Phase I/II Study of Preoperative Chemoradiotherapy With TEGAFIRI for Locally Advanced Rectal Cancer

Introduction

Chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer; however, the optimal chemotherapy sequence to administer simultaneously with radiotherapy remains unclear. We conducted a phase I/II study to test a new regimen, TEGAFIRI (combination tegafur, uracil [UFT], leucovorin [LV], irinotecan), for patients with locally advanced rectal cancer.

Prognostic Impact of Extranodal Extension in Rectal Cancer Patients Undergoing Radical Resection After Preoperative Chemoradiotherapy

BackgroundExtranodal extension (ENE) of nodal metastasis has emerged as an important prognostic factor in many malignancies, including rectal cancer. However, its significance in patients with rectal cancer receiving preoperative chemoradiotherapy (PCRT) has not been extensively investigated. We therefore assessed ENE and its prognostic impact in a large series of consecutive rectal cancer patients with lymph node metastasis after PCRT and curative resection.Patients and MethodsBetween January 2000 and December 2014, a total of 1925 patients with rectal cancer underwent surgical resection after PCRT. Medical records of 469 patients with pathologic node positivity were retrospectively reviewed.ResultsOf the 469 patients, 118 (25.2%) presented with ENE. ENE was observed more frequently in those with advanced tumor stage (higher ypT, ypN, and ypStage), lymphovascular invasion, and perineural invasion. Five-year disease-free survival rate was lower in patients with ENE-positive tumors than those with ENE-negative tumors (36.1% vs. 52.3%, P = .003). Similarly, 5-year overall survival rate was lower in patients with ENE-positive tumors than those with ENE-negative tumors (60.2% vs. 70.6%, P < .001). Multivariate analysis revealed that the presence of ENE was an independent poor prognostic factor for disease-free survival (hazard ratio = 1.412; 95% confidence interval, 1.074-1.857; P = .013) and overall survival (hazard ratio = 1.531; 95% confidence interval 1.149-2.039; P = .004).ConclusionThe presence of ENE in patients with rectal cancer undergoing PCRT is a negative prognostic factor, reflecting poor survival outcome.     

Predictive Factors for Pathologic Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer

Background: An accurate assessment of potential pathologic complete response(pCR) following neoadjuvant chemoradiotherapy(NCRT) is important for the appropriate treatment of rectal cancer. However, the factors that predict the response to neoadjuvant chemoradiotherapy have not been well defined. Therefore, this study analyzed the predictive factors on the development of pCR after neoadjuvant chemoradiation for rectal cancer. Methods: From January 2008 to January 2018, a total of 432 consecutive patients from a single institution patients who underwent a long-course neoadjuvant chemoradiotherapy were reviewed in this study. The clinicopathological features were analyzed to identify predictive factors for pathologic complete response in rectal cancer after neoadjuvant chemoradiation. Results: The rate of pathologic complete response in rectal cancer after neoadjuvant chemoradiation was 20.8%, patients were divided into the pCR and non-pCR groups. The two groups were well balanced in terms of age, gender, body mass index, ASA score, tumor stage, tumor differentiation, tumor location, surgical procedure, chemotherapy regimen and radiation dose. The multivariate analysis revealed that a pretreatment carcinoembryonic antigen (CEA) level of ≤5 ng/mL and an interval of ≥8 weeks between the completion of chemoradiation and surgical resection were independent risk factors of an increased rate of pCR. Conclusions: Pretreatment carcinoembryonic antigen (CEA) level of ≤5 ng/mL and an interval of ≥8 weeks between the completion of chemoradiation and surgical resection are predictive factors for pathologic complete response in rectal cancer after neoadjuvant chemoradiation. Using these predictive factors, we can predict the prognosis of patients and develop adaptive treatment strategies. A wait-and-see policy might be possible in highly selective cases.     

低位直肠癌术前同步放化疗的远期疗效及安全性研究

目的评估术前口服卡培他滨（希罗达）与放疗联合治疗局部进展期低位直肠癌的远期疗效及安全性。方法对局部进展期（T3／T4）低位直肠腺癌（距肛缘≤9Ccm）患者51例,术前给予口服卡培他滨（希罗达）并联合放疗。放疗结束后休息3—4周,按TME原则进行手术。结果3例患者临床完全消退（cCR）,占5．88％,未行手术;其余48例患者均行根治性切除术（R0）,实际保肛率90．20％（46／51）,10例术后病理检查未见肿瘤细胞,为病理消退（pCR）,总消退率为25．49％（13／51）。肿瘤降期41例,占80．39％。5年无病生存率为70．59％,总生存率为80．39％。放化疗过程中出现3、4级不良反应5例,无疾病进展、手术死亡者。结论术前口服卡培他滨联合放疗治疗局部进展期低位直肠癌是有效安全的。     

Adjuvant Treatment for Locally Advanced Rectal Cancer Patients After Preoperative Chemoradiotherapy: When,and for Whom?

BackgroundThe standard treatment for patients with locally advanced rectal cancer (clinical tumor, node, metastases [TNM] stage II or III) is radiotherapy before surgery (with or without concomitant fluoropyrimidine-based chemotherapy) followed by surgery. The role of adjuvant chemotherapy in this setting of patients is controversial in terms of the overall benefit on survival, the subgroup of patients who might not need it, and the best regimen (combination regimens vs. fluoropyrimidine alone).Patients and MethodsBased on the retrospective analysis of the clinical outcome of all patients with locally advanced rectal adenocarcinoma treated at our institute during the past 9 years, we comment on prognostic factors for local and distant metastases of patients who received neoadjuvant treatment followed by surgery, and the scientific evidence that can help to decide the adjuvant chemotherapy.ResultsWe conclude that pathological TNM stage after neoadjuvant chemoradiation (ypTNM) stage after surgery significantly affects disease-free and overall survival. In particular, patients with pathologically positive lymph nodes (ypN+) after surgery have a high probability of developing distant metastases.ConclusionypN+ patients are candidate for intensified adjuvant chemotherapy.     

直肠癌根治术后肝转移的危险因素分析

 目的分析与直肠癌根治术后肝转移的间隔时间、转移方式相关的危险因素,以提高有利证据预测及预防肝转移的发生。方法回顾性分析天津医科大学附属肿瘤医院自1995年收治的143例直肠癌患者,分析直肠癌根治术后肝转移发生间隔时间与肝转移方式的危险因素。结果原发肿瘤分化程度、Dukes分期及合并肝外转移情况与间隔时间有独立相关性。而肿瘤侵犯深度则是肝转移方式的独立危险因素。结论我们可以用原发肿瘤分化程度、Dukes分期及合并肝外转移情况估计直肠癌根治术后肝转移间隔时间,而肿瘤侵犯深度可用来估计肝转移方式。 关键词：     

DWI在直肠癌术前同步放化疗疗效预测中的作用

 目的 探讨DWI在局部进展期直肠癌（LARC）术前同步放化疗疗效预测中的作用。方法 将经内镜活检病理证实的LARC患者44例纳入分析。将患者术后病理分期与治疗前临床分期作比较,分为T-降期组和T-未降期组,比较放化疗前后以及组间ADC值、组间ADC变化量（ΔADC）以及变化率（ADC%）之间的差异,并根据ROC曲线得出疗效预测的最佳临界ADC值。结果 44例患者中7例（15.9%）获得pCR。患者同步放化疗前后ADC值差异有统计学意义（P=0.000）。同步放化疗前T-降期组ADC值明显低于T-未降期组,差异有统计学意义（P=0.007）。同步放化疗后T-降期组ADC值明显高于T-未降期组,差异有统计学意义（P=0.005）。T-降期组同步放化疗后ΔADC及ADC%均高于T-未降期组,差异有统计学意义（Z=-5.53, P=0.000; P=-5.09, P=0.000）。取治疗前ADC值0.87×10^-3 mm²/s作为预测T分期是否降期的临界值,ROC曲线下面积为0.697（95%CI: 0.539~0.855）,预测疗效的敏感度为87.5%,特异性为55.0%。结论 通过对ADC的定量分析可早期预测直肠癌患者对术前同步放化疗的敏感度,对术前同步放化疗疗效的判断也有一定的价值。     

直肠腔内超声在直肠癌新辅助放化疗的疗效评估中的应用价值

目的 探讨直肠腔内超声(ERUS)在直肠癌新辅助放化疗的疗效评估中的应用价值.方法 收取175例直肠癌患者的临床资料进行回顾性分析,按照是否进行新辅助放化疗分为A、B组.对新辅助化疗前后患者超声表现及参数进行考察,并对术前2组患者T分期、N分期准确率进行考察与比较.结果 A组患者中43例对新辅助放化疗反应良好,18例反应一般,21例反应较差.新辅助放化疗后患者肿瘤长短径明显缩短,与新辅助化疗前相较差异有统计学意义(P＜0.05),而与术中结果无统计学差异(P＞0.05).A组患者术前ERUS诊断T分期准确率为78.04％,诊断N分期准确率为80.49％,与B组患者准确率相较无统计学差异(P＞0.05).结论 直肠腔内超声可反映新辅助化疗前后直肠病灶改变,在直肠癌新辅助放化疗的疗效评估中具有一定价值.     

Pathological complete response may underestimate distant metastasis in locally advanced rectal cancer following neoadjuvant chemoradiotherapy and radical surgery: Incidence,metastatic pattern,and risk factors

AimTo evaluate the pattern of tumor relapse of pathological complete response (pCR) patients with locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME), and to identify predictive factors of distant metastasis in pCR patients after nCRT.MethodThis was a retrospective analysis of 118 LARC patients who achieved a pCR following nCRT and TME from 2008 to 2015. Clinicopathological and therapeutic parameters were evaluated as possible predictors of distant metastasis-free survival (DMFS), and COX regression analysis was performed.ResultsAfter a median follow-up of 57 months, the 5-year overall and disease-free survival rates were 94.7% and 88.1%, respectively. Overall, 6 patients (5.1%) died, no local recurrence occurred, 13 patients (11%) developed distant metastases, including lung (n = 5), liver (n = 2), bone (n = 3), lung and brain (n = 1), peritoneal (n = 1), and spleen (n = 1) metastasis. On univariate analysis, tumor distance from the anal verge (HR = 0.706, P = 0.039), acellular mucin pools (HR = 6.687, P = 0.002), and MUC1 expression (HR = 8.280, P < 0.001) were independently associated with DMFS. COX regression demonstrated that MUC1 expression (HR = 3.812, P = 0.041) remained to be an independent predictor of DMFS in pCR patients.ConclusionDistant metastasis still remained a major concern in pCR patients following nCRT and TME. Tumor distance from the anal verge, acellular mucin pools, and MUC1 expression were associated with distant metastasis in patients with pCR. MUC1 staining remained to be an independent risk factor for DMFS. Such information could facilitate treatment decision in these patients, such as adjuvant chemotherapy and follow-up.     

Positron emission tomography as predictor of rectal cancer response during or following neoadjuvant chemoradiation

Positron emission tomography (PET) shows great promise as a tool to evaluate the effectiveness of rectal cancer neoadjuvant therapy as it has demonstrated high predictive value in several studies. Creating a standardized method of using PET has the potential to reduce ineffective treatments. However, relevant studies have been heterogenous in approach, making any unified standard difficult to establish. PET related parameters used to assess treatment response include magnitude and change of standard uptake value, total lesion glycolysis, and visual response. Finding the best evaluation interval and parameters to use for interpreting PET results in the neo-adjuvant treatment of rectal cancer needs additional study.     

中晚期直肠癌的综合治疗

目的探讨中晚期直肠癌综合治疗方法。方法术前行股动脉插管化疗,然后行根治性手术切除。术后行静脉化疗和／或放疗。结果插管化疗后病人临床症状减轻,肿瘤变小。肿瘤缩小约＞50％3例,25-50％4例,＜25％1例,无明显变化1例。9例病人均行根治性手术切除,术后近期无局部复发,无肝转移。结论首先应用动脉插管化疗然后行手术、化疗和／或放疗,能够提高手术切除率、降低局部复发及肝转移,是治疗中晚期直肠癌较为合理的综合治疗模式。     

直肠癌术前CT分期与术后病理比较研究

目的探讨直肠癌术前CT分期与术后病理表现的关系.方法收集了经手术病理证实的直肠癌患者52例,分析其CT表现,并与术后病理结果对照.结果CT对侵犯深度判定的准确率达88.5%,对转移淋巴结判定的准确率达96%,能够很好显示病变范围、侵润程度、周围器官受侵及淋巴结转移情况.CT分期与病理分期基本相符.结论通过直肠癌的CT征象分析,对于术前推断肿瘤的恶性程度及患者的预后有重要价值.     

同步放化疗后联合化疗对局部晚期宫颈癌患者预后的研究

目的 探讨同步放化疗后巩固化疗对局部晚期宫颈癌患者预后的影响.方法 选择拟行宫颈癌同步放化疗的患者200例,随机分为观察组和对照组,观察组采用同步放化疗后巩固化疗治疗,对照组采用单纯同步放化疗治疗,比较两组患者近期疗效、不良反应发生率、2年生存率和局部无进展生存率.结果 观察组近期疗效总有效率、胃肠道反应、骨髓抑制发生率(92.0％,90.0％,98.％)与对照组(88.0％,84.0％,96.0％)比较差异无显著统计学意义(P＞0.05);但观察组2年生存率和局部无进展生存率(92.0％,88.0％)显著高于对照组(78.0％,65.0％),具有统计学意义(P＜0.01).结论 局部晚期宫颈癌患者同步放化疗后巩固化疗可有效改善患者预后,有望成为局部晚期宫颈癌患者的有效治疗手段.