Minimally invasive interval cytoreductive surgery for advanced ovarian cancer

With the increasing use of neoadjuvant chemotherapy, it has also become apparent that some patients will require a less extensive interval cytoreductive surgery which could be performed as a minimally invasive procedure. This observation, and expertise with minimally invasive surgery for other indications in gynecologic oncology, has driven surgeons in the United States and other countries to perform an increasing portion of interval cytoreductive surgery using minimally invasive techniques. Further observational and trial data will continue to inform which patients are best suited for this approach.     

Impact of neoadjuvant chemotherapy on the immune microenvironment in advanced epithelial ovarian cancer: Prognostic and therapeutic implications

Over the last decade, increasing evidence highlights the role of the host immune system in the control of tumor growth and the prognostic implications of tumor infiltrating lymphocytes (TILs) in ovarian cancer. Most data support a better prognosis with accumulation of CD3+ and CD8 + TILs and a poor outcome associated with increased regulatory T cells. However, only a small number of studies have focused on the effect of neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment. This review will provide an update on the prognostic value of TIL subpopulations at diagnosis and a comprehensive overview of the recent studies evaluating the impact of neoadjuvant chemotherapy on TILs and their relationship to clinical outcome in advanced ovarian cancer. This information could help in future investigations of immunotherapy as maintenance following primary treatment.     

Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer

Although normally restricted to activated T and B cells and mature dendritic cells, constitutive expression of CD70, a member of the tumor necrosis family, has been described in both hematological and solid tumors, where it increases tumor cell and regulatory T cell survival by signaling through its receptor, CD27.We have assessed the co-expression of CD70 and CD27 in non-small cell lung cancer (NSCLC) by immunohistochemistry to explore a correlation between expression of the protein and tumor histologic subtype, genetic aberrations and prognosis. Furthermore, we tested the ability of ARGX-110, a CD70-blocking antibody, to induce NK cell-mediated cytotoxicity.Our results revealed CD70 expression on the surface of both primary and metastatic NSCLC tumor cells and in the tumor microenvironment. Moreover, CD27-expressing tumor infiltrating lymphocytes were found adjacent to the tumor cells, suggesting active CD70-mediated signaling. Finally, we have shown that ARGX-110, has potent cytotoxic effects on CD70⁺ NSCLC cell lines.     

卵巢癌治疗新进展

卵巢癌是继子宫内膜癌及宫颈癌发生率居第三的妇科恶性肿瘤,而其死亡率却居妇科恶性肿瘤之首。卵巢癌的治疗一直是临床工作面临的最艰巨的挑战。传统的根治性手术联合辅助性化疗仍是其基本的治疗方法,新辅助化疗、放疗、生物治疗、免疫治疗和分子靶向治疗给中晚期的卵巢癌治疗提供了新的选择。本文综述卵巢癌的治疗现状及最新的研究进展。     

Role of chemotherapy in the management of epithelial ovarian cancer

The management of ovarian cancer continues to provide major challenges and debates about optimal treatment. For first-line therapy there remain discussions about optimal chemotherapy for early disease, the use of taxanes as standard for advanced newly diagnosed patients, whether there is a definite role for neoadjuvant chemotherapy and the question of maintenance treatment. For relapsed disease, the management hinges around the distinction between platinum-sensitive and -resistant cancer, and the recent AGO-2.5 and ICON-4 studies suggest that treating with carboplatin and paclitaxel or carboplatin and gemcitabine is recommended. Intraperitoneal chemotherapy remains an enigma with at least three studies showing survival advantage; however, there has been no move to incorporate it into standard management of those patients who achieve complete remission after first-line chemotherapy. Finally, neoadjuvant chemotherapy prior to debulking surgery is the subject of several ongoing clinical trials and may turn out to be one of the most important developments since the concept of interval debulking surgery was established and proven in Europe.     

新辅助化疗对比初始肿瘤细胞减灭术治疗Ⅲ-Ⅳ期卵巢癌的荟萃分析

目的:比较Ⅲ-Ⅳ期卵巢癌（International Federation of Gynecology and Obstetrics,FIGO）新辅助化疗（neoadjuvant chemotherapy,NACT)联合间隔减瘤手术与初始肿瘤细胞减灭术（primary debulking surgery,PDS）联合化疗两种治疗模式有效性及安全性差异。方法:计算机检索Pubmed、Cochrane Library、Embase、Web of Science、中国生物医学文献数据库、万方数据库和中国知网等数据库,查找NACT对比PDS治疗Ⅲ-Ⅳ期卵巢癌随机对照研究相关文献,应用Review Manager 5.3软件进行统计分析。结果:纳入4项研究,共计1 631例患者。NACT组与PDS组总生存期（HR=0.95,95％CI为0.84～1.07,P=0.38）和无进展生存期相似（HR=0.97,95%CI为0.88～1.08,P＝0.61）;NACT组肿瘤完整切除率较PDS组提高（RR=2.47,95%CI为1.50～4.05,P=0.000 4）。在不良反应和安全性方面,NACT组患者≥3级静脉血栓发生率（RR＝0.25,95％CI为0.10～0.62,P=0.003）、≥3级感染发生率（RR＝0.30,95％CI为0.16～0.56,P=0.000 2）和围手术期死亡率（RR＝0.17,95％CI为0.06～0.48,P=0.000 9）均降低。结论:在Ⅲ-Ⅳ期卵巢癌治疗中,两种治疗模式生存获益相当,但新辅助化疗联合间隔减瘤手术可以提高肿瘤完整切除率,具有更好的安全性。新辅助化疗联合间隔减瘤手术可作为Ⅲ-Ⅳ期卵巢癌患者一种推荐治疗方式。     

新辅助化疗结合间隔减瘤术治疗晚期卵巢癌的探讨

目的：探讨新辅助化疗结合间隔减瘤术治疗晚期卵巢癌的效果。方法：对我院在1998年1月至2003年12月间收治的51例晚期卵巢癌进行回顾性分析,先行新辅助化疗,CP方案全身化疗3疗程后行间隔减瘤术,术后继续化疗6疗程,分析3年及5年生存率。结果：明显提高肿瘤细胞减灭术的满意率,3年生存率80．4％,5年生存率58．8％。结论：新辅助化疗结合间隔减瘤术治疗晚期卵巢癌可以明显提高晚期卵巢癌患者手术满意率和生存率。     

新辅助化疗结合间隔减瘤术治疗晚期卵巢癌的探讨

目的:探讨新辅助化疗结合间隔减瘤术治疗晚期卵巢癌的效果.方法: 对我院在1998年1月至2003年12月间收治的51例晚期卵巢癌进行回顾性分析,先行新辅助化疗,CP方案全身化疗3疗程后行间隔减瘤术,术后继续化疗6疗程,分析3年及5年生存率.结果: 明显提高肿瘤细胞减灭术的满意率,3年生存率80.4%,5年生存率58.8%.结论: 新辅助化疗结合间隔减瘤术治疗晚期卵巢癌可以明显提高晚期卵巢癌患者手术满意率和生存率.     

Phase ii/iii study of intraperitoneal chemotherapy after neoadjuvant chemotherapy for ovarian cancer: ncic ctg ov.21

Three large randomized clinical trials have shown a survival benefit in women with stage iii epithelial ovarian cancer (eoc) who receive intraperitoneal (IP) chemotherapy after optimal primary debulking surgery. The most recent Gynecologic Oncology Group study, gog 172, showed an improvement in median overall survival of approximately 17 months. That result led to a U.S. National Cancer Institute (nci) clinical announcement recommending that IP chemotherapy be considered for this group of women with eoc. However, IP chemotherapy is associated with increased toxicity, and rates for completion of treatment are low (42% in gog 172). The optimal IP regimen and duration of treatment has yet to be defined. Women undergoing chemotherapy before optimal debulking surgery were not included in the studies or in the nci clinical announcement. The National Cancer Institute of Canada Clinical Trials Group has developed a protocol for a randomized phase ii/iii study which will examine whether IP platinum-taxane-based chemotherapy benefits women who have received neoadjuvant chemotherapy before optimal surgical debulking. To address whether the less systemically toxic carboplatin can be substituted for cisplatin IP, the first phase of the study will have 3 arms: 1 intravenous-only, and 2 IP-containing regimens. At the end of the first stage, and provided that IP therapy is feasible to administer in this patient population, one of the IP regimens, either IP carboplatin or IP cisplatin, will proceed into a phase iii comparison with the intravenous arm. This exciting new study has gathered international support.     

Alternating multiagent chemotherapy for advanced ovarian cancer

A chemotherapy regimen consisting of hexamethylmelamine (H) 150 mg/m2 orally days 1-14, cyclophosphamide (C) 500 mg/m2 IV day 1 of a 28-day cycle with Adriamycin (A) 40 mg/m2 IV day 1 alternating with cis-diamminechloroplatinum (C-P) 50 mg/m2 IV day 1 every other cycle was administered to 29 patients with advanced epithelial ovarian cancer. Toxicity to this regimen included alopecia, nausea, and vomiting in all patients. Mild paresthesias occurred in four patients. Hematologic toxicity required only minimal dose modification. There was no cardiac, renal, or auditory toxicity. The clinical response rate of 55% and median survival of 14 months compare favorably with that of other reported series. This chemotherapy regimen seems to be well tolerated without jeopardizing the patients' response.     

A prognostic model for ovarian cancer

About 6000 women in the United Kingdom develop ovarian cancer each year and about two-thirds of the women will die from the disease. Establishing the prognosis of a woman with ovarian cancer is an important part of her evaluation and treatment. Prognostic models and indices in ovarian cancer should be developed using large databases and, ideally, with complete information on both prognostic indicators and long-term outcome. We developed a prognostic model using Cox regression and multiple imputation from 1189 primary cases of epithelial ovarian cancer (with median follow-up of 4.6 years). We found that the significant (P< or = 0.05) prognostic factors for overall survival were age at diagnosis, FIGO stage, grade of tumour, histology (mixed mesodermal, clear cell and endometrioid versus serous papillary), the presence or absence of ascites, albumin, alkaline phosphatase, performance status on the ZUBROD-ECOG-WHO scale, and debulking of the tumour. This model is consistent with other models in the ovarian cancer literature; it has better predictive ability and, after simplification and validation, could be used in clinical practice.     

Neoadjuvant chemotherapy in ovarian cancer

Primary radical tumor debulking followed by platinum/taxane-based chemotherapy is considered standard for advanced stage ovarian carcinomas. The extent of postoperative residual disease is the most important prognostic factor. However, complete tumor resection is achieved in only 40–50% of advanced ovarian cancers. For the remaining patients, who have an unfavorable prognosis, the concept of neoadjuvant or primary chemotherapy followed by interval laparotomy has emerged. Two different strategies are pursued. One is to administer several courses of neoadjuvant chemotherapy in order to downstage the tumor prior to primary debulking surgery. The other is to administer chemotherapy after suboptimal debulking surgery to optimize cytoreduction during interval laparotomy. Numerous retrospective studies demonstrated that neoadjuvant chemotherapy followed by primary debulking surgery is a feasible and safe approach. It is becoming increasingly evident that the selection of appropriate patients is crucial. Some studies demonstrated that the volume of ascites proved to be an easily measurable biomarker that allowed prediction of tumor resectability. However, further investigations are needed to better define patients who will benefit from neoadjuvant chemotherapy. Despite promising results, neoadjuvant chemotherapy must still be considered experimental. Therefore, the potential advantages of neoadjuvant chemotherapy need to be confirmed in prospective randomized studies.     

Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer which does not respond to hormone therapy. Research of NEPC has been hampered by a lack of clinically relevant in vivo models. Recently, we developed a first-in-field patient tissue-derived xenograft model of complete neuroendocrine transdifferentiation of prostate adenocarcinoma. By comparing gene expression profiles of a transplantable adenocarcinoma line (LTL331) and its NEPC subline (LTL331R), we identified DEK as a potential biomarker and therapeutic target for NEPC. In the present study, elevated DEK protein expression was observed in all NEPC xenograft models and clinical NEPC cases, as opposed to their benign counterparts (0%), hormonal naïve prostate cancer (2.45%) and castration-resistant prostate cancer (29.55%). Elevated DEK expression was found to be an independent clinical risk factor, associated with shorter disease-free survival of hormonal naïve prostate cancer patients. DEK silencing in PC-3 cells led to a marked reduction in cell proliferation, cell migration and invasion. The results suggest that DEK plays an important role in the progression of prostate cancer, especially to NEPC, and provides a potential biomarker to aid risk stratification of prostate cancer and a novel target for therapy of NEPC.     

The therapeutic potential of targeting the EGFR family in epithelial ovarian cancer

The epithelial growth factor receptor (EGFR) family of receptor tyrosine kinases has been reported to have an active role in a number of malignancies. Amplifications and overexpression of various EGFR family members, including EGFR, Her2, and ErbB3, have been reported in epithelial ovarian cancer. Although anti-EGFR-targeted therapy has shown limited clinical activity in ovarian cancer to date, a recent report suggests that activation of ErbB3, one of the members of the EGFR family, may support the growth and proliferation of ovarian cancer cells and that ErbB3 may therefore serve as a potential therapeutic target in this disease. Here, we review the EGFR family and the clinical experience with anti-EGFR family member-directed therapies in ovarian cancer to date.     

新型抗Her-2药物T-DM1

T-DM1是新型抗体-药物偶联物,具有曲妥珠单抗类似的生物活性,可特异性的将强效抗微管药物DM1释放至Her-2过表达的肿瘤细胞内。T-DM1单药疗效优于拉帕替尼联合卡培他滨,有望成为Her-2阳性晚期乳腺癌的标准二线治疗药物。比较T-DM1与曲妥珠单抗联合紫杉类药物一线治疗晚期乳腺癌的试验正在进行中。该药是继曲妥珠单抗之后又一种全新的抗Her-2药物。美国FDA正式批准T-DM1作为治疗Her-2阳性晚期乳腺癌患者的药物。      

CD43 in the nucleus and cytoplasm of lung cancer is a potential therapeutic target

CD43 is a transmembrane sialoglycoprotein. Normally the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signaling, apoptosis, migration and proliferation. Two CD43 antibodies were used to interrogate 66 cases of non‐small cell lung cancer (NSCLC) and 24 cases of small cell lung cancer (SCLC). In addition, we engineered the CD43‐positive lung cancer cell line A549 to stably express either non‐targeted or CD43‐targeted small‐interfering RNA (siRNA). These lines were then subjected to in vitro assays of apoptosis, natural killer (NK) cell cytotoxicity, intercellular adhesion and transendothelial migration. A xenograft mouse model evaluated the ability of the lines to grow primary tumors in vivo. CD43 was found to be expressed in the majority of both SCLC and NSCLC. Inclusive of CD43‐negative tumors, differential patterns of nuclear and cytoplasmic expression of CD43 define four molecular subcategories of lung cancer. Targeting CD43 in A549 lung cancer cells, increased homotypic adhesion, decreased heterotypic adhesion and transendothelial migration, increased susceptibility to apoptosis and increased vulnerability to lysis by NK cells. Furthermore, targeting inhibited the growth of primary tumors in nude mice.