Concurrent nimotuzumab and intensity-modulated radiotherapy for elderly patients with locally advanced nasopharyngeal carcinoma.

Because of the common physical condition, reduced organ function, and comorbidities, elderly patients with nasopharyngeal carcinoma (NPC) are often underrepresented in clinical trials. The optimal treatment of elderly patients with locally advanced NPC remains unclear. The purpose of this study was to evaluate the efficacy of concurrent nimotuzumab combined with intensity-modulated radiotherapy (IMRT) in elderly patients with locally advanced NPC. We conducted a single-arm, phase II trial for elderly patients with stage III-IVA NPC (according to UICC-American Joint Committee on Cancer TNM classification, 8th edition). All patients received concurrent nimotuzumab (200 mg/week, 1 week prior to IMRT) combined with IMRT. The primary end-point was complete response (CR) rate. The secondary end-points were survival, safety, and geriatric assessment. Between March 13, 2017 and November 12, 2018, 30 patients were enrolled. In total, 20 (66.7%) patients achieved CR, and objective response was observed in 30 (100.0%) patients 1 month after radiotherapy. The median follow-up time was 56.05 months (25th-75th percentile, 53.45-64.56 months). The 5-year locoregional relapse-free survival, distant metastasis-free survival, cancer-specific survival, disease-free survival, and overall survival were 89.4%, 86.4%, 85.9%, 76.5%, and 78.8%, respectively. Grade 3 mucositis occurred in 10 (33%) patients and grade 3 pneumonia in 3 (10%) patients. Concurrent nimotuzumab combined with IMRT is effective and well-tolerated for elderly patients with locally advanced NPC.

Detection and staging of recurrent or metastatic nasopharyngeal carcinoma in the era of FDG PET/MR.

PURPOSE: The aim of this pilot study was to evaluate the accuracy of 18 fluorodeoxyglucose (FDG) PET/MR imaging in detection and staging of recurrent or metastatic NPC. PATIENTS AND METHODS: The PET/MR scans of 60 patients with clinically diagnosed recurrent or metastatic NPC between April 2017 and November 2019 were included in this study. Findings were evaluated according to the eighth edition of the American Joint Committee on Cancer staging system. Final diagnosis was confirmed at biopsy or imaging follow-up for at least 6 months. RESULTS: Of the 60 patients, 25, 26 and 42 had developed local lesions, regional nodal metastases and distant metastases, respectively. The overall accuracy of PET/MR imaging for staging of recurrent or metastatic NPC was 88.3%. CONCLUSIONS: For recurrent or metastatic NPC, 18 FDG PET/MRI might serve as a single-step staging modality.

[Prognostic significance of the number of positive lymph nodes, number of involved regions and metastatic lymph node ratio in hypopharyngeal cancer].

OBJECTIVE: To explore the relationship between positive lymph node number, involved region, positive lymph node ratio and the prognosis of patients with hypopharyngeal cancer. METHODS: Clinicopatological data of 81 patients with hypopharyngeal squamous cell carcinoma who underwent hypopharyngectomy and cervical lymph node dissection from January 2000 to December 2005 in our hospital were analyzed retrospectively. The relationship between positive lymph node number, involved region, positive lymph node ratio and the prognosis was analyzed. RESULTS: The rate of lymph node metastasis was 79.0% (64/81) in the 81 patients with hypopharyngeal cancer. Of which, the rates of unilateral metastasis and bilateral metastasis were 82.9% (53/64) and 17.1% (11/64), respectively. The rate of lymph node metastasis was increasing with advancing tumor stage. The median survival times were 81, 51 and 26 months in the patients with 0, 1-3 and ≥ 4 positive lymph nodes, respectively (P < 0.001), 84, 45 and 23 months in patients with 0, 1-2 and ≥ 3 involved regions, respectively (P < 0.001), and 84, 51 and 17 months in patients with positive lymph node ratio of 0, <10% and ≥ 10%, respectively (P < 0.001). Multivariable analysis showed that positive lymph node ratio, extracapsular infiltration, T classification and treatment modality were independent prognostic factors (P = 0.002). CONCLUSIONS: Positive lymph node ratio is an independent prognostic factor for hypopharyngeal cancer.

Intracavity hyperthermia in nasopharyngeal cancer: a phase III clinical study.

PURPOSE: To compare the local tumour control, survival, and acute mucous toxicity of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy (RT) combined with intracavity hyperthermia versus conventional RT alone. METHODS AND MATERIALS: Previously untreated NPC patients were assigned randomly into the conventional RT group and the hyperthermia group. In addition to curative RT, hyperthermia group patients received intracavity hyperthermia before or after RT; T90 was 42.5°-43°C for 50 min twice a week for 7 weeks. RESULTS: From August 2001 to July 2006, 180 eligible patients with NPC were enrolled in this study. The complete response (CR) rate in the two arms (RT plus hyperthermia versus conventional RT) was 95.6% and 81.1%, respectively (p = 0.003, χ² test). CR rates for T2 and T3 patients in the hyperthermia group were 97.1% and 96.9%, respectively, while in the conventional RT group they were 79.5% and 76.7%, respectively. The difference between the two groups was statistically significant (p = 0.03 and p = 0.024, respectively). The 5-year local control rate was 91.1% and 78.9% for the two arms, respectively (p = 0.022). Oral mucous toxicity in both arms was comparable. The 5-year PFS and 5-year OS rate for the hyperthermia arm vs. the conventional arm were 72.7% versus 63.1% (p = 0.039) and 78.2% versus 70.3% (p = 0.14), respectively. CONCLUSIONS: Conventional RT treatment followed by intracavity hyperthermia was well tolerated by the NPC patients. The addition of hyperthermia improved the local tumour control, and our results indicated a positive impact on PFS of NPC patients.

Combined radiotherapy and chemotherapy versus radiotherapy alone in elderly patients with nasopharyngeal carcinoma: A SEER population-based study.

ABSTRACT: Currently, the impact of chemotherapy (CT) on survival outcomes in elderly patients with nasopharyngeal carcinoma (NPC) receiving radiation therapy (RT) remains controversial. This retrospective study aims to investigate survival outcomes in a cohort of elderly NPC patients receiving RT alone or together with CT.Clinical data on 529 NPC patients aged 65 years and older extracted from the Surveillance, Epidemiology, and End Results registry (2004-2015) was collected and retrospectively reviewed. In this cohort, 74 patients were treated with RT alone and 455 individuals received RT and CT. We used propensity score matching with a 1:3 ratio to identify correlations between patients based on 6 different variables. Kaplan-Meier analysis was used to evaluate overall (OS) and cancer-specific survival (CSS). The differences in OS and CSS between the 2 treatment groups were compared using the Log-rank test and Cox proportional hazards models.The estimated 5-year OS and CSS rates for all patients were 49.5% and 59.3%, respectively. The combination of RT and CT provided longer OS than RT alone (53.7% vs 36.9%, P = .002), while no significant difference was observed in CSS (61.8% vs 51.7%, P = .074) between the 2 groups. Moreover, multivariate analysis demonstrated that the combination of CT and RT correlated favorably with OS and CSS. Subgroup analyses showed that the combination of RT and CT correlated better with both OS and CSS in patients with stage T3 or N2 or stage III.Among NPC patients aged 65 years and older, treatment with RT and CT provided longer OS than RT alone. Furthermore, the combination of RT and CT showed a better correlation with OS and CSS in NPC patients with stage T3 or N2 or stage III.

Different Risk Target Volumes for Nasopharyngeal Carcinoma Treated with Simultaneous Integrated Boost Intensity-Modulated Radiotherapy.

Background and Objectives: Although intensity-modulated radiotherapy (IMRT) provides promising survival advantages and fewer late complications in patients with nasopharyngeal cancer (NPC), appropriated target volumes and prescribed doses are still being explored. This study aimed to propose different risk target volumes and corresponding prescribed doses in our center and to evaluate the physical basis and efficacy of this protocol based on the long-term survival of NPC patients. Methods and Materials: We retrospectively assessed patients with histology-proven non-metastatic NPC treated with definitive IMRT using our protocol of different risk target volumes and corresponding prescribed doses based on the orderly stepwise pattern of tumor spread. We described the delineation for different risk target volumes and the design of IMRT planning for an NPC case. Additionally, we compared the dosimetric distributions between the China protocol and our protocol through two NPC cases. The patterns of failure and locoregional control were the primary endpoints. All survival outcomes were calculated using the Kaplan-Meier method. Results: From January 2013 to December 2014, a total of 335 patients were treated; the median follow-up for patients who survived was 70 months. All patients completed IMRT using our protocol. Twenty-five patients developed locoregional recurrence, and all recurrences occurred within the high-dose target volumes. The rates of locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival, and overall survival at 5 years were 92.2%, 92.1%, 85.9%, and 86.3%, respectively. The biological effective doses of the prescribed doses in our protocol were similar to those of the China and 0615 protocols. Moreover, our protocol offered a reduction in D1 and D2 in the primary gross tumor volume (GTV), while V30 and V40 in normal tissues were lower. Conclusion: Our protocol of different risk target volume delineations and corresponding prescribed doses based on the stepwise pattern of tumor spread resulted in favorable locoregional control with no relapse outside the GTV.

Therapeutic patterns and outcomes in older patients (aged ≥65 years) with stage II-IVB Nasopharyngeal Carcinoma: an investigational study from SEER database.

Purpose: Currently, the optimal treatment regimens for older nasopharyngeal carcinoma (NPC) patients remained unclear. The aim of this retrospective study is to investigate therapeutic patterns and survival outcomes for a cohort of older NPC patients receiving radiation therapy (RT) with or without chemotherapy (CT). Methods: The clinical data of 529 patients with aged ≥65 years and NPC, who were identified within the Surveillance, Epidemiology, and End Results (SEER) registry (years 2004-2015), were collected and retrospectively reviewed. Among these patients, 74 patients treated with RT alone and 455 cases were administrated for RT plus CT. Kaplan-Meier analysis was used to evaluate overall survival (OS) and cancer-specific survival (CSS). The differences in OS and CSS were compared using Log-rank test. Results: The estimated OS and CSS rates at 5 years were 48.9% and 59.6%, respectively. Univariate analysis indicated that age, histology, T stage, and clinical stage were independent prognosticators of OS and CSS, while treatment option was only associated with OS. Multivariate analysis demonstrated that age, T stage, histology, and therapeutic strategy were correlated with OS, while age, T stage and histology were independent prognostic factors of CSS. Subgroup analyses showed that the combination of RT and CT yielded better OS and CSS in patients with stage T3 or N2 or III. Conclusion: Among these NPC patients with aged ≥65 years reported in the SEER database, treatment with RT plus CT provided longer OS than those treated with radiation therapy alone. Moreover, the combination of RT and CT obtained favorable OS and CSS in NPC patient stage T3 or N2 or III.

A prospective randomized controlled trial on the value of prophylactic oral nutritional supplementation in locally advanced nasopharyngeal carcinoma patients receiving chemo-radiotherapy.

OBJECTIVES: We investigated the effect of prophylactic oral nutrition supplements (ONS) in locally advanced nasopharyngeal carcinoma patients receiving neoadjuvant chemotherapy and concurrent chemoradiotherapy (CCRT). METHODS: Eligible patients were randomly assigned to an intervention or control group. Patients in the intervention group were supported with prophylactic ONS from the beginning of CCRT. The control group received nutritional support only when necessary. Bodyweight, hematological indexes, nutritional status, and quality of life were measured at baseline and before, during, and after RT. RESULTS: We evaluated 114 patients from October 2016 to May 2018. More than half of patients experienced significant weight loss during CCRT, which continued for three months after radiotherapy (RT). Compared to baseline, the rate of weight loss ≥ 5% before, during, at the end of RT, and one and three months after RT were 3.5%, 28.9%, 51.8%, 61.4%, and 61.4%, respectively. Nutritional status and global health status scores progressively decreased during treatment. The rate of RT interruption was higher in the control group than in the intervention group (7.14% vs. 0%, χ2 = 4.29, P = 0.04). More patients experienced concurrent chemotherapy interruption in the control group than in the intervention group (28.57% vs 10.34%, χ2 = 6.08, P = 0.01). There were no significant differences in weight loss, nutritional status, quality of life, and global health status between two groups. CONCLUSIONS: Malnutrition and weight loss progressively increased during treatment. Prophylactic ONS can improve tolerance to CCRT, but it offers no advantage on short-term weight loss or nutritional assessment scores.

Nutritional Status and Its Association With Radiation-Induced Oral Mucositis in Patients With Nasopharyngeal Carcinoma During Radiotherapy: A Prospective Study.

BACKGROUND AND AIMS: Malnutrition is a concern in patients with nasopharyngeal carcinoma (NPC) during chemoradiotherapy (CRT)/radiotherapy (RT), which is considered to be related with radiation-induced oral mucositis (ROM). The study aimed to evaluate the nutritional status of NPC patients during RT and investigate its association with ROM. METHODS: A prospective study was conducted in NPC patients. Patients were divided into three subgroups (mild, moderate, and severe groups) based on the duration of severe ROM (≥ grade 3). Body weight, body mass index (BMI), albumin, prealbumin, NRS2002, and ROM grade were assessed on a weekly basis before and during CRT/RT. The statistical analysis was performed in the overall group and between three subgroups. RESULTS: A total of 176 patients were included. In the overall group, body weight and BMI kept decreasing since week 1 of RT, and NRS2002 score and ROM grade increased (p < 0.001). NRS2002 score and prealbumin levels were significantly different between each subgroup (p ≤ 0.046). Significant differences were observed in the proportion of patients receiving enteral nutrition, duration of parenteral nutrition, and total calories provided by nutritional support among three subgroups (p = 0.045-0.001). CONCLUSIONS: Malnutrition occurred early in NPC patients and worsened continuously during RT. ROM was strongly associated with nutritional status. Nutritional support should be provided at the start of RT, especially in patients at high-risk of severe ROM.

Paranasal Sinus Invasion in Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy.

PURPOSE: The aim of this study is to evaluate the prognostic significance of paranasal sinus invasion for nasopharyngeal carcinoma (NPC) and its suitable position in the T classification. MATERIALS AND METHODS: The magnetic resonance imaging (MRI) scans of 695 patients with previously untreated, biopsy-proven, non-metastatic NPC that was treated with intensity-modulated radiotherapy (IMRT) were reviewed retrospectively. RESULTS: The incidence of paranasal sinus invasion was 39.4% (274 of 695 patients). Multivariate analysis showed that paranasal sinus invasion was an independent negative prognostic factor for local failure-free survival (LFFS) (p < 0.05). According to the eighth American Joint Committee on Cancer (AJCC) staging system, 275 patients were classified as T3 classification. Of these, 78 patients (28.4%) developed paranasal sinus invasion (T3b) and 197 (71.6%) didn't (T3a). The estimated 5-year LFFS and overall survival (OS) rates for the patients with T3b and T3a classification were 88.6% versus 95.0% (p=0.047), and 84.5% versus 93.3% (p=0.183), respectively. The estimated 5-year LFFS and OS rates for the patientswith T4 classificationwere 89.5% and 83.2%,whichwere similarwith the outcomes of patients with T3b classification. CONCLUSION: MRI-determined paranasal sinus invasion is an independent prognostic factor of NPC treated by IMRT. Paranasal sinus invasion is recommended to classify as T4 classification in the 8th AJCC staging system for NPC.

Endostar Combined with Gemcitabine and Cisplatin Chemotherapy for Patients with Metastatic Nasopharyngeal Carcinoma: an Update.

OBJECTIVE: A previous phase-2 trial to assess the addition of Endostar to gemcitabine and cisplatin (GC) chemotherapy showed that it improves prognosis in metastatic nasopharyngeal carcinoma (M-NPC) but the study cohort was small. We wished to update that phase-2 trial by enrolling an additional 44 patients and to assess the benefit of Endostar+GC chemotherapy. METHODS: An analysis of 72 M-NPC patients treated between July 2010 and November 2016 was done. The treatment regimen was a combination of gemcitabine (1,000 mg/m2) on days 1 and 8, cisplatin (80 mg/m2) on day 1, and Endostar (15 mg/day) from day 1 to day 14 of a 21-day cycle for ≥2 cycles. The acute toxic effects and therapeutic efficacy were analyzed. RESULTS: The response rate was 77.8%. The median progression-free and overall survivals were 12 and 19.5 months, respectively. A total of 329 cycles of GC and 288 cycles of Endostar were delivered to 72 patients, with the median number of four (range, 2-10) cycles administered per patient. The main grade-3/4 hematologic toxicities were leukopenia (54.1%) and neutropenia (59.8%). The number of non-hematologic adverse events was minimal. The regimen was well-tolerated. CONCLUSIONS: Endostar+GC chemotherapy is an effective, well-tolerated regimen for M-NPC.

Locoregional extension and patterns of failure for nasopharyngeal carcinoma with intracranial extension.

OBJECTIVE: To evaluate the locoregional extension and patterns of failure for nasopharyngeal carcinoma (NPC) with intracranial extension to improve clinical target volume (CTV) delineation. PATIENTS AND METHODS: A total of 205 NPC patients with intracranial extension by magnetic resonance imaging (MRI) were retrospectively reviewed. RESULTS: According to the cumulative incidence rates of tumor invasion, we initially classified anatomic sites surrounding the nasopharynx into three risk grades: high risk (≥35%), medium risk (≥10-35%), and low risk (<10%). It was concluded that the anatomic sites at high risk of tumor invasion were the middle/posterior skull base and the anatomic sites adjacent to the nasopharynx. The rate of lymph node (LN) metastasis was 90.2% (185/205). Retropharyngeal region (RP) and level IIb were the most frequently involved regions. Skip metastasis occurred in only 1.6% (3/185). At their last follow-up visit, 53 patients (25.9%) had developed treatment failure. Of the 18 local failures, 12 were considered in-field failure; the other 5 were marginal; one of the patients had outside-field failure. Among the 5 patients with marginal failures, 4 occurred mainly intracranially, and 1 occurred in the floor and the left lateral wall of the nasopharynx. Of the 11 regional failures, 10 were considered in-field failures and most of them (8/10) occurred in the unilateral upper neck. CONCLUSION: For NPC with intracranial extension, primary disease and regional LN spread follow an orderly pattern and LN skipping was unusual. Clinical target volume reduction may be feasible for selected patients.

Neoadjuvant chemotherapy with different dose regimens of docetaxel, cisplatin and fluorouracil (TPF) for locoregionally advanced nasopharyngeal carcinoma: a retrospective study.

OBJECTIVE: Compare high- vs. low-dose TPF neoadjuvant chemotherapy with chemoradiotherapy in Chinese patients with locoregionally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Retrospective analysis of 210 stage III/IV NPC patients treated between April 1, 2012 and April 1, 2014; 138 received three cycles of high-dose TPF (H-TPF) every 3 weeks at Zhejiang Cancer Hospital and 72, three cycles of low-dose TPF (L-TPF) every 3 weeks at Sun Yat-Sen University Cancer Center. H-TPF was docetaxel (75 mg/m2; 1 h infusion), cisplatin (75 mg/m2; 0.5-3 h), then 5-fluorouracil (600 mg/m2/day; 4 days). L-TPF was docetaxel (60 mg/m2), cisplatin (65 mg/m2), then 5-fluorouracil (550 mg/m2/day; 5 days). All patients received chemoradiotherapy. RESULTS: During neoadjuvant chemotherapy, treatment delays were more frequent for H-TPF than L-TPF (33.3% vs. 19.4%; P = 0.034). During chemoradiotherapy, grade III-IV anemia, thrombocytopenia and neutropenia were more common for H-TPF than L-TPF (P < 0.001, P < 0.001, P = 0.048). Fewer patients in the H-TPF group finished two cycles of concurrent chemotherapy (81.2% vs. 100%, P < 0.001). Three-year PFS (84.5% vs. 80.6%, P = 0.484) and OS (91.1% vs. 93.5%, P = 0.542) were not significantly different between H-TPF and L-TPF. CONCLUSIONS: L-TPF neoadjuvant chemotherapy has substantially better tolerance and compliance rates and similar treatment efficacy to H-TPF neoadjuvant chemotherapy in locoregionally-advanced NPC.

Correlation between pretreatment serum LDL-cholesterol levels and prognosis in nasopharyngeal carcinoma patients.

PURPOSE: To investigate the correlations between long-term survival outcomes in patients with nasopharyngeal carcinoma (NPC) and pretreatment serum low-density lipoprotein cholesterol (LDL-C) levels. PATIENTS AND METHODS: Between January 2008 and December 2011, 935 patients with newly diagnosed NPC who were treated with intensity-modulated radiation therapy were included in this retrospective clinical analysis. Patients were divided into two groups based on pretreatment LDL-C levels: normal LDL-C (≤3.64 mmol/L; n=816) and elevated LDL-C (>3.64 mmol/L; n=119). Associations between pretreatment LDL-C levels and treatment outcome were analyzed by univariate and multivariate analyses. RESULTS: The overall patient follow-up rate was 95.1%, and 726 patients received more than 5 years of follow-up. Five-year overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) rates of the entire patient population were 87.1%, 91.1%, and 87.2%, respectively. Rates of 5-year OS, LC, and DMFS for the elevated versus normal LDL-C groups were 77.0% vs 89.1% (P<0.001), 85.8% vs 91.9% (P=0.041), and 81.1% vs 88.1% (P=0.038), respectively. Compared with normal LDL-C levels, elevated LDL-C levels were identified as an independent prognostic factor of a poorer OS (hazard ratio [HR] =2.171; 95% confidence interval [CI] =1.424-3.309), LC rate (HR =1.762; 95% CI =1.021-3.942), and DMFS (HR =1.594; 95% CI =1.003-2.532). CONCLUSION: This study found that elevated pretreatment LDL-C levels are negative prognostic indicators of NPC. Elevated LDL-C levels may be useful indicators of locoregional control and distant metastasis in NPC patients.

The C-reactive Protein/Albumin Ratio Is an independent Prognostic Factor for Overall Survival in Patients with Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy.

This study aims to investigate the prognostic value of the C-reactive protein/albumin (CRP/ALB) ratio in nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. A total of 719 patients with NPC treated between January 2007 and December 2012 were retrospectively reviewed. Serum albumin and CRP levels were measured before treatment. The associations between the CRP/ALB ratio and clinicopathological parameters were analyzed. Multivariate analyses using the Cox proportional hazards model were performed to identify significant prognostic factors associated with overall survival (OS). The prognostic value of the CRP/ALB ratio was determined using receiver operating characteristic (ROC) curve analysis. The optimal CRP/ALB ratio cutoff value was 0.141. High CRP/ALB ratio was significantly associated with older age (P < 0.001), more advanced T category (P < 0.001) and advanced TNM stage (P = 0.024). Patients with an elevated CRP/ALB ratio (≥ 0.141) had poorer OS than those with a CRP/ALB ratio < 0.141 (5-year OS rates: 91.9% vs. 78.1%; P < 0.001). Multivariate analysis suggested clinical T category [hazard ratio (HR) 2.284; 95% confidence interval (CI), 1.429-3.652; P = 0.001]; clinical N category (HR 1.575; 95% CI, 1.007-2.464; P = 0.047) and CRP/ALB ratio (HR 2.173; 95% CI, 1.128-3.059; P = 0.015) were independently associated with OS. In conclusion, pretreatment CRP/ALB ratio is an objective biomarker with significant prognostic value for OS in NPC. The CRP/ALB ratio can enhance conventional TNM staging to stratify patients and may help facilitate individualized treatment of high-risk cases.

A prognostic model combining CD4/CD8 ratio and N stage predicts the risk of distant metastasis for patients with nasopharyngeal carcinoma treated by intensity modulated radiotherapy.

This study aimed to evaluate the correlation between circulating lymphocyte subsets and clinical variables, and design an effective prognostic model for distant metastasis-free survival (DMFS) in NPC. In this study, subsets of circulating lymphocytes were determined in 719 non-metastatic NPC patients before treatment. Overall survival and DMFS was monitored. Significant prognostic factors were identified using univariate and multivariate analyses. Results showed that the percentage of CD19+ lymphocytes correlated negatively with TNM stage (r = -0.082, P = 0.028). Patients with higher CD4/CD8 ratios (≥ 1.77) showed better 5-year DMFS than patients with lower ratios (91.9% vs. 85.4%, P < 0.001). Multivariate analysis revealed that CD4/CD8 ratio (HR, 0.450; 95% confidence interval [CI], 0.266-0.760; P = 0.003) and N classification (HR, 2.294; 95% CI, 1.370-3.839; P = 0.002) were independently prognostic factors for DMFS. The prognostic N-R model was developed and divided patients into three groups: (1) low-risk (early N stage and CD4/CD8 ratio ≥ 1.77); (2) intermediate-risk (advanced N stage or CD4/CD8 ratio < 1.77) and (3) high-risk (advanced N stage and CD4/CD8 ratio < 1.77) of distant metastasis. In conclusion our prognostic model, based on clinical N stage and CD4/CD8 ratio, may predict the risk of distant metastasis, allowing individualized treatment for NPC.

Effect of capilliposide for induction apoptosis in human nasopharyngeal cancer CNE-2 cells through up-regulating PUMA expression.

OBJECTIVE: To observe the apoptosis of capilliposide against human nasopharyngeal cancer CNE-2 cells and to study its primary mechanisms. MATERIALS AND METHODS: Vectors pSilencer-PUMA-small interfering RNA (siRNA) were constructed to transcribe functional siRNA specially targeting PUMA. The interfering plasmids were used to transfect CNE-2 cells with lipofectamine 2000 transfection reagent. PUMA messenger RNA (mRNA) expression levels were analyzed by polymerase chain reaction. The proliferation of CNE-2 cells was detected using MTT colorimetry. Annexin V/propidium iodide double staining was applied to detect the apoptosis rate of CNE-2 cells. The protein levels of p53, PUMA, and Bax were detected using Western blot analysis. RESULTS: Recombinant siRNA expression vector targeting PUMA was constructed. MTT assays showed capilliposide inhibited the proliferation of CNE-2 cells in a concentration-dependent manner. The inhibition was strengthened along with increased concentrations. Apoptosis detected by flow cytometry in control group, drug group, siRNA group, and drug combined siRNA group was 9.3 ± 2.3%, 31.4 ± 5.6%, 12.3 ± 4.1%, and 13.2 ± 3.7%, respectively. After pretreated by capilliposide, PUMA protein was upregulated, and BAX was distributed to mitochondria in CNE-2 cells using Western blot analysis, but this effect can be interrupted by PUMA-siRNA. CONCLUSIONS: Capilliposide could induce the apoptosis of CNE-2 cells, which might be related with the increasing in PUMA-Bax pathway.

Effect of number and ratio of positive lymph nodes in hypopharyngeal cancer.

BACKGROUND: The number and ratio of positive lymph nodes are important prognostic factors in gastric cancer, but there is little data reported in hypopharyngeal cancer. METHODS: Medical data from 81 patients with hypopharyngeal cancer undergoing radical hypopharyngectomy and cervical lymph node dissection were reviewed. RESULTS: The median survival time was 84, 54, 30, and 13 months in patients with N0, N1, N2, and N3, respectively, and 84, 51, and 17 months with positive lymph node ratios (N ratio) 0, <10%, and >10%, respectively. Of the 24 N1 patients, the 20 patients that had an N ratio <10% had a better prognosis than the 4 patients with an N ratio >10%. Similar data was seen for the N2 patients. Tumor (T) classification, adjuvant therapy, and N ratio were independent prognostic factors in multivariate analysis. CONCLUSION: The positive lymph node ratio is complementary to the current N classification system.