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PURPOSE: Stereotactic radiosurgery (SRS) has become a standard approach for the treatment of patients with few metastatic brain lesions. However, the optimal treatment approach for the use radiotherapy in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs) remain unclear. This study aimed to compare the survival outcomes and intracranial local control in NSCLC patients with 1-4 BMs who are treated with SRS using linear accelerators (LINAC-SRS), whole-brain radiotherapy (WBRT), or WBRT plus radiotherapy boost (WBRT + RTB). MATERIALS AND METHODS: We retrospectively analyzed 156 NSCLC patients with 1-4 BMs who received LINAC-SRS, WBRT, and WBRT + RTB. The median overall survival (OS), intracranial progression-free survival (iPFS), and distant brain failure-free survival (DBF-FS) and related prognostic factors were analyzed. RESULTS: The median follow-up period was 31.6 months. The median OS times in the LINAC-SRS, WBRT, and WBRT + RTB groups were not reached, 33.3 months and 27.9 months, respectively. The difference in survival rate was non-significant (P = 0.909). The 2-year iPFS and DBF-FS rates in the LINAC-SRS, WBRT and WBRT + RTB groups were 51.6% and 37.5%; 42.0% and 50.4%; and 51.1% and 56.1%, respectively. There was no significant difference in 2-year iPFS or DBF-FS among the three groups (P = 0.572 for iPFS, P = 0.628 for DBF-FS). Multivariate analysis showed that the independent adverse prognostic factors for OS, iPFS, and DBF-FS were neurological symptoms, recursive partitioning analysis (RPA) class, and targeted therapy. CONCLUSION: LINAC-SRS did not result in significantly superior survival times or intracranial local control compared to WBRT or WBRT + RTB in the treatment of NSCLC patients with 1-4 BMs.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Radiocirugia , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Irradiación Craneana/efectos adversos , Humanos , Neoplasias Pulmonares/cirugía , Radiocirugia/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Recent studies have found that the acetaldehyde dehydrogenase 1A3 (ALDH1A3) gene is a marker of glioma stem cells. A total of 115 brain glioma specimens were collected and classified into grade I-IV, while non-tumor brain tissue specimens, taken from 12 patients of vascular malformation surgery, were used as control. ALDH1A3 gene promoter methylation in glioma tissues was detected by pyrosequencing, while immunohistochemistry and western blot were used to detect ALDH1A3 protein expressions in different grades of glioma tissues and normal brain tissues. The expression of ALDH1A3 in the glioma cell line U87 was detected by quantitative real-time polymerase chain reaction and RNA-Seq technology was applied to investigate differentially expressed genes before and after silencing the ALDH1A3 gene. Among the 115 glioma tissue specimens, 50 (43.48%) showed low and 65 (56.52%) high expression of ALDH1A3, but no expression was detected in the control. Univariate and multivariate COX regression analyses showed that the patient's tumor pathological grade, the methylation status of ALDH1A3 promoter, and the expression of ALDH1A3 protein were risk factors for progression-free survival (PFS) and overall survival (OS) (all P < 0.05) and the OS of mice with silenced ALDH1A3 in a glioma nude mouse model was prolonged. U87 experiments revealed that ALDH1A3 expression had significant effects on apoptosis, proliferation, cell cycle, mitochondrial membrane potential, glucose consumption, lactate production, invasion ability, and expression of the pyruvate kinase M2 (PKM2) and hexokinase 2 (HK2) in glioma cells. ALDH1A3 protein expression is a marker for poor PFS and OS in glioma patients.
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Aldehído Oxidorreductasas/metabolismo , Neoplasias Encefálicas/mortalidad , Regulación Neoplásica de la Expresión Génica , Glioma/mortalidad , Glucosa/metabolismo , Ácido Láctico/metabolismo , Adolescente , Adulto , Aldehído Oxidorreductasas/genética , Animales , Apoptosis , Biomarcadores de Tumor , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Ciclo Celular , Proliferación Celular , Progresión de la Enfermedad , Femenino , Glioma/metabolismo , Glioma/patología , Humanos , Masculino , Ratones , Ratones SCID , Persona de Mediana Edad , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Pronóstico , Transducción de Señal , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Radiation Pneumonitis (RP) is one of the most common and severe complication in patients receiving thoracic radiotherapy. The release of cytokines contribute to activating the RP process. Macrophages also play an important role in the pathogenesis of RP. The differential activation of macrophages is regulated by microRNA (miRNA). Exosomes containing miRNAs are one of the important ways to mediate cellular communication. However, the exosomes mediate communication between tumor cells and macrophages during the pathogenesis of RP remains understudied. In this study, we isolated and characterized the exosomes secreted by lung cancer cells after irradiation. Co-culture of exosomes with macrophages revealed that exosomes could induce macrophage proliferation activation and M2 polarization. miRNA array was used to analyze the differential expression of miRNAs in exosomes, and it was found that miR-4655-5p was stably and highly expressed in exosomes. The function of miR-4655-5p in macrophages was confirmed by overexpression/inhibition of miR-4655-5p expression in macrophages. The targeting association between miR-4655-5p and MID1 was determined by bioinformatics prediction followed by a confirmatory dual luciferase reporter assay. We showed that miR-4655-5p regulate the macrophage proliferation and inflammatory response by forming a negative regulatory loop that alters MID1 activity and its downstream PP2Ac. Overall, our results indicated that exosomal miR-4655-5p secreted by lung cancer cells after irradiation promoted the proliferation and M2 polarization of macrophages. It can be speculated that exosomes play an immunomodulatory role in the pathogenesis of RP and provided a new target for the prevention and treatment of RP.
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Exosomas , Neoplasias Pulmonares , MicroARNs , Humanos , Exosomas/genética , MicroARNs/genética , MicroARNs/metabolismo , Macrófagos/metabolismo , Comunicación Celular , Neoplasias Pulmonares/patología , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Background: There is a close relationship between radiotherapy and autophagy in tumors, but the prognostic role of radiotherapy-related autophagy genes (RRAGs) in lung adenocarcinoma (LUAD) remains unclear. Methods: Data used in the current study were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Weighted gene co-expression network analysis (WGCNA) was executed to recognize module genes associated with radiotherapy. The differentially expressed genes (DEGs) between different radiotherapy response groups were filtered via edgeR package. The differentially expressed radiotherapy-related autophagy genes (DERRAGs) were obtained by overlapping the module genes, DEGs, and autophagy genes (ATGs). Then, prognostic autophagy genes were selected by Cox analyses, and a risk model and nomogram were subsequently built. Gene Set Enrichment Analysis (GSEA) and single-sample Gene Set Enrichment Analysis (ssGSEA) were performed to investigate potential mechanisms through which prognostic autophagy signatures regulate LUAD. Radiotherapy-resistant cell lines (A549IR and PC9IR) were established after exposure to hypo-fractionated irradiation. Ultimately, mRNA expression was validated by quantitative real-time PCR (qRT-PCR), and relative protein levels were measured in different cell lines by western blot. Results: A total of 11 DERRAGs were identified in LUAD. After Cox analyses, SHC1, NAPSA, and AURKA were filtered as prognostic signatures in LUAD. Then, the risk score model was constructed using the prognostic signatures, which had a good performance in predicting the prognosis, as evidenced by receiver operating characteristics curves. Furthermore, Cox regression analyses demonstrated that risk score was deemed as an independent prognostic factor in LUAD. Moreover, GSEA and ssGSEA results revealed that prognostic RRAGs may regulate LUAD by modulating the immune microenvironment and affecting cell proliferation. The colony formation assay showed that the radiosensitivity of radiation-resistant cell lines was lower than that of primary cells. The western blot assay found that the levels of autophagy were elevated in the radiotherapy-resistant cell lines. Moreover, the expression of DERRAGs (SHC1, AURKA) was higher in the radiotherapy-resistant cells than in primary cells. Conclusion: Our study explored the role of RRAGs in the prognosis of LUAD and identified three biomarkers. The findings enhanced the understanding of the relationship between radiotherapy, autophagy, and prognosis in LUAD and provided potential therapeutic targets for LUAD patients.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Aurora Quinasa A/genética , Aurora Quinasa A/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/metabolismo , Regulación Neoplásica de la Expresión Génica , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/radioterapia , Pronóstico , Autofagia/genética , Microambiente TumoralRESUMEN
Purpose: Radiotherapy is a promising treatment option for lung cancer, but patients' responses vary. The purpose of the study was to investigate the potential of radiomics and clinical signature for predicting the radiotherapy sensitivity and overall survival of inoperable stage III and IV non-small-cell lung cancer (NSCLC) patients. Materials: This retrospective study collected 104 inoperable stage III and IV NSCLC patients at the Yunnan Cancer Hospital from October 2016 to September 2020. They were divided into radiation-sensitive and non-sensitive groups. We used analysis of variance (ANOVA) to select features and support vector machine (SVM) to build the radiomic model. Furthermore, the logistic regression method was used to screen out clinically relevant predictive factors and construct the combined model of radiomics-clinical features. Finally, survival was estimated using the Kaplan-Meier method. Results: There were 40 patients in the radiation-sensitive group and 64 in the non-sensitive group. These patients were divided into training set (73 cases) and testing set (31 cases) according to the ratio of 7:3. Nine radiomics features and one clinical feature were significantly associated with radiotherapy sensitivity. Both the radiomics model and combined model have good predictive performance (the areas under the curve (AUC) values of the testing set were 0.864 (95% confidence interval [CI]: 0.683-0.996) and 0.868 (95% CI: 0.689-1.000), respectively). Only platelet level status was associated with overall survival. Conclusion: The combined model constructed based on radiomics and clinical features can effectively identify the radiation-sensitive population and provide valuable clinical information. Patients with higher platelet levels may have a poor prognosis.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Estudios Retrospectivos , ChinaRESUMEN
Purpose: Finding a better treatment position (prone or supine) for whole-breast irradiation for Chinese female patients diagnosed with breast cancer by identify the associations between predictive somatotype parameters and dosimetric gains. Materials and methods: Two volumetric-modulated arc therapy (VMAT) plans were deployed for whole-breast irradiation in supine and prone position with a total dose of 50 Gy in 25 fractions. Dose-volume parameters were compared and analysed both in the target volume and organs at risk, and equivalent uniform dose-based figure-of-merit (fEUD) models were further used to quantitatively evaluate the overall merits of the two plans. Body shape parameters, including body mass index (BMI), body surface area (BSA), breast shape, cup size, bust size and chest size, were collected. Anatomic features such as the central heart distance (CHD) were measured on supine CT. Spearman's correlation analysis, receiver operating characteristic (ROC) curve analysis, and the linear regression models were conducted. Results: Doses to the heart and left anterior descending coronary artery (LADCA) are greater in left-sided breast cancer (BC) patients in the prone position than in the supine position, and the opposite was true for right-sided BC patients (p<0.001). 19 of 63 patients (5 left-sided and 14 right-sided BC) achieved greater benefit from the prone position according to the fEUD score. Right-sided BC patients with a bust size ≥92.25 cm, drop-type breasts and cup size ≥B are very likely to benefit from prone-position radiotherapy. The CHD is significantly positively associated with â³fEUD among right-sided BC patients (rho=0.506, p=0.004). Using a cut-off point of 2.215, the CHD had 71.4% sensitivity and 81.2% specificity in predicting a successful prone plan. Conclusions: Right-sided BC patients had better dosimetric gain in the prone position than left-sided BC patients. The CHD is an especially good and novel predictor that could help to select prone-benefitting right-sided BC patients.
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Increasing evidence has implicated the modification of 7-methylguanosine (m7G), a type of RNA modification, in tumor progression. However, no comprehensive analysis to date has summarized the predicted role of m7G-related gene signatures in lung adenocarcinoma (LUAD). Herein, we aimed to develop a novel prognostic model in LUAD based on m7G-related gene signatures. The LUAD transcriptome profiling data and corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus datasets. After screening, we first obtained 29 m7G-related genes, most of which were upregulated in tumor tissues and negatively associated with overall survival (OS). According to the expression similarity of m7G-related genes, the combined samples from the TCGA-LUAD and GSE68465 datasets were further classified as two clusters that exhibit distinct OS rates and genetic heterogeneity. Then, we constructed a novel prognostic model involving four genes by using 130 differentially expressed genes among the two clusters. The combined samples were randomly divided into a training cohort and an internal validation cohort in a 1:1 ratio, and the GSE72094 dataset was used as an external validation cohort. The samples were divided into high- and low-risk groups. We demonstrated that a higher risk score was an independent negative prognostic factor and predicted poor OS. A nomogram was further constructed to better predict the survival of LUAD patients. Functional enrichment analyses indicated that cell cycle and DNA replication-related biological processes and pathways were enriched in the high-risk group. More importantly, the low-risk group had greater infiltration and enrichment of most immune cells, as well as higher ESTIMATE, immune, and stromal scores. In addition, the high-risk group had a lower TIDE score and higher expressions of most immune checkpoint-related genes. We finally noticed that patients in the high-risk group were more sensitive to chemotherapeutic agents commonly used in LUAD. In conclusion, we herein summarized for the first time the alterations and prognostic role of m7G-related genes in LUAD and then constructed a prognostic model based on m7G-related gene signatures that could accurately and stably predict survival and guide individualized treatment decision-making in LUAD patients.
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A 60-year-old Chinese male with a hard mass, pressure pain, and ulcerous skin under his left axilla was first diagnosed with apocrine carcinoma, most likely metastasis from breast cancer. PET/CT scan detected multiple bone metastasis and enlarged lymph nodes at left axilla, mediastinal area 7, and left pulmonary hilus. Lumpectomy was performed to remove the mass followed by chemotherapy and radiotherapy against focal bone metastasis, left axillary lesion, and left subcutaneous chest wall. PET/CT examination showed progressive disease after the completion of the treatments. Two nontender hard nodules were noticed on the patient's left upper arm and multiple immobile nodules were palpated under his left axillary skin. Immunohistochemistry (HER2++, ER+, PR+, AR-) of the biopsy tissue combined with histopathology indicated invasive ductal carcinoma with neuroendocrine differentiation. Metastatic Luminal B subtype breast cancer was preferred. Anti-estrogen endocrine therapy was then performed and PET/CT scan showed partial remission after one month's fulvestrant administration. Two significant somatic mutations, AR R616H and GATA3 S408Afs*99, were detected in the biopsy tissue by next-generation sequencing. GATA3 is associated with estrogen receptor signaling and was identified as a driver gene of female breast cancer. However, the function of GATA3 in male breast cancer remains controversial. Report of this case hopefully will contribute to exploring the role of GATA3 mutation in molecular mechanisms and endocrine therapy of male breast cancer.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama Masculina/tratamiento farmacológico , Neoplasias de la Mama Masculina/genética , Factor de Transcripción GATA3/genética , Mutación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Mama/patología , Neoplasias de la Mama Masculina/diagnóstico por imagen , Neoplasias de la Mama Masculina/secundario , Sistema Endocrino/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
PURPOSE: This study aimed to evaluate (1) the performance of the Auto-Planning module embedded in the Pinnacle treatment planning system (TPS) with 30 left-side breast cancer plans and (2) the dose-distance correlations between dose-based patients and overlap volume histogram-based (OVH) patients. METHOD: A total of 30 patients with left-side breast cancer after breast-conserving surgery were enrolled in this study. The clinical manual-planning (MP) and the Auto-Planning (AP) plans were generated by Monaco and by the Auto-Planning module in Pinnacle respectively. The geometric information between organ at risk (OAR) and planning target volume (PTV) of each patient was described by the OVH. The AP and MP plans were ranked to compare with the geometry-based patients from OVH. The Pearson product-moment correlation coefficient (R) was used to describe the correlations between dose-based patients (APs and MPs) and geometry-based patients (OVH). Dosimetric differences between MP and AP plans were evaluated with statistical analysis. RESULT: The correlation coefficient (mean R = 0.71) indicated that the AP plans have a high correlation with geometry-based patients from OVH, whereas the correlation coefficient (mean R = 0.48) shows a weak correlation between MP plans and geometry-based patients. The dosimetric comparison revealed a statistically significant improvement in the ipsilateral lung V5Gy and V10Gy, and in the heart V5Gy of AP plans compared to MP plans, while statistical reduction was seen in PTV V107% for MP plans compared to AP plans. CONCLUSION: The overall results of AP plans were superior to MP plans. The dose distribution in AP plans was more consistent with the distance-dose relationship described by OVH. After eliminating the interference of human factors, the AP was able to provide more stable and objective plans for radiotherapy patients.
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Neoplasias de la Mama/radioterapia , Órganos en Riesgo , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada , Neoplasias de la Mama/cirugía , Femenino , Corazón , Humanos , Pulmón , Mastectomía Segmentaria , Dosis de Radiación , Radioterapia AdyuvanteRESUMEN
PURPOSE: The purpose of the present study was to evaluate the feasibility of using 4-dimensional computed tomography (4DCT)-ventilation-weighted dose analysis to predict radiation-induced pneumonia probability (RIPP). METHODS AND MATERIALS: The study population for this retrospective analysis included 16 patients with stage III lung cancer. Each patient's 4DCT images, including end-inhale and end-exhale sequences, were used for the deformable image registration, and the Hounsfield units (HU) density-change was used to calculate the ventilation. A previously established equation was used to convert the original dose (OD) D 0, i in the lungs in the original plan (OP) to the weighted-dose (WD) D w, i in the weighted plan (WP). The patients were divided into 2 groups, one with radiation-induced pneumonia (RIP), and one without. The Spearman correlation analysis was used to analyze the correlation of RIP with ΔV20 (ΔV x = V w, x in the WP - V 0, x in the OP), ΔMLD (ΔMLD = mean lung dose (MLD) in the WP - MLD in the OP), and ΔV5. RESULTS: The results showed that 5 of the 16 patients were suffering from acute RIP, 4 of which had higher ΔV20 and ΔMLD values than the rest of the patients. The results of the Spearman correlation analysis for those 4 patients were as follows: RIP vs. ΔV20, r = 0.5123; RIP vs. ΔMLD, r = 0.5119; RIP vs. ΔV5, r = 0.1904. CONCLUSIONS: The 4DCT-ventilation-based weighted-dose analysis showed some correlation between RIPP and both ΔV20 and ΔMLD, when comparing the weighted-dose and the conventional dose-volume histogram (DVH) analyses.
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With the massive use of computers, the growth and explosion of data has greatly promoted the development of artificial intelligence (AI). The rise of deep learning (DL) algorithms, such as convolutional neural networks (CNN), has provided radiation oncologists with many promising tools that can simplify the complex radiotherapy process in the clinical work of radiation oncology, improve the accuracy and objectivity of diagnosis, and reduce the workload, thus enabling clinicians to spend more time on advanced decision-making tasks. As the development of DL gets closer to clinical practice, radiation oncologists will need to be more familiar with its principles to properly evaluate and use this powerful tool. In this paper, we explain the development and basic concepts of AI and discuss its application in radiation oncology based on different task categories of DL algorithms. This work clarifies the possibility of further development of DL in radiation oncology.
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Aprendizaje Profundo , Neoplasias/radioterapia , Humanos , Imagen por Resonancia Magnética , Neoplasias/diagnóstico por imagen , Órganos en Riesgo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Oncología por Radiación , Radioterapia/efectos adversos , Radioterapia/métodos , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
BACKGROUND: Triple-negative breast cancer constitutes approximately 12%-17% of all breast cancer cases, and >33% of patients develop distant metastases. Systemic cytotoxic chemotherapy is the primary treatment for patients with metastatic triple-negative breast cancer; however, the role of first-line platinum-based chemotherapy in these patients remains controversial. This meta-analysis evaluated the efficacy and safety of platinum-based first-line chemotherapy for patients with metastatic triple-negative breast cancer. METHODS: We systematically searched the PubMed, Embase, Cochrane, and Clinical Trials registry databases up to June 1, 2020 to identify randomized controlled trials that investigated platinum-based vs. first-line platinum-free chemotherapy in patients with metastatic triple-negative breast cancer. We used fixed and random effects models to calculate pooled hazard ratios and odds ratios with 95% confidence intervals for progression-free and overall survival, objective response rates, and grade 3 and 4 adverse events. RESULTS: Four randomized controlled trials (N = 590 patients) were included. Platinum-based chemotherapy significantly increased the objective response rates from 43.1% to 62.7% (odds ratio 2.34, 95% confidence interval 1.66-3.28, P < 0.001). Three randomized controlled trials (N = 414 patients) reported survival outcomes. Patients administered platinum-based regimens showed significantly longer progression-free survival (hazard ratio 0.55, 95% confidence interval 0.37-0.82, P = 0.004) and a nonsignificant trend toward improved overall survival (hazard ratio 0.76, 95% confidence interval 0.57-1.00, P = 0.05). Only 2 studies reported the rates of grade 3 and 4 adverse events; grade 3-4 thrombocytopenia was more commonly associated with platinum-based chemotherapy (odds ratio 7.54, 95% confidence interval 1.37-41.60, P = 0.02) and grade 3-4 fatigue with platinum-free chemotherapy (odds ratio 0.23, 95% confidence interval 0.08-0.68, P = 0.008). CONCLUSIONS: First-line platinum-based chemotherapy was associated with significantly increased objective response rates, longer progression-free survival, and a nonsignificant trend toward improved overall survival in patients with metastatic triple-negative breast cancer at the high risk of grade 3-4 thrombocytopenia.
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Antineoplásicos/uso terapéutico , Platino (Metal)/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Femenino , Humanos , Pronóstico , Tasa de Supervivencia , Neoplasias de la Mama Triple Negativas/secundarioRESUMEN
AIM: Ionizing radiation (IR) can induce local and systemic antitumour immune responses to some degree and augment immunotherapeutic efficacy. IR may also increase residual tumour cell invasion and elicit immunosuppression in the tumour microenvironment (TME). It remains poorly understand, whether IR leads to immune negative response or invasive capacity increases in lung adenocarcinoma (LAC). MATERIALS AND METHODS: RNA interference (RNAi) was used to silence pituitary tumour-transforming gene-1 (PTTG1) and SMAD3 expression in LAC cells. A coculture system of tumour cells and PBMCs was constructed. Cells were exposed to different doses (0, 4 and 8 Gy) of X-ray irradiation. Flow cytometric analysis and Transwell assays were applied. An orthotopic Lewis lung cancer (LLC) mouse tumour model was established. Bioluminescence imaging (BLI) was used. LLC tumours were exposed to a single 15 Gy dose of X-ray irradiation. KEY FINDINGS: PTTG1 knockdown reinforced the inhibitory effect of IR on the invasive ability of A549 cells and enhanced the antitumour T cell immunity induced by IR via the transforming growth factor-ß1 (TGF-ß1)/SMAD3 pathway. Positive antitumour immune response and immunosuppression were simultaneously triggered by a single 15 Gy dose of local tumour irradiation. PTTG1 knockdown weakened invasive capacity and promoted the immune response balance induced by IR to tilt towards active immunity, which contributed to reduce metastasis and prolonged overall survival (OS) in orthotopic LLC tumour-bearing mouse. SIGNIFICANCE: Targeted blockade of PTTG1 and the TGF-ß1/SMAD3 pathway may ameliorate the immunosuppressive TME and enhance the systemic antitumour immune response induced by a single high-dose IR treatment.
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Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/metabolismo , Securina/metabolismo , Células A549 , Adenocarcinoma del Pulmón/genética , Animales , Carcinoma Pulmonar de Lewis/inmunología , Carcinoma Pulmonar de Lewis/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , China , Regulación Neoplásica de la Expresión Génica/genética , Técnicas de Silenciamiento del Gen/métodos , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Securina/genética , Transducción de Señal , Proteína smad3 , Factor de Crecimiento Transformador beta1 , Microambiente Tumoral/fisiología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVES: To test the effectiveness of quantitative linear-quadratic-based (qLQB) model on evaluating irradiation-induced liver injury (ILI) and establish the relation between the damaged ratio/percent (DRP) in qLQB model and normal tissue complication probility (NTCP). MATERIALS AND METHODS: We established the qLQB model to calculate the ratio/percent (RP) between damaged cell/functional subunit (FSU) and entire cell/FSU of liver for radiation dose response, tested the qLQB against the Lyman-Kutcher-Burman (LKB) model, and established relation between the RP and NTCP through analyzing the dose of 32 patients with cancer of abdominal cavity who were treated with radiation therapy at our department. Based on varied α/ß and varied parameters for NTCP, we put the calculated results into varied arrays for the next analysis. We named the 2 groups of RPs: RP1 (α/ß = 3.0, α = 0.03) and RP2 (α/ß = 8.0, α = 0.26), and named the 2 groups of NTCPs: NTCP1 (n = 0.32, m = 0.15, TD50(1) = 4000 cGy) and NTCP2 (n = 1.10, m = 0.28, TD50(1) = 4050 cGy). RESULTS: Spearman correlation analysis was used to analyze the correlations among the groups, the results were as follows: RP1 vs NTCP1, rs = 0.83827, p < 0.0001; RP1 vs NTCP2, rs = 0.83827, p < 0.0001; RP2 vs NTCP2, rs = 0.79289, p < 0.0001; and RP2 vs NTCP1, rs = 0.79289, p < 0.0001. CONCLUSIONS: There is a significant correlation between RP value and NTCP for evaluating ILI, and there is no difference between qLQB model and LKB model on evaluating ILI.
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BACKGROUND: Induction chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) is a standard treatment regimen for locally advanced nasopharyngeal carcinoma (LA-NPC). However, the increased acute toxicity of this intensified chemotherapy may counteract its efficacy. The results of studies focusing on the omission of concurrent chemotherapy (CC) regimens are controversial. Therefore, we carried out a meta-analysis to elucidate the efficacy and toxicity of IC + CCRT versus IC plus radiotherapy alone (IC + RT) for LA-NPC. METHODS: Studies available on PubMed, Embase, Cochrane Library and ClinicalTrails.gov were independently searched by two investigators from inception to March 1, 2020. Review Manager software 5.3 (RevMan 5.3) was employed to calculate pooled hazard ratios (HRs), risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Eight studies with a total of 2605 patients were analysed. The results showed that no significant difference between IC + RT and IC + CCRT for disease-free survival (HR = 1.09, 95% CI: 0,85-1.39, P = 0.50), overall survival (HR = 0.92, 95% CI: 0.78-1.09, P = 0.34), local recurrence-free survival (HR = 1.26, 95% CI: 0.95-1.67; P = 0.10), or distant metastasis-free survival (HR = 1.03, 95% CI: 0.84-1.26, P = 0.79). Notably, the incidence of treatment-related grade 3/4 acute haematological toxicity during radiation was higher in the IC + CCRT group. Subgroup analysis showed similar survival outcomes for IC + CCRT and IC + RT with and without the two-dimensional RT technique. CONCLUSIONS: IC + RT was as effective as IC + CCRT for the management of LA-NPC. The IC + RT regimen has the possibility of replacing the IC + CCRT regimen for LA-NPC in the future due to the lower toxicity, although more high-level evidence is urgently needed for verification.
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Quimioradioterapia , Quimioterapia de Inducción , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Sesgo , Quimioradioterapia/efectos adversos , Quimioradioterapia/mortalidad , Intervalos de Confianza , Supervivencia sin Enfermedad , Humanos , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/mortalidad , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/secundario , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Modelos de Riesgos Proporcionales , Radioterapia/efectos adversos , Radioterapia/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios RetrospectivosRESUMEN
OBJECTIVE: Concurrent chemoradiation (cCHRT) has been confirmed as the standard treatment for local advanced non-small-cell lung cancer (NSCLC). This study is to assess the appropriate timing of radiotherapy and cycles of induction chemotherapy for those patients. METHODS: 227 inoperable stage III NSCLC patients were selected, we analyzed the potential prognostic factors and the influence of induction chemotherapy was evaluated. RESULTS: The median survival time was 20.7 months; only 25 patients chose chemotherapy alone (11.0%), 137 patients underwent sequential chemoradiation (sCHRT, 60.4%), and 65 patients received cCHRT (28.6%). Multivariate analyses showed radiation therapy (P = 0.001), the Eastern Cooperative Oncology Group (ECOG) score (P = 0.000) and the lymph node stage (P = 0.001) were independent prognostic factors. cCHRT was not found to be superior (P = 0.330). We selected patients received 60-66 Gy and found the cCHRT groups achieved a relatively better outcome, with a median Overall Survival (OS) of 25.2 months vs 20.1 months in the sCHRT group (P = 0.019). We also found cycles of induction chemotherapy did not compromise survival; however, ≥3 cycles resulted in more grade 3-4 hematology toxicities, with a proportion of 18/99 compared with 53/103 among patients who underwent ≤3 cycles. In addition, higher grade hematology toxicities and poor ECOG were also the most common reasons for abandoning cCHRT. CONCLUSIONS: For inoperable stage III NSCLC, cCHRT showed its superiority only when the radiotherapy dose was 60-66 Gy. Cycles of induction chemotherapy did not interfere with survival; however, ≥3 cycles resulted in more grade 3-4 hematology toxicities, leading to the cessation of cCHRT.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/métodos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Dosificación Radioterapéutica , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: The present study was aimed at exploring the role of long noncoding RNA (lncRNA) FOXD2-AS1 in the development and progression of glioma and the underlying mechanism of FOXD2-AS1/miR-185-5p/HMGA2 network in glioma via regulation of PI3K/Akt signaling pathway. METHODS: Microarray analysis was used for preliminary screening for candidate lncRNAs and mRNAs in glioma tissues. qRT-PCR and Western blot were used to determine the expression of FOXD2-AS1. The potential effects of FOXD2-AS1 on the viability, mobility and apoptosis of glioma cells were evaluated using MTT assay, Transwell assays and flow cytometry. The xenograft tumor model was performed to examine the influence of the lncRNA FOXD2-AS1/miR-185-5p/HMGA2 network on the biological functions of glioma cells. Luciferase assay and immunoprecipitation assay were examined to dissect molecular mechanisms. RESULTS: LncRNA FOXD2-AS1 was overexpressed in human glioma, and upregulated FOXD2-AS11 expression indicated higher WHO grade (p < 0.05). MiR-185-5p was downregulated, whereas HMGA2 was upregulated in glioma tissues in comparison with para-carcinoma tissues. FOXD2-AS1 could regulate the expression of HMGA2 via miR-185-5p. Knockdown of FOXD2-AS1 significantly inhibited proliferation and metastatic potential of glioma cells, whereas endogenous expression FOXD2-AS1 inhibited the glioma cell activity through targeting HMGA2. CONCLUSIONS: lncRNA FOXD2-AS1 acted as a sponge of miR-185-5p and influenced the PI3K/Akt signaling pathway through regulating HMGA2. LncRNA FOXD2-AS1 modulated HMGA2 and PI3K/Akt downstream signaling through sponging miR-185-5p, thereby promoting tumorigenesis and progression of glioma.
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Factores de Transcripción Forkhead/metabolismo , Glioma/metabolismo , Proteína HMGA2/metabolismo , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Factores de Transcripción Forkhead/genética , Regulación Neoplásica de la Expresión Génica , Glioma/patología , Proteína HMGA2/genética , Humanos , Ratones , Ratones Desnudos , MicroARNs/genética , Neoplasias Experimentales , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , ARN Largo no Codificante , Transducción de SeñalRESUMEN
Radiotherapy (RT) is one of most common treatments for cancer. However, overcoming the failure and side effects of RT as well as radioresistance, recurrence and metastasis remains challenging in cancer treatment. Cellular senescence (CS) is permanent arrested state of cell division induced by various factors, including exposure to ionizing radiation (IR). CS induced by IR contributes to tumour cell control and often even causes side effects in normal cells. Improvement of the therapeutic RT ratio is dependent on more cancer cell death and less normal cell damage. In addition, the biological behaviour of tumour cells after IR has also been linked to CS. This review summarizes our understanding of CS in IR, which may be beneficial for providing new insight for improving the therapeutic outcomes of RT.
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Muerte Celular , Senescencia Celular/efectos de la radiación , Neoplasias/radioterapia , Animales , Humanos , Radiación IonizanteRESUMEN
Purpose: To compare the differences in survival and intracranial local control between patients treated with whole-brain radiotherapy (WBRT) and WBRT plus a radiotherapy boost (RTB) in non-small-cell lung cancer (NSCLC) patients with brain metastases (BMs). Patients and methods: Between May 2010 and October 2017, 206 NSCLC patients with BMs were treated with brain radiotherapy; among these patients, 140 patients underwent WBRT alone (group A) and 66 patients underwent WBRT plus RTB (group B). The endpoints included intracranial local progression-free survival and regional progression-free survival time (iLPFS and iRPFS, respectively) and overall survival (OS). Results: Between the two groups, not all baseline clinical factors were well-balanced. The median iLPFS was 17.9 months in group A and 22.3 months in group B. The 2-year iLPFS rates were significantly lower in group A than in group B (34.5% vs 49.3%, P=0.041); however, no significant differences were observed in OS or iRPFS. Multivariate analyses revealed that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy was significantly associated with good OS, iLPFS, and iRPFS. Among the patients treated with TKIs (n=62), there were no differences in OS (P=0.190), iLPFS (P=0.334), or iRPFS (P=0.338) between groups A and B. In the patients without TKI treatment (n=102), the median iLPFS was significantly longer in group B than in group A (16.7 vs 12.0 months, P=0.032), but no significant differences were found in OS (p=0.182) or iRPFS (P=0.837) between the two groups. Conclusion: WBRT plus RTB significantly improved iLPFS compared with WBRT alone, especially in patients without EGFR-TKI treatment. However,there were no significant differences in iRPFS or OS between the two groups. Patients treated with EGFR-TKIs may not benefit from WBRT plus RTB.
RESUMEN
INTRODUCTION: Although Multidisciplinary Team Management (MDT) is integrated in most international head and neck cancer treatment guidelines, its applications and proceedings were rarely described. The present study explores a 6-year real-life experience in a French Comprehensive Cancer Care Center. METHODS: Patients, tumor and meeting characteristics of all consecutive cases discussed in head and neck MDT meetings between 2010 and 2015 were retrospectively reviewed. RESULTS: From 2010 to 2015, 1849 cases (accounting for 1786 patients) were discussed in 138 MDT meetings. Median age was 62 (range: 15-96). When reported (nâ¯=â¯310, 16.8%), performance status was ≥2 in 36.1% of patients. Tumors were mainly squamous cell carcinomas (nâ¯=â¯1664, 91.5%) of the larynx/hypo-pharynx (nâ¯=â¯630, 34.4%), oropharynx (nâ¯=â¯518; 28.3%) and oral cavity (nâ¯=â¯339; 18.5%). Tumors were diagnosed at a locally (nâ¯=â¯358, 25%), locally advanced (nâ¯=â¯946, 66%) or metastatic setting (nâ¯=â¯53, 3.7%). Mean number of discussed patients per MDT meeting was 16 (range: 3-32). Most patients were discussed once (nâ¯=â¯1663, 97%). Most patients (nâ¯=â¯969, 52%) underwent treatment before MDT meetings: mainly surgery (nâ¯=â¯709, 73.2%). The mean time between MDT meeting and first radiation course was 21â¯days (range: 1-116). DISCUSSION: Optimal multimodal treatment management is based on MDT meetings and results from the interaction and coordination of surgeons, medical and radiation oncologists. In the present series, most patients were discussed once despite the number of expected recurrences, suggesting that the management of tumor progression was not discussed in head and neck MDT meetings. Furthermore, most patients had surgery before MDT meeting, pointing out that MDT role and place still needs to be improved. Finally, the present population significantly differed from patients included in phase III clinical trials, with more advanced age and poorer condition. It calls for the necessity of a high-quality head and neck MDT meeting since evidence-based recommendations should be adapted to patient's frailties.