National Institutes of Health's Clinical Center sets new policy on use of herbal and other alternative supplements by patients enrolled in clinical trials

The nationwide concern over the escalating use of herbal and other alternative dietary supplements is prompting a call for action in health care organizations. Not only is there mounting evidence to support a strong concern for patient safety, but the use of these products by people participating in biomedical research protocols has an added impact on the integrity of the research design and data gathering. These issues are of increasing concern to the National Institutes of Health's hospital for biomedical research, the Warren Grant Magnuson Clinical Center. Surveys completed in 2000 showed that 25-45% of Clinical Center patients reported taking herbal and other alternative dietary supplements. In 2001, the Clinical Center moved forward to develop and implement a policy to guide hospital staff in the management of patient use of herbal and alternative supplements. The policy established the requirement for all patients to be screened for supplement use upon admission or outpatient visit. Continued use of supplement products during hospitalization and/or outpatient enrollment on protocol require a physician's authorizing order. The implementation of this policy has increased awareness and provided an important step forward in protecting patient safety and preserving the scientific integrity of the research at the NIH's Clinical Center.     

预测结果儿童弥漫内在脑桥脑胶质瘤使用多参数成像

神经肿瘤杂志。2011个月;13（8）：904-9。2011月13课件。海马中,steffen-smith,哈穆德,世勋,弯曲,沃伦克。小儿肿瘤科,国家癌症研究所,癌症研究中心,美国国立卫生研究院,贝塞斯达20892,医学博士,美国sean.hipp@us.army.mil     

The history and future of the Urologic Oncology Study Group (UOSG) of the Japan Clinical Oncology Group (JCOG)

The Urologic Oncology Study Group (UOSG) of the Japan Clinical Oncology Group was founded in 2001. At the beginning, 41 collaborative institutions participated, and the first group representative was Kenichi Tobisu, from the Shizuoka Cancer Center. In the last 10 years, three JCOG studies have been conducted. In two of them, patient registration has been closed and they are now in the follow-up period. The third study has just started registration in 2011. At present, we have not yet completed the final data analyses in any of the studies. In the meantime, however, we have performed a few retrospective analyses by collecting clinical data from each of the participating institutions, and the results were published as important Japanese data. All the activities of the investigation were supported by the Health and Labor Sciences Research Grants for Clinical Research in Japan. The UOSG encountered great difficulties in planning the prospective study, completing the sophisticated protocol and recruiting the expected number of patients. It usually took a longer time than expected to achieve the final goal. This was probably due to insufficient experience in conducting sophisticated protocol studies and immaturity in managing a study group. Now, the UOSG consists of 38 institutions and is gradually overcoming these problems. In 2011, the UOSG changed its group representative to Yoshiyuki Kakehi from Kagawa University and continues to strive to meet the challenge of becoming a more active group. In this review, we provide an overview of the history and achievements of the UOSG over the past 10 years, along with a list of participating institutions.     

The Breast Health Center at Women & Infants Hospital: origin, philosophy, and features

The Breast Health Center, a component of the program in Women's Oncology at Women & Infants Hospital, is a multidisciplinary center devoted to the treatment and study of benign and malignant breast diseases. The philosophy, structure, and function of The Breast Health Center are described along with its specific components. The Breast Health Center's three fundamental missions of patient care, education, and research are discussed.     

β-catenin及EZH2阳性表达在原发性肝细胞肝癌中的诊断价值

目的探讨β-联蛋白(β-catenin)及zeste 2多梳抑制复合物2亚基增强子(EZH2)阳性表达在原发性肝细胞肝癌(HCC)中的诊断价值和机制。方法选取疑似原发性HCC患者92例,经病理检查确诊为HCC 50例,肝硬化23例,肝血管瘤19例。观察β-catenin及EZH2联合诊断后与甲胎蛋白(AFP)联合诊断的诊断试验结果;检测不同组织中β-catenin及EZH2的阳性表达情况;分析HCC患者组织和血液中β-catenin及EZH2表达的相关性,并观察信号转导及转录激活因子3(STAT3)与二者的相关性。结果以病理检查为"金标准",β-catenin单独诊断HCC的准确度、灵敏度、特异度、阳性预测值、阴性预测值、Kappa值分别为67.4%、78.0%、54.8%、67.2%、67.6%、0.33,EZH2单独诊断HCC的上述指标分别为66.3%、70.0%、61.9%、68.6%、63.4%、0.32;二者与AFP联合诊断HCC的上述指标分别为89.1%、90.0%、88.1%、90.0%、88.1%、0.78。HCC组织中β-catenin和EZH2阳性表达率均高于正常组织、肝硬化组织和癌旁组织,差异均有统计学意义(P<0.05)。血浆中β-catenin及EZH2的表达情况与HCC组织中阳性表达情况均呈正相关(r=0.638、0.920,P<0.05)。HCC组织中STAT3的表达与β-catenin及EZH2的表达均呈正相关(r=0.652、0.423,P<0.05)。结论β-catenin和EZH2在原发性HCC组织中表达水平较高,可以作为原发性HCC的辅助诊断手段,能够提高AFP诊断的准确度,且STAT3可能参与了β-catenin和EZH2的高表达过程。     

A multidisciplinary approach to honest broker services for tissue banks and clinical data: a pragmatic and practical model

BACKGROUND.

Honest broker services are essential for tissue‐ and data‐based research. The honest broker provides a firewall between clinical and research activities. Clinical information is stripped of Health Insurance Portability and Accountability Act‐denoted personal health identifiers. Research material may have linkage codes, precluding the identification of patients to researchers. The honest broker provides data derived from clinical and research sources. These data are for research use only, and there are rules in place that prohibit reidentification. Very rarely, the institutional review board (IRB) may allow recontact and develop a recontact plan with the honest broker. Certain databases are structured to serve a clinical and research function and incorporate ‘real‐time’ updating of information. This complex process needs resolution of a variety of issues regarding the precise role of the HB and their interaction with data. There also is an obvious need for software solutions to make the task of deidentification easier.

METHODS.

The University of Pittsburgh has implemented a novel, IRB‐approved mechanism to address honest broker functions to meet the specimen and data needs of researchers. The Tissue Bank stores biologic specimens. The Cancer Registry culls data and annotating information as part of state‐ and federal‐mandated functions and collects data on the clinical progression, treatment, and outcomes of cancer patients. The Cancer Registry also has additional IRB approval to collect data elements only for research purposes. The Clinical Outcomes Group is involved in patient safety and health services research. Radiation Oncology and Medical Oncology provide critical treatment related information. Pathology and Oncology Informatics have designed software tools for querying availability of specimens, extracting data, and deidentifying specimens and annotating data for clinical and translational research. These entities partnered and submitted a joint IRB proposal to create an institutional honest broker facility. The employees of this conglomerate have honest broker agreements with the University of Pittsburgh and the Medical Center. This provides a large group of honest brokers, ensuring availability for projects without any conflict of interest.

RESULTS.

The honest broker system has been an IRB‐approved institutional entity at the University of Pittsburgh since 2003. The honest broker system currently includes 33 certified honest brokers encompassing the multiple partners of this system. The honest broker system has handled >1600 requests over the past 4 years with a 25% increase in volume each year.

CONCLUSIONS.

The current results indicate that the collaborative honest broker model described herein is robust and provides a highly functional solution to the specimen and data needs for critical clinical and translational research activities. Cancer 2008. © 2008 American Cancer Society.     

Health center and epidemiological research of cancer

There are 851 Health Centers in Japan. The staffs of Health Centers are doctors, dentists, public health nurses and other co-medical staffs. The total number of Health Center staffs is about 35,000. The main functions of Health Centers for community health are prevention of various diseases, health education and survey for environmental problems and Cancer prevention. Especially, Surveillance System of tuberculosis and communicable diseases was taken effect in Jan. 1987. Sometimes, Epidemiological Research of Cancer may be carried out by using the network of Health Centers. But this research system is not yet authorized by national level. The problem on the new functions of Health Centers in the future is discussed now by the special committee on Health Center in which the relationship between Epidemiological Research of Cancer and the function of Health Center will be one of the main theme.     

HPV E6/E7 mRNA和HPV DNA检测技术在宫颈上皮内瘤变中的诊断价值分析

目的比较人乳头瘤病毒(HPV)E6/E7 mRNA和HPV DNA检测技术对宫颈上皮内瘤变(CIN)2级及以上(CIN2+)患者的诊断价值,并评价HPV E6/E7 mRNA检测结果在不同实验室间的一致性。方法采用HPV E6/E7 mRNA和HPV DNA检测技术对212例门诊体检的健康者和住院的宫颈病变患者的宫颈脱落细胞学标本进行检测。以病理诊断结果为金标准,评价两种检测技术诊断CIN2+的灵敏度和特异度。北京市迪安中心实验室和北京市怀柔妇幼保健院实验室均采用HPV E6/E7 m RNA检测技术检测同一批标本,评价实验室间检测的一致性。结果HPV E6/E7 m RNA检测的阳性率为38.7%,与HPV DNA的阳性率43.9%比较,差异无统计学意义(P﹥0.05)。HPV E6/E7 mRNA和HPV DNA的检测阳性率均随着病理分级的升高而增加(P<0.01)。HPV E6/E7mRNA检测CIN2+的灵敏度为92.96%,与HPV DNA的90.14%相比,差异无统计学意义(P﹥0.05),而HPV E6/E7mRNA检测CIN2+的特异度为88.65%,高于HPV DNA的79.43%,差异有统计学意义(P<0.05)。两个实验室采用HPV E6/E7 m RNA检测阳性一致的标本例数为78,阴性一致的标本例数为121,总一致率为93.87%,Kappa=0.872,一致性较好。结论与HPV DNA检测技术相比,HPV E6/E7 mRNA检测宫颈病变的特异度更具优势,实验室间重复性检测的一致率较高,有望成为中国宫颈癌HPV筛查的首选方法。     

The transition of breast cancer treatment and Japan Clinical Oncology Group research over two decades

The Japanese Breast Cancer Study Group (JABCSG) was established before the Japan Clinical Oncology Group (JCOG). The JABCSG became the JCOG Breast Cancer Group 20 years ago. The first chairman of the Breast Cancer Group was Dr Kaoru Abe (National Cancer Center Hospital). Since 1978, five doctors have chaired the Breast Cancer Group. Sixteen clinical trials (eight phase III and eight phase I/II) have been conducted by the Breast Cancer Group since 1985. The Breast Cancer Group was restructured in 2010, and in June 2011 a new clinical trial (JCOG 1017) was initiated. Standard treatment for breast cancer (surgery, radiotherapy and systemic therapy) has changed dramatically over the last two decades. This review describes the transition of breast cancer treatment along with the history of JCOG research in this setting.     

Establishing the multidisciplinary care of patients with cancer in the state of Delaware

Delaware has the fifth highest cancer death rate in the U.S. As part of a comprehensive program to decrease the cancer mortality and incidence in the state, an infrastructure to establish the multidisciplinary care of patients with cancer was established. In May 2002, Christiana Care Health Services opened the Helen F. Graham Cancer Center to meet the specific need for coordinated and centralized comprehensive cancer care. This effort took the cooperation of many individuals in a community-based teaching hospital, the largest of six acute care hospitals in the state. These efforts have led to a 13% accrual rate to the Community Clinical Oncology Program funded by the National Cancer Institute. The effort also led to the establishment of multidisciplinary disease site centers with representation from the three major physician disciplines of surgery, medical oncology, and radiation oncology. In addition, translational research projects, a tissue procurement center, and genetic counseling and testing with the establishment of a high-risk family cancer registry and collaborative efforts with hospitals across the state were established. The current article reviewed the continued success of this program in the state of Delaware in the effort to reduce the cancer incidence and mortality.     

Translating research into evidence‐based practice

The recent rapid acceleration of basic science is reshaping both our clinical research system and our healthcare delivery system. The pace and growing volume of medical discoveries are yielding exciting new opportunities, yet we continue to face old challenges to maintain research progress and effectively translate research into practice. The National Institutes of Health and individual government programs increasingly are emphasizing research agendas that involve evidence development, comparative‐effectiveness research among heterogeneous populations, translational research, and accelerating the translation of research into evidence‐based practice as well as building successful research networks to support these efforts. For more than 25 years, the National Cancer Institute Community Clinical Oncology Program has successfully extended research into the community and facilitated the translation of research into evidence‐based practice. By describing its keys to success, this article provides practical guidance to cancer‐focused, provider‐based research networks as well as those in other disciplines. Cancer 2010. © 2010 American Cancer Society.     

Message from the Editor-in-Chief

Two years have passed since I was appointed Editor-in-Chiefof the Japanese Journal of Clinical Oncology (JJCO), when Iwas promoted to President of the National Cancer Center (NCC)on April 1, 2002. It seems appropriate at this point to lookback on our past activities regarding JJCO and contemplate futureplans. The last two years have been exciting for the editorsand we do hope the same for authors and     

The revision of Guidelines for Clinical Evaluation Methods of Anti-Cancer Drugs in Japan

It has been ten years since the Ministry of Health and Welfare in Japan issued Guidelines for Clinical Evaluation Methods of anti-cancer Drugs in February, 1991. The circumstance surrounding anti-cancer drugs have now changed dramatically with the development of molecular-targeting drugs, introduction of clinical data in overseas countries for approval of new drugs in Japan, etc. Based on these changes, this guideline was revised in November 2005.     

Abstracts

Opinion statement  Adults with glioblastoma multiforme (GBM), the most common primary brain tumor, have an unacceptably poor outcome with conventional cytotoxic therapies. Malignant gliomas are remarkably angiogenic, and vascular endothelial growth factor (VEGF) is the dominant pro-angiogenic factor. Recent clinical trials targeting VEGF signaling have achieved unprecedented rates of durable radiographic and clinical response, while also confirming adequate safety among recurrent malignant glioma patients. An array of additional clinical trials evaluating anti-angiogenic strategies are underway for both recurrent and newly diagnosed malignant glioma patients. Promising results of these approaches suggest that the treatment of GBM may represent an emerging paradigm of anti-angiogenic therapy. Supported by National Institutes of Health Grant nos. 1-P50-CA108786-01, NS20023, and CA11898 and by Grant no. MO1 RR 30 through the General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health.     

Clinical cancer advances 2011: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology

A message from ASCO'S President. It has been forty years since President Richard Nixon signed the National Cancer Act of 1971, which many view as the nation's declaration of the "War on Cancer." The bill has led to major investments in cancer research and significant increases in cancer survival. Today, two-thirds of patients survive at least five years after being diagnosed with cancer compared with just half of all diagnosed patients surviving five years after diagnosis in 1975. The research advances detailed in this year's Clinical Cancer Advances demonstrate that improvements in cancer screening, treatment, and prevention save and improve lives. But although much progress has been made, cancer remains one of the world's most serious health problems. In the United States, the disease is expected to become the nation's leading cause of death in the years ahead as our population ages. I believe we can accelerate the pace of progress, provided that everyone involved in cancer care works together to achieve this goal. It is this viewpoint that has shaped the theme for my presidential term: Collaborating to Conquer Cancer. In practice, this means that physicians and researchers must learn from every patient's experience, ensure greater collaboration between members of a patient's medical team, and involve more patients in the search for cures through clinical trials. Cancer advocates, insurers, and government agencies also have important roles to play. Today, we have an incredible opportunity to improve the quality of cancer care by drawing lessons from the real-world experiences of patients. The American Society of Clinical Oncology (ASCO) is taking the lead in this area, in part through innovative use of health information technology. In addition to our existing quality initiatives, ASCO is working with partners to develop a comprehensive rapid-learning system for cancer care. When complete, this system will provide physicians with personalized, real-time information that can inform the care of every patient with cancer as well as connect patients with their entire medical teams. The rapid learning system will form a continuous cycle of learning: securely capturing data from every patient at the point of care, drawing on evidence-based guidelines, and evaluating quality of care against those standards and the outcomes of other patients. Clinical trials are another area in which collaboration is critical. Increasing clinical trial participation will require commitment across the cancer community from physicians, patients, insurers, hospitals, and industry. A 2010 report by the Institute of Medicine described challenges to participation in trials by both physicians and patients and provided recommendations for revitalizing clinical trials conducted through the National Cancer Institute's Cooperative Group Program. ASCO has pledged its support for the full implementation of these recommendations. More broadly, ASCO recently outlined a bold vision for translational and clinical cancer research for the next decade and made recommendations to achieve that vision. Accelerating Progress Against Cancer: ASCO's Blueprint for Transforming Clinical and Translational Research, released in November, calls for a research system that takes full advantage of today's scientific and technologic opportunities and sets a high-level agenda for policy makers, regulators, and advocates. Cancer research has transformed cancer care in the past forty years, and this year's Clinical Cancer Advances illustrates how far we have come in the past year alone. We now have a tremendous opportunity to use today's knowledge and collaborate across all facets of cancer care to conquer this deadly disease. Michael P. Link, MD President American Society of Clinical Oncology.     

An ET-CURE Pilot Project Supporting Undergraduate Training in Cancer Research, Emerging Technology, and Health Disparities

The National Cancer Institute's Center to Reduce Cancer Health Disparities has created pilot training opportunities under the "Continuing Umbrella of Research Experiences" program that focus on emerging technologies. In this pilot project, an 18-month cancer biology research internship was reinforced with: instruction in an emerging technology (proteomics), a transition from the undergraduate laboratory to a research setting, education in cancer health disparities, and community outreach activities. A major goal was to provide underrepresented undergraduates with hands-on research experiences that are rarely encountered at the undergraduate level, including mentoring, research presentations, and participation in local and national meetings. These opportunities provided education and career development for the undergraduates, and they have given each student the opportunity to transition from learning to sharing their knowledge and from being mentored to mentoring others. Here, we present the concepts, curriculum, infrastructure, and challenges for this training program along with evaluations by both the students and their mentors.     

Psychosocial and supportive-care needs in high-grade glioma

The diagnosis and management of high-grade glioma has profound effects on patients and their families. Guidance issued by the UK National Institute of Health and Clinical Excellence in 2006 highlighted the lack of good studies of palliative care for patients with this disease. We describe new studies published from 2000 to 2007. High-grade glioma is undoubtedly a challenging research area, and many studies are poorly defined and have small and biased samples. Nevertheless the data reveal this to be a heterogeneous group of patients with complex needs that differ from those of patients with other cancers. Improvements in care require a united input from neurology and neurosurgery, oncology, and palliative care. The main research priorities are the development and assessment of psychosocial or supportive interventions and the investigation of service provision of specialist palliative and end-of-life care, which have hitherto been neglected.     

Cole's precancerous hyperplasia of the breast

Due to his recognition as the discoverer of the first test for visualization of the gallbladder, his profile research on dissemination of cancer and his stimulation and interest in stress and immunity, one of Warren Cole's most significant reports has not been accorded due recognition. In 1944, Cole presented data at the Southern Surgical Association Meeting which clearly identified the premalignant histologic change in the breast. In the published report, Cole and Rossiter [Ann Surg 119:573-590, 1944] presented a classification of benign breast histology: 1) adenofibrosis, 2) parenchymatous hyperplasia, 3) precancerous hyperplasia, and 4) cystic disease. Following the work of Warren in 1940 [Surg Gynecol Obstet 71:257-273], who stated that the chronic cystic mastitis had an incidence of breast cancer over 3 times the expected rate, this report of Cole and Rossiter focused on the worrisome lesion atypical epithelial hyperplasia. Since then, Haagensen ["Diseases of the Breast," Philadelphia: Saunders] has stressed that gross cystic disease is the lesion most associated with increased risk of cancer. In an attempt to resolve these seeming contraindications, we reviewed the charts of patients referred to a private breast clinic. With the advent of mammography, sonography, and thermography, the incidence and management of benign breast diseases has changed over the years. This study focuses on the current management of breast masses and reinforces the significance of Cole's classification.     

Colorectal cancer and solar radiation

It has been suggested that sunlight might have a role in the prevention of colorectal cancer via a mechanism involving vitamin D. We used data from nine population-based cancer registries in the United States to analyze incidence rates for colon and rectal cancer during 1973–84 as a function of regional variation in the levels of available solar radiation. Data were restricted to include only those persons born and diagnosed in the same state. Incidence rates of colon and rectal cancer among men tended to increase with decreasing levels of solar radiation. Compared to rates in New Mexico and Utah, for example, rates in the Detroit area (MI), Connecticut, and western Washington were 50 percent to 80 percent higher. Among women, colon cancer rates showed a similar trend, though of smaller magnitude; rates of rectal cancer among women did not vary in relation to levels of available solar radiation.Dr Emerson, at the time of this research, was with Dr Weiss at the Department of Epidemiology, University of Washington, School of Public Health and Community Medicine, Seattle, WA and the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Address correspondence to Dr Emerson at her current address: Arizona Cancer Center, Room 2942, University of Arizona, Tucson, AZ 85724, USA. This research was supported in part by Grant No. 1-R35-CA39779 and Grant No. 5-T32-CA09168-13 from the National Cancer Institute.     

Department of Defense Prostate Cancer Clinical Trials Consortium: A New Instrument for Prostate Cancer Clinical Research

Background

In 2005, the US Department of Defense, through the US Army Medical Research and Materiel Command, Office of the Congressionally Directed Medical Research Programs, created a funding mechanism to form a clinical trials consortium to conduct phase I and II studies in prostate cancer. This is the first report of the Prostate Cancer Clinical Trials Consortium (PCCTC).

Patients and Methods

The Department of Defense award supports a consortium of 10 prostate cancer research centers. Memorial Sloan-Kettering Cancer Center was awarded the Coordinating Center grant for the consortium and charged with creating an infrastructure to conduct early-phase multicenter clinical trials. Each participating center was required to introduce ≤1 clinical trial per year and maintain accrual of a minimum of 35 patients per year.

Results

The PCCTC was launched in 2006 and now encompasses 10 leading prostate cancer research centers. Fifty-one trials have been opened, and 1386 patients have been accrued at member sites. Members share an online clinical trial management system for protocol tracking, electronic data capture, and data storage. A legal framework has been instituted, and standard operating procedures, an administrative structure, editorial support, centralized budgeting, and mechanisms for scientific review are established.

Conclusion

The PCCTC fulfills a congressional directive to create a clinical trials instrument dedicated to early-phase prostate cancer studies. The member institutions have built an administrative, informatics, legal, financial, statistical, and scientific infrastructure to support this endeavor. Clinical trials are open and accruing in excess of federally mandated goals.