老年性直肠癌放射治疗及相关影响因素
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摘要
研究目的：
研究高龄直肠癌放疗患者的疗效、预后及可能的高危因素,为临床对高龄直肠癌患者的治疗策略选择提供依据及佐证。
材料及方法：
从上海复旦大学附属肿瘤医院的病史资料库中,收集了2002年4月至2011年1月期间以直肠癌为第一诊断,接受过放射治疗且放射治疗时年龄大于等于70周岁的患者145人。通过排除标准,排除直肠癌患者行盆腔外转移病灶姑息放疗的患者16人后的129人进行病史相关信息收集,详细记录了直肠病灶情况,手术治疗信息,术后病理(包括：肿瘤的组织学类型,分化程度,肿瘤的浸润深度,周围淋巴结浸润等),放疗及放化疗治疗的具体信息,治疗期间急性毒性反应、辅助化疗及患者的生存情况、疾病进展等。统计分析软件,STATA10.0软件。对毒性反应采用对可能相关因素分组的卡方检验。对生存率和无病生存率采用单因素分析法(Kaplan-Meier法)及多因素分析法(Cox回归模型分析)对获取的参数进行分析。
结果：
129例70岁及以上老年患者中126例(97.7%)完成放疗计划,2年生存率：72.2%,3年生存率：59%。其中接受新辅助放化疗的8例患者的2年生存率100%,3年生存率66.7%；术后辅助放化疗的患者2年生存率为88.2%,3年生存率83%,2年DFS：85.3%,3年DFS：75.8%；无远处转移行直肠病灶根治性放疗的患者2年生存率48%,3年生存率16%；局部复发行病灶根治性放疗的患者2年生存率58.9%；伴远处转移行直肠病灶根治性放疗的患者2年生存率：45.7%,3年生存率：22.8%。单因素生存分析显示在性别、年龄分组(70-75,76及以上)、高血压、糖尿病、基础疾病数目、肿瘤AJCC分期、放射治疗模式、同期化疗、辅助化疗中,仅年龄分组(P=0.0025)、肿瘤AJCC分期(P=0.0057)、放射治疗模式(P=0.001)为70岁及以上老年患者生存预后的相关因素,提示更高的年龄组的患者可能预后更差；分期较早预后较好,较晚则较差；而不同放射治疗模式患者预后不同,其中同手术联合的新辅助及辅助治疗模式组的患者预后较好,仅采用病灶根治性放疗的患者预后较差。多因素分析显示：年龄分组(P=0.001)和放射治疗模式(P=0.047)是该组老年患者生存预后的独立影响因素。更高的年龄,预后往往更差,不同治疗模式之间的差异,也以新辅助及辅助治疗组的预后较好,而仅行病灶根治剂量的放疗者预后较差。在接受辅助放化疗的患者中,进一步分析发现N分期为术后辅助放化疗组影响生存预后的相关因素(P=0.0151)。本研究中的老年患者未观察到Ⅳ度急性毒性反应,Ⅲ度急性毒性反应43例(34.1%),以性别、年龄、糖尿病、病灶位置、放射治疗剂量、同期化疗有无,同期单药化疗及联合化疗分组,发现同期化疗的患者Ⅲ度急性放化疗毒性的发生率：45.2%,较未行同期化疗的患者的发生率高：18.9%(P=0.002)。
结论
1、70岁以上老年患者中,整组患者2年及3年生存率分别为72.2%和59%与非老年的其他年龄组生存相似。年龄是影响生存的独的预后影响因素,高于75岁的老年直肠癌患者的预后较差。
2、肿瘤AJCC分期是70岁及以上老年直肠癌患者生存预后相关的影响因素,但不是独立的预后影响因素。在TNM分期中,N分期是影响术后辅助放化疗组生存及无病生存的预后相关因素及独立影响因素。NO患者显示有较好的预后；N2的患者预后最差,N1的患者预后介于NO和N2之间。
3、不同的放疗治疗模式是影响老年直肠癌患者生存预后的相关因素及独立影响因素.接受根治性手术和辅助治疗的老年患者,生存与年轻患者相似.
4、合并的基础疾病最常见为高血压和糖尿病.但未发现两者与预后相关.未观察到合并基础疾病数目对老年直肠癌患者的生存影响。
5、70岁及以上老年人治疗可耐受放疗和放化疗。同期化疗可能增加70岁及以上老年直肠癌患者放化疗Ⅲ度急性毒性反应的发生率。
Background and Purpose
1) To investigate the efficacy, prognosis and potential risk factors for elderly rectal cancer patients who received radiation therapy.
2) To analyze treatment toxicities and tolerence in elderly rectal cancer patient with pelvic radiation.
3) To provide baseline parameters of elderly rectal cancer patients treated with radiation+-chemotherapy for further randomized trial in this group of patients.
Methods
We reviewed129cases of rectal cancer patients who received radiation therapy in Department of radiation therapy at Shanghai cancer center of Fudan University. All patients were>=70years. Parameters we analyzed including:gender, age, co-morbidities, tumor charicteristics, treatment received pathological findings and treatmet induced toxicities. Kaplan-Meier were used to analyzed OS and DFS. χ2tests were applied evaluate toxicities. Multivariate analysis was used to find independent prognositic of clinical outcome.
Result
There were126patients (97.7%) who completed whole course of radiation therapy as planed. The2,3-years OS:were72.2%and59%respectively.2,3years OS:100%, and66.7%in neo-adjuvant chemo-radiation therapy group.2,3years OS:88.2%and83%, and2,3years DFS:85.3%and75.8%in adjuvant chemo-radiation therapy group.2,3years OS:48%and16%in esclusive radiation therapy group for non-metastases patients.2-years OS:58.9%in patients who suffered local recurrence of rectal cancer with no metastases.2,3years OS:45.7%and22.8%in stage IV patients received esclusive radiation therapy for rectal lesion.Our analysis results showed that age (P=0.0025), AJCC staging (P=0.0057), purpose of the radiation therapy (P=0.001) were the significant unitivarate factors of OS. Multivariate analysis showed that only age (P=0.001) and purpose of the radiation therapy (P=0.047) were the independent prognostic factor of OS. N stage (P=0.0151) was the unitivarate factors of OS and DFS in adjuvant chemo-radiation therapy group. There was no grade IV acute toxicity observed. More Grade III toxicity was observed in the group of patients received concurrent-chemotherapy (P=0.002).
Conclusion
1The2-,3-years overall survival of the whole group with age>70are72%and59%respectively.Age was the significant unitivarate factors of OS and independent prognostic factor of OS in this group of>70years old rectal cancer patients.Patients over75had poor prognosis.
2Stage was the significant unitivarate factors of OS but not the independent prognostic factor of OS in this group of≥70years old rectal cancer patients. N stage was the unitivarate factors of OS and DFS in adjuvant chemo-radiation therapy group. NO had favourable prognosis, while N2showed poor prognosis,and N1was in the middle.
3Different purpose of the radiation therapy were the significant unitivarate factor and independent prognostic factor of OS in elderly patients. Neo-adjuvant and adjuvant radiation therapy group had the similar prognosis as younger patients.
4Hypertension and diabetes were the most common co-morbidities in elderly patients. but we didn't find them associate to OS. There were no influence from co-morbidities to prognosis had been obersved.
5The rectal cancer patients≥70showed well tolorent to radiation or chemo-radiation. Concurrent chemotherapy possibly incrsased Grade Ⅲ toxicity in these rectal cancer patients≥70.
研究高龄直肠癌放疗患者的疗效、预后及可能的高危因素,为临床对高龄直肠癌患者的治疗策略选择提供依据及佐证。
材料及方法：
从上海复旦大学附属肿瘤医院的病史资料库中,收集了2002年4月至2011年1月期间以直肠癌为第一诊断,接受过放射治疗且放射治疗时年龄大于等于70周岁的患者145人。通过排除标准,排除直肠癌患者行盆腔外转移病灶姑息放疗的患者16人后的129人进行病史相关信息收集,详细记录了直肠病灶情况,手术治疗信息,术后病理(包括：肿瘤的组织学类型,分化程度,肿瘤的浸润深度,周围淋巴结浸润等),放疗及放化疗治疗的具体信息,治疗期间急性毒性反应、辅助化疗及患者的生存情况、疾病进展等。统计分析软件,STATA10.0软件。对毒性反应采用对可能相关因素分组的卡方检验。对生存率和无病生存率采用单因素分析法(Kaplan-Meier法)及多因素分析法(Cox回归模型分析)对获取的参数进行分析。
结果：
129例70岁及以上老年患者中126例(97.7%)完成放疗计划,2年生存率：72.2%,3年生存率：59%。其中接受新辅助放化疗的8例患者的2年生存率100%,3年生存率66.7%；术后辅助放化疗的患者2年生存率为88.2%,3年生存率83%,2年DFS：85.3%,3年DFS：75.8%；无远处转移行直肠病灶根治性放疗的患者2年生存率48%,3年生存率16%；局部复发行病灶根治性放疗的患者2年生存率58.9%；伴远处转移行直肠病灶根治性放疗的患者2年生存率：45.7%,3年生存率：22.8%。单因素生存分析显示在性别、年龄分组(70-75,76及以上)、高血压、糖尿病、基础疾病数目、肿瘤AJCC分期、放射治疗模式、同期化疗、辅助化疗中,仅年龄分组(P=0.0025)、肿瘤AJCC分期(P=0.0057)、放射治疗模式(P=0.001)为70岁及以上老年患者生存预后的相关因素,提示更高的年龄组的患者可能预后更差；分期较早预后较好,较晚则较差；而不同放射治疗模式患者预后不同,其中同手术联合的新辅助及辅助治疗模式组的患者预后较好,仅采用病灶根治性放疗的患者预后较差。多因素分析显示：年龄分组(P=0.001)和放射治疗模式(P=0.047)是该组老年患者生存预后的独立影响因素。更高的年龄,预后往往更差,不同治疗模式之间的差异,也以新辅助及辅助治疗组的预后较好,而仅行病灶根治剂量的放疗者预后较差。在接受辅助放化疗的患者中,进一步分析发现N分期为术后辅助放化疗组影响生存预后的相关因素(P=0.0151)。本研究中的老年患者未观察到Ⅳ度急性毒性反应,Ⅲ度急性毒性反应43例(34.1%),以性别、年龄、糖尿病、病灶位置、放射治疗剂量、同期化疗有无,同期单药化疗及联合化疗分组,发现同期化疗的患者Ⅲ度急性放化疗毒性的发生率：45.2%,较未行同期化疗的患者的发生率高：18.9%(P=0.002)。
结论
1、70岁以上老年患者中,整组患者2年及3年生存率分别为72.2%和59%与非老年的其他年龄组生存相似。年龄是影响生存的独的预后影响因素,高于75岁的老年直肠癌患者的预后较差。
2、肿瘤AJCC分期是70岁及以上老年直肠癌患者生存预后相关的影响因素,但不是独立的预后影响因素。在TNM分期中,N分期是影响术后辅助放化疗组生存及无病生存的预后相关因素及独立影响因素。NO患者显示有较好的预后；N2的患者预后最差,N1的患者预后介于NO和N2之间。
3、不同的放疗治疗模式是影响老年直肠癌患者生存预后的相关因素及独立影响因素.接受根治性手术和辅助治疗的老年患者,生存与年轻患者相似.
4、合并的基础疾病最常见为高血压和糖尿病.但未发现两者与预后相关.未观察到合并基础疾病数目对老年直肠癌患者的生存影响。
5、70岁及以上老年人治疗可耐受放疗和放化疗。同期化疗可能增加70岁及以上老年直肠癌患者放化疗Ⅲ度急性毒性反应的发生率。
Background and Purpose
1) To investigate the efficacy, prognosis and potential risk factors for elderly rectal cancer patients who received radiation therapy.
2) To analyze treatment toxicities and tolerence in elderly rectal cancer patient with pelvic radiation.
3) To provide baseline parameters of elderly rectal cancer patients treated with radiation+-chemotherapy for further randomized trial in this group of patients.
Methods
We reviewed129cases of rectal cancer patients who received radiation therapy in Department of radiation therapy at Shanghai cancer center of Fudan University. All patients were>=70years. Parameters we analyzed including:gender, age, co-morbidities, tumor charicteristics, treatment received pathological findings and treatmet induced toxicities. Kaplan-Meier were used to analyzed OS and DFS. χ2tests were applied evaluate toxicities. Multivariate analysis was used to find independent prognositic of clinical outcome.
Result
There were126patients (97.7%) who completed whole course of radiation therapy as planed. The2,3-years OS:were72.2%and59%respectively.2,3years OS:100%, and66.7%in neo-adjuvant chemo-radiation therapy group.2,3years OS:88.2%and83%, and2,3years DFS:85.3%and75.8%in adjuvant chemo-radiation therapy group.2,3years OS:48%and16%in esclusive radiation therapy group for non-metastases patients.2-years OS:58.9%in patients who suffered local recurrence of rectal cancer with no metastases.2,3years OS:45.7%and22.8%in stage IV patients received esclusive radiation therapy for rectal lesion.Our analysis results showed that age (P=0.0025), AJCC staging (P=0.0057), purpose of the radiation therapy (P=0.001) were the significant unitivarate factors of OS. Multivariate analysis showed that only age (P=0.001) and purpose of the radiation therapy (P=0.047) were the independent prognostic factor of OS. N stage (P=0.0151) was the unitivarate factors of OS and DFS in adjuvant chemo-radiation therapy group. There was no grade IV acute toxicity observed. More Grade III toxicity was observed in the group of patients received concurrent-chemotherapy (P=0.002).
Conclusion
1The2-,3-years overall survival of the whole group with age>70are72%and59%respectively.Age was the significant unitivarate factors of OS and independent prognostic factor of OS in this group of>70years old rectal cancer patients.Patients over75had poor prognosis.
2Stage was the significant unitivarate factors of OS but not the independent prognostic factor of OS in this group of≥70years old rectal cancer patients. N stage was the unitivarate factors of OS and DFS in adjuvant chemo-radiation therapy group. NO had favourable prognosis, while N2showed poor prognosis,and N1was in the middle.
3Different purpose of the radiation therapy were the significant unitivarate factor and independent prognostic factor of OS in elderly patients. Neo-adjuvant and adjuvant radiation therapy group had the similar prognosis as younger patients.
4Hypertension and diabetes were the most common co-morbidities in elderly patients. but we didn't find them associate to OS. There were no influence from co-morbidities to prognosis had been obersved.
5The rectal cancer patients≥70showed well tolorent to radiation or chemo-radiation. Concurrent chemotherapy possibly incrsased Grade Ⅲ toxicity in these rectal cancer patients≥70.
引文
[1]Talarico C et al., Long-term outcome after colorectal cancer resection.Patients'self-reported quality of life.sexual dysfunction and surgeons "awareness of patients'needs[J]Tumori.2008 Jan-Feb;94(1)30-5
[2]http://www.who.int/
[3]Fabrice LORCHEL et al., Preoperative radiotherapy in elderly patients with rectal cancer.[J]Gastroenteral Clin Biol 2007.31.436-441.
[3]Saucr R et al., Preoperative Versus Postoperative Chemoradiotherapy for Locally advanced Rectal Caner:Result of Greman CAO/ARO/AIO-94 Randomized Phase Ⅲ Trial After a Median Follow up to 11 years.[J] Clin Oncol 2012.Apr 23[Epub ahead of print]
[4]Saucr R et al.,Preoperative versus postoperative chemoradiotherapy for rectal cancer. [J] N Enq J Med Oct 21:351(17):1731-40
[5]Fabrice LORCHEL et al., Preoperative radiotherapy in elderly patients with rectal cancer.[J]Gastroenteral Clin Biol 2007.31.436-441.
[6]F.Fiorica et al.Adjuvant radiotherapy on older and oldest eldly rectal cancer patients. [J] Archives of Gerontology and Geriatrics 2009.49.54-59.
[7]Tougeron D., et al., Safety and outcome of chemoradiotherapy in elderly patients with rectal cancer:Result from two French teriary centers [J] Dig Liver Dis 2011 Nov 24 [Epub ahead of print]
[8]Wong CS et al., Treatment of local recurrent rectal carcinoma-results and prognosis factors [J] Int J Radiat Oncol Bio Phys 1998; 40:427-35
[9]Endreseth,B.H.,et al.,The Norwegian Rectal Cancer Group,2005.Rectal cancer treatment of the elderly.[J] Colorectal Dis.2005.8,471-479.
[10]Ayanian,J.Z,Zaslavsky,A.M.,et al., Use of adjuvant cchemotherapy and radiation therapy for colorectal cancer in a population-based cohort. [J] Clin.Oncol.2003.21,1293-1300.
[11]Bouvier,A.M.,Launoy,G.,et al.,Trends in the management and survival of digestive tract cancers among patients aged over 80 years.[J] Aliment Pharmacol.Ther.2005.22,223-241.
[12]Endreseth,B.H.,et al.,The Norwegian Rectal Cancer Group,2005.Rectal cancer treatment of the elderly.[J] Colorectal Dis.2005.8,471-479.
[13]Pignon,T.,et al.,Age is not a limiting factor for radical radiotherapy in pelvic malignancies. [J] Radiother.Oncol.1997.42,107-120.
[14]Pasetto,L.M.,et al.,Drtermining therapeutic approaches in the elderly with rectal cancer.[J]Durgs Aging 2007.24.781-790
[15]Chang,G.J.,et al.,Are we undertreating rectal cancer in the elderly? An epidemiologic study.Ann.Surg. [J] Ann.Surg,2007.246,215-221.
[16]Schrag,D.,et al.,Who gets adjuvant treatment for stage II and stage III rectal cancer? Insight from surveillance,epidemiology.and end results Medicare. [J] Clin.Oncol.2001.19,3712-3718.
[17]Vironen,J.H.,et al.,Complications and survival after surgery for rectal cancer in patients younger than and aged 75 years old or older.[J]Dis Colon Rectum 2004.47,1225-1231.
[18]Bosset JF et al., Preoperative chemoradiotherapy vrtsus preoperative radiotherapy in rectal cancer patients:assessment of acute toxicity and treatment compliance. Report of 22921 randomised trial conclucted by EORTC Radiotherapy Group. [J]Eur J Cancer 2004.40(2) 219-24
[19]Rodel C et al; Mutlicenter phase Ⅱ trail of chemoradiation with oxaliplatin for rectal cancer.[J] Clin Oncol 2007 May 20:25(15) 2149
[20]Gunderson L L et al, Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer:a pooled analysis. [J] Clin Oncol 2004; 22(10):1785-1796.
[21]Gerard JP et al., Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer:result of the phase Ⅲ trial ACCORD 12/0405-Prodige 2. [J] J Clin Oncol 2010 Apr 1;28(10):1638-44.Epub 2010 Mar 1.
[22]Aschele C et al, Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer:pathologic results of the STAR-01 randomized Phase III trial. [J] Clin Oncol.2011 Jul 10;29(20):2773-80
[23]Lee JH,. Long-Term Follow-Up of Preoperative Pelvic Radiation Therapy and Concomitant Booost Irradiation in locally Advanced Rectal Cancer Patients:A Mulit-Institutional Phase II Study(KROG 04-01) [J] Int J Radiat Oncol Biol Phys.2012 Apr 24 Epub ahead of print.
[24]Andre T, Improved overall survival with oxaliplatin,fluorouracil,and leucovorin as adjuvant treatment in stage II or III colonrectal cancer in the MOSAIC trial. [J] Clin Oncol 2009 Jul 1;27(19)3109-16.
[25]Potosky AL et al., Age, sex,and racial differences in the use of standard adjuvant therapy for colorectal cancer. [J] Clin Oncol 2002:20(5):1192-1202
[2]http://www.who.int/
[3]Fabrice LORCHEL et al., Preoperative radiotherapy in elderly patients with rectal cancer.[J]Gastroenteral Clin Biol 2007.31.436-441.
[3]Saucr R et al., Preoperative Versus Postoperative Chemoradiotherapy for Locally advanced Rectal Caner:Result of Greman CAO/ARO/AIO-94 Randomized Phase Ⅲ Trial After a Median Follow up to 11 years.[J] Clin Oncol 2012.Apr 23[Epub ahead of print]
[4]Saucr R et al.,Preoperative versus postoperative chemoradiotherapy for rectal cancer. [J] N Enq J Med Oct 21:351(17):1731-40
[5]Fabrice LORCHEL et al., Preoperative radiotherapy in elderly patients with rectal cancer.[J]Gastroenteral Clin Biol 2007.31.436-441.
[6]F.Fiorica et al.Adjuvant radiotherapy on older and oldest eldly rectal cancer patients. [J] Archives of Gerontology and Geriatrics 2009.49.54-59.
[7]Tougeron D., et al., Safety and outcome of chemoradiotherapy in elderly patients with rectal cancer:Result from two French teriary centers [J] Dig Liver Dis 2011 Nov 24 [Epub ahead of print]
[8]Wong CS et al., Treatment of local recurrent rectal carcinoma-results and prognosis factors [J] Int J Radiat Oncol Bio Phys 1998; 40:427-35
[9]Endreseth,B.H.,et al.,The Norwegian Rectal Cancer Group,2005.Rectal cancer treatment of the elderly.[J] Colorectal Dis.2005.8,471-479.
[10]Ayanian,J.Z,Zaslavsky,A.M.,et al., Use of adjuvant cchemotherapy and radiation therapy for colorectal cancer in a population-based cohort. [J] Clin.Oncol.2003.21,1293-1300.
[11]Bouvier,A.M.,Launoy,G.,et al.,Trends in the management and survival of digestive tract cancers among patients aged over 80 years.[J] Aliment Pharmacol.Ther.2005.22,223-241.
[12]Endreseth,B.H.,et al.,The Norwegian Rectal Cancer Group,2005.Rectal cancer treatment of the elderly.[J] Colorectal Dis.2005.8,471-479.
[13]Pignon,T.,et al.,Age is not a limiting factor for radical radiotherapy in pelvic malignancies. [J] Radiother.Oncol.1997.42,107-120.
[14]Pasetto,L.M.,et al.,Drtermining therapeutic approaches in the elderly with rectal cancer.[J]Durgs Aging 2007.24.781-790
[15]Chang,G.J.,et al.,Are we undertreating rectal cancer in the elderly? An epidemiologic study.Ann.Surg. [J] Ann.Surg,2007.246,215-221.
[16]Schrag,D.,et al.,Who gets adjuvant treatment for stage II and stage III rectal cancer? Insight from surveillance,epidemiology.and end results Medicare. [J] Clin.Oncol.2001.19,3712-3718.
[17]Vironen,J.H.,et al.,Complications and survival after surgery for rectal cancer in patients younger than and aged 75 years old or older.[J]Dis Colon Rectum 2004.47,1225-1231.
[18]Bosset JF et al., Preoperative chemoradiotherapy vrtsus preoperative radiotherapy in rectal cancer patients:assessment of acute toxicity and treatment compliance. Report of 22921 randomised trial conclucted by EORTC Radiotherapy Group. [J]Eur J Cancer 2004.40(2) 219-24
[19]Rodel C et al; Mutlicenter phase Ⅱ trail of chemoradiation with oxaliplatin for rectal cancer.[J] Clin Oncol 2007 May 20:25(15) 2149
[20]Gunderson L L et al, Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer:a pooled analysis. [J] Clin Oncol 2004; 22(10):1785-1796.
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