Prognoses and Long-Term Outcomes of Nasopharyngeal Carcinoma in Han and Uyghur Patients Treated with Intensity-Modulated Radiotherapy in the Xinjiang Autonomous Region of China

Objectives

The objective of this study was to investigate the long-term outcomes and prognostic factors for nasopharyngeal carcinoma (NPC) in Han and Uyghur patients treated with intensity-modulated radiotherapy (IMRT) in the Xinjiang region of China.

Materials and Methods

One hundred twenty-one Han and 60 Uyghur patients with newly diagnosed NPC without distant metastasis received IMRT at the Affiliated Tumor Hospital of Xinjiang Medical University between 2005 and 2008. The Kaplan-Meier method was used to estimate survival rates, and the log-rank test was used to evaluate differences in survival.

Results

Comparing Han and Uyghur patients, the 5-year overall survival (OS), disease-free survival (DFS), local control (LC), regional control (RC), and distant metastasis-free survival (DMFS) rates were 81.9% vs 77.6% (P = 0.297), 72.1% vs 65.6% (P = 0.493), 88.3% vs 86.5% (P = 0.759), 95.0% vs 94.6% (P = 0.929), and 79.1% vs 75.2% (P = 0.613), respectively. Multivariate Cox proportional hazards regression identified the following independent prognostic factors in Han patients: N stage (P = 0.007) and age (P = 0.028) for OS, and age (P = 0.028) for DFS. OS differed significantly between Han and Uyghur patients >60 years old group (P = 0.036). Among Uyghur patients, the independent prognostic factors were age for OS (P = 0.033), as well as N stage (P = 0.037) and age (P = 0.021) for DFS. Additionally, Uyghur patients were less likely to experience mucositis and dermatitis than Han patients.

Conclusion

Han and Uyghur patients with NPC had statistically significant differences in age, smoking history, and N staging. There was no significant difference in overall treatment outcomes with IMRT between these 2 ethnic populations in Xinjiang, China.     

A Large Cohort Study Reveals the Association of Elevated Peripheral Blood Lymphocyte-to-Monocyte Ratio with Favorable Prognosis in Nasopharyngeal Carcinoma

Background

Nasopharyngeal carcinoma (NPC) is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20–30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients.

Methods

A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional recurrence-free survival (LRRFS), respectively.

Results

Univariate analysis revealed that higher LMR level (≥5.220) was significantly associated with superior OS, DFS and DMFS (P values <0.001). The higher lymphocyte count (≥2.145×10⁹/L) was significantly associated with better OS (P = 0.002) and DMFS (P = 0.031), respectively, while the lower monocyte count (<0.475×10⁹/L) was associated with better OS (P = 0.012), DFS (P = 0.011) and DMFS (P = 0.003), respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR  = 0.558, 95% confidence interval or 95% CI  = 0.417–0.748; P<0.001), DFS (HR  = 0.669, 95% CI  = 0.535–0.838; P<0.001) and DMFS (HR = 0.543, 95% CI  = 0.403–0.732; P<0.001), respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053) and DMFS (P = 0.080).

Conclusions

The elevated pretreatment peripheral LMR level was a significant favorable factor for NPC prognosis and this easily accessed variable may serve as a potent marker to predict the outcomes of NPC patients.     

Comparison of Long-Term Survival and Toxicity of Cisplatin Delivered Weekly versus Every Three Weeks Concurrently with Intensity-Modulated Radiotherapy in Nasopharyngeal Carcinoma

Background

We aimed to compare the long-term survival outcomes and acute toxicity of cisplatin administered weekly versus every three weeks concurrently with intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC).

Methods

This was a retrospective review of 154 patients with histologically proven, non-disseminated NPC who were treated using IMRT between January 2003 and December 2007. Seventy-three patients (47.4%) received 5–7 weeks of 30–40 mg/m² cisplatin weekly; 81 patients (52.6%) received two or three cycles of 80 mg/m² cisplatin every three weeks. IMRT was delivered at 68 Gy/30 fractions to the nasopharyngeal gross target volume and 60–66 Gy to the involved neck area.

Results

The clinical characteristics and treatment factors of the two groups were well-balanced. The median follow-up was 74 months (range, 6–123 months), and the 5-year overall survival, disease-free survival, locoregional relapse-free survival, and distant metastasis–free survival rates were 85.2% vs. 78.9% (P = 0.318), 71.6% vs. 71.0% (P = 0.847), 93.5% vs. 92.6% (P = 0.904), and 80.9% vs. 80.1% (P = 0.925) for the group treated every three weeks and weekly, respectively. Subgroup analyses indicated no significant differences in the survival rates of the two groups among patients with early- or advanced-stage disease. The incidence of acute toxicities was similar between groups.

Conclusion

IMRT with concurrent cisplatin administered weekly or every three weeks leads to similar long-term survival outcomes and acute toxicity in NPC regardless of whether patients have early- or advanced-stage disease.     

Radiation-Induced Temporal Lobe Injury for Nasopharyngeal Carcinoma: A Comparison of Intensity-Modulated Radiotherapy and Conventional Two-Dimensional Radiotherapy

Background

To compare the radiation-induced temporal lobe injury (TLI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT).

Patients and Methods

1276 cases of NPC treated with IMRT or 2D-CRT were retrospectively reviewed. A diagnosis of TLI was made on follow-up magnetic resonance imaging (MRI).

Results

The crude incidence of TLI was 7.5% and 10.8% (P = 0.048), and the actuarial 5-year incidence was 16% and 34.9% (P<0.001) for the IMRT and 2D-CRT groups, respectively. Multivariate analysis revealed both T stage (P<0.001) and radiation technique (P<0.001) as independent predictors. Patients with T1, T2 and T3 disease had a significantly higher risk when treated with 2D-CRT (P = 0.005, 0.016, <0.001, respectively). This trend was not evident for T4 patients (P = 0.680). The 2D-CRT group had a longer latency for the development of TLI (P<0.001). Those with T4 disease had a shorter median time to TLI (P = 0.006, 0.042, <0.001 when compared with T1, T2 and T3, respectively).

Conclusions

IMRT is superior to 2DRT for the management of T1-T3 NPC in terms of sparing the temporal lobe. The high incidence of TLI in T4 disease needs to be addressed.     

The Pretreatment Albumin to Globulin Ratio Has Predictive Value for Long-Term Mortality in Nasopharyngeal Carcinoma

Background

Low serum albumin is predictive of poor survival in nasopharyngeal carcinoma (NPC). We evaluated the ability of the pretreatment albumin/globulin ratio (AGR) to predict long-term mortality in patients with NPC.

Methods

This retrospective study examined an unselected cohort of 694 patients with NPC who had documented pretreatment total serum protein and serum albumin levels (ALB). AGR was calculated as [AGR = ALB/(total serum protein - ALB)]. Survival analysis was used to evaluate the predictive value of AGR.

Results

Multivariate analysis demonstrated that a low pretreatment serum AGR (<1.4) was an independent predictor of poor OS (P  = 0.029) and DMFS (P  = 0.033). A low AGR was significantly associated with advanced stage disease (P<0.001), high white blood cell count (P  = 0.033), high neutrophil count (P  = 0.047), high total serum protein (P<0.001) and low ALB (P<0.001).

Conclusion

The pretreatment AGR may represent a simple, potentially useful predictive biomarker for evaluating the long-term prognosis of patients with undifferentiated NPC.     

Clinical Outcomes of Patients with Oral Cavity Squamous Cell Carcinoma and Retropharyngeal Lymph Node Metastasis Identified by FDG PET/CT

Purpose

Retropharyngeal lymph node (RPLN) metastasis is an uncommon finding in patients with oral cavity squamous carcinoma (OSCC). We sought to investigate the clinical outcomes, clinicopathological characteristics, and the priority of treatment with curative intent in OSCC patients with RPLN involvement.

Methods and Materials

Between January 2007 and January 2011, we identified 36 patients with primary RPLN metastases (n = 10) or RPLN relapse (n = 26). The follow-up continued until June 2013. Disease-specific survival (DSS), disease-free survival (DFS), and the potential benefits of salvage therapy served as the main outcome measures.

Results

The 2-year DSS and DFS rates of untreated patients with RPLN involvement were 20% and 24%, respectively. Level IV/V neck lymph node involvement was an adverse prognostic factor for DSS (P = 0.048) and DFS (P = 0.018). All of the patients presenting with neck lymph node involvement at level IV/V died within 6 months. Among patients who were treated for RPLN relapse, the 2-year DSS and DFS rates from the relapse day were 12.8% and 9.6%, respectively. Concomitant contralateral neck lymph node metastases (N2c) were associated with lower 2-year DSS (P = 0.005) and DFS (P = 0.011) rates. Moreover, five (55%) of the nine patients with recurrent disease in the contralateral RPLN had distant metastases within 6 months. Salvage therapy yielded the maximum survival benefit in patients without N2c disease and ipsilateral RPLN involvement alone (P = 0.005).

Conclusion

OSCC patients with RPLN involvement have poor outcomes. The risk factor for definitive treatment in OSCC patients with FDG PET/CT defined RPLN disease in primary disease was neck lymph node involvement at level IV/V and N2c and/or contralateral RPLN disease in recurrent disease. Treatment efforts with curative intent should be tailored according to individual risk factors.     

Clinical Outcomes for Gastric Cancer following Adjuvant Chemoradiation Utilizing Intensity Modulated versus Three-Dimensional Conformal Radiotherapy

Purpose/Objective(s)

To determine if intensity modulated radiation therapy (IMRT) in the post-operative setting for gastric cancer was associated with reduced toxicity compared to 3D conformal radiation therapy (3DCRT).

Materials/Methods

This retrospective study includes 24 patients with stage IB-IIIB gastric cancer consecutively treated from 2001–2010. All underwent surgery followed by adjuvant chemoradiation. Concurrent chemotherapy consisted of 5-FU/leucovorin (n = 21), epirubicin/cisplatin/5FU (n = 1), or none (n = 2). IMRT was utilized in 12 patients and 3DCRT in 12 patients. For both groups, the target volume included the tumor bed, anastomosis, gastric stump, and regional lymphatics.

Results

Median follow-up for the entire cohort was 19 months (range 0.4–8.5 years), and 49 months (0.5–8.5 years) in surviving patients. The 3DCRT group received a median dose of 45 Gy, and the IMRT group received a median dose of 50.4 Gy (p = 0.0004). For the entire cohort, 3-year overall survival (OS) was 40% and 3-year disease free survival (DFS) was 41%. OS and DFS did not differ significantly between the groups. Acute toxicity was similar. Between 3DCRT and IMRT groups, during radiotherapy, median weight lost (3.2 vs. 3.3 kg, respectively; p = 0.47) and median percent weight loss were similar (5.0% vs. 4.3%, respectively; p = 0.43). Acute grade 2 toxicity was experienced by 8 patients receiving 3DCRT and 11 receiving IMRT (p = 0.32); acute grade 3 toxicity occurred in 1 patient receiving 3DCRT and none receiving IMRT (p = 1.0). No patients in either cohort experienced late grade 3 toxicity, including renal or gastrointestinal toxicity. At last follow up, the median increase in creatinine was 0.1 mg/dL in the IMRT group and 0.1 mg/dL in the 3DCRT group (p = 0.78).

Conclusion

This study demonstrates that adjuvant chemoradiation for gastric cancer with IMRT to 50.4 Gy was well-tolerated and compared similarly in toxicity with 3DCRT to 45 Gy.     

TGFβ1 Polymorphisms Predict Distant Metastasis–Free Survival in Patients with Inoperable Non-Small-Cell Lung Cancer after Definitive Radiotherapy

Purpose

Transforming growth factor (TGF) -β1 signaling is involved in cancer-cell metastasis. We investigated whether single nucleotide polymorphisms (SNPs) at TGFβ1 were associated with overall survival (OS) and distant metastasis-free survival (DMFS) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiotherapy, with or without chemotherapy.

Methods

We genotyped TGFβ1 SNPs at rs1800469 (C–509T), rs1800471 (G915C), and rs1982073 (T+29C) by polymerase chain reaction-restriction fragment length polymorphism in blood samples from 205 NSCLC patients who had had definitive radiotherapy at one institution in November 1998–January 2005. We also tested whether the TGF-β1 rs1982073 (T+29C) SNP affected the migration and invasion of A549 and PC9 lung cancer cells.

Results

Median follow-up time for all patients was 17 months (range, 1–97 months; 39 months for patients alive at the time of analysis). Multivariate analysis showed that the TGFβ1 rs1800469 CT/CC genotype was associated with poor OS (hazard ratio [HR] = 1.463 [95% confidence interval {CI} = 1.012–2.114], P = 0.043) and shorter DMFS (HR = 1.601 [95% CI = 1.042–2.459], P = 0.032) and that the TGFβ1 rs1982073 CT/CC genotype predicted poor DMFS (HR = 1.589 [95% CI = 1.009–2.502], P = 0.046) and poor brain MFS (HR = 2.567 [95% CI = 1.155–5.702], P = 0.021) after adjustment for age, sex, race, performance status, smoking status, tumor histology and volume, stage, receipt of concurrent radiochemotherapy, number of chemotherapy cycles, and radiation dose. Transfection with TGFβ1+29C (vs. +29T) stimulated the migration and invasion of A549 and PC9 cells, suggesting that TGFβ1+29C may be linked with increased metastatic potential.

Conclusions

TGFβ1 genotypes at rs1800469 and rs1982073 could be useful for predicting DMFS among patients with NSCLC treated with definitive radiation therapy. These findings require validation in larger prospective trials and thorough mechanistic studies.     

Similar Prognoses for Invasive Micropapillary Breast Carcinoma and Pure Invasive Ductal Carcinoma: A Retrospectively Matched Cohort Study in China

Purpose

Invasive micropapillary breast carcinoma (IMPC) is a rare pathological finding. Few studies have compared IMPC with invasive ductal breast carcinoma (IDC) according to matched nodal status and age. To better illustrate the difference between IMPC and IDC prognoses, we conducted this cohort study.

Methods

51 mixed or pure IMPC patients and 102 pure IDC patients were matched for nodal status and age. Clinical and biological features as well as disease-free survival (DFS) were compared between groups.

Results

More than one-half of IMPC consisted of mostly or exclusively IMPC component (meaning greater than 75%) and these tumors significantly correlated with a higher histologic grade (P = 0.016) and LVI positivity (P = 0.036) compared with mixed IMPC. IMPC displayed a significantly higher rate of estrogen receptor (ER) positivity and lymphovascular invasion (LVI) compared to matched IDC. Women diagnosed with IMPC had a slight, but not significant, reduced frequency for recurrence and metastasis compared to women with IDC (15.7% vs. 21.6%, P = 0.518). In the subgroup analysis, IMPC patients demonstrated significantly reduced survival (P = 0.018) compared to IDC patients in the T₁N_2–3 subpopulation, whereas IDC patients demonstrated significantly increased recurrence and metastasis (P = 0.024) compared to IMPC patients in the T₂N_2–3 subgroup. No difference was observed in patients with 3 or less positive lymph nodes (LNs).

Conclusion

Although no difference in DFS was observed between IMPC and LN-matched IDC patients, IMPC patients demonstrated a significantly poorer outcome compared to IDC patients with smaller tumors and 4 or more positive LNs. The opposite results were observed in larger tumors and patients with 4 or more positive LNs. Therefore, we might advise more proactive treatment for IMPC patients with a smaller tumor size and extensive LN involvement. Furthermore, correlative IMPC studies should focus on this subset of patients to elucidate the genetic and/or biologic differences that contribute to metastatic potential.     

Identification of Biological Properties of Intralymphatic Tumor Related to the Development of Lymph Node Metastasis in Lung Adenocarcinoma

Background

Intralymphatic tumors in the extratumoral area are considered to represent the preceding phase of lymph node metastasis. The aim of this study was to clarify the biological properties of intralymphatic tumors susceptible to the development of lymph node metastasis, with special reference to the expression of cancer initiating/stem cell (CIC/CSC) related markers in cancer cells and the number of infiltrating stromal cells.

Material and Methods

Primary lung adenocarcinomas with lymphatic permeation in the extratumoral area were retrospectively examined (n = 107). We examined the expression levels of CIC/CSC related markers including ALDH1, OCT4, NANOG, SOX2 and Caveolin-1 in the intralymphatic cancer cells to evaluate their relationship to lymph node metastasis. Moreover, the number of infiltrating stromal cells expressing CD34, α-smooth muscle actin, and CD204 were also evaluated.

Results

Among the intralymphatic tissues, low ALDH1 expression in cancer cells, high SOX2 expression in cancer cells, and a high number of CD204(+) macrophages were independent predictive factors for lymph node metastasis (P = 0.004, P = 0.008, and P = 0.028, respectively). Among these factors, only low ALDH1 expression in cancer cells was significantly correlated with the farther spreading of lymph node metastasis (mediastinal lymph node, pathological N2) (P = 0.046) and the metastatic lymph node ratio (metastatic/resected) (P = 0.028). On the other hand, in the primary tumors, ALDH1 expression in the cancer cells was not associated with lymph node metastasis. Intralymphatic cancer cells expressing low ALDH1 levels exhibited lower E-cadherin expression levels than cancer cells with high levels of ALDH1 expression (P = 0.015).

Conclusions

Intralymphatic cancer cells expressing low levels of ALDH1 and infiltrating macrophages expressing CD204 have a critical impact on lymph node metastasis. Our study also highlighted the significance of evaluating the biological properties of intralymphatic tumors for tumor metastasis.     

Prognostic Significance of Cyclin D1 Expression in Colorectal Cancer: A Meta-Analysis of Observational Studies

Objective

Cyclin D1 plays a vital role in cancer cell cycle progression and is overexpressed in many human cancers, including colorectal cancer (CRC). However, the prognostic value of cyclin D1 overexpression in colorectal cancer is conflicting and heterogeneous. We conducted a meta-analysis to more precisely evaluate its prognostic significance.

Methods

A comprehensive literature search for relevant studies published up to January 2014 was performed using PubMed, EMBASE, and ISI Web of Science. The pooled hazard ratio (HR) with 95% confidence intervals (CI) was used to estimate the effects.

Results

22 studies with 4150 CRC patients were selected to evaluate the association between cyclin D1 and overall survival (OS), disease-free survival (DFS) and clinicopathological parameters. In a random-effects model, the results showed that cyclin D1 overexpression in CRC was significantly associated with both poor OS (HR = 0.73, 95% CI: 0.63–0.85, P<0.001) and DFS (HR = 0.60, 95% CI: 0.44–0.82, P = 0.001). Additionally, cyclin D1 overexpression was significantly associated with more relative older patients (≥60 years) (OR 0.62, 95% CI 0.44–0.89, P = 0.009), T3,4 tumor invasion (OR 0.70, 95% CI 0.57–0.85, P<0.001), N positive (OR 0.75, 95% CI 0.60–0.95, P = 0.016) and distant metastasis (OR 0.60, 95% CI 0.36–0.99, P = 0.047) of CRC.

Conclusion

The meta-analysis results indicated that cyclin D1 is an unfavorable prognostic factor for CRC. Cyclin D1 overexpression might be associated with poor clinical outcome and some clinicopathological factors such as age, T category, N category and distant metastasis in CRC patients.     

Predictors of the Extent of Carotid Atherosclerosis in Patients Treated with Radiotherapy for Nasopharyngeal Carcinoma

Objective

To determine the predictors of the extent of carotid atherosclerosis in patients treated with radiotherapy (RT) for nasopharyngeal carcinoma (NPC).

Methods

The present study investigated 129 post-RT NPC patients. Carotid atherosclerotic parameters, such as carotid intima-media thickness, carotid arterial stiffness and carotid plaque burden (plaque score, the presence of plaque and ≥50% stenosis) were assessed using ultrasonography. The association between carotid atherosclerotic parameters and nine potential predictors, including age, gender, post-RT duration, radiation dose, chemotherapy, diabetes mellitus, hypertension, hypercholesterolemia, and smoking, were determined using multiple regression. The cutoff values of age, post-RT duration and number of cardiovascular risk factors for the presence of carotid plaque or ≥50% carotid stenosis were analyzed using receiver operating characteristic (ROC) curve analysis. Multiple testing was corrected using Benjamini-Hochberg false discovery rate.

Results

Age, post-RT duration and number of cardiovascular risk factors were significantly associated with carotid plaque burden (corrected P value, P_cor<0.05). Age of 44.5 years (sensitivity = 99.2% and specificity = 50%, P_cor<0.01) and post-RT duration of 8.5 years (sensitivity = 75.7% and specificity = 64.3%, P_cor<0.001) were the cutoff values for detecting carotid plaque, while post-RT duration of 13.5 years (sensitivity = 66.7% and specificity = 71.6%, P_cor<0.001) and 1.5 cardiovascular risk factors (sensitivity = 40.7% and specificity = 84.3%, P_cor<0.05) were the cutoff values for screening ≥50% carotid stenosis.

Conclusions

Age, post-RT duration and number of cardiovascular risk factors are significant predictors of carotid atherosclerosis in post-RT NPC patients. Post-RT NPC patients, who are at least 45 years old, with post-RT duration of 9 years or above, and/or have ≥2 cardiovascular risk factors, are more susceptible to carotid atherosclerosis.     

Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

Background

N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT).

Patients and Methods

Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy.

Results

With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ² = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups.

Conclusion

IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute toxicity rate.     

An Elevated Peripheral Blood Lymphocyte-to-Monocyte Ratio Predicts Favorable Response and Prognosis in Locally Advanced Breast Cancer following Neoadjuvant Chemotherapy

Purpose

Neoadjuvant chemotherapy (NCT) is a standard treatment option for locally advanced breast cancer. However, the lack of an efficient method to predict treatment response and patient prognosis hampers the clinical evaluation of patient eligibility for NCT. An elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with a favorable prognosis for certain hematologic malignancies and for nasopharyngeal carcinoma; however, this association has not been investigated in breast cancer. The purpose of this study was to evaluate whether pre-NCT LMR analysis could predict the prognosis of patients with locally advanced breast cancer.

Methods

A retrospective cohort of 542 locally advanced breast cancer patients (T3/T4 and/or N2/N3 disease) receiving NCT followed by radical surgery was recruited between May 2002 and August 2011 at the Fudan University Shanghai Cancer Center. Counts for pre-NCT peripheral absolute lymphocytes and monocytes were obtained and used to calculate the LMR.

Results

Univariate and multivariate analysis revealed that higher LMR levels (≥4.25) were significantly associated with favorable DFS (P = 0.009 and P = 0.011, respectively). Additionally, univariate analysis revealed that a higher lymphocyte count (≥1.5×10⁹/L) showed borderline significance for improved DFS (P = 0.054), while a lower monocyte count (<0.4×10⁹/L) was associated with a significantly better DFS (P = 0.010).

Conclusions

An elevated pre-NCT peripheral LMR level was a significantly favorable factor for locally advanced breast cancer patient prognosis. This easily obtained variable may serve as a valuable marker to predict the outcomes of locally advanced breast cancer.     

A Novel Statistical Prognostic Score Model That Includes Serum CXCL5 Levels and Clinical Classification Predicts Risk of Disease Progression and Survival of Nasopharyngeal Carcinoma Patients

Background

Aberrant expression of C-X-C motif chemokine 5 (CXCL5) contributes to the progression of various cancers. This study analyzed the clinical significance of serum CXCL5 (sCXCL5) levels of nasopharyngeal carcinoma (NPC) patients, with the goal of building a novel prognostic score model.

Experimental Design

Serum samples were collected prior to treatment from 290 NPC patients for the detection of sCXCL5 with ELISA. Half of the patients (n = 145) were randomly assigned to the training set to generate the sCXCL5 cutoff point using receiver operator characteristic (ROC) analysis, while the other half (n = 145) were assigned to the testing set for validation. Associations between sCXCL5 levels and clinical characteristics were analyzed. A prognostic score model was built using independent predictors derived from multivariate analysis. A concordance index (C-Index) was used to evaluate prognostic ability.

Results

The sCXCL5 cutoff point was 0.805 ng/ml. Sex, age, histology, T classification, clinical classification and local recurrence were not associated with sCXCL5 levels. However, sCXCL5 levels were positively associated with N classification, distant metastasis and disease progression (P<0.05). A high sCXCL5 level predicted poor 6-year overall survival (OS), poor 6-year distant metastasis-free survival (DMFS), and poor 6-year progression-free survival (PFS). A prognostic score model was subsequently constructed based on sCXCL5 levels and clinical classification (C-C model), which are independent predictors of OS, DMFS, and PFS, as confirmed by the multivariate analysis. Furthermore, this novel model successfully divided the patients into four risk subgroups in the training set, the testing set and the entire set of patients. The C-Indices were 0.751 and 0.762 for the training set and the testing set, respectively.

Conclusions

sCXCL5 level was determined to be an independent prognostic factor for NPC patients. The novel statistical C-C model, which includes sCXCL5 levels and clinical classification, could be helpful in predicting the prognosis of NPC patients.     

Clinicopathological Correlation and Prognostic Significance of Protein Kinase Cα Overexpression in Human Gastric Carcinoma

Objectives

This study investigated the PKCα protein expression in gastric carcinoma, and correlated it with clinicopathological parameters. The prognostic significance of PKCα protein expression in gastric carcinoma was analyzed.

Methods

Quantitative real-time PCR test was applied to compare the PKCα mRNA expression in tumorous and nontumorous tissues of gastric carcinoma in ten randomly selected cases. Then PKCα protein expression was evaluated in 215 cases of gastric carcinoma using immunohistochemical method. The immunoreactivity was scored semiquantitatively as: 0 = absent; 1 = weak; 2 = moderate; and 3 = strong. All cases were further classified into two groups, namely PKCα overexpression group with score 2 or 3, and non-overexpression group with score 0 or 1. The PKCα protein expression was correlated with clinicopathological parameters. Survival analysis was performed to determine the prognostic significance of PKCα protein expression in patients with gastric carcinoma.

Results

PKCα mRNA expression was upregulated in all ten cases of gastric carcinoma via quantitative real-time PCR test. In immunohistochemical study, eighty-eight out of 215 cases (41%) of gastric carcinoma revealed PKCα protein overexpression, which was statistically correlated with age (P = 0.0073), histologic type (P<0.0001), tumor differentiation (P = 0.0110), depth of invasion (P = 0.0003), angiolymphatic invasion (P = 0.0373), pathologic stage (P = 0.0047), and distant metastasis (P = 0.0048). We found no significant difference in overall and disease free survival rates between PKCα overexpression and non-overexpression groups (P = 0.0680 and 0.0587). However, PKCα protein overexpression emerged as a significant independent prognostic factor in multivariate Cox regression analysis (hazard ratio 0.632, P = 0.0415).

Conclusions

PKCα protein is upregulated in gastric carcinoma. PKCα protein expression is statistically correlated with age, histologic type, tumor differentiation, depth of invasion, angiolymphatic invasion, pathologic stage, and distant metastasis. The PKCα protein overexpression in patients with gastric carcinoma is a significant independent prognostic factor in multivariate Cox regression analysis.     

Serum CXCL9 Levels Are Associated with Tumor Progression and Treatment Outcome in Patients with Nasopharyngeal Carcinoma

Objectives

The aim of this cohort study was to examine the role of the chemokine (C-X-C motif) ligand 9 (CXCL9) on nasopharyngeal carcinoma (NPC).

Materials & Methods

Sera from 205 NPC patients and 231 healthy individuals, and 86 NPC tumor samples were enrolled. CXCL9 expression in tissue samples was analyzed by quantitative real-time PCR and immunohistochemistry. CXCL9 serum concentrations were measured by enzyme-linked immunosorbent assay.

Results

CXCL9 expression was significantly higher in tumors than in normal epithelium. CXCL9 serum concentrations were also significantly higher in NPC patients compared to those in healthy individuals (516.8±617.6 vs. 170.7±375.0 pg/mL, P<0.0001). Serum CXCL9 levels were significantly higher in NPC patients with higher tumor stages, nodal stages, and overall stages (P<0.001, P = 0.001, and P<0.001, respectively). We found a statistically significant correlation between the concentrations of CXCL9 and EBV DNA load in the NPC patients (Spearman’s correlation analysis; r = 0.473, P<0.001; 95% confidence interval, 0.346–0.582). Moreover, NPC patients with higher CXCL9 levels (>290 pg/mL, median) before treatment had worse prognoses for overall survival and disease-free survival (P = 0.045 and P = 0.008, respectively). Multivariate logistic regression analyses also indicated that higher CXCL9 serum levels were an independent prognostic factor for disease-free survival (P = 0.015).

Conclusion

Our study demonstrated that CXCL9 is associated with tumor burden and aggressiveness of NPC tumors and the serum level of this ligand may be useful as a prognostic indicator.     

Chewing Betel Quid and the Risk of Metabolic Disease,Cardiovascular Disease,and All-Cause Mortality: A Meta-Analysis

Background

Betel nut (Areca nut) is the fruit of the Areca catechu tree. Approximately 700 million individuals regularly chew betel nut (or betel quid) worldwide and it is a known risk factor for oral cancer and esophageal cancer. We performed a meta-analysis to assess the influence of chewing betel quid on metabolic diseases, cardiovascular disease, and all-cause mortality.

Methodology/Principal Findings

We searched Medline, Cochrane Library, Web of Science, and Science Direct for pertinent articles (including the references) published between 1951 and 2013. The adjusted relative risk (RR) and 95% confidence interval were calculated using the random effect model. Sex was used as an independent category for comparison.

Results

Of 580 potentially relevant studies, 17 studies from Asia (5 cohort studies and 12 case-control studies) covering 388,134 subjects (range: 94 to 97,244) were selected. Seven studies (N = 121,585) showed significant dose-response relationships between betel quid consumption and the risk of events. According to pooled analysis, the adjusted RR of betel quid chewers vs. non-chewers was 1.47 (P<0.001) for obesity (N = 30,623), 1.51 (P = 0.01) for metabolic syndrome (N = 23,291), 1.47 (P<0.001) for diabetes (N = 51,412), 1.45 (P = 0.06) for hypertension (N = 89,051), 1.2 (P = 0.02) for cardiovascular disease (N = 201,488), and 1.21 (P = 0.02) for all-cause mortality (N = 179,582).

Conclusion/Significance

Betel quid chewing is associated with an increased risk of metabolic disease, cardiovascular disease, and all-cause mortality. Thus, in addition to preventing oral cancer, stopping betel quid use could be a valuable public health measure for metabolic diseases that are showing a rapid increase in South-East Asia and the Western Pacific.     

Poor Prognosis of Phosphatase of Regenerating Liver 3 Expression in Gastric Cancer: A Meta-Analysis

Background

Overexpression of phosphatase of regenerating liver 3 (PRL-3) has been implicated in gastric cancer (GC) metastasis. Epidemiological studies have evaluated the relationship between PRL-3 expression and prognosis in GC. However, results still remains controversial. In this study, a meta-analysis was performed to evaluate the association of PRL-3 expression with overall survival (OS) and clinicopathological characteristics.

Methods

Literature databases were searched to identify eligible studies dated until April 2013. Summary hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% CI) were calculated to estimate the association.

Results

A total of 1380 GC patients from six studies were included in the meta-analysis. Overall, the combined HR estimate for OS in a random-effect model was 1.89 (95% CI = 1.38–2.60; P<0.001). Results showed that PRL-3 overexpression was significantly associated with OS, indicating that it may be a biomarker for poor prognosis of GC. Both subgroup and sensitivity analyses further identified the prognostic role of PRL-3 expression in GC patients. Moreover, PRL-3 overexpression was significantly associated with tumor stage (OR = 2.25; 95% CI = 1.63–3.12; P<0.001), depth of invasion (OR = 2.03; 95% CI = 1.38–2.98; P<0.001), vascular invasion (OR = 2.52; 95% CI = 1.79–3.56; P<0.001), lymphatic invasion (OR = 3.74; 95% CI = 2.49–5.63; P<0.001), and lymph node metastasis (OR = 4.56; 95% CI = 2.37–8.76; P<0.001). However, when age, sex, tumor size, and tumor differentiation were considered, no obvious association was observed.

Conclusions

This meta-analysis reveals significant association of PRL-3 overexpression with OS and some clinicopathological features in GC. PRL-3 may be a predicative factor of poor prognosis and aggressive tumor behavior in GC patients.     

Prognostic Significance of Circulating Tumor Cells in Non-Small-Cell Lung Cancer Patients: A Meta-Analysis

Background

The prognostic significance of circulating tumor cells (CTCs) detected in patients with non-small-cell lung cancer (NSCLC) is still inconsistent. We aimed to assess the prognostic relevance of CTCs using a meta-analysis.

Methods

We searched PubMed, Web of Science and EMBASE for relevant studies that assessed the prognostic relevance of CTCs in NSCLC. Statistical analyses were conducted to calculate the summary incidence, odds ratio, relative risks (RRs) and 95% confidence intervals (CIs) using fixed or random-effects models according to the heterogeneity of included studies.

Results

A total of 20 studies, comprising 1576 patients, met the inclusion criteria. In identified studies, CTCs were not correlated with histology (adenocarcinoma vs squamous cell carcinoma) (odds ratio [OR]  =  0.88; 95% confidence interval [CI]: 0.59–1.33; Z = –0.61; P = 0.545). However, pooled analyses showed that CTCs were associated with lymph node metastasis (OR = 2.06; 95% CI: 1.18–3.62; Z = 2.20; P = 0.027) and tumor stage (OR  = 1.95; 95% CI: 1.08–3.54; Z = 2.53; P = 0.011). Moreover, CTCs were significantly associated with shorter overall survival (relative risk [RR]  = 2.19; 95% CI: 1.53–3.12; Z = 4.32; P<0.0001) and progression-free/disease-free survival (RR  = 2.14; 95% CI: 1.36–3.38; Z = 3.28; P<0.0001).

Conclusion

The presence of CTCs indicates a poor prognosis in patients with NSCLC. Further well-designed prospective studies are required to explore the clinical applications of CTCs in lung cancer.