非小细胞肺癌的大分割放疗临床研究进展

 在局部晚期或不能手术的非小细胞肺癌（NSCLC）的治疗中，放射治疗一直起着主导作用。常规分割放疗已沿用了半个世纪，然而疗效并不满意，NSCLC采用60～70Gy的常规放疗，由于残存的肿瘤细胞会出现加速再增殖，有80％局部肿瘤不能被控制，加大放疗剂量会使总生存率升高，但势必增加治疗时间。Mehta等发现NSCLC是一种增殖较快的肿瘤，倍增时间为2．5～3．3天，治疗时间超过6周，每延长1天生存率就减少1．6％。     

非小细胞肺癌后程加速超分割放疗疗效观察

目的：通过前瞻性的研究非小细胞肺癌（ＮＳＣＬＣ）后程加速超分割放疗的疗效，寻找ＮＳＣＬＣ的最佳治疗手段。方法：对１９９３年１月～１９９６年７月我院收治的７０例ＮＳＣＬＣ患随机分组研究。常规组３５例：用＾６０Ｃｏ或８Ｍｖ－ｘ，５次／Ｗ，２Ｇｙ／次，总剂量７０Ｇｙ／３５次／７～８Ｗ。后程加速超分割组３５例：放疗前程为常规分割，２Ｇｙ／次，４０Ｇｙ／２０次／４Ｗ后改野，５天／Ｗ，２次／天，１．８Ｇｙ／     

大分割适形放疗在非小细胞肺癌患者中的临床研究

目的 探讨大分割适形放疗与常规分割适形放疗在非小细胞肺癌(NSCLC)中的临床效果.方法 选取68例NSCLC患者作为研究对象,按照随机数字表法分为两组,每组34例.其中对照组患者给予常规分割适形放疗,研究组患者给予大分割适形放疗,观察对比两组患者的近期临床疗效、不良反应发生率及生存率.结果 研究组患者治疗总有效率为94.1%,高于对照组患者的73.5%(P﹤0.05);研究组患者3年、5年的生存率分别为88.2%、58.8%,均高于对照组患者的64.7%、32.4%(P﹤0.05);对两组Ⅰ、Ⅱ期及Ⅲ期患者进行分层分析,在早期(Ⅰ、Ⅱ期)患者中,研究组生存率优于对照组(P﹤0.05),而在局部中晚期(Ⅲ期)患者中差异无统计学意义(P﹥0.05);根据肿瘤体积进行分层分析,在肿瘤体积≤90 cm3的NSCLC患者中,研究组生存率优于对照组(P﹤0.05),而在肿瘤体积﹥90 cm3的NSCLC患者中,研究组与对照组比较差异无统计学意义(P﹥0.05);研究组患者不良反应发生率为32.4%,与对照组患者的38.2%比较,差异无统计学意义(P﹥0.05).结论 大分割适形放疗治疗NSCLC的临床疗效较好,可有效提高患者生存率,减少不良反应,是一种值得在临床中推广应用的治疗方式.     

局部晚期非小细胞肺癌三维适形大分割放射治疗疗效观察

目的 探讨大分割三维适形放射治疗局部晚期非小细胞肺癌的近期疗效及副反应.方法 88 例NSCLC随机分为两组,三维适形放疗组(治疗组)46例和常规放疗组(对照组)42例.治疗组予3DCRT照射,隔日1次,每次4～8Gy,总照射量40～64Gy;对照组予常规分割照射,每周治疗5次,每次1.8～2.0Gy,总照射量60～70Gy.结果 治疗组和对照组近期疗效比较,两组有效率(CR+PR)分别为95.5%、59.5%(P<0.05),1、2年生存率分别为71.7%、45.2%(P<0.05)和43.4%、33.3%(P>0.05).两组不良反应均能耐受,但对照组不良反应重于治疗组.结论 三维适形大分割放射治疗局部晚期非小细胞肺癌安全、可靠,近期疗效较好,但远期疗效有待进一步随访.     

非手术非小细胞肺癌的大分割放射治疗

非小细胞肺癌约占原发肺癌的85%,对于不可手术或拒绝手术的非小细胞肺癌患者,放射治疗成为治疗的主要手段。随着影像和放疗技术的发展,大分割放疗在非小细胞肺癌中的应用取得了较好的疗效。本文旨在对非小细胞肺癌大分割放疗的放射生物学基础和非手术非小细胞肺癌大分割放疗的最新临床研究进行系统性回顾。     

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.     

非小细胞肺癌加速超分割放疗临床Ⅰ／Ⅱ期试验

目的观察非小细胞肺癌（ＮＳＣＬＣ）加速超分割（ＨＡＲＴ）放疗的副反应及疗效。材料与方法１９９１年１２月～１９９４年１２月，６９例进入本研究（９例未完成放疗计划）。ＨＡＲＴ放疗，３次／天，１．１Ｇｙ／次，间隔４小时，总刑量７２－７６Ｇｙ／６６－６９次／３３（２９－４２）天。对照组（ＣＦＩ），１次／天，１．８－２．０Ｇｙ／次，总剂量６２－６５Ｇｙ／３２－３６次／４８（４５－５２）天。结果（１）急性放射性食管炎：ＨＡＲＴ组８７％（５２例），ＣＦＩ组４４％（２２例）（Ｐ＜０．００１）。（２）两组肺急性及后期放疗反应均无差异（Ｐ值均＞０．０５）。（３）即期嵙菩В海龋粒遥宰榛航饴剩ǎ茫遥校遥┪福埃ィ庞冢茫疲勺榈模常福ィǎ校迹埃埃埃保＃ǎ矗┥媪菩В海保玻衬晟媛剩龋粒遥宰槲罚玻ィ矗罚ィ玻福ィ茫疲勺槲叮埃ィ保福ィ叮ィǎ校迹埃埃埃保＃龋粒遥宰榫挚芈室灿庞冢茫疲勺椋ǎ校剑埃埃埃保洞ψ坡氏灾儆冢茫疲勺椋ǎ校剑埃埃玻保＞茫希囟嘁蛩胤治鼋峁荆龋粒遥蕴岣吡松婕熬挚芈剩档土嗽洞ψ坡省＝崧郏ǎ保龋遥粒灾瘟颇芪蠖嗍危樱茫蹋媚褪埽ǎ玻龋粒遥苑帕铺岣吡松媪菩А     

Ⅲ期非小细胞肺癌放疗加化疗疗效分析

目的：评价Ⅲ期非小细胞肺癌（NSCLC）放疗加化疗的疗效及毒副反应。方法;对80例Ⅲ期NSCLC患者随机分为两组,其中40例接受放射治疗加化疗（治疗组）,另40例接受单纯放疗（对照组）。放射治疗采用6MV X线常规外放射,照射野包括肺原发灶及纵隔淋巴引流区DT66Gy/33f/6-7W,化疗采用PEC方案（顺铂、足叶乙甙、环磷酰胺）。结果：放疗加化疗组与单纯放疗组的1年、2年生存率分别为67．5％和30．0％、37．5％和12．5％（P＜0．05）,其3年、5年生存率分别为17．5％和7．5％、7．5％和2．5％（P＞0．05）。化疗的毒副作用主要是骨髓抑制和消化道反应,但均能耐受,其后期并发症两组无统计学差异。结论：同步放疗加化疗治疗Ⅲ期NSCLC,毒性反应可耐受,能明显提高1年,2年生存率,其3年、5年生存率无影响。     

三维适形低分割放疗治疗Ⅲ、Ⅳ期非小细胞肺癌疗效观察

目的:探讨低分割放疗治疗Ⅲ、Ⅳ期非小细胞肺癌的临床疗效。方法:分析接受胸部放疗肺癌患者43例,分割剂量2.5Gy/天,5次/周,总剂量50Gy;TNM分期Ⅲ、Ⅳ期17、26例。结果:随访4-12个月,随访率100%。放射性食管炎发生率34.9%,2级以上放射性肺炎发生率1 1.6%。近期疗效:CR 2 5.6%、PR5 1.2%、SD 1 4.0%、PD 9.3%;1年生存率65.1%。结论:三维适形低分割放疗对Ⅲ、Ⅳ期非小细胞肺癌患者近期疗效确切,放疗毒副反应可以耐受。     

A prospective, randomised study to compare two palliative radiotherapy schedules for non-small-cell lung cancer (NSCLC)

A prospective randomised study compared two palliative radiotherapy schedules for inoperable symptomatic non-small-cell lung cancer (NSCLC). After stratification, 100 patients were randomly assigned to 20 Gy/5 fractions (fr)/5 days (arm A) or 16 Gy/2 fr/day 1 and 8 (arm B). There were 90 men and 10 women aged 47-81 years (mean 66), performance status 1-4 (median 2). The major clinical characteristics and incidence and degree of initial disease-related symptoms were similar in both groups. Treatment effects were assessed using patient's chart, doctor's scoring of symptomatic change and chest X-ray. Study end points included degree and duration of symptomatic relief, treatment side effects, objective response rates and overall survival. A total of 55 patients were assigned to arm A and 45 to arm B. In all, 98 patients received assigned treatment, whereas two patients died before its termination. Treatment tolerance was good and did not differ between study arms. No significant differences between study arms were observed in the degree of relief of all analysed symptoms. Overall survival time differed significantly in favour of arm B (median 8.0 vs 5.3 months; P=0.016). Both irradiation schedules provided comparable, effective palliation of tumour-related symptoms. The improved overall survival and treatment convenience of 2-fraction schedule suggest its usefulness in the routine management of symptomatic inoperable NSCLC.     

大分割适形放射治疗在非小细胞肺癌中的应用

大分割适形放疗技术较常规分割技术能给予肿瘤更高的生物有效剂量,近年来研究显示,对早期不能手术非小细胞肺癌（NSCLC）患者,大分割适形放疗高效低毒,是可选择的治疗方案。许多临床Ⅰ、Ⅱ期研究显示,局部晚期NSCLC患者对大分割适形放疗耐受性良好。放射物理学模型和相关临床研究显示,与常规分割放疗模式相比大分割适形放疗不会增加放射性肺炎发生率。     

Outcomes of accelerated hypofractionated radiotherapy in stage i non-small-cell lung cancer

Purpose

Outcomes after treatment with accelerated hypofractionated radiotherapy in stage i medically inoperable non-small-cell lung cancer (nsclc) patients were determined.

Methods

Our single-institution retrospective review looked at medically inoperable patients with T1–2N0M0 nsclc treated with accelerated hypofractionated curative-intent radiotherapy between 1999 and 2009. Patients were staged mainly by computed tomography imaging of chest and abdomen, bone scan, and computed tomography/magnetic resonance imaging of brain. Positron-emission tomography (pet) staging was performed in 6 patients. Medical charts were reviewed to determine demographics, radiotherapy details, sites of failure, toxicity (as defined by the Common Terminology Criteria for Adverse Events, version 3.0) and vital status. The cumulative incidence of local and distant failure was calculated. Overall (os) and cause-specific (css) survival were estimated by the Kaplan–Meier method.

Result

In the 60 patients treated during the study period, the dose regimens were 50 Gy in 20 fractions (n = 6), 55 Gy in 20 fractions (n = 8), 60 Gy in 20 fractions (n = 42), and 60 Gy in 25 fractions (n = 4). All patients were treated once daily. The median follow-up was 27 months (range: 4–94 months). The os rates at 2 and 5 years were 61% [95% confidence interval (ci): 50% to 75%] and 19% (95% ci: 10% to 34%) respectively. The css rates at 2 and 5 years were 79% (95% ci: 68% to 91%) and 39% (95% ci: 24% to 63%) respectively. The cumulative incidence of local failure was 20% at 5 years. The cumulative incidence of distant failure was 28% at 5 years. No patients experienced grade 3 or greater pneumonitis or esophagitis.

Conclusions

Accelerated hypofractionated regimens are well tolerated and provide good local control in medically inoperable patients with stage i nsclc. Such regimens may be a reasonable treatment alternative when stereotactic body radiation therapy is not feasible.     

后程X线立体定向放射治疗局部晚期非小细胞肺癌的研究

目的探讨后程大分割X线立体定向放射治疗在局部晚期非小细胞肺癌放射治疗中的作用。方法106例初治局部晚期(Ⅲa、Ⅲb期)非小细胞肺癌病例随机分为单纯常规放射治疗组(CRT)和后程立体定向放射治疗组(LCHSRT),完成治疗并且资料完整者共91例,CRT组43例,LCHSRT组48例。CRT组常规剂量分割大野对穿照射至43.5Gy后对原发肿瘤和转移淋巴结缩野加量至65.2Gy。LCHSRT组常规剂量分割大野对穿照射至44.4Gy后对原发肿瘤和转移淋巴结行大分割立体定向放射治疗,LCHSRT照射方式为圆形准直器非共面弧形照射,计划靶区体积边缘处方剂量4～7Gy/次,隔日1次,总剂量(22.8±5.5)Gy。结果CRT组和LCHSRT组放射性肺炎的发生率分别为11.6%和14.6%。放射治疗结束后3个月CT检查CRT与LCHSRT组局部肿瘤全消率分别为30.2%和63.5%(P<0.01);1年局部控制率分别为62.0%和86.5%(P>0.05);1年生存率分别为55.8%和79.2%(P<0.05)。两组急慢性放射性肺损伤差异均无显著性意义(χ2值分别为0.68和2.90,P值均>0.05)。结论圆形准直器非共面弧形照射后程大分割立体定向放射治疗提高了局部晚期非小细胞肺癌的局部肿瘤全消率和局部控制率,但其适形性和靶区内剂量均匀性不够理想,而且当照射剂量≥25Gy时放射性肺纤维化发生率明显增加。     

Palliative thoracic radiotherapy for lung cancer

Despite an increasing use of chemotherapy in the palliative setting for lung cancer, the role of palliative thoracic radiotherapy should not be disregarded. It offers quick and efficient palliation, with improvement observed in approximately two-thirds of treated patients. There is evidence that the short and long radiotherapy schedules are equally effective for poor performance patients. Higher radiation doses delivered via protracted schedules give a modest survival benefit for good performance patients. The current review covers the issues related to the use of palliative thoracic radiotherapy, such as total dose, fractionation, delayed versus immediate use, external-beam radiotherapy versus endobronchial brachytherapy, combination with chemotherapy, re-irradiation and palliation with radiation in small-cell lung cancer.     

A study of acute side-effects related to palliative radiotherapy treatment of lung cancer

Two recent studies carried out by the Medical Research Council Lung Cancer Working Party have suggested that large fraction radiotherapy to the chest in either 10-Gy single fraction or 17-Gy two-fraction doses, 1 week apart, is safe and effective for patients who require palliation for bronchogenic cancer.
The Beatson Oncology Centre, Glasgow, participated in the original MRC trial and anecdotal reports of acute chest pains, fevers, sweats and rigors in some patients during the first 24-hour period after radiotherapy treatment were noted. These acute side-effects were not monitored during the Medical Research Council trials. It was felt that this area warranted further evaluation in order to identify the incidence of such acute side-effects and to what extent they caused a reduction in the patients'remaining quality of life.
A pilot study of 10 patients confirmed the manifestation of the side-effects reported anecdotally in the MRC trial. It was on this basis that the study was extended, with a further 51 patients being invited to participate over a 4-month period.
The findings indicate a significant incidence of adverse side-effects in patients receiving large fraction radiotherapy to the chest in either 10-Gy single fraction or 17-Gy two-fraction doses, but that these are transient and do not cause unacceptable disruption to the patients over an extended period.     

A review of hypofractionated palliative radiotherapy

Radiotherapy commonly is employed to address symptoms in patients with symptoms caused by cancer. For this article, the authors reviewed data supporting the use of hypofractionated palliative radiotherapy. In addition to single-fraction treatment for painful bony metastasis, the available literature suggested that courses of 2 to 14 external-beam fractions may provide equivalent relief to longer course treatment in patients with a poor prognosis who have primary cancers of the lung, rectum, bladder, prostate, head and neck, spleen, and gynecologic system. Hypofractionated treatment delivers palliation that is time efficient, cost effective, and minimally toxic. Evidence suggests that the reluctance of radiation oncologists to provide single-fraction treatment acts as a barrier to referrals from palliative care professionals. Collaboration in education, research, and patient advocacy will advance the common objectives of the 2 specialties and lead to an appropriate increase in the use of palliative hypofractionated radiotherapy.     

Optimising stereotactic body radiotherapy for non-small cell lung cancer with volumetric intensity-modulated arc therapy--a planning study

Aims

The potential advantages of stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC) over conventional fractionated radiotherapy include a higher biological effective dose, a reduction in accelerated repopulation, greater patient convenience and reduced demand on radiotherapy resources. Before introducing SBRT in our department, a review of planning and delivery was undertaken, starting with an assessment of optimum beam number and arrangement.

Materials and methods

Radiotherapy planning computed tomography scans for five patients previously treated for T1 peripheral NSCLC were selected. In each the contoured tumour had planning target volume (PTV) margins of 1 cm in all directions. Forward-planned three-field coplanar and non-coplanar plans and a seven-field coplanar plan were produced and optimised. In-house inverse-planning software (AutoBeam) was used to generate three-, five-, seven- and nine-field coplanar and non-coplanar plans and two volumetric intensity-modulated arc therapy (VMAT) plans. The resulting V₂₀, V₁₁, PTV₉₀, PTV₉₅ and mean lung dose were compared.

Results

Analysis of variance showed non-coplanar plans to have lower V₁₁ and higher PTV₉₀ and PTV₉₅ than coplanar plans. VMAT showed equivalent V₂₀ and target coverage when compared with the best non-coplanar plans, but with a faster delivery time (2 min 8 s versus 12 min 40 s).

Conclusions

Inverse-planned five-field non-coplanar plans and VMAT improve target coverage while minimising the higher dose to normal lung tissue for SBRT of NSCLC compared with coplanar beam arrangements. VMAT is preferable because of significantly shorter treatment delivery times.     

大分割三维适形放疗在非小细胞肺癌治疗中的应用

背景与目的：采用常规分割放射治疗治疗非小细胞肺癌其局部控制率较低，在适形放疔技术下可以采用大分割放疗，有望提高其局部控制率，但合适的分割剂量和毒性还需要深入研究。本研究前瞻性评估采用大分割三维适形放疗治疗非小细胞肺癌的安全性和有效性。方法：根据剂量体积直方图V20（受到20Gy以上照射的肺的体积占全肺体积的比例）水平将患者分成3组治疗：①低V20组（V20≤20％组），②中V20组（20％〈V20〈30％组），③高V20组（V20≥30％组），每5例患者为一组依次进入上述3个V20水平进行试验，放疗方法为三维适形放疔，每次3Gy，总剂量57～66Gy，4～5周完成。最大耐受剂量定义为10例患者中有至少有8例患者能耐受剂量限制毒性（≥Ⅲ级的放射性损伤）。放射毒性分级采用美国肿瘤放射治疗协作组（RTOG）早期和晚期损伤标准。所有患者不进行同期放化疔。结果：低V20组，共10例患者完成试验，无≥HI级的放射性肺炎发生；中V20组，先5例患者中有1例发生Ⅲ级放射性肺炎，再增加5例患者后无发生≥Ⅲ级的放射性肺炎；高V20组，5例患者中有2例发生Ⅲ级放射性肺炎，1例发生Ⅳ级放射性肺炎而死亡。没有≥Ⅲ级的放射性食管炎：25例患者中有8例达到完全缓解（32％），13例达到部分缓解（52％）．3例稳定（12％），1例进展（4％）。结论：进行大分割三维适形放疗时，把V20控制在30％以下是可行的，当V20≥30％时应改为姑息性放疗。其有效性需要进一步研究。