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1.
Urol Clin North Am ; 47(4): 457-467, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008496

RESUMO

Biochemically recurrent prostate cancer represents a stage of prostate cancer where conventional (continued on next page) computed tomography and technetium Tc 99m bone scan imaging are unable to detect disease after curative intervention despite rising prostate-specific antigen. There is no clear standard of care and no systemic therapy has been shown to improve survival. Immunotherapy-based treatments potentially are attractive options relative to androgen deprivation therapy due to the generally more favorable side-effect profile. Biochemically recurrent prostate cancer patients have a low tumor burden and likely lymph node-based disease, which may make them more likely to respond to immunotherapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Imunoterapia/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/patologia , Idoso , Terapia Combinada , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Seleção de Pacientes , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Medição de Risco , Papel (figurativo) , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
2.
Lancet Oncol ; 21(10): 1331-1340, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002437

RESUMO

BACKGROUND: Adjuvant radiotherapy has been shown to halve the risk of biochemical progression for patients with high-risk disease after radical prostatectomy. Early salvage radiotherapy could result in similar biochemical control with lower treatment toxicity. We aimed to compare biochemical progression between patients given adjuvant radiotherapy and those given salvage radiotherapy. METHODS: We did a phase 3, randomised, controlled, non-inferiority trial across 32 oncology centres in Australia and New Zealand. Eligible patients were aged at least 18 years and had undergone a radical prostatectomy for adenocarcinoma of the prostate with pathological staging showing high-risk features defined as positive surgical margins, extraprostatic extension, or seminal vesicle invasion; had an Eastern Cooperative Oncology Group performance status of 0-1, and had a postoperative prostate-specific antigen (PSA) concentration of 0·10 ng/mL or less. Patients were randomly assigned (1:1) using a minimisation technique via an internet-based, independently generated allocation to either adjuvant radiotherapy within 6 months of radical prostatectomy or early salvage radiotherapy triggered by a PSA of 0·20 ng/mL or more. Allocation sequence was concealed from investigators and patients, but treatment assignment for individual randomisations was not masked. Patients were stratified by radiotherapy centre, preoperative PSA, Gleason score, surgical margin status, and seminal vesicle invasion status. Radiotherapy in both groups was 64 Gy in 32 fractions to the prostate bed without androgen deprivation therapy with real-time review of plan quality on all cases before treatment. The primary endpoint was freedom from biochemical progression. Salvage radiotherapy would be deemed non-inferior to adjuvant radiotherapy if freedom from biochemical progression at 5 years was within 10% of that for adjuvant radiotherapy with a hazard ratio (HR) for salvage radiotherapy versus adjuvant radiotherapy of 1·48. The primary analysis was done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT00860652. FINDINGS: Between March 27, 2009, and Dec 31, 2015, 333 patients were randomly assigned (166 to adjuvant radiotherapy; 167 to salvage radiotherapy). Median follow-up was 6·1 years (IQR 4·3-7·5). An independent data monitoring committee recommended premature closure of enrolment because of unexpectedly low event rates. 84 (50%) patients in the salvage radiotherapy group had radiotherapy triggered by a PSA of 0·20 ng/mL or more. 5-year freedom from biochemical progression was 86% (95% CI 81-92) in the adjuvant radiotherapy group versus 87% (82-93) in the salvage radiotherapy group (stratified HR 1·12, 95% CI 0·65-1·90; pnon-inferiority=0·15). The grade 2 or worse genitourinary toxicity rate was lower in the salvage radiotherapy group (90 [54%] of 167) than in the adjuvant radiotherapy group (116 [70%] of 166). The grade 2 or worse gastrointestinal toxicity rate was similar between the salvage radiotherapy group (16 [10%]) and the adjuvant radiotherapy group (24 [14%]). INTERPRETATION: Salvage radiotherapy did not meet trial specified criteria for non-inferiority. However, these data support the use of salvage radiotherapy as it results in similar biochemical control to adjuvant radiotherapy, spares around half of men from pelvic radiation, and is associated with significantly lower genitourinary toxicity. FUNDING: New Zealand Health Research Council, Australian National Health Medical Research Council, Cancer Council Victoria, Cancer Council NSW, Auckland Hospital Charitable Trust, Trans-Tasman Radiation Oncology Group Seed Funding, Cancer Research Trust New Zealand, Royal Australian and New Zealand College of Radiologists, Cancer Institute NSW, Prostate Cancer Foundation Australia, and Cancer Australia.


Assuntos
Adenocarcinoma/radioterapia , Prostatectomia , Neoplasias da Próstata/radioterapia , Terapia de Salvação , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Austrália , Progressão da Doença , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Humanos , Masculino , Doenças Urogenitais Masculinas/epidemiologia , Doenças Urogenitais Masculinas/etiologia , Pessoa de Meia-Idade , Nova Zelândia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Radioterapia Adjuvante/efeitos adversos , Terapia de Salvação/efeitos adversos , Resultado do Tratamento
3.
Nat Commun ; 11(1): 4965, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009371

RESUMO

Next-generation sequencing (NGS) can identify novel cancer targets. However, interpreting the molecular findings and accessing drugs/clinical trials is challenging. Furthermore, many tumors show resistance to monotherapies. To implement a precision strategy, we initiated a multidisciplinary (basic/translational/clinical investigators, bioinformaticians, geneticists, and physicians from multiple specialties) molecular tumor board (MTB), which included a project manager to facilitate obtaining clinical-grade biomarkers (blood/tissue NGS, specific immunohistochemistry/RNA expression including for immune-biomarkers, per physician discretion) and medication-acquisition specialists/clinical trial coordinators/navigators to assist with medication access. The MTB comprehensively reviewed patient characteristics to develop N-of-One treatments implemented by the treating physician's direction under the auspices of a master protocol. Overall, 265/429 therapy-evaluable patients (62%) were matched to ≥1 recommended drug. Eighty-six patients (20%) matched to all drugs recommended by MTB, including combinatorial approaches, while 38% received physician's choice regimen, generally with unmatched approach/low degree of matching. Our results show that patients who receive MTB-recommended regimens (versus physician choice) have significantly longer progression-free (PFS) and overall survival (OS), and are better matched to therapy. High (≥50%) versus low (<50%) Matching Score therapy (roughly reflecting therapy matched to ≥50% versus <50% of alterations) independently correlates with longer PFS (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50-0.80; P < 0.001) and OS (HR, 0.67; 95% CI, 0.50-0.90; P = 0.007) and higher stable disease ≥6 months/partial/complete remission rate (52.1% versus 30.4% P < 0.001) (all multivariate). In conclusion, patients who receive MTB-based therapy are better matched to their genomic alterations, and the degree of matching is an independent predictor of improved oncologic outcomes including survival.


Assuntos
Neoplasias/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , DNA Tumoral Circulante/genética , Intervalo Livre de Doença , Feminino , Genoma Humano , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Medicina de Precisão , Resultado do Tratamento , Adulto Jovem
4.
Medicine (Baltimore) ; 99(40): e22203, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019395

RESUMO

Breast cancer (BC) is a disease of high mortality rate because of high malignant, while early diagnosis and personal management may make a better prognosis possible. This study aimed to establish and validate lncRNAs signatures to improve the prognostic prediction for BC.RNA sequencing data along with the corresponding clinical information of patients with BC were gained from The Cancer Genome Atlas (TCGA). Prognostic differentially expressed lncRNAs were obtained using differentially expressed lncRNAs analysis (P value <.01 and |fold change| > 2) and univariate cox regression (P value <.05). By applying least absolute shrinkage and selection operation (LASSO) Cox regression analysis along with 10-fold cross-validation, 2 lncRNA-based signatures were constructed in the training, test and whole set.A 14-lncRNAs signature and a 10-lncRNAs signature were built for overall survival (OS) and relapse-free survival (RFS) respectively in the 3 sets. BC patients were divided into high-risk groups and low-risk groups depended on median risk score value. Significant differences were found for OS and RFS between 2 groups in the 3 sets. The time-dependent receiver operating characteristic (ROC) curves analysis demonstrated that our lncRNAs signatures had better predictive capacities of survival and recurrence for BC patients as well as enhancing the predictive ability of the tumor node metastasis (TNM) stage system.These results indicate that the 2 lncRNAs signatures with the potential to be biomarkers to predict the prognosis of BC for OS and RFS.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Curva ROC
5.
Medicine (Baltimore) ; 99(40): e22447, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019430

RESUMO

The aim of this study was to investigate the relationship between textbook outcome and survival in patients with surgically treated colon cancer. A total of 804 surgical cases were enrolled between June 1, 2010 and December 31, 2014. Textbook outcome was defined as patients who had colon cancer surgery and met the six healthcare parameters of surgery within 6 weeks, radical resection, lymph node (LN) yield ≥12, no ostomy, no adverse outcome and colonoscopy before/after surgery within 6 months. The effect of textbook outcome on 5-year disease-specific survival (DSS) was calculated using the Kaplan-Meier method. A Cox regression model was used to find significant independent variables and stratified analysis used to determine whether text-book outcome had a survival benefit. A textbook outcome was achieved in 59.5% of patients undergoing colon cancer surgery. Important obstacles to achieving textbook outcome were no stomy, no adverse outcome and LN yield ≥12. Patients with text-book outcome had statistically significant better 5-year DSS compared to those with-out (80.1% vs. 58.3%). Multivariate analyses indicated that colon cancer patients with textbook outcome had better 5-year DSS after adjusting for various confounders ([aHR], 0.44; 95% CI, 0.34-0.57). Thus, besides being an index of short-term quality of care, textbook outcomes could be used as a prognosticator of long-term outcomes, such as 5-year survival rates.


Assuntos
Neoplasias do Colo/cirurgia , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Idoso , Neoplasias do Colo/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida
6.
Urologiia ; (4): 79-83, 2020 Sep.
Artigo em Russo | MEDLINE | ID: mdl-32897659

RESUMO

OBJECTIVE: To study the survival rate of patients without biochemical recurrence according to the Stuttgart and Phoenix criteria in terms of their correlation with four different PSA nadir values as predictors of clinical recurrence in patients with localized prostate cancer who underwent total HIFU prostate ablation. MATERIAL AND METHODS: The object of the study was patients with morphologically proven localized RP by biopsy results, who were treated with prostate cancer by HIFU ablation on the Ablatherm Integrated Imaging apparatus (EDAP TMS, France). The study included 658 patients in whom HIFU ablation was used as primary treatment of localized prostate cancer (stages T1 - T2) without previous use of other methods (hormonal, radiation therapy) For the analysis, a continuous sample of patients was selected, which were divided into four groups depending on the PSA nadir level: less or equal 0.2 ng / ml (1 group), 0.21-0.5 ng / ml (group 2), 0.51-1 ng / ml (group 3) and> 1 ng / ml (group 4). sensitivity, specificity, predictive value, and 5-year biochemical relapse-free survival according to the Stuttgart definition and the Phoenix definition in the PSA nadir groups. RESULTS: The median (range) of the observation period for the patients was 5.3 (3-7) years, the mean time to reaching PSA nadir was 14.5+/-2.6 weeks. PSA nadirs less or equal 0.2, 0.21-0.5, 0.51-1.0 and > 1 ng/ml were achieved in 231 (35.1%), 132 (20.0%), 105 (15, 9%) and 190 (28.8%) patients, respectively. Survival without biochemical relapse in accordance with the Stuttgart definition in the four groups allocated for the PSA nadir was 82, 65, 43 and 32%, respectively (p<0.001), according to the Phoenix definition - 94, 74, 66 and 47% (p<0.001) respectively. According to the results of the control biopsy, 601 (91.3%) patients in the 1st and 2nd groups had a negative oncological status (approximately 85%). CONCLUSION: This study confirms that PSA nadir after HIFU ablation predicts biochemical recurrence-free survival and is a reliable marker that is easy to integrate into routine clinical practice.


Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata/terapia , Ultrassom Focalizado Transretal de Alta Intensidade , Intervalo Livre de Doença , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia , Neoplasias da Próstata/patologia , Resultado do Tratamento
7.
Medicine (Baltimore) ; 99(35): e21304, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871861

RESUMO

To determine the efficacy of neoadjuvant chemoradiotherapy (NCRT) between young and old patients with locally advanced rectal cancer (LARC) in terms of tumor response and survival outcome.LARC patients undergoing NCRT and radical surgery from 2011 to 2015 were included and divided into: young (aged ≤50 years) and old group (aged >50 years). Multivariate analyses were performed to identify risk factors for local recurrence. Least absolute shrinkage and selection operator analysis was performed to identify risk factors for overall survival. Predicting nomograms and time-indepent receiver operating characteristic curve analysis were performed to compare the models containing with/withour age groups.A total of 572 LARC patients were analyzed. The young group was associated with higher pathological TNM stage, poorly differentiated tumors, and higher rate of positive distal resection margin (P = .010; P = .019; P = .023 respectively). Young patients were associated with poorer 5-year disease-free survival and local recurrence rates (P = .023, P = .003 respectively). Cox regression analysis demonstrated that age ≤50 years (Hazard ratio = 2.994, P = .038) and higher pathological TNM stage (Hazard ratio = 3.261, P = .005) were significantly associated with increased risk for local recurrence. Least absolute shrinkage and selection operator analysis and the time-indepent receiver operating characteristic curve analysis demonstrated that including the age group were superior than that without age group.Young patients were associated with poorer disease free survival (DFS) and a higher risk for local recurrence in LARC following NCRT. The predicting model basing based on the age group had a better predictive ability. More intense adjuvant treatment could be considered to improve DFS and local control for young patients with LARC following NCRT.


Assuntos
Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/mortalidade , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Adulto , Idoso , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Nomogramas , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
8.
Anticancer Res ; 40(10): 5343-5349, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988852

RESUMO

BACKGROUND/AIM: The present study aimed to examine the association of the controlling nutritional status (CONUT) score with outcomes in patients undergoing esophagectomy for esophageal cancer (EC). MATERIALS AND METHODS: A systematic literature review was carried out to investigate the impact of the CONUT score in EC. Next, meta-analysis of long-term outcomes was performed. RESULTS: The search found six eligible retrospective studies, and five studies with 952 patients were included in the meta-analysis. Meta-analysis found a significant association of the CONUT score with outcomes including overall survival [hazard ratio (HR)=2.51, 95% confidence interval (CI)=1.75-3.60, p<0.001], cancer-specific survival (HR=2.60, 95%CI=1.53-4.41, p<0.001), and recurrence free survival (HR=2.08, 95%CI=1.39-3.12, p<0.001). CONCLUSION: The CONUT score may be an independent predictor associated with prognosis in patients undergoing esophagectomy for EC. However, further studies are needed to clarify the association of the CONUT score with postoperative outcomes in EC patients.


Assuntos
Neoplasias Esofágicas/metabolismo , Estado Nutricional/fisiologia , Complicações Pós-Operatórias/metabolismo , Intervalo Livre de Doença , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Modelos de Riscos Proporcionais
9.
Anticancer Res ; 40(10): 5405-5409, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988860

RESUMO

AIM: To investigate the clinical significance of ATP-binding cassette transporter 11 (ABCC11) protein expression in colon cancer. MATERIALS AND METHODS: One hundred thirty nine patients with colon cancer resection between 2009 and 2011 were enrolled. The relationship with immunohistochemical ABCC11 staining and clinicopathological factors was retrospectively analyzed. RESULTS: Median age was 70 years including 67 males and 72 females. The patients with Stage 0, 1, 2, 3a and 4 were 4, 20, 43, 35, 7 and 30, respectively. The patients with curability (Cur) A, B and C were 109, 11 and 19, respectively. Positive expression of ABCC11 was observed in 31 patients (22.3%). There were no significant differences regarding age, gender, location, serum tumor markers, T category, lymphatic invasion and stage in relation to ABCC11 protein expression. Cases with node metastasis and venous invasion as well as unresectable cases were significantly more often found negative for ABCC11 protein (p=0.0246, 0.0285 and 0.0422, respectively). Concerning the 3 year disease free survival (DFS) and the 5 year overall survival (OS) in Stage 2/3 and in Stage 3 with adjuvant chemotherapy, no significant differences were found. However, OS in ABCC11 negative cases was 81.1%, which was significantly lower compared to positive cases, where OS was 96.2%. CONCLUSION: There was significant correlation with ABCC11 expression and lymph node metastasis, venous invasion and curability. The prognosis in ABCC11 negative cases was poor because of increased cases without curative resection.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Proliferação de Células/genética , Neoplasias do Colo/genética , Metástase Linfática/genética , Idoso , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/patologia , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
10.
N Engl J Med ; 383(12): 1139-1148, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32877599

RESUMO

BACKGROUND: In the previously reported primary analysis of this phase 3 trial, 12 months of adjuvant dabrafenib plus trametinib resulted in significantly longer relapse-free survival than placebo in patients with resected stage III melanoma with BRAF V600E or V600K mutations. To confirm the stability of the relapse-free survival benefit, longer-term data were needed. METHODS: We randomly assigned 870 patients who had resected stage III melanoma with BRAF V600E or V600K mutations to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. The primary end point was relapse-free survival. Here, we report 5-year results for relapse-free survival and survival without distant metastasis as the site of the first relapse. Overall survival was not analyzed, since the required number of events to trigger the final overall survival analysis had not been reached. RESULTS: The minimum duration of follow-up was 59 months (median patient follow-up, 60 months for dabrafenib plus trametinib and 58 months for placebo). At 5 years, the percentage of patients who were alive without relapse was 52% (95% confidence interval [CI], 48 to 58) with dabrafenib plus trametinib and 36% (95% CI, 32 to 41) with placebo (hazard ratio for relapse or death, 0.51; 95% CI, 0.42 to 0.61). The percentage of patients who were alive without distant metastasis was 65% (95% CI, 61 to 71) with dabrafenib plus trametinib and 54% (95% CI, 49 to 60) with placebo (hazard ratio for distant metastasis or death, 0.55; 95% CI, 0.44 to 0.70). No clinically meaningful between-group difference in the incidence or severity of serious adverse events was reported during the follow-up period. CONCLUSIONS: In the 5-year follow-up of a phase 3 trial involving patients who had resected stage III melanoma with BRAF V600E or V600K mutations, 12 months of adjuvant therapy with dabrafenib plus trametinib resulted in a longer duration of survival without relapse or distant metastasis than placebo with no apparent long-term toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov number, NCT01682083; EudraCT number, 2012-001266-15.).


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imidazóis/uso terapêutico , Melanoma/tratamento farmacológico , Oximas/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Neoplasias Cutâneas/genética , Análise de Sobrevida
11.
Ann Hematol ; 99(11): 2639-2648, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32889611

RESUMO

Extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) continues to remain a clinical challenge. The data on EMR in acute lymphoblastic leukemia (ALL) are currently limited. Herein, a retrospective analysis of 268 adult ALL patients who underwent allo-HSCT in our center between March 2008 and December 2017 was performed to analyze post-HSCT EMR. Ninety patients (33.58%) experienced relapse; 51(19.03%) experienced bone marrow relapse (BMR), whereas 39 (14.55%) experienced EMR. The 5-year cumulative EMR incidence (CEMRI) revealed that matched sibling donor (MSD)-HSCTs were more likely to develop EMR than unrelated donor (URD)- and haploidentical-related donor (HRD)-HSCTs (CEMRI: 24.02%, 7.69%, and 14.69% for MSD, URD, and HRD, respectively). Notably, MSD-HSCTs (URD vs MSD hazard ratio (HR) = 0.26, p = 0.015; HRD vs MSD HR = 0.46, p = 0.032), history of extramedullary disease (EMD) (HR = 2.45, p = 0.041), and T cell ALL (HR = 2.80, p = 0.012) were independent risk factors for EMR in the multivariate analysis. The median overall survival (OS) for all patients was 15.23 months. However, the OS of EMR patients was significantly longer (19.50 months) than that of BMR patients (12.90 months) (p = 0.003). Multivariate analyses revealed that the leading risk factors for post-relapse deaths were shorter intervals between HSCT and relapse (> 12 months vs ≤ 12 months, HR = 0.30, p < 0.001) and BMR (HR = 0.41, p = 0.002). In conclusion, EMR patients have better survival than BMR patients. ALL patients with allo-HSCT from MSDs, a history of EMD, and the T cell type were significantly associated with EMR.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Aloenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
12.
Ann Hematol ; 99(11): 2539-2546, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32939674

RESUMO

Decitabine is a hypomethylating drug that is used to treat myelodysplastic syndrome (MDS) at a recommended dose and schedule (20 mg/m2 per day, for 5 consecutive days). However, due to its relatively high incidence of side effects and its effects on neoplastic cells, many studies have begun to explore the clinical application of a low dose of decitabine for treating MDS. In this retrospective study, we examined the effects of a very-low-dose decitabine schedule for treating MDS. A total of 13 patients diagnosed with de novo MDS received a schedule of intravenous decitabine administration at 6 mg/m2 per day for 7 days, repeated every 4 weeks. The complete response rate was 30.8%, and the overall response rate was 69.2%. In patients with complete remission, the median time to granulocyte recovery greater than 0.5 × 109/L during complete remission (CR) was 15 days. In patients with remission, the median time to granulocyte recovery greater than 0.5 × 109/L was 10.5 days. The 1-year survival rate was 72.7% and the median survival was 28.0 months. In summary, we demonstrated that a very-low-dose decitabine schedule has an appreciable response and survival rate, as well as appreciable tolerance and medical compliance for treating MDS.


Assuntos
Decitabina/administração & dosagem , Síndromes Mielodisplásicas , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
13.
Ann Hematol ; 99(11): 2577-2586, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32945942

RESUMO

Although treatment outcomes for diffuse large B cell lymphoma (DLBCL) have improved with the introduction of rituximab, approximately half of patients experience relapsed/refractory (r/r) disease. Furthermore, no standard salvage therapy has yet been established to date, while limitations in treatment options exist due to toxicity and restricted tolerability among elderly patients and/or those with comorbidities. The ICE (ifosfamide, cyclophosphamide, and etoposide) regimen is often used as salvage therapy for r/r DLBCL. Several modified ICE regimens not requiring continuous ifosfamide infusion are available, which can be used in outpatient clinics. This study analyzed the efficacy and toxicity of fractionated ICE with rituximab (f-R-ICE) as a salvage regimen among 47 patients with relapsed/refractory DLBCL (median age upon f-R-ICE initiation, 71 years). The whole cohort had an overall (ORR) and complete response rate of 53.1% (n = 25) and 25.5% (n = 12), respectively, and an estimated 1-year overall survival after f-R-ICE initiation of 57%. Comorbidities were evaluated using the Charlson Comorbidity Index (CCI) upon f-R-ICE initiation. Patients with low CCI scores (68%) had a higher ORR than those with high CCI scores (36.4%) upon f-R-ICE initiation (P = 0.042). In contrast, no significant differences in overall survival (OS) were observed between the low and high CCI groups (1-year OS 56.6% vs. 52.2%; median OS 24 vs. 22.8 months) after initiating f-R-ICE. Our results suggest that f-R-ICE is a safe and effective salvage therapy for r/r DLBCL and can be used for older patients and/or those with high CCI scores in outpatient clinics.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Comorbidade , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Taxa de Sobrevida
14.
Ann Hematol ; 99(11): 2619-2628, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32960314

RESUMO

In the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended as a standard approach for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) achieving complete remission (CR). However, the role of autologous hematopoietic stem cell transplantation (auto-HSCT) in adult patients achieving complete molecular remission (CMR) is an alternative, less toxic treatment options, especially for the patients who lack suitable donors and are unfit for allo-HSCT. Thus, we conducted a systematic review and meta-analysis to compare the efficacy of allo-HSCT and auto-HSCT for the treatment of adult patients with Ph+ ALL. We searched the PubMed, Embase, Scopus, and Cochrane Library for studies published before June 2019 without language restriction. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS) and relapse-free survival (RFS) and odds ratios (ORs) and 95% CIs for relapse rate (RR) and treatment-related mortality (TRM). Four prospective studies and one retrospective study were included with a total of 810 patients. We found auto-HSCT was superior to allo-HSCT in OS (HR = 1.42, 95% CI: 1.06-1.91, P = 0.02), and there was no difference between allo-HSCT and auto-HSCT for RFS (HR = 1.10, 95% CI: 0.86-1.40, P = 0.44) and RR (OR = 0.53, 95% CI: 0.22-1.26, P = 0.15). The risk of TRM for patients undergoing allo-HSCT was significantly higher than that of the patients who received auto-HSCT (OR = 5.06, 95% CI: 1.03-24.75, P = 0.05). Our meta-analysis shows that auto-HSCT may be an attractive and alternative treatment option for adult Ph+ ALL patients achieving CMR, with similar or better outcomes than allo-HSCT in the era of TKIs.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Aloenxertos , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Taxa de Sobrevida
15.
Ann Hematol ; 99(11): 2629-2637, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32980890

RESUMO

Treatment of acute lymphoblastic leukemia (ALL) requires the combination of multiple drugs to integrate a complete remission. The different prognostic factors (age, leukocytes, risk, cytogenetic alterations) allow identifying those patients with a high risk of relapse, but there are few described factors that impact the induction response. The objective was to identify the utility of different risk factors (overexpression of the ABCB1 drug resistance gene, favorable response to steroids (FRS) and early response at day + 8 of treatment) on the percentage of complete remissions and overall survival. This is a prospective, observational study in adult patients with B-ALL without specific cytogenetic alterations, who started induction treatment based on a pretreatment with prednisone and subsequently vincristine (1.6 mg/m2 subcutaneous) plus daunorubicin (45 mg/m2 subcutaneously) on days + 1, + 8, + 15. The ABCB1 resistance gene was evaluated at diagnosis, the FRS at the end of the pretreatment and the early response during day + 8. A total of 53 adult patients diagnosed with ALL Philadelphia negative chromosome (Ph-), with immunophenotype B, with a normal karyotype, were studied. Cases with genetic abnormalities with a poor prognosis were excluded in order to reduce bias. The mean age was 48 years (range 17-68 years). 62.3% of patients were at high risk of relapse. When analyzing the risk factors, 30.2% showed high levels of the ABCB1 resistance gene, without showing an impact on the induction response (OR: 1.218, p = 0.743), but its overexpression was associated with a poor response to steroids as in the absence of early response. Individually, both the FRS (OR: 5.7, p = 0.004) and the absence of early response to day + 8 (OR: 6.42, p = 0.002) showed significance. By combining the different factors, having more than 2 was directly related to a failure (OR: 9.514, p = 0.000). The identification of factors such as FRS such as the persistence of blasts at the end of the first week of treatment is useful to identify patients at risk of failure in induction.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Quimioterapia de Indução , Proteínas de Neoplasias/biossíntese , Leucemia-Linfoma Linfoblástico de Células Precursoras , Subfamília B de Transportador de Cassetes de Ligação de ATP/biossíntese , Adolescente , Adulto , Idoso , Daunorrubicina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prednisolona/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Vincristina/administração & dosagem
16.
Zhonghua Fu Chan Ke Za Zhi ; 55(9): 589-599, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32957747

RESUMO

Objective: To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 (lymph-vascular space invasion-positive, LVSI+)- Ⅰb1 cervical cancer patients with different tumor sizes. Methods: Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 (LVSI+)-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results: (1) A total of 4 891 patients with stage Ⅰa1 (LVSI+)-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.367, 95%CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups (94.1% vs 95.4%, P=0.151). While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS (HR=1.420, 95%CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS (P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups (P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.705, 95%CI: 1.088-2.674, P=0.020). Conclusions: For patients with stage Ⅰa1 (LVSI+)-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.


Assuntos
Laparoscopia/métodos , Laparotomia/métodos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , China/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia/métodos , Excisão de Linfonodo/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento
17.
Zhonghua Fu Chan Ke Za Zhi ; 55(9): 600-608, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32957748

RESUMO

Objective: To investigate the efficacy and safety of laparoscopic radical hysterectomy for early cervical adenocarcinoma. Methods: A retrospective observational study was performed by reviewing medical records of patients with staging Ⅰb1-Ⅱa2 International Federation of Gynecology and Obstetrics (FIGO, 2009) cervical adenocarcinoma who underwent laparoscopic or abdominal radical hysterectomy from 2007 to 2017 in the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. The difference among clinicopathologic characteristics, surgery-related parameters and complications, and prognosis were analyzed between the laparoscopic group and abdominal group. Results: Two hundreds and ninety-three patients were included with 88 cases in laparoscopic group and 205 cases in abdominal group. (1) There was no significant difference in clinicopathologic characteristics between the two groups (all P>0.05), including age, body mass index, menopause status, history of abdominal surgery, clinical stage, tumor diameter, neoadjuvant chemotherapy, differentiation, lymph-vascular space invasion, positive of surgical margin, parametrial invasion, and lymph node metastasis. But the abdominal group showed a higher proportion of deep stromal invasion (38.5% vs 25.0%, P<0.05). No significant difference was observed between two groups with number of lymph nodes resected, urinary catheter retention, short-term surgical complications (including ureteral injury, ileus, infection, hydronephrosis and poor wound healing), and long-term complications (including voiding dysfunction, defecation dysfunction and lower limb edema; all P>0.05). (2) The laparoscopic group was significantly associated with a longer operation time [(260±51) minutes vs (244±53) minutes, P<0.05], but less bleeding (100 ml vs 300 ml, P<0.01), shorter hospital stay [(13±5) days vs (16±8) days, P<0.01] and lower incidence of lymphedema (12.5% vs 27.8%, P<0.01). (3) The 5-year progression-free survival (PFS; 85.7% vs 86.4%, P=0.971) and 5-year overall survival (OS; 91.4% vs 93.0%, P=0.657) of laparoscopic group were comparable to that of abdominal group. (4) Multivariate analysis demonstrated that lymph node metastasis (HR=2.44, 95%CI: 1.16-5.15, P=0.019) was independent poor prognostic factors related to PFS, while adenosquamous carcinoma (HR=2.54, 95%CI: 1.02-6.35, P=0.046), lymph-vascular space invasion (HR=3.86, 95%CI: 1.60-9.33, P=0.003) and lymph node metastasis (HR=5.92, 95%CI: 2.45-14.34, P<0.01) were independent poor prognostic factors related to OS. The laparoscopy surgery was not an independent poor prognostic factor (P=0.396). Conclusion: The laparoscopic radical hysterectomy for early cervical adenocarcinoma has comparable prognosis to abdominal radical hysterectomy with a higher surgery quality.


Assuntos
Adenocarcinoma/cirurgia , Histerectomia/efeitos adversos , Laparoscopia , Excisão de Linfonodo , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , China/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
18.
Zhonghua Fu Chan Ke Za Zhi ; 55(9): 609-616, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32957749

RESUMO

Objective: To compare the prognosis of patients with cervical cancer in stage Ⅰb2-Ⅱa2 undergoing laparoscopic radical hysterectomy or abdominal radical hysterectomy. Methods: From January 1, 2009 to December 31, 2018, patients with stage Ⅰb2-Ⅱa2 who underwent laparoscopic or abdominal radical hysterectomy (laparoscopic group and abdominal group) in Peking University People's Hospital were collected. The clinicopathological data were retrospectively analyzed. There were 237 cases in this study, including 115 cases in laparoscopic group and 122 cases in abdominal group. The clinicopathological characteristics, surgery-related complications, recurrence and death were analyzed between the two groups. The related factors of recurrence and death were also analyzed.During laparoscopic surgery, the pressure of the carbon dioxide pneumoperitoneum were controlled, to try avoid the tumor tissue in the vagina from being exposed to the abdominal cavity when taking out the uterine specimen through the vagina, and fully flushed the abdominal cavity with sterile water after the specimen was taken out. Results: (1) Clinicopathological characteristics: there was no significant differences between the two groups among age, pathological type, pathological grade, clinical stage, depth of interstitial infiltration, lymph node metastasis,parametrial infiltration, vaginal stump infiltration, lymph-vascular space invasion (LVSI), neoadjuvant chemotherapy, and postoperative adjuvant treatments (all P>0.05). (2) Surgery-related complications: the incidence of surgery-related complications in the laparoscopic group and the abdominal group were 32.2% (37/115) and 25.4% (31/122), respectively. There was no statistically significant difference between the two groups (P>0.05). (3) Recurrence and death: during the follow-up period, the recurrence rates of the laparoscopic group and the abdominal group were respectively 15.7% (18/115) and 12.3% (15/122). There was no statistically significant difference between the two groups (P=0.456). The 5-year overall survival rates of the laparoscopic group and the open group were 86.8% and 87.8%, and the 5-year tumor-free survival rates were 81.7% and 84.6%, respectively. There were no statistically significant differences between the two groups (P=0.405, P=0.429). (4) Analysis of related factors of recurrence and death: univariate analysis showed that neoadjuvant chemotherapy, lymph node metastasis, vaginal stump infiltration, LVSI and interstitial infiltration depth were risk factors for postoperative recurrence of cervical cancer patients (all P<0.05); neoadjuvant chemotherapy, lymph node metastasis, parametrial infiltration, vaginal stump infiltration, LVSI and interstitial infiltration depth were risk factors for postoperative death in patients with cervical cancer (all P<0.05). Multivariate analysis showed that neoadjuvant chemotherapy and lymph node metastasis were independent risk factors for postoperative recurrence and death of cervical cancer patients (P<0.05). Conclusion: There is no significant difference in the prognosis of patients with cervical cancer in stage Ⅰb2-Ⅱa2 undergoing laparoscopic radical hysterectomy with non-touch operative technique and abdominal radical hysterectomy.


Assuntos
Histerectomia/efeitos adversos , Laparoscopia/métodos , Excisão de Linfonodo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia/métodos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade
20.
Medicine (Baltimore) ; 99(38): e21840, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957308

RESUMO

BACKGROUND: The prognostic significance of preoperative prognostic nutritional index (PNI) in ovarian cancer (OC) is uncertain, and this study is aimed to clarify the prognostic significance. METHODS: We used 4 common databases for conducting a systematic review and meta-analysis, and eligible studies were included in the analysis. The association of preoperative PNI with overall survival (OS), progression-free survival (PFS), and clinicopathological parameters was analyzed. RESULTS: A total of 2050 patients with OC receiving the surgical treatment were analyzed in this study. Patients with low PNI tended to have a shorter OS (hazard ratio [HR] = 1.82, 95% CI = 1.30-2.55, P < .01) and PFS (HR = 1.91, 95% CI = 1.53-2.39, P < .01) compared with those with high PNI. Besides, low PNI was significantly associated with more advanced International Federation of Gynecology and Obstetrics stage (P < .01), the occurrence of ascites (P < .01), larger residual tumor (P < .01), insensitive to chemotherapy (P < .01), and higher CA125 (P < .01) compared with high PNI in OC. CONCLUSION: Low preoperative PNI is associated with shorter OS, shorter PFS, and worse clinicopathological parameters in OC. Low preoperative PNI is an unfavorable prognostic indicator of patients with OC.


Assuntos
Estado Nutricional/fisiologia , Neoplasias Ovarianas/mortalidade , Antígeno Ca-125/sangue , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Proteínas de Membrana/sangue , Prognóstico , Modelos de Riscos Proporcionais
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