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BACKGROUND: Invasive mucinous adenocarcinoma (IMA) is distinct from non-mucinous adenocarcinoma, but studies on recurrent IMA are scarce. Thus, this study aimed to evaluate the recurrence patterns of IMA and the role of pulmonary local therapy (LT) in resectable pulmonary recurrence of IMA. METHODS: The study reviewed 403 patients with surgically resected IMA between 1998 and 2018. The recurrence patterns were categorized as solitary pulmonary recurrence (SPR), multiple pulmonary recurrence (MPR), and extra-pulmonary recurrence (EPR). The clinicopathologic characteristics, overall survival (OS), and post-recurrence survival (PRS) were analyzed according to the recurrence pattern and LT administration. RESULTS: Recurrences were found in 91 (22.6%) patients, including 18 patients with SPR, 37 patients with MPR, and 36 patients with EPR. Compared with the MPR and EPR groups, the SPR group had a longer disease-free interval (32.5 vs. 9.6 vs. 10.1 months, respectively; p < 0.01) and a better OS (5-year OS: 88.5%, 41.5%, and 22.9%, respectively; p < 0.01). In case of resectable pulmonary recurrence, pulmonary LT was administered to 15 patients with SPR and 3 patients with MPR. These patients showed a better 5-year PRS than the other patients with pulmonary recurrence (86.3% vs. 30.4%; p < 0.01). Notably, long-term survival was observed for one patient with MPR undergoing LT and two patients with SPR undergoing a second LT for a second pulmonary recurrence. CONCLUSIONS: In this series, the patients with recurrent IMA showed different prognoses according to the recurrence pattern. The patients with pulmonary recurrence of IMA undergoing LT showed a favorable prognosis, suggesting the potential role of LT for resectable pulmonary recurrence of IMA.
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Adenocarcinoma Mucinoso , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia/cirugía , Adenocarcinoma Mucinoso/cirugía , Pulmón/patología , Adenocarcinoma/patología , Pronóstico , Estudios RetrospectivosRESUMEN
AIMS: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for adjuvant immunotherapy and has been linked to poor differentiation in lung adenocarcinoma. However, its prevalence and prognostic role in the context of the novel histologic grade has not been evaluated. METHODS: We analysed a cohort of 1233 patients with resected lung adenocarcinoma where PD-L1 immunohistochemistry (22C3 assay) was reflexively tested. Tumour PD-L1 expression was correlated with the new standardized International Association for the Study of Lung Cancer (IASLC) histologic grading system (G1, G2, and G3). Clinicopathologic features including patient outcome were analysed. RESULTS: PD-L1 was positive (≥1%) in 7.0%, 23.5%, and 63.0% of G1, G2, and G3 tumours, respectively. PD-L1 positivity was significantly associated with male sex, smoking, and less sublobar resection among patients with G2 tumours, but this association was less pronounced in those with G3 tumours. PD-L1 was an independent risk factor for recurrence (adjusted hazard ratio [HR] = 3.25, 95% confidence intervals [CI] = 1.93-5.48, P < 0.001) and death (adjusted HR = 2.69, 95% CI = 1.13-6.40, P = 0.026) in the G2 group, but not in the G3 group (adjusted HR for recurrence = 0.94, 95% CI = 0.64-1.40, P = 0.778). CONCLUSION: PD-L1 expression differs substantially across IASLC grades and identifies aggressive tumours within the G2 subgroup. This knowledge may be used for both prognostication and designing future studies on adjuvant immunotherapy.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Antígeno B7-H1 , Neoplasias Pulmonares , Humanos , Masculino , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Prevalencia , Pronóstico , Estudios RetrospectivosRESUMEN
Despite the recognition of various molecular subtypes in small cell lung cancer (SCLC), most information has been derived from tissue microarrays or biopsy samples. Using whole sections of curatively resected SCLCs, we aimed to elucidate the clinicopathologic relevance and prognostic significance of the molecular subtypes. Whole-section immunohistochemistry was conducted for 73 resected SCLC samples using antibodies representative of molecular subtypes: ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1. Furthermore, multiplexed immunofluorescence was performed to evaluate the spatial relationship of YAP1 expression with other markers. The molecular subtype was correlated with clinical and histomorphologic features, and its prognostic role was explored in this cohort and validated in a previously published surgical cohort. Overall, the molecular subtypes were SCLC-A (54.8%), SCLC-N (31.5%), SCLC-P (6.8%), and SCLC-TN (triple negative, 6.8%). We found significant enrichment of SCLC-N (48.0%; P = .004) among combined SCLCs. Although a distinct subtype with high YAP1 expression was not found, YAP1 expression was reciprocal with ASCL1/NEUROD1 at the cellular level within tumors and was increased in areas with non-small cell-like morphology. Furthermore, the YAP1-positive SCLCs showed significantly increased recurrence at mediastinal lymph nodes (P = .047) and are an independent poor prognostic factor after surgery (adjusted hazard ratio, 2.87; 95% CI, 1.20-6.86; P = .017). The poor prognostic impact of YAP1 was also validated in the external surgical cohort. Our whole-section analysis in resected SCLCs reveals the highly heterogeneous nature of the molecular subtype and its clinicopathologic relevance. Although YAP1 is not a subtype delineator, YAP1 relates to the phenotypic plasticity of SCLC and may serve as a poor prognostic factor in resected SCLC.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/genética , Neoplasias Pulmonares/genética , Pronóstico , Modelos de Riesgos Proporcionales , Inmunohistoquímica , Regulación Neoplásica de la Expresión GénicaRESUMEN
AIMS: The prognostic role of EGFR mutations remains controversial. We aimed to evaluate the prognostic role of EGFR mutation in consideration of the IASLC histological grade in patients with resected early-stage lung adenocarcinoma. METHODS AND RESULTS: A total of 3297 patients with stages I-IIA resected lung adenocarcinoma who had had EGFR mutation tests between January 2014 and December 2019 at the Samsung Medical Center, Seoul, Korea were included. Recurrence-free survival (RFS) was compared by EGFR mutation status (EGFR-M+ versus EGFR-WT) and IASLC histological grade (G1, G2 and G3). Cox proportional hazards models were used to estimate the adjusted HRs (aHRs) and 95% confidence intervals (CIs). RESULTS: Compared to the EGFR-WT group, the EGFR-M+ group had a significantly lower proportion of G3 tumour (16 versus 33%, P < 0.001). During a median follow-up of 41.4 months, 376 patients experienced recurrence. After adjusting for histological grade, the aHR for recurrence comparing the EGFR-M+ to the EGFR-WT was 1.30 (95% CI = 1.04-1.62, P = 0.022). The EGFR-M+ group had a significantly lower 5-year RFS than the EGFR-WT group among G3 patients (58.4 versus 71.5%, P < 0.001), but not among G1 and G2 patients. CONCLUSIONS: EGFR mutation status was associated with a risk of recurrence after consideration of the IASLC histological grading, especially in G3 tumours. The results of this study would be useful for developing a new staging system and identifying a subset of patients who may benefit from adjuvant targeted therapy.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Pronóstico , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Receptores ErbB/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma/genética , Adenocarcinoma/cirugía , Mutación , Estudios RetrospectivosRESUMEN
BACKGROUND: Healthcare organisations and teams perform improvement activities to facilitate high-quality healthcare. The use of an improvement coach who provides support and guidance to the healthcare team may facilitate improvement activities; however, no systematic review exists on the facilitators and barriers to implementing an improvement coach. AIMS: We conducted a qualitative evidence synthesis to examine the facilitators and barriers to the implementation of improvement coaching. METHODS: We searched MEDLINE® , Embase and CINAHL. The final search was in March 2021. The screening eligibility criteria included the following: interdisciplinary team receiving the coaching, improvement coaching, designs with a qualitative component and primary purpose of evaluating practice facilitation in OECD countries. An ecologically-informed consolidated framework for implementation research (CFIR) served as the framework for coding. Patterns of barriers and facilitators across domains were identified through matrix analysis. Risk of bias was assessed using Critical Appraisal Skills Program. PRISMA reporting guidelines served as a guide for reporting this review. RESULTS: Nineteen studies with a qualitative component met the inclusion criteria. Four themes of barriers and facilitators crossed multiple CFIR domains: adaptability (e.g. making adjustments to the project; process, or approach); knowledge and skills (e.g. understanding of content and process for the project); engagement (e.g. willingness to be involved in the process) and resources (e.g. assets required to complete the improvement process). CONCLUSION: Improvement coaching is a complex intervention that influences the context, healthcare team being coached and improvement activities. Improvement coaches should understand how to minimise barriers and promote facilitators that are unique to each improvement project across the domains. Limitations of the study are related to the nature of the intervention including potential publication bias given quality improvement focus; the variety of terms similar to improvement coaching or selection of framework.
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Atención a la Salud , Tutoría , Humanos , Grupo de Atención al Paciente , Investigación CualitativaRESUMEN
The purpose of this study was to determine the prognostic impact of fat loss after immune checkpoint inhibitor (ICI) treatment in patients with metastatic clear cell renal cell carcinoma (ccRCC). Data from 60 patients treated with ICI therapy for metastatic ccRCC were retrospectively analyzed. Changes in cross-sectional areas of subcutaneous fat (SF) between the pre-treatment and post-treatment abdominal computed tomography (CT) images were expressed as percentages and were divided by the interval between the CT scans to calculate ΔSF (%/month). SF loss was defined as ΔSF < -5%/month. Survival analyses for overall survival (OS) and progression-free survival (PFS) were performed. Patients with SF loss had shorter OS (median, 9.5 months vs. not reached; p < 0.001) and PFS (median, 2.6 months vs. 33.5 months; p < 0.001) than patients without SF loss. ΔSF was independently associated with OS (adjusted hazard ratio (HR), 1.49; 95% confidence interval (CI), 1.07-2.07; p = 0.020) and PFS (adjusted HR, 1.57; 95% CI, 1.17-2.12; p = 0.003), with a 5%/month decrease in SF increasing the risk of death and progression by 49% and 57%, respectively. In conclusion, Loss of SF after treatment initiation is a significant and independent poor prognostic factor for OS and PFS in patients with metastatic ccRCC who receive ICI therapy.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Renales/patología , Estudios RetrospectivosRESUMEN
BACKGROUND: A culture of improvement is an important feature of high-quality health care systems. However, health care teams often need support to translate quality improvement (QI) activities into practice. One method of support is consultation from a QI coach. The literature suggests that coaching interventions have a positive impact on clinical outcomes. However, the impact of coaching on specific process outcomes, like adoption of clinical care activities, is unknown. Identifying the process outcomes for which QI coaching is most effective could provide specific guidance on when to employ this strategy. METHODS: We searched multiple databases from inception through July 2021. Studies that addressed the effects of QI coaching on process of care outcomes were included. Two reviewers independently extracted study characteristics and assessed risk of bias. Certainty of evidence was assessed using GRADE. RESULTS: We identified 1983 articles, of which 23 cluster-randomized trials met eligibility criteria. All but two took place in a primary care setting. Overall, interventions typically targeted multiple simultaneous processes of care activities. We found that coaching probably has a beneficial effect on composite process of care outcomes (n = 9) and ordering of labs and vital signs (n = 6), and possibly has a beneficial effect on changes in organizational process of care (n = 5), appropriate documentation (n = 5), and delivery of appropriate counseling (n = 3). We did not perform meta-analyses because of conceptual heterogeneity around intervention design and outcomes; rather, we synthesized the data narratively. Due to imprecision, inconsistency, and high risk of bias of the included studies, we judged the certainty of these results as low or very low. CONCLUSION: QI coaching interventions may affect certain processes of care activities such as ordering of labs and vital signs. Future research that advances the identification of when QI coaching is most beneficial for health care teams seeking to implement improvement processes in pursuit of high-quality care will support efficient use of QI resources. PROTOCOL REGISTRATION: This study was registered and followed a published protocol (PROSPERO: CRD42020165069).
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Tutoría , Mejoramiento de la Calidad , Atención a la Salud , Servicios de Salud , Humanos , Calidad de la Atención de SaludRESUMEN
BACKGROUND: De-implementation requires understanding and targeting multilevel determinants of low-value care. The objective of this study was to identify multilevel determinants of imaging for prostate cancer (PCa) and asymptomatic microhematuria (AMH), two common urologic conditions that have contributed substantially to the annual spending on unnecessary imaging in the US. METHODS: We used a convergent mixed-methods approach involving survey and interview data. Using a survey, we asked 33 clinicians (55% response-rate) to indicate their imaging approach to 8 clinical vignettes designed to elicit responses that would demonstrate guideline-concordant/discordant imaging practices for patients with PCa or AMH. A subset of survey respondents (N = 7) participated in semi-structured interviews guided by a combination of two frameworks that offered a comprehensive understanding of multilevel determinants. We analyzed the interviews using a directed content analysis approach and identified subthemes to better understand the differences and similarities in the imaging determinants across two clinical conditions. RESULTS: Survey results showed that the majority of clinicians chose guideline-concordant imaging behaviors for PCa; guideline-concordant imaging intentions were more varied for AMH. Interview results informed what influenced imaging decisions and provided additional context to the varying intentions for AMH. Five subthemes touching on multiple levels were identified from the interviews: National Guidelines, Supporting Evidence and Information Exchange, Organization of the Imaging Pathways, Patients' Clinical and Other Risk Factors, and Clinicians' Beliefs and Experiences Regarding Imaging. Imaging decisions for both PCa and AMH were often driven by national guidelines from major professional societies. However, when clinicians felt guidelines were inadequate, they reported that their decision-making was influenced by their knowledge of recent scientific evidence, past clinical experiences, and the anticipated benefits of imaging (or not imaging) to both the patient and the clinician. In particular, clinicians referred to patients' anxiety and uncertainty or patients' clinical factors. For AMH patients, clinicians additionally expressed concerns regarding legal liability risk. CONCLUSION: Our study identified comprehensive multilevel determinants of imaging to inform development of de-implementation interventions to reduce low-value imaging, which we found useful for identifying determinants of de-implementation. De-implementation interventions should be tailored to address the contextual determinants that are specific to each clinical condition.
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Encuestas y Cuestionarios , Humanos , MasculinoRESUMEN
BACKGROUND: Extensive literature support telehealth as a supplement or adjunct to in-person care for the management of chronic conditions such as congestive heart failure (CHF) and type 2 diabetes mellitus (T2DM). Evidence is needed to support the use of telehealth as an equivalent and equitable replacement for in-person care and to assess potential adverse effects. OBJECTIVE: We conducted a systematic review to address the following question: among adults, what is the effect of synchronous telehealth (real-time response among individuals via phone or phone and video) compared with in-person care (or compared with phone, if synchronous video care) for chronic management of CHF, chronic obstructive pulmonary disease, and T2DM on key disease-specific clinical outcomes and health care use? METHODS: We followed systematic review methodologies and searched two databases (MEDLINE and Embase). We included randomized or quasi-experimental studies that evaluated the effect of synchronously delivered telehealth for relevant chronic conditions that occurred over ≥2 encounters and in which some or all in-person care was supplanted by care delivered via phone or video. We assessed the bias using the Cochrane Effective Practice and Organization of Care risk of bias (ROB) tool and the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation. We described the findings narratively and did not conduct meta-analysis owing to the small number of studies and the conceptual heterogeneity of the identified interventions. RESULTS: We identified 8662 studies, and 129 (1.49%) were reviewed at the full-text stage. In total, 3.9% (5/129) of the articles were retained for data extraction, all of which (5/5, 100%) were randomized controlled trials. The CHF study (1/5, 20%) was found to have high ROB and randomized patients (n=210) to receive quarterly automated asynchronous web-based review and follow-up of telemetry data versus synchronous personal follow-up (in-person vs phone-based) for 1 year. A 3-way comparison across study arms found no significant differences in clinical outcomes. Overall, 80% (4/5) of the studies (n=466) evaluated synchronous care for patients with T2DM (ROB was judged to be low for 2, 50% of studies and high for 2, 50% of studies). In total, 20% (1/5) of the studies were adequately powered to assess the difference in glycosylated hemoglobin level between groups; however, no significant difference was found. Intervention design varied greatly from remote monitoring of blood glucose combined with video versus in-person visits to an endocrinology clinic to a brief, 3-week remote intervention to stabilize uncontrolled diabetes. No articles were identified for chronic obstructive pulmonary disease. CONCLUSIONS: This review found few studies with a variety of designs and interventions that used telehealth as a replacement for in-person care. Future research should consider including observational studies and studies on additional highly prevalent chronic diseases.
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Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Enfermedad Pulmonar Obstructiva Crónica , Telemedicina , Envío de Mensajes de Texto , Adulto , Enfermedad Crónica , HumanosRESUMEN
We report our experience in treating a ruptured dissecting posterior inferior cerebellar artery (PICA) aneurysm. To our knowledge, this is the first reported case of overlapping stenting without coils for a ruptured dissecting aneurysm of the proximal PICA. A 66-year-old male patient presented with sudden altered mental state and a subarachnoid hemorrhage (SAH). The cerebral angiography revealed a long segmental dissecting aneurysm on proximal PICA. Overlapping stents were deployed to the dissecting site, and angiogram showed intact distal PICA flow and decreased contrast staining in the dissecting site. Successful flow diversion was achieved with stents. Procedure-associated complications did not occur. The patient's postoperative course was uneventful. In follow-up cerebral angiography, dissecting aneurysm achieved complete remodeling. The decision that led to the choice of treatment is discussed.
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Disección Aórtica , Anciano , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Arterias , Angiografía Cerebral , Humanos , Masculino , Stents , Resultado del TratamientoRESUMEN
BACKGROUND: Clinical practice guidelines recommend active surveillance as the preferred treatment option for low-risk prostate cancer, but only a minority of eligible men receive active surveillance, and practice variation is substantial. The aim of this study is to describe barriers to urologists' recommendation of active surveillance in low-risk prostate cancer and explore variation of barriers by setting. METHODS: We conducted semi-structured interviews among 22 practicing urologists, evenly distributed between academic and community practice. We coded barriers to active surveillance according to a conceptual model of determinants of treatment quality to identify potential opportunities for intervention. RESULTS: Community and academic urologists were generally in agreement on factors influencing active surveillance. Urologists perceived patient-level factors to have the greatest influence on recommendations, particularly tumor pathology, patient age, and judgements about the patient's ability to adhere to follow-up protocols. They also noted cross-cutting clinical barriers, including concerns about the adequacy of biopsy samples, inconsistent protocols to guide active surveillance, and side effects of biopsy procedures. Urologists had differing opinions on the impact of environmental factors, such as financial disincentives and fear of litigation. CONCLUSIONS: Despite national and international recommendations, both academic and community urologists note a variety of barriers to implementing active surveillance in low risk prostate cancer. These barriers will need to be specifically addressed in efforts to help urologists offer active surveillance more consistently.
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Adhesión a Directriz/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Neoplasias de la Próstata/terapia , Urólogos/estadística & datos numéricos , Espera Vigilante/estadística & datos numéricos , Estudios Transversales , Femenino , Humanos , Masculino , Pautas de la Práctica en Medicina/normas , Estudios Retrospectivos , Encuestas y Cuestionarios/estadística & datos numéricos , Urólogos/normas , Espera Vigilante/normasRESUMEN
The effect of using an Intense Pulse Light system has been studied on zinc sulfide thin films and Cu(In, Ga)Se2 solar cells. The deposition of thin films on the zinc sulfide buffer layer is carried out on the glass and Cu(In, Ga)Se2 using the chemical bath deposition process. These zinc sulfide thin films were then subjected to treatment at different irradiation light intensities from 500 W to 2000 W, and then the effects on the layer were compared to a thermal annealed layer. The morphology and optical transmittance of the zinc sulfide layer were analyzed by field emission scanning electron microscopy and ultraviolet-visible spectrophotometry, respectively. This methodology was also applied to fabricate and investigate the efficiency, short-circuit current density, and external quantum efficiencies of the solar cells. This analysis shows that the treatments significantly change the properties of the zinc sulfide buffer layer and performance of the Cu(In, Ga)Se2 thin film solar cells.
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The use of dental implants in replacing missing teeth is proven to be a valid treatment with a high success rate. To achieve the best treatment outcome in all implant systems, the implant has to be able to integrate with the surrounding tissue. However, dental implants are affected by peri-implant diseases and may fail as a result. As the number of implants placed continues to increase, the prevalence of peri-implant disease will also increase. This requires preventive measures to inhibit the development of the disease and stop its progression. Clinical Relevance: Understanding how to maintain healthy peri-implant tissue as well as diagnosis and treatment of disease are vital for every dentist and dental student.
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Implantes Dentales , Periimplantitis/etiología , Estomatitis/etiología , Implantes Dentales/efectos adversos , Humanos , Oseointegración/fisiología , Periimplantitis/diagnóstico , Periimplantitis/prevención & control , Estomatitis/diagnóstico , Estomatitis/prevención & control , Análisis de SupervivenciaRESUMEN
The accurate diagnosis and classification of gliomas are essential for appropriate treatment planning and prognosis prediction. This study aimed to investigate the molecular diagnostics of IDH-wildtype diffuse astrocytic gliomas and identify potential genetic variants that could differentiate glioblastoma (GBM) from lower-grade gliomas when DNA methylation analysis is not feasible. In total, 479 H3-and IDH-wildtype diffuse astrocytic gliomas were included in this study. All the cases were diagnosed according to the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors. Panel sequencing data were collected, and clinicopathological information was retrieved from medical records. Genetic alterations and histological findings were analyzed to determine their diagnostic utility and prognostic implications. Out of 479 cases, 439 (91.6%) were diagnosed with GBM, including 28 cases that were molecularly diagnosed as GBM. However, 40 (8.4%) cases could not be classified according to the 2021 WHO classification and were diagnosed as lower-grade diffuse astrocytic glioma, IDH-wildtype, not elsewhere classified (LGNEC). In addition to the three genetic alterations included in the diagnostic criteria of GBM, PTEN and EGFR mutations were found to be enriched in GBM. Patients harboring mTOR pathway mutations demonstrated a more favorable prognosis and often exhibited morphology resembling subependymal giant cell astrocytoma, along with a high tumor mutational burden. Among patients with mTOR pathway mutations, those lacking molecular diagnostic features of GBM exhibited outstanding survival outcomes, even in the presence of grade 4 histology. Integration of molecular features enhanced the diagnostic accuracy of IDH-wildtype gliomas. Some molecular alterations enriched in GBM offer valuable insights for molecular diagnosis and glioma classification. Furthermore, high-grade diffuse astrocytic gliomas featuring mTOR pathway mutations in the absence of molecular diagnostic features of GBM could represent more favorable tumor types distinct from GBM.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Secuenciación de Nucleótidos de Alto Rendimiento , Isocitrato Deshidrogenasa , Mutación , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/diagnóstico , Adulto , Isocitrato Deshidrogenasa/genética , Glioblastoma/genética , Glioblastoma/diagnóstico , Glioblastoma/patología , Glioma/genética , Glioma/diagnóstico , Glioma/patología , Anciano , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Adulto Joven , Adolescente , Fosfohidrolasa PTEN/genética , Niño , Receptores ErbB/genética , PronósticoRESUMEN
The World Health Organization Classification of Tumors of the Central Nervous System recently incorporated histological features, immunophenotypes, and molecular characteristics to improve the accuracy of glioblastoma (GBM) diagnosis. FGFR3::TACC3 (F3T3) fusion has been identified as an oncogenic driver in IDH-wildtype GBMs. Recent studies have demonstrated the potential of using FGFR inhibitors in clinical trials and TACC3-targeting agents in preclinical models for GBM treatment. However, there is limited information on the clinicopathological and genetic features of IDH-wildtype GBMs with F3T3 fusion. The aim of this study was to comprehensively investigate the clinical manifestations, histological features, and mutational profiles of F3T3-positive GBMs. Between September 2017 and February 2023, 25 consecutive cases (5.0%) of F3T3-positive GBM were extracted from 504 cases of IDH-wildtype GBM. Clinicopathological information and targeted sequencing results obtained from 25 primary and 4 recurrent F3T3-positive GBMs were evaluated and compared with those from F3T3-negative GBMs. The provisional grades determined by histology only were distributed as follows: 4 (26/29; 89.7%), 3 (2/29; 6.9%), and 2 (1/29; 3.4%). Grade 2-3 tumors were ultimately diagnosed as grade 4 GBMs based on the identification of the TERT promoter mutation and the combined gain of chromosome 7 and loss of chromosome 10 (7+/10-). F3T3-positive GBMs predominantly affected women (2.6 females per male). The mean age of patients with an F3T3-positive GBM at initial diagnosis was 62 years. F3T3-positive GBMs occurred more frequently in the cortical locations compared to F3T3-negative GBMs. Imaging studies revealed that more than one-third (12/29; 41.4%) of F3T3-positive GBMs displayed a circumscribed tumor border. Seven of the seventeen patients (41.2%) whose follow-up periods exceeded 20 months died of the disease. Histologically, F3T3-positive GBMs more frequently showed curvilinear capillary proliferation, palisading nuclei, and calcification compared to F3T3-negative GBMs. Molecularly, the most common alterations observed in F3T3-positive GBMs were TERT promoter mutations and 7+/10-, whereas amplifications of EGFR, PDGFRA, and KIT were not detected at all. Other genetic alterations included CDKN2A/B deletion, PTEN mutation, TP53 mutation, CDK4 amplification, and MDM2 amplification. Our observations suggest that F3T3-positive GBM is a distinct molecular subgroup of the IDH-wildtype GBM. Both clinicians and pathologists should consider this rare entity in the differential diagnosis of diffuse astrocytic glioma to make an accurate diagnosis and to ensure appropriate therapeutic management.
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Digital health technologies (DHTs) have the potential to modernize drug development and clinical trial operations by remotely, passively, and continuously collecting ecologically valid evidence that is meaningful to patients' lived experiences. Such evidence holds potential for all drug development stakeholders, including regulatory agencies, as it will help create a stronger evidentiary link between approval of new therapeutics and the ultimate aim of improving patient lives. However, only a very small number of novel digital measures have matured from exploratory usage into regulatory qualification or efficacy endpoints. This shows that despite the clear potential, actually gaining regulatory agreement that a new measure is both fit-for-purpose and delivers value remains a serious challenge. One of the key stumbling blocks for developers has been the requirement to demonstrate that a digital measure is meaningful to patients. This viewpoint aims to examine the co-evolution of regulatory guidance in the United States (U.S.) and best practice for integration of DHTs into the development of clinical outcome assessments. Contextualizing guidance on meaningfulness within the larger shift towards a patient-centric drug development approach, this paper reviews the U.S. Food and Drug Administration (FDA) guidance and existing literature surrounding the development of meaningful digital measures and patient engagement, including the recent examples of rejections by the FDA that further emphasize patient-centricity in digital measures. Finally, this paper highlights remaining hurdles and provides insights into the established frameworks for development and adoption of digital measures in clinical research.
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INTRODUCTION: Accurate diagnostic criteria for tumor invasion are essential for precise pathologic tumor (pT) staging. Recently, the International Association for the Study of Lung Cancer (IASLC) Pathology Committee suggested a new set of criteria for assessing tumor invasion, but the clinical usefulness of the proposed criteria has not been evaluated. METHODS: The study included 1295 patients with resected part-solid lung adenocarcinoma from January 2017 to December 2019 at the Samsung Medical Center, Seoul, Korea. The revised pT stage was determined by the extent of the newly measured invasive component using the IASLC criteria. The primary outcome was to compare the performance of the revised pT stage with the original pT stage in predicting recurrence-free survival and proof of invasion status (i.e., recurrence or lymph node metastasis). The secondary outcome was the correlation with radiologic surrogates of tumor invasiveness (consolidation-to-tumor ratio and maximum standardized uptake value) and pathologic risk factors. RESULTS: The re-evaluation resulted in a 22% downstaging and 2.5% upstaging of pT, which improved the correlation with radiologic (consolidation-to-tumor ratio and maximum standardized uptake value) and pathologic risk factors. The revised pT staging allowed for more accurate discrimination of recurrence-free survival than the original pT staging (c-index = 0.794 versus 0.717). Moreover, the revised pT staging significantly improved the prediction of recurrence or lymph node metastasis (area under the curve = 0.818 versus 0.741, p < 0.001). CONCLUSIONS: To our knowledge, this is the first study evaluating the clinical significance of the IASLC-proposed criteria for invasion. The proposed IASLC criteria offered better alignment with clinicopathologic risk factors and improved prognostication. Further studies are warranted to assess the impact of the IASLC criteria on treatment decisions and patient outcomes.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Metástasis Linfática , Relevancia Clínica , Adenocarcinoma del Pulmón/cirugía , Adenocarcinoma del Pulmón/patología , Adenocarcinoma/cirugía , Estadificación de Neoplasias , Invasividad Neoplásica/patología , Estudios Retrospectivos , PronósticoRESUMEN
Purpose: To develop an MRI-based radiomics model to predict high-risk pathologic features for lung adenocarcinoma: micropapillary and solid pattern (MPsol), spread through air space (STAS), and poorly differentiated patterns. Materials and Methods: As a prospective study, we screened clinical N0 lung cancer patients who were surgical candidates and had undergone both 18F-fluorodeoxyglucose (FDG) positron emission tomography-CT (PET/CT) and chest CT from August 2018 to January 2020. We recruited patients meeting our proposed imaging criteria indicating high-risk, that is, poorer prognosis of lung adenocarcinoma, using CT and FDG PET/CT. If possible, these patients underwent an MRI examination from which we extracted 77 radiomics features from T1-contrast-enhanced and T2-weighted images. Additionally, patient demographics, SUVmax (maximum standardized uptake value) on FDG PET/CT, and the mean ADC value on DWI, were considered together to build prediction models for high-risk pathologic features. Results: Among 616 patients, 72 patients met the imaging criteria for high-risk lung cancer and underwent lung MRI. The MR-eligible group showed a higher prevalence of nodal upstaging (29.2% vs. 4.2%, p<0.001), vascular invasion (6.5% vs. 2.1%, p=0.011), high-grade pathologic features (p<0.001), worse 4-year disease free survival (p<0.001) compared with non-MR-eligible group. The prediction power for MR-based radiomics model predicting high-risk pathologic features was good, with mean area under the receiver operating curve (AUC) value measuring 0.751-0.886 in test sets. Adding clinical variables increased the predictive performance for MPsol and the poorly differentiated pattern using the 2021 grading system (AUC 0.860 and 0.907, respectively). Conclusion: Our imaging criteria can effectively screen high-risk lung cancer patients and predict high-risk pathologic features by our MR-based prediction model using radiomics.
RESUMEN
OBJECTIVES: The use of tumor-informed circulating tumor DNA (ctDNA) testing in patients with early-stage disease before surgery is limited, mainly owing to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected NSCLC. METHOD: We analyzed presurgical plasma samples from 895 patients with EGFR and anaplastic lymphoma kinase-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histologic diagnosis, histologic subtypes, and clinical-to-pathologic TNM upstaging. RESULTS: Presurgical ctDNA detection was observed in 55 of 414 patients (13%) with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (2-year recurrence-free survival 69% versus 91%; log-rank p < 0.001), approaching that of clinical stage II LUAD. Presurgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict presurgical ctDNA detection. Moreover, presurgical ctDNA detection was predictive of the postsurgical discovery of International Association for the Study of Lung Cancer grade 3 tumors (p < 0.001) and pathologic TNM upstaging (p < 0.001). Notably, presurgical ctDNA detection strongly correlated with higher programmed death-ligand 1 expression in tumors (positive rates 28% versus 55%, p < 0.001), identifying a subgroup likely to benefit from anti-programmed death-ligand 1 therapies. CONCLUSION: These findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need for tumor tissue profiling. Furthermore, it is clinically useful in identifying patients at high risk who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.