Dosimetric consequences of tumor volume changes after kilovoltage cone-beam computed tomography for non-operative lung cancer during adaptive intensity-modulated radiotherapy or fractionated stereotactic radiotherapy

Objective The aim of this study was to investigate tumor volume changes with kilovoltage cone-beam computed tomography （kV-CBCT） and their dosimetric consequences for non-operative lung cancer during intensity-modulated radiotherapy （IMRT） or fractionated stereotactic radiotherapy. Methods Eighteen patients with non-operative lung cancer who received IMRT consisting of 1.8-2.2 Gy/fraction and five fractions per week or stereotactic radiotherapy with 5-8 Gy/fraction and three fractions a week were studied, kV-CBCT was performed once per week during IMRT and at every fraction during stereotactic radiotherapy. The gross tumor volume （GTV） was contoured on the kV-CBCT images, and adaptive treatment plans were created using merged kV-CBCT and primary planning computed tomogra- phy image sets. Tumor volume changes and dosimetric parameters, including the minimum dose to 95% （D95） or 1% （D1） of the planning target volume （PTV）, mean lung dose （MLD）, and volume of lung tissue that received more than 5 （Vs）, 10 （Vl0）, 20 （V20）, and 30 （V30） Gy were retrospectively analyzed. Results The average maximum change in GTV observed during IMRT or fractionated stereotactic radio- therapy was -25.85% （range, -13.09% --56.76%）. The D95 and Dr of PTV for the adaptive treatment plans in all patients were not significantly different from those for the initial or former adaptive treatment plans. In patients with tumor volume changes of 〉20% in the third or fourth week of treatment during IMRT, adap- tive treatment plans offered clinically meaningful decreases in MLD and V5, V10, V20, and V30; however, in patients with tumor volume changes of 〈 20% in the third or fourth week of treatment as well as in patients with stereotactic radiotherapy, there were no significant or clinically meaningful decreases in the dosimetric parameters. Conclusion Adaptive treatment planning for decreasing tumor volume during IMRT may be beneficial for patients who experience tumor volume changes of 〉20% in the third or fourth week of treatment.

Feasibility Study on Deformable Image Registration for Lung SBRT Patients for Dose-Driven Adaptive Therapy

The purpose of the study was to evaluate a treatment dose using planning computed tomography (pCT) that was deformed to pre-treatment cone beam computed tomography (CBCT) for lung stereotactic body radiation therapy (SBRT) treatment. Five lung SBRT patients were retrospectively selected, and their daily CBCTs were employed in this study. Dosimetric comparison was performed between the original and recalculated plans from the deformed pCT (dose per fraction) by comparing a target coverage and organs at risk. Dose summation of five fractions was computed and compared to the original plan. A phantom study was conducted to evaluate the dosimetric accuracy for the dose per fraction. In the phantom study, the difference between the mean Hounsfield Unit (HU) values of the original and deformed pCTs is less than 0.5%. In patient study, the mean HU deviation of the five deformed pCTs compared to that of the original pCT was within ±5%, which is dosimetrically insignificant. While the internal target volume (ITV) shrank by 17% on average among the five patients, mean lung dose (MLD) increased by up to 7%, and D95% of PTV decreased slightly but stayed within 5%. Results showed that MLD might be a better indicative metric of normal lung dose than V20Gy as the ITV volume decreases. This study showed a feasibility to use a deformed pCT for evaluation of the dose per fraction and for a possible plan adaptation in lung SBRT cases. Readers should be cautious in selecting patients before clinical application due to the image quality of CBCT.

The Inhibitory Effects of Rh-endostatin(YH-16) in Combination with Radiotherapy on Lung Adenocarcinoma A549 in Mice and the Underlying Mechanisms

In order to investigate the inhibitory effects of Endostar(rh-endostatin,YH-16)in combination with radiotherapy on lung adenocarcinoma A549 in mice and the interaction mechanisms of combined therapy,the transplantation tumor models of A549 lung adenocarcinoma were established.When the largest diameter of tumor reached 1.0cm,all nude mice were randomly divided into 4 groups:Endostar group,radiotherapy group,radiotherapy plus Endostar(combined treatment)group,and control group(n=6 in each group).The largest d...

Phase Ⅰ/Ⅱ study of gemcitabine and oxaliplatin chemotherapy in combination with concurrent 3-D conformal radiotherapy for locally advanced non-small cell lung cancer

Background and objective Recent studies have showed that combination of chemotherapy and radiotherapy might result in better outcome for locally advanced non-small cell lung cancer (NSCLC). The aim of this study is to determine the maximal tolerance dose (MTD) and efficacy of full-dose gemcitabine and oxaliplatin when given concurrently with 3-dimentional radiation therapy (3D-RT) for locally advanced NSCLC. Methods Oxaliplatin was administered at a fixed dose of 130mg/m^2, and gemcitabine was administered at a starting dose of 800mg/m^2 with an incremental dose gradient of 200mg/m^2 for 3 dose levels. MTD was defined as the immediate dose level lower than the dose at which dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered at 3-week cycle. The RT was given as 3-D conformal manner at a single daily dose of 2Gy for 5 days per week. Results Twenty-two patients were evaluable and distributed to three different dose levels: 6 at level 1, 8 at level 2 and 8 at level 3. Pulmonary toxicity, esophageal and hematologic toxicity were the main DLT. Grade Ⅲ acute pulmonary toxicity occurred in one patient each at level 2 and level 3, both with V20>20%, and grade Ⅲ esophagitis in two patients at level 3. The MTD of gemcitabine in this study was 1000mg/m^2. The overall response rate was 75.0% (9/12). The 1- and 2-year survival rate was 70.0% and 30.5% respectively. The median time to progression was 8.7 months (range 5--11.8 months). Conclusion With reduced radiation volume, gemcitabine of 1000mg/m^2 in combination with oxaliplatin of 130mg/m^2 was effective and could be safely administered for NSCLC.

Factors influencing comfort level in head and neck neoplasm patients receiving radiotherapy

Objective:To determine factors that influence comfort in head and neck neoplasm patients receiving radiotherapy.Methods:In total,200 head and neck neoplasm patients receiving radiotherapy were recruited from three tertiary first class hospitals.They were assessed by Radiotherapy Comfort Questionnaire for patients with head and neck neoplasm,Social Support Scale,and Medical Coping Modes Questionnaire.Results:The total score of comfort was 60.54±8.32.Multiple linear regression analysis indicated that number of radiation treatments,family accompaniment,educational level,resignation coping mode,complications due to diabetes,accompanying chemotherapy,and the utilization of social support significantly influenced comfort level(p<0.05).Among these,number of radiation treatments,complications due to diabetes,accompanying chemotherapy,and resignation coping were negative factors.Conclusion:Encouraging utilization of social support systems and a positive coping mode is important for increasing comfort level in head and neck neoplasm patients during radiotherapy.Nurses should pay particular attention to those patients during later stages of radiotherapy or chemotherapy,with diabetes,without family accompaniment,and with lower education level.

Analysis of the Long-term Effect of Intraoperative Radiotherapy (IORT) for Non-Small Cell Lung Carcinoma (NSCLC)

OBJECTIVE To analyze the long-term effects of treatment with an op-eration + postoperative irradiation (A group) and an operation+intraoperative radiotherapy+postoperative irradiation (B group) in non-small cell lung cancer patients. METHODS Through a prospective randomized clinical trial, a total of 154 patients with non-small cell lung carcinoma were divided into two groups of 77 cases. Among the 154 cases, there were 134 squamous carcinomas, 17 adenocarcinomas and 3 adeno-squamous carcinomas. TNM staging: there were 17 in StageⅠ, 76 in Stage Ⅱ and 61 in Stage Ⅲ. A dosage of 15～25 Gy IORT, energy 9～16 MeV electrons, was delivered to the tumors. The doses given were 40～60 Gy postoperation. RESULTS The local control rates in A and B groups were 49.4% and 62.3% respectively (P<0.05). The survivals at 3, 5 and 7 years for group A were 40.3%, 27.3%, and 5.2% and for group B 44.2%, 28.6% and 6.5% (P>0.05). There were 16 deaths from radiotherapy complications, with 2 cases in group A and 14 in group B. CONCLUSION IORT+postoperative irradiation can enhance the local control rate of non-small cell lung cancer patients and reduce the recurrent rates, but it can not improve long-term survival.

Carbon ion radiotherapy for synchronous choroidal melanoma and lung cancer: A case report

BACKGROUND Despite being the most common intraocular malignancy among adults,choroidal melanoma is a rare cancer type,even more so when accompanied by lung cancer.We report a patient with synchronous choroid melanoma and lung cancer treated with carbon ion radiotherapy(CIRT).CASE SUMMARY A 41-year-old woman was transferred to our center with a diagnosis of choroidal melanoma in her right eye.During the examination,we found a right lung tumor that was histologically diagnosed as lung cancer.The patient was treated with CIRT for both malignant neoplasms.The CIRT dose was 70 photon equivalent doses(GyE)in five fractions for the right eye choroidal melanoma and 72 GyE in 16 fractions for the right lung cancer.At 3 mo after CIRT,the choroidal melanoma completely disappeared,as did the right lung cancer 7 mo after;the patient was in complete remission.CONCLUSION CIRT may be an effective treatment for double primary lung cancer and choroid melanoma.

End of Life Experience of Symptom Cluster and Their Management in Hong Kong Chinese Patients with Lung Cancer Who Receive Palliative Radiotherapy

Breathlessness, fatigue, and anxiety are distressing symptoms for patients with advanced lung cancer, however, they are not relieved by palliative RT and are often viewed as neglected areas of clinical practice. This paper aims to review def initions of, and explore patients' experiences of, breathlessness, fatigue, and anxiety. Further, it will outline existing approaches, both pharmacological and non-pharmacological, to treat them. Current treatments and perceptions of these symptoms will be discussed in the context of Hong Kong health care service. The review of literature also shows that breathlessness, fatigue and anxiety appears to have similar emotional origins. A contemporary approach of using a common pyschoeducational intervention to treat these symptoms together as a cluster in end of life care will be discussed.

A Phase Ⅰ trial of dose escalation of topotecan combined with whole brain radiotherapy for brain metastasis in lung cancer

Objective The aim of this study was to define the maximum-tolerated dose (MTD) and observe the toxicity of escalating topotecan combined whole brain radiotherapy for brain metastasis in lung cancer.

Radioenhancing effect of earthworm capsule medication on radiotherapy in the treatment of patients with carcinoma of esophagus or lung

Earthworm capsule is an extract from earthworm made in our laboratory.From1986 to 1989,486 patients with carcinoma of esophagus or lung were randomly divided into 2groups,one group received radiotherapy alone(control group)and the other radiotherapycombined with earthworm capsules(treatment group).All cases were diagnosedpathologically or cytologically.In a two-month treatment course,earthworm capsuleswere given orally twice a day,2～3 capsules each time,each capsule containing 60 mg ofthe extract.Compared with the control group,the CR(complete remission)rate andCR+PR(partial remission)rate in patients with carcinoma of esophagus treated byradiotherapy in combination with earthworm capsule increased 9.7%(P【0.01) and 9.6%(P【0.05),while in patients with carcinoma of lung,they increased 10.6%(P【0.05)and13.5%(P【0.05),respectively.The earthworm capsule caused irritation in the alimentarytract,the patients displaying slight nausea and vomiting(16.7% in thecombination treatment group and 10.0% in the control group).However,these side ef-fects could be alleviated when capsules were taken after meal or with honey concomitantly.No deleterious effects on the heart,liver,kidney,skin,hematopoietic or nervous systemwere seen.

A Rare Case of Non-small Cell Lung Carcinoma Squamous Phenotype with Epstein-Barr Virus Positivity with Prolonged Response to both Chemotherapy and Radiotherapy

We present a rare challenging case of metastatic non-small cell lung cancer with Epstein-Barr virus positivity that was also diagnosed with pulmonary tuberculosis at the same time. Palliative chemotherapy gemcitabine and carboplatin was started after two weeks of anti-tuberculosis treatment with the hopes that this period would be sufficient to keep acid fast bacilli non-viable to minimise risk of tuberculosis re-activation due to chemotherapy induced immunosuppression. She completed four cycles of chemotherapy and six months of anti-tuberculosis treatment with good results and minimal side effects. Two years later, there was disease recurrence in cervical and mediastinal lymph nodes which was treated with local treatment i.e. surgery and palliative radiotherapy. It has been two years since last radiotherapy and overall more than five years since diagnosis with no active disease at present. Given the complexity and rarity of this case, significant multidisciplinary team involvement, including oncologists and radiation oncologists, pulmonologists with special interest in tuberculosis and pathologists was necessary throughout.

Initial outcome of induction chemotherapy followed by radiotherapy and concurrent weekly paclitaxel for stage Ⅲ non-small cell lung cancer

Objective： The aim of our study was to evaluate the toxicity and efficacy of induction chemotherapy （ICT） followed by three-dimensional conformal radiotherapy （3D CRT） and concurrent weekly paclitaxel on unresectable non-small cell lung cancer （NSCLC）. Methods： Stage III NSCLC patients with favorable conditions were treated with 2 to 4 cycles of carboplatin （AUC = 5-6, dl） combined with paclitaxel （175 mg/m〈 dl）, then followed by weekly paclitaxel （40 mg/m2） and concurrent 3D CRT within 3-4 weeks. The prescription dose was given as high as possible under the condition that V20 〈 31% and spinal cord dose 〈 50 Gy. Results： Thirty-one patients were enrolled. ICT was well tolerated. During the concurrent chemoradiotherapy, the treatment of 3 patients was ended ahead of the schedule because of severe pulmonary and heart toxicities; the treatment of 2 patients was delayed for 7 and 12 days because of fatigue. Myelosuppression was mild （16/31）： all were grade 1-2 except 1 was grade 3. Lymphocytopenia was more obvious （29/31, grade 3 in 21）. Three patients developed grade 3 radiation-induced esophagitis, and 2 developed grades 3-4 radiation-induced pneumonitis. Two developed grade 3 esophageal stricture. No grades 3-4 pulmonary fibrosis was observed. The overall response rate was 74.1%. The 1-, 2-, 3-year overall survival rates were 74.2%, 41.9%, and 34.6%, respectively, with the median survival time of 18.5 months. The 1-, 2-, 3-year local progression-freely survival rates were 64.5%, 32.3%, and 20.5%, respectively, with the median local progression-freely survival time of 14.3 months. Conclusion： The program of ICT followed by weekly paclitaxel and 3D CRT is accomplished in most of the favorable stage III NSCLC patients. The toxicity is tolerable, and the response rate is inspiriting.

适应性免疫放疗非小细胞肺癌的潜力与疗效

以免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)为主的药物联合治疗,为驱动基因阴性晚期非小细胞肺癌(nonsmall cell lung cancer,NSCLC)带来了突破性进展,但目前仍然面临未满足临床需求的挑战。近期放疗免疫基础与临床转化研究成果,为迎接该挑战带来了希望。适应性免疫放疗(adaptive immunotherapy radiotherapy,AIRT)是一种具有潜能的治疗模式。AIRT的适用性与普及性,能够为大多数免疫化疗的患者带来可及性,以及潜在更好的临床疗效。但这也是放疗医师面对的挑战:需要更多的基础研究与临床试验加以证明。

系统免疫炎症指数对根治性放疗Ⅲ期肺鳞癌患者长期生存的预测价值

目的探讨系统免疫炎症指数(SII)对接受根治性放疗的Ⅲ期肺鳞癌患者长期生存的预测价值。方法回顾性收集接受根治性放疗的Ⅲ期肺鳞癌患者的临床资料。计算患者放疗前1周内的SII及相关炎症指标,同时应用X-Tile软件确定最佳截断值。分析患者的生存情况以及SII对患者总生存(OS)及无进展生存(PFS)的影响。结果共纳入了453例患者,低SII组336例(<1277.3),高SII组117例(≥1277.3)。高SII组的中位OS和中位PFS均较低SII组缩短(OS:20.8个月vs.31.0个月,Log-rankχ2=18.015,P<0.01;PFS:13.0个月vs.21.0个月,Log-rankχ2=15.062,P<0.01)。多因素Cox回归分析显示,高SII是患者OS(HR=1.628,95%CI:1.294~2.047,P<0.001)和PFS(HR=1.559,95%CI:1.240~1.961,P<0.001)的独立危险因素,其他的影响因素包括较晚的TNM分期、放疗疗效欠佳,HALP评分下降。结论SII可作为接受根治性放疗Ⅲ期肺鳞癌患者长期生存的评价指标,SII升高提示预后较差。

miR-448对肺腺癌A549细胞的放疗增敏作用及其机制

目的探讨miR-448对肺腺癌A549细胞的放疗增敏作用,并探讨其作用机制。方法取肺腺癌A549细胞,随机分为空白对照组、放疗组、放疗+miR-448-mimics组、放疗+NC-mimics组,放疗+miR-448-mimics组、放疗+NCmimics组先分别转染miR-448-mimics和NC-mimics 24 h,然后给予10 Gy放疗照射,放疗组仅给予放疗照射,空白对照组正常培养。采用MTT法、细胞克隆实验分别检测四组细胞增殖活性和细胞存活情况,Transwell试验检测细胞迁移和侵袭能力,流式细胞术检测细胞凋亡,Western blotting法检测T-框蛋白3(TBX3)、磷酸酶与张力蛋白同源物(PTEN)蛋白,qPCR法检测miR-448及TBX3、PTEN mRNA,双荧光素酶报告试验验证PTEN与miR-448的结合位点。结果与空白对照组比较,放疗组细胞增殖、迁移、侵袭能力降低,细胞凋亡增加(P均<0.05);与放疗组、放疗+NCmimics组比较,放疗+miR-448-mimics组细胞增殖、迁移、侵袭能力降低,细胞凋亡增加(P均<0.05)。与放疗组、放疗+NC-mimics组比较,放疗+miR-448-mimics组细胞PTEN蛋白及mRNA表达升高,TBX3 mRNA表达降低(P均<0.05)。miR-448能够与PTEN的3'UTR特异性结合。结论miR-448可增强肺腺癌A549细胞的放疗敏感性,其机制可能是通过调控TBX3和PTEN表达发挥作用。

肺癌临床试验全球概览

肺癌作为全球发病率排名第二、死亡率居高不下的癌种威胁全人类生命健康。通过开展临床试验,肺癌的治疗手段逐渐丰富,治疗时机的把握和认知更为清晰,肺癌患者的预后也得到了显著改善,然而仍然存在未被满足的临床需求。本文回顾了全球肺癌治疗领域的临床研究发展情况,阐述了临床试验在设计、实施和监管等方面的变化:研究终点的变革有利于缩短研发周期、加速药物上市,研究人群、药物靶点的细化有利于实现精准治疗的最大化疗效,综合多元化的治疗手段、防治结合有利于改善生存、减少社会负担,并对未来发展方向提出展望。

In vitro study of radiosensitization by β-Elemene in A549 cell line from adenocarcinoma of lung

Objective： To explore the effect and possible mechanism in vitro of radiosensitization by β-Elemene in A549 cell line from adenocarcinoma of lung. Methods： The A549 cell line from adenocarcinoma of lung was chosen for the study to determine the inhibition ratio by using MTT assay. Morphologic change, growth curve, cloning efficiency, divisional index were observed. Change of cell cycle and apoptosis rate were analyzed by FCM and the expressions of gene P53 and Bcl-2 were detected. Results： Reproductive activity of the group which was under irradiation and β-Elemene was significantly suppressed and its cloning efficiency and divisional index also declined. The apoptosis rate of the group which was under irradiation and β-Elemene was significantly higher at 48 h and 72 h, which was analyzed by FCM. The expression of P53 without Bcl-2 was observed in the group under irradiation and β-Elemene and the group under β-Elemene only at the 48th hour point, while the expression of Bcl-2 without p53 was observed in the group under irradiation only and the control group. Conclusion： β-Elemene is good at radiosensitization and its mechanism may be relevant to the up-regulation of P53, down-regulation of Bcl-2 and inducing apoptosis.

Adaptive Radiotherapy for Lung Cancer

The concept of adaptive radiotherapy(ART) was proposed 20 years ago, and since then a variety of methodologies and techniques have been developed to accommodate different clinical requirements, including both online and offline plan adaptations. Compared with pre-treatment planning, plan adaptation involves more computational tasks and consequently has increased complexity and computational burden. While ART can benefit many cancer patients, challenges still exist in development and implementation of high-quality ART programs. In this short review, we will focus on the development of offline ART for lung cancer. We will also discuss the advantages and disadvantages of different clinical implementations of ART.

能谱CT参数变化预测放射及化学治疗中晚期非小细胞肺癌效果

目的观察能谱CT参数变化预测放射及化学治疗(放化疗)用于中晚期非小细胞肺癌(NSCLC)效果的价值。方法前瞻性纳入119例中晚期NSCLC患者,根据放化疗3个周期后效果分为有效组(n=42)及无效组(n=77)。比较组间及组内各时间点能谱曲线斜率(k)、碘浓度(IC)及其降低值的差异,分析能谱CT参数与放化疗效果的关系;以多因素logistic回归分析筛选放化疗效果的预测因素,绘制受试者工作特征曲线,评估以放化疗后能谱CT参数降低值预测疗效的价值。结果治疗前组间能谱CT参数差异均无统计学意义(P均>0.05)。放化疗1个及3个周期后,有效组动脉期k_(40~70 keV)、动脉期k_(40~100 keV)、静脉期k_(40~70 keV)、动脉期IC及静脉期IC均低于无效组(P均<0.05)及自身治疗前(P均<0.05);其动脉期k_(40~70 keV)、动脉期k_(40~100 keV)、静脉期k_(40~70 keV)、动脉期IC及静脉期IC降低值则均高于无效组(P均<0.05),且各参数降低值均与放化疗效果呈正相关(r:0.584~0.846,P均<0.001)。3个周期后动脉期k_(40~70 keV)、动脉期k_(40~100 keV)、静脉期k_(40~70 keV)、动脉期IC及静脉期IC为疗效的独立预测因素(P均<0.05)。联合应用1个及3个周期后各能谱CT参数降低值预测放化疗效果的曲线下面积分别为0.930和0.942,均优于各单一参数(P均<0.05),应用3个周期优于1个周期(P<0.05)。结论能谱CT参数变化可预测放化疗用于中晚期NSCLC效果。

原发性肺癌术后继发或第二原发气管内肿瘤:系列病例报道及文献综述

背景与目的原发性肺癌根治术后出现继发或第二原发气管内肿瘤患者的临床特征、治疗手段及疗效、预后尚不清楚。本文将通过归纳总结相关病例,对以上问题进行详细阐述。方法搜索广东省人民医院病历,筛选出5例肺癌术后出现气管肿物的患者,同时搜索PubMed从其他文献中筛选出9例病例。结果本单位的5例患者中4例的气管内肿瘤被认为是继发于肺癌。在治疗方面,对这5例患者的气管内肿瘤分别进行了根治性切除术(n=2)、同步放化疗(concurrent chemoradiotherapy,CCRT)(n=1)、化疗(n=1)和姑息治疗(n=l)。接受CCRT治疗的患者获得最长的无进展生存期,为29.5个月。对于从其他文献中筛选到的9例患者,其中8例患者的气管内肿瘤被定义为转移。这9例患者的10个气管肿瘤分别进行了单独放疗(n=4)、CCRT(n=2)、单独化疗(n=2)和手术(n=2)。其中,1例单独接受放疗及1例接受CCRT的患者气管病灶均获得了完全缓解。结论肺癌术后的患者出现气管内肿物应需引起足够重视。CCRT是原发性肺癌术后气管内新发肿瘤的有效治疗手段。