Guidance for peptide vaccines for the treatment of cancer

Recent progress in fundamental understanding of tumor immunology has opened a new avenue of cancer vaccines. Currently, the development of new cancer vaccines is a global topic and has attracted attention as one of the most important issues in Japan. There is an urgent need for the development of guidance for cancer vaccine clinical studies in order to lead to drug development. Peptide vaccines characteristically have the effect of indirectly acting against cancer through the immune system – a mechanism of action that clearly differs from anticancer drugs that exert a direct effect. Thus, the clinical development of cancer peptide vaccines should be planned and implemented based on the mechanism of action, which differs significantly from conventional anticancer drug research. The Japanese Society for Biological Therapy has created and published Guidance for peptide vaccines for the treatment of cancer as part of its mission and responsibilities towards cancer peptide vaccine development, which is now pursued globally. We welcome comments from regulators and business people as well as researchers in this area.     

对鼻咽癌2008分期的评价与建议

鼻咽癌2008分期的优点:①采用MRI为主要分期手段;②舍弃了主观性的因素,纳入了新的独立预后因素如咽后淋巴结、RTOG颈部分区概念;③对T分期进行了简化;④N分期和总临床分期可以很好地预测远处转移风险及总生存率.这些改变适应了现代诊疗模式,具有很高的实用性.而对现行标准进行前瞻性、多中心的临床验证,进而修正完善,则符合分期的发展性和科学性原则.不足的是:①鼻腔、口咽等解剖结构的定义过于局限,咀嚼肌间隙的表达不够直观;②淋巴结大小等指标的循证医学证据不足;③T分期之间的风险差异性不显著:④与国际UICC/AJCC第六版分期标准基本概念如口咽、颈部分区上的差异,将有碍于国内外资料的交流.     

改变乳腺癌临床实践的重要临床试验的回顾与评述

近20年来,开展了一系列乳腺癌辅助治疗临床试验,其中一些重要临床试验改变了乳腺癌的临床实践,从而使乳腺癌从单一手术治疗模式过渡到今天被广泛接受的综合治疗模式。本文就这些重要临床试验作一介绍和评述。     

Clinical characteristics and outcomes for a modern series of primary gliosarcoma patients

BACKGROUND:

Primary gliosarcoma (PGS) is a rare central nervous system tumor with limited experience reported in the literature. In the current study, the authors present a modern series of confirmed PGS cases treated in the era of magnetic resonance imaging (MRI), after the accepted glioblastoma management of resection, radiation, and temozolomide.

METHODS:

Using a retrospective review, patients with confirmed PGS were identified (1996‐2008). Cases were determined to be PGS by central pathology review using the 2007 World Health Organization criteria. Extensive chart review was performed to gather clinical and pathologic data on these cases.

RESULTS:

All but 1 patient had undergone a preoperative MRI, with 1 patient receiving a computed tomography scan due to a cardiac pacemaker. A total of 10 patients received radiotherapy with concurrent and adjuvant temozolomide chemotherapy, and 8 patients received radiotherapy alone or in combination with other chemotherapeutic agents. In 2 patients, the history of adjuvant treatment could not be confirmed. The overall median survival was 13.9 months (range, 2.2‐22.9 months). Patients with gliosarcomas resembling meningioma were found to have a significantly prolonged median survival compared with patients harboring gliosarcoma resembling glioblastoma multiforme (16 months vs 9.6 months; P = .011). However, no difference in survival was noted between patients who received concurrent radiotherapy and temozolomide compared with those who did not (10.4 months vs 13.9 months; P = .946).

CONCLUSIONS:

The results of the current study support previous hypotheses that there are 2 distinct types of PGS. The type mimicking the appearance of a meningioma appears to carry a significantly more favorable prognosis, most likely due to an increased chance at achieving macroscopic total resection. Cancer 2010. © 2010 American Cancer Society.     

Hope for a cure and altruism are the main motives behind participation in phase 3 clinical cancer trials

It is necessary to carry out randomised clinical cancer trials (RCTs) in order to evaluate new, potentially useful treatments for future cancer patients. Participation in clinical trials plays an important role in determining whether a new treatment is the best therapy or not. Therefore, it is important to understand on what basis patients decide to participate in clinical trials and to investigate the implications of this understanding for optimising the information process related to study participation. The aims of this study were to (1) describe motives associated with participation in RCTs, (2) assess if patients comprehend the information related to trial enrolment, and (3) describe patient experiences of trial participation. Questionnaires were sent to 96 cancer patients participating in one of nine ongoing clinical phase 3 trials at the Department of Oncology, Uppsala University Hospital in Sweden. Eighty‐eight patients completed the questionnaire (response rate 92%); 95% of these were patients in adjuvant therapy and 5% participated in clinical trials on palliative care. Two main reasons for participation were identified: personal hope for a cure and altruism. Patients show adequate understanding of the information provided to them in the consent process and participation entails high patient satisfaction.     

A telephone‐delivered multiple health behaviour change intervention for colorectal cancer survivors: making the case for cost‐effective healthcare

In patients with colorectal cancer, a trial of a telephone‐delivered multiple health behaviour change intervention, using acceptance commitment therapy strategies, found benefits for health and psychosocial outcomes including increased physical activity, improved dietary habits and lower body mass index. Our aim was to address the health economic outcomes by assessing the health system cost and health utility impacts of the intervention. A cost‐consequences analysis was performed using data from a two‐group randomised controlled intervention trial (n = 410). Outcomes included health‐related quality of life (HRQoL), health utility and health system costs. At 12 months, clinically meaningful improvements were found for SF‐6D over time but no significant differences were found between groups (P = 0.95). The cost of delivering the 6‐month intervention was on average €280 per person and made up 21% of overall healthcare costs for participants during the intervention period. Excluding intervention costs, costs were similar for health professional visits and medications across groups. Despite significant positive intervention effects on health behaviours, health utility and HRQoL scores were similar across groups. On the basis that intervention costs were small and physical activity, diet and weight management improved, on balance the intervention is potentially a worthwhile investment in healthcare funds. Trial registration: ACTRN12608000399392.     

Von Hippel-Lindau病特点分析及外科处理

目的提高对VHL病的认识,改善VHL病的综合诊疗水平。方法 2010年至2012年收治的2个VHL家系,通过基因分析证实为家族性,共13例患者,1例携带者。通过回顾性分析该组患者的临床表现、实验室检查、影像学检查、基因检测以及手术和病理情况,总结VHL病的特点及外科处理手段。结果患者中有男性8例,女性5例,中位发病年龄为32岁,男性中位发病年龄为28岁,女性中位发病年龄为34岁。13例患者中,8例患者因神经系统原因就诊(61.5%),3例患者因视力下降就诊(23.1%),1例患者因体检发现肾占位就诊(7.7%),另有1例患者无特殊临床表现。目前7例患者(50%)已经死亡,其中男性5例,女性2例,中位死亡年龄为45岁,主要死亡原因为脑出血(5/7),其次为晚期肾癌(2/7)。主要治疗方法为手术切除肿瘤。对于晚期肾癌患者可以使用靶向药物治疗。基因筛查可以发现早期病例。结论 VHL病为遗传性疾病,常呈家族性、多器官发病,应提高对该病这两个特点的认识。对其家族成员应进行基因筛查,可以发现早期病例。诊断应全面,术前准备应充分,可一次性切除多处病灶,根据情况可选择腹腔镜手术,对于晚期肾癌患者可以使用靶向药物。     

Chemotherapy for metastatic gastric cancer in Japan

Until the 1990s, there were no chemotherapy regimens with old-generation anticancer agents showing a survival benefit over 5-fluorouracil (FU) alone, and standard chemotherapy for metastatic gastric cancer had not been established. In the late 1990s, several new active agents were developed and some phase III trials with these agents were conducted; the new agent S-1 showed noninferiority to 5-FU in these trials. S-1 plus cisplatin is the first doublet chemotherapy to have shown a survival benefit over monotherapy with S-1. It has been demonstrated that capecitabine and oxaliplatin (OHP) can replace 5-FU and cisplatin (CDDP), offering more convenient treatment options. Thus, combination chemotherapy with an oral fluoropyrimidine (S-1 or capecitabine) and platinum (CDDP or OHP) has been recognized as standard chemotherapy for metastatic gastric cancer all over the world. However, it can be said that none of these new combination chemotherapies have shown remarkable progress from 5-FU plus cisplatin regimens. It is expected that triplet chemotherapy with a taxane; the use of molecular targeting agents; and the establishment of treatment strategies including second line chemotherapy, will lead to remarkable progress in personalized medicine in the near future.     

原发性肺癌521例临床特点分析

目的：分析原发性肺癌的临床特点.方法：回顾性分析521例确诊为原发性肺癌且有完整资料患者的临床特点.结果：男377例,女144例,年龄15-80岁,中位年龄58岁.鳞癌、腺癌、小细胞癌和其他病理类型肺癌分别占32.44％、35.12％、25.14％和7.29％.女性患者腺癌发生率高于男性,鳞癌发生率较男性低.吸烟主要与鳞癌的发生有关.男性患者的平均发病年龄高于女性患者.最常见的转移部位从高到低依次为骨、脑、对侧肺及肝脏,其中腺癌的骨、脑、肺转移发生率均高于其他病理类型.结论：腺癌仍是目前肺癌的主要病理类型,吸烟、性别均是肺癌病理类型的影响因素,骨、脑是肺癌最常见的转移部位.     

吉西他滨治疗晚期胆管癌临床疗效评价

目的:观察吉西他滨治疗晚期胆管癌的临床疗效及不良反应。方法:回顾分析近10年收治的晚期胆管癌患者42例,分为吉西他滨化疗组（G）和非吉西他滨化疗组（NG）,比较两组临床疗效。结果:G组与NG组客观有效率分别为33.3%、5.6%,疾病控制率分别为75.0%、44.4%,中位生存时间分别为10.6个月、7.4个月,两组生活质量改善分别为79.2%、50%,差异均有显著性。不良反应可耐受,除血小板下降外余无明显差异。结论:晚期胆管癌接受含吉西他滨方案化疗可提高近期疗效,改善生活质量,延长生存时间。     

进展期胃癌术后腹腔化疗的临床疗效分析

目的:观察分析进展期胃癌术后早期连续腹腔化疗的疗效及毒副反应。方法:对2002-03-2007-03胃癌根治术后的69例进展期患者,早期用腹腔化疗的病例进行回顾性分析,并以同期行静脉化疗的61例患者作对照。分析比较两组患者生存率、复发率和不良反应的差异。结果:腹腔化疗组1、2和3年生存率分别为89.86%、79.71%和65.22%,静脉化疗组1、2和3年生存率分别为77.05%、68.85%和59.01%。而连续腹腔化疗组不良反应(除腹痛、腹胀外)及复发率均低于静脉化疗组。结论:进展期胃癌术后早期腹腔化疗简单实用、安全、全身毒副反应小,可有效预防腹腔内复发和转移,提高术后生存质量和生存率。     

Treatment of Askin Rosai tumor--need for a more aggressive approach

Fifteen cases of histologically proven Askin Rosai tumor were treated at Tata Memorial Hospital over a period of 3 years. Patients included 12 men and three women. Clinical features included chest wall mass (14), pain (11), bony involvement (6), fever (4), dyspnoea (4), weight loss (1), cough (1), and hemoptysis (1). Previously treated patients received different treatment protocols, which made evaluation difficult. Of our ten patients who have completed induction therapy, five received vincristine and cyclophosphamide, whereas the other five received more aggressive chemotherapy. Complete remission has been achieved in two and four of these patients, respectively. One patient in each group had recurrence of the disease, in both cases at the local site. Thus, from our preliminary data, we suggest that Askin Rosai tumor should be treated with complete surgical excision followed by an aggressive combination of chemotherapy and local radiotherapy.     

源自右半结肠癌淋巴结清扫范围(RELARC)研究的启示

外科医师的日常诊疗行为非常符合临床研究的Patients、Interventions、Comparisons和Outcomes(PICO)原则,适合开展临床研究.研究者需要善于将工作中的临床问题转化为科学问题,早期、积极地与统计方法学专家沟通,确立开展研究的目标和研究性质,根据自身能力选择合适的临床研究.实施过程中及时...     

The Effectiveness and Safety of Oral Linezolid for the Primary and Secondary Treatment of Osteomyelitis

Abstract

The pharmacokinetic profile of oral linezolid makes it an attractive alternative for the treatment of osteomyelitis. Few studies have described the efficacy of linezolid in the treatment of osteomyelitis. A retrospective, observational analysis was conducted at Edward Hines, Jr. VA Hospital. Patients who received oral linezolid from June 2000 to December 2002 were identified from pharmacy records. Fortytwo patients who received oral linezolid for osteomyelitis at our institution were identified. Only patients who had received at least six weeks of linezolid therapy were evaluated for clinical effectiveness. Patients were also evaluated for adverse drug reactions due to linezolid.

The clinical cure rate was 55% for the 20 patients who received at least six weeks of therapy. Adverse events included gastrointestinal disturbances (15%), thrombocytopenia (10%), anemia (10%), neutropenia (5%) and rash (5%).

The authors conclude that oral linezolid is an alterative to intravenous antibiotics for the treatment of osteomyelitis.     

Combining progression-free survival and overall survival as a novel composite endpoint for glioblastoma trials

Background

The use of auxiliary endpoints may provide efficiencies for clinical trial design, but such endpoints may not have intrinsic clinical relevance or clear linkage to more meaningful endpoints. The purpose of this study was to generate a novel endpoint that considers both overall survival (OS) and earlier events such as progression-free survival (PFS) and determine whether such an endpoint could increase efficiency in the design of glioblastoma clinical trials.

Methods

Recognizing that the association between PFS and OS varies depending on therapy and tumor type, we developed a statistical model to predict OS based on PFS as the trial progresses. We then evaluated the efficiency of our model using simulations of adaptively randomized trials incorporating PFS and OS distributions from prior published trials in neuro-oncology.

Results

When treatment effects on PFS and OS are concordant, our proposed approach results in efficiency gains compared with randomization based on OS alone while sacrificing minimal efficiency compared with using PFS as the primary endpoint. When treatment effects are limited to PFS, our approach provides randomization probabilities that are close to those based on OS alone.

Conclusion

Use of OS as the primary endpoint, combined with statistical modeling of the relationship between OS and PFS during the course of the trial, results in more robust and efficient trial designs than using either endpoint alone.     

肾癌根治术166例经验总结

目的 分析我院根治性肾切除术的手术时间、出血量、住院日、并发症和患者的生存率,总结根治性肾切除术治疗肾癌的经验.方法 1999年10月至2005年12月对166例肾细胞癌患者施行了根治性肾切除术.男108例,女58例;中位年龄51岁(14～83岁);无症状肾癌70例;肿瘤最大径中位数60mm(11～145 mm).统计手术时间、出血量、住院日和并发症,对全部患者进行随访,计算生存率.结果 中位手术时间150分钟(60～360分钟),术中出血中位值为200ml(50～10000 ml),输血16例(9.6%),平均输血量为11.5个单位红细胞(1～75个单位).术中出血量≥500ml者24例(占14.5%),其中6例同时取腔静脉癌栓,无手术死亡.术后中位住院日15天(6～46天).术中并发症脾脏损伤2例,腔静脉撕裂并十二指肠损伤1例,血管损伤2例,经术中处理无后遗症.术后并发症心衰1例,不完全性肠梗阻2例,经保守治疗治愈.随访6～78.6个月,平均23.6个月.1年、3年和5年总生存率分别为93.6%、84.1%、74.8%;病理分期Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期患者1年总生存率分别为100%、100%、88.2%和61.5%,3年生存率分别为97.0%、95.5%、75.6%和52.7%.5年生存率分别为88.8%(Ⅰ期)、86.8%(Ⅱ期)、0%(Ⅳ期).结论 根治性肾切除术严重并发症少,治疗肾癌疗效确切,早期肾癌病人(Ⅰ期、Ⅱ期)绝大部分可以获得治愈.