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PubMed1999

The myelodysplastic syndromes: predictive value of eight prognostic systems in 143 cases from a single institution.

BACKGROUND AND OBJECTIVE: Despite the fact that several prognostic systems for myelodysplastic syndromes (MDS) have been proposed, few studies have been designed to test their effectiveness in independent patient populations. The aim of this study was to compare the prognostic value of 8 previously described prognostic systems in a series of consecutive MDS patients observed at a single institution over a 10-year period. DESIGN AND METHODS: One hundred and forty-three patients were diagnosed as having myelodysplastic syndrome (MDS) according to the French-American-British (FAB) criteria. They were studied retrospectively in order to assess the prognostic value of the FAB classification and 7 other prognostic systems. RESULTS: On the basis of data at diagnosis, all investigated systems effectively stratified patients into groups with different life expectancies and identified a subset of patients with poor clinical outcome. However, the systems had different outcomes concerning median survival of patients classified as low-risk, ranging from less than 3 years for the Mufti scoring system to more than 8 years for the FAB classification modified according to Rosati et al. Moreover, patient distribution into different risk categories was quite different with the different prognostic systems. INTERPRETATION AND CONCLUSIONS: When applied to our case series, some of the prognostic systems had a much lower prognostic value than in the patient population from which they derived. This evidence suggests that testing of prognostic systems in independent case series is necessary before using the systems in clinical practice.

Adult↗

PubMedDate not supplied

A multifactorial prognostic model for adult soft tissue sarcoma considering clinical, histopathological and molecular data.

Soft tissue sarcomas (STS) are malignant mesenchymal lesions with a high degree of prognostic variability. Different prognostic markers such as grading, staging, tumour type and localisation are known. The establishment of these markers was based on the evaluation at results of extensive cohorts of patients. Therefore, only the established markers provide us with information about probabilities in relation to other qualities. Considering as many different markers as possible in one prognostic statement should increase the value of the resultant information. Therefore, we developed a model involving known prognostic markers to formulate an individual prognostic index. In a retrospective analysis, different prognostic factors of 198 adult STS patients with histological tumour free resection margins were evaluated using a multifactorial analysis. On the basis of a Cox-Regression-Model with proportional hazards, the prognostic factors (tumour type, staging, localisation and type of surgical resection) were selected using previous knowledge and a statistical step backward selection procedure adjusting the immunohistochemical status of p53/Mdm2 expression. On the basis of the baseline survival function of our cohort (S0 (t)), the cumulative probability of survival for two S (2) and five S (5) years was estimated. As a result of our analysis the equations S (2) = (e-00393)P and S (5) = (e-00869)P can be used to estimate the individual two and five-year probability of survival in our cohort. Here p is the result of the amount of the estimated regression-coefficients of the exact variables of the respective individual patient. This model makes it possible to include all the evaluated prognostic factors which, in turn, increases the accuracy of the prognostic information for individual patients underlining the proportional hazards assumption.

Abdominal Neoplasms↗

PubMed2001

Not traditional prognostic factors in human conventional renal carcinoma.

The evaluation of know prognostic factors is an essential step of the assessment of the patients affected by primary renal carcinoma. As long as the major biological mechanisms of renal carcinomas remain unknown, it will be impossible to achieve an accurate prognostic judgement. The TNM classification has always been the main source of information. Nevertheless, recently several investigations evaluated the prognostic power of serum and cellular markers. The aim of this study is to identify those markers which show statistical reliability and can be used in the clinical practice. A literature search was performed on MEDLINE to identify potential not traditional prognostic factors for patients with renal cell carcinoma edited from January 1997 through April 2000 using prognosis and clear cell carcinoma and kidney as keywords. We considered also articles cited in references of first selected manuscript. The analysis of serum and cellular prognostic markers does not allow the identification of specific factors, reliable, independent, easy to dose, widely useful and whose informations are repeatable. Currently classical prognostic factors (staging, grading, hystologic type, patient clinical conditions, anaemia, presentation modalities, etc.) represent the only useful elements after surgical time in RCC patients. Among serum prognostic factors, CRP and ferritin play a crucial role. These proteins appear ideal in monitoring the disease over time, due to simple test execution and specimens repeatability. Among RCC molecular markers, proliferation index result promising for their reliability and reproducibility, the easy dosage and high series number tested. Literature data suggest that the ideal marker for renal carcinomas has not been identified yet. However, C-reactive protein, ferritin and the proliferative activity indexes (Ki67 and AgNOR) appear to be, at present, the best prognostic tools. To confirm obtained results and to use biomolecolar markers on a routinary base further studies on wide surgical series will be required. The improvement of technical tool and costs reduction represent also a necessary step toward the identification of efficient prognostic markers in RCC.

Biomarkers↗

PubMedDate not supplied

The prognostic value of pre-operative serum tetranectin, CA-125 and a combined index in women with primary ovarian cancer.

OBJECTIVE: To study the prognostic value of pre-operative serum tetranectin (TN), CA125 levels and a mathematical formula (Index1) in primary ovarian cancer. MATERIALS AND METHODS: The study group consisted of sixty-six patients with varying FIGO stages I-IV. The end-point was death from ovarian cancer. Evaluation was by univariate life-tables analyses and the multivariate Cox analysis. In the Cox analyses, the variables were tested respectively in actual values and as dichotomy variables with different cut-off levels: 6.7, 7.3 and 8.2 mg/l for TN, 35, 65, 100 and 165 U/ml for CA125. RESULTS: In stages I+II only CA125 was found to be significantly prognostic, whereas TN was of no prognostic value by univariate statistics. For stages III+IV patients significantly better survivals were found for patients with TN levels above the respective cut-offs compared to patients with low TN levels, whereas no significant value was found for CA125 by univariate statistics. In the Cox analyses, FIGO stage was the strongest and TN the second most prognostic variable, followed by age. CA125, Index1 and tumor types were of no prognostic value. The strongest prognostic value for TN was found at the cut-off level 8.2 mg/l (relative hazard for FIGO stages = 3.3 and for TN = 2.6). CONCLUSION: TN was a strong prognostic variable in patients with advanced ovarian cancer. To the contrary, CA125 was a strong prognostic factor in patients with a localised ovarian cancer and of no prognostic value in patients with advanced cancer. The variables may be useful in the selection of patients with a poor outcome for new treatment strategies.

Adult↗

PubMed2004

[Prognostic factors in patients with stage III and IV non-small cell lung cancer].

OBJECTIVE: To investigate the prognostic factors in non-small cell lung cancer (NSCLC) at stage III and IV and establish a reliable model of clinical prognostic index. METHODS: Kaplan-Meier and Cox regression were used to analyze the relationship between the prognostic factors and survival time in 114 cases of NSCLC. The prognostic factors included clinical-pathological features and serum levels of cytokeratin fragment 19 (Cyfra21-1), CEA, neuron-specific enolase (NSE), CA125, interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R). RESULTS: Kaplan-Meier analysis showed that KPS, sex, disease stage, treatment, Cyfra21-1, sIL-2R and CA125 were related to prognosis. Multivariate analysis indicated that Cyfra21-1, stage and treatment were independent prognostic factors. When Cyfra21-1 > 3.5 mg/L, stage IV and chemotherapy < 3 cycles, the relative risk (RR) was 1.691, 2.229 and 3.035, respectively. In patients given 3 or more cycles of chemotherapy, serum Cyfra21-1, sIL-2R and stage at diagnosis were significantly independent prognostic factors. Three of these prognostic factors were used to establish a prognostic index (PI) model based on a simple algorithm: PI = Cyfra21-1 + sIL-2R + stage. The median survival period of patients with 3 or more cycles of chemotherapy were 18 months if PI = 0, 8 months if PI = 1 or 2, and 5 months if PI = 3. CONCLUSION: The serum Cyfra21-1, sIL-2R and disease stage in unresectable NSCLC were independent prognostic factors. PI calculated on the basis of Cyfra21-1, sIL-2R and stage is recommended to predict the survival period of NSCLC.

Antigens, Neoplasm↗

PubMed2006

[Feasibility study of application of international prognostic score on prediction of prognosis for advanced Hodgkin's lymphoma].

BACKGROUND & OBJECTIVE: Currently, 60% patients with advanced Hodgkin's lymphoma could be cured by receiving standard treatments. The international prognostic factor project on advanced Hodgkin's lymphoma has developed a concept of international prognostic score (IPS) based on seven adverse prognostic factors consisting of male sex, age 45 years or older, stage IV disease, leukocytosis, lymphocytopenia, low hemoglobin and low serum albumin for newly diagnosed advanced Hodgkin's lymphoma patients. This study was to explore the feasibility of the international prognostic score in advanced Hodgkin's lymphoma. METHODS: We performed a retrospective review of 141 patients with untreated advanced Hodgkin's lymphoma in Cancer Center of Sun Yat-sen University between January 1980 and December 2004. IPS was defined as the number of adverse prognostic factors presented at diagnosis. The rates of failure free survival (FFS) and overall survival (OS) were estimated using the method of Kaplan-Meier and compared according to IPS by log-rank test. Cox proportional hazard model was used in multivariate analysis. RESULTS: The 5-year FFS and OS for 141 advanced Hodgkin's lymphoma patients were 57.6%, 68.1% respectively. Estimated 5-year FFS was 67.7%, 63.2%, 61.8%, 34.9% for patients with 0-1, 2, 3, > or =4 of the adverse prognostic factors respectively. Estimated 5-year OS was 81.0%, 75.5%, 70.3%, 42.3% for patients with 0-1, 2, 3, > or =4 of the adverse prognostic factors respectively. The 5-year FFS for low risk patients with IPS=0-2 and high risk patients with IPS> or =3 were 65.4%, 48.9% respectively (log-rank test: P=0.012); the 5 year OS for patients with IPS=0-2 and IPS> or =3 were 78.4%, 57.1% respectively (log-rank test: P=0.004). Low risk patients with IPS=0-2 had superior overall survival than high risk patients with IPS> or =3 when treated with ABVD or MOPP. The FFS and OS of the advanced HL patients at high risk treated with ABVD were better than those treated with MOPP. Multivariate analysis demonstrated that B symptoms, extranodal disease and MOPP chemotherapy were independent adverse prognostic factors for FFS and OS. CONCLUSIONS: The IPS shows good prognostic power in advanced HL. High risk advanced HL patients treated with MOPP have inferior survival than those treated with ABVD, thus we recommend patients to be treated with ABVD or more intensive regimen.

Adolescent↗

PubMed1997

[Molecular biological prognostic markers in lung cancer].

Recent advance in cell-molecular biological studies have revealed various prognostic factors in lung cancer. The aim of this paper is to critically review the current status of molecular biological prognostic markers in non-small cell lung cancer. DNA ploidy, AgNORs and PCNA as marker of tumor cellular proliferative activity are reported to be a prognostic marker but still remain controversial. The proteases such as uPA, MMPs and CB catalyze degradation of the extracellular matrix and basement membranes. Although the prognostic implications of the uPA and MMPs still remain unclear, cathepsin B appears to be one of the most useful prognostic markers so far reported for non-small cell lung cancer. In a number of studies, genetic abnormalitis has been reported to be a prognostic marker in cancer patients. In non-small cell lung cancer, the prognostic implication of the altered p53 expression or ras p21 expression still remain unclear, especially p53 is conflicting. The most useful clinical prognostic marker may be obtained by the combined analysis of some prognostic information.

Biomarkers, Tumor↗

PubMed1997

Prognostic value of desmoplastic reaction and lymphocytic infiltration in the management of breast cancer.

OBJECTIVE: To ascertain whether the prognostic value of desmoplastic reaction and lymphocytic infiltration are a good prognostic index to estimate survival in breast cancer patients. METHODS: From 1987 to 1994, the authors have evaluated the prognostic value of desmoplastic reaction and lymphocytic infiltration related to rode state in 34 patients with breast cancer. For statistical analysis and comparison of means the "t"-test was used. The significance level was 0.01. RESULTS: The group of patients with abundant desmoplastic reaction shows an overall survival rate lower than the group with poor desmoplastic reaction (p < 0.01) and the survival of the group with abundant desmoplastic reaction was related to lymphnodal status. CONCLUSIONS: Many prognostic factors have been shown during these years, some connected to patient, some connected to neoplasm and others connected to the treatment. Recently many other prognostic factors have been recognized, among which the possible prognostic role of desmoplasia has been carefully valued. Certainly, today the prognostic value of desmoplastic reaction and lymphocytic infiltration cannot take the place of usual prognostic factors in the evaluation of breast cancer patient yet the desmoplastic reaction is a good prognostic index to estimate the survival in these patients.

Adult↗

PubMedDate not supplied

Prognostic value of biological variables in B-cell chronic lymphocytic leukemia. Can we improve upon clinical parameters?

BACKGROUND AND OBJECTIVE: Cellular and molecular features including tumor cell proliferation, immunophenotype, adhesion molecule expression and release, and karyotypic abnormalities have been linked with survival in B-cell chronic lymphocytic leukemia (CLL) patients. Although information provided from these studies makes it possible to better appreciate the biological heterogeneity of the disease, it is not clear whether they may substitute clinical features in the prognostic assessment of CLL patients. The objective of this article is to analyze the performance of new prognostic variables, keeping in mind that clinicians should give priority to less expensive biological assays. INFORMATION SOURCES: In the present review, we examined personal papers in this field, and articles or abstracts published in journals covered by the Science Citation Index and Medline. STATE OF ART: Clinico-prognostic staging systems do not provide criteria accurate enough to identify patients with progressive disease. Although several in vitro methods have been utilized to evaluate tumor cell proliferation and to correlate this parameter with long-term survival, it is difficult to translate the results of kinetic studies into prognosis. Interestingly, prognostic implications of kinetic parameters are exemplified by clinical studies based on lymphocyte doubling time (LDT). Attempts to correlate immunophenotype with prognosis have yielded inconclusive results. This is probably due to the absence of strict immunological criteria. The membrane instability of CD23, rapidly cleaved into a soluble form, provides a highly specific and reliable serum marker. Expression of myelomonocytic antigens (i.e., CD11b, CD13) appears to be restricted to patients with CD5- CLL. Both cellular expression and release in the serum of some adhesion molecules (i.e., CD54, CD44 standard) have been linked with prognosis. The increased use of fluorescence in situ hybridization (FISH) techniques, which make it possible to identify karyotypic abnormalities even in cases with inadequate mytoses, has contributed to a better definition of incidence and clinical relevance of karyotypic abnormalities in CLL. Trisomy 12 is significantly associated with atypical morphological and/or immunological features, high proliferative activity and poor prognosis; the prognostic effect of 11q deletions is consistent in patients under 55 years of age. Usually, in absence of the rearrangement of the bcl-2 locus, B-CLL cells express bcl-2 gene product, whose intracellular levels do not correlate with clinical stages but do correlate with survival, thereby suggesting a possible independent prognostic value. Finally, p53 tumor suppressor gene has been associated with resistance to therapy with fludarabine. PERSPECTIVES: Even though prognostic assessment of CLL patients is generally based on clinical staging systems new biological parameters which reflect the clinical heterogeneity of the disease are under evaluation. Whether in the future clinicians will substitute biological variables for clinical features is matter of debate. The prognostic value of biological parameters is hampered, in some instances, by the small number of patients presenting these features (i.e., 11q deletions in 20%, p53 mutations in 15%). More likely, biological parameters might be incorporated into clinico-prognostic models thus leading to the formulation of a clinical-biological system for CLL.

Cell Division↗

PubMed2026

Development and internal validation of a six-gene prognostic model based on galactose metabolism for overall survival in lung adenocarcinoma.

BACKGROUND: Lung cancer remains a leading cause of cancer incidence and mortality globally. Metabolic reprogramming promotes tumor progression and shapes an immunosuppressive tumor microenvironment. Galactose metabolism is involved in multiple malignancies, but its prognostic value in lung adenocarcinoma (LUAD) remains unclear. This study aimed to develop and internally validate a galactose metabolism-related multigene prognostic model for LUAD. METHODS: A retrospective prognostic model development and internal validation study was performed using RNA sequencing (RNA-seq) and clinical data from 585 LUAD patients in The Cancer Genome Atlas (TCGA). Differential expression, functional enrichment, univariate and multivariate Cox regression were applied to construct a prognostic gene signature. Internal validation was performed using bootstrap resampling. Model performance was evaluated by time-dependent receiver operating characteristic (ROC), C-index, calibration, and Kaplan-Meier analysis. Associations between the model and immune infiltration, immunotherapy responsiveness, and tumor stemness were also analyzed. RESULTS: A six-gene prognostic model (GALT, GANC, PGM1, GALM, B4GALT1, PGM2) was developed. The model showed good discrimination with 1-, 3-, and 5-year area under the curve (AUC) values of 0.719, 0.693, and 0.684, respectively. The low-risk group exhibited significantly longer survival, increased antitumor immune infiltration (CD8+ T cells, M1 macrophages, activated CD4+ memory T cells), higher expression of T cell proliferation-related genes, lower immune checkpoint expression, better predicted immunotherapy response, and lower tumor stemness compared with the high-risk group. CONCLUSIONS: We developed and internally validated a six-gene prognostic model for LUAD based on galactose metabolism. The model shows moderate prognostic performance and is associated with antitumor immunity and tumor stemness. It may be used for prognostic risk stratification and to guide personalized immunotherapy in LUAD.

Galactose metabolism↗

PubMed1997

Prognostic implications of different cell cycle analysis models of flow cytometric DNA histograms of 1,301 breast cancer patients: results from the Multicenter Morphometric Mammary Carcinoma Project (MMMCP).

Conflicting prognostic results with regard to DNA flow cytometric cell cycle variables have been reported for breast cancer patients. An important reason for this may be related to differences in the interpretation of DNA histograms. Several computer programs based on different cell cycle fitting models are available resulting in significant variations in percent S-phase and other cell cycle variables. Our present study evaluated the prognostic value of percent S-phase cells obtained using 5 different cell cycle analysis models. Flow cytometric DNA histograms obtained from 1,301 fresh frozen breast cancer samples were interpreted with 5 different cell cycle analysis models using a commercially available computer program. Model 1 used the zero order S-phase calculation and "sliced nuclei" debris correction, model 2 added fixed G2/M- to G0/G1-phase ratio, and model 3 added correction for aggregates. Model 4 applied the first-order S-phase calculation and sliced debris correction. Model 5 fixed the coefficients of variation CVs of the G0/G1- and G2/M-phases in addition to applying the sliced nuclei debris correction and zero order S-phase calculation. The different models yielded clearly different prognostic results. The average percent S-phase cells of the aggregate correction model (model 3) provided the best prognostic value in all cases for overall survival (OS) as well as disease-free survival (DFS) (OS: p < 0.0001; DFS: p < 0.0001), in lymph node-positive cases (OS: p < 0.0001; DFS: p = 0.004) and in DNA-diploid subgroups (OS: p = 0.004; DFS: p = 0.001). For the lymph node negative and DNA-non-diploid subgroups, the percent S-phase of the second cell cycle reached slightly better prognostic significance than the average percent S-phase cells. In multivariate analysis, the average percent S-phase of the aggregate correction model had the best additional prognostic value to tumor size and lymph node status. In conclusion, different cell cycle analysis models yield clearly different prognostic results for invasive breast cancer patients. The most important prognostic percent S-phase variable was the average percent S-phase cells when aggregate correction was included in cell cycle analysis.

Adult↗

PubMed1986

The use of prognostic factors in clinical trials.

Numerous examples exist of prognostic factors that have been conclusively established and that can segregate the target patient population into subgroups with vastly different outcomes. At the same time, we can expect, in the majority of trials being conducted, that if a new treatment turns out to be successful, it generally results in only a modest improvement in patient outcome. This has contributed to a major emphasis on the identification and use of prognostic factors in clinical trials. Besides the inherent descriptive information for predicting patient outcome, prognostic factors are increasingly used in trial design and analysis with the hope of reducing or correcting bias that could otherwise occur from simple patient allocation schemes and unadjusted comparisons of treatment groups, and tailoring therapy so that the best treatments are selected in patient subgroups. Although the above objectives are reasonable, numerous misunderstandings and misuses of prognostic factors regularly occur. These involve such issues as the inappropriate application of clinical/statistical criteria for identification and confirmation of such factors, the sometimes undue emphasis on selection of best subdivisions of prognostic factors, the overreliance on prognostic factors and statistical models by proponents of historical control studies, the exaggerated importance of prognostic factors in special randomization schemes, etc. However, if a thorough understanding of such issues is combined with a careful approach to the use of prognostic factors, significant benefit to the design, conduct, and ultimate scientific information from clinical trials will result.

Age Factors↗

PubMed1993

Quantitative histopathology in the prognostic evaluation of patients with transitional cell carcinoma of the urinary bladder.

BACKGROUND: Morphologic grading of malignancy is considered to be of prognostic value in patients with transitional cell carcinomas of the urinary bladder (TCC). This qualitative approach is, however, associated with low reproducibility. Grading of malignancy can be carried out on a reproducible, quantitative scale. METHODS: A retrospective, prognostic study of 110 patients treated for TCC in clinical Stages Ta-T4 (median follow-up time, 6 years) was performed, evaluating various grading techniques. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vV), nuclear volume fraction, estimates of nuclear mean profile area (aH(nuc)), nuclear profile density index (NI), and mitotic profile density index (MI) were obtained by stereologic and morphometric techniques. RESULTS: The T-stage and morphologic grade of malignancy were closely cross-correlated (+0.63 < Kendall tau < +0.71, 2P < 6.7 x 10(-16)). The estimation of nuclear vV was highly efficient, with more than 85% of the associated variation attributable to differences between tumors. A positive significant correlation between estimates of nuclear vV and aH(nuc) was detected (r = +0.79), whereas an inverse correlation was documented between nuclear vV and NI (r = -0.63). Estimates of nuclear volume fraction showed no correlation with nuclear vV. Comparisons between categorical and quantitative data revealed the following: a decrease in averaged estimates of NI for tumors in advanced T-stage and malignancy grade (2P < 0.0008); and nuclear vV and aH(nuc) increased on average, in tumors of high T-stage and malignancy grade. Estimates of MI were also positively correlated with the T-stage and the malignancy grade (+0.42 < Kendall tau < +0.49). Single-factor analyses showed prognostic effect of T-stage, grade of malignancy, and, apart from nuclear volume fraction, all quantitative histopathologic variables with regard to overall survival (2P < 0.03). None of the morphometric and stereologic parameters were of prognostic values with regard to recurrence-free survival (2P > 0.26). Multiple hazards regression analysis (Cox models) revealed that clinical stage of disease was the sole independent prognostic variable. Only estimates of nuclear vV added significant independent prognostic prediction with regard to recurrence-free survival in the 48 patients with Ta tumors (2P = 0.03). CONCLUSIONS: The results suggested that estimates of nuclear vV are prognostically superior to morphologic grading of malignancy in noninvasive TCC, whereas both morphologically and quantitatively based malignancy grading are without prognostic value in invasive TCC.

Adult↗

PubMed2001

International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group.

BACKGROUND: The International Neuroblastoma Pathology Classification was established in 1999 for the prognostic evaluation of patients with neuroblastic tumors (NTs). METHODS: Pathology slides from 746 NTs (the Children's Cancer Group [CCG]-3881 and CCG-3891 studies) were evaluated according to the International Classification. First, prognostic effects of the morphologic indicators (grade of neuroblastic differentiation: undifferentiated [U], poorly differentiated [PD] and differentiating [D]; and mitosis-karyorrhexis index [MKI]: low [L-MKI], intermediate [I-MKI], and high [H-MKI]) for tumors in the neuroblastoma (NB) category were tested. Then, prognostic significance of the International Classification for all NTs in four categories (neuroblastoma [NB]; ganglioneuroblastoma, intermixed [GNBi]; ganglioneuroma [GN]; and ganglioneuroblastoma, nodular [GNBn]) was analyzed. Finally, age distribution of the patients in the four categories as well as three subtypes (based on the grade of differentiation) in the NB category was compared. RESULTS: There were 630 NB tumors, 30 GNBi tumors, 10 GN tumors, and 76 GNBn tumors. In the NB category, prognostic effects of the indicators (three grades of differentiation and three mitosis-karyorrhexis index [MKI] classes: low [L], intermediate [I], and high [H]) were affected significantly by the age of the patients. The age-linked evaluation of the indicators according to the International Classification successfully distinguished two prognostic subgroups: the favorable histology (FH) subgroup (PD/D and L/I-MKI tumors in patients age < 1.5 years, D and L-MKI tumors in patients ages 1.5-5.0 years; 90.4% 5-year event free survival [EFS]) and the unfavorable histology (UH) subgroup (U and/or H-MKI tumors in patients of any age, PD and/or I-MKI tumors in patients ages 1.5-5.0 years, any grade of differentiation, and any MKI class in patients age > or = 5 years; 26.9% EFS) (P < 0.0001). The International Classification also distinguished the FH group (FH subgroup with NB, GNBi, and GN tumors) and the UH group (UH subgroup with NB and GNBn tumors) for all NTs (90.8% EFS and 31.2% EFS, respectively; P < 0.0001) and provided independent prognostic information on both patient age and disease stage (P < 0.0001). Among patients with FH tumors, the median ages of patients with the PD and D subtype tumors in the NB category were 0.43 years (range, 0-1.50 years) and 1.50 years (range, 0.02-4.65 years), respectively, and the median ages of patients with GNBi and GN tumors were 3.51 years (range, 0.96-14.85 years) and 4.80 years (range, 1.94-17.05 years), respectively. In contrast, patients with UH tumors generally were older when they were diagnosed, and with median ages of 2.99 years (range, 1.30-8.84 years) for patients with U subtype tumors, 2.59 years (range, 0.0-12.57 years) for patients with PD subtype tumors, 2.16 years (range, 0.35-9.90) for patients with D subtype tumors, and 3.26 years (range, 0.57-15.90 years) for patients with GNBn tumors. CONCLUSIONS: This study confirmed the prognostic significance of the International Classification, substantiated age-linked prognostic effects of the morphologic indicators for patients with the tumors in the NB category, and supported the concept of an age-appropriate framework of maturation for patients with the tumors in the FH group.

Adolescent↗

PubMed2001

Optimizing flow cytometric DNA ploidy and S-phase fraction as independent prognostic markers for node-negative breast cancer specimens.

Developing a reliable and quantitative assessment of the potential virulence of a malignancy has been a long-standing goal in clinical cytometry. DNA histogram analysis provides valuable information on the cycling activity of a tumor population through S-phase estimates; it also identifies nondiploid populations, a possible indicator of genetic instability and subsequent predisposition to metastasis. Because of conflicting studies in the literature, the clinical relevance of both of these potential prognostic markers has been questioned for the management of breast cancer patients. The purposes of this study are to present a set of 10 adjustments derived from a single large study that optimizes the prognostic strength of both DNA ploidy and S-phase and to test the validity of this approach on two other large multicenter studies. Ten adjustments to both DNA ploidy and S-phase were developed from a single node-negative breast cancer database from Baylor College (n = 961 cases). Seven of the adjustments were used to reclassify histograms into low-risk and high-risk ploidy patterns based on aneuploid fraction and DNA index optimum thresholds resulting in prognostic P values changing from little (P < 0.02) or no significance to P < 0.000005. Other databases from Sweden (n = 210 cases) and France (n = 220 cases) demonstrated similar improvement of DNA ploidy prognostic significance, P < 0.02 to P < 0.0009 and P < 0.12 to P < 0.002, respectively. Three other adjustments were applied to diploid and aneuploid S-phases. These adjustments eliminated a spurious correlation between DNA ploidy and S-phase and enabled them to combine independently into a powerful prognostic model capable of stratifying patients into low, intermediate, and high-risk groups (P < 0.000005). When the Baylor prognostic model was applied to the Sweden and French databases, similar significant patient stratifications were observed (P < 0.0003 and P < 0.00001, respectively). The successful transference of the Baylor prognostic model to other studies suggests that the proposed adjustments may play an important role in standardizing this test and provide valuable prognostic information to those involved in the management of breast cancer patients.

Breast Neoplasms↗

PubMed2004

Construction and validation of a prognostic model across several studies, with an application in superficial bladder cancer.

Many models for clinical prediction (prognosis or diagnosis) are published in the medical literature every year but few such models find their way into clinical practice. The reason may be that since in most cases models have not been validated in independent data, they lack generality and/or credibility. In this paper we consider the situation in which several compatible, independent data sets relating to a given disease with a time-to-event endpoint are available for analysis. The aim is to construct and evaluate a single prognostic model. Building a multivariable model from the available prognostic factors is accomplished within the Cox proportional hazards framework, stratifying by study. Non-linear relationships with continuous predictors are modelled by using fractional polynomials. To assess the discrimination or separation of a survival model, we use the D statistic of Royston and Sauerbrei. D may be interpreted as the separation (log hazard ratio) between the survival distributions for two independent prognostic groups. To evaluate the generality of a prognostic model across the data sets, we propose 'internal-external cross-validation' on D: each study is omitted in turn, the model parameters are estimated from the remaining studies and D is evaluated in the omitted study. Because the linear predictor of a survival model tells only part of the story, we also suggest a method for investigating heterogeneity in the baseline distribution function across studies which involves fitting completely specified, flexible parametric survival models (Royston and Parmar). Our final models combine the prognostic index (obtained with stratification by study) with the pooled baseline survival distribution (estimated parametrically). By applying this methodology, we construct two prognostic scores in superficial bladder cancer. The simpler of the two scores is more suited to clinical application. We show that a three-group prognostic classification scheme based on either score produces well-separated survival curves for each of the data sets, despite identifiable heterogeneity among the baseline distribution functions and to a lesser extent among the prognostic indexes for the individual studies.

Adult↗

PubMed2000

Modern pathology: prognostic parameters in squamous cell carcinoma of the esophagus.

In the present study the prognostic impact of new histological and molecular parameters were tested retrospectively in a series of 149 patients with esophageal squamous cell carcinoma (SCC) who underwent potentially curative resection therapy. In addition, the prognostic value of various molecular markers was investigated in a group of 38 patients with locally advanced esophageal SCC treated using combined therapy modalities. In the surgically treated carcinomas, the following morphological parameters proved to be prognostically significant in univariate survival analysis and multivariate survival analysis: pattern of invasion, inflammatory response, and lymph vessel invasion. In contrast, tumor grading according to the criteria of the WHO and tumor cell proliferation did not show significant prognostic impact. Concerning the prognostic influence of molecular parameters, strong expression of the proliferation regulating molecule p21WAF1 and weak expression of the apoptosis regulating molecule Bcl-XL were predictors of poor survival in univariate and multivariate survival analysis. No prognostic impact was shown in relation to the expression of p53 and the apoptosis regulating molecules Bcl-2 and Bax. In the multimodally treated esophageal cancer patients, strong expression of p21WAF1 and accumulation of p53 were predictors of poor survival, whereas expression of Bcl-2, Bax, and Bcl-XL had no prognostic significance. In conclusion, morphological and molecular parameters may provide important prognostic information for esophageal cancer patients.

Carcinoma, Squamous Cell↗

PubMed1994

Age as a prognostic factor in the malignant melanoma population.

BACKGROUND: The incidence of malignant melanoma is increasing faster than any other cancer, and the state of Florida has one of the highest incidence of melanoma in the United States. This increased incidence is thought to be due to the intense sunlight exposure and ultraviolet radiation exposure in the elderly population. With the increased emphasis on issues of aging, it is appropriate to study the role of age as a prognostic factor for malignant melanoma in the Florida population. METHODS: A retrospective, computer-aided search identified 442 consecutively registered patients with malignant melanoma at the Cutaneous Oncology Program. All patients had stage 1 or 2 disease (cutaneous disease only) at diagnosis. Prognostic variables analyzed included the most powerful factors for stage 1 and 2 melanoma, tumor thickness, ulceration, and Clark level of invasion. Other prognostic variables included in the analysis were the clinical variables of sex and primary site (axial vs. extremity). The population was divided into patients < or = 65 and > 65 years of age. RESULTS: Significant disease-free survival differences were encountered in the older population, with only 55% of the elderly population being disease free at 5 years compared with 65% for the younger population (p = 0.0073). However, a greater percentage of patients with melanoma who were > 65 years of age had ulcerated lesions (17.5% vs. 12.9%) and a greater percentage of thick lesions at diagnosis (67.2% vs. 62.7%). Both of these prognostic factors would bias the older population with a poorer survival. A stepwise regression analysis of the entire population was performed, treating age as a continuous variable. Surprisingly, increasing age along with tumor thickness were the only significant predictors for disease-free survival. After inclusion of these two prognostic variables, none of the other prognostic factors, including Clark level, ulceration, sex, and primary site, added to the prognostic model. CONCLUSIONS: From this analysis, it is apparent that geriatric patients with melanoma have a worse prognosis than a younger control population, even after the correction for the more commonly cited prognostic factors. This information should be used in mathematical modeling to identify high-risk populations who are candidates for perhaps more aggressive primary or adjuvant therapies.

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