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Prognostic factors in cancer.

Diagnosis, prognosis, and treatment are the three core elements of the art of medicine. Modern medicine pays more attention to diagnosis and treatment but prognosis has been a part of the practice of medicine much longer than diagnosis. Cancer is a heterogeneous group of disease characterized by growth, invasion and metastasis. To plan the management of an individual cancer patient, the fundamental knowledge base includes the site of origin of the cancer, its morphologic type, and the prognostic factors specific to that particular patient and cancer. Most prognostic factors literature describes those factors that directly relate to the tumor itself. However, many other factors, not directly related to the tumor, also affect the outcome. To comprehensively represent these factors we propose three broad groupings of prognostic factors: 'tumor'-related prognostic factors, 'host'-related prognostic factors, and 'environment'-related prognostic factors. Some prognostic factors are essential to decisions about the goals and choice treatment, while others are less relevant for these purposes. To guide the use of various prognostic factors we have proposed a grouping of factors based on their relevance in everyday practice; these comprise 'essential,' 'additional,' and 'new and promising factors.' The availability of a comprehensive classification of prognostic factors assures an ordered and deliberate approach to the subject and provide safeguard against skewed approaches that may ignore large parts of the field. The current attention to tumor factors has diminished the importance of 'patient' (i.e., 'host'), and almost completely overshadows the importance of the 'environment'. This ignores the fact that the latter presents the greatest potential for immediate impact. The acceptance of a generic prognostic factor classification would facilitate communication and education about this most important subject in oncology.

Humans↗

Syntactic structure analysis in invasive breast cancer: analysis of reproducibility, biologic background, and prognostic value.

The reproducibility, biologic background, and prognostic value of syntactic structure analysis were studied in a group of 94 patients with invasive primary breast cancer. Using an interactive digitizing video overlay system, the centers of malignant breast cancer nuclei were marked in the five (subjectively) most cellular fields of vision for each case at a final magnification of X1,200, and the corresponding minimum spanning tree was composed for each field. From each minimum spanning tree, 10 syntactic structure features were derived; subsequently, the mean, standard deviation, minimum, and maximum values of the five fields analyzed were calculated for further statistical analysis. Forty statistics thus were available for each case. The reproducibility of repeatedly measuring the same field (independent of nuclearity) and the same patient twice by the same or different observers was good for most of the syntactic structure features. When comparing the statistics of the syntactic structure features with other established prognosticators, correlations were found with (in this order) standard deviation and mean nuclear area (expressing nuclear differentiation), volume percentage epithelium (expressing architectural differentiation), and mitotic activity index. In univariate survival analysis several syntactic structure statistics yielded prognostic significance, the best being the maximum of the number of nuclei with two neighbors (P = .002; Mantel-Cox test, 12.4). Multivariate analysis revealed that syntactic structure features did not provide additional prognostic values with regard to each other. However, they did show additional prognostic values with regard to the multivariate prognostic index (currently one of the best prognosticators in breast cancer), which combines the mitotic activity index, lymph node status, and tumor size. Measurement of syntactic structure features could therefore contribute to an improved prediction of prognosis of breast cancer patients. In conclusion, syntactic structure analysis is a simple, fast, and highly reproducible technique that shows prognostic value in invasive breast cancer and also has important prognostic value with regard to the well-established and prognostically strong morphometric features. It seems to be a promising new method of analyzing tissue architecture in breast cancer and perhaps in many other tumors.

Breast Neoplasms↗

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↗

Identification of prognostic factors in patients with brain metastases: a review of 1292 patients.

PURPOSE: Prognostic factors in 1292 patients with brain metastases, treated in a single institution were identified in order to determine subgroups of patients suitable for selection in future trials. MATERIALS AND METHODS: From January 1981 through December 1990, 1292 patients with CT-diagnosed brain metastases were referred to the Department of Radiation Oncology, Daniel den Hoed Cancer Center, Rotterdam. The majority of patients were treated with whole brain radiotherapy (84%), the remainder were treated with steroids only or surgery and radiotherapy. Information on potential prognostic factors (age, sex, performance status, number and distribution of brain metastases, site of primary tumor, histology, interval between primary tumor and brain metastases, systemic tumor activity, serum lactate dehydrogenase, response to steroid treatment, and treatment modality) was collected. Univariate and multivariate analyses were performed to determine significant prognostic factors. Results were compared with literature findings using a review of prognostic factors in 18 published reports. RESULTS: Overall median survival was 3.4 months, with 6-month, 1-year, and 2-year survival percentages of 36%, 12%, and 4% respectively. Survival was statistically significantly different between treatment modalities, with median survival of 1.3 months in patients treated with steroids only, 3.6 months in patients treated with radiotherapy, and 8.9 months in patients treated with neurosurgery followed by radiotherapy (p < 0.0001). Multivariate analysis confirmed literature findings of the major prognostic value of treatment modality on survival of patients with brain metastases. Performance status, response to steroid treatment, systemic tumor activity, and serum lactate dehydrogenase were independent prognostic factors with the strongest impact on survival, second only to treatment modality. Site of primary tumor, age, and number of brain metastases were also identified as prognostic factors in our material, although with lesser importance. In patients with lung primaries, sex was found to have significant impact on survival. In patients with breast primaries, interval between primary tumor and development of brain metastases appeared to be a statistically significant prognostic factor. Histology in patients with lung primaries and distribution of brain metastases were not found to be statistically significant in multivariate analysis. CONCLUSIONS: In this large database, the value of established prognostic factors was confirmed and, furthermore, some less well-recognized parameters such as response to steroid treatment, serum lactate dehydrogenase, age, sex in lung primaries, and site of primary tumor were established. From the three strongest prognostic factors--performance status, response to steroids, and evidence of systemic disease--simple identification of favorable and unfavorable subgroups of patients with brain metastases can be constructed.

Adolescent↗

Factors influencing the prognostic role of oestrogen and progesterone receptor levels in breast cancer--results of the analysis of 670 patients with 11 years of follow-up.

In the last two decades, the prognostic role of the steroid hormone receptors has been the subject of a myriad of publications. Nevertheless, its relevance after long-term follow-up is still not clear. The confusion about the prognostic value is mainly due to the difficulty in comparing analyses. Despite different study-designs and statistical approaches, oestrogen (ER) and progesterone (PR) receptors are widely accepted as prognostic factors. Data from 670 breast cancer patients with a median follow-up of 11.4 years were analysed retrospectively. ER and PR were measured by the dextran-coated charcoal (DCC) assay. To investigate the time dependence of the prognostic relevance of ER and PR, separate analyses were done for follow-up shorter and longer than 5 years. Special focus was directed at patients < or =50 and >50 years, node-negative women, in particular those without adjuvant therapy. Univariate and multivariate analyses were performed. In univariate analysis, ER and PR were associated with a significantly longer overall survival at the cut-off levels 10, 20 or 100 fmol/mg protein. The significant survival benefit occurred in the first 5 years of follow-up and remained unchanged in the following period. In the multivariate analyses, only the PR was of significant prognostic value (for PR> or =20 fmol/mg P=0.036, for PR> or =100 P=0.01, Cox analysis). In patients younger than 51 years, only PR was an independent prognosticator at the cut-off level of 100 fmol/mg protein, while in patients >50 years both hormone receptors were not significant. In N0 patients, only the PR reached long-term prognostic independence at a cut-off point of > or =100 fmol/mg (P=0.018). In addition, in the group of node-negative women < or =50 years without adjuvant therapy the PR level reached prognostic significance. The hormone receptor status was a prognostic factor only during the first 5 years of follow-up. Our data suggest that age, lymph node status, length of follow-up and probably the ER/PR assay are important for the evaluation of ER and PR as prognostic variables. In most analyses, PR appeared to be superior to ER in predicting the prognosis of primary breast cancer patients.

Adult↗

Prognostic significance of urokinase (uPA) and its inhibitor PAI-1 for survival in advanced ovarian carcinoma stage FIGO IIIc.

Strong evidence has accumulated on the prognostic value of tumour-associated proteolytic factors in patients afflicted with solid malignant tumours, including advanced ovarian cancer. We evaluated the prognostic impact of the protease urokinase plasminogen activator (uPA) and its inhibitor PAI-1 on overall survival in patients with advanced ovarian cancer stage FIGO IIIc in order to select patients at risk. uPA and PAI-1 antigen were determined by ELISA in primary tumour tissue extracts of 86 ovarian cancer patients FIGO stage IIIc enrolled in a prospective study. Univariate and multivariate analyses were performed using the Cox proportional hazard model. The time-varying coefficient model of Gray was used to assess the time-dependent strength of prognostic factors tumour mass, uPA and PAI-1 on overall survival. In all patients, uPA and PAI-1 (optimized cut-offs of 2.0 and 27.5 ng mg(-1) protein respectively), in addition to the traditional prognostic parameters of residual tumour mass, nodal status, grading and ascites volume, were of prognostic significance in univariate analysis for overall survival. Even in patients with residual tumour mass (n = 43), the statistically independent prognostic impact of PAI-1 persisted, allowing further discrimination between low- and high-risk patients. In multivariate analysis, residual tumour mass (P < 0.001, relative risk (RR) 4.5), PAI-1 (P < 0.001; RR 3.1) and nodal status (P = 0.022, RR 2.6) turned out to be strong, statistically independent prognostic parameters. Evaluation of the time-dependent prognostic impact of residual tumour mass and PAI-1 on overall survival (n = 86, 50 months) revealed that the prognostic power of these factors increased with time. In patients with advanced ovarian cancer, both residual tumour mass and PAI-1 are statistically independent strong prognostic factors. Even within patient subgroups with or without residual tumour mass, PAI-1 allowed selection of patients at risk who might benefit from individualized therapy protocols.

Adult↗

Validation of genomics-based prognostic tests in malignant pleural mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm with limited pretreatment prognostication strategies. In this report, we examine the accuracy of a previously proposed prognostic test in an independent cohort of MPM patients. This test uses simple ratios of gene expression levels to provide a novel prognostication scheme. EXPERIMENTAL DESIGN: Gene expression data using high-density oligonucleotide microarrays (approximately 22,000 genes) were obtained for a new cohort of human MPM tumors from patients undergoing similar treatments (n = 39). The relative expression levels for specific genes were also determined using real-time quantitative reverse transcription-PCR. We also used a subset of these tumors associated with widely divergent patient survival (n = 23) as a training set to identify new treatment-specific candidate prognostic molecular markers and gene ratio-based prognostic tests. The predictive nature of these newly discovered markers and gene ratio-based prognostic tests were then examined in an independent group of tumors (n = 52) using microarray data and quantitative reverse transcription-PCR. RESULTS: Previously described MPM prognostic genes and gene ratio-based prognostic tests predicted clinical outcome in 39 independent MPM tumor specimens in a statistically significant manner. Newly discovered treatment-specific prognostic genes and gene ratio-based prognostic tests were highly accurate and statistically significant when examined in an independent group of 52 tumors from patients undergoing similar treatment. CONCLUSIONS: The data support the use of gene ratios in translating gene expression data into easily reproducible, statistically validated clinical tests for the prediction of outcome in MPM.

Adult↗

Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma.

PURPOSE: To validate the Motzer et al prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma (RCC) and to identify additional independent prognostic factors. PATIENTS AND METHODS: Data were collected on 353 previously untreated metastatic RCC patients enrolled onto clinical trials between 1987 and 2002. RESULTS: Four of the five prognostic factors identified by Motzer were independent predictors of survival. In addition, prior radiotherapy and presence of hepatic, lung, and retroperitoneal nodal metastases were found to be independent prognostic factors. Using the number of metastatic sites as surrogate for individual sites (none or one v two or three sites), Motzer's definitions of risk groups were expanded to accommodate these two additional prognostic factors. Using this expanded criteria, favorable risk is defined as zero or one poor prognostic factor, intermediate risk is two poor prognostic factors, and poor risk is more than two poor prognostic factors. According to Motzer's definitions, 19% of patients were favorable risk, 70% were intermediate risk, and 11% were poor risk; median overall survival times for these groups were 28.6, 14.6, and 4.5 months, respectively (P < .0001). Using the expanded criteria, 37% of patients were favorable risk, 35% were intermediate risk, and 28% were poor risk; median overall survival times of these groups were 26.0, 14.4, and 7.3 months, respectively (P < .0001). CONCLUSION: These data validate the model described by Motzer et al. Additional independent prognostic factors identified were prior radiotherapy and sites of metastasis. Incorporation of these additional prognostic factors into the Motzer et al model can help better define favorable risk, intermediate risk, and poor risk patients.

Adult↗

Prognostic factors in 677 patients in Singapore with nondisseminated nasopharyngeal carcinoma.

BACKGROUND: The objective of the current study was to describe the survival of nasopharyngeal carcinoma (NPC) patients in Singapore, verify the prognostic value of the revised 1997 TNM staging system, and develop a multivariate prognostic model for NPC. In addition, the authors also examined the prognostic value of characteristics of lymph node spread and parapharyngeal involvement. METHODS: A prospectively maintained database containing clinical and computed tomography scan data was used to reclassify 677 NPC patients treated between 1992 and 1994 according to the new staging system. Records were linked with the death registry to ascertain the patient's vital status and date of death. Overall and stage specific survival were analyzed using the Kaplan-Meier method and the log rank test. Univariate and multivariate Cox proportional hazards regression analysis were used to obtain prognostic models. RESULTS: Two hundred seventy-four deaths (40.5%) occurred. The 5-year survival rate was 56.6% (95% confidence interval [95% CI], 52.3%, 60.7%). The stage specific 5-year survival rates were: Stage I, 88%; Stage IIA, 75%; Stage IIB, 74%; Stage III, 60%; Stage IVA, 35%; and Stage IVB, 28%. TNM stage was found to be a statistically significant prognostic factor (P < 0.0001). Cranial nerve (hazard ratio [HR]: 2.77), orbit (HR: 5.71), and intracranial involvement (HR: 2.46) conferred a particularly bad prognosis in univariate analysis. Independently significant prognostic factors were age; lymph node status; and paraoropharyngeal, cranial nerve, orbit, and nasal involvement. Among lymph node positive patients, independently significant prognostic lymph node characteristics were Ho level and laterality. Although parapharyngeal involvement appeared to be prognostically unimportant, paraoropharyngeal involvement distinguished a subgroup with a poorer prognosis (HR: 1.84; 95% CI, 1.45, 2.34; P < 0.0001). Lateral spread to the medial infratemporal fossa and beyond also was found to confer a poorer prognosis. CONCLUSIONS: The results of the current study show that the revised 1997 TNM staging system is prognostically useful. Subdivision into paraoropharyngeal involvement and using the medial infratemporal fossa to delineate prognostically significant lateral spread should be considered in future revisions.

Adolescent↗

Prognostic significance of p53, bcl-2 and Ki-67 in high risk superficial bladder cancer.

BACKGROUND: Although tumor grade and stage are the most accurate prognostic factors in the evaluation of transitional cell bladder cancer, they cannot always predict the true tumor biological potential since superficial tumors of the same stage and grade may have completely different clinical courses. This study was performed in order to examine whether p53, bcl-2 and Ki-67 have any validity in predicting the course of superficial bladder tumors, with high risk for recurrence or progression, over the traditional prognostic factors that are currently used. Furthermore, we investigated whether any one of these markers maintains its prognostic capability after one course of intravesical instillations of IFN gamma. MATERIALS AND METHODS: The immunohistochemical evaluation of bladder tumor specimens, that were obtained transurethrally for the expression of p53, bcl-2 and Ki-67, was performed in 58 patients. After meticulous selection of cut-off values for the expression of the aforementioned markers, twenty-eight patients were treated only with transurethral resection (TURBT only group) while 30 patients received adjuvantly intravesical instillations of interferon gamma. The times to first recurrence and progression were recorded during the follow-up period which ranged from 3 to 36 months (mean 11.7 months). The prognostic significance of tumor stage, grade, presence of CIS, p53, bcl-2 and Ki-67 in determining the risk for recurrence, was studied with both univariate (log-rank test) and multivariate (Cox regression) methods of analysis, separately for the TURBT only group of patients and for those who received instillations. The same analysis was employed for the risk of progression in the overall number of progressed patients. RESULTS: According to both uni- and multivariate analysis of the prognostic significance for tumor stage (T), grade (G), presence of CIS, p53, Ki-67 and bcl-2 in each group of patients, the Ki-67 index was the only independent prognostic factor for recurrence in patients treated with TURBT only (p = 0.0044 univariate, p = 0.031 multivariate). None of the factors which were studied proved to have prognostic significance for recurrence in the group of patients who received adjuvant intravesical instillation with the immunomodulating agent. Although in the univariate analysis all the studied parameters except tumor stage seem to be associated in a statistically significant manner with higher risk for progression, the multivariate analysis did not yield any independent significant prognosticator. The same evaluation was performed only for the patients with grade 2 disease (28) and yielded statistically significantly higher risk for recurrence, both in uni- (p = 0.0081) and in multivariate analysis (p = 0.044) only in the patients with overexpression of Ki-67 who were treated with TURBT alone. CONCLUSION: The Ki-67 proliferative index has an independent validity in predicting those patients with high risk superficial bladder tumors who may recur in a short follow-up period. A similar relationship of Ki-67 overexpression to progression was not detected. The expression of p53 and bcl-2 does not seem to offer any prognostic information in predicting either recurrence or progression over the prognostic factors that are currently used in clinical practice.

Administration, Intravesical↗

[Prognostic factors in patients with small cell lung cancer].

OBJECTIVE: To investigate the prognostic factors of small cell lung cancer (SCLC) and establish a reliable model of clinical prognostic index. METHODS: Kaplan-Meier and Cox regression were used to analyze the relationship between survival time and prognostic factors in 60 cases of SCLC. The prognostic factors included clinical and laboratory parameters, serum cytokeratin fragment 19 (CYFRA21-1), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), CA125, interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R). RESULTS: Kaplan-Meier analysis showed that poor prognosis was in patients with KPS < 80 or extensive disease and unrelated to other clinical parameters such as age, sex and smoking index, and in patients with serum NSE > 30 micro g/L, CEA > 5.0 micro g/L, CA125 > 37 KU/L and sIL-2R > 500 KU/L. Serum IL-2 and CYFRA21-1 were also elevated, but had no significant prognostic value. Multivariate analysis indicated that serum NSE, stage and treatment of disease were independent prognostic factors. The three prognostic factors enabled establishment of a prognostic index (PI) based on a simple algorithm: PI = NSE (0 if < or = 30 micro g/L, 1 if > 30 microg/L) + stage (0 = LD, 1 = ED) + CEA (0 if < or = 5.0 microg/L, 1 if > 5.0 microg/L). CONCLUSION: The stage of disease, systemic treatment and the level of serum NSE are independent prognostic factors. Without considering the influence of treatment-related factors on survival, the levels of serum CEA, NSE and stage of disease before treatment are significant independent prognostic factors. PI calculated on the basis of CEA, NSE and stage is recommended to predict the survival of SCLC.

Adult↗

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↗

Renal cell carcinoma: current prognostic factors. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC).

BACKGROUND: Renal cell carcinomas include several distinct entities with a range of biologic and clinical behavior from relatively indolent to extremely aggressive. Although conventional prognostic factors such as stage and grade are quite useful, other clinical, laboratory, and pathologic findings are now believed to have additional predictive value. METHODS: A review of the literature on the evaluation of prognostic factors in general and on the current status of prognostic factors in renal cell carcinoma in particular was undertaken. A working classification of prognostic factors, as recommended by the College of American Pathologists, was used. For clarity, the prognostic indicators were grouped according to whether each was a patient-related or tumor-related factor. RESULTS: Patient-related prognostic factors include symptomatic presentation, significant weight loss, poor performance status, anemia, hypercalcemia, elevated alkaline phosphatase and, perhaps, elevated serum ferritin. The most widely used tumor-related prognostic factors include stage, grade, and histologic type. Recently proposed biomarkers still under investigation include DNA content, as well as markers of cellular proliferation, apoptosis, and angiogenesis, among others. CONCLUSIONS: Current prognostic factors for renal cell carcinoma yield considerable information for assisting with patient management and predicting clinical outcome. Traditional prognostic factors remain the most valuable, even though a variety of other patient-related and tumor-related factors may significantly contribute to prognostic information. A number of recently described biomarkers show great promise but the current data are insufficient to recommend their use.

Aneuploidy↗

Prognostic value of p53 and urokinase-type plasminogen activator in node-negative human breast cancers.

We measured the levels of p53 and urokinase-type plasminogen activator (uPA) in 634 tumor tissues from 634 different node-negative primary breast cancer patients who underwent locoregional surgery in the Center Oscar Lambret between July 1989 and September 1994. p53 and uPA were assayed using commercially available kits in cytosols prepared for estradiol receptor (ER) and progesterone receptor (PgR) assays. The optimum clinical thresholds were chosen for prognostic studies: 4 ng/ml for p53 and 0.5 ng/ml for uPA. p53 was elevated in 13.7% of the tumors, and uPA was elevated in 27.5% of the tumors; they were negatively related (chi 2 test) to ER and PgR and positively related to histoprognostic grading (HPG) and tumor diameter. uPA was negatively correlated to ER and PgR, and p53 and uPA were positively correlated to each other (P = 0.0001; Spearman test). In the prognostic studies, the 316 patients who did not receive adjuvant chemotherapy were included to avoid treatment interference; this number corresponds to all of the patients operated on between 1989 and 1992. The mean duration of follow-up of living patients was 4 years. In overall survival studies, Cox univariate analyses demonstrated a prognostic value of p53 (P = 0.011; risk ratio, 1.59), uPA (P = 0.038; risk ratio, 2.32), PgR, HPG, and tumor diameter. In Cox multivariate analyses, only HPG had a statistically significant prognostic value. In relapse-free survival studies, univariate analyses demonstrated prognostic values of uPA (P = 0.0011) and of age, and both parameters retained their prognostic value in multivariate analyses (uPA: P = 0.0004). This study demonstrates not only that p53 and uPA have prognostic value but also that these two parameters are linked to other classical clinical, histological, or biological prognostic parameters, as well as to each other. Moreover, because uPA is of prognostic value in multivariate relapse-free survival studies, uPA is an important prognostic factor in node-negative breast cancer patients.

Adult↗

Non-small cell lung cancer and tumor-educated platelets: screening of biomarkers and construction of a prognostic model.

BACKGROUND: Lung cancer is a leading cause of cancer-related mortality worldwide, emphasizing the urgent need for effective early detection strategies. Traditional Chinese medicine (TCM) provides a unique perspective on tumor pathogenesis, focusing on concepts such as "long-term stasis leading to accumulation". Tumor-educated platelets (TEPs) offer potential as biomarkers due to their ability to reflect cancer heterogeneity and facilitate less invasive diagnostic approaches. This study aims to identify TEP-related prognostic biomarkers for non-small cell lung cancer (NSCLC) and to construct and validate a multigene prognostic model by integrating platelet transcriptomic data with tumor tissue datasets. METHODS: We performed comprehensive analysis of gene expression datasets obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repositories to characterize transcriptomic differences among lung cancer specimens, normal tissue samples, and TEPs. Using R software, we identified Differentially expressed genes (DEGs) and subsequently applied a multi-stage analytical pipeline to TEP-associated DEGs, incorporating univariate Cox proportional hazards regression, least absolute shrinkage and selection operator (LASSO) regression, multivariate Cox regression, and stepwise regression modeling to pinpoint genes with prognostic significance. These prognostically relevant genes served as the foundation for developing a risk stratification model. We computed individual risk scores across both training and validation cohorts, enabling patient stratification into high- and low-risk categories. Model robustness was assessed through internal cross-validation and external validation procedures, while predictive performance was quantified using risk calibration metrics and receiver operating characteristic (ROC) curve analysis. RESULTS: Through systematic bioinformatics screening, we identified a four-gene prognostic signature comprising NELL2, C4orf48, PRAM1, and KLHL35, which served as the foundation for developing our risk stratification algorithm. Rigorous internal cross-validation and external cohort validation substantiated the moderate predictive performance of this signature. Comprehensive clinicopathological correlation analysis revealed that elevated risk indices, advanced pathological staging (stage III-IV), increased primary tumor dimensions, regional lymph node metastasis, and distant organ dissemination each demonstrated statistically significant associations with diminished overall survival (OS) outcomes in lung cancer patients. The clinical nomogram exhibited acceptable calibration, with calibration plots showing reasonable concordance between predicted and observed survival probabilities across all time points. Discriminative capacity assessment via time-dependent ROC analysis yielded area under the curve (AUC) values consistently surpassing 0.6, confirming moderate prognostic discrimination. Furthermore, decision curve analysis (DCA) demonstrated that our integrated multi-gene model conferred potential net clinical benefit compared to individual prognostic variables across the full spectrum of clinically relevant threshold probabilities (0-1 range), thereby establishing its potential utility for risk-informed clinical decision-making. CONCLUSIONS: This study identified NELL2, C4orf48, PRAM1, and KLHL35 as candidate TEP-related prognostic biomarkers for non-small cell lung cancer (NSCLC). The developed prognostic model shows preliminary potential for patient stratification, but its clinical application, particularly as a platelet-based liquid biopsy tool, requires further validation in independent TEP-based cohorts.

Tumor-educated platelets (TEPs)↗

Prognostic scoring in colorectal cancer liver metastases: development and validation.

HYPOTHESIS: A prognostic scoring system for colorectal cancer liver metastases that is derived from unselected patients referred for hepatic resection would improve the applicability and increase the accuracy of prognostication. DESIGN: Retrospective analysis of prospectively documented data; validation against an unrelated cohort from another institution. The median follow-up was 16.4 months (95% confidence interval, 15.0-17.8 months) (original cohort). SETTING: Two tertiary referral centers at unrelated university hospitals. PATIENTS: Independent prognosticators of survival were derived from 337 patients with colorectal cancer liver metastases referred for consideration of liver resection, and prognostic scores were calculated in 269 patients (79.8%) (original cohort). Calculation of prognostic scores was also applied to 193 patients referred and treated in an unrelated institution (validation cohort). MAIN OUTCOME MEASURES: Kaplan-Meier survival curve analysis (log-rank test) between different prognostic groups in the original and the validation cohorts. RESULTS: Independent prognosticators of survival were Dukes stage, number of metastases, and serum concentrations of carcinoembryonic antigen, alkaline phosphatase, and albumin. Significant differences were found in cumulative overall survival between patients assigned to good, moderate, and poor prognoses in the original and validation cohorts (P<.05). Liver resection improved survival in all prognostic groups. However, no patient with poor prognosis and only 19.7% (13 of 66) of patients with moderate prognosis survived 5 years, compared with 62.5% (10 of 16) of patients with good prognosis (P<.001). CONCLUSIONS: This prognostic scoring system is derived from and can be applied to patients with colorectal cancer liver metastases at the time of referral for consideration of surgery. Patients with poor prognosis have no long-term benefit from curative liver resection and should therefore be considered for combined multimodal treatment.

Adult↗

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↗