Technical aspects of the deep inspiration breath-hold technique in the treatment of thoracic cancer

PURPOSE: The goal of this paper is to describe our initial experience with the deep inspiration breath-hold (DIBH) technique in conformal treatment of non-small-cell lung cancer with particular emphasis on the technical aspects required for implementation. METHODS AND MATERIALS: In the DIBH technique, the patient is verbally coached through a modified slow vital capacity maneuver and brought to a reproducible deep inspiration breath-hold level. The goal is to immobilize the tumor and to expand normal lung out of the high-dose region. A physicist or therapist monitors and records patient breathing during simulation, verification, and treatment using a spirometer with a custom computer interface. Examination of internal anatomy during fluoroscopy over multiple breath holds establishes the reproducibility of the DIBH maneuver for each patient. A reference free-breathing CT scan and DIBH planning scan are obtained. To provide an estimate of tumor motion during normal tidal breathing, additional scan sets are obtained at end inspiration and end expiration. These are also used to set the spirometer action levels for treatment. Patient lung inflation is independently verified over the course of treatment by comparing the distance from the isocenter to the diaphragm measured from the DIBH digitally reconstructed radiographs to the distance measured on the portal films. Patient breathing traces obtained during treatment were examined retrospectively to assess the reproducibility of the technique. RESULTS: Data from the first 7 patients, encompassing over 250 treatments, were analyzed. The inferred displacement of the centroid of gross tumor volume from its position in the planning scan, as calculated from the spirometer records in over 350 breath holds was 0.02 +/- 0.14 cm (mean and standard deviation). These data are consistent with the displacements of the diaphragm (-0.1 +/- 0.4 cm; range, from -1.2 to 1.1 cm) relative to the isocenter, as measured on the (92) portal films. The latter measurements include the patient setup error. The patient averaged displacement of the tumor during free breathing, determined from the tumor displacement between end inspiration and end expiration, was 0.8 +/- 0.5 cm in both the superior-inferior and anterior-posterior directions and 0.1 cm (+/- 0.1 cm) medial-laterally. CONCLUSION: Treatment of patients with the DIBH technique is feasible in a clinical setting. With this technique, consistent lung inflation levels are achieved in patients, as judged by both spirometry and verification films. Breathing-induced tumor motion is significantly reduced using DIBH compared to free breathing, enabling better target coverage.     

深吸气屏气技术在放疗中的运用

在胸腹部肿瘤的放疗中,呼吸运动对放疗的负面影响贯穿放疗全流程。深吸气屏气(DIBH)是放疗中呼吸运动管理的一种方法,能够在放疗全流程中减少呼吸运动对放疗带来的负面影响。同时,DIBH技术与其他呼吸运动管理措施(四维CT、门控技术、追踪等)相比有其自身的特点和操作要求。本文的目的是对DIBH技术的优缺点及应用现状进行介绍。     

左侧乳腺癌保乳术后放疗采用深吸气屏气技术肺部剂量Meta分析

目的:通过Meta分析探究左侧乳腺癌保乳术后放疗使用深吸气屏气技术对左肺剂量的影响。方法:2020年11月01日前检索PubMed、EMBASE、Web of Science寻找符合纳入标准的期刊文章,评价指标为左肺V20及左肺Dmean,通过Stata 12.0对提取的研究数据行Meta分析。结果:纳入20篇文献,共663例患者,异质性分析结果I2 检验(I-squared=69.5%)及Q检验(P=0.000)提示纳入20项研究间异质性较大。亚组分析结果:40例及以上组I2检验（I-squared=0%）及Q检验(P=0.909)提示各研究间无异质性;40例以下组I2检验（I-squared=76.8%）及Q检验(P=0.000) 提示异质性显著,说明异质性来源可能为样本量过小。最终对40例及以上组7项研究进行效应量合并,左肺V20在DIBH与自由呼吸（FB）两组间差异具有统计学意义［SMD=-0.28,95%CI（-0.41,-0.15）,Z=4.16,P=0.000］;左肺Dmean在DIBH与FB两组间差异具有统计学意义［SMD=-0.20,95%CI（-0.33,-0.07）,Z=2.96,P=0.003］。Egger回归检验结果提示本研究不存在明显的发表偏倚V20（P=0.971>0.05）及Dmean（P=0.666>0.05）。结论:左侧乳腺癌保乳术后放疗使用DIBH技术可以降低肺部照射剂量,从而减少放射性肺炎的发生概率,具有一定的临床价值。     

BRONCHIAL ARTERY CHEMOTHERAPY FOR INOPERABLE NON-SMALL-CELL LUNG CANCER

ＢＲＯＮＣＨＩＡＬＡＲＴＥＲＹＣＨＥＭＯＴＨＥＲＡＰＹＦＯＲＩＮＯＰＥＲＡＢＬＥＮＯＮ－ＳＭＡＬＬ－ＣＥＬＬＬＵＮＧＣＡＮＣＥＲＹａｎｇＺｅｑｕａｎ；杨泽泉；ＹａｎｇＹｕｅ；杨跃；ＬｉｕＷｅｎｈａｉ；刘文海；ＬｉＹｕｅｍｉｎ；李曰民；ＣｈｅｎＨｏｎｇ...     

Accelerated fractionation regimens in radiotherapy of inoperable non-small-cell lung cancer

The results of definitive radiation treatment (1988-2000) for 375 patients with inoperable non-small cell lung cancer were analyzed. Three regimens of fractionation were used: (1) accelerated fractionation (AF)--(133), 2.5 Gy, 3 days a week, to a total of 47.5--55 Gy; (2) accelerated hyperfractionation (AHF)--(93), 1.25 Gy, daily, to a total of 60-72.5 Gy and standard fractionation (SF)--(149), 2 Gy, daily, to a total of 58-68 Gy. The advantages of AHF were established as regards complete regression rate (54.9% vs. 18.6%--SF and 18.1%--AF; p(0.001), median survival (30.5(2.4 months vs. 18.9 (1%--SF (p = 0.004) and 20.4 (2.4--AF (p = 0.004)), and 3-year survival (36.6% vs. 16.7%--SF (p = 0.005) and 15.5%--AF (p = 0.005). 17.9%, 9.0% (p = 0.11) and 8.1% (p = 0.08) have survived, respectively. Overall survival in the AHF group was superior in stages IIB--III; in stage I, the results were identical. Immediate response to radical radiotherapy appeared the only statistically significant factor of survival (p = 0.005-0.008) in all the groups.     

左侧乳腺癌保乳术后采用深吸气屏气放疗的心脏剂量学分析

目的 探究左侧乳腺癌保乳术后放疗患者采用深吸气屏气(DIBH)技术对心脏剂量的改善情况,分析可能影响心脏剂量的解剖因素。方法 前瞻性入组 15例左侧乳腺癌保乳术后行全乳放疗患者,符合呼吸控制要求。分别在自由呼吸(FB)和DIBH状态下进行2次模拟CT扫描,在DIBH图像上制定全乳放疗计划。比较FB和DIBH状态下心肺位置和体积变化以及心肺剂量差异,探究FB状态下各解剖因素与心脏剂量的相关性。对计数资料组间行非参数Wilcoxon秩和检验,双变量相关分析采用Pearson法。结果 DIBH与FB状态下心脏体积相似(P=0.773),而双肺体积明显增加(P=0.001)。心脏、冠脉左前降支、左心室、右心室和左肺 Dmean、Dmax和V5—V40均明显降低(P<0.05)。DIBH使肺体积增加越显著,心脏平均剂量下降幅度越大。FB状态下乳腺体积、心肺体积比、乳腺下界与心脏下界距离、最大心脏切缘距离分别与心脏剂量呈线性相关,其中心肺体积比、最大心脏切缘距离与心脏剂量具有独立相关性。结论 左侧乳腺癌保乳术后采用DIBH技术行全乳放疗较FB状态明显降低心肺剂量。肺体积的变化是改善心脏相对解剖位置的基础。心肺体积比、最大心脏切缘距离或许可以作为进行DIBH技术治疗的参考标准。     

Combined-modality therapy for inoperable non-small-cell lung cancer using gemcitabine

Combined-modality therapy with chemotherapy and radiation appears to be the most efficacious therapeutic modality for patients with locally advanced non-small-cell lung cancer. Most of the trials exploring this approach have utilized older agents such as cisplatin, vinblastine, and etoposide. Recent data suggest that gemcitabine may be superior to these agents therapeutically, with the ability to produce similar or improved outcomes and a milder overall toxicity profile. Moreover, gemcitabine is able to sensitize tumor cells to radiation-induced apoptosis as well as lead to induction of cells in the radioresistant S phase of the cell cycle. These results have suggested that gemcitabine should be tested in concurrent chemoradiotherapy regimens. Significant toxicities seen in the initial trials have led to a number of trials modifying the regimen so that efficacy might be maintained without adverse effects. These modifications have included lowered gemcitabine doses and reduced radiation field sizes. The results of these newer studies suggest that this approach can be highly efficacious, with 1-year survival rates > 50% and response rates as high as 88%.     

Concurrent chemoradiotherapy for inoperable stage III non-small-cell lung cancer

Chemoradiotherapy has become the standard treatment for patients with locally advanced non-small-cell lung cancer on the basis of several large randomized trials. Despite an increase in median survival from 10 months with radiotherapy alone to 16 to 17 months with concurrent chemoradiotherapy, long-term survival in this disease remains modest at best. With the advent of new biologic agents targeting specific cellular pathways associated with malignant progression, combined-modality therapy has the potential to target tumors selectively with less toxicity.     

Phase II study of fotemustine in untreated inoperable non-small-cell lung cancer

A total of 43 patients with advanced, previously untreated non-small-cell lung cancer (NSCLC) were treated with a novel nitrosourea, fotemustine, given at 100 mg/m² on days 1 and 8. Maintenance treatment consisted of a single injection of 100 mg/m² given every 21 days. 37 patients were evaluable for respone. Of these, 5 patients had a partial response (13.5%; 95% confidence interval, 6%–28%). Toxicity comprised mainly anaemia and thrombocytopenia. Other toxicities were mild. This phase II study confirms that fotemustine is a moderately active and well-tolerated drug in NSCLC.This study was supported by a grant from Servier     

Combined chemotherapy and radiotherapy versus best supportive care in the treatment of inoperable non-small-cell lung cancer.

Between October 1984 and July 1988, 119 patients with limited-stage inoperable non-small-cell lung cancer (NSCLC) were randomized to receive either active treatment (arm 1) or best supportive treatment (arm 2). Arm 1 patients received 3 courses of chemotherapy with cisplatin (100 mg/m2, day 1) and etoposide (125 mg/m2 i.v., day 1; 250 mg/m2 p.o., day 2-3), followed by radiotherapy (4,000 cGy/20 fractions/4 weeks). Arm 2 patients only received best supportive care. Fifty-three and 66 patients were randomized to arms 1 and 2, respectively. Thirty-eight patients in arm 1 and 57 in arm 2 were evaluable for survival. Median survivals of arms 1 and 2 were 12.4 and 8.7 months, respectively (p = 0.047). In the multivariate analysis, only age and histology were independent prognostic variables in predicting survival. The overall response rate after chemotherapy was 20.6% (complete remission 5.9%, partial remission 14.7%). Toxicities were mainly anemia, leukopenia, vomiting and alopecia. This study suggests that active treatment has marginal survival benefit in NSCLC though with considerable toxicities.     

左侧乳腺癌保乳术后采用深吸气屏气放疗技术的应用与摆位误差

目的 了解左侧乳腺癌保乳术后采用深吸气屏气(DIBH)技术行全乳放疗(WBI)的治疗时间与放疗计划的相关性,明确放疗分次间重复性,观察治疗时心脏位置及剂量学变化,计算DIBH技术对左侧乳腺癌术后WBI摆位误差的影响。方法 前瞻性入组15例左侧乳腺癌保乳术后行WBI的患者,符合DIBH控制要求。比较治疗时间与计划射野数和跳数的关系,采用CBCT计算放疗分次间的摆位误差及PTV外放边界。将CBCT与计划CT图像融合,以验证放疗时心脏位置和剂量的准确性。组间数据行非参数Firedman检验。结果 采用DIBH技术放疗的平均单次治疗时间为4.6 min,治疗时间与调强野最大子野数、总子野数和总跳数相关。平均心脏位移体积为19.1 cm³(3.8%),CBCT与计划CT的心脏Dmean相差5.1 cGy,心脏V5-V30差异无统计学意义(P>0.05)。摆位误差的系统误差(Σ)和随机误差(σ)在左右、头脚、前后方向上分别为1.9、2.1、2.0 mm和1.3、1.3、1.4 mm。三维外扩的最小边界左右、头脚、前后方向上分别为5.7、6.2、6.0 mm。结论 左侧乳腺癌保乳术后采用DIBH技术行WBI未明显延长治疗时间,且治疗时间与放疗计划相关。DIBH技术各治疗分次间重复性良好,起到了保护心脏的作用。     

Phase II study of carboplatin in untreated,inoperable non-small-cell lung cancer

Summary A total of 51 previously untreated patients with non-small-cell lung cancer (NSCLC) were treated with 130 mg/m² carboplatin given every 4 weeks as an i. v. infusion on days 1, 3, and 5. Ten patients achieved a partial response and five, a minor response. The overall response rate was 20% (95% confidence limits, 8%–32%). The median duration of response was 3 months and the median overall survival was 4.5 months. Leucopenia, thrombocytopenia and anemia of WHO grade 3 occurred in 4%–6% of patients and grade 3 nausea and vomiting was observed in 8% of our subjects. Grade 4 thrombocytopenia occurred in 3 (6%) patients. Apart from nausea and vomiting, nonhematologic toxicities above grade 2 were not observed. Further trials using carboplatin in NSCLC as a single agent or in combination with other chemotherapeutic agents or radiation are warranted.     

深吸气屏气技术在左侧乳腺癌保乳术后动态容积旋转调强放疗中的剂量学分析

目的:比较深吸气屏气(deep inspiration breath-hold,DIBH)和自由呼吸(free breathing,FB)两种呼吸模式在左侧乳腺癌保乳术后动态容积旋转调强（volumetric modulated arc therapy,VMAT）放疗中的剂量学差异,探寻左侧乳腺癌保乳术后放疗最佳呼吸模式。方法:选取11例左侧乳腺癌保乳术后女性患者,分别在DIBH-CT和FB-CT图像上设计切线弧t-VMAT计划。结果:DIBH呼吸模式下心脏V5、V10、V20、V30、Dmean、左冠状动脉前降支Dmean、左肺Dmean、右肺V5、Dmean及右侧乳腺V5、Dmean均低于FB呼吸模式,且差异均有统计学意义（P均＜0.05）,其中心脏、左冠状动脉前降支LAD及左肺平均剂量分别下降26.2%、47.7%和11.8%。结论:DIBH呼吸模式显著降低了心脏及左冠状动脉前降支等危及器官的受照剂量,采用t-VMAT计划缩短了深吸气屏气技术的治疗时间,提高了患者舒适度,更好的保证治疗顺利进行。     

非小细胞肺癌表皮生长因子受体靶向治疗

表皮生长因子受体(EGFR)对于正常上皮细胞的生长是不可缺少的,但其异常表达会影响细胞的增殖和凋亡.EGFR突变和过表达是许多肿瘤的特征之一.因此针对EGFR的靶向治疗,包括小分子酪氨酸激酶抑制剂和单克隆抗体,已成为治疗非小细胞肺癌(NSCLC)的研究方向.     

Bevacizumab in the treatment of non-small-cell lung cancer

Lung cancer is the leading cause of cancer death in the United States. The majority of patients present with advanced disease, and treatment with standard cytotoxic chemotherapy improves survival and quality of life in patients with a preserved functional status. However, the prognosis is poor with the majority of patients dying in less than a year. Treatment with standard cytotoxic chemotherapy has reached a therapeutic plateau, and new therapeutic approaches have investigated therapies that target the specific molecular pathways involved in carcinogenesis and angiogenesis. The most promising strategy for inhibiting angiogenesis involves agents that either target the proangiogenesis growth factor, vascular endothelial growth factor A (VEGF) by preventing binding to the receptor or inhibiting the downstream signaling of the vascular endothelial growth factor receptor. The only therapeutic agent approved for the treatment of lung cancer is bevacizumab, a monoclonal antibody that binds to VEGF. A recent phase III trial revealed a statistically significant improvement in response rate, progression free and overall survival with combination of bevacizumab with chemotherapy over chemotherapy alone. Attempts to identify surrogate markers of antiangiogenesis activity are currently ongoing, and may assist in the selection of patients for antiangiogenesis therapy and the development of this class of agents.     

血管内皮抑制素在非小细胞肺癌中的应用

Endostatin is a novel anti-angiogenic drug which through multiple pathway inhibits vascular endothelial growth factor expression, to achieve the purpose of the inhibition of tumor angiogenesis. The drug in the treatment of non-small-cell lung cancer in pre-clinical study and clinical application show that: used alone have anti-tumor effect; combined with radiotherapy and chemotherapy can obtain short-term curative effect, and does not increase treatment related toxicity. The adverse effect of the drug is mild and can be well tolerated.     

Dosimetric comparison of moderate deep inspiration breath-hold and free-breathing intensity-modulated radiotherapy for left-sided breast cancer

PurposeThis study determined the dosimetric comparison of moderate deep inspiration breath-hold using active breathing control and free-breathing intensity-modulated radiotherapy (IMRT) after breast-conserving surgery for left-sided breast cancer.Patients and methodsThirty-one patients were enrolled. One free breathe and two moderate deep inspiration breath-hold images were obtained. A field-in-field-IMRT free-breathing plan and two field-in-field-IMRT moderate deep inspiration breath-holding plans were compared in the dosimetry to target volume coverage of the glandular breast tissue and organs at risks for each patient.ResultsThe breath-holding time under moderate deep inspiration extended significantly after breathing training (P < 0.05). There was no significant difference between the free-breathing and moderate deep inspiration breath-holding in the target volume coverage. The volume of the ipsilateral lung in the free-breathing technique were significantly smaller than the moderate deep inspiration breath-holding techniques (P < 0.05); however, there was no significant difference between the two moderate deep inspiration breath-holding plans. There were no significant differences in target volume coverage between the three plans for the field-in-field-IMRT (all P > 0.05). The dose to ipsilateral lung, coronary artery and heart in the field-in-field-IMRT were significantly lower for the free-breathing plan than for the two moderate deep inspiration breath-holding plans (all P < 0.05); however, there was no significant difference between the two moderate deep inspiration breath-holding plans.ConclusionThe whole-breast field-in-field-IMRT under moderate deep inspiration breath-hold with active breathing control after breast-conserving surgery in left-sided breast cancer can reduce the irradiation volume and dose to organs at risks. There are no significant differences between various moderate deep inspiration breath-holding states in the dosimetry of irradiation to the field-in-field-IMRT target volume coverage and organs at risks.