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Prognostic factors in Greek patients with small cell lung cancer (SCLC). A Hellenic Cooperative Oncology Group study.

BACKGROUND: Prognostic factors among Greek patients with SCLC were evaluated. PATIENTS AND METHODS: Data from 516 patients with SCLC treated by the Hellenic Cooperative Oncology Group were analyzed. Multivariate analysis was performed. RESULTS: Complete response (CR) was achieved in 26.8% and partial response in 40.1% of patients. The median duration of response was 7.4 months, the median survival 10.5 months and the 2-year survival rate 12%. The stage of the disease was a dominant prognostic factor for survival and response. PS 0-1 was a major prognostic factor for survival, duration of response and CR. Female gender was a favorable predictor for CR. Superior vena cava syndrome was a poor prognostic factor for survival and duration of response. Weight loss and age > or = 60 were poor predictors for response. The sites of metastases affected survival, duration of response and response. Normal alkaline phosphatase was a favorable prognostic factor for survival, duration of response and response. Normal lactate dehydrogenase and thoracic irradiation were favorable prognostic factors for survival and duration of response.

Adult↗

[Medullary carcinoma of the thyroid gland. Prognostic factors].

OBJECTIVE: To analyze the clinical features and possible prognostic factors involved in the clinical course of a series of 26 patients with the diagnosis of thyroid medullar carcinoma (TMC). MATERIALS AND METHODS: An analysis was made of the variables age, sex, clinical course to diagnosis, paraneoplastic manifestations (flush, diarrhoea), clinical type (sporadic, non-associated, familial MEN IIa associated TMC, familial MEN IIb associated TMC), histologic uni or multicentricity, and stage of disease as possible predictive factors for the evolution. RESULTS: The most remarkable prognostic factor was tumoral stage. The likelihood of a patient diagnosed with stage I or II being free of metastatic disease was 1, 0.66 and 0.33 at 15, 16 and 17 years, respectively. In contrast, those patients in stage III at diagnosis had a likelihood of being free from metastasis 5 years after diagnosis and therapy of 0. With regard to sex, a better clinical course was observed among males than among females, statistically significant at 3 and 5, but not at 10 years. No statistical significance was reached with the other possible prognostic factors investigated. CONCLUSION: Given the obvious influence of tumoral stage of disease on prognosis, an early access to medical attention is desirable for diagnosis and treatment of TMC, as well as an early detection of family cases by a screening test.

Adolescent↗

Prognostic factors of renal cell carcinoma.

PURPOSE: Determination of prognostic factors is essential for the management of renal cell carcinoma. Stage, histological grade and type, and performance status are now well known and commonly used. During the last decade numerous predictors of patient outcome were tested. This review summarizes the most important studies, explores and compares the results, and tries to respond to the question, "Today, what do we expect of clinical, molecular and genetic factors concerning survival of patients with renal cell carcinoma?" MATERIALS AND METHODS: Based on MEDLINE literature searches we comprehensively reviewed the literature on the prognostic factors associated with the tumor, the patient and the treatment. RESULTS: During the last decades numerous factors have been studied but few of them maintained independent significance in terms of overall survival as assessed by multivariate analysis. Results are more often controversial from one series to another. No known molecular or cytogenetic tumor marker has been identified to help diagnose, manage or confirm renal cell carcinoma remission, progression or relapse. CONCLUSIONS: The classical prognostic factors remain histological grade, histological type, performance status, patient age, number and location(s) of metastatic sites, time to appearance of metastases and prior nephrectomy. The only striking advancement during the last few years has been the proven contribution of radical nephrectomy for metastatic disease in patients with good performance status.

Apoptosis↗

Extremity sarcomas: an analysis of prognostic factors from the Intergroup Rhabdomyosarcoma Study III.

PURPOSE: Prognostic factors for extremity sarcomas have been reported previously, after analysis of Intergroup Rhabdomyosarcomas Studies (IRS) I and II. This report reviews the experience of IRS III (1984-1992), in light of these reported factors, and the pretreatment factors used in the staging system currently being evaluated in IRS IV. The results of treatment of extremity sarcomas in IRS III are reported. METHODS: The charts of all patients entered in IRS III with an extremity-site tumor were reviewed. This group included patients with shoulder girdle and buttock sites. All patients were treated according to IRS III protocols. Survival rates were estimated by the method of Kaplan and Meier, and comparisons among groups of patients were made using a log-rank test. A multivariate analysis was performed to analyze all pretreatment factors that were significant by univariate analysis. RESULTS: Of the 189 patients entered in IRS III with extremity sites, 88 (47%) had the most common alveolar histology. Fifty-nine patients were in group I at the time of presentation (completely resected disease), 48 in group II (microscopic residual disease), 36 in group III (gross residual disease), and 46 in group IV (metastatic disease). By univariate analysis, the significant prognostic factors affecting survival were clinical group, age at time of diagnosis, tumor size, distant metastases, nodal metastases, and local and distant recurrence. By multivariate analysis of pretreatment factors, age at time of diagnosis, nodal metastases, and distant metastases were significant prognostic factors affecting survival; tumor size approached significance. Both the clinical group system and pretreatment staging system (Lawrence/Gehan) predicted significant differences in survival between groups of patients. The lower survival rate among group II and III node-negative patients with a distal tumor (who, with more extensive surgery, could have been in group I) in comparison to group I patients with a distal lesion, approached significance. In patients without distant metastases, survival was significantly different in those patients that had negative nodes from those in whom nodes were not biopsied. CONCLUSION: This review confirms that both clinical grouping and the new pretreatment staging system used in IRS IV can predict the likelihood of survival of children with extremity sarcomas. By multivariate analysis of the elements included in the staging system, nodal metastases, distant metastases, and tumor size were useful in predicting survival. In addition, age was a significant predictor. This study confirms previous suggestions that complete excision with gross and microscopically negative margins is preferable in the treatment of children with extremity rhabdomyosarcomas.

Adolescent↗

Prognostic factors in metastatic prostate cancer.

Androgen deprivation therapy is the initial treatment choice for metastatic disease. When enrolling patients into androgen deprivation trials, it is important to consider stratification of enrollees based on prognostic factors that have been identified as important in determining the likelihood of response. Prognostic factors are also helpful in identifying which patients are less likely to respond to treatment; this information also would help to counsel patients. Performance status is an important prognostic factor; however, its impact is minimal because the great majority of men who receive treatment for advanced disease have a normal performance status. Hemoglobin, alkaline phosphatase, and a semiquantitative grading scale for the number of metastatic foci on the bone scan are useful prognostic factors. The pretreatment serum testosterone level is a powerful prognostic factor. Patients with a low serum testosterone level have a shorter progression-free survival than men whose pretreatment serum testosterone level is above normal. The prognostic importance of pretreatment serum testosterone level has been evaluated in studies using treatment methods that lower this level to castrate levels. Recently, we found that serum testosterone level was not a prognostic factor for men taking the nonsteroidal antiandrogen, Casodex (Zeneca, Wilmington, DE), which does not alter the serum testosterone level. The pretreatment serum prostatic-specific antigen also is a prognostic factor. This antigen may be the best single method for monitoring patients in regard to response to or progression following therapy. The return of the prostatic-specific antigen level to normal (< 4 ng/ml), or the decline in the prostatic-specific antigen level of > 90% indicates a prolonged progression-free survival. In the future, it will be interesting to incorporate both the initial prognostic factors as well as monitor the prostatic-specific antigen into a multivariate analysis, which will be highly predictive of a man's response to treatment.

Acid Phosphatase↗

Prognostic factors in patients with unresectable locally advanced pancreatic adenocarcinoma treated with chemoradiation.

BACKGROUND: Although patients with locally advanced pancreatic cancer (LAPC) have an extremely poor prognosis, they are a heterogeneous group. Prognostic factors are inadequately defined for disease-free survival and overall survival in patients with LAPC who are receiving chemoradiation, so more definitive prognostic factors would be very useful for designing clinical trials. METHODS: Between December 1993 and July 2005, 247 patients with nonmetastatic LAPC were treated at M. D. Anderson Cancer Center (Houston, Tex) with concurrent chemoradiation (CRT). Median radiation dose was 30 Gy (range, 15-52.2 Gy). Radiosensitizers included 5-fluorouracil (54%), gemcitabine (33%), and capecitabine (13%). Actuarial univariate and multivariate statistical methods were used to determine significant prognostic factors for disease-free survival and overall survival. RESULTS: Median follow-up was 4.3 months (range, 1-63 months). Median disease-free survival and overall survival were 4.2 months and 8.5 months, respectively. On univariate analysis, prognostic factors for improved disease-free survival were a Karnofsky performance scale (KPS) status of >80 (P < .01) and a hemoglobin (Hgb)level at presentation of >/=12 (P = .03). On multivariate analysis, KPS was the only independent prognostic factor for disease-free survival. Median disease-free survival was 4.9 months among patients with a KPS score of >80 and was 3.9 months among those with a KPS score of </=80. On univariate analysis, prognostic factors for improved overall survival were an Hgb level of >/=12 (P = .02), KPS>80 (P < .001), and <5% weight loss (P = .03). On multivariate analysis, Hgb and KPS were independent prognostic factors for overall survival. CONCLUSIONS: In the current study, KPS score was an independent prognostic factor for disease-free and overall survival among patients treated with chemoradiation for LAPC. The pretreatment Hgb level was an additional independent prognostic factor for overall survival.

Adenocarcinoma↗

[Evaluation of prognostic factors in malignant synovioma].

Prognostic factors in 78 patients (36 males and 42 females) aged 9 to 68 treated for malignant synovioma in Warsaw Institute of Oncology between 1950 and 1988 have been assessed. Case history ranged from 1 month to 18 years. The neoplasm was found primarily within lower limb- 45 cases (58%), upper limb- 23 (29%), head, neck and trunk were the sites in 10 patients (13%). In 37 cases tumor diameter was less then 5 cm (T1) and in 37 more (T2 and T3). The diameter remained unknown in 4 patients. Monophase structure was found in 50 cases, biphase structure in 28. Five years survival constituted 48%, 10 years- 28%. The best prognostic value had size of the tumor and the duration of the symptoms. The size below 5 cm gave 58% years survival, above 5 cm only 34%. The history longer then 12 months offered 70% of 5 years survival and shorter one only 27%. Patients with longer history and smaller size of the tumor had significantly better prognosis then those with short history and tumor exceeding 5 cm in size. Females with tumor larger than 5 cm had much better changes then males. Remote metastases worsened the prognosis markedly. The age, localization and histological type of the neoplasm had no prognostic value.

Adolescent↗

Prognostic factors in soft tissue sarcoma. Tissue microarray for immunostaining, the importance of whole-tumor sections and time-dependence.

In adult soft tissue sarcoma (STS) of the extremities and trunk wall, improved prognostic factors are needed to identify patients at high-risk for metastasis. Various factors are included in the many prognostic systems currently in use and the prognostic value of immunohistochemical (IHC) expression of biological markers is unclear. The tissue-preserving, high throughput tissue microarray (TMA) technique for analysis of immunohistochemical expression of biological markers was validated for Ki-67, and was found to yield results comparable to conventional staining methods. TMA was used to study the IHC expression of multiple markers (Ki-67, p53, cyclin A, bcl-2, beta-catenin, CD44, and Pgp) in 218 malignant fibrous histiocytomas (MFH) and in 140 mixed STS. In the MFH series, tumor size and Ki-67, as the only IHC marker, provided independent prognostic information. In the mixed STS series whole-tumor sections were used and TMA was performed in the peripheral tumor growth zone. Whole-tumor sections facilitated assessment of the strong independent prognostic factors for metastasis vascular invasion, hazard ratio (HR) 3.5, tumor necrosis (HR 2.8), and tumor growth pattern (HR 3.2), and the latter also correlated with local recurrence (LR). In comparison, histological malignancy grade, tumor size, and depth were not of independent prognostic value. When TMA was performed from the peripheral tumor growth zone, the IHC expression of Ki-67 (HR 1.9), beta-catenin (HR 2.7), CD44 (HR 2.1) and Pgp (HR 2.4) were independent prognostic factors. Finally, prognostic factors were found to be time-dependent, and most had lost their prognostic value after 2 years, whereas LR was a strong prognostic factor for metastasis whenever it occurred.

Adult↗

Metastatic gastric lymph node rate is a significant prognostic factor for resectable stage IV stomach cancer.

BACKGROUND: Stage IV gastric carcinoma is rarely curatively resected and almost invariably carries a poor prognosis. Several clinicopathologic factors are involved, but lymphatic spread of the cancer may significantly affect survival. STUDY DESIGN: A retrospective study was designed to evaluate whether the nodal metastatic rate (number of lymph node metastases/number of resected lymph nodes) is a parameter of lymphatic spread and could provide a significant prognostic factor. Several prognostic factors were assessed by multivariate analysis in 153 stage IV gastric carcinoma patients with histopathologic data on nodal metastasis. RESULTS: A significant difference in survival was observed in the stage IV cancer patients with total nodal or gastric nodal metastatic rates < 50% versus those with rates > 50%. Multivariate analysis revealed that a total nodal or gastric nodal metastatic rate > 50% was a highly significant prognostic factor. The gastric nodal metastatic rate can be used in patients who do not undergo an extended lymphadenectomy. CONCLUSIONS: Lymphatic spread of gastric carcinoma expressed in terms of the total nodal or gastric nodal metastatic rate is a significant prognostic factor. The latter can be calculated without pathologic data derived from extended lymphadenectomy, and so it is universally applicable.

Humans↗

Prognostic factors including neoadjuvant chemotherapy in Mexican children with neuroblastoma.

INTRODUCTION: There are several prognostic factors in children with neuroblastoma that have been outlined in the international literature. MATERIAL AND METHODS: A retrospective study was carried out analysing the medical records of patients with the pathological diagnosis of neuroblastoma seen at the Department of Oncology from the Instituto Nacional de Pediatriá (Mexico) between January 1984 to January 1997. A total of 32 clinical prognostic factors were assess in our population. RESULTS: Fifty five patients whose age ranged from 1 to 168 months old, mean of 35 months were included. Out of 32 prognostic factors only 6 including sex (p= 0.0039), metastatic disease to bone (p= 0.003), bone marrow involvement (p= 0.0027), staging system (p= 0.000015), surgical treatment (p 0,0022) and neoadjuvant chemotherapy (p.005) were the most significant. CONCLUSIONS: It was concluded that besides the prognostic factors outlined, neoadjuvant chemotherapy is of utmost importance. It decreases tumor volume and allows surgery to be more successful, therefore believing that this variable represents a specific prognostic factor in cases of advanced neuroblastoma.

Adolescent↗

Prognostic factors in rheumatoid arthritis.

To determine prognostic factors that predict the course of rheumatoid arthritis (RA) from an early phase of the disease, we reviewed publications on possible prognostic factors. We excluded studies with patients with long standing disease, studies with a followup less than one year, studies providing insufficient methodological information, and studies using noninformative outcome measures. We identified individual factors associated with worse outcome: presence of serum rheumatoid factor (RF), HLA-DR4, signs of high disease activity [number of swollen or tender joints, elevated C-reactive protein (CRP)], rheumatoid nodules, radiological abnormalities, poor grip strength, and poor functional status. The accuracy of prediction of these individual factors is low. Therefore, in several studies, combinations of entry variables were investigated for accuracy in predicting the severity of radiological abnormalities. IgM RF in combination with radiographic damage at onset of RA and either clinical measures of disease activity and/or laboratory measures such as erythrocyte sedimentation rate (ESR) or CRP and/or a functional ability score, and/or HLA-DR4 could predict radiological abnormalities with an accuracy of 70-80%. Further research should be directed to find more specific disease markers and to validate an internationally accepted combination of prognostic criteria.

Arthritis, Rheumatoid↗

Prognostic factors in renal cell carcinoma.

The identification of prognostic factors in patients with renal cell carcinoma (RCC) represents an area of increasing interest. The tumor, node, metastasis (TNM) staging system is currently the most extensively used tool for providing prognostic information for RCC. Data published in the last few years have led to significant controversies as to whether further revisions are needed in current staging systems and whether improvements can be made with the introduction of new, more accurate and predictive prognostic factors not currently included in traditional staging systems. While integrated staging systems have improved the staging of RCC, the recent discovery of molecular tumor markers is expected to revolutionize the staging of RCC in the future and lead to the development of new therapies based on molecular targeting. The aim of the current review is to highlight such controversies and provide an update on current staging modalities and prognostic factors for RCC.

Biomarkers, Tumor↗

[Prognostic factors of small cell bronchial carcinomas].

Prognostic factors in small cell lung carcinoma have a great importance with regard to the interpretation of treatment results. The main prognostic factors are the extent of the disease, performance status, age and sex. Other factors are discussed.

Age Factors↗

Preserved Smad4 expression in the transforming growth factor beta signaling pathway is a favorable prognostic factor in patients with advanced gastric cancer.

The signals of the transforming growth factor beta (TGF-beta) superfamily are conveyed through cell surface serine/threonine kinase receptors to the intracellular mediators known as Smads. Activation of Smads causes their translocation from the cytoplasm to the nucleus, where they function to control gene expression. The present study analyzed the expression of Smad4 and TGF-beta1 to determine their prognostic significance in advanced gastric cancer. Of 249 cases of advanced gastric cancer, 41 had invaded the muscular layer, 114 had invaded the subserosal layer, and 94 had invaded the serosa. Anti-Smad4 and TGF-beta1 antibodies were used for immunohistochemical staining. Reduced expression of Smad4 was 75.1%, whereas positive expression of TGF-beta1 was 39.6% in gastric cancer. Smad4 expression was related to the depth of tumor invasion (P < 0.05), and TGF-beta1 expression correlated with tumor gross type (P < 0.05). Postoperative survival analysis indicated that patients who had a tumor with reduced Smad4 expression had a poorer clinical outcome than those with preserved expression (P < 0.05). Furthermore, in patients with TGF-beta1-positive tumors, survival rate was significantly better in patients with preserved Smad4 expression than in those with reduced Smad4 expression (P < 0.05). According to multivariate analysis, Smad4 expression acted as an independent prognostic factor. Smad4 expression, particularly in the TGF-beta pathway, is an effective predictor of outcome for patients with advanced gastric cancer.

Adult↗

Prognostic factors of whiplash-associated disorders: a systematic review of prospective cohort studies.

We present a systematic review of prospective cohort studies. Our aim was to assess prognostic factors associated with functional recovery of patients with whiplash injuries. The failure of some patients to recover following whiplash injury has been linked to a number of prognostic factors. However, there is some inconsistency in the literature and there have been no systematic attempts to analyze the level of evidence for prognostic factors in whiplash recovery. Studies were selected for inclusion following a comprehensive search of MEDLINE, EMBASE, CINAHL, the database of the Dutch Institute of Allied Health Professions up until April 2002 and hand searches of the reference lists of retrieved articles. Studies were selected if the objective was to assess prognostic factors associated with recovery; the design was a prospective cohort study; the study population included at least an identifiable subgroup of patients suffering from a whiplash injury; and the paper was a full report published in English, German, French or Dutch. The methodological quality was independently assessed by two reviewers. A study was considered to be of 'high quality' if it satisfied at least 50% of the maximum available quality score. Two independent reviewers extracted data and the association between prognostic factors and functional recovery was calculated in terms of risk estimates. Fifty papers reporting on twenty-nine cohorts were included in the review. Twelve cohorts were considered to be of 'high quality'. Because of the heterogeneity of patient selection, type of prognostic factors and outcome measures, no statistical pooling was able to be performed. Strong evidence was found for high initial pain intensity being an adverse prognostic factor. There was strong evidence that for older age, female gender, high acute psychological response, angular deformity of the neck, rear-end collision, and compensation not being associated with an adverse prognosis. Several physical (e.g. restricted range of motion, high number of complaints), psychosocial (previous psychological problems), neuropsychosocial factors (nervousness), crash related (e.g. accident on highway) and treatment related factors (need to resume physiotherapy) showed limited prognostic value for functional recovery. High initial pain intensity is an important predictor for delayed functional recovery for patients with whiplash injury. Often mentioned factors like age, gender and compensation do not seem to be of prognostic value. Scientific information about prognostic factors can guide physicians or other care providers to direct treatment and to probably prevent chronicity.

Cohort Studies↗

Prognostic factors in small cell lung cancer: a simple prognostic index is better than conventional staging.

Conventional staging in small cell lung cancer (SCLC) is only of limited prognostic value and is often based on elaborate investigations. We have carried out univariate and multivariate analysis of possible prognostic factors at presentation in 333 consecutive patients with SCLC. Fifteen parameters were found to have individual prognostic significance, of which the most powerful were serum albumin, bone marrow aspirate, disease extent and performance status (all P less than 0.00005). Factors which were not of prognostic significance included age, sex, SVC obstruction, and pleural involvement. Multivariate analysis excluded many factors including bone marrow aspirate as not being independently variable, and a simple combination of clinical performance status, serum albumin and alanine transaminase could be used to define 3 groups (good; medium; poor) of better prognostic significance (survival at 1 year 50% vs. 27% vs. 3%) than conventional limited/extensive disease staging (1 year survival 48% vs. 18%). Other simple combinations of biochemical parameters including plasma sodium and alkaline phosphatase achieved almost as good prognostic groupings. We suggest that consideration should be given to replacing the conventional limited/extensive disease staging system with a simpler system along the lines we have described.

Adult↗

Relationship between epidermal growth factor receptor (EGF-R) and various prognostic factors in human endometrial carcinoma.

Eighty primary endometrial carcinomas were analyzed for the presence of epidermal growth factor receptors (EGF-R) by the use of a single point (1ng 125I-EGF) EGF-R assay. Fifty percent of the analyzed specimens were EGF-R positive (EGF-R(+)) with binding capacities > 1 fmol mg-1 and 15% bound > 7 fmol mg-1. The EGF-R status was correlated with different clinically relevant prognostic factors and the survival rates were analyzed. The correlations revealed no significant differences in the grade of tumor differentiation and in the depth of myometrial invasion. The advanced tumor stages III and IV and tumors with a squamous cell component in the histologic examination expressed EGF-R in a higher percentage. Between the EGF-R and the steroid receptor status existed a weak negative correlation. Estrogen receptor positive tumors were in 47% and progesterone receptor positive tumors in 45% EGF-R (+). The corresponding number for the receptor negative tumors were 57 and 65%. Life table analyses were performed with different cut-off limits for specific EGF binding ranging from > 1, > 3, > 5 and > 7 fmol mg-1. Dependent on the cut-off limits the analysis demonstrates a reduced survival probability for patients with EGF-R+ tumors. These differences were mainly found in the small group with a high number of EGF-R's (> 7 fmol). The analysis of tissue extracts for the presence of factors binding to the EGF-R revealed in some specimens high concentrations of EGF-like factors. By the use of TGFa (transforming growth factor alpha) immunohistochemistry we were able to demonstrate that the tumor cells produce TGFa, whereas the stroma is TGFa negative. We assume that the EGF-like factors consist mainly of TGFa.

Journal Article↗

Prognostic factors in breast cancer: the value of the Nottingham Prognostic Index for patients treated in a single institution.

PURPOSE: The Nottingham Prognostic Index (NPI) is used to predict survival in patients with breast cancer. This index is based on tumor size, lymph node stage, and histological grade and allows the stratification of patients into three different prognostic groups. Our aim was to verify the effect of some prognostic variables on survival and to establish the independent influence of each of these variables by a survival regression analysis. We applied the NPI to the same group of patients to assess its predictive power and reproducibility. METHODS: We evaluated 311 women with breast cancer treated between January 1993 and December 1998. RESULTS: In a multivariate analysis (Cox proportional hazard model), only size, lymph node involvement, and histological grade were independent prognostic factors. The survival curves obtained after applying the NPI were similar to those for the factors with independent prognostic significance derived from our multivariate analysis. CONCLUSION: The NPI allows us to accurately predict prognosis, and we advocate its standardized use.

Adult↗