Objective:To compare 5-year overall survival (OS) and disease free survival (DFS) between preoperative three dimensional conformal radiotherapy (3DCRT) and volumetric medulated arc therapy (VMAT) concurrently combined with chemotherapy for locally advanced rectum cancer (LARC), and analyze the value of induction and/or consolidation chemotherapy in these circumstances.Methods:334 patients with LARC treated with preoperative 3DCRT (172 cases) and VMAT (162 cases) concurrently combined with chemotherapy, main protocol XELOX (capecitabine plus oxaplatin), and subsequent surgery in Sun Yat-sen University from May 2007 to April 2013 were retrospectively analyzed. The radiation prescription dose for VMAT group was 50 Gy 25 fractions for planning target volume1(PTV 1), and 46 Gy 25 fractions for PTV 2. The radiation prescription dose for 3DCRT group was 46 Gy 23 fractions for PTV 2. One hundred and eighty-five cases of all received preoperative concurrent chemoradiotherapy (namely, CCRT group), 149 cases received preoperative concurrent chemoradiotherapy plus median 2 courses (1-7 courses) induction and/or consolidation chemotherapy (namely, CCRT±induction chemotherapy±consolidation chemotherapy group), whose main chemotherapy protocol was XELOX. Difference of 5-year OS and DFS between 3DCRT and VMAT group was compared. The rate differences of acute toxicity during chemoradiotherapy, postoperative complications, ypCR, and survival between CCRT group and CCRT±induction chemotherapy±consolidation chemotherapy group were analyzed. Results:After a median follow-up of 62.3 months (2.4-119months) for the 334 patients, no any significant difference for 5-year OS (79.0% vs. 83.2%, P=0.442) and 5-year DFS (77.0% vs. 82.1%, P=0.231) between 3DCRT and VMAT group was observed. There was no any significant difference for the Grade 3 hematological toxicity (7.0% vs. 12.1%, P=0.114) and non-hematological toxicity (14.1% vs. 16.8%, P=0.491) during chemoradiotherapy, postoperative complications (17.3% vs. 17.4%, P=0.971), ypCR rate (25.4% vs. 30.2%, P=0.329), 5-year OS (80.5% vs. 82.0%, P=0.714) and 5-year DFS (78.8% vs. 81%, P=0.479) between CCRT group and CCRT±induction chemotherapy±consolidation chemotherapy group. Conclusions:Compared with 3DCRT, the physics advantage of VMAT technique does not significantly convert into clinical benefits and improve 5-year OS and DFS, even further boosting radiation dose to the gross tumor volume. It is safe for median 2 courses of induction and/or consolidation chemotherapy before and or after preoperative concurrent chemoradiotherapy in the treatment of LARC, though it does not significantly improve ypCR rate and survival.

Objective To evaluate the impact of three to four cycles of neoadjuvant chemotherapy (NACT) on the survival of patients with N2-N3 nasopharyngeal carcinoma (NPC).Methods The clinical data of 915 patients with T1-4N2-3M0 NPC from 2007 to 2010 were retrospectively analyzed.A total of 179 patients treated with 3-4 cycles of NACT (NACT≥3 group) were matched with 358 patients treated with 2 cycles of NACT (NACT=2 group) and 179 patients treated without NACT (NACT =0 group,concurrent chemoradiotherapy group) for age,N stage,pathological subtype,and NACT regimen.The Kaplan-Meier method was used to calculate overall survival (OS),disease-free survival (DFS),recurrence-free survival (RFS),and distant metastasis-free survival (DMFS) rates,the log-rank test was used for survival difference analysis and univariate prognostic analysis,and the Cox proportional hazards model was used for multivariate prognostic analysis.Results For the NACT≥ 3,NACT =2,and NACT =0 groups,the 5-year OS rates were 89.4％,81.6％,and 73.7％,respectively (P=O.000),the 5-year DFS rates were 83.2％,69.8％,and 64.2％,respectively (P=O.000),the 5-year RFS rates were 86.0％,76.0％,and 69.3％,respectively (P=0.001),and the 5-year DMFS rates were 86.6％,76.0％,and 68.3％,respectively (P=0.000).Three to four cycles of NACT was an independent protective factor for OS,DFS,RFS,and DMFS in patients with N2-N3 NPC.Conclusion Three to four cycles of NACT can significantly improve the survival of patients with N2-N3 NPC.

Objective To investigate the efficacy and toxicities of neoadjuvant chemoradiotherapy (neoCRT) in the management of unresectable locally advanced adherent colon cancer (LAACC).Methods A retrospective analysis was performed on the clinical records of 40 patients with initially diagnosed unresectable LAACC who received preoperative neoCRT in our center from October 2010 to December 2015.Results Thirty-nine patients completed the preoperative neoCRT.Thirty-four patients underwent radical resection after neoCRT, and the R0 resection rate, pathological complete response rate (pCR), tumor downstaging rate, nodal downstaging rate, and clinical downstaging rate were 91%, 24%(8/34patients), 76%(26/34patients),100%(32/32patients), and 94%(32/34patients), respectively.Among the 21 patients with bladder invasion, the full bladder was preserved in 7 patients (33%) and partial cystectomy was performed in 11 patients (52%).During the course of neoCRT, the grade 3-4 hematologic toxicity rate, grade 3 hand-foot syndrome rate, grade 3 radiodermatitis, and incomplete intestinal obstruction rate were 23%, 3%, 3%, and 5%, respectively.The 3-year sample size was 25 patients.For all the patients, the 3-year overall survival (OS) and progression-free survival (PFS) rates were 75% and 80%, respectively.Of the 34 patients who received surgical radical resection, the 3-year OS and disease-free survival (DFS) rates were 87% and 81%, respectively.In addition, local tumor recurrence was identified in 3 patients, and distant metastasis was identified in 6 patients.Conclusions NeoCRT is an effective treatment for unresectable LAACC that results in significant tumor downstaging and enhanced R0 resection rate without an increase in surgical complications.The patients treated with radical surgical resection after neoCRT show a satisfactory short-term outcome.Further studies will be required to determine the clinical value of neoCRT in treating LAACC.

Objective:To develop a national secondary reference material of Urea and Creatinine in frozen human serum as a standard for metrological traceability.Methods:According to JJF1343-2012 "General and Statistical Principles for Characterization of Reference Materials" and JJF 1006-1994 " Technical Norm of Primary Reference Material ", the homogeneity, stability, and commutability were evaluated;Using the JCTLM recommended methods, the value of the reference materials was assigned through collaboration with 6 accredited reference laboratories from Guangdong Provincial Hospital of Chinese Medicine, Beijing Aerospace General Hospital, Shenzhen Mindray Bio-Medical Electronics, Maccura Biotechnology, Beijing Leadman Biochemistry, and Zhejiang MedicalSystem Biotechnology. Uncertainty components including inhomogeneity, stability and value assignment were evaluated.Results:The results of one-way analysis of variance of homogeneity for the reference materials showed P>0.05, and the stability evaluation was less than the critical value of the t-test. The measured values were in the 95% confidence interval in the four conventional detection systems for commutability, and the certified values and expanded uncertainties were urea:(14.7±0.3) mmol/L ( k=2),Cr:(313.9±14.5) μmol/L ( k=2). Conclusion:The prepared secondary reference materials of urea and creatinine had promising homogeneity, stability, and commutable, the values of urea and creatinine concentration in reference materials were accurate and reliable.

Objective:To establish a candidate reference method for serum progesterone using isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS) in our laboratory, validate the analytic performance of five clinical routine detection systems to explore the comparability of serum progesterone detection by different detection systems.Methods:A candidate reference method for serum progesterone using ID-LC/MS/MS method was established. The sample was pretreated by liquid-liquid extraction method, and the reversed phase liquid phase separation in positive ion mass spectrometry mode was used to detect progesterone in human serum, and the detection time of a single sample was controlled within 5 minutes by gradient elution. In order to improve the accuracy of the method, the bracketing calibration method (BCM) was used to establish the standard curve. The sensitivity, accuracy, precision and specificity of BCM and classical calibration curve method were evaluated according to CLSI C62-A, EP15-A2, EP6-A2 and EP9-A3, and the analytical performance and comparability of five clinical routine progesterone detection systems were evaluated,compared with ID-LC/MS/MS method, the bias at medical decision level 2 and 25 ng/ml was evaluated to see if they were <1/2TEa (12.5%).Results:The limit of detection (LOD) of ID-LC/MS/MS was 0.005 ng/ml. The recoveries of BCM method and classical calibration curve method are 97.95%-101.58% and 96.88%-110.70%, respectively. The measurement results of BCM method for certified reference materials are within its declared uncertainty range. The intra-and inter-assay coefficient of variation ( CV) of BCM method was less than 3.0%, which was better than that of classical calibration curve method ( CV: 2.48%-9.33%). The precision and linear range of the five clinical routine detection systems can meet the detection requirements. The measurement bias of detection system 1, 3 and 5 at 25 ng/ml of medical decision level was less than 1/2TEa, and the measurement bias at 2 ng/ml of medical decision level was more than 1/2TEa. The measurement bias of detection system 2 and 4 at two medical decision levels was less than 1/2TEa. Conclusion:The candidate reference method for serum progesterone ID-LC/MS/MS established in our laboratory meets the requirements of the reference method. BCM has better detection performance than classical calibration curve method. The precision and linearity of the five progesterone clinical detection systems are satisfactory. The five clinical detection systems could meet the clinical requirements at the medical determination level of 25 ng/ml, however, only two of the five clinical detection systems meet the clinical requirements at the medical determination level of 2 ng/ml.

Objective To investigate the feasibility of non-operative management (NOM) by comparing the therapeutic effects between NOM and total mesorectal excision (TME) for rectal cancer patients with clinical complete response (cCR) after neo-adjuvant chemoradiotherapy.Methods A total of 135 patients with stage Ⅱ/Ⅲ rectal cancer who obtained cCR after neo-adjuvant chemoradiotherapy in Sun Yat-sen University Cancer Center from 2006 to 2016 were recruited and assigned into the NOM (n =43) and standard operative management (SOM) groups (n=92).The local recurrence rate,accumulative local control (LC) rate after salvage therapy,disease-free survival (DFS),overall survival (OS) and sphincter preservation rate were statistically compared between two groups.Kaplan-Meier analysis and log-rank test were utilized to calculate the LC,OS and DFS.Chi-square test was performed to calculate the sphincter preservation rate.Results The mean follow-up duration was 39 months (range:10-127 months).Of 135 patients,the local recurrence rate and distant metastasis rate were 3.7％ and 11.1％,and the 3-year DFS and OS were 90.5％ and 97.0％.In the NOM and SOM groups,the 3-year DFS were 87％ and 93％,and the 5-year DFS were 73％ and 87％(P=0.089).The 3-year OS were 98％ and 99％,and the 5-year OS were 98％ and 97％ (P=0.578).In the NOM group,the local recurrence rate was 12％ (n =5),80％ of patients received salvage treatment and the accumulative LC rate was calculated as 98％.In the SOM group,the local recurrence rate was 0,which was significantly lower than that in the NOM group (P=0.O10).In the NOM group,the sphincter preservation rate was 93％,significantly higher compared with 70％ in the SOM group (P=0.030).Conclusions It is feasible for rectal cancer patients with cCR to receive NOM following neo-adjuvant chemoradiotherapy.Partial locally recurrent patients can be healed by timely salvage therapy,thereby averting TME and relevant complications and enhancing the quality of life of rectal cancer patients.

Objective To investigate the prognostic value of American Joint Committee on Cancer-tumor regression grading ( AJCC-TRG) combined with ypTN stage in patients with locally advanced rectal cancer (LARC),who were treated with neoadjuvant chemoradiotherapy,and to identify the subgroups with the worst prognosis. Methods A total of 263 patients with LARC,including 176 males and 87 females,with a median age of 55 years,were admitted to Sun Yat-sen University Cancer Center from 2004 to 2012.All the patients received neoadjuvant chemoradiotherapy before surgery and underwent total mesorectal excision at 6 to 8 weeks after radiotherapy. All the surgical specimens were reevaluated according to the AJCC ( 7th edition)-TRG system and ypTN staging criteria. The prognostic prediction by TRG combined with ypTN was evaluated using survival analysis. The Kaplan-Meier method was used to calculate the rates of overall survival ( OS ) , disease-free survival ( DFS ) , local recurrence-free survival ( LRFS ) , and distant metastasis-free survival ( DMFS ) . The log-rank test was used for survival comparison and univariate prognostic analysis. Results The median follow-up was 601 months. The 5-year rates of OS, DFS, LRFS, and DMFS for all patients were 800%,750%,970%,and 810%,respectively. There were significant differences in OS, DFS,and DMFS between different ypT/TRG subgroups and different ypN/TRG subgroups (all P<005). ypT3-4/TRG 2-3 and ypN1-2/TRG 2-3 subgroups showed the worst prognosis. The 5-year rates of OS,DFS, and DMFS of the two subgroups were 669%/560%, 522%/414%, and 609%/460%, respectively. Conclusions A combination of AJCC-TRG system and ypTN staging can better predict the prognosis of LARC and identify the subgroups with the worst prognosis, which may provide a clinical guidance for postoperative individualized decision on adjuvant therapy for LARC.

Objective: To identify the definition of heat wave based on mortality risk assessment in different regions of China. Methods: Daily mortality (from China Information System for Disease Control and Prevention) and meteorological data (from National Meteorological Information Center in China) from 66 counties with a population of over 200 000 were collected from 2006-2011. With the consideration of climate type and administrative division, China was classified as seven regions. Firstly, distributed lag non-linear model (DLNM) was used to estimate community-specific effects of temperature on non-accidental mortality. Secondly, a multivariate meta-analysis was applied to pool the estimates of community-specific effects to explore the region-specific temperature threshold and the duration for definition of heat wave. Results: We defined regional heat wave of Northeast, North, Northwest, East, Central and Southwest China as being two or more consecutive days with daily mean temperature higher than or equal to the P₆₄, P₇₁, P₈₅, P₆₇, P₇₅ and P₇₇ of warm season (May to October) temperature, respectively, while the thresholds of temperature were 21.6, 23.7, 24.3, 25.7, 28.0 and 25.3 ℃. The heat wave in South China was defined as five or more consecutive days with daily mean temperature higher than or equal to the P₉₃ (30.4 ℃) of warm season (May to October) temperature. Conclusion The region-specific definition of heat wave developed in our study may provide local government with the guidance of establishment and implementation of early heat-health response systems to address the negative health outcomes due to heat wave.