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1.
Inflammation ; 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38492185

RESUMEN

Advanced intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy characterized by limited response to standard therapeutic modalities, such as radiotherapy, chemotherapy, and targeted therapy. The prognosis for patients with advanced ICC is exceedingly bleak, with an overall survival of less than 1 year. In recent years, personalized neoantigen vaccines have emerged as a promising approach to augment the immune response against tumors. Clinical investigations are currently underway to evaluate the efficacy of neoantigen-based peptide, DNA, and dendritic cell vaccines. Herein, we present a noteworthy case of advanced ICC patients who experienced disease progression following relapse and subsequently received immunotherapy with a personalized neoantigen nanovaccine. This innovative treatment strategy involved the administration of a custom-designed neoantigen-based peptide nanovaccine tailored to the patient's specific gene mutation profile subsequent to failure of first-line therapy. The clinical efficacy and anti-tumor immune responses were evaluated using various methods, including imaging, interferon-γ ELISPOT assay, and intracellular cytokine staining. Notably, the neoantigen nanovaccine elicited a robust and specific tumor-killing effect mediated by T cells, resulting in a durable response lasting up to 25 months. These findings highlight the potential of neoantigen-based immunotherapy as a novel therapeutic avenue for the management of advanced ICC.

2.
J Hepatocell Carcinoma ; 11: 305-316, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38348098

RESUMEN

Background: Stereotactic body radiotherapy (SBRT) has emerged as an alternative approach for patients with hepatocellular carcinoma (HCC), and we aim to find potential prognostic biomarkers for HCC patients who received SBRT. Methods: In this study, we retrospectively analyzed HCC patients who underwent SBRT in our institution from January 2018 to December 2022. The inflammatory parameters, along with baseline patients' characteristics were collected to elucidate the potential relationship with survival benefits and liver toxicities. Results: Overall, 35 patients were enrolled in our study. For the efficacy population (25 patients who underwent SBRT for primary liver lesions), the objective response rate (ORR) and disease control rate (DCR) were 60% and 100%, respectively. The median progression-free survival (PFS) was 9.9 months [95% confidence interval (CI) 5.6-14.1 months], and the median overall survival (OS) was 18.5 months (95% CI 14.2-22.8 months). We further confirmed that higher baseline lymphocyte-C-reactive protein ratio (LCR) (≥2361.11) was positively related to both longer PFS (12.0 vs 4.3 months, P = 0.002) and OS (21.9 vs 11.4 months, P = 0.022). Moreover, patients with diabetes and higher alpha-fetoprotein (AFP) (≥400 ng/mL) were also found to be associated with worse OS. The most common hepatotoxicity was elevated gamma-glutamyl transferase (GGT) (84.0%). Conclusion: In conclusion, for patients with inoperable HCC, SBRT resulted in satisfactory local control, survival benefits, and acceptable liver toxicity. Pre-radiotherapy LCR might be an independent and readily available predictor for survival, which facilitates us to find the most appropriate treatment options.

3.
Clin Transl Immunology ; 13(1): e1483, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38223257

RESUMEN

Objectives: To assess the safety and efficacy of anlotinib (a multi-targeted tyrosine kinase inhibitor) combined with toripalimab (a PD-1 monoclonal antibody) in the treatment of unresectable biliary tract cancer (BTC). Methods: In this prospective, single-arm, single-centre exploratory clinical study, patients with locally progressed or metastatic BTC were included. Patients were treated with anlotinib (12 mg, PO, QD, for 2 weeks and then stopped for a week, 21 days for a cycle) and toripalimab (240 mg, IV, Q3W). The primary endpoint of the study was the objective response rate (ORR), as defined in RECIST version 1.1 criteria. Results: In this study, 15 BTC patients who met the criteria were enrolled. The ORR was 26.7%, the median progression-free survival (mPFS) was 8.6 months (95% CI: 2.1-15.2), the median overall survival (mOS) was 14.53 months (95% CI: 0.8-28.2) and the disease control rate (DCR) was 87.6%. A patient with hilar cholangiocarcinoma was successfully converted after three cycles of treatment and underwent surgical resection. Furthermore, patient gene sequencing revealed that STK11 was mutated more frequently in patients with poor outcomes. In addition, patients with a CD8/Foxp3 ratio > 3 had a longer survival than those with a CD8/Foxp3 ratio ≤ 3 (P = 0.0397). Conclusions: In patients with advanced BTC, the combination of anlotinib and toripalimab demonstrated remarkable anti-tumor potential, with increased objective response rates (ORR), longer overall survival (OS) and progression-free survival (PFS). Moreover, STK11 and CD8/Foxp3 may be as biomarkers that can predict the effectiveness of targeted therapy in combination with immunotherapy.

4.
Cancer Med ; 12(22): 20699-20711, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37930138

RESUMEN

BACKGROUND: Immune checkpoint inhibitor (ICI) combination therapies have shown promise in the first-line treatment of advanced biliary tract cancer (BTC). However, the best partner remains to be validated. Moreover, progress on biomarkers predicting the efficacy of ICI in BTC is slow. This study aimed to assess the efficacy and investigate reliable predictive biomarkers of programmed cell death protein-1 (PD-1) antibody combination therapy in the first-line treatment of advanced BTC. METHODS: Clinical data from patients with advanced BTC who received chemotherapy or anti-PD-1 combination therapy as first-line were collected. The primary outcome was overall survival (OS). Biomarkers, including peripheral blood inflammation scores, genetic alterations, and tumor microenvironment were investigated. FINDINGS: Sixty-four patients were recruited and divided into four treatment groups: chemotherapy, anti-PD-1 plus chemotherapy, anti-PD-1 plus targeted therapy, and triple group (anti-PD-1 plus chemotherapy and targeted therapy). The median OS was 7.9, 11.3, 12.8, and 28.7 months, respectively. Compared to chemotherapy, mOS significantly prolonged in the triple group (p = 0.031). It showed that patients with five different peripheral blood inflammation scores had significantly prolonged mOS (p < 0.05). Genetic testing results suggested that patients with poor survival all had TP53 mutations and higher levels of KRAS and ERBB2 mutations. Low FOXP3/CD8 ratio was associated with prolonged OS (p = 0.029). With CD4-low, CD8-high, CD56-positive, CD163-high, FOXP3-high and MPO-high in TME as one factor, we calculated PLUS score according to the number of factors. The high-PLUS (>2) group showed significantly superior OS (p = 0.003). INTERPRETATION: First-line anti-PD-1 combination therapy was superior to chemotherapy, and triple therapy significantly improved survival. Peripheral blood immune-inflammation score, FOXP3/CD8 ratio, and PLUS have potential as biomarkers for predicting the efficacy of first-line anti-PD-1 therapy in advanced BTC.


Asunto(s)
Neoplasias de los Conductos Biliares , Inhibidores de Puntos de Control Inmunológico , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Biomarcadores de Tumor/genética , Factores de Transcripción Forkhead , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inflamación/etiología , Estudios Retrospectivos , Microambiente Tumoral
5.
Cancer Biol Med ; 20(8)2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37553810

RESUMEN

Colorectal cancer (CRC) remains an enormous challenge to human health worldwide. Unfortunately, the mechanism underlying CRC progression is not well understood. Mounting evidence has confirmed that exosomes play a vital role in CRC progression, which has attracted extensive attention among researchers. In addition to acting as messengers between CRC cells, exosomes also participate in the CRC immunomodulatory process and reshape immune function. As stable message carriers and liquid biopsy option under development, exosomes are promising biomarkers in the diagnosis or treatment of CRC. In this review we have described and analyzed the biogenesis and release of exosomes and current research on the role of exosomes in immune regulation and metastasis of CRC. Moreover, we have discussed candidate exosomal molecules as potential biomarkers to diagnose CRC, predict CRC progression, or determine CRC chemoresistance, and described the significance of exosomes in the immunotherapy of CRC. This review provides insight to further understand the role of exosomes in CRC progression and identify valuable biomarkers that facilitate the clinical management of CRC patients.


Asunto(s)
Neoplasias Colorrectales , Exosomas , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Biomarcadores de Tumor
6.
Antioxid Redox Signal ; 39(7-9): 472-490, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37002890

RESUMEN

Significance: Redox dysregulation under pathological conditions results in excessive reactive oxygen species (ROS) accumulation, leading to oxidative stress and cellular oxidative damage. ROS function as a double-edged sword to modulate various types of cancer development and survival. Recent Advances: Emerging evidence has underlined that ROS impact the behavior of both cancer cells and tumor-associated stromal cells in the tumor microenvironment (TME), and these cells have developed complex systems to adapt to high ROS environments during cancer progression. Critical Issues: In this review, we integrated current progress regarding the impact of ROS on cancer cells and tumor-associated stromal cells in the TME and summarized how ROS production influences cancer cell behaviors. Then, we summarized the distinct effects of ROS during different stages of tumor metastasis. Finally, we discussed potential therapeutic strategies for modulating ROS for the treatment of cancer metastasis. Future Directions: Targeting the ROS regulation during cancer metastasis will provide important insights into the design of effective single or combinatorial cancer therapeutic strategies. Well-designed preclinical studies and clinical trials are urgently needed to understand the complex regulatory systems of ROS in the TME. Antioxid. Redox Signal. 39, 472-490.


Asunto(s)
Neoplasias , Microambiente Tumoral , Humanos , Especies Reactivas de Oxígeno , Estrés Oxidativo , Neoplasias/patología , Oxidación-Reducción
7.
Invest New Drugs ; 41(1): 162-167, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36763233

RESUMEN

OBJECTIVE: Targeted therapy combined with immunotherapy has become the main treatment option for hepatocellular carcinoma (HCC). This trial assessed the safety and efficacy of fibroblast growth factor receptor 4 inhibitor (BLU-554) in combination with the anti-PD-L1 monoclonal antibody (CS1001) in patients with locally advanced or metastatic HCC. PATIENTS AND METHODS: This Phase Ib/II trial enrolled patients with locally advanced or metastatic HCC who were FGF19-positive. The patients were intravenously administered with CS1001 (1200 mg) every three weeks and orally administered with BLU-554 (600 mg) daily. The primary endpoint was objective response rate (ORR), as assessed according to RECISTv1.1. RESULTS: Four patients were treated with BLU-554 combined with CS1001. The trial revealed a 50% ORR and 100% DCR. The main adverse reactions that were attributed to BLU-554 in combination with CS1001 were diarrhoea, liver function impairments and skin rashes. Only one patient had immune-related adverse reactions. CONCLUSION: Preliminary data showed that BLU-554 in combination with CS1001 is safe and effective for treatment of patients with locally advanced or metastatic HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos
8.
Clin Exp Med ; 23(3): 569-577, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36001163

RESUMEN

Hepatocellular carcinoma (HCC), a primary malignancy of the liver, is a threat to the health of all humans as a prevalent malignancy and is the sixth most common cancer worldwide. It is difficult to diagnose because symptoms do not show up until late in the disease, and patients often progress to the point where transplantation, resection, or even local treatment cannot be performed. The progression of HCC is regulated by the immune system, and immunotherapy enables the body's immune system's defenses to target liver cancer cells; therefore, immunotherapy has brought a new hope for the treatment of HCC. Currently, the main types of immunotherapies for liver cancer are: immune checkpoint inhibitors, liver cancer vaccines and cellular therapies. In this review, the progress of immunotherapy for the treatment of HCC is summarized.


Asunto(s)
Vacunas contra el Cáncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Inmunoterapia , Vacunas contra el Cáncer/uso terapéutico
9.
Front Pharmacol ; 13: 805966, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35656305

RESUMEN

Objective: The aim was to evaluate the efficacy and safety of vancomycin or daptomycin (VAN/DAP), antistaphylococcal ß-lactam (ASBL), trimethoprim-sulfamethoxazole (TMP-SMX), and combination therapy of VAN/DAP + ASBL in the management of methicillin-resistant Staphylococcus aureus (MRSA). Methods: Databases including PubMed, Cochrane Library, Embase database, and google scholar were searched on 1 September 2021. The randomized control trials (RCTs) and comparable clinical studies of VAN/DAP, VAN/DAP + ASBL, ASBL, and TMP-SMX in the management of MRSA were identified. A network meta-analysis was conducted with STATA 14.0. Results: Seven RCTs and two matched cohorts with 1,048 patients were included in the analysis. The pooled results showed that VAN/DAP + ASBL had a significantly lower rate of persistent bacteremia >3 days than VAN/DAP alone [OR:0.46, 95%CI (0.26, 0.81), p < 0.001]. No obvious differences were observed in the outcomes of all-cause mortality, relapsed bacteremia, microbiological treatment failure, embolic or metastatic infection, and total adverse events. However, the ranking results showed that VAN/DAP + ASBL had slightly better efficacy (all-cause mortality, persistent bacteremia >3 days, duration of bacteremia, microbiological treatment failure, and relapsed bacteremia) but slightly higher adverse events than VAN/DAP alone. No obvious differences in the comparisons of VAN/DAP vs. ASBL, and VAN/DAP vs TMP-SMX in the analyzed outcomes. The ranking results revealed that ASBL and TMP-SMX did not have better efficacy or lower adverse events compared with the treatment of VAN/DAP. Conclusion: The efficacy of VAN/DAP + ASBL was slightly but not significantly better than VAN/DAP alone in the management of MRSA.

10.
Asian J Surg ; 45(1): 1-7, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33867239

RESUMEN

The aim of this study was to evaluate the benefits and safety of transperitoneal and retroperitoneal pyeloplasty for ureteropelvic junction obstruction by a meta-analysis. We searched the databases including PubMed, Cochrane Library and Embase database from their inception to December 1st, 2020. Relevant literatures comparing retroperitoneal pyeloplasty with transperitoneal pyeloplasty were identified. A meta-analysis was conducted with Revman 5.3. The main outcomes included success rate, operative time, hospital stay, conversion rate of open surgery, overall complications, and detailed postoperative complications/indicators. 15 studies with 1881 patients were included. The results revealed that there were no significant differences between two approaches in success rate [OR = 1.51, 95%CI (0.94, 2.41), p = 0.09], hospital stay [MD = 0.21, 95%CI (-0.12, 0.54), p = 0.21] and overall complications [OR = 1.07, 95%CI (0.76, 1.50), p = 0.69]. The retroperitoneal approach was associated with longer operative time [MD = -26.91, 95%CI (-40.97, -12.84), p < 0.001], higher conversion rate [OR = 0.23, 95%CI (0.11, 0.47), p < 0.001] than the transperitoneal approach. As for the detailed postoperative complications/indicators, there were no significant differences between two approaches in the urinary leak, mild hematuria, fever, UPJO recurrence, infection and subcutaneous emphysema, as well as split renal function, renal pelvis anteroposterior diameter. The funnel plots showed that there were no obvious publication biases in our analysis. Therefore, we concluded that transperitoneal and retroperitoneal approaches had similar benefits and safety in success rate, hospital stay, overall complications and detailed postoperative complications/indicators. However, retroperitoneal was associated with longer operative time and higher conversion rate than transperitoneal approach. With the limitations of our study, additional high-quality studies are still essential for further evaluation.


Asunto(s)
Laparoscopía , Uréter , Obstrucción Ureteral , Humanos , Riñón/fisiología , Pelvis Renal , Resultado del Tratamiento , Obstrucción Ureteral/cirugía , Procedimientos Quirúrgicos Urológicos
11.
Biomed Res Int ; 2021: 4092635, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34746301

RESUMEN

Hepatocellular carcinoma (HCC) is an aggressive cancer type with poor prognosis; thus, there is especially necessary and urgent to screen potential prognostic biomarkers for early diagnosis and novel therapeutic targets. In this study, we downloaded target data sets from the GEO database, and obtained codifferentially expressed genes using the limma R package and identified key genes through the protein-protein interaction network and molecular modules, and performed GO and KEGG pathway analyses for key genes via the clusterProfiler package and further determined their correlations with clinicopathological features using the Oncomine database. Survival analysis was completed in the GEPIA and the Kaplan-Meier plotter database. Finally, correlations between key genes, cell types infiltrated in the tumor microenvironment (TME), and hypoxic signatures were explored based on the TIMER database. From the results, 11 key genes related to the cell cycle were determined, and high levels of these key genes' expression were focused on advanced and higher grade status HCC patients, as well as in samples of TP53 mutation and vascular invasion. Besides, the 11 key genes were significantly associated with poor prognosis of HCC and also were positively related to the infiltration level of MDSCs in the TME and the HIF1A and VEGFA of hypoxic signatures, but a negative correlation was found with endothelial cells (ECs) and hematopoietic stem cells. The result determined that 11 key genes (RRM2, NDC80, ECT2, CCNB1, ASPM, CDK1, PRC1, KIF20A, DTL, TOP2A, and PBK) could play a vital role in the pathogenesis of HCC, drive the communication between tumor cells and the TME, and act as probably promising diagnostic, therapeutic, and prognostic biomarkers in HCC patients.


Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Ciclo Celular/genética , Biología Computacional/métodos , Bases de Datos Genéticas , Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Pronóstico , Mapas de Interacción de Proteínas , Transducción de Señal , Análisis de Supervivencia , Transcriptoma , Microambiente Tumoral/genética
12.
RSC Adv ; 11(46): 28651-28658, 2021 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-35478532

RESUMEN

Polyelectrolyte-protein nanocomplexes prepared under mild and simple conditions which could have biological activity arising from protein have emerged as fascinating protein delivery systems. However, common polyelectrolytes have problems of biocompatibility and metabolism in vivo, which may limit their further applications. Herein, a novel polyethylene glycol polyelectrolyte was synthesized and used for carrying protein drugs. Different from previously reported polyelectrolyte-protein nanoclusters, the polyethylene glycol polyelectrolyte-protein nanoclusters avoid organic solvent and protein modification, and the structure and bioactivity of proteins are well preserved. Moreover, the polyethylene glycol polyelectrolyte-protein nanoclusters have good hemocompatibility and biocompatibility. These novel polyethylene glycol polyelectrolyte-protein nanoclusters would provide a potent tool for fabrication of versatile protein drug carriers.

13.
Oncotarget ; 7(16): 22711-9, 2016 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-26992206

RESUMEN

The outcomes for patients with esophageal cancer (EC) underwent standard-dose radical radiotherapy were still disappointing. This phase II study investigated the feasibility, safety and efficacy of radiation dose escalation using simultaneous modulated accelerated radiotherapy (SMART) combined with chemotherapy in 60 EC patients. Radiotherapy consisted of 66Gy at 2.2 Gy/fraction to the gross tumor and 54Gy at 1.8 Gy/fraction to subclinical diseases simultaneously. Chemotherapy including cisplatin and 5fluorouracil were administered to all patients during and after radiotherapy. The data showed that the majority of patients (98.3%) completed the whole course of radiotherapy and concurrent chemotherapy. The most common ≥ grade 3 acute toxicities were neutropenia (16.7%), followed by esophagitis (6.7%) and thrombopenia (5.0%). With a median follow-up of 24 months (5-38) for all patients and 30 months (18-38) for those still alive, 11 patients (18.3%) developed ≥ Grade 3 late toxicities and 2 (3.3%) of them died subsequently due to esophageal hemorrhage. The 1- and 2-year local-regional control, distant metastasis-free survival, disease-free survival and overall survival rates were 87.6% and 78.6%, 86.0% and 80.5%, 75.6% and 64.4%, 86.7% and 72.7%, respectively. SMART combined with concurrent chemotherapy is feasible in EC patients with tolerable acute toxicities. They showed a trend of significant improvements in local-regional control and overall survival. Further follow-up is needed to evaluate the late toxicities.


Asunto(s)
Quimioradioterapia/métodos , Neoplasias Esofágicas/radioterapia , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/mortalidad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Dosificación Radioterapéutica
14.
Head Neck ; 37(2): 209-14, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24375647

RESUMEN

BACKGROUND: A prognostic model should be established for distant metastasis in locally advanced nasopharyngeal carcinoma (NPC) after concurrent chemoradiotherapy (CCRT). METHODS: Patients with locally advanced NPC who received CCRT were divided into a construction set (230 patients) and a validating set (115 patients). The constructed index was derived on the former and then tested on the latter. RESULTS: The prognostic score was defined as the number of adverse prognostic factors: age >45, N3 category, hemoglobin <11.0 g/dL and lactate dehydrogenase ≥240 U/L. The score predicted the 5-year distant metastasis-free survival as follows: 0, 91%; 1, 74%; 2, 51%; and ≥3, 12%. In the validating set, the observed 5-year distant metastasis-free survival of these 4 groups with scores of 0, 1, 2, 3, or higher were 81%, 68%, 47%, and 15%, respectively. CONCLUSION: The established model might be useful for predicting the risk of distant metastasis in patients with locally advanced NPC who underwent CCRT and may identify the patients' need for intensified adjuvant chemotherapy.


Asunto(s)
Carcinoma/patología , Carcinoma/terapia , Modelos Estadísticos , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/terapia , Metástasis de la Neoplasia , Factores de Edad , Quimioradioterapia , Femenino , Hemoglobinas/análisis , Humanos , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
15.
World J Gastroenterol ; 20(38): 13973-80, 2014 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-25320535

RESUMEN

AIM: To establish the feasibility of simultaneous modulated accelerated radiation therapy (SMART) in esophageal cancer (EC). METHODS: Computed tomography (CT) datasets of 10 patients with upper or middle thoracic squamous cell EC undergoing chemoradiotherapy were used to generate SMART, conventionally-fractionated three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (cf-IMRT) plans, respectively. The gross target volume (GTV) of the esophagus, positive regional lymph nodes (LN), and suspected lymph nodes (LN ±) were contoured for each patient. The clinical target volume (CTV) was delineated with 2-cm longitudinal and 0.5- to 1.0-cm radial margins with respect to the GTV and with 0.5-cm uniform margins for LN and LN(±). For the SMART plans, there were two planning target volumes (PTVs): PTV66 = (GTV + LN) + 0.5 cm and PTV54 = CTV + 0.5 cm. For the 3DCRT and cf-IMRT plans, there was only a single PTV: PTV60 = CTV + 0.5 cm. The prescribed dose for the SMART plans was 66 Gy/30 F to PTV66 and 54 Gy/30 F to PTV54. The dose prescription to the PTV60 for both the 3DCRT and cf-IMRT plans was set to 60 Gy/30 F. All the plans were generated on the Eclipse 10.0 treatment planning system. Fulfillment of the dose criteria for the PTVs received the highest priority, followed by the spinal cord, heart, and lungs. The dose-volume histograms were compared. RESULTS: Clinically acceptable plans were achieved for all the SMART, cf-IMRT, and 3DCRT plans. Compared with the 3DCRT plans, the SMART plans increased the dose delivered to the primary tumor (66 Gy vs 60 Gy), with improved sparing of normal tissues in all patients. The Dmax of the spinal cord, V20 of the lungs, and Dmean and V50 of the heart for the SMART and 3DCRT plans were as follows: 38.5 ± 2.0 vs 44.7 ± 0.8 (P = 0.002), 17.1 ± 4.0 vs 25.8 ± 5.0 (P = 0.000), 14.4 ± 7.5 vs 21.4 ± 11.1 (P = 0.000), and 4.9 ± 3.4 vs 12.9 ± 7.6 (P = 0.000), respectively. In contrast to the cf-IMRT plans, the SMART plans permitted a simultaneous dose escalation (6 Gy) to the primary tumor while demonstrating a significant trend of a lower irradiation dose to all organs at risk except the spinal cord, for which no significant difference was found. CONCLUSION: SMART offers the potential for a 6 Gy simultaneous escalation in the irradiation dose delivered to the primary tumor of EC and improves the sparing of normal tissues.


Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Radioterapia Conformacional , Radioterapia de Intensidad Modulada , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Quimioradioterapia , China , Ensayos Clínicos Fase II como Asunto , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Estudios de Factibilidad , Humanos , Ganglios Linfáticos/patología , Ganglios Linfáticos/efectos de la radiación , Metástasis Linfática , Dosis de Radiación , Planificación de la Radioterapia Asistida por Computador , Radioterapia Conformacional/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
16.
World J Gastroenterol ; 19(10): 1639-44, 2013 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-23539205

RESUMEN

AIM: To evaluate long-term outcomes and prognostic factors for esophageal squamous cell carcinoma (SCC) treated with three dimensional conformal radiotherapy (3D-CRT). METHODS: Between January 2005 and December 2006, 153 patients (120 males, 33 females) with pathologically confirmed esophageal SCC and treated with 3D-CRT in Cancer Hospital of Shantou University were included in this retrospective analysis. Median age was 60 years (range: 37-84 years). The proportion of tumor location was as follows: upper thorax (including the cervical region), 73 (48%); middle thorax, 73 (48%); lower thorax, 7 (5%), respectively. The median radiation dose was 64 Gy (range: 50-74 Gy). Fifty four cases (35%) received cisplatin-based concurrent chemotherapy. Univariate and multivariate analysis were performed to determine the association between the correlative factors and prognosis. RESULTS: The five-year overall survival rate was 26.3%, with a median follow-up of 49 mo (range: 3-66 mo) for patients who were still alive. On univariate analysis, lesion location, lesion length by barium esophagogram, computed tomography imaging characteristics including Y diameter (anterior-posterior, AP, extent of tumor), gross tumor volume of primary lesion (GTV-E), volume of positive lymph nodes (GTV-LN), and the total target volume (GTV-T = GTV-E + GTV-LN) were prognostic for overall survival. By multivariate analysis, only the Y diameter [hazard ratio (HR) 2.219, 95%CI 1.141-4.316, P = 0.019] and the GTV-T (HR 1.372, 95%CI 1.044-1.803, P = 0.023) were independent prognostic factors for survival. CONCLUSION: The overall survival of esophageal carcinoma patients undergoing 3D-CRT was promising. The best predictors for survival were GTV-T and Y diameter.


Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Radioterapia Conformacional , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Quimioterapia Adyuvante , China , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Femenino , Hospitales Universitarios , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Radioterapia Conformacional/efectos adversos , Radioterapia Conformacional/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Carga Tumoral
17.
Asian Pac J Cancer Prev ; 13(5): 2101-7, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22901177

RESUMEN

Treatment responses of N0 stage nasopharyngeal carcinoma were firstly analyzed comprehensively to evaluate long term outcomes of patients and identify prognostic factors. A total of 610 patients with N0 NPC, undergoing definitive radiotherapy to their primary lesion and prophylactic radiation to upper neck, were reviewed retrospectively. Concomitant chemotherapy was administrated to 65 out of the 610. Survival rates of the patients were calculated using the Kaplan-Meier method and compared by log-rank test. Prognostic factors were identified by the Cox regression model. The study revealed the 5-year and 10-year overall, disease-free, disease-specific, local failure-free, regional failure-free, locoregional failure-free and distant metastasis-free survival rates to be 78.7% and 66.8%, 68.8% and 55.8%, 79.9% and 70.4%, 81.2% and 72.5%, 95.8% and 91.8%, 78.3% and 68.5%, 88.5% and 85.5%, respectively. There were 192 patients experiencing failure (31.5%) after radiotherapy or chemoradiotherapy. Of these, local recurrence, regional relapse and distant metastases as the first event of failure occurred in 100 (100/610, 16.4%), 15(15/610, 2.5%) and 52 (52/610, 8.5%), respectively. Multivariate analysis showed that T stage was the only independent prognostic factor for patients with N0 NPC (P=0.000). Late T stage (P=0.000), male (P=0.039) and anemia (P=0.007) were independently unfavorable factors predicting disease-free survival. After treatment, satisfactory outcome wasgenerally achieved in patients with N0 NPC. Local recurrence represented the predominant mode of treatment failure, while T stage was the only independent prognostic factor for overall survival. Late T stage, male gender, and anemia independently predicted lower possibility of the disease-free survival.


Asunto(s)
Neoplasias Óseas/mortalidad , Neoplasias Hepáticas/mortalidad , Neoplasias Pulmonares/mortalidad , Neoplasias Nasofaríngeas/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Adolescente , Adulto , Anciano , Neoplasias Óseas/secundario , Neoplasias Óseas/terapia , Carcinoma , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/terapia , Metástasis Linfática , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/terapia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
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