T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival

PURPOSE: Preoperative chemoradiation therapy is used widely in the treatment of rectal cancer. The predictive value of response to neoadjuvant remains uncertain. We retrospectively evaluated the impact of response to preoperative and, specifically, of T-level downstaging, nodal downstaging, and complete pathologic response after chemoradiation therapy on oncologic outcome of patients with locally advanced rectal cancer. METHODS: There were 88 patients with ultrasound Stage T3/T4 midrectal (n = 37) and low rectal (n = 51) cancers (63 males; mean age 62.6 years). All patients were treated by preoperative 5-fluorouracil-based chemotherapy and pelvic radiation followed by surgical resection in six weeks or longer (56 sphincter-preserving resections). RESULTS: T-level downstaging after neoadjuvant treatment was demonstrated in 36 (41 percent) of 88 patients, and complete pathologic response was observed in 16 (18 percent) of the 88. Of the 42 patients with ultrasound-positive nodes, 27 had no evidence of nodal involvement on pathologic evaluation (64 percent). The overall response rate (T-level downstaging or nodal downstaging) was 51 percent. At a median follow-up of 33 months, 86.4 percent of patients were alive. The overall recurrence rate was 10.2 percent (three patients had local and six had metastatic recurrences). Patients with T-level downstaging and complete pathologic response were characterized by significantly better disease-free survival (P = 0.03, P = 0.04) and better overall survival (P = 0.07, P = 0.08), according to Wilcoxons test comparing Kaplan-Meier survival curves. None of the patients with complete pathologic response developed recurrence or died during the follow-up period. CONCLUSION: T-level downstaging and complete pathologic response after preoperative chemoradiation therapy followed by definitive surgical resection for advanced rectal cancer resulted in decreased recurrence and improved disease-free survival. Advanced rectal cancers that undergo T-level downstaging and complete pathologic response after chemoradiation therapy may represent subgroups that are characterized by better biologic behavior.     

Lymph node micrometastasis in stage II distal rectal cancer following neoadjuvant chemoradiation therapy

Objective The objective was to determine the presence and frequency of micrometastasis in lymph nodes of patients with rectal cancer treated by preoperative chemoradiation followed by curative resection.Patients and methods All 56 patients included were treated with 5-FU and leucovorin plus 5,040 cGy, followed by radical surgery and were diagnosed with stage II distal rectal adenocarcinoma after complete pathological examination (ypT3-4N0M0). Immunohistochemistry was assessed with cytokeratin monoclonal antibody AE1/AE3. Three 4-m paraffin sections were obtained from each lymph node, cut at 50 m apart from each other. The results were reviewed by two independent pathologists.Results Mean number of lymph nodes was 9.6 per patient. Four patients (7%) and seven lymph nodes (1.35%) were positive for micrometastasis. Three patients had pT3 and one a pT4 tumor. One of the patients had positive micrometastasis and the presence of mucinous deposits. One other patient had mucinous deposits without any micrometastasis. All four patients are alive with no evidence of recurrent disease. Fourteen patients negative for micrometastasis had recurrent disease (25%), eight systemic (14.7%) and six locoregional (10.3%). There were two cancer-related deaths. The mean follow-up period was 39 months.Conclusion Patients with rectal cancer treated by preoperative chemoradiation showed a surprisingly low rate of micrometastasis detection (7%), even in high-risk patients (T3 and T4 tumors). Lymph node micrometastasis was not associated with decreased overall or disease-free survival. The identification of mucinous deposits on lymph nodes with no viable tumor cells may be direct evidence of lymph node downstaging. The downstaging effect of preoperative chemoradiation therapy may be significant in reducing even micrometastasis detection in low rectal cancer managed by this treatment strategy.     

Assessment of neoadjuvant chemotherapy for patients with advanced squamous cell carcinoma of the esophagus

Background  Neoadjuvant chemotherapy for advanced esophageal cancer is beneficial for responders, whereas it may provide no clinical benefits or even prove harmful in non-responders. Methods  This study retrospectively compared the pathological findings and prognosis of 60 patients with UICC non-T4 stage III and IV, who received chemotherapy followed by surgery, and 96 patients with non-T4 stage III and IV cancer, who underwent surgery alone. The treatment regimen of cisplatin (70 mg/m²/day on day 1), adriamycin (30 mg/m²/day on day 1), and 5-fluorouracil (750 mg/m²/day on days 1–7) was administered for two cycles. Responders represented patients with histological effect of grade 1b-3 following therapy; non-responders represented those with grade 0-1a histological effect. Results  Survival was not significantly different between the neoadjuvant chemotherapy group and the surgery-alone group. Responders showed a tendency of earlier postoperative pStages than preoperative cStages (P = 0.08), better survival (P = 0.10), significantly fewer metastatic nodes, and significantly less extensive lymphatic invasion than the surgery-alone group. However, non-responders showed no significant differences in the degree of downstaging, number of metastatic nodes, extent of lymphatic and venous invasion, and survival rate as compared with the surgery-alone group. Comparison of overall survival between the chemotherapy and surgery-alone groups after matching for pathological stage showed that the survival of pStage II patients of the chemotherapy group was significantly better than the pStage II patients of the surgery-alone group (P = 0.04), whereas that of pStage III and IV patients of the chemotherapy group was not significantly different from the same-stage patients of the surgery-alone group. Conclusions  These results suggest that chemotherapy improves prognosis of responders significantly more than those who show downstaged pathological stage. However, the chemotherapy does not give any clinical benefit for non-responders.     

Clinical parameters predicting pathologic tumor response after preoperative chemoradiotherapy for rectal cancer

PURPOSE: To identify pretreatment clinical parameters that could predict pathologic tumor response to preoperative chemoradiotherapy (CRT) for rectal cancer. METHODS AND MATERIALS: The study involved 351 patients who underwent preoperative CRT followed by surgery between October 2001 and July 2006. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and tumor regression. Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. RESULTS: Tumor downstaging (defined as ypT2 or less) was observed in 167 patients (47.6%), whereas tumor regression (defined as Dworak's Regression Grades 3 or 4) was observed in 103 patients (29.3%) and complete regression in 51 patients (14.5%). Multivariate analysis found that predictors of downstaging were pretreatment hemoglobin level (p = 0.045), cN0 classification (p < 0.001), and serum carcinoembryonic antigen (CEA) level (p < 0.001), that predictors of tumor regression were cN0 classification (p = 0.044) and CEA level (p < 0.001), and that the predictor of complete regression was CEA level (p = 0.004). CONCLUSIONS: The data suggest that pretreatment CEA level is the most important clinical predictor of pathologic tumor response. It may be of benefit in the selection of treatment options as well as the assessment of individual prognosis.     

Predicting tumor response after preoperative chemoradiation using clinical parameters in rectal cancer

AIM: To evaluate the clinical parameters and identify a better method of predicting pathological complete response (pCR). METHODS: We enrolled 249 patients from a database of 544 consecutive rectal cancer patients who underwent surgical resection after preoperative chemoradiation therapy (PCRT). A retrospective review of morphological characteristics was then performed to collect data regarding rectal examination findings. A scoring model to predict pCR was then created. To validate the ability of the scori...     

大肝癌58例患者经肝动脉插管化疗栓塞降期治疗体会

目的 探讨大肝癌经肝动脉插管化疗栓塞降期治疗后,实施二期肝切除和肝脏移植手术的可行性.方法 回顾性分析2006年6月至2010年3月58例首次诊断为切除困难的大肝癌患者(直径＞5 cm),实施肝动脉插管化疗栓塞降期治疗后,分别实施肝移植术(36例),二期肝切除(22例).利用Kaplan-Meier法和COX风险比例模型计算累积总体生存率、无瘤生存率和影响预后的因素.结果 58例患者术后中位随访22个月,平均生存时间为(23.57±1.54)个月.肝移植组(36例)1、2、3年总体生存率(OS)、无瘤生存率(RFS)分别是94%、84%、73%和88%、75%、64%.肿瘤平均复发时间为(12.3±6.4)个月(3～23个月).其中28例患者降期至Milan标准,1、2、3年总体生存率和无瘤生存率优于非降期组(OS%%、88%、75%vs 92%、48%、48%P=0.067;RFS95%、95%、79%vs 76%、40%、40%P=0.002).肝切除组1、2、3年总体生存率、无瘤生存率分别为100%、64%、52%和72%、49%、49%,平均复发时间为(9.3±4.5)个月.经TACE肝移植组患者远期预后优于肝切除组(OS,P=0.178;RFS,P=0.139).多因素分析只有病理肿瘤总直径≥7 cm(P=0.002,RR=6.578)、微血管侵犯(P=0.001,RR=5.737)、低分化(P=0.048,RR=4.335)因素与肿瘤复发显著相关.结论 部分大肝癌经肝动脉栓塞化疗治疗降期后可以成功实施根治性肝切除和肝移植,并获得满意的远期预后.

Abstract：

Objective To evaluate the feasibility of sequential liver resection or liver transplantation following downstaging of larger hepatocellular carcinoma (HCC) by transcatheter arterial chemoembolization (TACE). Methods A retrospective study was conducted. And a total of 58 patients with unresectable larger HCC (diameter ＞5 cm) from June 2006 to March 2010 underwent TACE. According the outcomes of TACE, they received liver transplantation ( LT, n = 36) and liver resection ( LR, n = 22) respectively. The overall survival (OS) and recurrence-free survival (RFS) rates were calculated by the Kaplan-Meier method. The multivariate analyses for the influencing factors were evaluated by the Cox proportional hazard model. Results The median follow-up period of 58 cases was 22 months and the median survival time 23.57±1.54 months. The 1 -, 2 - , 3 - year OS and RFS rates after LT was 94%, 84% & 73% and 88% , 75%& 64% respectively. The median recurrence time was 12. 3 ± 6. 4 months ( range: 3 - 23). Twenty-eight patients had adequate downstaging to qualify for LT under the Milan criteria The 1 - , 2 - , 3 - year OS and RFS of the downstaging group was better than those of the non-downstaging group (OS: 96%, 88%, 75%vs92%,48%,48% P=0.067; RFS:95%,95%,79% vs76%,40%, 40% P=0.002). The1-,2 -, 3 -years OS and RFS after LR was 100%, 64% & 52% and 72%, 49% & 49% respectively. The median recurrence time was 9.3 ±4.5 months (range:3 -23). The long-term results of LT group following TACE were better than those of LR group( OS, P =0. 178; RFS, P =0. 139). The multivariate analyses showed that only pathologic total tumor diameter ＞7 cm (P =0. 002, RR =6. 578) , microvascular invasion ( P =0. 001, RR = 5. 737 ) and poor differentiation (P=0.048, RR = 4. 335 ) were significantly correlated with tumor recurrence. Conclusion Sequential liver resection and liver transplantation after downstaging by TACE are feasible for some larger HCCs. And the long-term prognosis is satisfactory.     

新辅助治疗评分预测临床Ⅲ期中低位直肠癌预后研究

目的 探讨临床Ⅲ期中低位直肠癌经术前同步放化疗后降期以及新辅助治疗评分(NAR)对预后的影响。方法 分析2006—2014年间本中心收治的经盆腔核磁或腹盆CT确诊的cⅢ期中低位直肠癌195例患者,术前放疗42.0~50.4 Gy (中位数50 Gy,93.8%患者放疗剂量≥50 Gy),卡培他滨±奥沙利铂同步化疗于同步放化疗后4—15周(中位数7周) TME手术(R0切除)。分析患者降期(yp0—Ⅱ期)及NAR评分(根据cT、ypT/N分期计算)对预后影响,应用Kaplan-Meier法计算3年DFS并Logrank法检验。结果 全组患者中位随访44个月(6.7~125.5个月),3年DFS为76.8%。术前同步放化疗后降期显著影响3年DFS (92.2%∶56.8%,P=0.000)。全组患者中位NAR评分15.0分(0~65.0分),其中评分低者3年DFS优于评分高者[≤15.0分(90.1%)∶>15.0分(57.0%),P=0.001];在降期患者中低NAR评分仍可获得更好的预后[≤8.4分(95.1%)∶>8.4分(87.5%),P=0.022]。结论 cⅢ期中低位直肠癌经术前同步放化疗后降期者预后相对较好,NAR评分可有效预测患者预后。     

Downstaging Hepatocellular Carcinoma with Yttrium-90 radioembolization: Resection or transplantation?

Trans Arterial Radio Embolization with Yttrium 90 in the treatment of Hepatocellular Carcinoma is becoming a new interesting tool in the treatment of patients that are considered non resectable and non transplantable. A successful downstaging could improve the number of patients that could benefit from a resection or a liver transplantation, but some points still need to be addressed.