RESUMEN
Aims: To obtain real-world data on ramucirumab use and effectiveness for the treatment of advanced gastric cancer (AGC) or gastroesophageal junction adenocarcinoma (GEJ). Methods: Observational, retrospective study carried out in 20 Spanish hospitals, in patients who started ramucirumab treatment between December 2015 and December 2018. Descriptive analysis was conducted for patient characteristics, treatment patterns and effectiveness outcomes. Results: Three hundred seventeen patients were included (93.7% treated with ramucirumab-paclitaxel and 6.3% with ramucirumab); age 62.5 (11.3) years; 66.9% male. Median progression-free survival and overall survival were 3.9 months (95% CI: 3.4-4.3) and 7.4 (95% CI: 6.4-8.9) in combination regimen and 2.0 (1.1-2.8) and 4.3 (95% CI: 1.9-7.3) in monotherapy, respectively. Conclusion: The study findings were consistent with available real-world studies and randomized clinical trials.
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Adenocarcinoma/terapia , Anticuerpos Monoclonales Humanizados/administración & dosificación , Paclitaxel/administración & dosificación , Neoplasias Gástricas/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/efectos adversos , Quimioterapia Adyuvante/métodos , Quimioterapia Adyuvante/estadística & datos numéricos , Unión Esofagogástrica/patología , Unión Esofagogástrica/cirugía , Femenino , Gastrectomía , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/estadística & datos numéricos , Paclitaxel/efectos adversos , Supervivencia sin Progresión , Estudios Retrospectivos , España/epidemiología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , RamucirumabRESUMEN
BACKGROUND: Treatment with nab-paclitaxel plus gemcitabine increases survival in patients with metastatic pancreatic cancer. However, the assessment of treatment efficacy and safety in non-selected patients in a real-life setting may provide useful information to support decision-making processes in routine practice. METHODS: Retrospective, multicenter study including patients with metastatic pancreatic cancer, who started first-line treatment with nab-paclitaxel plus gemcitabine between December 2013 and June 2015 according to routine clinical practice. In addition to describing the treatment pattern, overall survival (OS) and progression-free survival (PFS) were assessed for the total sample and the exploratory subgroups based on the treatment and patients' clinical characteristics. RESULTS: All 210 eligible patients had a median age of 65.0 years (range 37-81). Metastatic pancreatic adenocarcinoma was recurrent in 46 (21.9%) patients and de novo in 164 (78.1%); 38 (18%) patients had a biliary stent. At baseline, 33 (18.1%) patients had an ECOG performance status ≥2. Patients received a median of four cycles of treatment (range 1-21), with a median duration of 3.5 months; 137 (65.2%) patients had a dose reduction of nab-paclitaxel and/or gemcitabine during treatment, and 33 (17.2%) discontinued treatment due to toxicity. Relative dose intensity (RDI) for nab-paclitaxel, gemcitabine, and the combined treatment was 66.7%. Median OS was 7.2 months (95% CI 6.0-8.5), and median PFS was 5.0 months (95% CI 4.3-5.9); 50 patients achieved either a partial or complete response (ORR 24.6%). OS was influenced by baseline ECOG PS, NLR and CA 19.9, but not by age ≥ 70 years and/or the presence of hepatobiliary stent or RDI < 85%. All included variables, computed as dichotomous, showed a significant contribution to the Cox regression model to build a nomogram for predicting survival in these patients: baseline ECOG 0-1 vs. 2-3 (p = 0.030), baseline NLR > 3 vs. ≤ 3 (p = 0.043), and baseline CA 19.9 > 37 U/mL vs. ≤37 U/mL (p = 0.004). CONCLUSIONS: Nab-Paclitaxel plus gemcitabine remain effective in a real-life setting, despite the high burden of dose reductions and poorer performance of these patients. A nomogram to predict survival using baseline ECOG performance status, NLR and CA 19.9 is proposed.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/mortalidad , Adulto , Anciano , Albúminas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Comorbilidad , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Neoplasias Pancreáticas/patología , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
BACKGROUND: The choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS). METHODS: We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of 'treatment-by-histology' interaction, was used to estimate treatment effect. RESULTS: Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046. CONCLUSIONS: As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sistema de Registros , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Antraciclinas/administración & dosificación , Chile , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Docetaxel , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Receptor ErbB-2 , España , Neoplasias Gástricas/clasificación , Taxoides/administración & dosificación , Resultado del TratamientoRESUMEN
OBJECTIVES: To analyze the role of audiometry in considering change to a less ototoxic treatment in head and neck cancer (HNC) patients. METHODS: Consecutive patients prescribed high-dose cisplatin (100 mg/m2) between January 2013 and February 2015 were enrolled. Audiometry was performed at baseline and before cisplatin. Change to a less ototoxic agent or reduced cisplatin dose was considered with audiometric decreases >25 dB. RESULTS: A total of 103 patients were included; the median age of the patients was 59 years (range 18-75). Cisplatin was intended curative (58%), adjuvant (32%), or palliative (10%). Forty-two participants (41%) did not commence high-dose cisplatin because of baseline audiometric alterations. Of 61 patients treated with high-dose cisplatin, 40 (66%) showed marked ototoxicity at the end of treatment. The mean hearing loss between initial and final audiometries showed a hearing loss at 4 and 8 kHz in both ears (p = 0.002). Thirteen patients switched to carboplatin and 15 to a lower dose of cisplatin. The outcome was not significantly altered when cisplatin was replaced with carboplatin or cetuximab. CONCLUSIONS: Audiometric alterations are common in HNC with high-dose cisplatin, and switching to a less ototoxic regimen does not adversely affect outcome. Audiometric examination could help to prevent hearing loss in this population.
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Antineoplásicos/efectos adversos , Audiometría , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Pérdida Auditiva/inducido químicamente , Compuestos Organoplatinos/efectos adversos , Adolescente , Adulto , Anciano , Algoritmos , Antineoplásicos/administración & dosificación , Umbral Auditivo/efectos de los fármacos , Toma de Decisiones Clínicas , Cóclea/efectos de los fármacos , Cóclea/fisiopatología , Femenino , Neoplasias de Cabeza y Cuello/complicaciones , Pérdida Auditiva/fisiopatología , Pérdida Auditiva/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Estudios Prospectivos , España , Adulto JovenRESUMEN
BACKGROUND: Trastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC. METHODS: This Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression. RESULTS: The rate of HER2 testing increased steadily over time, from 58.3 % in 2008 to 92.9 % in 2016. HER2 was positive in 194 tumors (21.3 %). In the stratified Cox PH regression, each 1 % increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3 % increase in the risk of death: hazard ratio, 1.0035 (CI 95 %, 1.001-1.005), P = 0.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2. CONCLUSION: Patients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner.
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Biomarcadores de Tumor/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , España , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Trastuzumab/administración & dosificaciónRESUMEN
BACKGROUND: There is currently no consensus regarding first-line chemotherapy for patients with advanced gastric cancer (AGC) who are ineligible to receive trastuzumab. The objective of this study was to evaluate the efficacy and tolerance of triplets versus doublets by analyzing a national gastric cancer registry. PATIENTS AND METHOD: Patients with AGC treated with polychemotherapy without associating trastuzumab were included from 2008 through 2016. The effect of triplets versus doublets was compared using 3 methods: Cox proportional hazards regression, propensity score matching (PSM), and coarsened exact matching (CEM). RESULTS: A total of 970 patients were recruited (doublets: n=569; triplets: n=401). In the multivariate Cox model, the use of triplets was associated with better overall survival (OS), with a hazard ratio (HR) of 0.84 (95% CI, 0.72-0.98; P=.035). After PSM, the sample contained 340 pairs. A significant increase in OS, 11.14 months (95% CI, 9.60-12.68) versus 9.60 months (95% CI, 8.44-10.75), was seen in favor of triplets (HR, 0.77; 95% CI, 0.65-0.92; stratified log-rank test, P=.004). The effect appeared to be comparable for anthracycline-based (HR, 0.78; 95% CI, 0.64-0.94) or docetaxel-based triplets (HR, 0.78; 95% CI, 0.60-1.009). The trend was similar after applying the CEM algorithm, with an HR of 0.78 (95% CI, 0.63-0.97; P=.03). Triplet therapy was viable and relative dose intensities exceeded 85%, except for cisplatin in DCX (docetaxel, cisplatin, capecitabine). Triplets had more severe toxicity overall, especially hematologic, hepatic, and mucosal adverse events. CONCLUSIONS: With the limitations of a retrospective study that examines a heterogeneous set of chemotherapy regimens, we found that triplets are feasible in daily practice and are associated with a discreet benefit in efficacy at the expense of a moderate increase in toxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Neoplasias Gástricas/patología , Adulto JovenAsunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Fluorouracilo/efectos adversos , Neumatosis Cistoide Intestinal/inducido químicamente , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Terapia Combinada , Neoplasias Esofágicas/tratamiento farmacológico , Unión Esofagogástrica , Fluidoterapia , Fluorouracilo/administración & dosificación , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Masculino , Terapia por Inhalación de Oxígeno , Cuidados Paliativos , Neumatosis Cistoide Intestinal/diagnóstico por imagen , Neumatosis Cistoide Intestinal/terapia , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
PURPOSE: The outcome of locally advanced adenocarcinoma of the esophagogastric junction (AEG) treated with preoperative chemoradiotherapy is heterogeneous, and favorable response to this treatment is a key factor in the patient's prognosis. The aim of this study was to evaluate F-FDG PET/CT in assessing metabolic response in patients with AEG. MATERIALS AND METHODS: This prospective study evaluated all consecutive patients with potentially operable locally advanced AEG who were candidates for neoadjuvant chemoradiotherapy. PET/CT and contrast-enhanced thoracoabdominal CT were performed at baseline and 2 weeks after completion of chemoradiotherapy for response evaluation. The response rate was assessed using Response Evaluation Criteria in Solid Tumors criteria for contrast-enhanced thoracoabdominal CT and Positron Emission Tomography Response Criteria in Solid Tumors criteria for PET/CT. The regression rate was assessed using a 5-grade histopathology scoring system of the surgically resected tumor. Metastatic lesions were confirmed by histopathology examination or imaging and clinical follow-up at 6 months. RESULTS: A total of 40 cases were finally included in the study. Distant metastases were found in the baseline PET/CT in 6 of 40 cases (retroperitoneal [2] or mediastinal/hiliar [1] lymph nodes and liver [2] or bone [1] metastases) and were therefore excluded from surgery. Pathologic response correlated with the ΛSUVmax threshold of ≤45% (P = 0.033). CT response correlated well with both the baseline SUVmax (P = 0.039) and the ΛSUVmax (P = 0.001). Five-year survival curves for AEG correlated with the ΛSUVmax using a threshold of ≤45% for both progression-free and overall survival. CONCLUSIONS: F-FDG PET/CT is useful for diagnosing nonsuspected metastasis before neoadjuvancy in potentially operable AEG. The ΛSUV correlates with pathologic response and is a long-term independent prognostic factor of survival.
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Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/terapia , Quimioradioterapia , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/terapia , Unión Esofagogástrica/patología , Fluorodesoxiglucosa F18 , Terapia Neoadyuvante , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adenocarcinoma/patología , Neoplasias Esofágicas/patología , Unión Esofagogástrica/diagnóstico por imagen , Unión Esofagogástrica/efectos de los fármacos , Unión Esofagogástrica/efectos de la radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Second-line treatments boost overall survival in advanced gastric cancer (AGC). However, there is a paucity of information as to patterns of use and the results achieved in actual clinical practice. MATERIALS AND METHODS: The study population comprised patients with AGC in the AGAMENON registry who had received second-line. The objective was to describe the pattern of second-line therapies administered, progression-free survival following second-line (PFS-2), and post-progression survival since first-line (PPS). RESULTS: 2311 cases with 2066 progression events since first-line (89.3%) were recorded; 245 (10.6%) patients died during first-line treatment and 1326/2066 (64.1%) received a second-line. Median PFS-2 and PPS were 3.1 (95% CI, 2.9-3.3) and 5.8 months (5.5-6.3), respectively. The most widely used strategies were monoCT (56.9%), polyCT (15.0%), ramucirumab+CT (12.6%), platinum-reintroduction (8.3%), trastuzumab+CT (6.1%), and ramucirumab (1.1%). PFS-2/PPS medians gradually increased in monoCT, 2.6/5.1 months; polyCT 3.4/6.3 months; ramucirumab+CT, 4.1/6.5 months; platinum-reintroduction, 4.2/6.7 months, and for the HER2+ subgroup in particular, trastuzumab+CT, 5.2/11.7 months. Correlation between PFS since first-line and OS was moderate in the series as a whole (Kendall's τ = 0.613), lower in those subjects who received second-line (Kendall's τ = 0.539), especially with ramucirumab+CT (Kendall's τ = 0.413). CONCLUSION: This analysis reveals the diversity in second-line treatment for AGC, highlighting the effectiveness of paclitaxel-ramucirumab and, for a selected subgroup of patients, platinum reintroduction; both strategies endorsed by recent clinical guidelines.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sistema de Registros/estadística & datos numéricos , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Compuestos de Platino/administración & dosificación , Compuestos de Platino/uso terapéutico , Neoplasias Gástricas/patología , Análisis de SupervivenciaRESUMEN
OBJECTIVES: In the EXTREME trial, a combination of cisplatin or carboplatin plus 5-fluorouracil (5-FU) and cetuximab was superior to cisplatin/carboplatin plus 5-FU for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). With the aim of improving fluoropyrimidine-related tolerance without decreasing its efficacy, the safety and efficacy of carboplatin plus the oral fluoropyrimidine tegafur and cetuximab were investigated. METHODS: A retrospective analysis of 104 patients with recurrent or metastatic HNSCC was conducted. Patients were treated with carboplatin (area under the curve: 5 mg/mL/min) on day 1, oral tegafur (250 mg/m2 twice daily) for 21 consecutive days, and cetuximab (400 mg/m2 as an initial 2-hour intravenous infusion, then 250 mg/m2 as a 1-hour weekly infusion for 3 weeks) for ≤6 cycles. Patients who responded to the therapy then received weekly cetuximab maintenance therapy. RESULTS: Treatment was well tolerated with a high level of compliance (relative dose intensity: 96%, 88%, and 81% for carboplatin, tegafur, and cetuximab, respectively). Grade 3-4 adverse events (AEs) were observed in 38% of patients (skin reactions in 17% of patients, anemia 4%, and neutropenia 3%). Grade 1-2 AEs included skin reactions (52% of patients), hypomagnesemia (20%), asthenia (19%), and anemia (13%). No venous thrombosis related to chemotherapy perfusion was observed. Over a median follow-up of 21 months, the median overall and progression-free survival were 11 and 6 months, respectively, and the overall response rate was 35%. CONCLUSIONS: Carboplatin plus oral tegafur and cetuximab is a safe, well-tolerated first-line therapy for recurrent or metastatic HNSCC.
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Carcinoma de Células Escamosas/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Anciano , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidad , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Inmunosupresores/administración & dosificación , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , España/epidemiología , Carcinoma de Células Escamosas de Cabeza y Cuello , Tasa de Supervivencia/tendencias , Resultado del TratamientoRESUMEN
PURPOSE: The aim of this study was to evaluate F-FDG PET/CT compared with conventional imaging techniques in the clinical management of patients with locally advanced gastric cancer (LAGC). METHODS: A prospective study between January 2010 and December 2011 in patients with suspected LAGC was conducted in our hospital. F-FDG PET/CT, contrast-enhanced CT (CECT), endoscopic ultrasound, and laparoscopy were performed in all cases. Standard whole-body F-FDG PET/CT images were obtained centered on the stomach at 1 and 2 hours after injection of 4.0 MBq/kg of F-FDG. Findings were confirmed by histopathology or by imaging follow-up in nonoperable patients. RESULTS: Fifty consecutive patients with confirmed LAGC (20 women, 30 men) with a mean ± SD age of 65.7 ± 12.1 years were included. Using Lauren classification, 24 patients were intestinal subtype, and 26 were diffuse subtype. Thirty-five patients with locoregional lymph node involvement and 22 with distant metastases were confirmed as peritoneal metastases (n = 15), retroperitoneal (n = 2) or mediastinal lymph nodes (n = 1), and liver (n = 3) or bone metastases (n = 1). Patients with signet ring carcinoma showed significantly less F-FDG uptake (P = 0.001). SUVmax correlated with tumor grading (P < 0.05). Standard and delayed F-FDG PET/CT and CECT images identified LAGC in 24, 27, and 28 of 30 patients, respectively. The sensitivity and specificity for F-FDG PET/CT and CECT to detect metastases were 68% and 100% and 64% and 93%, respectively. Contrast-enhanced CT and F-FDG PET/CT diagnosed only 6 of the 15 patients with confirmed peritoneal metastases. The impact in therapeutic management of F-FDG PET/CT and CECT was 24% and 22%, respectively. Kaplan-Meier survival curves for the LGAC showed a significant correlation between SUVmax and overall survival using an SUVmax threshold of less than 3.96 (P = 0.04). CONCLUSIONS: F-FDG PET/CT should be recommended for staging of LAGC; however, F-FDG PET/CT and CECT cannot replace laparoscopy to rule out peritoneal metastases. Delayed F-FDG PET/CT images show an increase of F-FDG uptake in most cases, improving LAGC detection. The grade of F-FDG uptake represents a significant prognostic tool in this series.
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Adenocarcinoma/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/normas , Neoplasias Gástricas/diagnóstico por imagen , Adenocarcinoma/patología , Adulto , Anciano , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos , Neoplasias Gástricas/patologíaRESUMEN
OBJECTIVE: Advanced gastric cancer (AGC) is a common neoplasm in older adults. Nevertheless, there are few specific management data in the literature. The aim of this study was to assess non-inferiority of survival and efficacy-related outcomes of chemotherapy used in older vs non-older patients with AGC. MATERIALS AND METHODS: We recruited 1485 patients from the AGAMENON registry of AGC treated with polychemotherapy between 2008-2017. A statistical analysis was conducted to prove non-inferiority for overall survival (OS) associated with the use of chemotherapy schedules in individuals ≥70 vs.<70years. The fixed-margin method was used (hazard ratio [HR]<1.176) that corresponds to conserving at least 85% efficacy. RESULTS: 33% (n=489) of the cases analyzed were ≥70 years. Two-agent chemotherapies and combinations with oxaliplatin (48% vs. 29%) were used more often in the older patients, as were modified schedules and/or lower doses. Toxicity grade 3-4 was comparable in both groups, although when looking at any grade, there were more episodes of enteritis, renal toxicity, and fatigue in older patients. In addition, toxicity was a frequent cause for discontinuing treatment in older patients. The response rate was similar in both groups. After adjusting for confounding factors, the non-inferiority of OS associated with schedules administered to the older vs. younger subjects was confirmed: HR 1.02 (90% CI, 0.91-1.14), P (non inferiority)=0.018, as well as progression-free survival: HR 0.97 (90% CI, 0.87-1.08), P(non-inferiority)=0.001. CONCLUSION: In this AGC registry, the use of chemotherapy with schedules adapted to patients ≥70 years provided efficacy that was not inferior to that seen in younger cases, with comparable adverse effects.
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Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Sistema de Registros , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Adulto JovenRESUMEN
Docetaxel-based chemotherapy is the standard first-line therapy in metastatic castration-resistant prostate cancer (CRPC). However, most patients eventually develop resistance to this treatment. In this study, we aimed to identify key molecular genes and networks associated with docetaxel resistance in two models of docetaxel-resistant CRPC cell lines and to test for the most differentially expressed genes in tumor samples from patients with CRPC. DU-145 and PC-3 cells were converted to docetaxel-resistant cells, DU-145R and PC-3R, respectively. Whole-genome arrays were used to compare global gene expression between these four cell lines. Results showed differential expression of 243 genes (P < 0.05, Bonferroni-adjusted P values and log ratio > 1.2) that were common to DU-145R and PC-3R cells. These genes were involved in cell processes like growth, development, death, proliferation, movement, and gene expression. Genes and networks commonly deregulated in both DU-145R and PC-3R cells were studied by Ingenuity Pathways Analysis. Exposing parental cells to TGFB1 increased their survival in the presence of docetaxel, suggesting a role of the TGF-ß superfamily in conferring drug resistance. Changes in expression of 18 selected genes were validated by real-time quantitative reverse transcriptase PCR in all four cell lines and tested in a set of 11 FFPE and five optimal cutting temperature tumor samples. Analysis in patients showed a noteworthy downexpression of CDH1 and IFIH1, among others, in docetaxel-resistant tumors. This exploratory analysis provides information about potential gene and network involvement in docetaxel resistance in CRPC. Further clinical validation of these results is needed to develop targeted therapies in patients with CRPC that can circumvent such resistance to treatment.