Conversion therapy

转化疗法
  • 文章类型: Case Reports
    转移性胆管癌(CCA)的化学疗法和免疫疗法的结合提供了超越传统治疗的有希望的生存率和反应率的改善。TOPAZ-1和KEYNOTE-966已经证明了联合免疫治疗(durvalumab和pembrolizumab)与化疗的疗效,即使在胆囊癌(GBC)中,TOPAZ-1试验的完全缓解率为2.7%。用免疫疗法组合治疗的晚期CCA显示出受高程序性死亡配体1(PD-L1)或EB病毒表达影响的完全反应。通过将放射疗法与程序性细胞死亡蛋白1(PD-1)阻断相结合来增强这些应答。一名62岁的男子被诊断出患有无法切除的GBC,远处淋巴转移,和局部侵入肝段4i和5,结肠肝曲,十二指肠球部,还有胰头.免疫组织化学检查显示低分化鳞状细胞癌,不表达PD-L1。下一代测序显示ERBB2R678Q的突变和微卫星稳定肿瘤。患者于2022年6月开始使用顺铂-吉西他滨联合durvalumab进行化学免疫治疗。八个周期后,据报道,肿瘤体积和标志物显著减少,durvalumab的治疗一直维持到2023年11月.随后的计算机断层扫描显示肿瘤体积进一步减小,并进行了手术切除。组织学检查证实没有残留肿瘤或淋巴结转移。截至2024年6月,患者没有出现疾病复发的迹象。存在一些关于GBC转换手术的报告,但术前化疗免疫疗法的数据有限.此外,CCA和GBC无病理证实的完全缓解引发了一些关于免疫治疗后是否需要手术的问题.尽管在晚期GBC中已经报道了有效的疾病控制和肿瘤消退,联合抗细胞毒性T淋巴细胞相关蛋白4和抗PD-1药物和化疗,由于与PD-L1表达或肿瘤突变负荷的相关性不明确,因此需要进一步的研究来鉴定可靠的预测性生物标志物.总的来说,化学免疫疗法已有效治疗转移性CCA,特别是当针对特定的分子特征定制时。这些治疗可能导致完全的反应和新的策略。
    The combination of chemotherapy and immunotherapy for metastatic cholangiocarcinoma (CCA) offers promising improvements in survival and response rates beyond traditional treatments. TOPAZ-1 and KEYNOTE-966 have demonstrated the efficacy of combining immunotherapy (durvalumab and pembrolizumab) with chemotherapy, even in gallbladder cancer (GBC), with a complete response rate of 2.7% in the TOPAZ-1 trial. Advanced CCA treated with immunotherapy combinations has shown complete responses influenced by high programmed death-ligand 1 (PD-L1) or Epstein-Barr virus expression. These responses were enhanced by combining radiotherapy with programmed cell death protein 1 (PD-1) blockade. A 62-year-old man was diagnosed with unresectable GBC, distant lymphatic metastases, and local invasion of liver segments 4i and 5, the colonic hepatic flexure, the duodenal bulb, and the pancreatic head. Immunohistochemical examination revealed poorly differentiated squamous cell carcinoma, without expression of PD-L1. Next generation sequencing revealed the mutation of ERBB2 R678Q and a microsatellite stable tumour. The patient started chemo-immunotherapy with cisplatin-gemcitabine plus durvalumab in June 2022. After eight cycles, a significant reduction in tumour volume and markers was reported, and therapy with durvalumab was maintained through November 2023. The subsequent computed tomography scans showed further reduction in the tumour volume, and surgical resection was performed. Histological examinations confirmed the absence of residual tumour or lymph node metastases. As of June 2024, the patient has shown no signs of disease recurrence. Several reports of conversion surgery in GBC exist, but data on pre-surgical chemo-immunotherapy are limited. Furthermore, a complete response without pathological confirmation in CCA and GBC raises several questions regarding the need for surgery after immunotherapy. Although effective disease control and tumour regression have been reported in advanced GBC with combined anti-cytotoxic T-lymphocyte associated protein 4 and anti-PD-1 agents and chemotherapy, further studies are needed to identify reliable predictive biomarkers due to unclear associations with PD-L1 expression or tumour mutational burden. Overall, chemo-immunotherapy has been effective in treating metastatic CCA, especially when tailored to specific molecular profiles. These treatments may lead to complete responses and novel strategies.
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  • 文章类型: Letter
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  • 文章类型: Case Reports
    肝细胞癌(HCC)是全球第六大最常见的恶性肿瘤,大多数患者在最初诊断为局部晚期或转移性疾病,排除了治愈性手术干预的机会。随着局部治疗的探索和进步,新型分子靶向疗法,抗血管生成剂,和免疫调节药物,在HCC的治疗中,客观缓解率提高,缓解持续时间延长,显著增强了中晚期不可切除HCC患者转诊为可切除疾病的可能性.在这里,我们介绍了巴塞罗那临床肝癌B期不可切除的HCC,经动脉化疗栓塞联合阿特珠单抗加贝伐单抗治疗两个疗程后,肿瘤显著减少.根据实体瘤的反应评估标准1.1,部分反应最终导致成功的治愈性手术切除。住院期间无药物相关不良反应发生,在术后11个月的随访中没有复发。对于巴塞罗那临床肝癌B期(中期)不可切除的HCC患者,经肝动脉化疗栓塞联合阿特珠单抗加贝伐单抗方案可改善治疗结果,从而提高转换治疗的成功率,因此,改善生存。
    Hepatocellular carcinoma (HCC) ranks as the sixth most common malignancy globally, with the majority of patients presenting at the initial diagnosis with locally advanced or metastatic disease, precluding the opportunity for curative surgical intervention. With the exploration and advancement of locoregional treatments, novel molecular-targeted therapies, anti-angiogenic agents, and immunomodulatory drugs, the management of HCC has seen an increase in objective response rates and prolonged duration of response significantly enhancing the potential for conversion to resectable disease in intermediate and advanced-stage unresectable HCC. Herein, we present a case of Barcelona Clinic Liver Cancer stage B unresectable HCC, where after two courses of treatment with transarterial chemoembolization combined with atezolizumab plus bevacizumab significant tumor reduction was achieved. Per Response Evaluation Criteria in Solid Tumors 1.1, partial response culminated in successful curative surgical resection. No drug-related adverse reactions occurred during hospitalization, and there has been no recurrence during the 11-month postoperative follow-up. For patients with Barcelona Clinic Liver Cancer stage B (intermediate-stage) unresectable HCC, the transarterial chemoembolization combined with atezolizumab plus bevacizumab regimen may offer improved therapeutic outcomes leading to a higher success rate of conversion therapy and, thus, improved survival.
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  • 文章类型: Case Reports
    转移性结直肠癌需要多学科和个性化的方法。在这里,我们报道了1例年轻女性被诊断为转移性直肠癌,该女性接受了个体化多模式治疗策略,获得了显著的生存率.这个案子有几个特别的方面,比如疾病的早期发作,转换疗法的成功使用,液体活检指导治疗的应用,以及骨转移的特异性。为转移性结直肠癌患者应对这些挑战提供更多见解,我们进行了文献综述,以找到更多与此病例的特殊性相关的数据。早发性结直肠癌的发病率呈上升趋势。数据表明,它在病理方面与老年结直肠癌不同,流行病学,解剖学,新陈代谢,和生物学特征。转换治疗和手术干预为转移性结直肠癌的治愈和改善预后提供了机会。重要的是要单独处理每种情况,因为每一位局限性肝病患者都应被视为二次切除的候选人.此外,液体活检在转移性结直肠癌患者的个体化治疗中具有重要作用,因为它为治疗决策提供了额外的信息。
    Metastatic colorectal cancer requires a multidisciplinary and individualized approach. Herein, we reported the case of a young woman diagnosed with metastatic rectal cancer who received an individualized multimodal treatment strategy that resulted in a remarkable survival. There were several particular aspects of this case, such as the early onset of the disease, the successful use of conversion therapy, the application of liquid biopsy to guide treatment, and the specific nature of the bone metastasis. To offer more insights for navigating such challenges in patients with metastatic colorectal cancer, we have conducted a literature review to find more data related to the particularities of this case. The incidence of early onset colorectal cancer is on the rise. Data suggests that it differs from older-onset colorectal cancer in terms of its pathological, epidemiological, anatomical, metabolic, and biological characteristics. Conversion therapy and surgical intervention provide an opportunity for cure and improve outcomes in metastatic colorectal cancer. It is important to approach each case individually, as every patient with limited liver disease should be considered as a candidate for secondary resection. Moreover, liquid biopsy has an important role in the individualized management of metastatic colorectal cancer patients, as it offers additional information for treatment decisions.
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  • 文章类型: Case Reports
    肝细胞癌是一种相当常见的恶性肿瘤。大多数肝细胞癌患者在晚期接受诊断,手术切除不再合适。越来越多的研究已经证明了常规治疗对中期肝细胞癌患者的价值,而具体的应用方案和治疗指南尚不完善。新兴的临床研究表明,酪氨酸激酶抑制剂与免疫检查点抑制剂联合使用是不可切除的肝细胞癌的合理策略。然而,关于阿帕替尼和卡姆瑞珠单抗治疗肝细胞癌的疗效的报道相对较少.在阿帕替尼(每天口服250mg)和卡莫瑞珠单抗(每2周静脉注射200mg)进行8个周期的转换治疗后,我们能够成功清除一名患者的肝细胞癌。患者在肝切除术后继续接受相同剂量的16个周期的阿帕替尼和卡姆瑞珠单抗。到了这项研究的时候,患者已完成18个月的随访,肿瘤标志物及影像学检查均未发现肿瘤复发或转移。阿帕替尼联合卡姆瑞珠单抗是治疗晚期肝细胞癌的有效药物,这种转换治疗后的手术切除可能为患者提供长期的肿瘤学益处。然而,这需要更多的样本来验证结论。
    Hepatocellular carcinoma is a rather common malignant tumor. Most patients with hepatocellular carcinoma receive their diagnosis at an advanced stage, at which surgical resection is no longer appropriate. A growing body of research has demonstrated the value of convention therapy for patients with intermediate-stage hepatocellular carcinoma, while specific application protocols and treatment guidelines are not well developed. Emerging clinical researches suggest that a tyrosine kinase inhibitor in combination with an immune checkpoint inhibitor is a reasonable strategy for unresectable hepatocellular carcinoma. However, there are relatively few reports on the efficacy of apatinib and camrelizumab in the treatment of hepatocellular carcinoma. We were able to successfully remove one patient\'s hepatocellular carcinoma after 8 cycles of conversion therapy with apatinib (250 mg orally every day) and camrelizumab (200 mg intravenously every 2 weeks). The patient continued to receive the same dose of 16 cycles of apatinib and camrelizumab after hepatectomy. By the time of this study, the patient has completed 18 months of follow-up, and no tumor recurrence or metastasis was found in tumor markers and imaging examinations. Apatinib in combination with camrelizumab is an effective therapy for the treatment of advanced hepatocellular carcinoma, and surgical resection after this conversion therapy may provide patients with long-term oncological benefits. However, this requires more samples to validate the conclusion.
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  • 文章类型: Case Reports
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  • 文章类型: Case Reports
    将免疫检查点抑制剂与靶向治疗相结合的协同有效性已显示出有望提高不可切除的肝细胞癌(HCC)患者的转化率至潜在可切除状态。然而,这种方法在肝癌肝外转移的情况下的疗效仍有待最终确定。
    我们报告了一例罕见的晚期肝癌肝外转移病例,通过全身治疗(sintilimab和sorafenib)联合腹腔镜肝切除术获得长期生存。一名63岁的男子出现在我们医院,腰部右侧不适。随后通过CT扫描发现右肝叶肿块增大。病人的病史,包括先前感染过乙型肝炎病毒,肝硬化和甲胎蛋白(AFP)水平为41.28ng/ml,证实了HCC的临床诊断。10月30日,2019年,患者静脉注射200毫克辛替利玛(q3w)加200-400毫克BID索拉非尼口服,以及抗病毒治疗。经过六个周期,他的疾病达到部分反应(PR)。4月26日,2021年,他接受了腹腔镜肝切除术。患者在切除后2.5年内实现了无疾病证据的持续期,并在2年内实现了无药生存。他目前的总生存期估计约为4年。
    此病例突出了组合sintilimab和sorafenib在将具有肝外转移的HCC转化为适合手术切除的条件方面的潜力,表明这种治疗方法,接着是手术,可能导致完全缓解。
    UNASSIGNED: The synergistic effectiveness of combining immune checkpoint inhibitors with targeted therapies has shown promise in improving the conversion rate for unresectable hepatocellular carcinoma (HCC) patients to a potentially resectable status. However, the efficacy of this approach in the context of HCC with extrahepatic metastasis remains to be conclusively determined.
    UNASSIGNED: We report a rare case of advanced HCC with extrahepatic metastasis who achieved long-term survival by a combination of systemic therapy (sintilimab and sorafenib) followed by laparoscopic hepatectomy. A 63-year-old man presented at our hospital with discomfort on the right side of his waist. An enlarged right hepatic lobe mass was subsequently revealed by CT scan. The patient\'s medical history, including a prior infection with hepatitis B virus, cirrhosis of the liver and an alpha-fetoprotein (AFP) level measuring 41.28 ng/ml substantiated the clinical diagnosis of HCC. On October 30th, 2019, the patient received 200 mg sintilimab intravenously (q3w) plus 200-400 mg BID sorafenib orally, along with antiviral therapy. After six cycles, his disease achieved partial response (PR). On April 26th, 2021, He underwent a laparoscopic hepatectomy. The patient achieved a sustained period of no evidence of disease for 2.5 years and with drug-free survival for 2 years after the resection. His current overall survival is estimated at approximately 4 years.
    UNASSIGNED: This case highlights the potential of combining sintilimab and sorafenib in transforming HCC with extrahepatic metastasis into a condition amenable to surgical resection, suggesting that this treatment approach, followed by surgery, may lead to complete remission.
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  • 文章类型: Review
    由于DNA错配修复(dMMR)系统缺陷,免疫疗法已在一小部分具有微卫星不稳定性(MSI-H)状态的结直肠癌(CRC)患者的治疗前景中发挥了作用。对免疫检查点抑制剂(ICIs)的显着反应现在正在局部CRC的新辅助设置中进行测试。其中dMMR/MSI-H状态可以在多达15%的患者中发现,在NICHE2和3项试验中获得了显著的结果,在其他人中。本病例系列旨在报告我们在三级中心的经验,并全面分析如果将ICIs确立为新辅助治疗的标准,可能需要克服的问题和挑战。以及它们可能不仅在局部晚期CRC中而且在寡转移疾病中作为转化疗法的潜在作用。
    Immunotherapy has demonstrated a role in the therapeutic landscape of a small subset of patients with colorectal carcinoma (CRC) that harbor a microsatellite instability (MSI-H) status due to a deficient DNA mismatch repair (dMMR) system. The remarkable responses to immune checkpoint inhibitors (ICIs) are now being tested in the neoadjuvant setting in localized CRC, where the dMMR/MSI-H status can be found in up to 15% of patients, with remarkable results obtained in NICHE2 and 3 trials, among others. This case series aims to report our experience at a tertiary center and provide a comprehensive analysis of the possible questions and challenges to overcome if ICIs were established as standard of care in a neoadjuvant setting, as well as the potential role they may have as conversion therapy not only in locoregional advanced CRC but also in oligometastatic disease.
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  • 文章类型: Review
    背景:恶性间皮瘤(MM)是一种起源于胸膜的肿瘤,腹膜,或心包腔。它分为弥漫性和局限性恶性间皮瘤,弥漫性MM有四种亚型:上皮样,肉瘤样,去可塑性,和双相的,双相不太常见。这个肿瘤的发病是阴险的,在某些情况下预后极差,中位生存期为6-18个月,过去没有标准治疗方案。目的:我们报告了一例腹膜恶性间皮瘤,并通过转化疗法成功治疗。并对相关文献进行综述,以期为此类患者的治疗和病理诊断提供参考。方法:对腹膜恶性间皮瘤的病例进行处理,并对不同阶段的活检标本进行常规报道。结果与结论:我们报告一例起源于肝肾隐窝的恶性肿瘤,通过活检被诊断为双相恶性间皮瘤。免疫组织化学检测显示PD-L1表达。经过多学科的讨论,病人接受了转化性治疗,包括联合免疫疗法的试验。肿瘤明显缩小,患者获得了根治性手术切除的机会。显微镜检查显示病变区域有明显的胶原化,几乎没有残留肿瘤.经过19个月的综合治疗,患者在双肺胸膜下出现多个蓬松的混浊。CT引导下经胸芯针活检,病理显示机化性肺炎,根据既往治疗史,将其视为由免疫治疗引起的迟发性间质性肺炎。此例腹膜恶性间皮瘤成功综合治疗,病人已经活了33个月没有疾病的证据,长期随访。在这个过程中,病理学家有三次病理诊断的机会,这需要了解病人的病史,注意标本的临床目的,并对不同阶段的形态变化提供准确的反应,以及相应的描述和诊断,为临床治疗提供有效的信息。
    Background: Malignant mesothelioma (MM) is a tumor originating from the pleura, peritoneum, or pericardial cavity. It is divided into diffuse and localized malignant mesothelioma, with four subtypes in diffuse MM: epithelioid, sarcomatoid, desmoplastic, and biphasic, with biphasic being less common. The onset of this tumor is insidious, and the prognosis is extremely poor in some cases, with a median survival of 6-18 months and no standard treatment options in the past. Aims: We report a case of peritoneal malignant mesothelioma that was successfully treated with transformative therapy. We also review the literature in the hope of providing reference for the treatment and pathological diagnosis of such patients. Methods: The case of the peritoneal malignant mesothelioma was processed and reported in the routine manner for biopsy specimens at different stages. Results and conclusion: We report a case of a malignant tumor originating in the hepatorenal recess, which was diagnosed as biphasic malignant mesothelioma through a biopsy. Immunohistochemical testing showed PD-L1 expression. After multidisciplinary discussion, the patient received transformative treatment, including a trial of combined immunotherapy. The tumor significantly shrank, and the patient obtained a chance for curative surgical resection. Microscopic examination showed significant collagenization in the lesion area, with almost no residual tumor. After 19 months of comprehensive treatment, the patient developed multiple fluffy opacities under the pleura of both lungs. Transthoracic core needle biopsy under CT guidance, the pathology showed organizing pneumonia, considering it as delayed interstitial pneumonitis due to immunotherapy based on previous treatment history. Successful comprehensive treatment was achieved for this case of peritoneal malignant mesothelioma, and the patient has been alive without evidence of disease for 33 months, with long-term follow-up. In this process, the pathologist had three opportunities for pathological diagnosis, which required understanding the patient\'s medical history, being attentive to the clinical purpose of the specimen, and providing accurate responses to morphological changes at different stages, along with corresponding descriptions and diagnoses to provide effective information for clinical treatment.
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  • 文章类型: Case Reports
    肝转移是结直肠癌患者最常见的死亡原因之一。因此,提高结直肠癌肝转移癌的治疗效果也是提高结直肠癌患者生存时间的有效途径之一。结直肠癌肝转移的主要治疗方法是术前静脉新辅助化疗。然而,没有人报道通过动脉灌注化疗联合靶向药物和PD-1单克隆抗体治疗结直肠癌肝转移患者的转化治疗方法.本文报道了肝动脉灌注化疗(HAIC)对结直肠癌肝转移的转化治疗方法,辛替利玛注射液联合乐伐替尼治疗后实现肝转移癌的根治性切除。
    该患者是一名69岁的男性,此前曾接受腹腔镜左半结肠切除术治疗下行结肠直肠癌,以及多种介入和手术治疗肝细胞癌。在这个治疗过程中,患者接受了放射学和血清学检查,原发性肝癌在初始诊断阶段被考虑。因此,该肝脏恶性肿瘤病变在手术切除前按照原发性肝癌治疗方案进行治疗。因此,患者接受HAIC联合辛替利玛注射液和乐伐替尼治疗。三个治疗周期后,放射学检查显示没有明显的肿瘤活动,甲胎蛋白(AFP)降至正常,维生素K缺失或拮抗剂II(PIVKAII)诱导的蛋白质显着降低,疗效评价为完全缓解。随后,我们对该肝脏病变进行了手术切除。左叶肿瘤病理反应为部分缓解(PR)。大多数肿瘤坏死,坏死率大于95%。少量的活肿瘤组织仍然存在(<5%)。经病理科多项肿瘤指标免疫组化染色证实该肿瘤病理分类为中分化腺癌。在治疗期间,在该患者中未观察到显著的药物不良事件。
    肝动脉灌注化疗联合sintilmab注射液和lenvatinib转换疗法为结直肠癌肝转移的根治性手术切除提供了机会。
    Liver metastasis is one of the most common causes of death in patients with colorectal cancer. Therefore, improving the treatment effect of liver metastatic carcinoma of colorectal cancer is also one of the effective ways to improve the survival time of patients with colorectal cancer. The main treatment method for liver metastasis of colorectal cancer is preoperative neoadjuvant chemotherapy through intravenous administration. However, no one has reported a conversion therapy approach for the treatment of colorectal cancer liver metastases patients through arterial infusion chemotherapy combined with targeted agents and PD-1 monoclonal antibody. This case reports a conversion therapy method of liver metastases of colorectal cancer by hepatic arterial infusion chemotherapy (HAIC), sintilimab injection combined with lenvatinib to achieve radical resection of liver metastatic carcinoma after treatment.
    The patient was a 69-year-old man who had previously undergone laparoscopic left hemicolectomy for descending colorectal cancer and multiple interventional and surgical treatments for hepatocellular carcinoma. During this treatment, the patient underwent radiological and serological tests, and primary liver cancer was considered at the initial diagnosis stage. Therefore, this liver malignant tumor lesion was treated according to the primary liver cancer treatment protocol before surgical resection. Therefore, the patient received HAIC combined with sintilimab injection and lenvatinib. After three treatment cycles, radiological examination showed no obvious tumor activity, alpha-fetoprotein (AFP) decreased to normal, protein induced by vitamin K absence or antagonist II (PIVKA II) decreased significantly, and the curative effect was evaluated as complete remission. Subsequently, we performed surgical resection of this liver lesion. The pathological response of left lobe tumor was partial remission (PR). Most of the tumors were necrotic and the necrosis rate was greater than 95%. A small amount of live tumor tissue remains (<5%). The pathological classification of this tumor was confirmed as moderately differentiated adenocarcinoma by immunohistochemical staining of multiple tumor indicators in the pathology department. No significant adverse drug events were observed in this patient during treatment.
    Hepatic arterial infusion chemotherapy combined with sintilimab injection and lenvatinib conversion therapy provides the opportunity for radical surgical resection of colorectal cancer liver metastases.
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