Survival differences between definitive radiotherapy and surgery followed by adjuvant radiotherapy in supraglottic and hypopharyngeal carcinoma / 中华医学杂志(英文版)

Background@#Organ preservation has long been a consideration in the treatment of supraglottic and hypopharyngeal carcinoma to improve the quality of life (QOL). Definitive radiotherapy (DRT) with or without systematic treatment, such as chemotherapy, is always the first choice to achieve improved QOL. This retrospective study focused on the survival differences between DRT and surgery followed by adjuvant radiotherapy (S + RT) in supraglottic and hypopharyngeal carcinoma.@*Methods@#This study included adult patients with supraglottic or hypopharyngeal carcinoma undergoing single-modality treatment with either DRT or S + RT between January 2012 and August 2016. A total of 59 patients were identified, of whom 31 were treated with DRT, and 28 were treated with S + RT. In the 31 cases of DRT, 23 cases were treated with concurrent chemoradiotherapy (CRT), one case was treated with DRT plus cetuximab, and seven cases were treated with DRT alone. Of the other 28 cases of S + RT, 15 cases were treated with adjuvant concurrent CRT. Survival analysis was used to compare the overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) between DRT and S + RT groups.@*Results@#The median follow-up was 20 months (range, 4-67 months). The patients of the two groups were similar with respect to mean age, original sites, and tumor stages. The 1-, 2-, and 5-year OS rates were 80.6%, 53.4%, and 24.7% for the DRT group and 85.7%, 67.1%, and 24.7% for the S + RT group, respectively. There was no significant difference between the two groups (χ2 = 3.183, P = 0.074). The 1-, 2-, and 5-year LRFS and DMFS were 90.4%, 61.7%, and 18.0% and 87.4%, 49.2%, and 9.9%, respectively, and no statistical difference was observed between the two groups (LRFS: χ2 = 0.028, P = 0.868; DMFS: χ2 = 3.347, P = 0.067). No significant difference was found between the two groups in acute radiotoxicity.@*Conclusions@#Without loss of laryngeal function, the survival of DRT is comparable to that of S + RT in supraglottic and hypopharyngeal carcinoma.

Survival differences between definitive radiotherapy and surgery followed by adjuvant radiotherapy in supraglottic and hypopharyngeal carcinoma / 中华医学杂志(英文版)

BACKGROUND@#Organ preservation has long been a consideration in the treatment of supraglottic and hypopharyngeal carcinoma to improve the quality of life (QOL). Definitive radiotherapy (DRT) with or without systematic treatment, such as chemotherapy, is always the first choice to achieve improved QOL. This retrospective study focused on the survival differences between DRT and surgery followed by adjuvant radiotherapy (S + RT) in supraglottic and hypopharyngeal carcinoma.@*METHODS@#This study included adult patients with supraglottic or hypopharyngeal carcinoma undergoing single-modality treatment with either DRT or S + RT between January 2012 and August 2016. A total of 59 patients were identified, of whom 31 were treated with DRT, and 28 were treated with S + RT. In the 31 cases of DRT, 23 cases were treated with concurrent chemoradiotherapy (CRT), one case was treated with DRT plus cetuximab, and seven cases were treated with DRT alone. Of the other 28 cases of S + RT, 15 cases were treated with adjuvant concurrent CRT. Survival analysis was used to compare the overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) between DRT and S + RT groups.@*RESULTS@#The median follow-up was 20 months (range, 4-67 months). The patients of the two groups were similar with respect to mean age, original sites, and tumor stages. The 1-, 2-, and 5-year OS rates were 80.6%, 53.4%, and 24.7% for the DRT group and 85.7%, 67.1%, and 24.7% for the S + RT group, respectively. There was no significant difference between the two groups (χ = 3.183, P = 0.074). The 1-, 2-, and 5-year LRFS and DMFS were 90.4%, 61.7%, and 18.0% and 87.4%, 49.2%, and 9.9%, respectively, and no statistical difference was observed between the two groups (LRFS: χ = 0.028, P = 0.868; DMFS: χ = 3.347, P = 0.067). No significant difference was found between the two groups in acute radiotoxicity.@*CONCLUSION@#Without loss of laryngeal function, the survival of DRT is comparable to that of S + RT in supraglottic and hypopharyngeal carcinoma.

Considerations of treatment standardization from the procession of NCCN guideline of esophageal cancer / 癌症

Esophageal carcinoma is one of the most common malignant tumors, especially in China which is the high incidence area. As a result of mild symptoms of early-stage esophageal cancer, the majority of patients cannot be diagnosed until they develop to advanced cancer, and the treatment outcome of surgery or chemoradiotherapy is still unsatisfactory at present. The guidelines of esophageal cancer issued by National Comprehensive Cancer Network (NCCN) are regarded as important reference tools by clinical oncologists, and provide uniform criteria for the diagnosis and treatment of esophageal carcinoma. However, the guidelines are not always suitable for Chinese patients because the data come from European and American population which have significant ethnical difference from Chinese. We retrospectively analyzed the changes of treatment strategy of esophageal cancer in NCCN guidelines and the advance of treatment for esophageal carcinoma in China, aiming to provide our oncologists with new research ideas. We also hope to set up clinical cancer cooperation organizations, and release our own cancer guidelines to serve Chinese patients and oncologists.

Differential gene expression profiles of DNA repair genes in esophageal cancer cells after X-ray irradiation / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Various factors affect the radioresistance of tumor cells, with unknown molecular mechanism(s). Many genes have been found to associate with the radioresistance of tumor cells, however, the precise mechanism of these genes have not been elucidated. This paper was to analyze the differential expressions of DNA repair genes in esophageal carcinoma cells at different time after X-ray irradiation, and to investigate the role of these DNA repair genes in radiation resistance.</p><p><b>METHODS</b>Esophageal cancer parental cells Seg-1 were treated with continuous 2 Gy of fractionated irradiation until the total dose reached 60 Gy to establish the radioresistant cell line Seg-1R. Total RNA was extracted from each cell line at 0, 8, and 24 h after irradiation. Illumine Human-6 V3 microarray was used to identify differentially expressed genes between parental and radioresistant cells. Ten genes involved in DNA repair were obtained and their expressions at different time points after irradiation were analyzed by Gene Ontology analysis.</p><p><b>RESULTS</b>Ten DNA repair associated genes were found to be differentially expressed. Three of these genes, SLK, HMGB1, and PMS1, were not only differentially expressed between parental and radioresistant cell lines, but also expressed differently at different time points after irradiation in the same cell line.</p><p><b>CONCLUSIONS</b>PMS1 may be an important factor involved in the mechanism of radioresistance of esophageal carcinoma cells.</p>

Literature analysis of radiotherapy for esophageal cancer in China / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Many patterns of treatment have been used to treat esophageal carcinoma in the past years, however, an optimal treatment is still the key issue to be explored. Therefore, we analyzed the published literature about radiotherapy for esophageal cancer in recent 15 years in China, and observed the survival rate, local control rate, adverse events, and so on.</p><p><b>METHODS</b>A total of 56 eligible papers about radiotherapy for esophageal squamous cell carcinoma published in Chinese core periodicals between 1994 and 2009 were selected. The survival rates, local control rates, and adverse events were analyzed.</p><p><b>RESULTS</b>The 1-, 2-, 3-, and 5-year overall survival rates of the patients reported in the 56 papers were (67.99 ± 12.55)%, (49.59 ± 11.79)%, (34.50 ± 11.49)%, and (23.31 ± 10.21)%, respectively. The 1-, 2-, 3-, and 5-year local control rates were (73.04 ± 13.37)%, (61.60 ± 15.50)%, (51.77 ± 15.00)%, and (50.15 ± 21.36)%, respectively. The acute esophageal toxicity rate was (44.84 ± 25.71)% in 32 papers reported in recent 15 years, and the acute esophageal toxicity over grade II accounted for (35.93 ± 22.90)%. The rates of acute esophageal toxicity were (26.84 ± 13.12)% for conventional radiation, (53.72 ± 21.82)% for late course accelerated hyperfractionation radiation, (61.33 ± 28.69)% for concurrent chemoradiotherapy, and (40.31 ± 27.22)% for other ways of radiation. The late toxicity rate described in 23 papers was (5.13 ± 4.07)% in recent 15 years. The late toxicity rates were (5.66 ± 3.42)% for conventional radiation, (4.53± 4.07)% for late course accelerated hyperfractionation radiation, (2.24±1.31)% for concurrent chemoradiotherapy, and (7.34 ± 5.06)% for other ways of radiation. The Meta analysis indicated that concurrent chemoradiotherapy was better than late course accelerated hyperfractionation radiation and conventional radiation.</p><p><b>CONCLUSIONS</b>The long-term survival of patients with esophageal cancer is still disappointed in recent years. Concurrent chemoradiotherapy shows advantages in treating esophageal cancer and, currently, is the best non-surgical treatment of esophageal cancer.</p>

Identification of differentially expressed genes related to radioresistance of human esophageal cancer cells / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Radioresistant cells in esophageal cancer is one of the important reasons for the local failure of radiotherapy. In recent years, some researchers used gene chip technology to screen the differentially expressed genes between parental and radioresistant human esophageal cancer cells. But there were some problems in these studies, for example comparing cells at only one time interval, and genetic background not matching. In this study, we selected 3 different pairs of parental and radioresistant human esophageal cancer cells, and compared the gene expression profiles by cDNA microarray at 3 time intervals to identify and analyze the differentially expressed genes between parental and radioresistant human esophageal cancer cells.</p><p><b>METHODS</b>We compared the gene expression profiles between parental cells (TE13, Seg-1, Kyse170) and radioresistant cells (TE13R, Seg-1R, Kyse170R) before, and at 8 h and 24 h after irradiation with a cDNA microarray consisting of 48 000 genes (Human Genome). We identified differentially expressed genes by Pathway and GO analyses, and verified the differentially expressed genes LEF1 and CTNNB1 by RT-PCR.</p><p><b>RESULTS</b>A total of 460, 451, and 397 differentially expressed genes were found before, and at 8 h and 24 h after irradiation. After Pathway and GO analyses, 14 differentially expressed genes, participating in cell growth, apoptosis, cell cycle regulation, gene repair and signal transmission, were selected to further research. LEF1 and CTNNB1 were verified by RT-PCR, and the results were consistent with those of cDNA microarray.</p><p><b>CONCLUSIONS</b>The WNT signal pathway may be an important pathway participating in the formation of radioresistance of esophageal cancer cells. LEF1 and CTNNB1 may be the important genes causing the esophageal cancer cell radioresistance.</p>

Meta-analysis of late course accelerated hyperfractionated radiotherapy combined with FP chemotherapy for esophageal carcinoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Although there are many randomized clinical trials of late course accelerated hyperfractionated radiotherapy (LCAHFR) combined with FP chemotherapy for esophageal cancer, the efficacy and toxicity are controversial. This study was to evaluate the efficacy and toxicity of LCAHFR combined with FP chemotherapy in treating esophageal cancer.</p><p><b>METHODS</b>Reports of randomized clinical trials on LCAHFR combined with FP chemotherapy for esophageal cancer published between January 1999 and January 2009 were researched through Wanfang, CNKI, and PubMed databases. RevMan4.2 software was used for Meta-analysis.</p><p><b>RESULTS</b>Twenty-one reports, including 2030 patients, were included in the meta-analysis. Of the 2030 patients, 1006 underwent LCAHFR (LCAHFR group), and 1024 underwent LCAHFR combined with FP chemotherapy (combination group). Compared with those of the LCAHFR group, the 1-, 2-, 3-, 5-years survival rates and 1-, 2-, 3-year local control rates of the combination group were significant increased, and the acute toxicity was also increased, but chronic toxicity showed no significant difference.</p><p><b>CONCLUSIONS</b>LCAHFR combined with FP chemotherapy can improve the survival rate and the local control rate of the patients with esophageal cancer. The increased acute toxicity need to be concerned, whereas the chronic toxicity needs a long-term observation.</p>

Relationship between NRAGE and the radioresistance of esophageal carcinoma cell line TE13R120 / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>The mRNA levels of 59 genes, detected by cDNA microarray, were up-regulated in the radioresistant human esophageal cacinoma cell line TE13R120 as compared with its parental cell line TE13 before and after radiation, and the expression of NRAGE gene showed a gradually up-regulating tendency. This study aimed to further detect the differences of NRAGE gene and protein expression and apoptosis between TE13R120 and TE13 cells, and to investigate the relationship between the NRAGE and the radioresistance of TE13R120 cells and its mechanism.</p><p><b>METHODS</b>The two cell lines were irradiated by ⁶⁰Co γ-ray at different conditions. Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunocytochemistry were used to detect the expression of NRAGE. Flow cytometry (FCM) was used to detect the cell apoptosis before and after irradiation.</p><p><b>RESULTS</b>The mRNA level of NRAGE was higher in TE13R120 cells than in TE13 cells before and after irradiation (before radiation: 0.25 ± 0.03 vs. 0.49 ± 0.03; 4 Gy 4 h: 0.31 ± 0.03 vs. 0.53 ± 0.02; 4 Gy 16 h: 0.32 ± 0.04 vs. 0.59 ± 0.04; 4 Gy 24 h: 0.36 ± 0.05 vs. 0.72 ± 0.04; 2 Gy 12 h: 0.32 ± 0.02 vs. 0.64 ± 0.04; 6 Gy 12 h: 0.36 ± 0.02 vs. 0.79 ± 0.05; 10 Gy 12 h: 0.46 ± 0.04 vs. 0.85 ± 0.01; P < 0.01), and the mRNA level of NRAGE was increased gradually with the increase of radiation dose and time in the two cell lines (P < 0.05 and P < 0.01). Western blot results showed no difference of NRAGE protein level in cytoplasm between TE13R120 cells and TE13 cells before and after irradiation, but its level in nuclei was higher in TE13R120 cells than in TE13 cells at different radiation time and dosages. Immunocytochemistry showed similar results as Western blot. FCM showed no significant difference in apoptosis rate between TE13R120 and TE13 cells before and after radiation.</p><p><b>CONCLUSION</b>NRAGE may play an important role in the radiation responses of the two cell lines, and may participate in the formation of radioresistance of TE13R120 cells by changing its subcellular localization, but its relationship with cell apoptosis has not been confirmed.</p>

Using CT imaging to delineate the prostatic apex for radiation treatment planning / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>In computed tomography (CT)-based radiotherapy planning for prostate cancer, it is difficult to precisely delineate the prostatic apex because of its relationship with the urogenital diaphragm and bulbospongiosus musculature. In this retrospective study, we analyzed the magnetic resonance imaging (MRI) and CT scans of the patients with prostate cancer to investigate the relationship between the prostatic apex and the anatomic structure visible on CT, and to provide evidence for localizing the prostatic apex in radiotherapy planning.</p><p><b>METHODS</b>MRI and CT scans of 108 patients with prostate cancer were analyzed to measure the distances between the prostatic apex and the bottom of ischial tuberosities, the bottom of obturator foramen, the bottom of pubic symphysis, and the bulb of the penis. The volume of the prostate was measured to analyze its relationship with the localization of the prostatic apex.</p><p><b>RESULTS</b>The prostatic apex was located (13.1±3.3) mm above the bulb of the penis, (11.0±5.4) mm above the bottom of the obturator foramen, (31.3±5.5) mm above the ischial tuberosities, and (7.1±4.7) mm above the bottom of the symphysis pubis. There was no correlation between the size of the prostate and the localization of the prostatic apex.</p><p><b>CONCLUSIONS</b>The variance of the distance between the prostatic apex and the bulb of the penis is smaller than that of the distance between the apex and bony anatomy. Delineating the target to 6 mm above the bulb of the penis can cover the prostatic apex in 95% of the patients with prostate cancer, delineating to the bottom of obturator foramen can cover the prostatic apex in 100% of the patients.</p>

Assessment of injury to the pancreas,the abdominal tissues and organs of swine in vivo by high intensity focused ultrasound combined with radiotherapy / 中华医学超声杂志（电子版）

Objective To observe the injury of high intensity focused ultrasound combined with radiotherapy (RT) to the pancreas,the unintended abdominal tissues and organs of swine in vivo.MethodsAccording to the criterion to grade the gross and histological injury of the pancreas and the unintended tissue,the scores of injury between the groups to get the data of safety and feasibility of high intensity focused ultrasound(HIFU)combined with RT were compared.Results There was a better tolerance in each group and no fatal complication was observed.For the pancreas there was significant difference for the combined group compared with the other groups.For the unintended target tissue there was no significance difference except the control group with the other groups.Conclusion HIFU combined with RT can increase the injury to the pancreas of the swine compared with HIFU alone; while there was no increase for the injury to the unintended target tissue.The main toxicity of combination treatment is the toxicity of RT and can be tolerated by the animals.If the HIFU treatment is strictly controlled,the combination of HIFU and RT is safe and feasible.

Multi-center phase II clinical trial of humanized anti-epidermal factor receptor monoclonal antibody h-R3 combined with radiotherapy for locoregionally advanced nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safty of the humanized anti-epidermal factor receptor monoclonal antibody h-R3 in combination with radiotherapy for locoregionally advanced nasopharyngeal carcinoma.</p><p><b>METHODS</b>Totally, 137 patients from 7 medical center around China were randomly divided into combined therapy group or control group. There was no difference in Karnofsky performance score between two groups. All patients in both groups received radical conventionally fractionated radiotherapy to the total dose of D(T) 70-76 Gy. For the combined therapy group, h-R3 was added at a dose of 100 mg i.v. weekly for 8 weeks started at the beginning of radiotherapy.</p><p><b>RESULTS</b>Of the 137 eligilbe patients, 70 were in the combined therapy group treated by h-R3 plus radiotherapy and 67 in the control group by radiotherapy alone. The intent-to-treat (ITT) population consisted of 130 patients, while the per-protocol (PP) population was composed of 126 patients. The efficacy was assessed respectively at three point of time: the end of treatment, the 5th- and 17th-week after treatment. The complete response (CR) of the combined therapy group was significantly higher than that of the control group in both ITT and PP (ITT: 65.63%, 87.50%, 90.63% versus 27.27%, 42.42%, 51.52%; PP: 67.21%, 90.16%, 93.44% versus 27.69%, 43.08%, 52.31%; P < 0.05, respectively). The most common h-R3-related adverse reactions were fever (4.3%), hypotension (2.9%), nausea (1.4%), dizziness (2.9%) and rash (1.4%), which could be reversible if treated properly. Radiotherapy combined with 100 mg h-R3 i. v. weekly was tolerable and did not aggravate the side effects of radiation. The quality of life in the combined therapy group was comparable to that in the control group.</p><p><b>CONCLUSION</b>This phase 1 multicenter clinical trial shows that h-R3 in combination with radiotherapy is effective and well-tolerated for the treatment of locoregionally advanced nasopharyngeal carcinoma.</p>

Portal size of prophylactic postoperative radiotherapy for esophageal carcinoma / 中华放射肿瘤学杂志

Objective To compare and analyze the effect of prophylactic postoperative radiotherapy for esophageal carcinoma.Methods 102 such patients were treated with prophylactic radiotherapy after radical resection,to a total dose of 50-60 Gy.The extensive portal included supraclavicular region on both sides,entire mediastinum,the site of anastomosis and left gastric lymph node region in 43 patients.The re- gional portal range was different according to the different location of primary lesion in 59 patients.Results The 1-,3- and 5-year survival rate was 76%,51% and 43% respectively,with a median survival of 30 months.The 1-,3- and 5-year survival rate was 77%,52% and 41% in the extensive portal and 76%, 49% and 45% in the regional portal,respectively(P=0.884).According to multivariate analysis,N stage, number of metastatic lymph nodes and tumor length were independent prognostic factors.Conclusions Regional portal does not lower the survival rate when prophylactic postoperative radiotherapy is used in e- sophageal carcinoma.

Dose escalation of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma / 中华放射肿瘤学杂志

Objective To define the maximum-tolerated dnse(MTD)and observe the side effect of escalating cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma in Chinese,with toxicity studied.Methods Previously untreated fifteen Chinese patients suffering from esophageal carcinoma received conventional fractionafiun radiotherapy,with 5 daily fractions of 2.0 Gy per week.The total radiation dose was 60 Gy.Concurrent chemotherapy dose escalation was given by the relatively safe and kidney-sparing modified Fibonacci sequence.The starting dose was cisplatin 37.5 mg/m~2 D1 and 5-fluorouracil 500 mg/m~2 D1-5, respectively.This regimen was repeated 4 times every 28 days.Escalation dose was eisplatin 7.5mg/m~2 and 5- fluorouracil 100mg/m~2.Every cohort contained at least 3 patients.If no dose-limiting toxicity(DLT)was observed, the next dose level was opened for entry.These courses were repeated until DLT appeared.MTD was declared as one dose level below which DLT appeared.Results DLT was defined as grade 3 radiation-induced esophngitis at the level of cisplatin 60 mg/m~2,5-fluorouracil 700 mg/m~2.MTD was defined as eisplafin 52.5 mg,/m~,5- fluorouracil 700 mg/m~2.The major side effect were radiation-induced esophagitis,leucopenia,nausea,vomiting and anorexia.Conclusion Maximun tolerated dose of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy in the Chinese people with esophageal carcinoma were eisplatin 52.5 mg/m~2 D1,5-fluorouracil 700 mg/m~2 D1-5,repeated 4 times every 28 days.