Stage Ⅳ non-small cell lung cancer with multiple metastases to the small intestine leading to intussusception: A case report

BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors can also present with diverse complications,some of which require urgent intervention.CASE SUMMARY In this report,we detail a unique case of stage IV lung cancer,where the presence of small intestine tumors led to intussusception.Subsequent to a small intestine resection,pathology confirmed that all three tumors within the small intestine were metastases from adenocarcinoma of the lung.The postoperative follow-up period extended beyond 14 mo.CONCLUSION In patients with stage IV NSCLC,local tumor control can be achieved with various treatments.However,if small intestinal metastasis occurs,surgical intervention remains necessary,as it may improve survival.

Icotinib, an EGFR-TKI, for the treatment of brain metastases in non-small cell lung cancer:a retrospective study

Objective Treatment of brain metastases from non-small cell lung cancer(NSCLC) is a challenge because of the poor prognosis. Icotinib is a new type of oral epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI) used in the treatment of advanced NSCLC. The aim of this study was to evaluate the efficacy of icotinib in NSCLC patients with brain metastasis.Methods This study reviewed records of 51 NSCLC patients with brain metastases who took icotinib 125 mg, 3 times a day. Response rate, progression free survival, and overall survival were analyzed. SPSS software version 17.0 was used for univariate analysis, and Cox regression analysis to analyze factors affecting survival. Results Thirty-six cases had partial response, 6 cases had stable disease, and 10 cases had progressive disease. In 31 cases, EGFR gene mutation test were performed. EGFR was mutated in 26 cases and was with wild-type in 5 cases. In patients with EGFR mutations, 23 patients responded to icotinib [the disease control rate(DCR) was 88.5%], significantly higher than in patients with wild-type EGFR(1 patient, DCR 20%)(P = 0.005). The overall median progression-free survival(PFS) was 7.6 months. PFS was longer in the patients with EGFR mutations than in those with wild type EGFR(7.8 months vs 1.2 months, P = 0.03). The overall median overall survival(OS) time was 10.7 months. OS was longer in patients with EGFR mutations than in those with wild type EGFR(15.1 months vs 6.7 months, P = 0.003). The main side effects of the treatment were skin rash and diarrhea; no stage 3 or 4 toxic effects occurred. Univariate analysis demonstrated that OS was related to sex, Eastern Cooperative Oncology Group performance status(ECOG PS), smoking history, and EGFR mutation. Multivariate analysis showed that OS was independently related to sex, ECOG PS, and EGFR mutations.Conclusion Icotinib has a favorable effect on NSCLC patients with brain metastases harboring EGFR mutations. Icotinib can be a new choice of treatment for brain metastases in patients with NSCLC harboring EGFR mutations.

High plasma fibrinogen concentration and platelet count unfavorably impact survival in non–small cell lung cancer patients with brain metastases

High expression of fibrinogen and platelets are often observed in non–small cell lung cancer(NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age ≥ 65 years(P = 0.011), smoking status(P = 0.009), intracranial symptoms(P = 0.022), clinical T category(P = 0.010), clinical N category(P = 0.003), increased partial thromboplastin time(P < 0.001), and platelet count(P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration(median, 17.3 months versus 11.1 months; P ≤ 0.001). A similar result was observed for platelet counts(median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases(R2 = 1.698, P < 0.001 and R2 = 1.699, P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

Recursive Partitioning Analysis Classification and Graded Prognostic Assessment for Non-Small Cell Lung Cancer Patients with Brain Metastasis:A Retrospective Cohort Study

Objective：To assess prognostic factors and validate the effectiveness of recursive partitioning analysis （RPA） classes and graded prognostic assessment （GPA） in 290 non-small cell lung cancer （NSCLC） patients with brain metastasis （BM）.Methods：From Jan 2008 to Dec 2009,the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation,systemic chemotherapy and tyrosine kinase inhibitors （TKIs） in two institutes were analyzed.Survival was estimated by Kaplan-Meier method.The differences of survival rates in subgroups were assayed using log-rank test.Multivariate Cox＇s regression method was used to analyze the impact of prognostic factors on survival.Two prognostic indexes models （RPA and GPA） were validated respectively.Results：All patients were followed up for 1-44 months,the median survival time after brain irradiation and its corresponding 95% confidence interval （95% CI） was 14 （12.3-15.8） months.1-,2-and 3-year survival rates in the whole group were 56.0%,28.3%,and 12.0%,respectively.The survival curves of subgroups,stratified by both RPA and GPA,were significantly different （P0.001）.In the multivariate analysis as RPA and GPA entered Cox＇s regression model,Karnofsky performance status （KPS） ≥ 70,adenocarcinoma subtype,longer administration of TKIs remained their prognostic significance,RPA classes and GPA also appeared in the prognostic model.Conclusion：KPS ≥70,adenocarcinoma subtype,longer treatment of molecular targeted drug,and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.

Surgery Versus Stereotactic Radiosurgery for Single Synchronous Brain Metastasis from Non-Small Cell Lung Cancer

Objective： The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery （SRS） for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer. Methods： Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years （range, 32-85 years）. At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients （21.4%）, lobectomies in 30 （71.4%）, and wedge resection in 3 （7.2%）. 48 patients （90.5%） underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS. Results： There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients （28.3%） had no evidence of lymph node metastases （No）, 20 patients （37.7%） had hilar metastases （N1）, and 18 patients （34%） had mediastinal metastases （N2）. The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant （P〉0.05）. In lymph node negative patients （No）, the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases （N1-2）. The difference was significant （P〈0,01）. For adenocarcinomas, the 5-year survival rate was 5%. The correspondent data for squamous cell lung cancers was 3%. The difference was not significant （P〉0.05）. Conclusion： Although the overall survival rate for patients who have brain metastases from NSCLC is poor, surgical resection or radiosurgery may be beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.

Durable response to pulsatile icotinib for central nervous system metastases from EGFR-mutated non-small cell lung cancer: A case report

BACKGROUND Central nervous system(CNS) metastases are a catastrophic complication of nonsmall cell lung cancer(NSCLC), including brain and leptomeningeal carcinomatosis, and are always accompanied by a poor prognosis. Despite the continuous development of existing treatments, the therapy of CNS metastases remains challenging.CASE SUMMARY We report a patient who was definitively diagnosed with brain and leptomeningeal metastases from NSCLC with a targeted mutation in epidermal growth factor receptor(EGFR). A standard dosage of icotinib(125 mg three times daily) was implemented but ineffective. CNS lesions developed despite stable systemic control, so pulsatile icotinib(1125 mg every 3 d) was administered. This new strategy for administration has lasted 25 mo so far, and resulted in complete remission of neurological symptoms, almost vanished lesions, and longer survival with no notable side effects.CONCLUSION This is the first successful example of pulsatile icotinib for treating isolated CNS progression from EGFR mutation-positive NSCLC, providing a new alternative for the local treatment of CNS metastases.

Perioperative considerations in patients with non small cell lung cancer and metastases in mediastinal lymph nodes

Since the latest revision of the TNM system reclassified T3N0 tumours into the ⅡB stage, N2 lesions became the major determinant of the ⅢA stage. Concerning the minority of patients with T3N1 tumours in this stage,

Surgical strategies in the therapy of non-small cell lung cancer

Lung cancer represents the leading cause of cancer mortality worldwide. Despite improvements in preoperative staging, surgical techniques, neoadjuvant/adjuvant options and postoperative care, there are still major difficulties in significantly improving survival, especially in locally advanced non-small cell lung cancer(NSCLC). To date, surgical resection is the primary mode of treatment for stage?Ⅰ?and Ⅱ NSCLC and has become an important component of the multimodality therapy of even more advanced disease with a curative intention. In fact, in NSCLC patients with solitary distant metastases, surgical interventions have been discussed in the last years. Accordingly, this review displays the recent surgical strategies implemented in the therapy of NSCLC patients.

Immune checkpoint inhibitors for the treatment of non-small cell lung cancer brain metastases

Lung cancer has the highest risk of brain metastasis(BM)among all solid carcinomas.The emergence of BM has a significant impact on the selection of oncologic treatment for patients.Immune checkpoint inhibitors(ICIs)are the most promising treatment option for patients without druggable mutations and have been shown to improve survival in patients with non-small cell lung cancer(NSCLC)BM in clinical trials with good safety.Moreover,ICI has shown certain effects in NSCLC BM,and the overall intracranial efficacy is comparable to extracranial efficacy.However,a proportion of patients showed discordant responses in primary and metastatic lesions,suggesting that multiple mechanisms may exist underlying ICI activity in BM.According to studies pertaining to tumor immune microenvironments,ICIs may be capable of provoking immunity in situ.Meanwhile,systematic immune cells activated by ICIs can migrate into the central nervous system and exert antitumor effects.This review summarizes the present evidence for ICI treatment efficacy in NSCLC BM and proposes the possible mechanisms of ICI treatment for NSCLC BMs based on existing evidence.

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.

GOECP/SEOR radiotherapy guidelines for small-cell lung cancer

Small cell lung cancer(SCLC)accounts for approximately 20%of all lung cancers.The main treatment is chemotherapy(Ch).However,the addition of radiotherapy significantly improves overall survival(OS)in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to Ch.Prophylactic cranial irradiation reduces the risk of brain metastases and improves OS in both metastatic and non-metastatic patients.The 5-year OS rate in patients with limited-stage disease(non-metastatic)is slightly higher than 30%,but less than 5%in patients with extensive-stage disease(metastatic).The present clinical guidelines were developed by Spanish radiation oncologists on behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Society of Radiation Oncology to provide a current review of the diagnosis,planning,and treatment of SCLC.These guidelines emphasise treatment fields,radiation techniques,fractionation,concomitant treatment,and the optimal timing of Ch and radiotherapy.Finally,we discuss the main indications for reirradiation in local recurrence.

Role of Recursive Partitioning Analysis and Graded Prognostic Assessment on Identifying Non-Small Cell Lung Cancer Patients with Brain Metastases Who May Benefit from Postradiation Systemic Therapy

Background：The role ofpostradiation systemic therapy in non-small cell lung cancer （NSCLC） patients with brain metastasis （BM） was controversial.Thus,we explored the role of Radiation Therapy Oncology Group recursive partitioning analysis （RTOG-RPA） and graded prognostic assessment （GPA） in identifying population who may benefit from postradiation systemic therapy.Methods：The clinical data of NSCLC patients with documented BM from August 2007 to April 2015 of two hospitals were studied retrospectively.Cox regression was used for multivariate analysis.Survival of patients with or without postradiation systemic therapy was compared in subgroups stratified according to RTOG-RPA or GPA.Results：Of 216 included patients,67.1% received stereotactic radiosurgery （SRS）,24.1% received whole-brain radiation therapy （WBRT）,and 8.8% received both.After radiotherapy,systemic therapy was administered in 58.3% of patients.Multivariate analysis found that postradiation systemic therapy （yes vs.no） （hazard ratio [HR] =0.36 l,95% confidence interval [CI] =0.202-0.648,P =0.001）,radiation technique （SRS vs.WBRT） （HR =0.462,95% CI =0.238-0.849,P =0.022）,extracranial metastasis （yes vs.no） （HR =3.970,95% CI =1.757-8.970,P =0.001）,and Kamofsky performance status （〈70 vs.≥70） （HR =5.338,95% CI =2.829-10.072,P 〈 0.001） were independent factors for survival.Further analysis found that subsequent tyrosine kinase inhibitor （TKI） therapy could significantly reduce the risk of mortality of patients in RTOG-RPA Class IⅡ （HR =0.411,95% CI =0.183-）.923,P =0.031） or with a GPA score of 1.5-2.5 （HR =0.420,95% CI =0.182-0.968,P =0.042）.However,none of the subgroups stratified according to RTOG-RPA or GPA benefited from the additional conventional chemotherapy.Conclusion：RTOG-RPA and GPA may be useful to identify beneficial populations in NSCLC patients with BM ifTKIs were chosen as postradiation systemic therapy.

Eye metastasis in lung adenocarcinoma mimicking anterior scleritis:A case report

BACKGROUND The eye is a rare site for lung cancer metastasis. Indeed, ocular metastasis is one of the greatest challenges to quality of life in a cancer patient. Here we present a patient with lung adenocarcinoma and ocular metastasis.CASE SUMMARY The patient was a 70-year-old man diagnosed with lung adenocarcinoma who developed eye metastasis mimicking anterior scleritis. Brain magnetic resonance imaging showed an abnormal signal in the right eye. Based on next generation sequencing of the surgical specimen, the patient was shown to have a KRAS point mutation(p.G12D).CONCLUSION Multidiscipline expertise collaboration is needed to make the early diagnosis and determine the prompt treatment in patients. We hope to increase the awareness of the possibility of lung cancer metastasizing to the eye.

不同剂量脑立体定向放疗联合PD-1/PD-L1抑制剂治疗非小细胞肺癌脑转移的疗效及安全性

目的不同剂量脑立体定向放疗联合PD-1/PD-L1抑制剂治疗非小细胞肺癌脑转移的疗效及安全性。方法选取50例非小细胞肺癌脑转移患者作为研究对象,根据患者脑立体定向放疗分割剂量分为A组(n=15)、B组(n=15)和C组(n=20),患者均接受脑立体定向放疗联合生存PD-1/PD-L1抑制剂治疗,A组脑立体定向放疗剂量为4 Gy/f,12 f,B组为5 Gy/f,8 f组,C组为7 Gy/f,5 f。对比三组患者治疗后临床疗效、不良反应发生率以及生存情况;对比三组患者治疗前后KPS评分。结果三组患者临床总有效率比较差异具有统计学意义(P<0.05);C组临床总有效率比较显著高于A组和B组(P<0.05);三组患者不良反应总发生率对比差异无统计学意义(P>0.05);A组、B组和C组患者中位生存期分别为2.70个月、2.40个月和6.60个月。Log-rank检验结果提示,三组患者中位生存期比较,差异具有统计学意义(P<0.05);治疗后,三组患者的KPS评分均显著升高,组间比较差异显著,且C组患者较A组和B组显著更高(P<0.05)。结论对于非小细胞肺癌脑转移患者,7 Gy/f,5 f分割剂量相比于4 Gy/f,12 f和5 Gy/f,8 f联合PD-1/PD-L1抑制剂改善患者的临床疗效更明显,延长生存时间和生存质量更为明显。

联合免疫检查点抑制剂治疗驱动基因阴性非小细胞肺癌脑转移的研究进展

非小细胞肺癌(non-small cell lung cancer,NSCLC)是肺癌中最常见的组织学类型,约66%的患者在确诊时就被发现伴有远处转移。脑转移是最常见的转移部位之一,约13%的患者在初诊时即发现颅内受累,严重影响生活质量,预后不佳。驱动基因阳性的NSCLC脑转移患者靶向治疗可以达到较好的颅内控制率,但驱动基因阴性的患者治疗手段较为局限。近年来,随着免疫治疗的兴起,免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)被广泛运用于临床,ICIs联合放疗的治疗模式为驱动基因阴性NSCLC脑转移患者的治疗带来了新希望。本文就放疗联合免疫治疗在敏感驱动基因阴性NSCLC脑转移患者中的临床研究进展进行综述,以期为临床治疗方案的选择提供参考。

卡瑞利珠单抗对晚期非小细胞肺癌脑转移患者的疗效及驱动基因突变关联分析

目的探索卡瑞利珠单抗对Ⅲb期-Ⅳ期非小细胞肺癌(NSCLC)患者脑转移的疗效,以及驱动基因突变对疗效的影响。方法回顾性分析淮北市职业技术学院附属医院2020年1月至2022年1月收治合并脑转移的NSCLC患者,按照是否联合使用卡瑞利珠单抗分为对照组(51例)和观察组(47例)。对照组和观察组患者进行同步放化疗和立体定向放射外科治疗;此外,观察组患者额外接受注射用卡瑞利珠单抗治疗。观察组患者根据其脑转移情况分为单发脑转移和多发脑转移两个亚组,根据驱动基因突变情况分为驱动基因阳性和阴性两个亚组。比较观察组和对照组以及观察组亚组间的客观缓解率和预后的差异。结果治疗结束后,两组患者近期疗效比较显示,观察组客观缓解率高于对照组[36.17%(17/47)vs 23.53%(12/51),χ^(2)=4.305,P<0.05]。经1年随访,观察组无进展生存期[(9.45±1.16)个月vs(6.34±1.05)个月,χ^(2)=6.385,P<0.05]和总生存期[(13.69±2.15)个月vs(10.41±1.19)个月,χ^(2)=7.743,P<0.05],均差异有统计学意义。观察组有18例为单发脑转移患者,29例为多发脑转移患者。单发脑转移患者客观缓解率(χ^(2)=4.748,P<0.05)、无进展生存期(χ^(2)=7.458,P<0.05)和总生存期(χ^(2)=9.401,P<0.05)均高于多发脑转移患者。脑转移患者中,有6例为驱动基因突变者,41例无驱动基因突变者。有驱动基因突变患者总生存期时间[(15.46±3.16)个月vs(7.86±1.85)个月]和无进展生存期[(12.03±1.96)个月vs(5.41±1.17)个月]均高于无驱动基因突变者,差异有统计学意义(χ^(2)=11.254,6.988,均P<0.05)。结论联用卡瑞利珠单抗治疗脑转移临床疗效更佳,单发脑转移患者客观缓解率高于多发脑转移,合并驱动基因突变者对卡瑞利珠单抗敏感性更高。

血清CA125、CA199、CYFRA-21及CEA联合检测对非小细胞肺癌患者脑转移的诊断价值

目的分析糖类抗原125(CA125)、糖类抗原199(CA199)、细胞角蛋白19片段(CYFRA-21)、癌胚抗原(CEA)对非小细胞肺癌(NSCLC)患者脑转移的诊断价值。方法选取NSCLC患者共96例,根据其是否存在脑转移将其划分为转移组(32例)及未转移组(64例);另将行体检的75例健康体检者纳入健康组。抽取全部研究对象的晨起空腹静脉血,检测血清CA125、CA199、CYFRA-21及CEA水平。绘制受试者工作曲线(ROC),分析CA125、CA199、CYFRA-21、CEA联合检测对NSCLC患者脑转移的诊断价值。结果转移组的CA125、CA199、CYFRA-21、CEA水平高于未转移组、健康组,且未转移组的CA125、CA199、CYFRA-21、CEA水平高于健康组,差异有统计学意义(P<0.05)。ROC结果显示,CA125、CA199、CYFRA-21、CEA联合检测诊断NSCLC患者脑转移的曲线下面积(AUC)高于CA125、CA199、CYFRA-21、CEA单独诊断。结论CA125、CA199、CYFRA-21、CEA在出现脑转移的NSCLC患者血清中的表达较高,四者联合检测能够有效诊断出患者是否存在脑转移,具有一定的诊断价值。

立体定向放疗联合贝伐珠单抗及PD-1免疫治疗对非小细胞肺癌脑转移的疗效分析

目的:探讨立体定向放疗(stereotactic radiotherapy, SRT)联合贝伐珠单抗及程序性死亡受体1(programmed cell death-1,PD-1)免疫治疗方案在晚期非鳞非小细胞肺癌(non-squamous non-small cell lung cancer, ns-NSCLC)脑转移(brain metastases, BM)患者中的疗效和不良事件(adverse event, AE)。方法:回顾性收集中国人民解放军联勤保障部队第九〇四医院和江南大学附属医院于2019年5月至2021年12月收治的119例ns-NSCLC BM患者的临床资料,并继续随访。根据疗法分为3组:SP组:SRT+化疗;SBIP组:SRT+贝伐珠单抗+PD-1抑制剂免疫治疗+化疗;SBI组:SRT+贝伐珠单抗+PD-1抑制剂免疫治疗。比较各组的短期疗效、生存期及AE。进行亚组分析探索,并对试验进行危险因素分析。结果:SBIP组、SBI组在疾病控制率(disease control rate, DCR)、无进展生存期(progress-free survival, PFS)和总生存期(overall survival, OS)上差异无统计学意义,但均优于SP组,差异有统计学意义,SBI组在AE分级上与SBIP组有统计学差异,且AE发生率低于SBIP组。年龄、分化程度、治疗方案、体力状态(performance status, PS)评分、脑膜转移、程序性死亡受体配体1(programmed cell death-ligand 1,PD-L1)表达水平、确诊BM时肺原发灶直径为ns-NSCLC BM患者预后的独立危险因素。在亚组分析中,表皮生长因子受体(epidermal growth factor receptor, EGFR)阳性组与阴性组在OS上差异无统计学意义。结论:SRT联合贝伐珠单抗和免疫治疗能有效提升ns-NSCLC BM患者的疗效,且AE较少,安全性更高。

帕博利珠单抗治疗驱动基因阴性的非小细胞肺癌脑转移患者的效果

目的探讨帕博利珠单抗治疗驱动基因阴性的非小细胞肺癌脑转移患者的效果。方法选取140例驱动基因阴性的非小细胞肺癌脑转移患者作为研究对象,随机分为研究组与对照组,各70例。对照组患者单纯行脑部放射治疗(立体定向放射治疗/全脑放射治疗),研究组患者在脑部放射治疗的基础上联合应用帕博利珠单抗治疗。比较两组患者临床疗效、无进展生存期、总生存期及不良反应发生情况。结果研究组患者临床疗效优于对照组,缓解率及控制率高于对照组,无进展生存期及总生存期长于对照组,食欲减退发生率低于对照组,皮疹/瘙痒、中性粒细胞减少发生率高于对照组(P<0.05)。结论在放射治疗的基础上联合应用帕博利珠单抗治疗驱动基因阴性的非小细胞肺癌脑转移患者能够提高治疗效果,延长患者生存期,且安全性较高。