping markers did not correlate with response. MHC-I protein expression increased in 4/4 patients with paired biopsies, including 3/3 responders; two responders demonstrated subtype switching on treatment.
CONCLUSIONS
Valemetostat and irinotecan was not tolerated but demonstrated efficacy in recurrent SCLC. Valemetostat may warrant further investigation in SCLC.
PubMed: 38940666
DOI: 10.1158/1078-0432.CCR-23-3383 -
The Oncologist Jun 2024There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due...
BACKGROUNDS
There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer.
METHODS
Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest.
RESULTS
Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05).
CONCLUSION
ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.
PubMed: 38940446
DOI: 10.1093/oncolo/oyae134