Role of Combined-Modality Therapy in the Management of Locally Advanced Rectal Cancer

The majority of patients with nonmetastatic rectal cancer are candidates for an aggressive multimodality approach with curative intent. Preoperative staging is critical in determining which patients should be offered neoadjuvant therapy. Available staging tools include digital rectal examination, transrectal ultrasound, computed tomography, positron-emission tomography, and magnetic resonance imaging scans. Magnetic resonance imaging has emerged as the most accurate staging modality in experienced centers. Multidisciplinary preoperative patient evaluation, better staging techniques, neoadjuvant chemoradiation, acceptance of shorter distal rectal margins, and transanal excision of T1 N0 rectal tumors in close proximity to the anal sphincter have resulted in decreased rates of abdominoperineal resections. Total mesorectal excision has been adopted as the standard surgical approach because of a reduction in rates of pelvic relapse. Preoperative and postoperative radiation therapy was shown to decrease the local recurrence rate, but not overall survival, in patients with resectable rectal cancer. The addition of chemotherapy to radiation was consistently shown to improve local control, and in some trials, improved overall survival. Neoadjuvant combined chemotherapy and radiation therapy are superior to adjuvant combined-modality therapy because of higher rates of sphincter preservation, less toxicity, and lower local recurrence rates. For patients with stage II or III disease, neoadjuvant continuous-infusion 5-fluorouracil (5-FU), concurrently with pelvic radiation, followed by postoperative 5-FU–based chemotherapy, remains the standard multimodality approach. Ongoing trials are testing the integration of newer cytotoxic agents such as capecitabine, oxaliplatin, irinotecan, and biologic agents such as cetuximab and bevacizumab to chemoradiation.     

Preoperative or Postoperative Therapy for Stage II or III Rectal Cancer: An Updated Practice Guideline

AimsUncertainty remains regarding the optimal therapy for patients with stage II or III rectal cancer. Systematic reviews and practice guidelines on preoperative and postoperative therapy for rectal cancer were published by the Gastrointestinal Cancer Disease Site Group in 2003 and 2000, respectively. The systematic reviews were updated and revised and new recommendations for preoperative and postoperative therapy were developed based on the updated body of evidence. The following research questions were addressed: After appropriate preoperative staging tests, should patients with resectable clinical stage II or III rectal cancer be offered preoperative radiotherapy (with or without chemotherapy)? What is the role of postoperative radiotherapy and/or chemotherapy for patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy, in terms of improving survival and delaying local recurrence?Materials and methodsThe MEDLINE, EMBASE and Cochrane Library databases, as well as meeting proceedings from the American Society of Clinical Oncology, were searched for reports of randomised controlled trials and meta-analyses comparing preoperative or postoperative therapy with surgery alone or other preoperative or postoperative therapy for stage II or III rectal cancer. The draft practice guideline and systematic reviews were distributed through a mailed survey to 129 health care providers in Ontario for review.ResultsSystematic reviews on preoperative and postoperative therapy for rectal cancer were developed. On the basis of the evidence contained in these reviews, the Gastrointestinal Cancer Disease Site Group drafted recommendations. Of the 33 practitioners who responded to the mailed survey, 97% agreed with the draft recommendations as stated, 88% agreed that the report should be approved as a practice guideline and 94% indicated that they were likely to use the guideline in their own practice.ConclusionsPreoperative chemoradiotherapy is preferred, compared with standard fractionation preoperative radiotherapy alone, to decrease local recurrence. Preoperative chemoradiotherapy is also preferred, compared with a postoperative approach, to decrease local recurrence and adverse effects. For patients with relative contraindications to chemotherapy in the preoperative period, an acceptable alternative is preoperative radiotherapy alone followed by surgery. Patients with resected stage II or III rectal cancer who have not received preoperative radiotherapy should be offered postoperative therapy with concurrent chemoradiotherapy plus fluoropyrimidine-based chemotherapy.     

Adjuvant radiation therapy of patients with rectal cancer

The standard in rectal cancer has been to add adjuvant radiation therapy to surgery in patients with stage II and III disease. Total mesorectal excision has led to lower local recurrence rates, and, if properly performed, may make adjuvant radiation unnecessary for certain stage II and III patients, such as T3 N0 patients with proximal lesions. There is also debate about the best method of delivering adjuvant radiotherapy. Preoperative radiotherapy at low dose per fraction with concurrent chemotherapy offers the advantages of maximizing sphincter preservation and greater tolerability. However, this will occasionally result in treating patients who are overstaged by ultrasound and may lead to greater postoperative morbidity and mortality than postoperative radiation. Preoperative radiotherapy has stronger data to support a survival advantage when added to surgery than postoperative radiation. Two randomized, phase III European studies may answer the question of which radiation technique is best for the near future. Protracted venous infusion of 5-fluorouracil (5-FU) is the standard method of radiosensitization. However, studies are ongoing using concurrent oxaliplatin, irinotecan, and oral 5-FU prodrugs. For now, we recommend that stage II and III rectal cancer patients receive protracted venous infusion 5-FU concurrent with preoperative radiation.     

Therapy for early-stage colorectal cancer

Surgery is the only curative option for patients with colorectal cancer. The goal of other modalities, such as chemotherapy, immunotherapy, and radiotherapy, is to prolong survival and reduce the risk of recurrence. Adjuvant treatment is mandatory for patients with stage III colon cancer. At present, 6 months of fluorouracil (5-FU) plus leucovorin (folinic acid) can be considered standard therapy. The data on stage II colon cancer are less convincing, and perhaps only subgroups benefit from adjuvant therapy. Patients with stage II disease should be encouraged to participate in randomized trials. Outside of such trials, one can consider prognostic factors in the decision to offer adjuvant therapy. Patients with T3 or N1-3 M0 rectal cancer should receive combined-modality therapy, i.e., 5-FU-based chemotherapy and irradiation. Until ongoing trials answer the question of whether a patient should be irradiated preoperatively or postoperatively, the type of surgery determines the timing of irradiation. If the tumor is amenable to a sphincter-preserving operation, surgery can be followed by radiation therapy. In patients with fixed tumors and those in whom resectability is an issue, prolonged preoperative radiotherapy is more appropriate. Ongoing trials should optimize existing adjuvant therapy (by achieving an ideal balance between toxicity and effectiveness) and integrate the advantages of recently approved drugs.     

T3N0 rectal cancer: radiation for all?

The optimal oncologic management for patients with T3N0 rectal cancer is currently controversial. Patients with pathologic T3N0 disease may have an "intermediate" risk of disease recurrence, suggesting that perhaps trimodality therapy may not be indicated for all patients. Adverse prognostic features, including a greater depth of perirectal fat invasion, poor tumor differentiation, the presence of lymphovascular invasion, abnormally elevated pretreatment carcinoembryonic antigen levels (>5 ng/mL), circumferential margin involvement, and a low-lying position may identify T3N0 patients at high risk for local recurrence who may benefit from the addition of radiation therapy. However, recent randomized data suggest an improvement in local control and disease-free survival with preoperative radiation therapy compared with selective postoperative radiation therapy in all patient subgroups, arguing in favor of routine preoperative therapy. Additionally, rates of clinical understaging may exceed 20%, representing the percentage of patients who would require the delivery of postoperative radiotherapy with its associated sequelae. Future prospective randomized studies of T3N0 patients with upfront stratification by known prognostic factors and studies evaluating the molecular profile of rectal cancers hold the promise of better classifying patients at high risk of local and systemic recurrence, and thus, in need of adjuvant radiation and chemotherapy.     

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.     

Preoperative chemoradiotherapy with capecitabine versus protracted infusion 5-fluorouracil for rectal cancer: a matched-pair analysis

PURPOSE: To retrospectively compare the acute toxicity, pathologic response, relapse rates, and survival in rectal cancer patients treated with preoperative radiotherapy (RT) and either concurrent capecitabine or concurrent protracted infusion 5-fluorouracil (5-FU). METHODS: Between June 2001 and February 2004, 89 patients with nonmetastatic rectal adenocarcinoma were treated with preoperative RT and concurrent capecitabine, followed by mesorectal excision. These patients were individually matched by clinical T and N stage (as determined by endoscopic ultrasound and CT scans) with 89 control patients treated with preoperative RT and concurrent protracted infusion 5-FU between September 1997 and August 2002. RESULTS: In each group, 5 patients (6%) had Grade 3-4 toxicity during chemoradiotherapy. The pathologic complete response rate was 21% with capecitabine and 12% with protracted infusion 5-FU (p = 0.19). Of the 89 patients in the capecitabine group and 89 in the 5-FU group, 46 (52%) and 55 (62%), respectively, had downstaging of the T stage after chemoradiotherapy (p = 0.20). The estimated 3-year local control (p = 0.15), distant control (p = 0.86), and overall survival (p = 0.12) rate was 94.4%, 86.3%, and 89.8% for patients treated with capecitabine and 98.6%, 86.6%, and 96.4% for patients treated with protracted infusion 5-FU, respectively. CONCLUSION: Preoperative concurrent capecitabine and concurrent protracted infusion 5-FU were both well tolerated, with similar, low rates of Grade 3-4 acute toxicity. No significant differences were seen in the pathologic response, local and distant recurrence, or overall survival among patients treated with preoperative RT and concurrent capecitabine compared with those treated with RT and concurrent protracted infusion 5-FU.     

Adjuvant and neoadjuvant chemoradiation therapy for primary colorectal cancer

The management of rectal cancer presents substantial challenges. Patients with T3 and/or node-positive rectal cancers are at high risk for local failure and distant metastases (DM). Adjuvant radiation has been shown to decrease local recurrence (LR) rates; however, this local therapy has not been demonstrated to improve survival when compared to surgery alone. In several prospective randomized trials adjuvant chemoradiation with 5-fluorouracil-(5-FU)-based chemotherapy improved LR rates, DM rates, and overall survival (OS). The optimal chemotherapeutic regimen has not been determined; however, studies comparing standard IV bolus 5-FU administration with continuous infusion (CI) 5-FU demonstrated that CI administration was superior. Preoperative therapy has potential advantages over adjuvant therapy such as less acute bowel toxicity and improved sphincter preservation. Preoperative chemoradiation has been shown in several studies to improve LR rates and OS when compared to surgery alone. Our current approach to patients with resectable T3 or N1 cancer in the distal two-thirds of the rectum on preoperative staging is preoperative chemoradiation with planned postoperative chemotherapy. This regimen offers the best chance for local control and disease-free survival while potentially downstaging the tumor and improving sphincter preservation.     

Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114.

PURPOSE: The gastrointestinal Intergroup studied postoperative adjuvant chemotherapy and radiation therapy in patients with T3/4 and N+ rectal cancer after potentially curative surgery to try to improve chemotherapy and to determine the risk of systemic and local failure. PATIENTS AND METHODS: All patients had a potentially curative surgical resection and were treated with two cycles of chemotherapy followed by chemoradiation therapy and two additional cycles of chemotherapy. Chemotherapy regimens were bolus fluorouracil (5-FU), 5-FU and leucovorin, 5-FU and levamisole, and 5-FU, leucovorin, and levamisole. Pelvic irradiation was given to a dose of 45 Gy to the whole pelvis and a boost to 50.4 to 54 Gy. RESULTS: One thousand six hundred ninety-five patients were entered and fully assessable, with a median follow-up of 7.4 years. There was no difference in overall survival (OS) or disease-free survival (DFS) by drug regimen. DFS and OS decreased between years 5 and 7 (from 54% to 50% and 64% to 56%, respectively), although recurrence-free rates had only a small decrease. The local recurrence rate was 14% (9% in low-risk [T1 to N2+] and 18% in high-risk patients [T3N+, T4N]). Overall, 7-year survival rates were 70% and 45% for the low-risk and high-risk groups, respectively. Males had a poorer overall survival rate than females. CONCLUSION: There is no advantage to leucovorin- or levamisole-containing regimens over bolus 5-FU alone in the adjuvant treatment of rectal cancer when combined with irradiation. Local and distant recurrence rates are still high, especially in T3N+ and T4 patients, even with full adjuvant chemoradiation therapy.     

Progress in adjuvant therapy for colorectal cancer

The progress and role of adjuvant therapy for resectable colorectal cancers are reviewed herein. 5-FU/leucovorin is considered the standard treatment in the postoperative adjuvant chemotherapy for Dukes'C colon cancer. The oral 5-FU prodrugs, such as UFT and capecitabine, will replace 5-FU infusion in the adjuvant chemotherapy in the near future. In Dukes'B colon cancer, the results of postoperative adjuvant chemotherapy are controversial. Many randomized trials in the USA and Europe have demonstrated that pre- or postoperative radiation therapy for rectal cancer decreases local recurrences but has no additional benefit on survival compared with 5-FU-based adjuvant chemotherapy. Adjuvant radiation therapy for rectal cancer is not widely used in Japan, while chemotherapy is considered the adjuvant treatment of choice. The local recurrences of rectal cancer is a surgeon-related phenomenon: the surgical technique used and the skill of the surgeon are major factors influencing outcome.     

Improving chemoradiotherapy in rectal cancer

The optimal management of rectal cancer remains a major challenge for oncologists. The treatment of stage II/III rectal cancer has historically been associated with a high risk of local recurrence and poor survival, which led to the development of adjuvant treatments in the hope of improving outcomes. The approach to adjuvant therapy for rectal cancer currently varies widely between Europe and the U.S. Postoperative adjuvant chemoradiation is the standard of care in the U.S. In contrast, in Europe, because there is a greater emphasis placed on preoperative imaging, meticulous surgical technique, and accurate pathologic reporting of the circumferential or radial margin, preoperative treatment (radiotherapy and chemoradiation) is used widely. The aims of preoperative radiotherapy and chemoradiation are to facilitate a curative resection (R0) and to increase the chance of performing sphincter-sparing procedures, and, therefore, to improve both survival and quality of life. This article reviews the clinical trials that led to these diverging standards of care. An interesting new approach in chemoradiation is the use of the oral fluoropyrimidine capecitabine as a combination partner for radiotherapy. Preclinical studies have demonstrated that the combination of capecitabine and radiotherapy has highly enhanced antitumor activity. This is most likely attributable to the upregulation of thymidine phosphorylase (the rate-limiting enzyme needed to convert capecitabine to 5-fluorouracil [5-FU]) in tumor cells following radiotherapy. A phase I study has consequently been performed to establish a feasible chemoradiotherapy combination. Capecitabine has the potential to replace bolus or continuous infusion 5-FU as the standard treatment for rectal cancer and offers a potentially enhanced therapeutic ratio. Oral chemotherapy has the additional advantage of simplifying chemoradiation and providing a treatment that is more appealing to patients.     

Patterns of locoregional recurrence after surgery and radiotherapy or chemoradiation for rectal cancer

PURPOSE: To identify patterns of locoregional recurrence in patients treated with surgery and preoperative or postoperative radiotherapy or chemoradiation for rectal cancer. METHODS AND MATERIALS: Between November 1989 and October 2001, 554 patients with rectal cancer were treated with surgery and preoperative (85%) or postoperative (15%) radiotherapy, with 95% receiving concurrent chemotherapy. Among these patients, 46 had locoregional recurrence as the first site of failure. Computed tomography images showing the site of recurrence and radiotherapy simulation films were available for 36 of the 46 patients. Computed tomography images were used to identify the sites of recurrence and correlate the sites to radiotherapy fields in these 36 patients. RESULTS: The estimated 5-year locoregional control rate was 91%. The 36 patients in the study had locoregional recurrences at 43 sites. There were 28 (65%) in-field, 7 (16%) marginal, and 8 (19%) out-of-field recurrences. Among the in-field recurrences, 15 (56%) occurred in the low pelvis, 6 (22%) in the presacral region, 4 (15%) in the mid-pelvis, and 2 (7%) in the high pelvis. Clinical T stage, pathologic T stage, and pathologic N stage were significantly associated with the risk of in-field locoregional recurrence. The median survival after locoregional recurrence was 24.6 months. CONCLUSIONS: Patients treated with surgery and radiotherapy or chemoradiation for rectal cancer had a low risk of locoregional recurrence, with the majority of recurrences occurring within the radiation field. Because 78% of in-field recurrences occur in the low pelvic and presacral regions, consideration should be given to including the low pelvic and presacral regions in the radiotherapy boost field, especially in patients at high risk of recurrence.     

Ⅱ期和Ⅲ期直肠癌根治术后卡培他滨同期放化疗疗效及失败原因分析

目的 分析Ⅱ、Ⅲ期直肠癌根治术后卡培他滨同期放化疗Ⅱ期临床研究结果.方法 2005-2007年间共131例病理诊断明确的Ⅱ、Ⅲ期直肠癌患者纳入研究,所有患者均接受根治术后同期化放疗和辅助化疗.治疗方案为全盆腔放疗50 Gy分25次,放疗期间同期应用卡培他滨1600mg/m2,每天分2次服用,连用2周停l周.结果 同期放化疗期间3+4级不良反应发生率为28.2％.随访率为93.9％,3年总生存率、无局部区域复发生存率和无远处转移生存率分别为85.1％、96.7％和79.5％.共31例出现复发,包括5例局部区域复发和28例远处转移.单因素分析提示病理低分化或中低分化、未接受辅助化疗、ⅢC期和淋巴结阳性率＞30％是影响总生存的因素(x2=15.49、15.85、8.80和9.76,P=0.000、0.000、0.011和0.002),ⅢC期、未接受辅助化疗和淋巴结阳性率＞30％是影响无远处转移生存的因素(x2 =6.51、11.57和9.70,P=0.034、0.001和0.002).但未接受辅助化疗者中病理为低分化或T4期的患者更多(x2 =7.20、6.48,P=0.027、0.039).结论 Ⅱ、Ⅲ期直肠癌根治术及卡培他滨同期放化疗后局部区域控制率高,远处转移是主要失败原因.     

直肠癌根治术后复发转移特点及危险因素分析

目的 研究直肠癌根治术后复发转移特点及其相关危险因素,为术后随访监测、防治复发转移提供依据.方法 回顾性研究中国医学科学院肿瘤医院1999年1月至2004年12月内初次根治手术治疗的1039例直肠癌病例资料,分析术后复发转移的特点及危险因素.结果 随访期间发生复发344例,占33.2％;常见的复发形式依次是局部复发（13.6％）、肝转移（6.9％）、肺转移（6.0％）.单因素分析显示：围手术期输血、病理大体类型、肿瘤大小、肿瘤位置、脉管瘤栓、癌结节、分化程度、T分期、N分期、M分期是复发转移的相关因素（P＜0.05）.多因素分析显示：术前CEA、肿瘤位置、脉管瘤栓、瘤结节、T分期、N分期是复发转移的独立危险因素（P＜0.05）.结论 直肠癌术后存在好发复发转移部位和与复发转移相关的独立危险因素;术后辅助放化疗等多学科综合治疗是降低直肠癌术后复发转移、延长生存期的有效手段.     

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.     

Evaluation of intra-arterial infusion chemotherapy associated with radiotherapy for two cases of local recurrence of rectal cancer

We evaluated the effect of intra-arterial infusion chemotherapy associated with radiotherapy for two cases of local recurrence of rectal cancer. We performed an intra-arterial infusion chemotherapy (5-FU was injected continuously: 250 mg/day/body x 28 days, CDDP was injected weekly: 5 mg/day x 5 days) associated with radiotherapy (2-3 Gy/day x 20-30 days) for local recurrence of rectal cancer with the aim of pain-relief. Both patients markedly tended to feel less pain after the radiotherapy. Radiotherapy has been useful for pain-relief of the localized bone metastasis. The present intra-arterial infusion chemotherapy associated with radiotherapy was a possible local therapy for local recurrence of rectal cancer in the pelvis. Although the survival benefit depends on the presence of other site of recurrence, this procedure is useful for the improvement of QOL by relieving the pain of the patients.     

Significance of surgery in the multimodality treatment of rectal cancer

Since the NIH recommendations in 1990 the majority of patients with rectal cancer are treated by a multimodality approach. The last decade has seen considerable improvements in the overall management of rectal cancer, therefore a certain reorientation seems justified. Although many questions remain to be answered, some general recommendations for the treatment of rectal cancer focussed on the small pelvis can be given. Surgery with total mesorectal excision is the standard therapy for cancers of the middle and low rectum in stages T1/2 N0. Adjuvant radiochemotherapy and shortterm pre-operative radiotherapy are both feasible approaches for the treatment of stage II and stage III rectal carcinomas. The superiority of either concept awaits clarifying randomised trials. Patients with T4 rectal cancers should undergo long-term neoadjuvant radiochemotherapy with consecutive oncological resection. The exact mode of the neoadjuvant regimen combining high remission rates with low treatment-associated morbidity needs further refinements. Local excision should be restricted to patients with well-differentiated, less than semi-circumferential T1 carcinomas. Tumours with less favourable histologies should not be treated locally unless general patient conditions forbid oncological resections. In these instances, additional radiochemotherapy appears able to reduce the risk of local recurrence.     

Neoadjuvant chemoradiation for rectal cancer: is more better?

Neoadjuvant chemoradiation is now considered the clear preferable adjuvant standard of care in the management of stage II/III rectal cancer. Neoadjuvant fluorouracil (5-FU) plus radiation results in a decrease in local relapse rates and a favorable toxicity profile in comparison with postoperative adjuvant 5-FU plus radiation therapy. Recent nonrandomized comparative studies have shown that capecitabine (Xeloda) plus radiation result in downstaging and pathologic complete responses equivalent to those of 5-FU plus radiation, making this combination an acceptable alternative neoadjuvant treatment. The addition of oxaliplatin (Eloxatin) or irinotecan (Camptosar) to 5-FU or capecitabine concurrently with radiation therapy appears to result in more favorable pathologic responses in phase I/II trials. These combinations should be investigated further in larger phase III studies before they are endorsed in the routine neoadjuvant treatment of rectal cancer. This article will review the progress of chemoradiation over the past 2 decades, current standards of care, and investigational treatments in the neoadjuvant treatment of rectal cancer.     

不同放化疗模式治疗局部晚期乳腺癌的疗效分析

目的探讨不同治疗模式对局部晚期乳腺癌疗效的影响。方法回顾性分析278例T3～4、N0～3期乳腺癌的临床资料。其中82例患者先给予放疗,放疗后续行6周期化疗。另外196例患者均为先化疗者。在先行化疗的196例患者中,102例患者接受三明治疗法(即3周期化疗+放疗+3周期化疗),94例患者完成6周期化疗后行局部放疗。使用SPSS 10.0统计软件进行局部复发、远处转移及生存率的相关因素分析。结果3组治疗组间5年生存率无显著性差异,但化放夹心组较先化后放组局部复发率明显下降,而较先放后化组远处转移率降低,且不良反应较两者相比发生率低。结论三明治疗法可做为一种理想的乳腺癌术后辅助治疗选择。     

Comparative effectiveness of postoperative chemotherapy among older patients with non-metastatic rectal cancer treated with preoperative chemoradiotherapy

ObjectivePostoperative chemotherapy is standard following preoperative chemoradiation therapy (CRT) and curative resection for clinically staged II/III rectal cancer. Recent trials have questioned whether postoperative chemotherapy improves overall survival. The objective of the study was to evaluate the comparative effectiveness of postoperative chemotherapy following CRT or radiation therapy (RT) with specific attention to the impact of age on postoperative chemotherapy effectiveness.Materials and MethodsPatients treated with CRT or RT then resection of pathologically staged 0-III rectal cancer diagnosed from 2004 to 2009 were identified from the Surveillance, Epidemiology and End Results program-Medicare database. Propensity score weighted Cox proportional hazards models and Kaplan Meier methods were used to compare the effectiveness of 1) postoperative 5-fluorouracil (5-FU) or capecitabine to no treatment and 2) postoperative oxaliplatin + 5-FU/capecitabine to 5-FU/capecitabine alone on mortality. Results were stratified by age.ResultsWe identified 1316 patients; 49% received postoperative chemotherapy, 341 (52%) included oxaliplatin. After weighting, postoperative 5-FU/capecitabine alone was associated with decreased mortality in patients aged 66–74 (adjusted hazard ratio (aHR) = 0.46, 95% CI: 0.30, 0.72), corresponding to a 5-year risk difference of − 0.23, (95% CI: − 0.33, − 0.12). No further mortality reduction from adding oxaliplatin to 5-FU/capecitabine was seen in patients aged 66–74 (aHR = 1.57, 95% CI: 0.93, 2.65). No mortality reduction for 5-FU/capecitabine alone was observed among patients aged 75 + (aHR = 1.11, 95% CI: 0.76, 1.63).ConclusionsAmong patients < 75 years, postoperative 5-FU/capecitabine was associated with reduced mortality after preoperative CRT/RT and surgical resection; however, the addition of oxaliplatin was not associated with further mortality reduction. Decisions regarding postoperative chemotherapy after age 75 warrant consideration of individual patient risks and preferences, as benefits may be limited.