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Welcome in the new version of Pubbedeurope.com, please vote the pool. |
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| Using protein expressions to predict survival in clear cell renal carcinoma. |
| on Saturday, October 29, 2005 - 11:55 AM CET Posted by : Admin |
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Kim HL, Seligson D, Liu X, Janzen N, Bui MH, Yu H, Shi T, Figlin RA, Horvath S, Belldegrun AS.
Departments of Urology, Pathology and Laboratory Medicine, Biostatistics, Human Genetics and Biostatistics, and Medicine and Urology, University of California School of Medicine, Los Angeles, California.
PURPOSE: An accurate system for predicting survival for patients with solid tumors will allow for better patient selection for both established and novel therapies. We propose a staging system for clear cell variants of renal cell carcinoma (RCC) that includes molecular predictors and standard clinical predictors such as tumor-node-metastasis (TNM) stage, histological grade, and performance status (PS). EXPERIMENTAL DESIGN: A custom tissue array was constructed using clear cell RCC from 318 patients, representing all stages of localized and metastatic RCC, and immunohistochemically stained for molecular markers Ki67, p53, gelsolin, CA9, CA12, PTEN, EpCAM, and vimentin. We present a strategy for evaluating individual candidate markers for prognostic information and integrating informative markers into a multivariate prognostic system. RESULTS: The overall median follow-up and the median follow-up for surviving patients were 28 and 55 months, respectively. A prognostic model based primarily on molecular markers included metastasis status, p53, CA9, gelsolin, and vimentin as predictors and had high discriminatory power: its statistically validated concordance index (C-index) was found to be 0.75. A prognostic model based on a combination of clinical and molecular predictors included metastasis status, T stage, Eastern Cooperative Oncology Group PS, p53, CA9, and vimentin as predictors and had a C-index of 0.79, which was significantly higher (P < 0.05) than that of prognostic models based on grade alone (C = 0.65), TNM stage alone (C = 0.73), or the University of California Los Angeles integrated staging system (C = 0.76). CONCLUSIONS: Protein expressions obtained using widely available technology can complement standard clinical predictors such as TNM stage, histological grade, and PS.
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| Combined histopathological and molecular cytogenetic stratification |
| on Saturday, October 29, 2005 - 11:55 AM CET Posted by : Admin |
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of medulloblastoma patients.
Lamont JM, McManamy CS, Pearson AD, Clifford SC, Ellison DW.
Northern Institute for Cancer Research, University of Newcastle, Newcastle-upon-Tyne, United Kingdom.
This study examined the utility of stratifying children with medulloblastomas by a combination of refined histopathological classification and molecular cytogenetic evaluation. Detailed histopathological classification of tumors from a cohort of patients (n = 87) composed mainly of children entered into the International Society of Pediatric Oncology (SIOP)/United Kingdom Children's Cancer Study Group PNET3 trial (n = 65), included identification of the large cell/anaplastic phenotype. Fluorescence in situ hybridization was used to detect chromosome 17 abnormalities, losses of 9q22 and 10q24, and amplification of the MYCC and MYCN oncogenes. The large cell/anaplastic phenotype, which was present in 20% of medulloblastomas, emerged as an independent prognostic indicator. Loss of 17p13.3 (38% of medulloblastomas) was found across all of the histopathological variants, whereas MYCC/MYCN amplification (6%/8% of medulloblastomas) was significantly associated with the large cell/anaplastic phenotype. Both of these genetic abnormalities emerged as prognostic indicators. Loss of 9q22 was associated with the nodular/desmoplastic medulloblastoma variant, whereas loss of 10q24 was found in all of the variants. Together with metastatic tumor at presentation, the large cell/anaplastic phenotype, 17p13.3 loss, or high-frequency MYC amplification defined a high-risk group of children whose outcome was significantly (P = 0.0002) poorer than a low-risk group without these tumor characteristics. Combined evaluation of novel histopathological features and molecular cytogenetic abnormalities promises to allow stratification of patients with medulloblastoma, such that those likely to be cured will be spared the side effects of maximal therapy, which can be targeted at those with aggressive disease. |
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| Prognostic Significance of E-Cadherin Protein Expression |
| on Saturday, October 29, 2005 - 11:54 AM CET Posted by : Admin |
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n Pathological Stage I-III Endometrial Cancer.
Mell LK, Meyer JJ, Tretiakova M, Khramtsov A, Gong C, Yamada SD, Montag AG, Mundt AJ.
Departments of Radiation and Cellular Oncology, Pathology and Obstetrics and Gynecology, University of Chicago, and Department of Radiation Oncology, University of Illinois at Chicago, Chicago, Illinois.
PURPOSE: Decreased expression of E-cadherin in endometrial cancer cells is associated with adverse prognostic features. This study aimed to evaluate the prognostic significance of decreased E-cadherin expression in patients with endometrial cancer. EXPERIMENTAL DESIGN: Between 1992 and 1999, 102 endometrial cancer patients with stage I-III disease underwent primary surgery at the University of Chicago. Representative tissue specimens were immunostained with a monoclonal antibody to E-cadherin. A semiquantitative evaluation scale was developed based on the percentage of endometrial cancer cells with membranous E-cadherin staining. Tissue sections were scored as "3" if >75%, "2" if 25-75%, "1" if 5-25%, and "0" if <5% of cells stained. E-Cadherin staining was correlated with overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and extrapelvic progression. Multivariate Cox proportional hazards modeling was used to estimate hazard ratios, controlling for clinicopathological characteristics and adjuvant treatment. Median follow-up for the study group was 58.5 months. RESULTS: E-Cadherin staining was scored as 0, 1, 2, and 3 in 29.4%, 18.6%, 26.5%, 25.5% of cases, respectively. E-Cadherin expression was positively correlated with myometrial invasion (Kendall tau: 0.30, P < 0.01), and negatively correlated with grade (Kendall tau: -0.13, P = 0.15) and papillary serous or clear cell histology (Kendall tau: -0.14, P = 0.12). Five-year actuarial OS, CSS, PFS, and extrapelvic recurrence rates for negative (score = 0), heterogeneous (score = 1-2), and positive (score = 3) staining were as follows: OS, 69.2 versus 75.7 versus 81.0% (P = 0.64); CSS, 78.8 versus 91.2 versus 95.5% (P = 0.19); PFS, 69.1 versus 88.6 versus 92.2% (P = 0.079), and extrapelvic progression, 20.8 versus 7.3 versus 4.0% (P = 0.17). On multivariate Cox regression, a higher E-cadherin expression score was associated with decreased overall mortality [hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.34-1.03; P = 0.066), and statistically significant decreases in endometrial cancer mortality (HR, 0.23; 95% CI, 0.055-0.94; P = 0.040), disease progression (HR, 0.28; 95% CI, 0.10-0.77; P = 0.014), and extrapelvic recurrence (HR, 0.24; 95% CI, 0.062-0.97; P = 0.045). CONCLUSIONS: Decreased E-cadherin expression is an independent prognostic factor for disease progression and mortality in pathological stage I-III endometrial cancer. Evaluation of E-cadherin expression may aid in the selection of patients for more aggressive adjuvant therapy.
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| Loss of Fhit Expression in Head and Neck Squamous Cell Carcinoma.. |
| on Saturday, October 29, 2005 - 11:54 AM CET Posted by : Admin |
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and Its Potential Clinical Implication.
Tai SK, Lee JI, Ang KK, El-Naggar AK, Hassan KA, Liu D, Lee JJ, Ren H, Hong WK, Mao L.
Departments of Thoracic/Head and Neck Medical Oncology, Radiation Oncology, Pathology, and Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, and Department of Otolaryngology, National Yang Ming University, Taipei Veteran General Hospital, Taipei, Taiwan.
PURPOSE: Abnormalities of FHIT, a candidate tumor suppressor gene, have frequently been found in multiple malignancies, including head and neck squamous cell carcinoma (HNSCC). To define its role in HNSCC treated with surgery and postoperative radiotherapy (PORT), the Fhit protein expression status was investigated in 80 patients enrolled in a prospective Phase III clinical trial addressing the dose and fractionation regimen of PORT. EXPERIMENTAL DESIGN: Immunohistochemical staining of HNSCC tissue sections for Fhit expression was performed. The Fhit expression status was correlated with the clinicopathological characteristics and clinical course. The median follow-up duration was 4.9 years. RESULTS: Loss of Fhit expression was found in 52 of the 80 study patients (65%). There was not a significant association between Fhit expression and clinical characteristics. Patients whose tumor exhibited negative Fhit expression had a significantly worse 5-year overall survival duration [hazard ratio = 0.49; 95% confidence interval, 0.23-1.03; P = 0.05 (log-rank test)] than did those whose tumor exhibited positive Fhit expression. One third of the patients with a Fhit-negative tumor had distant metastasis during the follow-up period. Paradoxically, patients classified as high risk who had a Fhit-negative tumor experienced locoregional recurrence less often (18%) than did high-risk patients who had a Fhit-positive tumor (33%). CONCLUSIONS: Loss of Fhit expression is a poor prognostic indicator in patients with HNSCC. However, tumors lacking Fhit expression may be more sensitive to PORT and therefore more susceptible to locoregional control. |
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| Geriatric oncology: a clinical approach to the older patient with cancer. |
| on Saturday, October 29, 2005 - 11:54 AM CET Posted by : Admin |
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Repetto L, Venturino A, Fratino L, Serraino D, Troisi G, Gianni W, Pietropaolo M.
U.O. Oncologia Istituto Nazionale di Riposo e Cura per Anziani (INRCA), Via Cassia 1167, 00189 Rome, Italy. l.repetto@inrca.it
Due to the ageing of the population and the sharp increase in life expectancy, cancer in the older person has become an increasingly common problem in the Western world. Although several authors have stressed that elderly cancer patients deserve special attention as a target group for research efforts, older aged patients are still less likely to be offered participation in clinical trials. The cellular and molecular mechanisms regulating the physiological process of ageing and senescence are far from understood, although inflammation is likely to play an important role, at least in some cancers. In addition, the relationship between ageing and cancer risk is also far from understood. One of the most intriguing aspects of ageing is how different the ageing process is from person to person; the basis for this variation is largely unknown. Population-based studies and longitudinal surveys have shown that comorbidity and physical and mental functioning are important risk factors; thus, a meaningful assessment of comorbidity and disability should be implemented in clinical practice. Modern geriatrics is targeted towards patients with multiple problems. Such patients are not simply old, but are geriatric patients because of interacting psychosocial and physical problems. As a consequence, the health status of old persons cannot be evaluated by merely describing the single disease, and/or by measuring the response, or survival after treatment. Conversely, it is necessary to conduct a more comprehensive investigation of the 'functional status' of the aged person. A geriatric consultation provides a variety of relevant information and enables the healthcare team to manage the complexity of health care in the elderly; this process is referred to as the Comprehensive Geriatric Assessment (CGA). The use of CGA is now being introduced into oncological practice. The definition of frailty is still controversial and represents a major issue of debate in clinical geriatrics. As the frail population increases, clinical trials in frail persons are needed. The usefulness of these trials requires a consensus as to the definition of frailty. Clearly, the management of older persons with cancer requires the acquisition of special skills in the evaluation of the older person and in the recognition and management of emergencies as well as experience in geriatric case management. |
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| The frailty syndrome: a critical issue in geriatric oncology |
| on Saturday, October 29, 2005 - 11:54 AM CET Posted by : Admin |
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Ferrucci L, Guralnik JM, Cavazzini C, Bandinelli S, Lauretani F, Bartali B, Repetto L, Longo DL.
Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. ferrucci@dada.it
Evidence exists that the geriatric intervention guided by Comprehensive Geriatric Assessment (CGA) has positive effects on a number of important health outcomes in frail older patients. Although a number of observational studies, editorials, special articles and clinical reports, suggest that CGA should be used to guide the assessment and clinical decision-making in older cancer patients, there is limited support to this view in the literature. Older patients that are diagnosed with cancer are usually healthier and less problematic than persons of the same age who are randomly sampled from the general population. In these persons, the cancer dominates the clinical picture and, therefore, instruments especially tuned for the frail elderly may provide little information. The concept of the frailty syndrome, characterized by high susceptibility, low functional reserve and unstable homeostasis, has recently received a lot of attention by the geriatric community. A CGA approach, which also evaluates elements of the frailty syndrome, may be of great interest for those oncologists who want to identify older patients likely to develop severe toxicity and severe side effects in response to aggressive treatment. Improvements in the definition of the frailty syndrome may profit from the clinical experience of oncologists.
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| Geriatric oncology |
| on Saturday, October 29, 2005 - 11:54 AM CET Posted by : Admin |
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Balducci L.
Division of Medical Oncology and Hematology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, FL 33612, USA. balducci@moffitt.usf.edu
The discussion of breast cancer in the older woman implies an outline of unique aspects of cancer and aging. In this analysis, five aspects are highlighted because they pertain to breast cancer control: the diversity of the older population; the age-related increase in cancer susceptibility; the changes in tumor biology that occur with aging; and the implication of these factors for the prevention and treatment of cancer. The comprehensive geriatric assessment accounts for the diversity of the older population in terms of functional reserve and life expectancy and allows an individualized approach to the elderly. The increased susceptibility of the aged to environmental carcinogens has multiple causes and provides theoretical support to cancer prevention to the older individuals. The natural behavior of cancer may change with age due to intrinsic changes in the tumor cells as well as in the tumor host and may lead to both increased and decreased aggressiveness of the neoplasm. In the case of breast cancer, age seems associated with a more indolent tumor. Cancer screening seems effective in older patients with a life-expectancy of 5 or more years. Treatment of cancer with chemotherapy may be associated with increased risk of complications, especially mucositis and neutropenia. The latter may be ameliorated by prophylactic use of growth factors and correction of anemia. |
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| Guidelines for the treatment of elderly cancer patients. |
| on Saturday, October 29, 2005 - 11:54 AM CET Posted by : Admin |
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Lichtman SM.
Don Monti Division of Medical Oncology, North Shore University Hospital, Manhasset, NY 11030, USA. slichtma@suffolk.lib.ny.us
BACKGROUND: The management of elderly patients with cancer is influenced by several factors that can vary widely among aging individuals. As the proportion of elderly individuals increases, the need for specific care guidelines for this population is critical. The National Comprehensive Cancer Network (NCCN) has developed guidelines to address these factors when formulating optimal treatment regimens for elderly patients and to avoid significant toxicity and maintain their quality of life. METHODS: Factors that influence the appropriate treatment choices for the elderly, such as functional status, comorbidity, polypharmacy, and the presence of anemia, are reviewed, and the guidelines developed by the NCCN for treatment elderly patients are discussed. RESULTS: The guidelines address these factors when defining the goal of therapy and formulating individualized treatment approaches for the elderly to provide optimal care for these patients, avoid significant toxicity, and maintain their quality of life. CONCLUSIONS: The goal of therapy must be clearly defined, whether survival, remission, cure, or palliation of symptoms. Enrollment of elderly cancer patients onto clinical trials is encouraged so the guidelines can be validated.
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| Geriatric assessment in elderly patients with prostate cancer. |
| on Saturday, October 29, 2005 - 11:54 AM CET Posted by : Admin |
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Terret C, Albrand G, Droz JP.
Geriatric Oncology Program, Centre Leon Berard, Lyon, France. terret@lyon.fnclcc.fr
As a result of demographic evolution, oncologists will treat more and more elderly patients with prostate cancer. Aging is frequently associated with the coexistence of several medical complications that can increase the complexity of cancer treatment decision-making. Unfortunately, clinical oncologists need to be more familiar with the multidimensional assessment of elderly patients. To acquire this skill, we implemented a multidimensional geriatric assessment program at our cancer center. This instrument prospectively assessed 60 elderly patients with prostate cancer. Herein, we describe geriatric aspects detected in our patient sample and report treatment options proposed to elderly patients with prostate cancer at different disease stages. The minimal comprehensive geriatric assessment (mini-CGA) procedure revealed that 66% of our patient population was dependent in one or more of the Katz Activities of Daily Living and 87% were dependent in 1 or more of the Lawton Instrumental Activities of Daily Living; all patients had significant comorbidity according to the Cumulative Illness Rating Scale-Geriatrics, 75% having at least one severe comorbidity. We identified 19 cases of drug interaction. We also observed that half of these patients had a risk of falling and some physical disability; 45% had cognitive disorders requiring more investigation; one third had depressive symptoms. Finally, 65% of the patients were either malnourished or at risk of malnutrition. Many of these problems were unknown before the mini-CGA processing and may interfere with cancer and cancer treatment. Thus, the correct management of elderly patients with cancer requires comprehensive geriatric assessment as well as relevant disease staging at diagnosis. This approach will help us to propose the most appropriate treatment with the main aim of preserving quality of lif |
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| The surgical management of elderly cancer patients. |
| on Saturday, October 29, 2005 - 11:53 AM CET Posted by : Admin |
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recommendations of the SIOG surgical task force.
Audisio RA, Bozzetti F, Gennari R, Jaklitsch MT, Koperna T, Longo WE, Wiggers T, Zbar AP.
University of Liverpool, Whiston Hospital, Prescot, UK. raudisio@doctors.org.uk
Although cancer in the elderly is extremely common, few health professionals in oncology are familiar with caring for series of oncogeriatric patients. Surgery is at present the first choice, but is frequently delivered suboptimally: under-treatment is justified by concerns about unsustainable toxicity, whilst over-treatment is explained by the lack of knowledge in optimising preoperative risk assessment. This article summarises the point of view of the Surgical Task Force @ SIOG (International Society for Geriatric Oncology), pointing out differences from, and similarities to, the younger cohorts of cancer patients, and highlighting the latest updates and trends specifically related to senior cancer patients. |
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Italian Research Multiple Sclerosis |
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