The current status and future perspectives of CSPOR-BC

The Comprehensive Support Project for Oncology Research in Breast Cancer (CSPOR-BC) was initiated in 2000 as part of the investigation project of the Stress Science Research Institute, which was founded by the Public Health Research Foundation. The main objective of CSPOR-BC is to comprehensively support investigator-initiated clinical trials, research related to health-related quality of life (HR-QOL), and epidemiological research for breast cancer. After its initiation, 6 randomized controlled trials (RCTs) on adjuvant therapy for breast cancer and 2 RCTs on metastatic breast cancer have been conducted. To date, patient recruitment has been completed in 3 trials on adjuvant therapy and 1 trial on metastatic breast cancer. In addition to the assessment of efficacy and quality of life, treatment-related side effects have been evaluated. Large cohort studies have been accompanied by some RCTs to evaluate the effect of lifestyle, use of complementary and alternative medicine, sociopsychological factors, and supportive therapies on prognoses of patients with primary breast cancer. These subanalyses are unique to clinical trials conducted by CSPOR-BC. In this report, the current status and future perspectives of CSPOR-BC are described.     

Upper gastrointestinal tumors: current status and future perspectives

Recent therapeutic developments that have provided new promising and successful approaches to the treatment of solid tumors are in large part due to the increasing understanding of their molecular biology. Despite this progress, these new therapies have provided minimal benefit in the treatment of upper gastrointestinal (GI) malignancies. Hence, the overall survival of patients with upper GI tumors remains dismal. These disappointing results are largely due to the lack of early detection strategies, inadequate medical treatments and the poor understanding of upper GI tumor biology. Clinically, the treatment paradigm has been evolving for these malignancies. Esophageal cancer is now commonly treated with preoperative chemoradiation in the USA, in both academic and community cancer centers, due to its theoretical advantages. Adjuvant chemotherapy and chemoradiation are also frequently used in patients with pancreatic cancer. Exciting prospects remain in the medical and surgical treatment of these malignancies with the inclusion of biologic agents in many protocols, newer chemotherapeutic agents (such as S-1 in the treatment of gastric cancer), and the use of minimally invasive procedures for the treatment of premalignant and, possibly, early malignant lesions of the esophagus and stomach. This review focuses on the current practice in the management of upper GI tumors and summarizes the recent advances in the field.     

Upper gastrointestinal tumors: current status and future perspectives

Recent therapeutic developments that have provided new promising and successful approaches to the treatment of solid tumors are in large part due to the increasing understanding of their molecular biology. Despite this progress, these new therapies have provided minimal benefit in the treatment of upper gastrointestinal (GI) malignancies. Hence, the overall survival of patients with upper GI tumors remains dismal. These disappointing results are largely due to the lack of early detection strategies, inadequate medical treatments and the poor understanding of upper GI tumor biology. Clinically, the treatment paradigm has been evolving for these malignancies. Esophageal cancer is now commonly treated with preoperative chemoradiation in the USA, in both academic and community cancer centers, due to its theoretical advantages. Adjuvant chemotherapy and chemoradiation are also frequently used in patients with pancreatic cancer. Exciting prospects remain in the medical and surgical treatment of these malignancies with the inclusion of biologic agents in many protocols, newer chemotherapeutic agents (such as S-1 in the treatment of gastric cancer), and the use of minimally invasive procedures for the treatment of premalignant and, possibly, early malignant lesions of the esophagus and stomach. This review focuses on the current practice in the management of upper GI tumors and summarizes the recent advances in the field.     

Radiation oncology facilities in Turkey: current status and future perspectives

Background and purpose: An analysis of the current radiotherapy status in Turkey was conducted to establish a comprehensive baseline. Turkey’s future demand analysis in view of international benchmarks was conducted. Moreover, the ministerial plans are shared to present an example for making a comprehensive planning in developing countries. Methods: The data from all radiotherapy centers in Turkey was collected through a survey and cross-checked with primary research and government data. Survey covered the status of radiotherapy centers in terms of major equipment and personnel. Data regarding manpower currently working is obtained from relevant academic centers and occupational associations. Results: The latest ministerial registry data demonstrated 150,000 new cancer cases each year with 400,000 patients living with cancer in Turkey. Around 100,000 patients are estimated to need radiotherapy each year - a figure expected to reach around 170,000 by 2023. The current numbers for radiotherapy centers, megavoltage equipment, radiation oncologists, medical physicists and radiotherapy technicians are 90, 186, 446, 130 and 600 respectively. By 2023, Turkey will need around 680 radiation oncologists, 624 medical physicists, 2,650 radiotherapy technicians and 379 megavoltage machines. Conclusion: Turkey faces a slight oversupply of radiation oncologists in contrast to undersupply in megavoltage machines and other personnel. Careful planning is required to allocate limited resources. The purchase of the equipment and employment policies should be structured as part of national cancer control program.     

Thalidomide therapy for myelodysplastic syndromes: current status and future perspectives

Thalidomide exerts in vitro heterogeneous biological effects on hematopoiesis which have supported its possible use in treating myelodysplastic syndromes (MDS). Some recent clinical trials have confirmed that thalidomide may improve anemia and, less frequently, other cytopenias, in a proportion of younger patients with low-risk MDS (11-56%, on intention-to-treat analysis). Of interest, erythroid responses may be achieved also in transfusion-dependent subjects with high serum levels of endogenous erythropoietin, a subset of MDS patients with little chance of responding to recombinant erythropoietin, alone or in combination with G-CSF. Older patients, however, often do not tolerate the drug even at very low doses. How thalidomide acts in MDS is not clear. Some data suggest several mechanisms possibly involving stimulation of erythropoiesis through activation of physiological compensative mechanisms and reduction of apoptosis. The combination of thalidomide with other molecules active on hematopoiesis and the use of more effective and less toxic analogs are currently under clinical investigation.     

乳腺癌抗血管生成治疗:现状与前景

Tumor angiogenesis plays an important role in the growth, invasion and metastasis of breast cancer, therefore re-cently a very active area of breast cancer research involves the addition of antiangiogenic therapy. Numerous clinical studies for several antiangiogenic agents have recently been conducted in breast cancer patients and have shown clinically significant improvement in outcomes. This review gives a brief background to breast cancer angiogenesis, also focusing on current prog-ress in the field of a...     

Glycoimmunomics of human cancer: current concepts and future perspectives

Future strategies for the treatment of human cancer require a full appreciation of the intracellular and extracellular changes that accompany neoplastic transformation. The changes may involve a variety of micro- and macro-molecules, including, but not restricted to, peptides, proteins (with sugar and/or lipid moieties), oligosaccharides, glycolipids (neutral or acidic, e.g., gangliosides), ceramides, fatty acids and other lipids. Although several therapeutic approaches have been well developed in recent years, most of the reported studies focus on proteins and peptides. Glycoantigens and lipoantigens have been neglected. Elucidation of the profiles and properties of all molecules associated with tumor progression is required to develop a successful strategy to treat human cancer. This review describes the unique immunomics of tumor-associated glycoantigens and explains why the field of glycoimmunomics may yield clinically important biomarkers and treatments for the management of human cancer.     

胃癌的诊治现状和展望

胃癌死亡率在世界上仅次于肺癌、高居癌症病死率的第2位、是我国消化道恶性肿瘤第1位.除了日本有大规模的人群筛查外,其他国家多数胃癌患者就诊时,疾病已达进展期.患者的预后和生存与就诊时的肿瘤分期明显相关,但治疗的方式是否影响远期疗效仍还有争论.     

Etoposide: current status and future perspectives in the management of malignant neoplasms

Etoposide has demonstrated highly significant clinical activity against a wide variety of neoplasms, including germ-cell malignancies, small-cell lung cancer, non-Hodgkin's lymphomas, leukemias, Kaposi's sarcoma, neuroblastoma, and soft-tissue sarcomas. It is also one of the important agents in the preparatory regimens given prior to bone marrow and peripheral stem-cell rescue. Despite its high degree of efficacy in a number of malignancies, the optimal dose, schedule, and dosing form remain to be defined. It is possible that continuous or prolonged inhibition of the substrate, i.e., topoisomerase II, may be the key factor for the cytotoxic effects of etoposide. Clinical studies have shown the activity of etoposide to be schedule-dependent, with prolonged dosing, best accomplished by the oral dosing form, offering a therapeutic advantage. This benefit awaits validation by prospective randomized studies, some of which are in progress. Recent clinical investigations have focused on the use of etoposide in combination with (a) cytokines to ameliorate myelosuppression, the dose-limiting toxicity of etoposide; (b) agents such as cyclosporin A and verapamil to alter the p-glycoprotein (mdr 1) function; and (c) topoisomerase I inhibitors to modulate the substrate upon which it acts. There is continued interest in the development of etoposide to its maximal clinical dimensions and in the examination of alternative biochemical and mechanistic approaches to further our understanding of this highly active agent.Paper presented at the Topoisomerase Inhibitors Conference, University of Maryland Cancer Center, 27–30 October 1993, Monterey, California USA. Supported in part by Bristol Myers Oncology Division     

Planning of nuclear medicine in Turkey: current status and future perspectives

Background and Purpose: An analysis of the current nuclear medicine (NM) status and future demand inTurkey in line with the international benchmarks was conducted to establish a comprehensive baseline reference.Methods: Data from all NM centers on major equipment and manpower in Turkey were collected througha survey and cross-checked with the primary research and governmental data. Data regarding manpowercurrently working were obtained from the relevant academic centers and occupational societies. Results: Thecurrent numbers of NM laboratories, NM specialists, gamma cameras, PET/CT scanners, radioiodine treatmentunits for thyroid cancer are 217, 474, 287, 75 and 39, respectively. There was personnel and equipment needunderestimated in the field compared to developed countries. Equipment insufficiency was more significant inthe Ministry of Health (MoH) hospitals. These gaps should be eliminated with strategic planning of equipmentand NM laboratories. Currently, the number of the PET/CT devices is at the level of the developed countries.The number of specialists in the field should reach the expected goal in 2023. By 2023, Turkey will need around820 NM specialists, 498 gamma cameras and 99 PET/CT devices. In addition, further studies should be maderegarding other related staff, particularly for health physicians, radiopharmacists and NM technicians.Conclusion: There is an insufficiency of personnel and equipment in Turkey’s NM field. Comprehensive strategicplanning is required to allocate limited resources and the purchase of the equipment and employment policiesshould be structured as part of “National Special Feature Requiring Health Service Plan”.     

Targeted therapy for gastrointestinal stromal tumors: current status and future perspectives

Gastrointestinal stromal tumors (GISTs) present 80% of gastrointestinal tract mesenchymal tumors, with systemic chemotherapy and radiotherapy being unable to improve survival of patients with advanced disease. The identification of activating mutations in either KIT cell surface growth factor receptor or platelet-derived growth factor receptor alpha, which lead to ligand-independent signal transduction, paved the way for the development of novel agents that selectively inhibit key molecular events in disease pathogenesis. The development of imatinib mesylate in the treatment of metastatic GIST represents a therapeutic breakthrough in molecularly targeted strategies, which crucially improved patients’ prognosis while its usefulness in adjuvant and neoadjuvant setting is under study. Sunitinib malate is available in the second-line setting, with ongoing studies evaluating its role in an earlier disease stage, while other targets are under intense investigation in order to enrich the therapeutical armamentarium for this disease. GIST phenotype seems to be an essential indicator of treatment response; thus, obtaining genotype information of each patient may be critical in order to tailor individualized treatment strategies and achieve maximal therapeutic results.     

Treatment strategies in follicular lymphomas: current status and future perspectives.

Although little progress has been made in the treatment of follicular lymphomas (FL) within the last few decades, several new therapeutic modalities have recently demonstrated promising activity. These include myeloablative therapy followed by autologous stem cell transplantation in younger patients in first remission revealing a significant prolongation of remission duration in three prospective randomized trials, whereas the impact on overall survival still needs to be determined. Adding the anti-CD20 antibody rituximab to conventional chemotherapy resulted in a significant increase in remission rate, remission duration and in two of four currently available prospective randomized studies even in a longer overall survival. A prolongation of remission duration was also seen when rituximab was administered as maintenance after cytoreductive therapy or by prolonged application as a single agent. Radioimmunotherapy (RIT) with radioisotopes coupled to monoclonal antibodies revealed encouraging data in several phase II studies. Prospective randomized studies are warranted, however, to define the impact of RIT on FL therapy. New therapeutic perspectives also emerge from increasing insights into the biology of the disease that unravel molecular targets for novel agents, some of which have entered clinical evaluation already.     

TNM staging system for renal-cell carcinoma: current status and future perspectives

The Tumour, Nodes, and Metastasis (TNM) staging system is a method of stratifying patients with cancer and is based on data obtained from large multicentre studies that involved large numbers of patients, and have a good level of evidence. However, despite continual revisions to the methodology to incorporate evidence from new clinical studies, the optimum stratification of patients with renal-cell carcinoma (RCC) using the TNM staging system remains controversial and further revisions, in our opinion, are needed. Revision of the TNM staging system for renal-cell cancer could also result in the simultaneous update of the integrated prognostic systems that are currently used along side this traditional method of staging. These integrated systems could become key instruments for guiding patient counselling, for appropriate follow up strategies, for patient selection for clinical trials, and for appropriate assessment of results if the perception that they are complex is overcome. This perception is driven by the presence of more than one system, the heterogeneity of clinical and pathological variables included in the methodology, and the need for robust comparative studies between the various systems. Therefore, in everyday clinical practice, the TNM system is regarded as a more reliable method of staging. In this Essay, we aim to highlight the problems associated with the current version of the TNM staging system and highlight areas in which this grading instrument can be improved in future to become a more refined and standardised method of communication between all clinicians involved in clinical management of RCC.     

Monoclonal antibodies-based treatment in gastric cancer: current status and future perspectives

Gastric cancer (GC) is the second leading cause of cancer-related death, and despite having improved treatment modalities over the last decade, for most patients, only modest improvements have been seen in overall survival. Recent progress in understanding the molecular biology of GC and the related signaling pathways offers, from the clinical point of view, promising advances for selected groups of patients. In the past, targeted therapies have significantly impacted the treatment strategy of several common solid tumors such as breast, colorectal, and lung cancers. Unfortunately, translational and clinical research shows fewer encouraging targeted treatments with regards to the GC. To date, only two monoclonal antibodies (mAb), named trastuzumab and ramucirumab, are approved for the treatment of advanced GC, suggesting that in GC, maybe more than in other cancers, effective targeted therapy requires patient selection based on precise predictive molecular biomarkers. The aim of this review is to summarize the available data on the clinical advantages offered by the use of mAbs in the treatment of advanced/metastatic GC. Future perspective is also discussed.     

Breast cancer surgery--historical evolution, current status and future perspectives

The diagnosis and management of breast cancer have changed dramatically over the past two decades in response not only to new technologies but also to cultural and social aspects of the disease. Mastectomy (either radical or modified radical) was the historical mainstay of the treatment of breast cancer for decades. Although mastectomy continues to be appropriate for some patients, breast conservation has become the preferred method of treatment for many patients. Meeting the dual goal of optimum cosmesis and minimal rates of in-breast recurrences after breast-conservation therapy requires the selection and integration of appropriate diagnostic methods (including breast imaging techniques and breast biopsy techniques) as well as therapeutic methods (breast irradiation techniques, and systemic cytotoxic and hormonal therapy). To achieve optimal breast-conservation treatment, a multidisciplinary approach is necessary. Mastectomy followed by breast reconstruction is a valuable alternative for patients who require or choose mastectomy. After tumor downstaging with induction chemotherapy, a large percentage of patients with large or locally advanced tumors will be able to undergo breast-conservation therapy. Partial (levels I and II) axillary lymph node dissection remains the standard of care in the surgical management of patients with invasive breast cancer. Recently, there has been intense interest in selective axillary lymph node dissection, focused mainly on the identification of patients who are likely to benefit from axillary lymph node dissection, using sentinel lymph node biopsy.     

Treatment of HER2-positive breast cancer: current status and future perspectives

The advent of HER2-directed therapies has significantly improved the outlook for patients with HER2-positive early stage breast cancer. However, a significant proportion of these patients still relapse and die of breast cancer. Trials to define, refine and optimize the use of the two approved HER2-targeted agents (trastuzumab and lapatinib) in patients with HER2-positive early stage breast cancer are ongoing. In addition, promising new approaches are being developed including monoclonal antibodies and small-molecule tyrosine kinase inhibitors targeting HER2 or other HER family members, antibodies linked to cytotoxic moieties or modified to improve their immunological function, immunostimulatory peptides, and targeting the PI3K and IGF-1R pathways. Improved understanding of the HER2 signaling pathway, its relationship with other signaling pathways and mechanisms of resistance has also led to the development of rational combination therapies and to a greater insight into treatment response in patients with HER2-positive breast cancer. Based on promising results with new agents in HER2-positive advanced-stage disease, a series of large trials in the adjuvant and neoadjuvant settings are planned or ongoing. This Review focuses on current treatment for patients with HER2-positive breast cancer and aims to update practicing clinicians on likely future developments in the treatment for this disease according to ongoing clinical trials and translational research.     

Non-Hodgkin's lymphomas—current status of therapy and future perspectives

Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of disorders which can either be classified according to their biology, represented by corresponding counterparts of normal lymphocyte development as in the Kiel classification, or according to their clinical course, used in the Working Formulation. The recently proposed Revised European-American Lymphoma (R.E.A.L.) classification may unify both aspects and facilitate the comparability of international studies. Besides histology, the extent of disease still comprises the major determinant of therapy. In high-grade lymphomas combination chemotherapy with cyclophosphamide, hydroxydaunorubin, vincristine and prednisone (CHOP) represents the treatment of first choice, and may be restricted to 3–4 cycles in patients with limited stages of the disease when followed by involved field radiotherapy. In more extended, bulky stage II to IV disease, treatment must be extended to six courses of CHOP and, potentially, additional irradiation. Even in advanced states of the disease, long-term remission and potential cure are achieved in 30–50% of cases. In low-grade lymphomas, most patients present with advanced stages III and IV for which chemotherapy can be applied with palliative intention only. Hence, a watch-and-wait approach still seems appropriate outside clinical investigations until the disease requires therapeutic intervention. This consists preferentially of chemotherapy of moderate intensity such as cyclophosphamide, vincristine and prednisone (COP) or prednimustine and mitoxantrone (PmM). In responding patients, maintenance therapy with interferon-α is currently being explored and may result in prolongation of disease-free and, possibly also, overall survival. In both high- and low-grade lymphomas, intensification of therapy by myeloablative chemotherapy or combined chemoradiotherapy followed by autologous bone marrow transplantation (ABMT) or peripheral stem cell transplantation provides a promising and potentially curative perspective. In addition, new cytostatic agents such as the purine analogues—fludarabine, chlorodeoxyadenosine and deoxycoformycin—enlarge the therapeutic spectrum. More experimental approaches consist of the application of immunotoxins or radioisotypes, coupled to monoclonal antibodies directed against lymphoma-specific antigens. Overall, the substantial advances that have been achieved in the understanding of the biology and pathogenesis of malignant lymphomas, as well as the current achievements of therapy and the new promising perspectives, justify the hope that curative therapy can soon be offered to an increasing proportion of patients with NHL.     

Early phase oncology clinical trials in Malaysia: current status and future perspectives

Historically, the majority of oncology clinical trials are conducted in Western Europe and North America. Globalization of drug development has resulted in sponsors shifting their focus to the Asia-Pacific region. In Malaysia, implementation of various government policies to promote clinical trials has been initiated over a decade ago and includes the establishment of Clinical Research Malaysia, which functions as a facilitator and enabler of industry-sponsored clinical trials on a nationwide basis. Although oncology clinical trials in Malaysia have seen promising growth, there are still only a limited number of early phase oncology studies being conducted. Hence, the Phase 1 Realization Project was initiated to develop Malaysia's early phase clinical trial capabilities. In addition, the adaptation of good practices from other countries contribute to the effective implementation of existing initiatives to drive progress in the development of early phase drug development set up in Malaysia. Furthermore, holistic approaches with emphasis in training and education, infrastructure capacities, strategic alliances, reinforcement of upstream activities in the value chain of drug development, enhanced patient advocacy, coupled with continued commitment from policy makers are imperative in nurturing a resilient clinical research ecosystem in Malaysia.     

Drug development for metastatic castration-resistant prostate cancer: current status and future perspectives

Prostate cancer represents a third of all newly diagnosed cancers in men in the USA with an estimated incidence of 192,280 cases and 27,360 deaths in 2009. It continues to be a major cause of cancer-related morbidity and mortality, and there is an urgent need for new treatments. Historically, systemic therapy options were limited after progression on docetaxel-based chemotherapy. This article reviews current data on the novel therapeutics demonstrating activity in metastatic castration-resistant prostate cancer and their future role in the treatment of this disease with a poor prognosis.