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Prognostic factors for survival in patients with inoperable lung cancer.

Seventy-seven prognostic factors were considered in an evaluation of more than 5,000 patients with inoperable bronchogenic carcinoma of the lung; these patients were entered on the Veterans Administration Lung Group protocols 9-15 (1968-78). Fifty prognostic factors for survival were identified, and their relative contributions to patient survival were considered. The three most important prognostic factors affecting survival were the Karnofsky initial performance status score, extent of disease, and weight loss in the previous 6 months. These factors denoted three general prognostic components: current physical status, current disease status, and prior physical status. Initial performance status was the dominant prognostic factor. Characterization of patient's function status with the use of the Karnofsky scale was preferred to a summarized scale or a dichotomization into ambulatory versus nonambulatory. The current practice of dichotomizing factors resulted in the loss of much prognostic information. Other factors, such as tumor size, histologic type, and institution, appeared to be important when considered alone. However, their contribution was relatively minor after a correction was made for the effects of initial performance status, extent of disease, and prior weight loss. Depending on these three prognostic factors alone, median survival varied between 6 weeks and over a year. Reporting of results without the consideration of such prognostic factors severly hampers any comparisons that may be made between investigations.

Actuarial Analysis↗

Prognostic factors for patients with diffuse large cell or immunoblastic non-Hodgkin's lymphomas: experience of the non-Hodgkin's Lymphoma Pathologic Classification Project.

Prognostic factors for long-term survival of 312 patients with diffuse large cell or immunoblastic non-Hodgkin's lymphoma are presented based on analysis of the multiinstitution clinicopathologic study sponsored by the National Cancer Institute. At the time of analysis, 75% of the patients had died and the median follow-up for patients still alive was 11 years. The distribution of Ann Arbor stages was 21% stage I, 32% stage II, 17% stage III, and 30% stage IV. Factors of prognostic significance for survival included age, stage, histologic subtype, presence of B symptoms, size of the largest lesion, number of extra-lymphoid organs involved, and extent of lymphatic involvement. Recursive partitioning analysis suggested a prognostic classification system based on stage, age, size of the largest lesion, and presence of mediastinal involvement. Stage I patient less than 50 years of age had a 10 year survival rate of 65% compared to 36% for older stage I patients. Stage II patients less than 65 years old without bulky lesions or mediastinal involvement had a 10 year survival rate of 45% compared to 10% for the poorer risk stage II patients. Although statistically significant prognostic factors were identified for the stage III/IV patients, they were not strong discriminants of 5-10 year survival rate. Because of the correlation among potential prognostic factors, there is no uniquely best classification system. Reasons for discrepancies among reported prognostic factor analyses are discussed, and a prognostic grouping that synthesizes our results with those of others is proposed.

Adult↗

[Prognostic factors in uterine cervical and corpus cancer].

We have studied the prognostic factors for cancer of uterine cervix and corpus. Prognostic factors for cervical cancer include clinical stage, histological type, pelvic and paraaortic lymph node metastasis and CPL classification of carcinoma. Prognostic factors for cancer of uterine corpus are concerned with clinical stage, histological type and histological differentiation, muscle invasion, lymph node metastasis, perineal washing cytology and so forth. The clinical stage of course, reflects the prognosis. Although one of the important prognostic factors is lymph no metastasis, there may be recurrence in patients with a poor prognosis in cases in which lymph node metastasis has not been observed. In order to distinguish such cases and to improve their prognosis, it is important to provide treatment individually but combined chemotherapy or radiation therapy, for example, with efforts to detect various prognostic factors.

Female↗

Prognostic factors in patients with advanced biliary tract cancer receiving chemotherapy.

BACKGROUND/AIMS: Prognostic factors in patients with advanced biliary tract cancer receiving chemotherapy have not been fully examined. This study investigated prognostic factors in patients with advanced biliary tract cancer receiving chemotherapy. METHODOLOGY: Sixty-five consecutive chemo-naive patients with advanced biliary tract cancer, who received chemotherapy, were analyzed retrospectively to investigate prognostic factors. RESULTS: Median survival time and overall survival rates at 1 and 2 years were 180 days, 21%, and 5%, respectively. By multivariate analysis using the Cox proportional hazards model, performance status of 0, 1, serum C-reactive protein level of < or = 1.0mg/dL, serum albumin level of > or = 3.5g/dL, serum lactate dehydrogenase level of < or = 500 U/L, and being female were independent favorable prognostic factors. A prognostic index based on the coefficients of these prognostic factors was used to classify patients into three groups with good, intermediate, and poor prognoses. The median survival times for these three groups were 246, 152, and 33 days, respectively. CONCLUSIONS: The results may be helpful for predicting life expectancy, determining treatment strategies, and designing future clinical trials in patients with advanced biliary tract cancer.

Adult↗

Reappraisal of internal mammary node metastases as a prognostic factor in patients with breast cancer.

Clinical, histologic, and biologic prognostic factors were examined in 144 patients with invasive breast cancer. It was determined whether variable prognostic factors, especially internal mammary lymph node metastases, would serve as a basis for the prognosis of breast cancer. In a univariate study, overall survival was significantly correlated with tumor size, axillary lymph node status, axillary and internal mammary lymph node metastases, and DNA ploidy status. Especially among patients with one to three positive axillary nodes, survival in case of internal mammary involvement were significantly lower than without internal mammary involvement. In a multivariate study, only axillary and internal mammary lymph node metastases were recognized as important, independent prognostic factors of survival, but neither axillary lymph node status nor DNA ploidy status appeared as important prognostic factors. It was concluded that internal mammary lymph node metastases is additional prognostic factor, especially in patients with one to three positive axillary nodes. Because axillary and internal mammary lymph node metastases could not be predicted from their clinical assessment, axillary lymph node dissection and biopsy of internal mammary nodes may be a useful staging procedure for these patients.

Adenocarcinoma, Mucinous↗

Analysis of prognostic factors in squamous cell carcinomas of the head and neck.

It appears that prognostic factors of proven value in the management of other malignancies have marginal value in the treatment of patients with squamous cell carcinomas of the head and neck (SCCHN). For example, age, sex, and performance status do not correlate with treatment outcome. Similarly, histologic differentiation has little predictive value, with undifferentiated carcinomas of nasopharyngeal origin being a possible exception. On the other hand, primary tumor site may be an important prognostic factor, with tumors arising from the nasopharynx, oral cavity, and possibly the oropharynx having a more favorable outcome, whereas tumors of the hypopharynx appear to be the least favorable. A tumor's TNM stage is also highly predictive of response to treatment and survival. Overall stage of disease is an effective predictor of relapse and survival only for patients with limited disease and only after the primary site is specified. Independent of primary tumor site, an inverse correlation clearly exists between T and N stage and either response to treatment or overall survival. Flow cytometry, a relatively new test, appears to be one of the most significant predictors of response to chemotherapy, relapse, and survival in patients with SCCHN. As a prognostic factor, DNA tumor content may be independent of all other known clinical and pathologic factors. Patients with diploid tumors have a superior relapse-free and overall survival as compared with patients whose tumors are aneuploid. Another parameter of significant value is the patient's response to induction chemotherapy, with responding patients demonstrating a far superior relapse-free and overall survival compared with nonresponders. In summary, the site of the primary tumor, its T stage, N stage, and DNA content, and the magnitude of its response to induction chemotherapy are the most valuable prognostic factors in SCCHN. It is assumed, however, that as new and more effective therapies are developed for patients with SCCHN, previously significant prognostic factors will cease to have clinical or scientific value. Similarly, as new diagnostic tests and staging tools are developed, a new generation of prognostic factors with greater biologic and clinical relevance is likely to emerge. In the evolution of new therapies for patients with SCCHN, prognostic factors such as those mentioned here or ones yet to be evaluated will be central to the design of clinical studies and the identification of specific patients for specific therapies. Once treatment is initiated, treatment-related prognostic factors may further identify patients for whom modifications of the initial therapeutic plan would be appropriate.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

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

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

Adult↗

Prognostic factors in clinical cancer trials.

Differences in nontreatment-related covariates ("prognostic factors") often account for differences between treatments in clinical cancer trials. This is true even in randomized trials in which the number of patients randomized is less than 200. Hence analysis of prognostic factors is crucial in historically controlled and small randomized trials. However, it is known that factors found prognostic in one series are often not prognostic in another. This is a result of the increased type I error inherent in most methods used to identify the optimal cutpoint of a potential prognostic factor. This report describes new graphical methods, based on Martingale residuals, that can be used to better identify the relationship between outcome and a covariate. For example, use of these methods indicated that the effect of antecedent hematological disorder on survival in acute myelogenous leukemia/myelodysplastic syndrome is continuous (the longer the length of antecedent hematological disorder, the shorter the survival) rather than dichotomous (antecedent hematological disorder present = unfavorable). This report also discusses the use of graphical methods to test the assumption of proportional hazards crucial to the Cox model and to account for any time-varying effects of a prognostic factor. The graphical methods discussed here provide a better fit of a statistical model to the data and provide more reliable estimates of the effect of a particular variable.

Clinical Protocols↗

Thymoma. Analysis of prognostic factors.

OBJECTIVE: We evaluated the prognostic factors for thymoma that remain controversial. METHODS: We studied 72 consecutive patients treated for thymoma during the period between 1966 and 1997. Recurrence-free interval rates and overall survival rates calculated by the Kaplan-Meier method were compared using log-rank test by the Masaoka stage, extent of surgical resection, histology, or associated disease(s). Multivariate analysis was performed using Cox's proportional hazards model. RESULTS: Thirty-two thymomas were at Masaoka stage I, 9 at stage II, 15 at stage III, and 16 were at stage IV. There were 56 complete resections, 7 incomplete resections (2 at stage III and 5 at stage IV), and 9 biopsies (1 at stage III and 8 at stage IV). Forty-one thymomas were cortical, 16 medullary, and 15 were mixed form. Association of myasthenia gravis was found in 20 patients, and pure red cell aplasia in 7. After an average follow-up period of 103 months, the recurrence-free 5-, 10-, 15-year interval rate was 89%, 80%, 80%, respectively, and overall 5-, 10-, 15-year survival rate was 86%, 71%, 59%, respectively. Factors influencing the recurrence-free interval and overall survival included the Masaoka stage, extent of surgical resection, and association with pure red cell aplasia. Multivariate analysis revealed stage IV tumor and association with pure red cell aplasia as risk factors for recurrence. Pure red cell aplasia indicated poor prognosis for overall survival. CONCLUSIONS: Masaoka stage, extent of surgical resection, and association with pure red cell aplasia were prognostic factors for thymoma. Multidisciplinary treatment for stage IV tumors and better control of pure red cell aplasia, if associated, should be investigated.

Adult↗

Upper urinary tract tumors after primary superficial bladder tumors: prognostic factors and risk groups.

PURPOSE: We evaluated the prognostic factors of primary superficial bladder cancer that may predict a metachronous upper urinary tract tumor. We also determined whether the incidence of upper urinary tract disease varies according to risk group based on primary superficial bladder tumor classification. MATERIALS AND METHODS: We studied disease evolution in a cohort of 1,529 patients with a primary superficial bladder tumor. To determine the prognostic factors of upper urinary tract cancer we performed multivariate analysis using Cox regression. Independent variables were grade, T stage, multiplicity, tumor size, carcinoma in situ association, previous or synchronous upper urinary tract tumor and intravesical instillation. We also performed the chi-square test and Kaplan-Meier survival analysis to assess the variable incidence of upper urinary tract tumors according to primary superficial bladder tumor risk group classification. RESULTS: The incidence of upper urinary tract cancer was 2.6%. The only factor prognostic for an upper urinary tract tumor was multiplicity (relative risk 2.7, 95% confidence interval [CI] 1.06 to 6.84). All patients with an upper urinary tract tumor had a previously recurrent primary superficial bladder tumor. In the low, intermediate and high risk groups the incidence of upper urinary tract cancer was 0.6% (relative risk 1), 1.8% (relative risk 3.1, 95% CI 0.4 to 23.9) and 4.1% (relative risk 8.3, 95% CI 1.1 to 61.6), respectively (chi-square and log rank tests p = 0.007 and p <0.05, respectively). CONCLUSIONS: A higher risk of upper urinary tract cancer must be expected in cases of multiple primary superficial bladder tumors. This finding supports the multicentricity theory of transitional cell carcinoma. Primary superficial bladder tumor classification by risk group is also useful for predicting the various risks of metachronous upper urinary tract cancer.

Carcinoma, Transitional Cell↗

Importance of prognostic factors in cancer clinical trials.

The importance of prognostic factors in the design, analysis, and reporting of clinical trials is discussed. For many kinds of cancer, the variability in prognosis among patients is greater than the size of treatment differences usually seen. Consequently, failure to understand and adequately account for patient heterogeneity easily leads to unreliable claims and inefficient trials. Identified prognostic factors are generally of sufficient importance to demand attention in design and analysis, but rarely are sufficiently explanatory to render randomization unnecessary. Improvement in knowledge of prognostic factors is important for sharpening the focus and for improving the reliability, efficiency, and interpretability of clinical trials. Problems in the conduct of prognostic factor studies are also discussed, and the calculation of the proportion of variability explained by logistic regression models is illustrated for two examples.

Bone Marrow↗

Nonanatomic prognostic factors in resected nonsmall cell lung carcinoma: the importance of perineural invasion as a new prognostic marker.

BACKGROUND: A number of prognostic factors have been reported for resected nonsmall cell lung carcinoma. Although none of them reported to have greater prognostic impact than the TNM staging system, which is based on anatomical descriptions of tumors, the prognoses of a significant number of patients are not in agreement with real survival of the patients. Moreover, certain histopathologic properties of the tumor (such as lymphatic and vascular invasion) could help to predict the survival of the patients. METHODS: A retrospective study was conducted on 82 surgically resected nonsmall cell lung carcinomas, and the following prognostic factors were evaluated in univariate analysis: age, gender, clinical and surgical-pathologic T and N status, histologic type of tumor, grade of differentiation, lymphatic invasion, vascular invasion, and perineural invasion. RESULTS: Lymphatic invasion and perineural invasion of the tumor were found to be significant prognostic factors (p = 0.02 and p = 0004). Blood vessel invasion (venous or arterial involvement) had no prognostic impact (p > 0.05). According to multivariate analyses, three factors were selected as prognostic indicators: (1) clinical N status (p = 0.027), (2) lymphatic invasion (p = 0.027) and (3) perineural invasion (p = 0.0148). By combining these factors we identified a poor prognostic subgroup of patients with stage I disease. CONCLUSIONS: Our study showed that lymphatic vessel and perineural invasion of the tumor could be prognostic factors, along with anatomical determinants such as cN and surgical-pathologic stage of the pulmonary carcinoma.

Aged↗

Do we really need prognostic factors for breast cancer?

The role of prognostic factors in optimizing treatment for breast cancer patients has clearly changed with the trend toward general use of adjuvant therapy. Nevertheless, there are at least three situations in which prognostic factors could be helpful. The first is to identify patients whose prognosis is so good that adjuvant therapy after local surgery would not be cost-beneficial. The second is to identify patients whose prognosis is so poor that a more aggressive adjuvant approach would be warranted. The third is to identify patients likely to be responsive or resistant to particular forms of therapy. Here we will discuss all of these situations, together with the appropriate cutpoint analyses and validation of individual prognostic factors and their combination into prognostic indexes which may make the discrimination of patient subsets more reliable.

Biomarkers, Tumor↗

Prognostic factors in juvenile idiopathic arthritis.

Prognostic factors in juvenile arthritis are related to many variables that must be evaluated according to the different subtypes. The International League of Associations of Rheumatologists (ILAR) recently proposed six different categories referred to as the Durban criteria, under the eponym of juvenile idiopathic arthritis (JIA). The aim of this classification was to define homogeneous groups according to their clinical and biologic features. The prognostic factors were classified into the different categories of JIA. A poor outcome in the systemic form correlated with markers of disease activity, such as fever and polyarticular involvement, within the first 6 months. The risk of joint destruction in oligoarthritis correlated with the severity of arthritis within the first 2 years. Polyarthritis with positive rheumatoid factor is associated with marked disability in adulthood. In a group of psoriatic patients, the risk of developing sacroiliitis is higher in male and HLA-B27-positive patients. Patients with enthesitis-related arthritis with lower limb, knee, and tarsal involvement also are at greater risk of developing sacroiliitis. Chronic uveitis is a complication of JIA observed mainly in patients with oligoarthritis associated with positive antinuclear antibodies in serum. Secondary amyloidosis is observed mainly in children with systemic JIA. The long-term outcome must be discussed according to the various therapies. Corticosteroids contribute to growth retardation and osteoporosis, for which the use of human recombinant growth hormone and biphosphonates may be an option. Newer encouraging therapies such as anticytokines have been proposed for children with active disease. Autologous stem cell transplantation is being evaluated in some centers with promising results; however, it has a high rate of mortality. Further discussion regarding which patients should undergo autologous stem cell transplantation is needed, as is further discussion regarding the technical adaptations necessary.

Adolescent↗

Diffuse large cell lymphomas: identification of prognostic factors and validation of the International Non-Hodgkin's Lymphoma Prognostic Index. A Hellenic Cooperative Oncology Group Study.

Several clinical prognostic factors have been identified that predict treatment outcome in patients with diffuse large cell lymphomas. An International Non-Hodgkin's Lymphoma Prognostic Index (IPI) has been recently formulated. We tried to identify the clinical prognostic factors that predict treatment outcome in Greek patients with diffuse large cell lymphomas and validated the IPI in these patients. The possible prognostic variables for tumor response, relapse-free (RFS) and overall survival (OS) were analyzed in 239 consecutive patients treated with anthracycline-based chemotherapy regimens. In univariate analysis, factors associated with poor response were stages III-IV, performance status (PS) >/=2, spleen and bone marrow involvement, more than one extranodal site involved, increased lactate dehydrogenase (LDH) value, hemoglobin (Hb) <12 g/dl, albumin <3.5 g/dl, erythrocyte sedimentation rate (ESR) >50 mm/h. Multivariate analysis identified stage, PS, more than one extranodal site involved, increased LDH level, and ESR > 50 mm/h as the factors more predictive of poor response. For RFS, multiple Cox analysis found stages III-IV and bone marrow involvement to be statistically significant. For OS, multiple Cox analysis identified stage III-IV, PS >/=2, bone marrow involvement, more than one extranodal site involved, increased LDH level and ESR > 50 mm/h as negative prognostic factors. Patients stratified in the different risk groups of the IPI had a significantly different outcome regarding complete response (CR) rate, RFS and OS. In conclusion, although age >60 years was not recognized as an adverse factor in this analysis, our patients stratified in the different groups of the IPI had significant differences in CR rate, 2-year RFS and OS verifying the prognostic significance of the index. Bone marrow involvement and ESR > 50 mm/h, parameters that are not included in the IPI, adversely affected survival.

Adult↗

[Multivariate analysis of prognostic factors in endometrial carcinoma].

BACKGROUND & OBJECTIVE: A number of prognostic factors have been evaluated in endometrial carcinoma. Among them, only a few factors have been recognized as major adverse factors affecting prognosis independently. This study was to explore the independent prognostic factors in endometrial carcinoma. METHODS: A total of 265 patients who accepted primary surgical treatment in our hospital from Jan. 1990 to Dec. 2000 were studied retrospectively. Prognostic factors were analyzed using univariate model and multivariate regression model. RESULTS: The 5-year recurrence-free survival rate of all patients was 83.3%, and 5-year overall survival rate was 84.3%. The univariate model revealed that clinical stage, pathological stage, pathologic grade, pathologic subtype, depth of muscularis invasion, cervical invasion, lymph node metastasis, peritoneal cytology, lymph-vascular invasion, and adnexa metastasis significantly associated with 5-year recurrence-free survival, and 5-year overall survival (P< 0.05), while age, and complications have no significant association with prognosis (P >0.05). However,on multivariate regression analysis, only pathohistological stage, pathologic grade, depth of muscularis invasion, and cervical invasion significantly correlated with 5-year recurrence-free survival, and 5-year overall survival (P< 0.05); clinical stage correlated with 5-year recurrence-free survival significantly (P< 0.001), but not with 5-year overall survival (P=0.074). Hematogenous dissemination rate of patients with muscularis invasion of >50% was significantly higher than that with muscularis invasion of <or=50% (12.9% vs 0.6%, P< 0.001). Lymphatic failure rate of patients with cervical invasion was significantly higher than that without cervical invasion (21.1% vs 3.6%, P< 0.001). CONCLUSIONS: FIGO stage, pathologic grade, depth of muscularis invasion, and cervical invasion are independent prognostic factors in endometrial carcinoma. Comparing with clinical stage, pathohistological stage could assess prognosis more objectively. Deep muscularis invasion is the strongest predictor of hematogenous dissemination; and cervical invasion increases the lymphatic failure rate.

Adult↗

Comparison of Lauren's, Ming's and WHO histological classifications of gastric cancer as a prognostic factor for operated patients.

The prognostic significance of the above mentioned histological classifications is evaluated. The survival data of 259 supposedly radically resected patients is analyzed. The survival curves have been calculated according to the Kaplan-Meier method and compared with the Mantel-Cox test. The most important prognostic factors have been found and used in the stratification analysis. The diffuse type of cancer (according to Lauren) has significantly worse prognosis than the intestinal type only considering the same pT (pT3) and sex (male) or age group from 50 to 70 years. The infiltrative type of cancer (according to Ming) has a worse prognosis than expansive. The difference is insignificant even after stratification analysis. Worse prognosis of diffuse (or infiltrative) cancer is influenced more by the infiltration of regional lymph nodes than by the depth of infiltration, age or sex. WHO classification is less important as a prognostic factor. Signet ring cell type cancer has a worse prognosis considering age group 50-70 years.

Female↗

The relative importance of prognostic factors in studies of survival.

The relative importance of prognostic factors in regression can be measured either by standardized regression coefficients or by percentages of explained variation in a dependent variable. One advantage of using explained variation is the direct comparability of qualitative prognostic factors with others, or of groups of prognostic factors. The description of relative importance can be accomplished within marginal or partial effects analyses. It is demonstrated that it is possible not only to provide a descriptive ranking of prognostic factors according to their statistically determined importance, but also to make inferences concerning their relative importance, employing bootstrap techniques and procedures for multiple comparisons. The methods presented, which are new in the context of Cox regression, are exemplified by analyses of studies of lung cancer and breast cancer.

Adult↗