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1.
Front Oncol ; 11: 712760, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900669

RESUMO

Background: The clinical role of deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) in gastric cancer (GC) is still controversial. We aimed to analyze the relationship between dMMR/MSI-H and clinicopathological features along with survival. Methods: Patients who were diagnosed with GC at the three big cancer centers in China from 2015 to 2020 were evaluated retrospectively. MMR/MSI status was assessed using immunohistochemistry/PCR. Clinical and pathological data were collected from the medical record system. Results: A total of 196 patients with dMMR/MSI-H status were enrolled for analysis. The prevalence of MSI-H/dMMR in GC was 6.6%. Another 694 proficient MMR (pMMR) GC patients were enrolled for comparison. Compared with pMMR patients, dMMR/MSI-H patients were associated with older age, female predominance, distal location in the stomach, earlier TNM stage, intestinal subtype, better differentiation, and more negative HER2 status. The median overall survival (OS) of the dMMR/MSI-H group was better than that of the pMMR/microsatellite stability (MSS) group (not reached vs. 53.9 months, p = 0.014). Adjuvant chemotherapy had no impact in both disease-free survival (DFS) and OS of dMMR/MSI-H patients (p = 0.135 and 0.818, respectively). dMMR/MSI-H patients had poorer response and progression-free survival (PFS) of first-line chemotherapy, though they were statistically significant (p = 0.361 and 0.124, respectively). Conclusions: dMMR/MSI-H GC patients have specific clinicopathological characteristics and better prognosis than pMMR patients.

2.
Gastroenterol Rep (Oxf) ; 9(6): 560-570, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34925853

RESUMO

Background: Due to its limited efficacy and potential toxicity, anti-PD-1 monoclonal antibody is not suitable for all advanced gastric cancer (AGC) patients and predictive biomarkers identifying patients who can benefit from it are urgently needed. This study aimed to evaluate the predictive and prognostic value of inflammatory markers in the context of the systemic inflammatory status and tumour microenvironment. Methods: The study included 58 patients from a prospective study investigating the safety and efficacy of toripalimab in chemorefractory AGC patients. Patient characteristics, treatment outcomes, and haematological parameters were analysed. Immune-cell infiltration and gene expression in tumour tissue were examined using transcriptome sequencing. Results: In this cohort, the median follow-up time was 4.5 months, the median progression-free survival was 1.9 months, and the median overall survival (OS) was 4.8 months. The objective response rate was 12.1% and th disease control rate (DCR) was 39.7%. Both the baseline blood neutrophil-to-lymphocyte ratio (bNLR) with a cut-point of 2.7 and the early elevated dynamic change of the bNLR (dNLR) with a cut-point of 1.5 were prognostic factors of survival. Patients in the high bNLR or dNLR group had remarkably poor DCR (25.8% vs 59.1%, P = 0.023; 15.8% vs 54.6%, P = 0.008). In multivariate analysis, bNLR and tumour mutational burden were independent prognostic factors of OS. Tumour RNA-seq analysis revealed enriched neutrophil infiltration and a higher tumour NLR in the bNLR-high group. Corresponding tumour gene-expression profiles were associated with neutrophil recruitment and inflammatory cytokine aggregation. Conclusions: Our study demonstrated the potential clinical utility of NLR as a biomarker for patient selection and clinical management in predicting the prognosis of AGC patients as well as response to anti-PD-1 therapy. In addition, high bNLR reflected the imbalance of tumour-tissue-infiltrating neutrophils and lymphocytes, and was associated with an immunosuppressive and pro-tumour microenvironment.

3.
Am J Cancer Res ; 11(10): 5006-5015, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765307

RESUMO

Gastric cancer (GC) patients with Epstein-Barr virus (EBV) positivity have demonstrated promising response with immunotherapy. We assessed the efficacy and safety of camrelizumab as salvage treatment in EBV-positive mGC. In this single-arm, phase 2 prospective clinical trial (NCT03755440), stage IV EBV-positive GC patients who failed/could not tolerate previous lines of chemotherapy were given intravenous camrelizumab 200 mg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response, and toxicity. Exploratory analysis included the associations between treatment response and tumor mutation burden (TMB), programmed cell death ligand-1 (PD-L1) expression. Six eligible patients were enrolled in the first stage of the study. No patient achieved an objective response; thus, the study did not proceed to the second stage. The DCR was 67% (4/6). The median PFS rate was 2.2 months (95% CI: 1.5-not reached [NR]) and median OS was 6.8 months (95% CI: 1.7-NR). All treatment-related adverse events were grade 1-2, with reactive cutaneous capillary endothelial proliferation (n=4 [67%]) being the most commonly observed event. The only patient with PD-L1 combined positive score >1 had disease progression. Two stable disease and one disease progression were observed in three patients with TMB >10 Mut/Mb. EBV positivity may not be a good predictor for response to camrelizumab in mGC. Newer biomarkers are needed to identify EBV-positive mGC respondents who might benefit from immunotherapy.

4.
Cell Rep Med ; 2(9): 100383, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34622226

RESUMO

This is a phase Ib/II study of regorafenib plus toripalimab for colorectal cancer. The objective response rate (ORR) is 15.2% and the disease control rate is 36.4% in evaluable patients with recommended phase II dose (80 mg regorafenib plus toripalimab). The median progression-free survival (PFS) and the median overall survival are 2.1 months and 15.5 months, respectively. Patients with liver metastases have lower ORR than those without (8.7% versus 30.0%). All patients (3/3) with lung-only metastasis respond, whereas no patients (0/4) with liver-only metastasis respond. 94.9% and 38.5% of patients have grade 1 and grade 3 treatment-related adverse events, respectively. Gut microbiome analysis of the baseline fecal samples shows significantly increased relative abundance and positive detection rate of Fusobacterium in non-responders than responders. Patients with high-abundance Fusobacterium have shorter PFS than those with low abundance (median PFS = 2.0 versus 5.2 months; p = 0.002).

5.
Jpn J Ophthalmol ; 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655347

RESUMO

PURPOSE: To investigate the association between metabolic syndrome (MetS) and diabetic retinopathy (DR), as well as the association between MetS and retinal vessel caliber, among Chinese patients with type 2 diabetes mellitus in north-eastern China. STUDY DESIGN: Cross-sectional study. PATIENTS AND METHODS: The patients were recruited from a community-based study, the Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT). The presence of DR was determined using a modified version of the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. The central retinal arteriolar equivalent (CRAE) and the central retinal venular equivalent (CRVE) were identified by use of Integrative Vessel Analysis software. The presence of MetS was defined according to the Joint Interim Statement proposed in 2009. RESULTS: The prevalence of DR was significantly higher among female patients with MetS than among those without it (47.2% vs 30.9%, P = 0.002), and it increased as the number of MetS components increased (P = 0.003). Furthermore, the presence of MetS (odds ratio 2.43, 95% CI 1.39-4.26) as well as higher numbers of MetS components were significantly associated with DR in female patients, after adjustment for potential risk factors. Patients with MetS (multivariate ß coefficient, 95% CI - 6.9, - 10.0, to - 3.8) or a higher number of Mets components tended to have significantly smaller CRAE. CONCLUSION: In this study cohort, female patients with MetS had a higher prevalence of DR. Patients tended to have thinner central retinal arterioles as the number of MetS components increased.

6.
Biomolecules ; 11(9)2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34572480

RESUMO

The prognostic heterogeneity in patients with BRAF V600E metastatic colorectal cancer (mCRC) remains poorly defined. Real-world data of 93 BRAF V600E mCRC patients from Sun Yat-sen University Cancer Center were evaluated using the prognostic factors affecting overall survival (OS). Treatment of metastases served as an independent prognosticator, where curative locoregional interventions (LRIs) were associated with superior clinical outcomes (adjusted hazard ratio (HR): 0.46, 95% confidence interval (CI): 0.22-0.98; p = 0.044). The LRIs group showed an improved median OS of 49.4 months versus 18.3 months for the palliative treatments (PTs) group. The median OS of patients with colorectal liver metastasis (CRLM) was significantly prolonged after undergoing LRIs (42.4 vs. 23.7 months; HR: 0.11, 95% CI: 0.01-1.22; p = 0.030), and patients in the LRIs plus liver-limited or lung-limited metastasis (LLM) group benefited more than those in the LRIs plus non-LLM group when compared to the PTs group (LLM from LRIs vs. PTs, HR: 0.16, 95% CI: 0.04-0.68; p = 0.006. Non-LLM from LRIs vs. PTs, HR: 0.47, 95% CI: 0.21-1.05; p = 0.074). In conclusion, we confirmed the positive prognostic value of LRIs in BRAF V600E mCRC, particularly in patients with CRLM or LLM.

7.
Gut ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489309

RESUMO

OBJECTIVE: Circulating tumour DNA (ctDNA) sequencing is increasingly used in the clinical management of patients with colorectal cancer. However, the genomic heterogeneity in ctDNA during treatments and its impact on clinical outcomes remain largely unknown. DESIGN: We conducted a prospective cohort study (NCT04228614) of 171 patients with unresectable metastatic colorectal cancer (mCRC) who underwent first-line treatment and prospectively collected blood samples with or without tumour samples from patients at baseline and sequentially until disease progression or last follow-up. RESULTS: The RAS/BRAF alterations in paired baseline tissue and plasma samples from 63 patients displayed a favourable concordance (81.0%, 51/63). After a period of first-line treatment (median time between baseline and last liquid biopsy, 4.67 months), 42.6% (26/61) of RAS-mutant patients showed RAS clearance and 50.0% (5/10) of BRAF-mutant patients showed BRAF clearance, while 3.6% (3/84) and 0.7% (1/135) of patients showed new RAS or BRAF mutations in ctDNA. Patients with plasma RAS/BRAF clearance showed similar progression-free survival (PFS) and overall survival (OS) with patients who remained RAS/BRAF wild-type, while much better outcomes than those who remained RAS/BRAF mutant. Patients who gained new RAS/BRAF mutations showed similar prognosis as those who maintained RAS/BRAF mutations, and shorter PFS and OS than those who remained RAS/BRAF wild-type. CONCLUSION: This prospective, serial and large-scale ctDNA profiling study reveals the temporal heterogeneity of mCRC-related somatic variants, which should be given special attention in clinical practice, as evidenced by the finding that the shift in plasma RAS/BRAF mutational status can yield a drastic change in survival outcomes.

8.
Transl Pediatr ; 10(8): 2044-2051, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34584874

RESUMO

Background: The surface topography index (STI) has great potential in both routine computed tomography (CT) scan and emerging optical imaging systems. However, the diagnostic accuracy and stability of the STI as a deformity severity assessment index has not been fully confirmed. Therefore, the aim of the present study was to determine the diagnostic performance of the STI as a novel deformity severity assessment index for pectus excavatum. Methods: The present study consisted of 722 chest CT images from a single center. The standard CT index (CTI) and STI were calculated for all patients. The between-group difference and the level of compliance between the CTI and STI was analyzed by t-test and Pearson correlation. The diagnostic value and optimum discriminatory values of the CTI and STI were calculated by a receiver-operating characteristic (ROC) curve and DeLong's test. Results: The distributions of the CTI and STI were similar and showed a slight overlap between the pectus excavatum (PE) and non-PE groups. Both the CTI and STI significantly differed between the 2 groups (P<0.001). The STI demonstrated a strong Pearson correlation with the CTI (r=0.91, 95% confidence interval: 0.88-0.91, P<0.001). The ROC curves showed that STI =1.58 (sensitivity: 0.93, specificity: 0.95) could be considered equivalent to CTI =2.72 (sensitivity: 0.93, specificity: 0.97) as the optimum discriminatory values. DeLong's test showed no significant difference in the ROC curve results between the CTI and STI (Z=0.90, P=0.37). Conclusions: The STI has comparative discrimination ability in PE diagnosis and deformity severity assessment when used with the standard CTI. The STI as a novel index is not only an ideal evaluation metric of PE deformity but also an objective trait for PE patients just as weight and height for everyone.

9.
Cancer Commun (Lond) ; 41(8): 747-795, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34197702

RESUMO

There exist differences in the epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selections between gastric cancer patients from the Eastern and Western countries. The Chinese Society of Clinical Oncology (CSCO) has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually. Taking into account regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China. The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis, treatment, follow-up, and screening of gastric cancer. Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines, this updated guideline integrates the results of major clinical studies from China and overseas for the past year, focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations. For the comprehensive treatment of non-metastatic gastric cancer, attentions were paid to neoadjuvant treatment. The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated. For the comprehensive treatment of metastatic gastric cancer, recommendations for immunotherapy were included, and immune checkpoint inhibitors from third-line to the first-line of treatment for different patient groups with detailed notes are provided.


Assuntos
Neoplasias Gástricas , China , Humanos , Oncologia , Sociedades Médicas , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamento farmacológico
11.
Transl Pediatr ; 10(4): 715-722, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34012821

RESUMO

Background: Mediastinal neuroblastoma (NB) can invade the spinal canal and result in spinal cord compression. Some patients go on to develop severe spinal deformities after decompression of the spinal cord. The optimal therapeutic strategy for mediastinal NB with intraspinal extension is still unclear. Our study is to assess the therapeutic strategies for such patients. Methods: A total of 77 patients suffered mediastinal tumors with intraspinal extension between March 2015 and Aug 2019 were enrolled in the study. According to the primary therapy, NB were classified into 4 groups: chemotherapy, video-assisted thoracoscopic surgery (VATS)/thoracotomy, neurosurgical decompression, and a combined thoracic-neurosurgical approach. Clinical features, including patient demographics, neurologic recovery and survival rate, were assessed. Results: Among the 77 patients suffered mediastinal tumors with intraspinal extension, neurological symptoms were present in 44 patients. Neurological deficits improved in 76.5% of patients who underwent neurosurgical intervention and 50% of the other patients (P=0.094). Compression manifestations of ≤4 weeks duration showed an improved outcome compared to a longer compression time, with complete recovery of neurological function in 60% of patients versus 28.6% for patients with a longer symptom duration (P=0.04). NB constituted 49.4% of the 77 patients. An overall survival rate of 90.0%±9.5% was achieved for patients in the combined thoracic-neurosurgical group, 59.5%±15.0% in the thoracotomy group, 40.0%±29.7% in laminectomy group, and 37.0%±20.2% in the chemotherapy group. Complete regression of the tumor was demonstrated in 80% of combined group, which was greater than that of patients in the other groups (P=0.001). Conclusions: Neurological recovery was correlated with the type of initial treatment and the duration of neurological symptoms. Mediastinal NB with intraspinal extension can be effectively managed with a combined neurosurgical and thoracic surgical approach.

12.
Oncologist ; 26(7): e1161-e1170, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33844372

RESUMO

BACKGROUND: The impact of HER2 somatic mutations in colorectal carcinoma (CRC) has not been well studied and its relationship with microsatellite instability-high (MSI-H) is yet to be fully elucidated. MATERIALS AND METHODS: From February 2017 to February 2020, the data of patients with CRC who underwent next-generation sequencing and had detailed record of clinicopathological information were investigated. HER2 alteration and its relationship with MSI-H were analyzed. RESULTS: Among 731 patients who underwent sequencing, 55 patients (7.5%) had HER2 alteration, including 29 (4.0%) with HER2 somatic mutations, 24 (3.3%) with HER2 gene amplification, and 2 patients (0.2%) with both HER2 mutations and amplification. R678Q was the most common mutated kinase domain, and no HER2 kinase domain in-frame insertions/deletions were found in HER2 mutated cases. MSI-H was found in 5.2% of our cohort and 36.8% of MSI-H patients had HER2 mutation. For HER2 mutated cases, 48.3% were MSI-H, whereas none of the HER2 amplification cases were MSI-H. MSI-H patients with HER2 mutation had significantly worse median progression-free survival for programmed death-1 (PD-1) antibody than those without HER2 alteration (p = .036). CONCLUSION: High MSI-H rate was found in HER2 mutated cases, but no MSI-H was found in HER2 amplification cases. MSI-H patients with HER2 mutated had worse progression-free survival for PD-1 antibody than those without. IMPLICATIONS FOR PRACTICE: This study highlights the high microsatellite instability-high (MSI-H) rate in HER2 mutated cases but no MSI-H in HER2 amplification cases. Moreover MSI-H patients with HER2 mutated had worse progression-free survival for programmed death-1 antibody than those without. Further research to explore the internal relationship between HER2 alteration and MSI-H is needed.


Assuntos
Adenocarcinoma , Neoplasias Colorretais , Adenocarcinoma/genética , Neoplasias Colorretais/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Instabilidade de Microssatélites , Mutação , Intervalo Livre de Progressão
13.
JAMA Netw Open ; 4(4): e215250, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33835174

RESUMO

Importance: The prevention of chemotherapy-induced nausea and vomiting has an important role in the overall management of cancer treatment. Objective: To evaluate whether adding aprepitant to palonosetron and dexamethasone can further prevent the incidence and severity of nausea and vomiting caused by FOLFIRI (fluorouracil, leucovorin, and irinotecan) or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) chemotherapy regimens among women with gastrointestinal cancer at higher risk. Design, Setting, and Participants: This phase 3, double-blind, placebo-controlled randomized clinical trial recruited young women (age ≤50 years) who drank little or no alcohol and had gastrointestinal cancer for which they received FOLFOX or FOLFIRI chemotherapy. A total of 248 women were enrolled and assigned in the ratio 1:1 to intervention and control groups from August 4, 2015, to March 31, 2020. Intention-to-treat analysis was used to evaluate patient baseline characteristics and efficacy. The analysis was conducted on October 30, 2020. Interventions: Patients were randomly assigned to the aprepitant group (aprepitant, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 6 mg, orally 30 minutes before chemotherapy initiation on day 1) or the placebo group (placebo, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally on each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 12 mg, orally 30 minutes before chemotherapy initiation on day 1). Main Outcomes and Measures: The primary end point was the complete response (CR) rate, defined as the proportion of patients without emesis episodes or rescue medication use during the overall phase of the first cycle. Other efficacy indicators, such as no vomiting and no nausea, were measured as the secondary and exploratory end points. Results: A total of 248 women from 4 clinical centers in China entered this study, and 243 patients (aprepitant regimen, 125 patients [51.4%]; placebo regimen, 118 patients [48.5%]) were evaluable for efficacy and safety; mean (SD) age of the total population was 40.1 (7.3) years. The CR rate was significantly higher in the aprepitant group vs the control group overall (107 [87.0%] vs 80 [66.7%]; P < .001) and in the acute (114 [92.7%] vs 91 [75.8%]; P = .001) and delayed (109 [88.6%] vs 84 [70.0%]; P = .001) phases of the trial. The incidence of adverse events was similar between the 2 groups (100 [80.0%] vs 96 [81.3%]; P = .79), and no grade 3 or 4 aprepitant treatment-related adverse events were observed. Multivariable analysis revealed that aprepitant use was the only independent factor associated with CR during the overall phase. Conclusions and Relevance: The combination of aprepitant with palonosetron and dexamethasone provided increased antiemetic efficacy in the FOLFOX or FOLFIRI chemotherapy regimen and was well tolerated by younger women with gastrointestinal cancer who have a history of little or no alcohol consumption. Trial Registration: ClinicalTrials.gov Identifier: NCT03674294.


Assuntos
Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Aprepitanto/administração & dosagem , Náusea/prevenção & controle , Neoplasias Gástricas/tratamento farmacológico , Vômito/prevenção & controle , Adulto , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , China , Método Duplo-Cego , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Pessoa de Meia-Idade , Náusea/etiologia , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Vômito/etiologia
14.
Ann Transl Med ; 9(4): 310, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33708937

RESUMO

Background: Increasing evidence suggests that the immune score is significantly associated with cancer prognosis. However, the prognostic role of primary tumor immune score in colorectal cancer liver metastases (CRLM) after hepatectomy in Chinese patients has not been reported. The present study is designed to investigate whether the immune score of primary tumor can predict the postoperative survival of liver metastases in Chinese patients. Methods: A total of 131 patients diagnosed with CRLM were included, and the corresponding primary tumor and liver metastasis specimens were acquired. An immune score ranging from 0 to 4 was established based on the counts and densities of CD3+ and CD8+ T cells in the core tumor (CT) and the invasive margin (IM). Relapse-free survival (RFS) and overall survival (OS) were analyzed by Kaplan-Meier curves to assess the prognostic role of primary tumor immune score. Furthermore, we conducted a comprehensive search of the Gene Expression Omnibus (GEO) and selected stage IV colorectal cancer (CRC) patients with liver metastasis to compare the tumor-infiltrating T cell profiles of the primary tumor and liver metastases by CIBERSORT. Results: Patients with high immune scores in the primary tumor has no significantly better RFS and OS after hepatectomy than those with low immune scores [median RFS (95% CI): 19.13 (10.07-28.20) vs. 27.13 (15.97-38.29) months, P=0.604; median OS (95% CI): 64.37 (35.96-92.78) vs. 40.07 (32.54-47.59) months, P=0.652]. Data collected from the GEO indicates that the proportion of CD8+ T cells and total T cells in the primary tumor and liver metastatic lesion are also not significantly correlated (CD8+ T cells: r2 =0.030, P=0.468; total T cells: r2 =0.165, P=0.076). Conclusions: The immune score of the primary tumor fails to predict the prognosis of CRLM after hepatectomy in Chinese patients.

15.
Front Cell Dev Biol ; 9: 639233, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33693004

RESUMO

Cell-free DNA (cfDNA) is easily accessible in peripheral blood and can be used as biomarkers for cancer diagnostics, prognostics, and therapeutics. The applications of cfDNA in various areas of cancer management are attracting attention. In this review article, we discuss the potential relevance of using cfDNA analysis in clinical oncology, particularly in cancer screening, early diagnosis, therapeutic evaluation, monitoring disease progression; and determining disease prognosis.

16.
Ther Adv Med Oncol ; 13: 1758835921988996, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613701

RESUMO

Background: We previously reported tumor mutation burden (TMB) as a potential prognostic factor for patients with advanced gastric cancer (AGC) receiving immunotherapy. We aimed to comprehensively understand the impact of tumor burden and TMB on efficacy and prognosis in immunotherapy-treated AGC patients. Methods: A total of 58 patients with refractory AGC receiving PD-1 inhibitor monotherapy from a phase Ib/II clinical trial (ClinicalTrials.gov identifier: NCT02915432) were retrospectively included. Univariate and multivariate logistical regression analyses and the Cox proportional hazards model were performed for prognostic value of baseline factors. Factors reflecting baseline tumor burden, including baseline lesion number (BLN), the maximum tumor size (MTS) and the sum of target lesion size (SLS) were analyzed. The objective response rate (ORR) and disease control rate (DCR) were compared by Chi-square test. Results: In univariate analysis, high BLN was associated with poor median progression-free survival (mPFS) [1.7 months versus 3.4 months; hazard ratio (HR), 2.696, p < 0.05] and median overall survival (mOS) (3.2 months versus 7.6 months; HR, 1.997, p < 0.05), while high TMB was a positive prognostic factor. In multivariable analysis, both BLN and TMB were independent prognostic factors for mOS (BLN: HR, 2.782, p < 0.05; TMB: HR, 0.288, p < 0.05), while MTS or SLS had no association with survival. Better ORR and DCR were observed in the low BLN group (15.4% versus 5.3%, p > 0.05; 86.96% versus 54.29%, p < 0.05). When combining BLN and TMB, the best efficacy and survival were observed in the BLNlowTMBhigh group (ORR: 37.5%, DCR: 62.5%, mPFS and mOS: not reached). The worst efficacy and survival were shown in the BNLhighTMBlow group [ORR: 0% (0/15); DCR: 13.3%; mPFS: 1.7 months; mOS: 2.7 months (all p < 0.05)]. Conclusions: BLN, rather than factors regarding baseline tumor size, is perhaps a potential predictor for benefit from immunotherapy and its combination with TMB could further risk-stratify patients with AGC receiving immunotherapy.

17.
Cancer Med ; 10(5): 1535-1544, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33539664

RESUMO

PURPOSE: We aimed to construct a nomogram to predict personalized post-recurrence survival (PRS) among colorectal cancer liver metastasis (CRLM) patients with post-hepatectomy recurrence. METHODS: Colorectal cancer liver metastasis patients who received initial hepatectomy and had subsequent recurrence between 2001 and 2019 in Sun Yat-sen University Cancer Center from China were included in the study. Patients were randomly assigned to a training cohort and a validation cohort on a ratio of 2:1. Univariable analysis was first employed to select potential predictive factors for PRS. Then, the multivariable Cox regression model was applied to recognize independent prognostic factors. According to the model, a nomogram to predict PRS was established. The nomogram's predictive capacity was further assessed utilizing concordance index (C-index) values, calibration plots, and Kaplan-Meier curves. RESULTS: About 376 patients were finally enrolled, with a 3-year PRS rate of 37.3% and a 5-year PRS rate of 24.6%. The following five independent predictors for PRS were determined to construct the nomogram: the largest size of liver metastases at initial hepatectomy, relapse-free survival, CEA level at recurrence, recurrent sites, and treatment for recurrence. The nomogram displayed fairly good discrimination and calibration. The C-index value was 0.742 for the training cohort and 0.773 for the validation cohort. Patients were grouped into three risk groups very well by the nomogram, with 5-year PRS rates of 45.2%, 23.3%, and 9.0%, respectively (p < 0.001) in the training cohort and 36.0%, 9.2%, and 4.6%, respectively (p < 0.001) in the validation cohort. CONCLUSION: A novel nomogram was built and validated to enable the prediction of personal PRS in CRLM patients with post-hepatectomy recurrence. The nomogram may help physicians in decision making.


Assuntos
Carcinoma Hepatocelular/mortalidade , Neoplasias Colorretais/mortalidade , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Nomogramas , Complicações Pós-Operatórias/mortalidade , Análise de Variância , Antígeno Carcinoembrionário/sangue , Carcinoma Hepatocelular/secundário , Carcinoma Hepatocelular/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Prognóstico , Modelos de Riscos Proporcionais , Distribuição Aleatória , Fatores de Risco , Carga Tumoral
18.
Invest New Drugs ; 39(3): 836-845, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33411209

RESUMO

Background Gemcitabine plus cisplatin is regarded as the standard first-line therapy for patients with advanced biliary tract cancer (BTC); however, no standard chemotherapy has yet been recommended after treatment failure. Modified FOLFIRINOX (mFOLFIRINOX) appears to be a better-tolerated regimen, which leads to improved survival in metastatic pancreatic cancer that has histological and molecular similarities with BTC. We assessed the efficacy and safety of mFOLFIRINOX as salvage therapy in advanced BTC patients who were refractory to previous chemotherapy. Methods A total of 15 consecutive patients with documented unresectable locally advanced or metastatic BCT who received the mFOLFIRINOX regimen were included in the study. Patients were intravenously administrated with oxaliplatin (65 mg/m2), leucovorin (400 mg/m2), irinotecan (150 mg/m2), and continuous infusion of fluorouracil (2400 mg/m2) over 46 h. The objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were recorded. Results At least three cycles of mFOLFIRINOX regimen were delivered to 15 patients with a median number of 6.0 cycles (IQR 5.5-11.0). The median duration of treatment was 3.8 months (IQR 2.9-8.5). Four patients (26.7%) achieved an ORR, and 12 patients (80.0%) had a DCR. The median PFS and OS were 6.7 months (95%CI 2.3-11.1) and 13.2 months (95%CI 7.3-19.1), respectively. Five patients (33.3%) had treatment-related grade 3/4 AEs. The most common grade 3/4 AE was neutropenia (n = 3, 20.0%), while there was no occurrence of febrile neutropenia. Conclusion Treatment with mFOLFIRINOX has promising efficacy and favorable tolerance as salvage therapy in patients with refractory advanced BCT.

19.
J Clin Oncol ; 39(7): 704-712, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33492986

RESUMO

PURPOSE: As yet, no checkpoint inhibitor has been approved to treat nasopharyngeal carcinoma (NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chemotherapy. PATIENTS AND METHODS: In this single-arm, multicenter phase II study, patients with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). The secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: Among all 190 patients, the ORR was 20.5% with median DOR 12.8 months, median PFS 1.9 months, and median OS 17.4 months. Among 92 patients who failed at least two lines of systemic chemotherapy, the ORR was 23.9%. The ORRs were 27.1% and 19.4% in PD-L1+ and PD-L1- patients, respectively (P = .31). Patients with ≥ 50% decrease of plasma Epstein-Barr virus (EBV) DNA copy number on day 28 had significantly better ORR than those with < 50% decrease, 48.3% versus 5.7% (P = .0001). Tumor mutational burden had a median value of 0.95 muts/mega-base in the cohort and had no predictive value for response. Whole-exome sequencing results from 174 patients revealed that the patients with genomic amplification in 11q13 region or ETV6 genomic alterations had poor responses to toripalimab. CONCLUSION: The POLARIS-02 study demonstrated a manageable safety profile and durable clinical response of toripalimab in patients with chemorefractory metastatic NPC. An early decrease in plasma EBV DNA copy number correlated with favorable response.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Recidiva Local de Neoplasia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , China , Cromossomos Humanos Par 11 , DNA Viral/genética , Progressão da Doença , Feminino , Herpesvirus Humano 4/genética , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/secundário , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Intervalo Livre de Progressão , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-ets/genética , Proteínas Repressoras/genética , Fatores de Tempo , Carga Viral , Adulto Jovem
20.
Invest New Drugs ; 39(2): 516-523, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33070249

RESUMO

Background The prognosis of esophageal squamous cell carcinoma (ESCC) are still poor. Nedaplatin/paclitaxel regimen has shown activity with lower toxicity in metastatic ESCC. Recombinant human endostatin (Rh-endostatin), an inhibitor of angiogenesis, has shown inhibitory effects on ESCC xenograft. We assessed the activity and safety of Rh-endostatin plus paclitaxel/nedaplatin in patients with recurrent or metastatic advanced ESCC. Methods In this single-center, open-label, single-arm, phase II study, patients with recurrent/metastatic or unresectable advanced ESCC were recruited. Eligible patients received the multidrug combination therapy with Rh-endostatin (30 mg/day on days 1-14), paclitaxel (150 mg/m2 on day 4) and nedaplatin (80 mg/m2 on day 4) every 3 weeks. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate, disease control rate, overall survival. Results Between Jan 29, 2015 and Dec 31, 2019, 53 patients were enrolled and received at least one dose of Rh-endostatin. Median progression-free survival was 5.1 months (95% CI: 3.7-6.6), with a 6 month progression-free survival of 41% (95% CI: 25-56). Median overall survival was 13.2 months (95% CI: 8.0-18.4), with a 1-year overall survival of 51% (95% CI: 36-67). 21 (42%, 95% CI: 28-56) of 50 patients had an objective response and 35 (70.00%, 95% CI: 57-83) had a disease control. Treatment-related adverse events of grade 3 or worse were reported in 13 (24.5%) patients. The most common grade 3 or 4 treatment-related adverse events were neutropenia (9 patients [17%]) and anaemia (2 [3.8%]). No treatment-related death occurred. Conclusions Rh-endostatin plus paclitaxel/nedaplatin has anti-tumour activity with acceptable tolerability in patients with recurrent or metastatic advanced ESCC. Randomized controlled trial is needed to confirm the efficacy of this regimen.

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