Search

Background The preliminary result of the TORCH trial has showed promising complete response (CR) for managing locally advanced rectal cancer (LARC) with neoadjuvant short-couse radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor. For locally advanced colon cancer (LACC) with bulky nodal disease and/or clinically T4, neoadjuvant chemotherapy followed by colectomy with en bloc removal of regional lymph nodes is the suggested treatment. However, the CR rate is less than 5%. TORCH-C will aim to investigate neoadjuvant short-couse radiotherapy combined with chemotherapy and PD-1 inhibitor in LACC.Methods TORCH-C is a randomized, prospective, multicentre, double-arm, open, phase Ⅱ trial of SCRT combined with chemotherapy and immunotherapy in LACC with microsatellite-stable (MSS) patients and cT4 or bulky nodes. Eligible patients will be identified by the multidisplinary team. 120 patients will be randomized 1:1 to the intervention or control arm. The patients in the control arm will receive 4 cycles of capecitabine plus oxaliplatin (CAPOX). The patients in the intervention arm will receive SCRT, followed by 4 cycles of CAPOX and PD-1 inhibitor (Serplulimab). Both arms will receive curative surgery, followed by 4 cycles of CAPOX. The primary endpoint is pathologic complete regression (pCR).Discussion TORCH-C trial aims to investigate whether the combination of immunotherapy and chemoradiotherapy improves the treatment effect in LACC with MSS. TORCH-C will establish the TORCH platform, a key part of our long-term strategy to develop neoadjuvant treatment for colorectal cancer (CRC).Trial registration: The trial has been registered in ClinicalTrials.gov on Feburary 16, 2023 (Registration No. NCT05732493).

Background For patients with locally recurrent rectal cancer (LRRC), R0 resection of pelvic recurrent tumour is most important prognostic factor influencing survival. However, only approximately 40% of patients with recurrent rectal cancer can undergo R0 resection. Recent studies have shown promising synergistic effects of the combination of immunotherapy (PD-1/PD-L1 antibodies) and neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Thus, for LRRC patients, addition of immunotherapy to preoperative CRT is likely to further improve the rate R0 resection and prognosis. Methods TORCH-R is a prospective, single-center, single-arm phase II trial of preoperative hypofractionated radiotherapy, chemotherapy and immunotherapy in LRRC. A total of 75 locally recurrent rectal cancer (LRRC) patients will be recruited and receive 25-40Gy/5Fx irradiation or 15-25Gy/5Fx reirradiation, 6 cycles of CAPOX and toripalimab, followed by multidisciplinary team (MDT) for decision: radical surgery, sustained treatment until resectable or exit. The primary endpoint is the R0 resection rate of pelvic recurrent tumour. The secondary endpoints include the overall response rate (ORR), progression-free survival (PFS), overall survival (OS), safety and tolerability. Discussion TORCH-R will investigate whether hypofractionated radiotherapy combined with chemotherapy and Toripalimab can achieve better R0 resection rates, good tolerance and prognosis in LRRC patients. This is the first clinical trial to induce immunotherapy and consolidative chemoradiotherapy in LRRC patients. Trial registration: Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT05628038, November 17, 2022.

For locally advanced (T3-4/N+M0) rectal cancer (LARC), neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment. It was demonstrated to decrease the local recurrence rate and increase the tumor response grade. However, the distant metastasis remains an unresolved issue. And the demand for anus preservation and better quality of life increases in recent years. Radiotherapy and immunotherapy can be supplement to each other and the combination of the two treatments has a good theoretical basis. Recently, multiple clinical trials are ongoing in terms of the combination of nCRT and immunotherapy in LARC. It was reported that these trials achieved promising short-term efficacy in both MSI-H and MSS rectal cancers, which could further improve the rate of clinical complete response (cCR) and pathological complete response (pCR), so that increase the possibility of ‘Watch and Wait (W&W)’ approach. However, the cCR and pCR is not always consistent, which occurs more frequent when nCRT is combined with immunotherapy. Thus, the efficacy evaluation after neoadjuvant therapy is an important issue for patient selection of W&W approach. Evaluating the cCR accurately needs the combination of multiple traditional examinations, new detective methods, such as PET-CT, ctDNA-MRD and various omics studies. And finding accurate biomarkers can help guide the risk stratification and treatment decisions. And large-scale clinical trials need to be performed in the future to demonstrate the surprising efficacy and to explore the long-term prognosis.

Background For patients with locally advanced (T3-4/N +) rectal cancer (LARC), the standard treatment is neoadjuvant chemoradiotherapy combined with total mesorectal resection, which greatly decreases local recurrence but does not improve overall survival. For patients who achieve a complete clinical response (cCR) after nCRT, a “Watch & Wait” (W&W) approach can be received to improve quality of life. Currently, total neoadjuvant therapy (TNT) has been demonstrated to increase the complete response rate and achieve early control of distant metastasis. Recent studies have shown promising synergistic effects of the combination of immunotherapy (PD-1/PD-L1 antibodies) and radiotherapy. Thus, for LARC patients, the combination of immunotherapy and TNT is likely to further improve the rate of complete response and prognosis. The disparities between induction therapy and consolidation therapy need to be investigated. Methods TORCH is a randomized, prospective, multicentre, double-arm, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and immunotherapy in LARC. 130 LARC patients will be treated with the TNT approach and assigned to the consolidation arm and induction arm. The consolidation arm will receive SCRT, followed by 6 cycles of capecitabine plus oxaliplatin (CAPOX) and Toripalimab. The induction arm will first receive 2 cycles of CAPOX and Toripalimab, then receive SCRT, followed by 4 cycles of CAPOX and Toripalimab. Both groups will receive curative surgery or the W&W strategy. The primary endpoint is the complete response rate (rate of pCR plus cCR). The secondary endpoints include the grade 3–4 acute adverse effects rate, 3-year disease-free survival (DFS) rate, 3-year local recurrence-free survival (LRFS) rate, 3-year OS rate, rate of surgical complications and quality of life (QoL) scores. The “pick the winner” method is used to investigate the better treatment regimen. The trial was opened on 13th April 2021, and the first patient was recruited on 6th May 2021. Discussion TORCH will investigate whether SCRT combined with chemotherapy and Toripalimab can achieve better complete response rates, good tolerance and prognosis in LARC patients. This is the first clinical trial to compare the efficacy of induced immunotherapy and consolidative immunotherapy based on the TNT strategy. Trial registration Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT04518280, August 15, 2020.

e15598 Background: 5-FU-based regimens are the mainstay treatment for colorectal cancer. However, the limited response rate to 5-FU-based regimens hampered the increase in the treatment efficacy of locally advanced rectal cancer. During the drug screening in the rectal cancer organoid biobank (n = 106), we found out that more than half of the organoids that were resistant to 5-FU monotherapy and sensitive to irinotecan maintained sensitive status to the treatment of 5-FU combined with irinotecan (combination-sensitive), while a quite proportion of them turn to become remarkably resistant to 5-FU plus irinotecan (combination-resistant). Some studies suggested the mechanism of 5-FU-based resistance was associated with the activation of some oncogenic pathways. However, the mechanism of the addition of 5-FU promoting the resistance to irinotecan is still unclear. Methods: To investigate the relationship between the combination-resistant organoids and corresponding patient responses, we collected patient clinical responses and survival outcomes. RNA sequencing and ATAC sequencing were performed to identify differential genes and their enrichment pathways. Moreover, small molecule inhibitors were used to try to reverse the resistance induced by 5-FU. Results: Twenty-one organoids showed sensitivity to irinotecan and resistance to 5-FU. Among them, 8 organoids (38.1%) were combination-resistant and 13 organoids (61.9%) showed sensitivity to combination treatment. Combination-resistant organoids corresponding patients had worse pathologic tumor regression grades (pTRGs) distribution (8/8, 100% had TRGs of 2-3 versus 100% had TRGs of 0-1 in combination-sensitive patients; p < 0.05) and disease-free survival (DFS) rates (HR:11.57, 95% IC:1.025-130.5; p = 0.0047) than patients whose organoids were combination-sensitive. Combination-resistant organoids had higher expression of Ki-67 and CD44 and reduced cleaved-caspase 3 in the combination treatment group and 5-FU group compared with the irinotecan group and control. Furthermore, we identified hedgehog pathway activation after adding 5-FU to irinotecan in combination-resistant organoids through RNA sequencing and ATAC sequencing. GANT-61, an inhibitor of the hedgehog pathway, increased sensitivity to the combination of 5-FU and irinotecan in combination-resistant organoids. Conclusions: We found that organoids which are sensitive to irinotecan turn to become resistant to 5-FU combined with irinotecan. Moreover, corresponding patients had worse responses and a lower DFS rate. The hedgehog pathway is activated in these organoids after the addition of 5-FU to irinotecan, and GANT-61 could reverse the resistance caused by 5-FU. However, more organoid-associated trials with large-scale patients are warranted to reverse the 5-FU-based resistance in the future.

e15602 Background: For patients with locally advanced rectal cancer (LARC), the standard treatment is neoadjuvant chemoradiotherapy combined with curative surgery. Total neoadjuvant therapy (TNT) has been used to increase rates of complete response and organ preservation, and achieve early control of distant metastasis. Recently, hypofractionated radiotherapy shows better synergistic effects in combination with PD-1/PD-L1 antibodies than conventional fractionated radiotherapy, as well as less impact on peripheral lymphocytes and more abscopal effects. Thus, the combination of immunotherapy and short-course radiotherapy (SCRT) based TNT is likely to further improve both tumor response and prognosis for LARC patients. Methods: TORCH is a randomized, prospective, multicentre, double-arm, phase II trial. 130 LARC (T3-4/N+M0, distance from anus ≤10cm) patients will be treated with TNT approach and assigned to the consolidation arm (A) and induction arm (B). Arm A will receive SCRT (25Gy/5Fx), followed by 6 cycles of Toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Arm B will first receive 2 cycles of ToriCAPOX, then receive SCRT, followed by 4 cycles of ToriCAPOX. Both groups will receive curative surgery or W&W strategy. The primary endpoint is the rate of complete response (CR, pCR plus cCR). The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, 3-year DFS rate, 3-year OS rate, etc. The “pick the winner” method is used to investigate the better regimen. Results: Up to Jan 20th 2022, 67 patients have been recruited in the trial (arm A: 35; arm B: 32). A total of 11 patients (all MSS) have completed all neoadjuvant therapy. Most of them showed high risk factors of recurrence, including lower location (≤5cm, 10/11), deeper primary lesion invasion (cT4/MRF+, 6/11) and more positive lymph nodes (cN2, 6/11). Finally, 2 patients (both arm B) achieved cCR and received W&W strategy. 9 patients received surgery and the pathological results showed 7 cases of pCR (arm A:3; arm B: 4), one near-pCR (arm A) and one non-pCR (arm A). Thus, the CR rate was amazingly high (CR rate: 81.8%, 9/11; pCR rate: 77.8%, 7/9). Even 5 patients who were evaluated as ycT3/N+/MRF+/EMVI+ before surgery was still demonstrated to be pCR after strict pathological examination. The only grade 3 AE was thrombocytopenia (4/11). And no grade 4 AE was observed. Conclusions: SCRT base TNT approach combined with Toripalimab have achieved surprisingly excellent CR rate and good tolerance in LARC patients (in our cohort), which has great clinical value in improving organ preservation. In the future, this ongoing trial will demonstrate this efficacy and compare the two arms by larger sample size. Clinical trial information: NCT04518280.

Implicit aggression is a kind of indirect aggression in the conflict between the two, which occurs more among female than male. The aggression form is more secret. When students are in school, they interact more frequently, which is prone to conflicts and leads to implicit aggression. The purpose of this paper is to study the relationship among female students, learn the real examples of implicit aggression through interviews, and analyze the cause of implicit aggression among female students as well as the way they deal with it. It is found that the occurring of implicit aggression among female students and the way they deal with it have noting to do with one’s status in a relationship but is more related to one’s background and living environments. Therefore, to solve this problem, changes should be made by female students’ parents, teachers, as well as themselves.

Gastric cancer has high incidence and fatality rates, making chemoprevention agents necessary. There is an ongoing debate about aspirin/nonsteroidal anti-inflammatory drugs (NSAIDs) use can significant reduce the risk of GC. We conducted a meta-analysis of existing studies evaluating the association of anti-inflammatory drug and GC. We performed a systematic literature search of PubMed, Web of Science, Embase, OVID, Cochrane Library and Clincialtrials.gov up to August 31, 2015. Either a fixed-effects or a random-effects model using was based on the result of homogeneity analysis. Subgroup, sensitivity, meta-regression, and publication bias analyses were evaluated. Forty-seven studies were finally included in this meta-analysis. The overall GC risk reduction benefit associated with anti-inflammatory drug use represented an RR of 0.78 (95% CI 0.71 to 0.85) and an adjusted RR of 0.74 (95% CI 0.71 to 0.77). Besides, the prevention benefit of aspirin/NSAIDs ingestion appeared to be confined to those patients with regiment of short or middle-term (≤5 years), high-frequency (>30 times per month) and low dose (30 times per month) and low dose (

The study built Albedo-NDVI feature space model by using Landsat TM remote sensing image during 2007-2013, analyzed desertification situation of Acukeerqin Banner. The results showed that: these years, Mild desertification area of study area increased from 466.73 hm2 to 495.96 hm2, increased by 29.23 hm2. By 2013, the slight desertification area reached 591.82 hm2, have accounted 40.2% of whole area. During the study period, the moderate desertification area increased from 316.06 hm2 to 345.16 hm2, increased by 29.1 hm2, but the servere desertification land area decreased 43.82 hm2. It is shown that the land desertification problem has improved, overall has a good trend, severe desertification has slowed down under the management of preventive measures, as it change into moderate or mild desertification interval. The main causes of desertification in the study area are the excessive reclamation, population growth, reduction of rainfall and temperature rise.

Dongsheng district as Chinese important resource of energy rich region, and belongs to the typical ecological fragile zone, the contradiction between the development of energy resources and the protection of the ecological environment has become increasingly acute, and land use change is the embodiment of the contradiction. This paper takes the land use change of Dongsheng as the research object, 1993, 2005 and 2014 land use database as the data source, using GIS software, combined with the land use changes spatial dynamic degree and land use change trend index model and other research methods, analysis of the Dongsheng District of various temporal and spatial variation of land use types and influencing factors during twenty-one years. Research shows that: the grassland, woodland and arable land changed most frequently. The area of agricultural land reduced the 125.514 km2, construction land increased 125.275 km2, agricultural land and construction land area changes in relative balance. In space, the change in spatial distribution characteristics of arable land and construction land is most obvious. The effects of land use change in Dongsheng region is mainly affected by the implementation of the national economic and social development and reform policy.