A case of advanced rectal cancer responding to 5-fluorouracil based preoperative chemoradiation therapy

We report a case of a 67-year-old female with advanced rectal cancer that showed a significant response after administration of preoperative chemoradiation therapy. 5-fluorouracil (5-FU, 300 mg/m2/day) was administered by 24-hour continuous intravenous infusion after the cancer had been decreased in size by radiation (2 Gy) administered for 20 days preoperatively. Consequently, the patient underwent a low anterior resection with lymph node dissection (D 2), which resulted in a curative resection of the cancer cells macroscopically. Histological examination revealed no residual cancer cells in the resected specimen (CR). Preoperative chemoradiation therapy appears a promising regimen for patients with advanced lower rectal cancer, and can be considered to extend the indication for laparoscopic operations for advanced rectal cancer.     

Long-term complete response in a case of unresectable rectal cancer following chemoradiation

We report a case of unresectable rectal cancer in a 53-year-old male treated with chemoradiation. Radiation therapy was delivered with a total pelvic dose of 45 Gy together with oral administration of 5'-DFUR (1,200 mg/day). The patient received one course of combination chemotherapy consisting of cisplatin, 100 mg/body x 1 day, and 5-FU, 1,000 mg/body x 5 days, followed by radiation therapy. Oral administration of tegafur-uracil (300 mg/day) was continued for five years following the chemoradiation. The patient is now disease-free 75 months after the initial surgery. Chemoradiation can be managed to obtain a complete remission of some locally advanced rectal cancers.     

Two cases of advanced low rectal cancer, preoperative chemo-radiation therapy leading to complete histological response

We report two cases of advanced low rectal cancer, with preoperative chemo-radiation therapy leading to a complete histological response. Case 1 was a 74-year-old male who was diagnosed as advanced low rectal cancer. Preoperative chemo-radiation (a total of 45 Gy radiation+oral 5'-DFUR 800 mg/day for 3 weeks) was performed. Then, 30 days after chemo-radiation, we conducted a low anterior resection with lymph node dissection. Histological examination revealed no residual cancer cells in the resected specimen. Case 2 was a 35-year-old male who was diagnosed as advanced low rectal cancer. Preoperative chemo-radiation (a total of 45 Gy radiation+5-FU 500 mg/day+CDDP 10 mg/day for 3 weeks) was performed. 28 days after chemo-radiation, we conducted an abdominoperineal resection with lymph node dissection and a partial resection of the liver. Histological examination revealed well-differentiated adenocarcinoma in the resected liver tissue, but a rectal tumor was replaced by scar tissue with no viable cells.     

直肠癌的辅助放疗和临床研究的进展

手术是直肠癌治疗的主要手段。根治性手术后，局部复发的发生与原发肿瘤肠壁侵润的深度和淋巴结转移直接相关，也是直肠癌最常见的治疗失控部位。早期临床研究提示T1-2N0M0的局部失败率低于10％，T3N0M0和T1N1M0的局部失控在15％～35％，T3-4N1-2M0则可达45％-65％。尽管远处转移是治疗失败的重要原因，但主要原因却是局部复发，这也是在可切除直肠癌治疗中采用辅助治疗的理由。随机临床研究已证实辅助放疗联合化疗的综合治疗，较单纯手术或术后单纯放疗可显著提高肿瘤的局部控制。放疗在直肠癌综合治疗中的目标是：提高局控，增加保肛的机率和功能，提高生存率及生活质量。对临床可切除的肿瘤，辅助放疗的模式主要有两种：一种为先手术，如肿瘤为T3和（或）N1-2，再接受术后的联合治疗；另一种为术前的联合治疗，放疗或放化疗，然后手术。术前放疗（或放化疗）的优点为减少术中种植；肿瘤退缩、分期降低从而增加肛门括约肌保留的机会；肿瘤细胞富氧，对放射较敏感；放射治疗的毒性反应较小。     

A case report of locally advanced rectal carcinoma effectively treated with preoperative chemoradiotherapy

The patient was an 80-year-old woman who was diagnosed with locally advanced low rectal cancer. It was unresectable and we performed chemoradiotherapy combined with S-1 (S-1 80 mg/m2, RT 1.8 Gy × 25, total 45 Gy). An effective reduction of primary region resulted in curative resection (super low anterior resection, D3 lymph node dissection, covering ileostomy) with preserving the anal sphincter. Histopathologically, therapeutic efficacy was Grade 2. Preoperative chemoradiation has been a standard therapy in Western countries and would control local recurrence. This case indicated that CRT could improve a rate of curative resection in patients with locally advanced rectal carcinomas.     

18F-FDG positron emission tomography staging and restaging in rectal cancer treated with preoperative chemoradiation

PURPOSE: To assess the information supplied by FDG-PET in patients with locally advanced rectal cancer both in the initial staging and in the evaluation of tumor changes induced by preoperative chemoradiation (restaging). METHODS AND MATERIALS: Twenty-five consecutive patients with rectal cancer were included, with tumor stages (c)T(2-4)N(x)M(0), during the period 1997-1999. We prospectively performed two FDG-PET scans in all patients to assess disease stage (1) at initial diagnosis and (2) presurgically, 4 to 5 weeks after protracted chemoradiation. Protracted chemoradiation was carried out during 5-6 weeks with 45-50 Gy, plus concurrent oral tegafur 1200 mg/day or 5-fluorouracil 500-1000 mg/m(2) administered as a 24-h continuous i.v. infusion on Days 1-4 and 21-25 of the radiotherapy treatment. Tumors were staged with CT in 95% of patients, whereas endorectal ultrasound was used in 90% of patients. Maximum standardized uptake value (SUVmax) was used as the quantitative parameter to estimate the tumor:tissue metabolic ratio. RESULTS: Preoperative chemoradiation significantly decreased the SUVMAX: 5.9 (mean SUVmax at initial staging) vs. 2.4 (mean SUVmax after chemoradiation) with p < 0.001. Unknown liver metastases were detected by FDG-PET in 2 patients, in 1 of them with the initial staging FDG-PET scan, and with the restaging FDG-PET scan in the other. After an average follow-up of 39 months, the value of SUVmax > or =6 allowed us to discriminate for survival at 3 years: 92% vs. 60% (p = 0.04). T downstaging (total 62%) was significantly correlated with SUVmax changes: 1.9 vs. 3.3 (p = 0.03). The degree of rectal cancer response to chemoradiation, established as mic vs. mac categories, was not associated with SUVmax differences (mean values of 2.0 vs. 2.7). CONCLUSION: Preliminary results observed suggest the potential utility of FDG-PET as a complementary diagnostic procedure in the initial clinical evaluation (8% of unsuspected liver metastases) as well as in the assessment of chemoradiation response (any T downstaged event) of locally advanced rectal cancer. Initial SUVmax might be of prognostic value related to long-term patient outcome.     

Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer

PURPOSE: Capecitabine (Xeloda) is a new orally administered fluoropyrimidine carbamate that was rationally designed to exert its effect by tumor-selective activation. We attempted to evaluate the efficacy and toxicity of preoperative chemoradiation using capecitabine in locally advanced rectal cancer. METHODS AND MATERIALS: Between July 1999 and March 2001, 45 patients with locally advanced rectal cancer (cT3/T4 or N+) were treated with preoperative chemoradiation. Radiation of 45 Gy/25 fractions was delivered to the pelvis, followed by a 5.4 Gy/3 fractions boost to the primary tumor. Chemotherapy was administered concurrent with radiotherapy and consisted of 2 cycles of 14-day oral capecitabine (1650 mg/m(2)/day) and leucovorin (20 mg/m(2)/day), each of which was followed by a 7-day rest period. Surgery was performed 6 weeks after the completion of chemoradiation. RESULTS: Thirty-eight patients received definitive surgery. Primary tumor and node downstaging occurred in 63% and 90% of patients, respectively. The overall downstaging rate, including both primary tumor and nodes, was 84%. A pathologic complete response was achieved in 31% of patients. Twenty-one patients had tumors located initially 5 cm or less from the anal verge; among the 18 treated with surgery, 72% received sphincter-preserving surgery. No Grade 3 or 4 hematologic toxicities developed. Other Grade 3 toxicities were as follows: hand-foot syndrome (7%), fatigue (4%), diarrhea (4%), and radiation dermatitis (2%). CONCLUSION: These preliminary results suggest that preoperative chemoradiation with capecitabine is a safe, well-tolerated, and effective neoadjuvant treatment modality for locally advanced rectal cancer. In addition, this preoperative treatment has a considerable downstaging effect on the tumor and can increase the possibility of sphincter preservation in distal rectal cancer.     

新辅助治疗在进展期低位直肠癌术前的应用

背景与目的提高进展期低位直肠癌的根切率和保肛率是一个难题,本研究探讨术前联合放化疗(新辅助治疗)在进展期低位直肠癌中的疗效。方法23例进展期低位直肠癌患者,按术前评价均需行腹-会阴联合切除术的患者进行术前联合放化疗。放疗每周5d,每次200cGy,共4周20次,总剂量4000cGy。化疗的给药方式以放疗期间持续静脉滴注,采用草酸铂(Oxa)130mg/(m2·d1),5-FU500mg/(m2·d1-5),加CF300mg/(m2·d1-5),休息4~6周进行手术。结果15例的病例肿瘤分期降级,施行了保留肛门的直肠癌根治术,保肛率达65%(15/23),其中82%的患者肛门括约肌功能良好。结论进展期低位直肠癌的患者在接受新辅助治疗后,能使肿瘤降期,切除率增加,提高保肛率,同时副反应轻,患者依顺性较好。     

Have the changes in treatment of rectal cancer made a significant difference to our patients?

The treatment for patients with locally advanced, resectable rectal cancer has evolved over the years. Various combinations and sequences of chemotherapy, radiation therapy, and total mesorectal excision (TME)-based surgery are the mainstay of current therapy. Preoperative combined chemoradiation, followed by surgery, is now the preferred treatment strategy, with the majority of patients receiving either infusion fluorouracil (5-FU) or capecitabine (Xeloda) with radiation. Clinical trials with oxaliplatin (Eloxatin)-based neoadjuvant chemoradiation have not shown improvement in the pathologic complete response rate (pCR) compared with 5-FU; however, final data addressing local recurrence rates and disease-free survival are pending.The use of adjuvant chemotherapy following preoperative chemoradiation and surgery has not been optimally defined. Some studies have shown that patients who obtained significant pathologic downstaging after chemoradiation and surgery have improved survival with the use of adjuvant chemotherapy. Since FOLFOX (folinic acid, 5-FU, and oxaliplatin) is the preferred adjuvant chemotherapy regimen for stage III colon cancer based on randomized clinical trial results, FOLFOX is also recommended for rectal cancer patients as an adjuvant therapy approach.     

胃上部癌术前放化疗的有效性及安全性分析

目的:探讨进展期胃上部癌术前放化疗的短期有效性、治疗安全耐受性及生存预后情况。方法:回顾性分析北京大学肿瘤医院胃肠肿瘤外科2011年11月至2014年11月间收治的行术前放化疗或术前化疗并后续标准D 2 根治手术的62例进展期胃上部癌患者病历资料,分析比较两组患者各项短期疗效指标、安全性指标及不良反应的差异,并进行随访资料的生存分析。结果:术后病理结果中术前放化疗组pT4 期及pN3 患者数量明显减少（P < 0.05）,手术安全性及放化疗不良反应两组间差异无统计学意义,生存分析两组间差异无统计学意义。结论:术前放化疗可改良胃上部癌患者生存预后。相较于术前化疗,术前放化疗没有增加手术难度及风险,放化疗毒性在可控范围内。术前放化疗能有效提高局部控制率尤其是区域淋巴转移,其客观缓解率与术前化疗相当。但是,生存预后的最终结论仍有待于长期随访的进一步分析。      

Long-term results of chemoradiation therapy for the patients with locally advanced (T4) esophageal cancer

The prognosis of patients with advanced esophageal cancer is still poor. Recently, concurrent chemoradiation therapy for esophageal cancer is being utilized with increasing frequency. In this study, we reported concurrent chemoradiation for patients with T4 esophageal cancer. From July 2000, we treated 21 consecutive patients with radiation and concurrent chemotherapy using intermittent low-dose FP chemoradiation (40 Gy radiation, 2 Gy/day, for 4 weeks 280/m(2) 5-FU intermittent 24 continuous, CDDP 8 mg/m(2)/intermittent). All patients who underwent the treatment with concurrent CRT completed the planned chemoradiation. Out of 21 patients, 2 (9.5%) showed a complete response and 9 patients (42.8%) showed a partial response. The 5-year survival rate of the T4 patients with CRT was almost the same as for those who underwent surgery alone. Concurrent chemoradiation therapy for T4 esophageal cancer patients is feasible and seems to be a standard treatment for T4 esophageal cancer patients. The results indicated that CRT is an effective therapy for advanced esophageal cancer.     

高位直肠癌辅助性放疗的问题与争议探讨

局部晚期直肠癌的治疗强调多学科综合治疗,除高质量的直肠全系膜切除术（total mesorectal excision,TME）之外,放化疗的加入也进一步降低了局部复发、延长了总生存,尤其是对于中低位直肠癌。但是,目前对于局部晚期高位直肠癌,放疗的价值仍未明确,国内外各共识指南对高位直肠癌的定义并不完全统一,关于是否放疗的推荐也存在一定差异,目前尚缺乏大型前瞻性随机对照试验,既往的研究结果也存在诸多矛盾之处。同时,盆腔放疗也不可避免的带来一系列不良反应。因此,局部晚期高位直肠癌的治疗应该如何决策,如何基于复发风险进行分层治疗,放疗是否能带来获益,均值得进一步探索。本文旨在针对高位直肠癌辅助放疗的问题与争议进行综述。      

局部晚期直肠癌术前调强放疗同步化疗的疗效评价及预后因素分析

目的:观察并分析术前调强放疗同步化疗治疗局部晚期直肠癌的病理降期情况、临床疗效和预后因素.方法:回顾性分析2010年1月1日至2013年7月31日间接受术前同步放化疗随后行根治性手术的60例初治Ⅱ、Ⅲ期直肠癌患者的临床资料.全部患者接受调强放射治疗,总剂量为50Gy/25次,同期行氟尿嘧啶为基础的化疗,放化疗结束后间隔4~8周行手术治疗.结果:肿瘤病理退缩分级(tumor regression grading,TRG)0级为8例、1级为 12例、2级 为11例、3级为 20例、4级即病理完全缓解(complete responce rate,pCR)为9例,pCR率为15%,病理有效率为86.7%,T分期降期55%,N分期降期51.9%.手术并发症发生率为25.0%.3年总生存率(OS)为88.3%,3年无瘤生存率(DFS)为85.5%,3年局部复发率(LRR)为11.6%,3年远处转移率(DMR)为13.3%,3年无局部复发生存率(LRFS)为88.3%,3年无远处转移生存率(DRFS)为 86.7%.Kaplan-Meier分析及COX回归分析均表明TRG分级对患者总生存期的影响具有统计学意义.结论:局部晚期直肠癌术前调强放疗同期化疗能使肿瘤降期,提高手术切除率和生存率,3年局部控制好.pCR 和接近pCR 患者有更好的生存期.     

Early clinical results from chemoradiation with 5-fluorouracil and oxaliplatin for locally advanced rectal cancer

Purpose: Preoperative chemoradiation with 5-fluorouracil (5-FU) has improved local control and resectability in patients with locally advanced rectal adenocarcinoma. The possible benefit of adding oxaliplatin is being investigated. We present background on the use of oxaliplatin as well as institutional experience assessing treatment tolerability and early outcome data. Patients and Methods: From August 2001 to August 2006, 15 patients were treated with concurrent 5-FU, oxaliplatin, and radiation. Each had locally advanced rectal carcinoma with staging as follows: T3 (10 patients), T4 (5 patients), N1 (3 patients), and M1 (1 patient). Three patients were treated for local recurrence; 2 had received previous radiation therapy. All patients received continuous-infusion 5-FU at 225 mg/m2 per day. The oxaliplatin dose was 70 mg/m2 in 1 patient and 85 mg/m2 in the others, administered every other week x 3 weeks starting on day 1 of radiation. Resection followed completion of radiation by 6 weeks. Results: The treatment was tolerable, with the most frequent hematologic toxicity being grade 1/2 anemia. Twelve patients were evaluable, with 11 treated preoperatively. All were able to undergo resection with negative margins, with T stage at resection as follows: T4 (2 patients, 1 with 5% viable tumor), T3 (4 patients), T2 (1 patient), T1 (2 patients); there were pathologic complete responses in 4 patients. At resection, 2 patients had N2 disease; 1 of these was also found to have a peritoneal metastasis. Two patients with clinical N1 disease initially were N0 at resection. With median follow-up of 13 months (range, 4-36 months), 9 patients have clinically no evidence of disease. There have been no local recurrences and 1 death from disease. Conclusion: We present tolerability and early clinical efficacy data for patients treated with concurrent 5-FU and oxaliplatin chemoradiation. The oxaliplatin-based regimen was tolerable. All patients were able to undergo resection with negative margins, with encouraging downstaging, local control, and survival.     

A case report of pathologically complete response of rectal cancer after preoperative treatment of CPT-11, S-1, and radiation therapy

A 52-year-old woman diagnosed with lower rectal cancer was referred to our hospital for the operation of anal sphincter preservation. Rectal examination and colonoscopy showed a type 2 semicircular tumor on the posterior wall at 4 .5-7 cm from anal verge with incomplete mobility (cT3). She was diagnosed as the moderately differentiated tubular adenocarcinoma by biopsy. Computed tomography and magnetic resonance imaging showed no sign of invasion to the surrounding organs and metastasis to lymph nodes or the other organs (cN0, cM0). We performed a preoperative chemoradiotherapy (CRT) combined with S-1 and CPT-11. Radiation (1.8 Gy) was administered a total of 45 Gy( day 1-5, 8-12, 15-19, 22-26, 29-33). S-1 was taken orally( 100 mg/day: day 1-5, 8-12, 22-26, 29-33), and CPT-11 was administered intravenously (60 mg/m2: day 1, 8, 22, 29). Endoscopy after CRT showed a reduction of the tumor size (from semicircular to quarter-circular) and lowering of marginal wall. Rectal examination revealed an improvement of tumor mobility. Eight weeks after CRT, the patient underwent ISR with partial ESR and covering ileostomy pathological examination demonstrated no residual cancer cell in the primary lesion and lymph node (Grade 3, pCR). Preoperative CRT can be a promising tool for locally advanced rectal cancer.     

A case of long-term survival after resection of advanced undifferentiated rectal cancer treated by short-term preoperative chemoradiotherapy and postoperative adjuvant chemotherapy

A 75-year-old man with advanced undifferentiated rectal cancer, diagnosed by endoscopic biopsy, underwent preoperative short-term chemoradiotherapy (whole pelvis, 4 Gy × 5 day with UFT 400 mg/day × 7 day). Tumor size and lymph node swellings were reduced after radiation therapy. Down-staging was achieved from cT3, cN2, cStage III b to cT3, cN1, cStage III a. A curative low anterior resection with D3 lymphadenectomy including lateral lymph node dissection, was performed 4 weeks after the completion of chemoradiotherapy. Pathological findings of resected specimen showed undifferentiated carcinoma with regional lymph node involvement (pT2, pN1, pStage III a). The histological change in response to chemoradiation was evaluated as Grade 2. The postoperative course was uneventful and postoperative adjuvant chemotherapy (UFT+Uzel) was performed for six months (5 courses). No sign of recurrence has been found until 51 months after the operation. Undifferentiated rectal cancer is a rare condition with extremely poor prognosis according to the Japanese literature. Nine cases have been reported so far with only one long-term survivor. This combination of preoperative short-term chemoradiotherapy and adjuvant chemotherapy, which is one of the standard strategies for advanced rectal cancer in Western countries, but not common in Japan, may be a promising option for treatment of undifferentiated rectal cancer.     

Induction chemotherapy with capecitabine and oxaliplatin followed by chemoradiotherapy before total mesorectal excision in patients with locally advanced rectal cancer

Background Preoperative chemoradiation in patients with locally advanced rectal cancer has no impact on overall survival (OS) and distant recurrences. The aim of the study was to evaluate local downstaging, toxicity and long-term outcome in patients with locally advanced rectal cancer after induction therapy with capecitabine and oxaliplatin (CAPEOX) followed by radiotherapy concomitant with capecitabine [chemoradiotherapy (CRT)] before total mesorectal excision (TME). Patients and methods Patients with T4 tumors, all T3N+ tumors or T3 tumors involving or with a distance ≤1 mm to the mesorectal fascia were included. Patients were planned for two cycles of CAPEOX followed by radiotherapy concomitant with capecitabine. TME was carried out 6 weeks after the completion of CRT. Results Of 84 consecutively admitted patients starting induction CAPEOX, 77 patients underwent surgery. R0 resection was seen in 94% and T downstaging in 69%. In the intention-to-treat group, pathological complete response was seen in 23%. Five-year disease-free survival (DFS) and OS were 63% [95% confidence interval (CI), 52.2% to 73.7%] and 67% (95% CI, 56.1% to 77.3%), respectively. Grade 3/4 toxicity was seen in 18%, and four deaths occurred within 2 months of therapy. Conclusion Induction chemotherapy before CRT and surgery showed a high local control rate and promising long-term outcome as OS and DFS.     

Contemporary imaging for colorectal cancer

With improvements in therapy for colorectal cancer, accurate imaging has taken on an increased significance. Preoperative diagnosis of metastatic disease helps identify patients who could undergo combined resection or might benefit from systemic therapy before surgery. Accurate imaging of rectal cancer is critical in evaluating locally advanced disease treatable by combined modality therapy, including chemoradiation and surgery. Postoperative imaging enhances identification of recurrent disease that might be amenable to salvage surgery.     

Double blind randomized phase II study with radiation + 5-fluorouracil ± celecoxib for resectable rectal cancer

Purpose

To assess the feasibility and efficacy of the COX-2 inhibitor celecoxib in conjunction with preoperative chemoradiation for patients with locally advanced rectal cancer in a double blind randomized phase II study.

Materials and methods

Thirty-five patients of the initially planned 80 patients with locally advanced rectal cancer were treated with preoperative radiation (45 Gy; 1.8 Gy/fraction, 5 days/week) combined with 5-fluorouracil (continuous infusion, 225 mg/m²/day) and celecoxib (2 × 400 mg/day) or placebo. Pathological response and toxicity of study treatment were evaluated, as well as expression of COX-2 and Ki67 in tumor tissue and IL-6 in plasma as possible molecular correlates and predictors of response to treatment.

Results

Patients treated with celecoxib tended to show a better response (61%) when compared to those treated with placebo (35%), although not significant (p = 0.13). T-downstaging and N-downstaging were also slightly higher with celecoxib. Plasma IL-6 levels and intratumoral COX2 or Ki67 were altered by chemoradiation, but were not further altered by celecoxib treatment and therefore not useful for prediction of treatment benefit. Celecoxib therapy in conjunction with chemoradiation was not associated with additional toxicity and seemed to help mitigate therapy-related pain.

Conclusions

Addition of celecoxib to preoperative chemoradiation is feasible for patients with locally advanced rectal cancer. To study the individual effect of COX-2 inhibitors on pathological response phase III studies are required.     

A case report of effective chemoradiation with 5'-DFUR and concomitant preoperative radiotherapy of the lower rectum

We treated a lower rectal carcinoma patient with preoperative radiation and chemotherapy, resulting in a downstaging, and the findings are reported herein. The patient is a 55-year-old woman endoscopically diagnosed with advanced rectal carcinoma at a site 3 cm from the dental line. Preoperative radiation and chemotherapy included whole pelvis irradiation (44 Gy in total) and 800 mg/day of 5'-DFUR administered until one day before the operation. On the 20th day after completing irradiation, a low anterior resection of the rectum was conducted. During the operation, we found serositis of the small intestine and retroperitoneal fibrosis thought to be due to the irradiation. Histopathologic findings showed: invasion degree, sm2; stage I with N0; and histologic grading, Grade 2. The patient started drinking water from postoperative day 1, and was discharged on postoperative day 11. At present, in Europe and the USA, large scale studies are being conducted to evaluate preoperative radiation and chemotherapy in patients with lower rectal carcinoma. We think that this therapy is an effective treatment, since a distance (AW) from the lower margin of the tumor and the cut edge of the anal end can be established.