高级别胶质瘤放射及化学治疗后假性进展

目的 探讨高级别胶质瘤患者放射、化学治疗后假性进展的临床特点、诊断与处理.方法 分析2008年6月-2009年6月接受综合治疗的31例高级别胶质瘤患者临床资料,对假性进展的患者进行回顾分析,按照实体瘤疗效评判标准应用磁共振进行疗效评价.结果 31例术后病理诊断为高级别胶质瘤的患者,替莫唑胺(TMZ)同期放射、化学治疗后...     

晚期肺癌免疫治疗现状及影像学疗效评价和预测

免疫治疗是近年新兴的治疗手段,为部分传统治疗疗效不佳的肿瘤患者提供新的治疗思路,已成为部分晚期肺癌患者的一线治疗方案。目前,实体瘤疗效评价标准(response evaluation criteria in solid tumors, RECIST)仍是实体瘤疗效评价的主流标准。但免疫治疗因其治疗反应的特殊性,传统RECIST评估不能及时准确评价肿瘤治疗疗效。而影像学成像已进入功能化成像新时代,可提供微观分子及代谢改变信息。人工智能与放射影像组学通过挖掘图像背后更多的数学规律,可提供更多具有诊断价值的信息,有望为肺癌免疫治疗的疗效评价与预测提供新方法和新思路。本文就晚期肺癌免疫治疗的机制、现状及评价标准作一综述,重点分析影像学疗效评价与预测,并对其作出展望。     

基于增强CT影像组学特征预测难治性恶性黑色素瘤肺转移患者的免疫治疗疗效

目的 探讨基于胸部增强CT影像组学特征预测免疫治疗用于难治性恶性黑色素瘤肺转移疗效的价值.方法 回顾性分析49例难治性恶性黑色素瘤肺内转移患者,均接受程序性死亡受体(PD-1)单抗免疫治疗,采用实体瘤疗效评价标准(RECIST)1.1评价疗效,并将患者分为进展组(n=17)和未进展组[n= 32,包括稳定组(n=16)...     

RECIST 1.1与Choi标准在舒尼替尼治疗胃肠胰神经内分泌肿瘤早期疗效评估的比较

目的比较实体瘤疗效评价标准(response evaluation criteria in solid tumors version 1.1,RECIST 1.1)和Choi标准评估舒尼替尼对晚期胃肠胰神经内分泌肿瘤(gastroenteropancreatic neuroendocrine neoplasms,GEP-NENs)的早期疗效。方法18例使用舒尼替尼治疗的晚期GEP-NENs患者。所有患者治疗前后均行CT检查。测量治疗前及治疗后2~3个月肿瘤大小及密度变化并根据两种评价标准分别评估肿瘤的早期应答。记录肿瘤进展时间(TTP)并用Kaplan Meier法比较各组间的TTP。结果 18例患者中,使用RECIST 1.1标准评价早期疗效时,4例(22%)为部分缓解(PR),9例(50%)为疾病稳定(SD),和5例(28%)出现疾病进展(PD),PR、SD和PD组的中位TTP分别为16.6、10.8和2.3个月。根据Choi标准,8例(44%)为PR,4例(22%)为SD,6例(33%)为PD,PR、SD和PD组的中位TTP分别为未达到10.8和2.3个月。根据RECIST 1.1标准,PR和PD组、SD和PD组的TTP有显著差异(分别为P=0.007和P0.001),但PR和SD组的TTP差异不具有统计学意义(P=0.131)。根据Choi标准,PR组的TTP较SD组和PD组长,且差异具有统计学意义(P=0.026和P0.001),SD组的TTP显著长于PD组(P=0.006)。结论评估舒尼替尼对GEP-NENs的早期疗效时,使用Choi标准能够较RECIST 1.1标准识别出更多的缓解病例,且Choi标准的分组TTP具有统计学差异,较RECIST 1.1标准得到更为客观的评效结果。     

结直肠癌肝转移TACE后疗效评价的RECIST和mRECIST对比研究

目的比较实体瘤疗效价标准(RECIST)和改良实体瘤疗效评价标准(mRECIST),为结直肠癌肝脏转移瘤经肝动脉化疗栓塞治疗找到更为合适的疗效评价方法。方法 30例确诊为结直肠癌肝转移接受两次经肝动脉化疗栓塞术(TACE)。术前1周内、治疗后4周患者接受CT或MR三期扫描。根据RECIST和mRECIST标准评价肿瘤缓解程度。两种方法评价结果的比较采用卡方检验。结果据RECIST和mRECIST标准分别评价疗效,达完全缓解、部分缓解、稳定、进展患者例数分别为0、6、17、7例,0、14、9、7例;据两种标准评价治疗的缓解率分别为20.0%和46.7%,差异有统计学意义(P=0.028)。结论 RECIST标准与mRECIST标准相比,低估了结直肠癌肝转移瘤TACE后治疗效果,由于mRECIST标准在测量时强调避开肿瘤液化坏死区域和碘油沉积区域只测量动脉期存活肿瘤,故而对疗效的评价更加准确。     

脑胶质瘤治疗后假性进展与复发的影像学鉴别研究进展

脑胶质瘤源自于神经上皮细胞,是颅内最常见的原发性肿瘤,其治疗方案为手术切除及后续的同步放化疗,但多达30%的患者会出现新的磁共振成像内的强化病变,这可能不是早期肿瘤进展(early progression,EP),而是放化疗导致的假性进展(pseudo-progression,PSP)。假性进展由于病变较轻且预后较好,只需对其进行对症治疗,而肿瘤复发时临床医生对其处理方式与假性进展不同,复发可能要选择再次手术或者使用放化疗等其他治疗方式,因此,如果胶质瘤的假性进展与复发被误诊,患者的最佳治疗时机将会受到耽误。常规磁共振成像不可能可靠地区分PSP和EP,目前一些更先进的成像方法有望对其进行准确鉴别。     

MRI在乳腺癌脑转移疗效评价中的应用

目的 探讨MRI在乳腺癌脑转移疗效评价中的价值,以合理选择检查方法.方法 选择明确诊断的乳腺癌脑转移瘤患者65例,在放疗前和放疗后1月行头颅MRI常规平扫及增强(T1WI、FLAIR),采用实体瘤疗效评价标准(RECIST) 1.1版作为评价脑转移肿瘤放疗疗效的标准.结果 65例患者放疗后,头颅MRI平扫及增强复查,以RECIST1.1评价结果显示,完全缓解8例(12.3％),部分缓解37例(56.9％),稳定16例(24.6％),进展4例(6.2％).放疗前后平扫FLAIR序列中瘤周水肿显示较佳;DWI序列中瘤周水肿与脑室及脑沟脑积液无明显交通者,瘤周水肿显示较佳;增强T1WI、FLAIR序列中肿瘤大小和瘤周水肿显示较佳.结论 MRI可从多个体位评价病灶,同时可从平扫FLAIR、DWI和增强T1WI、FLAIR序列进行综合疗效评价.     

能谱CT对晚期肺癌非手术治疗的疗效评价研究进展

近年来肺癌是发病率和死亡率最高的恶性肿瘤之一,由于早期症状不明显,很多病人就诊时已进入晚期,失去了最佳手术机会。随着医学技术的发展,晚期肺癌的非手术治疗方式也取得了一些进步。例如传统的放疗化疗、分子靶向治疗及免疫治疗等逐步应用于临床,其疗效评价是依据实体瘤疗效评价标准来判定的。多种影像学技术可应用于评估实体瘤疗效,其中能谱CT成像的基物质图像,在肺癌的疗效评价中能提供更多的功能学信息。本文就能谱CT在晚期肺癌的疗效评价中的应用价值进行综述。     

树突状细胞瘤苗抗肿瘤临床应用进展

树突状细胞(DC)是目前功能最强的抗原提呈细胞,在机体抗肿瘤免疫中发挥重要作用。近年来,DC瘤苗抗肿瘤临床应用取得较大进展,现对DC瘤苗的制备及其在肿瘤免疫治疗中的临床应用以及存在问题作一综述。     

常规超声与动态增强MRI预测乳腺癌新辅助化疗疗效的应用研究

目的 探讨常规超声及MRI在评估乳腺癌新辅助化疗(neoadjuvant chemotherapy,NAC)疗效中的临床价值.方法 依据《实体瘤疗效评估标准》(RECIST)常规超声及MRI监测乳腺癌NAC前后肿瘤最大径变化.结果 超声与MRI评价病理完全缓解特异性均为94.3％、敏感性分别为52.5％和47.6％、准确性分别为46.7％和41.9％.结论 超声与MRI依据RECIST在乳腺癌新辅助化疗疗效临床实践中具有一定的局限性.     

Rapid subcutaneous progression after immunotherapy in pretreated patients with metastatic carcinoma: two case reports

There is heterogeneity in cancer patients’ responses to immune checkpoint inhibitors (ICIs), including hyperprogression, which is very rapid tumor progression following immunotherapy, and pseudoprogression, which is an initial increase followed by a decrease in tumor burden or in the number of tumor lesions. This heterogeneity complicates clinical decisions because either premature withdrawal of the treatment or prolonged ineffective treatment harms patients. We presented two patients treated with ICIs with heterogeneous responses. One patient had Merkel cell carcinoma in the right thigh, and the other had nasopharyngeal squamous carcinoma. The first patient was treated with sintilimab and the second with sintilimab combined with abraxane. In the first patient, subcutaneous lesions grew substantially after the first cycle of treatment with sintilimab. In the second patient, subcutaneous lesions grew gradually after the second cycle of treatment with sintilimab combined with abraxane. In both cases, biopsy examination confirmed that newly emerged lesions were metastases of the primary tumor. These two cases remind clinicians that when subcutaneous nodules appear after treatment with ICIs, pathological biopsy is needed to determine the nature—pseudoprogression or rapid progression—of the disease course.     

B-cell depletion using an anti-CD20 antibody augments antitumor immune responses and immunotherapy in nonhematopoetic murine tumor models

The role played by B cells in cancer biology is complex and somewhat controversial. Previous studies using genetically engineered mice suggest that B cells may be immunosuppressive and inhibit tumor rejection. However, the effects of B-cell depletion employing an antibody in mice bearing solid tumors has not been tested owing to difficulties in making an effective antimouse CD20 antibody (similar to rituximab). Injection of a newly developed antimouse CD20 antibody was effective in depleting circulating B cells from blood and lymph nodes, although depletion was less complete in the spleen. B-cell depletion slowed the growth of new solid tumors (not expressing CD20) and retarded the growth of established tumors but did not induce tumor regression. However, when the antibody was combined with an active immunotherapy approach using an adenovirus vaccine expressing the human papilloma virus-E7 gene (Ad.E7) in mice bearing TC1 tumors (murine lung cancer cells expressing human papilloma virus-E7), we noted enhanced antitumor effects and increased numbers of tetramer+/CD8+ T cells within the spleens and activated CD8+ T cells within tumors. B-cell depletion using an anti-CD20 antibody was thus effective in retarding tumor growth in multiple solid tumor models and augmenting immunotherapy in a tumor vaccine model. These studies raise the possibility that B-cell depletion may be a useful adjunct in human immunotherapy trials.     

Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors

Treatment of advanced, poorly immunogenic tumors in animal models, considered the closest simulation available thus far for conditions observed in cancer patients, remains a major challenge for cancer immunotherapy. We reported previously that established tumors in mice receiving an agonistic mAb to the T cell costimulatory molecule 4-1BB (CD137) regress due to enhanced tumor antigen-specific cytotoxic T lymphocyte responses. In this study, we demonstrate that several poorly immunogenic tumors, including C3 tumor, TC-1 lung carcinoma, and B16-F10 melanoma, once established as solid tumors or metastases, are refractory to treatment by anti-4-1BB mAb. We provide evidence that immunological ignorance, rather than anergy or deletion, of tumor antigen--specific CTLs during the progressive growth of tumors prevents costimulation by anti-4-1BB mAb. Breaking CTL ignorance by immunization with a tumor antigen-derived peptide, although insufficient to stimulate a curative CTL response, is necessary for anti--4-1BB mAb to induce a CTL response leading to the regression of established tumors. Our results suggest a new approach for immunotherapy of human cancers.     

Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice.

The salient feature of solid tumor growth is the strict dependence on local angiogenesis. We have previously demonstrated that IL-8 is an angiogenic factor present in freshly isolated specimens of human non-small cell lung cancer (NSCLC). Using a model of human NSCLC tumorigenesis in SCID mice, we now report that IL-8 acts as a promoter of human NSCLC tumor growth through its angiogenic properties. Passive immunization with neutralizing antibodies to IL-8 resulted in more than 40% reduction in tumor size and was associated with a decline in tumor-associated vascular density and angiogenic activity. IL-8 did not act as an autocrine growth factor for NSCLC proliferation. The reduction in primary tumor size in response to neutralizing antibodies to IL-8 was also accompanied by a trend toward a decrease in spontaneous metastasis to the lung. These data support the notion that IL-8 plays a significant role in mediating angiogenic activity during tumorigenesis of human NSCLC, thereby offering a potential target for immunotherapy against solid tumors.     

Cellular therapy for the treatment of solid tumors

Adoptive cellular therapy (ACT) is a form of cancer immunotherapy in which lymphocytes are removed from patient blood or tumor samples, expanded and/or genetically modified to improve tumor-fighting capabilities, and infused back into the patient. The main forms of ACT include tumor infiltrating lymphocytes (TILs), engineered T cell receptor (TCR) T cells, and chimeric antigen receptor (CAR) T cells. While ACT has had success in hematological malignancies, particularly in B cell lymphomas targeted with CAR T cells, these favorable outcomes have yet to be replicated in solid tumors. Appropriate solid tumor target antigens are difficult to identify for ACT. Trafficking to tumor sites and infiltrating solid tumor burdens remains a problem for ACT cells. Persistence of ACT cells, which is important in creating a durable response, is also a major challenge, partly attributed to the formidable microtumor environment conditions. The costly and time-intensive manufacturing process for ACT is also an obstacle to widespread adoption. In this review, we discuss the challenges of ACT therapy in the treatment of solid tumors and explore the ongoing efforts to improve this immunotherapy approach in non-hematological malignancies.     

Allogeneic hematopoietic stem cell transplantation for solid tumors in the United States: a review

The field of bone marrow transplantation has undergone dramatic changes over the past few decades. Not only has the terminology changed (e.g., hematopoietic stem-cell transplantation), but the role of allogeneic transplantation has been modified from supportive to immunotherapeutic and the applications have expanded from hematologic malignancies to solid tumors. The development of nonmyeloablative conditioning regimen has greatly increased the number of patients eligible for this kind of treatment. Use of hematopoietic stem-cell transplantation as a form of adoptive immunotherapy in the treatment of cancer depends on advances in tumor immunology, particularly the identification of tumor antigens and mechanisms of immunotherapy. The earliest use of allogeneic transplantation of immunogenic cells for the treatment of solid tumors in the late 1960s and early 1970s produced no definite graft-versus-tumor effects. However, as conventional allogeneic hematopoietic stem-cell transplantation methods for the treatment of hematologic malignancies have matured, these methods have reestablished the foundation for expanding their application to solid tumors. From the first case reports on medulloblastoma and breast cancer to subsequent case series reports on breast cancer and renal cell carcinoma, allogeneic hematopoietic stem-cell transplants have demonstrated graft-versus-tumor effect. At present, the most common solid tumor for which this treatment is used is advanced renal cell carcinoma, but allogeneic hematopoietic stem-cell transplants have proven feasible for other solid tumors as well. Directions for future study include the identification of the definitive tumor antigens involved in the graft-versus-tumor effect and means of selecting those patients who will benefit the most from this form of treatment. This review summarizes the peer-reviewed literature on the use of allogeneic transplantation for solid tumors based on US studies.     

Novel angiogenesis inhibitors for molecular target therapy of cancer

Angiogenesis, neovascularization from pre-existing vasculature, is essential to allow growth of primary solid tumors and to enable metastasis. Recent biological studies in both tumor and endothelial cells have begun to present a wide variety of molecular targets for developing angiogenesis inhibitors. Therefore, angiogenesis inhibitors including anti-angiogenic agents as well as anti-vascular targeting agents have become promising drugs in cancer chemotherapy. However current unsolved problems in anti-angiogenic therapy are the lack of surrogate markers for therapeutic efficacy, as well as of establishment of effective combinations with other therapeutic approaches including conventional anticancer therapy, radiotherapy, and immunotherapy. This article focuses on the promising drugs with anti-angiogenic activity and their molecular targets under clinical trials, as well as the significance of clinical evaluation for anti-angiogenic therapies.     

Cytokine induced killer cells as adoptive immunotherapy strategy to augment graft versus tumor after hematopoietic cell transplantation

Donor lymphocyte infusion (DLI) is used to increase the graft versus tumor (GVT) effect after allogeneic hematopoietic cell transplant (HCT). The limited spectrum of activity and high risk of graft versus host disease (GVHD) remain major limitations of this approach. The finding of new cell populations for adoptive immunotherapy, with the ability to separate GVT from GVHD, would be useful. Here we review the main basic, preclinical and clinical research on cytokine-induced killer (CIK) cells, highlighting the aspects of their antitumor and alloreactive potentials that might favourably affect the balance between GVT and GVHD. CIK cells are ex vivo-expanded T lymphocytes sharing NK markers and endowed with a potent MHC-unrestricted antitumor activity against haematological and solid malignancies. Studies in preclinical animal models have demonstrated their low GVHD potential when infused across MHC-barriers, and recent clinical studies seem to confirm these findings in patients with hematological malignances relapsing after HCT. If consolidated with larger clinical trials, adoptive immunotherapy with CIK cells might represent an effective alternative to classic DLI, helping HCT to succesfully meet current challenges like the extension across major HLA-barriers and application to solid tumors.