Randomized phase II study of sunitinib versus standard of care for patients with previously treated advanced triple-negative breast cancer

PurposeThis randomized, open-label phase II study compared the efficacy of sunitinib monotherapy with that of single-agent standard-of-care (SOC) chemotherapy in patients with previously treated advanced triple-negative breast cancer (TNBC).MethodsPatients with advanced TNBC, relapsed after anthracycline- and taxane-based chemotherapy, were randomized to receive either sunitinib (37.5 mg/day) or the investigator's choice of SOC therapy. Progression-free survival was the primary endpoint.ResultsMedian progression-free survival was 2.0 months with sunitinib and 2.7 months with SOC chemotherapy (one-sided P = 0.888). Median overall survival was not prolonged with sunitinib (9.4 months) compared with SOC chemotherapy (10.5 months; one-sided P = 0.839). The objective response rate was 3% with sunitinib and 7% with SOC chemotherapy (one-sided P = 0.962).ConclusionsSunitinib monotherapy did not improve efficacy compared with SOC chemotherapy in patients with previously treated advanced TNBC, for which identification of effective treatments and therapeutic targets remains an urgent need.Trial registrationNCT00246571.     

Purely subcortical tumors in eloquent areas: Awake surgery and cortical and subcortical electrical stimulation (CSES) ensure safe and effective surgery

Objective

To analyze the efficacy and safety of cortical and subcortical electrical stimulation CSES and awake surgery to approach purely subcortical tumors in highly functional locations, particularly in guiding the choice of the best transcortical path.

Patients and methods

Prospective analysis of the surgical, neurological, and radiological outcome of patients harboring supratentorial, subcortically located brain tumors or vascular malformations who are operated on through awake surgery and CSES. Functional magnetic resonance (fMRI; either sensory-motor or language, based on the location) was performed in order to confirm the proximity to functional cortical areas. Major white matter tracts were investigated by MRI diffusion tensor fiber tracking (DTI-ft). The Rankin modified score was chosen to express the pre and postoperative functional neurological status. Immediate postoperative MRI was used to evaluate the extent of resection.

Results

Seventeen patients were selected. The main distance of the tumors from the cortical surface was 18.2 mm (range 9–48 mm). Neuronavigation was used to show the most direct route to the tumor (transsulcal or transgyral), but CSES was fundamental to adapt the surgical corridor to the functional topography both cortically and subcortically. If the transgyral route was chosen, CSES helped to detect a non-eloquent area. When a transsulcal route was preferred, CSES documented the presence or absence of function in the deep sulcus. The transient postoperative morbidity was 76.4%, but at last follow-up (range 4–20 months), all the patients regained preoperative status and 2 improved. Postoperative MRI demonstrated complete resection in all cases.

Conclusions

Approaching purely subcortical tumors requires microsurgical skills, but in eloquent areas, functional topography monitoring is mandatory to allow safe surgery. CSES in an awake patient is a method that produces very good results in terms of resection and neurological outcome.     

Bridging Hepatocellular Carcinoma to Transplant: Transarterial Chemoembolization Response,Tumor Biology,and Recurrence after Transplantation in a 12-Year Transplant Cohort

PurposeTo evaluate tumor response to transarterial chemoembolization as well as biologic characteristics of the tumor as predictors of recurrence after transplantation in patients with hepatocellular carcinoma (HCC) who were bridged or down-staged to liver transplantation.Materials and MethodsAn institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, single-institution retrospective analysis was performed on all patients with HCC who were treated with the use of conventional transarterial chemoembolization or transarterial chemoembolization with drug-eluting embolics (DEE) over a 12-year period and who subsequently underwent liver transplantation (n = 142). Treatment response was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) imaging criteria and then correlated with tumor characteristics and recurrence. Of the 142 patients followed after transplantation, 127 had imaging after transarterial chemoembolization but before transplantation. Imaging response and post-transplantation recurrence were correlated with patient demographics, liver function, and tumor morphology. HCC recurred in 9 patients (mean time from transplantation, 526 days). Recurrence was analyzed with the use of univariate and multivariate statistics. Kaplan-Meier recurrence-free survival curves were calculated based on immediate imaging response before transplantation with the use of the log-rank test.ResultsBefore transplantation, 57% of patients (72/127) demonstrated complete response (CR) and 24% (31/127) showed partial response (PR). Complete pathologic necrosis occurred in 54% (39/72) of CR patients and 20% (6/31) of PR patients. Poor treatment response, defined as stable disease (SD) or progressive disease (PD), occurred in 18% of patients (24/127) before transplantation and was present in 67% of cases of recurrence (6/9; P < .001). Post-transplantation recurrence was present in 1.4% of patients (1/71) with CR and in 6.5% of patients (2/31) with PR. In patients with SD after transarterial chemoembolization, HCC recurred in 18.8% of transplant patients (3/16) and in 43% of patients (3/7) with PD. Larger pretreatment tumor size (P = .05), higher Child-Pugh score (P = .002), higher tumor grade at explantation (P = .04), and lymphovascular invasion at explantation (P = .008) also were associated with increased incidence of post-transplantation recurrence.ConclusionsPoor tumor response to transarterial chemoembolization before transplantation identifies patients at increased risk for post-transplantation recurrence.     

Yttrium-90 Transarterial Radioembolization for Chemotherapy-Refractory Intrahepatic Cholangiocarcinoma: A Prospective,Observational Study

PurposeTo evaluate the safety and efficacy of yttrium-90 transarterial radioembolization (TARE) for the treatment of unresectable, chemotherapy-refractory intrahepatic cholangiocarcinoma (ICC).MethodsA prospective, observational study was carried out in 10 centers between 2013 and 2017. TARE plus standard care was delivered to patients with unresectable, chemotherapy-refractory or chemotherapy-intolerant ICC. Primary outcome was overall survival. Secondary outcomes included safety, progression-free survival (PFS), and liver-specific progression-free survival (LPFS).ResultsSixty-one patients were treated with TARE. Patients were 53% male; median age was 64 years; 91% had performance status 0/1; 92% had received prior chemotherapy; and 59% had no extrahepatic disease. Median follow-up was 13.9 months (95% confidence interval [CI], 9.6–18.1). Overall survival was 8.7 months (95% CI, 5.3–12.1), and 37% of patients survived to 12 months. PFS was 2.8 months (95% CI, 2.6–3.1), and LPFS was 3.1 months (95% CI, 1.3–4.8). One severe complication (abdominal pain) occurred at the time of the TARE procedure. Thirty patients experienced a total of 49 adverse events, of which 8% were grade ≥3; most common were grade 1–2 fatigue and abdominal pain. A total of 77 abnormal laboratory value events were recorded, of which 4% were grade ≥3.ConclusionsPatients with advanced ICC have limited therapeutic options and a poor prognosis. This prospective study examined the survival of patients with unresectable, chemotherapy-refractory primary ICC treated with TARE in real-world practice. The results demonstrate that this treatment merits further investigation in this patient cohort in a larger study, including collection of patient-reported outcomes.     

泛素特异性肽酶22基因与肿瘤发展和预后的研究进展

泛素特异性肽酶22（ubiquitin—specificprocessingpeptidase22,USP22）是一种新型的去泛素化酶家族基因,是hSAGA复合物的亚单位。越来越多的实验研究结果证明泛素特异性肽酶22（USP22）是癌干细胞标记物中的一种,在肿瘤形成及发展的病理过程中扮演关键的角色,并与不良预后有着密切的关系。     

原发性小肠肿瘤44例临床分析

原发性小肠肿瘤非常少见，临床早期诊断困难。目的：探讨原发性小肠肿瘤的临床常见表现、诊断和治疗方法。方法：回顾性分析1990年1月-2007年1月北京友谊医院确诊的44例原发性小肠肿瘤患者的临床资料。结果：原发性小肠肿瘤患者男女比例为3：1。主要临床表现为柏油样便、腹部包块、腹痛和肠梗阻症状。原发性小肠肿瘤以空肠最为常见，良恶性比为1：3．4。44例原发性小肠肿瘤患者中，29例（65．9％）为间质瘤，其中良性6例，低度恶性7例，高度恶性16例；5例（11．4％）为非霍奇金淋巴瘤；4例（9．1％）为腺癌；3例（6．8％）为平滑肌瘤；1例（2_3％）为平滑肌肉瘤；1例（2．3％）为类癌；1例（2．3％）为绒毛管状腺瘤。所有患者均行手术治疗。结论：原发性小肠肿瘤临床表现无特异性，病理类型多样，结合常见临床表现和有效检查方法有助于尽早诊断该病。     

The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors

OBJECTIVE:

Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors.

METHODS:

A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody.

RESULTS:

Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis.

CONCLUSIONS:

The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2.     

无功能性胰腺神经内分泌肿瘤临床诊断与手术治疗的研究进展

胰腺神经内分泌肿瘤（pNEN）是一种罕见的异质性肿瘤,具有多种恶性潜能。随着横断面成像的广泛应用,无症状的无功能性胰腺神经内分泌肿瘤（NF-pNEN）被诊断的频率逐年升高,但仍存在临床确诊难度大,手术治疗不及时等诸多方面的不足。加深对NF-pNEN的认识有助于提高临床诊断率,进而采取及时有效的治疗。笔者就NF-pNEN在临床诊断与外科治疗中存在的争议问题进行综述,以期为临床提供参考。     

伊马替尼对胃肠间质瘤患者Foxp3+ Treg影响的研究进展

胃肠间质瘤(GIST)是胃肠道最常见的间叶源性肿瘤,多数GIST发病机制是c-Kit基因发生功能获得性突变,表达Kit蛋白并持续激活其下游信号通路使肿瘤细胞持续增殖。作为酪氨酸激酶抑制剂,伊马替尼在GIST中的应用使得靶向治疗成为手术治疗以外最为重要的治疗方式,已深刻影响了GIST的治疗模式。Foxp3~+Treg是体内重要的调节性T细胞,通过抑制CTL、NK细胞等肿瘤抑制细胞的功能,负向调节机体的抗肿瘤免疫反应。研究显示,伊马替尼不仅可通过靶向治疗机制,也可能通过抑制Foxp3~+Treg细胞而增强机体对肿瘤的免疫反应,从免疫途径发挥治疗GIST的作用。笔者就伊马替尼对GIST患者外周血中Foxp3~+Treg细胞及其亚群影响的相关研究作一综述。     

儿童第四脑室-小脑脚-脑干区肿瘤的手术治疗

目的 研究第四脑室-小脑脚-脑干区肿瘤的形态学特点，以及安全地切除此部位肿瘤的手术方法。方法 儿童（15岁以下）第四脑室-小脑脚-脑干区肿瘤（室管膜瘤和星形细胞瘤）23例。术前头颅MRI证实瘤体起源于小脑脚或侧隐窝，分别向第四脑室，脑干，CPA和斜坡生长。采用枕下正中外侧拐入路，术中分区域切除肿瘤，结果 全切除肿瘤12例，近全切除9例，大部切除2例，无手术死亡，术后病理证实室管膜瘤13例，恶性室管膜瘤2例，星形细胞瘤8例。结论 起源于小脑脚或侧隐窝的肿瘤，以脑干为中心呈半弧形生长，肿瘤侵袭范围包括第四脑室，小脑脚，脑干，CPA和斜坡，合适的手术入路和术中分区域切除肿瘤的技术，可以做到安全地全切除和/或近全切除肿瘤。