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PURPOSE: To assess the ability of circulating tumor DNA (ctDNA)-based testing to identify patients with HER2 (encoded by ERBB2)-positive gastric/gastroesophageal adenocarcinoma (GEA) who progressed on or after trastuzumab-containing treatments were treated with combination therapy of anti-HER2 and anti-PD-1 agents. METHODS: ctDNA analysis was performed retrospectively using plasma samples collected at study entry from 86 patients participating in the phase 1/2 CP-MGAH22-05 study (NCT02689284). RESULTS: Objective response rate (ORR) was significantly higher in evaluable ERBB2 amplification-positive vs - negative patients based on ctDNA analysis at study entry (37% vs 6%, respectively; P = .00094). ORR was 23% across all patients who were evaluable for response. ERBB2 amplification was detected at study entry in 57% of patients (all HER2 positive at diagnosis), and detection was higher (88%) when HER2 status was determined by immunohistochemistry fewer than 6 months before study entry. ctDNA was detected in 98% (84/86) of patients tested at study entry. Codetected ERBB2-activating mutations were not associated with response. CONCLUSIONS: Current ERBB2 status may be more effective than archival status at predicting clinical benefit from margetuximab plus pembrolizumab therapy. ctDNA testing for ERBB2 status prior to treatment will spare patients from repeat tissue biopsies, which may be reserved for reflex testing when ctDNA is not detected.
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Adenocarcinoma , DNA Tumoral Circulante , Neoplasias Gástricas , Humanos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Receptor ErbB-2/genética , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Trastuzumab/uso terapêuticoRESUMO
PURPOSE: The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified. PATIENTS AND METHODS: This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25. RESULTS: In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P < .0001). The 3-year DFS rates were 83.7% and 84.7% in the 6-month and 3-month arms, respectively, with an HR of 0.953 (95% CI, 0.769 to 1.180; test for noninferiority, P = .0065) within the noninferiority margin. Among patients with stage III CRC treated by capecitabine plus oxaliplatin, the 3-year DFS of the 3-month arm was noninferior as compared with that of the 6-month arm with an HR of 0.713 (95% CI, 0.530 to 0.959; P = .0009). However, among patients with high-risk stage II and stage III CRC treated by infusional fluorouracil, leucovorin, and oxaliplatin, the noninferiority of the 3-month arm compared with the 6-month arm was not proven. CONCLUSION: This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481).
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Neoplasias do Colo , Compostos Organoplatínicos , Oxaliplatina , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina/uso terapêuticoRESUMO
Urethral clear cell carcinoma is an aggressive tumor rarely observed in the urinary tract. To date, the diagnostic workup of such cases has not yet been standardized, and there has been no established standard treatment approach. The present study reports a rare case of urethral clear cell carcinoma successfully treated with organ preservation strategies and adjuvant chemoradiation with the goal of organ preservation. This treatment approach could be used for patients who refuse radical surgery and patients with concerns about severe morbidity from radical surgery, even in advanced-stage urethral clear cell carcinoma.
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BACKGROUND: Colorectal cancer is the third most common malignant disease and the second leading cause of death worldwide. Previous studies showed improved bioavailability and cytotoxicity of ginsenoside-modified nanostructured lipid carrier containing curcumin (G-NLC) in human colon cancer cell lines. This study aimed to evaluate the safety and tolerability with long-term survival rates in patients with colorectal cancer with unresectable metastases after treatment with first-line bevacizumab/FOLFIRI (folinic acid, bolus/continuous fluorouracil, and irinotecan) in combination with a dietary supplement of G-NLC. METHODS: This study was a prospective, observational, single-group analysis. The enrolled patients had colorectal cancer with unresectable metastases and were administered bevacizumab and FOLFIRI in combination with daily oral G-NLC as first-line treatment. Overall survival, progression-free survival, tumor response, and adverse events were evaluated. RESULTS: A total of 44 patients were enrolled between 2015 and 2019. The median age was 65 (range 45-81) years and the sex ratio was 31:13 (male:female). The primary tumor locations were the colon (31 patients) and rectum (13 patients). The metastatic sites included, liver only (n = 20), lung only (n = 6), both liver and lung (n = 12), and others (n = 6). The median duration of curcumin supply was 7.9 (range 0.9-16.6) months. The most common grade 3 or higher adverse events were neutropenia (n = 15, 34.1%), followed by nausea (n = 4, 9.1%) and vomiting (n = 4, 9.1%). Within the median follow-up period of 22.8 months, the median overall survival was 30.7 months, and the median progression-free survival was 12.8 months. None of the patients achieved complete response (CR); however, 9 patients showed partial response (PR), and 3 patients underwent conversion surgery. CONCLUSIONS: Bevacizumab/FOLFIRI with G-NLC as first-line chemotherapy in patients with colorectal cancer with unresectable metastases presented comparable long-term survival outcomes with acceptable toxicity outcomes. Additional randomized controlled studies are needed to establish definitive conclusions regarding this new regimen for metastatic colorectal cancer.
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Neoplasias do Colo , Neoplasias Colorretais , Curcumina , Ginsenosídeos , Neoplasias Retais , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/efeitos adversos , Camptotecina/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Curcumina/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Ginsenosídeos/uso terapêutico , Humanos , Lipídeos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: The additive or synergistic sustained antitumour effect of immune checkpoint inhibitors in combination with oxaliplatin-based chemotherapy has previously been reported. We investigated the efficacy of nivolumab plus oxaliplatin-based chemotherapy versus placebo plus oxaliplatin-based chemotherapy as first-line therapy for patients with HER2-negative, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer. METHODS: We did a randomised, multicentre, double-blind, placebo-controlled, phase 2-3 trial (ATTRACTION-4) at 130 centres (hospitals, cancer centres, and medical centres) across Japan, South Korea, and Taiwan. We enrolled patients aged 20 years and older with previously untreated (except for neoadjuvant or adjuvant chemotherapy completed ≥180 days before recurrence), HER2-negative, unresectable, advanced or recurrent gastric or gastro-oesophageal junction cancer (regardless of PD-L1 expression), at least one measurable lesion per Response Evaluation Criteria in Solid Tumours guidelines (version 1.1), and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned (1:1) to chemotherapy every 3 weeks (intravenous oxaliplatin 130 mg/m2 on day 1 plus either oral S-1 40 mg/m2 [SOX] or oral capecitabine 1000 mg/m2 [CAPOX], twice daily on days 1-14), in addition to either 360 mg nivolumab intravenously every 3 weeks (nivolumab plus chemotherapy group) or placebo (placebo plus chemotherapy group). Randomisation was done using an interactive web response system with block sizes of four and stratified by intensity of PD-L1 expression, ECOG performance status score, disease status, and geographical region. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoints were centrally assessed progression-free survival and overall survival in the intention-to-treat population, which included all randomly assigned patients. Safety was assessed in all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT02746796. Trial recruitment is complete and follow-up is ongoing. FINDINGS: Between March 23, 2017, and May 10, 2018, 724 patients were randomly assigned to treatment: 362 patients to the nivolumab plus chemotherapy group and 362 to the placebo plus chemotherapy group. At the time of data cutoff on Oct 31, 2018, with a median follow-up of 11·6 months (IQR 8·7-14·1), median progression-free survival at a prespecified interim analysis was 10·45 months (95% CI 8·44-14·75) in the nivolumab plus chemotherapy group and 8·34 months (6·97-9·40) in the placebo plus chemotherapy group (hazard ratio [HR] 0·68; 98·51% CI 0·51-0·90; p=0·0007). At the time of data cutoff on Jan 31, 2020, with a median follow-up of 26·6 months (IQR 24·1-29·0), median overall survival at the final analysis was 17·45 months (95% CI 15·67-20·83) in the nivolumab plus chemotherapy group and 17·15 months (15·18-19·65) in the placebo plus chemotherapy group (HR 0·90; 95% CI 0·75-1·08; p=0·26). The most common treatment-related grade 3-4 adverse events were neutrophil count decreased (71 [20%] of 359 patients in the nivolumab plus chemotherapy group vs 57 [16%] of 358 patients in the placebo plus chemotherapy group) and platelet count decreased (34 [9%] vs 33 [9%]). Treatment-related serious adverse events of any grade were observed in 88 (25%) patients in the nivolumab plus chemotherapy group and in 51 (14%) in the placebo plus chemotherapy group, of which the most common was decreased appetite (18 [5%] vs ten [3%]). Six treatment-related deaths occurred: three in the nivolumab plus chemotherapy group (one each of febrile neutropenia, hepatic failure, and sudden death) and three in the placebo plus chemotherapy group (one each of sepsis, haemolytic anaemia, and interstitial lung disease). INTERPRETATION: Nivolumab combined with oxaliplatin-based chemotherapy significantly improved progression-free survival, but not overall survival, in Asian patients with untreated, HER2-negative, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer, and could potentially be a new first-line treatment option for these patients. FUNDING: Ono Pharmaceutical and Bristol-Myers Squibb.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Masculino , Receptor ErbB-2/análise , Neoplasias Gástricas/mortalidadeRESUMO
OBJECTIVES: Treatment with trastuzumab and chemotherapy significantly improves the outcome in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). CT-P6 (trastuzumab-pkrb; Herzuma) is a trastuzumab biosimilar approved for the treatment of HER2-positive gastric cancer. In this study, we aimed to compare the efficacy and safety of CT-P6 and reference trastuzumab as first-line treatment for HER2-positive AGC. MATERIALS AND METHODS: The medical records of 102 patients with HER2-positive AGC treated with first-line trastuzumab-based chemotherapy were retrospectively reviewed. These patients were treated with either reference trastuzumab (n=72) or a biosimilar (n=30). Treatment outcomes, such as objective response rate, progression-free survival (PFS), and overall survival (OS), were compared between the reference and biosimilar groups. RESULTS: The objective response rate of both groups (52.8% and 56.8% in the reference and biosimilar groups, respectively) were comparable (P=0.72). No statistically significant difference was observed with the reference versus biosimilar trastuzumab for PFS (median PFS, 6.9 vs. 5.4 mo; P=0.98) or OS (median OS, 12.3 mo vs. not reached; P=0.42). Safety profiles were similar between the 2 groups. CONCLUSIONS: Biosimilar trastuzumab showed equivalent outcome to reference trastuzumab, with similar adverse events. Biosimilar trastuzumab can suitably and safely replace trastuzumab as a reference for the treatment of HER2-positive AGC.
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Antineoplásicos Imunológicos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Trastuzumab/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Ramucirumab as monotherapy or in combination with paclitaxel is a second-line treatment option recommended for patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, real-world data from large study cohorts focused on ramucirumab plus paclitaxel in gastric cancer are limited. METHODS: The study population comprised all patients with gastric or GEJ cancer who received ramucirumab plus paclitaxel in South Korea between 1 May 2018 and 31 December 2018. We included patients with advanced gastric or GEJ adenocarcinoma and disease progression after first-line platinum and fluoropyrimidine-containing combination chemotherapy. RESULTS: In total, 1063 patients were included in the present study. The objective response rate and disease control rate were 15.1% and 57.7%, respectively. The median progression-free survival was 4.03 months (95% confidence interval, 3.80-4.27) and the median overall survival was 10.03 months (95% confidence interval, 9.33-10.73). Grade 3 or higher treatment-related adverse events with incidence of ⩾5% were neutropenia (35.1%) and anemia (10.5%). Based on multivariable analysis, overall survival was negatively associated with Eastern Cooperative Oncology Group performance status ⩾2, weight loss ⩾10% in the previous 3 months, GEJ of primary tumor, poor or unknown histologic grade, number of metastatic sites ⩾3, presence of peritoneal metastasis, no prior gastrectomy, and time to second-line since first-line treatment <6 months. CONCLUSION: Our large-scale, nationwide, real-world data analysis of an unselected real-world population adds evidence for the efficacy and safety of second-line ramucirumab plus paclitaxel in patients with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.
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BACKGROUND: We investigated the feasibility and safety of an exercise intervention in patients with metastatic solid cancer. METHODS: Patients scheduled to receive first-line chemotherapy for metastatic cancer with a life expectancy of ≥4 months, no brain metastases, and no high risk of fracture were recruited to participate in a 12-week, combined resistance and aerobic exercise program consisting of supervised, hospital-based (2×/week) and home-based training (3×/week) during palliative chemotherapy. Feasibility and safety of the exercise intervention were the primary outcomes. The secondary outcomes were skeletal muscle mass and strength, functional capacity, quality of life (QoL), and fatigue. RESULTS: Nineteen patients were enrolled in this pilot study. Five patients withdrew consent before the exercise intervention due to fear of exacerbating cancer-related symptoms (n=2), transportation issues (n=2), and unknown reasons (n=1). Ten patients (71.4%) completed the 12-week exercise program. Mean attendance rate of the supervised exercise sessions was 64.9% (range, 16.7-95.8%). No adverse events or skeletal complications occurred during the supervised exercise sessions. Among participants, there were no significant changes in muscle area at the third lumbar level (mean change =-0.7 cm2, P=0.869) or appendicular skeletal muscle mass (mean change =0.1 kg, P=0.661). The overall QoL assessed using the Functional Assessment of Cancer Therapy-General significantly improved post-exercise interventions (P=0.037). There were significant improvements in the QoL subdomains of emotional well-being and physical, social, and cognitive functions. CONCLUSIONS: Exercise interventions are feasible and safe in patients with metastatic cancer. Exercise interventions can improve QoL and prevent skeletal muscle loss during palliative chemotherapy.
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Neoplasias , Qualidade de Vida , Exercício Físico , Terapia por Exercício , Humanos , Neoplasias/tratamento farmacológico , Projetos PilotoRESUMO
BACKGROUND: The efficacy of modified FOLFIRINOX (mFOLFIRINOX) as a second-line chemotherapy treatment for metastatic pancreatic adenocarcinoma (mPAC), remains unclear. This multi-center randomised phase III trial aimed to elucidate the efficacy of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients with good performance status. PATIENTS AND METHODS: Eighty mPAC patients (age, 19-75 years) refractory to first-line gemcitabine-based chemotherapy were randomly selected to receive mFOLFIRINOX or S-1. mFOLFIRINOX comprised oxaliplatin (65 mg/m2), irinotecan (135 mg/m2), and leucovorin (400 mg/m2) on day 1 and continuous 5-FU infusion (1000 mg/m2) over 24 h on days 1-2 every 2 weeks. S-1 comprised body surface area-dependent oral S-1, divided into two doses per day on days 1-28 every 6 weeks. RESULTS: Overall survival was the primary endpoint. The objective response and disease control rates were higher in the mFOLFIRINOX than in the S-1 group (15% versus 2%; p = .04 and 67% versus 37%; p = .007). The median progression-free survival rates were 5.2 and 2.2 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted hazard ratio [HR]: .4; 95% confidence interval [CI]: .2-.6; p < .001). The median overall survival rates were 9.2 and 4.9 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted HR: .4; 95% CI: .2-.7; p = .002). Grade 3-4 adverse events occurred in 56% and 17% of the patients in the mFOLFIRINOX and S-1 groups, respectively (p < .001). CONCLUSION: Administration of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients refractory to gemcitabine-based chemotherapy resulted in increased survival rates than S-1 treatment alone.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Ácido Oxônico/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Tegafur/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Irinotecano/efeitos adversos , Irinotecano/uso terapêutico , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaliplatina/efeitos adversos , Oxaliplatina/uso terapêutico , Ácido Oxônico/efeitos adversos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Qualidade de Vida , Tegafur/efeitos adversos , GencitabinaRESUMO
PURPOSE: Evaluation of symptoms and signs for the management of neuropathic cancer pain (NCP) is challenging. This study aimed to identify clinical predictors of NCP and symptoms and signs most relevant of those in Korean patients. METHODS: This nationwide, descriptive, cross-sectional, multicenter, observational study included 2,003 cancer patients aged ≥20 years who reported a visual analog scale (VAS) score ≥1 for pain and provided informed consent for participation. The Douleur Neuropathic (DN4) questionnaire (score ≥4) was used to determine symptoms and signs as well as the presence of NCP. RESULTS: The prevalence of NCP was associated with age <65 years [OR, 1.57; 95% CI, 1.270-1.934], disease duration >6 months (OR, 1.57; 95% CI, 1.232-2.012), stage IV cancer (OR, 0.75; 95% CI, 0.593-0.955), history of chemotherapy (OR, 1.74; 95% CI, 1.225-2.472), and moderate-to-severe cancer pain (OR, 2.05; 95% CI, 1.671-2.524) after multivariate analysis. The most common descriptive symptoms of NCP were tingling, electric shock, and pins and needles. For NCP patients in the presence or absence of the clinical predictors, pins and needles (p = 0.001) and painful cold (p<0.001) symptoms were significantly frequent in patients with moderate-to-severe pain. Tingling, numbness, and touch hypoesthesia (p = 0.022, 0.033, 0.024, respectively) were more frequent in those with longer cancer duration and hyperesthesia (p = 0.024) was more frequent in young patients. CONCLUSION: Age <65 years, disease duration >6 months, stage IV cancer, history of chemotherapy, and moderate-to-severe cancer pain, were identified as predictors of NCP. Some symptoms and signs of NCP were associated with these predictors. Further studies are warranted on the pathogenesis and management of NCP with respect to the symptoms and signs, and factors associated with pain severity in Korean patients.
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Dor do Câncer , Neoplasias , Neuralgia , Medição da Dor , Inquéritos e Questionários , Fatores Etários , Idoso , Dor do Câncer/diagnóstico , Dor do Câncer/epidemiologia , Dor do Câncer/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Neoplasias/fisiopatologia , Neuralgia/diagnóstico , Neuralgia/epidemiologia , Neuralgia/fisiopatologia , PrevalênciaRESUMO
OBJECTIVES: Trastuzumab is used as an agent against human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). The aim of this study was to determine how HER2 gene amplification and neutrophil-to-lymphocyte ratio (NLR) could predict long-term survival in AGC patients that underwent trastuzumab-based chemotherapy. METHODS: We retrospectively reviewed medical records of 112 patients between 28 and 91 years old (median of 66 y) with AGC treated with first-line trastuzumab-based chemotherapy. The level of HER2 gene amplification was determined by the HER2/centromere enumerator probe 17 (CEP17) ratio and HER2 gene copy number (GCN). NLR was calculated as the neutrophil count divided by the lymphocyte counts. RESULTS: Median HER2/CEP17 ratio, HER2 GCN, and NLR values were 2.85, 7.1, and 2.81, respectively. Objective response rate in both high HER2/CEP17 ratio (59.4% vs. 28.1%, P=0.012) and HER2 GCN groups (62.1% vs. 33.3%, P=0.032) was higher than that of each group. High NLR correlated with significantly worse median overall survival (OS) (median OS, 8.2 vs. 18.9 mo, P=0.002) and progression free survival (PFS) (median PFS: 5.1 vs. 8.0 mo, P=0.005). However, median OS and PFS were not significantly different according to HER2/CEP17 ratio or HER2 GCN. In the multivariate analysis, high NLR, Eastern Cooperative Group performance status, and poorly differentiated/signet ring cell type were independent factors for OS. CONCLUSIONS: NLR was a significant predictor of long-term survival in AGC patients treated with first-line trastuzumab-based chemotherapy. Future validation of prospective trials with larger patient populations will be needed.
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Antineoplásicos Imunológicos/uso terapêutico , Amplificação de Genes , Linfócitos/patologia , Neutrófilos/patologia , Receptor ErbB-2/genética , Neoplasias Gástricas/mortalidade , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
Purpose: Curative treatment is challenging in patients with locally advanced rectal cancer and unresectable metastases. The aim of this study was to evaluate the clinical outcomes of short-course radiotherapy (RT) followed by systemic chemotherapy for patients with rectal cancer with mesorectal fascia (MRF) involvement and unresectable distant metastases. Methods: The study included consecutive patients diagnosed as having metastatic mid-to-low rectal cancer treated with short-course RT followed by systemic chemotherapy for conversion radical or palliative surgery between 2014 and 2019 at Gil Medical Center. The patients had primary rectal tumors involving the MRF and unresectable distant metastases. The treatment strategies were determined in a multidisciplinary team discussion. Results: Seven patients (five men and two women) underwent short-course RT (5×5 Gy) and preoperative systemic chemotherapy. The median age was 68 years (range, 46-84 years), and the median distance from the anal verge to the primary tumor was 6.0 cm (range, 2.0-9.0 cm). During the median follow-up period of 29.4 months, three patients underwent conversion radical surgery with R0 resection, two underwent palliative surgery, and two could not undergo surgery. No postoperative major morbidity or mortality occurred. The patients who underwent conversion complete radical surgery showed good long-term survival outcomes, with an overall survival time of 29.4-48.8 months and progression-free survival time of 14.7-41.1 months. Conclusion: Short-course RT followed by systemic chemotherapy could provide patients with unresectable stage IV rectal cancer a chance to undergo to conversion radical surgery with good long-term survival outcomes.
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BACKGROUND: Clinical Decision Support Systems (CDSSs) have recently attracted attention as a method for minimizing medical errors. Existing CDSSs are limited in that they do not reflect actual data. To overcome this limitation, we propose a CDSS based on deep learning. METHODS: We propose the Colorectal Cancer Chemotherapy Recommender (C3R), which is a deep learning-based chemotherapy recommendation model. Our model improves on existing CDSSs in which data-based decision making is not well supported. C3R is configured to study the clinical data collected at the Gachon Gil Medical Center and to recommend appropriate chemotherapy based on the data. To validate the model, we compared the treatment concordance rate with the National Comprehensive Cancer Network (NCCN) Guidelines, a representative set of cancer treatment guidelines, and with the results of the Gachon Gil Medical Center's Colorectal Cancer Treatment Protocol (GCCTP). RESULTS: For the C3R model, the treatment concordance rates with the NCCN guidelines were 70.5% for Top-1 Accuracy and 84% for Top-2 Accuracy. The treatment concordance rates with the GCCTP were 57.9% for Top-1 Accuracy and 77.8% for Top-2 Accuracy. CONCLUSIONS: This model is significant, i.e., it is the first colon cancer treatment clinical decision support system in Korea that reflects actual data. In the future, if sufficient data can be secured through cooperation among multiple organizations, more reliable results can be obtained.
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Neoplasias do Colo , Neoplasias Colorretais , Sistemas de Apoio a Decisões Clínicas , Aprendizado Profundo , Neoplasias Colorretais/tratamento farmacológico , Humanos , República da CoreiaRESUMO
BACKGROUND: Margetuximab, a novel, investigational, Fc-engineered, anti-HER2 monoclonal antibody, is designed to more effectively potentiate innate immunity than trastuzumab. We aimed to evaluate the safety, tolerability, and antitumour activity of margetuximab plus pembrolizumab (an anti-PD-1 monoclonal antibody) in previously treated patients with HER2-positive gastro-oesophageal adenocarcinoma. METHODS: CP-MGAH22-05 was a single-arm, open-label, phase 1b-2 dose-escalation and cohort expansion study done at 11 academic centres in the USA and Canada and 15 centres in southeast Asia (Korea, Taiwan, and Singapore) that enrolled men and women aged 18 years or older with histologically proven, unresectable, locally advanced or metastatic, HER2-positive, PD-L1-unselected gastro-oesophageal adenocarcinoma, with an Eastern Cooperative Oncology Group performance status of 0 or 1, who had progressed after at least one previous line of therapy with trastuzumab plus chemotherapy in the locally advanced unresectable or metastatic setting. In the dose-escalation phase, nine patients were treated: three received margetuximab 10 mg/kg intravenously plus pembrolizumab 200 mg intravenously every 3 weeks and six received the recommended phase 2 dose of margetuximab 15 mg/kg plus pembrolizumab 200 mg intravenously every 3 weeks. An additional 86 patients were enrolled in the phase 2 cohort expansion and received the recommended phase 2 dose. The primary endpoints were safety and tolerability, assessed in the safety population (patients who received at least one dose of either margetuximab or pembrolizumab) and the objective response rate as assessed by the investigator according to both Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, in the response-evaluable population (patients with measurable disease at baseline and who received the recommended phase 2 dose of margetuximab and pembrolizumab). This trial is registered with ClinicalTrials.gov, NCT02689284. Recruitment for the trial has completed and follow-up is ongoing. FINDINGS: Between Feb 11, 2016, and Oct 2, 2018, 95 patients were enrolled. Median follow-up was 19·9 months (IQR 10·7-23·1). The combination therapy showed acceptable safety and tolerability; there were no dose-limiting toxicities in the dose-escalation phase. The most common grade 3-4 treatment-related adverse events were anaemia (four [4%]) and infusion-related reactions (three [3%]). Serious treatment-related adverse events were reported in nine (9%) patients. No treatment-related deaths were reported. Objective responses were observed in 17 (18·48%; 95% CI 11·15-27·93) of 92 evaluable patients. INTERPRETATION: These findings serve as proof of concept of synergistic antitumour activity with the combination of an Fc-optimised anti-HER2 agent (margetuximab) along with anti-PD-1 checkpoint blockade (pembrolizumab). FUNDING: MacroGenics.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Mesenchymal stem cells (MSCs) intrinsically possess unique features that not only help in their migration towards the tumor-rich environment but they also secrete versatile types of secretomes to induce nerve regeneration and analgesic effects at inflammatory sites. As a matter of course, engineering MSCs to enhance their intrinsic abilities is growing in interest in the oncology and regenerative field. However, the concern of possible tumorigenesis of genetically modified MSCs prompted the development of non-viral transfected MSCs armed with nanotechnology for more effective cancer and regenerative treatment. Despite the fact that a large number of successful studies have expanded our current knowledge in tumor-specific targeting, targeting damaged brain site remains enigmatic due to the presence of a blood-brain barrier (BBB). A BBB is a barrier that separates blood from brain, but MSCs with intrinsic features of transmigration across the BBB can efficiently deliver desired drugs to target sites. Importantly, MSCs, when mediated by nanoparticles, can further enhance tumor tropism and can regenerate the damaged neurons in the central nervous system through the promotion of axon growth. This review highlights the homing and nerve regenerative abilities of MSCs in order to provide a better understanding of potential cell therapeutic applications of non-genetically engineered MSCs with the aid of nanotechnology.
Assuntos
Neoplasias Encefálicas/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Nanotecnologia/métodos , Regeneração Nervosa , Animais , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Humanos , TropismoRESUMO
Backgrounds/Aims: Watson for Oncology (WFO) is a cognitive technology that processes medical information by analyzing the latest evidence and guidelines. However, studies of the concordance rate between WFO and clinicians for advanced gastric cancer (AGC) are lacking. Methods: We retrospectively reviewed 65 patients with AGC who consulted WFO and the Gachon Gil Medical Center multidisciplinary team (GMDT) in 2016 and 2017. The recommendations of WFO were compared with the opinions of the GMDT. WFO provided three treatment options: recommended (first treatment option), for consideration (second treatment option), and not recommended. Results: In total, 65 patients (mean age 61.0 years; 44 males and 21 females) were included in the study. The concordance rate between WFO and the GMDT was 41.5% (27/65) at the recommended level and 87.7% (57/65) at the for consideration level. The main causes of discordance between WFO and the GMDT were as follows. First, WFO did not consider the medical history. Second, WFO recommended the use of agents that are considered outdated in Korea. Third, some patients wanted to be involved in a clinical trial. Fourth, some patients refused to use the biologic agents recommended by WFO for financial reasons as they were not covered by medical insurance. Conclusions: The concordance rate at the recommended level was relatively low but was higher at the for consideration level. Discordances arose mainly from the different medical circumstances at the Gachon Gil Medical Center (GMC) and the Memorial Sloan Kettering Cancer Center (MSKCC), the main WFO consulting center. The utility of WFO as a tool for supporting clinical decision making could be further improved by incorporating regional guidelines.
Assuntos
Sistemas de Apoio a Decisões Clínicas/normas , Aceitação pelo Paciente de Cuidados de Saúde , Equipe de Assistência ao Paciente/organização & administração , Neoplasias Gástricas/terapia , Idoso , Fatores Biológicos/administração & dosagem , Fatores Biológicos/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Watson for oncology (WFO) is a cognitive computing system providing decision support. We evaluated the concordance rates between the treatment options determined by WFO and those determined by a multidisciplinary team (MDT). METHODS: We reviewed the medical charts of patients diagnosed with colorectal cancer who visited the MDT at a single tertiary medical center from November 2016 to April 2017. WFO classified the treatment options for specific patients into three categories: 'Recommended', 'For consideration', and 'Not recommended'. Concordance rates between the WFO- and MDT-determined chemotherapy options, and the factors that potentially influence the concordance rate, were analyzed. RESULTS: Sixty-nine patients with colorectal cancer met with the MDT from Nov. 2016 to Feb. 2017. The mean age of the patients was 62 years (range: 34-86 years), and more patients were male (47/69) than female. Of the 69 patients, 51 (73.9%) were diagnosed with colon cancer, of whom 46.4% received the same regimen recommendation from WFO ('Recommended') as they did from the MDT. After inclusion of the 'For consideration' category from WFO, the concordance rate increased to 87.0%. The concordance rate between MDT and NCCN guidelines was 97.1%, and that between the WFO and NCCN guidelines was 88.4%. The concordance rates between WFO and MDT were significantly lower in patients with stage II, IIIC, or IV disease (P<0.001), and the colorectal cancer stage was the only statistically significant factor discriminating between WFO and MDT. CONCLUSIONS: The concordance rate between chemotherapy regimens for colorectal cancer determined by MDT versus WFO recommendations was 46.4%. After including the 'For consideration' category from WFO, the concordance rate increased to 88.4%. Further modification and improvement of the WFO prioritizing algorithm used to recommend treatment may increase the usefulness of WFO in the clinic.
Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Sistemas de Apoio a Decisões Clínicas , Sistemas Inteligentes , Oncologia/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Computadores , Feminino , Humanos , Comunicação Interdisciplinar , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Equipe de Assistência ao Paciente , Guias de Prática Clínica como Assunto , Reprodutibilidade dos Testes , República da Coreia , Estudos Retrospectivos , Software , Resultado do Tratamento , Interface Usuário-ComputadorRESUMO
BACKGROUND: Pathologic diagnosis of central nervous system (CNS) neoplasms is made by comparing light microscopic, immunohistochemical, and molecular cytogenetic findings with clinicoradiologic observations. Intraoperative frozen cytology smears can improve the diagnostic accuracy for CNS neoplasms. Here, we evaluate the diagnostic value of cytology in frozen diagnoses of CNS neoplasms. METHODS: Cases were selected from patients undergoing both frozen cytology and frozen sections. Diagnostic accuracy was evaluated. RESULTS: Four hundred and fifty-four cases were included in this retrospective single-center review study covering a span of 10 years. Five discrepant cases (1.1%) were found after excluding 53 deferred cases (31 cases of tentative diagnosis, 22 cases of inadequate frozen sampling). A total of 346 cases of complete concordance and 50 cases of partial concordance were classified as not discordant cases in the present study. Diagnostic accuracy of intraoperative frozen diagnosis was 87.2%, and the accuracy was 98.8% after excluding deferred cases. Discrepancies between frozen and permanent diagnoses (n = 5, 1.1%) were found in cases of nonrepresentative sampling (n = 2) and misinterpretation (n = 3). High concordance was observed more frequently in meningeal tumors (97/98, 99%), metastatic brain tumors (51/52, 98.1%), pituitary adenomas (86/89, 96.6%), schwannomas (45/47, 95.8%), high-grade astrocytic tumors (47/58, 81%), low grade astrocytic tumors (10/13, 76.9%), non-neoplastic lesions (23/36, 63.9%), in decreasing frequency. CONCLUSIONS: Using intraoperative cytology and frozen sections of CNS tumors is a highly accurate diagnostic ancillary method, providing subtyping of CNS neoplasms, especially in frequently encountered entities.
RESUMO
Lung cancer is a highly malignant tumor, and targeted delivery of anti-cancer drugs to deep lung tumor tissue remains a challenge in drug design. Here, it is demonstrated that bone marrow mesenchymal stem cells armed with nanodrugs are highly targeted and mutually destructive with malignant lung cancer cells and successfully eradicate lung tumors tissues. Using this approach, the current clinical dose of anti-cancer drugs for the treatment of malignant lung tumors can be decreased by more than 100-fold without triggering immunotoxicity.
RESUMO
BACKGROUND: Ramucirumab improves survival in gastric cancer patients. The efficacy and safety of ramucirumab outside of a clinical trial were evaluated using an expanded access program (EAP). METHODS: Advanced gastric cancer patients treated with ramucirumab in combination with paclitaxel or with ramucirumab monotherapy in a Korean EAP were evaluated. Baseline characteristics were assessed for progression-free survival (PFS) and overall survival (OS), and adverse events were evaluated according to the treatment regimen. RESULTS: Of 265 patients, 228 received ramucirumab plus paclitaxel, and 37 received ramucirumab monotherapy. Grade 3 or 4 neutropenia was more common with ramucirumab plus paclitaxel than with ramucirumab monotherapy (46.7 vs. 8.1%). Gastrointestinal (GI) perforation developed in seven patients (3.1%) in the ramucirumab plus paclitaxel group. The overall response and disease control rates were 16.6 and 66.3% in the ramucirumab plus paclitaxel group, and 5.4 and 37.8% in the ramucirumab monotherapy group, respectively. PFS and OS were 3.8 and 8.6 months in the ramucirumab plus paclitaxel group, and 1.8 and 6.4 months in the ramucirumab monotherapy group, respectively. In multivariate analysis, alkaline phosphatase, albumin, and neutrophil-to-lymphocyte ratio (NLR) were the independent prognostic factors for PFS, while albumin, NLR, number of metastatic sites, and large amount of ascites were independent prognostic factors for OS. CONCLUSION: In the Korean EAP cohort, ramucirumab showed similar efficacy to the results of the previous trials for gastric cancer. However, the level of GI perforation was slightly increased in the ramucirumab plus paclitaxel group.