Day 2 :
Keynote Forum
Kenichiro Hasumi
Hasumi International Research Foundation, Tokyo, Japan
Keynote: Intra-tumoral injection of dendritic cells induces specific anti- tumor killer T-cell activity
Time : 10:00-10:30
Biography:
Kenichiro Hasumi, M.D. has completed medical education at Saitama Medical University in 1978. He is chairperson of Hasumi International Research Foundation in United States and visiting proffessor of Thomas Jefferson University. Dendritic cell based clinical research works satrted in 1995 in Japan.rnDean L Mann MD received is meidical education at St Louis University School of Medicie, St.Louis MO. He currently is Professor of Pathology and Head of Immunogenetics at The University of Maryland School of Medicine, Baltimore MD USA
Abstract:
A therapeutic approach to treat cancer patients with extensive disease was developed wherein tumor specific immunity is initiated in the antigenic enviornment of the individual tumor. Patients with advanced or treatment refractory cancers were enrolled in a safety/feasibility study combining a conventional treatment modality, intensity modulated radiotherapy (IMRT), with direct intra-tumoral injection of autologous dendritic cell. The rational for this approach follows. Radiation reduces cancer cell proliferation and leads to cell apoptosis and release of potential tumor antigens. Additional radiation effects include depletion of the number of immune regulatory cells and the release of proinflamatory cytokines that support the induction of an antitumor cytotoxic killer T-cells (CTL) by the intra-tumoral injected immature dendritic cells (iDC). The metastatic sites targeted for treatment were identified by PET-CT, injected with iDC combined with a cytokine-based adjuvant and KLH (keyhole limpet hemocyanin). 24hr later autologous T cells expanded in-vitro with anti-CD3 and IL-2 were administered by IV-infuion (AT). Seven (7) days later, the iDC injected lesions were radiated by IMRT and followed by repeat injection of intra-tumoral iDC and IV-infused AT. No toxicity was observed with iDC injection or AT infusion while occasional mild radiation related side effects were observed. After 6 weeks later of second iDC injection, PET-CT evaluated the efficacy if treated sites are still active and/or untreated new lesions are activated. The majority of patients developed KLH antibodies suggesting that the co-injected iDC are functional with the capacity to accquire antigens from their environment and generate an adoptive immune response. Both cellular and humoral immune responses were observed, the former by CTL activity to autologous tumor cell lines established from several patients, the later by increasing titer of anti-mesothelin antibodies in cells and serum samples drawn before and after treatment. Therapeutic responses were related to size and number of lesion present. In 1 year follow up 23/37 patients with 5 or less lesions that were 3 cm or less in diameter achieved complete response (CR) and 5 of this group PR. Delivery of this treatment regimen relative to prior therapy appears to influence response. In 57 cases of stage IV or recurrent NSCLC only one of 41 cases who chemo-resistant in their treatment history showed complete response (CR) while 4 of 6 cases who were chemo-naive reached CR. In summary this treatment protocol wherein radiation is combined with immunotherapy has shown to be effective in inducing therapeutic responses in patients with advanced cancers.
Keynote Forum
James R Mansfield
Director of Tissue Applications PerkinElmer, Inc, USA United State of America
Keynote: Imaging in cancer immunology: Phenotyping of multiple immune cell subsets in situ in FFPE tissue sections
Time : 10:30-11:00
Biography:
James Mansfield is a scientist with over 25 years of experience in spectral imaging, in-vivo spectroscopy and applied data analysis, directed towards finding of novel optical methods for the diagnosis and monitoring of medical conditions. He is currently the Director of Quantitative Pathology Applications at PerkinElmer where he is the senior application scientist for their multispectral and digital pathology product lines. He is an associate editor of the American Journal of Nuclear Medicine and Molecular Imaging, holds 6 patents, has over 50 publications and has served as an invited speaker, session chair and organizer at a variety of international conferences.
Abstract:
There has been a rapid grown in the field of tumor immunobiology in recent years as a result of recent successes in cancer immunotherapies and it is becoming clear that immune cells play many sometimes conflicting roles in the tumor microenvironment. However, obtaining phenotypic information about the various immune cells that play these roles in and around the tumor has been a challenge. Existing methods can either deliver phenotypic information on homogenous samples (e.g., flow cytometry or PCR) or morphologic information on single immunomarkers (standard IHC). We present here a methodology for delivering quantitative per-cell marker expression and phenotyping, analogous to that obtained from flow cytometry but from cells imaged in situ in FFPE tissue sections. This methodology combines: The sequential multi-marker labeling of up to 6 antigens using antibodies all of the same species in a single section; automated multispectral imaging (MSI) to remove the typically problematic FFPE tissue auto fluorescence and correct cross-talk between fluorescent channels and an automated image analysis that can quantitate the per-cell marker expression, determine the cellular phenotype, count these cells separately in the tumor compartment and in the stroma and provide high-resolution images of their distributions. We present here several examples of this new methodology in breast, lung and head and neck cancers. Each application example will show 6-plex multiplexed staining, per-cell quantitation of each marker and multi-marker cellular phenotyping from multispectral images of standard clinical biopsy sections, as well as methods to explore the spatial distributions of the phenotyped cells in and around the tumor.
- 3 Immune System Tumors
10 Immune checkpoint inhibitors
12 Combining Cancer Immunotherapies
14 Cancer Micro & Immuno Environment
17 Tumor biology
Location: Melbourne, Australia
Session Introduction
MarÃa del Rosario Dávalos Gamboa
University of San Simón, Bolivia
Title: Immune system, emotional problems and stress in kids and tenns with cancer of cochabamba, bolivia
Time : 11:15-11:40
Biography:
MarÃadel Rosario Dávalos Gamboa has completed her PhD at the Universidad Mayor Real and Pontifical San Francisco Xavier de Chuquisaca, Bolivia and Specialty in Clinical Biochemistry and Immunology at University of San Simón in Cochabamba, Bolivia. She was the Director of the Research Institute of the Faculty of Dentistry at the University of San Simón in Cochabamba, Bolivia. She is currently a Professor of the subject of Biochemistry of Faculty of Dentistry UMSS and is also majority shareholder of the industrial unit" Asociada Internacional de aceites y carbones SRL ACECAB" of Bolivia. She has published more than 10 articles in leading journals.
Abstract:
Introduction: In the Plurinational State of Bolivia is little known as influenced, of the status immunological, emotional problems and stress in cancer of children and adolescents. Objectives: The objective of this study was to determine the influence they had, the immune system, emotional problems and stress for the development of different types of cancer in children and adolescents in the region of Cochabamba, Bolivia. Methods: Cross-sectional study realized in January and February 2016, in children and adolescents who regularly attend in Hospital Manuel Ascencio Villarroel, with aged 2 months to 16 years of age (n=45) in the region of Cochabamba (Bolivia). Parents and or guardians of participants were surveyed. A descriptive analysis was performed. Results: They had two or more signs and symptoms (low immunity) that the immune system was weakened 86.67%. They were usually affected by influenza and viruses 51.11% had muscle pain and joint constant 44.44%, had watery eyes and nose running 35.55%, had persistent headache 40%, much tired and fatigued despite the rest 35.56%, sick regularly 31.11%, was delayed recovery of disease 28.88%, exhibited a fixed pattern of disease 28.88% and quarreled endlessly with the disease 24.44%. They had two or more warning signs, symptoms and physical changes in stress 79.26%. Especially, headache and stomach 53.33%, disturbance in food 51.11%, they felt anxious 48.89%, were too sensitive 46.67%, were tired 44.44%, had nightmares 37.77 %, they were distracted or thoughtful 33.33%, were concerned 31.11%, her hands sweat 22.22%. They had one or more emotional problems mismanaged, for loss, failure or trauma 60.0%. Often they felt: Distressed 40%, depressed or anxious 37.78%, exhausted 33.33%, felt fear or loneliness 22.22%, angry 20%, extreme anxiety 15.56% and nervous anguish 15.56%. Conclusions: This study found that for the development of cancer suffered by children and adolescents, they influenced both mismanaged emotional problems, as stress and especially the immune system weakened in them, as a result of psychosomatic disorders that exposed them to the disease.
Ben Tran
Eliza Hall Institute of Medical Research, Australia
Title: Immune profile and survival outcomes in stage 2 colon cancer
Time : 11:20-11:45
Biography:
Ben Tran is an medical oncologist who is heavily involved in drug development, molecular profiling and personalised medicine aiming to develop better treatments for cancer through laboratory research and clinical trials. His research focuses on matching people with the best treatment for their individual cancer. In particular, I am studying how the genome of cancer cells interacts with the body’s anti-tumour immune response. He is particularly interested in personalising cancer treatments, assessing potential new anti-cancer drugs through early phase clinical trials. He is also also pursuing studies of cancer immunotherapy. His medical practice focuses on urological and colorectal cancers, and He is currently conducting clinical trials using novel immunotherapeutic targeting these cancers.
Abstract:
Background Tumor associated immune response impacts outcomes in cancer. In colon cancer (CC), a good immune response, as represented by a dense lymphocytic infiltrate, is known to be associated with improved overall survival (OS). To date studies have used a subjective scoring system and OS benefits have been presumed to solely be the consequence of reduced cancer recurrence. The relationship with deficient mismatch repair (dMMR) status, a good prognostic marker that is typically associated with an immune infiltrate, remains unexplored. We examined an objectively determined Immune Profile (IP) and survival outcomes in stage 2 CC. Methods Stage 2 CC cases were identified from a hospital registry that prospectively records comprehensive point of care data, including recurrence free survival (RFS) and OS. MMR status was determined by immunohistochemistry. The density of CD3 and CD8 T-cells within each tumor was assessed by immunostaining and automated image analysis. A pattern recognition algorithm scored CD3 and CD8 density at the tumor core (TC) and invasive margin (IM). Raw scores for each region (CD3TC, CD3IM, CD8TC and CD8IM) were added and categorised as IP High or IP Low. Survival analyses used the Kaplan–Meier method and log-rank test. Results We included 463 subjects with stage II CC, median age 70.4 years, with median follow-up 57.7 months. 93 (16.5%) tumors were dMMR. 220 (47.5%) tumors were categorised as IP high. IP High was associated with improved survival outcomes compared to IP Low, including RFS (HR 0.25, p<0.001), post-recurrence survival (HR 0.20, p<0.001), cancer-specific survival (HR 0.08, p<0.001) and OS (HR 0.10, p<0.001). The improved RFS for IP high cases was independent of MMR status (dMMR: HR 0.10, p = 0.03; pMMR: HR 0.27, p<0.001). In patients without recurrence IP High was associated with reduced non-cancer deaths (HR 0.10, p<0.001). Conclusion Using an automated and objective measure, we have confirmed that immune infiltration is strongly associated with improved RFS and OS in stage II CC, independent of MMR status. We have also shown that a good immune response (IP High) is associated with post recurrence survival (where cancer recurs), and with reduced non-cancer mortality in patients that remain recurrence free.
Yoshihiro Komohara
Kumamoto University, Japan
Title: The significance of lymph node macrophages in the induction of anti-cancer immune response
Time : 11:45-12:10
Biography:
Yoshihiro Komohara has completed his PhD at the age of 29 years from Kumamoto University. He is a pathologist and now working at Kumamoto University as Associate Professor. He has studied tumor-associated macrophages for around 10 years and has published more than 20 papers related to CD163-positive tumor-associated macrophages. He has also focused on the relationship between cancer immunology and lymph node macrophages.
Abstract:
It is well known that many macrophages are distributed in lympho-reticular organs including spleen and lymph node (LN). Spleen and LNs are respectively involved in the filtration of lymph and blood flow, and immune responses are induced by activation of lymphocytes and natural killer cells which are dependent on antigen presenting cells (APCs) including dendritic cells and macrophages. CD169 (sialoadhesin) is a sialic acid receptor that is specifically expressed on macrophages, including lymph node sinus macrophages. Animal studies suggested that CD169+ macrophages in lymph nodes have tumor preventing properties; however, the role of these cells in the pathogenesis of human tumors has not been clarified. In order to determine the significance of CD169+ macrophages in cancer patients, we employed tissue samples from patients with malignant tumor including malignant melanoma and colorectal cancer and evaluated the relationships of this expression with overall survival and various clinicopathological factors. The high density of CD169+ cells was found to be significantly associated with a longer overall survival in the patients with malignant melanoma, colorectal cancer, and endometrial cancer. Positive correlations were noted between the density of CD169+ macrophages and the density of CD8+ cytotoxic T cells infiltrating tumor tissues. CD169+ macrophages in lymph node are suggested to be involved in T cell-mediated antitumor immunity and may be a useful marker for assessing the clinical prognosis and monitoring antitumor immunity in patients with malignant tumors.
Nalini Kant Pati
Australian National University, Canberra, Australia
Title: Autoimmune disorders and Lymphoma
Time : 12:10-12:35
Biography:
Dr Nalini Pati is currently working as a consultant Adult and Paediatric Haematologist in Haematology Oncology in Canberra Hospital, Canberra and Clinical Senior Lecturer at Australian National University Medical School, Canberra, Australia. He has published more than 20 papers in reputed journals and has been serving as an editorial board member of few journal.
Abstract:
When autoimmunity began to emerge as a recognized disease process around 1950s, numerous studies linked several different autoimmune diseases with benign and malignant lympho-proliferative disorders in humans as well as animal models. Cuttner et al have investigated the relationship of prior autoimmune disease to the development of non-Hodgkin's lymphoma (NHL). Patients with NHL (n=278) seen during the 10 years period were compared with the controls, (n=317) seen at the same time. A comparison between these patient groups was performed based on various statistical analysis as well as logistic regression analysis to ascertain the risk of autoimmunity in NHL. 36 (13%) NHL patients had a prior autoimmune disease compared to 5% of controls (p=0.001). 69% of NHL patients with a prior autoimmune disease were female compared to 43% without a prior autoimmune disease and this was similar in control patients, 69% and 48%, respectively. 20% of all women with NHL had a history of autoimmune disease compared to 7% of women in the control group (p=0.001). 19 of the NHL patients with autoimmune disease (56%) received immunosuppressive treatment compared to 5 (38%) in the controls. Strength of association Existing clinical data on the autoimmunity-lymphoma association are rather meagre because many of the clinical studies have been anecdotal case collections rather than well studied prospective studies2. However, adequate studies establish strong associations between B cell lymphomas and Sjögren’s syndrome, autoimmune thyroiditis and autoimmune haemolytic anaemia. Apoptosis The role of defective apoptosis in the genesis of lymphoproliferation, autoimmunity and lymphoma was dramatically illustrated by the autoimmune lymphoproliferative syndrome (ALPS) of childhood. ALPS is the result of dominant heterozygous inheritance of a mutated (inactive) gene, (NIH), lymphoma occurred in 6 of 46 individuals, 13% of patients, usually long after the onset of ALPS at intervals from 6–48 years. Sustained antigen drive An example of such mechanism would be the chronic H. pylori infection that drives the host response, with T cell stimulation, ultimately generates an active lympho proliferating in B cell population. The ensuing MALT lymphoma will regress up to a certain point if H. pylori is eradicated. However, acquisition of particular chromosomal translocations among reactive B cells are lymphomogenic. Mutagenicity among B cells The third mechanism: B cell mutagenicity. Early B cell developmental events in the bone marrow operate to generate the B cell antigen receptor (BCR). Leading to further diversification of the BCR and developmwnt of lymphoproliferative disorder. Hodgkin’s disease: Personal history of autoimmune diseases is consistently associated with increased risk of non-Hodgkin’s lymphoma.6 Recent data also indicate that the risk of HL is increased following autoimmune diseases.7–9 Kristinsson et al, recently analyzed the association of a personal history of autoimmune conditions in 7,476 HL patients compared to 18,573 controls, and found several autoimmune conditions to be strongly associated with HL, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sarcoidosis, and immune thrombocytopenic purpura (ITP). It was found that an overall 2.7-fold increased risk for all systemic autoimmune diseases combined.
Purwati
Universitas Airlangga, Indonesia
Title: The role of immunotherapy for stem cell cancer
Time : 13:25-13:50
Biography:
Purwati has finished in general practitioner from Airlangga University in 1997, has completed in internal med. Specialist in 2008 from Airlangga University also and taken Doctoral program in Airlangga University 2010-2012. Interest in stem cell field from 2008, be secretary of stem cell laboratory of Airlangga University and also secretary of Surabaya Regenerative Medicine Centre. 2015 be a chairman of stem cell research and development centre Universitas Airlangga Surabaya Indonesia. Have almost 50 publication in journals, papers, and seminar.
Abstract:
Aim: The role of immunotherapy for stem cell cancer. Method: Type of cancer are Carcinoma: Cancer of endo or ectoderm e.g., skin or epithelial lining of organs, Sarcomas: Cancer of mesoderm e.g., bone, Leukemias and Lymphomas: Cancers of hematopoietic cells. Molecular basis of cancer are dividing into three: The first is mutation was caused by radiation, chemicals and viruses; the second is up regulation of the proto oncogens and the third is down regulation of tumor suppressor genes. Cancer growth from cancer of stem cell with modality treatment of cancer was surgery, radiation, chemotherapy, Cryotherapy, radiofrequency, PBMCT, BMCT, until immunotherapy. Treatment modality was chosen depending on staging of cancer, but cancer of stem cell was known to resistance with conventional treatment, so for eliminated that the newest issue with immunotherapy. And also patients with metastasis staging of cancer usually also refracted with conventional treatment. So stem cell transplantation combination with immunotherapy will promise to give solution for that problem. Result: Haematopetic stem cell transplantation (HSCT) is a procedure to restoration bone marrow function as the result of giving cytotoxic drugs with or without whole body radiation. Source of stem cell from peripheral blood (PBMCs) or bone marrow or umbilical cord blood (UMCB) is autologus or allogenic. Conclusion: Stem cell combination with immunotherapy process was given separate or together, immunotherapy with NK cell or DCs autologous or allogenic. In vitro co culture between NK cell and leukemia cell, this cell could reduce the leukemia cell population, and also used in animal trial. Clinical trial on patient with solid tumor were treatment with immunotherapy with NK cell with the result of reducing of tumor size, with the reason because of NK cell have specific receptor as anti tumor, and also if given together with allogenic could prevent or decreasing rejection HSCT because of the unique properties of NK cell.
Roberta Mazzieri
The University of Queensland Diamantina Institute, Australia
Title: Tumor associated Tie2+ macrophages: Novel targets and effectors of anti-breast cancer therapies
Time : 13:50-14:15
Biography:
Roberta Mazzieri has obtained her PhD in Genetic Science from the University of Pavia, Italy and subsequently undertook one Post-doctoral position at the New York University, USA and two at the San Raffaele Scientific Institute in Milan, Italy. In 2012, she was nominated by the Young Ambassadors from the Metastasis Research Society (MRS) to speak at MRS meeting in recognition of her potential to launch independent research and contribute to high-quality publications. The same year she was recruited by the University of Queensland, Brisbane to establish her own research group to continue her work on targeting pro-tumoral macrophages.
Abstract:
While advances in treatment and screening have greatly improved outcomes for most breast cancer patients, major unmet needs remain for treatment of patients with metastatic disease. Breast cancer has not benefitted to the same extent as other cancers from the recent introduction of immunotherapies due to poor inherent immunogenicity of breast tumors associated with a highly immunosuppressive microenvironment. New strategies are needed to overcome these limitations. We identified and characterized a subpopulation of pro-tumoral macrophages: The Tie2-expressing monocytes/macrophages (TEMs) endowed with pro-angiogenic and immunosuppressive activities, both involving signaling through the ANG2/TIE2 pathway. Indeed we demonstrated that blocking the ANG2/TIE2 pathway disables the pro-angiogenic activity of TEMs resulting in inhibition of tumor angiogenesis, growth and metastasis in mouse models of breast carcinogenesis. We are now investigating whether the in vivo blockade of ANG2 is not only inhibiting the pro-angiogenic activity of TEMs, but also reverting their immunosuppressive activity, thus providing a strong rational for the development and testing of new combination therapies. Moreover, by exploiting the tumor homing ability of TEMs we turned them into an efficient vehicle for the tumor-targeted delivery of a potent immune-stimulatory molecule: Interferon-alpha (IFNα). We think that the multiple activities of type I IFNs in the complex network of cell interactions that lead to activation and deployment of immune responses may represent a valid strategy to promote and improve the outcome of cancer immunotherapy for the treatment of advanced breast cancer including lung and bone metastasis.
- Poster Presentation
Location: Melbourne, Australia
Session Introduction
Hussein A. Kaoud
Cairo University, Giza-Egypt
Title: Molecular Tumor Markers: Diagnosis and Therapy
Time : 14:15-15:35
Biography:
Hussein Abd Elhay Kaoud is a full Professor at Cairo University, Egypt. He has published more than 190 articles and scientific books and patents. He is a Member of several Egyptian and international societies. He is the Editor and Reviewer of many international journals and received many awards.
Abstract:
Molecular tumor markers can be produced directly by tumor or non tumor cells as a response to the presence of a tumor. Most tumor markers are tumor antigens but not all tumor antigens can be used as tumor markers. Molecular markers are diagnostic, prognostic or predictive. The article discussed the molecular tumor markers; significance of each markers and its role in diagnosis, prognosis and prediction of tumor and tests used. It is used to distinguish tumor from normal tissue or to detect the presence of a tumor on the basis of measurements in the blood or secretions. And it is currently being put new molecular markers with an increased understanding of the molecular environment of the cell tumor and other disease cells. It can produce tumor markers directly from the tumor or by non-cancer cells in response to the presence of a tumor. Most tumor markers are tumor antigens but not all tumor antigens can be used as tumor markers. Concerning drug evaluation and check effects of drug treatment on the tumor, biomarkers perhaps can determine the appropriate dose in the early stages of a new antidepressant medication for cancer clinical development. Biomarkers and prognostic expects the natural course of cancer and excellence as a result of the tumor. They also help determine who to treat, how aggressively to treat and which candidates are likely to respond to a particular drug and the dose is most effective. Theranostic, use a combination of diagnosis and therapy sessions and can be different perception. Imaging can be used to track drug delivery within the body. However, imaging can also be used to stimulate drug releasing from the outside by external influences. These external influences to be laser light, temperature or ultrasound, for example. In the forefront, smart probes represent new innovative concepts for clinical application. Nanoparticles can be used to make selective surfaces for molecular interactions target. For example the population H biomarker present in the blood will be characterized fully, pads harvesting nano-particle has a great potential to improve the detection of the disease at an early stage and more treatable.
Afaf Ibrahim
Alexandria University, Egypt
Title: Determination of a cut-off point for Prostatic Specific Antigen (PSA) to avoid unjustified biopsy among asymptomatic Egyptians
Time : 14:15-15:35
Biography:
Afaf Gaber Ibrahim Salama Elhanash is currently a Professor of Public Health, Social and Preventive Medicine. Community medicine and Public Health Department, Alexandria Faculty of Medicine. Egypt. She is also a Head of Evidence based clinical practice guidelines center affiliated to Healthcare Quality Directorate of Alexandria university hospitals. (Founded Nov. 2008, Member of Guidelines International Network (G-I-N Since May 2009 ), Visiting professor in Arabic Bierut University in Lebanon in 2001, WHO Short term consultant: Participated as an international supervisor in conducting Retrospective Crude Mortality survey conducted in Greater Darfur Region, Sudan in May-June 2005 & Visiting Professor at Arab Academy for Science ,Technology and maritime transport as course instructor of Best Practice Guidelines course for Master of health care management. She has published many articles in reputed journals.
Abstract:
Introduction & Objectives: In Egypt, there is no national screening program for prostate cancer. The Urology Department in Alexandria University established a screening program for prostate cancer among men aged more than 55 years in January 2012. The aim of the present study was to determine a PSA cut-off point for performing Transrectal Ultrasonography (TRUS) guided biopsy among asymptomatic men. Material & Methods: This study included 1207 men aged more than 55 year of age who were attending Urology Department, Alexandria University for non prostatic symptoms and accepted to be screened. Digital Rectal Examination (DRE) and PSA level measurement were performed for all included subjects. Transrectal ultrasonography (TRUS) guided biopsy was done for those who found to have PSA>4 ng/ml and or suspicious DRE. Results: A minority of screened subjects (13%) had PSA of more than 4 ng/ml. Transrectal ultrasonography (TRUS) guided biopsy was performed for 157 subjects who had PSA>4 ng/ml and or suspicious DRE findings. One patient with a PSA>4 ng/ml who had suspicious DRE finding proved by TRUS biopsy to have prostate cancer giving PPV=100. Among those who have PSA level of 4.1-10, PPV is 54 among those with suspicious DRE findings as compared to 0 among those with non suspicious DRE. A higher PPV is observed for those who had PSA level of 10.1-20 and >20 with suspicious DRE findings (77 and 100 respectively). The mean serum total PSA was 77 and 0.6 ng/ ml for patients with and without prostatic cancer respectively (p=0.0001). The yield of cancer prostate among all screened patients was 103/1207=8% and 103/157=65% among those with PSA>4 ng/ml and were biopsied. Considering all the patients who had biopsy based on PSA and or DRE, ROC curve could derive a cut-off value of 10.05 ng/ml with a sensitivity of 92 percent and a specificity of 92.6 percent (area under curve, AUC 0.973±0.012, 95% CI (.950-0.997 P<0.000). The likelihood ratio is sensitivity/1-specificity=12.43. Conclusions: In a country of relatively low prevalence of prostate cancer like Egypt, a cut-off point of PSA in combination with DRE for doing TRUS biopsy could be 10.05 ng per ml among asymptomatic men of more than 55 years of age with a likelihood ratio of 12.43
Takehiko Okamura
Anjo Kosei Hospital, Aichi Prefecture 446-8602, Japan
Title: Neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor for long-term interleukin-2 (IL-2) use in metastatic renal cell carcinoma
Time : 14:15-15:35
Biography:
Takehiko Okamura has completed his Doctorate in Medical Genetics in 1988. From 1989 to 1991, he was a Research Fellow at the Department of Pathology and Microbiology, University of Nebraska Medical Center, under a famous researcher of bladder carcinogenesis, Dr. Samuel M. Cohen. He studied bladder carcinogenesis and molecular biology. Over the past 30 years, he has continued to conduct clinical and translational research, mainly on BCG immunotherapy for non-muscle invasive bladder cancer. He has published more than 25 papers as a first author.
Abstract:
Because of the introduction of molecular targeted drugs, the treatment of renal cell carcinoma has greatly evolved and patient prognosis has remarkably improved. Molecular targeted drugs are now used for patient therapies instead of cytokines alone. However, treatment of this disease is affected by the drug administration method or when the drug is changed; although sequential therapy with molecular targeted drugs has attracted attention, a clear parameter to judge its effectiveness does not exist. On the other hand, the effectiveness of immunotherapy, which set the transverse axis of the T-cell, can be evaluated by the appearance of anti-PD-1 antibody. In this study, we retrospectively examined three cases of metastatic renal cell carcinoma, which were treated with the long-term use of interleukin-2 (IL-2), with regard to the usefulness of the neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor. All three cases were males; 2 were in their 50s and the other was in his 60s. The cases were administered IL-2 for 2.5, 3 and 7 years, respectively. For all cases, interferon-alpha was administered before IL-2 and after IL-2 administration, all cases were switched to molecular targeted drugs and each case could continue cancer treatment more than 3 years after starting IL-2. And finally, NLR have not raised, less than 2.7 during IL-2 treatment. The results suggested that NLR might serve as a useful marker for therapies when determining prognosis. Further studies including a prospective study in Japan and comparison with large-scale databases will be necessary.