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[The importance of prognostic signs in malignant diseases].

The paper deals with the general importance of prognostic signs in malignant tumours. The author defines basic terms such as disease, illness, sign etc. Diagrams describe individual stages and the complexity of the diagnostic and therapeutic procedure and the main factors which influence its result, the patient's recovery. From the aspect of assessment of the accurate diagnosis signs assembled during the diagnostic process are divided into three prognostic groups as the correct diagnosis is the prerequisite of rational therapy and thus can influence the prognosis of the disease. In the first group are only signs associated with the aetiopathogenesis of the disease, in the second group signs associated with the patient's general condition and in the third group signs of the patient's normal phenotype. The signs in each of these groups have as a rule a different prognostic value. The author emphasizes the great dependence of prognostic signs on the type of applied treatment as well as the fact that with improving treatment the majority of signs lose their prognostic importance.

Humans↗

Relationship between prognostic factors and therapy in high-grade non-Hodgkin's lymphomas over two decades.

We considered the prognostic factors in high-grade non-Hodgkin's lymphomas (HG-NHL) over the past two decades. In an effort to clarify the relationship between prognostic factors and therapy, we pooled the literature reports concerning 3,480 patients into four different periods according to the mean years of the clinical trials. The most important prognostic factors discovered in period A (mean year prior to 1970) were histology, symptoms and stage. In period B (1970 through 1975), in addition to the former indicators, two new factors were pointed out: bone marrow involvement and serum lactic dehydrogenase. In period C (1976 through 1980) the significance of stage was reduced, while bulk and measures of lymph nodal and extranodal involvement (LSI, ESI) were found to be better prognostic factors. In studies related to this period the prognostic role of albumin, hemoglobin and erythrocyte sedimentation rate were also emphasized. Period D (1980 through 1985) was characterized by a decrease in the importance of the Kiel and Working Formulation (WF) classifications by virtue of the better outcome, in different reports, of HG-NHL with respect to low-grade NHL. The conclusion of our analysis is that symptoms, ESI, bulk, LDH, albumin and hemoglobin should be the most important factors used today in planning the therapy and management of patients with HG-NHL. In addition, an update of the WF is necessary.

Humans↗

Prognostic factors in small cell lung cancer: multivariate analysis in the National Cancer Center Hospital (Japan).

Consecutive series involving 172 patients with small cell lung cancer were analyzed retrospectively using eight pretreatment and two treatment-related prognostic factors in respect of their influence on survival. All the patients received chemotherapy with or without chest irradiation, according to phase II or phase III trial protocols of the National Cancer Center Hospital, Tokyo, from 1970 to 1987. The influence on survival of the various factors was investigated using univariate methods and Cox's proportional hazards model. In patients who survived for more than one year, a performance status of 0-1, limited disease, an age greater than 60 years, the absence of liver metastasis, radiotherapy to primary site and response to chemotherapy were determined by univariate analysis to be favorable prognostic factors. By multivariate analysis, performance status (P = 0.005), age (P = 0.026) and response to induction chemotherapy (P = 0.0001) proved to be valuable prognostic survival factors. The extent of disease which had been considered one of the most significant prognostic factors, was shown not to be a significant independent variable by multivariate analysis. Staging procedures may influence the prognostic analysis. Although classifying the limited or extensive stage of disease is still recommended, the current staging system lacks stringency and may not, in fact, reflect the tumor burden accurately. A simpler and meaningful staging system needs to adopted universally in order to continue the build-up of data for comparison from all institutions.

Antineoplastic Combined Chemotherapy Protocols↗

[Multivariate analysis of prognostic factors influencing survival in chronic myelogenous leukemia].

Prognostic significance of disease features obtained at the time of initial diagnosis was analyzed in 90 patients with chronic myelogenous leukemia (CML) in chronic phase. Median survival of this population was 45.9 months. Univariate analysis revealed that splenomegaly, bone marrow basophils, bone marrow blasts, peripheral blood blasts, and bone marrow eosinophils were significant prognostic factors for survival, and that peripheral blood leukocytes counts, hemoglobin concentration, performance status, age and lymphadenopathy were factors with border line significance. There were multiple interrelationship among these disease features. Multivariate regression analysis identified that age, hemoglobin concentration, and bone marrow blasts were independent primarily significant prognostic factors for survival. The Cox model generated with three variables of age, hemoglobin concentration, and percent blasts in bone marrow provided a useful representation of risk status in the population. A hazard function derived from the patients population segregated patients into three groups with significantly different survival patterns: A lower risk group, an intermediate group and a high risk group of patients with median survival of 57.8, 49.8 and 38.4 months respectively. Survival after CML blast crisis was short and overall median survival of 54 patients with CML blast crisis was 6.4 months. A sole prognostic factor for survival in blast crisis identified by multivariate analysis was blast cell type at CML blast crisis and patients with lymphoid phenotype had a good prognosis with median survival of 9.8 months. Median survival of myeloid crisis was 4.2 months. No other disease features were identified as significant prognostic factors in the present patient population.

Adult↗

[Prediction of survival in myelodysplastic syndrome. Analysis of 2 scoring systems with prognostic value].

The wide prognostic variability of myelodysplastic syndromes (MDS) complicates decision-making regarding the choice and evaluation of alternative treatments to transfusional and antiinfectious supportive measures. Due to its simplicity the Bournemouth scoring system seems to have achieved wide acceptance for establishing the prognosis in MDS patients. The aims of this study were to examine the Bournemouth system in a series of 370 patients with MDS and to evaluate the capability of the prognostic index recently proposed by our group to better define the outcome predicted by the former. The Bournemouth scoring system identified 3 risk groups, A (0-1 points), B (2-3 points) and C (4 points), in the whole series (p less than 0.0001) and it allowed us to stratify refractory anemia (RA), RA with excess of blasts (RAEB) and RAEB in transformation (RAEB-t) patients into two distinct prognostic groups (p = 0.03 and p = 0.01, respectively). This scoring system did not show a significant value in RA with ringed sideroblasts (RARS) and chronic myelomonocytic leukemia (CMML) patients (p greater than 0.05). Our prognostic index clearly segregated patients in the whole series into low- (0-1 points), intermediate- (2-3 points) and high-risk (4-5 points) groups (p less than 0.00001) as well as stratifying ARSA (p = 0.0005), CMML (p less than 0.0001) and RAEB and RAEB-t patients (p less than 0.00001) into different prognostic subset, although it failed to demonstrate a significant predictive value in RA patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

DNA grading of malignancy in breast cancer. Prognostic validity, reproducibility and comparison with other classifications.

The prognostic significance of the "DNA malignancy grade" (DNA-MG) was tested in a series of 104 breast cancer patients in comparison with TNM staging, histomorphologic grading according to Bloom and Richardson, mean nuclear area (MNA) and DNA-histogram classification according to Auer. The reproducibility and representativity of the grading systems were investigated, and their results in primary tumors and lymph node metastases were compared. The scalar DNA-MG was assessed on monolayer smears prepared from paraffin-embedded tissues; the smears were automatically Feulgen stained and used for rapid interactive DNA cytometric evaluation by an automated microscope and a TV image-analysis system. TNM staging showed the highest correlation with survival, followed by histomorphologic grading and DNA-MG; MNA and the DNA-histogram classification failed to give statistically significant prognostic information. Both histomorphologic grading and DNA-MG were identified as parameters adding independent prognostic information to the TNM staging. However, only DNA-MG demonstrated an acceptable reliability, with small 95% ranges between repeated measurements within the primary tumor (+/- 0.3 DNA-MG) and a strong correlation between the results in the primary tumor and its lymph node metastases. These findings show that the DNA-MG is a valid and reliable prognostic index that adds significant prognostic information to TNM staging.

Aged↗

Prognostic factors in myelodysplasic syndromes: a multivariante analysis in 138 patients.

A multivariate analysis of clinical, biochemical and hematologic data was performed in 138 patients with myelodysplastic syndromes (MDS) in order to evaluate their prognostic significance. The most important individual variables, isolated in a previous univariate analysis, were placed in a multiple regression modeling procedure to identify major prognostic factors. Multivariate analysis tends to identify prognostic variables containing significant predictive information. Characteristics were examined on both continuous and binary bases. The FAB classification was the first parameter entered in regression equations of both models, followed by platelet count, systemic symptoms, bone marrow blast and infection. Our analysis confirms FAB classification as the best prognostic factor in MDS. It supports the previously predictive value of platelet count, hemoglobin level and bone marrow blast and recognizes the importance of systemic symptoms and infection as prognostic characteristics in MDS.

Adult↗

[Prognostic factors in unresectable lung cancer].

Seventy-seven prognostic factors influencing survival time in patients with unresectable lung cancer treated from 1964 to 1983 at Aichi Cancer Center Hospital were analyzed using univariate analysis by log rank test and multivariate analysis by proportional hazard model of Cox. Statistical significance using univariate analysis was identified in 19 factors in small cell lung cancer patients, and in 40 factors in non-small cell lung cancer patients. The string prognostic factors determined by multivariate analysis were, in the order of importance, serum LDH level, chest pain, peripheral lymphocyte count, bone marrow metastasis, brain metastasis, age, and performance status in small cell lung cancer patients. These 7 factors had a p value of less than 0.01. On the other hand, they were the number of metastatic sites, performance status, serum albumin level, serum LDH level, sex, BUN level, N category according to TNM staging system in non-small cell lung cancer patients, with a p value of less than 0.001. The most important prognostic factors were serum LDH level in small cell lung cancer, and the number of metastatic sites and performance status in non-small cell lung cancer. A metastasis to bone marrow or brain was a more important prognostic factor than overall M category in small cell lung cancer patients, and the number of metastatic sites rather than clinical stage classification or TNM staging system in non-small cell lung cancer patients with respect to staging system. Accurate evaluation of the treatment results in unresectable lung cancer patients must take the strong prognostic factors into account.

Aged↗

Steroid receptors and other prognostic factors in primary breast cancer.

A review and update of published studies on prognostic factors support the following conclusions: The number of axillary lymph nodes involved with tumor remains the most important prognostic factor for women with primary breast cancer. In stage I disease, the lack of estrogen receptor (ER) seems to be the most important factor for predicting earlier recurrence and poorer survival. In stage II breast cancer, progesterone receptor (PgR) content appears to be better than ER content in predicting disease-free and overall survival. Measurement of proliferative activity (S-phase DNA) by thymidine labeling or flow cytometry (FCM) and of aneuploidy by FCM also provides prognostic information. Patients with aneuploid tumors, or with high S-phase diploid tumors, are at increased risk for relapse. Amplification of oncogenes, particularly HER-2/neu, may provide additional prognostic information in combination with other established prognostic factors.

Breast Neoplasms↗

[Prognostic significance of different therapeutic procedures in stage I endometrial cancer].

The prognostic importance of the different lines of therapeutic management are retrospectively reviewed from 230 patients who have been primarily operated on for endometrial carcinoma stage I (FIGO). The postoperative radiation therapy taking into consideration the prognostic significance of the tumour criteria (tumour type, degree of differentiation and extent of myometrial invasion) as well as the age and the general condition of the patient would largely be individualized. 56 (24%) patients has been operated on only. There were no significant prognostic differences for vaginal and abdominal hysterectomies with bilateral salpingo-oophorectomy. Extensive operative measures have been carried out seldom and could not yet be included in the evaluation. A simultaneous gestagen administration in 39 (17%) of the cases with invasively growing carcinomas (greater than 1/3 myometrial invasion), independent from the previous therapeutic regimen, is shown not to have improved the healing results. The favourable prognosis of women mostly with lower primary risk and operated on only as opposed to postoperatively radiated ones underlines the primary prognostic significance of morphological characteristics of the tumour although no definite conclusions can be derived from the concurrent effectivity of the adjuvant radiotherapy for early tumour stages. A postoperative radiation therapy, because of its late consequences which have been observed during tumour follow up, is indicated only in those cases with unfavourable prognostic criteria.

Adult↗

Prognostic indicators in acute variceal hemorrhage after treatment by schlerotherapy.

The purpose of the study was to evaluate prognostic indicators in patients receiving endoscopic injection sclerosis for bleeding esophageal varices. The results below were obtained from a prospective nonrandomized study in which the patients were subdivided into the following groups (subsets): elective sclerotherapy--10, active variceal bleeding at endoscopy--47, active variceal bleeding with spontaneous resolution at the time of endoscopy--21, and gastric variceal bleeding--nine. The data were analyzed as follows: 14 variables possibly affecting 6-wk survival were evaluated by stepwise logistic regression analysis. Variables examined were subset, age, sex, Child's classification, ascites, comorbid conditions, SGOT, bilirubin, protime, albumin, volume of initial bleed, volume of rebleed, rebleed rate, and Blakemore tube use. Survival curves were also compared using the Kaplan-Meier methodology. The following results were obtained. First, the subsets above had significantly different survival curve patterns with the elective endoscopic injection sclerosis group having the best prognosis and the gastric variceal bleeders a significantly poorer survival. Second, stepwise logistic regression analysis revealed the following four significant variable prognostic indicators: comorbid factors, subset, Child's classification, and serum albumin. Although the latter two variables, Child's class (p = 0.03) and albumin (p = 0.1) had an impact on six week survival, this was no longer seen when subset (p = 0.0124) and comorbid factors (p = 0.003) were taken into account. We conclude that comorbid factors and subsets of variceal bleeding in themselves were the only two prognostic indicators showing a statistically significant association with 6-wk and long-term survival. In contrast, the more usual clinical prognostic parameters, i.e., the physical findings and biochemical test of liver function in patients with cirrhosis and acute variceal bleeding, were of lesser prognostic magnitude.

Acute Disease↗

The adjuvant prognostic value of nuclear morphometry in stage I malignant melanoma of the skin. A multivariate analysis.

In order to evaluate the adjuvant prognostic value to tumor thickness of other clinical, qualitative histologic and morphometric features, a multivariate analysis was performed in 68 patients with stage I cutaneous malignant melanoma and at least five years of follow-up. Stepwise linear regression analysis confirmed that tumor thickness is the most important prognostic factor; the only additional significant feature was the nuclear correlation coefficient (NCC), which is a measure for the roundness versus ellipsoidicity, regularity and homogeneity of the shape of the nuclei in tissue sections. In general, tumors with ellipsoid (spindle-shaped) nuclei were associated with a better prognosis, even in thick tumors, and tumors with predominantly round nuclei were associated with a poorer prognosis. If the NCC was below 0.94, the prognosis was good irrespective of the tumor thickness: all patients with such a low NCC have survived. Further analysis of this feature showed it to be strongly correlated with the nuclear axes ratio (longest axis divided by the shortest axis). The subtlety of the differences in nuclear shape makes it practically impossible to subjectively detect the significant prognostic level of ellipsoidity, especially in borderline cases. The advantage of the application of morphometry is that it allows the objective description of subjective impressions, and minor shape differences can be detected. The significant adjuvant prognostic value of nuclear morphometry to tumor thickness makes it worthwhile to consider these features together in future prognostic studies concerning malignant melanoma. Furthermore, inclusion of nuclear shape morphometry in clinical pathology reports seems advisable.

Analysis of Variance↗

Prognostic factors in metastatic breast cancer treated with combination chemotherapy.

Six hundred nineteen patients with metastatic breast cancer, treated with a combination of 5-fluorouracil, Adriamycin, and cyclophosphamide, or close variations of this program, with or without immunotherapy were analyzed retrospectively to identify those host, tumor, or treatment characteristics that might be of prognostic importance in predicting response to chemotherapy and survival from onset of the 5-fluorouracil-Adriamycin-cyclophosphamide treatments. Primary tumor characteristics such as size of primary, number of axillary nodes involved, stage at diagnosis, and type of surgery used for primary treatment were not found to be of prognostic significance. Host characteristics such as age, menstrual status, or family history of breast cancer were similarly unrelated to outcome. Non-Caucasian patients had a lower response rate and somewhat shorter survival than did Caucasians. Pretreatment weight loss, poor performance status, and abnormal biochemical and hematological values were of adverse prognostic significance. An estimate of total extent of disease based on criteria for rating extent of involvement at 12 potential sites was a much more important prognostic factor related to response and survival than actual sites of involvement or the traditional "dominant site" classification. There was a trend, however, for patients with bone involvement to have a longer survival than did patients with metastases to other organ sites. Shorter survival times were observed among patients exposed to extensive prior radiotherapy and those who failed to respond to prior hormonal treatment. The prognostic variables identified in this paper should be used for the design and comparison of clinical trials in the future.

Adult↗

Laboratory parameters as an alternative to performance status in prognostic stratification of patients with small cell lung cancer.

Pretreatment performance status (PS)is a major prognostic factor for both treatment response and survival duration in cancer clinical trials. PS is, however, a subjective index that may be markedly influenced by acute self-limited events. The objective of this study was to develop a prognostic index, based on pretreatment laboratory results, that might serve as an alternative to PS in patients with small cell anaplastic lung cancer. Results have been analyzed in 56 newly diagnosed patients with a minimum followup of 10 months and a median followup of 21 months. Patients were divided into high and low groups for each laboratory parameter based on readings either above or below the median value. Patients with high hemoglobin or albumin levels or low serum alpha-1 globulins, gamma globulins, or LDH survived significantly longer than patients with the opposite levels. When these factors were evaluated by multivariate analysis, albumin and hemoglobin were the most influential prognostic factors for survival. After inclusion of these two laboratory parameters, PS was no longer a significant prognosticator of survival. An objective prognostic index based on pretreatment laboratory results appears feasible in patients with small cell lung cancer.

Carcinoma, Small Cell↗

[The problem of the prognostic significance of perforations of the kidney hollow system and its vascular system; involvement of the lymphatic system and of surrounding organs in patients with hypernephroid kidney cancers].

On the basis of 51 patients with a hypernephroid renal carcinoma the prognostic importance of the size of the tumour, of the infraction into the renal hollow system, the invasion of lymphatic and vascular system as well as of the border of the organ after tumour nephrectomy and a 5-year observation time was discussed. While the isolated infraction into the hollow system was not relevant in smaller tumours, it implies an additional prognostically negative factor in advanced tumours. In the same measure the invasion of renal capsule or perihilary tissue resulted in a prognostically negative factor. Invasion of blood or lymphatic vessels proved to be very bad prognostically and resulted in a decrease of the survival rate of about 2/3. The prognostically worst hint was the simultaneous infraction into various systems with a decrease of the survival rate of more than 3/4.

Adenocarcinoma↗

Transarterial oily chemoembolization for the treatment of hepatocellular carcinoma: a multivariate analysis of prognostic factors.

A total of 84 patients with hepatocellular carcinoma and cirrhosis were analyzed retrospectively to investigate prognostic factors. All patients received transarterial oily chemoembolization as the only anticancer therapy. The follow-up range was 1 to 39 mo (median, 9.5 mo). The overall actuarial survival rates at 12, 24 and 30 mo were 62%, 31% and 24%, respectively. According to univariate analysis, variables significantly associated with survival were age, Child-Pugh grade, total serum bilirubin, Okuda stage, tumor size, degree of labeling of the tumor with Lipiodol, gelatin foam use, changes with treatment in tumor size and changes with treatment in alpha-fetoprotein concentration. Two multivariate analyses were performed. When pretreatment and treatment variables were considered, parameters with independent prognostic value were age, Child-Pugh grade, total serum bilirubin, tumor size and degree of Lipiodol labeling of the tumor. When follow-up variables were also considered, we (a) confirmed the prognostic significance of all these parameters (age, Child-Pugh grade, total serum bilirubin, tumor size) and (b) found the independent prognostic value of the change in tumor size (or change in alpha-fetoprotein concentration). Both models yielded different risk coefficients for each class of each variable. Two simple prognostic indexes, based on these coefficients, are proposed: an "initial" index (including pretreatment and treatment variables) and a "follow-up" index (also including follow-up variables). According to the two indexes, the patients were classified into three groups with different prognoses: good (93% and 100% actuarial survival at 1 yr for the initial and follow-up indexes, respectively), intermediate (65% and 53%, respectively) and poor (27% for both indexes).

Actuarial Analysis↗

Prognostic value of quantitatively measured AgNORs in ductal mammary carcinoma.

Argyrophilic proteins of nucleolar organizer regions (AgNOR proteins) were stained by a modified silver staining technique. Paraffin sections from 137 cases of invasive ductal carcinoma of the breast were investigated. The nuclei and AgNOR dots were quantitatively measured by means of a semiautomatic image analysis system. Follow-up data for about 120 months (mean, 102 +/- 47) and clinical/histologic and DNA distribution parameters were available for all patients. The prognostic significance of AgNOR parameters was tested by Cox regression analysis. Four AgNOR features showed a significant univariate correlation with survival time. In multivariate analysis offering all the available parameters, one AgNOR parameter (coefficient of variation of relative AgNOR area) ranked at the third position beyond the standard deviation of DNA distribution and pTNM/staging. When considering the distant recurrence-free survival of patients, the same AgNOR feature provided significant additional prognostic information. Performing survival analysis for the prognostically defined subgroup of pTNM/stage I patients and offering all DNA and AgNOR features the same AgNOR parameter yielded the highest prognostic validity. These results show that quantitatively measured AgNORs yield prognostic factors in breast cancer.

Breast Neoplasms↗

Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group.

High serum level of bioactive interleukin-6 (IL-6) is regarded as a predictor of poor prognosis in multiple myeloma (MM). On the other hand, the reported levels of immunoreactive IL-6 have been highly variable, and the prognostic value of immunoreactive IL-6 in MM is not clear. We have analyzed the prognostic significance of serum immunoreactive IL-6, as measured by a sensitive immunosorbent assay, in 210 patients with newly diagnosed MM subsequently treated with intermittent melphalan and prednisone. The serum levels of acute phase proteins C-reactive protein (CRP), alpha 1-antitrypsin (alpha 1AT), and acid alpha 1-glycoprotein (orosomucoid; OM) were evaluated as surrogates for IL-6. Serum IL-6, CRP, alpha 1AT, and OM levels were raised in 42%, 40%, 41%, and 24% of the patients, respectively. There was a significant correlation between the clinical stage of the patients and serum IL-6 (P = .006), alpha 1AT (P = .001), and OM (P = .004) levels at diagnosis. At 3 years, 52% of the patients were alive. Univariate logistic regression analysis showed that high levels of IL-6 (P = .002), CRP (P = .02), alpha 1AT (P < .001), OM (P = .007), beta 2-microglobulin (beta 2M; P < .001), and thymidine kinase (P < .05) were all associated with 3-year mortality. In multivariate regression analysis, beta 2M (P < .0001) and alpha 1AT (P = .01) had independent prognostic significance. The patients with high levels of both beta 2M and alpha 1AT or IL-6 were at very high risk of dying within 3 years from diagnosis (16% and 21% of the patients in these groups were alive, respectively). When the patients were stratified according to the clinical stage, the prognostic significance of serum IL-6 and alpha 1AT was especially evident in stage II patients. When the patients were divided into two groups according to normal or raised serum IL-6 levels, the patients with high IL-6 levels had more frequent osteolytic bone lesions (P = .03) and a more aggressive disease. We conclude that serum immunoreactive IL-6 is a significant prognostic marker in MM.

Acute-Phase Proteins↗