The Application of Evidence-Based Medicine in Individualized Medicine.

The fundamental aim of healthcare is to improve overall health of the population by providing state-of-the-art healthcare for individuals at an affordable cost. The foundation for this system is largely referred to as "evidence-based medicine". Too often, evidence-based medicine is based solely on so-called "best research evidence", collected through randomized controlled trials while disregarding clinical expertise and patient expectations. As healthcare gravitates towards personalized and individualized medicine, such external clinical (research) evidence can inform, but never replace, individual clinical expertise. This applies in particular to orphan diseases, for which clinical trials are methodologically particularly problematic, and evidence derived from them is often questionable. Evidence-based medicine constitutes a complex process to allow doctors and patients to select the best possible solutions for each individual based on rapidly developing new therapeutic directions. This requires a revisit of the foundations of evidence-based medicine. A proposition as to how to manage evidence-based data in individualized immune-oncology is presented here.

Stem cells-derived natural killer cells for cancer immunotherapy: current protocols, feasibility, and benefits of ex vivo generated natural killer cells in treatment of advanced solid tumors.

Nowadays, natural killer (NK) cell-based immunotherapy provides a practical therapeutic strategy for patients with advanced solid tumors (STs). This approach is adaptively conducted by the autologous and identical NK cells after in vitro expansion and overnight activation. However, the NK cell-based cancer immunotherapy has been faced with some fundamental and technical limitations. Moreover, the desirable outcomes of the NK cell therapy may not be achieved due to the complex tumor microenvironment by inhibition of intra-tumoral polarization and cytotoxicity of implanted NK cells. Currently, stem cells (SCs) technology provides a powerful opportunity to generate more effective and universal sources of the NK cells. Till now, several strategies have been developed to differentiate types of the pluripotent and adult SCs into the mature NK cells, with both feeder layer-dependent and/or feeder laye-free strategies. Higher cytokine production and intra-tumoral polarization capabilities as well as stronger anti-tumor properties are the main features of these SCs-derived NK cells. The present review article focuses on the principal barriers through the conventional NK cell immunotherapies for patients with advanced STs. It also provides a comprehensive resource of protocols regarding the generation of SCs-derived NK cells in an ex vivo condition.

Position paper: new insights into the immunobiology and dynamics of tumor-host interactions require adaptations of clinical studies.

INTRODUCTION: Prospective double-blind placebo-controlled randomized clinical trials (RCTs) are considered standard for the proof of the efficacy of oncologic therapies. Molecular methods have provided new insights into tumor biology and led to the development of targeted therapies. Due to the increasing complexity of molecular tumor characteristics and of the individuality of specific anti-tumor immune reactivity, RCTs are unfortunately only of limited use. AREAS COVERED: The historical methods of drug research and approval and the related practices of reimbursement by statutory and private health insurance companies are being questioned. New, innovative methods for the documentation of evidence in personalized medicine will be addressed. Possible perspectives and new approaches are discussed, in particular with regard to glioblastoma. EXPERT OPINION: Highly specialized translational oncology groups like the IOZK can contribute to medical progress and quick transfer 'from bench to bedside.' Their contribution should be acknowledged and taken into account more strongly in the development of guidelines and the reimbursement of therapy costs. Methodological plurality should be encouraged.

Long-term survival of a breast cancer patient with extensive liver metastases upon immune and virotherapy: a case report.

Liver metastases in breast cancer are associated with a poor prognosis. We report long-term survival of a patient with breast cancer and liver metastases. After operation the patient declined further standard therapy. Instead, she was treated with local hyperthermia, Newcastle disease virus and dendritic cell vaccination at the Immunological and Oncological Center Cologne (IOZK), Germany. A continuous high quality of life was reported and the patient survived more than 66 months after initial diagnosis. No recurrence or further metastases developed under treatment. Following treatment, a long-lasting tumor-reactive memory T-cell responsiveness could be documented. This possibly explains the favorable course of disease. Since this combination of therapies is not restricted to a particular tumor type, further exploration is warranted.

Long-term remission of prostate cancer with extensive bone metastases upon immuno- and virotherapy: A case report.

The present study reports the case of a patient with hormone-refractory metastatic prostate cancer who had failed standard therapy, but then achieved complete remission following combined treatment with local hyperthermia (LHT), Newcastle disease virus and dendritic cell (DC) vaccination, which was an unusual combination. In August 2005, the patient underwent a radical prostatectomy. Despite standard treatment, the patient developed progressive bone metastases and stopped conventional therapy in June 2007. Starting in October 2007, the patient was treated with LHT, oncolytic virotherapy and DC vaccination. Prostate-specific antigen (PSA)-levels, with the highest level of 233.8 ng/ml in January 2008, decreased to 0.8 ng/ml in late February 2008. In March 2008, a reduction in bone metastases could be detected by positron emission tomography/computed tomography. Since then, the PSA levels have remained low and the patient is doing well. The treatment induced a long-lasting antitumor memory T-cell response. This possibly explains the long-term effectiveness of this novel experimental combined treatment approach.