Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To evaluate the prognostic significance of neoadjuvant rectal (NAR) score and downstaging depth score (DDS) after neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC).Methods:Retrospective analysis was performed for 200 patients with LARC (T 3-T 4 and/or N 1-N 2, M 0), who were initially treated in the Cancer Hospital of Chinese Academy of Medical Sciences from 2015 to 2018. All patients had baseline MRI data and received preoperative nCRT and radical resection. All patients received preoperative radiotherapy with a dose of 45-50Gy combined with concurrent capecitabine. The effect of NAR and DDS scores on clinical prognosis was statistically compared. The 3-year disease-free survival (DFS) was calculated using the Kaplan- Meier method and compared by the log- rank test. Cox proportional hazards model was used to perform multivariate survival analysis. The predictive performance for 3-year DFS was calculated using the receiver operating characteristic (ROC) curve. Results:The median follow-up time was 30.5(10.6-54.0) months. In terms of DDS, the 3-year DFS rate was 56.4% in the DDS ≤0 group, significantly lower than 83.0% in the DDS >0 group ( P=0.002). In terms of NAR score, the 3-year DFS rates were 90.1%, 73.8% and 53.6% in NAR score ≤8, 8-16 and>16 groups, respectively ( P<0.001). In the whole cohort, the area under the ROC curve (AUC) of DDS and NAR scores for predicting 3-year DFS were 0.683 and 0.756( P=0.037). In yp0-I stage patients ( n=72), the AUC of DDS and NAR scores for predicting 3-year DFS were 0.762 and 0.569( P=0.032). Conclusions:High DDS and low NAR scores after nCRT indicate good prognosis for patients with LARC. NAR score yields better accuracy than DDS in predicting clinical prognosis, but DDS is significantly better than NAR score in yp0-I stage population.

Objective:To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) model of" neoadjuvant chemoradiotherapy plus consolidation neoadjuvant chemotherapy (CNCT) followed by surgery" for locally advanced gastric cancer.Methods:From 2018 to 2020, 28 patients clinically diagnosed with locally advanced gastric adenocarcinoma or Siewert Ⅱ/Ⅲ adenocarcinoma gastroesophageal junction cancer were prospectively enrolled. The neoadjuvant chemoradiotherapy (NCRT) was delivered with a total dose of 45 Gy, 1.8 Gy/f. Concurrent chemotherapy was S-1 at a dose of 40-60 mg twice daily. Then, patients received four to six cycles of CNCT of SOX regimen at three weeks after neoadjuvant chemoradiotherapy. D 2 lymphadenectomy was performed at 4-6 weeks after CNCT. Results:A total of 28 patients completed the whole therapy. Grade 3 or above adverse events occurred in 3 cases (11%) during CCRT, including thrombocytopenia, leukopenia and anorexia; 2 cases (7%) developed leukopenia and 3 cases (11%) of thrombocytopenia during CNCT. Twenty patients (71%) completed the surgery. The proportion of patients with pathological complete remission (pCR) was 50%. Three patients experienced surgical complications including anastomotic leak, anastomotic stenosis and intra-abdominal sepsis. All were recovered after symptomatic treatment.Conclusion:Interim analysis results demonstrate that TNT can yield significant down-staging for patients with locally advanced gastric cancer, which causes tolerable adverse events and postoperative complications.

Objective:To investigate the relationship between MRI parameters and clinical prognosis before and after chemoradiotherapy in patients with locally advanced rectal cancer.Methods:Clinical and follow-up data of 96 patients with locally advanced rectal cancer who were initially treated in the Cancer Hospital of Chinese Academy of Medical Sciences from 2015 to 2017 were retrospectively analyzed. All patients received preoperative chemoradiotherapy, followed by delayed radical surgery at 6-13 weeks after radiotherapy. MRI assessment was performed twice around radiotherapy which were within 4 weeks before the treatment and 4-8 weeks after it. Correlation analysis was utilized to determine the association between MRI assessment and 3-year disease-free survival (DFS).Results:Of the all patients, 80 (83%) had T 3 stage, 16(17%) had T 4 stage, 14 (15%) had N 0 stage, and 82 (86%) had N 1-2 stage. Among them, 69(72%) and 58(60%) patients were positive for MRF and EMVI. The median dose of radiotherapy was 50 Gy, and all patients were sensitized by simultaneous capecitabine. After chemoradiotherapy, T-downstage rate of the whole group was 24%, and 50% for the N-downstage rate. The MRF-and EMVI-positive rates were significantly decreased to 37% and 27% after chemoradiotherapy (both P<0.001). Univariate and multivariate analyses showed that N staging and EMVI status change were significantly correlated with the 3-year DFS. Conclusion:MRI after concurrent chemoradiotherapy reveals that positive EMVI throughout the treatment and N 1-N 2 staing are poor prognostic factors of DFS, suggesting the need for improving the treatment.

Objective To investigate the pattern of nodal recurrence after curative resection in adenocarcinoma of the gastroesophageal junction ( AGE ) , and to provide a basis for delineation of the radiation range in the high-risk lymphatic drainage area.Methods A retrospective analysis was performed in 78 patients with locally advanced AGE who were newly treated in our hospital from January 2009 to December 2013 and had complete clinical data.All patients received curative resection and were pathologically diagnosed with stage T3/T4 or N (+) AGE.Those patients were also diagnosed with SiewertⅡor Ⅲ AGE by endoscopy, upper gastroenterography, macroscopic examination during operation, and pathological specimens.None of the patients received preoperative or postoperative radiotherapy.All patients were diagnosed by imaging with postoperative nodal recurrence.The computed tomography images of those
patients were accessible and had all the recurrence sites clearly and fully displayed.Results The median time to recurrence was 10 months ( 1-48 months) , and 90%of the recurrence occurred within 2 years after surgery.The lymph nodes with the highest risk of recurrence were No.16b1( 39%) , No.16a2( 37%) , No.9 (30%), and No.11p (26%), respectively.There was no significant difference in the recurrence rate within each lymphatic drainage area between patients with SiewertⅡandⅢAGE ( P=0.090-1.000) .The lymph nodes with the most frequent recurrence were No.16b1, No.16a2, No.9, No.16b2, No.11p, and No.7 in patients with stage N3 AGE and No.11p, No.16b1, No.16a2, No.9, No.8, and No.7 in patients with stage non-N3 AGE.Patients with stage N3 AGE had a significantly higher recurrence rate in the para-aortic regions (No.16a2-b2) than those with stage non-N3 AGE (67%vs.33%, P=0.004, OR=4.00, 95% CI=1.54-10.37) .Conclusions The lymph nodes with the highest risk of recurrence are located in the celiac artery, proximal splenic artery, and retroperitoneal areas ( No.16a2 and No.16b1) in patients with SiewertⅡorⅢlocally advanced AEG.Moreover, patients with stage N3 AGE have a higher risk of retroperitoneal recurrence.The above areas should be involved in target volume delineation for postoperative radiotherapy.

Objective To compare target dosimetric distribution and normal tissue radiation between different static intensity?modulated radiation therapy ( IMRT) plans and volumetric modulated arc therapy ( VMAT) and to identify the best IMRT plan for patients with primary mediastinal B?cell lymphoma ( PMBCL) . Methods A total of 16 patients ( 8 males and 8 females) with early?stage ( Ann?Arbor stageⅠ) PMBCL were enrolled in this study,with doses of 45 Gy for primary gross tumor volume ( PGTV) and 40 Gy for planning target volume (PTV).Four plans were designed for each patient,consisting of static IMRT (5F?IMRT,7F?IMRT,9F?IMRT) and VMAT,and the target dosimetric distribution,normal tissue radiation dose,and efficiency of each plan were evaluated. The difference of dose was analyzed by analysis of variance. Results The mean conformity index ( CI) and homogeneity index ( HI) for PGTV in 5F?,7F?,9F?IMRT and VMAT were 1. 01 and 1. 10, 1. 01 and 1. 10, 1. 01 and 1. 10, and 1. 01 and 1. 11 ( P= 0. 963 and 0. 843) ,respectively,while these two indices for PTV were 1. 04 and 1. 22,1. 03 and 1. 19,1. 03 and 1. 17, and 1. 08 and 1. 14( P=0. 964 and 0. 969) ,respectively. The parameters of volume and dose were similar on normal tissue ( P= 0. 192?1. 000 ) . The treatment time and number of monitor units in 9F?IMRT were significantly higher than those in other static IMRT plans and VMAT ( P=0. 000,0. 000) ,and among these plans,VMAT had the lowest number of monitor units ( 13 345. 0 MU) and the shortest treatment time ( 5. 9 min) . Conclusions The target volume coverage of 7F?and 9F?IMRT is better than that of 5F?IMRT and VMAT.For early?stage PMBCL,VMAT is not superior to IMRT in terms of dosimetry,especially with a larger area of low?dose radiation to the breast,but it is highly efficient in practice.

This study was aimed to investigate the comprehensive ecological factors of Hippophae rhamnoides L. and their regional suitability in China. Based on field survey, specimen examination and literature investigation, ecologi-cal factors and appropriate production areas were analyzed by Traditional Chinese Medicine Geographic Information System (TCMGIS-II). The results showed that the proper region (with similarity of 95%~100%) of H. rhamnoides L. accounts for 737 994.71 km2, including 15 provinces/municipalities and 387 counties/cities. The largest area among them is Tibet autonomous region with area of 313 857.73 km2 (42.53%), followed by Sichuan province (223 987.02 km2, 30.35%), Gansu province (66 314.43 km2, 8.99%) and Shanxi province (4 237.79 km2, 0.57%). There are also certain appropriate production areas distributed in Liaoning province, Beijing, Chongqing and Hubei province. It was concluded that this system is much valuable to the recognition of the formation of the producing area, the division of adaptive area, introduction and acclimatization of medicinal materials. It also provided a scientific reference for the introduction and cultivation of H. rhamnoides L. Through further field study and experiments, these new areas have the potential to be developed into suitable production region of H. rhamnoides L. in the future.

Host genetic, environmental and viral factors are classified as three categories that determine clinical outcomes of hepatitis B virus (HBV) infection. The objective of this study was to detect the associations between polymorphisms rs346473 and rs346482 in Rho GTPase-activating protein 24 (ARHGAP24) gene and disease progression of HBV infection in Han Chinese population. These two SNPs were found by our DNA pooling using Affymetrix Genome-Wide Human Mapping SNP6.0 Array in HBV carriers, and verified by using TaqMan 7900HT Sequence Detection System with 758 progressed HBV carriers versus 300 asymptomatic HBV carriers (AsC) in a discovery phase and 971 progressed HBV carriers versus 328 AsC in a replication phase. Multivariable logistic regression revealed that individuals with genotype TT at variant rs346473 displayed remarkable correlations with disease progression of HBV infection both in the discovery phase (OR, 2.693; 95% CI, 1.928-3.760; P=6.2×10(-9); additive model) and the replication phase (OR, 1.490; 95% CI, 1.104-2.012; P=9.0×10(-3); additive model). These two SNPs were in strong linkage disequilibrium with D'=0.99 and r (2)=0.951, and haplotype TT disclosed an increased susceptibility to HBV progression (OR, 1.980; 95% CI, 1.538-2.545; P=8.1×10(-8)). These findings suggest that polymorphism rs346473 in the ARHGAP24 gene might be a part of the genetic variants underlying the susceptibility of HBV carriers to disease progression.

Host genetic,environmental and viral factors are classified as three categories that determine clinical outcomes of hepatitis B virus (HBV) infection.The objective of this study was to detect the associations between polymorphisms rs346473 and rs346482 in Rho GTPase-activating protein 24 (ARHGAP24) gene and disease progression of HBV infection in Han Chinese population.These two SNPs were found by our DNA pooling using Affymetrix Genome-Wide Human Mapping SNP6.0 Array in HBV carriers,and verified by using TaqMan 7900HT Sequence Detection System with 758 progressed HBV carriers versus 300 asymptomatic HBV carriers (AsC) in a discovery phase and 971 progressed HBV carriers versus 328 AsC in a replication phase.Multivariable logistic regression revealed that individuals with genotype TT at variant rs346473 displayed remarkable correlations with disease progression of HBV infection both in the discovery phase (OR,2.693; 95％ CI,1.928-3.760; P=6.2× 10-9;additive model) and the replication phase (OR,1.490; 95％ CI,1.104-2.012; P=9.0× 10-3; additive model).These two SNPs were in strong linkage disequilibrium with D'=0.99 and r2=0.951,and haplotype TT disclosed an increased susceptibility to HBV progression (OR,1.980; 95％ CI,1.538-2.545;P=8.1× 10-8).These findings suggest that polymorphism rs346473 in the ARHGAP24 gene might be a part of the genetic variants underlying the susceptibility of HBV carriers to disease progression.