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1.
BMC Surg ; 21(1): 160, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33757489

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been the standard treatment for locally advanced breast cancer for the purpose of downstaging or for conversion from mastectomy to breast conservation surgery (BCS). Locoregional recurrence (LRR) rate is still high after NAC. The aim of this study was to determine predictive factors for LRR in breast cancer patients in association with the operation types after NAC. METHODS: Between 2005 and 2017, 1047 breast cancer patients underwent BCS or mastectomy after NAC in Chang Gung Memorial Hospital, Linkou. We obtained data regarding patient and tumor characteristics, chemotherapy regimens, clinical tumor response, tumor subtypes and pathological complete response (pCR), type of surgery, and recurrence. RESULTS: The median follow-up time was 59.2 months (range 3.13-186.75 months). The mean initial tumor size was 4.89 cm (SD ± 2.95 cm). Of the 1047 NAC patients, 232 (22.2%) achieved pCR. The BCS and mastectomy rates were 41.3% and 58.7%, respectively. One hundred four patients developed LRR (9.9%). Comparing between patients who underwent BCS and those who underwent mastectomy revealed no significant difference in the overall LRR rate of the two groups, 8.8% in BCS group vs 10.7% in mastectomy group (p = 0.303). Multivariate analysis indicated that independent factors for the prediction of LRR included clinical N2 status, negative estrogen receptor (ER), and failure to achieve pCR. In subgroups of multivariate analysis, only negative ER was the independent factor to predict LRR in mastectomy group (p = 0.025) and hormone receptor negative/human epidermal growth factor receptor 2 positive (HR-/HER2 +) subtype (p = 0.006) was an independent factor to predict LRR in BCS patients. Further investigation according to the molecular subtype showed that following BCS, non-pCR group had significantly increased LRR compared with the pCR group, in HR-/HER2 + subtype (25.0% vs 8.3%, p = 0.037), and HR-/HER2- subtype (20.4% vs 0%, p = 0.002). CONCLUSION: Clinical N2 status, negative ER, and failure to achieve pCR after NAC were independently related to the risk of developing LRR. Operation type did not impact on the LRR. In addition, the LRR rate was higher in non-pCR hormone receptor-negative patients undergoing BCS comparing with pCR patients.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Mastectomia , Terapia Neoadjuvante/efeitos adversos , Recidiva Local de Neoplasia/patologia , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Receptor ErbB-2/uso terapêutico , Receptores Estrogênicos/uso terapêutico , Estudos Retrospectivos
2.
Medicine (Baltimore) ; 100(10): e24960, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725859

RESUMO

INTRODUCTION: (Neo-)adjuvant chemotherapy for breast cancer has a deleterious impact on muscle tissue resulting in reduced cardiorespiratory fitness, skeletal muscle mass and function. Physical exercise during treatment may counteract some of these negative effects. However, the effects of resistance training (RT) alone have never been explored. The present study aims to investigate if heavy-load RT during (neo-)adjuvant chemotherapy counteracts deleterious effects on skeletal muscle in women diagnosed with breast cancer. We hypothesize that (neo-)adjuvant treatment with chemotherapy will reduce muscle fiber size, impair mitochondrial function, and increase indicators of cellular stress and that RT during treatment will counteract these negative effects. We also hypothesize that RT during (neo-)adjuvant chemotherapy will increase muscle and blood levels of potential antitumor myokines and reduce treatment-related side effects on muscle strength and cardiorespiratory fitness. METHODS: Fifty women recently diagnosed with breast cancer scheduled to start (neo-)adjuvant chemotherapy will be randomized to either randomized to either intervention group or to control group.The intervention group will perform supervised heavy-load RT twice a week over the course of chemotherapy (approximately 16-weeks) whereas the control group will be encouraged to continue with their usual activities. Muscle biopsies from m. vastus lateralis will be collected before the first cycle of chemotherapy (T0), after chemotherapy (T1), and 6 months later (T2) for assessment of muscle cellular outcomes. The primary outcome for this study is muscle fiber size. Secondary outcomes are: regulators of muscle fiber size and function, indicators of cellular stress and mitochondrial function, myokines with potential antitumor effects, muscle strength, and cardiorespiratory fitness. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Regional Ethical Review Board in Uppsala, Sweden (Dnr:2016/230/2). Results will be disseminated through presentations at scientific meetings, publications in peer-reviewed journals, social media, and patient organizations. TRIAL REGISTRATION NUMBER: NCT04586517.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/terapia , Terapia por Exercício/métodos , Fadiga Muscular/fisiologia , Treinamento de Resistência , Adulto , Biópsia , Aptidão Cardiorrespiratória/fisiologia , Quimioterapia Adjuvante/efeitos adversos , Feminino , Seguimentos , Humanos , Mastectomia , Pessoa de Meia-Idade , Fadiga Muscular/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Força Muscular/fisiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Músculo Esquelético/fisiologia , Terapia Neoadjuvante/efeitos adversos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
3.
Anticancer Res ; 41(3): 1579-1586, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788752

RESUMO

BACKGROUND/AIM: Histological changes induced by neoadjuvant chemotherapy (NAC) have rarely been reported in histological subtypes other than ovarian high-grade serous carcinoma (HGSC). CASE REPORT: We report a 49-year-old woman whose tumors in interval debulking surgery (IDS) specimen exhibited prominent papillary growth pattern and severe nuclear pleomorphism due to NAC. In the initial microscopic examination, ovarian HGSC was the most likely candidate; however, immunostaining results were not compatible with HGSC. We detected areas resembling mucinous cystadenoma and borderline tumor, and finally diagnosed this case as ovarian mucinous carcinoma. CONCLUSION: Although the tumor mimicked histologically HGSC, its clinical features differed from those of advanced-stage HGSC. It is important for pathologists to recognize NAC-induced histological changes, be aware of the diagnostic mimics and pitfalls, and to identify the correct histological subtype by considering the patient's previous history, clinical features, preoperative imaging findings, and histological features.


Assuntos
Adenocarcinoma Mucinoso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/tratamento farmacológico , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patologia , Quimioterapia Adjuvante/efeitos adversos , Cistadenocarcinoma Seroso/diagnóstico , Erros de Diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Neoplasias Ovarianas/patologia , Proteínas WT1/análise
4.
Nat Commun ; 12(1): 1047, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594075

RESUMO

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of anti-OX40 on lymphocyte subsets in the tumor and blood. Neoadjuvant anti-OX40 was well tolerated and did not delay surgery, thus meeting the primary endpoint. Peripheral blood phenotyping data show increases in CD4+ and CD8+ T cell proliferation two weeks after anti-OX40 administration. Comparison of tumor biopsies before and after treatment reveals an increase of activated, conventional CD4+ tumor-infiltrating lymphocytes (TIL) in most patients and higher clonality by TCRß sequencing. Analyses of CD8+ TIL show increases in tumor-antigen reactive, proliferating CD103+ CD39+ cells in 25% of patients with evaluable tumor tissue (N = 4/16), all of whom remain disease-free. These data provide evidence that anti-OX40 prior to surgery is safe and can increase activation and proliferation of CD4+ and CD8+ T cells in blood and tumor. Our work suggests that increases in the tumor-reactive CD103+ CD39+ CD8+ TIL could serve as a potential biomarker of anti-OX40 clinical activity.


Assuntos
Epitopos/imunologia , Terapia Neoadjuvante , Receptores OX40/antagonistas & inibidores , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Biópsia , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células , Células Clonais , Intervalo Livre de Doença , Papillomavirus Humano 16/fisiologia , Humanos , Estimativa de Kaplan-Meier , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos/imunologia , Linfócitos do Interstício Tumoral/imunologia , Terapia Neoadjuvante/efeitos adversos , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores OX40/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Células Estromais/metabolismo
5.
Nat Med ; 27(2): 256-263, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33558721

RESUMO

Neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma in the phase 1b OpACIN ( NCT02437279 ) and phase 2 OpACIN-neo ( NCT02977052 ) studies1,2. While the results are promising, data on the durability of these pathologic responses and baseline biomarkers for response and survival were lacking. After a median follow-up of 4 years, none of the patients with a pathologic response (n = 7/9 patients) in the OpACIN study had relapsed. In OpACIN-neo (n = 86), the 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (P < 0.001). High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-γ score) were associated with pathologic response and low risk of relapse; pRR was 100% in patients with high IFN-γ score/high TMB; patients with high IFN-γ score/low TMB or low IFN-γ score/high TMB had pRRs of 91% and 88%; while patients with low IFN-γ score/low TMB had a pRR of only 39%. These data demonstrate long-term benefit in patients with a pathologic response and show the predictive potential of TMB and IFN-γ score. Our findings provide a strong rationale for a randomized phase 3 study comparing neoadjuvant ipilimumab plus nivolumab versus standard adjuvant therapy with antibodies against the programmed cell death protein-1 (anti-PD-1) in macroscopic stage III melanoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ipilimumab/administração & dosagem , Melanoma/tratamento farmacológico , Nivolumabe/administração & dosagem , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Intervalo Livre de Doença , Feminino , Humanos , Imunoterapia/efeitos adversos , Interferon gama/genética , Ipilimumab/efeitos adversos , Masculino , Melanoma/imunologia , Melanoma/patologia , Pessoa de Meia-Idade , Mutação/genética , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Nivolumabe/efeitos adversos , Recidiva
6.
Nat Med ; 27(2): 301-309, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33558722

RESUMO

The association among pathological response, recurrence-free survival (RFS) and overall survival (OS) with neoadjuvant therapy in melanoma remains unclear. In this study, we pooled data from six clinical trials of anti-PD-1-based immunotherapy or BRAF/MEK targeted therapy. In total, 192 patients were included; 141 received immunotherapy (104, combination of ipilimumab and nivolumab; 37, anti-PD-1 monotherapy), and 51 received targeted therapy. A pathological complete response (pCR) occurred in 40% of patients: 47% with targeted therapy and 33% with immunotherapy (43% combination and 20% monotherapy). pCR correlated with improved RFS (pCR 2-year 89% versus no pCR 50%, P < 0.001) and OS (pCR 2-year OS 95% versus no pCR 83%, P = 0.027). In patients with pCR, near pCR or partial pathological response with immunotherapy, very few relapses were seen (2-year RFS 96%), and, at this writing, no patient has died from melanoma, whereas, even with pCR from targeted therapy, the 2-year RFS was only 79%, and OS was only 91%. Pathological response should be an early surrogate endpoint for clinical trials and a new benchmark for development and approval in melanoma.


Assuntos
Melanoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Imunoterapia/efeitos adversos , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Masculino , Melanoma/genética , Melanoma/imunologia , Melanoma/patologia , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Terapia Neoadjuvante/efeitos adversos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Adulto Jovem
8.
Lancet Oncol ; 22(1): e18-e28, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33387500

RESUMO

Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/terapia , Mastectomia Segmentar/normas , Oncologia/normas , Terapia Neoadjuvante/normas , Antineoplásicos/efeitos adversos , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Tomada de Decisão Clínica , Consenso , Técnica Delfos , Feminino , Humanos , Mastectomia Segmentar/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Resultado do Tratamento
9.
J Thorac Cardiovasc Surg ; 161(3): 836-843.e1, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33485662

RESUMO

OBJECTIVES: We sought to determine the safety and feasibility of esophagectomy after neoadjuvant immunotherapy and chemoradiotherapy in clinical trial patients with locally advanced esophageal cancer. METHODS: We retrospectively identified patients who were treated with neoadjuvant immunotherapy and chemoradiotherapy (n = 25) or chemoradiotherapy alone (n = 143) at our institution between 2017 and 2020. The primary end point was risk of 30-day major complications (Clavien-Dindo classification system grade ≥ 3), which was assessed between groups using a multivariable log-binomial regression model to obtain adjusted relative risk ratios. Secondary end points were interval to surgery, 30-day readmission rate, and 30-day mortality. RESULTS: All included patients successfully completed neoadjuvant therapy and underwent esophagectomy with negative margins. Age, sex, performance status, clinical stage, histologic subtype, procedure type, and operative approach were similar between groups. Neoadjuvant immunotherapy was not associated with a statistically significantly increased risk of developing a major pulmonary (relative risk, 1.43; 95% confidence interval, 0.53-3.84; P = .5), anastomotic (relative risk, 1.34; 95% confidence interval, 0.45-3.94; P = .6), or other complication (relative risk, 1.29; 95% confidence interval, 0.26-6.28; P = .8). Median (interquartile range) interval to surgery was 54 days (47-61 days) in the immune checkpoint inhibitor group versus 53 days (47-66 days) in the control group (P = .6). Minimally invasive approaches were successful in 72% of cases, with only 1 conversion. Thirty-day mortality and readmission rates were 0% and 17%, respectively, in the immune checkpoint inhibitor group and 1.4% and 13%, respectively, in the control group. CONCLUSIONS: On the basis of our preliminary experience, esophagectomy appears to be safe and feasible following combined neoadjuvant immunotherapy and standard chemoradiotherapy for locally advanced esophageal cancer.


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante , Neoplasias Esofágicas/terapia , Esofagectomia , Imunoterapia , Terapia Neoadjuvante , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Idoso , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Bases de Dados Factuais , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidade , Esofagectomia/efeitos adversos , Esofagectomia/mortalidade , Estudos de Viabilidade , Feminino , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Readmissão do Paciente , Segurança do Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
10.
Anticancer Res ; 41(1): 359-368, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419832

RESUMO

BACKGROUND/AIM: Surgical resection for soft tissue sarcomas (STSs) is the gold standard for a curative oncologic therapy in combination with neoadjuvant or adjuvant radiation therapy (NRT/ART). The aim of this study was to determine prognostic factors influencing the survival of patients with STS undergoing NRT or ART considering various parameters in a retrospective, single-centre analysis over 15 years. PATIENTS AND METHODS: We included 119 patients (male 59) and the median follow-up period was 69 months (4-197). The patients received NRT (n=64) or ART (n=55). We recorded the histopathologic subtype of STS, tumour grade, localization, tumour margins, complications, survival, local recurrence, and metastases. Survival analysis was performed using the Kaplan-Meier method. RESULTS: The overall survival rate was 68.9% at 5 years. The localization (epifascial/subfascial), resection margin and type of radiation therapy (NRT/ART) had no significant impact on survival. Tumour grade, tumour size, local recurrence and metastases were significantly correlated with patient survival (p<0.05). Local recurrence was significantly higher in patients with ART (p=0.044). CONCLUSION: Tumour grade and tumour size were independently associated with disease-specific survival, and patients with local recurrence and metastases had lower survival rates.


Assuntos
Sarcoma/mortalidade , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/cirurgia , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Retratamento , Estudos Retrospectivos , Sarcoma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Resultado do Tratamento
11.
Lancet Oncol ; 22(1): 43-50, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33316218

RESUMO

BACKGROUND: Watch and wait is a novel management strategy in patients with rectal cancer who have a clinical complete response after neoadjuvant chemoradiotherapy. Surveillance of these patients is generally intensive, because local regrowth (with the potential for salvage) occurs in 25% of patients, and distant metastases occur in 10% of patients. It is unclear for how long these patients should be followed up. To address this issue, we did conditional survival modelling using the International Watch & Wait Database (IWWD), which is a large-scale registry of patients with a clinical complete response after neoadjuvant chemotherapy who have been managed by a watch-and-wait strategy. METHODS: We did a retrospective, multicentre registry study using a dataset from the IWWD, which includes data from 47 clinics across 15 countries. We selected patients (aged ≥18 years) with rectal cancer who had a clinical complete response after neoadjuvant chemotherapy, and who were subsequently managed by a watch-and-wait strategy between Nov 25, 1991, and Dec 31, 2015. Patients who had not achieved a clinical complete response or who had undergone any surgical procedure were excluded. The criteria used for defining a clinical complete response and the specific surveillance strategies were at the discretion of each participating centre. We used conditional survival modelling to estimate the probability of patients remaining free of local regrowth or distant metastasis for an additional 2 years after sustaining a clinical complete response or being distant metastasis-free for 1, 3, and 5 years from the date of the decision to commence watch and wait. The primary outcomes were conditional local regrowth-free survival at 3 years, and conditional distant metastasis-free survival at 5 years. FINDINGS: We identified 793 patients in the IWWD with clinical complete response who had been managed by a watch-and-wait strategy. Median follow-up was 55·2 months (IQR 36·0-75·6). The probability of remaining free from local regrowth for an additional 2 years if a patient had a sustained clinical complete response for 1 year was 88·1% (95% CI 85·8-90·9), for 3 years was 97·3% (95·2-98·6), and for 5 years was 98·6% (97·6-100·0). The probably of remaining free from distant metastasis for a further 2 years in patients who had a clinical complete response without distant metastasis for 1 year was 93·8% (92·3-95·9), for 3 years was 97·8% (96·6-99·3), and for 5 years was 96·6% (94·0-98·9). INTERPRETATION: These results suggest that the intensity of active surveillance in patients with rectal cancer managed by a watch-and-wait approach could be reduced if they achieve and maintain a clinical complete response within the first 3 years of starting this approach. FUNDING: European Registration of Cancer Care, financed by the European Society of Surgical Oncology, the Champalimaud Foundation Lisbon, the Bas Mulder Award, granted by the Alpe d'HuZes Foundation and the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre.


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante , Terapia Neoadjuvante , Neoplasias Retais/terapia , Conduta Expectante , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Idoso , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Recidiva Local de Neoplasia , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Sistema de Registros , Indução de Remissão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
Lancet Oncol ; 22(2): 277-288, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33357510

RESUMO

BACKGROUND: Platinum-based neoadjuvant chemotherapy followed by delayed primary surgery (DPS) is an established strategy for women with newly diagnosed, advanced-stage epithelial ovarian cancer. Although this therapeutic approach has been validated in randomised, phase 3 trials, evaluation of response to neoadjuvant chemotherapy using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and cancer antigen 125 (CA125) has not been reported. We describe RECIST and Gynecologic Cancer InterGroup (GCIG) CA125 responses in patients receiving platinum-based neoadjuvant chemotherapy followed by DPS in the ICON8 trial. METHODS: ICON8 was an international, multicentre, randomised, phase 3 trial done across 117 hospitals in the UK, Australia, New Zealand, Mexico, South Korea, and Ireland. The trial included women aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, life expectancy of more than 12 weeks, and newly diagnosed International Federation of Gynecology and Obstetrics (FIGO; 1988) stage IC-IIA high-grade serous, clear cell, or any poorly differentiated or grade 3 histological subtype, or any FIGO (1988) stage IIB-IV epithelial cancer of the ovary, fallopian tube, or primary peritoneum. Patients were randomly assigned (1:1:1) to receive intravenous carboplatin (area under the curve [AUC]5 or AUC6) and intravenous paclitaxel (175 mg/m2 by body surface area) on day 1 of every 21-day cycle (control group; group 1); intravenous carboplatin (AUC5 or AUC6) on day 1 and intravenous dose-fractionated paclitaxel (80 mg/m2 by body surface area) on days 1, 8, and 15 of every 21-day cycle (group 2); or intravenous dose-fractionated carboplatin (AUC2) and intravenous dose-fractionated paclitaxel (80 mg/m2 by body surface area) on days 1, 8, and 15 of every 21-day cycle (group 3). The maximum number of cycles of chemotherapy permitted was six. Randomisation was done with a minimisation method, and patients were stratified according to GCIG group, disease stage, and timing and outcome of cytoreductive surgery. Patients and clinicians were not masked to group allocation. The scheduling of surgery and use of neoadjuvant chemotherapy were determined by local multidisciplinary case review. In this post-hoc exploratory analysis of ICON8, progression-free survival was analysed using the landmark method and defined as the time interval between the date of pre-surgical planning radiological tumour assessment to the date of investigator-assessed clinical or radiological progression or death, whichever occurred first. This definition is different from the intention-to-treat primary progression-free survival analysis of ICON8, which defined progression-free survival as the time from randomisation to the date of first clinical or radiological progression or death, whichever occurred first. We also compared the extent of surgical cytoreduction with RECIST and GCIG CA125 responses. This post-hoc exploratory analysis includes only women recruited to ICON8 who were planned for neoadjuvant chemotherapy followed by DPS and had RECIST and/or GCIG CA125-evaluable disease. ICON8 is closed for enrolment and follow-up, and registered with ClinicalTrials.gov, NCT01654146. FINDINGS: Between June 6, 2011, and Nov 28, 2014, 1566 women were enrolled in ICON8, of whom 779 (50%) were planned for neoadjuvant chemotherapy followed by DPS. Median follow-up was 29·5 months (IQR 15·6-54·3) for the neoadjuvant chemotherapy followed by DPS population. Of 564 women who had RECIST-evaluable disease at trial entry, 348 (62%) had a complete or partial response. Of 727 women who were evaluable by GCIG CA125 criteria at the time of diagnosis, 610 (84%) had a CA125 response. Median progression-free survival was 14·4 months (95% CI 9·2-28·0; 297 events) for patients with a RECIST complete or partial response and 13·3 months (8·1-20·1; 171 events) for those with RECIST stable disease. Median progression-free survival for women with a GCIG CA125 response was 13·8 months (95% CI 8·8-23·4; 544 events) and 9·7 months (5·8-14·5; 111 events) for those without a GCIG CA125 response. Complete cytoreduction (R0) was achieved in 187 (56%) of 335 women with a RECIST complete or partial response and 73 (42%) of 172 women with RECIST stable disease. Complete cytoreduction was achieved in 290 (50%) of 576 women with a GCIG CA125 response and 30 (30%) of 101 women without a GCIG CA125 response. INTERPRETATION: The RECIST-defined radiological response rate was lower than that frequently quoted to patients in the clinic. RECIST and GCIG CA125 responses to neoadjuvant chemotherapy for epithelial ovarian cancer should not be used as individual predictive markers to stratify patients who are likely to benefit from DPS, but instead used in conjunction with the patient's clinical capacity to undergo cytoreductive surgery. A patient should not be denied surgery based solely on the lack of a RECIST or GCIG CA125 response. FUNDING: Cancer Research UK, UK Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, and Cancer Australia.


Assuntos
Carboplatina/administração & dosagem , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Idoso , Austrália , Antígeno Ca-125 , Carboplatina/efeitos adversos , Intervalo Livre de Doença , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Tubas Uterinas/patologia , Feminino , Humanos , Irlanda , Proteínas de Membrana , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Nova Zelândia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/efeitos adversos , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Critérios de Avaliação de Resposta em Tumores Sólidos
13.
Zhonghua Fu Chan Ke Za Zhi ; 55(12): 848-856, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33355760

RESUMO

Objective: To investigate the diagnosis, treatment and prognosis of uterine serous carcinoma (USC), and further analyze the prognostic factors. Methods: USC patients who underwent surgery with complete follow-up at Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: (1) Diagnosis and treatment: the study included 71 USC patients. Only 32 patients (45%, 32/71) were diagnosed preoperatively with USC, and 25 cases of them (35%, 25/71) underwent USC standard comprehensive staging surgery. Of the 25 patients, 10 cases (40%, 10/25) had up-staged after operation. (2) Prognosis: the 5-year disease free survival (DFS) rate and overall survival (OS) rate for all patients were 76.5% and 80.6%, respectively. (3) The results of prognostic factors analysis: univariate analysis on age, range of lymphadenectomy, peritoneal cytology, the depth of myometrial invasion, adnexal and (or) serosa involvement and omentum metastasis were significantly associated with 5-year DFS rate (all P<0.05); range of lymphadenectomy, range of surgical staging, peritoneal cytology, adnexal and (or) serosa involvement and postoperative adjuvant treatment were significantly associated with 5-year OS rate (all P<0.05). Multivariate analysis on range of surgical staging (HR=5.18, 95%CI: 1.04-25.70, P=0.044) and adnexal and (or) serosa involvement (HR=8.41, 95%CI: 2.28-31.05, P=0.001) were independent prognostic factors for 5-year DFS rate; range of lymphadenectomy [no lymphadenectomy vs pelvic lymphadenectomy (PLN)+para-aortic lymphadenectomy (PALN), HR=27.76, 95%CI: 1.76-437.78, P=0.018;PLN vs PLN+PALN, HR=5.98, 95%CI: 1.11-32.27, P=0.038] and peritoneal cytology (HR=5.47, 95%CI: 1.18-25.39, P=0.030) were independent prognostic factors for 5-year OS rate. Conclusions: The preoperative pathological diagnosis of USC is difficult, resulting in incomplete surgical staging and inaccurate staging. Range of surgical staging, adnexal and (or) serosa involvement, peritoneal cytology and range of lymphadenectomy are independent prognostic factors, which deserve much attention in clinical practice.


Assuntos
Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/terapia , Procedimentos Cirúrgicos em Ginecologia/métodos , Terapia Neoadjuvante/métodos , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirurgia , China/epidemiologia , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Cuidados Pós-Operatórios , Prognóstico , Estudos Retrospectivos , Neoplasias Uterinas/mortalidade
14.
Yonsei Med J ; 61(11): 935-941, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33107236

RESUMO

PURPOSE: Salvage second-line chemotherapy is usually recommended for patients with advanced epithelial ovarian cancer (AEOC) who develop progressive disease (PD) after neoadjuvant chemotherapy (NAC). Herein, we investigated the role of cytoreductive surgery (CRS) for such patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 36 patients with AEOC who developed PD after receiving NAC at two tertiary academic centers with different treatment strategies between 2001 and 2016. Patients who developed PD after NAC were consistently treated with CRS at one hospital (group A; n=13) and second-line chemotherapy at another (group B; n=23). The clinical characteristics and treatment outcomes were compared between the groups. RESULTS: Overall survival (OS) was longer in group A than in group B (19.4 months vs. 7.9 months; p=0.011). High-grade serous histology was associated with longer OS than non-high-grade serous types. In group A, optimal surgery resection (<1 cm) was achieved after CRS in 6 patients (46%). Multivariate analysis showed that the treatment option was the only independent predictive factor for OS (hazard ratio, 2.30; 95% confidence interval, 1.02-5.17; p=0.044). CONCLUSION: CRS may result in a survival benefit even in patients with AEOC who develop PD after NAC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Neoplasias Ovarianas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Procedimentos Cirúrgicos de Citorredução/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante/mortalidade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
15.
Zhonghua Wai Ke Za Zhi ; 58(10): 741-744, 2020 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-32993258

RESUMO

The low surgical resection rate and high postoperative recurrence rate of hepatocellular carcinoma(HCC) are urgent clinical problems to be solved. Therefore, it is important to develop effective perioperative treatment. In recent years, a growing number of studies have shown that systemic therapy is expected to break through the limitations of traditional local treatment and play an important role in preoperative treatment. For example, some novel targeted agents and immunocheckpoint inhibitors have shown excellent potential as neoadjuvant treatment for HCC. Meanwhile, researchers have explored the application of systemic therapy as adjuvant therapy, but due to different criteria for patient selection, no consensus is reached on its efficacy. By far, there is no standard procedure for the application of systemic therapy in HCC perioperative period, little is known about the efficacy and safety of targeted drugs and immunotherapy. This article discusses the feasibility of systemic therapy as neoadjuvant and adjuvant treatment of HCC, as well as its adverse events, with an aim to provide new horizons of HCC systemic therapy in the perioperative period.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Terapia Neoadjuvante , Assistência Perioperatória , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/terapia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Terapia Combinada/tendências , Hepatectomia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/tendências , Assistência Perioperatória/tendências
16.
Lancet Oncol ; 21(11): 1413-1422, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32979984

RESUMO

BACKGROUND: Non-small-cell lung cancer (NSCLC) is terminal in most patients with locally advanced stage disease. We aimed to assess the antitumour activity and safety of neoadjuvant chemoimmunotherapy for resectable stage IIIA NSCLC. METHODS: This was an open-label, multicentre, single-arm phase 2 trial done at 18 hospitals in Spain. Eligible patients were aged 18 years or older with histologically or cytologically documented treatment-naive American Joint Committee on Cancer-defined stage IIIA NSCLC that was deemed locally to be surgically resectable by a multidisciplinary clinical team, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received neoadjuvant treatment with intravenous paclitaxel (200 mg/m2) and carboplatin (area under curve 6; 6 mg/mL per min) plus nivolumab (360 mg) on day 1 of each 21-day cycle, for three cycles before surgical resection, followed by adjuvant intravenous nivolumab monotherapy for 1 year (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was progression-free survival at 24 months, assessed in the modified intention-to-treat population, which included all patients who received neoadjuvant treatment, and in the per-protocol population, which included all patients who had tumour resection and received at least one cycle of adjuvant treatment. Safety was assessed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03081689, and is ongoing but no longer recruiting patients. FINDINGS: Between April 26, 2017, and Aug 25, 2018, we screened 51 patients for eligibility, of whom 46 patients were enrolled and received neoadjuvant treatment. At the time of data cutoff (Jan 31, 2020), the median duration of follow-up was 24·0 months (IQR 21·4-28·1) and 35 of 41 patients who had tumour resection were progression free. At 24 months, progression-free survival was 77·1% (95% CI 59·9-87·7). 43 (93%) of 46 patients had treatment-related adverse events during neoadjuvant treatment, and 14 (30%) had treatment-related adverse events of grade 3 or worse; however, none of the adverse events were associated with surgery delays or deaths. The most common grade 3 or worse treatment-related adverse events were increased lipase (three [7%]) and febrile neutropenia (three [7%]). INTERPRETATION: Our results support the addition of neoadjuvant nivolumab to platinum-based chemotherapy in patients with resectable stage IIIA NSCLC. Neoadjuvant chemoimmunotherapy could change the perception of locally advanced lung cancer as a potentially lethal disease to one that is curable. FUNDING: Bristol-Myers Squibb, Instituto de Salud Carlos III, European Union's Horizon 2020 research and innovation programme.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Nivolumabe/administração & dosagem , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Nivolumabe/efeitos adversos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Espanha/epidemiologia , Resultado do Tratamento
17.
Lancet Oncol ; 21(10): 1366-1377, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32941794

RESUMO

BACKGROUND: Unlike for extremity sarcomas, the efficacy of radiotherapy for retroperitoneal sarcoma is not established. The aim of this study was to evaluate the impact of preoperative radiotherapy plus surgery versus surgery alone on abdominal recurrence-free survival. METHODS: EORTC-62092 is an open-label, randomised, phase 3 study done in 31 research institutions, hospitals, and cancer centres in 13 countries in Europe and North America. Adults (aged ≥18 years) with histologically documented, localised, primary retroperitoneal sarcoma that was operable and suitable for radiotherapy, who had not been previously treated and had a WHO performance status and American Society of Anesthesiologists score of 2 or lower, were centrally randomly assigned (1:1), using an interactive web response system and a minimisation algorithm, to receive either surgery alone or preoperative radiotherapy followed by surgery. Randomisation was stratified by hospital and performance status. Radiotherapy was delivered as 50·4 Gy (in 28 daily fractions of 1·8 Gy) in either 3D conformal radiotherapy or intensity modulated radiotherapy, and the objective of surgery was a macroscopically complete resection of the tumour mass with en-bloc organ resection as necessary. The primary endpoint was abdominal recurrence-free survival, as assessed by the investigator, and was analysed in the intention-to-treat population. Safety was analysed in all patients who started their allocated treatment. This trial is registered with ClinicalTrials.gov, NCT01344018. FINDINGS: Between Jan 18, 2012 and April 10, 2017, 266 patients were enrolled, of whom 133 were randomly assigned to each group. The median follow-up was 43·1 months (IQR 28·8-59·2). 128 (96%) patients from the surgery alone group had surgery, and 119 (89%) patients in the radiotherapy and surgery group had both radiotherapy and surgery. Median abdominal recurrence-free survival was 4·5 years (95% CI 3·9 to not estimable) in the radiotherapy plus surgery group and 5·0 years (3·4 to not estimable) in the surgery only group (hazard ratio 1·01, 95% CI 0·71-1·44; log rank p=0·95). The most common grade 3-4 adverse events were lymphopenia (98 [77%] of 127 patients in the radiotherapy plus surgery group vs one [1%] of 128 patients in the surgery alone group), anaemia (15 [12%] vs ten [8%]), and hypoalbuminaemia (15 [12%] vs five [4%]). Serious adverse events were reported in 30 (24%) of 127 patients in the radiotherapy plus surgery group, and in 13 (10%) of 128 patients in the surgery alone group. One (1%) of 127 patients in the radiotherapy plus surgery group died due to treatment-related serious adverse events (gastropleural fistula), and no patients in the surgery alone group died due to treatment-related serious adverse events. INTERPRETATION: Preoperative radiotherapy should not be considered as standard of care treatment for retroperitoneal sarcoma. FUNDING: European Organisation for Research and Treatment of Cancer, and European Clinical Trials in Rare Sarcomas.


Assuntos
Terapia Neoadjuvante , Neoplasias Retroperitoneais/radioterapia , Sarcoma/radioterapia , Idoso , Intervalo Livre de Doença , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , América do Norte , Radioterapia Adjuvante/efeitos adversos , Radioterapia Conformacional/efeitos adversos , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/cirurgia , Sarcoma/patologia , Sarcoma/cirurgia , Resultado do Tratamento
18.
Cancer Causes Control ; 31(11): 1021-1026, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32888164

RESUMO

BACKGROUND: Patients with residual nodal disease after neoadjuvant chemotherapy for breast cancer have a poor prognosis. We wanted to evaluate whether lymphopenia after treatment for breast cancer impacted clinical outcomes. MATERIALS AND METHODS: We assessed 99 patients with node-positive disease after neoadjuvant chemotherapy. Absolute lymphocyte count was recorded 1 year after radiation. Dates of local, regional, and distant failure were recorded. Time to event outcomes were evaluated using Kaplan-Meier analysis. Multivariable analysis determined factors predictive for overall survival. RESULTS: Median follow-up was 44 months (range 3-150). Median age was 48 years (range 23-79). Twenty-six patients (26%) had lymphopenia 1 year after RT. Patients with lymphopenia had a greater incidence of regional (p = 0.03) and distant failure (p = 0.009) compared to those with normal lymphocyte counts and had a 6.05 greater risk of death (p = 0.0002). CONCLUSIONS: In patients with residual nodal disease after neoadjuvant chemotherapy, lymphopenia after breast cancer treatment was associated with overall survival. The relationship between lymphopenia and breast cancer outcomes warrants further investigation.


Assuntos
Neoplasias da Mama/terapia , Linfopenia/epidemiologia , Terapia Neoadjuvante/métodos , Adulto , Idoso , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfopenia/etiologia , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Adulto Jovem
19.
Surgery ; 168(3): 486-496, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32620303

RESUMO

BACKGROUND: To compare outcomes of total mesorectal excision with or without lateral pelvic lymph node dissection for the treatment of rectal cancer. METHODS: The electronic data sources were explored to capture all studies comparing total mesorectal excision with and without lateral pelvic lymph node dissection in patients undergoing operation for rectal cancer. Random effects modelling was utilized for the analyses. The uncertainties associated with varying follow-up periods among the included studies were resolved by analysis of time-to-event outcomes. RESULTS: Eighteen comparative studies enrolling 6,133 patients were eligible. No difference was found between the 2 groups in terms of overall survival (hazard ratio: 0.92, 95% confidence interval 0.77-1.10, P = .36, I2 = 67%), overall survival at maximum follow-up (odds ratio: 1.02, 95% confidence interval 0.83-1.25, P = .86, I2 = 22%), 5-year overall survival (odds ratio: 1.01, 95% confidence interval 0.78-1.30, P = .94, I2 = 50%), disease-free survival (hazard ratio: 1.25, 95% confidence interval 0.87-1.82, P = .23, I2 = 74%), disease-free survival at maximum follow-up (odds ratio 1.07, 95% confidence interval 0.88-1.31, P = .50, I2 = 0%), 5-year disease-free survival (odds ratio: 1.07, 95% confidence interval 0.86-1.32, P = .54, I2 = 0%), local recurrence (odds ratio: 1.01, 95% confidence interval 0.72-1.42, P = .97, I2 = 34%), distant recurrence (odds ratio: 0.96, 95% confidence interval 0.62-1.46, P = .84, I2 = 18%), and total recurrence (odds ratio: 0.97, 95% confidence interval 0.72-1.29, P = .82, I2 = 0%). Total mesorectal excision with lateral pelvic lymph node dissection resulted in longer operative time (mean difference: 116.02, 95% confidence interval 89.20-142.83, P < .00001, I2 = 68%) and higher risks of postoperative complications (odds ratio: 1.59, 95% confidence interval 1.14-2.24, P = .007, I2 = 0%), urinary dysfunction (odds ratio: 6.66, 95% confidence interval 3.31-13.39, P < .00001, I2 = 23%), and sexual dysfunction (odds ratio: 9.67, 95% confidence interval 2.38-39.26, P = .002; I2 = 51%). The results remained consistent through separate analyses for randomized trials, observational studies, and patients with or without neoadjuvant chemoradiotherapy. CONCLUSION: The available evidence suggests that lateral pelvic lymph node dissection results in greater postoperative morbidity, urinary dysfunction, and sexual dysfunction without improving recurrence and survival. Further evidence is needed from randomized controlled trials to enable experts in the nerve-sparing surgical experiences and neoadjuvant therapy experience to advise on the best treatment strategies for the management of rectal cancer patients including those with possible positive nodes on pretreatment imaging.


Assuntos
Excisão de Linfonodo/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Protectomia/efeitos adversos , Neoplasias Retais/terapia , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/métodos , Intervalo Livre de Doença , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/prevenção & controle , Estudos Observacionais como Assunto , Pelve/cirurgia , Complicações Pós-Operatórias/etiologia , Protectomia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia
20.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(7): 657-660, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32683826

RESUMO

The standard treatment for advanced gastric cancer remains surgery-based comprehensive treatment. The D2 radical surgery has made outstanding contributions to the standarlization of gastric cancer surgery, which has improved patients' prognosis and quality of life. In recent years, neoadjuvant chemotherapy has achieved a certain effect on the treatment of advanced gastric cancer. With the continuous development of the concept of membrane anatomy in gastric cancer surgery, new surgical challenges have also been raised. For patients after neoadjuvant therapy, there is heated controversy in the possibility of completing radical gastrectomy with membrane anatomical concept for gastric cancer. We believe that if neoadjuvant therapy pushes mesenteric cancer cell back into the mesentery, theoretically membrane anatomy combined with neoadjuvant therapy is beneficial to the treatment efficacy of advanced gastric cancer. However, membrane anatomy has two important problems when combined with neoadjuvant therapy: (1) After neoadjuvant chemotherapy, there are varying degrees of edema around the stomach tissue, which will affect the visualization of anatomic planes. In addition, because the patients' coagulation function is damaged to a certain extent, it is difficult to avoid bleeding or minimize bleeding during the operation. Therefore, it is still controversial whether the patients with gastric cancer after neoadjuvant chemotherapy can undergo radical gastrectomy with membrane anatomy. (2) For patients with complete pathological remission, whether to obtain the maximum rate of pathological remission through intensive neoadjuvant therapy, or to obtain the survival benefit of patients with membrane anatomy surgery in clinic is still controversial. Faced with these confusions, multi-center clinical researches on the application of membrane anatomy surgery after neoadjuvant therapy is the only solution.


Assuntos
Gastrectomia/métodos , Mesentério/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Edema/etiologia , Gastrectomia/efeitos adversos , Humanos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Mesentério/anatomia & histologia , Mesentério/irrigação sanguínea , Mesentério/patologia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Prognóstico , Qualidade de Vida , Neoplasias Gástricas/patologia
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