汉防己甲素防治放射性肺损伤的临床观察

目的:观察汉防已甲素(Tet)防治放射性肺损伤的安全性疗效.方法:122例胸部放疗患者分为实验组(RT+Tet)52例,对照组(RT)70例.放疗均采用3D-CRT技术,DT56～70 Gy.肺V20控制在(20±6)%.实验组于放疗中每周1～6 d口服Tet 100 mg/次,3次/d.观察药物毒副反应和放射性肺损伤情况.结果:两组均顺利完成治疗计划,未发生药物相关不良反应.急性放射性肺损伤,实验组:0级20例,Ⅰ级29例,Ⅱ级3例.对照组:0级41例,Ⅰ级27例,Ⅱ级2例;晚期放射性肺损伤,实验组:0级41例,Ⅰ级9例,Ⅱ级2例.对照组:0级51例,Ⅰ级13例,Ⅱ级6例.两组急性和晚期放射性肺损伤发生情况,差异均无统计学意义,P值分别为0.083和0.536.对照组临床中激素应用率为39%(27/70),明显高于实验组19%(10/52),P=0.022.结论:Tet在胸部放疗中使用安全,对急性和晚期放射性肺损伤的防治作用尚未显现.激素的应用可能是观察放射性肺损伤的主要影响因素之一.     

Ⅲ+Ⅳ期非小细胞肺癌三维适形放疗正常肺V_5、V_(10)预测放射性肺损伤前瞻性临床研究

目的 探讨非小细胞肺癌三维适形放疗正常肺低剂量体积对放射性肺损伤的预测作用.方法 采用三维适形后程加速超分割放疗经病理或细胞学证实的非小细胞肺癌患者100例.Ⅲ期14例,Ⅲb期36例,Ⅳ期50例.鳞癌49例,腺癌48例,腺鳞癌3例.初治79例、术后复发8例,术后残留12例,术后辅助1例.单纯放疗9例,放化疗91例.放疗剂量60～80 Gy,60～69 Gy 24例,≥70 Gy76例.化疗方案采用紫杉类+铂类一线方案.用剂量体积直方图计算正常肺V_5、V_(10)、V_(20)、V_(30)和平均肺剂量(MLD).肺损伤评估根据CTC 3.0标准.结果 全组V_5为37%～98%,中位值65%;V_(10)为27%～78%,中位值47.5%;V_(20)为17%～54%,中位值31%;V_(30)为9%～31%,中位值24%.100例患者中发生放射性肺炎(RP)1级34例,2级27例,3级8例,4级1例,5级1例.75例患者中发生放射性肺纤维化1级46例,2级14例,3级2例.V_5、V_(10)、V_(20)、MLD与≥1级RP相关,V_(5)、V_(20)、V_(30)、MLD与≥2级RP相关,V_5与≥3级RP相关.V_(5)、V_(20)、V_(30)、分别>65%、31%、24%时发生≥2级RP概率增加,V_(5)、V_(20)分别>65%、31%时发生≥3级RP概率增加,V_(20)>31%时发生≥1级RP概率增加.大体肿瘤体积、计划靶体积与≥1级RP、≥2级放射性肺纤维化相关.性别、年龄、临床分期、处方剂量、照射野数目与各级放射性肺损伤无关.结论 剂量体积参数V_(5)、V_(10)与RP发生相关,可能成为放射肺损伤有效的预测因子.     

食管癌术后调强放疗致放射性肺损伤的相关因素分析

目的 探讨食管癌术后调强放疗致放射性肺损伤的相关因素.方法 回顾性分析采用调强放疗的65例食管癌术后患者的相关临床资料.患者给予计划靶区37.5 ～60 Gy/19～ 30 W2 Gy的处方剂量.行同步化疗的患者采取TP方案(紫杉醇+顺铂),观察年龄、性别、吸烟史、有无同步化疗以及放射物理参数V5、V10、V20、V30、Dmean与放射性肺损伤发生的相关性.结果 食管癌术后实行调强放疗的放射性肺损伤发生率为26.2％,年龄、性别、吸烟史和有无同步化疗与放射性肺损伤的发生无显著相关性(均P＞0.05),V5、V10、V20、V30、Dmean与放射性肺损伤的发生均显著相关(均P＜0.05).结论 食管癌术后放疗患者放射性肺损伤的发生与V5、V10、V.、V30、Dmean具有密切的相关性,在制定放疗计划时应考虑与放射性肺损伤有关的危险因素.     

V20、MLD与放射性肺损伤的相关性研究

目的研究V20、MLD与放射性肺损伤发生的相关性,指导临床放疗计划的制定,避免或减少放射性肺损伤,提高局部控制率,改善患者生存质量。方法自2008年8月至2010年6月,47例符合研究条件的肺癌患者入组。所有患者均接受三维适形放疗,应用6MVX-线照射,剂量50～70Gy/25～35f。制定放疗计划,生成剂量-体积直方图(DVH),得到物理参数V20及MLD,分析以上参数及其他临床因素对放射性肺损伤的影响,放疗计划要求V20≤30%,脊髓总量≤45Gy。放疗结束后定期行胸片及CT复查,根据辅助检查结果及临床表现诊断放射性肺损伤的发生,依据RTOG分级标准评价放射性肺损伤的程度。结果 47例中有15例发生放射性肺损伤,放射性肺损伤发生率为31.9%(15/47)。当V20≤25%和>25%时,放射性肺损伤发生率分别为14.3%和46.2%,差异有统计学意义﹙P<0.05﹚。当MLD≤15Gy和>15Gy时,放射性肺损伤发生率分别为14.3%和57.9%,差异有统计学意义﹙P<0.05﹚。结论 V20、MLD与放射性肺损伤有相关性,对预测放射性肺损伤有一定价值。     

非小细胞肺癌大分割三维适形放疗的剂量递增研究

目的:探讨非小细胞肺癌大分割三维适形放疗的最大耐受剂量和毒性.方法:采用三维适形放疗,分割剂量3Gy/次,每周5次.据肺V20(照射剂量≥20Gy的肺的体积占双肺体积的百分比)进行剂量递增.V20≤20%组从66Gy开始剂量递增,20%＜V20≤30%组从60Gy开始剂量递增.每个剂量级别至少入组3例患者.结果:2005年6月至2007年5月共有32例非小细胞肺癌患者进入临床试验.V20≤20%组,总剂量66Gy 3例,69Gy 3例,72Gy 3例,75Gy 7例,在75Gy剂量水平有2例患者出现3级急性放射性肺炎和晚期放射性肺损伤.20%＜V20≤30%组,总剂量60Gy 3例,63Gy 3例,66Gy 3例,69Gy 7例,在69Gy剂量水平有2例患者出现3度急性放射性肺炎和晚期放射性肺损伤.治疗结束后评价近期疗效完全缓解为19%(6/32),部分缓解为72%(23/32),稳定为9%(3/32),有效率为89%(29/32).中位随访时间19个月(10～32个月),34.3%(11/32)患者出现病情进展,1年疾病无进展率为65.7%(21/32).结论:非小细胞肺癌采用三维适形放疗技术3Gy(次大分割照射是可行的,肺V20≤20%的最大耐受剂量为75Gy,20%＜V20≤30%为69Gy,今后还需要更多病例来验证其疗效和远期毒性.     

肺癌患者急性放射性肺损伤发生的相关因素分析

[目的]分析肺癌患者放射治疗后急性放射性肺损伤发生的影响因素。[方法]选取171例肺癌放射治疗的患者,采用Logistic回归分析研究性别、年龄、是否化疗、放疗剂量、V5、V20、平均肺剂量(MLD)等因素与患者3级及以上急性放射性肺损伤发生率的相关性。[结果]171例肺癌放射治疗的患者中,发生3级及以上急性放射性肺损伤50例(29.3%)。单因素分析发现,吸烟、放疗前化疗周期数多、同期放化疗、V5>40%、V20>25%、V20>28%、MLD>10Gy、MLD>13Gy均可导致肺癌患者3级及以上放射性肺损伤发生率的升高。多因素分析显示,吸烟、放疗前化疗周期数多、V20>28%、MLD>13Gy与3级及以上放射性肺损伤发生率有关。[结论]在肺癌放疗计划设计中,应针对中国肺癌患者的特点,设定适合的物理参数;此外,还需考虑患者的吸烟史、化疗史等个体化因素,尽可能降低急性放射性肺损伤的发生率。     

血浆内皮素-1与放射性肺损伤的关系

目的探讨肺癌放疗前、中、后血浆内皮素－1（ET-1）的水平和肺剂量体积因素V20与发生放射性肺损伤的相关性。方法接受三维适形放疗的48例原发性非小细胞肺癌患者,肿瘤总照射剂量62～66Gy,常规分割2Gy/次,5次/周。计划控制V20≤30％,脊髓剂量≤45Gy。ELISA方法对每位患者放疗前、放疗40Gy及放疗后血浆ET-1的浓度进行定量检测。结果全组放射性肺损伤的发生率为27.1%（13/48)。放疗40Gy时,ET-1升高的患者放射性肺损伤的发生率为41.7％,高于ET-1水平正常者12.5％（P=0.023）;放疗结束时ET 1水平升高者放射性肺损伤发生率为44％,显著高于ET-1水平正常者的8.7％（P=0.006）; V20≥25%,放疗结束时ET-1升高,放射性肺损伤的发生率为69.2%,明显高于其他组别;而V20＜25％,放疗结束时ET-1正常的患者放射性肺损伤的发生率为5.9％,明显低于其他组别。结论放疗中及放疗结束后血浆内皮素-1水平升高与放射性肺损伤密切相关。V20≥25%同时放疗结束时血浆ET-1升高者,属于发生放射性肺损伤的高危人群,可作为放射性肺损伤的预测指标,值得临床进一步研究。     

血浆TGF-β1与放射性肺损伤的相关性研究

目的探讨放疗前后血浆TGF-β1的水平和V20与发生放射性肺损伤的相关性。方法受三维适形放疗的53例肺癌患者,肿瘤总照射剂量40～70Gy,常规分割2Gy/次,5次/周。计划控制V20≤35%,脊髓剂量≤45Gy。应用ELISA方法对患者放疗前后血浆TGF-β1的浓度进行定量检测。结果全组放射性肺损伤的发生率为32.1%(17/53),其中Ⅱ级或Ⅱ级以上发生率为13.2%。放疗结束时,TGF-β1水平升高者放射性肺损伤的发生率为51.9%,明显高于TGF-β1水平正常者(11.5%)(P=0.002),而放疗前TGF-β1水平升高或在正常范围,放射性肺损伤发生率无显著差异(P=0.315)。V20>25%,放疗结束时TGF-β1水平升高,放射性肺损伤的发生率为62.5%,明显高于其它组别;而V20≤25%,放疗结束时血浆TGF-β1正常的患者没有发生放射性肺损伤。结论放疗结束时TGF-β1水平升高与放射性肺损伤密切相关。V20>25%,放疗结束时TGF-β水平升高者,属于发生放射性肺损伤的高危人群。     

V20、MLD与放射性肺损伤的相关性研究

目的研究V20、MLD与放射性肺损伤发生的相关性,指导临床放疗计划的制定,避免或减少放射性肺损伤,提高局部控制率,改善患者生存质量。方法自2008年8月至2010年6月,47例符合研究条件的肺癌患者人组。所有患者均接受三维适形放疗,应用6MVX-线照射,剂量50—70Gy／25—35f。制定放疗计划,生成剂量-体积直方图（DVH）,得到物理参数V20及MLD,分析以上参数及其他临床因素对放射性肺损伤的影响,放疗计划要求V20≤30％,脊髓总量≤45Gy。放疗结束后定期行胸片及CT复查,根据辅助检查结果及临床表现诊断放射性肺损伤的发生,依据RTOG分级标准评价放射性肺损伤的程度。结果47例中有15例发生放射性肺损伤,放射性肺损伤发生率为31．9％（15／47）。当V20≤25％和〉25％时,放射性肺损伤发生率分别为14．3％和46．2％,差异有统计学意义（P〈0．05）。当MLD≤15Gy和〉15Gy时,放射性肺损伤发生率分别为14．3％和57．9％,差异有统计学意义（P〈0．05）。结论V20、MLD与放射性肺损伤有相关性,对预测放射性肺损伤有一定价值。     

适形放疗与常规放疗结合治疗Ⅲ期肺鳞癌疗效分析

自 1996年 10月 -2 0 0 0年 10月对 118例Ⅲ期肺鳞癌常规放射治疗 40～ 5 0Gy(平均 44 6Gy)后的残留病灶再行适形放疗。肿瘤边缘单次处方剂量平均为 6 8Gy ,间隔 1～ 2d ,总照射剂量平均为 39 4Gy。肿瘤靶体积 (GTV) 0 8cm3～ 14 8 6cm3,平均 36 6cm3,计划靶体积 (PTV ) 3 6cm3～ 2 13 5cm3,平均 5 1 4cm3。近期肿瘤退缩率分别为CR30 5 % ( 36 118)、PR 5 3 4% ( 63 118)、NR 11 9% ( 14 118)和PD 4 2 % ( 5 118) ,总有效率 (CR +PR ) 83 9%。 1、2、3年生存率分别为 68 6% ( 81 118)、35 6% ( 31 87)和 12 2 % ( 6 49) ,局部控制率分别为 92 4% ( 10 9 118)、85 1% ( 74 87)和79 6% ( 39 49)。急性放射性肺炎Ⅰ～Ⅱ级 2 7 1% ( 32 118) ,Ⅲ级 3 4% ( 4 118) ,Ⅳ级 0 ( 0 118)。急性放射性食管炎Ⅰ～Ⅱ级 16 1% ( 19 118) ,Ⅲ～Ⅳ级 0 ( 0 118)。骨髓抑制Ⅰ～Ⅱ级 9 3% ( 11 118) ,Ⅲ～Ⅳ级 0 ( 0 118)。晚期放射性食管反应Ⅲ级 1例 ,放射性肺损伤Ⅱ级 1例。结果说明 ,对Ⅲ期肺鳞癌常规放疗后再行适形放疗局部加量照射 ,患者可耐受 ,疗程短 ,提高肿瘤控制率 ,延长生存期 ,是局部剂量升级的有效方法     

Lung carcinoma

Chemotherapy for patients with advanced lung carcinoma at an early period of diseases contributes to prolonged survival. However, since survivals are limited to around 1 year, it is critical for patients to stay at home and continue their social activities under chemotherapy. As active agents such as paclitaxel, docetaxel, gemcitabine, vinorelbine and irinotecan were introduced into clinical practice, and new techniques for preventing side effects such as emesis and neutropenia were developed, chemotherapy for outpatients become feasible also in Japan. In addition, the outpatient chemotherapy, preventing oncologic emergency and early starting of palliative care are also very important for patients'quality of life (QOL) at home. This review summarizes the present status of taking care for outpatients with lung cancer.     

Lung cancer

Although surgery offers the best chance of cure for patients with early stage (I-resectable III A) non-small cell lung cancer (NSCLC), the overall 5-year survival rate is modest, and systematic improvements are needed. In the 1990s, two small prospective randomized phase III trials demonstrated striking results with neo-adjuvant chemotherapy and therefore several randomized trials were performed. However, there was no statistical significant trial among them. The recent systematic meta-analysis based on 8 trials revealed hazard ratio was 0.88 (95%CI: 0.76-1.01), although these data suggested a 12% relative benefit with the neoadjuvant chemotherapy, equivalent to an absolute improvement in survival of 5% at 5 years. For patients with stage N2-III A NSCLC, US intergroup trial (INT0139) also demonstrated there was no statistical difference between chemoradiotherapy following surgery and chemoradiotherapy on overall survival. At present, there is no scientific evidence of the neoadjuvant strategy for early stage NSCLC in practice. This invasive treatment is still investigational and should be done as the clinical trial base.     

Lung cancer

The number of lung cancer deaths in Japan has been continuously increasing for decades, mainly because of the growing size of the elderly population. In contrast, age-specific lung cancer death rates for those aged under 79 years plateaued recently, reflecting the decreasing smoking rates since 1966. However, the smoking rate for males (54% in 1999) is still extraordinarily high in Japan compared to other developed countries, so it is necessary to further promote anti-smoking activities. It is reported that the relative risk for lung cancer due to cigarette smoking increases 4-5 fold (current smokers versus non-smokers) for males and 2-3 fold for females, and that the population attributable risk is 70% for males and 15-25% for females in Japan, which indicates that cigarette smoking is the most influential risk factor for lung cancer. However, the magnitude of the relative risk and population attributable risk is not as high as those observed in other developed countries. In order to clarify the reasons for this, it is necessary to further accumulate findings from actual epidemiological studies in Japan. In addition to cigarette smoking, occupational exposures, dietary habits (low intake of vegetables and fruits), atmospheric air pollution, environmental tobacco smoke, cooking and heating fuels, indoor radon and previous lung diseases are reported to increase the risk of lung cancer.     

Lung cancer

Aging society is coming now, the ratio of elderly patients among all lung cancer patients has currently been increasing. It is necessary for elderly patients who are under-represented in clinical trials to study their suitable regimen. Thus, phase II and III clinical trials have been performed specifically for elderly non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients all over the world. As for single agent chemotherapy, there is a strong rationale for docetaxel and vinorelbine in elderly patients with advanced NSCLC. Recently, there are phase I and II clinical trial for CPT-11 monotherapy, and gefitinib and TS-1 are reasonable options for elderly patients. Alimta is tolerable for elderly, and subset analysis is performed for the elderly with recurrent NSCLC. As platinum-based chemotherapy, there are several elderly subset analyses and JCOG 0207, which is a phase III trial now in progress comparing weekly cisplatin+weekly docetaxel and weekly docetaxel. In SCLC, there is no evidence of single agent chemotherapy but combination chemotherapy such as carboplatin+etoposide is recommended. A phase III study of carboplatin+etoposide versus amrubicin under way. These studies should aim to optimize several agents for elderly patients and prolong survival, palliative care.     

Lung Cancer and Lung Transplantation: A Review

With the increase in the number of lung transplants, it is expected that there will be a corresponding increase in the number of lung cancers reported in these patients. Longevity of the transplant recipients, lung transplantation for chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, a history of smoking, and the increasing age of the lung donors make lung cancer more likely. Nodules and masses seen in chest imaging in lung transplant patients call for work up until a final diagnosis is achieved because there is a high likelihood of a serious infection or malignancy. The presence of a native lung is a major risk factor for lung cancer occurring in the transplant setting. Lung cancer of donor origin is rare. Bronchioloalveolar carcinoma confined to one lung can potentially be treated by transplanting the affected lung. Treatment for patients with lung cancer in the lung transplant setting has to be individualized because of the complexity of their medical problems and multiple medications. Attention needs to be focused on detecting lung cancer early in these patients to achieve a favorable outcome.