免疫检查点抑制剂在微卫星稳定结直肠癌患者中的应用现状

<正>结直肠癌(colorectal cancer,CRC)是消化系统常见的恶性肿瘤。全球范围内,结直肠癌发病率居恶性肿瘤第3位,病死率居第2位,仅次于肺癌^[1]。早期结直肠癌预后良好,但部分结直肠癌患者在初诊时已是晚期,给临床治疗带来挑战。随着科学技术的发展,免疫检查点抑制剂(ICI)因其疗效显著已成为结直肠癌治疗中的研究热点。ICI能改善微卫星不稳定(MSI)结直肠癌患者的疗效、生存率和生活质量^[2],但MSI患者仅占全部结直肠癌患者的5%,而占95%的微卫星稳定(MSS)患者对于ICI治疗反应不佳,这与其肿瘤抗原数量少和易发生免疫逃逸的特性有关^[3]。研究证明大多数MSS晚期结直肠患者对免疫单药治疗无反应或无持久的临床反应,为提高疗效,基于ICI的联合治疗值得探索,本文就此问题综述。     

妇科恶性肿瘤基因检测、靶向治疗及免疫治疗现状

<正>随着基因组学、蛋白质组学和高通量测序等新技术的发展与应用,对肿瘤进行精准基因诊断、靶向治疗和免疫治疗成为肿瘤诊疗的新模式。尤其是抗血管生成药物和免疫检查点抑制剂在肿瘤治疗应用上取得了突破性进展,其应用于晚期/复发妇科肿瘤患者亦具有一定的疗效。本文就妇科恶性肿瘤的基因检测、靶向治疗及免疫治疗的现状及进展进行概述。1基因检测技术在妇科恶性肿瘤中应用1.1基因检测技术及其发展常用基因检测技术主要分为：(1)一代测序技术（sanger测序）：其测序过程操作简便,价格低廉,可靠性好,目前应用广泛。     

血清恶性肿瘤相关物质群检测在妇科恶性肿瘤高能聚束热化疗中的意义

目的:观察血清恶性肿瘤相关物质群在妇科恶性肿瘤高能聚束热疗联合化疗(热化疗)、纯化疗法中的表达并探讨其应用价值。方法:采用比色法测定49例妇科恶性肿瘤患者进行热化疗治疗前、后肿瘤相关物质群的水平,并与47例对照组纯化疗治疗前、后肿瘤相关物质群的水平进行比较。结果:2组治疗后肿瘤相关物质群水平均较治疗前下降(P<0.05),热化疗组较纯化疗组下降明显,二者比较差异有统计学意义(P<0.05)。结论:热化疗较纯化疗治疗妇科恶性肿瘤疗效好,血清肿瘤相关物质群可作为观察妇科恶性肿瘤热化疗疗效及预后的重要指标之一。     

调强适形放射治疗复发性妇科恶性肿瘤临床观察

目的探讨调强适形放射治疗复发性妇科恶性肿瘤的临床治疗效果。方法回顾性分析安阳市肿瘤医院收治的48例复发性妇科恶性肿瘤患者的临床资料,在治疗的过程中对48例患者使用调强适形放射治疗,在治疗之后对患者病情进行评分,对其治疗效果进行统计学分析。结果本组48例患者均完成全程放射治疗。在治疗结束之后,完全缓解17例,部分缓解26例,好转5例,近期总缓解率为92.3%。18例患者出现Ⅰ～Ⅱ级消化道反应,19例出现Ⅰ～Ⅱ度骨髓抑制,8例出现Ⅰ级皮肤反应。结论调强适形放射治疗复发性妇科恶性肿瘤可以有效控制患者病情,患者的治疗效果优良,其可以有效提高患者的生存率,值得在临床治疗中进行推广使用。     

异环磷酰胺、足叶乙甙、顺铂联合方案在妇科恶性肿瘤中的临床应用

<正>妇科恶性肿瘤多采用手术、化疗、放疗为主的综合治疗,对部分晚期肿瘤治疗后复发耐药的患者,再次治疗比较困难[1]。本研究采用IEP方案[异环磷酰胺(IFO)+足叶乙甙(Vp-16)+顺铂(DDP)]治疗耐药性妇科肿瘤患者36例,疗效确切,现报告如下。     

妇科肿瘤术后并发下肢深静脉血栓21例

目的探讨妇科肿瘤术后患者下肢深静脉血栓形成（DVT）的原因及预防措施。方法对21例妇科肿瘤术后DVT患者的原因、临床特点以及诊断、治疗和预防方法进行回顾性分析。结果发生DVT的高危因素是盆腔恶性肿瘤,老年妇女,合并高血压病、糖尿病,输血,术后应用止血药物等,治疗采用低分子右旋糖酐、肝素、尿激酶等,取得满意效果。结论对有DVT高危因素的妇科肿瘤患者,手术前后应加强预防措施,抗凝、祛聚、溶栓治疗,对DVT有较好疗效。     

中晚期恶性肿瘤介入治疗39例临床观察

目的 探讨妇科中晚期恶性肿瘤介入治疗的临床疗效。方法 39例妇科中晚期恶性肿瘤患者采用Selding’s穿刺法经股动脉穿刺，行髂内动脉、子宫动脉灌注化疗。1—3个疗程。其中灌注化疗后行髂内动脉栓塞11例、子宫动脉栓塞19例、肠系膜下动脉栓塞1例、肝固有动脉灌注化疗并栓塞1例；22例介入治疗后进行手术。结果 介入治疗后完全缓解和部分缓解33例，占84．6％。其中2例术后无癌细胞存在。介入治疗后1例出现较严重的腹痛，1例发热，对症治疗后缓解，余未发现严重并发症。结论 妇科恶性肿瘤采用介入治疗对缓解症状、抑制肿瘤生长、手术前降低肿瘤分期效果确切，可作为妇科肿瘤综合治疗的一种辅助方法。     

国产PD-1抑制剂在妇科肿瘤中的研究现状

妇科肿瘤是威胁女性生命的恶性疾病,其中最常见的是宫颈癌、卵巢癌和子宫内膜癌,其发病率逐年上升。妇科肿瘤治疗的基础是手术、放疗和化疗的联合治疗,但综合治疗后仍有患者因耐药或复发而死亡。目前PD-1/PD-L1免疫抑制剂应用于妇科恶性肿瘤已初见成效,有望成为未来最有潜力攻克妇科恶性肿瘤的药物。本文主要对当前国产PD-1免疫治疗在妇科肿瘤中的临床研究结果作一综述,以期概括国内妇科肿瘤免疫治疗思路,寻找合适的免疫治疗策略,延长晚期患者的生存期。     

Musashi-1在妇科恶性肿瘤发生发展中的作用

妇科恶性肿瘤严重威胁女性健康,尽管目前治疗策略相对有效,但复发及耐药仍是影响整体生存率的重要因素。研究表明肿瘤的复发及耐药与具有自我更新、无限增殖、多向分化潜能及高致瘤性的肿瘤干细胞(cancer stem cells,CSCs)亚群密切相关。Musashi-1是一种最新研究报道的CSCs标志物,多数研究认为其通过Notch、Wnt等信号通路发挥作用,在多种肿瘤组织中异常表达,在妇科恶性肿瘤中高表达,且与肿瘤的分期、分化、血管浸润及化学药物治疗耐药等密切相关。深入研究其在妇科恶性肿瘤中的作用机制,可为妇科恶性肿瘤的临床治疗提供新思路。现就Musashi-1在妇科恶性肿瘤中的表达情况及作用机制进行综述。     

Research progress and clinical application of predictive biomarker for immune checkpoint inhibitors

Introduction: Immune checkpoint inhibitors (ICIs) have emerged as epochal milestones in the ?eld of anti-cancer immunotherapy. With promising clinical effectiveness, ICIs can significantly prolong the overall survival of patients with advanced cancer of different types. Although their remarkable effectiveness has been demonstrated in clinical application, ICIs display limitations in terms of unique response patterns. Only a subset of patients exhibits objective responses, while others show rapid disease progression. Considering that there is a fair representation of both subsets of patients (responders and non-responders), clinicians ought to effectively stratify patients who will potentially benefit from ICI therapy, and optimize a strategy for patient selection.

Areas covered: In this review, the authors have summarized several key factors involved in the biomarker development of ICI therapy, such as neoantigen production and presentation, the tumor microenvironment, and alternation in specific gene signaling pathways.

Expert opinion: Considering the extreme complexity of the immune system, a single biomarker may fail to appropriately stratify patients for ICI therapy. Therefore, future biomarker research should focus on designing an integrated biomarker system that will successfully guide combination therapies to overcome resistance to immunotherapy.     

Oncologic treatment of pancreatic cancer

The management of patients who have unresectable or recurrent pancreatic adenocarcinoma represents a challenge to the practicing oncologist. Complications such as biliary or gastrointestinal obstruction, pain, and malnutrition must be controlled if there is to be a prospect of meaningful clinical benefit from presently available nonsurgical treatment. Although some reports have suggested favorable objective tumor response rates after combination chemotherapy, there has been no evidence from controlled clinical trials that the survival rates exceed those associated with single-agent therapy. Combined radiation therapy plus 5-fluorouracil has been shown to extend longevity in patients with locally unresectable pancreatic cancer, compared with radiation alone. Newer radiation therapy techniques, such as intraoperative electron-beam radiation therapy and the use of radiation sensitizers, are currently under investigation for patients with locally unresectable disease.     

Pertuzumab: evolving therapeutic strategies in the management of HER2-overexpressing breast cancer

Colorectal cancer is an important public health problem worldwide. Gene therapy has therapeutic potential for patients with advanced or recurrent colorectal cancer, incurable by conventional treatments. To date, many strategies of gene therapy have been explored, including mutant gene correction, prodrug activation, immune stimulation and genetically-modified oncolytic viruses. Although the preclinical results of gene therapy for colorectal cancer have shown promise, gene therapy is still at an early stage of clinical development and has not yet shown a significant therapeutic benefit for patients. The main obstacles for introduction of gene therapy to patients are poor targeting selectivity of the vectors and inefficient gene transfer. As the science supporting tumour-selective vectors evolves, gene therapy may expand rapidly in the clinical practice of colorectal cancer treatment.     

Gene therapy for colorectal cancer

Colorectal cancer is an important public health problem worldwide. Gene therapy has therapeutic potential for patients with advanced or recurrent colorectal cancer, incurable by conventional treatments. To date, many strategies of gene therapy have been explored, including mutant gene correction, prodrug activation, immune stimulation and genetically-modified oncolytic viruses. Although the preclinical results of gene therapy for colorectal cancer have shown promise, gene therapy is still at an early stage of clinical development and has not yet shown a significant therapeutic benefit for patients. The main obstacles for introduction of gene therapy to patients are poor targeting selectivity of the vectors and inefficient gene transfer. As the science supporting tumour-selective vectors evolves, gene therapy may expand rapidly in the clinical practice of colorectal cancer treatment.     

Research status on immunotherapy trials of gastric cancer

The breakthrough of immune checkpoint inhibitor (ICI) therapy has created extensive opportunities for cancer immunotherapy. Especially, the block of programmed death-1/programmed death ligand 1 (PD-L1) axis using ICIs has become a new therapeutic strategy to treat advanced gastric cancer (GC). However, in the past decade, single-arm and randomized trials for single-drug ICI therapy showed that the therapeutic effect was not satisfactory, including clinical trials for advanced GC. However, after selecting suitable predictive biomarkers and developing a combination of anti-angiogenic targeted drugs and other chemotherapeutic drugs, the objective response rate and progression-free survival of patients with gastric cancer were improved significantly. The United States Food and Drug Administration has approved treatment with pembrolizumab for patients with advanced GC with PD-L1 expression or microsatellite instability-high/mismatch repair deficiency. In this review, the updated data from the latest trial results of combination immunotherapy for GC are presented. Based on the outcome of combination therapy, we discuss its possible molecular mechanism and summarize effective predictive biomarkers. We also discuss possible problems stemming from results of other clinical trials of ICI treatment and propose other directions for ICI therapy.     

Technology evaluation: Theratope, Biomira Inc

Active specific immunotherapy, the use of 'vaccines' to stimulate therapeutic tumor antigen-specific immune responses, holds promise as a complementary approach to chemotherapy, radiation and surgery for the treatment of patients with cancers that have a high risk of relapse or progressive disease. Important components of an agent used for active immunotherapy are immunogens in the form of tumor-associated antigen(s) and an adjuvant or carrier molecule to promote presentation of the antigen to the immune effector cells. Possible antigens include tumor-expressed proteins or carbohydrate structures such as the glycoprotein mucin and its epitopes. The Theratope vaccine, consisting of a synthetic mimic of the mucin-associated glycan epitope STn conjugated to the carrier molecule keyhole limpet hemocyanin, has been developed for immunizing patients with mucin-expressing tumors. In murine and human studies, the vaccine has been shown to stimulate anti-STn antibodies and mucin-specific T-cell responses. The immune response is augmented by pretreatment with intravenous cyclophosphamide that serves to inhibit suppressor T-cells. Phase II studies suggested a survival benefit for breast cancer patients who received the Theratope vaccine after intravenous cyclophosphamide. A multinational phase III study testing the Theratope vaccine in patients with metastatic breast cancer who have had a clinical response or stability of disease is ongoing. Other malignancies for which the vaccine may be applicable include ovarian and gastrointestinal cancers.     

Toripalimab in an advanced non-small cell lung cancer patient with poor general condition after multiline treatment: a case report

Several clinical trials have proven that immunotherapy can improve survival and benefit non-small cell lung cancer (NSCLC) patients. In patients who progress after chemotherapy, immune checkpoint inhibitor (ICI) monotherapy can prolong overall survival compared with patients receiving single-agent chemotherapy. A 61-year-old man diagnosed with advanced NSCLC and without driver variants received first-line chemotherapy but experienced recurrence. During subsequent treatment, the disease progressed rapidly, and his general condition deteriorated; therefore, toripalimab monotherapy was initiated. Surprisingly, he responded well, and symptoms were relieved after several treatment cycles despite pseudoprogression, shown in chest images. For driver gene-negative NSCLC patients who progress after chemotherapy and who develop poor performance status (PS), ICIs are an option to alleviate symptoms and improve survival. Furthermore, immunotherapy in patients with pseudoprogression may also provide a survival benefit.     

Ipilimumab in the treatment of melanoma

INTRODUCTION: Recent advances in the understanding of the complex cellular mechanisms regulating cancer immunity have led to new strategies in the development of cancer immunotherapy. Targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), a key negative regulator of immune activity, with the monoclonal antibody ipilimumab has shown promising clinical benefit in patients with advanced or metastatic melanoma. AREAS COVERED: This review illustrates the pharmacology of ipilimumab and highlights the clinical evidence regarding its efficacy and safety in patients with advanced or metastatic melanoma. The unique clinical response pattern and class-specific immune-related toxicity profile associated with this biologic agent are also characterized. A literature search using PubMed database was undertaken using search words ipilimumab, anti-cytotoxic T-lymphocyte-associated antigen 4, melanoma and tumor immunity barrier. EXPERT OPINION: Ipilimumab, approved by the FDA for patients with advanced or metastatic melanoma based on the overall survival benefit when compared with a peptide vaccine, is a major breakthrough in the treatment of melanoma. While clinicians are embracing this innovative biologic agent, special attentions in patient selection, class-specific immune-related toxicities and their management as well as treatment response evaluation are needed.     

Locally recurrent rectal cancer: what the radiologist should know

Despite advances in surgical techniques and chemoradiation therapy, recurrent rectal cancer remains a cause of morbidity and mortality. After successful treatment of rectal cancer, patients are typically enrolled in a surveillance strategy that includes imaging as studies have shown improved prognosis when recurrent rectal cancer is detected during imaging surveillance versus based on development of symptoms. Additionally, patients who experience a complete clinical response with chemoradiation therapy may elect to enroll in a “watch-and-wait” strategy that includes imaging surveillance rather than surgical resection. Factors that increase the likelihood of recurrence, patterns of recurrence, and the imaging appearances of recurrent rectal cancer are reviewed with a focus on CT, PET CT, and MR imaging.