Microbiota in colorectal cancer related to liver metastasis

The prevalence of colorectal cancer(CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum(F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However,little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis(CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of CRC.Subsequently, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.

Colorectal cancer, radiotherapy and gut microbiota

Colorectal cancer is closely related to inflammation and immune response. Radiotherapy, as a major treatment for colorectal cancer, plays a central role in cancer control. Inflammation caused by ionizing radiation can exert either anti-or pro-tumorigenic effects. Additionally, radiotherapy can elicit an anti-tumor response not only in radiation of target lesions but also in radiation of remote lesions. However, the immune mechanism underlying this effect has not been thoroughly elucidated yet. The combination therapeutic regimen of radiotherapy with other therapeutic methods, including chemotherapy and immunotherapy, has been applied in clinical practice. Meanwhile, radiation toxicity and radiosensitivity have long been problems that affect a patient's quality of life and morbidity.Researchers have found that the abovementioned problems are closely associated with gut microbiota. Here we discuss the impact of immune response induced by radiotherapy on tumor regression and the impact of intestinal flora on the consequent clinical efficacy.

对可切除的中/低位直肠癌是/否进行术前放化疗的全直肠系膜切除术研究:一项前瞻性、单中心、随机试验的长期分析

背景与目的我们的Ⅱ期随机试验的初步研究结果显示,对进行全直肠系膜切除术(total mesorectal excision,TME)的患者是/否进行术前同步放化疗(concurrent chemoradiotherapy,CCRT),二者的功能性括约肌保留率和短期生存结局相近。在经过中位71个月的随访后,现报告这一长期试验的结果。方法在2008年3月23日至2012年8月2日期间,192例患有T3–T4或淋巴结阳性、可切除的中/低直肠腺癌患者被随机分为接受或不接受术前CCRT组,之后均进行TME。评估以下终点:局部复发和远处转移的累积率、无病生存(disease?free survival,DFS)和总生存(overall survival,OS)。结果对入组的184例患者资料进行分析,其中TME组有94例,CCRT+TME组有90例。在整个队列中,5年DFS和OS率分别为84.8%和85.1%。CCRT+TME组的5年DFS率为85.2%,TME组为84.3%(P=0.969);CCRT+TME组的5年OS率为83.5%,TME组为86.5%(P=0.719)。在CCRT+TME和TME组中,局部复发的5年累积率分别为6.3%和5.0%(P=0.681),远处转移的5年累积率分别为15.0%和15.7%(P=0.881)。通过亚组分析,接受CCRT未观察到5年DFS和OS的显著改善。结论两种治疗方案的长期结局相近。因此,如果可以进行高质量的TME手术和强化化疗,建议选择性地对直肠癌患者进行术前CCRT。

Dosimetric Comparison of Volumetric Modulated Arc Therapy (VMAT), 5F Intensity Modulated Radiotherapy (IMRT) and 3D Conformal Radiotherapy (3DCRT) in Rectal Carcinoma Receiving Neoadjuvant Chemoradiotherapy

Objective: To investigate better dosimetric distribution of volumetric modulated arc therapy (VMAT) vs. 5F intensity modulated radiotherapy (IMRT) and 3D conformal radiotherapy (3DCRT) in patients with locally advanced rectal cancer (LARC) when treated with neoadjuvant chemoradiotherapy. Methods: 3D-CRT, 5F-IMRT and VMAT plans for preoperative radiotherapy were 66011designed in 12 patients with locally advanced rectal cancer. The conformity index (CI) and homogeneity index (HI) in target volume, and the dose and volume of the organs at risk (OAR) irradiated including small bowel, bladder and bilatera1 femoral heads were compared among the three plans. Results: The CI for planning target volume (PTV) 2 and HI for PTV1 of VMRT and 5F-IMRT were superior to 3D-CRT. The CI of VMAT, 5F-IMRT and 3D-CRT plans were 0.71, 0.69 and 0.62 (p = 0.011 and p = 0.019, respectively). The HI of the VMAT and 5F-IMRT plans were both 1.04 and 3D-CRT planning was 1.06 (p = 0.022 and p = 0.006, respectively). The V35 - V45 of small bowel in VMAT were significantly less than in 5F-IMRT and 3D-CRT. V35 was 47.0, 56.4, and 72.8 cm3 for VMAT, 5F-IMRT, and 3D-CRT (p = 0.021 and p = 0.034, respectively), while V40 was 30.5, 35.5, 45.1 cm3 (p = 0.024 and p = 0.032, respectively) and V45 was 15.1, 18.1, 30.0 cm3 (p = 0.033 and p = 0.032, respectively). The D5, V30 and V50 of bladder in 3D-CRT were less than in VMAT and 5F-IMRT planning (p = 0.034, 0.004, 0.002 and p = 0.027, 0.003, 0.002, respectively). The Dmean of left femoral head in VMAT and 5F-IMRT were less than in 3D-CRT planning (p = 0.028 and p = 0.022, respectively) and the Dmean, V30 of right femoral head in VMAT and 5F-IMRT were better than in 3D-CRT planning (p = 0.044, 0.036 and p = 0.023, 0.028, respectively). Conclusions: Dosimetric analyses demonstrated that IMRT is superior to 3D-CRT in the conformity and homogeneity of dose distribution to the target volume, and provide a better protection to OARs sparing in patients with locally advanced rectal cancer for preoperative radiotherapy. With similar target coverage, VMRT is superior to 5F-IMRT in normal tissue sparing.

Cycle number of neoadjuvant chemotherapy might influence survival of patients with T1-4N2-3M0 nasopharyngeal carcinoma

Objective： Stage N2-3 nasopharyngeal carcinoma（NPC） shows a high risk of distant metastasis, which will finally cause death. This study aimed to evaluate the impact of neoadjuvant chemotherapy（NACT） of various cycles before radical radiotherapy on distant metastasis and survival of patients with stage N2-3 diseases.Methods： In this study, a total of 1,164 consecutive patients with non-metastatic N2-3 NPC were recruited and prospectively observed. Then 231 patients who received NACT of 4 cycles（NACT=4 group） were matched 1：2：1 to 462 patients treated with NACT of 2 cycles（NACT=2 group） and 231 patients treated without NACT（NACT=0 group）, according to age, histological subtype, N stage and NACT regimen. Five candidate variables（sex, T stage, concurrent chemotherapy, intensity-modulated radiation therapy and cycle number of NACT） were analyzed for their association with patients＇ survival.Results： After matching, the overall survival（OS）, disease-free survival（DFS）, local-recurrence-free survival（RFS） and distant-metastasis-free survival（MFS） of the NACT=4 group（89.2%, 81.0%, 83.3% and 84.8%,respectively） were better than those of the NACT=2 group（83.3%, 72.5%, 81.2% and 77.9%, respectively） and the NACT=0 group（74.0%, 63.2%, 74.0% and 68.8%, respectively）. In multivariate analysis, the cycle number of NACT maintained statistical significance on the OS, DFS, RFS and MFS（all P〈0.05）.Conclusions： For N2-3 NPC, cycle number of NACT appeared to be an independent factor associated with an improvement of survival.

Total mesorectal excision with or without preoperative chemoradiotherapy for resectable mid/low rectal cancer: a long-term analysis of a prospective, single-center, randomized trial

Background:The preliminary results of our phase II randomized trial reported comparable functional sphincter pres-ervation rates and short-term survival outcomes between patients undergoing total mesorectal excision(TME)with or without preoperative concurrent chemoradiotherapy(CCRT).We now report the long-term results after a median follow-up of 71 months.Methods:Between March 23,2008 and August 2,2012,192 patients with T3-T4 or node-positive,resectable,mid/low rectal adenocarcinoma were randomly assigned to receive TME with or without preoperative CCRT.The following endpoints were assessed:cumulative rates of local recurrence and distant metastasis,disease-free survival(DFS),and overall survival(OS).Results:The data of 184 eligible patients were analyzed:94 patients in the TME group and 90 patients in the CCRT+TME group.In the whole cohort,the 5-year DFS and OS rates were 84.8%and 85.1%,respectively.The 5-year DFS rates were 85.2%in the CCRT+TME group and 84.3%in the TME group(P=0.969),and the 5-year OS rates were 83.5%in the CCRT+TME group and 86.5%in the TME group(P=0.719).The 5-year cumulative rates of local recur-rence were 6.3%and 5.0%(P=0.681),and the 5-year cumulative rates of distant metastasis were 15.0%and 15.7%(P=0.881)in the CCRT+TME and TME groups,respectively.No significant improvements in 5-year DFS and OS were observed with CCRT by subgroup analyses.Conclusions:Both treatment strategies yielded similar long-term outcomes.A selective policy towards preoperative CCRT is thus recommended for rectal cancer patients if high-quality TME surgery and enhanced chemotherapy can be performed.

Outcomes and toxicities of immune checkpoint inhibitors in colorectal cancer:a real-world retrospective analysis

Dear Editor,Colorectal cancer(CRC)is a common cancer in China and worldwide[1-2].Immune checkpoint blockade(ICB)has been proven effective for DNA mismatch repairdeficient(dMMR)/microsatellite instability-high(MSIH)CRC[3-10]but not for mismatch repair-proficient(pMMR)/microsatellite stable(MSS)CRC in clinical trials[3].No published data on the real-world application of ICB in CRC exist,and thus,whether the response to ICB in unselected patients is similar to that in patients from published trials remains unclear.