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Background: The molecular mechanisms underlying chemoresistance are still poorly understood in nasopharyngeal cancer; the protein expression of ERCC1 in DNA repair genes has been reported related t...

PURPOSEAs yet, no checkpoint inhibitor has been approved to treat nasopharyngeal carcinoma (NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chemotherapy.PATIENTS AND METHODSIn this single-arm, multicenter phase II study, patients with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). The secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).RESULTSAmong all 190 patients, the ORR was 20.5% with median DOR 12.8 months, median PFS 1.9 months, and median OS 17.4 months. Among 92 patients who failed at least two lines of systemic chemotherapy, the ORR was 23.9%. The ORRs were 27.1% and 19.4% in PD-L1+ and PD-L1− patients, respectively ( P = .31). Patients with ≥ 50% decrease of plasma Epstein-Barr virus (EBV) DNA copy number on day 28 had significantly better ORR than those with < 50% decrease, 48.3% versus 5.7% ( P = .0001). Tumor mutational burden had a median value of 0.95 muts/mega-base in the cohort and had no predictive value for response. Whole-exome sequencing results from 174 patients revealed that the patients with genomic amplification in 11q13 region or ETV6 genomic alterations had poor responses to toripalimab.CONCLUSIONThe POLARIS-02 study demonstrated a manageable safety profile and durable clinical response of toripalimab in patients with chemorefractory metastatic NPC. An early decrease in plasma EBV DNA copy number correlated with favorable response.

Purpose This study aimed to investigate radiomic features extracted from magnetic resonance imaging (MRI) scans performed before and after neoadjuvant chemoradiotherapy (nCRT) in predicting response of locally advanced rectal cancer (LARC). Methods and Materials Thirty-nine patients who underwent nCRT for LARC were included, with 294 radiomic features extracted from MRI that was performed before (pre-CRT) and 6 to 8 weeks after completing nCRT (post-CRT). Based on tumor regression grade (TRG), 26 patients were classified as having a histopathologic good response (GR; TRG 0-1) and 13 as non-GR (TRG 2-3). Tumor downstaging (T-downstaging) occurred in 25 patients. Univariate analyses were performed to assess potential radiomic and delta-radiomic predictors for TRG in pathologic complete response (pCR) versus non-pCR, GR versus non-GR, and T-downstaging. The support vector machine-based multivariate model was used to select the best predictors for TRG and T-downstaging. Results We identified 13 predictive features for pCR versus non-pCR, 14 for GR versus non-GR, and 16 for T-downstaging. Pre-CRT gray-level run length matrix nonuniformity, pre-CRT neighborhood intensity difference matrix (NIDM) texture strength, and post-CRT NIDM busyness predicted all 3 treatment responses. The best predictor for GR versus non-GR was pre-CRT global minimum combined with clinical N stage in the multivariate analysis. The best predictor for T-downstaging was the combination of pre-CRT gray-level co-occurrence matrix correlation, NIDM-texture strength, and gray-level co-occurrence matrix variance. The pre-CRT, post-CRT, and delta radiomic-based models had no significant difference in predicting all 3 responses. Conclusions Pre-CRT MRI, post-CRT MRI, and delta radiomic-based models have the potential to predict tumor response after nCRT in LARC. These data, if validated in larger cohorts, can provide important predictive information to aid in clinical decision making.

Background To evaluate the efficacy and safety of recombinant human serum albumin /granulocyte colony-stimulating factor (rHSA/G-CSF) in breast cancer following receipt of cytotoxic agents. Methods The phase 1b trial assessed the pharmacokinetics, pharmacodynamics, and safety of dose-escalation, ranging from rHSA/G-CSF 1800 μg, 2100 μg, and 2400 μg. Randomized controlled phase 2b trial was further conducted to ensure the comparative efficacy and safety of rHSA/G-CSF 2400 μg and rhG-CSF 5 μg/kg. In multicenter, randomized, open-label, parallel, phase 2 study, participants treated with anthracycline-containing chemotherapy were assigned in a ratio 1:1:1 to receive double delivery of rHSA/G-CSF 1200 μg, 1500 μg, and continuous rhG-CSF 5 μg/kg. Results Between December 16, 2014, to July 23, 2018, a total of 320 patients were enrolled, including 25 individuals in phase 1b trial, 80 patients in phase 2b trial, and 215 participants in phase 2 study. The mean duration of agranulocytosis during the first chemotherapeutic intermission was observed as 1.14 ± 1.35 days in rHSA/G-CSF 1500 μg, which was comparable with that of 1.07 ± 0.97 days obtained in rhG-CSF control (P = 0.71). Safety profiles were assessed to be acceptable ranging from rHSA/G-CSF 1800 μg to 2400 μg, while the double delivery of HSA/G-CSF 2400 μg failed to meet the noninferiority in comparison with rhG-CSF. Conclusion The prospective randomized controlled trials demonstrated that rHSA/G-CSF was efficacious and well-tolerated with an approachable frequency and expense of application for prophylactic management of agranulocytosis. The double delivery of rHSA/G-CSF 1500 μg in comparisons with paralleling G-CSF preparations is warranted in the phase 3 trial. Trial registration ClinicalTrials.gov identifiers: NCT02465801 (11/17/2014), NCT03246009 (08/08/2017), NCT03251768 (08/07/2017).

Background There are obviously ethnic differences between the UGT1A1 gene polymorphisms. Due to the difference of genetic background and environment, the treatment with colorectal cancer patients of Guangxi Zhuang should not completely follow the Euramerican or Chinese han patients. The study aimed to explore the correlation of UGT1A1 gene polymorphism of Guangxi Zhuang metastatic colorectal cancer (mCRC) with irinotecan -based chemotherapy, in order to develop an individualized irinotecan regimen for mCRC patients of Guangxi Zhuang. Methods From June 2013 and June 2015, a total of 406 patients of Guangxi who were histologically diagnosed as metastatic colorectal cancer with 102 patients of this cohort with three generations of Zhuang, and 86 patients that conformed to inclusion and exclusion criteria were competitively enrolled. The distribution of UGT1A1 gene polymorphism was analyzed-retrospectively in all patients. Pyrosequencing method was used to detect the UGT1A1*28 and*6 gene polymorphism in the 86 Guangxi Zhuang mCRC patients. After first-line chemotherapy with FOLFIRI regimen, the relationship between gene polymorphism of UGT1A1 and adverse reactions, and efficacy of Irinotecan were analyzed with χ2 test and Kaplan-Meier method. Results UGT1A1*28 wild-type (TA6/6), heterozygous mutant (TA6/7) and homozygous mutant (TA7/7) accounted for 69.8, 30.2 and 0%, respectively. UGT1A1*6 wild type (G/G), heterozygous mutation type (G/A) and homozygous mutant (A/A) accounted for 76.7%, 20.9 and 2.3%, respectively. UGT1A1*28 TA6/7 type could increase the risk of grade 3~4 diarrhea (p = 0.027), which did not increase the risk of grade 3~4 neutropenia (p = 0.092). UGT1A1*6G/A and A/A type could increase the risk of grade 3~4 diarrhea and neutropenia (p = 0.001; p = 0.017). After chemotherapy with FOLFIRI, there was no significant difference in response rate (RR) (p = 0.729; p = 0.745) or in median progression-free survival (mPFS) between the wild-type, mutant treatment of UGT1A1*28 and UGT1A1*6 (7.0 m vs 7.4 m, p = 0.427; 6.9 m vs 7.0 m p = 0.408). Conclusions The distribution of UGT1A1*28 and UGT1A1*6 gene polymorphism in Guangxi Zhuang patients were differed from the existing reported of European people and Chinese Han population. The UGT1A1 gene polymorphism with irinotecan chemotherapy-associated diarrhea and neutropenia were closely related. There was no significant association between UGT1A1 gene polymorphism and therapeutic efficacy of irinotecan.

Background: A Phase II, randomized, prospective, multicentric trial (NCT02237924) was conducted to evaluate the efficacy and safety of Endostar plus radiotherapy in patients with low-risk local advanced nasopharyngeal carcinoma (NPC). Methods: From 09/2014 to 08/2016, patients with low-risk local advanced NPC were randomly treated with Endostar plus radiotherapy (ERT group, n=60) and concurrent chemoradiotherapy (CCRT group, n=60). Primary endpoint was the 5-year overall survival (OS) rate. The secondary endpoints were 3-year progression free survival (PFS) rate, OS rate, loco-regional recurrence free survival (LRRFS) rates and distance metastasis free survival (DMFS) rates. Findings: After a median follow-up of 47 months, 3-year OS rates were 93.2% and 79.3%, 3-year PFS rates were 89.8% and 70.6%, 3-year DMFS rates were 93.2% and 80.7%, in two groups, respectively (P 0.05). Moreover, the incidences of complications were significantly lower in ERT group. For short-term curative effects, CR rates were 70.0% and 60.0% for primary tumor, 73.3%and 65.0% for cervical lymph nodes, in two groups, respectively (P 0.05). Interpretation: OS, PFS, and DMFS rates can be improved, adverse events be reduced, with better tolerability, by Endostar plus radiotherapy, when compared to concurrent chemoradiotherapy for local advanced low-risk NPC. Trial Registration: (NCT02237924). Funding Statement: This work was supported by National Natural Science Foundation of China (No. 81760542), the Projects for Research and Development of Medical and Health Appropriate Technology of Guangxi Zhuang Autonomous Region (No. S2018087), the Key Research and Development Program of Guangxi (No. Guike AB18281003), Guangxi Medical University Training Program for Distinguished Young Scholars, and Medical Excellence Award Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University, “139” Program for high-level medical talents in Guangxi, Innovation Team of the First Affiliated Hospital of Guangxi Medical University. Guangxi Science and Technology Program Project (GK AD17129013), Simcere. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of Guangxi Medical University. All procedures performed in the study involving human participants were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments. Written informed consent was obtained from the patient and his/her immediate families.

PURPOSE/OBJECTIVE(S) The progression-free survival (PFS) of metastatic nasopharyngeal carcinoma after first-line chemotherapy is not ideal, and the role of drug maintenance intervention in improving survival outcomes remains controversial. To investigate the safety and effect of Tegafur(S1) maintenance intervention in patients with metastatic nasopharyngeal carcinoma who benefit from the first-line treatment in a multicenter randomized controlled study, and to identify the related biological prognostic factors and guide the individualized treatment choice. MATERIALS/METHODS Patients with metastatic nasopharyngeal carcinoma in the Fourth Affiliated Hospital of Guangxi Medical University and other cancer centers who met the inclusion criteria were randomly divided into maintenance therapy group: S1 maintenance therapy until disease progression or intolerance; Observation group: follow-up to disease progression. PFS, overall survival (OS) and adverse reactions of S1 maintenance therapy were compared between the two groups. The correlation between EBV-DNA, human serum amyloid A (SAA) and prognosis was evaluated. RESULTS Follow-up was conducted to May 2020, with a median follow-up of 19.8 months (6.1-51.3 months), 183 cases were evaluable (88 cases in S1 maintenance treatment group, 95 cases in observation group). Compared with the observation group, the S1 maintenance treatment group significantly increased patients' median PFS (16.2 months vs. 8.7 months, P < 0.001) and median OS (32.1 months vs. 18.2 months, P < 0.001). Reduced the risk of poor prognosis for PFS and OS (PFS: HR 0.305, 95% CI 0.211-0.441, < 0.001; OS: HR 0.363, 95% CI 0.238-0.553, P < 0.001). In the maintenance treatment group, the median S1 treatment lasted for 14 courses (4-58 courses), and the main adverse reactions were grade 1 skin pigmentation, oral mucositis, hand-foot syndrome, nausea, etc. No grade 4 toxic reaction occurred, and it was well tolerated. Compared with observation patients with negative EBV-DNA, observation patients with positive EBV-DNA had a higher risk of poor prognosis for PFS (HR 1.764, 95% CI 1.078-2.887, P = 0.024). The risk of poor prognosis in patients with positive EBV-NDA was significantly reduced by 61.1% (< 0.001) for PFS and 65.5% (P = 0.001) for OS (P = 0.001). Compared with the observation group with stable SAA expression, S1 maintenance therapy significantly improved the prognosis of patients. Patients with continuous decline in SAA had a 61.9% lower risk of poor prognosis in PFS (P < 0.001) and a 60.2% lower risk of poor prognosis in OS (P = 0.007). CONCLUSION For patients with metastatic nasopharyngeal carcinoma who benefit from first-line treatment, maintenance therapy of S1 can significantly improve the survival prognosis and is well tolerated. Patients with positive EBV-DNA and continuous decline in SAA may benefit more from maintenance intervention.

Background Nimotuzumab (NTZ) is an anti-EGFR monoclonal antibody. However,the effect of targeted drugs combined with induction therapy in locally advanced nasopharyngeal carcinoma remains unclear. The aim of this study is to investigate the safety and efficacy of NTZ combined with cisplatin plus 5-fluorouracil (PF) as induction regimen in locally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent radiochemotherapy. Methods This was a multicenter randomized controlled study performed in eight Guangxi hospitals in 2015–2017. Eligible patients with NPC were randomized into nimotuzumab/PF (NPF group) and docetaxel/PF (DPF group) regimens, respectively, as induction therapy. After 2 cycles of induction therapy, all patients received cisplatin and concurrent intensity modulated radiation therapy (IMRT). Then, the two groups were compared for safety and efficacy. Results A total of 118 patients with stage III-IVa NPC were assessed, with 58 and 60 in the NPF and DPF groups, respectively. Compared with DPF treatment, NPF induction therapy showed a more pronounced effect on cervical lymph nodes (P = 0.036), with higher response rate (RR) (81% vs 60%). Compared with the DPF group, the NPF group showed significantly reduced leukopenia, neutropenia and gastrointestinal reactions (all P P P = 0.033). Conclusion For locally advanced NPC patients receiving follow-up cisplatin and IMRT, nimotuzumab/PF for induction therapy has better lymph node response rate and milder adverse reactions than the DPF regimen. In addition, the patients have better tolerance in subsequent concurrent radiotherapy and chemotherapy; however, long-term efficacy needs further follow-up evaluation. Trial registration The registration number of the clinical trial is ChiCTR-OIC-16008201 and retrospectively registered on March 31, 2016.

Purpose In rectal cancer, the presence of extramesorectal/lateral pelvic lymph node (LPN) is associated with higher risk of locoregional and distant recurrences. LPNs are not typically resected during a standard total mesorectal excision (TME) procedure, and the optimal management for these patients is controversial. We assessed the safety and efficacy of adding a radiation therapy boost to clinically positive LPN during neoadjuvant chemoradiation therapy for rectal cancer. Methods and Materials We analyzed nonmetastatic, lymph node positive rectal adenocarcinoma patients treated with neoadjuvant chemoradiation therapy followed by TME between May 2011 and February 2018. Patients without LPN involvement received external beam radiation therapy (45 Gy in 25 fractions) to the primary tumor and regional draining lymph node basins followed by a boost (5.4 Gy in 3 fractions) to gross disease. Patients with clinically positive LPN that would not be removed during TME received an additional boost (up to a total dose between 54.0 and 59.4 Gy) to the involved LPNs. We compared locoregional control, overall survival, progression-free survival, and treatment-related toxicity between these 2 groups. Results Fifty-three patients were included in this analysis with median follow-up of 30.6 months for the LPN– group (n = 41) and 19.9 months for the LPN+ group (n = 12). There was no difference in 3-year overall survival (90.04% vs 83.33%, P = .890) and progression-free survival (80.12% vs 80.21%, P = .529) between the 2 groups. We did not observe any LPN recurrences. There were no differences in rates of acute grade 3+ or chronic toxicities. Conclusions Despite the well-documented negative prognostic effect of LPN metastasis, we observed promising outcomes for LPN+ patients treated with an additional radiation boost. Our results suggest that radiation therapy boost to clinically involved, unresected LPN is an effective treatment approach with limited toxicity. Additional studies are needed to optimize treatment strategies for this unique patient subset.

6050 Background: A Phase II, randomized, prospective, multicentric trial was conducted to evaluate the efficacy and safety of Endostar plus radiotherapy in patients with low-risk local advanced nasopharyngeal carcinoma (NPC). This study reported the preliminary results of NCT02237924. Methods: From 09/2014 to 08/2016, patients with low-risk local advanced NPC were randomly treated with Endostar plus radiotherapy (ERT group, n=60) and concurrent chemoradiotherapy (CCRT group, n=60). Primary endpoint was the 5-year overall survival (OS) rate. The secondary endpoints were 3-year OS rate, progression free survival (PFS) rate, loco-regional recurrence free survival (LRRFS) rate and distance metastasis free survival (DMFS) rate. Results: After a median follow-up of 47 months, 3-year OS rate were 93.2% and 79.3% (p=0.032), 3-year PFS rate were 89.8% and 70.6% (p=0.011), 3-year DMFS rate were 93.2% and 80.7%, in two groups, respectively (P=0.042). 3-year LRRFS rate were 96.6% and 92.0% in two groups, respectively (but P=0.565). For short-term curative effects, CR rate were 71.2% and 60.0% for primary tumor, 74.6％and 63.3％for cervical lymph nodes, in two groups, respectively (P < 0.05). Moreover, the incidences of adverse events were significantly lower in ERT group compared with in CCRT group. The grade 3/4 Hyponatraemia (0 [0%] vs 3 [5%], p=0·04), the grade 1/2 vomiting (10 [16.7%] vs 52 [86.7%], p=0.000), dry mouth (45 [75.0%] vs 56 [93.3%], p=0.012), leukopenia (22 [36.7%] vs 42 [70.0%], p=0.000) and weight loss (30 [50.0%] vs 45 [75.0%], p=0.005). No patients died of treatment-related causes. Conclusions: OS, PFS, and DMFS rates can be improved, adverse events be reduced, with better tolerability, by Endostar plus radiotherapy, when compared to concurrent chemoradiotherapy for local advanced low-risk NPC. Clinical trial information: NCT02237924. [Table: see text]

6035 Background: The role of drug maintenance intervention in improving survival outcomes remains controversial.To investigate the safety and effect of Tegafur(S1) maintenance intervention in patients with metastatic nasopharyngeal carcinoma who benefit from the first-line treatment in a multicenter randomized controlled study, and to identify the related biological prognostic factors and guide the individualized treatment choice. Methods: Patients with metastatic nasopharyngeal carcinoma in the Fourth Affiliated Hospital of Guangxi Medical University and other cancer centers who met the inclusion criteria were randomly divided into maintenance therapy group: S1 maintenance therapy until disease progression or intolerance; Observation group: follow-up to disease progression. PFS, overall survival (OS) and adverse reactions of S1 maintenance therapy were compared between the two groups. The correlation between EBV-DNA, human serum amyloid A (SAA) and prognosis was evaluated. Results: Follow-up was conducted to May 2020, with a median follow-up of 19.8 months (6.1-51.3 months), 183 cases were evaluable (88 cases in S1 maintenance treatment group, 95 cases in observation group). Compared with the observation group, the S1 maintenance treatment group significantly increased patients' median PFS (16.2 months vs. 8.7 months, P < 0.001) and median OS (32.1 months vs. 18.2 months, P < 0.001). Reduced the risk of poor prognosis for PFS and OS (PFS: HR 0.305, 95%CI 0.211-0.441, < 0.001; OS: HR 0.363, 95%CI 0.238-0.553, P < 0.001). In the maintenance treatment group, the median S1 treatment lasted for 14 courses (4-58 courses), and the main adverse reactions were grade 1 skin pigmentation, oral mucositis, hand-foot syndrome, nausea, etc. No grade 4 toxic reaction occurred, and it was well tolerated. Compared with observation patients with negative EBV-DNA, observation patients with positive EBV-DNA had a higher risk of poor prognosis for PFS (HR 1.764, 95%CI 1.078-2.887, P = 0.024). The risk of poor prognosis in patients with positive EBV-NDA was significantly reduced by 61.1% ( < 0.001) for PFS and 65.5% (P = 0.001) for OS (P = 0.001). Compared with the observation group with stable SAA expression, S1 maintenance therapy significantly improved the prognosis of patients. Patients with continuous decline in SAA had a 61.9% lower risk of poor prognosis in PFS (P < 0.001) and a 60.2% lower risk of poor prognosis in OS (P = 0.007). Conclusions: For patients with metastatic nasopharyngeal carcinoma who benefit from first-line treatment, maintenance therapy of S1 can significantly improve the survival prognosis and is well tolerated. Patients with positive EBV-DNA and continuous decline in SAA may benefit more from maintenance intervention. Clinical trial information: ChiCTR-IOR-16007939.

Background: A well-established first-line chemotherapy standard for metastatic nasopharyngeal carcinoma is yet lacking. Objectives: To compare the efficacy and safety of gemcitabine plus platinum versus docetaxel plus platinum regimen as first-line therapies for distal metastatic nasopharyngeal carcinoma. Study Design and Participants: A single center, randomized, open-label, parallel-arm study. The study included 120 patients with metastatic nasopharyngeal carcinoma who met the study requirements. Interventions: Participants were randomized in a 1:1 ratio through a sealed envelope selection. Gemcitabine 1000 mg/m2/d intravenously (IV) for >30 min (days 1 and 8) or docetaxel 75 mg/m2/d IV for 1 h (day 1) were administered to the respective group participants. Nedaplatin 75 mg/m2/d, IV (day 1), cisplatin 75 mg/m2/d IV (day 1) or carboplatin (area under the curve set as 5) IV (day 1) were used in both groups. One cycle duration was 21 days, with 4–6 cycles for all participants. Outcomes: The primary assessed outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were short-term efficacy [i.e., response rate (RR) and disease control rate (DCR)] and safety. Results: Seven patients withdrew from the study, and efficacy and adverse reactions were obtained for 113 patients (gemcitabine: 56; docetaxel: 57). Compared with the docetaxel plus platinum group, the gemcitabine plus platinum group had significantly higher RR (71.4% vs. 52.6%, P < 0.05); mPFS (9.7 vs. 7.8 months, P < 0.05), and mOS (20.6 vs. 16.8 months, P < 0.01). The significance was not associated with increased adverse reactions, as both groups showed similar Grades 3 and 4 adverse reactions (P > 0.05). DCR was non-significantly higher in the gemcitabine group (85.7% vs. 75.4%, P > 0.05). Multivariable analysis revealed that time to disease progression, number of involved organs, liver metastasis, and grouping were associated with mPFS and mOS (all P < 0.05). Conclusion: The combination of gemcitabine with platinum is likely superior to that of docetaxel with platinum as first-line treatment for metastatic nasopharyngeal carcinoma.

6542 Background: Metastatic nasopharyngeal cancer (mNPC) patients progressed after standard therapy have limited treatment options. This study is to evaluate the clinical efficacy and safety of toripalimab in mNPC patients refractory to standard chemotherapy treatment (Clinical trial ID: NCT02915432). Methods: Patients receive 3 mg/kg toripalimab Q2W via IV infusion until disease progression, unacceptable toxicity, or voluntary withdrawal. Clinical response is assessed every 8 weeks according to RECIST v1.1. Tumor PD-L1 expression, plasma EBV titer and other biomarkers will be evaluated for correlation with clinical response. Results: From Dec 2016 to Feb 2019, 190 mNPC patients were enrolled from 17 participating centers in China. The median age was 46 years with 83% male. Patients were heavily pretreated with a median of 2 lines of prior systemic treatments. By the cutoff date of Jan 17, 2020, 97% patients experienced treatment related adverse events (TRAE). Most common TRAE included anemia, hypothyroidism, AST increased, proteinuria and fever. Grade 3+ TRAE occurred in 28% patients. Among 190 patients assessed by Independent Review Committee per RECIST v1.1, 6 CR, 33 PR and 40 SD were observed for an ORR of 20.5% and a DCR of 41.6%. The median DOR was 12.9 months. The median PFS and median OS were 1.9 months and 18.6 months respectively. PD-L1+ patients (n=48) had higher ORR than PD-L1- patients (n=134), 27.1% versus 19.4%. By tumor histology, ORR was higher in keratinizing NPC (n=8) than non-keratinizing NPC (n=168), 62.5% versus 19.0%. 144 patients had valid plasma EBV titer measured every 28 days during the study. An average drop of 101-fold plasma EBV titer from baseline was observed in patients with objective responses. Patients with 2-fold+ drop in plasma EBV titer on day 28 (n=60) went on to have 48.3% ORR and 76.7% DCR, whereas patients with less than 2-fold drop (n=88) had 5.7% ORR and 25.0% DCR. 14 responding patients who later developed progressive disease had at least 2-fold+ increase of plasma EBV tier 3-months (median) before radiographic identification of disease progression. Conclusions: Toripalimab demonstrated encouraging clinical activity with a manageable safety profile in mNPC patients refractory to standard chemotherapy. Patients with 2-fold+ drops in plasma EBV titer on day 28 from baseline had favorable clinical response of 48.3% ORR, which might be used as a predictive biomarker. Clinical trial information: NCT02915432 .

The p-carbon polarimeter working in the dp/p Coulomb Nuclear Interference (CNI) region has been used in the Brookhaven Alternating Gradient Synchrotron (AGS ) for many years. It has gone though several upgrades to improve its performance. With targets sweeping through beam vertically and horizontally, the polarimeter can provide polarization profile information. To preserve polarization, a pair of horizontal tune jump quads have been used to overcome horizontal intrinsic resonances. Recently, the polarization measurement on the energy ramp has been used to decide the beam energy as function of time on the ramp. This paper summarize the recent operation experience of AGS p-carbon CNI polarimeter.

6017 Background: Metastatic nasopharyngeal cancer (NPC) patients progressed afterstandardtherapy have limited treatment options. Toripalimab, also known as JS001, a humanized IgG4 antibody specific for human PD-1, has been approved for 2nd line treatment of metastatic melanoma in China. Here we report the results from a phase IIstudy in metastatic NPC patients treated with toripalimab.(Clinical trial ID: NCT02915432). Methods: This multi-center, open-label, phase II registration study is designed to evaluate the safety and efficacy of toripalimab in metastaticNPC patients who have failed systemic treatment. Toripalimabis given at 3 mg/kg IV Q2W until disease progression or intolerable toxicity.Tumor PD-L1 expression, plasma EBV DNA level and other biomarkerswill be correlatedwith clinical response. Results: Enrollment of 190chemo-refractory metastatic NPCpatients was completed by Feb 2019 from 17 participating centers. The median age was 46 years, with 89.5% patients received at least 2 lines of prior systemic therapies. Treatment related adverse events (TRAE)occurred in 92% patients, which were mostly grade 1 or 2.Common TRAE includedanemia, hypothyroidism, AST increased, proteinuria, pyrexia, cough, constipation, ALT increased, hypoalbuminemia and pruritus.Grade 3 or higherTRAEoccurred in 25% patients.By the cut-off date of Jan 7 2019, among 135 evaluable patients, 3 complete responses, 31 partial responses and 40 stable diseaseswere observed for an objective response rate (ORR) of 25.2% and a disease control rate of 54.8%. PD-L1 expression results were obtained from 125 patients and 45.6% (57/125) were PD-L1+.PD-L1+ patientsachieved slightly higherORR than PD-L1- patients, 29.8% versus 22.1%. In addition, an average drop of 47-fold plasma EBV DNA copy number was observed in responding patients, which typically proceeded the radiographic identification of clinical benefit. Conclusions: Toripalimab has demonstrated a manageable safety profileand encouraging clinical activity in the largest check-point blockade study in NPC to date. A change in plasma EBV DNA copy number might serve as a predictive marker for favorable clinical response. Patients will be continuously monitored for additional safety and survival readouts. Clinical trial information: NCT02915432.

// Baoyu He 1, * , Jianchao Zeng 1, * , Wei Chao 1 , Xiaoli Chen 1 , Yujie Huang 1 , Kaifeng Deng 1 , Zhizhuo Huang 1 , Jinwan Li 1 , Meiyu Dai 1 , Shaojun Chen 2 , Haixin Huang 2 and Shengming Dai 1 1 Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545005, China 2 Department of Oncology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545005, China * These authors have contributed equally to this work Correspondence to: Haixin Huang, email: 13507726193@163.com Shengming Dai, email: daishm@sina.com Keywords: long non-coding RNA, serum, nasopharyngeal carcinoma, early diagnosis, prognostic prediction Received: December 01, 2016 Accepted: March 22, 2017 Published: April 13, 2017 ABSTRACT Circulating RNAs in serum, plasma or other body liquid have emerged as useful and highly promising biomarkers for noninvasive diagnostic application. Herein, we aimed to establish a serum long non-coding RNAs (lncRNAs) signature for diagnosing nasopharyngeal carcinoma (NPC). In this study, we recruited a cohort of 101 NPC patients, 20 patients with chronic nasopharyngitis (CN), 20 EBV carriers (EC) and 101 healthy controls. qRT-PCR was performed with NPC cells and serum samples to screen a pool of 38 NPC-related lncRNAs obtained from the LncRNADisease database. A profile of three circulating lncRNAs (MALAT1, AFAP1-AS1 and AL359062) was established for NPC diagnosis. By Receiver Operating Characteristic (ROC) curve analysis, this three-lncRNA signature showed high accuracy in discriminating NPC from healthy controls (AUC = 0.918), CN (AUC = 0.893) or EC (AUC = 0.877). Furthermore, high levels of these three lncRNAs were closely related to advanced NPC tumor node metastasis stages and EBV infection. Serum levels of these three lncRNAs declined significantly in patients after therapy. Our present study indicates that circulating MALAT1, AFAP1-AS1 and AL359062 may represent novel serum biomarkers for NPC diagnosis and prognostic prediction after treatment.

Lung cancer stem cells are a subpopulation of cells critical for lung cancer progression, metastasis, and drug resistance. Thioridazine, a classical neurological drug, has been reported with anticancer ability. However, whether thioridazine could inhibit lung cancer stem cells has never been studied. In our current work, we used different dosage of thioridazine to test its effect on lung cancer stem cells sphere formation. The response of lung cancer stem cells to chemotherapy drug with thioridazine treatment was measured. The cell cycle distribution of lung cancer stem cells after thioridazine treatment was detected. The in vivo inhibitory effect of thioridazine was also measured. We found that thioridazine could dramatically inhibit sphere formation of lung cancer stem cells. It sensitized the LCSCs to chemotherapeutic drugs 5-FU and cisplatin. Thioridazine altered the cell cycle distribution of LCSCs and decreased the proportion of G0 phase cells in lung cancer stem cells. Thioridazine inhibited lung cancer stem cells initiated tumors growth in vivo. This study showed that thioridazine could inhibit lung cancer stem cells in vitro and in vivo. It provides a potential drug for lung cancer therapy through targeting lung cancer stem cells.

116 Background: Patients with Esophageal squamous cell carcinoma (EC) often present with advanced and metastatic stage disease, which has poor prognosis and limited treatment options, and represent an important unmet medical need especially in China/Asia. JS001, a humanized recombinant IgG4 antibody against PD-1, selectively blocks the interactions of PD-1 with its ligands PD-L1 and PD-L2, and promotes antigen specific T-cell activation. A phase I study of JS001 in Chinese patients with heavily pretreated solid tumors has demonstrated an acceptable safety profile in doses up to 10 mg/kg Q2W. Here we report the safety and efficacy of JS001 in a phase Ib/II clinical study in Chinese patients with refractory/metastatic EC. (Clinical trial ID: NCT02915432) Methods: Refractory/metastatic EC Patients receive JS001 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease will be assessed for clinical response every 8 weeks according to the RECIST 1.1 criteria. Tumor PD-L1 expression as well as additional potential predictive biomarkers are monitored for correlation with clinical response. Results: Between Apr 19 2017 and Sep 11 2017, 56 EC pts (84.9% received at least 2 Lines of treatment) were enrolled into the study. Treatment related adverse events occurred were mostly grade 1 or 2. As of Sep 11 2017, 34 EC pts have been evaluated for clinical efficacy. Among these pts, 8 PR (partial response) and 14 SD (stable disease) were observed (ORR 23.5% and DCR 64.7%). The PD-L1 expression positivity (defined as positive staining ³1% on Tumor Cell [TC] or on Immune Cell [IC] by SP142) in EC tumor tissue was 21.4% (12/56). 2/10 (20%) PD-L1+ patients and 6/24 (25%) PD-L1 negative patients achieved partial responses. Conclusions: JS001 showed a promising preliminary clinical activity in heavily pre-treated metastatic EC pts with a manageable safety profile. Clinical response was not correlated with PD-L1 expression. Pts will be continuously monitored for safety and efficacy upon JS001 treatment. Clinical trial information: NCT02915432.

Exosomes are small membrane vesicles that are secreted by a multitude of cell types. The exosomes derived from dendritic cells (Dex), tumor cells (Tex), and malignant effusions demonstrate immunomodulatory functions, and are even under clinical trial for cancer treatments. In this study we report the phase I clinical trial of the ascites-derived exosomes (Aex) in combination with the granulocyte-macrophage colony-stimulating factor (GM-CSF) in the immunotherapy of colorectal cancer (CRC). The Aex isolated by sucrose/D(2)O density gradient ultracentrifugation are 60-90-nm vesicles that contain the diverse immunomodulatory markers of exosomes and tumor-associated carcinoembryonic antigen (CEA). Totally 40 patients (HLA-A0201(+)CEA(+)) with advanced CRC were enrolled in the study, and randomly assigned to treatments with Aex alone or Aex plus GM-CSF. Patients in both groups received a total of four subcutaneous immunizations at weekly intervals. We found that both therapies were safe and well tolerated, and that Aex plus GM-CSF but not Aex alone can induce beneficial tumor-specific antitumor cytotoxic T lymphocyte (CTL) response. Therefore, our study suggests that the immunotherapy of CRC with Aex in combination with GM-CSF is feasible and safe, and thus can serve as an alternative choice in the immunotherapy of advanced CRC.

To explore the association of the X-ray repair cross-complementing gene 1 (XRCC1) codon 399 single-nucleotide polymorphism (SNP) with acute radiation dermatitis and oral mucositis in nasopharyngeal carcinoma (NPC) patients treated by intensity-modulated radiation therapy (IMRT).Polymerase ch

6063 Background: A prospective, randomized, and multicentric phase II study was performed to evaluate the short-term efficacy and safety of Endostar plus intensity-modulated radiotherapy (IMRT) versus concurrent chemoradiotherapy(CCRT) in locally advanced low-risk nasopharyngeal carcinoma(NPC). Methods: From September 2014 to August 2016, 120 patients with low-risk NPC at stages III-IVa from 9 centers were randomly divided into experimental group (Endostar plus radiotherapy (ERT); n = 60) and control group (CCRT; n = 60). ERT patients were given Endostar (7.5 mg/m2/day) by continuous intravenous infusion (CIV) from 5 days before radiotherapy for consecutive 10 days for 2 cycles with an interval of 14 days. Then, ERT patients received 2 cycles of 10 days of maintenance treatment with Endostar after radiotherapy. The CCRT patients were given cisplatin (100 mg/m2) on days 1, 22, and 43 for 3 cycles. Immediate and 3-month efficacy and adverse effects were evaluated between the two groups. ClinicalTrials registration number was NCT02237924. Results: All patients were eligible for toxicity and response analysis. Regarding immediate efficacy, the complete response(CR) rates were 45.0% for ERT arm and 33.3% for CCRT arm in nasopharynx (P = 0.190), and 43.3% for ERT arm and 36.7% for CCRT arm in regional nodes (P = 0.456). Three months after RT, the CR rates were 71.2% for ERT arm and 60.0% for CCRT arm in nasopharynx (P = 0.151), and 74.6% for ERT arm and 63.3% for CCRT arm in regional nodes (P = 0.172). The rate and severity of leukopenia, hemoglobin reduction and thrombocytopenia in ERT arm were significantly lower than CCRT arm (P < 0.01). The occurrence rates of Xerostomia, oral mucositis, nausea / vomiting, constipation and weight loss in ERT arm were significantly lower than those in CCRT arm (P < 0.01). Conclusions: The present study demonstrates that ERT has similar short-term efficacy on locally advanced low-risk NPC compared with CCRT, but the acute adverse effects of ERT are fewer, and the compliance and tolerability of patients are better. Clinical trial information: NCT02237924.

Tongtai Bridge in Zhangjiakou across Qinshui River is a special type of arch bridge with skewed arch and curved beam. Different from general arch bridge, suspenders tensioning of which in construction process are more difficult and complex owing to particularly coupling effects in space. The paper is based on the analysis of traditional tensioning methods and considers the constraint condition of the structure, as well as the permissible capacity of the tensioning devices, to give an optimized suspender tensioning method, i.e. the split method of tensioning force which is developed from the influence matrix of tensioning force and the functional extremum principle. The process of suspender tensioning on the Tongtai Bridge shows that this method greatly decreases tensioning times, resulting that the finished state is reached by adding tension only three times, and hence, shorteningng the construction schedule. Furthermore, the method given here can provide a good reference for the construction of similar bridges in the future.

In light of the shortcomings of current analysis methods, such as the parabola method, the segmental parabola method, and the segmental catenaries method, in calculating the main cable curve of a suspension bridge with inclined hangers between the main cable and the stiffening girder, the improved segmental catenaries method was put forward here. Nonlinear equations were deduced to express the main cable curve of a suspension bridge with inclined hangers. At the same time, a more efficient and simple nonlinear finite element calculation method was obtained through establishing the parameterized calculation model based on the APDL language in ANSYS software and by using the dynamic prediction method. The calculation results of Xinhai Bridge show that the proposed method here markedly enhances the calculating precision of the main cable curve and is feasible and effective in practical engineering.

The idea of using multiple partial helical magnets was applied successfully to the AGS synchrotron, to preserve the proton beam polarization. In this paper we explore in details the idea of using four helical magnets placed symmetrically in the AGS ring. This modification provides many advantages over the present setup of the AGS that uses two partial helical magnets. First, it provides a larger 'spin tune gap' for the placement of the vertical betatron tune of the AGS during acceleration, second, the vertical spin direction during the beam injection and extraction is closer to vertical, third, the symmetric placement of the snakes allows for a better control of the AGS optics, and for reduced values of the beta and eta functions, especially near injection, fourth, the optical properties of the helical magnets also favor the placement of the horizontal betatron tune in the 'spin tune gap', thus eliminating the horizontal spin resonances. In this paper we provide results on the spin tune and on the optics of the AGS with four partial helical magnets, and we compare these results with the present setup of the AGS that uses two partial helical magnets.

Self4anchored cable4stayed suspension Bridges ，as a new type of bridge is rarely investigated. Based on simulating turbulent wind fields, the effects of some factors such as geometrical nonlinearity, lateral aerodynamic memory effect, and fluctuating wind on main cables on buffeting response of the Dalian Harbor Sea4routine Bridge, a self4anchored cable4stayed su spension with 800m main span, are analyzed and the characteristics of buffeting response for the new type of bridge are summarized. It is worthy of concern in results that fluctuating winds on the cables causes the vibration of main cables and brings coupling vibration of the stiffing girder, which makes a greater effect on the girder of a self4anchored cable4stayed suspension bridge than those on the girder of a general suspension bridge.

A new polarimeter based on proton carbon elastic scattering in the CNI (Coulomb Nuclear Interference) region has been proposed for RHIC and one pC CNI polarimeter has been installed in the blue ring of RHIC. This paper summarizes the design and parameters of this new polarimeter. It is a simple, compact, and cost effective polarimeter.

Picture archiving and communication systems (PACS) are now clinically available in limited radiologic applications. The benefits, acceptability, and reliablity of these systems have thus far been mainly speculative and anecdotal. This paper discusses the evaluation of a PACS module implemented in the pediatric radiology section of a 700-bed teaching hospital. The PACS manages all pediatric inpatient images including conventional x-rays and contrast studies (obtained with a computed radiography system), magnetic resonance images, and relevant ultrasound images. A six-monitor workstation is available for image review.

We have integrated a dedicated digital projectional radiographic system for the Chest Radiology Section at UCLA. The system has been running since September, 1988 and is undergoing clinical evaluation. This paper describes the image acquisition, communication, storage, and display components of this system. An implementation of the system as a full PACS module in the Chest Radiology Section is in progress.

A digital optical disk archive has been running continuously in the Pediatric Radiology Section at UCLA for over one year. During this year both the computerized patient registration system and the optical disk image archive have been accumulating patient and image data. Statistics derived from one year's operation are combined with a pediatric film library survey to summarize system use and to project departmental archive requirements. L INTRODUCTION Picture Archiving and Communication Systems (PACS) can succeed in a clinical environment if they are in­ troduced in a modular fashion and are carefully guided in their implementation and growth. The Department of Radiological Sciences at UCLA began full operation of its pediatric PACS acquisition and storage subsystems in November of 1986. The clinical* and technical^ aspects of this system are discussed elsewhere in this volume. This paper presents statistics derived from the pediatric patient and image databases in order to assess and project the growth of the pediatric module. These data are used to predict storage requirements for a department-wide PACS operation.The main databases employed by the clinical PACS are those associated with the Pediatric Radiology Patient Registration System (PRPRS) and the Clinical Radiology Imaging System (CRIS). The former is responsible for registering patient procedures and the latter for image tracking. An analysis of these two related databases provides insight into the patient population in pediatric radiology and the nature of images generated by pediatric procedures. Because pediatric radiology operated without the benefit of digital technology until a year ago, we draw upon a pediatric film library survey to provide additional information on long-term image storage. These three sources of information, PRPRS, CRIS, and the film library provide the basis for this study conducted on data for the year from December 1, 1986 to November 30, 1987.

The details of a clinical PACS module for Pediatric radiology are discussed. The system operates as a large queueing network allowing several processes to execute concurrently in a prioritized and coordinated fashion. This paper presents clinical data accumulated since March 1987 on system workload, system performance, and workstation optimization techniques.

As a critical care unit that functions under strict time constraints, the coronary care unit (CCU) requires rapid access to radiological information of the patient. In order to meet this clinical demand, a digital remote viewing system was developed and has been in clinical operation since March 1987. The system delivers the softcopy of chest images to the intensive care unit. During the nine months of continuous clinical operation, the system was evaluated by analyzing the utilization and performance statistics.

One clinical environment which can immediately benefit from the implementation of a radiologic PACS is the intensive care unit (ICU). Our previous study has demonstrated the feasibility and timeliness of routine image transmission to an ICU. In anticipation of future expansion of this service, we have investigated two different models for a hospital-wide ICU PACS. These models included a centralized and a distributed processing PACS configuration. Their comparison indicated that although the distributed model offers some major advantages over the centralized model, the latter may hold a rightful place in the inter-departmental service, especially if the cost issue is a critical factor.

Establishing control of the image data flow between a computed radiography system and a host computer presents many problems in a centralized PACS system design. Dedicating the main computer of the PACS system to service on-line acquisition devices will soon overload the system, especially when multiple image acquisition units are present. At UCLA, our approach is to distribute the task of buffering the input image data to a smart file server. Using a low-cost microcomputer as our image file server, we can reduce the burden to the central PACS computer when an image is to be acquired. This paper describes the design of the smart file server for a PCR/SP computed radiography system.

A receiver operator characteristic (ROC) experiment designed to evaluate the diagnostic performance of 512, 1024 and 2048 monitors as compared to conventional analog films viewed on a lightbox was conducted. Fifty radiographs, 25 with and 25 without a simulated solitary nodule placed on the lung fields of an anthropomorphic chest phantom were used. These images were interpreted by six radiologists under the following six conditions: 512 and 1024 line resolution both with and without interactive contrast enhancement, and 2048 line resolution with contrast enhancement, and analog film on a conventional lightbox. As determined by the area under the ROC curve, which was the measure of diagnostic accuracy the 512 and 1024 line monitors performed below the analog film, the 2048 line monitor proved to be a viable alternative to the analog film.

A picture archiving and communication system (PACS) module for CT, MR, and US images is being developedin our department. The PACS module is composed of three subsystems: (1) image acquisition, (2) data management, and (3) image display. A digital communication network links these subsystems into a functional unit. The systemhardware configuration is described. Daily and yearly totals for the amount of CT, MR, and US images generatedin our department are provided. The software modules for the system operation are presented. We also report onour previous experience with a MR/US PACS module for a single radiology section. 1. Introduction An increasing number of digital images are being generated by radiology departments. These images are distributed over several locations and therefore retrieval of image for a multi -modality patient is not easy. To improve the situation, a centralized archiving system with distributed viewing stations for CT/MR/US images is being implemented in our department. The system hardware configuration is described in the

A direct link between a clinical pediatric PACS module and a FONAR MRI image network was implemented. The original MR network combines together the MR scanner, a remote viewing station and a central archiving station. The pediatric PACS directly connects to the archiving unit through an Ethernet TCP-IP network adhering to FONAR's protocol. The PACS communication software developed supports the transfer of patient studies and the patient information directly from the MR archive database to the pediatric PACS. In the first phase of our project we developed a package to transfer data between a VAX-111750 and the IBM PC I AT-based MR archive database through the Ethernet network. This system served as a model for PACS-to-modality network communication. Once testing was complete on this research network, the software and network hardware was moved to the clinical pediatric VAX for full PACS integration. In parallel to the direct transmission of digital images to the Pediatric PACS, a broadband communication system in video format was developed for real-time broadcasting of images originating from the MR console to 8 remote viewing stations distributed in the radiology department. These analog viewing stations allow the radiologists to directly monitor patient positioning and to select the scan levels during a patient examination from remote locations in the radiology department. This paper reports (1) the technical details of this implementation, (2) the merits of this network development scheme, and (3) the performance statistics of the network-to-PACS interface.