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1.
Head Neck ; 44(9): 2030-2039, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35915863

RESUMO

BACKGROUND: Optimal treatment strategies for patients with stage IVa-b hypopharyngeal squamous cell carcinoma (HSCC) remain controversial. This study aimed to examine the high-risk factors of postoperative tumor recurrence after surgical resection of HSCC and devise individualized postoperative adjuvant treatment (POAT). METHODS: Overall, 218 patients with stage IVa-b HSCC who received surgery as initial treatment and with negative surgical margins were evaluated. Independent risk factors of recurrence were identified, and survival outcomes were compared according to recurrence risk and POAT use. RESULTS: POAT significantly improved recurrence-free survival (RFS) and overall survival (OS) only in the high-risk patients (p = 0.003 and 0.018, respectively). Compared with postoperative radiotherapy alone, postoperative chemoradiotherapy (pCRT) achieved significantly better RFS (p = 0.035) and OS (p = 0.048). CONCLUSIONS: POATs are recommended for high-risk patients with stage Iva-b HSCC, with pCRT achieving superior outcomes. Regular re-examination after tumor resection is sufficient for low-risk patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Hipofaríngeas , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Hipofaríngeas/patologia , Melanoma , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco , Neoplasias Cutâneas , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
2.
Nat Commun ; 13(1): 4517, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922426

RESUMO

Deciphering Multiple Myeloma evolution in the whole bone marrow is key to inform curative strategies. Here, we perform spatial-longitudinal whole-exome sequencing, including 140 samples collected from 24 Multiple Myeloma patients during up to 14 years. Applying imaging-guided sampling we observe three evolutionary patterns, including relapse driven by a single-cell expansion, competing/co-existing sub-clones, and unique sub-clones at distinct locations. While we do not find the unique relapse sub-clone in the baseline focal lesion(s), we show a close phylogenetic relationship between baseline focal lesions and relapse disease, highlighting focal lesions as hotspots of tumor evolution. In patients with ≥3 focal lesions on positron-emission-tomography at diagnosis, relapse is driven by multiple distinct sub-clones, whereas in other patients, a single-cell expansion is typically seen (p < 0.01). Notably, we observe resistant sub-clones that can be hidden over years, suggesting that a prerequisite for curative therapies would be to overcome not only tumor heterogeneity but also dormancy.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Filogenia , Tomografia por Emissão de Pósitrons , Sequenciamento Completo do Exoma
3.
Nat Commun ; 13(1): 4587, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933466

RESUMO

The tumour stroma, and in particular the extracellular matrix (ECM), is a salient feature of solid tumours that plays a crucial role in shaping their progression. Many desmoplastic tumours including breast cancer involve the significant accumulation of type I collagen. However, recently it has become clear that the precise distribution and organisation of matrix molecules such as collagen I is equally as important in the tumour as their abundance. Cancer-associated fibroblasts (CAFs) coexist within breast cancer tissues and play both pro- and anti-tumourigenic roles through remodelling the ECM. Here, using temporal proteomic profiling of decellularized tumours, we interrogate the evolving matrisome during breast cancer progression. We identify 4 key matrisomal clusters, and pinpoint collagen type XII as a critical component that regulates collagen type I organisation. Through combining our proteomics with single-cell transcriptomics, and genetic manipulation models, we show how CAF-secreted collagen XII alters collagen I organisation to create a pro-invasive microenvironment supporting metastatic dissemination. Finally, we show in patient cohorts that collagen XII may represent an indicator of breast cancer patients at high risk of metastatic relapse.


Assuntos
Neoplasias da Mama , Colágeno Tipo XII/metabolismo , Metástase Neoplásica , Microambiente Tumoral , Neoplasias da Mama/patologia , Colágeno , Colágeno Tipo I , Matriz Extracelular/patologia , Feminino , Humanos , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Proteômica
4.
Sci Rep ; 12(1): 13548, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941209

RESUMO

The extent of surgery among patients with T2 papillary thyroid carcinoma (PTC) remains controversial. Thus, we herein aimed to evaluate the risk factors for recurrence, particularly based on the extent of surgery, among patients with T2 PTC at a single tertiary institution. We assessed 251 patients who underwent thyroid surgery for T2 PTC from January 2009 to December 2014 at Seoul St. Mary's Hospital (Seoul, Korea). The mean follow-up duration was 100.7 months. Eleven (4.4%) patients had recurrence. The recurrence rates did not significantly differ in terms of the extent of surgery (p = 0.868). Patients with a high lymph node ratio (LNR) had a significantly higher recurrence rate than those with a low LNR (p < 0.001). According to a recurrence pattern analysis, five of six patients in the lobectomy group had recurrence in the ipsilateral lateral compartment. A multivariate analysis revealed that a high LNR was a significant risk factor for recurrence (hazard ratio: 11.025, p = 0.002). Our results suggest that patients without clinical evidence of any lymph node metastases and those with limited lesions in the thyroid gland can undergo lobectomy and LNR can serve as an independent risk factor for predicting recurrence in T2 PTC.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Humanos , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia
5.
PLoS One ; 17(8): e0272696, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35944056

RESUMO

INTRODUCTION: According to the World Health Organization, the tall cell variant (TCV) is an aggressive subtype of papillary thyroid carcinoma (PTC) comprising at least 30% epithelial cells two to three times as tall as they are wide. In practice, applying this definition is difficult causing substantial interobserver variability. We aimed to train a deep learning algorithm to detect and quantify the proportion of tall cells (TCs) in PTC. METHODS: We trained the deep learning algorithm using supervised learning, testing it on an independent dataset, and further validating it on an independent set of 90 PTC samples from patients treated at the Hospital District of Helsinki and Uusimaa between 2003 and 2013. We compared the algorithm-based TC percentage to the independent scoring by a human investigator and how those scorings associated with disease outcomes. Additionally, we assessed the TC score in 71 local and distant tumor relapse samples from patients with aggressive disease. RESULTS: In the test set, the deep learning algorithm detected TCs with a sensitivity of 93.7% and a specificity of 94.5%, whereas the sensitivity fell to 90.9% and specificity to 94.1% for non-TC areas. In the validation set, the deep learning algorithm TC scores correlated with a diminished relapse-free survival using cutoff points of 10% (p = 0.044), 20% (p < 0.01), and 30% (p = 0.036). The visually assessed TC score did not statistically significantly predict survival at any of the analyzed cutoff points. We observed no statistically significant difference in the TC score between primary tumors and relapse tumors determined by the deep learning algorithm or visually. CONCLUSIONS: We present a novel deep learning-based algorithm to detect tall cells, showing that a high deep learning-based TC score represents a statistically significant predictor of less favorable relapse-free survival in PTC.


Assuntos
Carcinoma Papilar , Aprendizado Profundo , Neoplasias da Glândula Tireoide , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Humanos , Recidiva Local de Neoplasia/patologia , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia
6.
Front Immunol ; 13: 920253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911687

RESUMO

Background: Patients with early-stage laryngeal cancer, even stage T1-2N0, are at considerable risk of recurrence and death. The genetic and immunologic characteristics of recurrent laryngeal cancer remain unclear. Methods: A total of 52 T1-2N0 laryngeal cancer patients were enrolled. Of these, 42 tissue samples were performed by targeted DNA sequencing, and 21 cases were performed by NanoString immuno-oncology targeted RNA sequencing to identify the distinct molecular bases and immunologic features associated with relapse in patients with early laryngeal cancer, respectively. Results: To the best to our knowledge, we present for the first time an overview of the genomic mutation spectrum of early-stage laryngeal cancers. A total of 469 genomic alterations were detected in 211 distinct cancer-relevant genes, and the genes found to be mutated in more than five patients (>10%) included tumor protein p53 (TP53, 78.5%), FAT atypical cadherin 1 (FAT1, 26%), LDL receptor related protein 1B (LRP1B, 19%), cyclin dependent kinase inhibitor 2A (CDKN2A, 17%), tet methylcytosine dioxygenase 2 (TET2, 17%), notch receptor 1 (NOTCH1, 12%) and neuregulin 1 (NRG1, 12%). Recurrent laryngeal cancer demonstrated a higher tumor mutation burden (TMB), as well as higher LRP1B mutation and NOTCH1 mutation rates. Univariate and multivariate analyses revealed that high TMB (TMB-H) and NOTCH1 mutation are independent genetic factors that are significantly associated with shorter relapse-free survival (RFS). Simultaneously, the results of the transcriptome analysis presented recurrent tumors with NOTCH1 mutation displayed upregulation of the cell cycle pathway, along with decreased B cells score, T cells score, immune signature score and tumor-infiltrating lymphocytes (TILs) score. The Cancer Genome Atlas (TCGA)-laryngeal cancer dataset also revealed weakened immune response and impaired adhesion functions in NOTCH1-mutant patients. Conclusions: Genomic instability and impaired immune response are key features of the immunosurveillance escape and recurrence of early laryngeal cancer after surgery. These findings revealed immunophenotypic attenuation in recurrent tumors and provided valuable information for improving the management of these high-risk patients. Due to the small number of patients in this study, these differences need to be further validated in a larger cohort.


Assuntos
Neoplasias Laríngeas , Receptor Notch1 , Inibidor p16 de Quinase Dependente de Ciclina , Humanos , Imunidade/genética , Neoplasias Laríngeas/complicações , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/cirurgia , Mutação , Recidiva Local de Neoplasia/patologia , Receptor Notch1/genética , Receptor Notch1/imunologia
7.
BMC Cancer ; 22(1): 875, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948946

RESUMO

OBJECTIVE: We studied the prognosis and clinicopathological background of lung adenocarcinoma predominance among patients who underwent lobectomy using data from the Japanese Joint Committee of Lung Cancer Registry. METHODS: Two thousand eight hundred sixty-three cases were extracted. Recurrence free survival (RFS) rates, overall survival (OS) rates and clinicopathological factors and epidermal growth factor receptor (EGFR) mutation status were examined. RESULTS: Median follow-up period was 65.5 months. Adenocarcinoma predominance was sub-grouped according to OS and RFS rate. In pathological stage I, 5-year RFS and OS rates were respectively 92.2% and 95.8% in group A (adenocarcinoma-in-situ + minimally invasive adenocarcinoma), 89.3% and 92.1% in group B (lepidic), 79.2% and 89.7% in group C (papillary + acinar + variants) and 69.0% and 79.0% in group D (solid + micropapillary). In pathological stage II + IIIA, they were, 43.6% and 72.4% in B, 39.5% and 66.9% in C and 31.0% and 53.7% in D. Group D showed significant worst outcome both in stage I and II + IIIA. Up stage rate from clinical stage I to pathological stage II + IIIA was 0.0%, 3.7%, 15.9% and 33.3%. The frequency of lymph-vessel, vascular, pleura invasion and positive EGFR mutation were 0.0%, 0.0%, 0.0% and 57.1% in group A, 15.6%, 10.0%, 12.1% and 55.1% in B, 36.6%, 31.8%, 29.7% and 44.9% in C, 50.2%, 57.8%, 38.9% and 21.3% in D. In group D, lymph-vessel, vascular and pleura invasion were most, EGFR mutation was least frequent not only in pathological stage I but also stage II + IIIA. In multivariate analysis, age, pathological stage, vascular invasion, and group D were independent factors affected RFS and OS. CONCLUSION: Limited to lobectomy cases, solid + micropapillary was independent prognostic factor both in early and locally advanced stage. Its malignant degree was related to the frequency of pathological invasive factors and EGFR mutation status.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Receptores ErbB/genética , Humanos , Japão/epidemiologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Sistema de Registros , Estudos Retrospectivos
8.
Sci Transl Med ; 14(656): eabn1128, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35921473

RESUMO

Glioblastoma multiforme (GBM) remains incurable despite aggressive implementation of multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin around the initial resected lesion due to postsurgery residual glioma stem cells (GSCs). Tracking and eradicating postsurgery residual GSCs is critical for preventing postoperative relapse of this devastating disease, yet effective strategies remain elusive. Here, we report a cavity-injectable nanoporter-hydrogel superstructure that creates GSC-specific chimeric antigen receptor (CAR) macrophages/microglia (MΦs) surrounding the cavity to prevent GBM relapse. Specifically, we demonstrate that the CAR gene-laden nanoporter in the hydrogel can introduce GSC-targeted CAR genes into MΦ nuclei after intracavity delivery to generate CAR-MΦs in mouse models of GBM. These CAR-MΦs were able to seek and engulf GSCs and clear residual GSCs by stimulating an adaptive antitumor immune response in the tumor microenvironment and prevented postoperative glioma relapse by inducing long-term antitumor immunity in mice. In an orthotopic patient-derived glioblastoma humanized mouse model, the combined treatment with nanoporter-hydrogel superstructure and CD47 antibody increased the frequency of positive immune responding cells and suppressed the negative immune regulating cells, conferring a robust tumoricidal immunity surrounding the postsurgical cavity and inhibiting postoperative glioblastoma relapse. Therefore, our work establishes a locoregional treatment strategy for priming cancer stem cell-specific tumoricidal immunity with broad application in patients suffering from recurrent malignancies.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Receptores de Antígenos Quiméricos , Animais , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Glioblastoma/genética , Glioma/patologia , Glioma/terapia , Hidrogéis , Macrófagos/patologia , Camundongos , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/patologia , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
9.
J Natl Compr Canc Netw ; 20(8): 866-878, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35948037

RESUMO

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non-muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non-muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody-drug conjugates for metastatic bladder cancer.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Administração Intravesical , Carcinoma de Células de Transição/patologia , Humanos , Masculino , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/terapia
10.
Medicine (Baltimore) ; 101(31): e29929, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35945736

RESUMO

OBJECTIVE: We meta-analyzed available evidence on fertility, survival, and cancer recurrence in patients with stage I epithelial ovarian cancer (EOC) after fertility-sparing surgery (FSS). METHODS: We systematically reviewed PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials to identify studies reporting reproductive and oncological outcomes of patients with stage I EOC who underwent FSS. Random-effects models were used to calculate pooled rates of disease outcomes, along with 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to identify sources of heterogeneity in the data. RESULTS: We included 23 observational retrospective studies involving 1126 patients. The pooled pregnancy rate was 30% (95% CI, 0.26-0.34), while the pooled natural conception rate was 26% (95% CI, 0.20-0.33). The pooled live birth rate was 27% (95% CI, 0.22-0.32). The pooled rate of EOC recurrence was 12% (95% CI, 0.09-0.14), which did not differ significantly from the rate among patients who underwent radical surgery (odds ratio, 0.77; 95% CI, 0.45-1.33). CONCLUSIONS: FSS is associated with good oncological outcomes but less than satisfactory reproductive outcomes. All in all, the procedure appears to be a safe alternative to radical surgery for EOC patients who want to preserve fertility.


Assuntos
Preservação da Fertilidade , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Feminino , Preservação da Fertilidade/métodos , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Gravidez , Estudos Retrospectivos
11.
Medicine (Baltimore) ; 101(31): e29727, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35945757

RESUMO

There are debates on the management of immature ovarian teratoma and its recurrence. This study aimed to report the incidence of pelvic masses after surgery for immature ovarian teratoma and to identify prognostic factors of disease-free survival after surgery, discussing aspects of primary treatment and postoperative management. Data on the diagnosis and treatment of patients with immature teratomas were collected. Follow-up data were acquired from clinic visits and telephone interviews. Disease-free survival was defined as the time interval between the initial surgery for immature ovarian teratoma and the diagnosis of a new pelvic mass. Survival curves were drawn using the Kaplan-Meire method, and multivariate analysis was performed using the Cox proportional hazard regression model using PASW statistics software. The estimated 5-year disease-free survival and overall survival were 74.3% (95%CI 63.9%-84.7%) and 96.5% (95%CI 91.6%-100.0%), respectively. The incidence of growing teratoma syndrome and immature teratoma relapse at a median follow-up of 46 months were 20.0% and 7.7%, respectively. Two patients died of repeated relapses or repeated growing teratoma syndrome. Rupture of initial lesions (RR 4.010, 95%CI 1.035-5.531), lymph node dissection (RR 0.212, 95%CI 0.051-0.887) and adjuvant chemotherapy (RR 0.143, 95%CI 0.024-0.845) were independent prognostic factors for disease-free survival. The development of growing teratoma syndrome is more prevalent than relapse after treatment of immature ovarian teratomas. Lymph node dissection and chemotherapy are recommended to reduce recurrence. Close surveillance and active surgical intervention are important for the diagnosis and appropriate management of new pelvic masses.


Assuntos
Anormalidades do Sistema Digestório , Neoplasias Ovarianas , Teratoma , Intervalo Livre de Doença , Feminino , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/cirurgia , Recidiva , Síndrome , Teratoma/diagnóstico , Teratoma/epidemiologia , Teratoma/cirurgia
12.
Zhonghua Yi Xue Za Zhi ; 102(26): 1999-2004, 2022 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-35817724

RESUMO

Objective: To explore the clinical prognosis and fertility outcomes in patients with borderline ovarian tumors (BOT) who underwent fertility-sparing surgery, and evaluate the related risk factors. Methods: The study examined the clinicopathological characteristics of 280 patients diagnosed with BOT from Qilu Hospital of Shandong University between January 2009 and December 2019. According to the surgery plan, the patients were divided into the fertility-sparing group (167 cases) and the radical surgery group (113 cases). The information of the patients' age, preoperative serum CA-125 level, surgery method, pathological type, FIGO stage (2014), tumor location, and whether focal canceration combined were collected. The Kaplan-Meier method was used to compare disease-free survival (DFS) between the fertility-sparing surgery group and the radical surgery group. The univariate and multivariate Cox proportional hazard regression analysis was used to explore high-risk factors associated with DFS. Results: A total of 280 BOT patients were identified in the study, with a median age of 35.0 (26.0, 51.0) years old. The median follow-up time was 55.2 (34.7, 79.3)months. 25 patients (15.0%) developed recurrence in the fertility-sparing surgery group, 11 patients (8.7%) developed recurrence in the radical surgery group. There was no significant difference in 5-year DFS rate between the two groups (84.4% vs 90.1%, P=0.223). Only FIGO stage was found to be related to DFS through the univariable and multivariable Cox proportional hazard regression analysis, and patients with FIGO Ⅱ/Ⅲ had higher risk of recurrence [HR (95%CI) 2.872(1.283-6.431)] (P=0.010); Fertility-sparing surgery does not increase the recurrence risk of BOT patients (P=0.116). Pregnancies were reported in 39 patients (54.2%), among whom 37 patients gave birth successfully, and 2 patients selected to terminate pregnancy. Conclusions: The fertility-sparing surgery does not increase the risk of recurrence in BOT patients, and patients who underwent the fertility-sparing surgery have a favorable outcome. FIGO stage is the independent risk factor of DFS in BOT patients.


Assuntos
Neoplasias Ovarianas , Feminino , Fertilidade , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Gravidez , Prognóstico , Estudos Retrospectivos
13.
Future Oncol ; 18(24): 2639-2649, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35815644

RESUMO

Poorly differentiated neuroendocrine carcinomas such as small-cell lung cancer (SCLC) have poor survival and high relapse rates. DLL3 is found on these carcinomas and has become a target of increasing interest in recent years. The bispecific DLL3/CD3 T-cell engager BI 764532 has been shown to induce complete tumor regression in a human T cell-engrafted mouse model. Here, we describe the study design of a first-in-human, phase I, multicenter, open-label, non-randomized, dose-escalation study in patients with SCLC or other DLL3-positive neuroendocrine carcinomas. The study will determine the maximum tolerated dose and evaluate safety, tolerability, pharmacokinetics and preliminary efficacy of BI 764532 monotherapy.


DLL3 is a protein involved in development of the embryo during pregnancy. It has also been found on the surface of cells involved in the development of certain types of lung cancer and other tumors. The T-cell engager BI 764532 binds to DLL3 and cells of the immune system simultaneously, resulting in the death of tumor cells. Here we describe the rationale for, and design of, a clinical study of BI 764532 in patients with small-cell lung cancer and other tumors containing DLL3. The aim of the study is to find the highest acceptable dose of BI 764532 that can be tolerated by patients, and explore the safety and efficacy of BI 764532. Clinical Trial Registration: NCT04429087 (ClinicalTrials.gov).


Assuntos
Anticorpos Biespecíficos , Carcinoma Neuroendócrino , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Animais , Anticorpos Biespecíficos/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Ensaios Clínicos Fase I como Assunto , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Camundongos , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/patologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética , Linfócitos T
14.
J Natl Compr Canc Netw ; 20(7): 845-849, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35830885

RESUMO

Retroperitoneal sarcoma comprises a small subset of all soft tissue sarcoma and includes various histopathologic subtypes, each with unique patterns of behavior and differential risks for local recurrence and hematogenous metastatic spread. The primary treatment modality is surgery, although even with complete macroscopic resection, recurrence is common. The rationale for the addition of radiotherapy to resection is to improve local control; however, the use of radiation therapy for retroperitoneal sarcoma is controversial, and existing data are suboptimal to guide management. Treatment decisions should be determined with multidisciplinary input and shared decision-making. When used in selected patients, radiation therapy should be delivered preoperatively; postoperative treatment is not recommended.


Assuntos
Neoplasias Retroperitoneais , Sarcoma , Neoplasias de Tecidos Moles , Terapia Combinada , Humanos , Recidiva Local de Neoplasia/patologia , Neoplasias Retroperitoneais/radioterapia , Sarcoma/patologia , Sarcoma/radioterapia
15.
Can J Gastroenterol Hepatol ; 2022: 3421078, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35775069

RESUMO

Background: Patients with early gastric cancer undergoing noncurative endoscopic submucosal dissection (ESD) have a risk of tumor recurrence and metastasis, and some patients need additional surgery. The purpose of this study was to explore the risk factors of cancer residue and lymph node (LN) metastasis after noncurative ESD for early gastric cancer and to compare the short outcome of early and delayed additional surgery. Methods: The clinicopathological characteristics of 30 early gastric cancer patients who received noncurative ESD and additional surgery were studied retrospectively. Multivariable regression was utilized to examine the independent risk factors for residual cancer and LN metastasis. Receiver operating characteristic curve was used to analyze the multivariable model's predictive performance. Furthermore, the perioperative safety and radical tumor performance of early surgery (≤30 days, n = 11), delayed surgery (>30 days, n = 11) after ESD, and upfront surgery (n = 59) were compared. Results: Multivariable regression showed that diffuse type of Lauren classification, submucosal invasion, and positive human epidermal growth factor receptor-2 (HER-2) were risk factors for residual cancer. Undifferentiated carcinoma, vascular invasion, and positive vertical margin were risk factors for LN metastasis. The area under the curve (AUC) of the multifactor model predicting cancer residue and LN metastasis was 0.761 and 0.792, respectively. The early surgery group experienced higher intraoperative blood loss and a longer operation time than the delayed surgery and upfront surgery groups. There was no significant difference in the number of LN dissections, LN metastasis rate, and postoperative complications among the three groups. Conclusion: Diffuse type of Lauren classification, submucosal invasion, and positive HER-2 are risk factors for residual cancer, while undifferentiated carcinoma, vascular invasion, and positive vertical margin are risk factors for LN metastasis. Delayed additional surgery after ESD (>30 days) has higher intraoperative safety, without affecting the radical resection in early gastric cancer patients.


Assuntos
Carcinoma , Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Carcinoma/patologia , Ressecção Endoscópica de Mucosa/efeitos adversos , Gastrectomia/efeitos adversos , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Humanos , Metástase Linfática/patologia , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Neoplasia Residual/cirurgia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
17.
Sci Rep ; 12(1): 12477, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864130

RESUMO

Peritoneal dissemination is a common form of gastric cancer (GC) recurrence, despite surgery with curative intent. This study aimed to evaluate the prognostic value of intraperitoneal lavage One-Step Nucleic Acid Amplification (OSNA) assay in advanced GC patients. OSNA assay targeting CK-19 mRNA was applied to detect free cancer cells (FCC) in intraperitoneal lavage samples obtained during gastrectomy. A total of 82 GC patients were enrolled to investigate the correlation between OSNA assay and patient's prognosis. Of the 82 patients, OSNA assay was positive in 25 (30.5%) patients. The median OS in OSNA positive patients was significantly lower than in OSNA negative patients (19 vs 45 months). Positive OSNA assay result was a significant unfavourable prognostic factor in both, univariable (HR 3.45, 95% CI 0.95-12.48; p = 0.0030) and multivariable analysis (HR 3.10, 95% CI 1.22-8.54; p = 0.0298). Positive OSNA assay in intraperitoneal lavage is a valuable indicator of poor survival in advanced GC patients after multimodal treatment. After further confirmation on larger sample size, OSNA assay of peritoneal washings could be considered an adjunct tool to conventional cytology, the current gold standard, to provide precise intraoperative staging and additional prognostic information.


Assuntos
Neoplasias Gástricas , Humanos , Queratina-19/genética , Metástase Linfática , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Técnicas de Amplificação de Ácido Nucleico , Prognóstico , RNA Mensageiro/genética , Biópsia de Linfonodo Sentinela , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia
18.
Front Biosci (Landmark Ed) ; 27(7): 208, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35866394

RESUMO

BACKGROUND: Disseminated tumor cells (DTCs) in bone marrow aspirates of patients with primary breast cancer may serve as independent prognostic markers associated with impaired survival. Due to limited therapy options and high risk of recurrence particularly, women diagnosed with the aggressive triple negative breast cancer (TNBC) require personalized treatment choices. Genetic profiling of circulating cell-free tumor DNA (ctDNA) might help to find individual treatment options and to monitor disease course. METHODS: Here we report the case of a 66-year-old patient with TNBC. She received neoadjuvant chemotherapy (NACT) that had to be interrupted due to intolerance. Surgical resection of the residual tumor resulted in pathologic complete response (pCR), though. RESULTS: Bone marrow aspiration during surgery revealed an unusual high number of DTCs and thus elevated risk for recurrence. Analysis of pre-surgical blood and urine samples revealed the presence of plasma-derived and urinary ctDNA after NACT and indicated poor prognosis. Subsequent targeted sequencing showed that pathogenic variants occurred in urinary and plasma-derived ctDNA emphasizing the potential of liquid biopsy usage for early detection of relapse. Despite the detection of residual molecular disease after NACT, the presented patient reached pCR and could benefit from standard treatment until present. CONCLUSIONS: In this case, liquid biopsy based biomarkers did not necessarily correlate to clinical outcome. Further, ctDNA analysis did not reveal approved therapeutic options to target the identified pathogenic variants. Adjuvant bisphosphonate treatment was applied based on the positive DTC status and may improve the patients' prognosis. Further investigations are required to identify TNBC patients at risk for recurrence.


Assuntos
Neoplasias da Mama , DNA Tumoral Circulante , Células Neoplásicas Circulantes , Neoplasias de Mama Triplo Negativas , Idoso , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Feminino , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Células Neoplásicas Circulantes/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética
19.
Front Biosci (Landmark Ed) ; 27(7): 201, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35866399

RESUMO

Locally advanced rectal cancer (RC) is treated with neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery. Currently, organ-sparing approaches and/or "watch-and-wait" strategies other than unnecessary surgery have been suggested as the best option for patients who achieve complete regression after neoadjuvant treatment. However, patients respond differently to nCRT, hence the urgent need for effective methods to predict whether individual rectal cancer patients could benefit from this treatment. In this review, we summarize the biomarkers reported to be potential predictors of the therapeutic response of RC to nCRT. Biomarkers that are associated with genes, ribonucleic acid (RNA) and proteins are summarized and described first, followed by other types including immune and tumour microenvironment-related biomarkers, imaging biomarkers, microbiome-associated biomarkers, and blood-based biomarkers.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Biomarcadores , Quimiorradioterapia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Resultado do Tratamento , Microambiente Tumoral
20.
Jt Dis Relat Surg ; 33(2): 440-448, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35852206

RESUMO

OBJECTIVES: The aim of this study was to identify the demographic characteristics of chondrosarcoma (CS) and prognostic factors affecting survival. PATIENTS AND METHODS: A total of 87 patients (45 males, 42 females; median age: 51.3 years; range, 19 to 77 years) with CS treated in our clinic between January 2007 and June 2020 were retrospectively analyzed. Demographic characteristics, whether it was primary/secondary, tumor location, histopathological features, tumor grade and stage, clinical follow-up period, surgical treatment methods, use of radiotherapy and chemotherapy, and the presence of local recurrence and metastasis in the postoperative period were recorded. The relationship of these factors with prognosis was analyzed and survival rates were compared. RESULTS: Histological subtype, tumor grade, pathological stage and presence of metastasis were defined as independent predictors in both overall survival and disease-free survival analysis of CS. Overall and disease-free five-year and 10-year survival rates were found to be the highest in the clear cell chondrosarcoma group. While mortality increased in the first five years in the patient groups with histological Grade 2 and 3, all groups were followed in a balanced manner over time. The mortality rate in the group with metastatic disease (M2) was approximately four times higher than the other groups at 10-year follow-up. According to the surgical margins, we found that the five-year survival rates of the R1 (marginal resection) and R2 (residual tumor) groups were similar, with the highest rate being in the R0 (wide resection) group with 78.3%. In multivariate analysis, only grade and stage had a significant association with disease-specific survival. Surgical resection combined with adjuvant radiotherapy was found to increase survival in both overall and disease-free survival of patients with dedifferentiated chondrosarcoma compared to other treatments. CONCLUSION: Histological subtype, grade, stage and presence of metastasis were the independent prognostic factors for survival in CS. However, marginal resection was a risk factor for local recurrence (LR), but there was no significant difference in overall survival in patients with or without LR. Although it is not significant, radiotherapy could increase survival in dedifferentiated CS variants.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Adulto , Idoso , Neoplasias Ósseas/cirurgia , Condrossarcoma/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
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