Small-cell lung cancer

小细胞肺癌
  • 文章类型: Case Reports
    小细胞肺癌(SCLC)仍然是一种预后不良的疾病,特别是在广泛阶段SCLC(ES-SCLC)。目前的标准治疗包括铂类药物化疗和依托泊苷+阿特珠单抗或durvalumab免疫治疗,在临床试验中,其平均总生存期为12-13个月。然而,ES-SCLC的长期生存,即使增加了免疫疗法,仍然是罕见的。我们介绍了一名诊断为ES-SCLC的中年男性患者,该患者接受了四个周期的诱导化疗(卡铂和依托泊苷)和阿特珠单抗治疗,此后每21天开始阿替珠单抗维持治疗,和胸部放疗。9个月后,他经历了轻微的疾病进展,并接受了6个周期的卡铂和依托泊苷治疗,并继续接受阿特珠单抗治疗。随后的成像显示几乎完全的疾病消退,此后一直持续。自诊断以来,他继续使用阿替珠单抗维持治疗,总生存期为60个月,无进展生存期为44个月。在整个治疗过程中,他保持了较高的功能能力,仅经历了一次与免疫相关的不良事件。我们的患者代表了能够实现对免疫疗法的持久反应的一小部分,他的病例强调需要进一步研究以阐明驱动这种反应的临床和生物学因素。
    Small-cell lung cancer (SCLC) remains a disease with poor prognosis, particularly in extensive-stage SCLC (ES-SCLC). Current standard-of-care treatment includes chemotherapy with platinum agents and etoposide plus immunotherapy with atezolizumab or durvalumab, which has achieved a mean overall survival of 12-13 months in clinical trials. However, long-term survival in ES-SCLC, even with the addition of immunotherapy, continues to be rare. We present the case of a middle-aged male patient diagnosed with ES-SCLC who was treated with four cycles of induction chemotherapy (carboplatin and etoposide) and atezolizumab, starting maintenance atezolizumab every 21 days thereafter, and thoracic radiotherapy. After 9 months, he experienced mild disease progression and was rechallenged with six cycles of carboplatin and etoposide with continued atezolizumab. Subsequent imaging showed near-complete disease resolution which has been sustained since. He has continued on maintenance atezolizumab since diagnosis and has achieved 60 months overall survival and 44 months progression-free survival. Throughout treatment, he has maintained a high functional capacity and only experienced one immune-related adverse event. Our patient is representative of a small subset who are capable of achieving durable responses to immunotherapy and his case highlights the need for further research to elucidate the clinical and biological factors driving this response.
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  • 文章类型: Case Reports
    来自免疫检查点抑制剂(ICIs)的免疫相关不良事件之一是皮肤毒性。口服皮质类固醇是严重皮肤免疫相关不良事件的一线治疗。然而,皮质类固醇可能与ICIs的疗效相冲突.一名有寻常型银屑病病史的55岁日本男子被诊断为小细胞肺癌(ⅣA期),并进行了联合化学免疫治疗,包括阿妥珠单抗,导致牛皮癣恶化。作为回应,他接受了生物制剂治疗,如抗IL-23和IL-17抗体,risankizumab,苏金单抗,分别,并通过阿司珠单抗持续治疗实现长期生存.该病例报告表明,生物制剂可能是ICI治疗引起的自身免疫相关不良事件的最佳治疗方案。
    One of the immune-related adverse events from immune checkpoint inhibitors (ICIs) is skin toxicity. Oral corticosteroids are the first-line treatment for severe cutaneous immune-related adverse events. However, corticosteroids may conflict with the efficacy of ICIs. A 55-year-old Japanese man with a history of psoriasis vulgaris was diagnosed with small-cell lung cancer (Stage ⅣA) and administered combined chemoimmunotherapy, including atezolizumab, which resulted in exacerbation of psoriasis. In response, he was treated with biological agents, such as anti-IL-23 and IL-17 antibodies, risankizumab, and secukinumab, respectively, and achieved long-term survival with continued treatment with atezolizumab. This case report suggests that biological agents might be the best course of treatment against autoimmune-related adverse events caused by ICI therapy.
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  • 文章类型: Journal Article
    Small-cell lung cancer (SCLC) is an aggressive form of lung cancer with limited treatment options, especially for extensive-stage (ES) patients. We present a case of a 70-year-old male with ES-SCLC and asymptomatic brain metastasis who opted for immune monotherapy with serplulimab (an anti-PD-1 antibody). After four cycles, the patient achieved a confirmed partial response and a progression-free survival of over 1 year. Moreover, we observed a consistent decline in tumor biomarkers, and brain MRI indicated reduced metastatic activity. Remarkably, the patient tolerated the treatment well, with only mild diarrhea. This case highlights serplulimab\'s potential as a first-line treatment in select ES-SCLC patients, emphasizing the importance of further research on immunotherapy predictive biomarkers.
    Small-cell lung cancer (SCLC) is a severe type of lung cancer that often does not have many treatment options, especially in its advanced stages. This article discusses the experience of a 70-year-old man with advanced SCLC who also had cancer spread to his brain but did not show symptoms. He chose to try a new kind of cancer treatment called serplulimab, which works by helping the immune system fight the cancer. After receiving this treatment four-times, his cancer showed significant improvement, and he did not experience further cancer growth for more than 1 year. Tests also revealed that his cancer markers decreased, and the cancer in his brain became less active. Notably, he tolerated this agent with only mild diarrhea occurring. This case is important because it suggests that serplulimab could be an effective first treatment for some patients with advanced SCLC, and it highlights the need for more research to find ways to predict who will benefit from this type of therapy.
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  • 文章类型: Case Reports
    大多数小细胞肺癌患者是中央型肺癌。小细胞肺癌常侵入大气层和大血管,从而引起严重的气管支气管狭窄和上腔静脉综合征。此外,恶性肿瘤患者,尤其是那些呼吸衰竭和严重缺氧的患者,会并发血栓栓塞性疾病.我们报道了一名65岁的女性,患有严重的气管狭窄,右主支气管合并急性呼吸衰竭采用支气管镜和支架植入术治疗,以改善患者的呼吸困难,从而成功接受化疗和及时治疗。化疗后,肿瘤缩小,气管和右主支气管狭窄得到改善。先后拔除右主支气管支架和气管支架,提高患者生活质量。我们管理了癌症和恶化相关因素,以改善患者的医疗状况,使患者能够接受及时和适当的治疗。
    Most of the small-cell lung cancer patients are of the central type of lung cancer. Small-cell lung cancer often intrudes into the atmospheric tract and large blood vessels, thus causing severe tracheobronchial stenosis and superior vena cava syndrome. In addition, patients with malignant tumors, especially those with respiratory failure and severe hypoxia, can be complicated with thromboembolic diseases. We reported a 65-year-old woman with severe stenosis of the trachea, and right main bronchus complicated with acute respiratory failure was treated with bronchoscopy and stent implantation to improve the patient\'s dyspnea, thus successfully receiving chemotherapy and timely treatment. After chemotherapy, the tumor shrank and the stenosis of the trachea and right main bronchus improved. We removed the right main bronchus stent and the tracheal stent successively to improve the quality of life of the patients. We managed both the cancer and exacerbation-related factors to improve the patient\'s medical conditions so that the patient could receive timely and suitable treatment.
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  • 文章类型: Case Reports
    广泛期小细胞肺癌(ES-SCLC)是高度恶性的,早期转移和高复发。由于治疗选择有限,ES-SCLC的特点是生存期短,预后极差。免疫检查点抑制剂(ICIs)和抗血管生成药物的组合可以在ES-SCLC患者中作为二线或后续治疗获得有希望的疗效和安全性,在一定程度上延长生存时间。然而,临床结局大多不令人满意,有时会受到治疗相关不良事件的影响.
    一名患有ES-SCLC的57岁女性患者接受了阿特珠单抗(PD-L1抑制剂)和安洛替尼[一种口服多靶向酪氨酸激酶抑制剂(TKI)]的联合治疗。她活了22个月,在28个疗程的治疗过程中没有疾病进展。出乎意料的是,尽管没有哮喘病史,患者在接受该方案时出现哮喘.这可能与T细胞活化和肿瘤免疫微环境有关,在PD-L1阻断后诱导过敏性炎症。
    这是首例哮喘阴性ES-SCLC患者在接受阿特珠单抗联合安洛替尼后发展为哮喘的报告。虽然这种联合治疗可以有效延长SCLC患者的生存期,应密切监测哮喘症状。
    Extensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, with early metastasis and high recurrence. Since therapeutic options are limited, ES-SCLC has a characteristically short survival period and extremely poor prognosis. A combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic drugs can achieve promising efficacy and safety in patients with ES-SCLC as a second-line or subsequent treatment, extending survival to some extent. However, the clinical outcomes remain mostly unsatisfactory and are sometimes affected by treatment-related adverse events.
    A 57-year-old woman with ES-SCLC was administered a combination therapy of atezolizumab (a PD-L1 inhibitor) and anlotinib [an oral multi-targeted tyrosine kinase inhibitor (TKI)]. She survived for 22 months, with no disease progression during the 28 courses of therapy. Unexpectedly, despite having no history of asthma, the patient developed asthma while receiving this regimen. This is possibly related to T-cell activation and the tumor immune microenvironment, which induce allergic inflammation after PD-L1 blockade.
    This is the first report of an asthma-negative ES-SCLC patient who developed asthma after receiving atezolizumab plus anlotinib. Although this combination therapy may effectively extend survival in SCLC patients, asthmatic symptoms should be closely monitored.
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  • 文章类型: Review
    背景:作为中国新批准的免疫检查点抑制剂,serplulimab已广泛用于肿瘤的免疫治疗。然而,免疫检查点抑制剂的免疫相关不良事件不容忽视.尽管免疫检查点抑制剂诱导的1型糖尿病是一种罕见的并发症,它可能导致糖尿病酮症酸中毒,危及患者的生命。
    方法:本病例报告描述了一名55岁的中国汉族男性,在接受serplulimab治疗68周后,诊断为小细胞肺癌伴多发转移,出现1型糖尿病不良事件。患者出现典型的糖尿病酮症酸中毒症状,包括严重的口渴,恶心,呕吐,深呼吸,和愚蠢。尽管没有糖尿病相关的自身抗体,患者的胰岛素和C肽释放水平极低.排除了糖尿病的其他潜在原因,确认病情为serplulimab诱导的免疫检查点抑制剂诱导的1型糖尿病。在积极治疗以纠正糖尿病酮症酸中毒后,患者的血糖水平稳定,糖尿病症状明显改善,虽然长期胰岛素维持治疗是必要的。
    结论:这个案例突出了一种罕见的,免疫检查点抑制剂诱导的1型糖尿病的迟发性不良事件在使用serplulimab治疗期间可能被忽视.治疗后期不能放松对血糖水平和糖尿病早期体征和症状的监测,即使患者在治疗前和治疗中期期间血糖水平没有升高。
    BACKGROUND: As a newly approved immune checkpoint inhibitor in China, serplulimab has been widely used in the immunotherapy of tumors. However, the immune-related adverse events of immune checkpoint inhibitors should not be ignored. Although immune checkpoint inhibitor-induced type 1 diabetes mellitus is a rare complication, it may cause diabetic ketoacidosis and endanger the lives of patients.
    METHODS: This case report describes a 55-year-old male of Han nationality from China diagnosed with small-cell lung cancer with multiple metastases who experienced an adverse event of type 1 diabetes mellitus 68 weeks after receiving serplulimab therapy. The patient presented with typical symptoms of diabetic ketoacidosis, including severe thirst, nausea, vomiting, deep respirations, and stupor. Despite the absence of diabetes-related autoantibodies, the patient had extremely low levels of insulin and C-peptide release. Other potential causes of diabetes were ruled out, confirming the condition as serplulimab-induced immune checkpoint inhibitor-induced type 1 diabetes mellitus. After aggressive treatment to correct diabetic ketoacidosis, the patient\'s blood glucose levels stabilized and symptoms of diabetes improved significantly, although long-term insulin maintenance therapy was necessary.
    CONCLUSIONS: This case highlights a rare, late-onset adverse event of immune checkpoint inhibitor-induced type 1 diabetes mellitus that may be overlooked during treatment with serplulimab. The monitoring of blood glucose levels and early signs and symptoms of diabetes cannot be relaxed at the late stage of treatment, even if patients do not have elevated blood glucose levels before and during the middle stage of treatment.
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  • 文章类型: Case Reports
    副肿瘤综合征是由肿瘤细胞产生的异常化学信号分子或机体对肿瘤本身的免疫反应引起的罕见且多样的疾病。这些综合症可以表现在一个变量中,多系统且通常是非特异性的方式构成了诊断挑战。我们报告了一个81岁的女性,她表现出严重的低钾血症,代谢性碱中毒,和恶化的高血糖症。该研究与促肾上腺皮质激素(ACTH)依赖性库欣综合征一致,最终,患者被诊断为IV期原发性小细胞肺癌(SCLC).已知SCLC与副肿瘤综合征有关,包括由异位促肾上腺皮质激素(ACTH)分泌引起的库欣综合征。尽管与非常糟糕的结果有关,管理这些综合征可能具有挑战性,并且可能具有预后意义.
    Paraneoplastic syndromes are rare and diverse conditions caused by either an abnormal chemical signaling molecule produced by tumor cells or a body\'s immune response against the tumor itself. These syndromes can manifest in a variable, multisystemic and often nonspecific manner posing a diagnostic challenge. We report the case of an 81-year-old woman who exhibited severe hypokalemia, metabolic alkalosis, and worsening hyperglycemia. The investigation was consistent with adrenocorticotropin (ACTH)-dependent Cushing\'s syndrome and, eventually, the patient was diagnosed with stage IV primary small-cell lung cancer (SCLC). SCLC is known to be associated with paraneoplastic syndromes, including Cushing\'s syndrome caused by ectopic adrenocorticotropin (ACTH) secretion. Despite being associated with very poor outcomes, managing these syndromes can be challenging and may hold prognostic significance.
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  • 文章类型: Case Reports
    阿特珠单抗和化疗的联合治疗已成为小细胞肺癌的标准治疗方法。在免疫检查点抑制剂施用期间可能发生免疫相关不良事件(irAE)。阿特珠单抗治疗后,纯红细胞再生障碍(PRCA)作为irAE存在一些报道。PRCA的特征是正常细胞-正常色素性贫血,网织红细胞明显减少,骨髓成红细胞减少.这里,我们报告一例阿替珠单抗诱导的PRCA.
    一名69岁的男性患者被带到急诊科,主诉为癫痫发作。观察到多发性转移性脑肿瘤和怀疑是右肺门区域的原发病灶。脑活检后,他被诊断为小细胞肺癌(cT1cN0M1c阶段IVB)。他接受了四个疗程的卡铂,依托泊苷,阿替珠单抗联合全脑照射,这导致了部分反应。经过六个疗程的阿替珠单抗维持治疗,严重贫血(血红蛋白,观察到3.4g/dL)。使用红细胞输注期间进行的骨髓活检诊断由阿特珠单抗诱导的PRCA。用泼尼松龙25mg/天(0.5mg/kg/天)开始治疗。贫血好转,剂量逐渐减少至5mg/天。
    PRCA作为irAE的报告很少见,但很重要;因此,我们报告了这个病例。
    UNASSIGNED: Combination therapy of atezolizumab and chemotherapy has become the standard treatment for small-cell lung cancer. Immune-related adverse events (irAEs) can occur during immune checkpoint inhibitor administration. A few reports exist on pure red cell aplasia (PRCA) as an irAE after atezolizumab treatment. PRCA is characterized by normocytic-normochromic anemia, a marked decrease in reticulocytes, and a decrease in bone marrow erythroblasts. Here, we report a case of atezolizumab-induced PRCA.
    UNASSIGNED: A 69-year-old male patient was brought to the emergency department with the chief complaint of seizures. Multiple metastatic brain tumors and a mass suspected to be the primary lesion in the right hilar region were observed. After a brain biopsy, he was diagnosed with small-cell lung cancer (cT1cN0M1c stage IVB). He received four courses of carboplatin, etoposide, and atezolizumab in combination with whole-brain irradiation, which led to a partial response. After six courses of atezolizumab maintenance therapy, severe anemia (hemoglobin, 3.4 g/dL) was observed. PRCA induced by atezolizumab was diagnosed using a bone marrow biopsy performed during red blood cell transfusion. Treatment was started with prednisolone 25 mg/day (0.5 mg/kg/day). Anemia improved, and the dose was gradually reduced to 5 mg/day.
    UNASSIGNED: Reports of PRCA as an irAE are rare but important; hence, we reported this case.
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  • 文章类型: Case Reports
    Durvalumab是一种免疫检查点抑制剂(ICIs),用于治疗恶性肿瘤,如肺癌和黑色素瘤。ICI与免疫相关的不良事件相关,包括自身免疫性脑炎,尽管副肿瘤现象和ICI治疗都可能导致自身免疫。
    我们描述了一位72岁的男性小细胞肺癌患者,在Durvalumab辅助治疗期间,患者出现了GABABR1和GAD65抗体,同时出现了糖尿病和自身免疫性边缘叶脑炎.因为作为治疗研究的一部分,他被前瞻性地追踪,在发展为脑炎和糖尿病之前,随着时间的推移,我们可以获得重复的血清样本和认知评估,除了以后的评估。高滴度的GABABR1抗体出现早期,而GAD65抗体出现较晚,滴度较低,与糖尿病的发展平行。当他随后出现脑炎的临床症状时,通过脑电图和脑部MRI证实,他也有CSFGABABABR1抗体.停用Durvalumab,并开始随后血浆置换的类固醇治疗,导致CSF和血清抗体水平降低。脑炎的临床体征逐渐好转。
    此案例说明了意识到可能的严重自身免疫不良反应的重要性,包括神经系统综合征,如脑炎,用ICIs治疗癌旁病变高风险患者时。此外,该病例显示随着时间的推移自身抗体的发展。
    Durvalumab is an immune checkpoint Inhibitor (ICIs) that is used in the treatment of malignant tumors, such as lung cancer and melanoma. ICIs are associated with immune-related adverse events including autoimmune encephalitis, although both paraneoplastic phenomena and ICI treatment may lead to autoimmunity.
    We describe a 72-year old male patient with small-cell lung cancer, who during adjuvant treatment with Durvalumab developed GABABR1 and GAD65 antibodies and both diabetes and autoimmune limbic encephalitis. Because he was followed prospectively as part of a treatment study, we had access to repeated serum samples and cognitive assessments over time prior to developing encephalitis and diabetes, in addition to later assessments. A high titer of GABABR1 antibodies appeared early, while GAD65 antibodies appeared later with a lower titer in parallel with the development of diabetes. As he subsequently developed clinical signs of encephalitis, verified by EEG and brain MRI, he also had CSF GABABR1 antibodies. Durvalumab was discontinued and steroid treatment with subsequent plasmapheresis were started, resulting in reduction of both CSF and serum antibody levels. Clinical signs of encephalitis gradually improved.
    This case illustrates the importance of being aware of possible serious autoimmune adverse reactions, including neurological syndromes such as encephalitis, when treating patients with high risk of para-neoplasia with ICIs. In addition, the case shows the development of autoantibodies over time.
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  • 文章类型: Journal Article
    目前,晚期小细胞肺癌(SCLC)的一线标准治疗方法是化疗和免疫疗法的结合。然而,在现实生活中很少有疗效数据,包括虚弱的病人。这项研究的目的是描述未经选择的SCLC人群中化学免疫疗法的真实疗效。我们进行了一项回顾性多中心研究,比较了在大巴黎地区六个学术中心接受治疗的未治疗转移性SCLC的两组患者。队列1包括2017年1月至2018年12月接受化疗的患者,队列2包括2019年1月至2020年12月接受化学免疫治疗的患者。共纳入153名连续患者(队列1:n=96;队列2:n=57)。两组患者的临床特征相似。队列2(中位生存期15.47个月)的总生存期(OS)高于队列1(中位生存期9.5个月)(p=0.0001)。表现状态≥2的患者和≥70岁的患者的OS在两个队列之间没有统计学差异。在脑或肝转移的情况下,化学免疫疗法的疗效优于单独的化学疗法。总之,转移性SCLC中化学免疫治疗的组合似乎提供了真实的OS获益.需要专门的临床试验来测试这种策略在功能受损或高龄的患者中。
    The current first-line standard treatment for advanced small cell lung cancer (SCLC) is a combination of chemotherapy and immunotherapy. However, few efficacy data are available in a real-life settings, including frail patients. The aim of this study is to describe the real-life efficacy of chemoimmunotherapy in an unselected SCLC population. We conducted a retrospective multicenter study, which compared two cohorts of patients with treatment-naive metastatic SCLC treated in six academic centers in the Greater Paris area. Cohort 1 included patients treated with chemotherapy between January 2017 and December 2018, and cohort 2 included patients treated with chemoimmunotherapy between January 2019 and December 2020. A total of 153 consecutive patients were included (cohort 1: n = 96; cohort 2: n = 57). Clinical characteristics were similar between the two cohorts. Overall survival (OS) was statistically higher in cohort 2 (median survival 15.47 months) than in cohort 1 (median survival 9.5 months) (p = 0.0001). OS for patients with a performance status ≥2 and for patients ≥70 years old was not statistically different between the two cohorts. Chemoimmunotherapy efficacy was better compared to chemotherapy alone in case of brain or liver metastases. In conclusion, the combination of chemoimmunotherapy in metastatic SCLC appears to provide a real-life OS benefit. Dedicated clinical trials are needed to test this strategy in patients with impaired performance status or advanced age.
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