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PubMed2001

[Criteria for evaluating prognostic factors].

In oncology prognostic factors are defined as variables (covariates) with independent influence on outcome. Toxicity and complications of treatment are not considered. The significance and independence of a putative prognostic factor has to be proven by multivariate analysis. The results of prognostic factor analysis differ depending on tumor entity and residual tumor status. Sometimes differences are observed for various endpoints and certain patient subgroups. For identification of prognostic factors a systematic step-wise procedure is recommended. A checklist of important methodological aspects is suggested. The acceptance of new prognostic factors requires a standardized way to determine the factors, adequate evidence of significance and independence and the demonstration of additional prognostic information and its clinical relevance. By integration of multiple prognostic factors the present tumor classification will be extended to prognostic systems.

Humans↗

PubMed1990

Proposal for a simple synthesis prognostic staging system in chronic myelogenous leukemia.

PURPOSE: Several prognostic models or staging systems have been published that identify different risk groups in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). The aims of this study were (1) to test, in an independent population, the prognostic reproducibility of these staging systems; and (2) to develop a synthesis staging system that could be easily applied in clinical practice. PATIENTS AND METHODS: A total of 406 patients with newly diagnosed Ph-positive CML were evaluated by the four published staging systems of Tura, Cervantes, Sokal, and our group. The proposed synthesis staging system was developed based on the most consistent prognostic characteristics, and the presence or absence of accelerated disease features at diagnosis. The staging systems were compared according to survival outcome, as well as by looking for differences of survival outcomes within a specific stage of a defined system, when patients in this stage were subclassified by a second staging system. RESULTS: Whereas the staging system of Cervantes et al identified only two prognostic groups (median survivals of 49 versus 40 months; p = 0.01), the remaining three staging systems were able to segregate patients into stage 1, 2, and 3 risk groups with respective median survivals of 56 to 57, 41 to 42, and 28 to 36 months, respectively (p less than 0.001 to p less than 0.002). The new proposed staging system, based on the existence of zero to one (stage 1), two (stage 2), or three or more unfavorable (stage 3) characteristics, or the presence of accelerated disease features (stage 4), categorized patients into four prognostic groups with median survivals of 56, 45, 30, and 30 months, respectively (p less than 0.001), the latter stage (stage 4) being associated with a higher one-year mortality rate (29%). The synthesis staging system was also able to subclassify patients within most of Tura's and Sokal's stages into significantly different prognostic groups by survival outcome. CONCLUSION: The predictive prognostic capacity of three of the four published staging systems was confirmed in this independent or test population. The new proposed staging system was superior to the staging systems of Tura and Sokal in identifying different prognostic subgroups.

Humans↗

PubMed2004

Prognostic indexes in breast cancer: comparison of the Nottingham and Adelaide indexes.

The search for single independent prognostic factors in breast cancer has often produced conflicting results. Therefore, prognostic indexes have been compiled by combining several parameters. In this study we compare the Nottingham Prognostic Index (NPI), which is based on traditional prognostic factors (diameter of the neoplasm, lymph node status and histological grade) with the Adelaide Prognostic Index (API), which is based on the tumour diameter and two biological parameters: oestrogen receptors and cell kinetics. We considered 82 cases of breast cancer observed over the period 1987-1990 with a minimum follow-up of 60 months. The NPI gives a better definition of the prognostic profile for each patient. Our results indicate three prognostic groups (good, moderate, unfavourable), which differ with respect to disease-free survival (DFS; P=0.0024) and overall survival (OS; P=0.0033). In contrast, the API scores showed no significant correlation with OS or DFS. The use of prognostic indexes, especially when compiled using traditional parameters, is a useful aid to the clinician, since they can provide a reliable indication of how individual tumours will evolve.

Adult↗

PubMed2006

Assessing the prognostic significance of transrectal ultrasound extracapsular extension in prostate cancer.

AIMS: To determine the prognostic value of transrectal ultrasound (TRUS)-detected extraprostatic disease for prostate cancer in patients receiving radical external-beam radiation therapy (EBRT). MATERIALS AND METHODS: A chart review of 181 patients treated with radical EBRT for prostate cancer was conducted. All patients underwent TRUS assessment by one radiologist. The median radiation dose delivered to the prostate was 66 Gy (range 53-70 Gy) in 33 fractions (range 20-39 fractions). Median follow-up time for all patients was 6.5 years. Sixty-four (35%) out of 181 patients were found to have extracapsular disease on TRUS. Clinical relapse was defined as the first occurrence of either salvage hormonal therapy administration by the treating oncologist or clinical, radiological, and/or pathologic evidence of recurrent or progressive disease. In terms of biochemical failure, two prognostic variable analyses were carried out using both the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus guidelines and the Houston definition of biochemical failure. The primary end point for the prognostic variable analyses was time to first clinical or biochemical failure (CBF). RESULTS: For time to CBF using the ASTRO consensus guidelines for biochemical failure, univariable analysis revealed that the prostate-specific antigen (PSA) (P = 0.018), clinical T stage (P = 0.002), Gleason score (P = 0.021), adjuvant hormonal therapy (P = 0.032) and TRUS T staging (P = 0.0001) were statistically significant prognostic factors. On multivariable analysis, clinical T stage (P = 0.051) was of borderline statistical significance, whereas PSA (P = 0.036), TRUS T stage (P = 0.0002) and adjuvant hormonal therapy (P = 0.015) were found to be independent prognostic factors. For time to CBF using the Houston definition of biochemical failure, univariable analysis revealed that PSA (P = 0.001), Gleason score (P = 0.026) and prostate volume (P = 0.013) were statistically significant prognostic factors. On multivariable analysis, PSA (P = 0.002), Gleason score (P = 0.012), and adjuvant hormonal therapy (P = 0.041) were found to be independent prognostic factors. TRUS T staging was not found to be independently significant. CONCLUSIONS: A clear role for TRUS staging as an independent prognostic factor, in the setting of other more established variables, such as Gleason grade, PSA, and digital rectal examination (DRE) T stage, was not confirmed in this study, population.

Aged↗

PubMed2006

Prognostic factors for progression of childhood optic pathway glioma: a systematic review.

A systematic literature review was carried out to evaluate best existing evidence on prognostic factors for progression of childhood optic pathway glioma. Databases were searched for relevant articles and articles selected independently by two authors. Information about study design, population, treatment, outcome and prognostic analysis were abstracted and the quality of each article was assessed. A total of 23 articles met the inclusion criteria. Many studies had important methodological limitations, regarding external and internal validity. Eleven studies evaluated possible prognostic factors in a multivariate analysis. Three high-quality studies indicated age<1 year as an independent prognostic factor for a worse progression-free survival. Three studies with multivariate analysis, including one high-quality study, found that children with neurofibromatosis type 1 (NF-1) have a better progression-free survival than those without NF-1. Two studies with multivariate analysis found tumour site to be a prognostic factor, both with some methodological limitations. In conclusion, this systematic review demonstrates that only a few of the prognostic factors proposed have been proven to be clinically relevant. Age<1 year is a clear and independent prognostic factor for progression-free survival. Other prognostic factors, such as NF-1, tumour site and others, are suggested, but are still without solid evidence and need further high-quality studies to be clearly proven.

Disease Progression↗

PubMed2005

Recurrent epithelial ovarian cancer: validation and improvement of an established prognostic index.

OBJECTIVES: To validate and improve an established prognostic index in patients with recurrent ovarian cancer. METHODS: A Canadian three-covariate prognostic index (tumour grade at diagnosis, initial performance status, and time to relapse/primary progression (TRP)) was validated in a well-defined cohort of comparable Danish patients. Potential parameters to be included in an improved prognostic index were revealed by univariate and multivariate analyses in the Danish validation group. RESULTS: The Canadian index validated in the Danish patient population (n=189) found a statistical significant difference in survival between the prognostic groups good and intermediate (P<0.0001), whereas there was no significant difference in survival between the prognostic groups intermediate and poor (P=0.51). In order to improve the accuracy of the index, the candidate parameters, treatment free interval (TFI), CA125 level and performance status, at time of relapse/primary progression, were added, whereas the parameters, tumour grade, and initial performance status, from the Canadian index were excluded. As the correlation coefficient between TRP and TFI was very high (r=0.91), TRP was substituted with TFI in the improved prognostic model. The final model was: 0.8 (performance status)+0.33 log (CA125)-1.31 log (TFI). The improved model was a good predictor of one-year survival (AUC 0.85; logistic regression; P<0.0001). The median survival (with 95% CI) of the four prognostic groups (A-D) was 50.6 (34.0-not available), 25.0 (22.1-33.6), 11.3 (8.5-12.9), and 5.2 (3.5-6.3) months, respectively. CONCLUSIONS: A novel prognostic model (the Copenhagen index) for patients with recurrent ovarian cancer is presented.

Cohort Studies↗

PubMed2005

Angiogenesis in non-small cell lung cancer: the prognostic impact of neoangiogenesis and the cytokines VEGF and bFGF in tumours and blood.

BACKGROUND: Due to a dismal prognosis of advanced lung cancer, novel screening tools and more effective treatments are clearly needed. Lately, an increasing number of tumour-released angiogenic cytokines which affect vessel formation, tumour growth, invasion, and metastasis have been identified. Vascular endothelial growth factors (VEGFs) and basic fibroblast growth factor (bFGF) are among the most important angiogenic factors. Based on available literature, we have explored the mechanisms of angiogenesis and its prognostic significance in non-small cell lung cancer, estimated by microvessel density (MVD) and the presence of VEGF and bFGF in the tumour and blood from NSCLC patients. METHODS: Several comprehensive Pubmed searches for the period January 1993 to May 2005 were performed using strategic combinations of the terms non-small cell lung cancer, angiogenesis, vascular endothelial growth factor, basic fibroblast growth factor, tumour expression, microvessel density, circulating, and serum. RESULTS: NSCLC neoangiogenesis, as measured by MVD, and tumour expression of VEGF are poor prognostic factors for survival (MVD, HR 1.8-2.0; VEGF, HR 1.5). bFGF tumour expression is also associated with poor survival and more aggressive disease. When evaluating the prognostic impact of elevated VEGF levels in blood, 10 of 16 studies (63%) indicated a negative prognostic impact. Of five studies on the prognostic value of circulating bFGF, three studies reported a negative prognostic impact, while one indicated bFGF as a good prognostic factor and one was inconclusive. CONCLUSION: Angiogenic factors are poor prognostic indicators for tumour aggressiveness and survival in NSCLC. Assessments of circulating levels of VEGF and possibly bFGF may be valuable future tools for treatment planning and monitoring of treatment effect and relapse. First, however, these blood tests need to be standardised and validated in large-scale prospective clinical trials.

Carcinoma, Non-Small-Cell Lung↗

PubMed1991

Prognosis of transitional cell bladder cancer: a multivariate prognostic score for improved prediction.

Clinical and histological prognostic factors were evaluated by means of Cox's analysis in 265 bladder cancer patients with a mean followup of 10 years. The parameters studied were obtained from the primary biopsies, which included clinical stage, World Health Organization grade, papillary status, morphometrically measured mean nuclear area, standard deviation of nuclear area, mean nuclear area of the 10 largest nuclei, mitotic activity index and volume corrected mitotic index. In univariate survival analysis all of the parameters predicted survival (p less than 0.001). In Cox's analysis the clinical stage was the most important prognosticator (p less than 0.001) followed by papillary status (p less than 0.001), volume corrected mitotic index (p = 0.011) and nuclear area of the 10 largest nuclei (p = 0.091). In stages Ta to T2, grades 1 to 2 tumors the papillary status (p = 0.001), mitotic activity index (p = 0.021) and T category (p = 0.029) showed independent prognostic value. Among the stages Ta to T1 tumors the papillary status included all of the available prognostic information (p = 0.001). In a separate analysis of histological features in all papillary tumors histological grade (p less than 0.001) and mitotic activity index (p = 0.021) were related independently to survival in Cox's analysis. In papillary stages Ta to T2, grades 1 to 2 tumors (mitotic activity index, p = 0.029) and in papillary stages Ta to T1 tumors (volume corrected mitotic index, p = 0.054) mitotic indexes showed independent prognostic value. In grade 2 tumors the papillary status p = 0.004) and mitotic activity index (p = 0.090) had independent prognostic value. The mitotic indexes predicted progression among stages Ta to T1 tumors (p less than 0.001) and within World Health Organization grades significantly. The combination of prognostic parameters into prognostic scores gave a more accurate estimate of survival than the single parameter approach. The results suggest morphometric grading of bladder tumors. However, papillary and nonpapillary tumors require different grade limits.

Aged↗

PubMed1998

Prognostic accuracy of the mean of the largest nucleoli, vascular patterns, and PC-10 in posterior uveal melanoma.

OBJECTIVE: This study aimed to compare the prognostic value and the predictive accuracy of the PC-10 cell cycling marker with the largest tumor diameter, the mean of the largest nucleoli, and vascular patterns in posterior uveal melanoma. DESIGN: The study design was a case-control study. PARTICIPANTS: Eyes enucleated for posterior uveal melanoma from patients who either died of metastatic melanoma or survived without signs of metastatic disease 10 years or more after surgery were studied. INTERVENTION: Three observers assessed the above prognostic indicators and standard histopathologic characteristics from microslides without access to survival data. MAIN OUTCOME MEASURES: Univariate and multivariate Cox models for survival were constructed, and a multiparameter prognostic index was calculated for each patient, based on covariates obtained from the final Cox model. The prognostic accuracy was determined by receiver operating characteristic curve analysis. RESULTS: The log PC-10 count, vascular networks, mean of the largest nucleoli, largest tumor diameter, age of patient, and prognostic index were independently associated with outcome. However, each of these indicators had no more than a poor-to-moderate predictive accuracy, and only the prognostic index was significantly better than the largest tumor diameter. CONCLUSIONS: The PC-10 count retains a prognostic value in uveal melanoma when adjusting for the effect of the mean of the largest nucleoli and diverse vascular patterns. A prognostic index combining two or more indicators may improve the predictive precision.

Adult↗

PubMed2004

[Prognostic value of DNA ploidy and nuclear morphometry in metastatic prostate cancer].

PURPOSE: To assess the prognostic value of DNA ploidy and nuclear morphometry in metastatic prostate cancer after androgenic deprivation treatment. METHODS: Fifty four patients with prostate cancer and bone metastases who had undergone androgenic suppression treatment were retrospectively studied. The deoxyribonucleic acid (DNA) content was analysed by flow cytometry. Nuclear morphometry characterized 14 nuclear descriptors. The study also included age, Gleason score, T classification, haematocrite, serum albumin, serum alkaline phosphatase, serum prostatic acid phosphatase and the amount of metastatic foci detected during radioisotope bone scan. Univariate survival analyses were performed and Cox's proportional hazards model was used to identify significant prognostic factors. To assess how the experimental factors improve the capacity of the classical factors for predicting the patients who reach median survival, logistic regression multivariate analysis was performed for the classical prognostic factors only and after added experimental variables (DNA content and Nuclear Area). RESULTS: The univariate survival analyses assigned a prognostic value to T category, level of albumin, alkaline phosphatase, Gleason score, bone scan, DNA ploidy and mean nuclear area. In the case of the Cox regression model only Gleason score, bone scan, mean nuclear area and DNA ploidy provided independent prognostic information. In logistic regression for classic prognostic factors only Gleason score is significant (sensibility 89.3%, specificity 64%). However, when the experimental factors are added, in addition to Gleason score, radioisotope bone scan and DNA ploidy are of prognostic value (sensibility 90% and specificity 72%). CONCLUSIONS: The study of DNA content and nuclear morphometry in the primitive tumor provides independent prognostic information in survival analysis for patients with metastatic prostate cancer. However, there is limited improvement with respect to the classical factors in predicting survival. This questions its utility in the daily clinical usage.

Adenocarcinoma↗

PubMed2001

Treatment results and prognostic factors of advanced T3--4 laryngeal carcinoma: the University of California, San Francisco (UCSF) and Stanford University Hospital (SUH) experience.

PURPOSE: To review the UCSF-SUH experience in the treatment of advanced T3--4 laryngeal carcinoma and to evaluate the different factors affecting locoregional control and survival. METHODS AND MATERIALS: We reviewed the records of 223 patients treated for T3--4 squamous cell carcinoma of the larynx between October 1, 1957, and December 1, 1999. There were 187 men and 36 women, with a median age of 60 years (range, 28--85 years). The primary site was glottic in 122 and supraglottic in 101 patients. We retrospectively staged the patients according to the 1997 AJCC staging system. One hundred and twenty-seven patients had T3 lesions, and 96 had T4 lesions; 132 had N0, 29 had N1, 45 had N2, and 17 had N3 disease. The overall stage was III in 93 and IV in 130 patients. Seventy-nine patients had cartilage involvement, and 144 did not. Surgery was the primary treatment modality in 161 patients, of which 134 had postoperative radiotherapy (RT), 11 had preoperative RT, 7 had surgery followed by RT and chemotherapy (CT), and 9 had surgery alone. Forty-one patients had RT alone, and 21 had CT with RT. Locoregional control (LRC) and overall survival (OS) were estimated using the Kaplan--Meier method. Log-rank statistics were employed to identify significant prognostic factors for OS and LRC. RESULTS: The median follow-up was 41 months (range, 2--367 months) for all patients and 78 months (range, 6--332 months) for alive patients. The LRC rate was 69% at 5 years and 68% at 10 years. Eighty-four patients relapsed, of which 53 were locoregional failures. Significant prognostic factors for LRC on univariate analysis were primary site, N stage, overall stage, the lowest hemoglobin (Hgb) level during RT, and treatment modality. Favorable prognostic factors for LRC on multivariate analysis were lower N stage and primary surgery. The overall survival rate was 48% at 5 years and 34% at 10 years. Significant prognostic factors for OS on univariate analysis were: primary site, age, overall stage, T stage, N stage, lowest Hgb level during RT, and treatment modality. Favorable prognostic factors for OS on multivariate analysis were lower N stage and higher Hgb level during RT. CONCLUSION: Lower N-stage was a favorable prognostic factor for LRC and OS. Hgb levels > or = 12.5 g/dL during RT was a favorable prognostic factor for OS. Surgery was a favorable prognostic factor for LRC but did not impact on OS. Correcting the Hbg level before and during treatment should be investigated in future clinical trials as a way of improving therapeutic outcome in patients with advanced laryngeal carcinomas.

Adult↗

PubMed1998

Prognostic factors in patients with carcinoma of the uterine cervix treated with external beam irradiation and IR-192 high-dose-rate brachytherapy.

PURPOSE: Prognostic factors in cancer of the cervix for patients treated with external beam irradiation (EBR) and low-dose-rate (LDR) brachytherapy have been characterized. However, despite the increasing use of high-dose-rate (HDR) intracavitary placements (ICP), few studies with adequate follow-up have analyzed prognostic factors. This study investigates pretreatment and treatment factors for their correlation with treatment outcome after EBR and HDR-ICP. METHODS AND MATERIALS: Between September 1985 and December 1994, 181 patients with carcinoma of the cervix FIGO stages IB-IV received EBR and HDR brachytherapy. Hemoglobin (Hb) levels were maintained above a level of 11 g/dl during the treatment by transfusion. Patient age ranged from 34 to 84 years (median: 66). The median follow-up time for patients at risk is 69 months (range: 23-140). Pretreatment and treatment parameters analyzed to determine their prognostic value included age, FIGO stage, tumor size, tumor type and grade, pretreatment Hb level, number of HDR-ICP, total dose from HDR-ICP, overall dose to point A, and overall treatment time. Also evaluated was the prognostic value of enlarged lymph nodes noted on pretreatment CAT scan of the abdomen and pelvis. Endpoints studied in uni- and multivariate analyses were disease-specific survival (DSS), freedom from disease (FFD), pelvic control (PC), and probability of distant metastases (DM). RESULTS: At 5 years the DSS, FFD, and PC rates for all patients were 60%, 58%, and 67%, respectively. The 5-year FFD by stage was: IB: 94%; II: 63%; IIIB: 43%; and IV: 0%. The PC rates were 94%, 66%, 59%, and 0%, respectively. In univariate analysis the prognostic factors identified for FFD were FIGO stage, tumor size, initial Hb level, and enlarged pelvic and/or paraaortic nodes (all: p < 0.0001). Age was inversely correlated with outcome (p = 0.0081). The 5-year FFD rates for tumors (< 3, > or = 3 < 6, > or = 6 cm) were 97%, 65%, and 24%; patients with initial Hb levels < or = 11g/dl had a FFD of 26% versus 69% for patients with levels > 11g/dl; and those with pelvic and/or paraaortal nodes > or = 1 cm had a survival of 32% versus 68% in patients with negative readings. The same factors were also prognostically significant for DSS, PC, and DM. Patients with persistent disease or pelvic failures had a significantly higher incidence of DM than patients in whom pelvic disease was controlled (p < 0.0001).Histological and treatment parameters including overall treatment time were not of prognostic significance for any of the endpoints studied. In multivariate analysis tumor size was the most powerful parameter for DSS, FFD, PC (p < 0.0001) and DM (p = 0.0001), followed by low initial Hb level (DSS: p = 0.0004, FFD: p = 0.0009, PC: p = 0.0012, DM: p = 0.0265), and enlarged pelvic and/or paraaortic nodes which were predictive for DSS (p = 0.0210) and DM (p = 0.0011). CONCLUSION: This study confirms that prognostic factors for patients treated with HDR brachytherapy are similar to those reported in previous series that employed LDR brachytherapy. The significance of tumor size, pretreatment Hb level, and enlarged pelvic and/or paraaortic lymph nodes on CAT scan over FIGO stage of disease were demonstrated. Future prospective trials should be undertaken to confirm the validity of these factors and to elucidate their therapeutic implications.

Adult↗

PubMed1998

Prognostic significance of CT contrast enhancement within histological subgroups of intracranial glioma.

UNLABELLED: We report the prognostic significance of tumor CT contrast enhancement within histological subgroups in 831 consecutive adult glioma patients of high-grade (n = 516) and low-grade (n = 315) histology. In the present report, a negative prognostic factor is associated with shortened survival. METHODS: Survival analysis including Kaplan-Meier plots, log-rank tests, Cox analysis, and Aalen's linear model as implemented in SPSS and S-PLUS. RESULTS: Sensitivity and specificity of contrast enhancement as a test for high-grade glioma was 0.87 and 0.79, respectively. Enhancement was a strong negative prognostic factor comparable to high-grade histology in the total patient population. Enhancement was also a negative prognostic factor within the subgroups adult high-grade (Grade 3-4), anaplastic (Grade 3), and low-grade (Grade 1-2) gliomas (p < 0.001). The prognostic implications of initial enhancement declined in high-grade patients surviving beyond 36 months. Tumor contrast enhancement or calcifications (in parentheses) were present in 96% (3.6%) of glioblastomas, in 87% (7.4%) of high-grade gliomas, in 56.5% of anaplastic gliomas, and in 21% (16.2%) of low-grade gliomas. Calcification was a positive prognostic factor within the high-grade group of patients (p < 0.0001). CONCLUSION: Enhancement was a major prognostic factor comparable to high-grade histology in this glioma patient population. Enhancement was a negative prognostic factor within each of the adult subgroups high-grade, anaplastic (grade 3), and low-grade gliomas. Enhancement was strongly associated with but not pathognomonic for high-grade histology.

Adult↗

PubMed1997

Decrease of interleukin-2 secretion is a new independent prognostic factor associated with poor survival in patients with small-cell lung cancer.

BACKGROUND: We have previously shown that suppression of interleukin-2 (IL-2) secretion was mediated by transforming growth factor (TGF) beta 1 secreted by small-cell lung cancer (SCLC) tumor cells. We have also shown that IL-2 secretion was significantly impaired in patients with SCLC at the time of diagnosis. Reconstitution of cytokine secretion correlated with reduction of tumor load. These data suggested that the immune system was suppressed by the tumor. To address the clinical relevance of cytokine suppression in SCLC, we investigated the correlation of the level of IL-2 secretion with survival. PATIENTS AND METHODS: The significance of correlations between single parameters in the test groups was calculated by using the linear regression analysis, the Wilcoxon rank sum test and the exact test according to Fisher. Using the Kaplan-Meier method, the log-rank test and the Cox-regression model, we analysed the relation of IL-2 secretion in whole blood cell cultures from 52 patients with SCLC at the time of diagnosis to established prognostic factors relevant for survival in SCLC. RESULTS: Impairment of IL-2 secretion significantly correlates to survival in SCLC (P = 0.004). Further univariate and multivariate analysis showed that this prognostic factor is independent from other factors of prognostic relevance in SCLC, namely stage of disease, neurone specific enolase (NSE), lactate dehydrogenase (LDH), age, and sex. More important, the prognostic value of IL-2 secretion is comparable to the most predominant prognostic factors for survival in SCLC identified so far. In the final model of the cox regression analysis, the P-value for IL-2 secretion in relation to stage of disease was 0.012 and 0.019, respectively. CONCLUSIONS: IL-2 secretion at the time of diagnosis represents an independent prognostic factor for survival in SCLC. Although its prognostic value has to be confirmed in a larger group of patients, our results demonstrate that IL-2 secretion may play an important role in diagnosis and treatment of SCLC. Moreover, in contrast to other prognostic factors, impairment of IL-2 secretion may help to understand immunosuppression in SCLC and, thus, important elements of the pathogenesis of this disease.

Adult↗

PubMed2002

Tumor size, axillary lymph node status and steroid receptor expression in breast cancer: prognostic relevance 5 years after surgery.

Tumor size, axillary lymph node status and expression of steroid receptors are well-established prognostic factors in breast cancer. However, it is not clear if these prognostic factors are time-dependent variables and lose their significance after several years of disease-free survival. To analyse how long these factors keep their prognostic relevance survival of 1162 breast cancer patients was analysed retrospectively. The post-operative follow-up period was split into consecutive 2-year intervals and each interval was analysed for rate of recurrence and rate of tumor depending deaths. Furthermore, a multivariate analysis was performed for the total follow-up time and for the follow-up period starting 5 years after surgery. Multivariate analysis revealed tumor size, axillary lymph node status and estrogen receptor status as independent prognostic parameters. Analysing separately the rate of recurrences and tumor-related deaths during consecutive 2-year intervals, only the tumor size was a constant prognostic parameter, whereas prognostic relevance of lymph node status decreased. Estrogen receptor status associated with favourable prognosis during the first years after surgery changed to an unfavourable prognostic factor 4 years after surgery. To summarize, prognostic factors obtained at the time of surgery can lose their significance with increasing disease-free survival.

Adult↗

PubMed1993

Serum lactate dehydrogenase level as a prognostic factor in Hodgkin's disease.

The efficacy of currently available treatments for Hodgkin's disease (HD) has led to a substantial modification in the prognosis of this disease; nevertheless there is still a group of patients that cannot be cured with conventional treatments and who will be candidates for alternative therapy. In the present work we analysed the prognostic influence of the most relevant clinico-biological characteristics of HD in a consecutive series of 137 patients diagnosed and treated in a single institution. Univariate analyses identified six variables with significant prognostic influence, both on achieving complete remission (CR) and overall survival (OS); LDH > 320 U ml-1, age > 45 years, stages IIB, III and IV, extranodal involvement, alkaline phosphatase > 190 UI dl and ESR > 40 mm h. In addition, Hb < 12.5 gr dl-1 and abdominal disease were statistically relevant for CR while a poor performance score (ECOG > or = 2) affected a lower survival. In the multivariate analysis only LDH, age and the clinical stage retained a significant prognostic influence for achieving CR, while the two first factors above, together with performance status were the variables with independent prognostic value with respect to OS. Moreover, only LDH > 320 U ml-1 had prognostic influence in the probability of relapse and disease free survival (DFS), both in the univariate and multivariate analyses. According to the three independent factors obtained in the multivariate analysis for CR (LDH, age and stage) a predictive model was established that allows the stratification of patients into two prognostic groups: one with poor prognosis that includes patients with the three adverse prognostic factors, or two if one of them was elevated LDH, and the other with good prognosis that includes the remaining patients. This model was also able to separate two independent groups of patients with respect to OS and to DFS. In conclusion, the present study shows that LDH is one of the most important prognostic factors in HD.

Adolescent↗

PubMed1997

Time-varying prognostic impact of tumour biological factors urokinase (uPA), PAI-1 and steroid hormone receptor status in primary breast cancer.

In breast cancer, several investigations have demonstrated that the tumour biological factors uPA urokinase-type plasminogen activator) and its inhibitor PAI-1 are statistically independent, strong prognostic factors for disease-free (DFS) and overall survival (OS). However, statistical analyses performed for varying follow-up periods suggested a time variation of prognostic strength. We therefore investigated the time-dependent prognostic power of uPA, PAI-1 and steroid hormone receptor status applying the time-varying coefficient model of Gray. uPA and PAI-1 were analysed by enzyme-linked immunosorbent assay in tumour tissue extracts from 314 breast cancer patients. Hormone receptors (oestrogen and progesterone) were determined by radioligand binding or by immunohistochemistry. Univariate and multivariate analyses (Cox proportional hazards model) of DFS and OS were performed for all patients, including 147 node-negative patients. Median follow-up of patients still alive at time of analysis (n = 232) was 58 months. Although initially of high prognostic impact, a continuous decrease over time in the prognostic power of hormone receptor status and uPA was observed. In contrast, the prognostic impact of PAI-1 increased over time and reached similar strength as the lymph node status. The time-dependent risk profile of prognostic factors may have important clinical implications in regard to follow-up and patients' individual risk situation. Evaluation of time dependency of prognostic factors may also give a more profound insight into the dynamics of breast cancer metastasis.

Adult↗

PubMed2000

Hot spot microvessel density and the mitotic activity index are strong additional prognostic indicators in invasive breast cancer.

AIMS: Recent studies have drawn attention to intratumoral microvessel density (MVD) as a prognostic factor in invasive breast cancer. Various methods have been applied to assess MVD and the prognostic value of MVD in different studies varies considerably. Counting of microvessels in the most highly vascularized area (hot spot) of a tumour is the method most widely used. In this study we compared three counting methods. METHODS AND RESULTS: To assess MVD in 112 cases of invasive breast cancer with long-term follow-up we performed microvessel counting in the hot spot of the tumour in four and 10 fields of vision (HS-MVD4 and HS-MVD10) and microvessel counting in 10 fields of vision distributed systematically over the whole tumour area (global MVD). The HS-MVD4, HS-MVD10 and global MVD showed good correlations with each other. HS-MVD4 provided the highest number of microvessels (median value 71) followed by HS-MVD10 and global MVD, with median values of 58 and 39, respectively. HS-MVD4 showed the best prognostic value for overall survival (P = 0.0001) whereas HS-MVD10 showed less (P = 0.01) and the global MVD showed no (P = 0.75) prognostic value. In univariate analysis, the HS-MVD4 was the second strongest prognostic factor after tumour size. In multivariate survival analysis, the HS-MVD4, mitotic activity index (MAI), lymph node status and tumour size were found to be independent prognostic factors. When combining MVD4 and MAI in lymph node negative patients, none of the patients with low MVD (< 71/mm2) and a low MAI (< 10 per 10 HPF) died, in contrast to patients with a high MVD or high MAI who have a 10-year survival of 57%. CONCLUSIONS: These data suggest that the hot spot MVD in four fields of vision is a major independent prognostic factor for overall survival in invasive breast cancer. For the first time, it is shown that hot spot MVD provides additional prognostic information to well established factors like lymph node status and the MAI, and may therefore be useful for designing treatment strategies in invasive breast cancer.

Breast Neoplasms↗