Prognostic significance of alterations in fibrinogen level and fibrinogen-to-lymphocyte ratio after radiotherapy on survival outcomes in glioblastoma.

Background: Fibrinogen (FIB) plays an important role in tumor initiation, progression, and metastasis, but its clinical significance in glioblastoma has not been studied. We intend to explore the prognostic value by retrospectively analyzing the changes in FIB and fibrinogen-to-lymphocyte ratio (FLR) in glioblastoma patients before and after radiotherapy, and study the impact of radiotherapy on them. Methods: This study retrospectively included 104 patients who were newly diagnosed with glioblastoma between February 2017 and February 2022 and analysed their clinical data from before to after radiotherapy. The cut-off values for FLR and FIB were calculated using a receiver operating characteristic curve. For inter-group comparisons, the Mann-Whitney U or t-test was applied. The prognostic importance of FIB and FLR was evaluated using the Kaplan-Meier curve and the Cox regression model. Spearman correlation coefficients were calculated to evaluate the association of FIB and FLR with radiotherapy-related dose-volume parameters. Results: The mean progression-free survival (PFS) and overall survival (OS) of the high FIB and high FLR groups were significantly lower than those of the low FIB and low FLR groups (P<0.05). Larger planning target volume (PTV), mean brain dose, and mean brainstem dose were independent prognostic factors for poor PFS and OS in patients with glioblastoma. Conclusions: FLR was a unique and very accurate predictor for the prognosis of glioblastoma, and FIB rise after radiation was a predictive sign of poor survival. Both PTV volume and dose volume for involved organs could significantly affect the FIB and FLR values in patients with glioblastoma.

A novel immune cell signature for predicting glioblastoma after radiotherapy prognosis and guiding therapy.

Background: Glioblastoma, a highly aggressive brain tumor, poses a significant clinical challenge, particularly in the context of radiotherapy. In this study, we aimed to explore infiltrating immune cells and identify immune-related genes associated with glioblastoma radiotherapy prognosis. Subsequently, we constructed a signature based on these genes to discern differences in molecular and tumor microenvironment immune characteristics, ultimately informing potential therapeutic strategies for patients with varying risk profiles. Methods: We leveraged UCSC Xena and CGGA gene expression profiles from post-radiotherapy glioblastoma as verification cohorts. Infiltration ratios were stratified into high and low groups based on the median value. Differential gene expression was determined through Limma differential analysis. A signature comprising four genes was constructed, guided by Gene Ontology (GO) functional enrichment results and Kaplan-Meier survival analysis. We evaluated differences in cell infiltration levels, Immune Score, Stromal Score, and ESTIMATE Score and their Pearson correlations with the signature. Spearman's correlation was computed between the signature and patient drug sensitivity (IC50), predicted using Genomics of Drug Sensitivity in Cancer (GDSC) and CCLE databases. Results: Notably, the infiltration of central memory CD8+T cells exhibited a significant correlation with glioblastoma radiotherapy prognosis. Samples were dichotomized into high- and low-risk groups based on the optimal signature threshold (2.466642). Kaplan-Meier (K-M) survival analysis revealed that the high-risk group experienced a significantly poorer prognosis (p = .0068), with AUC values exceeding 0.82 at 1, 3, and 5 years, underscoring the robust predictive potential of the signature scoring system. Independent validation sets substantiated the validity of the signature. Statistically significant differences in tumor microenvironments (p < .05) were observed between high- and low-risk groups, and these differences were significantly correlated with the signature (p < .05). Furthermore, there were significant correlations between high and low-risk groups regarding immune checkpoint expressions, Immune Prognostic Score (IPS), and Tumor Immune Dysfunction and Exclusion (TIDE) scores. Conclusion: The immune cell signature, comprising SDC-1, PLAUR, FN1, and CXCL13, holds promise as a predictive tool for assessing glioblastoma prognosis following radiotherapy. This signature also offers valuable guidance for tailoring treatment strategies, emphasizing its potential clinical relevance in improving patient outcomes.

Clinical study on changes of peripheral blood immune function indicators in adults with newly diagnosed glioblastoma during the peri-radiotherapy period.

To analyze the changes of immune function-related indicators with newly diagnosed glioblastoma before and after radiotherapy and their clinical significance. Clinical data of 104 patients were analyzed. The independent samples t-test or chi-square test was used to compare changes in immune function indicators and to ascertain the differences between groups with different doses or volumes. The grading of the lowest lymphocyte count during radiotherapy was compared. The log-rank (Mantel - Cox) test of the Kaplan - Meier method was used to compare the survival rate, and the relationship of radiotherapy-related parameters, with the survival rate was evaluated by using the Spearman correlation coefficient. A Cox regression model was used to determine the relationship between various immune function indicators and prognosis. The percentages of total T lymphocytes and CD4+ T cells, the CD4-to-CD8 subset ratio, and the percentages of B cells and NKT cells showed an overall decreasing trend, whereas the percentages of CD8+ T cells and NK cells displayed an overall increasing trend. The lower CD4+ T cell percentage and CD4/CD8 ratio after radiotherapy were independent risk factors for OS. Short OS was observed in patients with grade 3 or 4 lymphopenia or with low levels of hemoglobin and serum albumin before radiotherapy. The percentage of CD4+ T cells and the CD4/CD8 ratio were higher in patients with the low tumor-irradiated volume and irradiated volume and dose of the OAR, than in patients from the corresponding high indicator group. Different irradiation dose or volume can differentially alter various immune function indicators.

Donepezil ameliorates oxygen-glucose deprivation/reoxygenation-induced brain microvascular endothelial cell dysfunction via the SIRT1/FOXO3a/NF-κB pathways.

Ischemic stroke is a disease in which brain tissue is damaged by a sudden rupture or blockage of a blood vessel in the brain that prevents blood from flowing to the brain. Extensive literature has demonstrated the neuroprotective effect of donepezil on brain injury, and this paper attempts to further reveal the effect of donepezil on brain microvascular endothelial cells dysfunction. Human brain microvascular endothelial cells (HBMECs) were treated with oxygen-glucose deprivation/reoxygenation (OGD/R) to induced brain microvascular endothelial cell dysfunction. The OGD/R-induced cell were added with different doses of donepezil with or without Sirtuin-1 (SIRT1) inhibitor EX527. Cell viability of HBMECs was examined by cell counting kit (CCK)-8 assay. OGD/R-treated cell migration was assessed by wound healing assay while angiogenesis in HBMECs was examined by tube formation assay and Western blot analysis. Endothelial cell dysfunction was assessed employing fluorescein isothiocyanate-dextran assay and Western blotting. SIRTI/FOXO3a/NF-kB signaling pathway-related protein expressions were detected using Western blotting. After pretreatment with SIRT1 inhibitor EX527, the above experiments were done again. Donepezil increased cell viability of OGD/R-induced HBMECs, promoted cell migration and angiogenesis, decreased cell permeability, and upregulated the expressions of tight junction proteins. In addition, donepezil regulated the expressions of SIRT1/FOXO3a/NF-κB signaling pathways. However, pretreatment with the SIRT1 inhibitor EX527 reversed the protective effect of donepezil on OGD/R-induced HBMECs. In summary, Donepezil ameliorates OGD/R-induced brain microvascular endothelial cell dysfunction via the SIRT1/FOXO3a/NF-κB pathways.

Visual analysis on the research of monocarboxylate transporters based on CiteSpace.

BACKGROUND: Monocarboxylate transports (MCTs), a family of solute carrier protein, play an important role in maintenance of cellular stability in tumor cells by mediating lactate exchange across membranes. The objective of this paper is to evaluate the knowledge structure, development trend, and research hotspot of MCTs research field systematically and comprehensively. METHODS: Based on the 1526 publications from 2010 to 2020 retrieved from "Web of Science Core Collection" (WoSCC), we visually analyzed the MCTs research in terms of subject category, scientific collaboration network, keywords, and high-frequency literature using CiteSpace. RESULTS: The number of publications exhibits an upward trend from 2010 to 2020 and the top 5 countries in the MCTs research were the United States, China, Japan, Germany, and England. Visser TJ was the most prolific author, while Halestrap AP was the most influential author with the highest citations. Analysis of the 7 cluster units from the co-cited references and keywords revealed that high expression of MCTs induced by oxidative stress and glycolysis was the pivotal point in the MCTs research field, while regulation of metabolism in tumor microenvironment, prognostic markers of cancer, and targeted inhibitors are the top 3 research frontiers topics. CONCLUSION: This study will help the new researcher to understand the MCTs related field, master the research frontier, and obtain valuable scientific information, thus providing directions for follow-up research.

Pathogens distribution and antimicrobial resistance in bloodstream infections in twenty-five neonatal intensive care units in China, 2017-2019.

BACKGROUND: Overcrowding, abuse of antibiotics and increasing antimicrobial resistance negatively affect neonatal survival rates in developing countries. We aimed to define pathogens and their antimicrobial resistance (AMR) of early-onset sepsis (EOS), hospital-acquired late-onset sepsis (HALOS) and community-acquired late-onset sepsis (CALOS) in 25 neonatal intensive care units (NICUs) in China. STUDY DESIGN: This retrospective descriptive study included pathogens and their AMR from all neonates with bloodstream infections (BSIs) admitted to 25 tertiary hospitals in China from January 1, 2017, and December 31, 2019. We defined EOS as the occurrence of BSI at or before 72 h of life and late-onset sepsis (LOS) if BSI occurred after 72 h of life. LOS were classified as CALOS if occurrence of BSI was ≤ 48 h after admission, and HALOS, if occurrence was > 48 h after admission. RESULTS: We identified 1092 pathogens of BSIs in 1088 infants from 25 NICUs. Thirty-two percent of all pathogens were responsible for EOS, 64.3% HALOS, and 3.7% CALOS. Gram-negative (GN) bacteria accounted for a majority of pathogens in EOS (56.7%) and HALOS (62.2%). The most frequent pathogens causing EOS were Escherichia coli (27.2%) and group B streptococcus (GBS; 14.6%) whereas in CALOS they were GBS (46.3%) and Staphylococcus aureus (41.5%). Klebsiella pneumoniae (27.9%), Escherichia coli (15.7%) and Fungi (12.8%) were the top three isolates in HALOS. Third-generation cephalosporin resistance rates in GN bacteria ranged from 9.7 to 55.6% in EOS and 26% to 63.3% in HALOS. Carbapenem resistance rates in GN bacteria ranged from 2.7 to 31.3% in HALOS and only six isolates in EOS were carbapenem resistant. High rates of multidrug resistance were observed in Klebsiella pneumoniae (60.7%) in HALOS and in Escherichia coli (44.4%) in EOS. All gram-positive bacteria were susceptible to vancomycin except for three Enterococcus faecalis in HALOS. All-cause mortality was higher among neonates with EOS than HALOS (7.4% VS 4.4%, [OR] 0.577, 95% CI 0.337-0.989; P = 0.045). CONCLUSIONS: Escherichia coli, Klebsiella pneumoniae and GBS were the leading pathogens in EOS, HALOS and CALOS, respectively. The high proportion of pathogens and high degree of antimicrobial resistance in HALOS underscore understanding of the pathogenesis and emphasise the need to devise effective interventions in developing countries.

Positive Thyroid Peroxidase Antibody and Thyroglobulin Antibody are Associated With Better Clinicopathologic Features of Papillary Thyroid Cancer.

OBJECTIVE: To compare the thyroid autoantibody status of patients with papillary thyroid cancer (PTC) and benign nodular goiter as well as possible associations between thyroid autoantibodies and clinicopathologic features of PTC. METHODS: A total of 3934 participants who underwent thyroidectomy were enrolled in this retrospective study. Patients were divided into PTC and benign nodule groups according to pathological diagnosis. Based on the preoperative serum antibody results, PTC patients were divided into thyroid peroxidase antibody (TPOAb)-positive, thyroglobulin antibody (TgAb)-positive, dual TPOAb- and TgAb-positive, or antibody-negative groups. RESULTS: Of the 3934 enrolled patients, 2926 (74.4%) were diagnosed with PTC. Multivariate regression analyses suggested that high thyroid-stimulating hormone levels (adjusted odds ratio [OR] = 1.732, 95% CI [1.485-2.021], P < .001), positive TgAb (adjusted OR = 1.768, 95% CI [1.436-2.178], P < .001), and positive TPOAb (adjusted OR = 1.452, 95% CI [1.148-1.836], P = .002) were independent risk factors for predicting malignancy of thyroid nodules. Multinomial multiple logistic regression analyses indicated that positive TPOAb alone was an independent predictor of less central lymph node metastasis in PTC patients (adjusted OR = 0.643, 95% CI [0.448-0.923], P = .017), whereas positive TgAb alone was significantly associated with less extrathyroidal extension (adjusted OR = 0.778, 95% CI [0.622-0.974], P = .028). PTC patients with dual-positive TPOAb and TgAb displayed a decreased incidence of extrathyroidal extension (adjusted OR = 0.767, 95% CI [0.623-0.944], P = .012) and central lymph node metastasis (adjusted OR = 0.784, 95% CI [0.624-0.986], P = .037). CONCLUSION: Although preoperative positive TPOAb and TgAb are independent predictive markers for PTC, they are also associated with better clinicopathologic features of PTC.

Identification of MiR-211-5p as a tumor suppressor by targeting ACSL4 in Hepatocellular Carcinoma.

BACKGROUND: Liver cancer is among the most common malignancy worldwide. Hepatocellular carcinoma (HCC), the principal histological subtype of liver cancer, is globally the third most common cause of cancer-related mortality. The high rates of recurrence and metastasis contribute to the poor prognosis of HCC patients. In recent years, increasing evidence has shown that microRNAs (miRNAs) are involved in the tumorigenesis, progression, and prognosis of HCC. METHODS: To screen for key candidate miRNAs in HCC, three microarray datasets were downloaded from Gene Expression Omnibus (GEO). The sole common differentially expressed miRNA (DEmiR) observed in the above three datasets using a Venn diagram was microRNA-211-5p (miR-211-5p). The expression of miR-211-5p from HCC tissues was measured in several HCC cell lines. Additionally, using Kaplan-Meier plots, the potential prognostic value of miR-211-5p in HCC was analyzed. Cell counting kit-8 (CCK-8) and transwell assays examined the ability of miR-211-5p to induce cell proliferation, migration, and invasion in HCC cultures. The interaction of miR-211-5p and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) was assessed both theoretically and using a luciferase reporter assay. Finally, the ability of miR-211-5p to modulate tumorigenesis in HCC in vivo was assessed after establishing a xenograft model. RESULTS: qRT-PCR demonstrated that the relative expression of miR-211-5p was considerably down-regulated in HCC tissues and cell lines compared with normal tissue. Kaplan-Meier plots indicated that HCC patients with decreased expression of miR-211-5p had poor overall survival. Upregulation of miR-211-5p in vitro consistently suppressed cell proliferation, migration, and invasion. In contrast, enhanced expression of ACSL4 promoted a malignant phenotype in HCC cells. Importantly, we discovered that ACSL4 was a direct downstream target of miR-211-5p in HCC, and that miR-211-5p suppressed the malignant phenotype by inhibition of ACSL4 expression. Furthermore, miR-211-5p overexpression impaired tumorigenesis and growth of HCC in vivo. CONCLUSIONS: Targeting miR-211-5p and the downstream gene ACSL4 will possibly provide novel insight and represents a promising approach to future therapy of HCC patients.

In vitro effect of pachymic acid on the activity of Cytochrome P450 enzymes.

Pachymic acid is a wildly used traditional Chinese medicine with various pharmacological features. It also exists in many drugs which are wildly used in pediatric.The effect of pachymic acid on the activity of eight major CYP isoforms was investigated in human liver microsomes.The effects of pachymic acid on eight human liver CYP isoforms (i.e. 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs), and the enzyme kinetic parameters were calculated.The activity of CP3A4, 2E1, and 2C9 was inhibited by pachymic acid in a concentration-dependent manner with IC50 values of 15.04, 27.95, and 24.22 µM, respectively. Pachymic acid is a non-competitive inhibitor of CYP3A4, with the Ki value of 6.47 µM. While the inhibition of CYP2E1 and 2C9 was performed in a competitive manner, with the Ki value of 11.96 and 10.94 µM, respectively. Moreover, the inhibition of CYP3A4 was in a time-dependent manner with the KI/Kinact value of 7.77/0.048 min-1 µM-1.The in vitro inhibitory effect of pachymic acid on the activity of CYP3A4, 2E1, and 2C9 indicated the potential drug-drug interaction with the drugs that metabolized by CYP3A4, 2E1, and 2C9. Further clinical and in vivo studies are needed to evaluate the significance of this interaction.

Dynamic Change of Thyroid Hormones With Postmenstrual Age in Very Preterm Infants Born With Gestational Age <32 Weeks: A Multicenter Prospective Cohort Study.

Background: At present, the relationship between thyrotropin (TSH) and free thyroxine (FT4) in relation to postmenstrual age (PMA) in preterm infants is still unclear, and there is no reliable standard thyroid hormone reference ranges, resulting in different diagnostic criteria for congenital hypothyroidism been used by different newborn screening programs and different countries. Objectives: To investigate the relationship between TSH/FT4 and PMA in very preterm infants (VPIs) born with gestational age (GA) <32 weeks and to derive thyroid function reference charts based on PMA. Methods: A prospective cohort study was performed on VPIs born with GA<32 weeks and born in or transferred to the 27 neonatal intensive care units from January 1, 2019 to December 31, 2019. Serial TSH and FT4 values were measured at the end of each week during the first month after birth and also at PMA36 weeks, PMA40 weeks and at discharge, respectively. The 2.5th, 5th, 50th, 95th, and 97.5th percentiles of TSH and FT4 of different PMA groups were calculated to draw the percentile charts based on PMA. Results: 1,093 preterm infants were included in this study. The percentile charts of TSH and FT4 levels based on PMA were drawn respectively, and the result indicated that the percentile charts of TSH values were gradually increased initially and then decreased with increasing PMA. The 97.5th percentile chart reached the peak at PMA30 weeks (17.38µIU/ml), and then decreased gradually, reaching the same level as full-term infants (9.07µIU/ml) at PMA38-40 weeks. The 2.5th percentile chart of FT4 was at its lowest point at PMA26-27 weeks (5.23pmol/L), then increased slowly with PMA and reached the same level as full-term infants at PMA38-40 weeks (10.87pmol/L). At PMA36 weeks, the reference intervals of the 2.5th to 97.5th percentiles of TSH and FT4 were 1.18-12.3µIU/ml and 8.59-25.98pmol/L, respectively. Conclusion: The percentile charts of TSH and FT4 in VPIs showed characteristic change with PMA. The results prompt that age-related cutoffs, instead of a single reference range, might be more useful to explain the thyroid function of VPIs. And repeated screening is necessary for preterm infants.

Correlation of CT texture changes with treatment response during radiation therapy for esophageal cancer: An exploratory study.

PURPOSE: To analyze the change of CT texture features of esophageal squamous cell carcinoma (ESC) during RT delivery and to correlate these changes with the RT responses and survival. METHODS: A total of 61 ESC patients received radical RT were screened. Weekly CTs (4-6 sets for each patient) were acquired during RT. The tumors, normal esophageal mucosa tissue (NEC) of 5 cm and the spinal cord in the relevant area were delineated. CT texture features were extracted with a home-made tool. The changes of these features were analyzed by t-test. The correlations of the changes of features with RT responses and with patient survival were investigated by Pearson analysis. RESULTS: The average changes were increased by 0.00072 ±0.00197 for coarseness, by 0.14 ±0.40 for entropy, and by 2.34 ±3.56 for strength. In addition, the average changes were reduced by 8.88 ±15.71cc for volume and by 0.07 ±0.11 for busyness. The changes of the coarseness, strength, STD and entropy in ESC were different for the good and poor response groups. The survival rate of the patients was significantly correlated with the change of coarseness and strength (P = 0.0027 and P = 0.0001). CONCLUSIONS: During RT, changes of CT texture features of ESC, e.g., coarseness, strength, STD, entropy and volume are correlated with radiation response and survival rate. With more clinical data and robust research, CT features, e.g., coarseness and strength, can be selected as outstanding imaging biomarkers for prediction of RT prognosis of ESC.

MicroRNA­339­5p inhibits cell proliferation of acute myeloid leukaemia by directly targeting SOX4.

In recent decades, microRNAs (miRNAs) have been considered novel gene regulators. Dysregulated miRNAs serve crucial roles in the formation and progression of acute myeloid leukaemia (AML). Therefore, the roles of differentially expressed miRNAs in AML require extensive investigation to obtain insight into the treatment of patients with AML. The present study demonstrated significant miR­339­5p downregulation in AML samples and cell lines. miR­339­5p overexpression attenuated AML cell proliferation by inducing cell cycle arrest and promoting cell apoptosis. Additionally, sex­determining region Y­related high­mobility group box 4 (SOX4) was identified as a direct target gene of miR­339­5p in AML. Furthermore, SOX4 expression was significantly upregulated in AML samples; this upregulation was inversely correlated with the expression levels of miR­339­5p. Additionally, a series of rescue experiments demonstrated that SOX4 resumption reversed the effects of miR­339­5p overexpression on cell proliferation, cycle status and apoptosis of AML. In conclusion, miR­339­5p may serve its antiproliferative role in AML by directly targeting SOX4, which suggests that miR­339­5p may be considered an effective novel therapeutic target for treating patients with such an aggressive haematological malignancy.

Normal Tissue Complication Probability Model for Radiation-induced Temporal Lobe Injury after Intensity-modulated Radiation Therapy for Nasopharyngeal Carcinoma.

PURPOSE: To identify predictors for the development of temporal lobe injury (TLI) after intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma. MATERIALS AND METHODS: Data in 351 patients with nasopharyngeal carcinoma treated with IMRT were reviewed retrospectively according to institutional ethics committee approval. Clinical factors associated with TLI were analyzed. Dose-volume histograms for 550 evaluable temporal lobes were analyzed, and the predictive value of therapy-associated and patient-associated factors for the occurrence of TLI was evaluated. Survival curves were depicted by using the Kaplan-Meier method and compared by using the log-rank test. Logistic regression analysis was used for multivariate analyses. RESULTS: Median follow-up was 76 months (range, 6-100 months). Twenty-nine of 351 patients (8.3%) developed TLI; 21 patients had unilateral TLI, and eight had bilateral TLI. Median latency from IMRT until first TLI was 33 months (range, 12-83 months) among patients with TLI. The actuarial TLI-free survival rates were 94.4% and 91.3% at 3 and 5 years after radiation therapy, respectively. Logistic regression analysis demonstrated that dose delivered to a 1-cm(3) volume of the temporal lobe (D1cc) was the only independent predictor for TLI. The biologically equivalent tolerance doses at 2 Gy for a 5% and 50% probability of developing TLI were 62.83-Gy equivalents (95% confidence interval: 59.68, 65.97) and 77.58-Gy equivalents (95% confidence interval: 74.85, 80.32), respectively. CONCLUSION: D1cc is predictive for radiation-induced TLI, suggesting that delivery of a high dose of radiation to a small volume of the temporal lobe is unsafe. A D1cc of 62.83 Gy by using a correction formula for varying fraction size may be the dose tolerance of the temporal lobe.

Retrospective analysis of 234 nasopharyngeal carcinoma patients with distant metastasis at initial diagnosis: therapeutic approaches and prognostic factors.

PURPOSE: The purpose of this retrospective study was to identify the independent prognostic factors and optimize the treatment for nasopharyngeal carcinoma (NPC) patients with distant metastasis at initial diagnosis. METHODS: A total of 234 patients referred between January 2001 and December 2010 were retrospectively analyzed. Among the 234 patients, 94 patients received chemotherapy alone (CT), and 140 patients received chemoradiotherapy (CRT). Clinical features, laboratory parameters and treatment modality were examined with univariate and multivariate analyses. RESULTS: The median overall survival (OS) time was 22 months (range, 2-125 months), and the 1-year, 2-year, 3-year overall survival rates were 82.2%, 51.3% and 34.1%. The overall response and disease control rates of metastatic lesions after chemotherapy were 56.0% and 89.8%. The factors associated with poor response were karnofsky performance score (KPS) <80, liver metastasis, lactate dehydrogenase (LDH)>245 IU/L, and number of chemotherapy cycles <4. The 3-year OS of patients receiving CRT was higher than those receiving CT alone (48.2% vs. 12.4%, p<0.001). Subgroup analysis showed that significantly improved survival was also achieved by radiotherapy of the primary tumor in patients who achieved complete remission (CR)/partial remission (PR) or stable disease (SD) of metastatic lesions after chemotherapy. Significant independent prognostic factors of OS were KPS, liver metastasis, levels of LDH, and multiple metastases. Treatment modality, response to chemotherapy and chemotherapy cycles were also associated with OS. CONCLUSION: A combination of radiotherapy and chemotherapy seems to have survival benefits for selected patients with distant metastases at initial diagnosis. Clinical and laboratory characteristics can help to guide treatment selection. Prospective randomized studies are needed to confirm the result.

Intensity-modulated radiotherapy for stage IVA/IVB nasopharyngeal carcinoma: clinical outcomes and patterns of failure in an endemic area in China.

PURPOSE: The purpose of this study was to analyze the mode of relapse patterns and survival of 209 patients with stage IVA and IVB nasopharyngeal carcinoma (NPC). PATIENTS AND MATERIALS: A total of 209 patients who underwent magnetic resonance imaging (MRI) and were subsequently histologically diagnosed with nondisseminated stage IV NPC received intensity-modulated radiotherapy (IMRT) as their primary treatment and were included in this retrospective study. RESULTS: Median follow-up time was 65 months (range, 3-108 months). The 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates for patients with stage IVA and stage IVB NPC were 72.7 vs. 60.0 % (p = 0.319), 62.9 vs. 51.3 % (p = 0.070), 82.9 vs. 93.1 % (p = 0.070), 82.9 vs. 82.9 % (p = 0.897), 76.4 vs. 58.5 % (p = 0.003), respectively. Age older than 44 years was found to be a statistically significant adverse independent prognostic factor for OS. Patients with advanced N status had worse OS, DFS, and DMFS rates. Patients with a primary gross tumor volume (GTV-P) ≥ 55.11 ml had worse OS, DFS, and LRRFS rates. CONCLUSION: The results of treating stage IVA NPC with IMRT were excellent. Distant metastasis remains the most difficult treatment challenge for patients with stage IVA and IVB NPC, and more effective systemic chemotherapy should be explored.

Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities.

BACKGROUND AND PURPOSE: To evaluate the long-term survival outcomes and toxicity of NPC patients treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: From May 2001 to October 2008, 868 non-metastatic NPC patients treated by IMRT were analyzed retrospectively. The Radiation Therapy Oncology Group (RTOG) criteria were used to assess toxicity. RESULTS: With a median follow-up of 50 months (range, 5-115 months), the 5-year estimated disease specific survival (DSS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) were 84.7%, 91.8%, 96.4% and 84.6%, respectively. Of the 868 patients, 186 (21.3%) developed failure after treatment. Distant metastasis was the major failure pattern after treatment. The 5-year OS rate in patients with stage I, II, III, and IVa-b were 100.0%, 94.3%, 83.6%, and 70.5%, respectively. The 5-year LRFS rate in patients with stage T1, T2, T3, and T4 disease were 100.0%, 96.0%, 90.4%, and 83.3%, respectively (χ(2) = 26.32, P<0.001). The 5-year DMFS for N0, N1, N2, and N3 patients were 96.1%, 85.6%, 73.7%, and 62.1%, respectively (χ(2) = 65.54, P<0.001). Concurrent chemotherapy failed to improve survival rates for patients with advanced locoregional disease. The most common acute toxicities were mainly in grade 1 or 2. Compared with IMRT alone, IMRT plus concurrent chemotherapy increased the severity of acute toxicities. The incidence of brain radiation damage was relatively high (5.5%, 48/868 cases), and was not observed in patients with stage T1-2. CONCLUSION: IMRT for NPC yielded excellent survival outcomes, and distant metastasis was the most commonly seen failure pattern after treatment. The role of concurrent chemotherapy for advanced locoregional stage NPC patients needs to be further investigated. Treatment-related toxicities were well tolerable. However, the incidence of brain radiation damage was relatively high, especially for patients with advanced T-stage.

Comparative study on prophylactic irradiation to the whole neck and to the upper neck for patients with neck lymph node-negative nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to investigate the prophylactic irradiation volume to neck drainage areas for patients with N0 classification nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). METHODS: From January 2003 to October 2008, 270 patients with N0 classification (American Joint Committee on Cancer [AJCC] 2002 staging system) NPC who had undergone IMRT were retrospectively analyzed. Among all the patients, 171 patients received prophylactic upper-neck irradiation, and 99 patients received prophylactic whole-neck irradiation. RESULTS: At a median follow-up of 65.1 months (range, 4-106 months). The 5-year overall survival (OS), nodal recurrence-free survival (NRFS), and distant metastasis-free survival (DMFS) rates of the upper neck group and the whole neck group were 93.6% vs 90.9% (p = .553), 99.4% vs 99.0% (p = .278), and 98.8% vs 94.9% (p = .128), respectively. A total of 3 neck recurrences were found, including 2 from the whole neck group and 1 from the upper neck group. The latter (0.6%) was an out-of-field recurrence. CONCLUSION: Prophylactic irradiation to the upper neck (levels II, III, and VA) may be feasible for patients with neck lymph node-negative NPC.

[Concurrent chemotherapy with different dose regimens of cisplatin for nasopharyngeal carcinoma using intensity-modulated radiation therapy: a phase II prospective randomized controlled trial].

OBJECTIVE: To explore the acute toxic effects and early curative efficacy of concurrent chemotherapy with different doses of cisplatin for Chinese nasopharyngeal carcinoma (NPC) patients using intensity-modulated radiation therapy (IMRT). METHODS: Eighty-eight untreated stage II/III nasopharyngeal cancer patients receiving IMRT and concurrent cisplatin were randomized into two groups receiving different doses of cisplatin. The standard group (DDP 100 mg/m² q3w, n = 44) and the study group (DDP 80 mg/m² q3w, n = 44). The acute toxic effects and 3-month therapeutic efficacy (early curative efficacy) in patients of the two groups who completed treatment were compared and analyzed. RESULTS: During the treatment, grade III-IV acute toxic effects were observed in more patients of the standard group compared with that in the study group (72.7% vs. 59.1%), but the difference was statistically not significant (P = 0.18). Significant difference was only seen in upper gastrointestinal reaction (P = 0.01) and anemia (P = 0.03) among the non-hematological and hematological adverse events. No significant differences in other adverse events were found between the two groups (P < 0.05). Three months after the completion of radiotherapy, 80 cases of the whole group achieved complete remission (CR) in the nasopharynx and neck MRI. In both the standard group and study group, 40 patients had CR and 4 patients had residual disease, respectively, showing a non-significant difference (P = 0.51) between the two groups. CONCLUSIONS: During the IMRT course, patients received cisplatin 80 mg/m² q3w, experienced less grade III-IV acute toxic effects. Concurrent chemoradiotherapy with cisplatin 80 mg/m² q3w or 100 mg/m² q3w, demonstrate similar early curative efficacy in II/III stage NPC patients in endemic regions of China.

Comparing treatment outcomes of different chemotherapy sequences during intensity modulated radiotherapy for advanced N-stage nasopharyngeal carcinoma patients.

BACKGROUND: N-stage is related to distant metastasis of nasopharyngeal carcinoma (NPC) patients. We performed this study to compare the efficacy of different chemotherapy sequences in advanced N-stage (N2 and N3) NPC patients treated with intensity modulated radiotherapy (IMRT). METHODS: From 2001 to 2008, 198 advanced N-stage NPC patients were retrospectively analyzed. Thirty-three patients received IMRT alone. Concurrent chemoradiotherapy (CCRT) was delivered to 72 patients, neoadjuvant chemotherapy (NACT) + CCRT to 82 patients and CCRT + adjuvant chemotherapy (AC) to 11 patients. RESULTS: The 5-year overall survival rate, recurrence-free survival rate, distant metastasis-free survival rate and progress-free survival rate were 47.7% and 73.1%(p<0.001), 74.5% and 91.3% (p = 0.004), 49.2% and 68.5% (p = 0.018), 37.5% and 63.8% (p<0.001) in IMRT alone and chemoradiotherapy group. Subgroup analyses indicated that there were no significant differences among the survival curves of CCRT, NACT + CCRT and CCRT + AC groups. The survival benefit mainly came from CCRT. However, there was only an improvement attendency in distant metastasis-free survival rate of CCRT group (p = 0.107) when compared with RT alone group, and NACT + CCRT could significantly improve distant metastasis-free survival (p = 0.017). CONCLUSIONS: For advanced N-stage NPC patients, NACT + CCRT might be a reasonable treatment strategy.

Prognostic analysis of early-stage squamous cell carcinoma of the vulva.

AIM: The aim of this study was to analyze prognostic factors of early-stage squamous cell carcinoma of the vulva. METHODS: A retrospective analysis was conducted on 35 patients who were treated for early-stage squamous cell carcinoma of the vulva at Sun Yat-sen University Cancer Center from January 1980 to December 2005. The Statistical Package for Social Science (SPSS) was used to compare the different strategies of operation and to analyze the prognostic factors. RESULTS: Thirty-five patients had early-stage squamous cell carcinoma of the vulva. Of these cases, 26 were well differentiated, seven were moderately differentiated, and two were poorly differentiated. The five-year survival rate was 77.1%. Five cases were in FIGO stage 1a and 30 cases were in stage 1b; median survival times were 182.3 months and 152.5 months, and the five-year survival rates were 100% and 81.5% (P >0.05), respectively. The five-year survival of the patients who underwent local excision; radical vulvectomy and en bloc resection of inguinofemoral lymphadenectomy; orradical vulvectomyen bloc resection of inguinofemoral lymphadenectomy, and pelvic lymph nodes was 50%, 81.8%, and 83.9%, respectively. For these cases, 74.3% of the tumors were medial while 25.7% were lateral, and the five-year survival rates of patients according to tumor location were 87.0% and 64.8% (P <0.05), respectively. The inguinal lymph node not increased and active were 16 cases (45.7%), and increased, active and hard were 17 cases (48.6%), and syncretic were two cases (5.7%), five-year survival rates were 73.3%, 92.9% and 50% (P <0.05), respectively. Of these cases, 74.3% of the tumors were cauliflower-like and 25.7% were nodular; five-year survival rates by tumor type were 91.3% and 66.7% (P <0.05), respectively. CONCLUSIONS: For patients with early-stage squamous cell carcinoma of the vulva, surgical operation is the primary, yet the best, treatment. The related prognostic factors were tumor location (lateral/medial), stage, gross morphology, and clinical state of the inguinal lymph node.