Significant improvements in disease-free survival (DFS) and overall survival (OS) have been obtained with the extensive

use of adjuvant systemic therapies, which are largely empirically based. The possibility to have strong prognostic and/or predictive markers is of utmost importance for clinicians in order to identify patients at higher risk of relapse and to select the most appropriate systemic treatment for an individual patient. Prognostic factors are those that predict the risk of recurrence or of death from BC independently of treatment. Predictive factors are those that distinguish between patients who are more or less likely to respond to a given therapy. However, the distinction between the prognostic and predictive value of each marker is not straightforward. The retrospective nature of the great majority of these studies may jeopardize their results. Among the reasons for these ambiguous results are: (1) the retrospective nature of the great majority of studies; (2) the utilization of archived materials handled and preserved in different conditions; (3) the relatively small numbers of patients analyzed and the fact that the group of patients included in the translational research study is always a subset of the clinical trial population, hence inducing bias; (4) the heterogeneity of the population of patients evaluated; (5) the different methods used to assess the expression of biological and molecular markers, as well as the threshold values to define their expression; (6) the lack of standardization and quality control evaluation of different methods; and, sometimes (7) the relatively short duration of the median follow-up. Nevertheless, important messages can be derived from these studies, even if a publication selection bias cannot be ruled out. First, proliferative activity seems to have an important role in defining the behavior of BC, with theoretically possible implications for the selection of treatments, such as dose dense CT. Secondly, a standardization of the evaluation methods with intra- and interlaboratory quality controls is the first requisite to evaluate a marker. Thirdly, it is crucial to properly design large prospective trials trying to include more than one proliferative marker in order to select the best ones or the best combinations with prognostic/predictive value. International collaboration and close interaction between the basic and clinical research worlds (through translational research) are essential to avoid the duplication of efforts and fragmentation of research, and to lead to the needed level 1 evidence. In the era of high throughput technologies, such as microarray gene profiling and proteomics, there is a greater chance to develop multimarker models that might turn out to be powerful prognostic or predictive tools. In the post-operative setting, there is clear evidence that offering adjuvant therapy significantly improves survival in stage III CRC, however, the management of stage II disease is an area of controversy and debate. The 5-year survival for stage II patients is approximately 75%, indicating that the majority are cured by surgery alone, and many patients who would have been cured by surgery undergo chemotherapy unnecessarily. Furthermore, some patients who are not recommended to receive adjuvant treatment may benefit from chemotherapy. Recent studies have started to define prognostic molecular markers that identify those patients at risk of relapse after surgery and who may benefit most from chemotherapy (Table 1). Furthermore, molecular markers are being identified that predict whether a tumour will respond to a particular chemotherapy. In addition, some markers may have therapeutic value by predicting the degree of systemic toxicity for a particular treatment. For such studies tumour DNA can be analysed to identify genetic changes such as point mutations, loss of heterozygosity (LOH), gene

amplification and microsatellite instability (MSI). In addition, the expression of individual genes can be assessed at the levels of mRNA and protein using the techniques of real-time reverse transcription PCR and immunohistochemistry (IHC) respectively. The ultimate goal of this research is the tailoring of treatment to the molecular phenotypes of tumour and patient. This review highlights potentially important prognostic and predictive markers in CRC.

Treatment Option Overview There are different types of treatment for patients with gastric cancer. Different types of treatments are available for patients with gastric cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. Before starting treatment, patients may want to think about taking part in a clinical trial. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Clinical trials are taking place in many parts of the country. Information about ongoing clinical trials is available from the NCI Web site. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team. Four types of standard treatment are used: Surgery Surgery is a common treatment of all stages of gastric cancer. The following types of surgery may be used: * Subtotal gastrectomy: Removal of the part of the stomach that contains cancer, nearby lymph nodes, and parts of other tissues and organs near the tumor. The spleen may be removed. The spleen is an organ in the upper abdomen that filters the blood and removes old blood cells. * Total gastrectomy: Removal of the entire stomach, nearby lymph nodes, and parts of the esophagus, small intestine, and other tissues near the tumor. The spleen may be removed. The esophagus is connected to the small intestine so the patient can continue to eat and swallow. If the tumor is blocking the opening to the stomach but the cancer cannot be completely removed by standard surgery, the following procedures may be used: * Endoluminal stent placement: A procedure to insert a stent (a thin, expandable tube) in order to keep a passage (such as arteries or the esophagus) open. For tumors blocking the opening to the stomach, surgery may be done to place a stent from the esophagus to the stomach to allow the patient to eat normally. * Endoscopic laser surgery: A procedure in which an endoscope (a thin, lighted tube) with a laser attached is inserted into the body. A laser is an intense beam of light that can be used as a knife. * Electrocautery: A procedure that uses an electrical current to create heat. This is sometimes used to remove lesions or control bleeding. Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated. Radiation therapy Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated. Chemoradiation Chemoradiation combines chemotherapy and radiation therapy to increase the effects of both. Chemoradiation treatment given after surgery to increase the chances of a cure is called adjuvant therapy. If it is given before surgery, it is called neoadjuvant therapy. New types of treatment are being tested in clinical trials. These include the following: Biologic therapy Biologic therapy is a treatment that uses the patients immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the bodys natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy. This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site. Treatment Options by Stage Stage 0 Gastric Cancer (Carcinoma in Situ) Treatment of stage 0 gastric cancer is usually surgery (total or subtotal gastrectomy). Stage I and Stage II Gastric Cancer Treatment of stage I and stage II gastric cancer may include the following: * Surgery (total or subtotal gastrectomy). * Surgery (total or subtotal gastrectomy) followed by chemoradiation therapy. * A clinical trial of chemoradiation therapy given before surgery. This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site. Stage III Gastric Cancer

Treatment of stage III gastric cancer may include the following: * Surgery (total gastrectomy). * Surgery followed by chemoradiation therapy. * A clinical trial of chemoradiation therapy given before surgery. This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site. Stage IV Gastric Cancer Treatment of stage IV gastric cancer that has not spread to distant organs may include the following: * Surgery (total gastrectomy) followed by chemoradiation therapy. * A clinical trial of chemoradiation therapy given before surgery. Treatment of stage IV gastric cancer that has spread to distant organs may include the following: * Chemotherapy as palliative therapy to relieve symptoms and improve the quality of life. * Endoscopic laser surgery or endoluminal stent placement as palliative therapy to relieve symptoms and improve the quality of life. * Radiation therapy as palliative therapy to stop bleeding, relieve pain, or shrink a tumor that is blocking the opening to the stomach. * Surgery as palliative therapy to stop bleeding or shrink a tumor that is blocking the opening to the stomach. This summary section refers to specific treatments under study in clinical trials, but it may not mention every new treatment being studied. Information about ongoing clinical trials is available from the NCI Web site.

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Source(s):
http://www.americanheart.org/presenter.j... Origin of the proposal

Gastrointestinal cancers remain a significant cause of morbidity and mortality. While increasing therapeutic options have improved outcomes for many patients, they have also complicated treatment decision-making. Unfortunately, most patients with advanced gastrointestinal malignancies die from their disease. Prognostic and predictive markers could improve treatment significantly by identifying patients who may or may not require a given therapy, and determining those most likely to benefit from a therapy. Currently, clinicopathologic staging of cancer though not providing sufficient prognostic information remains the standard for assessing patient risk and supporting treatment decisions. Strategies are required to improve prognostic assessment and provide the ability to determine likelihood of response to therapies. A number of biomarkers chromosome losses and gains, gene expression variation and altered expression of certain proteins are being investigated for this purpose. Early incorporation of translational research and new technologies with clinical trials are needed to prospectively validate these biological markers and allow their use in clinical practice. The present study has originated from this concept.