Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Therapeutic Effect of First-line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI)Combined with Whole Brain Radiotherapy on Patients with EGFR Mutation-positive Lung Adenocarcinoma and Brain Metastases

This study compared the therapeutic effect of first-line epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)with that of EGFR-TKI plus whole brain radiotherapy(WBRT)on patients with EGFR mutation-positive lung adenocarcinoma and brain metastases.A total of 139 patients with lung adenocarcinoma and brain metastases treated with first-line EGFR-TK1therapy from September 2008 to December 2017 were enrolled in this study.The study endpoints were intracranial time to progression(TTP)and overall survival(OS).The effects of clinical pathological parameters and EGFR gene status on the study endpoints were compared.The results showed that the intracranial TTP was significantly longer in EGFR-TKI plus WBRT group than in EGFR-TKI group (median 30.0 vs.18.2 months,χ2=10.824,P=0.001),but no significant difference in the OS was noted between the two groups (median 48.0 vs.41.1 months,χ2=0.012, P=0.912).Also,there was no statistically significant difference in the OS between patients treated with early and late radiotherapy (P=0.849)and between those with asymptomatic and those with symptomatic intracranial metastases (P=0.189).The OS and intracranial TTP of patients with intracranial oligometastases (≤3metastatic sites)were not significantly different from those of patients with multiple intracranial metastases (P=0.104 and P=0.357,respectively),and exon 19 and exon 21 mutations didn't show significant effects on the OS and intracranial TTP of patients (P=0.418 and P=0.386,respectively).In conclusion,there was no statistically significant difference in the OS between the EGFR-TKI alone group and EGFR-TK1 plus WBRT group.However, simultaneous use of WBRT was found to significantly prolong intracranial TTP and improve cerebral symptoms,and thus EGFR-TKI and WBRT combined may be clinically beneficial for patients with EGFR mutation-positive lung adenocarcinoma and brain metastases.

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.

Efficacy and nursing of stereotactic radiotherapy in lung cancer patients with brain metastases

Objective: To observe the efficacy of stereotactic radiotherapy (SRT) in lung cancer patients with brain metas-tases and explore the nursing for those patients. Methods: From June 2002 to December 2006, 43 patients of lung cancer with brain metastases were treated with SRT, 8 of them were treated with the association of whole-brain radiotherapy (WBRT) and 6 of them were treated with combination of chemotherapy. During the period of SRT, the patients were applied with active psychological nursing and diet nursing. We also tried to prevent patients from epicranium injury, and meanwhile, patients were asked to took active convalesce exercise. Results: All patients finished SRT without serious reaction and complication. Local control rate was 81.4%, nervous system symptoms relief rate was 76.7% and KPS score was raised significantly. Survival time ranged from 2 to 34 months, median survival time was 8.5 months, and 6-month, 1-and 2-year survival rates were 58.9%, 26.2%, and 6.0% respectively. Conclusion: SRT was one of the effective palliation treatments for the lung cancer patients with brain metastases, and with the assistance of effective nursing, which would prolong their survival time and improved quality of life.

Efficacy of Temozolomide Combined with Whole Brain Radiotherapy in the Treatment of Cerebral Metastases from Lung Cancer

[Objectives] To observe the clinical efficacy,adverse reaction and survival time of temozolomide combined with whole brain radiotherapy in the treatment of lung cancer. [Methods] A total of 43 patients with lung cancer and cerebral metastases were reviewed and analyzed. Three-dimensional conformal radiotherapy(3D-CRT) technique was used to perform whole brain radiotherapy,one time a day and5 times a week. At the same time of radiotherapy,temozolomide chemotherapy was performed,150 mg/( m2·d),continuous oral administration of 5 d,every 28 days were a cycle( those patients who continue receiving temozolomide chemotherapy did not receive other related antitumor therapy,such as systemic chemotherapy and molecular targeted therapy,etc.),and drugs were administered for 4-6 cycles according to tolerance of patients. Kaplan-Meier method was used to calculate the survival rate. [Results]The objective response rate of 43 patients was79. 0%(34/43),in which CR was 6/43,PR was 28/43,and 9 cases had PD. By December 31,2016,7 patients in 43 cases died,one patient died of cerebral hernia due to intracranial lesions and 6 patients died of failure of other important organs due to metastasis. The OS and PFS of the whole group of patients in one year were 49. 1% and 56. 9% respectively. The adverse reactions were mild and the patients could tolerate such treatment. [Conclusions] Temozolomide combined with whole brain radiotherapy in the treatment of lung cancer with cerebral metastases has excellent clinical efficacy,while patients can tolerate such treatment.

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.

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.

Therapy for non-small-cell lung cancer patients with brain metastasis

Brain metastasis is a major cause of poor prognosis and high mortality for non-small cell lung cancer patients. The prognosis of non-small-cell lung cancer(NSCLC) patients with brain metastasis is generally poor and more effective treatment is required to improve their prognosis. Whole-brain radiotherapy, surgery, stereotactic radiosurgery, chemotherapy and targeted therapy are the main treatment for brain metastasis. This review focuses on the five therapeutic strategy and in particular, on targeted therapy.

Updates in the management of brain(leptomeningeal) metastasis of lung cancer

Brain(leptomeningeal) metastasis is one of the most common and severe complications of lung cancer. This article interprets expert consensus on the treatment advice for brain(leptomeningeal) metastasis of lung cancer, expounding on its epidemiology, diagnostic standards, efficacy assessment, treatment advice, and other aspects.

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.

基于脑MRI的机器学习预测非小细胞肺癌T790M突变

目的:本研究基于脑部T_(1)C和T_(2)W MRI建立人工智能模型,预测肺癌脑转移患者在靶向治疗中的耐药性T790M突变。方法:本研究收集80例肺癌脑转移患者(2017年6月—2019年12月)的T_(1)C和T_(2)W MRI影像和临床数据进行回顾性分析(患者按照2∶1的比例分成训练集和测试集)。采用无监督k-means算法将肿瘤区域划分为高亮度区域和低亮度区域,提取不同区域的影像组学图像特征构建模型,评估每个模型的诊断效果。绘制受试者工作特征(Receiver operating characteristic,ROC)曲线,计算ROC曲线下面积(Area under curve,AUC)、特异性和敏感性作为模型评价指标,分析模型的潜在临床应用价值。结果:对T_(1)C和T_(2)W MRI和临床特征融合的统计计算表明,本研究建立的模型对T790M突变具有良好的预测能力,在训练集和测试集上的AUC分别为0.899和0.818。结论:本研究建立的计算机模型可以有效预测肺癌脑转移患者T790M突变,具有潜在的临床辅助诊断价值。

基于肺部CT生境模型预测表皮生长因子受体突变型肺腺癌脑转移

目的观察基于肺部CT生境模型预测表皮生长因子受体(EGFR)突变型肺腺癌脑转移(BM)的价值。方法回顾性分析198例EGFR突变型肺腺癌患者肺部平扫CT资料,按7∶3比例将其分为训练集(n=138)与测试集(n=60)并进一步划分BM亚组与非BM亚组。筛选训练集亚组间差异有统计学意义的变量构建逻辑回归(LR)临床模型;分别于瘤体及瘤体亚区提取特征,基于随机森林、高斯过程(GP)及支持向量机(SVM)算法构建影像组学及生境模型并筛选其中泛化能力最佳者,基于泛化能力最佳影像组学、生境模型及临床模型预测值构建LR联合模型;绘制受试者工作特征曲线,计算曲线下面积(AUC),评估各模型预测EGFR突变型肺腺癌BM的效能,以Spearman相关分析观察EGFR突变型肺腺癌Ki-67水平与生境特征的相关性。结果LR临床模型、GP影像组学模型、SVM生境模型及LR联合模型预测训练集EGFR突变型肺腺癌BM的AUC分别为0.700、0.726、0.801及0.834,在测试集分别为0.754、0.600、0.715及0.848。LR联合模型在训练集的AUC高于LR临床模型(P<0.001)、在测试集的AUC高于GP影像组学模型(P=0.010);其在训练集的效能相比GP影像组学模型及SVM生境模型均有显著正向提高[综合判别改善指数(IDI)=8.60%、8.55%,P均<0.001]。EGFR突变型肺腺癌Ki-67水平与生境图谱中的habitatmap_original_glszm_lalgle呈低度正相关(│rs│=0.201,P=0.004)。结论基于肺部CT生境模型可有效预测EGFR突变型肺腺癌BM。

奥西替尼联合全脑放疗对非小细胞肺癌的疗效分析

目的探讨奥西替尼联合全脑放疗对非小细胞肺癌的治疗效果。方法选取2019年6月至2020年6月确诊为非小细胞肺癌并伴随脑转移的86例患者,随机数字表法分为试验组和对照组,每组43例。对照组采取常规化疗方式联合全脑放疗进行治疗,试验组在常规化疗联合全脑放疗的基础上联合奥西替尼治疗,比较2组患者的近期疗效、血清肿瘤标志物含量、不良反应情况以及生存情况。结果试验组治疗有效率为88.4%高于对照组的62.8%(P<0.05)。试验组患者血清的CD4^(+)、CD8^(+)和CD4^(+)/CD8^(+)显著高于对照组(P<0.05);试验组的血清CYFRA21-1水平显著低于对照组(P<0.05)。试验组的患者的无病生存时间中位数为8个月,对照组为5个月,Log-rank检验显示,试验组的无病生存时间显著高于对照组(P<0.05)。结论奥西替尼联合全脑放疗作为治疗非小细胞肺癌脑转移患者的治疗方式,治疗效果较好,能延长患者的无病生存时间并且能提高患者的生存质量,值得临床推广应用。

肺癌脑转移患者早期死亡预测模型的构建与验证

目的构建并验证一个模型以预测肺癌脑转移(lung cancer with brain metastases,LCBM)患者确诊后三个月内死亡的风险。方法本研究纳入监测,流行病学和最终结果(Surveillance,Epidemiology and End Results,SEER)数据库内2010年1月至2015年12月期间确诊为LCBM的患者。以是否发生早期死亡为研究终点将患者分为早期死亡组和非早期死亡组。以8∶2为比例将数据分为训练集和验证集。在训练集上采用最小绝对值收缩和筛选算子(least absolute shrinkage and selection operator,LASSO)回归法筛选预测因子,并使用多因素Logistic回归构建预测模型并创建列线图。使用受试者工作特征(receiver operating characteristic,ROC)曲线、校准曲线和临床决策曲线(decision curve analysis,DCA)分别在训练集和验证集上评估模型性能。结果共纳入5035例患者,早期死亡发生率28.3%。LASSO回归筛选出13个变量,Logistic回归最终保留了13个与LCBM患者早期死亡相关的危险因素,包括年龄、从诊断到开始治疗时间、肿瘤大小、肿瘤部位、肿瘤分化程度和组织学类型、T分期、N分期、手术、放疗、化疗、肝转移和骨转移。验证集的一致性指数(concordance index,C-index)为0.84,校准曲线和DCA显示模型具有较好的预测效能和临床净效益。结论基于多因素Logistic回归构建的LCBM患者发生早期死亡的预测模型的区分度较好,能够为临床决策提供一定的帮助。

伽玛刀立体定向放射治疗肺癌脑转移瘤患者预后不良的影响因素

目的:分析伽玛刀立体定向放射治疗肺癌脑转移瘤患者预后不良的影响因素。方法:回顾性分析2022年1月至2023年1月在该院接受伽马刀立体定向放射治疗的121例肺癌脑转移瘤患者的临床资料。统计伽玛刀立体定向放射治疗肺癌脑转移瘤患者的预后情况,采用Logistic回归分析伽玛刀立体定向放射治疗肺癌脑转移瘤患者预后不良的影响因素。结果:121例伽马刀立体定向放射治疗肺癌脑转移瘤患者预后不良40例,设为预后不良组,预后良好81例,设为预后良好组;预后不良组脑转移瘤最大直径≥3 cm、血清鳞状细胞癌抗原(SCC-Ag)≥3.80 ng/mL、血清细胞角蛋白19片段(CYFRA21-1)≥7.52 ng/mL、血清神经元特异性烯醇化酶(NSE)≥50.81μg/L占比均高于预后良好组,差异有统计学意义(P<0.05);Logistic回归分析结果显示,血清SCC-Ag≥3.80 ng/mL、血清NSE≥50.81μg/L均为伽玛刀立体定向放射治疗肺癌脑转移瘤患者预后不良的危险因素(OR>1,P<0.05)。结论:血清SCC-Ag≥3.80 ng/mL、血清NSE≥50.81μg/L均为伽玛刀立体定向放射治疗肺癌脑转移瘤患者预后不良的危险因素。