老年直肠癌患者盆腔放疗的急性血液学毒性

目的探究老年直肠癌患者盆腔放疗的急性血液学毒性反应的发生率及其影响因素。 方法回顾分析2006年1月至2014年8月在本院行盆腔放疗的50例75岁及以上直肠癌患者的临床资料。选取同一时期行盆腔放疗的111例75岁以下直肠癌患者作为非老年患者组进行比较。采用卡方检验及Logistic多因素回归模型分析不同临床因素与3~4度血液学毒性发生率的相关性。 结果老年患者组中0度、1~2度、3~4度急性血液学毒性发生率分别为6.0%、78.0%和16.0%,非老年患者组中0度、1~2度、3~4度急性血液学毒性发生率分别为24.3%、68.5%和7.2%。老年患者的3~4血液学毒性反应发生率高于非老年患者（P=0.009）。多因素分析显示体重指数与老年患者的3~4度急性血液学毒性反应发生显著相关（P=0.038）。 结论老年直肠癌患者盆腔放疗的急性血液学毒性反应是可耐受的,高体重指数可能与老年患者盆腔放疗的严重血液学毒性反应相关。     

口服希罗达联合放疗提高直肠癌切除患者肛门保留率观察

29例肿瘤距齿状线3～5cm中晚期直肠癌患者，5周内分25次接受总量37．5～45．0Gy放疗，期间121服希罗达750mg／m^2，2次／d；放疗5—7周后手术切除肿瘤。结果全组放化疗耐受性良好，总显效率为79．3％；19例患者成功保留肛门，其中根治17例；术后3～7周康复出院，均未出现严重并发症，肛门功能良好。认为术前放疗联合化疗可有效提高直肠癌肛门保留率。     

结直肠癌肝转移立体定向消融放疗

全身治疗和转移灶局部治疗可以改善结直肠癌肝转移(CRLM)患者的生存。体部立体定向放射治疗,又称立体定向消融放疗(SABR),不仅是转移灶局部治疗的有效手段,还对全身免疫状态具有一定的影响。SABR可以直接杀伤肿瘤细胞,也通过对肿瘤细胞和非肿瘤细胞的影响改变肿瘤免疫微环境。SABR联合免疫治疗可能通过影响免疫应答的各个环节增加照射区域之外病灶远隔效应的发生率。立体定向近距离消融(SABT)是一种独立的微创治疗体系,具有疗程短、精确性高、疗效确切的特点。现就SABR和SABT在CRLM中的应用进行综述。     

直肠癌放疗的标准流程

因特异性症状的缺乏,大多数直肠癌患者就诊时已处于晚期或局部晚期。对于局部晚期直肠癌（II/III期）患者,放射治疗联合根治性的全直肠系膜切除TME手术能显著的提高患者的局部控制率并延长总的生存时间。目前,调强放射治疗技术已广泛开展。然而,各医疗中心在直肠癌放疗实施过程,治疗流程中存在显著差异。本文现对我院直肠癌的放疗标准流程做一简单介绍以供参考。     

SATB1在直肠癌新辅助放疗中的作用

目的探讨SATB1在直肠癌新辅助放疗中的作用。 方法选取142例直肠癌患者作为研究对象,其中68例接受术前短程放疗,74例未接受术前放疗。采用组织芯片方法检测直肠癌组织（n=142）和正常黏膜组织（n=107）、术前活检癌组织（n=84）以及转移淋巴结（n=43）中SATB1表达情况,探讨SATB1表达对直肠癌患者预后的影响,并通过生物信息学方法分析SATB1表达与多个放疗相关因子的关系。 结果在未接受术前放疗的患者中,SATB1在正需组织中的表达低于肿瘤组织（χ²=5.396,P=0.032）而肿瘤组织中的表达高于淋巴结转移组织（χ²=6.405,P=0.002）。在接受术前放疗的患者中,SATB1表达与不良的OS（HR,0.516;P=0.039;95% CI：0.274~0.969）和DFS（HR,0.558;P=0.025;95% CI：0.335~0.930）相关。放疗可以降低直肠癌组织中SATB1的表达。在放疗的直肠癌肿瘤组织中SATB1表达与ATM和pRb2/p130表达负相关（χ²=5.427,P=0.032;χ²=4.610, P=0.047）,而与Ki-67和TEM1表达正相关（χ²=4.339,P=0.037;χ²=7.376,P=0.014）。网络和蛋白-蛋白相互作用分析证实了SATB1与这些蛋白的相互联系。 结论放疗能降低SATB1表达,后者可通过参与一些放疗反应相关的信号通路,赋予接受术前放疗的直肠癌患者生存获益。     

结直肠癌寡转移的放射治疗策略

结直肠癌寡转移是目前研究的重要领域之一。肝转移、肺转移及多部位寡转移的立体定性放射治疗研究逐步开展。直肠癌寡转移患者的盆腔放疗,国际上已经形成了推荐转移性直肠癌接受盆腔放疗的多学科共识。     

重视直肠癌患者的全盆腔脏器切除与盆底缺损重建

全盆腔脏器切除术作为一种根治性手术,对于复发和晚期直肠癌患者的治疗有重要意义。但目前此术式在国内开展并不普遍。笔者就全盆腔脏器切除术的发展历史,目前的应用现状和手术的治疗要点等诸多方面加以阐述,以使医师们对此术式有更深入的理解,更好地指导临床应用。     

盆腔肿瘤放疗致放射性肠炎的临床观察

盆腔肿瘤尤其是宫颈癌和直肠癌在放疗过程中常伴有盆腔正常组织不同程度的损伤,其中最常发生的是不同程度的放射性肠炎,而慢性迟发性肠炎往往是增加死亡率的一个重要原因[1].本文对盆腔肿瘤患者放疗后放射性肠炎的发生情况及治疗效果进行临床观察与分析.     

同时性结直肠癌肝转移患者的生存分析

目的分析结直肠癌合并同时性肝转移患者的生存状况和相关影响因素。 方法回顾性分析2000年至2010年复旦大学附属中山医院收治的1061例结直肠癌合并同时性肝转移患者的病例。收集所有患者的临床资料、病理特征、治疗策略、住院费用、随访状况等,进行生存状况分析,并采用单因素和Cox比例风险回归模型等分析影响结直肠癌肝转移生存的相关因素。 结果肝转移灶可切除患者中,同期切除肠道原发灶和肝转移灶与分期切除患者的住院费用分别为25693元、34129元(P<0.05),手术并发症(分别为24.5%、20.5%)和总生存期方面(分别为48.5月、47.0月)无显著差异。肝转移灶不可切除且原发灶无症状的患者中,原发灶切除的患者总体中位生存时间明显好于原发灶未切除的患者(分别为19.0月、9.3月,P<0.001)。肠道原发灶分化Ⅲ～Ⅳ级、肝转移灶≥4个、最大肝转移灶直径≥5 cm、肝外转移、肠道原发灶未手术切除和肝转移灶非手术治疗是影响肠癌同时性肝转移患者预后的独立危险因素。将上述6个危险因素各设定为1分,所有患者分为低风险组(0～1分)、中风险组(2～3分)和高风险组(4～6分),5年存活率分别为51%、16%和0%(P<0.001)。 结论结直肠癌合并同时性肝转移患者中,原发灶和转移灶均可切除的可予以同期切除,原发灶可切除且无出血梗阻症状的不可切除的肝转移仍建议在合适时机切除肠道原发灶。根据上述6个独立预后因素所建立的预测模型可以指导临床采取合适的治疗方案。     

Three-dimensional conformal radiotherapy combined with FOLFOX4 chemotherapy for unresectable recurrent rectal cancer

AIM: To investigate the effect of three-dimensional conformal radiotherapy (3-DCRT) in combination with FOLFOX4 chemotherapy for unresectable recurrent rectal cancer. METHODS: Forty-eight patients with unresectable recurrent rectal cancer were randomized and treated by 3-DCRT or 3-DCRT combined with FOLFOX4 chemotherapy between September 2001 and October 2003. For the patients without prior radiation history, the initial radiation was given to the whole pelvis by traditional methods with tumor dose of 40 Gy, followed by 3-DCRT for the recurrent lesions to the median total cumulative tumor dose of 60 Gy (range 56-66 Gy); for the post-radiation recurrent patients, 3-DCRT was directly given for the recurrent lesions to the median tumor dose of 40 Gy (36-46 Gy). For patients in the study group, two cycles chemotherapy with FOLFOX4 regimen were given concurrently with radiotherapy, with the first cycle given simultaneously with the initiation of radiation and the second cycle given in the fifth week for patients receiving conventional pelvis radiation or given in the last week of 3-DCRT for patients receiving 3-DCRT directly. Another 2-4 cycles (average 3.6 cycles) sequential FOLFOX4 regimen chemotherapy were given to the patients in the study group, beginning at 2-3 wk after chemoradiation. The outcomes of symptoms relieve, tumor response, survival and toxicity were recorded and compared between the study group and the control group. RESULTS: For the study group and the control group, the pain-alleviation rates were 95.2% and 91.3% (P>0.05); the overall response rates were 56.5% and 40.0% (P>0.05); the 1-year and 2-year survival rates were 86.9%, 50.2% and 80.0%, 23.9%, with median survival time of 25 mo and 16 mo (P<0.05); the 2-year distant metastasis rates were 39.1% and 56.0% (P=0.054), respectively. The side effects, except peripheral neuropathy which was relatively severer in the study group, were similar in the the two groups and well tolerated. CONCLUSION: Three-dimensional conformal radiotherapy combined with FOLFOX4 chemotherapy for unresectable recurrent rectal cancer is a feasible and effective therapeutic approach, and can reduce distant metastasis rate and improve the survival rate.     

Long-term efficacy of preoperative radiotherapy for locally advanced low rectal cancer

Background and aims The purpose of this study was to assess the long-term efficacy of preoperative radiotherapy for locally advanced low rectal cancer. Materials and methods Between April 1990 and June 2005, all patients who underwent surgery for low rectal cancer with a pretreatment diagnosis of T3 or resectable T4 without distant metastasis were enrolled. The total dose of radiation was 45 Gy. Patients with a partial or complete response were defined as radiotherapy responders (RT-R) and the others as radiotherapy non-responders (RT-NR). Patients who did not receive radiotherapy were termed the non-radiotherapy group (NRT). The endpoint of this study was overall survival and local and/or distant metastasis. Results There were 24 patients in RT-R, 26 in RT-NR, and 40 in NRT. Gastrointestinal complications were commonly observed in all groups. RT-R had a significantly higher incidence of genitourinary complications. Five-year overall survival rate was 79.6% in RT-R, 58.9% in RT-NR, and 58.8% in NRT. The difference was significant in favor of RT-R over the others (P = 0.015, 0.024, respectively). Five-year local recurrence-free survival rate was 100% in RT-R, 81.5% in RT-NR, and 74.9% in NRT. RT-R had significantly improved local control compared with the others (P = 0.034, 0.021, respectively). Five-year distant metastasis-free survival was not statistically different among all groups. Conclusions Survival benefit of preoperative radiotherapy was limited to responders. Considering the increased risk of adverse effects, identification of predictors of radiosensitivity is required in order to provide the most suitable treatment for individual patients.     

Intensity-modulated radiotherapy with a belly board for rectal cancer

Background and aim Intensity-modulated radiotherapy (IMRT) techniques can reduce the irradiated small bowel volume in rectal cancer patients, but combined use of IMRT and a belly board is yet to be reported on for rectal cancer patients. The aim of this study was to determine whether additional use of a belly board reduced the irradiated small bowel volume observed using IMRT alone in rectal cancer patients. Materials and methods Twenty patients scheduled to receive preoperative radiotherapy for rectal cancer underwent two series of CT scans, with and without a belly board. IMRT planning was performed using 6-MV photon beams and seven equispaced fields. The bladder, small bowel, and planning target volume (PTV) were analyzed for doses between 10% and 100% of the prescribed dose at 10% intervals. Data were analyzed using Wilcoxon signed rank tests. Results There were no significant differences between patients undergoing IMRT with a belly board and those without a belly board in terms of total small bowel volumes, bladder, and PTV (p=0.571, p=0.841, and p=0.870, respectively). Statistical analysis showed that the irradiated small bowel volume with a belly board was smaller than that without a belly board (p<0.05 at 20–100% dose levels), with the mean relative reduction in the irradiated small bowel volume being 37.8±32.8%. Conclusion IMRT with a belly board is more effective than IMRT alone in reducing the irradiated small bowel volume. These findings suggest that the use of a belly board with IMRT may reduce small bowel complications in preoperative radiotherapy.     

Outcome of patients with clinical stage II or III rectal cancer treated without adjuvant radiotherapy

Background  To clarify the indications for preoperative adjuvant radiotherapy for rectal cancer, the outcome of patients who underwent curative surgery without adjuvant radiotherapy was investigated. Methods  A total of 817 consecutive patients who underwent curative surgery for clinical stage II or III rectal cancer without preoperative adjuvant radiotherapy between 1988 and 2002 were reviewed. Results  The actuarial 5-year local recurrence rate in the examined patients was 6.2%. Univariate analysis showed that sex, pathological T classification (pT), clinical N classification (cN), pathological N classification (pN), tumor site, distance from the anal verge, type of surgery, pathological stage, a positive radical margin, lymphatic invasion, and venous invasion were significantly correlated with local recurrence. Multivariate analysis of preoperative factors identified cN, distance from the anal verge, and sex as statistically significant risk factors for local recurrence. In patients with rectal cancer located less than 5 cm from the anal verge and with positive cN, the local recurrence rate was more than 10%. Conclusions  Patients with rectal cancer located less than 5 cm from the anal verge and with clinically positive lymph nodes should be given preoperative adjuvant radiotherapy.     

Short-term preoperative radiotherapy is a safe approach for treatment of locally advanced rectal cancer

Background and aims The Swedish Rectal Cancer Trial (SRCT) demonstrated that a short term regimen of high-dose preoperative radiotherapy (5×5 Gy) not only reduces the risk of local recurrence but also improves overall survival rate. An increase in postoperative mortality and morbidity has also been observed, however. We therefore evaluated early postoperative complications in patients treated with neoadjuvant radiotherapy for locally advanced rectal adenocarcinoma.Patients/methods Between 2000 and 2004, 85 patients with locally advanced rectal tumors were treated in our institution. Preoperative staging was based on CT scan and, in several cases, on endorectal ultrasonography. They were 55 men and 30 women, with a median age of 68 years. They were retrospectively divided into two groups: Group A, which included 40 patients undergoing preoperative radiotherapy (25 Gy in five fractions) followed by surgery within 1 week, and Group B, which included 45 patients with rectal cancer receiving surgery immediately after diagnosis. Both groups were homogeneous regarding age, gender and preoperative stage of the disease. The two groups were compared for both technical difficulties during operation and rate of postoperative complications.Results/findings No postoperative deaths were recorded in either group. Low anterior resection with total mesorectal excision was performed in all group A patients, whereas eight patients in group B underwent abdominoperineal resection (P<0.05). Diverting stoma was performed in seven patients of group A and it was closed 3–6 months later on every occasion. Postoperative morbidity was not statistically significant between the two groups (40 vs 39%). The rate of postoperative hemorrhage, pelvic or abdominal wound infection, acute urinary infection, and delayed ileus was similar. The percentage of major anastomotic leak was also equivalent (5 vs 6.6%).Interpretation/conclusion Short-term preoperative radiotherapy does not increase the rate of postoperative complications and is a safe therapeutic adjunct for the treatment of locally advanced rectal cancer.     

直肠癌术前新辅助放疗进展

术前同步放化疗是局部进展期可切除直肠癌的标准治疗。取得了与术后同步放化疗相似的生存率,并进一步降低了局部复发率,同时提高了保肛率。通过术前同步放化疗达到病理完全缓解的患者有更好的预后。本文将介绍直肠癌术前放疗的进展。     

Sphincter-saving surgery in patients with rectal cancer treated by radiotherapy and transanal endoscopic microsurgery: 10 years’ experience

Background/Aims. Transanal endoscopic microsurgery (TEM) is a technique which allows minimally invasive full-thickness local excision of rectal tumours with perirectal fat dissection.

Methods. Our study examined a group of 137 selected patients with rectal cancer treated by TEM excision combined with preoperative radiotherapy. The definitive histology was as follows: 37 patients with pT1 stage rectal cancer (27%), 59 with pT2 (43%) and 23 with pT3 (17%). In 18 (13%) patients who underwent a full dose of radiotherapy and TEM, the pathologist did not find cancer cells in the specimen (pT0).

Results. Eleven (8%) patients developed minor complications, whereas three (2%) developed major complications. The perioperative mortality was nil. At the mean follow-up of 46 months (range 6–115 months), we observed seven (5%) local recurrences. Of those, three patients died from systemic spread of the disease at follow-up. The disease-free survival rate in T0 and T1 patients was 100%. The disease-free survival rates in T2 and T3 patients were 81 and 59%, respectively, at a mean follow-up of 46 months.

Conclusions. The application of preoperative radiotherapy and TEM in the treatment of rectal tumours appears feasible, safe and effective in the present study, with optimal preservation of anal sphincter function.     

Morbidities of adjuvant chemotherapy and radiotherapy for resectable rectal cancer

PURPOSE: Although adjuvant chemoradiotherapy may improve outcomes after surgery for high-risk rectal cancer, its toxicities are not well documented. This is a review of complications associated with adjuvant therapy in randomized, controlled trials. METHODS: A MEDLINE and literature search was performed for randomized, controlled trials of adjuvant therapy for rectal cancer. Modalities of adjuvant therapy evaluated included preoperative radiotherapy, preoperative chemoradiotherapy, postoperative radiotherapy, and postoperative chemoradiotherapy. All documented complications were analyzed, including any effect on pelvic floor function and quality of life. RESULTS: Short-term (acute) complications of preoperative radiotherapy include lethargy, nausea, diarrhea, and skin erythema or desquamation. These acute effects develop to some degree in most patients during treatment but are usually self-limiting. With preoperative radiotherapy the incidence of perineal wound infection increases from 10 to 20 percent. The acute toxicities after postoperative radiotherapy for rectal cancer occur in 4 to 48 percent of cases, and serious toxicities, requiring hospitalization or surgical intervention, occur in 3 to 10 percent of cases. Postoperative radiotherapy is associated with more complications than preoperative radiotherapy. The main problems with postoperative radiotherapy are small-bowel obstruction (5–10 percent), delay in starting radiotherapy caused by delayed wound healing (6 percent) and postoperative fatigue (14 percent), and toxicities precluding completion of adjuvant therapy (49–97 percent). The morbidity and mortality of both preoperative and postoperative radiotherapy are higher in elderly patients and when two-portal rather than three-portal or four-portal radiation technique is used. Meticulous radiation technique is important, and multiple fields of irradiation are mandatory. After combined adjuvant chemotherapy and radiotherapy acute hematologic and gastrointestinal toxic effects are frequent (5–50 percent). Delayed radiation toxicities include radiation enteritis (4 percent), small-bowel obstruction (5 percent), and rectal stricture (5 percent). Pelvic floor function and quality of life have not been well evaluated in randomized, controlled trials. CONCLUSION: Adjuvant therapy for rectal cancer has considerable adverse effects. Adverse effects on bowel and sphincter function and quality of life have not been defined.Dr. Ooi is supported in part by the Irene and Margaret Stewardson Charitable Trusts.