Extensive surgery after high-dose preoperative chemoradiotherapy for locally advanced recurrent rectal cancer

PURPOSE: This was a pilot study of high-dose preoperative concurrent radiation and chemotherapy before extensive surgery in patients with locally advanced recurrent rectal cancer. Here we report on curative resectability, acute toxicities during chemoradiotherapy, surgical complications, local control, and three-year survival rates achieved with this aggressive multimodal regimen. METHODS: Between 1994 and 1997, 35 previously nonirradiated patients with pelvic recurrence of rectal cancer were entered in the study. All patients presented with tumor contiguous or adherent to adjacent pelvic organs and were not deemed amenable to primary curative surgery. A total radiation dose of 50.4 Gy with a small-volume boost of 5.4 to 9 Gy was delivered in conventional fractionation (single dose, 1.8 Gy). 5-Fluorouracil was scheduled as a continuous infusion of 1,000 mg/m²/day on Days 1 to 5 and 29 to 33. Six weeks after completion of chemoradiotherapy, patients were reassessed for resectability, and radical surgery was attempted whenever feasible. RESULTS: After preoperative chemoradiotherapy 28 of 35 patients (80 percent) underwent resection with curative intent. In 16 of 35 patients (57 percent) extended resection of adjacent organs was performed. Resections with negative margins were achieved in 17 patients (61 percent); 9 patients had microscopic, and 2 patients had gross residual disease. There was no postoperative mortality. Fourteen patients (44 percent) experienced postoperative complications. Toxicity from chemoradiotherapy occurred mainly as diarrhea (National Cancer Institute Common Toxicity Criteria Grade 3; 23 percent), dermatitis (Grade 3; 11 percent), and leucopenia (Grade 3; 11 percent). One patient died of tumortoxic multiple organ failure during chemoradiotherapy. With a median follow-up of 27 months, local re-recurrence after curative resection was observed in only three patients (18 percent); six patients developed distant metastases. Three-year actuarial survival rate was significantly improved after complete resection (82 percent) as compared with noncurative surgery (38 percent;P=0.03). CONCLUSION: A combination of high-dose preoperative chemoradiotherapy followed by extended surgery can achieve clear resection margins in more than 60 percent of patients with recurrent rectal tumor not amenable to primary surgery. An encouraging trend evolved for this multimodal treatment to improve long-term local control and survival rate.Presented at the meeting of the German Society for Radiation Oncology, Radiation Biology and Medical Physics (DEGRO), Nürnberg, Germany, November 7 to 10, 1998.     

A prospective analysis of patient outcome following treatment of T3 rectal cancer with neo-adjuvant chemoradiotherapy and transanal excision

Background

Local excision is an alternative to anterior or abdomino-perineal resection in patients with early rectal cancer. In more advanced disease, neo-adjuvant therapy (CRXT) can result in significant disease regression such that local excision may be considered. The primary aim was to assess oncological outcome in patients with T3 rectal cancer treated with CRXT and local excision due to unsuitability for or aversion to anterior resection and stoma. The secondary aim was to examine oncological outcomes in patients treated in a similar way in the published literature.

Methods

Between July 2006 and July 2009, patients with rectal cancer staged T3, N0/N1, M0 who were deemed unfit for or who refused anterior resection were offered long-course CRXT. Patients were restaged 8 weeks following completion. If there was a good response (regression grade 2 or 3 clinically and radiologically), full thickness transanal excision was performed. All patients were followed regularly (monthly CT abdomen/pelvis and annual endoscopy) to assess for recurrence of disease. A literature search of PubMed was performed to identify all prospective data available of T3 rectal cancers managed with CRXT and local excision.

Results

Ten patients were treated over 3 years. Six patients had complete pathological response, while four patients had a partial response. The resection margins following local excision were clear in all. There was no local recurrence (median follow-up 24 months, range 9–42 months).

Conclusion

Neo-adjuvant chemoradiotherapy and local excision is an option in patients unfit for or averse to major surgical resection if there is a good response to CRXT.

     

Safety and factors contributing to the difficulty of laparoscopic surgery for rectal cancer treated with preoperative chemoradiotherapy

Background

The safety of laparoscopic surgery for rectal cancer following chemoradiotherapy (CRT) has not been fully established. The aim of our retrospective study was to examine the outcomes and the factors contributing to the difficulty of laparoscopic surgery after CRT.

Methods

Eighty-seven consecutive rectal cancer patients treated with CRT were analyzed. Clinicopathological factors were compared between laparoscopic surgery (n = 57) and open surgery (n = 30) groups, and factors that correlated with operation time and blood loss were analyzed in low anterior resection (LAR) cases in the laparoscopic surgery group (n = 46).

Results

There was less blood loss in the laparoscopic surgery group than in the open surgery group (191 vs. 1,043 ml, p = 0.0001), and the operation time in the two groups was similar (329 vs. 322 min, p = 0.8). The rate of conversion from laparoscopic surgery to open surgery was 1.8 %. There was no significant difference in the morbidity rate (laparoscopic surgery 22.8 % vs. open surgery 33.3 %, p = 0.3). All circumferential resection margins were clear. Three-year cumulative rates of local recurrence were as follows: laparoscopic surgery: 1.9 % vs. open surgery: 8.4 % (p = 0.4), and distant recurrence was 28.5 % in laparoscopic surgery vs. 22.7 % in open surgery (p = 0.8) and these rates were not significantly different. In laparoscopic LAR cases, a shorter distance of the tumor from the anal verge was associated with a longer operation time. A high computed tomography Hounsfield units value of the mesorectum (CTV) was associated with increased blood loss in the first 23 cases, but not in the other 23 cases.

Conclusions

Laparoscopic surgery following CRT was safe and feasible. A shorter anal verge was associated with a longer operation time. Blood loss increased in cases with high CTV, but this can likely be mitigated by experience.     

直肠癌术前放疗进展

2004年德国CAO/ARO/AIO-94临床研究奠定了局部晚期直肠癌术前新辅助放化的治疗策略。近年来,全世界对于如何进一步提高放化疗疗效和个体化治疗在放疗同期药物配比、新辅助放化疗前加入诱导化疗、延长新辅助放化疗至手术间隔期、放化疗后器官保留和中国患者适应性等五方面进行了探索,本文将对上述方面进行阐述。     

Impression of prognosis regarding pathologic stage after preoperative chemoradiotherapy in rectal cancer

AIM: To ascertain pathologic stage as a prognostic indicator for rectal cancer patients receiving preoperative chemoradiotherapy(PCRT).METHODS: Patients with mid- and low rectal carcinoma(magnetic resonance imaging- based clinical stage Ⅱ or Ⅲ) between 2000 and 2009 and treated with curative radical resection were identified. Patients were divided into two groups: PCRT and No-PCRT. Recurrence-free survival(RFS) was examined according to pathologic stage and addition of adjuvant treatment.RESULTS: Overall, 894 patients were identified. Of these, 500 patients received PCRT. Adjuvant chemotherapy was delivered to 81.5% of the No-PCRT and 94.8% of the PCRT patients. Adjuvant radiotherapy was given to 29.4% of the patients in the No PCRT group. The 5-year RFS for the No-PCRT group was 92.6% for StageⅠ, 83.3% for Stage Ⅱ, and 72.9% for Stage Ⅲ. The 5-year RFS for the PCRT group was 95.2% for yp Stage 0, 91.7% for yp StageⅠ, 73.9% for yp Stage Ⅱ, and 50.7% for yp Stage Ⅲ.CONCLUSION: Pathologic stage can predict prognosis in PCRT patients. Five-year RFS is significantly lower among PCRT patients than No-PCRT patients in pathologic stage Ⅱ and Ⅲ. These results should be taken into account when considering adjuvant treatment for patients treated with PCRT.     

The timing of surgery after preoperative short-course S-1 chemoradiotherapy with delayed surgery for T3 lower rectal cancer

Purpose

The purpose of this study was to analyze the influence of variations in clinical practice regarding the timing of surgery with short-course chemoradiotherapy with delayed surgery (SCRT-delay) for lower rectal cancer.

Methods

A total of 171 patients with T3 N0-2 lower rectal cancer treated with SCRT-delay (25 Gy/10 fractions/5 days (S-1); days 1–10) were retrospectively evaluated. The median waiting period of 30 days was used as a discriminator (group A: waiting period, ≤30 days; group B: waiting period, ≥31 days). Preoperative treatment responses and oncological outcomes were analyzed.

Results

The mean waiting periods for groups A and B were 24.4?±?5.3 and 41.4?±?12.3 days, respectively. There were no statistically significant differences between the two groups in any of the clinical variables. The clinicopathological outcomes were as follows: T downstaging (43.5 vs 37.2 %; p?=?0.400), negative yp N (67.1 vs 75.6 %; p?=?0.218), pCR (7.1 vs 1.2 %; p?=?0.119). The 5-year local recurrence-free survival (89.3 vs 87.6 %; p?=?0.956), the recurrence-free survival (82.2 vs 78.8 %; p?=?0.662), and the overall survival (88.5 vs 84.4 %; p?=?0.741), all of which were similar between the two groups.

Conclusions

The longer waiting period did not increase the tumor downstaging and not improve the oncological outcomes for T3 lower rectal cancer treated with SCRT-delay. In addition, considering that the impaired leukocyte response occurred during the sub-acute period, any time after the sub-acute period (day 12) up to 30 days after radiotherapy would be a suitable waiting period.     

Hyperfibrinogenemia after preoperative chemoradiotherapy predicts poor response and poor prognosis in rectal cancer

Purpose  

Although hyperfibrinogenemia has been reported in patients with colorectal cancer, neither its clinical implications nor the effect of chemoradiotherapy (CRT) on the fibrinogen levels have been fully investigated. We investigated the clinical significance of pre- and post-CRT fibrinogen levels in patients with rectal cancer.     

Comparative study for preoperative staging of rectal cancer

A comparative study of preoperative evaluation of rectal cancer is presented. Sixty-eight patients with rectal cancer were examined digitally and by computerized tomography and transrectal ultrasound. Preoperative staging was compared with pathologic findings at surgery. Digital examination and transrectal ultrasound were accurate in 82.8 and 76.2 percent, respectively and were superior to CT, which was accurate in 65.5 percent of cases for assessment of rectal wall invasion. All three modes play a role in preoperative assessment, but digital examination and rectal ultrasound appear to be more effective.     

Randomized controlled study on preoperative chemoradiotherapy followed by surgery versus surgery alone for esophageal squamous cell cancer in a single institution

The purpose of the present study was to compare the clinical results between preoperative chemoradiotherapy followed by surgery (CRT group) and surgery alone (Surgery group) by a randomized controlled study. Twenty-two patients were assigned to the CRT group and 23 to the Surgery group. A total radiation dose of 40 Gy was applied and in the same period, intravenous chemotherapy was performed using cisplatin (7 mg over 2 h) and 5-fluorouracil (5-FU; 350 mg over 24 h). Surgical treatment was performed in 20 patients in the CRT group except for two patients with bone metastasis after CRT. According to histological effects of primary tumors, the number of patient with Grades 1, 2 and 3 was 11, 7 and 3, respectively. Frequency of lymphatic and venous invasion was significantly lower in the CRT group than in the Surgery group. The 5-year survival rate was 57% in the CRT group and 41% in the Surgery group (P = 0.58). According to the histological effect in the CRT group, 5-year survival was 30% for Grade 1, 83% for Grade 2 and 100% for Grade 3 (P = 0.0069). This randomized trial did not demonstrate a statistically significant survival difference between the CRT group and the Surgery group.     

Comparison of the erectile function in male patients with rectal cancer treated by preoperative radiotherapy followed by surgery and surgery alone

Purpose  

This study evaluates the erectile function of male patients treated by preoperative radiotherapy followed by surgery and surgery alone for locally advanced rectal cancer.     

术前联合放化疗与单纯手术治疗食管癌疗效的Meta分析

目的:比较术前联合放化疗联合手术与单纯手术对可切除食管癌患者的影响.方法:使用计算机及手工检索两种方法在Pubmed和Embase中搜索相关随机对照实验,以确保无文献遗漏.结果:共纳入包含1544名患者的12篇文献.术前联合放化疗较单纯手术明显提高了患者的1年、3年和5年生存率,其OR(95%CI,P值)分别为1.28(1.01-1.64,P=0.05);1.84(1.29-2.63,P=0.00);1.53(1.17-2.00,P=0.00).术前放化疗增加了术后死亡率,但并不增加术后的并发症发生率,其OR(95%CI;P值)分别为1.71(1.06-2.76,P=0.03)和1.15(0.89-1.49,P=0.28).术前放化疗降低了肿瘤局部复发率,但对远处转移无影响,其对应的OR(95%CI,P值)分别为0.64(0.41-0.99,P=0.04)和0.94(0.58-1.31,P=0.73).结论:术前放化疗联合手术可显著改善食管癌患者的生存率,值得临床应用推广.     

Impact of interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer patients

BACKGROUND Epidemiologically, in China, locally advanced rectal cancer is a more common form of rectal cancer. Preoperative neoadjuvant concurrent chemoradiotherapy can effectively reduce the size of locally invasive tumors and improve disease-free survival(DFS) and pathologic response after surgery. At present, this modality has become the standard protocol for the treatment of locally advanced rectal cancer in many centers, but the optimal time for surgery after neoadjuvant therapy is still controversial.AIM To investigate the impact of time interval between neoadjuvant therapy and surgery on DFS and pathologic response in patients with locally advanced rectal cancer.METHODS A total of 231 patients who were classified as having clinical stage II or III advanced rectal cancer and underwent neoadjuvant chemoradiation followed by surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from November 2014 to August 2017 were involved in this retrospective cohort study. The patients were divided into two groups based on the different time intervals between neoadjuvant therapy and surgery: 139(60.2%) patients were in group A(≤ 9 wk), and 92(39.2%) patients were in group B( 9 wk). DFS and pathologic response were analyzed as the primary endpoints. The secondary endpoints were postoperative complications and sphincter preservation.RESULTS For the 231 patients included, surgery was performed at ≤ 9 wk in 139(60.2%) patients and at 9 wk in 92(39.8%). The patients' clinical characteristics, surgical results, and tumor outcomes were analyzed through univariate analysis combined with multivariate regression analysis. The overall pathologic complete response(p CR) rate was 27.2%(n = 25) in the longer time interval group( 9 wk) and 10.8%(n = 15) in the shorter time interval group(≤ 9 wk, P = 0.001). The postoperative complications did not differ between the groups(group A, 5% vs group B, 5.4%; P = 0.894). Surgical procedures for sphincter preservation were performed in 113(48.9%) patients, which were not significantly different between the groups(group A, 52.5% vs group B, 43.5%; P = 0.179). The p CR rate was an independent factor affected by time interval(P = 0.009; odds ratio [OR] = 2.668; 95%CI: 1.276-5.578). Kaplan-Meier analysis and Cox regression analysis showed that the longer time interval( 9 wk) was a significant independent prognostic factor for DFS(P = 0.032; OR = 2.295; 95%CI: 1.074-4.905), but the time interval was not an independent prognostic factor for overall survival(P 0.05).CONCLUSION A longer time interval to surgery after neoadjuvant therapy may improve the p CR rate and DFS but has little impact on postoperative complications and sphincter preservation.     

Accuracy of transrectal ultrasound in predicting pathologic stage of rectal cancer before and after preoperative radiation therapy

Transrectal ultrasound (TRUS) and CT scan staging of rectal cancers before, and TRUS staging after, 45 Gy of irradiation were compared with the pathologic stage of the resected specimen in 19 patients. Accuracy of TRUS before and after irradiation, and of CT scan before irradiation, was 32 percent, 63 percent, and 53 percent, respectively. CT scan before and TRUS after irradiation predicted lymph node involvement in 79 percent and 68 percent of cases, respectively. Positive predictive value for lymph node involvement before irradiation was 60 percent for CT scan and 37.5 percent for TRUS; after irradiation, it was 50 percent for TRUS. Negative predictive value was 100 percent for CT scan and TRUS before radiation and 88 percent for TRUS after irradiation. Preoperative radiation therapy makes TRUS and CT scan less effective as staging techniques. The absence of lymph nodes on TRUS and CT scan before and after irradiation is reliable.Read in part at the Tripartitate Meeting, Birmingham, England, June 19 to 22, 1989.     

Discharge destination following rectal cancer resection: an analysis of preoperative and intraoperative factors

International Journal of Colorectal Disease - Rectal cancer resections can be associated with long and complicated postoperative recoveries. Many patients undergoing these operations are discharged...     

Influence of erythropoietin on transfusion requirements in patients receiving preoperative chemoradiotherapy for rectal cancer

PURPOSE: Perioperative homologous blood transfusion has been suggested to have an adverse effect on survival in patients undergoing resection of colorectal cancers. Preoperative therapy is being increasingly used for rectal cancer patients and has an adverse effect on erythropoietic capacity. The objectives of this study were to evaluate the feasibility and safety of administration of recombinant human erythropoietin to patients receiving preoperative therapy for rectal cancer and to assess the impact of such treatment on blood transfusion requirements. METHODS: The study was an open-label, Phase I and II, nonrandomized, two-center trial. All patients received 50.4 Gy of irradiation with 5-fluorouracil infusions. Ten patients diagnosed with rectal cancer received 250 U/kg of recombinant human erythropoietin subcutaneously three times per week during preoperative radiation and chemotherapy. Oral iron was given to patients receiving erythropoietin. Ten contemporaneously treated patients who received both radiation and chemotherapy were used as controls. RESULTS: Of the 20 patients 13 were males; mean age was 64 years. Surgical procedures that patients underwent were abdominoperineal resection (14 patients), low anterior resection (4 patients), coloanal anastomosis (1 patient), or none (1 patient). There were no significant differences between groups in age, gender, stage or hemoglobin levels before therapy. No adverse reactions to erythropoietin were encountered. Hemoglobin levels were significantly higher in the treatment group during Weeks 1,3, and 5 (P<0.02 for each). Transfusion requirements were significantly decreased in patients who received erythropoietin (0.4vs. 3.7 units;P<0.0003). CONCLUSIONS: The data showed that use of erythropoietin during preoperative therapy can prevent the decline in hemoglobin that commonly occurs during therapy. Further, this was not associated with adverse events and significantly decreased the need for perioperative blood transfusions. This suggests that the use of erythropoietin in support of a preoperative chemoradiotherapy regimen for patients with rectal cancer is safe and should be considered. Whether such transfusion avoidance will translate into a survival benefit in this setting will require a large, prospective, clinical trial.Supported in part by a grant from Ortho-Biotech.Presented at the Experimental Therapeutics section of the Digestive Disease Week meeting, New Orleans, Louisiana, May 19 to 24, 1998. No reprints are available.