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.

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.

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。

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.

Value of transrectal ultrasonography for tumor node metastasis restaging in patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy

Objective:To explore the value of transrectal ultrasonography(TRUS)for tumor node metastasis(TNM)restaging for patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy(neo-CRT).Methods:One hundred and forty-nine patients with locally advanced rectal cancer(cT3-4 or cN+)who underwent TRUS after neo-CRT were retrospectively reviewed.TRUS restaging was compared with the results of post-operative pathological TNM findings.Results:After neo-CRT,the accuracy of TRUS for diagnosing T-staging was 30.9%,with 60.4%(90/149)of cases overestimated.The sensitivity of TRUS for T-staging(T0 vs T1 vs T2 vs T3 vs T4)were 16.3%,0%,12.5%,42.6%and 75.0%,respectively.The accuracy of TRUS for diagnosing N-staging after neo-CRT was 81.2%,with the sensitivities of N0 and N+were 93.3%and 31.0%,respectively.After neo-CRT,27.5%(41/149)of patients achieved pathologically complete response(pCR).The sensitivity,specificity,positive predictive value and negative predictive values of TRUS for pCR were 17.1%,99.1%,87.5%and 75.9%,respectively.Conclusions:TRUS can be applied for restaging T4 and N0,and has potential for screening out patients with pCR in those with locally advanced rectal cancer after neo-CRT,although some stages are overestimated for T-staging and its sensitivity for predicting pCR is low.