三维适形放疗联合CIK细胞治疗晚期原发性肝癌患者的疗效

目的 观察三维适形放疗（3D-CRT）联合细胞因子诱导的杀伤细胞（CIK）治疗晚期原发性肝癌患者的临床疗效。方法 选取2013年8月至2015年8月中国人民解放军第105医院肿瘤中心就诊的72例晚期原发性肝癌患者,依据治疗方法不同分为对照组和观察组,每组36例患者。观察组在接受3D-CRT后3个月内给予CIK细胞治疗2次。治疗后3个月,依据肝脏CT、甲胎蛋白（AFP）、流式细胞术检测治疗前后免疫功能的变化情况,综合分析3D-CRT联合CIK细胞治疗晚期原发性肝癌的疗效。结果 治疗结束3个月后,观察组的疾病控制率为80.6%,高于对照组的55.6%,差异有统计学意义（P<0.05）;两组治疗后肿瘤直径和AFP指标监测数据显示,观察组[（4.17±1.65）cm和（348.5±127.2）ng/mL]明显优于对照组[（5.32±1.63）cm和（464.9±134.8）ng/mL],差异均有统计学意义（P<0.05）;观察组CD₃⁺T细胞、CD₄⁺CD₈⁺T抑制/细胞毒性细胞及CD₁₆⁺CD₅₆⁺NK细胞均不同程度增加（P<0.05）。结论 在晚期原发性肝癌的治疗中,三维适形放疗联合CIK细胞治疗可以提高疾病的控制率、增强机体免疫力,有可行性,可进一步探讨。     

Amifostine: chemotherapeutic and radiotherapeutic protective effects

Amifostine (Ethyol?, Alza Pharmaceuticals) is an inorganic thiophosphate cytoprotective agent known chemically as ethanethiol, 2-[3- aminopropyl)amino]dihydrogen phosphate. It is a prodrug of free thiol (WR-1065) that may act as a scavenger of free radicals generated in tissues exposed to cytotoxic drugs and binds to reactive metabolites of such drugs. Amifostine was originally developed as a radioprotective agent in a classified nuclear warfare project. Following declassification of the project it was evaluated as a cytoprotective agent against toxicity of the alkylating drugs and cisplatin. Differences in the alkaline phosphatase concentration of normal versus tumour tissues can result in greater conversion of amifostine in normal tissues. Inside the cell, WR-1065 provides an alternative target to DNA and RNA for the reactive molecules of alkylating or platinum agents and acts as a potent scavenger of the oxygen free radicals induced by ionizing radiation and some chemotherapy agents. Preclinical animal studies have demonstrated that the administration of amifostine protects against a variety of chemotherapy-related toxicities including cisplatin-induced nephrotoxicity, cisplatin-induced neurotoxicity, cyclophosphamide- and bleomycin-induced pulmonary toxicity and the cytotoxicities (including cardiotoxicity) induced by doxorubicin and related chemotherapeutic agents. Amifostine has been shown to protect a variety of animal species from lethal doses of radiation. Amifostine gives haematological protection from cyclophosphamide, carboplatin, mitomycin C, fotemustine and radiotherapy; renal and peripheral nerve protection from cisplatin; mucosa, skin and salivary gland protection from radiotherapy. Multiple Phase I studies were carried out with amifostine in combination with chemotherapy for various neoplasms. Appropriate doses of amifostine were found to be 740 - 910 mg/m² in single-dose regimens and 340 mg/m² in multiple-dose regimens. In radioprotection, doses are generally 200 - 350 mg/m². For all these characteristics, amifostine has been recently approved and suggested in ASCO clinical practice guidelines as a radioprotector for head and neck cancer treatment and supportive agent during cisplatin-based chemotherapy, in lymphomas and solid tumours. Moreover, its spectrum of possible applications is enlarging. As data have been provided indicating that amifostine stimulates haematopoiesis, it has been employed with intriguing results in the treatment of myelodysplastic syndromes (MDS).     

Focal adhesion kinase: a promising target for anticancer therapy

Focal adhesion kinase (FAK) is a protein tyrosine kinase acting as an early modulator of the integrin signalling cascade, thus regulating various basic cellular functions. In transformed cells, upregulation of FAK protein expression and uncontroled signalling were held responsible for the promotion of malignant phenotypic characteristics, as well as resistance to chemotherapy and radiotherapy. Direct FAK targeting resulted in the inhibition of the malignant phenotype of cancer cells, whereas increased apoptotic rates of cancer cells, either used alone or in combination with conventional chemotherapeutic agents, radiotherapy or hormonal therapy. Furthermore, drugs used in cancer chemotherapy, besides their basic mode of action, were also shown to act through altering FAK signalling. Finally, positive results were noted by the transfection of cancer cells with fak mutants or genes that suppress FAK expression or activity, such as phosphatase and tensin homolog deleted on chromosome Ten (PTEN), ribonucleotide reductase M1 polypeptide (RRM1) and melanoma differentiation-associated gene-7 (mda-7). The purpose of this article is a comprehensive review of the existing data on the possible use of FAK targeting in anticancer therapy.     

Gastric and gastro-oesophageal cancer therapy

Gastric and gastro-oesophageal cancers represent a global health problem. In recent years, there has been a marked increase in the incidence of proximal gastric and distal oesophageal adenocarcinomas. Surgery is the primary therapy for localised gastric or gastro-oesophageal cancer; however, patients treated with surgery have high rates of local and distant relapse as well as an unacceptably low 5-year survival rate. Chemoradiation and preoperative chemotherapy can play an important role for these patients. The outcome of patients with metastatic disease is very poor but a number of newer chemotherapy agents, such as docetaxel, oxaliplatin and S-1, have been identified and some have shown promising results. This article reviews recent trials on localised and metastatic gastric and gastro-oesophageal cancers.     

Management of glioblastoma

Glioblastoma multiforme (GBM) are among the most devastating neoplasms claiming the lives of patients within a median of 1 year after diagnosis. Treatment of GBM requires a multidisciplinary approach. Treatments include surgery, radiotherapy, chemotherapy and so on. Temozolomide (TMZ) has emerged as an active agent against malignant gliomas. On the basis of the work by the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada, concurrent radiotherapy and the oral alkylating agent TMZ followed by adjuvant TMZ has become the standard of care for patients with newly diagnosed GBM, although the methylation status of the O⁶-mehylguanine-DNA methyltransferase promoter is predictive for survival of GBM patients. Gliadel is a biodegradable polymer wafer impregnated with carmustine. Gliadel has been one of the few treatment modalities to demonstrate a statistical benefit in patients with malignant glioma. These new FDA approved drugs advanced the treatment of malignant glioma, but more progress is needed. Patients require improvements in chemotherapy, surgery, radiotherapy, molecular targeted therapy, immunotoxin using the convection-enhanced delivery and more.     

New treatments on the horizon for chemoradiotherapy-induced nausea and vomiting

Introduction: Antiemetic prophylaxis for the prevention of chemotherapy-induced nausea and vomiting, and the development of new antiemetic drugs are expanding areas of research. However, studies of antiemetic prophylaxis in chemoradiotherapy have not been prioritised, and little is known about the proper timing, duration, and combination of antiemetic drugs for the prevention of chemoradiotherapy-induced nausea and vomiting (C-RINV).

Areas covered: The article summarises the available antiemetic studies, the evidence for antiemetic prophylaxis of C-RINV, and the future perspectives for antiemetic research in chemoradiotherapy.

Expert opinion: Antiemetic prophylaxis for patients receiving concomitant chemoradiotherapy has, for many years, been an orphan research area. The distinction between acute and delayed nausea and vomiting does not apply to fractionated radiotherapy, and prophylaxis should be considered to cover the entire course of treatment and not only the acute and delayed chemotherapy-induced nausea and vomiting. The best prophylaxis in women receiving fractionated radiotherapy and concomitant weekly cisplatin is a combination of the neurokinin receptor antagonist fosaprepitant with palonosetron and dexamethasone. Even with this three-drug combination nausea is a significant problem and the effect of multi-receptor targeting antiemetics such as olanzapine and amisulpride should be explored in this setting.     

Pattern of symptoms and symptomatic treatment in adults and the aged population: a retrospective analysis of advanced cancer patients followed at home

Context Data regarding symptom burden and symptomatic drugs in palliative population in different classes of age are lacking.

Objective The aim of this retrospective study was to assess the symptom burden, and the profile of symptomatic drugs in the last four weeks of life in adults and older cancer patients followed at home.

Methods Charts of 412 patients were retrospectively analyzed by using a backward analysis. Patients were divided into three groups: adults (<65 years, A), old (65–74 years, O1), very old (75–84 years, O2), and the oldest (≥85 years, O3).

Results At -4W Karnofsky status was significantly lower for older people (p?=?0.03). No significant effect of age on the vector of symptoms was found (p?=?0.07). A significant decrease in intensity of pain and nausea, and an increase in intensity of all other symptoms was found through the four weeks of the study (p?=?0.00). No differences of drug pattern among the age categories were found. The use of symptomatic drugs decreased over time, except for opioids. Age statistically affected NSAID use, neuroleptic use, and antiemetics over time.

Conclusion The burden of symptoms worsened in the last four weeks of life, except for pain and nausea, but did not differ among the age subgroups. The use of NSAIDs, neuroleptics, and antiemetics changed, while the frequency of opioid use was unchanged until death.     

高龄食管癌患者的适形放疗

目的应用适形放疗技术治疗高龄患者的食管癌,评价疗效和并发症。方法 37例未手术的高龄患者食管癌给予适形放射治疗。放疗剂量:1.8～2Gy/(次d),5次/周,共计60～66Gy/30～37次;3～9个适形照射野。结果治疗后1～6个月复查食管X线片和CT,近期有效率97.3%(36/37);1年、2年、3年、4年和5年生存率分别为79.38%、66.76%、49.73%、33.51%和24.41%。结论高龄患者食管癌的适形放射治疗,疗效较好,并发症少,是不能手术患者一种较好的治疗方式。     

脑转移瘤放疗相关认知损害

目的观察脑转移癌患者全脑放疗前后认知功能损害情况。方法用MMSE作为认知评估工具,脑转移癌患者全脑放疗前1周、后1周、放疗后1月,以后每月做认知评估,观察放疗前与放疗后、有症状放疗与无症状放疗认知改变。结果共人组患者41例,基线MMSE评分与放疗后1周比较差异显著[（28．146±0．528）掷（27．585±0．290）,P=0．006]其中放疗前无神经系统症状8例,放疗后4月MMSE减低最明显,其后有所提高,基线MMSE与放疗后4月比较差异显著[（29．125±0．579）vs（26．500±0．524）,P〈0．001）],差异显著;有神经系统症状组其中8例基线MMSE评分≤26,放疗后随着颅内病灶控制MMSE有所提高,放疗后4月提高最明显,基线MMSE与放疗后4月比较差异显著[（25．000±0．524）vs（27．500±0．370）,P=0．001]。结论全脑放疗对认知功能有损害,其损害是缓慢的病理过程,放疗后4月左右认知功能损害最明显,其后有所恢复;同时颅内病灶也对认知功能有影响。     

术前短期放疗联合腹腔镜根治直肠癌的手术效果观察

目的：探讨术前短期放疗联合腹腔镜根治直肠癌手术的临床效果,为治疗直肠癌提供临床依据。方法对2008年6月至2011年6月来我院治疗Dukes B和C期直肠癌的120例患者进行回顾性分析,随机分成A、B、C三组,每组40例,A组采用术前短期放疗联合腹腔镜方式,B组采用未短期放疗联合腹腔镜方式,C组采用未短期放疗联合开腹手术方式,观察三组的治疗效果。结果术前短期放疗联合腹腔镜方式根治直肠癌手术切除率和保肛率明显高于未短期放疗联合腹腔镜方式以及未短期放疗联合开腹手术方式,存在统计学意义（P＜0.05）;术前短期放疗联合腹腔镜方式根治直肠癌手术远处转移率、局部复发率和并发症发生率明显低于未短期放疗联合腹腔镜方式以及未短期放疗联合开腹手术方式,存在统计学意义（P＜0.05）。结论术前短期放疗联合腹腔镜根治直肠癌手术具有很好的保肛率和根治率,在临床上可大力推广。