Patterns of Failure and Survival Trends in 3,808 Patients with Stage II Nasopharyngeal Carcinoma Diagnosed from 1990 to 2012: A Large-Scale Retrospective Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the survival trends and patterns of failure in patients with stage II nasopharyngeal carcinoma (NPC) treated with radiotherapy (RT) and chemotherapy over the last 20 years. MATERIALS AND METHODS: Thirty-eight hundred and eight patients diagnosed with stage II NPC between January 1990 and December 2012 were involved in this retrospective cohort study. All patients were treated with RT. According to the main imaging techniques and RT technology, we categorized these patients into four calendar periods: 1990-1996, 1997-2002, 2003-2007, and 2008-2012. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis–free survival (DMFS) were served as the clinical outcome. RESULTS: After a median follow-up period of 84.7 months, we observed increasing trends in survival and disease control. The 3- and 5-year OS rates increased from 87.1% and 78.7% in the first calendar period to 97.4% and 94.5% in the last calendar period, respectively (p<0.001). Additionally, significant increasing trends could be seen in the PFS and LRFS during the four calendar periods. In the subgroup analysis, the LRFS in patients older than 50 years at diagnosis showed greater improvement than younger patients. However, the rate of distant metastasis was stable and relatively low, as the 5-year DMFS ranged from 90.5% to 94.7% among the four calendar periods. CONCLUSION: The survival rates in patients with stage II NPC showed increasing trends from 1990 to 2012. The advance of RT provided excellent locoregional control and enhanced OS.

Secular trend analysis of lung cancer incidence in Sihui city, China between 1987 and 2011 / 癌症

<p><b>BACKGROUND</b>With industrial and econom ic development in recent decades in South China, cancer incidence may have changed due to the changing lifestyle and environment. However, the trends of lung cancer and the roles of smoking and other environmental risk factors in the development of lung cancer in rural areas of South China remain unclear. The purpose of this study was to explore the lung cancer incidence trends and the possible causes of these trends.</p><p><b>METHODS</b>Joinpoint regression analysis and the age-period-cohort (APC) model were used to analyze the lung cancer incidence trends in Sihui, Guangdong province, China between 1987 and 2011, and explore the possible causes of these trends.</p><p><b>RESULTS</b>A total of 2,397 lung cancer patients were involved in this study. A 3-fold increase in the incidence of lung cancer in both sexes was observed over the 25-year period. Joinpoint regression analysis showed that while the incidence continued to increase steadily in females during the entire period, a sharp acceleration was observed in males starting in 2005. The full APC model was selected to describe age, period, and birth cohort effects on lung cancer incidence trends in Sihui. The age cohorts in both sexes showed a continuously significant increase in the relative risk (RR) of lung cancer, with a peak in the eldest age group (80-84 years). The RR of lung cancer showed a fluctuating curve in both sexes. The birth cohorts identified an increased trend in both males and females; however, males had a plateau in the youngest cohorts who were born during 1955-1969.</p><p><b>CONCLUSIONS</b>Increasing trends of the incidence of lung cancer in Sihui were dominated by the effects of age and birth cohorts. Social aging, smoking, and environmental changes may play important roles in such trends.</p>

Clinical findings and imaging features of 67 nasopharyngeal carcinoma patients with postradiation nasopharyngeal necrosis / 癌症

Postradiation nasopharyngeal necrosis is an important late effect of radiotherapy that affects prognosis in patients with nasopharyngeal carcinoma. In the present study, we reviewed the clinical and imaging features of 67 patients with pathologically diagnosed postradiation nasopharyngeal necrosis who were treated at Sun Yat-sen University Cancer Center between June 2006 and January 2010. Their clinical manifestations, endoscopic findings, and imaging features were analyzed. Early nasopharyngeal necrosis was limited to a local site in the nasopharyngeal region, and the tissue defect was not obvious, whereas deep parapharyngeal ulcer or signs of osteoradionecrosis in the basilar region was observed in serious cases. Those with osteoradionecrosis and/or exposed carotid artery had a high mortality. In conclusion, Postradiation nasopharyngeal necrosis has characteristic magnetic resonance imaging appearances, which associate well with clinical findings, but pathologic examination is essential to make the diagnosis.

Randomized study of sinusoidal chronomodulated versus flat intermittent induction chemotherapy with cisplatin and 5-fluorouracil followed by traditional radiotherapy for locoregionally advanced nasopharyngeal carcinoma / 癌症

Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma (NPC). Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear. This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin (DDP) and 5-fluorouracil (5-FU) followed by radiotherapy in patients with locoregionally advanced NPC. Patients with biopsy-diagnosed untreated stages III and IV NPC (according to the 2002 UICC staging system) were randomized to undergo 2 cycles of sinusoidal chronomodulated infusion (Arm A) or flat intermittent constant rate infusion (Arm B) of DDP and 5-FU followed by radical radiotherapy. Using a "MELODIE" multi-channel programmed pump, the patients were given 12-hour continuous infusions of DDP (20 mg/m2) and 5-FU (750 mg/m2) for 5 days, repeated every 3 weeks for 2 cycles. DDP was administered from 10:00 am to 10:00 pm, and 5-FU was administered from 10:00 pm to 10:00 am each day. Chronomodulated infusion was performed in Arm A, with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm. The patients in Arm B underwent a constant rate of infusion. Radiotherapy was initiated in the fifth week, and both arms were treated with the same radiotherapy techniques and dose fractions. Between June 2004 and June 2006, 125 patients were registered, and 124 were eligible for analysis of response and toxicity. The major toxicity observed during neoadjuvant chemotherapy was neutropenia. The incidence of acute toxicity was similar in both arms. During radiotherapy, the incidence of stomatitis was significantly lower in Arm A than in Arm B (38.1% vs. 59.0%, P = 0.020). No significant differences were observed for other toxicities. The 1-, 3-, and 5-year overall survival rates were 88.9%, 82.4%, and 74.8% for Arm A and 91.8%, 90.2%, and 82.1% for Arm B. The 1-, 3-, and 5-year progression-free survival rates were 91.7%, 88.1%, and 85.2% for Arm A and 100%, 94.5%, and 86.9% for Arm B. The 1-, 3-, and 5-year distant metastasis-free survival rates were 82.5%, 79.1%, and 79.1% for Arm A and 90.2%, 85.2%, and 81.7% for Arm B. Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.

Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis / 癌症

Systemic chemotherapy is the basic palliative treatment for metastatic nasopharyngeal carcinoma (NPC); however, it is not known whether locoregional radiotherapy targeting the primary tumor and regional lymph nodes affects the survival of patients with metastatic NPC. Therefore, we aimed to retrospectively evaluate the benefits of locoregional radiotherapy. A total of 408 patients with metastatic NPC were included in this study. The mortality risks of the patients undergoing supportive treatment and those undergoing chemotherapy were compared with that of patients undergoing locoregional radiotherapy delivered alone or in combination with chemotherapy. Univariate and multivariate analyses were conducted. The contributions of independent factors were assessed after adjustment for covariates with significant prognostic associations (P < 0.05). Both locoregional radiotherapy and systemic chemotherapy were identified as significant independent prognostic factors of overall survival (OS). The mortality risk was similar in the group undergoing locoregional radiotherapy alone and the group undergoing systemic chemotherapy alone [multi-adjusted hazard ratio (HR) = 0.9, P = 0.529]; this risk was 60% lower than that of the group undergoing supportive treatment (HR = 0.4, P = 0.004) and 130% higher than that of the group undergoing both systemic chemotherapy and locoregional radiotherapy (HR = 2.3, P < 0.001). In conclusion, locoregional radiotherapy, particularly when combined with systemic chemotherapy, is associated with improved survival of patients with metastatic NPC.

C-KIT overexpression and mutation in nasopharyngeal carcinoma cell lines and reactivity of Imatinib on these cell lines / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>We previously reported that C-KIT overexpression and mutation exist in biopsy samples of nasopharyngeal carcinoma (NPC). Yet whether Imatinib had an inhibitory effect on the proliferation of NPC in vitro was still unknown. So, this study examined whether sensitivities to Imatinib of other cell lines are different and whether C-KIT expression and mutations exist, to analyze the correlations between them.</p><p><b>METHODS</b>The expression of C-KIT in NPC cell lines, including CNE-1, CNE-2, Hone-1, C-666, SUNE-1, 5-8F, and nasopharyngeal epithelial (NPE) cell line NP-69, were detected by Western blot. Direct sequencing of polymerase chain reaction (PCR) products was performed to analyze the sequences of C-KIT from the above-mentioned cell lines. Inhibitory effects on proliferation by Imatinib on these cell lines were determined by CCK-8 assay. Pearson product moment correlation and t test were used to analyze the correlation betweeen C-KIT overexpression, C-KIT gene mutation, and the inhibitory effect of Imatinib.</p><p><b>RESULTS</b>Compared with NPE cell line NP-69, NPC cell lines CNE-1, CNE-2, Hone-1, C-666, SUNE-1, and 5-8F had significantly higher levels of C-KIT expression. Heterozygous IVS17+78T>C were found in CNE-1, CNE-2, Hone-1, and NP-69 cell lines, homozygous IVS17+78T>C was found in C-666, and no mutation was found in SUNE-1 or 5-8F. Imatinib had a dose-dependent inhibitory effect on proliferation for CNE-1, CNE-2, Hone-1, C-666, SUNE-1, and 5-8F. No significant correlation between the inhibitory effects of Imatinib, C-KIT overexpression, or C-KIT mutation was found.</p><p><b>CONCLUSION</b>C-KIT overexpression and intron mutation were found in NPC cell lines and Imatinib had a dose-dependent inhibitory effect on proliferation for NPC cell lines, yet no significant correlation between C-KIT overexpression, C-KIT mutation, or the inhibitory effect of Imatinib was found.</p>

Comparison of the short-term efficacy of two inductive chemotherapy regimens for locally advanced nasopharyngeal caricinoma: docetaxal plus carboplatin versus 5-fluorouracil plus carboplatin / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>The platinum-based chemotherapy combined with 5-fluorouracil (5-FU) is most frequently used for nasopharyngeal carcinoma (NPC), but the efficacy has been maintained at 50%-60%. Docetaxel is an effective drug for head and neck tumors, its administration is simple, and the administration time is short. This study was to compare the short-term efficacy and toxicity between TC regimen (inductive chemotherapy with docetaxol plus carboplatin) and FC regimen (5-FU plus carboplatin) in local advanced NPC so as to provide a new chemotherapeutic regimen for NPC.</p><p><b>METHODS</b>Fifty-eight local advanced NPC patients without previous treatment in Sun Yat-sen University Cancer Center were randomly assigned to receive either TC or FC regimen inductive chemotherapy, followed by concurrent chemoradiotherapy with two cycles of carboplatin (AUC=6) plus radiotherapy of 60-78 Gy to the nasopharynx and 60-70 Gy to the neck. The short-term efficacy and adverse events were observed.</p><p><b>RESULTS</b>More chemotherapy cycles were finished in TC group than in FC group (3.31 vs. 2.83, P = 0.043). There was no significant difference in short-term efficacy and 1-year survival rate between the two groups (P > 0.05). More grades 3-4 neutropenia appeared in TC group than in FC group (72.4% vs. 37.9%, P < 0.05) , whereas less thrombocytopenia and emesis occurred in TC than in FC group (P = 0.013 and 0.018, respectively).</p><p><b>CONCLUSIONS</b>The short-term efficacy of TC regimen in local advanced NPC is similar to that of FC regimen with tolerable adverse events. But the long-term outcomes and toxicities need to be further investigated.</p>

Prognostic factors in nasopharyngeal carcinoma in childhood and adolescence / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the prognostic factors affecting long-term result in pediatric or adolescent nasopharyngeal carcinoma.</p><p><b>METHODS</b>From January 1984 to December 1998, 117 cases of pediatric and adolescent nasopharyngeal carcinoma proven by pathology were treated by radiotherapy and/or chemotherapy. Their data were retrospectively analyzed. Of the 117 patients, 35 received chemotherapy before radiotherapy, 36 were treated with continuous radiotherapy and the other 81 with split-course radiotherapy. A dose of 56 - 80 Gy/6 - 13 weeks (66.32 +/- 4.72 Gy) was given in the nasopharynx and 47 - 73 Gy/5 - 13 weeks (57.90 +/- 5.80 Gy) in the neck. The survival rates were assessed by Kaplan-Meier analysis and the survival curves compared by Log-rank test. The multivariate analysis was conducted by Cox model.</p><p><b>RESULTS</b>The 1-, 3- and 5-year overall survival rate was 86.3%, 66.6% and 56.4%, respectively; and disease-free survival rate at 1, 3 and 5 years was 71.8%, 53.9% and 50.4%, respectively. A monovariate analysis showed that the age (P = 0.0015), mode of biopsy (P = 0.0234), N stage (P = 0.0001), mode of irradiation (P = 0.0027), chemotherapy (P = 0.0056) and short-term result (P = 0.0000) were the significant prognostic factors. The multivariate analysis demonstrated that the age (P = 0.027), N stage (P = 0.048), mode of irradiation (P = 0.009) and short-term result (P = 0.000) were the factors influencing prognosis of nasopharyngeal carcinoma in childhood and adolescence. Radiation-induced brain injuries were observed in 17 patients including brain stem injury in 1 (0.9%), temporal brain lobes in 3 (2.6%) and cranial nerves in 13 (11.1%).</p><p><b>CONCLUSION</b>The mode of irradiation, N stage and short-term result are the significantly influencing factors of prognosis in pediatric and adolescent nasopharyngeal carcinoma. Radiation-induced brain injuries during radiotherapy should not be overlooked.</p>

Influence of particle size and MePEG molecular weight on in vitro macrophage uptake and in vivo long circulating of stealth nanoparticles in rats / 药学学报

<p><b>AIM</b>To investigate the influence of particle size and methoxypolyethyleneglycol (MePEG) molecular weight on the in vitro macrophage uptake and in vivo long circulating of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha)-loaded stealth nanoparticles in rats.</p><p><b>METHODS</b>Three sizes (approximately 80, 70 and 240 nm) of poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles loading rHuTNF-alpha were prepared at different MePEG molecular weights (Mr 2,000, 5,000, 10,000) using the double emulsion method. The in vitro macrophage uptake and in vivo long circulating properties in rats were examined and compared.</p><p><b>RESULTS</b>The uptake by macrophages decreased and the half-life of rHuTNF-alpha in rat increased with the increase of MePEG molecular weight or the decrease of particle size. The linear-ships between particle size and MePEG molecular weight and the in vitro macrophage uptake and in vivo long circulating properties were fairly good. Having the highest MePEG surface density (1.32 nm(-2)) , the shortest average distance between neighboring MePEG chain (0.87 nm) and the thicker fixed aqueous layer thickness (FALT, 5.16 nm), PEG5,000-PHDCA nanoparticles (80.0 nm) earned the strongest potency of decreasing uptake by macrophages and prolonging the half-life of rHuTNF-alpha in rat.</p><p><b>CONCLUSION</b>Within the experimental limits, particle size and MePEG molecular weight had dramatic influence on in vitro macrophage uptake and in vivo long circulating properties of rHuTNF-alpha-loaded stealth nanoparticles.</p>

Stealth PEG-PHDCA niosomes: effects of chain length of PEG on niosomes in vitro complement consumption and phagocytic uptake / 药学学报

<p><b>AIM</b>Poly (methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate) (PEG-PHDCA) and PHDCA niosomes were prepared and the influence of the PEG chain length on the niosomes physicochemical characteristics, complement consumption and phagocytic uptake were studied.</p><p><b>METHODS</b>The physicochemical parameters of PEG-PHDCA niosomes were characterized in terms of particle size, zeta aqueous layer thickness. The relationship between physicochemical characteristics and in vitro complement consumption and phagocytic uptake was further illustrated.</p><p><b>RESULTS</b>Experimental results showed that PEG10,000-PHDCA had most loose structure and least PEG surface density among three groups. Configuration simulation through fixed aqueous layer thickness confirmed that PEG folding and less flexibility of the PEG chains of PEG10,000-PHDCA niosomes were accountable for its poor stealth effects. Compared with PEG2,000-PHDCA, PEG5,000-PHDCA showed a thicker fixed aqueous layer (FALT) of 4.20 nm, less negative zeta potential of -10.03 mV, and enhanced PEG surface density of 0.49 PEG x nm(-2), leading to the best effects of reduction of complement consumption and phagocytic uptake.</p><p><b>CONCLUSION</b>Excessive chain length of PEG was not necessary for stealth effects of PEG-PHDCA niosomes. PEG5,000-PHDCA niosomes had best effects on evading complement consumption and subsequent phagocytic uptake.</p>

Phase I study of capecitabine with concurrent radiotherapy in early-stage nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the dose-limiting toxicity (DLT), efficacy and maximum tolerated dose (MTD) of capecitabine with concurrent radiotherapy in patients with node-positive stage II nasopharyngeal cancer.</p><p><b>METHODS</b>From August 2002 to June 2003, 30 patients with node-positive stage II T(2)N(1)M(0) nasopharyngeal cancer were retrospectively reviewed. Median age 43 years (range 32 - 63 years), ECOG performance status <or= 2. Radiotherapy of 68 - 72 Gy/34 - 36 fractions was delivered to the nasopharynx and 64 - 70 Gy/32 - 35 fractions to the node-positive area. Capecitabine was administered orally on day 1 of radiotherapy by an intermittent schedule (14 days treatment; 7-day rest) at 3 weekly intervals for two cycles. Patients were alloted into one of four escalating dose cohorts (500, 750, 1000 and 1250 mg/m(2), bid). Dose escalation was done after six patients had completed 2 cycles of chemotherapy at the previous dose level with DLT assessed.</p><p><b>RESULTS</b>Twenty-eight patients were evaluable for toxicity and efficacy: CR 12 (42.9%), PR 13 (46.4%), SD 3 (10.7%), the overall response rate (CR + PR) was 89.3%. The CR response rate of the node-positive area and of the nasopharynx were 50.0% (14/28) and 46.4% (13/28). No DLT was observed at the dosage group of 500 mg/m(2) and 750 mg/m(2). Three of 9 patients experienced DLT at 1000 mg/m(2) with grade III stomatitis; 4 of 6 at 1250 mg/m(2) with grade III stomatitis (4/6), grade III diarrhea with grade IV febrile neutropenia (1/6) and grade III thrombocytopenia (1/6). The toxicity of grade I and II was hand-foot syndrome (4/28), fatigue (14/28), nausea and vomiting (19/28), diarrhea (5/27), and weight loss (21/28).</p><p><b>CONCLUSION</b>A dose of 750 mg/m(2) of capecitabine might be recommended for combination with radiotherapy. This regimen is tolerable and valid for nasopharyngeal carcinoma. A randomised phase III comparison with 5-Fu is justified.</p>