Hemolysin from Aeromonas hydrophila enhances the host's serum enzyme activity and regulates transcriptional responses in the spleen of Cyprinus rubrofuscus.

Aeromonas hydrophila is a conditional pathogen impacting public hygiene and safety. Hemolysin is a virulence factor of Aeromonas hydrophila that causes erythrocyte hemolysis, yet its transcriptional response to Cyprinus rubrofuscus remains unknown. Our investigation confirmed the hemolysis of hemolysin from A. hydrophila. Serum enzyme activity was evaluated weekly after C. rubrofuscus were immunized with hemolysin Ahh1. The results showed that the hemolysin enhances the serum superoxide dismutase (SOD), lysozyme (LZM), and catalase (CAT) activity, which reached a maximum on day 14. To elucidate the molecular interaction between hemolysin from A. hydrophila and the host, we performed transcriptome sequencing on the spleen of C. rubrofuscus 14 days post hemolysin infection. The total number of clean reads was 41.37 Gb, resulting in 79,832 unigenes with an N50 length of 1863 bp. There were 1982 significantly differentially expressed genes (DEGs), including 1083 upregulated genes and 899 downregulated genes. Transcript levels of the genes, such as LA6BL, CD2, and NLRC5, were significantly downregulated, while those of IL11, IL1R2, and IL8 were dramatically upregulated. The DEGs were mainly enriched in the immune disease, viral protein interaction with cytokine and cytokine receptor, and toll-like receptor pathways, suggesting that hemolysin stimulation can activate the transcriptional responses. RT-qPCR experiments results of seven genes, IL-8, STAT2, CTSK, PRF1, CXCL9, TLR5, and SACS, showed that their expression was highly concordant with RNA-seq data. We clarified for the first time the key genes and signaling pathways response to hemolysin from A. hydrophila, which offers strategies for treating and preventing diseases.

Estimation of the Annual Effective Dose Due to the Ingestion of 210Pb and 210Po in Crops from a Site of Coal Mining and Processing in Southwest China.

The exploitation of mineral resources may cause the environmental release of radionuclides and their introduction in the human trophic chain, affecting public health in the short and long term. A case study of the environmental radiation impact from coal mining and germanium processing was carried out in southwest China. The coal mines contain germanium and uranium and have been exploited for more than 40 years. The farmlands around the site of the coal mining and germanium processing have been contaminated by the solid waste and mine water to some extent since then. Samples of crops were collected from contaminated farmlands in the research area. The research area covers a radius of 5 km, in which there are two coal mines. 210Pb and 210Po were analyzed as the key radionuclides during the monitoring program. The average activity concentrations of 210Pb and 210Po in the crops were 1.38 and 1.32 Bq/kg in cereals, 4.07 and 2.19 Bq/kg in leafy vegetables and 1.63 and 1.32 Bq/kg in root vegetables. The annual effective doses due to the ingestion of 210Pb and 210Po in consumed crops were estimated for adult residents living in the research area. The average annual effective dose was 0.336 mSv/a, the minimum was 0.171 mSv/a and the maximum was 0.948 mSv/a. The results show that the crops grown on contaminated farmland contained an enhanced level of radioactivity concentration. The ingestion doses of local residents in the research area were significantly higher than the average level of 0.112 mSv/a in China, and the world average level of 0.042 mSv/a through 210Pb and 210Po in crop intake, respectively.

Adjuvant breast inversely planned intensity-modulated radiotherapy with simultaneous integrated boost for early stage breast cancer : Results from a phase II trial.

PURPOSE: To report early toxicity and 5­year clinical outcomes of adjuvant breast inversely planned intensity-modulated radiotherapy with simultaneously integrated boost (IMRT-SIB) after breast-conserving surgery for early stage breast cancer patients. PATIENTS AND METHODS: In all, 467 patients including 406 invasive breast cancer and 61 ductal carcinoma in situ (DCIS) were enrolled in a single institutional phase II trial. All patients underwent IMRT-SIB treatment to irradiate the whole breast and the tumor bed. Doses to whole breast and surgical bed were 45 and 60 Gy, respectively, delivered in 25 fractions over 5 weeks. The grade of maximum acute skin toxicity during treatment was recorded. Lung toxicity was noted within 6 months and patient-reported cosmetic outcomes were recorded at the 12 month follow-up after the end of radiotherapy. Clinical outcomes were assessed during follow-up. RESULTS: Median follow-up time was 5.46 years. Median age was 46 years old (range 22-70 years old). No patient with DCIS had a local recurrence or distant metastasis. Among 406 patients with invasive breast cancer, the unadjusted 5­year actuarial rate of locoregional control was 98.7% (95% confidence interval [CI] 97.5-100), and distant metastasis-free survival 98.7% (95% CI 97.4-100), respectively. Acute skin toxicity was recorded at grade 0-1 in 76.5% of patients, and grade 2 in 23.5% of patients. None of these patients had grade 3 or more than grade 3 skin toxicity. Grade 1 pneumonitis was found in 25.3% of patients. Assessment of patient reported cosmetic outcomes at the 12 month follow-up showed good or excellent outcome in 86.5% of cases. CONCLUSIONS: The use of inversely planned IMRT-SIB as part of breast-conserving therapy results in optimal 5­year tumor control and minor early toxicities.

Microbial Community and Metabolite Dynamics During Soy Sauce Koji Making.

Koji making is a pre-fermentation stage in soy sauce manufacturing that impacts final product quality. Previous studies have provided valuable insights into the microbial species present in koji. However, changes in microbial community functional potential during koji-making are not well-known, nor are the associations among microbial populations and flavoring characteristics. In the present study, we investigated the succession of microbial communities, microbial community functional potential, metabolite profiles, and associations among microbial community members/functions with metabolites during koji making using shotgun metagenomic and metabolomic analyses. Firmicutes, Proteobacteria, and Ascomycota were identified as the most abundant microbial phyla in early koji making (0-12 h). Aspergillus (fungi) and Weissella (bacteria) exhibited marked abundance increases (0.98-38.45% and 0.31-30.41%, respectively) after 48 h of fermentation. Metabolite analysis revealed that aspartic acid, lysine, methyl acetate, isovaleraldehyde, and isoamyl alcohol concentrations increased ∼7-, 9-, 5-, 49-, and 10-fold after 48 h of fermentation. Metagenomic profiling demonstrated that koji communities were dominated by genes related to carbohydrate metabolism and amino acid metabolism, but functional profiles exhibited marked shifts after 24 h of fermentation. The abundances of genes within the categories of carbohydrate and amino acid metabolism all increased during koji making, except for pyruvate metabolism, glycolysis/gluconeogenesis, and the citrate cycle. Correlational analyses indicated that Aspergillus, Lactococcus, Enterococcus, Corynebacterium, and Kocuria abundances were positively correlated with 15 amino acid concentrations (all p < 0.05), while Weissella abundances were positively correlated with concentrations of volatile flavor compounds, including eight amino acids, phenylacetaldehyde, acetic acid, 2,3-butanediol, ethyl acetate, and ethanol (p < 0.05). These results provide valuable information for understanding the microbial-associated mechanisms of flavor formation during koji making.

Comparative evaluation of the microbial diversity and metabolite profiles of Japanese-style and Cantonese-style soy sauce fermentation.

Microorganisms play essential roles in flavor formation during soy sauce fermentation. Different soy sauce fermentation types significantly affect flavor formation. However, comparisons of microbial communities and metabolites between different fermentation types have been little studied. Here, we investigated variation in microbial communities, metabolite profiles, and metabolic pathways during Japanese-type (JP) and Cantonese-type (CP) fermentation. Free amino acids and volatile compound profiles varied significantly between fermentation types, with JP samples containing higher contents of esters (39.84%; p < 0.05), alcohols (44.70%; p < 0.05) in the 120 d fermentation samples. Volatile compound profiles varied significantly between fermentation types, with JP samples containing higher contents of esters, alcohols, and free amino acids (p < 0.05). Metagenomic analysis indicated that both JP and CP communities were dominated by Tetragenococcus, Staphylococcus, Weissella (bacteria), and Aspergillus (fungi), but the two communities varied differently over time. Tetragenococcus drastically increased in abundance throughout the fermentation (from 0.02 to 59.2%) in JP fermentation, whereas Tetragenococcus (36.7%) and Staphylococcus (29.7%) dominated at 120 d of fermentation in CP fermentation. Metagenomic functional profiles revealed that the abundances of most genes involved with carbohydrate, amino acid, and lipid metabolism exhibited significant differences between fermentation types (p < 0.05) during the middle to late fermentation stages. Furthermore, predicted metabolic pathways for volatile substance biosynthesis differed between JP and CP fermentation, likely explaining the differences in flavor metabolite profiles. In addition, most of the genes associated with flavor generation were affiliated with Tetragenococcus, Weissella, Staphylococcus, Bacillus, and Aspergillus, suggesting that these microbes play important roles in flavor production during soy sauce fermentation. This study significantly improves our understanding of microbial functions and their metabolic roles in flavor formation during different soy sauce fermentation processes.

High-Throughput Sequencing and Metabolomics Reveal Differences in Bacterial Diversity and Metabolites Between Red and White Sufu.

Sufu is a traditional fermented soybean food produced in China. However, the microbial compositions and metabolites of different types of sufu have not been studied in detail. Accordingly, in this study, we evaluated the differences in bacterial communities and metabolites between commercial red sufu (RS) and white sufu (WS). Principal coordinate analysis and the unweighted pair group method with arithmetic means analysis of 16S rRNA genes revealed that the bacterial community structures of RS and WS differed dramatically. At the phylum level, the relative abundances of Firmicutes and Proteobacteria were significantly different between RS and WS (P < 0.01). Moreover, the abundances of Lactococcus and Tetragenococcus genera were significantly different between RS and WS (P < 0.01). Among metabolites, most free amino acids, few of volatile flavor compounds, and some organic acids showed significant differences between RS and WS (P < 0.05). Additionally, correlations between microbiota and metabolites were determined. Aggregated boosted tree analysis showed that formic acid had the highest relative influence (20.27%) on bacterial community diversity (Chao 1), following by arginine (5.38%), propanol (4.57%), oxalic acid (4.46%), and hexanol (4.43%). Moreover, Streptococcaceae and Moraxellaceae had the highest relative influence on the concentration of formic acid (12.84% and 8.75%, respectively). The profiles obtained in this study improve our understanding of the relationships between bacterial flora and metabolites in different types of sufu. These findings may help us interpret the roles of bacterial communities in the flavor and characteristics of sufu.

Estimation of radon release rate for an underground uranium mine ventilation shaft in China and radon distribution characteristics.

Radon, known to be a human carcinogen, is one of the most concerned radionuclides in uranium mining which need to be monitored and controlled. A large amount of radon is discharged to the atmosphere mainly through underground ventilation shafts for underground uranium mining. There are many studies on radon release of uranium mine, but the differences of the measured radon results are very big. In this paper, a typical underground uranium mine in China is chosen as a case study. This study finds that distribution of radon concentration and airflow speed inside the ventilation shaft are extremely uneven, but the distributions are respectively stable and regular for a fixed cross-section at the wellhead depth of 0-1 m. There is also a stable numerical relationship between the radon release rate and the product of radon concentration and airflow speed at the center for any cross-section in the shaft. Based on this regulation, a multipoint interpolation-integration method and a one-point method for calculating radon release from underground ventilation shaft are proposed in this paper. The results show that the difference between these two methods is 2-10%, the one-point method is more suitable and convenient to be applied for the long-term monitoring radon release rate from uranium mine ventilation. The research results in this paper can be applied in the estimation of radon release rate for other underground uranium ventilation shafts.

Single institution experience of split course radiotherapy in patients with desmoid tumors.

PURPOSE: This study aimed to assess the feasibility of split course radiotherapy (SCRT) and reports long-term outcomes in patients with desmoid tumors (DT). PATIENTS AND METHODS: Between 2001 and 2004, 31 patients with recurrent (n=19) or primary large desmoid fibromatosis (≥10 cm) (n=12) who were treated with SCRT were retrospectively analyzed. All patients were treated with two phases of radiotherapy with a median interval time of 99 days (range: 81-122 days) and a median total dose of 6,399 cGy (range: 5,013-7,039 cGy). The median dose for the first phase was 3,969 cGy/22 Fx (range: 2,999-4,305 cGy), and 2,495 cGy/14 Fx (range: 1,982-3,039 cGy) for the second phase. Progression-free survival (PFS) in response to radiotherapy was evaluated using the Kaplan-Meier method and compared using the log-rank test. The prognostic factors associated with survival were evaluated by univariate and multivariate analyses. RESULTS: The median age of all patients was 30 years (range, 7-58 years). With a median follow-up of 60.4 months (range, 2-187 months), eight patients experienced disease progression after treatment. The PFS rate at 3 and 5 years for the whole population was 90% and 71.3%, respectively. PFS for patients with split course of <100 days or ≥100 days interval was 100% vs 78.6% at 3 years, and 80.4% vs 62.9% at 5 years, respectively (P=0.189). In multivariate analysis, the radiotherapy (RT) interval time was an independent prognostic factor for PFS (≥100 days vs <100 days, HR 11.544, 95% CI 1.034-128.878, P=0.047). PFS was not significantly influenced by age, gender, surgery, tumor location, RT technology, or RT dose. Radiation-related acute complications occurred in nine (29%) patients after RT, and RT-related long-term complications occurred in three (9.7%) patients. CONCLUSION: SCRT with an appropriate treatment interval (<100 days) is well tolerated by DT patients with favorable long-term outcomes.

Identification of the Dominant Microbial Species of Spoiled Crisp Grass Carp ( Ctenopharyngodon idellus C. et V.) and Grass Carp ( Ctenopharyngodon idellus) Fillets during Cold Storage by Culture-Independent 16S rDNA Sequence Analysis.

A new freshwater cultivation species, crisp grass carp (CGC; Ctenopharyngodon idellus C. et V.) has a special texture and is popular with consumers; thus, we should pay close attention to its storage conditions and bacterial degradation. CGC and grass carp (GC; Ctenopharyngodon idellus) were commercialized as fillets and subsequently stored at 4 and 8°C. Microbial growth parameters (total viable counts, psychrotrophic bacteria, and Pseudomonas spp.), physicochemical data (pH and total volatile base nitrogen), and sensory analysis were monitored during the storage period. Dominant microorganisms were identified using a 16S rDNA clone library and restriction fragment length polymorphism (RFLP) analysis after the fillets had spoiled completely. The results showed that Pseudomonas spp. lagged behind the psychrotrophic population and the total viable counts initially and increased more rapidly after storage for 2 days. Total volatile base nitrogen contents were found to increase with storage time in both species, coinciding with ongoing microbial change. The pH results obtained for both species during storage showed an overall increase at the end of storage. Sensory evaluation showed a shelf life of 3 and 6 days for both species at 8 and 4°C, respectively. RFLP analysis of the 16S rDNA clone library revealed that there were seven and five distinct RFLP pattern groups in the microflora of the spoiled CGC and GC fillets, respectively. Through RFLP patterns and 16S rDNA sequencing from the clones, it was determined that CGC fillets stored at 4°C were dominated by Pseudomonas spp. at the point of sensory rejection, whereas GC fillets were dominated by populations affiliated with Pseudomonas sp., Acinetobacter sp., and Aeromonas sp.

Characterization of the Microbiota in Air- or Vacuum-Packed Crisp Grass Carp ( Ctenopharyngodon idella C. et V.) Fillets by 16S rRNA PCR-Denaturing Gradient Gel Electrophoresis and High-Throughput Sequencing.

The microbial communities in air- and vacuum-packed crisp grass carp ( Ctenopharyngodon idella C. et V.) fillets have not been characterized during chilled storage. High-throughput sequencing of bacterial 16S rRNA has now revealed that the bacterial community in fresh fillets is diverse and distinct from that in spoiled samples. The predominant phylum was Proteobacteria, and 66 genera were identified. In fresh fillets, the most abundant genera were Acinetobacter (53.3%), Wautersiella (6.3%), unclassified Alcaligenaceae (4.4%), Stenotrophomonas (3.8%), unclassified Enterobacteriaceae (3.8%), and Enhydrobacter (3.6%). These genera diminished during chilled storage and sometimes disappeared. At the end of storage, Aeromonas and Pseudomonas were the most abundant. Similar results were obtained by PCR-denaturing gradient gel electrophoresis. These data provide detailed insight into the evolving bacterial communities in air- and vacuum-packed crisp grass carp fillets during storage, revealing Aeromonas and Pseudomonas as major spoilage organisms. These data may be useful for improvement of crisp grass carp quality and shelf life during chilled storage.

Role of radiotherapy in patients with limited diffuse large B-cell lymphoma of Waldeyer's ring in remission after R-CHOP immunochemotherapy.

The standard treatment of waldeyer's ring DLBCL remains controversial. This retrospective study was designed to evaluate the role of consolidation radiotherapy (RT) in patients with stage I/II diffuse large B-cell lymphoma (DLBCL) limited in Waldeyer's ring (WR). We included 72 patients, 42 were treated with immunochemotherapy alone (CT group) and 30 were treated with immunochemotherapy followed by radiotherapy (CT + RT group). All patients received at least 3 cycles of R-CHOP regimen and achieved complete remission (CR) after immunochemotherapy. After 53 months median follow-up time, the 5-year progression-free survival (PFS) rates in CT + RT group vs. CT group were 93.3% vs. 92.5% (P = 0.896), the 5-year overall survival (OS) rates were 96.7% vs. 94.4% (P = 0.649). Patients with oropharyngeal primary had relatively better 5-year PFS and OS rates compared to nasopharyngeal primary (PFS: 98.2% vs. 73.3%, p = 0.001; OS: 100% vs. 79.0%, p < 0.001). Moreover, the primary site was the only independent prognostic factor for PFS in the multivariate analysis (p = 0.012, HR 16.858 [95% CI: 1.883-150.933]).

Stack releases of radionuclides from an integrated steel plant in China.

Crude steel production in China made up the majority of the global output, at 49.5% in 2014. High temperature smelting processes result in the release of natural radionuclides, including radon gas and other air pollutants into the atmosphere. This paper conducts an analysis of the raw materials, end products and flue gas sampled from an integrated steel plant from within China's Jiangxi Province, with annual production of 8.50 Mt of crude steel. Normalized stack emissions factors of radionuclides from steel production were first reported in China. The results showed that sintering was the main process that released natural radionuclides, and the main radionuclides released into the atmosphere were 222Rn (86.4 GBq/Mt), 210Pb (13.4 GBq/Mt), and 210Po (1.71 GBq/Mt). The results provided essential basic data for radiological impact assessment of steel production, as well as that of nuclear energy chain, coal chain and other electricity sources.

Late course accelerated hyperfractionated radiotherapy of nasopharyngeal carcinoma (LCAF).

BACKGROUND AND PURPOSE: To study the efficacy of late course accelerated fractionated (LCAF) radiotherapy in the treatment of nasopharyngeal carcinoma (NPC). The end-points were local control, radiation-induced complications, and factors influencing survival. PATIENTS AND METHODS: Between December 1995 and April 1998, 178 consecutive NPC patients were admitted for radiation treatment. The radiation beam used was (60)Co gamma or 6 MV X rays. For the first two-thirds of the treatment, two daily fractions of 1.2 Gy were given to the primary lesion, with an interval of > or =6h, 5 days per week to a total dose of 48 Gy/40 fractions, over a period of 4 weeks. For the last third of the treatment, i.e., beginning the 5th week of treatment, an accelerated hyperfractionated schedule was carried out. The dose per fraction was increased to 1.5 Gy, 2 fractions per day with an interval of > or =6h, the total dose for this part of the protocol was 30 Gy/20 fractions over 2 weeks. Thus the total dose was 78 Gy in 60 fractions in 6 weeks. RESULTS: All patients completed the treatment. Acute mucositis: none in 2 cases, Grade 1 in 43 cases, Grade 2 in 78 cases, Grade 3 in 52 cases, and Grade 4 in 3 cases. Local control rate: the 5 year nasopharyngeal local control rate was 87.7%, and the cervical lymph nodes local control rate was 85.7%. The 5-year distant metastasis rate was 26.1%, and 5 year survivals were 67.9%, 16 (9%) patients had radiation-induced cranial nerve palsy, 7(4%) patients had temporal lobe or brainstem damage. CONCLUSIONS: With this treatment schedule, patients' tolerance was good, local control and 5 year survivals were better than conventional fractionation schedules, and radiation-related late complications did not increase, as 5-year survival rates of conventional fractionation radiotherapy were only 58%. Randomized clinical trials are being carried out to further confirm the efficacy of LCAF for nasopharyngeal carcinoma.

The estimation of the number of underground coal miners and the annual dose to coal miners in China.

This paper introduces an estimation method for the number of underground coal miners and the annual dose to coal miners in China. It shows that there are about 6 million underground miners at present and the proportion is about 1, 1 and 4 million for national key coal mines, state-owned local coal mines, and township and private-ownership coal mines, respectively. The collective dose is about 1.65 x 10(4) person-Sv y(-1), of which township and private-ownership coal mines contribute about 91%. This paper also points out that the 2000 UNSCEAR report gives the number of miners of coal production and their collective dose, which are underestimated greatly because the report only includes the number of underground miners in national key coal mines, which only accounts for 1/6 of the workers all working under the best ventilation conditions in China.

The Estimation of the Number of Underground Coal Miners and Normalization Collective Dose at Present in China.

Due to the improvement of production technology and the adjustment of energy structure, as well as the town-ownership and private-ownership coal mines (TPCM) were closed or merged by national policy, the number of underground miner has changed comparing with 2004 in China, so collective dose and normalization collective dose in different type of coal mine should be changed at the same time. In this paper, according to radiation exposure by different ventilation condition and the annual output, the coal mines in China are divided into three types, which are named as national key coal mines (NKCM), station-owned local coal mines (SLCM) and TPCM. The number of underground coal miner, collective dose and normalization collective dose are estimated at present base on surveying annual output and production efficiency of raw coal in 2005-2014. The typical total value of the underground coal miners recommended in China is 5.1 million in 2005-2009, and in which there are respectively included 1 million, 0.9 million and 3.2 million for NKCM, SLCM and TPCM. There are total of 4.7 million underground coal miner in 2010-2014, and the respectively number for NKCM, SLCM and TPCM are 1.4 million, 1.2 million and 2.1 million. The collective dose in 2005-2009 is 11 335 man·Sv·y-1, and in which there are respectively included 280, 495 and 10 560 man·Sv·y-1 for NKCM, SLCM and TPCM. As far as 2010-2014, there are total of 7982 man·Sv·y-1, and 392, 660 and 6930 man·Sv·y-1 for each type of coal mines. Therefore, the main contributor of collective dose is from TPCM. The normalization collective dose in 2005-2009 is 0.0025, 0.015 and 0.117 man·Sv per 10 kt for NKCM, SLCM and TPCM, respectively. As far as 2010-2014, there are 0.0018, 0.010 and 0.107 man·Sv per 10 kt for each type of coal mines. The trend of normalization collective dose is decreased year by year.

Using corrected cone-beam CT image for accelerated partial breast irradiation treatment dose verification: the preliminary experience.

BACKGROUND: Accurate target localization is mandatory in the accelerated partial breast irradiation (APBI) delivery. Dosimetric verification for positional error will further guarantee the accuracy of treatment delivery. The purpose of this study is to evaluate the clinical feasibility of a cone beam computer tomographic (CBCT) image correction method in APBI. METHODS: A CBCT image correction method was developed. First, rigid image registration was proceeded for CTs and CBCTs; second, these images were separated into four parts; then, ratio images for each of the four parts of planning CTs/CBCTs were calculated and filtered to reduce the high spatial frequency; finally, the enhanced CBCT images were generated combing the four parts. An anthropomorphic thorax rando phantom was used to evaluate the feasibility and accuracy of the CBCT correction method. The CBCT images of consecutive 10 patients receiving APBI were corrected using the above method and dosimetric variations were evaluated. Each set of CBCT is composed of three images: one acquired after skin-marker setup, one after online setup correction and one after treatment delivery. RESULTS: The phantom study showed the improved accuracy of dose calculation with corrected CBCT. The Dose Volume Histogram (DVH) difference between the planning CT and corrected CBCT is less than the difference between the planning CT and original CBCT. The maximum dose difference between the corrected CBCT and planning CT is 0.8% in PTV_EVAL V100, which is 3.8% between original CBCT and planning. In the patient study, 67.4% of fractions benefit from CBCT setup corrections in PTV_EVAL D95, while in 47.4% of the fractions, reduced dose coverage was found on the post-treatment CBCT. Overall, the CBCT based initial setup correction guaranteed target dose coverage in 9 patients. CONCLUSIONS: A generic CBCT image correction algorithm was created and proved to be easily implemented in clinic. Compared to the original CBCT, the corrected CBCT has more accuracy in dose calculation. The CBCT guided APBI based on initial skin setup is not sufficient to guarantee the accurate dose delivery throughout each fraction. The long treatment delivery time may compromise the target coverage benefits in some patients.

Simultaneous integrated boost in breast conserving radiotherapy: is replanning necessary following tumor bed change?

Tumor bed (TB) change is often seen during the whole breast irradiation (WBI) in early breast cancer patients. The aims of this study were to evaluate change in seroma volume on repeat CTs and to explore whether replanning is necessary in breast conserving radiotherapy (RT) using the intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB). Thirty patients underwent WBI with 84 CT scans (24 with 3 CTs (CT1, CT2 and CT3) and 6 without CT3) during the 6 weeks of RT were reviewed. TB and other target volumes on all CTs were delineated and compared. IMRT-SIB treatment plans with 50.68 Gy to the whole breast and 64.4 Gy to the boost in 28 fractions were constructed in the CT1. Replan and hybrid plan (without replanning) in the CT2 were reproduced. Dosimetric differences between the replans and hybrid plans were also compared. The mean TB volumes for CT1, CT2 and CT3 were 42.1 cm(3), 20.1 cm(3), 17.0 cm(3), respectively. The mean TB volume reduction was 40.5% from the CT1 to CT2 and 4.3% from the CT2 to CT3. The difference of TB volumes between the CT1 and CT2 was statistically significance (p < 0.001), but not significant between the CT2 and CT3 (p = 1.000). For all patients, target coverage remained adequate with either hybrid plans or replans. However, replanning can significantly decrease the whole breast mean dose (35.2 vs. 35.6 Gy, p = 0.026) and breast volume outside the boost receiving 95% of the boost prescribed dose (39.5 vs. 68.2 cm(3), p < 0.001). In summary, boost volume could irradiate adequately after the significance shrinkage of tumor bed with the fractionated schedule of IMRT-SIB, but replanning on a second CT could avoid the undesired high dose irradiated breast tissue outside boost.

Treatment outcome of patients with stages I-II nasopharyngeal carcinoma after late course accelerated hyperfractionation radiotherapy alone.

OBJECTIVES: To follow up the efficacy and incidence of radiation-induced complications of late course accelerated fractionation (LCAF) radiotherapy in early-stage nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From December 1995 to November 2002, 158 patients with stages I-II NPC were admitted for radiotherapy alone. For the first two-thirds of the treatment, 2 daily fractions of 1.2 Gy were given to the primary lesion, 5 days per week to a total dose of 48 Gy/40 fractions, over a period of 4 weeks. From the 5th week, an accelerated hyperfractionation schedule was carried out. Two daily fractions of 1.5 Gy were given, to a total dose of 30 Gy/20 fractions over 2 weeks. Thus the total dose was 78 Gy in 60 fractions in 6 weeks. RESULTS: All patients completed the treatment. Acute mucositis: none in 3 patients, grade 1 in 32, grade 2 in 69, grade 3 in 51, and grade 4 in 3 patients. Five-year nasopharyngeal control and overall survival (OS) rate of T1 and T2 were 97.8%, 90.2% (p=0.380) and 88.6%, 81.4% (p=0.252), respectively. Five-year OS in N0 and N1 patients were 86.5% and 81.9% (p=0.033), respectively. Thirty-eight patients died, and the main cause of death was distant metastasis. Seventeen (11%) patients had radiation-induced cranial nerve palsy. CONCLUSION: With LCAF, treatment-related toxicities were acceptable. Five-year nasopharyngeal control and OS in T2 stage were improved. Main cause of death was distant metastasis. Patients with N1 had a relatively lower survival rate, which suggested that chemotherapy might be indicated for those patients.

The pattern of relapse and survival of elective irradiation of the upper neck for stage N0 nasopharyngeal carcinoma.

BACKGROUND: To investigate patterns of failure and survival rates of elective irradiation of upper neck in N0 nasopharyngeal carcinoma patients. METHODS: From February 1996 to November 2002, 97 patients without cervical lymph node involvement were admitted for radiotherapy alone. Before treatment, each patient underwent enhanced CT of nasopharynx and neck. All patients received radiotherapy to the nasopharynx, skull base, and upper neck drainage areas (including levels II, III, and VA). The upper neck was irradiated to a total dose of 50-56 Gy/25-28 fractions/5-5.6 weeks. For the primary tumor, 22 patients used conventional fractionation for a total dose of 70 Gy/35 fractions/7 weeks, and 75 patients used an accelerated hyperfractionationated schedule for a total dose of 78 Gy/60 fractions/6 weeks. RESULTS: The median follow-up of these 97 patients was 7.75 years. 10 patients had recurrences in the nasopharynx, 8 had distant metastasis, and 5 had recurrences in the cervical lymph nodes. Among the cervical lymph node failures, the areas of recurrence were in the II drainage areas in 4 patients who had neck dissections afterwards, and in IA drainage areas in 1 patient who also had recurrence in the nasopharynx. The causes of death were recurrence in the nasopharynx for 8 patients, 1 of these also had recurrence in the neck, distant metastases in 8 patients, and non-neoplastic diseases in 3 patients. CONCLUSIONS: The causes of failure of N0 patients with nasopharyngeal carcinoma after radiotherapy alone to the nasopharynx and upper neck were nasopharyngeal recurrence, distant metastasis, and cervical recurrence in order of frequency. Elective irradiation of upper neck (II, III, VA) is advised for stage N0 patients diagnosed by enhanced CT of neck. Cervical recurrence alone is rare, which did not greatly affect the long-term survival after salvage neck dissection.

A phase III study of late course accelerated hyperfractionated radiotherapy versus conventionally fractionated radiotherapy in patients with nasopharyngeal carcinoma.

OBJECTIVE: To compare the efficacy and toxicity of late course accelerated hyperfractionated radiotherapy (LCAF) with conventionally fractionated (CF) radiotherapy in the treatment of nasopharyngeal carcinoma (NPC). METHODS: Between March 1998 and November 2002, 200 eligible patients with NPC were randomized to receive either LCAF (48 Gy in 40 fractions, 2 fractions per day, 1.2 Gy/fraction, with an interval of ≥6 h, 5 d/wk, followed by 30 Gy in 20 fractions using 2 fractions per day, 1.5 Gy/fraction, 5 d/wk) or CF (35 fractions, 2.0 Gy/fraction/d, 5 d/wk, to a total dose of 70 Gy). RESULTS: All patients completed the treatment. Overall baseline characteristics of the study population of the 2 arms were well balanced. With a median follow-up of 6.9 years, the 5-year local control rate was higher in the LCAF arm (87.6% vs. 75.9%, P=0.044). The 5-year overall survival rates were 74.1% vs. 58.0% (P=0.024) for the LCAF arm and the CF arm, respectively. LCAF patients had a higher occurrence of acute mucositis and a more evident weight loss than CF patients, whereas incidence rates of radiation-induced damage to the central nervous system were similar in the 2 arms. CONCLUSIONS: LCAF achieved higher local control and overall survival rates than CF radiotherapy, without increasing radiation-related late complications such as cranial nerve palsy.