氩氦刀联合中药治疗老年晚期非小细胞肺癌的临床研究和预后分析
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摘要
[研究背景]
在我国,肺癌的发病率和死亡率在恶性肿瘤中居第一位。老年非小细胞肺癌(NSCLC)患者具有生理功能衰退、合并症多、确诊多为晚期等特点,制定治疗方案时不能照搬年轻患者的治疗模式。探索有效、安全、毒副作用小、耐受性好的治疗方法,改善老年晚期NSCLC患者生活质量,延长生存期成为肿瘤领域研究的重点。
氩氦刀冷冻消融术是一种新型微创治疗,具有靶向性强、创伤小、恢复快、无严重并发症等优点,为丧失手术切除机会的老年晚期NSCLC患者带来新的希望。北京中医药大学东方医院肿瘤科在国内率先开展了CT引导经皮穿刺氩氦刀治疗老年肺癌,大量的前期研究显示,氩氦刀能直接消融肿瘤局部病灶,疗效确切,安全性好,耐受性好,已广泛应用于治疗多种恶性肿瘤。中医药参与治疗肺癌是我国恶性肿瘤综合治疗的重要组成部分。我科坚持以中西医结合、局部治疗与全身治疗相结合、内治与外治相结合的思想指导恶性肿瘤治疗,提出了局部氩氦刀联合中药治疗恶性肿瘤这一独具特色的“绿色治疗”模式,将氩氦刀局部冷冻与中药治疗的各自优势结合。中药治疗恶性肿瘤是一个综合干预的过程,以辨证论治为基础,往往不拘泥于一病一方、一方一药,依据患者疾病阶段、证候特点、患者状况等,选择中药汤剂、中药注射液及中成药等治疗方式,以制定最佳的个体化治疗模式,充分体现中医“异病同治”、“同病异治”的学术思想。
[研究目的]
1.探讨氩氦刀联合中药治疗老年晚期NSCLC的临床疗效,分析氩氦刀联合中药治疗老年晚期NSCLC影响预后的因素,为优化氩氦刀治疗老年晚期NSCLC方案提供可靠的临床依据。
2.探讨氩氦刀治疗老年晚期NSCLC术前术后中医证候的分布情况及其演变规律,为中医证候规范化研究提供参考依据。
[研究方法]
本研究以年龄≥65岁的IIB期和Ⅳ期NSCLC并自愿接受氩氦刀治疗的患者为研究对象,以临床死亡为研究的终点事件,按照是否接受中药治疗分为中西医结合组和西医对照组。共收集符合纳入标准患者130例,分为中西医结合组65例和西医治疗组65例,中西医结合组氩氦刀术后在辨证论治基础上予中药治疗(包括中药注射液、中药汤剂和口服中成药)+最佳支持治疗(BSC),西医治疗组氩氦刀术后予西医综合治疗,包括按照NCCN指南予西医抗肿瘤治疗和BSC。主要观察指标包括无进展生存期、氩氦刀术后生存期和总生存期,次要观察指标包括影像学疗效评价和临床疗效评价,分别于术后1周、术后1月和术后3月随访患者的体力状况评分(PS评分)、生活质量评分(QOL评分)、临床症状评分和中医证候进行分析。
[研究结果]
1.基线资料比较
两组病例中,除吸烟指数以外,其他如年龄、性别、病理类型、分化程度转移部位等基线资料,差异均无统计学意义(P>0.05)。中西医结合组中吸烟指数高≥400(支*年)者46例比西医治疗组(33例)多,差异具有统计学意义(P<0.05)。
2.影像学疗效评价
两组氩氦刀治疗的手术部位、肿瘤病灶大小及手术次数、术中CT影像监测评价及术中有效率比较,差异均无统计学意义(P>0.05),两组接受氩氦刀手术情况具有可比性。实体瘤疗效结果显示,术后1月中西医结合组有效率为46.15%,比西医治疗组(41.54%)稍高,但差异无统计学意义(P>0.05)。术后3月两组比较,术后3月中西医结合组有效率(41.54%)比西医治疗组(32.31%)稍高,但差异无统计学意义(P>0.05)。
3.近期疗效评价
体力状况方面,术后1周两组体力状况(PS评分)比较,差异无统计学意义(P>0.05)。术后1月和术后3月,中西医结合组PS评分改善情况均优于西医治疗组,差异具有统计学意义(P<0.05)。
生活质量方面,中西医结合组术后3月QOL评分为(47.85±2.780),与术前1天评分(46.78±3.65)比较明显提高,差异具有统计学意义(P<0.05)；西医治疗组术后1周评分为(45.08±3.371),与术前1天评分比较(46.08±3.42)明显下降,差异具有统计学意义(P<0.05)；两组比较,术后3月中西医结合组评分(47.85±2.78)比西医治疗组评分(46.15±3.43)高,差异具有统计学意义(P<0.05)。
临床症状改善方面,术后1周比较两组临床症状改善情况,差异无统计学意义(P>0.05)。术后1月中西医结合组病例中咯痰、神疲乏力及食欲不振症状改善情况优于西医治疗组(P<0.05),术后3月中西医结合组咳嗽、咯痰、神疲乏力、口干咽燥及食欲不振5个症状改善情况优于西医治疗组(P<0.05)。
4.术后并发症
术后并发症发生率方面,两组比较差异无统计学意义(P>0.05)。以咳嗽加重最多见,其次为术后疼痛,第三为咯血/痰中带血,经对症治疗后能缓解,均未出现严重甚至致死性并发症
并发症缓解时间方面,中西医结合组咳嗽缓解时间为(5.11±2.17)天比西医治疗组(6.68±3.12)天短(P<0.05)；中西医结合组术后疼痛缓解时间为(3.47±1.92)天,比西医治疗组(5.35±2.06)天短(P<0.05)；中西医结合组术后咯血或痰中带血和手术相关性发热缓解时间比西医治疗组短,但差异无统计学意义(P>0.05)。
5.远期疗效
中西医结合组术后生存期为14个月,总生存期(OS)为23个月；西医治疗组术后生存期为12个月,OS为21个月,中西医结合组术后生存期和OS均比西医治疗组略长,但差异无统计学意义(P>0.05)。中西医结合组无进展生存期(PFS)为7个月,西医治疗组PFS为5个月,中西医结合组PFS比西医治疗组长(P<0.05)。
进一步分层分析,年龄≥75岁共26例,中西医结合组术后生存期为13个月,OS为22个月；西医治疗组术后生存期为8个月,OS为21个月,中西医结合组术后生存期比西医治疗组长(P<0.05)。ⅢB期共62例,中西医结合组术后生存期为26个月,比西医治疗组21个月长(P<0.05)。高分化组共32例,中西医结合组术后生存期26个月,比西医治疗组15个月长(P<0.05)。PS3分组病例共14例,中西医结合组术后生存期7个月,比西医治疗组4个月长(P<0.05)。
6.预后因素分析
对中西医结合组65例进行预后分析,单因素分析显中TNM分期、吸烟指数、PS评分、分化程度和CEA水平是影响氩氦刀联合中药治疗老年晚期NSCLC的预后因素；年龄、性别、手术部位、手术次数、肿瘤病理类型、肿瘤分型等均非预后的影响因素；COX多因素分析显示分化程度是影响预后的独立因素。
7.中医证候演变规律
证型分布方面,中西医结合组65例患者在4个时点共出现27个中医证候分型,单证6例,复证21例,主要以气虚+其他要素为主。
证候要素方面,虚以气虚、阴虚为主,实以痰湿、血瘀为主。气虚证素术后各时点频次与术前比较差异均无统计学意义(P>0.05)；阴虚证素术后1月频次比术前减少(P<0.05),其余时点与术前比较差异均无统计学意义(P>0.05)；痰湿证素术后各时点频次与术前比较差异均无统计学意义(P>0.05)；血瘀证素术后1月和术后3月频次均比术前增多(P<0.05),术后1周与术前比较差异无统计学意义(P>0.05)。
证候虚实方面,虚证术后3月为11例,比术前(22例)减少(P<0.05),其余时点与术前比较差异无统计学意义(P>0.05)；实证术后各时点例数与术前(7例)比较,差异均无统计学意义(P>0.05)；虚实夹杂证术后3月(47例)比术前(36例)增多(P<0.05)；其余时点与术前比较差异无统计学意义(P>0.05)。
[研究结论]
1.氩氦刀联合中药治疗老年晚期NSCLC能改善体力状况及临床症状,提高生活质量；氩氦刀治疗老年晚期NSCLC术后并发症较轻,耐受性好,中药治疗有利于促进术后并发症恢复；氩氦刀联合中药治疗是值得推广的治疗模式。
2.氩氦刀联合中药治疗能延长无进展生存期,对于年龄≥75岁、IIIB期、高分化、PS3分患者,更能从氩氦刀联合中药治疗模式获得生存益处。
3.单因素分析结果显示TNM分期、分化程度、吸烟指数、PS评分、CEA水平是影响氩氦刀联合中药治疗老年晚期NSCLC预后的因素；多因素分析显示分化程度是影响预后的独立因素
4.老年晚期NSCLC患者虚以气虚、阴虚为主,气虚贯穿疾病始终；实以痰湿、血瘀为主,血瘀随病程进展而加重；虚实夹杂证是氩氦刀术前术后的主要虚实证型,随病程推移而增多
[Background]
In our country, the morbidity and mortality of lung cancer ranks first in the malignant tumor. Elderly patients with non-small cell lung cancer (NSCLC) have unique physiological and pathological characteristics, such as physiological function degradation, more complications and lateness of correct diagnosis, so the oncologists can't simply copy the treatment of young patients when making treatment plans for elderly patients. Exploring effective, small side effects and good tolerance treatments, which can improve the quality of life and prolong survival in elderly patients with advanced NSCLC, has become the focus of cancer researches.
Argon-helium cryoablation which has many advantages such as small trauma, fast repair, no serious complications and strong targeting, has brought new hope for elderly patients with advanced NSCLC. A unique mode of "green treatment" has been presented by oncology department in Dongfang Hospital of Beijing university of Chinese medicine. It concludes a treatment of local argon-helium cryoablation combined with traditional Chinese medicine (TCM) on the basis of syndrome differentiation and treatment. Medicinal broth, Chinese patent medicine and injection of TCM can be used for treatment according to syndrome and stage of disease. Hope to provide reliable clinical data for formulating a better therapeutic regimen of advanced NSCLC.
[Objective]
1. To observe and assess the effect and security of argon-helium cryoablation combined with TCM, in order to provide reliable clinical data for formulating better therapeutic regimen of advanced NSCLC.
2. To investigate characteristic of distribution and developing of syndrome in advanced NSCLC after argon-helium cryoablation.
[Methods]
130NSCLC elderly patients with stage ⅢB and Ⅳ were included in this study. Patients were divided into2groups. The group of Combination of traditional Chinese and western medicine (group I) including65patients were given the treatments of TCM combined with best supportive care (BSC) after argon-helium cryoablation. The group of western medicine multi-modality (group II) including65patients were given the treatments of western medicine treatments. Western medicines were given based on the NCCN clinical practice guidelines of NSCLC in2011. The principle of TCM treatment including medicinal broth, Chinese patent medicine and injection were formulated according to syndrome differentiation and treatment. Main observation indexes included postoperative survival and overall survival. Secondary observation indexes included imaging evaluation and clinical curative effect evaluation. Besides, performance status (PS) scores, quality of life (QOL) scores, and TCM syndrome were observed and analyzed at1day before operation, postoperative1week, postoperative1month and postoperative3month respectively.
[Results]
1. Baseline data comparison The number of patients whose smoking index were more than400in group I was higher than group II, with statistical difference (P<0.05). There were no significant differences on the other baseline information such as gender, age, primary site of tumor, clinical classification, pathological type, TNM staging, PS score, metastatic sites, the degree of differentiation, basic diseases, pre-operative tumor markers between the two groups.
2. Imaging curative effect evaluation There were no significant differences on the size and location of surgical tumor, and the number of operation (P>0.05). The efficient of imaging evaluation during the surgery of group Ⅰ (95.38%) was higher than group Ⅱ (96.92%), but no statistical difference (P>0.05). There were no significant differences on the efficient of imaging evaluation1month after surgery of group I was46.15%, while group Ⅱ was41.54%. There were no statistical differences (P>0.05). The efficient of imaging evaluation of group Ⅰ (41.54%) was higher than group Ⅱ (32.31%)3month after surgery, but no statistical difference (P>0.05).
3. Short-term curative effect evaluation
①The PS score of group I was superior to group Ⅱ1month and3month after surgery respectively (P<0.05). There was no statistical difference1week after surgery (P>0.05).
②The QOL score of group I (47.85±2.78) was higher than group Ⅱ (46.15±3.43)3month after surgery, with statistical difference(P<0.05). The score of group I at3month after surgery(47.85±2.78) was higher than those before surgery(46.78±3.65), with statistical difference(P<0.05). The score of group Ⅱ at1week after surgery(45.08±3.37) was lower than those before surgery(46.78±3.65), with statistical difference(P<0.05).
③The improvement of expectoration, god fatigue, and loss of appetite in group I was superior to group II1month after surgery(P<0.05). The improvement of cough, expectoration,god fatigue, dry throat, and loss of appetite in group I was superior to group II3month after surgery(P<0.05).
4. Postoperative complications
There were no significant differences on the incidence of complications before surgery(P>0.05). The most common complications were aggravating cough, pain of surgical site, hemoptysis and blood in phlegm. The relief time of cough in group I (5.11±2.17d) was shorter than group II (6.68±3.12d), with statistical difference(P<0.05). The relief time of pain in group I (3.47±1.92d) was shorter than group II (5.35±2.06d), with statistical difference(P<0.05).
5. The long-term curative effect evaluation
The postoperative survival and the overall survival (OS) of group I was higher than group II respectively, but no statistical difference (P>0.05). The progression free survival time of group I (7months) was higher than group II (5months) respectively, with statistical difference(P<0.05).The patients who were more than75years old, or IIIB, or high differentiation, or PS score=3in group I benefited with significantly longer survival rates.
6. Prognostic factors analysis
It showed that TNM staging, smoking index, PS score, degree of differentiation, and CEA levels were the factors influencing prognosis in Kaplan Meier analysis. The COX regression analysis showed that degree of differentiation were independent prognosis factors
7. Evolutions of TCM syndromes
①There were27types of TCM syndromes in total.
②The mainly syndrome element could be mainly sum as4patterns:the deficiency of Qi, deficiency of Yin, phlegm-damp and blood stasis. There were no statistical differences on the frequency of deficiency of Qi, phlegm-damp at different time points respectively. The frequency of deficiency of Yin decreased1months after surgery, with statistical difference(P<0.05). The frequency of blood stasis increased1months and3months after surgery, with statistical difference(P<0.05).
③Syndrome of intermingled deficiency and excess was the main deficiency-excessiveness syndromes, which increased after surgery with the progression of the disease (P<0.05)
[Conclusion]
1. The treatment of argon-helium cryoablation combined with TCM could shorten the relief time of postoperative complications, and improve the PS scores, QOL scores, and clinical syndrome such as cough, expectoration, fatigue, dry throat, and loss of appetite. TCM treatment after surgery could help to alleviate postoperative complications. The treatment of argon-helium cryoablation combined with TCM is well worth spreading.
2. The treatment of argon-helium cryoablation combined with TCM could lengthen the PFS. The patients who were75years of age and older, or IIIB, or high differentiation, or PS score=3could get the survival benefit.3. TNM staging, smoking index, PS score, degree of differentiation and CEA
levels were the factors influencing prognosis in Kaplan Meier analysis. The COX regression analysis showed that the degree of differentiation were independent prognosis factors.
4. Deficiency of Qi, deficiency of Yin, phlegm-damp and blood stasis were the most common syndrome elements. Syndrome of intermingled deficiency and excess was the main deficiency-excessiveness syndromes, which increased after surgery with the progression of the disease.
在我国,肺癌的发病率和死亡率在恶性肿瘤中居第一位。老年非小细胞肺癌(NSCLC)患者具有生理功能衰退、合并症多、确诊多为晚期等特点,制定治疗方案时不能照搬年轻患者的治疗模式。探索有效、安全、毒副作用小、耐受性好的治疗方法,改善老年晚期NSCLC患者生活质量,延长生存期成为肿瘤领域研究的重点。
氩氦刀冷冻消融术是一种新型微创治疗,具有靶向性强、创伤小、恢复快、无严重并发症等优点,为丧失手术切除机会的老年晚期NSCLC患者带来新的希望。北京中医药大学东方医院肿瘤科在国内率先开展了CT引导经皮穿刺氩氦刀治疗老年肺癌,大量的前期研究显示,氩氦刀能直接消融肿瘤局部病灶,疗效确切,安全性好,耐受性好,已广泛应用于治疗多种恶性肿瘤。中医药参与治疗肺癌是我国恶性肿瘤综合治疗的重要组成部分。我科坚持以中西医结合、局部治疗与全身治疗相结合、内治与外治相结合的思想指导恶性肿瘤治疗,提出了局部氩氦刀联合中药治疗恶性肿瘤这一独具特色的“绿色治疗”模式,将氩氦刀局部冷冻与中药治疗的各自优势结合。中药治疗恶性肿瘤是一个综合干预的过程,以辨证论治为基础,往往不拘泥于一病一方、一方一药,依据患者疾病阶段、证候特点、患者状况等,选择中药汤剂、中药注射液及中成药等治疗方式,以制定最佳的个体化治疗模式,充分体现中医“异病同治”、“同病异治”的学术思想。
[研究目的]
1.探讨氩氦刀联合中药治疗老年晚期NSCLC的临床疗效,分析氩氦刀联合中药治疗老年晚期NSCLC影响预后的因素,为优化氩氦刀治疗老年晚期NSCLC方案提供可靠的临床依据。
2.探讨氩氦刀治疗老年晚期NSCLC术前术后中医证候的分布情况及其演变规律,为中医证候规范化研究提供参考依据。
[研究方法]
本研究以年龄≥65岁的IIB期和Ⅳ期NSCLC并自愿接受氩氦刀治疗的患者为研究对象,以临床死亡为研究的终点事件,按照是否接受中药治疗分为中西医结合组和西医对照组。共收集符合纳入标准患者130例,分为中西医结合组65例和西医治疗组65例,中西医结合组氩氦刀术后在辨证论治基础上予中药治疗(包括中药注射液、中药汤剂和口服中成药)+最佳支持治疗(BSC),西医治疗组氩氦刀术后予西医综合治疗,包括按照NCCN指南予西医抗肿瘤治疗和BSC。主要观察指标包括无进展生存期、氩氦刀术后生存期和总生存期,次要观察指标包括影像学疗效评价和临床疗效评价,分别于术后1周、术后1月和术后3月随访患者的体力状况评分(PS评分)、生活质量评分(QOL评分)、临床症状评分和中医证候进行分析。
[研究结果]
1.基线资料比较
两组病例中,除吸烟指数以外,其他如年龄、性别、病理类型、分化程度转移部位等基线资料,差异均无统计学意义(P>0.05)。中西医结合组中吸烟指数高≥400(支*年)者46例比西医治疗组(33例)多,差异具有统计学意义(P<0.05)。
2.影像学疗效评价
两组氩氦刀治疗的手术部位、肿瘤病灶大小及手术次数、术中CT影像监测评价及术中有效率比较,差异均无统计学意义(P>0.05),两组接受氩氦刀手术情况具有可比性。实体瘤疗效结果显示,术后1月中西医结合组有效率为46.15%,比西医治疗组(41.54%)稍高,但差异无统计学意义(P>0.05)。术后3月两组比较,术后3月中西医结合组有效率(41.54%)比西医治疗组(32.31%)稍高,但差异无统计学意义(P>0.05)。
3.近期疗效评价
体力状况方面,术后1周两组体力状况(PS评分)比较,差异无统计学意义(P>0.05)。术后1月和术后3月,中西医结合组PS评分改善情况均优于西医治疗组,差异具有统计学意义(P<0.05)。
生活质量方面,中西医结合组术后3月QOL评分为(47.85±2.780),与术前1天评分(46.78±3.65)比较明显提高,差异具有统计学意义(P<0.05)；西医治疗组术后1周评分为(45.08±3.371),与术前1天评分比较(46.08±3.42)明显下降,差异具有统计学意义(P<0.05)；两组比较,术后3月中西医结合组评分(47.85±2.78)比西医治疗组评分(46.15±3.43)高,差异具有统计学意义(P<0.05)。
临床症状改善方面,术后1周比较两组临床症状改善情况,差异无统计学意义(P>0.05)。术后1月中西医结合组病例中咯痰、神疲乏力及食欲不振症状改善情况优于西医治疗组(P<0.05),术后3月中西医结合组咳嗽、咯痰、神疲乏力、口干咽燥及食欲不振5个症状改善情况优于西医治疗组(P<0.05)。
4.术后并发症
术后并发症发生率方面,两组比较差异无统计学意义(P>0.05)。以咳嗽加重最多见,其次为术后疼痛,第三为咯血/痰中带血,经对症治疗后能缓解,均未出现严重甚至致死性并发症
并发症缓解时间方面,中西医结合组咳嗽缓解时间为(5.11±2.17)天比西医治疗组(6.68±3.12)天短(P<0.05)；中西医结合组术后疼痛缓解时间为(3.47±1.92)天,比西医治疗组(5.35±2.06)天短(P<0.05)；中西医结合组术后咯血或痰中带血和手术相关性发热缓解时间比西医治疗组短,但差异无统计学意义(P>0.05)。
5.远期疗效
中西医结合组术后生存期为14个月,总生存期(OS)为23个月；西医治疗组术后生存期为12个月,OS为21个月,中西医结合组术后生存期和OS均比西医治疗组略长,但差异无统计学意义(P>0.05)。中西医结合组无进展生存期(PFS)为7个月,西医治疗组PFS为5个月,中西医结合组PFS比西医治疗组长(P<0.05)。
进一步分层分析,年龄≥75岁共26例,中西医结合组术后生存期为13个月,OS为22个月；西医治疗组术后生存期为8个月,OS为21个月,中西医结合组术后生存期比西医治疗组长(P<0.05)。ⅢB期共62例,中西医结合组术后生存期为26个月,比西医治疗组21个月长(P<0.05)。高分化组共32例,中西医结合组术后生存期26个月,比西医治疗组15个月长(P<0.05)。PS3分组病例共14例,中西医结合组术后生存期7个月,比西医治疗组4个月长(P<0.05)。
6.预后因素分析
对中西医结合组65例进行预后分析,单因素分析显中TNM分期、吸烟指数、PS评分、分化程度和CEA水平是影响氩氦刀联合中药治疗老年晚期NSCLC的预后因素；年龄、性别、手术部位、手术次数、肿瘤病理类型、肿瘤分型等均非预后的影响因素；COX多因素分析显示分化程度是影响预后的独立因素。
7.中医证候演变规律
证型分布方面,中西医结合组65例患者在4个时点共出现27个中医证候分型,单证6例,复证21例,主要以气虚+其他要素为主。
证候要素方面,虚以气虚、阴虚为主,实以痰湿、血瘀为主。气虚证素术后各时点频次与术前比较差异均无统计学意义(P>0.05)；阴虚证素术后1月频次比术前减少(P<0.05),其余时点与术前比较差异均无统计学意义(P>0.05)；痰湿证素术后各时点频次与术前比较差异均无统计学意义(P>0.05)；血瘀证素术后1月和术后3月频次均比术前增多(P<0.05),术后1周与术前比较差异无统计学意义(P>0.05)。
证候虚实方面,虚证术后3月为11例,比术前(22例)减少(P<0.05),其余时点与术前比较差异无统计学意义(P>0.05)；实证术后各时点例数与术前(7例)比较,差异均无统计学意义(P>0.05)；虚实夹杂证术后3月(47例)比术前(36例)增多(P<0.05)；其余时点与术前比较差异无统计学意义(P>0.05)。
[研究结论]
1.氩氦刀联合中药治疗老年晚期NSCLC能改善体力状况及临床症状,提高生活质量；氩氦刀治疗老年晚期NSCLC术后并发症较轻,耐受性好,中药治疗有利于促进术后并发症恢复；氩氦刀联合中药治疗是值得推广的治疗模式。
2.氩氦刀联合中药治疗能延长无进展生存期,对于年龄≥75岁、IIIB期、高分化、PS3分患者,更能从氩氦刀联合中药治疗模式获得生存益处。
3.单因素分析结果显示TNM分期、分化程度、吸烟指数、PS评分、CEA水平是影响氩氦刀联合中药治疗老年晚期NSCLC预后的因素；多因素分析显示分化程度是影响预后的独立因素
4.老年晚期NSCLC患者虚以气虚、阴虚为主,气虚贯穿疾病始终；实以痰湿、血瘀为主,血瘀随病程进展而加重；虚实夹杂证是氩氦刀术前术后的主要虚实证型,随病程推移而增多
[Background]
In our country, the morbidity and mortality of lung cancer ranks first in the malignant tumor. Elderly patients with non-small cell lung cancer (NSCLC) have unique physiological and pathological characteristics, such as physiological function degradation, more complications and lateness of correct diagnosis, so the oncologists can't simply copy the treatment of young patients when making treatment plans for elderly patients. Exploring effective, small side effects and good tolerance treatments, which can improve the quality of life and prolong survival in elderly patients with advanced NSCLC, has become the focus of cancer researches.
Argon-helium cryoablation which has many advantages such as small trauma, fast repair, no serious complications and strong targeting, has brought new hope for elderly patients with advanced NSCLC. A unique mode of "green treatment" has been presented by oncology department in Dongfang Hospital of Beijing university of Chinese medicine. It concludes a treatment of local argon-helium cryoablation combined with traditional Chinese medicine (TCM) on the basis of syndrome differentiation and treatment. Medicinal broth, Chinese patent medicine and injection of TCM can be used for treatment according to syndrome and stage of disease. Hope to provide reliable clinical data for formulating a better therapeutic regimen of advanced NSCLC.
[Objective]
1. To observe and assess the effect and security of argon-helium cryoablation combined with TCM, in order to provide reliable clinical data for formulating better therapeutic regimen of advanced NSCLC.
2. To investigate characteristic of distribution and developing of syndrome in advanced NSCLC after argon-helium cryoablation.
[Methods]
130NSCLC elderly patients with stage ⅢB and Ⅳ were included in this study. Patients were divided into2groups. The group of Combination of traditional Chinese and western medicine (group I) including65patients were given the treatments of TCM combined with best supportive care (BSC) after argon-helium cryoablation. The group of western medicine multi-modality (group II) including65patients were given the treatments of western medicine treatments. Western medicines were given based on the NCCN clinical practice guidelines of NSCLC in2011. The principle of TCM treatment including medicinal broth, Chinese patent medicine and injection were formulated according to syndrome differentiation and treatment. Main observation indexes included postoperative survival and overall survival. Secondary observation indexes included imaging evaluation and clinical curative effect evaluation. Besides, performance status (PS) scores, quality of life (QOL) scores, and TCM syndrome were observed and analyzed at1day before operation, postoperative1week, postoperative1month and postoperative3month respectively.
[Results]
1. Baseline data comparison The number of patients whose smoking index were more than400in group I was higher than group II, with statistical difference (P<0.05). There were no significant differences on the other baseline information such as gender, age, primary site of tumor, clinical classification, pathological type, TNM staging, PS score, metastatic sites, the degree of differentiation, basic diseases, pre-operative tumor markers between the two groups.
2. Imaging curative effect evaluation There were no significant differences on the size and location of surgical tumor, and the number of operation (P>0.05). The efficient of imaging evaluation during the surgery of group Ⅰ (95.38%) was higher than group Ⅱ (96.92%), but no statistical difference (P>0.05). There were no significant differences on the efficient of imaging evaluation1month after surgery of group I was46.15%, while group Ⅱ was41.54%. There were no statistical differences (P>0.05). The efficient of imaging evaluation of group Ⅰ (41.54%) was higher than group Ⅱ (32.31%)3month after surgery, but no statistical difference (P>0.05).
3. Short-term curative effect evaluation
①The PS score of group I was superior to group Ⅱ1month and3month after surgery respectively (P<0.05). There was no statistical difference1week after surgery (P>0.05).
②The QOL score of group I (47.85±2.78) was higher than group Ⅱ (46.15±3.43)3month after surgery, with statistical difference(P<0.05). The score of group I at3month after surgery(47.85±2.78) was higher than those before surgery(46.78±3.65), with statistical difference(P<0.05). The score of group Ⅱ at1week after surgery(45.08±3.37) was lower than those before surgery(46.78±3.65), with statistical difference(P<0.05).
③The improvement of expectoration, god fatigue, and loss of appetite in group I was superior to group II1month after surgery(P<0.05). The improvement of cough, expectoration,god fatigue, dry throat, and loss of appetite in group I was superior to group II3month after surgery(P<0.05).
4. Postoperative complications
There were no significant differences on the incidence of complications before surgery(P>0.05). The most common complications were aggravating cough, pain of surgical site, hemoptysis and blood in phlegm. The relief time of cough in group I (5.11±2.17d) was shorter than group II (6.68±3.12d), with statistical difference(P<0.05). The relief time of pain in group I (3.47±1.92d) was shorter than group II (5.35±2.06d), with statistical difference(P<0.05).
5. The long-term curative effect evaluation
The postoperative survival and the overall survival (OS) of group I was higher than group II respectively, but no statistical difference (P>0.05). The progression free survival time of group I (7months) was higher than group II (5months) respectively, with statistical difference(P<0.05).The patients who were more than75years old, or IIIB, or high differentiation, or PS score=3in group I benefited with significantly longer survival rates.
6. Prognostic factors analysis
It showed that TNM staging, smoking index, PS score, degree of differentiation, and CEA levels were the factors influencing prognosis in Kaplan Meier analysis. The COX regression analysis showed that degree of differentiation were independent prognosis factors
7. Evolutions of TCM syndromes
①There were27types of TCM syndromes in total.
②The mainly syndrome element could be mainly sum as4patterns:the deficiency of Qi, deficiency of Yin, phlegm-damp and blood stasis. There were no statistical differences on the frequency of deficiency of Qi, phlegm-damp at different time points respectively. The frequency of deficiency of Yin decreased1months after surgery, with statistical difference(P<0.05). The frequency of blood stasis increased1months and3months after surgery, with statistical difference(P<0.05).
③Syndrome of intermingled deficiency and excess was the main deficiency-excessiveness syndromes, which increased after surgery with the progression of the disease (P<0.05)
[Conclusion]
1. The treatment of argon-helium cryoablation combined with TCM could shorten the relief time of postoperative complications, and improve the PS scores, QOL scores, and clinical syndrome such as cough, expectoration, fatigue, dry throat, and loss of appetite. TCM treatment after surgery could help to alleviate postoperative complications. The treatment of argon-helium cryoablation combined with TCM is well worth spreading.
2. The treatment of argon-helium cryoablation combined with TCM could lengthen the PFS. The patients who were75years of age and older, or IIIB, or high differentiation, or PS score=3could get the survival benefit.3. TNM staging, smoking index, PS score, degree of differentiation and CEA
levels were the factors influencing prognosis in Kaplan Meier analysis. The COX regression analysis showed that the degree of differentiation were independent prognosis factors.
4. Deficiency of Qi, deficiency of Yin, phlegm-damp and blood stasis were the most common syndrome elements. Syndrome of intermingled deficiency and excess was the main deficiency-excessiveness syndromes, which increased after surgery with the progression of the disease.
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