Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer

Background: Complete resection of locally advanced sigmoid colon cancer(LASCC) is sometimes difficult. Patients with LASCC have a dismal prognosis and poor quality of life, which has encouraged the evaluation of alternative multimodality treatments. This prospective study aimed to assess the feasibility and efficacy of neoadjuvant chemora?diotherapy(neo CRT) followed by surgery as treatment of selected patients with unresectable LASCC.Methods: We studied the patients with unresectable LASCC who received neo CRT followed by surgery between October 2010 and December 2012. The neoadjuvant regimen consisted of external?beam radiotherapy to 50 Gy and capecitabine?based chemotherapy every 3 weeks. Surgery was scheduled 6–8 weeks after radiotherapy.Results: Twenty?one patients were included in this study. The median follow?up was 42 months(range, 17–57 months). All patients completed neo CRT and surgery. Resection with microscopically negative margins(R0 resection) was achieved in 20 patients(95.2%). Pathologic complete response was observed in 8 patients(38.1%). Multivisceral resection was necessary in only 7 patients(33.3%). Two patients(9.5%) experienced grade 2 postopera?tive complications. No patients died within 30 days after surgery. For 18 patients with pathologic M0(yp M0) disease, the cumulative probability of 3?year local recurrence?free survival, disease?free survival and overall survival was 100.0%, 88.9% and 100.0%, respectively. For all 21 patients, the cumulative probability of 3?year overall survival was 95.2% and bladder function was well preserved.Conclusion: For patients with unresectable LASCC, preoperative chemoradiotherapy and surgery can be performed safely and may result in an increased survival rate.

Risk factors for sporadic colorectal cancer in southern Chinese

AIM:To investigate the role of smoking, alcohol drinking, family history of cancer, and body mass index(BMI) in sporadic colorectal cancer in southern Chinese.METHODS:A hospital-based case-control study was conducted from July 2002 to December 2008.There were 706 cases and 723 controls with their sex and age(within 5 years) matched.An unconditional logistic regression model was used to analyze the association between smoking, alcohol drinking, family history of cancer, BMI and sporadic colorectal cancer.RESULTS:No positive association was observed between smoking status and sporadic colorectal cancer risk.Compared with the non alcohol drinkers, the current and former alcohol drinkers had an increased risk of developing sporadic colorectal cancer(CRC)(adjusted OR = 8.61 and 95% CI = 6.15-12.05;adjusted OR = 2.30, 95% CI = 1.27-4.17).Moreover, the increased risk of developing sporadic CRC was significant in those with a positive family history of cancer(adjusted OR = 1.62, 95% CI = 1.12-3.34) and in those with their BMI ≥ 24.0 kg/m2(adjusted OR = 1.39, 95% CI = 1.10-1.75).Stratification analysis showed that the risk of developing both colon and rectal cancers was increased in current alcohol drinkers(adjusted OR = 7.60 and 95% CI = 5.13-11.25;adjusted OR = 7.52 and 95% CI = 5.13-11.01) and in those with their BMI ≥ 24.0 kg/m2(adjusted OR = 1.38 and 95% CI = 1.04-1.83;adjusted OR = 1.35 and 95% CI = 1.02-1.79).The risk of developing colon cancer, but not rectal cancer, was found in former alcohol drinkers and in those with a positive family history of cancer(adjusted OR = 2.51 and 95% CI = 1.24-5.07;adjusted OR = 1.82 and 95% CI = 1.17-2.82).CONCLUSION:Alcohol drinking, high BMI(≥ 24.0 kg/m2) and positive family history of cancer are the independent risk factors for colorectal cancer in southern Chinese.

Surgery with versus without preoperative concurrent chemoradiotherapy for mid/low rectal cancer: an interim analysis of a prospective, randomized trial

Introduction: Multimodality therapy, including preoperative chemoradiotherapy(CRT) and total mesorectal excision(TME), has effectively reduced local recurrence rates of rectal cancer over the past decade. However, the benefits and risks of the addition of neoadjuvant CRT to surgery need to be evaluated. This study was to compare the efficacy of TME with versus without preoperative concurrent chemoradiotherapy(CCRT) involving XELOX regimen(oxaliplatin plus capecitabine) in Chinese patients with stages II and III mid/low rectal adenocarcinoma.Methods: We randomly assigned patients to the TME group(TME without preoperative CCRT) or CCRT + TME group(TME with preoperative CCRT). The primary endpoint was disease-free survival(DFS); the secondary endpoints were overall survival(OS), local and distant recurrence, tumor response to CRT, toxicity, sphincter preservation, and surgical complications. An interim analysis of the potential inferiority of DFS in the CCRT + TME group was planned when the first 180 patients had been followed up for at least 6 months.Results: A total of 94 patients in the TME group and 90 patients in the CCRT + TME group were able to be evaluated. The 3-year DFS and OS rates were 86.3 % and 91.5 % in the whole cohort, respectively. The 3-year DFS rates of the TME and CCRT + TME groups were 85.7% and 87.9 %(P = 0.766), respectively, and the 3-year OS rates were 90.7 % and 92.3 %(P = 0.855), respectively. The functional sphincter preservation rates of the TME and CCRT +TME groups were 71.3 % and 70.0 %(P = 0.849), respectively. In the TME group, 16(17.0 %) patients were proven to have p TNM stage I disease after surgery. In the CCRT + TME group, 32(35.6 %) patients achieved a pathologic complete response(p CR).Conclusions: Preliminary results indicated no significant differences in the DFS, OS, or functional sphincter preservation rates between the TME and CCRT + TME groups. However, preoperative CCRT with XELOX yielded a high p CR rate. Newer techniques are needed to improve the staging accuracy, and further investigation is warranted.

Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases

Background: Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorecal cancer patients with liver metastases who underwent hepatectomy.However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients.Patients and methods: In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients.The pathologic response was evaluated according to the tumor regression grade(TRG).The prognostic role of pathologic response in recurrence-free survival(RFS) and overall survival(OS) was assessed using Kaplan-Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests.Results: Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy(median RFS: 9.9 vs.6.5 months, P = 0.009; median OS: 40.7 vs. 28.1 months, P = 0.040). Multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors,and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases(all P < 0.05). A decrease in the serum carcinoembryonic antigen(CEA) level after preoperative chemotherapy predicted an increased pathologic response rate(P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemotherapy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens.Conclusions: We found that the evaluation of pathologic response may predict the prognosis of Chinese colorectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.

Indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer

AIM To evaluate indoleamine-2,3-dioxygenase 1/cyclooxygenase 2(IDO1/COX2) expression as an independent prognostic biomarker for colorectal cancer(CRC) patients.METHODS We retrospectively studied the medical records of 95 patients who received surgical resection from August 2008 to January 2010. All patients were randomly assigned to adjuvant treatment with or without celecoxib groups after surgery. We performed standard immunohistochemistry to assess the expression levels of IDO1/COX2 and evaluated the correlation of IDO1/COX2 with clinicopathological factors and overall survival(OS) outcomes.RESULTS The expression of nuclear IDO1 was significantly correlated with body mass index(P < 0.001), and IDO1 expression displayed no association with sex, age, tumor differentiation, T stage, N stage, carcinoembryonic antigen, cancer antigen 19-9, CD3+ and CD8+ tumor infiltrating lymphocytes, and COX2. In univariate analysis, we found that nuclear IDO1(P = 0.039), nuclear/cytoplasmic IDO1 [hazard ratio(HR) = 2.044, 95% confidence interval(CI): 0.871-4.798, P = 0.039], nuclear IDO1/COX2(HR = 3.048, 95%CI: 0.868-10.7, P = 0.0049) and cytoplasmic IDO1/COX2(HR = 2.109, 95%CI: 0.976-4.558, P = 0.022) all yielded significantly poor OS outcomes. Nuclear IDO1(P = 0.041), nuclear/cytoplasmic IDO1(HR = 3.023, 95%CI: 0.585-15.61, P = 0.041) and cytoplasmic IDO1/COX2(HR = 2.740, 95%CI: 0.764-9.831, P = 0.038) have significantly poor OS outcomes for the CRC celecoxib subgroup. In our multivariate Cox model, high coexpression of cytoplasmic IDO1/COX2 was found to be an independent predictor of poor outcome in CRC(HR = 2.218, 95%CI: 1.011-4.48, P = 0.047) and celecoxib subgroup patients(HR = 3.210, 95%CI: 1.074-9.590, P = 0.037).CONCLUSION Our results showed that cytoplasmic IDO1/COX2 coexpression could be used as an independent poor predictor for OS in CRC.

奥沙利铂和卡培他滨联合贝伐单抗加放疗的新辅助方案治疗局部晚期直肠癌:单中心Ⅱ期研究结果

背景与目的新辅助放化疗后手术被推荐为局部晚期直肠癌的标准治疗方案,可降低局部复发但对远处转移无效。所以加强系统治疗是降低远处转移风险的必要措施。本研究旨在评价奥沙利铂和卡培他滨(XELOX)联合贝伐单抗加放疗的新辅助方案治疗局部晚期直肠癌的安全性和有效性。方法Ⅱ至Ⅲ期直肠癌患者接受1个疗程的诱导化疗及XELOX加贝伐单抗的同步放化疗。放疗结束后6–8周行手术治疗,并进行3个疗程XELOX和2个疗程卡培他滨的术后化疗。本研究的主要终点是病理学完全缓解(pathologic complete response,pCR)率和安全性,次要终点为3年总生存和无进展生存。结果 2013年2月至2015年4月间招募了45例患者。所有患者均完成了新辅助治疗。7例患者(15.6%)因个人原因拒绝了后续手术治疗,其余38例患者接受了根治性切除术,括约肌保留率为84.2%,pCR率为39.5%。毒性是可接受的,分别在6例和2例患者中观察到3–4级血液学毒性和腹泻。需要手术干预的吻合口瘘的发生率为13.3%。中位随访37个月后,5例患者出现疾病进展,2例患者因癌症死亡。3年总生存率和3年无进展生存率分别为95.3%和88.6%。结论增加贝伐单抗至新辅助放化疗中获得了令人满意的pCR率和3年生存率,但也增加了吻合口瘘的风险,因此该方案不宜作为局部晚期直肠癌的常规推荐方案。

The loss-of-function mutations and down-regulated expression of ASB3 gene promote the growth and metastasis of colorectal cancer cells

Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer(CRC).Methods: We used next?generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real?time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony for?mation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.Results: We found that ASB3 gene was frequently mutated(5.3%) and down?regulated(70.4%) in CRC cases. Knock?down of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild?type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial?mesenchymal transition, which was characterized by the up?regulation of β?catenin and E?cadherin and the down?regulation of transcription factor 8, N?cadherin, and vimentin.Conclusion: ASB3 dysfunction resulted from gene mutations or down?regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.

Temporal Change in Treatment Patterns of Metastatic Colorectal Cancer and Its Association with Patient Survival:A Retrospective Cohort Study Based on an Intelligent Big-Data Platform

There is a lack of high-quality,large-scale,real-world evidence from patients with metastatic colorectal cancer(mCRC),especially in China.It remains unclear whether efforts to improve the quality of care for mCRC would improve patient survival outcomes in real-world practice.On the basis of an intelligent bigdata platform,we established a large-scale retrospective cohort of mCRC patients.We investigated the temporal changes in the systemic and local treatment(resection,ablation,or radiation to liver,lung,or extrahepatic and/or extrapulmonary metastases)patterns of mCRC,and whether these changes were associated with improved overall survival(OS)over time.Between July 2012 and December 2018,3403 eligible patients were included in this research.The median OS was 42.8 months(95%confidence interval(CI),40.7–46.6)for the entire cohort,25.6 months(95%CI,24.7–26.9)for those treated with systemic therapy only,and not reached(95%CI,78.6 months–not reached)for those receiving local therapy.The utility rate of local therapy increased continuously from 37.9%in 2012–2014 to 46.9%in 2017–2018.A dramatic increase in the utility rate of either cetuximab or bevacizumab was observed since 2017(39.9%,43.2%,and 60.3%in 2012–2014,2015–2016,and 2017–2018,respectively).Compared with 2012–2014,the OS of the entire population significantly improved in 2015–2016(hazard ratio(HR)=0.87(95%CI,0.78–0.99);P=0.034),but not for patients receiving systemic therapy only(HR=0.99(95%CI,0.86–1.14);P=0.889),whereas an improved OS was found in 2015–2018 for both the entire population(HR=0.75(95%CI,0.70–0.81);P<0.001)and for patients receiving systemic therapy only(HR=0.83(95%CI,0.77–0.91);P<0.001).In summary,the quality of care for mCRC,as indicated by the utility rate of targeted and local therapies,has been continuously improving over time in this study cohort,which is associated with continuously improving survival outcomes for these patients.

ASB3基因功能缺失突变和表达下调促进结直肠癌细胞的生长和转移

背景与目的锚蛋白重复序列和SOCS盒蛋白3(ankyrin repeat and SOCS box protein 3, ASB3)是ASB家族成员,包含锚蛋白重复序列和SOCS盒结构域。以往研究表明,它介导肿瘤坏死因子受体2的泛素化和降解,并可能参与炎症反应。然而它对肿瘤发生的作用尚不清楚。本研究旨在探讨ASB3对结直肠癌(colorectal cancer, CRC)的生长与转移的影响。方法使用新一代测序或Sanger测序法检测结直肠癌标本或细胞系中的ASB3突变,并用实时定量PCR、蛋白免疫印迹、免疫组化或免疫荧光法来测定基因的表达。通过MTT和集落形成实验检测细胞的增殖,用流式细胞仪检测细胞周期分布,并用Transwell和划痕实验检测细胞迁移和侵袭。应用裸鼠实验来检测肿瘤细胞的成瘤性和肝转移。结果在结直肠癌病例中ASB3基因经常发生突变(5.3%)和下调(70.4%)。沉默内源性ABS3的表达在体外可促进结直肠癌细胞的增殖、迁移和侵袭,在体内可促进成瘤和肝转移。相反,过表达野生型ASB3可抑制肿瘤的生长和转移,而过表达ASB3突变体不具有这种抑制效应。进一步分析表明,ASB3通过上调β?catenin、E?cadherin和下调转录因子8、N?cadherin和vimentin阻止上皮?间充质转换来抑制结直肠癌转移。结论在结直肠癌中常存在ASB3基因突变或表达下调,在结直肠癌的发生和进展中起到重要作用。

Neoadjuvant oxaliplatin and capecitabine combined with bevacizumab plus radiotherapy for locally advanced rectal cancer: results of a single-institute phase II study

Background:Neoadjuvant chemoradiotherapy followed by surgery is recommended as the standard of care for locally advanced rectal cancer,reducing local recurrence but not distant metastasis.Intensified systemic therapy is warranted to reduce the risk of distant metastasis.The present study aimed to evaluate the safety and efficacy of neo-adjuvant oxaliplatin and capecitabine(XELOX)combined with bevacizumab plus radiotherapy for locally advanced rectal cancer.Methods:Patients with stages II to III rectal cancer received one cycle of induction chemotherapy and concurrent chemoradiotherapy with XELOX plus bevacizumab.Surgery was performed 6-8 weeks after completion of radiotherapy,and postoperative chemotherapy with three cycles of XELOX and two cycles of capecitabine were given.The primary endpoints were pathologic complete response(pCR)rate and safety,and the secondary endpoints were 3-year overall survival and progression-free survival.Results:Forty-five patients were enrolled between February 2013 and April 2015.All completed the neoadjuvant therapy.Seven patients(15.6%)refused subsequent surgical therapy for personal reasons,and the other 38 patients received radical resection,with a sphincter preservation rate of 84.2%and a pCR rate of 39.5%.Toxicity was acceptable,with grades 3-4 hematological toxicity and diarrhea observed in six and two patients,respectively.Incidence of anastomotic leak that required surgical intervention was 13.3%.After a median follow-up period of 37 months,five patients developed disease progression and two died of cancer.The 3-year overall survival rate and 3-year progres-sion-free survival rate were 95.3%and 88.6%,respectively.Conclusions:The addition of bevacizumab to neoadjuvant chemoradiotherapy resulted in a satisfying pCR rate and 3-year survival,but also may increase the risk of anastomotic leak,thus this regimen is not suitable to be considered for regular recommendation for locally advanced rectal cancer.

Expert opinions on immunotherapy for patients with colorectal cancer

1 BACKGROUND With the rapid development of immune checkpoint inhibitors(ICIs)over the past decades,they have become a major area of interest in the treatment of colorectal cancer(CRC)[1,2].There are evidence pointing that programmed cell death protein-1(PD-1)blockade,alone or in combination with anti-cytotoxic T-lymphocyte-associated protein 4(anti-CTLA4)therapy,achieved durable responses in patients with mismatch repair-deficient(dMMR)or microsatellite instability-high(MSI-H)metastatic CRC(mCRC)[3–6].However,the optimal diagnostic method for detecting dMMR/MSI-H disease as well as the optimal anti-PD-1-based treatment modality still remains controversial in this patient subset.In addition,for the majority of mCRC cases that are mismatch repair-proficient(pMMR)or microsatellite stable(MSS),the clinical benefits from these agents are generally minimal[3,7],driving extensive research efforts to develop effective combination therapies in this disease subset.Moreover,investigations of anti-PD-1-based treatments have also been initiated in the nonmetastatic settings of CRC,with some encouraging preliminary evidence[8].Medical oncologists and surgeons from the Committee of Colorectal Cancer of the Chinese Society of Clinical Oncology had a panel discussion on immunotherapy for patients with colorectal cancer during a seminar on June 16,2020,in Guangzhou,China.Herein,the expert opinions have been summarized along with relevant clinical evidence(Table 1)to guide real-world treatment decision-making regarding the use of ICIs in patients with CRC.

Germline mutational profile of Chinese patients under 70 years old with colorectal cancer

Background:Inherited susceptibility accounts for nearly one-third of colorectal cancer(CRC)predispositions and has an 80%-100%lifetime risk of this disease.However,there are few data about germline mutations of hereditary CRC-related genes in Chinese patients with CRC.This study aimed to assess the prevalence of gene mutations related to cancer susceptibility among Chinese patients with CRC,differences between Chinese and Western patients,and the phenotypegenotype correlation.Methods:We retrospectively collected tumor samples from 526 patients with CRC under 70 years old who underwent hereditary CRC genetic testing.A series of bioinformatic analyses,as well as statistical comparisons,were performed.Results:We found that 77 patients(14.6%)harbored functional variants of the 12 genes.The mutation frequencies of the top 5 mutated genes were 6.5%for MutL homolog 1(MLH1),5.1%for MutS homolog 2(MSH2),1.0%for MSH6,0.8%for PMS1 homolog 2(PMS2),and 0.8%for APC regulator of the WNT signaling pathway(APC).Our data showed much higher rates of mutations of MSH6 and PMS2 genes among all mismatch repair(MMR)genes as compared with those in Western populations.Mutations in MLH1,MSH2,and MSH6 were found to be mutually exclusive.Patients with MLH1 or MSH2 mutations had higher frequencies of personal history of cancer(MLH1:20.6%vs.8.7%;MSH2:25.9%vs.8.6%)and family history of cancer than those without these mutations(MLH1:73.5%vs.48.4%;MSH2:70.4%vs.48.9%),and the lesions were more prone to occur on the right side of the colon than on the left side(MLH1:73.5%vs.29.3%;MSH2:56.0%vs.31.0%).The proportion of stage I/II disease was higher in patients with MLH1 mutations than in those without MLH1 mutations(70.6%vs.50.7%),and the rate of polyps was higher in patients withAPC mutations than in those with wild-type APC(75.0%vs.17.4%).Conclusion:These results provide a full-scale landscape of hereditary susceptibility over 12 related genes in CRC patients and suggest that a comprehensive multi-gene panel testing for hereditary CRC predisposition could be a helpful analysis in clinical practice.

A frameshift mutation in exon 19 of MLH1 in a Chinese Lynch syndrome family: a pedigree study

Lynch syndrome (LS),an autosomal dominantly inherited disease previously known as hereditary non-polyposis coloreetal cancer (HNPCC),leads to a high risk of colorectal cancer (CRC)as well as malignancy at certain sites including endometrium,ovary,stomach,and small bowel (Hampel et al.,2008;Lynch et al.,2009).Clinically,LS is considered the most common hereditary CRC-predisposing syndrome, accounting for about 3% of all CRC cases (Popat et al., 2005).LS is associated with mutations of DNA mismatch repair (MMR)genes such as MLH1,MSH2, MSH6,PMS2,and EPCAM (Ligtenberg et al.,2009;Lynch et al.,2009),which can trigger a high frequency of replication errors in both microsatellite regions and repetitive sequences in the coding regions of various cancer-related genes.

Low prevalence of mismatch repair deficiency in Chinese colorectal cancers:a multicenter study

Background:Although universal testing for mismatch repair deficiency(dMMR)has been recommended to all colorectal cancer(CRC)patients,related evidence for the Chinese population is lacking.Here,we investigated the prevalence and clinicopathological features of dMMR patients in a large Chinese CRC cohort.Methods:We included 7,373 CRC patients treated at four Chinese medical centers between August 2010 and September 2016.Patients’baseline characteristics and pathological features were recorded.The clinicopathological features were compared between patients with MLH1/PMS2 deficiency(dMLH1/PMS2)and MSH2/MSH6 deficiency(dMSH2/MSH6).Results:Among the investigated patients,654(8.9%)were identified with dMMR CRCs and,of them,401(61.3%)were males,with a median age of 55 years(range,22-87 years);355(54.3%)had stage II CRC based on American Joint Committee on Cancer 8th edition.The prevalence of the dMLH1/PMS2 group and the dMSH2/MSH6 group were 51.5%(337/654)and 25.1%(164/654),respectively.Compared with dMSH2/MSH6 patients,those with dMLH1/PMS2 were older(57 vs 52 years,P<0.001),more likely to be female(45.7%vs 31.5%,P=0.004),prone to having tumors located in the right-hand side of the colon(59.0%vs 47.6%,P=0.015),and less likely to have a family history of tumors(29.7%vs 43.3%,P=0.003).Conclusions:The prevalence of dMMR in Chinese CRC patients was low,especially in the dMLH1/PMS2 group.The clinicopathological features were different between dMMR subgroups.

Oxaliplatin-containing adjuvant chemotherapy improves the survival of locally advanced rectal cancer patients with pathological complete response after pre-operative chemoradiotherapy

Background:The necessity for adjuvant chemotherapy(ACT)in locally advanced rectal cancer(LARC)patients who achieve pathological complete response(pCR)after pre-operative chemoradiotherapy(CRT)is still not identified.We aimed to investigate the therapeutic value of ACT in these patients.Methods:Clinical data were retrospectively collected from 105 consecutive LARC patients who achieved pCR after pre-operative CRT and underwent radical tumor resection between December 2008 and April 2014 in a comprehensive cancer center.Perioperative chemotherapy(CT)was administered by combining oxaliplatin with capecitabine(XELOX regimen).Disease-free survival(DFS)and overall survival(OS)rates of patients with or without ACT were compared.Results:Eighty-three(79.0%)patients received ACT and 22(21.0%)did not.With a median follow-up of 49 months,the ACT group had a significantly higher 3-year DFS rate(92.8 vs 86.4%,p=0.029)and 3-year OS rate(95.1 vs 86.1%,p=0.026)than the non-ACT group.In multivariable analyses,the presence of ACT was an independent prognostic factor for DFS(hazard ratio[HR]:0.271;95%confidence interval(CI):0.080–0.916;p=0.036)but not for OS.This benefit was more obvious in patients younger than 60 years via subgroup analysis(adjusted HR:0.106;95%CI:0.019–0.606;p=0.012).Conclusions:Oxaliplatin-containing ACT may confer survival benefits to patients with pCR,particularly younger patients.However,the routine use of ACT in patients with pCR needs further validation.

Programmed death-ligand 1 expression in the tumour stroma of colorectal liver oligometastases and its association with prognosis after liver resection

Background The clinical value of programmed death-ligand 1(PD-L1)expression in colorectal liver oligometastases(CLOs)remains undefined.This study aimed to detect PD-L1 in the microenvironment of CLOs and determine its association with patient prognosis.Methods We collected 126 liver-resection specimens from CLO patients who underwent curative liver resection between June 1999 and December 2016.Immunohistochemistry(IHC)was performed to assess PD-L1 expression in paraffinembedded specimens.Overall survival(OS)and recurrence-free survival(RFS)were analysed using the Kaplan–Meier method and log-rank test.Results PD-L1 was mainly expressed in the stroma of liver oligometastases.Patients with high PD-L1 expression had a higher proportion of clinical-risk scores(CRSs)of 2–4(67.7%vs 40.4%;P=0.004).With a median 58-month follow-up,patients with high PD-L1 expression had a significantly lower 3-year OS rate(65.5%vs 92.7%;P=0.001)and 3-year RFS rate(34.7%vs 83.8%;P<0.001)than patients with low PD-L1 expression.Multivariate Cox analysis demonstrated that high PD-L1 expression(hazard ratio[HR]=3.581;95%confidence interval[CI]2.301–9.972;P=0.015),CRS 2–4(HR=6.960;95%CI 1.135–42.689;P=0.036)and increased preoperative CA19-9(HR=2.843;95%CI 1.229–6.576;P=0.015)were independent risk factors for OS.High PD-L1 expression(HR=4.815;95%CI 2.139–10.837;P<0.001)and lymph-node metastasis(HR=2.115;95%CI 1.041–4.297;P=0.038)were independent risk factors for RFS.Conclusion This study found that PD-L1 was commonly expressed in the tumour stroma of CLOs and high PD-L1 expression was associated with poor prognosis.