Sequential Cytokine-Induced Killer Cell Immunotherapy Enhances the Efficacy of the Gemcitabine Plus Cisplatin Chemotherapy Regimen for Metastatic Nasopharyngeal Carcinoma.

In this study, we investigated the efficacy of sequential cytokine-induced killer cell (CIK) immunotherapy with gemcitabine plus cisplatin (GC) regimen chemotherapy in metastatic nasopharyngeal carcinoma (NPC) patients. Between September 2006 and April 2010, 222 NPC patients with distant metastasis after radiotherapy completion were retrospectively analyzed: 112 patients received 4-6 cycles of GC chemotherapy at 4-week intervals, followed by at least 4 cycles of CIK immunotherapy at 2-week intervals (GC+CIK group); the remaining 110 patients received 4-6 cycles of GC chemotherapy alone (GC group). The evaluation of long-term efficacy showed that the progression-free survival (PFS) rate was significantly higher in the GC+CIK group (log-rank test; p = 0.009), as was the overall survival (OS) rate (p = 0.006). In conclusion, sequential CIK treatment may be effective in enhancing the therapeutic efficacy of GC chemotherapy for metastatic NPC patients. This study provides a basis for alternative therapeutic strategies for metastatic NPC.

Proposal of a clinical typing system and generation of a prognostic model in patients with nasopharyngeal carcinoma from Southern China.

PURPOSE: To propose a novel clinical typing classification focusing on the distinct progression patterns of nasopharyngeal carcinoma (NPC), to supplement our knowledge of the clinical-biological behavior, to provide useful knowledge for treatment planning, and to contribute to basic research in NPC. METHODS: 632 consecutive patients were retrospectively reviewed and analyzed according to the novel typing system. We considered that NPC can be divided into 5 types as follows: limited (L), ascending (A), descending (D) ascending- descending (mixed) (AD), and distant metastasis types (M). The distribution of these clinical types, their association with Epstein-Barr virus (EBV) serology and prognostic value were explored. RESULTS: 55 (8.70%), 59 (9.34%), 177 (28.01%), 321 (50.79%) and 20 (3.16%) patients were classified as Type L, A, D, AD and M, respectively. EBV (VCA)-IgA titers, EBV early antigen (EA)-IgA serum titers, and capsid antigen lg(EBV DNA) were positively associated with the clinical typing (p<0.05). The 3-year overall survival (OS) rates for Types L, A, D, AD and M were 100, 100, 95.10, 88.20 and 59.30%, respectively (p<0.001). A prognostic model was constructed based on pretreatment lg (EBV DNA) and clinical type, which were independent predictors of OS (multivariate Cox proportional model). The prognostic model stratified patients into 4 risk subgroups. The 3-year OS rates of the low, intermediate, high and extremely high risk groups were 99.5, 90.0, 85.5 and 53.2%, respectively (p<0.001). Compared with the low-risk group, the risk of death was 4.96, 8.75 and 35.9 in the intermediate, high and extremely high risk groups, respectively (p<0.001). The model also predicted OS independently of TNM classification. CONCLUSION: This novel clinical typing system and prognostic model can supplement TNM classification, and may help design novel treatment strategies, evaluate risk stratification and investigate the varied biological characteristics of NPC.

Translation and validation of the Chinese version of the Quality OF Life Radiation Therapy Instrument and the Head & Neck Module (QOL-RTI/H&N).

BACKGROUND: To translate and validate the Chinese version of the Quality Of Life Radiation Therapy Instrument and the Head & Neck Module (QOL-RTI/H&N), a disease-specific scale to measure quality of life (QOL) for patients with head and neck cancer (HNC) who received radiotherapy. METHODS: The QOL-RTI/H&N was translated and validated according to the standard process: a translation and back-translation procedure, pilot testing and a validation study. HNC patients were enrolled from the Cancer Center of Sun Yat-sen University and assessed using the QOL-RTI/H&N, QLQ-C30 and QLQ-H&N35. Reliability (internal consistency reliability, split-half reliability and test-retest reliability), validity (content validity, construct validity, criterion validity and discriminant validity), and responsiveness analysis were performed to evaluate the psychometric characteristics of the QOL-RTI/H&N. RESULTS: A total of 238 patients (99.2%) completed the questionnaire. Item RTI23 had 16.0% missing data. Other items had low percentages of missing data (0.4% or 0.8%) or no missing data. The average time to finish the scale was 9.8 minutes. Cronbach's alpha of the domains ranged from 0.41 to 0.77. The split-half reliability coefficients ranged from 0.43 to 0.77. All of the intra-class correlation coefficients were equal to or greater than 0.8. All of the item-own domain correlation coefficients were greater than those of the item-other domain. Confirmatory factor analysis showed that Comparative Fit Index, Normed Fit Index and Non-Normed Fit Index were equal to 1.00. Root Mean Square Error of Approximation was 0.01, with 90% CI (0.00, 0.10). The domain scores of the QOL-RTI/H&N were significantly correlated with those of the QLQ-C30 or QLQ-H&N3. All domain scores of patients in different radiotherapy stages were statistically significant (P < 0.05), apart from the speech domain. CONCLUSIONS: The Chinese version of the QOL-RTI/H&N is a valid, reliable and responsive scale to measure QOL in HNC patients and can be used to assess the effects of radiotherapy treatment on these patients.

Serologic biomarkers of Epstein-Barr virus correlate with TNM classification according to the seventh edition of the UICC/AJCC staging system for nasopharyngeal carcinoma.

This study aimed to investigate the association between Epstein-Barr virus (EBV)-related biomarkers and TNM classification according to the seventh edition of AJCC/UICC staging system for nasopharyngeal carcinoma. Serum VCA-IgA and EA-IgA titers and plasma EBV-DNA load were quantified at baseline in 779 patients; the rates of positivity and titers/load were compared by TNM classification. The VCA-IgA-positive rate was significantly associated with advanced N classification and stage; the EA-IgA-positive rate with advanced T and N classifications and stage; the EBV-DNA-positive rate with advanced T, N and M classifications and stage. The percentage of triple-positive patients was higher in patients with advanced TNM classification. The VCA-IgA titer and EA-IgA titer correlated positively with T classification, N classification and disease stage (1:117 in Stage I, 1:188.4 in Stage II, 1:231.12 in Stage III, 1:265.91 in Stage IV, and 1:18.34 in Stage I, 1:32.11 in Stage II, 1:34.77 in Stage III, 1:37.65 in Stage IV, respectively). EBV DNA load correlated positively with T, N and M classification and stage [median lg (EBV DNA): 0 (IQ range 0-1.85) in Stage I, 1.32 (0-3.51) in Stage II, 3.33 (0-4.30) in Stage III, 3.83 (2.85-4.71) in Stage IV]. Serum VCA-IgA/EA-IgA titers and plasma EBV DNA correlated strongly with TNM classification according to the seventh edition of the AJCC/UICC; however, plasma EBV DNA load could accurately predict metastatic disease. EBV serological biomarkers may enhance the accuracy of TNM staging and help to avoid excessive imaging examinations in routine evaluation.

Prognostic value of tumor volume for patients with nasopharyngeal carcinoma treated with concurrent chemotherapy and intensity-modulated radiotherapy.

PURPOSE: We aimed to analyze prognostic factors in patients with nasopharyngeal carcinoma (NPC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT); in addition, we aimed to elucidate the value of primary gross tumor volume (GTVp) in predicting prognosis of patients. METHODS: Between February 2001 and December 2008, 321 patients with NPC treated with concurrent chemotherapy and IMRT were analyzed retrospectively. GTVp was calculated from treatment planning computed tomography scans. A receiver operating characteristics (ROC) curve was used to determine the best cutoff point of GTVp. RESULTS: The 5-year local failure-free survival (LFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) for NPC patients were 93.8, 80.1, 73.0, and 83.7 %, respectively. Univariate and multivariate analyses indicated that GTVp had exhibited a statistically significant correlation with LFFS, DMFS, DFS, and OS (P < 0.05, all), whereas T classification was not an independent prognostic factor. According to ROC curve analysis, 49 and 19 mL were determined as the cutoff points of GTVp for local control and distant metastasis, respectively. Based on this, 321 patients were divided into three volume subgroups. LFFS, DMFS, DFS, and OS demonstrated significant differences among patients in different volume subgroups (P < 0.001, all) and were superior to T classification for predicting prognosis of NPC patients. CONCLUSIONS: Primary gross tumor volume is an independent prognostic factor in local control, distant metastasis, disease-free survival, and overall survival in NPC. An adjusted TNM staging system that includes GTVp as a quantitative indicator to evaluate prognosis is warranted.

Using CT or MRI to assess locoregional spread to determine the radiotherapy target of hypopharyngeal carcinoma.

AIM: To identify the locoregional extension of hypopharyngeal carcinoma (HPC), particularly the invasion of the nasopharynx and skull base, and metastasis of level VI and retropharyngeal lymph node (RPLN) by investigating computed tomography (CT) and magnetic resonance (MR) images; together with the radiotherapy target of HPC. METHODS: CT and MR images of 186 patients with pathologically confirmed HPC between Aug 2000 and Dec 2010 were analyzed retrospectively. We used the χ(2) test and logistic regression to analyze local invasion and regional spread and to determine their relationships. RESULTS: Of the 186 patients, there was only one case of invasion of the nasopharynx without skull base involvement. The rate of regional node metastasis was 79%. There was no significant relationship between T stage and lymph node metastasis (P = 0.1). Level IV metastasis (P = 0.001), RPLN metastasis (P = 0.041) and esophageal invasion (P = 0.003) were significantly correlated with level VI metastasis. Primary tumor subsite (P = 0.024), bilateral cervical node metastasis (P < 0.001) and size of cervical nodes (P = 0.01) significantly contributed to the occurrence of RPLN metastasis. CONCLUSION: The locoregional spread of HPC occurs via certain routes. It is potentially unnecessary to routinely and prophylactically irradiate the nasopharynx and skull base. Patients with early stage HPC should receive bilateral cervical prophylactic irradiation. The decision regarding the administration of prophylactic irradiation to the level VI and RPLN areas should be according to the relative risk factors.

Correlation between nasopharyngeal carcinoma tumor volume and the 2002 International Union Against Cancer tumor classification system.

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

Analysis of risk factors for retropharyngeal lymph node metastasis in carcinoma of the hypopharynx.

BACKGROUND: The purpose of this study was to investigate the incidence of retropharyngeal lymph node (RPLN) metastasis and to explore the associated risk factors using CT and MRI, to direct clinical radiotherapy in hypopharyngeal carcinoma (HPC). METHODS: The CT and MRI images of 218 patients with pathologically confirmed HPC were analyzed retrospectively. The chi-square test and logistic regression were used for statistical analysis. RESULTS: The incidence of RPLN metastasis in HPC was 17.0%, and the highest rate of 36.4% was found in pharyngeal wall carcinoma. None of the patients with N0 classification exhibited RPLN metastasis. Univariate and multivariate analyses demonstrated that primary tumor subsites, bilateral cervical lymph node metastasis, the number and size of cervical lymph nodes, and level V metastasis were significantly associated with RPLN metastasis. CONCLUSIONS: Our findings demonstrated that primary carcinoma subsites and multiple metastatic cervical lymph nodes are the principal risk factors for RPLN metastasis.

Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma.

We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin-gemcitabine (GC) regimen (800 mg/m(2) gemcitabine on Days 1 and 8 and 20 mg/m(2) cisplatin on Days 1-5, every 4 weeks) (sGC-RT); sequential chemoradiotherapy with a cisplatin-fluorouracil (PF) regimen (20 mg/m(2) DDP and 500 mg/m(2) 5-FU on Days 1-5, every 4 weeks) (sPF-RT) and cisplatin-based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con-RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3-year overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates in the sGC-RT group were significantly higher than those observed in the Con-RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3-year OS, DFS and MFS rates between the Con-RT and the sPF-RT groups. The GC-RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC-RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.

Prognostic value of soluble MICA levels in the serum of patients with advanced hepatocellular carcinoma.

Serum levels of soluble MHC class I-related chain A (sMICA) are related with the prognosis of various types of cancer; however, few studies on the prognostic value of sMICA in hepatocellular carcinoma (HCC) have been reported. In this study, we retrospectively investigated the relationship between sMICA levels and clinical features of advanced HCC, and we assessed the prognostic value of sMICA in advanced HCC. Furthermore, the relationship of serum sMICA levels and natural killer group 2, member D (NKG2D) expression on natural killer (NK) cells was also evaluated. We detected sMICA levels in the serum of 60 advanced HCC patients using enzyme-linked immunosorbent assay (ELISA) and measured expression levels of NKG2D on NK cells using flow cytometry. We found that serum sMICA levels in HCC patients were in the range of 0.10-6.21 ng/mL. Chi-square analyses showed that sMICA level was significantly related with only tumor size. Survival analysis showed that a high sMICA level was significantly related with poor prognosis among HCC patients. Multivariate analyses indicated that sMICA was an independent prognostic factor. In addition, the levels of CD56+NKG2D+ NK cells were within the range of 11.2%-55.4%, and correlation analyses indicated that sMICA level was negatively correlated with the level of NKG2D+ NK cells. Our results suggest that serum sMICA levels may be an independent prognostic factor for advanced HCC.

Prognostic significance of tumor volume in patients with nasopharyngeal carcinoma undergoing intensity-modulated radiation therapy.

BACKGROUND: This study was undertaken to analyze the correlation between primary gross tumor volume (GTVp) and prognosis in patients with nasopharyngeal carcinoma (NPC) undergoing intensity-modulated radiation therapy (IMRT). METHODS: Between February 2001 and December 2006, 305 patients with NPC treated with IMRT were analyzed retrospectively. GTVp was calculated from treatment planning CT scans. RESULTS: Univariate and multivariate analyses indicated that GTVp had a statistically significant correlation to local control, distant metastasis, and overall survival in patients with NPC, whereas T classification was not an independent prognostic factor. Among patients classified with N0-1 and N2-3, there were significant differences in the rates of distant metastasis between those with GTVp smaller and larger than 25 mL (p < .001 and p = .002, respectively). CONCLUSIONS: GTVp is highly significant in evaluating local control, distant metastasis, and overall survival of patients with NPC treated with IMRT. Therefore, it is recommended that GTVp be included in the new TNM classification system.

[Imaging and clinical features of nasopharyngeal adenoid cystic carcinoma].

OBJECTIVE: To analyze the spreading patterns nasopharyngeal carcinoma and nasopharyngeal adenoid cystic carcinoma. METHODS: Eighteen pathologically confirmed consecutive cases of adenoid cystic carcinomas (ACC) and 182 cases of untreated nasopharyngeal carcinomas (NPC) were reviewed. RESULTS: Compared with NPC, ACC had higher rates of T4 disease (14.3% vs 38.9%,χ(2) = 7.197, P = 0.007) and paralyzed cranial nerve (6.0% vs 38.9%,χ(2) = 37.936, P < 0.001) . There was no significant difference in skull base invasion rates between 2 groups (53.3% vs 66.7%,χ(2) = 1.181, P = 0.277) . ACC had higher rates of MRI-detected cranial nerve canal invasion (32.4% vs 55.6%,χ(2) = 3.881, P = 0.049) and cavernous sinus invasion (13.7% vs 33.3%,χ(2) = 7.710, P = 0.028) than NPC. Lymph node metastasis occurred in 64.8% of ACC, and 11.1% of NPC (χ(2) = 19.699, P < 0.001) . CONCLUSION: ACC has a higher rate of cranial nerve invasion and NPC has a higher rate of lymphatic metastasis.

Quality of life and radiotherapy complications of Chinese nasopharyngeal carcinoma patients at different 3DCRT.

PURPOSE: the study aimed to compare the quality of life (QOL) and radiotherapy complications among Chinese nasopharyngeal carcinoma (NPC) patients at different 3-dimensional conformal radiotherapy (3DCRT) stages adjusting for other variables. METHODS: 511 NPC patients at different 3DCRT stages were enrolled. They were interviewed regarding SF-36, complications and socio-demographic variables and cancer- or treatment- related variables. Analysis of covariance (ANCOVA) based on SF-36, complications scores as dependent variables, 3DCRT stages as independent variables, and other variables as covariate were established. RESULTS: The influencing factors of PCS included 3DCRT stages and age group. The influencing factors of MCS included 3DCRT stages and income. Most QOL scores of NPC patients were significantly associated with 3DCRT stage, after accounting for other variables. QOL scores of the patients receiving 3DCRT were the lowest, QOL scores of people after 3DCRT gradually increased. PCS scores of people greater than 5 years after 3DCRT was improved to or even better than the level before 3DCRT. The complications with significantly different scores of patients at different 3DCRT status included xerostomia, throat ache, hypogeusia, caries, hearing loss, snuffles. CONCLUSIONS: Clinicians should pay more attention to older NPC patients and patients with lower income. When patients receive 3DCRT, measures should be taken to reduce radiation injury to improve the patients' QOL.

Primary nasopharyngeal adenocarcinoma: a review.

Primary nasopharyngeal adenocarcinoma (NAC) accounts for approximately 0.5% of all nasopharyngeal cancer. The diagnosis, staging and treatment of NAC has not been well described. This article presents a literature review on NAC and identifies its characteristics and management. The NAC group of diseases contains various pathological types and has a series of specific clinical characteristics, including slow progression, a low incidence of neck masses and frequent cranial neuropathy. The Epstein-Barr virus may not play an important role in NAC carcinogenesis. The rarity of the disease makes the staging classification and treatment strategies of NAC parallel to those recommended for nasopharyngeal squamous carcinoma. Some patients might benefit from surgery, and radiotherapy using precise techniques might achieve good control for treating NAC, but the roles of chemotherapy and target therapy are not clear. The proper staging system and optimal treatment strategies need to be established in NAC.

Autologous cytokine-induced killer cell transfusion in combination with gemcitabine plus cisplatin regimen chemotherapy for metastatic nasopharyngeal carcinoma.

In this study, we evaluate the efficacy of autologous cytokine-induced killer cells (CIK) transfusion used in combination with gemcitabine and cisplatin (GC) chemotherapy to treat nasopharyngeal carcinoma in patients with distant metastasis after radiotherapy. From September 2007 to August 2008, 60 patients with distant metastasis after radiotherapy were followed up and were randomly divided into 2 groups. The 30 patients in the GC+CIK group were treated with adoptive autologous CIK cell transfusion in combination with GC chemotherapy; the 30 patients in the GC group were treated with chemotherapy alone. Short-term efficacy evaluation revealed that in the GC+CIK group, there were 3 cases of complete remission, 18 cases of partial remission, 2 cases of stabilization of disease, and 7 cases of progression of disease and the total effective rate was 70% (21/30). In the GC group, there were 0 cases of complete remission, 14 cases of partial remission, 3 case of stable disease, and 13 cases of progressive disease and the total effective rate was 46.7% (14/21). Kaplan-Meier survival analysis showed that the overall survival of the GC+CIK group was higher than that of the GC group, but the difference was not significant (P=0.1374, log-rank test). However, the progression-free survival of the GC+CIK group was significantly higher than that of the GC group (P=0.0234, log-rank test). Thus, our study indicated that CIK cell transfusion therapy used in combination with GC chemotherapy may be a more effective treatment for postradiotherapy distant metastasis of nasopharyngeal carcinoma patients.

Interaction between ROS and p38MAPK contributes to chemical hypoxia-induced injuries in PC12 cells.

The present study investigated whether there is an interaction between reactive oxygen species (ROS) and p38 mitogen-activated protein kinase (MAPK) during chemical hypoxia-induced injury in PC12 cells. The results of the present study showed that cobalt chloride (CoCl2), a chemical hypoxia agent, markedly induced ROS generation and phosphorylation of p38MAPK, as well as neuronal injuries. N-acetylcysteine (NAC), a ROS scavenger, blocked CoCl2-induced phosphorylation of p38MAPK. In addition, SB203580, an inhibitor of p38MAPK attenuated not only CoCl2-induced activation of p38MAPK, but also ROS production. These results suggest that ROS and p38MAPK are capable of interacting positively during chemical hypoxia. Furthermore, NAC and SB203580 markedly prevented CoCl2-induced cytotoxicity, apoptosis and a loss of mitochondrial membrane potential. Taken together, our findings suggest that the positive interaction between CoCl2 induction of ROS and p38MAPK activation may play a significant role in CoCl2-induced neuronal injuries. We provide new insights into the mechanisms responsible for CoCl2-induced injuries in PC12 cells.

Surgery alone provides long-term survival rates comparable to those of surgery plus postoperative radiotherapy for patients with adenoid cystic carcinoma of the palate.

We compared the outcomes and rates of survival provided by surgery alone and surgery combined with postoperative radiotherapy for patients with adenoid cystic carcinoma of the palate (ACP), a rare, low-grade malignant tumor arising within the salivary glands. Fifty-eight patients with ACP were included in this retrospective study. ACP at stages T(1), T(2), T(3,) and T(4) was found in 11, 32, 5, and 10 patients, respectively. The patients were treated with surgery alone or underwent surgery combined with postoperative radiotherapy. The 5, 10, and 15year survival rates were 75%, 37.5%, and 25%, respectively, among the 24 patients who underwent surgery alone. These were not significantly different from the rates of 70.6%, 35.3%, and 20.8%, respectively, among the 34 patients who underwent surgery plus postoperative radiotherapy (P=0.21). The 5 and 10year survival rates were significantly greater among patients receiving ⩾60Gy of radiotherapy than those among patients receiving <60Gy of radiotherapy (83.3% and 45.8% vs. 40.0% and 10.0%, respectively) (P=0.04). ACP exhibited good long-term survival rates when treated with surgery alone. Addition of postoperative radiotherapy at doses of ⩾60Gy had no effect on survival, but postoperative radiotherapy at doses of <60Gy reduced survival. Recurrence within the palate was the main cause of treatment failure.

Long-term survival of induction chemotherapy plus surgery and postoperative radiotherapy in patients with stage IV hypopharyngeal cancer.

This study was conducted to evaluate the safety, efficacy, and tolerability of induction chemotherapy plus surgery and postoperative radiotherapy in patients with stage IV hypopharyngeal cancer. The patients received two to three cycles of induction chemotherapy before surgery, with cisplatin (100 mg/m(2)) by rapid intravenous (i.v.) infusion over 15-20 min on day 1, bleomycin (10 mg/m(2)) on days 1 and 5, and 5-fluorouracil (800 mg/m(2)/day) by continuous i.v. infusion on days 1 through 5, repeated every 21 days. Adjuvant radiotherapy was begun 4-6 weeks after surgery. From July 1999 to December 2004, a total of 52 patients were enrolled. After completion of two to three courses of induction chemotherapy, 22 cases of CR (complete response) and 16 cases of PR (partial response) in the primary site were confirmed, giving an overall response rate (ORR) of 73.1% [95% confidence interval (CI), 61.1-85.2%]. There were 17 CRs and 19 PRs in neck lymph nodes, giving an ORR of 69.2%. The combined primary tumor site and lymph node response was 17 CRs and 16 PRs, giving an ORR of 63.5% (95% CI, 50.4-76.6%). The median time to progression and overall survival for all the patients were 32 months (95% CI, 7.6-56.4 months) and 36 months (95% CI, 22.3-49.7 months), respectively. The estimate of time to progression and overall survival at 5 years was 24.5% (95% CI, 12.5-36.5%) and 35.9% (95% CI, 23.2-48.6%), respectively. In conclusion, induction chemotherapy plus surgery and postoperative radiotherapy is a treatment modality that is tolerated with encouraging activity and survival outcome in patients with stage IV hypopharyngeal cancer.

Analysis of cervical and retropharyngeal lymph node metastases in the patients with hypopharyngeal carcinoma with computed tomography and magnetic resonance imaging.

BACKGROUND AND OBJECTIVE: Hypopharyngeal carcinoma has a high risk for early regional lymphatic dissemination. However, reports about regional lymph node metastases, especially retropharyngeal lymph node metastases, are rare. This research explored the spread of hypopharyngeal carcinoma, especially metastases of the retropharyngeal lymph nodes by studying computed tomography (CT) and magnetic resonance imaging (MRI) images. METHODS: The CT/MRI images of 88 patients with pathologically confirmed hypopharyngeal carcinomas that were performed at our hospital between August 2000 and March 2009 were analyzed retrospectively. The interrelations among local stage and lymph nodes in various regions were analyzed by Chi2 test and multivariate logistical regression. RESULTS: The rate of regional lymph node metastasis for all patients was 73.9%, and the highest rates of positive lymph nodes were at levels IIa (61.4%), IIb (44.3%), and III (37.5%). Metastases to levels I, IV, V, and VI were rare, as were retropharyngeal lymph-node metastases, which were always combined with metastases at levels II and III. Univariate analysis showed that level-IV metastases correlated to metastases at levels Ib and III; retropharyngeal lymph node metastases were correlated to level IIb and bilateral cervical lymph node metastases. Multivariate analysis showed that level-VI metastases correlated to level IV and that retropharyngeal lymph-node metastases correlated to bilateral cervical lymph node metastases. CONCLUSIONS: Regional lymph node metastases in patients with hypopharyngeal carcinoma follow some regulations, and skip metastasis is rare. The highest rates of positive lymph nodes are at levels II and III. Bilateral lymph node metastases may be a risk factor for retropharyngeal lymph node metastases.

[Target volume including the nasopharynx for radiotherapy of hypopharyngeal squamous cell carcinoma: whether or not].

BACKGROUND AND OBJECTIVE: There is controversy in whether the nasopharynx should be included in target volume for radiotherapy of hypopharyngeal squamous cell carcinoma. This study was to analyze the necessity of radiotherapy including the nasopharynx for patients with hypopharyngeal squamous cell carcinoma. METHODS: Clinical data of 196 patients with hypopharyngeal squamous cell carcinoma treated in Cancer Center of Sun Yat-sen University from May 1994 to August 2006 were analyzed. Of the 196 cases of hypopharyngeal carcinoma, three were at stage I, 26 at stage II, 38 at stage III, and 129 at stage IV. Ninety-four patients received radiotherapy, 49 received surgery and 53 received surgery combined with radiotherapy. The nasopharynx was included in target volume in 78 patients, but excluded in 69 patients. The prognosis of the two groups were compared. RESULTS: The 3-year and 5-year overall survival rates were 38.57% and 21.69%. The 5-year survival rates were 100% in stage I patients, 43.08% in stage II patients, 27.57% in stage III patients, and 13.99% in stage IV patients, and were 13.90% in surgery group, 10.60% in radiotherapy group, and 44.08% in combined therapy group. Between nasopharynx-included and nasopharynx-excluded groups, there was no significant difference in 5-year overall survival rate (24.44 % vs. 20.68%, kappa2=0.10,P=0.76),5-year progression-free survival rate (15.99% vs. 10.91%, kappa2=0.65, P=0.42), relapse rate and metastasis rate (kappa2=1.56, P=0.21). Relapse in cervical lymph nodes occurred in 39 patients; no relapse in the nasopharynx was observed. CONCLUSIONS: Combined therapy is recommended for advanced hypopharyngeal squamous cell carcinoma. The target volume including the nasopharynx is not recommended. Controlling cervical lymph node metastasis may be helpful for prolonging survival.