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INTRODUCTION: This multicenter retrospective cohort study aimed to compare survival outcomes and adverse events between maintenance therapy with two poly (ADP-ribose) polymerase (PARP) inhibitors, olaparib and niraparib, in patients with BRCA-mutated, newly diagnosed advanced epithelial ovarian cancer (EOC) who responded to platinum-based chemotherapy. METHODS: We enrolled stage III-IV EOC patients with germline and/or somatic BRCA1/2 mutations that had received maintenance therapy with olaparib or niraparib. A 3:1 propensity score matching was conducted using two variables: residual disease size and the presence of germline variants. The primary outcome was progression-free survival (PFS), and the secondary outcomes were time to first subsequent therapy (TFST), overall survival (OS), and treatment-emergent adverse events (TEAEs). RESULTS: In the propensity score-matched analysis, 80 patients who received olaparib and 31 patients who received niraparib were matched (3:1). In the propensity score-matched cohort, median PFS with olaparib vs. niraparib was not reached vs 31.5 months (HR, 1.08; 95% CI, 0.47-2.52; p = 0.854). The median TFST was not reached vs 31.8 months (HR, 1.20; 95% CI, 0.51-2.81; p = 0.682), and neither olaparib nor niraparib reached the median OS (HR, 0.42; 95% CI, 0.01-17.61; p = 0.649). In terms of the incidence rates of any-grade hematologic or non-hematologic TEAEs, higher rates of thrombocytopenia (p = 0.021) and neutropenia (p = 0.011) were observed in the niraparib group. CONCLUSION: Advanced EOC patients with BRCA1/2 mutations exhibited no significant difference in OS between olaparib and niraparib, indicating the need to consider individualized strategies for selecting PARP inhibitors based on adverse event profiles.
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Indazóis , Neoplasias Ovarianas , Piperazinas , Piperidinas , Feminino , Humanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Quimioterapia de Manutenção , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Ftalazinas/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has emerged as a highly promising primary option for advanced or recurrent endometrial cancer (EC). The study aimed to evaluate treatment efficacy of ICIs with cytotoxic chemotherapy in EC. METHODS: We conducted a comprehensive review of randomized controlled trials up to November 11, 2023, focusing on immunotherapy combined with chemotherapy versus chemotherapy alone for EC. The primary endpoint was the pooled hazard ratio (HR), which was further analyzed across subgroups based on mismatch repair (MMR) status, race, histology, and programmed death-ligand 1 (PD-L1) status. The protocol was registered in PROSPERO (CRD42023475669). FINDINGS: Four trials with 2335 patients were analyzed. ICIs with chemotherapy significantly prolonged progression-free survival (PFS) (HR, 0.70; 95% CI, 0.62-0.79) and overall survival (OS) (HR, 0.75; 95% CI, 0.63-0.89) compared to chemotherapy alone. Stratification by MMR status showed substantial benefits for dMMR (PFS; HR, 0.33; 95% CI, 0.26-0.43; OS; HR, 0.37; 95% CI, 0.22-0.91) over pMMR cohorts in both PFS and OS. In the subgroup analysis, there was significant PFS advantage in Caucasian (HR, 0.63; 95% CI, 0.54-0.72) over non-Caucasian, in endometrioid histology (HR, 0.66; 95% CI, 0.56-0.78) over non-endometrioid, and in PD-L1 positive (HR, 0.39; 95% CI, 0.19-0.81) over PD-L1 negative population. INTERPRETATION: ICIs combined with platinum-based chemotherapy significantly prolonged PFS and OS in patients with advanced or recurrent EC. Patients with dMMR status, Caucasians, endometrioid histology, and positive PD-L1 status showed significant PFS benefits, emphasizing the need for personalized treatment approaches to improve outcomes.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Endométrio , Inibidores de Checkpoint Imunológico , Recidiva Local de Neoplasia , Humanos , Feminino , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Intervalo Livre de ProgressãoRESUMO
Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate pre and post operative biomarkers associated with thrombosis including deep vein thrombosis and pulmonary thromboembolism in patients treated for ovarian cancer. We collected pre and post operative blood samples from 133 patients undergoing surgery for ovarian cancer between December 2021 and August 2022. The measured parameters were white blood cell count, hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time, activated partial thromboplastin time, fibrinogen degradation products, antithrombin III, protein C, protein S, plasminogen, plasminogen activator inhibitor 1, homocysteine, N-terminal pro-brain natriuretic peptide, interleukin 6, thrombopoietin, soluble P-selectin and granulocyte stimulating factor. Body mass index of patients were collected. Differences between patients who developed thrombosis and those without were compared with Wilcoxon rank-sum test and we analyzed the continuous variables using logistic regression. Twenty-one (15.8%) patients developed thrombosis ranging from 6 to 146 days (median 15 days) after surgery. Pre operative values of homocysteine (p = 0.033) and IL-6 (p = 0.043) were significantly increased and post operative aPTT (p = 0.022) was prolonged and plasminogen (p = 0.041) was decreased in patients with thrombosis. It is important to find novel biomarkers for thrombosis to carefully manage patients who are prone to develop thrombosis despite preventive measures were applied.
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Neoplasias Ovarianas , Trombose , Humanos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/metabolismo , Trombose/etiologia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Plasminogênio , Biomarcadores , HomocisteínaRESUMO
OBJECTIVES: The treatment of fractures prioritizes the restoration of functionality through the realignment of fractured segments. Conventional methods, such as titanium plates, have been employed for this purpose; however, certain limitations have been observed, leading to the development of patient-specific plates. Furthermore, recent advancements in digital technology in dentistry enable the creation of virtual models and simulations of surgical procedures. The aim was to assess the clinical effectiveness of patient-specific plates utilizing digital technology in treating mandibular fractures compared to conventional titanium plates. MATERIALS AND METHODS: Twenty patients diagnosed with mandibular fractures were included and randomly assigned to either the study or control groups. The surgical procedure comprised reduction and internal fixation utilizing patient-specific plates generated through virtual surgery planning with digital models for the study group, while the control group underwent the same procedure with conventional titanium plates. Assessment criteria included the presence of malunion, infection, sensory disturbance, subjective occlusal disturbance and occlusal force in functional maximum intercuspation (MICP). Statistical analysis involved using the Chi-square test and one-way repeated measures analysis of variance. RESULTS: All parameters showed no statistically significant differences between the study and control groups, except for the enhancement in occlusal force in functional MICP, where a statistically significant difference was observed (p = 0.000). CONCLUSION: Using patient-specific plates using digital technology has demonstrated clinical effectiveness in treating mandibular fractures, offering advantages of time efficiency and benefits for less experienced surgeons. CLINICAL RELEVANCE: Patient-specific plates combined with digital technology can be clinically effective in mandibular fracture treatment.
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Placas Ósseas , Fixação Interna de Fraturas , Fraturas Mandibulares , Titânio , Humanos , Fraturas Mandibulares/cirurgia , Titânio/química , Masculino , Feminino , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade , Desenho Assistido por Computador , Cirurgia Assistida por Computador/métodosRESUMO
OBJECTIVES: Orthognathic surgery (OS) has evolved with technological advancements, notably through the implementation of computer-assisted orthognathic surgery (CAOS). This article aims to elucidate various types of CAOS and their efficiency and accuracy, supplemented by a thorough literature review focusing on their clinical applications in South Korea. STUDY SELECTION, DATA, AND SOURCES: A comprehensive search strategy was employed, including systematic reviews, meta-analyses, randomized controlled trials, and observational studies published until December 2023 in the PubMed, MEDLINE, and Google Scholar databases. The literature search was limited to articles written in English. RESULTS: Static CAOS demonstrated high precision, reduced operative time, and high accuracy, suggesting its potential reliability in orthognathic procedures. Dynamic CAOS presented a promising avenue for exploration, showing an accuracy comparable to that of traditional methods. The critical considerations for CAOS include accuracy, time efficiency, and cost-effectiveness. Recent studies have indicated advancements in the time efficiency of static CAOS. Static CAOS requires less equipment and is more cost-effective than dynamic CAOS. CONCLUSIONS: CAOS offers clear advantages over conventional OS in terms of surgical convenience and accuracy in implementing the surgical plan. To achieve recognition as the gold standard method for maxillofacial deformity treatment, CAOS must overcome its limitations and undergo continuous verification via well-designed studies. CLINICAL SIGNIFICANCE: The introduction of CAOS, mainly static CAOS with high precision and reduced surgical time, signifies a notable advancement in OS. However, rigorous studies are warranted to validate CAOS as the gold standard for treating maxillofacial deformities.
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Procedimentos Cirúrgicos Ortognáticos , Cirurgia Assistida por Computador , Humanos , Cirurgia Assistida por Computador/métodos , República da Coreia , Duração da CirurgiaRESUMO
BACKGROUND: This multicenter retrospective study aimed to investigate the prognostic value of the CA-125 elimination rate constant K (KELIM) in EOC patients who received platinum-based chemotherapy followed by PARP inhibitors, in either upfront or interval treatment settings. METHODS: Between July 2019 and November 2022, we identified stage III-IV EOC patients who underwent primary or interval cytoreductive surgery and received olaparib or niraparib. Individual KELIM values were assessed based on validated kinetics and classified into favorable and unfavorable cohorts. RESULTS: In a study of 252 patients undergoing frontline maintenance therapy with olaparib or niraparib, favorable KELIM (≥1) scores were associated with a higher PFS benefit in the primary cytoreductive surgery (PCS) cohort (hazard ratio (HR) for disease progression or death 3.51, 95% confidence interval (CI); 1.37-8.97, p = 0.009). Additionally, within the interval cytoreductive surgery (ICS) cohort, a favorable KELIM score (≥1) significantly increased the likelihood of achieving complete resection following cytoreductive surgery, with 59.4% in the favorable KELIM group compared to 37.8% in those with unfavorable KELIM. CONCLUSIONS: A favorable KELIM score was associated with improved PFS in patients with advanced EOC undergoing PCS. Furthermore, in the ICS cohort, a favorable KELIM score increased the probability of complete cytoreduction.
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OBJECTIVE: Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate laboratory parameters associated with deep vein thrombosis (DVT) in patients treated for ovarian cancer. METHODS: We retrospectively analyzed pre-operation laboratory data of patients with ovarian cancer for DVT at the National Cancer Center, Korea, between January 2000 and February 2021. The test items were white blood cell count, absolute neutrophil count (ANC), hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time (PT), activated partial thromboplastin time (aPTT), and body mass index (BMI). Differences between patients with and without DVT were compared with Wilcoxon rank-sum test. We analyzed the variables using logistic regression. Items with significant odds ratios were included in multivariate logistic regression. Significant variables were selected using backward elimination. Items were further categorized based on reference ranges. Univariate and multivariate analyses were performed to identify items with abnormal values associated with DVT. RESULTS: From 3,147 patient samples analyzed, 286 (9.1%) patients with DVT were selected. Differences between patients with vs without DVT were statistically significant for hemoglobin, monocyte, serum glucose, CA125, PT, aPTT, fibrinogen, D-dimer, and BMI. After univariate and multivariate analysis, monocyte, glucose, and PT remained significant. Among the categorical variables, low hemoglobin, high monocyte, high CA125, prolonged PT, and high BMI remained significant after univariate and multivariate analysis. CONCLUSION: Pre-operation laboratory data of low hemoglobin, high monocyte percentage, high serum glucose, high CA125, prolonged PT, and high BMI were associated with DVT.
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Índice de Massa Corporal , Antígeno Ca-125 , Produtos de Degradação da Fibrina e do Fibrinogênio , Fibrinogênio , Hemoglobinas , Neoplasias Ovarianas , Trombose Venosa , Humanos , Feminino , Trombose Venosa/etiologia , Trombose Venosa/sangue , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/complicações , Antígeno Ca-125/sangue , Idoso , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemoglobinas/análise , Fibrinogênio/análise , Adulto , Tempo de Tromboplastina Parcial , Glicemia/análise , Contagem de Leucócitos , Tempo de Protrombina , República da Coreia/epidemiologia , Monócitos , Período Pré-Operatório , Contagem de Plaquetas , Idoso de 80 Anos ou mais , Fatores de Risco , Proteínas de MembranaRESUMO
OBJECTIVES: Temporomandibular disorder (TMD) is a common condition that affects the temporomandibular joint (TMJ) and the muscles of the jaw, resulting in pain and dysfunction. TMD is affected by both behavioral and psychological factors. Digital therapeutics (DTx) can exert therapeutic effects by controlling behavioral factors through the delivery of appropriate interventions. Here, we report an open-label randomized control trial to evaluate the efficacy of DTx for TMD. METHODS: We recruited 40 participants diagnosed with TMD. Participants were randomly divided into an intervention group (DTx use, n = 20) and a control group (n = 20). The intervention group received the usual treatment process for TMD in addition to the use of the DTx. The control group received the usual treatments only. Patients in both groups were followed up for 3-4 weeks, and outcome data were collected and analyzed. RESULT: The intervention group showed a significant reduction in pain scores as measured by the numerical rating scale (NRS) (p = 0.016). Additionally, the intervention group showed a statistically significant increase in maximal mouth opening compared to the control group (p = 0.0079). However, there were no significant differences in improvement in the Jaw Functional Limitation Scale, Oral Behavior Checklist, and Patient Health Questionnaire-4 between the two groups (p = 0503, = 0.820, and = 0.943, respectively). CONCLUSION: This RCT reveals DTx potential in TMD, showing pain and mouth opening improvements with conventional treatment. But no significant changes were noted in other outcomes. The findings advocate for more extensive, long-term research to solidify DTx's role in TMD management. CLINICAL SIGNIFICANCE: This research underlines DTx potential to improve pain outcomes in TMD therapy, reinforcing its value as a complementary treatment modality.
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Dor Facial , Medição da Dor , Transtornos da Articulação Temporomandibular , Humanos , Feminino , Masculino , Projetos Piloto , Transtornos da Articulação Temporomandibular/terapia , Adulto , Dor Facial/terapia , Resultado do Tratamento , Pessoa de Meia-Idade , Amplitude de Movimento Articular/fisiologia , Adulto Jovem , Articulação Temporomandibular/fisiopatologia , Terapia Assistida por Computador/métodosRESUMO
OBJECTIVE: To investigate the prevalence of pathological findings and clinical outcomes of risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV). METHODS: This retrospective study enrolled asymptomatic carriers with germline HR gene PV/LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea. Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed. RESULTS: Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9-71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months. CONCLUSION: Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.
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Coating building envelopes with a passive daytime radiative cooling (PDRC) material has attracted enormous attention as an alternative cooling technique with minimal energy consumption and carbon footprint. Despite the exceptional performance and scalability of porous polymer coating (PPC), achieving consistent performance over a wide range of drying environments remains a major challenge for its commercialization as a radiative cooling paint. Herein, we demonstrate the humidity vulnerability of PPC during the drying process and propose a simple strategy to greatly mitigate the issue. Specifically, we find that the solar reflectance of the PPC rapidly decreases with increasing humidity from 30% RH, and the PPC completely losses its PDRC ability at 45% RH and even become a solar-heating material at higher humidity. However, by adding a small amount of polymer reinforcement to the PPC, it maintains its PDRC performance up to 60% RH, resulting in a 950% increase in estimated areal coverage compared to PPC in the United States. This study sheds light on a crucial consistency issue that has thus far been rarely addressed, and offers engineering guidance to handle this fundamental threat to the development of dependable PDRC paint for industrial applications.
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With the growing demand for orthognathic surgery and other facial treatments, the accurate identification of anatomical landmarks has become crucial. Recent advancements have shifted towards using three-dimensional radiologic analysis instead of traditional two-dimensional methods, as it allows for more precise treatment planning, primarily relying on direct identification by clinicians. However, manual tracing can be time-consuming, mainly when dealing with a large number of patients. This study compared the accuracy and reliability of identifying anatomical landmarks using artificial intelligence (AI) and manual identification. Thirty patients over 19 years old who underwent pre-orthodontic and orthognathic surgery treatment and had pre-orthodontic three-dimensional radiologic scans were selected. Thirteen anatomical indicators were identified using both AI and manual methods. The landmarks were identified by AI and four experienced clinicians, and multiple ANOVA was performed to analyze the results. The study results revealed minimal significant differences between AI and manual tracing, with a maximum deviation of less than 2.83 mm. This indicates that utilizing AI to identify anatomical landmarks can be a reliable method in planning orthognathic surgery. Our findings suggest that using AI for anatomical landmark identification can enhance treatment accuracy and reliability, ultimately benefiting clinicians and patients.