131I难治性分化型甲状腺癌分子靶向治疗进展

放射性碘难治性分化型甲状腺癌患者因病灶摄碘功能不佳而无法从131I等传统治疗方法中获益。近年来,甲状腺癌分子病理学研究新成果为甲状腺癌的分子诊断和靶向治疗提供了新的契机,相关分子靶向治疗的临床试验和荟萃分析均取得了可喜的结果。本文从临床角度对放射性碘难治性分化型甲状腺癌分子靶向治疗的最新进展进行综述。     

碘难治性分化型甲状腺癌靶向治疗新进展

近年来,靶向治疗为碘难治性分化型甲状腺癌带来了革命性的突破。新型靶向药物的研发,让更多晚期分化型甲状腺癌患者获得了更好的生存。以索拉非尼和仑伐替尼为代表的多靶点小分子酪氨酸激酶抑制剂显著提升了患者的无进展生存期。与此同时,靶向BRAF及靶向RET的新型酪氨酸激酶抑制剂同样也取得了瞩目的疗效,丰富了甲状腺癌的治疗手段。本文就靶向治疗在碘难治性分化型甲状腺癌中的最新研究进展进行综述。     

侵袭性纤维瘤的靶向治疗进展

侵袭性纤维瘤（aggressive fibromatosis,AF）,又称韧带样型纤维瘤病、韧带样肿瘤（desmoid tumor,DT）、肌肉腱膜纤维瘤病等。AF是一种介于良、恶性之间的肿瘤,虽然无包膜,局部浸润周围组织,可能是多灶性的,并且在术后易复发,但不易发生转移。目前,对于AF的治疗方法主要包括积极监测、手术、放疗、化疗、靶向治疗、内分泌与非甾体类药物治疗等。靶向治疗AF在过去的研究进展较为缓慢,疗效有限,因此通常被应用于其他常规治疗方法失败之后,作为补救治疗手段。但近年来随着靶向治疗基础研究的快速进展,一些新的靶向药物越来越多的用于AF的临床治疗,并且获得了较好的疗效。因此,如何预测这些靶向药物对AF治疗的疗效,其治疗机制又是如何,均是目前靶向治疗AF研究的热点。本文将就AF的靶向治疗新进展进行综述。      

难治性甲状腺癌靶向治疗Meta分析

目的 目前对于进展期甲状腺癌分子靶向治疗的研究多为单臂实验,RCT研究较少.本研究应用Meta分析方法,评价分子靶向治疗在难治性甲状腺癌中的疗效和安全性,以期为其应用提供理论基础.方法 检索纳入1989-01-2015-01 Medline、Web of science、Cochrane Central、EBSCO、Embase等英文数据库及中国学术期刊全文数据库、万方、维普等中文数据库中的文献.按照纳入与排除标准进行文献筛选和质量评价后,利用Cochrane中心提供的RevMan5.0软件对数据进行分析.主要评价指标是患者的无进展生存率及药物的不良反应.结果 共纳入4项随机对照试验研究,得到药物组总体样本730例,对照组(安慰剂组)总体样本493例.相比对照组,药物组6、12和18个月的无进展生存率均显著提高(6个月:RR=2.57,95％CI为1.97～3.35;12个月:RR=2.01,95％CI为1.53～2.65;18个月:RR=2.10,95％CI为1.54～2.87).药物组不良反应发生率高于对照组(RR=4.20,95％CI为2.82～6.24).主要是腹泻、疲劳、高血压、手足综合征和QT间期延长.结论 靶向药物可显著延长难治性甲状腺癌患者的无进展生存期.虽然其不良反应发生率显著高于对照组,但患者仍可耐受.靶向治疗为难治性甲状腺癌患者带来新的希望.     

甲状腺癌BRAF突变与分子靶向治疗

甲状腺癌是最常见的内分泌系统的恶性肿瘤,排女性第七位的恶性肿瘤,占全身恶性肿瘤的1%,男性占0.5%,女性占1.5%,近期的流行病学调查显示,在加拿大、美国、欧洲、中国和韩国,其发病率呈上升趋势[1]。甲状腺癌病理类型主要包括乳头状癌、滤泡状癌、髓样癌、未分化癌,乳头状癌和滤泡状癌属分化型甲状腺癌,     

精准医疗背景下进展期胃癌抗血管靶向治疗的现状与挑战

中国胃癌的发病率和病死率均居高不下,传统的手术和化疗等治疗手段对于晚期胃癌的疗效较差。针对HER-2 阳性胃癌的分子靶向治疗取得了一定成功,但由于胃癌患者中HER-2 阳性率极低,因此获益患者数量有限。胃癌的血管生成及其相关通路对胃癌的转移、复发起到了重要的促进作用。针对其关键分子的抗血管生成靶向治疗为提高晚期胃癌疗效提供了新的思路。目前抗血管生成靶向药物包括酪氨酸激酶抑制剂（tyrosine-kinase inhibitor,TKI）、单克隆抗体以及重组人血管内皮抑制素等几类,尽管一些TKI的疗效尚不尽如人意,但阿帕替尼和雷莫芦单抗等一系列临床研究表明,抗血管靶向治疗是改善晚期胃癌治疗新的希望。未来可通过二代测序技术探索新的分子靶点,并联合放疗、化疗和免疫治疗以及更为精准的个体化治疗进一步改善晚期胃癌抗血管靶向治疗的疗效。     

晚期甲状腺癌治疗的曙光——靶向和免疫治疗

近年来,甲状腺癌的发病率显著增加,大多数病例以分化型甲状腺癌为主,其特点是预后良好。然而,在初始治疗后仍有15%的患者出现疾病持续或复发,并且局部晚期或转移性癌症患者对既定治疗无效,最终有死亡的风险。国内外对于晚期甲状腺癌的治疗仍有争议,但都倾向于靶向和免疫治疗为主的综合治疗。随着对甲状腺癌分子发病机制的深入理解,临床上已批准了多种新的靶向治疗方法用于晚期甲状腺癌。中国临床肿瘤学会(CSCO)2021年指南和欧洲肿瘤内科学会(ESMO)2022年指南(更新)均将靶向治疗作为晚期甲状腺癌治疗的Ⅰ级推荐。本文将对晚期甲状腺癌临床治疗新进展作一综述。     

晚期胃肠间质瘤联合靶向药物治疗进展

胃肠间质瘤（gastrointestinal stromal tumors,GIST）是消化道最常见的间叶源性肿瘤,起源于Cajal间质细胞。所有的GIST均被认为具有一定程度的恶性潜能。KIT/血小板衍生生长因子受体α（platelet-derived growth factor receptor alpha,PDGFRA）基因突变导致的受体酪氨酸激酶编码蛋白异常激活,是目前已知GIST最主要的发病机制。酪氨酸酸激酶抑制剂（tyrosine kinase inhibitor,TKI）是治疗的主要选择,目前单药TKI序贯治疗是GIST的标准治疗方案,但一线治疗耐药以后,后线治疗的疗效有限。因此,针对不同靶点的药物联合治疗是目前重要的探索方向。在此,本文结合了近年来关于GIST联合靶向治疗的研究进展,包括两种TKI联合治疗、TKI与下游通路抑制剂联合治疗等,旨在对晚期GIST联合治疗的有效性及安全性进行全面的分析和讨论。     

肿瘤分子靶向治疗与生物化疗进展

肿瘤的生物化疗是指肿瘤生物治疗和化学治疗的联合。肿瘤生物化疗模式一经出现,即得到迅速发展,不仅为肿瘤治疗带来了全新的治疗方法,还为恶性肿瘤的治疗领域带来了全新的治疗理念。本文就生物化疗方案适应证的扩大、生物化疗独有的“无效不更方”、靶向治疗逆转化疗耐药、生物化疗的疗效预测、免疫治疗为基础的生物化疗的最新临床研究以及生物化疗的疗效评价等方面的新进展做一综述,以期管中窥豹。     

甲状腺癌的DNA甲基化研究进展

DNA甲基化是一种重要的表观遗传学改变,在肿瘤的发病、诊断、预后评估及治疗中都有重要的临床意义.甲状腺癌是临床最常见的内分泌系统恶性肿瘤,目前国内外关于甲状腺癌的DNA甲基化的研究相对较少,该文总结近年来甲状腺癌领域相关的基因甲基化研究,就甲状腺癌的DNA甲基化研究进展进行综述.     

晚期结直肠癌三药联合方案化疗的研究进展

化疗是晚期结直肠癌(colorectal cancer,CRC)的主要治疗手段.FOLFOXIRI三药联合方案(奥沙利铂+伊立替康+氟尿嘧啶)一线治疗晚期CRC较氟尿嘧啶单药或FOLFOX(奥沙利铂+氟尿嘧啶)、FOLFIRI(伊立替康+氟尿嘧啶)等两药联合方案可显著延长患者的无进展生存(progression fre...     

Chemotherapy and targeted therapy in the management of cervical cancer

Management of cervical cancer has undergone refinement in the past two decades; concurrent chemo-radiation (CCRT) (with cisplatin alone or in combination) is currently the standard treatment approach for patients with locally advanced disease (FIGO stage IIB-IVA). About 30%-40% of such patients fail to achieve complete response; alternative approaches are needed to improve outcome for them. Treatment with bevacizumab (an inhibitor of vascular endothelial growth factor) along with chemotherapy is associated with improved survival in patients with recurrent or metastatic cervical cancer. Weekly paclitaxel and carboplatin for 4-6 weeks as dose dense chemotherapy prior to CCRT is currently under study in a phase III, multicentric trial. Role of adjuvant chemotherapy after CCRT in patients with positive lymph nodes, larger tumor volume and those with stage III-IVA disease needs further exploration. Novel agents targeting molecular pathways are currently being studied. Recent development of immune check point inhibitors is exciting, results of ongoing studies are awaited with interest.     

碘难治性甲状腺癌的诊治进展

多数分化型甲状腺癌(differentiated thyroid cancer,DTC)经过规范的手术、选择性131I治疗及促甲状腺激素抑制治疗后预后良好,然而,仍有部分转移性DTC的患者在早期或131I治疗过程中失去了摄碘能力发展为碘难治性DTC(radioiodine-refractory DTC,RAIR-DTC)。RAIR-DTC病情进展快,死亡率高,为这些患者寻找有效的治疗手段一直是甲状腺癌领域研究的热点。该文对碘难治性甲状腺癌的诊断及治疗进展进行综述,为及早识别这些患者,并为其他可能获益的治疗手段如靶向治疗及放疗等的早期干预争取时间。     

Adjunctive management of thyroid cancer: chemotherapy

The majority of well-differentiated carcinoma of the thyroid can be effectively treated by surgery and thyroid hormone administration, or in combination with radioiodine therapy. Occasional patients with well-differentiated carcinoma, and patients with medullary carcinoma and anaplastic carcinoma should be considered for chemotherapy. Doxorubicin has been shown to be active in this neoplasm. In addition, there are chemotherapeutic agents shown to be active in small numbers of patients with this disease, but most of them have not received an adequate trial. Multiple-agent chemotherapy has also been tried in this disease. However, average response rate of multiple-agent chemotherapy appears to be only slightly better than that of doxorubicin single-agent chemotherapy. The importance of group approach in evaluating chemotherapy program is presented.     

Wire guided localisation for targeted axillary node dissection is accurate in axillary staging in node positive breast cancer following neoadjuvant chemotherapy

AimThis study investigated whether wire localisation of the histologically proven positive, clipped axillary lymph node (ALN) with subsequent targeted axillary dissection (TAD) following neoadjuvant chemotherapy (NACT) improves axillary staging in breast cancer.Materials and methodsWe performed a retrospective review of patients with primary breast cancer and core biopsy proven metastatic ALNs, that had an excellent nodal radiological response following NACT, treated at our centre between January 2016 and December 2018. The initial cohort of patients (Group 1) underwent sentinel lymph node biopsy (SLNB), with a minimum of three nodes were sampled. The subsequent cohort (Group 2) had a marker clip inserted in the metastatic ALN prior to NACT. This cohort underwent wire guided excision of the clipped node in addition to SLNB, with a minimum of three nodes sampled.ResultsA total of 47 patients were identified. Group 1 comprised 22 patients with a sentinel lymph node (SLN) identification rate (IR) of 95%. 25 patients (Group 2) underwent wire guided clip location and the SLN IR was 100% with a 92% clipped node IR. Evidence of pathological complete response (pCR) in the clipped node was associated with pCR in other nodes.ConclusionTargeted axillary dissection is a feasible technique following excellent response to NACT in selected patients with limited volume ALN metastasis, at diagnosis. The identification of the positive ALN during surgery is vital and the IR can be improved by clipping the node prior to NACT and wire guided localisation at the time of surgery.     

Feasibility of targeted axillary dissection for de-escalation of surgical treatment after neoadjuvant chemotherapy in breast cancer

BackgroundTargeted axillary dissection, which combines sentinel lymph node biopsy with removal of the proven involved node noted during the staging process, has been shown to improve axillary staging and decrease false negative rates after neoadjuvant chemotherapy in patients with breast cancer.Objective(s)The main goal of this study was to assess the ability to identify and remove the clipped node and the false negative rate of targeted axillary dissection.MethodsWe performed a prospective study among patients with biopsy-confirmed nodal metastases who received neoadjuvant chemotherapy. A clip was placed on the sample node prior systemic therapy. After neoadjuvant chemotherapy, all patients underwent sentinel lymph node biopsy (dual tracer), localization and excision of the clipped node and axillary lymph node dissection. The clipped node was preoperatively localized in all cases placing an iodine-125 seed guided by ultrasound. The pathology of the sentinel nodes and clipped node was compared with other nodes.ResultsA total of 455 patients with invasive breast cancer were studied. Of the 148 patients with NAC, 32 met the eligibility criteria and were enrolled in the study. Mean age at diagnosis was 52.3 years. Systematic lymphadenectomy was performed in all patients, with an average of 14.3 lymph nodes removed. Detection rate of the clipped node alone was 96.9%, and 100% for targeted axillary dissection. Ability of clipped node alone to predict nodal status showed a FNR of 10,5% while SLNB alone performed by dual tracer and targeted axillary dissection, showed FNRs of 5.3% and 5.0%, respectively. Sentinel lymph nodes matched clipped node in 23 patients (74.2%).Conclusion (s)In node positive breast cancer patients, targeted axillary dissection is a reliably approach for axillary staging after neoadjuvant chemotherapy. The preoperative location of the clipped node is mandatory to increase the detection rate and optimize the results of the technique.     

Clinical efficacy of local targeted chemotherapy for triple-negative breast cancer

Background

The aim of the study was to evaluate the clinical efficacy of superselective intra-arterial targeted neo-adjuvant chemotherapy in the treatment of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative (triple-negative) breast cancer.

Patients and methods.

A total of 47 triple-negative breast cancer patients (29 at stage II, 13 at stage III and 5 at stage IV) were randomly assigned to two groups: targeted chemotherapy group (n=24) and control group (n=23). Patients in the targeted chemotherapy group received preoperative superselective intra-arterial chemotherapy with CEF regimen (C: cyclophosphamide [600 mg/m²]; E: epirubicin [90 mg/m²]; F: 5-fluorouracil [600 mg/m²]), and those in the control group received routine neoadjuvant chemotherapy with CEF. The duration of the treatment, changes in lesions and the prognosis were determined.

Results

The average course of the treatment was 15 days in the targeted chemotherapy group which was significantly shorter than that in the control group (31 days) (P<0.01). The remission rate of lesions was 91.6% in the targeted chemotherapy group and 60.9% in the control group, respectively. Among these patients, 9 died within two years, including 2 (both at IV stage) in the targeted chemotherapy group and 7 (2 at stage II, 4 at stage III and 1 at stage IV) in the control group.

Conclusions

As an neoadjuvant therapy, the superselective intra-arterial chemotherapy is effective for triple-negative breast cancer, with advantages of the short treatment course and favourable remission rates as well as prognoses.     

S-1抗肿瘤药物在胃癌病人中的临床应用进展

药物治疗在胃癌治疗中具有重要地位.S-1作为一种新型口服抗肿瘤药物具有高效低毒、病人依从性好的优势,合理开展含S-1及S-1单药方案治疗胃癌的临床试验具有重要意义.     

Prospects for colorectal cancer treatment: oral chemotherapy and targeted biotherapy

Since the 1990s, the emergence of new drugs has modified the prognosis of metastatic colorectal cancer. This malignant disease has largely benefited from the development of new drugs and new therapeutic concepts, such as oral chemotherapy or targeted biotherapy. Although a significant improvement in survival has been reached with these new therapeutic approaches, the optimal strategy remains to be defined, particularly the best sequence of drug administration. This review will focus upon new anticancer drugs, some of them with original mechanism of action, and steps towards the goal of better understanding and anticipating new treatments in colorectal carcinoma.