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The identification of prognostic factors is an important area of cancer research. This article contains an introduction to the uses of prognostic factors, statistical methods for their identification, and a summary of the literature concerning the evolution of serum beta 2 microglobulin as a prognostic factor in multiple myeloma.
PURPOSE: To investigate the treatment outcome and prognostic factors of adult medulloblastoma patients who received postoperative craniospinal irradiation (RT). METHODS AND MATERIALS: Between 1983 and 2000, 30 adult patients (17 men and 13 women, age >or=16 years, median 27, range 16-45) underwent postoperative RT. The median duration of symptoms was 2 months (range 1-9). The tumor location was lateral in 16 (53%). A desmoplastic variant was seen in 12 (40%). Tumor resection was complete in 20 (67%) and incomplete in 10 (33%). All patients received craniospinal RT. The median dose to the whole brain was 40 Gy (range 36-51), to the posterior fossa 54 Gy (range 49-56), and to the spinal axis 36 Gy (range 24-40). The median interval between surgery and the start of RT was 31 days (range 12-69), and the median duration of RT was 45 days (range 34-89). Ten patients (33%) received adjuvant chemotherapy. The median follow-up was 51 months (range 5-215). RESULTS: The 5- and 8-year overall survival and disease-free survival rates were 65% and 51% and 63% and 50%, respectively. Twelve patients (40%) developed relapse, with a median follow-up of 51 months. The posterior fossa was the most common site of relapse (6 patients). The median time to relapse was 26 months (range 4-78). Fifty percent of the relapses occurred after 2 years, 17% after 5 years. In univariate analysis, M stage and the interval between surgery and the start of RT were significant prognostic factors for disease-free survival. At 5 years, 70% of M0 patients were estimated to be disease-free, but none of the 3 M3 patients reached 5 years without recurrence (p = 0.0002). The 5-year disease-free survival rate for the patients whose interval between surgery and the start of RT was <3 weeks, between 3 and 6 weeks, and >6 weeks was 0%, 85%, and 75%, respectively (p = 0.002). The 5-year posterior fossa control rate for patients who received >or=54 Gy or <54 Gy to the posterior fossa was 91% and 33%, respectively (p = 0.05). CONCLUSION: The survival results for medulloblastomas in adults compare favorably with those in children. However, late relapses, lateral tumor location, and desmoplastic histologic features are more frequent in adults. Spinal seeding at presentation is a poor prognostic factor for disease-free survival. A minimal dose of 54 Gy to the posterior fossa is essential for adequate tumor control. The interval between surgery and the start of RT, which was found to be a significant prognostic factor, is an interesting issue that requires further study.
Angiogenesis and other prognostic factors have been studied among 32 recurrences and 28 deaths of 420 patients with cervical carcinoma operated in the 1st Department of Obstetrics & Gynecology of Catania University. Prognostic factors were studied in comparison with a group of patients still alive and NED was followed for more than 60 months independently of stage and node involvement. Angiogenesis, nuclear grading 3, and lymphovascular invasion were factors common to all patients with negative prognosis. It seems that in the presence of these negative prognostic factors, we should adopt a more aggressive attitude in both our surgical strategies and adjuvant therapies, particularly preferring chemotherapy where angiogenesis is more significant.
OBJECTIVE: To investigate the prognostic factors in non-small cell lung cancer (NSCLC) at stage III and IV and establish a reliable model of clinical prognostic index. METHODS: Kaplan-Meier and Cox regression were used to analyze the relationship between the prognostic factors and survival time in 114 cases of NSCLC. The prognostic factors included clinical-pathological features and serum levels of cytokeratin fragment 19 (Cyfra21-1), CEA, neuron-specific enolase (NSE), CA125, interleukin-2 (IL-2) and soluble interleukin-2 receptors (sIL-2R). RESULTS: Kaplan-Meier analysis showed that KPS, sex, disease stage, treatment, Cyfra21-1, sIL-2R and CA125 were related to prognosis. Multivariate analysis indicated that Cyfra21-1, stage and treatment were independent prognostic factors. When Cyfra21-1 > 3.5 mg/L, stage IV and chemotherapy < 3 cycles, the relative risk (RR) was 1.691, 2.229 and 3.035, respectively. In patients given 3 or more cycles of chemotherapy, serum Cyfra21-1, sIL-2R and stage at diagnosis were significantly independent prognostic factors. Three of these prognostic factors were used to establish a prognostic index (PI) model based on a simple algorithm: PI = Cyfra21-1 + sIL-2R + stage. The median survival period of patients with 3 or more cycles of chemotherapy were 18 months if PI = 0, 8 months if PI = 1 or 2, and 5 months if PI = 3. CONCLUSION: The serum Cyfra21-1, sIL-2R and disease stage in unresectable NSCLC were independent prognostic factors. PI calculated on the basis of Cyfra21-1, sIL-2R and stage is recommended to predict the survival period of NSCLC.
The prognosis for glioblastoma multiforme is generally poor. However, it can be useful to identify groups of patients with varying prognosis. Based on data from 495 consecutive patients admitted to the Norwegian Radium Hospital during 1980-1994, multivariable methods were used to identify prognostic factors independently associated with length of survival. A prognostic index was derived in 384 randomly selected patients, and tested in 111 other patients. Performance status, dexamethasone dependency, age group, surgery and behavioural changes were prognostic discriminators. On this basis a prognostic index was made and three separate subsets with different survival prognoses could be identified. The prognostic index was then tested among 20% of the patients and shown to predict reliable survival curves. In the subset with the highest index (high risk subset) almost all patients in the main group as well as in the the test group were dead within 18 months.
The identification and assessment of prognostic factors is an important task in clinical cancer research. Quantitative prognostic factors are often categorized by using one or several cutpoints to obtain an easier interpretation with respect to prognosis of the resulting patients' subgroups. Considering the selection of a data-driven 'optimal' cutpoint as a 'prototype' of statistical model building, we demonstrate that prognostic relevance of a single factor with no effect can solely be produced by the statistical model building process. Furthermore, we show how to overcome these problems by using corrected P-values and shrinkage methods. The problem and its solutions are illustrated by using the data of two breast cancer studies.
BACKGROUND: Prognostic factors have been shown to be important when stratifying patients with prostate cancer into randomized trials and counseling the individual patient regarding his chances of response to treatment. However, there are no reports on prognostic factors in patients with Stage D2 prostate cancer treated with a pure antiandrogen as monotherapy. METHODS: The authors studied a variety of possible prognostic factors among 150 patients with metastatic prostate cancer treated with an antiandrogen (Casodex, Imperial Chemical Industries, Wilmington, DE). RESULTS: In a univariate analysis, performance status; extent of disease (EOD); pretreatment hemoglobin, alkaline phosphatase, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) levels; and extent of disease (EOD) on bone scan all were found to be significant prognostic factors (P < 0.05). Pretreatment serum testosterone levels, identified as one of the most important prognostic factors, was not identified as significant in the current study. CONCLUSIONS: Although the pretreatment testosterone level was shown to be an important prognostic factor in previous studies, using other modes of androgen ablation (reducing testosterone to below castrate levels), the current study suggest it may not be a helpful factor if the therapy used is antiandrogens as monotherapy. This may relate to the different mode of action of antiandrogens, which do not reduce serum testosterone levels.
PURPOSE: The International Prognostic Factor Index has been shown to predict the outcome of patients with predominantly B-cell lymphomas classified using traditional classifications, including the Working Formulation, but its prognostic importance has not been tested in a cohort of patients with exclusively T-cell lymphomas. This study was conducted to evaluate the prognostic significance of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: Seventy-eight patients (48 men and 30 women) with PTCL seen at a single institution between 1985 and 1995 were included in the analysis. The morphology and immunocytochemistry of all the original biopsy specimens were reviewed by a single pathologist and classified using the Revised European-American Lymphoma (REAL) classification. The International Prognostic Factor Index, as well as clinical and biochemical parameters, were evaluated by univariate and multivariate analyses to determine their association with patient outcome. RESULTS: The International Prognostic Factor Index strongly predicted survival when all patients were included in the analysis (P < .001). For patients < or = 60 years, the age-adjusted International Index significantly predicted long-term survival (P = .0218). For patients older than 60 years, the age-adjusted International Index also significantly predicted survival (P = .002). Liver involvement (P = .006) and bone marrow involvement (P = .014) were also significant prognostic factors in the univariate analysis, but only the International Index remained significant in the multivariate analysis (P = .001). CONCLUSION: The International Prognostic Factor Index, which significantly predicts outcome in patients with aggressive/intermediate-grade B-cell lymphomas, has similar prognostic importance in patients with PTCL.
PURPOSE: This retrospective 12-year study evaluated the prognostic value of initial and postoperative staging of rectal tumors. METHODS AND MATERIALS: Between 1985 and 1996, 297 patients were treated with preoperative radiotherapy (39 Gy in 13 fractions) and surgery for Stage T2-T4N0-N1M0 rectal adenocarcinoma. Pretreatment staging included a clinical examination and endorectal ultrasonography (EUS) since 1988. Clinical staging was performed by digital rectal examination and rigid proctoscopy. EUS was performed in 236 patients. Postoperative staging was performed by examination of the pathologic specimen. RESULTS: The median follow-up was 49 months. The overall 5-year survival rate was 67%, with a local failure rate of 9%. The rate of sphincter preservation was 65%. The clinical examination findings were strong prognostic factor for both cT stage (p < 0.001) and cN stage (p < 0.006) but had poor specificity for cN stage (only 25 lymph nodes detected). In both univariate and multivariate analyses, EUS had a statistically significant prognostic value for uT (p < 0.014) but not for uN (p < 0.47) stage. In contrast, pT and pN stages were strong prognostic factors (p < 0.001 and p < 0.001, respectively). CONCLUSION: Pretreatment staging, including clinical examination and EUS, seemed accurate enough to present a high prognostic value for the T stage. EUS was insufficient to stage lymph node involvement. Owing to its lack of specificity, uN stage was not a reliable prognostic factor. An improvement in N staging is necessary and essential. Despite downstaging, postoperative staging remained a very strong prognostic factor for both T and N stages.
PURPOSE: Defining prognostic factors for neocortical epilepsy surgery is important for the identification of ideal candidates and for predicting the prognosis of individual patients. We use multivariate analysis to identify favorable prognostic factors for neocortical epilepsy surgery. METHODS: One hundred ninety-three neocortical epilepsy patients, including 91 without focal lesions on MRI, were included. Sixty-one had frontal lobe epilepsy (FLE), 80 had neocortical temporal lobe epilepsy (nTLE), 21 had parietal lobe epilepsy (PLE), and 22 had occipital lobe epilepsy (OLE). The primary outcome variable was patient status >or=2 years after surgery (i.e., seizure free or not). Clinical characteristics and the recent presurgical diagnostic modalities were considered as probable prognostic factors. Univariate and standard multiple logistic regression analyses were used to identify favorable prognostic factors. RESULTS: The seizure-free rate was 57.5%. By univariate analysis, a focal lesion on MRI, localized ictal onset on surface EEG, epilepsies other than FLE, localized hypometabolism on fluorodeoxyglucose-positron emission tomography (FDG-PET), and pathologies other than cortical dysplasia were significantly associated with a seizure-free outcome (p<0.05). Multivariate analysis revealed that a focal lesion on MRI (p=0.003), correct localization by FDG-PET (p=0.007), and localized ictal onset on EEG (p=0.01) were independent predictors of a good outcome. CONCLUSIONS: The presence of a focal lesion on MRI, correct localized hypometabolism on FDG-PET, or localized ictal rhythms on EEG were identified as predictors of a seizure-free outcome. Our results suggest that these findings allow the selection of better candidates for neocortical epilepsy surgery.
OBJECTIVE: To define the most reliable prognostic factor, we studied the 5-year survival of patients after resection of pulmonary metastases from colorectal cancer in relation to various prognostic factors, including vascular endothelial growth factor expression in primary and metastatic tumors. METHODS: A retrospective study was undertaken in 49 patients who had undergone complete resection of pulmonary metastasis from colorectal carcinoma. All patients were retrospectively analyzed for sex, age, location and stage of primary tumor, number of pulmonary metastases, type of pulmonary resection, size of metastatic tumor, lymph node metastasis, and prethoracotomy carcinoembryonic antigen level. Furthermore, vascular endothelial growth factor expression of both primary and metastatic tumors was investigated. RESULTS: Overall 5-year survival was 34.3%. In the univariate analysis the number of pulmonary metastases (P =.007) and vascular endothelial growth factor expression in metastatic tumors (P =.008) and primary colorectal tumors (P =.011) were significantly associated with poor survival. In the multivariate analysis the number of pulmonary metastases (P =.0031), vascular endothelial growth factor expression in metastatic tumors (P =.0057), and stage of primary tumor (P =.0321) were characteristics that retained a significant independent prognostic effect on overall survival. A statistically significant difference was not found in the 5-year survival of patients with solitary and negative vascular endothelial growth factor expression in metastatic tumors (59.1%) versus those with multiple and positive vascular endothelial growth factor expression in metastatic tumors (10.0%; P <or=.0001). CONCLUSIONS: Vascular endothelial growth factor expression in metastatic pulmonary tumors is an important prognostic marker for patients with pulmonary metastasis from colorectal carcinoma. Our results suggested that patients with multiple and positive vascular endothelial growth factor expression in the metastatic tumor will not receive benefit from metastasectomy.
The prognostic assessment of cancer patients is of special importance clinically and scientifically. Prognostic factors are divided into three groups: patient-, treatment- and tumor-related factors. Only a minority of those factors, for example the UICC TNM classification, have been proven by multivariate studies to be of prognostic significance and have an impact on patient management, even then only as prognostic groups. The individual prognosis of a specific patient, which would allow an individualized therapy, cannot yet be adequately assessed. New prognostic factors may result in improved prognostic predictions; currently it is unclear whether this will be accomplished by molecular prognostic parameters assessed on the basis of the primary tumor or rather by the detection of disseminated cancer cells. Of major importance are well-designed clinical studies, in order to prove the clinical benefit of an individualized patient management.
Despite the introduction of the PAP smear screening technique, cervical carcinoma continues to be a significant disease worldwide in terms of prevalence, morbidity and mortality. This paper reviews the prognostic value of biomarkers from some oncogenes, including c-myc, ras and c-erb B-2, the cellular proliferation markers PCNA and Ki-67, and other more recently described biomarkers such as nm23-H1, MN protein and metalloproteinase. Emphasis is given at a practical level to markers which can preferentially be applied to tissue sections rather than involving other modalities of investigation which may require specialised equipment and technology. No single marker of those previously listed was found to have outstanding prognostic significance. Although some have shown promise in initial studies subsequent investigations have not provided corroborating evidence, or, in some situations, have also led to conflicting results. Difficulties inherent in establishing the prognostic value of individual markers also include the multifactorial complexity of cervical carcinogenesis itself. The future awaits a greater amount of data to be accrued across all stages of disease, with improved standisation of results.
OBJECTIVE: To assess the prognostic value of Führman's nuclear grade and to compare it to various clinical and histological prognostic factors of renal carcinomas. PATIENTS AND METHOD: Single-centre retrospective study of 102 patients operated for renal tumours between January 1985 and December 1990 (mean follow-up: 8.2 years). Prognostic assessment was studied from survival curves. RESULTS: The prognostic factors most closely correlated with survival were, in decreasing order, metastatic invasion, nuclear grade, stage of local extension and lymph node invasion. A significant (p < 0.01) survival difference was only observed between Führman grade 2 and grade 3 tumours. This difference was accentuated (p < 0.001) when grade 1 and 2 tumours were compared to grade 3 and 4 tumours. Führman's nuclear grade is independent of the side affected, the tumour volume, its multifocal nature, microscopic venous invasion and metastatic invasion at the time of diagnosis. Führman's nuclear grade is correlated with invasion of fat, the presence of a contingent of eosinophilic cells, stage of local extension, lymph node invasion and the subsequent development of metastases. CONCLUSION: This study confirms the importance of Führman's nuclear grade among the various prognostic factors of renal carcinomas and quantifies its value with respect to other prognostic factors.
PURPOSE: This study was retrospectively undertaken to identify prognostic factors in patients with advanced hepatocellular carcinoma (HCC) treated by hepatic arterial infusion chemotherapy with a percutaneously implantable port system inserted. MATERIALS AND METHODS: Eighty-eight patients underwent arterial infusion chemotherapy for portal venous invasion (n = 39), severe liver dysfunction (n = 6), or tumor regrowth after chemoembolization, percutaneous ethanol injection therapy, and surgery (n = 77). Twenty-five variables representing patients' characteristics, previous treatments, tumor characteristics, liver profiles, various staging systems, and therapeutic effect were analyzed with univariate and multivariate analyses. RESULTS: The 1- and 3-year survival rates were 55% and 24%, respectively, with a mean survival period of 19.5 months +/- 1.9 in all patients. Cancer of the Liver Italian Program (CLIP) score, Okuda stage, therapeutic effect, tumor extension, alkaline phosphatase and aspartate aminotransferase levels, ascites, and portal venous invasion were identified as significant prognostic factors by univariate analysis. Multivariate analysis identified CLIP score, Okuda stage, and therapeutic effect as significant independent prognostic factors. CONCLUSION: Although our results should be confirmed in future prospective studies, the prognostic factors identified in the present study should prove helpful in classifying patients with advanced HCC who are treated by arterial infusion chemotherapy and should serve as useful guidelines on arterial infusion chemotherapy in clinical practice.
To evaluate the prognostic factors and the outcome of treatment, a retrospective study was done on 141 patients with prostate cancer who were newly diagnosed at Kitano Hospital between January 1985 and November 1996. In recent years, the number of patients and the ratio of low stage cancer have increased. The overall 5-year crude survival rate was 49.9%. The 5-year crude survival rate for clinical stage A, B, C and D was 67%, 70%, 62% and 30% respectively. The overall 5-year disease-specific survival rate was 65.6%. The 5-year disease-specific survival rate for clinical stage A, B, C and D was 100%, 89%, 72% and 42%, respectively. By univariate analysis, clinical stage, Gleason score, prostate specific antigen (PSA) level, and patient age were prognostic factors for disease-specific survival of prostate cancer. According to Cox's regression analysis by the stepwise forward regression method, clinical stage and Gleason score were selected as more valuable prognostic factors than PSA level, patient age, comorbidity, and initial treatment. In Gleason score 2 to 8, the prognosis became significantly worse as clinical stage advanced, but in Gleason score 9 and 10 the prognosis was poor regardless of clinical stage.
At present time, we can see increasing interest in prognosis and prognostic factors. This review refers to the problems of prognostics in oncology and oncosurgery. Authors emphasize importance of prognosis and its integrating role in issues of treatment tactics and strategy selection. This article presents main classification of prognostic factors, e.g. the subject-based one, which consists of three groups-tumor-related, host-related and environment related factors. Factors that belong to the first group are anatomic extent of disease that is classified according to the TNM classification, tumor histopathologic factors and a great number of molecular and genetic factors. The question of clinical relevance of those factors is discussed. Host-related prognostic factors include inherent demographic characteristics, performance status, comorbid conditions and others. Environment-related prognostic factors involve physician, the health care system and society as a whole. This group of prognostic factors is less studied, despite the fact that namely these factors can have fundamental importance in questions of disease outcome.
We performed a retrospective analysis of prognostic factors in patients with stage III and IV and high-tumor burden follicular lymphoma (FL) treated with uniform schedules and with a long term follow-up. Eight-hundred and ten patients treated with intensive, anthracycline-based, chemotherapy and adjuvant radiotherapy to sites of initial bulky nodal disease were the basis of this analysis. Age >60 years, presence of B symptoms, bulky disease, >2 extranodal sites involved, high levels of LDH and the presence of serous effusions all identified as worse prognostic factors in univariate analysis were subject to multivariate analysis. Three factors remained significant: age >60 years old, presence of B symptoms and >2 extranodal sites involved and these were found to influence overall survival (OS) and progression-free survival (PFS). We developed a score system and only two groups (score 0 and 1 and score 2 and 3) showed statistical significance in OS. When the International Prognostic Index was applied to these patients, no statistical differences were observed in OS and PFS between the four groups. Comparison of our results with multiple previous studies showed a lack of uniform prognostic factors and adequate prognostic classification could not be performed. In conclusion, it is mandatory for multicentric international clinical analysis to define prognostic factors and search for a clinical classification, as in diffuse large B cell lymphoma, so as to define groups of FL for more aggressive or conservative therapy.