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1.
Lancet Oncol ; 21(11): 1443-1454, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33152284

RESUMO

BACKGROUND: Preoperative and perioperative aromatase inhibitor (POAI) therapy has the potential to improve outcomes in women with operable oestrogen receptor-positive primary breast cancer. It has also been suggested that tumour Ki67 values after 2 weeks (Ki672W) of POAI predicts individual patient outcome better than baseline Ki67 (Ki67B). The POETIC trial aimed to test these two hypotheses. METHODS: POETIC was an open-label, multicentre, parallel-group, randomised, phase 3 trial (done in 130 UK hospitals) in which postmenopausal women aged at least 50 years with WHO performance status 0-1 and hormone receptor-positive, operable breast cancer were randomly assigned (2:1) to POAI (letrozole 2·5 mg per day orally or anastrozole 1 mg per day orally) for 14 days before and following surgery or no POAI (control). Adjuvant treatment was given as per UK standard local practice. Randomisation was done centrally by computer-generated permuted block method (variable block size of six or nine) and was stratified by hospital. Treatment allocation was not masked. The primary endpoint was time to recurrence. A key second objective explored association between Ki67 (dichotomised at 10%) and disease outcomes. The primary analysis for clinical endpoints was by modified intention to treat (excluding patients who withdrew consent). For Ki67 biomarker association and endpoint analysis, the evaluable population included all randomly assigned patients who had paired Ki67 values available. This study is registered with ClinicalTrials.gov, NCT02338310; the European Clinical Trials database, EudraCT2007-003877-21; and the ISRCTN registry, ISRCTN63882543. Recruitment is complete and long-term follow-up is ongoing. FINDINGS: Between Oct 13, 2008, and April 16, 2014, 4480 women were recruited and randomly assigned to POAI (n=2976) or control (n=1504). On Feb 6, 2018, median follow-up was 62·9 months (IQR 58·1-74·1). 434 (10%) of 4480 women had a breast cancer recurrence (280 [9%] POAI; 154 [10%] control), hazard ratio 0·92 (95% CI 0·75-1·12); p=0·40 with the proportion free from breast cancer recurrence at 5 years of 91·0% (95% CI 89·9-92·0) for patients in the POAI group and 90·4% (88·7-91·9) in the control group. Within the POAI-treated HER2-negative subpopulation, 5-year recurrence risk in women with low Ki67B and Ki672W (low-low) was 4·3% (95% CI 2·9-6·3), 8·4% (6·8-10·5) with high Ki67B and low Ki672W (high-low) and 21·5% (17·1-27·0) with high Ki67B and Ki672W (high-high). Within the POAI-treated HER2-positive subpopulation, 5-year recurrence risk in the low-low group was 10·1% (95% CI 3·2-31·3), 7·7% (3·4-17·5) in the high-low group, and 15·7% (10·1-24·4) in the high-high group. The most commonly reported grade 3 adverse events were hot flushes (20 [1%] of 2801 patients in the POAI group vs six [<1%] of 1400 in the control group) and musculoskeletal pain (29 [1%] vs 13 [1%]). No treatment-related deaths were reported. INTERPRETATION: POAI has not been shown to improve treatment outcome, but can be used without detriment to help select appropriate adjuvant therapy based on tumour Ki67. Most patients with low Ki67B or low POAI-induced Ki672W do well with adjuvant standard endocrine therapy (giving consideration to clinical-pathological factors), whereas those whose POAI-induced Ki672W remains high might benefit from further adjuvant treatment or trials of new therapies. FUNDING: Cancer Research UK.


Assuntos
Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Antígeno Ki-67/genética , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Idoso , Inibidores da Aromatase/efeitos adversos , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/patologia , Pós-Menopausa/efeitos dos fármacos , Prognóstico , Receptor ErbB-2/genética
2.
Lancet Oncol ; 21(11): 1455-1464, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33152285

RESUMO

BACKGROUND: In early-stage HER2-positive breast cancer, escalation or de-escalation of systemic therapy is a controversial topic. As an aid to treatment decisions, we aimed to develop a prognostic assay that integrates multiple data types for predicting survival outcome in patients with newly diagnosed HER2-positive breast cancer. METHODS: We derived a combined prognostic model using retrospective clinical-pathological data on stromal tumour-infiltrating lymphocytes, PAM50 subtypes, and expression of 55 genes obtained from patients who participated in the Short-HER phase 3 trial. The trial enrolled patients with newly diagnosed, node-positive, HER2-positive breast cancer or, if node negative, with at least one risk factor (ie, tumour size >2 cm, histological grade 3, lymphovascular invasion, Ki67 >20%, age ≤35 years, or hormone receptor negativity), and randomly assigned them to adjuvant anthracycline plus taxane-based combinations with either 9 weeks or 1 year of trastuzumab. Trastuzumab was administered intravenously every 3 weeks (8 mg/kg loading dose at first cycle, and 6 mg/kg thereafter) for 18 doses or weekly (4 mg/kg loading dose in the first week, and 2 mg/kg thereafter) for 9 weeks, starting concomitantly with the first taxane dose. Median follow-up was 91·4 months (IQR 75·1-105·6). The primary objective of our study was to derive and evaluate a combined prognostic score associated with distant metastasis-free survival (the time between randomisation and distant recurrence or death before recurrence), an exploratory endpoint in Short-HER. Patient samples in the training dataset were split into a training set (n=290) and a testing set (n=145), balancing for event and treatment group. The training set was further stratified into 100 iterations of Monte-Carlo cross validation (MCCV). Cox proportional hazard models were fit to MCCV training samples using Elastic-Net. A maximum of 92 features were assessed. The final prognostic model was evaluated in an independent combined dataset of 267 patients with early-stage HER2-positive breast cancer treated with different neoadjuvant and adjuvant anti-HER2-based combinations and from four other studies (PAMELA, CHER-LOB, Hospital Clinic, and Padova) with disease-free survival outcome data. FINDINGS: From Short-HER, data from 435 (35%) of 1254 patients for tumour size (T1 vs rest), nodal status (N0 vs rest), number of tumour-infiltrating lymphocytes (continuous variable), subtype (HER2-enriched and basal-like vs rest), and 13 genes composed the final model (named HER2DX). HER2DX was significantly associated with distant metastasis-free survival as a continuous variable (p<0·0001). HER2DX median score for quartiles 1-2 was identified as the cutoff to identify low-risk patients; and the score that distinguished quartile 3 from quartile 4 was the cutoff to distinguish medium-risk and high-risk populations. The 5-year distant metastasis-free survival of the low-risk, medium-risk, and high-risk populations were 98·1% (95% CI 96·3-99·9), 88·9% (83·2-95·0), and 73·9% (66·0-82·7), respectively (low-risk vs high-risk hazard ratio [HR] 0·04, 95% CI 0·0-0·1, p<0·0001). In the evaluation cohort, HER2DX was significantly associated with disease-free survival as a continuous variable (HR 2·77, 95% CI 1·4-5·6, p=0·0040) and as group categories (low-risk vs high-risk HR 0·27, 0·1-0·7, p=0·005). 5-year disease-free survival in the HER2DX low-risk group was 93·5% (89·0-98·3%) and in the high-risk group was 81·1% (71·5-92·1). INTERPRETATION: The HER2DX combined prognostic score identifies patients with early-stage, HER2-positive breast cancer who might be candidates for escalated or de-escalated systemic treatment. Future clinical validation of HER2DX seems warranted to establish its use in different scenarios, especially in the neoadjuvant setting. FUNDING: Instituto Salud Carlos III, Save the Mama, Pas a Pas, Fundación Científica, Asociación Española Contra el Cáncer, Fundación SEOM, National Institutes of Health, Agenzia Italiana del Farmaco, International Agency for Research on Cancer, and the Veneto Institute of Oncology, and Italian Association for Cancer Research.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Prognóstico , Receptor ErbB-2/genética , Trastuzumab/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Trastuzumab/efeitos adversos , Resultado do Tratamento
3.
Georgian Med News ; (306): 76-81, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33130651

RESUMO

HCV infection and its complications, especially hepatocellular carcinoma, is a substantial public health burden. In 2015 "Nationwide hepatitis C elimination program" was launched in Georgia. According to the protocol, patients with HCC also receive DAA antiviral treatment. We study the effect of the different DAA therapy regiments on the incidence or recurrence of HCC and its prognosis. Overall, 408 patients were recruited in Georgian-French Joint Hepatology Clinic HEPA between April 2015-March 2016. The selection criteria were as follows: 1 - age 50-65 years; 2. Liver fibrosis level F3-F4 or cirrhosis at least 15 years of disease history; 3. HCV positive diagnosed by PCR method, whatever the level of viral load and genotype; 4. absence of previous complications of cirrhosis (ascites, gastrointestinal bleeding or HCC; 5. Child-Pugh class A or B; and 6. absence of severe extrahepatic disease. Essential clinical and biological parameters were recorded. Clinical monitoring and management of adverse events were performed on a regular base. HCV All patients included in the study received anti-HCV treatment with direct-acting antivirals (DAAs) within the national hepatitis C elimination program in accordance with national protocols. During April 2015-March 2016 treatment was provided with sofosbuvir (SOF) in combination with ribavirin (RBV), with or without pegylated interferon (IFN). Since March 2016, ledipasvir/sofosbuvir (LDV/SOF) was prescribed to all patients with or without RBV depending on the HCV genotype, level of fibrosis, and previous treatment experience. In conclusion, we find that neither different DAA regimens nor different treatment duration affects HCC risk after antiviral treatment. Moreover, there are no significant changes in mortality rate due to HCC in these groups. Therefore, it can be concluded, that HCC status is not a contraindication for DAA treatment, especially at the early stages of cancer, when a tumor is curative.


Assuntos
Antivirais , Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Criança , Quimioterapia Combinada , Genótipo , Georgia , República da Geórgia , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Recidiva Local de Neoplasia/tratamento farmacológico , Resultado do Tratamento
4.
Nat Commun ; 11(1): 5017, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024122

RESUMO

The survival and recurrence of residual tumor cells following therapy constitutes one of the biggest obstacles to obtaining cures in breast cancer, but it remains unclear how the clonal composition of tumors changes during relapse. We use cellular barcoding to monitor clonal dynamics during tumor recurrence in vivo. We find that clonal diversity decreases during tumor regression, residual disease, and recurrence. The recurrence of dormant residual cells follows several distinct routes. Approximately half of the recurrent tumors exhibit clonal dominance with a small number of subclones comprising the vast majority of the tumor; these clonal recurrences are frequently dependent upon Met gene amplification. A second group of recurrent tumors comprises thousands of subclones, has a clonal architecture similar to primary tumors, and is dependent upon the Jak/Stat pathway. Thus the regrowth of dormant tumors proceeds via multiple routes, producing recurrent tumors with distinct clonal composition, genetic alterations, and drug sensitivities.


Assuntos
Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Animais , Linhagem Celular Tumoral , Crizotinibe/farmacologia , Doxiciclina/farmacologia , Transição Epitelial-Mesenquimal/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Camundongos Nus , Recidiva Local de Neoplasia/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/genética , Receptor ErbB-2/genética , Análise de Célula Única , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Lancet Oncol ; 21(11): 1433-1442, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33035457

RESUMO

BACKGROUND: Activating mutations of EZH2, an epigenetic regulator, are present in approximately 20% of patients with follicular lymphoma. We investigated the activity and safety of tazemetostat, a first-in-class, oral EZH2 inhibitor, in patients with follicular lymphoma. METHODS: This study was an open-label, single-arm, phase 2 trial done at 38 clinics or hospitals in France, the UK, Australia, Canada, Poland, Italy, Ukraine, Germany, and the USA. Eligible patients were adults (≥18 years) with histologically confirmed follicular lymphoma (grade 1, 2, 3a, or 3b) that had relapsed or was refractory to two or more systemic therapies, had an Eastern Cooperative Oncology Group performance status of 0-2, and had sufficient tumour tissue for central testing of EZH2 mutation status. Patients were categorised by EZH2 status: mutant (EZH2mut) or wild-type (EZH2WT). Patients received 800 mg of tazemetostat orally twice per day in continuous 28-day cycles. The primary endpoint was objective response rate based on the 2007 International Working Group criteria for non-Hodgkin lymphoma, assessed by an independent radiology committee. Activity and safety analyses were done in patients who received one dose or more of tazemetostat. This study is registered with ClinicalTrials.gov, NCT01897571, and follow-up is ongoing. FINDINGS: Between July 9, 2015, and May 24, 2019, 99 patients (45 in the EZH2mut cohort and 54 in the EZH2WT cohort) were enrolled in the study. At data cutoff for the analysis (Aug 9, 2019), the median follow-up was 22·0 months (IQR 12·0-26·7) for the EZH2mut cohort and 35·9 months (24·9-40·5) for the EZH2WT cohort. The objective response rate was 69% (95% CI 53-82; 31 of 45 patients) in the EZH2mut cohort and 35% (23-49; 19 of 54 patients) in the EZH2WT cohort. Median duration of response was 10·9 months (95% CI 7·2-not estimable [NE]) in the EZH2mut cohort and 13·0 months (5·6-NE) in the EZH2WT cohort; median progression-free survival was 13·8 months (10·7-22·0) and 11·1 months (3·7-14·6). Among all 99 patients, treatment-related grade 3 or worse adverse events included thrombocytopenia (three [3%]), neutropenia (three [3%]), and anaemia (two [2%]). Serious treatment-related adverse events were reported in four (4%) of 99 patients. There were no treatment-related deaths. INTERPRETATION: Tazemetostat monotherapy showed clinically meaningful, durable responses and was generally well tolerated in heavily pretreated patients with relapsed or refractory follicular lymphoma. Tazemetostat is a novel treatment for patients with follicular lymphoma. FUNDING: Epizyme.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Benzamidas/administração & dosagem , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Linfoma Folicular/tratamento farmacológico , Piridonas/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas/efeitos adversos , Feminino , Humanos , Linfoma Folicular/genética , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Piridonas/efeitos adversos , Resultado do Tratamento
7.
Crit Rev Oncol Hematol ; 156: 103114, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33045493

RESUMO

BACKGROUND: Extended endocrine therapy (EET) with aromatase inhibitors (AIs) therapy can further reduce the risk of recurrence in breast cancer patients. But the conclusion that whether EET with AIs increases the risk of some side effects compared with nonextended endocrine therapy (NEET) is still controversial and not exhaustive. METHODS: We searched for Randomized controlled trials (RCT) trials published in EMBASE and PubMed between March 2008 and December 2019. Studies comparing the side effects of adjuvant EET with those of NEET were included. The objective was to determine whether EET with AIs increases the risk of side effects compared with NEET. RESULTS: Overall, 11 trials comprising 24,187 participants were identified. EET with AIs increased the risk of cardiotoxicity [odds ratio (OR) 1.19, 95 % confidence interval (CI) 1.04-1.36; P < 0.05; 438 vs 423], bone pain (OR 1.18, 95 % CI 1.02-1.36; P < 0.05; 446 vs 404), osteoporosis (OR 1.53, 95 % CI 1.35-1.72; P < 0.05; 866 vs 641), fractures (OR 1.33, 95 % CI 1.18-1.50; P < 0.05; 596 vs 438), arthralgia (OR 1.27, 95 % CI 1.19-1.36; P < 0.05; 2404 vs 2060), myalgia (OR 1.29, 95 % CI 1.16-1.43; P < 0.05; 960 vs 776), and hot flashes (OR 1.40, 95 % CI 1.15-1.69; P < 0.05; 2418 vs 2174) and was associated with opposite risk of vaginal bleeding (OR 0.74, 95 % CI 0.59-0.92; P < 0.05; 148 vs 197). However, the extended therapy did not increase the risk of hypertension (OR 1.03, 95 % CI 0.80-1.33; P = 0.80; 364 vs 353), hypercholesterolemia (OR 1.03, 95 % CI 0.91-1.16; P = 0.62; 643 vs 627), vaginal dryness (OR 1.19, 95 % CI 1.00-1.42; P = 0.05; 294 vs 257), fatigue (OR 1.20, 95 % CI 0.96-1.50; P = 0.12; 1501 vs 1462), dizziness (OR 1.04, 95 % CI 0.92-1.17; P = 0.55; 614 vs 595), headaches (OR 1.06, 95 % CI 0.95-1.18; P = 0.30; 885 vs 848), constipation (OR 0.91, 95 % CI 0.79-1.04; P = 0.15; 480 vs 522), nausea (OR 1.83, 95 % CI 0.49-6.83; P =0.37; 340 vs 325), and dyspnea (OR 0.96, 95 % CI 0.82-1.13; P = 0.64; 340 vs 351). The risk of grade ≥ 3 hot flashes increased following extended endocrine therapy (OR 2.01, 95 % CI 1.23-3.29; P < 0.05; 47 vs 23). We observed no evidence for a difference in the risk of grade ≥3 fatigue, arthralgia, myalgia, bone pain, osteoporosis, fractures, hypertension, and headache between both endocrine therapies. Secondary outcomes shows that after receive EET with AIs, patients can benefit from the control of the local recurrence, distant recurrence, contralateral breast cancer, and second cancers. CONCLUSIONS: Compared with NEET, EET with AIs significantly increased the risk of cardiotoxicity, bone pain, osteoporosis, fractures, hot flashes, arthralgia, myalgia, and grade ≥3 hot flashes, and EET with AIs can reduced the risks of local recurrence, distant recurrence, contralateral breast cancer, and second cancers. These findings offer an important guide for clinicians and patients.


Assuntos
Neoplasias da Mama , Segunda Neoplasia Primária , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Pós-Menopausa , Tamoxifeno/uso terapêutico
8.
Anticancer Res ; 40(11): 6473-6484, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109586

RESUMO

BACKGROUND/AIM: Glioblastoma multiforme (GBM) is an intractable tumor that has a very poor prognosis despite intensive treatment with temozolomide plus radiotherapy. PATIENTS AND METHODS: Sixteen newly diagnosed patients with high-grade gliomas were enrolled in a phase II study of the α-type-1 DC vaccine. Briefly, DCs obtained from the culture of enriched monocytes in the presence of a cytokine cocktail, were pulsed with a cocktail of 5 synthetic peptides and cryopreserved until injection into patients. RESULTS: The amount of IL-12 produced by activated DCs was higher than that previously reported. Among 15 evaluable patients, 10 showed positive CTL responses to any peptides in an ELISPOT assay. After 6 years of observation, five patients were still alive, and two of these patients were relapse-free. Moreover, a significant survival-prolonging effect was verified in DC-treated glioma patients. CONCLUSION: Peptide-cocktail-pulsed α-type-1 DC vaccines have a potential therapeutic effect on survival when used in combination with the standard regimen, which is partly based on IL-12-IFN-γ-mediated T-cell activation.


Assuntos
Vacinas Anticâncer/administração & dosagem , Células Dendríticas/imunologia , Glioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Vacinas Anticâncer/imunologia , Polaridade Celular/imunologia , Intervalo Livre de Doença , Feminino , Glioma/imunologia , Glioma/patologia , Humanos , Interferon gama/genética , Interleucina-12/genética , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/patologia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Linfócitos T/imunologia , Vacinação/métodos
9.
Medicine (Baltimore) ; 99(43): e22510, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120740

RESUMO

INTRODUCTION: Chimeric antigen receptor T cells (CAR-T) targeting CD19 have shown great potential for treatment of B-cell malignancies. For those patients who can not achieve complete remission (CR) or suffer from relapse after CAR-T therapy, further therapeutic strategies still remain elusive. Whether existing CAR-T cells can revitalize in vivo and eradicate tumor cells is still unknown. PATIENT CONCERNS: We report a case of diffused large B-cell lymphoma patient who had achieved CR after CD19 targeted CAR-T therapy but relapsed after 5 months. DIAGNOSIS: Five months after CAR-T cell infusion, the patient was confirmed a relapse by follow-up PET/CT scan and a mass biopsy. Flow cytometry showed a dramatically decreased percentage of CAR-T cells in peripheral blood (PB). INTERVENTIONS: A second anti-CD19 CAR-T therapy was planned with deliberation. Firstly, the patient received lymphodepletion chemotherapy with fludarabine (25 mg/m, d1-d3) and cyclophosphamide (500 mg/m d2-d3). OUTCOMES: After fludarabine and cyclophosphamide (FC) lymphodepletion chemotherapy, pre-existing CAR-T cells were revitalized and the patient developed grade 2 cytokine release syndrome (CRS) contributing to the regression of relapsed B-cell lymphoma. CONCLUSIONS: This case suggested that FC chemotherapy could revitalize CAR-T cells contributing to the regression of relapsed B-cell lymphoma. Nevertheless, further researches are required in the future as this report described only a single case.


Assuntos
Ciclofosfamida/uso terapêutico , Depleção Linfocítica , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Receptores de Antígenos Quiméricos/imunologia , Indução de Remissão , Linfócitos T/imunologia , Vidarabina/análogos & derivados , Adulto , Antígenos CD19/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Síndrome da Liberação de Citocina/etiologia , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Vidarabina/uso terapêutico
10.
Yonsei Med J ; 61(10): 844-850, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32975058

RESUMO

PURPOSE: We evaluated the efficacy and safety of pembrolizumab in patients with recurrent gynecologic cancers in real-world practice. MATERIALS AND METHODS: We conducted a retrospective, single-institution study of patients with recurrent gynecologic malignancies treated with pembrolizumab. The primary endpoints were the objective response rate (ORR) and safety. RESULTS: Thirty-one patients treated with pembrolizumab were included. The primary disease sites were the uterine cervix (n=18), ovaries (n=8), and uterine corpus (n=5). Fifteen of the 31 patients (48%) had an Eastern Cooperative Oncology Group performance status of ≥2. The median number of prior chemotherapy lines was 2 (range, 1-6), and 14 of 31 patients (45%) had received ≥ 3 prior lines of chemotherapy. The overall ORR was 22.6%: specifically, 22.3% (4 of 18 patients), 12.5% (1 of 8 patients), and 40% (2 of 5 patients) for cervical, ovarian, and endometrial cancers, respectively. During a median follow-up of 4.7 months (range, 0.2-35.3), the median time to response was 1.9 months (range, 1.4-5.7). The median duration of response was not reached (range, 8.8-not reached). The median progression-free survival was 2.5 months (95% confidence interval, 1.7-not reached). Adverse events occurred in 20 patients (64.5%), and only 3 (9.7%) were grade ≥3. There was one case of suspicious treatment-related mortality, apart from which most adverse events were manageable. CONCLUSION: In real-world practice, pembrolizumab was feasible and effective in heavily treated recurrent gynecologic cancer patients with poor performance status who may not be eligible for enrollment in clinical trials.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Neoplasias do Endométrio , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Estudos Retrospectivos
11.
Lancet Haematol ; 7(10): e724-e736, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32896301

RESUMO

BACKGROUND: Venetoclax combined with hypomethylating agents is a new standard of care for newly diagnosed patients with acute myeloid leukaemia (AML) who are 75 years or older, or unfit for intensive chemotherapy. Pharmacodynamic studies have suggested superiority of the longer 10-day regimen of decitabine that has shown promising results in patients with high-risk AML in phase 2 trials. We hypothesised that venetoclax with 10-day decitabine could have improved activity in patients with newly diagnosed AML and those with relapsed or refractory AML, particularly in high-risk subgroups. METHODS: This single centre, phase 2 trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). The study enrolled older patients (aged >60 years) with newly diagnosed AML, not eligible for intensive chemotherapy; secondary AML (progressed after myelodysplastic syndrome or chronic myelomonocytic leukaemia); and relapsed or refractory AML. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or less, white blood cell count less than 10 × 109 per L, and adequate end-organ function. Patients with favourable-risk cytogenetics (eg, t[15;17] or core-binding factor AML) or who had received previous BCL2-inhibitor therapy were excluded. Patients received decitabine 20 mg/m2 intravenously for 10 days with oral venetoclax 400 mg daily for induction, followed by decitabine for 5 days with daily venetoclax for consolidation. The primary endpoint was overall response rate. The secondary endpoints analysed within this report include safety, overall survival, and duration of response, in keeping with recommendations of European LeukemiaNet 2017 guidelines. All patients who received at least one dose of treatment were eligible for safety and response assessments. The trial was registered on ClinicalTrials.gov (NCT03404193) and continues to accrue patients. FINDINGS: Between Jan 19, 2018, and Dec 16, 2019, we enrolled 168 patients; 70 (42%) had newly diagnosed AML, 15 (9%) had untreated secondary AML, 28 (17%) had treated secondary AML, and 55 (33%) had relapsed or refractory AML. The median age was 71 years (IQR 65-76) and 30% of patients had ECOG performance status of 2 or higher. The median follow-up for all patients was 16 months (95% CI 12-18; actual follow-up 6·5 months; IQR 3·4-12·4). The overall response rate was 74% (125 of 168 patients; 95% CI 67-80) and in disease subgroups were: 89% in newly diagnosed AML (62 of 70 patients; 79-94), 80% in untreated secondary AML (12 of 15 patients; 55-93), 61% in treated secondary AML (17 of 28 patients; 42-76), and 62% in relapsed or refractory AML (34 of 55 patients; 49-74). The most common treatment-emergent adverse events included infections with grades 3 or 4 neutropenia (n=79, 47%) and febrile neutropenia (n=49, 29%). 139 (83%) of 168 patients had serious adverse events, most frequently neutropenic fever (n=63, 38%), followed by pneumonia (n=17, 10%) and sepsis (n=16, 10%). The 30-day mortality for all patients was 3·6% (n=6, 95% CI 1·7-7·8). The median overall survival was 18·1 months (95% CI 10·0-not reached) in newly diagnosed AML, 7·8 months (2·9-10·7) in untreated secondary AML, 6·0 months (3·4-13·7) in treated secondary AML, and 7·8 months (5·4-13·3) relapsed or refractory AML. The median duration of response was not reached (95% CI 9·0-not reached) in newly diagnosed AML, 5·1 months (95% CI 0·9-not reached) in untreated secondary AML, not reached (95% CI 2·5-not reached) in previously treated secondary AML, and 16·8 months (95% CI 6·6-not reached) in relapsed or refractory AML. INTERPRETATION: Venetoclax with 10-day decitabine has a manageable safety profile and showed high activity in newly diagnosed AML and molecularly defined subsets of relapsed or refractory AML. Future larger and randomised studies are needed to clarify activity in high-risk subsets. FUNDING: US National Institutes of Health and National Cancer Institute.


Assuntos
Antineoplásicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Decitabina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Sulfonamidas/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Decitabina/administração & dosagem , Decitabina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do Tratamento
12.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(9): 840-844, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32927506

RESUMO

In patients with recurrent or metastatic gastrointestinal stromal tumor (GIST), imatinib is the mainstay treatment, which has significantly improved outcome. However, approximately half of patients who have initial respose to imatinib will develop secondary resistance within 2 years, leading to progressive disease. Available data suggest that cytoreductive surgery may be considered in patients with metastatic GIST who respond to imatinib and have relatively low tumor burden, particularly in whom a R0/R1 resection is anticipated. The evidence of benefit from surgery in patients with focal tumor progression on imatinib is limited, but after surgical resection of progressive lesions, shifting to second line therapy should be initiated. Patients with multifocal progression are not suitable for surgical intervention. In the meantime, surgery for patients treated with sunitinib is feasible, yet survival benefit remains controversial. Thus, surgery should be considered in patients with metastatic GIST whose disease responds to imatinib with a goal of performing R0/R1 resection. On a case-by-case basis, surgical intervention should be determined after careful multidisciplinary consultation to achieve safety, improvement of symptoms and long-term survival benefits.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Mesilato de Imatinib/uso terapêutico , Recidiva Local de Neoplasia/cirurgia , Procedimentos Cirúrgicos de Citorredução , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/secundário , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Equipe de Assistência ao Paciente , Sunitinibe/uso terapêutico , Resultado do Tratamento , Carga Tumoral
13.
J Cancer Res Ther ; 16(4): 900-902, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930137

RESUMO

Objective: Aggressive fibromatosis (AF), also called desmoid tumor, is an uncommon soft-tissue neoplasm. Characteristically, it expands locally without metastatic potential. However, its tendency of relapse after curative resections has been well documented. Effective treatment options have been limited and there is a clear need for novel treatment strategies. Methods: We used combination therapy including multikinase tyrosine kinase inhibitor for treating AF. Results: We presented a case of an extra-abdominal AF who was successfully treated with meloxicam and sorafenib combination in our clinic. She tolerated this therapy well with only mild side effects. To our knowledge, this is the first case report of an extra-abdominal AF with a major partial response to sorafenib and meloxicam combination. Conclusion: Due to the favorable toxicity profile of sorafenib and meloxicam, this combination might be an effective treatment option for patients with locally aggressive and inoperable AF.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fibromatose Agressiva/tratamento farmacológico , Neoplasias Musculares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Feminino , Fibromatose Agressiva/diagnóstico por imagem , Fibromatose Agressiva/patologia , Humanos , Perna (Membro)/patologia , Imagem por Ressonância Magnética/métodos , Meloxicam/administração & dosagem , Neoplasias Musculares/diagnóstico por imagem , Neoplasias Musculares/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Sorafenibe/administração & dosagem , Resultado do Tratamento
14.
Lancet Oncol ; 21(11): 1465-1477, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32961119

RESUMO

BACKGROUND: Previously, findings from CheckMate 238, a double-blind, phase 3 adjuvant trial in patients with resected stage IIIB-C or stage IV melanoma, showed significant improvements in recurrence-free survival and distant metastasis-free survival with nivolumab versus ipilimumab. This report provides updated 4-year efficacy, initial overall survival, and late-emergent safety results. METHODS: This multicentre, double-blind, randomised, controlled, phase 3 trial was done in 130 academic centres, community hospitals, and cancer centres across 25 countries. Patients aged 15 years or older with resected stage IIIB-C or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) to receive nivolumab or ipilimumab via an interactive voice response system and stratified according to disease stage and baseline PD-L1 status of tumour cells. Patients received intravenous nivolumab 3 mg/kg every 2 weeks or intravenous ipilimumab 10 mg/kg every 3 weeks for four doses, and then every 12 weeks until 1 year of treatment, disease recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was recurrence-free survival by investigator assessment, and overall survival was a key secondary endpoint. Efficacy analyses were done in the intention-to-treat population (all randomly assigned patients). All patients who received at least one dose of study treatment were included in the safety analysis. The results presented in this report reflect the 4-year update of the ongoing study with a database lock date of Jan 30, 2020. This study is registered with ClinicalTrials.gov, NCT02388906. FINDINGS: Between March 30 and Nov 30, 2015, 906 patients were assigned to nivolumab (n=453) or ipilimumab (n=453). Median follow-up was 51·1 months (IQR 41·6-52·7) with nivolumab and 50·9 months (36·2-52·3) with ipilimumab; 4-year recurrence-free survival was 51·7% (95% CI 46·8-56·3) in the nivolumab group and 41·2% (36·4-45·9) in the ipilimumab group (hazard ratio [HR] 0·71 [95% CI 0·60-0·86]; p=0·0003). With 211 (100 [22%] of 453 patients in the nivolumab group and 111 [25%] of 453 patients in the ipilimumab group) of 302 anticipated deaths observed (about 73% of the originally planned 88% power needed for significance), 4-year overall survival was 77·9% (95% CI 73·7-81·5) with nivolumab and 76·6% (72·2-80·3) with ipilimumab (HR 0·87 [95% CI 0·66-1·14]; p=0·31). Late-emergent grade 3-4 treatment-related adverse events were reported in three (1%) of 452 and seven (2%) of 453 patients. The most common late-emergent treatment-related grade 3 or 4 adverse events reported were diarrhoea, diabetic ketoacidosis, and pneumonitis (one patient each) in the nivolumab group, and colitis (two patients) in the ipilimumab group. Two previously reported treatment-related deaths in the ipilimumab group were attributed to study drug toxicity (marrow aplasia in one patient and colitis in one patient); no further treatment-related deaths were reported. INTERPRETATION: At a minimum of 4 years' follow-up, nivolumab demonstrated sustained recurrence-free survival benefit versus ipilimumab in resected stage IIIB-C or IV melanoma indicating a long-term treatment benefit with nivolumab. With fewer deaths than anticipated, overall survival was similar in both groups. Nivolumab remains an efficacious adjuvant treatment for patients with resected high-risk melanoma, with a safety profile that is more tolerable than that of ipilimumab. FUNDING: Bristol Myers Squibb and Ono Pharmaceutical.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Ipilimumab/administração & dosagem , Melanoma/tratamento farmacológico , Nivolumabe/administração & dosagem , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/genética , Intervalo Livre de Doença , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Feminino , Humanos , Ipilimumab/efeitos adversos , Masculino , Melanoma/genética , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Nivolumabe/efeitos adversos , Resultado do Tratamento
15.
J UOEH ; 42(3): 261-266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879190

RESUMO

Radiation recall pneumonitis is a phenomenon in which a recall-triggering drug induces an acute inflammatory reaction in the lungs, corresponding to a previously irradiated area. Radiation recall reactions have been reported to occur following treatments with various cytotoxic anticancer agents and molecular-targeting drugs; however, only a few reports have described immune checkpoint inhibitor-induced radiation recall pneumonitis. We report a case of radiation recall pneumonitis induced by pembrolizumab in a patient with the postoperative local recurrence of non-small cell lung cancer. This case demonstrated that pembrolizumab might cause severe radiation recall pneumonitis, even after typical radiation pneumonitis has been resolved.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Doenças Assintomáticas , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Pneumonite por Radiação/etiologia , Radioterapia/efeitos adversos , Terapia Combinada , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia
16.
Medicine (Baltimore) ; 99(38): e22238, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957367

RESUMO

BACKGROUND: Systematic evaluation of the effectiveness and safety of combined procarbazine, lomustine, and vincristine for treating recurrent high-grade glioma. METHODS: Electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Library Central Register of Controlled Trials, WanFang, and China National Knowledge Infrastructure (CNKI) were used to search for studies related to the utilization of combined procarbazine, lomustine, and vincristine as a therapeutic method for recurrent high-grade glioma. Literature screening, extraction of data, and evaluation of high standard studies were conducted by 2 independent researchers. The robustness and strength of the effectiveness and safety of combined procarbazine, lomustine, and vincristine as a therapeutic methodology for recurrent high-grade glioma was assessed based on the odds ratio (OR), mean differences (MDs), and 95% confidence interval (CI). RevMan 5.3 software was used for carrying out the statistical analysis. RESULTS: These results obtained in this study will be published in a peer-reviewed journal. CONCLUSION: Evidently, the conclusion of this study will provide an assessment on whether combined procarbazine, lomustine, and vincristine provides an effective and safe form of treatment for recurrent high-grade glioma. SYSTEMATIC REVIEW REGISTRATION NUMBER: INPLASY202080078.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Metanálise como Assunto , Recidiva Local de Neoplasia/tratamento farmacológico , Revisões Sistemáticas como Assunto , Adolescente , Adulto , Neoplasias Encefálicas/patologia , Glioma/patologia , Humanos , Lomustina/efeitos adversos , Lomustina/uso terapêutico , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Procarbazina/efeitos adversos , Procarbazina/uso terapêutico , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto Jovem
17.
Lancet Oncol ; 21(9): 1224-1233, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32888454

RESUMO

BACKGROUND: Topotecan is currently the only drug approved in Europe in a second-line setting for the treatment of small-cell lung cancer. This study investigated whether the doublet of carboplatin plus etoposide was superior to topotecan as a second-line treatment in patients with sensitive relapsed small-cell lung cancer. METHODS: In this open-label, randomised, phase 3 trial done in 38 hospitals in France, we enrolled patients with histologically or cytologically confirmed advanced stage IV or locally relapsed small-cell lung cancer, who responded to first-line platinum plus etoposide treatment, but who had disease relapse or progression at least 90 days after completion of first-line treatment. Eligible patients were aged 18 years or older and had an Eastern Cooperative Oncology Group performance status 0-2. Enrolled patients were randomly assigned (1:1) to receive combination carboplatin plus etoposide (six cycles of intravenous carboplatin [area under the curve 5 mg/mL per min] on day 1 plus intravenous etoposide [100 mg/m2 from day 1 to day 3]) or oral topotecan (2·3 mg/m2 from day 1 to day 5, for six cycles). Randomisation was done using the minimisation method with biased-coin balancing for ECOG performance status, response to the first-line chemotherapy, and treatment centre. The primary endpoint was progression-free survival, which was centrally reviewed and analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02738346. FINDINGS: Between July 18, 2013, and July 2, 2018, we enrolled and randomly assigned 164 patients (82 in each study group). One patient from each group withdrew consent, therefore 162 patients (81 in each group) were included in the intention-to-treat population. With a median follow-up of 22·7 months (IQR 20·0-37·3), median progression-free survival was significantly longer in the combination chemotherapy group than in the topotecan group (4·7 months, 90% CI 3·9-5·5 vs 2·7 months, 2·3-3·2; stratified hazard ratio 0·57, 90% CI 0·41-0·73; p=0·0041). The most frequent grade 3-4 adverse events were neutropenia (18 [22%] of 81 patients in the topotecan group vs 11 [14%] of 81 patients in the combination chemotherapy group), thrombocytopenia (29 [36%] vs 25 [31%]), anaemia (17 [21%] vs 20 [25%]), febrile neutropenia (nine [11%] vs five [6%]), and asthenia (eight [10%] vs seven [9%]). Two treatment-related deaths occurred in the topotecan group (both were febrile neutropenia with sepsis) and no treatment-related deaths occurred in the combination group. INTERPRETATION: Our results suggest that carboplatin plus etoposide rechallenge can be considered as a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer. FUNDING: Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie).


Assuntos
Carboplatina/administração & dosagem , Etoposídeo/administração & dosagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Topotecan/administração & dosagem , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Etoposídeo/efeitos adversos , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/patologia , Topotecan/efeitos adversos
18.
Anticancer Res ; 40(10): 5715-5725, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988897

RESUMO

BACKGROUND/AIM: The platelet distribution width (PDW) and serum C-reactive protein (CRP) levels are known to be predictive of prognosis in various malignancies. Our aim was to determine whether combining PDW and serum CRP levels produces a prognostic indicator for esophageal cancer (EC) patients. PATIENTS AND METHODS: A total of 168 EC patients who underwent neoadjuvant therapy prior to esophagectomy were included in this study. RESULTS: We defined a combined PDW and CRP (CPC) score as follows: patients with both low pretherapeutic PDW (≤12.4 fl) and high postoperative serum CRP levels (≥0.5 mg/dl) were assigned a score of 2, while patients with one or neither of those were assigned a score of 1 or 0. A multivariable analysis showed that the CPC score was a significant risk factor for overall (p=0.006) and recurrence-free (p=0.004) survival. CONCLUSION: The CPC score is a strong prognostic indicator in EC patients.


Assuntos
Plaquetas/metabolismo , Proteína C-Reativa/metabolismo , Neoplasias Esofágicas/sangue , Prognóstico , Idoso , Plaquetas/patologia , Carcinoma de Células Escamosas , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Fatores de Risco
19.
BMC Infect Dis ; 20(1): 708, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993546

RESUMO

BACKGROUND: Intravesical administration of Bacillus Calmette-Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. CASE PRESENTATION: A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. CONCLUSIONS: We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.


Assuntos
Antituberculosos/uso terapêutico , Vacina BCG/efeitos adversos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/etiologia , Esteroides/uso terapêutico , Exacerbação dos Sintomas , Administração Intravesical , Idoso , Autopsia , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/prevenção & controle , Evolução Fatal , Humanos , Doenças Pulmonares Intersticiais/microbiologia , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium bovis/genética , Resultados Negativos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Pulsoterapia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/prevenção & controle
20.
PLoS One ; 15(9): e0238807, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32960887

RESUMO

PURPOSE: The optimal treatment for primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is still unknown. We evaluated unfavorable prognostic factors and pattern of failure in PG-DLBCL to determine the optimal treatment strategy. METHODS: Between April 2001 and November 2018, 120 patients with complete remission following rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy were retrospectively reviewed. According to the Lugano staging system, 80 patients (66.7%) had localized disease and 40 patients (33.3%) had advanced disease. A total of 93 (77.5%) patients had single gastric lesion and 27 (22.5%) patients had multiple gastric lesions. Ninety patients (75%) were treated with R-CHOP chemotherapy alone and 30 patients (25%) received R-CHOP chemotherapy with additional local treatment for gastric lesions. RESULTS: The 5-year locoregional failure-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) rates in patients treated with R-CHOP chemotherapy with local treatment were 100%, 100%, and 100%, respectively, whereas the LRFS, PFS, and OS rates in patients treated with R-CHOP chemotherapy alone were 86.3%, 78.2%, and 87.4%, respectively (p = 0.031, p = 0.095, and p = 0.025, respectively). During the follow-up period, 17 patients (14.2%) had disease recurrence. Only 3 of the 17 patients had relapse in a completely new site without relapse in the initial involved site. All, except 2, cases of local recurrence included gastric failure. In the multivariate analysis, performance status and number of gastric lesions were independent prognostic factors for treatment outcome. CONCLUSIONS: Patients with complete remission following R-CHOP chemotherapy showed a good prognosis. The main pattern of failure in patients with PG-DLBCL was local recurrence, especially in the stomach. Patients who received local treatment for gastric lesions showed improved gastric control. Therefore, in patients with unfavorable prognostic factors, we recommend R-CHOP chemotherapy with additional local treatment for gastric lesions.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Prednisona/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Rituximab/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/secundário , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto Jovem
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