m6A-enriched lncRNA LINC00839 promotes tumor progression by enhancing TAF15-mediated transcription of amine oxidase AOC1 in nasopharyngeal carcinoma.

Dysregulation of long noncoding RNAs (lncRNAs) contributes to tumorigenesis by modulating specific cancer-related pathways, but the roles of N6-methyladenosine (m6A)-enriched lncRNAs and underlying mechanisms remain elusive in nasopharyngeal carcinoma (NPC). Here, we reanalyzed the previous genome-wide analysis of lncRNA profiles in 18 pairs of NPC and normal tissues as well as in ten paired samples from NPC with or without post-treatment metastases. We discerned that an oncogenic m6A-enriched lncRNA, LINC00839, which was substantially upregulated in NPC and correlated with poor clinical prognosis, promoted NPC growth and metastasis both in vitro and in vivo. Mechanistically, by using RNA pull-down assay combined with mass spectrometry, we found that LINC00839 interacted directly with the transcription factor, TATA-box binding protein associated factor (TAF15). Besides, chromatin immunoprecipitation and dual-luciferase report assays demonstrated that LINC00839 coordinated the recruitment of TAF15 to the promoter region of amine oxidase copper-containing 1 (AOC1), which encodes a secreted glycoprotein playing vital roles in various cancers, thereby activating AOC1 transcription in trans. In this study, potential effects of AOC1 in NPC progression were first proposed. Moreover, ectopic expression of AOC1 partially rescued the inhibitory effect of downregulation of LINC00839 in NPC. Furthermore, we showed that silencing vir-like m6A methyltransferase-associated (VIRMA) and insulin-like growth factor 2 mRNA-binding proteins 1 (IGF2BP1) attenuated the expression level and RNA stability of LINC00839 in an m6A-dependent manner. Taken together, our study unveils a novel oncogenic VIRMA/IGF2BP1-LINC00839-TAF15-AOC1 axis and highlights the significance and prognostic value of LINC00839 expression in NPC carcinogenesis.

Prognostic significance of platelet­to­albumin ratio in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: a retrospective study of 858 cases.

BACKGROUND: Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. METHODS: We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram's predictive accuracy to rigorous independent validation. RESULTS: The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28-0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64-0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65-0.74). CONCLUSIONS: In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.

Identification of two microRNA signatures in whole blood as novel biomarkers for diagnosis of nasopharyngeal carcinoma.

BACKGROUND: Early diagnosis is critical to reduce the mortality caused by nasopharyngeal carcinoma (NPC). MicroRNAs (miRNAs) are dysregulated and play important roles in carcinogenesis. Therefore, this study aimed to identify diagnostically relevant circulating miRNA signatures in patients with NPC. METHODS: Total RNA was extracted from whole blood samples obtained from 120 patients with NPC, 30 patients with head-neck tumors (HNT), and 30 healthy subjects (HSs), and examined by using a custom microarray. The expression levels of four miRNAs identified by using the microarray were validated with quantitative real-time reverse transcription polymerase chain reaction. The 120 patients with NPC and 30 HSs were randomly assigned to training group-1 and validation group-1, respectively. By using significance analysis of microarray (SAM), the specific miRNA expression profiles in whole blood from patients with NPC are obtained. By using lasso regression and adaptive boosting, a diagnostic signature was identified in training group-1, and its accuracy was verified in validation group-1. By using the same methods, another signature to distinguish patients with NPC from those with HNT and HSs was identified in training group-2 and confirmed in validation group-2. RESULTS: There were 117 differentially expressed miRNAs (upregulated and downregulated fold change ≥ 1.5) between the patients with NPC and HSs, among which an 8-miRNA signature was identified with 96.43% sensitivity and 100% specificity [area under the curve (AUC) = 0.995] to diagnose NPC in training group-1 and 86.11% sensitivity and 88.89% specificity (AUC = 0.941) in validation group-1. Compared with traditional Epstein-Barr virus (EBV) seromarkers, this signature was more specific for NPC. Furthermore, a 16-miRNA signature to differentiate NPC from HNT and HS (HNT-HS) was established from 164 differentially expressed miRNAs, which diagnosed NPC and HNT-HS with 100% accuracy (AUC = 1.000) in training group-2 and 87.04% (AUC = 0.924) in validation group-2. CONCLUSIONS: The present study identified two miRNA signatures for the highly accurate diagnosis and differential diagnosis of patients with NPC from HSs and patients with HNT. The identified miRNAs might represent novel serological biomarkers and potential therapeutic targets for NPC.

Efficacy of controlled-release oxycodone for reducing pain due to oral mucositis in nasopharyngeal carcinoma patients treated with concurrent chemoradiotherapy: a prospective clinical trial.

BACKGROUND: Pain due to oral mucositis (OM) is a major problem during concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients. METHODS: We enrolled 56 NPC patients receiving CCRT and allocated them into two groups: moderate pain group (n = 27) and a severe pain group (n = 29) according to the degree of pain reported (moderate = numerical rating scale (NRS) score 4-6 or severe = NRS score 7-10) at initiation of controlled-release oxycodone (CRO) treatment. RESULTS: Total dose of CRO was significantly higher in severe pain patients than in moderate pain patients (791.60 ± 332.449 mg vs. 587.27 ± 194.940 mg; P = 0.015). Moderate pain patients had significantly better quality of life (P = 0.037), lower weight loss (P = 0.030) and more active CCRT response (90.9% vs. 64.0%; P = 0.041). Although 24-h pain control rate was comparable in the two groups (85.2% vs. 86.2%; P = 0.508), the moderate pain group score eventually stabilized at ~ 2 vs. 3 in the severe pain group (P < 0.001); the titration time to reach bearable pain (NRS ≤ 3) was also significantly shorter in moderate pain patients (2.45 ± 0.60 days vs. 3.60 ± 1.98 days; P = 0.012). Incidence of adverse events was comparable in both groups. CONCLUSIONS: The study findings suggest that early introduction of low-dose CRO at the moderate pain stage could help reduce the total dose required, provide better pain control, improve quality of life, and enhance CCRT response.

Predicting Survival of Patients with Nonmetastatic Breast Cancer Based on Fibrinogen-to-Albumin Ratio and Lymphocyte-to-Monocyte Ratio: A Nomogram-Based Assessment.

Background: Parameters of systemic inflammation have received attention as prognostic surrogates in various malignant tumors. Fibrinogen-to-albumin ratio (FAR) and lymphocyte-to-monocyte ratio (LMR) correlate with tumor growth and dissemination. We aimed to bring the combination of FAR and LMR (FAR-LMR) together to establish novel nomograms for survival and recurrence in nonmetastatic breast cancer patients. Methods: We retrospectively recruited 461 female patients with nonmetastatic breast cancer from January 2011 to December 2013 in our hospital and randomly assigned them into the training cohort (N = 318) and the validation cohort (N = 143). The potential predictive factors for overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Cox proportional hazards models and log-rank test. Results: Elevated FAR was associated with poor OS (p < 0.001) and DMFS (p = 0.02), whereas increased LMR was associated with satisfactory OS (p = 0.01) and LRFS (p = 0.01). High FAR combined with low LMR was associated with less favorable OS (p = 0.001), LRFS (p = 0.005), and DMFS (p = 0.003) Based on multivariate analysis, FAR-LMR, tumor size, lymph node metastasis, age, and pathologic status contributed to prognostic nomograms of OS, DMFS, and LRFS. Nomograms presented exceptional performance for 3-, 5-, and 8-year OS, DMFS, and LRFS prediction compared with clinical TNM stage. The C-index was significantly higher than that of TNM stage, either of FAR or LMR (3-year: 0.709 vs. 0.621 vs. 0.544 vs. 0.641, 5-year: 0.761 vs. 0.597 vs. 0.605 vs. 0.677, 8-year: 0.84 vs. 0.62 vs. 0.539 vs. 0.623). Conclusions: We developed and validated a convenient predictive model for the survival outcomes of patients with nonmetastatic breast cancer. The nomograms can be utilized as auxiliary tools to provide prognostic information.

Prognostic significance of the novel nutrition-inflammation marker of lymphocyte-C-reactive protein ratio in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy.

Background: Recent studies indicate that the novel lymphocyte-C-reactive protein ratio (LCR) is strongly associated with the survival of various tumors, but its prognostic value in nasopharyngeal carcinoma (NPC) is understudied. This study aimed to explore the relationship between LCR and overall survival (OS) in NPC and develop a predictive model. Methods: A total of 841 NPC patients who received concurrent chemoradiotherapy (CCRT) between January 2010 and December 2014 were retrospectively enrolled and randomly divided into a training cohort (n = 589) and a validation cohort (n = 252), and 122 patients between January 2015 and March 2015 were included as an additional validation cohort. Univariate and multivariate Cox analyses were performed to identify variables associated with OS and construct a predictive nomogram. The predictive accuracy of the nomogram was evaluated and independently validated. Results: The LCR score differentiated NPC patients into two groups with distinct prognoses (HR = 0.53; 95% CI: 0.32-0.89, P = 0.014). Multivariate analysis showed that age, T stage, N stage, EBV-DNA status, and LCR score were independently associated with OS, and a predictive nomogram was developed. The nomogram had a good performance for the prediction of OS [C-index = 0.770 (95% CI: 0.675-0.864)]. and outperformed the traditional staging system [C-index = 0.589 (95% CI: 0.385-0.792)]. The results were internally and additionally validated using independent cohorts. Conclusion: The pretreatment LCR could independently predict the overall survival in NPC patients. A novel LCR-based prognostic model of an easy-to-use nomogram was established, and it outperformed the conventional staging system in terms of predictive power. Further external verification remains necessary.

A Model Combining Skeletal Muscle Mass and a Hematological Biomarker to Predict Survival in Patients With Nasopharyngeal Carcinoma Undergoing Concurrent Chemoradiotherapy.

BACKGROUND: Using the current tumor lymph node metastasis (TNM) staging system to make treatment decisions and predict survival in patients with nasopharyngeal carcinoma (NPC) lacks sufficient accuracy. Patients at the same stage often have different survival prognoses. METHODS: In the current study 802 NPC patients who underwent concurrent radiotherapy and chemotherapy from January 2010 to December 2014 at Sun Yat-sen University Cancer Center in China were retrospectively assessed. The optimal cut-off points for skeletal muscle index (SMI) and monocyte-to-lymphocyte ratio (MLR) were determined via receiver operating characteristic curves. SMI-MLR (S-M) grade and a nomogram were developed and used as clinical indicators in NPC patients. The consistency index (C-index) and a calibration curve were used to measure the accuracy and discriminative capacity of prediction. RESULTS: The predictive performance of S-M grade was better than that of TNM staging (C-index 0.639, range 0.578-0.701 vs. 0.605, range 0.545-0.665; p = 0.037). In multivariate analysis S-M grade, T stage, and N stage were independent prognostic factors. These three factors were then combined, yielding a nomogram with a C-index of 0.71 (range 0.64-0.77), indicating good predictive capacity. CONCLUSION: We developed and validated a prognostic parameter, S-M grade, which increased prediction accuracy significantly and can be combined with TNM staging to predict survival in patients with NPC undergoing concurrent chemoradiotherapy.

Modeling Sarcopenia to Predict Survival for Patients With Nasopharyngeal Carcinoma Receiving Concurrent Chemoradiotherapy.

BACKGROUND: The present study aimed to construct a prognostic nomogram including Epstein-Barr virus DNA (EBV-DNA) and sarcopenia in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). METHODS: In this retrospective analysis, we studied 1,045 patients with NPC who had been treated with CCRT between 2010 and 2014. Sarcopenia was determined using routine pre-radiotherapy computed tomography scans of the third cervical vertebrae. A new S-E grade was constructed using a receiver-operating characteristic (ROC) curve analyses determined cutoff values of sarcopenia and plasma EBV-DNA. The nomogram was developed base on the sarcopenia-EBV (S-E) grade and traditional prognostic factors. A calibration curve, time-dependent ROC, decision curve analysis, and the concordance index (C-index) determined the accuracy of prediction and discrimination of the nomogram, and were compared with TNM staging system and a traditional nomogram. RESULTS: Patient survival was significantly different when sarcopenia (P < 0.001) or EBV-DNA (P = 0.001) were used and they continued to be independent prognostic factors for survival upon univariate (P < 0.001, P = 0.002, respectively) and multivariate (P < 0.001, P = 0.015, respectively) analyses. Predicting overall survival (OS) was more accurate using the S-E grade than using TNM staging and sarcopenia or EBV-DNA alone. Nomogram B (model with sarcopenia) or nomogram A (model without sarcopenia) were then developed based on the identified independent prognostic factors. Comparing nomogram prediction with actual observation showed good agreement among the calibration curves for probability of 1-, 3-, and 5-year OS. Predicted survival (C-index = 0.77) of nomogram B was statistically higher than that of nomogram A (0.676, P = 0.020) and TNM staging (0.604, P < 0.001). Risk group stratification could distinguish between survival curves within respective TNM stages (all stages, P < 0.001; stage III, P < 0.001; stage IV, P = 0.002). CONCLUSIONS: The sarcopenia-EBV DNA nomogram allowed more accurate prediction of prognosis for patients with NPC receiving CCRT.

IQGAP3 Overexpression Correlates With Poor Prognosis and Radiation Therapy Resistance in Breast Cancer.

Background: IQ motif-containing GTPase activating protein 3 (IQGAP3), the latest identified member of the IQGAP family, may act as a crucial factor in cancer development and progression; however, its clinical value in breast cancer remains unestablished. We explored the correlation between IQGAP3 expression profile and the clinicopathological features in breast cancer. Methods: IQGAP3 mRNA and protein levels were detected in breast cancer cell lines and tumor tissues by real-time PCR and western blotting and compared to the normal control groups. Protein expression of IQGAP3 was also evaluated immunohistochemically in archived paraffin-embedded specimens from 257 breast cancer patients, and the associations between IQGAP3 expression level, clinical characteristics, and prognosis were analyzed. We assessed the relationship between IQGAP3 expression and sensitivity to radiation therapy which was determined by subgroup analysis. Results: IQGAP3 was significantly upregulated in breast cancer cell lines and human tumor tissues at both the mRNA and protein level compared to controls. Additionally, high levels of IQGAP3 expression were detected in 110/257 (42.8%) of archived paraffin-embedded breast cancer specimens. High IQGAP3 expression level was significantly related to clinical stage (p = 0.001), T category (p = 0.002), N category (p = 0.001), locoregional recurrence (p = 0.002), distant metastasis (p = 0.001), and vital status (p = 0.001). Univariate and multivariate statistical analysis showed that IQGAP3 expression was an independent prognostic factor among all 257 breast cancer patients in our cohort (p = 0.003, p = 0.001). Subgroup analysis revealed IQGAP3 expression correlated with radioresistance and was also an independent predictor of radiotherapy outcome. Conclusion: Our findings suggest that high IQGAP3 expression predicts poor prognosis and radioresistance in breast cancer. Therefore, IQGAP3 may be a reliable prognostic biomarker in breast cancer and could be used to identify patients who may benefit from radiotherapy.

Erratum to prognostic value of skeletal muscle index and monocyte-to-lymphocyte ratio for lymph node-positive breast cancer patients after mastectomy.

[This corrects the article DOI: 10.21037/atm.2019.11.37.].

Prognostic Value of Preoperative Systemic Immune-Inflammation Index in Breast Cancer: A Propensity Score-Matching Study.

Purpose: It was reported that the novel preoperative systemic immune-inflammation index (SII) can predict survival in cases of many malignant tumors. However, the prognostic significance of preoperative SII in breast cancer remains unclear. The purpose of this study was to investigate the relationship between SII and survival in breast cancer patients. Methods: Breast cancer patients (1,026) who underwent a mastectomy at Sun Yat-sen University Cancer Center were retrospectively studied. The SII was determined using the following formula: neutrophil count × platelet count/lymphocyte count. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value for SII. Propensity score matching (PSM) was applied to develop comparable cohorts of high SII group and low SII group. Results: A total of 1,026 patients were included as the primary cohort, and 894 patients were matched and regarded as the matched cohort. Patients were divided into two groups based on SII value: SII <601.7 and high SII >601.7. In the primary cohort, the 5-years overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) rates for high SII group and low SII group were (85.6% vs. 91.3%, P = 0.016), (95.8% vs. 96.4%, P = 0.684), and (83.5% vs. 90.6%, P = 0.007), respectively. Univariate analysis showed that histological type, T stage, N stage, PR, HER2, Ki67, and SII all showed significant associations with OS; and histological type, T stage, N stage, and SII all showed significant associations with DMFS. Multivariate survival analysis revealed that SII can independently predict OS (P = 0.017) and DMFS (P = 0.007). Similar results were found in PSM cohort. Conclusions: Preoperative SII may be a reliable predictor of OS and DMFS in patients with operable breast cancer to provide personalized prognostication and assist in formulation of the clinical treatment strategy.

Sarcopenia is associated with higher toxicity and poor prognosis of nasopharyngeal carcinoma.

BACKGROUND: Given the growing evidence that sarcopenia is associated with toxicity and survival in various cancers, we investigated its significance in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). METHODS: In this retrospective analysis, we studied 862 NPC patients who had received CCRT between 2010 and 2014. Sarcopenia was determined using routine pre-radiotherapy computed tomography (CT) simulation scans at the third cervical vertebral level. Receiver-operating characteristic curve analyses were used to determine the optimal cutoff values. Propensity score matching (PSM) was applied to develop comparable cohorts of patients with or without sarcopenia. RESULTS: A total of 862 patients were included as the primary cohort, and 308 patients were matched and regarded as the matched cohort. In the primary cohort, the 5-year overall survival (OS), locoregional recurrence-free survival, and distant metastasis-free survival (DMFS) rates for the sarcopenia group versus non-sarcopenia group were 78.2% versus 93.6% (p < 0.001), 89.4% versus 87.9% (p = 0.918), and 82.5% versus 89.0% (p = 0.007), respectively. Univariate and multivariate survival analyses revealed that sarcopenia was an independent predictor of OS (p < 0.001 and p < 0.001) and DMFS (p = 0.009, p = 0.034). Patients with sarcopenia experienced significantly higher rates of treatment-related toxicities compared with patients without sarcopenia (p = 0.032). In addition, patients with sarcopenia also experienced significantly worse treatment response than those without sarcopenia (p = 0.004). Similar results were found in a PSM cohort. CONCLUSION: The current findings support that sarcopenia is a promising indicator for predicting clinical outcomes in NPC patients receiving CCRT. A simple and rapid analysis on CT simulation images can provide information about the therapeutic toxicity and survival prognosis, consequently guiding personalized multi-modality interventions during CCRT.

The preoperative systemic inflammation response index (SIRI) independently predicts survival in postmenopausal women with breast cancer.

The recently developed preoperative systemic inflammation response index (SIRI) was reported as a useful biomarker that could predict survival in certain types of malignant tumors. However, the prognostic value of preoperative SIRI in postmenopausal breast cancer remains unclear. This study aimed to explore the relationship between SIRI and survival in postmenopausal patients with breast cancer. A total of 390 postmenopausal patients with breast cancer who underwent a mastectomy at Sun Yat-sen University Cancer Center were retrospectively studied. SIRI was based on peripheral neutrophil, monocyte, and lymphocyte counts, calculated as: neutrophil count × monocyte count/lymphocyte count. The best cut-off value for SIRI was determined using receiver operating characteristic curve analysis. Patients were divided into 2 groups:Low SIRI < 0.54 and high SIRI > 0.54. High SIRI was significantly related to progesterone receptor status. Kaplan-Meier survival analysis showed that T stage, N stage, clinical stage, carcinoembryonic antigen, estrogen receptor, progesterone receptor, endocrinotherapy, and SIRI were significantly correlated with overall survival (OS). Multivariate analysis showed that SIRI could also independently predict OS. Preoperative SIRI may be a reliable predictor of OS in postmenopausal patients with operable breast cancer to provide personalized prognostication and to assist in the formulation of a clinical treatment strategy.

Prognostic significance of the skeletal muscle index and an inflammation biomarker in patients with breast cancer who underwent postoperative adjuvant radiotherapy.

BACKGROUND: Given the growing evidence that sarcopenia and inflammation influence the survival of patients with cancer, we evaluated the prognostic significance of the skeletal muscle index (SMI) combined with an inflammation marker in patients with breast cancer who underwent postoperative adjuvant radiotherapy. METHODS: We conducted a retrospective analysis of 301 patients with breast cancer who received postoperative adjuvant radiotherapy between 2010 and 2012. The SMI was measured using preradiotherapy computed tomography (CT) simulation images at the level of the fourth thoracic vertebra (T4). Receiver operating characteristic curve analyses were used to determine the optimal cutoff values for the SMI and inflammatory marker. Patients were divided into 2 groups (high SMI and low SMI), based on the SMI cutoff of 10.57 cm2/m2. RESULTS: Patients in the high-SMI group had a median overall survival (OS) of 62.4 months, which was significantly shorter than those in the low-SMI group, with a median OS of 68.5 months (P = 0.025). Patients in the high-SMI group had a median recurrence-free survival (RFS) of 62.3 months, which was shorter but not significantly than the median RFS of 65.2 months of the low-SMI group (P = 0.159). Univariate and multivariate survival analyses revealed SMI was an independent predictor of OS (P = 0.044). The SMI-MLR combination was found to be an independent predictor of OS (P = 0.006) and RFS (P = 0.009). CONCLUSIONS: The current findings support the SMI as a promising indicator for predicting clinical outcomes in patients with breast cancer receiving postoperative adjuvant radiotherapy. A high SMI accompanied by systemic inflammation was significantly associated with reduced OS and RFS.

Prognostic value of skeletal muscle index and monocyte-to-lymphocyte ratio for lymph node-positive breast cancer patients after mastectomy.

BACKGROUND: We aimed to assess the prognostic value of the skeletal muscle index (SMI) and monocyte-to-lymphocyte ratio (MLR) in lymph node-positive breast cancer patients after mastectomy. METHODS: We enrolled female lymph node-positive breast cancer patients who had undergone mastectomy between January 2011 and December 2013 with lymph node metastasis. Skeletal muscle tissue was measured using computed tomography (CT), and the patients were grouped based on the receiver operating characteristic curves to obtain the cut-off point for SMI; similarly, the optimal cutoff point for the MLR was obtained. Survival analysis was chiefly performed to determine overall survival (OS) among the patients. RESULTS: The median age of the 97 included patients was 46 years (range, 27-73 years), whereas the median follow-up duration was 62.5 months. Of these patients, 71 exhibited low SMI and 66 exhibited high MLR. Kaplan-Meier curves indicated that low SMI (5-year OS, 97.2% vs. 84.6%; log-rank P=0.021) and low MLR (5-year OS, 98.5% vs. 83.9%; log-rank P=0.004) were associated with better OS. Moreover, patients with both high SMI and MLR (high SMLR) had significantly worse OS (5-year OS, 66.7% vs. 96.6%; log-rank P<0.001), relative to the low SMLR group. Multivariate analysis indicated that patients with low SMI had a lower overall dying risk, relative to those with high SMI [hazard ration (HR), 0.188; P=0.038], whereas patients with high MLR had a higher risk of death as compared to those with low MLR (HR, 7.152; P=0.021). Furthermore, SMLR was an independent prognostic factor of poor OS (HR, 13.272; P=0.001). CONCLUSIONS: Low SMI and low MLR are both associated with better OS in lymph node-positive breast cancer patients after mastectomy. SMI combined with MLR (SMLR) may be powerful prognosis factor for OS among these patients.

When the Loss Costs Too Much: A Systematic Review and Meta-Analysis of Sarcopenia in Head and Neck Cancer.

Purpose: Whether or not skeletal muscle mass (SMM) depletion, known as sarcopenia, has significant negative effects on the prognosis of patients with head and neck cancer (HNC) is both new and controversial. In this meta-analysis, we aimed to determine the prognostic significance of sarcopenia in HNC. Methods: We searched PubMed, the Cochrane Library, Embase, and Web of Science, which contain trial registries and meeting proceedings, to identify related published or unpublished studies. We used the Newcastle-Ottawa Scale (NOS) to appraise the risk of bias of the included retrospective studies. Pooled hazard ratios (HR) and the I 2 statistic were estimated for the impact of sarcopenia on overall survival (OS) and relapse-free survival (RFS). Results: We analyzed data from 11 studies involving 2,483 patients (39.4% on average of whom had sarcopenia). Based on the univariate analysis data, the sarcopenia group had significantly poorer OS compared to the non-sarcopenia group [HR = 1.97, 95% confidence interval (CI): 1.71-2.26, I 2 = 0%]. In the cutoff value subgroup, group 1, defined as skeletal muscle index (SMI) of 38.5 cm2/m2 for women and 52.4 cm2/m2 for men (HR = 2.41, 95% CI: 1.72-3.38, I 2 = 0%), had much poorer OS. In the race subgroup, the results were consistent between the Asia (HR = 2.11, 95% CI: 1.59-2.81) and non-Asia group (HR = 1.92, 95% CI: 1.64-2.25). The sarcopenia group also had significantly poorer RFS (HR = 1.74, 95% CI: 1.43-2.12, I 2 = 0%). Conclusions: Presence of pre-treatment sarcopenia has a significant negative impact on OS and RFS in HNC compared with its absence. Further well-conducted studies with detailed stratification are needed to complement our findings.

The Value of Prognostic Nutritional Index (PNI) in Predicting Survival and Guiding Radiotherapy of Patients With T1-2N1 Breast Cancer.

Background: To investigate the significance of the prognostic nutrition index (PNI) as a predictor of survival and guide for treating T1-2N1 breast cancer. Methods: Patients with T1-2N1 breast cancer (N = 380) who underwent a mastectomy at our center were studied. PNI was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm3). The cutoff for the PNI was calculated using the time-dependent receiver operating characteristic (ROC) curve analysis by overall survival (OS) prediction. The associations between the PNI and the clinicopathologic characteristics were analyzed using Pearson's χ2 test. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Results: Subgroup analyses of patients with low PNI value (≤52.0) and high PNI value (>52.0) showed that a high PNI was significantly associated with HER2 status, the neutrophil-lymphocyte ratio (NLR), the monocyte-lymphocyte ratio (MLR), and KI 67 status. The OS of patients with a high PNI was significantly better than that of patients with a low PNI. We then conducted subgroup analyses based on PNI and radiotherapy. Among patients who received radiotherapy, the OS of those with a high PNI was significantly better than that of patients with a low PNI. Among patients with a high PNI, the OS of those who received radiotherapy was better than that of the patients who did not receive radiotherapy. However, among the patients with a low PNI, the OS of those who received radiation was worse than that of patients who did not receive radiotherapy. The Kaplan-Meier survival analysis and the multivariate analysis of patients with T1-2N1 breast cancer who received radiotherapy showed PNI independently predicted OS. Conclusions: The preoperative PNI may be a reliable predictor of OS of patients with operable T1-2N1 breast cancer, with the capacity to provide a personalized prognosis and facilitate the development of clinical treatment strategies. However, radiotherapy did not achieve satisfactory outcomes in patients with PNI ≤52.0; thus, further studies on treatment optimization are needed.

Low Skeletal Muscle Mass Impairs Quality of Life in Nasopharyngeal Carcinoma Patients Treated With Concurrent Chemoradiotherapy.

Background: Nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) frequently develop low skeletal muscle mass (SMM), but, little is known about the impacts of low SMM on health-related quality of life (QOL). Methods: We retrospectively assessed 56 patients with locoregionally advanced NPC enrolled in a prospective trial. Low SMM was determined on routine computed tomography simulation (CT-sim) scans taken before radiotherapy, at the third cervical (C3) vertebral level with validated sex-specific cutoffs. QOL was assessed using the World Health Organization Quality of Life Questionnaire-100 at baseline and after 3 weeks. Pain was scored every 24 h using a numerical rating scale (NRS). Characteristics related to low SMM were identified by logistic regression. The chi-square test was used to examine the association of low SMM with QOL and pain. Results: Of the 56 participants (mean age 44.20 ± 10.93 years), over half (60.71%) developed low SMM. Patients with low SMM were more likely to be older (P = 0.035), male (P = 0.066), have a lower body-mass index (BMI; P = 0.091), and have a higher pain score (P = 0.001). Older age (hazard ratio [HR] = 1.788, P = 0.016), being male (HR = 3.145, P = 0.010), lower BMI (HR = 0.761, P = 0.033), and lower prognostic nutritional index (HR = 0.186, P = 0.034) were associated with higher risk of low SMM. Low SMM was associated with poorer baseline QOL scores (P = 0.072), especially in the physical domain (P = 0.002) and its three facets: pain (P = 0.003), energy (P = 0.021), and sleep (P = 0.007). Low SMM was also associated with significantly worse QOL scores (P = 0.006) at 3 weeks, especially in the physical (P = 0.002), psychological (P = 0.046), independence (P = 0.003), social domains (P = 0.023), and in general health condition (P = 0.043). For pain score, low SMM group had worse overall changes from baseline to week 3 (P = 0.011). Conclusions: The incidence of low SMM, as evaluated using routine CT-sim scans, is high in patients receiving CCRT for locoregionally advanced NPC. Low SMM results in poorer QOL and higher pain scores, which underscores the requirement for nutritional and functional interventions to address low SMM early in the treatment course.

Prognostic impact of the pretreatment albumin to alkaline phosphatase ratio for nonmetastatic breast cancer patients.

Introduction: Albumin and alkaline phosphatase have been previously demonstrated as independent prognostic factors for various types of cancer. Here, we aimed to explore the potential value of pretreatment albumin to alkaline phosphatase ratio (AAPR) on overall survival (OS) in nonmetastatic breast cancer patients. Methods: A total of 746 nonmetastatic breast cancer patients were enrolled in this study. Receiver characteristic curve was used to analyze the AAPR threshold. Survival analysis was conducted using the Kaplan-Meier method and compared with the log-rank test. Both univariate and multivariate analyses were performed using Cox proportional hazards regression methodology. Results: The optimal cutoff value of AAPR in predicting OS in nonmetastatic breast cancer patients was 0.525. Increased pretreatment AAPR level was related to age at diagnosis (≥60 years vs <60 years, P=0.000), tumor size (T≤2 cm vs T>2 cm, P=0.034), estrogen receptor (positive vs negative, P=0.022), progesterone receptor (positive vs negative, P=0.025), carcino-embryonic antigen (abnormal vs normal, P=0.016), surgery (lumpectomy vs mastectomy, P=0.002), chemotherapy (yes vs no, P=0.004), radiotherapy (yes vs no, P=0.013), endocrine therapy (yes vs no, P=0.027) but not with lymph node involvement, HER-2 status or CA-153. The 5-year OS rate was 80.16% for the low AAPR group and 92.66% for the high AAPR group. Kaplan-Meier analysis indicated that patients with low-AAPR levels had shorter OS than patients with high-AAPR levels (P=0.001). N classification (P<0.05), Ki-67 (HR=3.603, 95% CI=1.046-12.414, P=0.042) and AAPR (HR=0.447, 95% CI=0.205-0.976, P=0.043) were related to OS in multivariate analyses, respectively. Conclusion: AAPR is an independent prognostic factor for OS in nonmetastatic breast cancer patients. Further prospective studies are required to confirm our findings.

21-Gene Recurrence Score Assay Could Not Predict Benefit of Post-mastectomy Radiotherapy in T1-2 N1mic ER-Positive HER2-Negative Breast Cancer.

Introduction: It is still controversial whether post-mastectomy radiotherapy (PMRT) is necessary for women with T1-2 N1mic ER-positive HER2-negative breast cancer. The 21-gene recurrence score (RS) assay has been validated in T1-2 N1 breast cancer to be prognostic of locoregional recurrence (LRR) and overall survival (OS). This study aims to evaluate the predict value of 21-gene recurrence score assay for the benefit of PMRT in T1-2 N1mic ER-positive HER2-negative breast cancer. Methods: A population-based cohort study was performed on women with T1-2 N1mic ER-positive HER2-negative breast cancer who underwent mastectomy and were evaluated using the 21-gene RS in the Surveillance, Epidemiology, and End Results (SEER) registry between 2004 and 2015. Clinical characteristics as well as OS and breast cancer-specific survival (BCSS) were compared between patients with and without PMRT in patients with a Low-, Intermediate-, and High-RS. Multivariate COX regression analysis was performed to investigate if the 21-gene RS assay could predict benefit of PMRT in this group of breast cancer patients. Results: A total of 1571 patients met the criteria of our study and were enrolled, including 970 patients in the Low-Risk group (score <18), 508 in the Intermediate-Risk group (score 18-30), and 93 patients in the High-Risk group (score >30). In the High-Risk group, there were more patients with age ≥50 (87.0 vs. 64.3%, P = 0.040) and received chemotherapy with a borderline significance (91.3 vs. 72.9%, P = 0.066) in the PMRT subgroup than in the no PMRT subgroup. In all three groups, OS was comparable between the PMRT subgroup and the no PMRT subgroup. Furthermore, multivariate analysis did not show any OS benefit for PMRT based on the 21-gene recurrence score. Conclusion: This study showed that the 21-gene RS assay was not able to predict the benefit of PMRT for OS in women with T1-2 N1mic ER-positive HER2-negative breast cancer. However, further prospective larger sample-size trials are warranted to determine if a benefit exists.