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Background: The predictive value of programmed death-ligand 1 (PD-L1) expression in nasopharyngeal cancer (NPC) patients receiving immune checkpoint inhibitors (ICIs) remains controversial. This study aimed to evaluate the optimal threshold of PD-L1 expression in predicting the efficacy of ICIs in patients with recurrent or metastatic (R/M) NPC. Methods: A meta-analysis was performed by retrieving relevant literature from PubMed, EMBASE, and Cochrane Library databases. Data on the pooled risk ratio (RR), mean overall survival (OS), progression-free survival (PFS), overall response rate (ORR) with 95% confidence interval, and 1%, 10%, and 25% PD-L1 expression cutoff points were obtained to examine the role of PD-L1 as a biomarker in R/M NPC patients receiving immunotherapy. Results: In total, 1,312 patients from 14 studies were included. An improvement in PFS was observed in both patients with PD-L1 ≥ 1% (RR = 0.76, 95% CI 0.62-0.92, P = 0.005) and those with PD-L1 < 1% (RR = 0.68, 95% CI: 0.35-1.32, P = 0.26) who received first-line treatment with immunotherapy, with no significant difference between these subgroups. The pooled ORR was significantly higher in patients with PD-L1 ≥ 1% (ORR = 0.37) than in those with PD-L1 < 1% (ORR = 0.22) (P < 0.01) undergoing subsequent-line treatment. However, when we used the PD-L1 cutoff values of 10% and 25%, there was no significant difference between the positive (PD-L1 expression ≥ the cutoff value) and negative (PD-L1 expression < the cutoff value) subgroups. PD-L1 ≥ 1% also tended to be associated with better PFS and OS. Conclusions: Our meta-analysis suggested that first-line immunotherapy could significantly improve PFS in R/M NPC patients, regardless of the PD-L1 expression levels. Positive PD-L1 expression (≥ 1%) might be a potential predictive biomarker for a better overall response to immunotherapy in R/M NPC patients in subsequent-line setting. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024495841 PROSPERO, identifier CRD42024495841. [ABSTRACT FROM AUTHOR]

Introduction: Approximately 50% of patients with primary colorectal carcinoma develop liver metastases. This study investigates the possible molecular discrepancies between primary colorectal cancer (pCRC) and their respective metastases. Methods: A total of 22 pairs of pCRC and metastases were tested. Mutation profiling of 26 cancer-associated genes was undertaken in 22/22primary-metastasis tumour pairs using next-generation sequencing, whilst the expression of a panel of six microRNAs (miRNAs) was investigated using qPCRin 21/22 pairs and 22 protein biomarkers was tested using Reverse Phase Protein Array (RPPA)in 20/22 patients' tumour pairs. Results: Among the primary and metastatic tumours the mutation rates for the individual genes are as follows:TP53 (86%), APC (44%), KRAS (36%), PIK3CA (9%), SMAD4 (9%), NRAS (9%) and 4% for FBXW7, BRAF, GNAS and CDH1. The primary-metastasis tumour mutation status was identical in 54/60 (90%) loci. However, there was discordance in heterogeneity status in 40/58 genetic loci (z-score = 6.246, difference = 0.3793, P < 0.0001). Furthermore, there was loss of concordance in miRNA expression status between primary and metastatic tumours, and 57.14–80.95% of the primary-metastases tumour pairs showed altered primary-metastasis relative expression in all the miRNAs tested. Moreover, 16 of 20 (80%) tumour pairs showed alteration in at least 3 of 6 (50%) of the protein biomarker pathways analysed. Conclusion: The molecular alterations of primary colorectal tumours differ significantly from those of their matched metastases. These differences have profound implications for patients' prognoses and response to therapy. [ABSTRACT FROM AUTHOR]

Background and Purpose: To investigate the prognostic value of retropharyngeal lymphadenopathy in nasopharyngeal carcinoma (NPC) after intensity‐modulated radiotherapy. Materials and Methods: Retrospective studies were performed in a total of 1197 patients. We evaluated the incidence of the retropharyngeal node (RPN) metastasis and the characteristics of the metastatic RPN including laterality, size, necrosis, and extranodal neoplastic spread. Results: RPN metastasis occured in 86.3% of patients. The RPN and level II metastasis shared similar survival outcomes. RPN metastasis was an independent prognostic factor for distant failure (hazard ratio = 1.615; 95% confidence interval, 1.063–2.452; P = 0.025), in which the laterality of RPN metastasis significantly influences both the distant failure (P = 0.006) and disease progression (P = 0.001). In N1 disease, the occurrence of unilateral and bilateral RPN metastasis resulted in significantly different outcomes of the disease‐specific survival (P = 0.045) and progression‐free survival (P = 0.049). The co‐occurrence of bilateral RPN and cervical lymph nodes (CLN) metastasis was an independent adverse prognostic factor (P < 0.01) for distant failure and disease progression but not for locoregional recurrence. Conclusion: Both the RPN and level II are the first stations of NPC lymph node metastasis. For N1‐stage NPC patients, RPN metastasis, especially co‐occurrence of bilateral RPN and CLN metastasis, have an adverse influence on survival outcomes. [ABSTRACT FROM AUTHOR]

Aim: Given a lack of standard of care treatment for recurrent/metastatic nasopharyngeal carcinoma (R/M NPC), we assessed treatment patterns and overall survival in the real-world setting. Materials & methods: A retrospective chart review was conducted in patients who initiated first-line systemic therapy in Taiwan and South Korea between January 2012 and June 2013 with follow-up through December 2015. Results: Among 154 R/M NPC patients, all patients in Taiwan (n = 104) had distant metastases, whereas in South Korea (n = 50) 42% had distant metastases. Patients with distant metastases generally received systemic therapy only (71%) for whom median overall survival was 23 months (95% CI: 18-32). Conclusion: Prognosis in R/M NPC with distant metastases remains poor, underscoring the need for more efficacious treatments. [ABSTRACT FROM AUTHOR]

Background: Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease. Method: A literature search was performed using the keywords 'nasopharyngeal neoplasm', 'cetuximab' and 'Erbitux'. Results: Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting. Conclusion: There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is rare in Western countries, but its incidence in China and Southeast Asia is notably high. NPC shows a high rate of distant metastasis including metachronous metastasis (mmNPC, metastasis after definitive chemo-radiotherapy) and synchronous metastasis (smNPC, metastasis at initial diagnosis). 4–10% of patients would be diagnosed as smNPC annually, and the survival outcomes of these patients are quite poor. As with few clinical trials exclusively focusing on this population, treatment on smNPC is not unified and many problems remain unsolved. To date, systematic chemotherapy (CT) still remains a fundamental treatment in smNPC. Although no randomized trial has been conducted to compare different CT regimens in smNPC, gemcitabine and taxanes in combination with platinum seem optimal in first-line setting. In second-line CT, there is no consensus: mono-chemotherapy with drugs such as gemcitabine, taxanes or capecitabine could be taken into consideration. Immunotherapy based on checkpoint inhibitors shows promising efficacy both in first-line and in the following lines of therapy. In addition to CT, local therapy in smNPC is also very important. Locoregional radiotherapy (RT) for primary tumor in combination with CT could strikingly increase OS with acceptable toxicities. And local treatment, such as surgery and RT, for metastatic lesions could bring extra survival benefit in patients with solitary or limited metastases. Overall, the present study provides an overview of the literature on the various studies of smNPC. [ABSTRACT FROM AUTHOR]

Background: To investigate the prognostic value of radiologic extra‐nodal extension (rENE) in stage II nasopharyngeal carcinoma (NPC). Methods: Stage II NPC patients with N1 category (n = 365) were enrolled and divided into three groups according to the situation of rENE: without rENE, suspected rENE, and confirmed rENE (grades: A, infiltration into surrounding fat; B, matted nodes; C, infiltration into adjacent structures). Results: Only high‐grade rENE (including matted nodes and infiltration into adjacent structures) could significantly influence the survival outcomes, patients with high‐grade rENE had significantly poorer survival than those without, with the 7‐year distant metastasis‐free survival and overall survival demonstrated to be 78.5% vs 93.0% (P < .001) and 81.9% vs 89.9% (P = .05), respectively. High‐grade rENE, as defined in our study, is a stable criterion, with high intra‐rater and inter‐rater consistency. Conclusion: High‐grade rENE was an evaluable predictor that could help with the selection of stage II patients with high risk of distant metastasis. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a malignancy that is common in Southern China, South-East Asia and North Africa. Platinum-based chemotherapy is currently the main treatment option for the first-line therapy of recurrent and/or metastatic NPC (RM-NPC). However, the outcome of patients with advanced disease remains poor after treatment with standard chemotherapy, as patients eventually became resistant to chemotherapy. Other strategies, such as targeted therapy and immunotherapy, offer alternative options for patients due to their reported efficacy and manageable toxicities. This suggests that these modalities, either as monotherapy or in combination with chemotherapy, may serve as viable treatment options for RM-NPC. The present review provides a comprehensive summary of the clinical data of targeted therapy and immunotherapy for RM-NPC, with the aim of broadening the understanding of RM-NPC management. [ABSTRACT FROM AUTHOR]

Background: Chemoradiotherapy (CRT) has improved organ preservation or overall survival (OS) of locoregionally advanced head and neck squamous cell cancer (LAHNSCC), but in clinical trials of conventional CRT, increasing CRT intensity has not been shown to improve OS. In the Adjuvant ChemoTherapy with S-1 after curative treatment in patients with Head and Neck Cancer (ACTS-HNC) phase III study, OS of curative locoregional treatments improved more with adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) than with tegafur/uracil (UFT). ACTS HNC study showed the significant efficacy of S-1 after curative radiotherapy in sub-analysis. We explored the efficacy of S-1 after curative CRT in a subset of patients from the ACTS-HNC study. Methods: Patients with stage III, IVA, or IVB LAHNSCC were enrolled in this study to evaluate the efficacy of S-1 compared with UFT as adjuvant chemotherapy after curative CRT in the ACTS-HNC study. Patients received S-1 at 80–120 mg/day in two divided doses for 2 weeks, followed by a 1-week rest, or UFT 300 or 400 mg/day in two or three divided doses daily, for 1 year. The endpoints were OS, disease-free survival, locoregional relapse-free survival, distant metastasis-free survival (DMFS), and post-locoregional relapse survival. Results: One hundred eighty patients (S-1, n = 87; UFT, n = 93) were included in this study. Clinical characteristics of the S-1 and UFT arms were similar. S-1 after CRT significantly improved OS (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.22–0.93) and DMFS (HR, 0.50; 95% CI, 0.26–0.97) compared with UFT. Conclusion: As adjuvant chemotherapy, S-1 demonstrated better efficacy for OS and DMFS than UFT in patients with LAHNSCC after curative CRT and may be considered a treatment option following curative CRT. For this study was not preplanned in the ACTS-HNC study, the results is hypothesis generating but not definitive. [ABSTRACT FROM AUTHOR]

Background and aim: To evaluate the impact of percutaneous endoscopic gastrostomy (PEG) tube on nutritional status, treatment-related toxicity, and treatment tolerance in patients with locally advanced nasopharyngeal carcinoma (NPC) who underwent chemoradiotherapy. Patients and methods: We enrolled 133 consecutive non-metastatic NPC (III/IV stage) patients, who were treated with prophylactic PEG feeding before the initiation of concurrent chemoradiotherapy (CCRT) between June 1, 2010 and June 30, 2014. Meanwhile, another 133 non-PEG patients, who were matched for age, gender, and tumor, node, metastases stage, were selected as historical control cohort. Weight and nutritional status changes from pre-radiotherapy to the end of radiotherapy were evaluated, and treatment tolerance and related acute toxicities were analyzed as well. Results: We found that significantly more patients (91.73%) in the PEG group could finish two cycles of CCRT, when compared with those in the non-PEG group (57.89%) (P<0.001). We also indicated that more patients (50.38%) in the non-PEG group experienced weight loss of ≥5%, while the phenomenon was only found in 36.09% patients in the PEG group (P=0.019). In addition, the percentage of patients who lost ≥10% of their weight was similar in these two groups. Changes in albumin and prealbumin levels during radiotherapy in the non-PEG group were higher than those obtained for the PEG group with significant differences (P-values of 0.023 and <0.001, respectively). Furthermore, patients in the PEG group had significantly lower incidence of grade III acute mucositis than those in the non-PEG group (22.56% vs 36.84%, P=0.011). Tube-related complications occurred only in 14 (10.53%) patients in the PEG group, including incision infection of various degrees. Conclusion: PEG and intensive nutrition support may help to minimize body weight loss, maintain nutritional status, and offer better treatment tolerance for patients with locally advanced NPC who underwent CCRT. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. Patients and methods: From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66-70 Gy, 63 Gy to clinical target volume, and 50.4-56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. Results: The median follow-up time was 52.2 months (range: 11-87 months). Epstein-Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range: 16-50 months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein-Barr virus were independent predictors for disease-free survival. Conclusion: Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein-Barr virus status before IMRT were important independent prognostic factors. [ABSTRACT FROM AUTHOR]

Purpose: The value of adding induction chemotherapy to chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains controversial, yet high-risk patients with LA-NPC have poor outcomes after chemoradiotherapy. We aimed to assess the survival benefits of induction chemotherapy in stage IVa-b NPC. Patients and Methods: A total of 602 patients with stage IVa-b NPC treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with or without induction chemotherapy were retrospectively analyzed. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, log-rank test and Cox regression analysis. Results: In univariate analysis, 5-year OS was 83.2% for induction chemotherapy plus concurrent chemotherapy and 74.8% for concurrent chemotherapy alone, corresponding to an absolute risk reduction of 8.4% (P = 0.022). Compared to concurrent chemotherapy alone, addition of induction chemotherapy improved 5-year DMFS (83.2% vs. 74.4%, P = 0.018) but not 5-year LRFS (83.7% vs. 83.0%, P = 0.848) or PFS (71.9% vs. 66.0%, P = 0.12). Age, T category, N category, chemotherapy strategy and clinical stage were associated with 5-year OS (P = 0.017, P = 0.031, P = 0.007, P = 0.022, P = 0.001, respectively). In multivariate analysis, induction chemotherapy plus concurrent chemotherapy was an independent favorable prognostic factor for OS (HR, 0.62; 95% CI, 0.43–0.90, P = 0.012) and DMFS (HR, 0.57; 95% CI, 0.38–0.83, P = 0.004). In subgroup analysis, induction chemotherapy significantly improved 5-year DMFS in stage IVa (86.8% vs. 77.3%, P = 0.008), but provided no significant benefit in stage IVb. Conclusions: In patients with stage IVa-b NPC treated with IMRT, addition of induction chemotherapy to concurrent chemotherapy significantly improved 5-year OS and 5-year DMFS. This study provides a basis for selection of high risk patients in future clinical therapeutic trials. [ABSTRACT FROM AUTHOR]

Background: With radiotherapy (RT) alone, the five-year overall survival (OS) rate for advanced nasopharyngeal carcinoma (NPC) can only reach 40%, the ratio of distant metastasis (DM) is 36-40%. This meta-analysis was performed to compare the clinical efficacy of concurrent chemoradiotherapy (CCRT) with RT alone in the treatment of locoregionally advanced NPC.Methods: The related literature were retrieved and reviewed by two independent investigators from the followed electronic databases: Review manager 5.3 software (Cochrane Collaboration, London, United Kingdom) was applied for statistical analysis.Results: A total of 16 trials with 2576 patients were recruited according to the criterion. The odds ratios of 3 and 5 years OS was 0.53 (95% confidence interval [95% CI]: 0.44-0.64) and 0.58 (95% CI: 0.48-0.71), which confirmed the significant improvement of CCRT compared with RT alone (P < 0.001). CCRT also reduced the risk of locoregional control failure and DM in locoregionally advanced NPC patients.Conclusions: The results suggested that CCRT was more beneficial when compared with RT alone in locoregionally advanced NPC patients. Further study is needed to perform to confirm this effect. [ABSTRACT FROM AUTHOR]

Background Although endoscopic nasopharyngectomy and intensity-modulated radiotherapy (IMRT) have been reported to be useful in treating isolated local recurrent nasopharyngeal carcinoma (NPC), their efficacy needs to be revaluated with comparison to 2D conventional radiotherapy (RT). Methods Four hundred ten patients with recurrent NPC were retrospectively analyzed, among whom the patients underwent IMRT, endoscopic nasopharyngectomy, and 2D conventional RT. Results The 5-year overall survival (OS) and distant metastasis-free survival were significantly higher in endoscopic nasopharyngectomy and IMRT groups than in 2D conventional RT group both in the entire series and in the subgroup of patients with recurrent T1 to 2 NPC ( p < .05), except in the subgroup of recurrent T3 to 4 stratifications (IMRT vs 2D conventional RT; 28.8% vs 16.8%; p = .351). Furthermore, endoscopic nasopharyngectomy was associated with better OS than IMRT in the recurrent T1 to 2 subgroup (79.2% vs 62.1%; p = .007). Multivariate analysis indicated therapeutic modality was an independent predictor of OS and distant metastasis-free survival ( p < .001). Conclusion Endoscopic nasopharyngectomy and IMRT are associated with an improved OS and distant metastasis-free survival of patients with recurrent NPC compared to 2D conventional RT in early recurrent disease. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1108-1115, 2015 [ABSTRACT FROM AUTHOR]

Background:Whether females have better survival than males in nasopharyngeal carcinoma is barely acknowledged and the exact explanations remain unknown.Methods:Overall, 5929 patients receiving treatment between January 2005 and December 2010 were separately stratified by stage into early and advanced stage groups, and by age into premenopausal (⩽45 years), menopausal (46-54 years) and postmenopausal (⩾55 years) groups. Matched males and females in each group were identified using the propensity score matching method. Differences in disease-free survival (DSS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were estimated by the Kaplan-Meier method and Cox regression model.Results:Overall, 398, 923, 744, 319 and 313 pairs of males and females were matched in early stage, advanced stage, premenopausal, menopausal and postmenopausal group, respectively. Females showed significant advantage over males across all end points in both early and advanced stage groups (P⩽0.042). However, this advantage persisted at premenopausal age (P⩽0.042), declined during menopause (DMFS, P=0.021; DSS, P=0.100; OS, P=0.693; LRFS, P=0.330) and totally disappeared at postmenopausal age (P⩾0.344).Conclusions:Sex significantly affects NPC survival, with a definite female advantage regardless of tumour stage. Intrinsic biologic traits appear to be the exact explanation according to the declining magnitude of sex effect with age. [ABSTRACT FROM AUTHOR]

Trastuzumab is established as standard care for patients with HER2-positive breast cancer both in the adjuvant and metastatic setting. However, approximately 50% of the patients do not respond to the trastuzumab therapy, and therefore new predictive biomarkers are highly warranted. MicroRNAs (miRs) constitute a new group of biomarkers and their cellular expression can be determined in tumor samples by in situ hybridization (ISH) analysis. miR-21 is highly prevalent and up-regulated in breast cancer and has been linked to drug resistance in clinical and in vitro settings. To determine expression patterns of miR-21 in high-grade breast cancers, we examined miR-21 expression in 22 HER2-positive tumors and 15 HER2-negative high-grade tumors by ISH. The histological examination indicated that patient samples could be divided into 3 major expression patterns: miR-21 predominantly in tumor stroma, predominantly in cancer cells or in both stromal and cancer cells. There was no obvious difference between the HER2-positive and HER2-negative tumors in terms of the miR-21 expression patterns and intensities. To explore the possibility that miR-21 expression levels and/or cellular localization could predict resistance to adjuvant trastuzumab in HER2-positive breast cancer patients, we analyzed additional 16 HER2-positive tumors from patients that were treated with trastuzumab in the adjuvant setting. Eight of the 16 patients showed clinical recurrence and were considered resistant. Examination of the miR-21 expression patterns and intensities revealed no association between the miR-21 scores in the cancer cell population (p=0.69) or the stromal cells population (p=0.13) and recurrent disease after adjuvant trastuzumab. Thus, our findings show that elevated miR-21 expression does not predict resistance to adjuvant trastuzumab. [ABSTRACT FROM AUTHOR]

Background The clinical outcomes for early-stage nasopharyngeal carcinoma (NPC) in northwest China were evaluated. Methods A retrospective study was performed from 69 patients with NPC patients treated with intensity-modulated radiation therapy (IMRT) with or without chemotherapy. Results Median follow-up was 34 months. World Health Organization (WHO) type II was the predominant histology (71%). All treatment failures occurred in T2N1 NPCs (14.5%), with metastasis the major reason. The 3-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were 93.3%, 94.1%, and 94.8% respectively. The 3-year survival rate for T2N1 and IMRT alone group were both significantly poorer than the T1N0, T2N0, and T1N1 groups and the chemoradiation group, respectively ( p < .05). N1 classification, T2N1 classification, and addition of chemoradiation were significant independent predictors ( p < .05). No grade IV toxicities were observed. Conclusion T2N1 classification is a unique subgroup with higher risk of distant metastasis. Improved outcomes of T2N1 NPC with predominantly WHO II histology after chemoradiation has not been reported. © 2013 Wiley Periodicals, Inc. Head Neck 36: 841-847, 2014 [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic cancer. N,N'-dinitrosopiperazine (DNP), a carcinogen with specificity for nasopharyngeal epithelium, facilitates NPC metastasis. However, the underlying mechanism is not known. Methods: Quantitative phosphoproteomics, using stable isotope labeling of amino acids in cell cultures, was employed to identify phosphoproteins associated with NPC metastasis mediated by DNP. NPC cell line 6-10B, which is relatively less metastatic, was used to investigate DNP-mediated metastasis. Boyden chamber invasion assay was used to measure DNP-induced motility and invasion, and nude mice were used to verify DNP-mediated metastasis in vivo. Several different phosphoproteins detected by proteomics analysis were verified by immunoblotting. DNP-mediated metastasis facilitated by lysine-rich CEACAM1 co-isolated protein (LYRIC) phosphorylation at serine 568 was confirmed using mutations targeting the phosphorylation site of LYRIC. DNP-mediated metastasis through LYRIC phosphorylation was confirmed in the NPC cell line CNE1. DNP-mediated LYRIC phosphorylation at serine 568 was also verified in metastatic tumors of BABL/c nude mice. Results: Boyden chamber invasion assay indicated that DNP mediated cell motility and invasion of NPC cell 6-10B in vitro, and experiments with nude mice indicated that DNP increased 6-10B metastasis in vivo. In the phosphoproteomics analysis, we detected 216 phosphorylation sites on 130 proteins; among these, 48 phosphorylation sites on 30 unique phosphopeptides were modulated by DNP by at least 1.5-fold. DNP mediated the expression of phosphorylated GTPase, ferritin, LYRIC, and RNA polymerase, and it decreased the expression of phosphorylated torsin-1A protein 1. Furthermore, DNP induced LYRIC phosphorylation at serine 568 to facilitate cell motility and invasion, whereas DNP-mediated motility and invasion was decreased when serine 568 in LYRIC was mutated. In another NPC cell line, CNE1, DNP also mediated cell motility and invasion followed by enhanced phosphorylation of LYRIC at serine 568. Finally, phosphorylated-LYRIC expression at serine 568 was significantly increased in metastatic tumors induced by DNP. Conclusion: DNP regulates multiple signaling pathways through protein phosphorylation, including the phosphorylation of LYRIC at serine 568, and mediates NPC metastasis. These findings provide insights on the complexity and dynamics of DNP-facilitated metastasis, and may help to gain a better understanding of the mechanisms by clarifying NPC-induced metastasis. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to analyze the surgical management of recurrent retropharyngeal lymph node metastasis after radiotherapy for nasopharyngeal carcinoma (NPC). Methods We conducted a prospective analysis of preoperative imaging, surgical approach, and oncological results. Results Between 1990 and 2011, 82 patients were included. The mean size of the retropharyngeal lymph node on MRI was 1.6 cm, and the mean standardized uptake value maximum (SUVmax) on positron emission tomography (PET) scan was 6.8. All the retropharyngeal lymph nodes were resected via the maxillary swing approach. Among the resected retropharyngeal lymph nodes, 87.8% contained viable tumor cells. The rate of microscopic extracapsular spread was 30.6%. The mean follow-up duration was 38 months. The 5-year actuarial tumor control and the overall disease-free survival of patients who underwent surgeries for isolated recurrent retropharyngeal lymph node metastasis was 79.6% and 59%, respectively. Conclusion A PET scan is potentially useful in diagnosing persistent or recurrent retropharyngeal lymph node after previous radiotherapy for NPC. The maxillary swing approach allows surgical resection with clear margins in order to achieve the best oncological outcome. © 2013 Wiley Periodicals, Inc. Head Neck 35: 1726-1731, 2013 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We evaluated the differential expression of several microRNAs (miRNAs) among malignant cells in ascites and matched omental metastasis in patients with epithelial ovarian cancer (EOC). Ascites and omental tumors were collected prospectively from five patients who were undergoing primary surgical cytoreduction. Patient samples were processed and treated with carboplatin, paclitaxel and combination chemotherapy. Cell viability was evaluated and miRNA profiling was performed on both tumor cells from ascites fluid and omental cake. Quantitative real-time PCR (RT-q-PCR) and western blots were used to evaluate expressions of miRNA-21 and miRNA -214 and associated proteins. Malignant cells in ascites showed greater cell viability when treated with carboplatin compared to omental metastasis. A significant up-regulation of miRNA-21 and miRNA-214 was observed in malignant cells of ascites compared to omental metastasis; this was confirmed by both cell viability assay and RT-q-PCR. Ours is the first report that demonstrates significant up-regulation of miRNA-21 and miRNA-214 in tumor cells from ascites of patients with EOC compared to omental metastasis. This finding has important implications for intrinsic carboplatin resistance in these patients. [ABSTRACT FROM AUTHOR]

Background The association between expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and the long-term outcomes in treated nasopharyngeal carcinoma (NPC) was studied. Methods Expression of COX-2, VEGF, and EGFR by immunohistochemical (IHC) staining was assessed in 128 patients with NPC. Overall survival (OS), disease-free survival (DFS), locoregional control, and distant metastasis-free survival rates were compared for different expression levels of each marker. Multivariate analysis was by the Cox regression model. Results Median follow-up after radiation therapy ± chemotherapy was 116 months. Univariate and multivariate analyses demonstrated that COX-2, VEGF, EGFR, and clinical stage were all independent predictors for OS, DFS, locoregional control, and distant metastasis-free survival rates. Conclusions High expression of COX-2, VEGF, and EGFR were independent adverse prognostic factors for long-term outcomes in nonmetastatic NPC independent of clinical stage. © 2012 Wiley Periodicals, Inc. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

Background: Qualitative alterations or abnormal expression of microRNAs (miRNAs) in colon cancer have mainly been demonstrated in primary tumors. Poorly overlapping sets of oncomiRs, tumor suppressor miRNAs and metastamiRs have been linked with distinct stages in the progression of colorectal cancer. To identify changes in both miRNA and gene expression levels among normal colon mucosa, primary tumor and liver metastasis samples, and to classify miRNAs into functional networks, in this work miRNA and gene expression profiles in 158 samples from 46 patients were analysed. Results: Most changes in miRNA and gene expression levels had already manifested in the primary tumors while these levels were almost stably maintained in the subsequent primary tumor-to-metastasis transition. In addition, comparing normal tissue, tumor and metastasis, we did not observe general impairment or any rise in miRNA biogenesis. While only few mRNAs were found to be differentially expressed between primary colorectal carcinoma and liver metastases, miRNA expression profiles can classify primary tumors and metastases well, including differential expression of miR-10b, miR-210 and miR-708. Of 82 miRNAs that were modulated during tumor progression, 22 were involved in EMT. qRT-PCR confirmed the down-regulation of miR-150 and miR-10b in both primary tumor and metastasis compared to normal mucosa and of miR-146a in metastases compared to primary tumor. The upregulation of miR-201 in metastasis compared both with normal and primary tumour was also confirmed. A preliminary survival analysis considering differentially expressed miRNAs suggested a possible link between miR-10b expression in metastasis and patient survival. By integrating miRNA and target gene expression data, we identified a combination of interconnected miRNAs, which are organized into sub-networks, including several regulatory relationships with differentially expressed genes. Key regulatory interactions were validated experimentally. Specific mixed circuits involving miRNAs and transcription factors were identified and deserve further investigation. The suppressor activity of miR-182 on ENTPD5 gene was identified for the first time and confirmed in an independent set of samples. Conclusions: Using a large dataset of CRC miRNA and gene expression profiles, we describe the interplay of miRNA groups in regulating gene expression, which in turn affects modulated pathways that are important for tumor development. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) in patients with residual nasopharyngeal carcinoma (NPC). Methods: From January 2000 to December 2009, 136 NPC patients with residual lesions after primary radiotherapy (RT) were treated by FSRT. The total dose of primary RT was 68.0-78.0 Gy (median, 70.0 Gy). The median time from the primary RT to FSRT was 24.5 days. Tumor volumes for FSRT ranged from 0.60 to 77.13 cm3 (median, 13.45 cm3). The total FSRT doses were 8.0-32.0Gy (median, 19.5 Gy) with 2.0-10.0 Gy per fraction. Results: Five-year local failure-free survival (LFFS), freedom from distant metastasis (FFDM), overall survival (OS), and disease free survival (DFS) rates for all patients were 92.5%, 77.0%, 76.2%, and 73.6%, respectively. No statistical significant differences were found in LFFS, DFS and OS in patients with stage I/II versus stage III/ IV diseases. Nineteen patients exhibited late toxicity. T stage at diagnosis was a significant prognostic factor for OS and DFS. Age was a prognostic factor for OS. Conclusion: FSRT after external beam radiotherapy provides excellent local control for patients with residual NPC. The incidence of severe late toxicity is low and acceptable. Further investigation of optimal fractionation regimens will facilitate reduction of long-term complications. [ABSTRACT FROM AUTHOR]

Purpose: There is no standard second-line regimen for recurrent and metastatic nasopharyngeal carcinoma patients after failure of cisplatin-based chemotherapy. A multicenter phase II study was conducted to evaluate the efficacy and toxicity of capecitabine combined with nedaplatin for these patients. Patients and methods: In the multicenter, open-label, single-arm phase II study, patients with recurrent and metastatic nasopharyngeal carcinoma who failed to previous cisplatin-based chemotherapy were enrolled. Patients received oral capecitabine (1,000 mg/m twice daily from day 1 to 14) and intravenous nedaplatin (80 mg/m, day 1) every 3 weeks for two cycles at least. Results: A total of forty-eight patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events. Treatment was well tolerated. Grade 3/4 toxicities included neutropenia (8.4 %), anemia (2.1 %), diarrhea (4.2 %), stomatitis (6.3 %), and hand-foot syndrome (HFS) (4.2 %). There were two complete response (4.2 %), eighteen partial responses (37.5 %), giving an overall response rate of 41.7 % [95 % confidence interval (CI) 27.7-55.8]. With a median follow-up period of 12.1 months, the median time to progression was 5.8 months (95 % CI 3.9-7.8 months) and median overall survival was 12.4 months (95 % CI 9.6-16.8 months). Conclusion: Capecitabine combined with nedaplatin offers a satisfactory clinical activity and an acceptable safety profile for recurrent and metastatic nasopharyngeal carcinoma patients after failure of cisplatin-based chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The correlation between primary tumor volume and nasopharyngeal carcinoma (NPC) UICC 2002 T classification, N classification and distant metastasis after radiation therapy was discussed to provide further evidence for the inclusion of tumor volume into the TNM classification staging system. Methods: Between February 2001 and December 2008, 666 patients with NPC treated with intensity-modulated radiation therapy (IMRT) were analyzed retrospectively. Primary gross tumor volume was calculated from treatment planning computed tomography scans. The Kruskal-Wallis and Mann-Whitney tests were used for comparison of continuous variables and the chi-square test was used for categorical variables. A logistic regression model was used for multivariate analysis. Results: Median primary tumor volume of the 666 patients was 20.35 ml (range, 0.44 - 192.63 ml), and it gradually increased with T classification. Statistically significant differences in tumor volume were observed between patients with different T classifications (p < 0.001). The cervical lymph node metastasis rate was 64.7% (430/666); the differences in primary tumor volume between patients with or without lymph node metastasis were statistically significant (p < 0.001). Posttreatment distant metastasis occurred in 100 NPC patients, and the five-year distant metastasis-free survival was 84.2%. Univariate and multivariate analyses showed that N classification (p < 0.001) and tumor volume (p = 0.007) were the main factors influencing distant metastasis. Conclusion: Tumor volume was correlated with T classification, cervical lymph node mestastasis and distant metastasis after radiation therapy in nasopharyngeal carcinoma, suggesting that tumor volume should be included into the TNM staging system. [ABSTRACT FROM AUTHOR]

Purpose: To analyze of survival curve and toxicity outcomes for patients treated for nasopharyngeal carcinoma (NPC) by intensity-modulated radiotherapy (IMRT) delivered by helical TomoTherapy (HT). Materials and methods: Since May 2006, 72 patients with primary NPC were treated. In 67 cases PET-CT was used to help delineate the gross tumor volume (GTV); in 4 of these cases distant metastases in bone, mediastinal lymph nodes and unexpected small neck nodes were detected by high SUV uptake. 3, 22, 19, and 27 patients, respectively, had AJCC stage I to IV disease. Patients received a median total dose of 72 Gy to the GTV, 64.8 Gy to the elective PTV, and 54 Gy to the clinically negative neck region. Results: At a median follow-up of 41 months (range 0.2 to 67 months), no patient has recurred locally. Two patients with stage IIb disease, both of whom received chemotherapy, recurred regionally. Ten patients developed distant metastases. One died from progressive disease with initial proved bony metastasis. Two patients with stage IIb disease, both of whom received chemotherapy, experienced neck node recurrence. 5-year locoregional control rate was 97%; freedom from distant metastases was 84.6% at 5 years. No evidence of disease was detected in 13 early stage (I/IIa/IIb) patients who did not receive chemotherapy. Acute grade 3 toxicity occurred in four patients and grade 4 in two patients. Late toxicities were low, with no grade 3+ xerostomia, grade 2 xerostomia in two patients (3%), and grade 3 hearing loss in two patients (3%). Conclusions: HT resulted in excellent long-term disease control and survival in heterogeneous NPC patients. Generally mild acute and late toxicity, with low rates of xerostomia, were obtained. Image-guided HT offers the ability to deliver conformal, OAR-sparing dose distributions to a wide variety of NPC patients with good long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: To evaluate the prognostic value of maximum primary tumor diameter (MPTD) in nasopharyngeal carcinoma (NPC).Methods: Three hundred and thirty-three consecutive, newly-diagnosed NPC patients were retrospectively reviewed. Kaplan-Meier analysis and the log-rank test were used to estimate overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS) and local relapse-free survival (LRFS). Cox proportional hazards regression analysis was used to assess the prognostic value of MPTD.Results: Median follow-up was 66 months (range, 2-82 months). Median MPTD in stage T1, T2, T3 and T4 was 27.9, 37.5, 45.0 and 61.3 mm, respectively. The proportion of T1 patients with a MPTD ≤ 30 mm was 62.3%; 72% and 62.9% of T2 and T3 patients had a MPTD > 30-50 mm, and 83.5% of T4 patients had a MPTD > 50 mm. For patients with a MPTD ≤ 30 mm, > 30-50 mm and > 50 mm, the 5-year OS, FFS, DMFS and LRFS rates were 85.2%, 74.2% and 56.3% (P < 0.001); 87%, 80.7% and 62.8% (P < 0.001); 88.7%, 86.4% and 72.5% (P = 0.003); and 98.2%, 93.2% and 86.3% (P = 0.012), respectively. In multivariate analysis, MPTD was a prognostic factor for OS, FFS and DMFS, and the only independent prognostic factor for LRFS. For T3-T4 patients with a MPTD ≤ 50 mm and > 50 mm, the 5-year OS, FFS and DMFS rates were 70.4% vs. 58.4% (P = 0.010), 77.5% vs. 65.2% (P = 0.013) and 83.6% vs. 73.6% (P = 0.047), respectively. In patients with a MPTD ≤ 30 mm, 5-year LRFS in T1, T2, T3 and T4 was 100%, 100%, 88.9% and 100% (P = 0.172).Conclusions: Our data suggest that MPTD is an independent prognostic factor in NPC, and incorporation of MPTD might lead to a further refinement of T staging. [ABSTRACT FROM AUTHOR]

Purpose: Accumulating evidences indicate that dysregulated microRNAs (miRNA) are involved in cancer tumorigenesis and progression. In the present study, we evaluated the expression of miR-182 in colorectal cancer and adjacent noncancerous tissues and explored its associations with clinicopathological characteristics and prognosis. Methods: Quantitative real-time PCR was used to analyze the expression of miR-182 in 148 pairs of colorectal cancer and adjacent noncancerous tissues. The relationship between miR-182 expression and clinicopathological characteristics in colorectal cancer tissues was estimated using Mann-Whitney U test or Kruskal-Wallis test, as appropriate. We calculated the survival curves and prognostic values of each variable by the Kaplan-Meier method and Cox proportional hazards regression analysis, respectively. Results: The expression of miR-182 was found up-regulated in colorectal cancer tissues compared with adjacent noncancerous tissues ( p < 0.001), and its up-regulation was significantly correlated with large tumor size ( p = 0.016), positive regional lymph node metastasis ( p = 0.008), and advanced tumor-node-metastasis stage ( p = 0.020). Furthermore, Kaplan-Meier analysis demonstrated that high miR-182 expression predicted poor survival ( p = 0.001), and Cox proportional hazards risk analysis indicated that miR-182 was an independent prognostic factor for colorectal cancer. Conclusions: MiR-182 was up-regulated in colorectal cancer tissues and correlated with adverse clinical characteristics and poor prognosis, indicating that miR-182 might be involved in colorectal cancer progression and could be used as a potential prognostic biomarker and therapeutic target in the management of colorectal cancer. [ABSTRACT FROM AUTHOR]

N,N′-Dinitrosopiperazine (DNP) is invovled in nasopharyngeal carcinoma (NPC) development and metastasis, and it shows organ specificity to the nasopharyngeal epithelium. Herein, we demonstrate that DNP induces heat-shock protein (HSP) 70-2 expression in NPC cells (6-10B) at a non-cytotoxic concentration. DNP induced HSP70-2 expression in a dose- and time- dependent manner, but showed no effect on other HSP70 family members. Furthermore, DNP also increased HSP70-2 RNA transcription through directly binding to the hypoxia-responsive elements (HRE) and heat shock elements (HSE) located in the HSP70-2 promoter. DNP-mediated HSP70-2 expression might act through enhancing the transcription of HSP70-2 RNA. Importantly, DNP induced motility and invasion of 6-10B cells dose- and time-dependently, and DNP-mediated NPC metastasis was confirmed in nude mice, which showed high HSP70-2 expression in the metastatic tumor tissue. However, the motility and invasion of NPC cells that were stably transfected using short interfering RNA against HSP70-2 could not effectively induce DNP. These results indicate that DNP induces HSP70-2 expression through increasing HSP70-2 transcription, increases the motility and invasion of cells, and promotes NPC tumor metastasis. Therefore, DNP mediated HSP70-2 expression may be an important factor of NPC-high metastasis. [ABSTRACT FROM AUTHOR]

Background The purpose of this prospective study was to investigate the predictive significance of Raf kinase inhibitory protein (RKIP) in locoregionally advanced nasopharyngeal carcinoma (NPC) and its effect on distant metastasis. Methods The usual immunohistochemical stainings were performed to detect RKIP expression of cancer tissues from 210 patients with advanced NPC. After DNA samples from pretreatment plasma from these patients were extracted, real-time polymerase chain reaction (PCR) was performed to quantitatively analyze plasma Epstein-Barr virus (EBV) DNA. Results RKIP expression was significantly different for different N classifications and WHO pathologic grades, respectively ( p < .05). Cox regression confirmed RKIP and EBV DNA were independent prognostic markers for 5-year distant metastasis-free survival (DMFS). In the high RKIP expression group, chemotherapy had a positive effect on improved DMFS, but not in the low RKIP expression group. Conclusions RKIP could be identified as an independent prognostic factor on DMFS. For each combined treatment modality, the different impact of chemotherapy on distant metastasis might be related to the RKIP expression level. © 2012 Wiley Periodicals, Inc. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

The purpose of this prospective study is to investigate the predictive and prognostic significance of the Raf kinase inhibitory protein (RKIP) in locoregionally advanced nasopharyngeal carcinoma (NPC). Immunohistochemical assays were performed to detect the RKIP protein expression of samples from 212 patients with locoregionally advanced NPC. All patients were assigned randomly into the inductive chemotherapy plus radiation therapy (IC + RT) group, the concurrent chemoradiotherapy (CCRT) group, the inductive chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) group, and the radiation therapy alone (RT) group. The patients in the IC + RT group were treated with IC using 2-3 cycles of cisplatin (80 mg/m) and fluorouracil (500 mg/m), repeated every 3 weeks, followed by radiotherapy. Those in the CCRT group were treated with weekly cisplatin (40 mg/m) for 6-7 cycles during radiotherapy. In the IC + CCRT group, the chemotherapy prior to radiation was similar to the cisplatin-fluorouracil regimen in the IC + RT group, whereas it cisplatin regimen was identical to that in the CCRT group. The results show that RKIP is an independent prognostic factor for 5-year distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS). Patients with high RKIP expression benefited more from reduced metastasis in the IC + RT and the IC + CCRT group, with improved OS and PFS in each treatment group compared with that among patients with low RKIP expression. In the high RKIP expression subgroup, chemotherapy combined with radiotherapy improved the DMFS when compared with the RT group, but this effect was not observed in the low RKIP expression subgroup. RKIP was predictive of distant metastasis with good sensitivity and specificity. Clinically, high RKIP expression inhibited distant metastasis in advanced NPC, and its detection might be used to predict distant metastasis with good sensitivity and specificity. The effect of chemotherapy on distant metastasis in combined chemoradiotherapy might be related to the RKIP expression level. Patients with high RKIP expression showed more improved OS and PFS than their low RKIP expression counterparts. Higher RKIP expression improves the DMFS of patients who receive inductive high-dose cisplatin-based chemoradiotherapy, with or without concurrent cisplatin. Low RKIP expression is also a predictive marker for cancer progression and metastasis, which could be used to stratify patients with high risk of metastasis and death. [ABSTRACT FROM AUTHOR]

Purpose: Platinum-based chemotherapy is the recognized first-line treatment for metastatic nasopharyngeal carcinoma (NPC). However, no standard treatment regimens have been established. This phase II study was designed to evaluate the efficacy and safety of a paclitaxel, cisplatin and 5-FU combination in metastatic and/or recurrent NPC. Methods: Patients with evaluable metastatic and/or recurrent NPC were entered into this study. Treatment consisted of paclitaxel at a dose of 135 mg/m on day 1, cisplatin 25 mg/m/day from day 1 to day 3 and 5-FU-continuous infusion for 120 h at a variable dosage from 600 to 1,000 mg/m/day according to prior radiation. This regimen was repeated every 3 weeks. Results: A total of 95 patients were enrolled; 92 patients were evaluable for response. The overall response and disease control rates were 78.9 and 93.6 %, respectively. At a median follow-up of 24.8 months, the respective median overall survival (OS) and progression-free survival were 22.7 months (95 % CI 18.6-26.9 months) and 8.6 months (95 % CI 7.7-9.5 months). Toxicities were moderate and manageable. Grade 3/4 toxicities included leucopenia (14.7 %), neutropenia (17.9 %), anemia (3.2 %), thrombocytopenia (6.4 %), nausea (4.2 %), vomiting (9.5 %), stomatitis (9.5 %), diarrhea (3.2 %), aminotransferase (2.2 %) and sensory neuropathy (3.2 %). Conclusion: Triplet combination chemotherapy with paclitaxel, cisplatin and 5-FU is an effective and safe option in the front-line treatment for recurrent and/or metastatic NPC. The encouraging results with high response rate and long OS suggest that this regimen might be especially considered where tumor shrinkage is required. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is known for its high incidence of neck lymph node metastasis, which represents poor prognosis. The present study aimed to examine the anti-metastatic properties of Selaginella tamariscina extract (STE) in human nasopharyngeal carcinoma HONE-1 cells in vitro. Methods: Cell viability was examined by MTT assay, whereas cell motility was measured by invasive, migration and would healing assays. Real-time PCR, and promoter assays confirmed the inhibitory effects of STE on matrix metalloproteinase-9 (MMP-9) mRNA level in HONE-1 cells. Results: The STE inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced HONE-1 cell migration and invasion in a concentration-dependent manner. By zymographic and Western blot analyses, STE was shown to inhibit the activities and expression of MMP-9. Treatment of STE on TPA-induced HONE-1 cells inhibited MMP-9 expression and ERK1/2 phosphorylation without affecting JNK and p38 phosphorylation. Conclusions: STE inhibits MMP-9 expression and HONE-1 cell metastasis. Its inhibitory effects may involve the Src/ FAK/ERK 1/2 pathway. STE may have the potential of being an anti-metastatic agent against NPC. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical outcomes and patterns of failure in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiotherapy (IMRT) in Northwest China. Methods and materials: From January 2006 to December 2009, 138 NPC patients were treated at Xijing Hospital. Of them, 25 cases with stage I-II received IMRT only, 113 cases with stage III-IVb received IMRT plus accomplished platinum-based chemotherapy. The IMRT prescribed dose was PTV 68-74 Gy to gross disease in nasopharynx and 66-72 Gy to positive lymph nodes in 30-33 fractions, and high risk and low risk region PTV was 60-63 Gy and 50.4~56 Gy in 30~33 and 28 fractions respectively. Plasma Epstein Barr virus (EBV) DNA load was measured before treatment. The clinical toxicities, outcomes and patterns of failure were observed. Results: The median follow up time was 23 months (range 2 to 53 months). EBV infection positive was only 15.9%. Overall disease failure developed in 36 patients, 99% belonged to stage III/IV disease. Among these, there were 26 distant metastases, 6 local recurrence, and 4 regional recurrence. The 3-year local control rate(LCR), distant metastasis-free survival (MFS), disease-free survival (DFS) and the overall survival (OS) was 93.9%, 79.5%, 70% and 83.1% respectively. Multivariate analyses revealed that age and anemia pre-radiotherapy were independent predictors for OS. Conclusion: IMRT with or without chemotherapy can improve the long term survival of NPC patients in Northwest China. Distant metastasis becomes the main cause of treatment failure. Age and anemia before radiotherapy were the main prognosis factors of NPC patients [ABSTRACT FROM AUTHOR]

Background and objective: No randomized trial has been reported comparing different chemotherapy regimens on disseminated nasopharyngeal carcinoma (NPC). This study aims to compare five cisplatin-based regimens including cisplatin + 5-fluororacil (PF), paclitaxel + cisplatin (TP), gemcitabine + cisplain (GP), paclitaxel + cisplatin + 5-fluororacil (TPF), and bleomycin + cisplatin + 5-fluororacil (BPF) regimen most frequently used as the first-line protocols for metastatic NPC retrospectively. Methods: Eight hundred and twenty-two patients with metastatic NPC were divided into five groups according to the regimen they received. Then, their response rate, toxicity, and long-term survival outcome as well as the prognostic factors were analyzed. Results: The higher response rates in GP and TPF regimens comparing to PF regimen were achieved ( Χ = 4.57, P = 0.033; Χ = 7.04, P = 0.008), as well as in TPF regimen comparing to TP regimen ( Χ = 5.579, P = 0.018). The occurrence rate of the major III-IV grade toxicity was significantly different between the five groups. However, no statistically significant difference was observed in progression-free survival (PFS; P = 0.247) and overall survival ( P = 0.127) among the five groups. Cox multivariate analysis identified the following independent prognostic factors: liver metastases, plasma Epstein Barr Virus (EBV)-DNA level, cycles of chemotherapy, and second-line chemotherapy. Conclusions: PF, TP, and GP are all effective regimens as the first-line chemotherapy for metastatic NPC, which can be well tolerated. Over four cycles of chemotherapy are recommended under no contraindication. Patients should transfer to the second-line regimen after the treatment failure of the first-line chemotherapy. [ABSTRACT FROM AUTHOR]

Background: This study was designed to evaluate the anti-tumor activity and toxicity of single agent pemetrexed in the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) who had been treated with platinum-based chemotherapy. Patients and methods: This is an open-label, single-arm phase II trial. All patients were treated with pemetrexed. Pemetrexed was given at the dosage of 500 mg/m on day 1, with folic acid and vitamin B12 supplementation, each cycle repeated every 3 weeks. Treatment continued until patient had disease progression or unacceptable toxicities. Results: Thirty-five patients were enrolled in this trial. Thirty patients of total were suitable for tumor response assessment. One (2.9 %) patient achieved partial response (PR); 14 (40.0 %) patients, stable disease (SD); and 15 (42.9 %), progressed disease (PD). The progress-free survival (PFS) was 1.5 months (range, 1.5-14.4 months) and median overall survival (OS) was 13.3 months (95 % CI 8.2-18.4 months). Treatment was well tolerated in most patients. Only one patient (2.9 %) experienced grade 4 toxicity of thrombocytopenia and neutropenia. The most seen toxicities were neutropenia (37.1 %), aminotransferase increase (31.4 %), and rash (22.9 %). Conclusions: Although pemetrexed induced a response in a patient, it has limited single-agent activity in advanced NPC patients pretreated with platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

Background Capecitabine is an oral fluoropyrimidine with single-agent activity in metastatic nasopharyngeal carcinoma (NPC). This multicenter phase II study was conducted to investigate the efficacy and safety of capecitabine plus cisplatin as a first-line treatment for metastatic NPC. Methods Patients with metastatic NPC received cisplatin 100 mg/m2 day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 6-8 cycles. The primary endpoint was overall response rate. Results Forty-four patients were enrolled; 39 patients were evaluable for efficacy. The overall response rate was 53.8% (95% confidence interval [CI], 37%-70%), including 1 complete response. Median time to tumor progression was 7.3 months (95% CI, 5.6-9.9 months) and median overall survival was 28.0 months (95% CI, 14.5 months-not reached). Common grade 3/4 adverse events were neutropenia (50%), vomiting (11%), thrombocytopenia (9%), and nausea (7%). Conclusions Capecitabine plus cisplatin is an active first-line combination in metastatic NPC that requires a short hospital stay. © 2011 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the efficacy and toxicity of cisplatin plus gemcitabine chemotherapy and intensity-modulated radiation therapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 54 patients (stage IIB: 6, stage III: 24, stage IVA-B: 24) with locoregionally advanced NPC were treated with cisplatin 25 mg/m intravenously on days 1-3, and gemcitabine 1,000 mg/m of 30-min intravenous infusion on days 1 and 8, every 3 weeks for two cycles as neoadjuvant chemotherapy. Two cycles of the same regimen were administered as adjuvant chemotherapy 28 days after the end of radiotherapy. The prescription doses were 66-70.4 Gy to the gross tumor volume (GTV), 66 Gy to positive neck nodes, 60 Gy to the high-risk clinical target volume and 54 Gy to the low-risk clinical target volume. The overall response rate to neoadjuvant chemotherapy was 88.6%. Toxicity was mainly grade 1/2 myelosuppression. All patients completed IMRT. The median follow-up duration was 30 months (range, 12-60 months). The 3-year locoregional control, metastasis-free rate and overall survival were 94.9%, 86.2% and 87.7%, respectively. Severe late toxicities included grade 3 trismus in one patient, grade 3 hearing impairment in one patient and cranial nerve XII palsy in one patient. No grade 4 late toxicities were observed. A combination of cisplatin plus gemcitabine chemotherapy and intensity-modulated radiotherapy for locoregionally advanced NPC is well-tolerated, convenient, effective and warrants further studies. [ABSTRACT FROM AUTHOR]

The significance of SOX2 in nasopharyngeal carcinoma (NPC), a tumor associated with Epstein-Barr virus (EBV), remains unclear. Here, we reported that, in the univariate analysis, SOX2 expression was correlated with a poorer distant metastasis-free survival (DMFS). The EBV-VCA/IgA titers in patients with NPC were also associated with a poorer overall survival (OS). Patients with NPC, who had both strong staining of SOX2 and high titers of EBV-VCA/IgA, had the poorest prognoses. Therefore, SOX2 or the combination of the SOX2 expression level and EBV-VCA/IgA titers could be valuable to predict distant metastasis or the prognosis of NPC. [ABSTRACT FROM AUTHOR]

Breast cancer that lacks expression of estrogen/progesterone receptors and overexpression of the human epidermal growth factor receptor2 (HER2), i.e. triple-negative breast cancer (TNBC), is not amenable to current targeted therapies and carries a poor prognosis. This review discusses the natural history of TNBC and published literature in the relevant treatment landscape, with a focus on newer therapies. Compared with other subtypes of breast cancer, TN tumors have higher response rates to neoadjuvant chemotherapy; however, this advantage is not clearly translated into the metastatic setting and has not improved these patients' overall survival. Numerous cytotoxic and targeted strategies have demonstrated efficacy or are under investigation. Strategies showing promise in this difficult-to-treat group of patients include cytotoxic therapy with platinum-containing agents, ixabepilone, and novel targeted approaches such as poly(ADP-ribose) polymerase inhibitors. [ABSTRACT FROM AUTHOR]

Background: Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene. This study aimed to investigate the impact of BRMS1 on metastasis in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic significance of BRMS1 in NPC patients. Methods: BRMS1 expression was examined in NPC cell lines using quantitative reverse transcription-polymerase chain reaction and Western blotting. NPC cells stably expressing BRMS1 were used to perform wound healing and invasion assays in vitro and a murine xenograft assay in vivo. Immunohistochemical staining was performed in 274 paraffin-embedded NPC specimens divided into a training set (n = 120) and a testing set (n = 154). Results: BRMS1 expression was down-regulated in NPC cell lines. Overexpression of BRMS1 significantly reversed the metastatic phenotype of NPC cells in vitro and in vivo. Importantly, low BRMS1 expression was associated with poor distant metastasis-free survival (DMFS, P < 0.001) and poor overall survival (OS, P < 0.001) in the training set; these results were validated in the testing set and overall patient population. Cox regression analysis demonstrated that low BRMS1 expression was an independent prognostic factor for DMFS and OS in NPC. Conclusions: Low expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in NPC patients. [ABSTRACT FROM AUTHOR]

Abnormalities in the expression and functional activity of cell adhesion molecules are implicated in the development and progression of the majority of colorectal cancers (CRC). Cell-cell adhesion molecule E-cadherin regulates cell polarity, differentiation, proliferation and migration through its intimate association to the actin cytoskeletal network. During colorectal carcinogenesis changes in intercellular adhesion and dynamic rearrangements in the actin cytoskeleton result in altered signalling and migration with loss of contact inhibition. The adenomatous polyposis coli (APC) protein, besides its established role in the β catenin/Wnt signalling pathway, can coordinate microtubule and actin organization during cell migration. The actin-bundling protein Fascin promotes cell motility and is overexpressed in CRC. Based on recent molecular and pathological studies, this review focusses on the role of these molecules sharing the common feature of being associated with the cytoskeletal network during colorectal carcinogenesis and metastasis. The potential use of these molecules as prognostic markers and/or therapeutic targets will also be discussed. [ABSTRACT FROM AUTHOR]

Retropharyngeal lymph node (RPLN) metastasis of primary head and neck cancer often receives less consideration than lymph node metastasis in the neck. With improvements in imaging techniques and reports of surgical pathology, there is an improved understanding of the risk and subsequently the need for treatment of RPLNs. The rates of RPLN metastasis from carcinomas of the nasopharynx, oropharynx, hypopharynx, postcricoid region, maxillary sinus, and cervical esophagus are sufficiently high to warrant routine treatment, either electively or therapeutically, of this region. Through improved diagnostic techniques and heightened awareness of RPLN metastasis, patients at risk of having these metastases can be treated more effectively. © 2010 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

The management of tumor cell invasion and metastasis is instrumental in cancer therapy, since metastases are the prime reason for cancer patient mortality. Various cellular mechanisms and underlying molecular pathways relevant for metastasis have been identified so far, providing a basis for antimetastatic drugs. MicroRNAs (miRNAs) are highly conserved, small noncoding RNA molecules that have been shown to regulate various cellular processes by interfering with protein expression through posttranscriptional repression or mRNA degradation. More importantly, beyond their roles in physiological processes, many miRNAs are aberrantly expressed in various pathologies including cancer and regulate tumor- and metastasis-associated genes. Their pivotal role in metastasis has emerged only recently. After an introduction into the mechanisms of miRNA action, this review article describes the roles of miRNAs in cancer invasion and metastasis. Various miRNAs are discussed with regard to their upstream regulators, downstream target genes, and pro-/antimetastatic effects. A table provides a comprehensive overview of miRNAs that are misregulated/relevant in metastasis and the current knowledge regarding their underlying molecular effects. Furthermore, therapeutic approaches based on miRNAs, either as drugs or as therapeutic targets, are described prior to the discussion of the delivery of miRNA-based therapeutics as novel strategy in antimetastatic treatment. [ABSTRACT FROM AUTHOR]

Recent researches have shed light on the biological importance of microRNAs (miRNAs) in colorectal cancer (CRC) genesis, progression and response to treatments. The potential utility of miRNAs in the preclinical stage have been explored and investigated. In this review, we explored the literature and reviewed the cutting edge progress in the discovery of noninvasive plasma and faecal miRNAs for CRC early diagnosis, as well as their measurability and predictability. We also discussed the utility of miRNAs as novel prognostic and predictive markers, and their association with CRC clinical phenotypes including recurrence, metastasis and therapeutic outcomes. Finally, we summarised miRNA-related single-nucleotide polymorphisms and their potential influence on sporadic CRC susceptibility and therapeutic response. In conclusion, the use of miRNAs as biomarker for CRC is still in its infancy and need further characterisation and evaluation. [ABSTRACT FROM AUTHOR]

Background: Lung metastases arising from nasopharyngeal carcinomas (NPC) have a relatively favourable prognosis. The purpose of this study was to identify the prognostic factors and to establish a risk grouping in patients with lung metastases from NPC.Methods: A total of 198 patients who developed lung metastases from NPC after primary therapy were retrospectively recruited from January 1982 to December 2000. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Actuarial survival rates were plotted against time using the Kaplan-Meier method, and log-rank testing was used to compare the differences between the curves.Results: The median overall survival (OS) period and the lung metastasis survival (LMS) period were 51.5 and 20.9 months, respectively. After univariate and multivariate analyses of the clinical variables, age, T classification, N classification, site of metastases, secondary metastases and disease-free interval (DFI) correlated with OS, whereas age, VCA-IgA titre, number of metastases and secondary metastases were related to LMS. The prognoses of the low- (score 0-1), intermediate- (score 2-3) and high-risk (score 4-8) subsets based on these factors were significantly different. The 3-, 5- and 10-year survival rates of the low-, intermediate- and high-risk subsets, respectively (P < 0.001) were as follows: 77.3%, 60% and 59%; 52.3%, 30% and 27.8%; and 20.5%, 7% and 0%.Conclusions: In this study, clinical variables provided prognostic indicators of survival in NPC patients with lung metastases. Risk subsets would help in a more accurate assessment of a patient's prognosis in the clinical setting and could facilitate the establishment of patient-tailored medical strategies and supports. [ABSTRACT FROM AUTHOR]

The article offers information on the research conducted on the factors that determine the survival of nasopharyngeal carcinoma, with lung metastasis. It states that lung metastasis was determined by chest X-ray or computed tomography (CT), however, when this was insufficient to confirm the metastasis, pathological confirmation by biopsy was carried out. It mentions that disease-free interval (DFI) more than 1-year and the combined modality treatment are good prognostic factors.

Background: Combination chemotherapy is standard treatment for metastatic colorectal cancer (MCRC). The aim of this study was to determine the efficacy and safety of capecitabine+irinotecan (2-weekly schedule), as first-line therapy of MCRC.Methods: Patients received irinotecan 175 mg m(-2) on day 1 and oral capecitabine 1000 mg m(-2) twice daily on days 2-8 every 2 weeks. For patients aged > or =65 years, the starting doses of irinotecan and capecitabine were reduced to 140 and 750 mg m(-2), respectively.Results: A total of 53 patients were enrolled: 29 (55%) were > or =65 years old. In an intention-to-treat analysis, complete response was achieved in three patients for an overall response rate (ORR) of 32%. The disease control rate (ORR + stable disease) was 66% and the median duration of response was 7.3 months. Median time to progression and overall survival were 9.0 and 19.2 months, respectively. Grade 4 neutropenia was reported in one patient: no other grade 4 toxicities were recorded. Grade 3 diarrhoea occurred in 8 (15%) patients and grade 1-2 hand-foot syndrome in 7 (13%) patients.Conclusion: Capecitabine and irinotecan, given every 2 weeks, as first-line treatment of MCRC is an active regimen with a manageable toxicity profile, even in older patients. [ABSTRACT FROM AUTHOR]

Cisplatin combined with 5-fluorouracil (5-Fu) is widely used in the management of advanced nasopharyngeal carcinoma (NPC). However, catheters and pumps are necessary for the continuous infusion of 5-Fu, which add to the cost, immobility and inconvenience of treatment. Capecitabine, an oral fluoropyrimidine, is a potentially more active and more convenient substitute to 5-Fu. A phase II study was conducted to evaluate the efficacy and safety of a capecitabine and cisplatin combination in metastatic NPC. In the multicenter, open-label, single-arm phase II study, patients with metastatic NPC who previously received no palliative chemotherapy were enrolled. Patients received oral capecitabine (1,000 mg/m2 twice daily from day 1 to 14) and intravenous cisplatin (80 mg/m2, day1) every 3 weeks. A total of 48 patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events. There were 3 patients (6.3%) with complete response and 27 patients (56.3%) with partial response, giving an overall response rate of 62.5% (95% CI, 49.1–76.4%). The median duration of response in the 30 responding patients was 7.5 months (range 1.4–22.4 months). With a median follow-up period of 13.3 months (range 2.3–50 months), the median time to progression and median overall survival for all patients were 7.7 months (95% CI, 6.3–9.2 months) and 13.3 months (95% CI, 9.4–17.2 months), respectively. Toxicities were moderate and manageable. Grade 3/4 toxicities included neutropenia (14.6%), anemia (4.2%) and thromocytopenia (2.1%), nausea (8.3%), vomiting (10.4%), diarrhea (8.3%), stomatitis (6.3%) and hand–foot syndrome (HFS) (4.2%). The combination of capecitabine and cisplatin is active and well tolerated as a first-line therapy for patients with metastatic NPC. [ABSTRACT FROM AUTHOR]