Sintilimab

辛替利玛
  • 文章类型: Journal Article
    背景:专注于在癌症患者的放射治疗方案中添加免疫检查点抑制剂(ICIs)的研究变得越来越普遍,揭示了疗效结果的有希望的改善。在局部区域晚期鼻咽癌(NPC)患者中,免疫治疗与放化疗相结合可以显著延长生存期,强调需要进行药物经济学研究,重点是临床采用这些创新的治疗方案。
    方法:根据随机3期CONTINUUM试验的临床数据,建立了三态马尔可夫模型,用于比较放化疗联合sintilimab(sintilimab组)与单纯放化疗(标准组)的成本效益,分析结果,包括增量成本效益比(ICER),增量净货币收益(INMB),和按支付意愿(WTP)阈值计算的递增净健康福利(INHB)值,对应于中国人均GDP的三倍(每个质量调整生命年[QALY]37035美元)。
    结果:sintilimab和标准组(QALYs[LYs])患者的总费用为$92116(6.68[10.03])和$53255(3.75[5.55]),分别,ICER为$13230/QALY($8672/LY),INMB为70021美元,INHB为1.89QALY。使用选定的WTP阈值。在标准WTP阈值上,在中国,以sintilimab为主要治疗药物的患病率为90.55%。模型的建立是稳定的。
    结论:在放化疗方案中添加sintilimab代表了一种创新且具有成本效益的方法,适用于中国局部晚期NPC管理患者。
    BACKGROUND: Research focused on the addition of immune checkpoint inhibitors (ICIs) to radiotherapeutic regimens in patients with cancer has become increasingly common, revealing promising improvements in efficacy outcomes. In patients with locoregionally advanced nasopharyngeal carcinoma (NPC), combining immunotherapy with chemoradiotherapy can facilitate the significant prolongation of survival, emphasizing the need for pharmacoeconomic studies focused on the clinical uptake of these innovative treatment regimens.
    METHODS: A three-state Markov model was developed based on clinical data from the randomized phase 3 CONTINUUM trial and used to compare the cost-effectiveness of chemoradiotherapy plus sintilimab (sintilimab group) to chemoradiotherapy alone (standard group), analyzing outcomes including incremental cost-effectiveness ratio (ICER), incremental net monetary benefit (INMB), and incremental net-health benefit (INHB) values at a willingness-to-pay (WTP) threshold corresponding to three times the Chinese GDP per capita ($37 035 per quality-adjusted life year [QALY]).
    RESULTS: The total costs for patients in the sintilimab and standard groups (QALYs [LYs]) were $92 116 (6.68 [10.03]) and $53 255 (3.75 [5.55]), respectively, for an ICER of $13 230/QALY ($8672/LY), an INMB of $70 021 with INHB of 1.89 QALYs. Using the selected WTP threshold. On the standard WTP threshold, the prevalence of sintilimab group as the primary treatment was 90.55% in China. The establishment of the model is stable.
    CONCLUSIONS: Adding sintilimab to chemoradiotherapeutic regimens represents an innovative and cost-effective means for patients with locoregionally advanced NPC management in China.
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  • 文章类型: Case Reports
    肾上腺皮质癌(ACC)是一种罕见的恶性肿瘤,发生在肾上腺皮质中。恶性程度高,总体预后较差。手术是局部ACC患者的标准治愈疗法。依托泊苷的联合方案,阿霉素,顺铂(EDP)加米托坦被认为是晚期ACC的标准化化疗方案。然而,针对转移性ACC的特定条件,出现了新的有效方案.
    我们报告一例66岁的男性患者,诊断为转移性ACC,其左肾上腺肿块大(110mm×87mm),双肺多发转移。患者接受EP和sintilimab治疗六个周期;第三个周期后引入安洛替尼。第二至第四周期后的随访发现,所有影像学检查均显示部分反应(PR)状态,肺转移明显减少。此后,患者接受辛替利玛加安洛替尼的维持治疗。直到最近,患者肺转移灶和左肾上腺区肿块(39mm×29mm)消失,并且没有观察到疾病进展。该患者的无进展生存期已延长至大约31个月,与大多数晚期ACC的中位生存时间为12个月形成鲜明对比。治疗期间的主要不良事件是食欲减退和I级骨髓抑制,仅显示I级高血压和I级甲状腺功能减退。
    该病例突出了我们患者的ACC对EP和辛替利玛联合安洛替尼的新型组合治疗的显着反应。我们的发现为肾上腺皮质癌患者提供了一种安全,更有效的联合治疗选择。
    UNASSIGNED: Adrenocortical carcinoma (ACC) is a rare malignant tumor that occurs in the adrenal cortex. It has a high degree of malignancy and comparatively poor overall prognosis. Surgery is the standard curative therapy for localized ACC patients. The combination regimen of etoposide, doxorubicin, cisplatin (EDP) plus mitotane has been considered as the standardized chemotherapy regimen for advanced ACC. However, new effective regimens are emerging for specific conditions in metastatic ACC.
    UNASSIGNED: We report a case of a 66-year-old man diagnosed with metastatic ACC who had a large left adrenal mass (110 mm × 87 mm) and multiple metastases in both lungs. The patient was treated with EP and sintilimab for six cycles; anlotinib was introduced after the third cycle. Follow-ups after the second to fourth cycles found significantly reduced lung metastases with all imaging examinations indicating partial response (PR) status. The patient received maintenance therapy thereafter with sintilimab plus anlotinib. Until recently, the patient\'s lung metastases and the left adrenal gland area mass (39mm × 29mm) have disappeared, and no disease progression has been observed. The progression-free survival of this patient has been extended to approximately 31 months, in sharp contrast to a median survival time of 12 months for majority of advanced ACC. The main adverse events during treatment were appetite loss and grade I myelosuppression and revealed only grade I hypertension and grade I hypothyroidism.
    UNASSIGNED: This case highlights the remarkable response of our patient\'s ACC to treatment with a novel combination of EP and sintilimab combined with anlotinib. Our findings suggest a safe and more effective combination therapeutic option for patients with adrenocortical carcinoma.
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  • 文章类型: Journal Article
    背景:靶向治疗和免疫治疗的结合改善了不可切除的肝细胞癌(HCC)的临床结果。然而,总体预后仍欠佳.这项研究旨在评估射频消融(RFA)与lenvatinib加sintilimab在不可切除的HCC中的新型组合的疗效和安全性。
    方法:在这项回顾性研究中,纳入了诊断为无法切除的HCC的患者,并将其分为两组:RFA联合lenvatinib+辛替利玛(R-L-S组)和lenvatinib+辛替利玛(L-S组).主要疗效终点是客观缓解率(ORR)和无进展生存期(PFS)。分析不良事件以评估安全性。
    结果:整个队列的中位随访期为14.0个月。R-L-S组(n=60)的ORR明显高于单独使用L-S组(n=62)(40.0%vs.20.9%;p=0.022)。此外,R-L-S组患者中位PFS改善(12vs.8个月;p=0.013)和中位总生存期(24vs.18个月;p=0.037),与单独的lenvatinib和sindilimab相比。两组治疗相关不良事件(TRAE)各等级无显著性差异。≥3级的最常见的TRAE在R-L-S组中是疲劳10.0%(6/60)和手足皮肤反应10.0%(6/60),在L-S组中是手足皮肤反应11.3%(7/62)。
    结论:在不可切除的HCC患者中,与单独使用lenvatinib+sintilimab相比,在lenvatinib+sintilimab中掺入RFA在不影响安全性的情况下显示出改善的疗效.
    BACKGROUND: The combination of targeted therapy and immunotherapy has improved the clinical outcomes of unresectable hepatocellular Carcinoma (HCC). However, the overall prognosis remains suboptimal. This study aims to evaluate the efficacy and safety of a novel combination of radiofrequency ablation (RFA) with lenvatinib plus sintilimab in unresectable HCC.
    METHODS: In this retrospective study, patients diagnosed with unresectable HCC were included and divided into two cohorts: RFA combined with lenvatinib plus sintilimab (R-L-S group) and lenvatinib plus sintilimab (L-S group). The primary efficacy endpoints were objective response rate (ORR) and progression free survival (PFS). Adverse events were analyzed to assess the safety profiles.
    RESULTS: The median follow-up periods for the entire cohort were 14.0 months. The R-L-S group (n = 60) had a significantly higher ORR than those with L-S alone (n = 62) (40.0% vs. 20.9%; p = 0.022). Moreover, patients in the R-L-S group had improved median PFS (12 vs. 8 months; p = 0.013) and median overall survival (24 vs. 18 months; p = 0.037), as compared with lenvatinib and sintilimab alone. No significant difference in treatment related adverse event (TRAE) of any grade between the two groups. The most common TRAEs of grade ≥ 3 were fatigue 10.0% (6/60) and hand-foot skin reaction 10.0% (6/60) in the R-L-S group and hand-foot skin reaction 11.3% (7/62) in the L-S group.
    CONCLUSIONS: In unresectable HCC patients, the incorporation of RFA to lenvatinib plus sintilimab demonstrated improved efficacy without compromising safety compared with lenvatinib plus sintilimab alone.
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  • 文章类型: Case Reports
    作为青少年和年轻人中最常见的原发性骨肉瘤类型之一,骨肉瘤局部浸润和远处转移的可能性很高,预后较差。
    这里,我们报道一例34岁晚期转移性骨肉瘤患者.考虑到PD-L1的高表达和患者不能耐受化疗,抗PD-1抗体(sintilimab200mg,q3w)和抗血管生成药物(安洛替尼8mgD1-14,q3w)。转移灶采用局部放疗治疗。患者获得了11.7个月的持续缓解期,他也享受着更好的生活质量。
    本病例证明辛替利玛联合安洛替尼可能是骨肉瘤患者可行的治疗方案。
    UNASSIGNED: As one of the most common types of primary bone sarcomas in adolescents and young adults, osteosarcoma has a high probability of local invasion and distant metastasis with a poor prognosis.
    UNASSIGNED: Here, we report the case of a 34-year-old patient with advanced metastatic osteosarcoma. Considering the high expression of PD-L1 and the inability of the patient to tolerate chemotherapy, anti-PD-1 antibody (sintilimab 200 mg, q3w) and anti-angiogenesis drug (anlotinib 8 mg D1-14, q3w) were administered. The metastatic lesions were treated with local radiotherapy. The patient obtained an 11.7-month-sustained remission period, and he also enjoyed a better quality of life.
    UNASSIGNED: This case demonstrates that sintilimab plus anlotinib may be a feasible treatment regimen for osteosarcoma patients.
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  • 文章类型: Case Reports
    在各种癌症中,免疫检查点抑制剂(ICIs)已显示出实质性的生存优势。然而,ICIs在临床中的广泛使用导致人们对免疫相关不良事件(irAEs)及其治疗方法的兴趣与日俱增.本文报告了一例成功治疗了三例连续严重irAE的患者。在接受两种方案的sintilimab联合化疗治疗晚期肺癌后,患者出现心肌炎合并肝炎。随后,患者在治疗缓解后出现肺炎。我们还讨论了IRAE的机制,治疗原则,并通过文献复习,对早期预测IRAE的生物标志物研究进展进行了综述。
    In a variety of cancers, immune checkpoint inhibitors (ICIs) have demonstrated substantial survival advantages. Nevertheless, the widespread use of ICIs in the clinic has resulted in a growing interest in immune-related adverse events (irAEs) and their treatment methods. This paper reports a case in which a patient with three sequential severe irAEs was successfully treated. After undergoing two regimens of sintilimab in conjunction with chemotherapy for advanced lung cancer, the patient developed myocarditis combined with hepatitis. Subsequently, the patient developed pneumonia following remission from treatment. We also discuss the mechanism of irAEs, principles of treatment, and progress in the study of biomarkers for early prediction of irAEs by reviewing the literature.
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  • 文章类型: Case Reports
    胸腺癌(TC)是一种罕见的胸腺上皮肿瘤。复发或难治性TC患者预后不良。免疫检查点抑制剂单一疗法可以作为这种情况的二线治疗。这项研究报告了一名TC患者,该患者对常规化疗和放疗无反应,但在使用抗程序性细胞死亡1抑制剂sintilimab进行三线治疗后,获得了持续17个月的长期部分缓解。该患者没有经历任何与sintilimab治疗相关的严重副作用。以上结果表明,辛替利玛可能是难治性TC患者的可行治疗选择。
    Thymic carcinoma (TC) is an uncommon type of thymic epithelial tumors. Patients with relapsed or refractory TCs have a poor prognosis. Immune checkpoint inhibitor monotherapy can be applied as a second-line treatment for such cases. This study reported a TC patient who did not respond to conventional chemotherapy and radiotherapy but achieved prolonged partial remission lasting 17 months following the third-line treatment with anti-programmed cell death-1 inhibitor sintilimab. This patient did not experience any serious side effects associated with sintilimab treatment. The above results demonstrated that sintilimab could be a feasible therapeutic option for refractory TC patients.
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  • 文章类型: Case Reports
    随着免疫检查点抑制剂(ICIs)在肿瘤中的广泛应用,报道了几种免疫相关的不良事件(irAE)。ICI相关的皮肤反应是最常见的,表现为黄斑丘疹,皮疹,瘙痒,白癜风,牛皮癣,和苔藓样皮疹.其中,瘙痒的发生率仅次于斑丘疹/皮疹,但两者往往共存。瘙痒的严重程度多为轻至中度,经抗组胺药物对症治疗后可缓解。严重瘙痒患者经常规治疗后症状略有缓解,但它很容易复发并最终发展为难治性瘙痒。患者的生活质量可能受到影响,也可能危及生命。我们报告了一例胆囊神经内分泌癌术后复发的患者,使用sintilimab后出现难治性瘙痒,常规药物治疗失败后输注纳洛酮后缓解。通过分析该典型病例使用sintilimab后免疫相关性难治性瘙痒的治疗方案,本报告讨论了临床药师如何利用他们的专业知识和临床医生在治疗临床疑难病例时的合作和补充,为患者提供个体化治疗。该病例报告可作为临床使用sintilimab治疗难治性瘙痒患者的参考。
    Several immune related adverse events (irAEs) were reported with the wide application of immune checkpoint inhibitors (ICIs) in tumors. ICI-related skin reactions are the most common, which are manifested as maculopapules, rash, pruritus, vitiligo, psoriasis, and lichenoid rash.Among them, the incidence of pruritus is second only to maculopapule/rash, but both often co-exist. The severity of pruritus is mostly mild to moderate and can be relieved after symptomatic treatment with antihistamines. Symptoms are slightly relieved after conventional treatment in patients with severe pruritus, but it easily recurs and eventually develops into refractory pruritus.The patient\'s quality of life may be affected and may also be life-threatening. We report a case of a patient with postoperative recurrence of gallbladder neuroendocrine carcinoma,who developed refractory pruritus after sintilimab use, which was relieved after naloxone infusion after unsuccessful conventional drug therapy. By analyzing the treatment plan of this typical case of immune-related refractory pruritus after using sintilimab, this report discusses how clinical pharmacists can provide individualized treatment of patients by using their expertise and clinicians\' cooperation and complementation in treating clinically difficult cases. This case report may be used as a reference in treating patients with refractory pruritus after the clinical use of sintilimab.
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  • 文章类型: Journal Article
    背景:胰腺腺癌,胰腺细胞中出现的恶性肿瘤,是一种病因不明,预后通常较差的毁灭性疾病。局部晚期胰腺癌,肿瘤已经显著生长但尚未扩散到远处器官的阶段,在治疗中提出了独特的挑战。本文旨在讨论当前的策略,挑战,以及局部晚期胰腺腺癌(LAPC)治疗的未来方向。
    目的:探讨程序性细胞死亡因子1(PD-1)抑制剂辛替利麦联合同步放化疗治疗LAPC的可行性和疗效。
    方法:符合条件的患者患有LAPC,东部合作肿瘤学组表现状态为0或1,器官和骨髓功能充足,之前没有抗癌治疗.在观察组中,参与者每3周接受一次静脉注射Sintilimab200毫克,并接受同步放化疗(同时进行常规分割放疗,计划目标体积50.4Gy和总肿瘤体积60Gy的剂量分为28个部分,在21天周期的第1-14天每天两次口服S-140mg/m2,在21天周期的第1天和第8天静脉注射吉西他滨1000mg/m2,持续8个周期,直至疾病进展,死亡,或不可接受的毒性)。在对照组中,参与者仅接受同步放化疗.从2020年4月到2021年11月,64名参与者最终被纳入,其中34名为观察组,30名为对照组。
    结果:34名患者完成了计划的放化疗疗程,观察组32例(94.1%)接受辛替利玛联合同步放化疗,2例停用辛替利玛。对照组30例患者完成了计划的放化疗疗程。根据实体瘤指南中的反应评估标准,对观察组的分析显示,11例患者(32.4%)出现部分缓解,19例患者病情稳定(55.9%),4例(11.8%)患者出现疾病进展;6例(20.0%)患者出现部分缓解,18例疾病稳定(60%),对照组中6例(20%)疾病进展。主要毒性作用是白细胞减少和恶心。观察组严重不良事件(AEs)(3级或4级)发生率为26.5%(9/34),对照组为23.3%(7/30)。没有治疗相关的死亡。与对照组相比,观察组的中位总生存期(22.1个月比15.8个月)(P<0.05)和无进展生存期(12.2个月比10.1个月)(P<0.05)明显更长。观察组与对照组严重不良事件发生率比较差异无统计学意义(P>0.05)。
    结论:Sindilimab联合同步放化疗对LAPC患者有效且安全,并需要进一步调查。
    BACKGROUND: Pancreatic adenocarcinoma, a malignancy that arises in the cells of the pancreas, is a devastating disease with unclear etiology and often poor prognosis. Locally advanced pancreatic cancer, a stage where the tumor has grown significantly but has not yet spread to distant organs, presents unique challenges in treatment. This article aims to discuss the current strategies, challenges, and future directions in the management of locally advanced pancreatic adenocarcinoma (LAPC).
    OBJECTIVE: To investigate the feasibility and efficacy of programmed cell death 1 (PD-1) inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC.
    METHODS: Eligible patients had LAPC, an Eastern cooperative oncology group performance status of 0 or 1, adequate organ and marrow functions, and no prior anticancer therapy. In the observation group, participants received intravenous sintilimab 200 mg once every 3 wk, and received concurrent chemoradiotherapy (concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-1 40 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression, death, or unacceptable toxicity). In the control group, participants only received concurrent chemoradiotherapy. From April 2020 to November 2021, 64 participants were finally enrolled with 34 in the observation group and 30 in the control group.
    RESULTS: Thirty-four patients completed the scheduled course of chemoradiotherapy, while 32 (94.1%) received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group. Thirty patients completed the scheduled course of chemoradiotherapy in the control group. Based on the Response Evaluation Criteria in Solid Tumors guidelines, the analysis of the observation group revealed that a partial response was observed in 11 patients (32.4%), stable disease was evident in 19 patients (55.9%), and 4 patients (11.8%) experienced progressive disease; a partial response was observed in 6 (20.0%) patients, stable disease in 18 (60%), and progressive disease in 6 (20%) in the control group. The major toxic effects were leukopenia and nausea. The incidence of severe adverse events (AEs) (grade 3 or 4) was 26.5% (9/34) in the observation group and 23.3% (7/30) in the control group. There were no treatment-related deaths. The observation group demonstrated a significantly longer median overall survival (22.1 mo compared to 15.8 mo) (P < 0.05) and progression-free survival (12.2 mo vs 10.1 mo) (P < 0.05) in comparison to the control group. The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group (P > 0.05).
    CONCLUSIONS: Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients, and warrants further investigation.
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  • 文章类型: Journal Article
    卡利单抗联合紫杉醇和卡铂(CTC)和辛替单抗联合吉西他滨和顺铂或卡铂(SGP)均已被国家药品监督管理局(NMPA)批准用于一线治疗局部晚期或转移性sqNSCLC。然而,在疗效或药物经济学方面,两种治疗作为一线治疗的比较几乎没有被研究过.为了深入了解两种治疗的成本和结果,这项工作直接比较了中国大陆地区局部晚期或转移性鳞状NSCLC一线治疗的成本-效果.
    首先根据三项临床试验进行了网络荟萃分析,即,CameL-Sq,ORIENT-12和C-TONG1002,以比较两种治疗的临床益处。应用Weibull近似来进一步计算两种治疗的预期寿命。接下来建立分区生存模型(PSM),并进行了单向敏感性分析和概率敏感性分析,以评估模型内基本参数值和假设的稳定性。
    CTC治疗增加了0.68QALY,花费了14764美元。SGP治疗增加了0.54QALY,花费了14584美元。CTC部门增加了0.14个QALY,比SGP部门高出179美元,ICER为$1,269/QALY,低于中国大陆人均GDP的1倍(2022年人均GDP为12734美元)。在概率敏感性分析中,当WTP从12,734-38,202美元(1-3倍,2022年中国人均GDP),CTC组比SGP组有更高的成本效益概率,从85.65%到88.38%不等。
    从付款人的角度来看,在中国大陆,卡姆瑞珠单抗联合化疗治疗局部晚期或转移性鳞状细胞肺癌的一线治疗与辛替利玛单抗联合化疗相比,具有成本效益.
    UNASSIGNED: Both camrelizumab plus paclitaxel and carboplatin (CTC) and sintilimab plus gemcitabine and cisplatin or carboplatin (SGP) have been approved by the National Medical Products Administration of China (NMPA) for the first-line treatment of local advanced or metastatic sqNSCLC. However, the comparison of the two treatments as first-line treatments in efficacy or pharmacoeconomics has barely been studied. To deeply understand the costs and outcomes of the two treatments, this work directly compared the cost-effectiveness for the first-line treatment of local advanced or metastatic squamous NSCLC in the Chinese mainland.
    UNASSIGNED: A network meta-analysis was first performed based on the three clinical trials, namely, CameL-Sq, ORIENT-12, and C-TONG1002, to compare the clinical benefits of the two treatments. The Weibull approximation was applied to further calculate the life expectancy of the two treatments. The partitioned survival model (PSM) was next established, and one-way sensitivity analysis and probabilistic sensitivity analysis were also performed to evaluate the stability of the underlying parameter values and assumptions within the model.
    UNASSIGNED: CTC treatment gained 0.68 QALYs and cost $14,764. SGP treatment gained 0.54 QALYs and cost $14,584. The CTC arm gained 0.14 additional QALYs and cost $179 more than the SGP arm, and the ICERs was $1,269/QALY, which was lower than one-fold GDP per capita in the Chinese mainland ($12,734 GDP per capita in 2022). In probabilistic sensitivity analysis, when the WTP ranged from $12,734-38,202 (1-3 folds, 2022 GDP per capita in China), the CTC group had higher probabilities than the SGP group for being cost effective, which ranged from 85.65% to 88.38%.
    UNASSIGNED: From the perspective of the payers, camrelizumab plus chemotherapy was cost-effective compared with sintilimab plus chemotherapy for the first-line treatment of local advanced or metastatic squamous NSCLC in the Chinese mainland.
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  • 文章类型: Case Reports
    原发性肺恶性外周神经鞘瘤(MPNST)是一种少见的软组织肉瘤,发病率低,预后差,治疗选择有限。本研究报告了一名63岁男性患者的肺部MPNST病例,没有任何肺部症状。肿瘤的免疫组织化学分析表明程序性死亡配体1(PD-L1)表达肿瘤比例评分为60%。该患者总共使用了六个疗程的sintilimab,并取得了显着的反应。总之,sintilimab单药免疫治疗可能是一种新的治疗肺部MPNST的方法。将来遇到类似案例时,肿瘤学家可以检测患者PD-L1的表达,以指导治疗的设计。
    Primary pulmonary malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma with a low incidence, poor prognosis and limited treatment options. The present study reported a case of lung MPNST in a 63-year-old male patient without any pulmonary symptoms. Immunohistochemical analysis of the tumor indicated a programmed death-ligand 1 (PD-L1) expression tumor proportion score of 60%. A total of six courses of sintilimab were used in this patient and a remarkable response was achieved. In summary, sintilimab single-agent immunotherapy may be a novel treatment for pulmonary MPNST. When encountering analogous cases in the future, oncologists can test for the expression of PD-L1 in patients to guide the therapy\'s design.
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