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Estrogen and progesterone receptor status as prognostic indicators in patients with optimally cytoreduced stage IIIc serous cystadenocarcinoma of the ovary.

BACKGROUND: Steroid receptor status as a prognostic indicator in gynecologic malignancies has been a focus of study for almost 20 years. Although shown to be of importance in assessing prognosis in some patients with endometrial cancer, their importance in assessing prognosis in patients with serous cystadenocarcinoma of the ovary is not established. METHODS: All cases of stage IIIc serous cystadenocarcinoma of the ovary operated on by the gynecologic oncology service from January 1, 1981, through December 31, 1989, were evaluated for their estrogen and progesterone receptor status, time to recurrence, length of survival, and level of primary cytoreduction as well as FIGO stage, grade, and histology, Fresh tissue was obtained and frozen at the time of surgery for the steroid assays. RESULTS: Ninety-six patients who had optimal primary cytoreductive surgery for their stage IIIc serous cystadenocarcinomas of the ovary and had their estrogen and progesterone receptor status established were found. Patients with an estrogen receptor level of less than or equal to 10 fmol/mg cytosol protein were shown to have a better mean survival (41 months) than patients with estrogen receptor levels greater than 10 fmol/mg cytosol protein (34 months) (P = 0.015). Five-year survival in the former group (38 patients) was 39.5% while 5-year survival in the latter group (58 patients) was 10.3% (P = 0.001). The was no correlation between progesterone status and survival (P > 0.05) in that same cohort of patients. CONCLUSIONS: In patients with optimally cytoreduced stage IIIc serous cystadenocarcinoma of the ovary, an estrogen receptor level of less than or equal to 10 fmol/mg cytosol protein may be indicative of a better prognosis. Progesterone receptor status does not appear to affect survival.

Adult↗

Molecular biology of sporadic gastric cancer: prognostic indicators and novel therapeutic approaches.

Both the availability of multiple treatment modalities and novel therapeutic targets make the correct prognostic stratification and the identification of truly predictive factors an issue of major debate in gastric cancer. Along with "classic" prognostic factors such as those related to the diffusion of the tumour at diagnosis (i.e., depth of gastric wall infiltration, locoregional lymph nodes or distant metastases) or those concerning the pathologic characteristics of the tumour, other, innovative, factors should be considered if a better definition of the characteristics of the tumour is to be given. These biological factors are often derived from the genetic process, which is thought to represent a crucial step to gastric cancer (DNA copy number changes, microsatellite instability, thymidilate synthase, E-cadherin, beta-catenin, mucin antigen, p53, c-erb B-2, COX-2, matrix metalloproteinases, VEGFR and EGFR). Some of those putative prognostic indicators can also be considered predictive of response to therapy as they are a molecular target either to chemotherapeutics (i.e., thymidilate synthase that is targeted by 5FU) or to a new class of antineoplastic molecules (i.e., c-erb B-2 targeted by trastuzumab, COX-2 by NSAIDs, matrix metalloproteinases, EGFR and VEGFR by specific inhibitors).

Apoptosis↗

p53 and mdm2 as prognostic indicators in patients with epithelial ovarian cancer: a multivariate analysis.

OBJECTIVE: The aim of the study was to investigate the prognostic significance of p53 and mdm2 protein expressions in epithelial ovarian cancer and their relationship with the clinicopathological variables. METHODS: Tumor biopsy specimens from 82 patients who were homogenously treated were examined immunohistochemically for expression of p53 and mdm2 proteins. Univariate and multivariate analyses were performed for prognostic factors, and correlations with clinicopathological parameters were examined. RESULTS: Fifty-four percent and 33% of cases stained positive for p53 and mdm2, respectively. p53 expression was associated with serous type, higher grade, positive cytology, residual tumor and stage of the disease. mdm2 expression predicted of chemosensitivity and it was related with higher grade but not with other clinicopathological variables. Significantly poorer survival was seen for those with p53 (P < 0.05) or mdm2 (P < 0.01) positive tumors than those with negative p53 or mdm2 staining. Coexpression of p53 and mdm2 was also related to poor outcome (P < 0.05). Multivariate analysis revealed that FIGO stage, mdm2 expression, response to chemotherapy and optimal cytoreduction were significant independent prognostic and predictive factors of survival. CONCLUSION: Although our findings showed that mdm2 may be used as a prognostic indicator in patients with epithelial ovarian cancer, these results should be supported by more and larger studies.

Biomarkers, Tumor↗

Risk factors and prognostic indicators of bacterial meningitis in a cohort of 3580 postneurosurgical patients.

In order to identify the incidence, risk factors and prognostic indicators of postneurosurgical bacterial meningitis, a 9-y retrospective cohort study was performed. The cohort comprised 3580 individuals who underwent neurosurgical operations at the Department of Neurosurgery of Catholic University, Rome, a 1,700-bed university hospital. We observed 52 episodes of postneurosurgical meningitis, with infection rates of 1.4/100 patients, 0.8/100 operations for craniotomies and 2.6/100 operations for internal cerebrospinal fluid (CSF) shunt or ventriculostomy with external drainage. The overall infection rate decreased from 2.5/100 operations in 1989 to 0.9/100 in 1997 (p = 0.03). Logistic regression analysis indicated that duration of ventriculostomy with external drainage [p < 0.01; odds ratio (OR) = 9.67; 95% confidence interval (CI) = 2.44-38.321 and increasing value of the APACHE III score (p <0.01; OR = 8.51; 95% CI = 2.15-33.68) were independent risk factors for development of meningitis. The overall case fatality rate was 8%. Predictors of mortality were low ( < 1.66 mmol/l) CSF glucose concentration (p = 0.001), increasing value of the APACHE IIl score (p = 0.002) and Gram-negative aetiology (p = 0.003).

APACHE↗

Hand grip strength--a simple prognostic indicator in surgical patients.

This study evaluates hand grip strength as an indicator of nutritional status and a predictor of postoperative complications. Hand grip strength and other parameters of nutritional status, namely, midarm muscle circumference, forearm muscle circumference, triceps skinfold, percentage ideal body weight, serum albumin, and percent usual weight were determined preoperatively in 205 patients. Complications occurred in 28 patients (14%). Patients with at least one abnormal nutritional parameter had a higher incidence of postoperative complications. Their length of total and postoperative hospitalization was greater by 6.2 and 4.6 days, respectively (p less than 0.01). Grip strength was the most sensitive single parameter, but forearm muscle circumference and percentage ideal body weight were the most specific indices. Hand grip strength is a simple measure of nutritional status and an accurate prognostic indicator that requires further clinical evaluation.

Adult↗

High-dose chemotherapy and stem-cell rescue in the treatment of high-risk breast cancer: prognostic indicators of progression-free and overall survival.

PURPOSE: To examine the predictive value of tumor- and treatment-specific prognostic indicators of relapse-free survival (RFS) and overall survival (OS) in patients with high-risk breast cancer (HRBC) treated with high-dose chemotherapy (HDCT) and stem-cell rescue. PATIENTS AND METHODS: Between June 1989 and September 1994, 114 patients with HRBC (stage II with > or = 10 axillary lymph nodes involved, stage IIIA, and stage IIIB inflammatory carcinoma) received adjuvant chemotherapy followed by HDCT with etoposide, cyclophosphamide, and either doxorubicin (CAVP) or cisplatin (CCVP). Variables analyzed included stage, tumor size, number of axillary nodes involved, grade and receptor status, and types of adjuvant chemotherapy and radiation therapy and HDCT. RESULTS: With a median follow-up time of 46 months (range, 23 to 93), Kaplan-Meier estimates of 3.5-year OS for stage II, IIIA, and IIIB HRBC are 82% (95% confidence interval [CI], 67% to 97%), 79% (95% CI, 67% to 91%), and 72% (95% CI, 53% to 91%); RFS estimates are 71% (95% CI, 56% to 85%), 57% (95% CI, 43% to 72%), and 50% (95% CI, 29% to 71%) irrespective of the HDCT regimen. In univariate analysis, the risk of relapse was lower for patients with progesterone receptor (PR)-positive tumors (risk ratio [RR], 0.43; 95% CI, 0.22 to 0.81; P = .01) and higher for patients with inflammatory carcinoma (RR, 2.20; 95% CI, 1.02 to 4.76; P = .05). OS was better for patients with PR (RR, 0.16; 95% CI, 0.05 to 0.55; P = .003) and estrogen receptor (ER)-positive tumors (RR, 0.42; 95% CI, 0.17 to 1.02; P = .05); OS was worse for patients with high-grade primary tumors (RR, 4.08; 95% CI, 1.21-13.7; P = .02). In multivariate analysis, PR positivity was associated with improved RFS (P = .01) and OS (P = .001). CONCLUSION: HDCT in selected patients with HRBC is safe and warrants further evaluation. Patients with receptor-negative, high-grade, or inflammatory tumors require improvement in their therapeutic options. Better assessment of the role of HDCT awaits completion of ongoing randomized trials.

Adult↗

Flow cytometric DNA-ploidy as a prognostic indicator in oral squamous cell carcinoma.

In an attempt to evaluate the significance of DNA-ploidy as an objective prognostic indicator of oral squamous cell carcinoma, a retrospective analysis of 70 paraffin-embedded specimens using flow cytometry was performed. Forty-one patients (58.6%) had aneuploid tumors and 29 patients (41.4%) had diploid DNA distribution patterns. There was a significant difference in 5-year disease-free survival rates between patients with aneuploid and diploid tumors. The difference in cervical metastatic rates between aneuploid and diploid group approximated statistical significance. No obvious correlation was observed between DNA indices and histologic grade, clinical stage or tumor size. It is concluded that patients with aneuploidy primary tumors have a significantly poorer prognosis and higher risk for regional metastases than those with diploid tumors.

Aneuploidy↗

The combination of angiogenesis and blood vessel invasion as a prognostic indicator in primary breast cancer.

This study was undertaken to examine the interaction between the combination of angiogenesis and blood vessel invasion (BVI) and haematogenous metastasis, and to determine the prognostic significance of that combination in predicting 20-year relapse-free survival (RFS) and overall survival (OS) rates in primary breast cancer. Five hundred and nine patients were studied. We investigated 11 factors, including average microvessel count (AMC)/BVI, lymph-node status (n), clinical tumour size (T), histological grade (HG), lymphatic vessel invasion (LVI), p53, proliferating cell nuclear antigen (PCNA), c-erbB-2, mitotic index (MI), apoptotic index, and tumour necrosis (TN). Blood vessel invasion was detected by both factor VIII-related antigen and elastica van Gieson staining. To evaluate the best objective method to quantify microvessel density in angiogenesis, AMC was employed. The rate of AMC-high and BVI-positive tumours was 32.6 and 29.3%, respectively. That of both AMC-high and BVI-positive tumours was 10.1%. Univariate analysis showed that AMC/BVI, n, T, HG, LVI, p53, PCNA, MI, and TN were significantly predictive of RFS and OS. By multivariate analysis, AMC/BVI was the strongest independent prognostic factor for 20-year RFS (relative risk (RR)=5.5; P<0.0001) and for 20-year OS (RR=4.3; P<0.0001). Lymph-node status was still considered a powerful prognostic indicator; however, the combination of AMC and BVI provided more reliable prognostic information than lymph-node status for haematogenous dissemination.

Adolescent↗

The pathology of breast cancer: staging and prognostic indicators.

The natural history of breast cancer is complex and the treatment modalities need to be adjusted to this heterogeneous disease. Several prognostic indicators have been described for breast cancer, including the extent of axillary nodal metastasis, the size of the primary tumor mass, various histopathologic characteristics, estrogen and progesterone receptor content, tumor proliferation index, detection of oncogenes, tumor suppressor genes, loss of heterozygosity, and growth factors. Although no single parameter or combination of parameters can definitively predict the outcome of the disease, combined criteria such as tumor estrogen receptor content, cell proliferative index, and lymph node status are relevant for identifying subsets of breast cancer patients that may require different therapeutic modalities. Detection of oncogenes, tumor suppressor genes, and growth factors need further evaluation to determine their usefulness as prognostic factors.

Breast Neoplasms↗

The fucosylation index of alpha-fetoprotein as a possible prognostic indicator for patients with hepatocellular carcinoma.

BACKGROUND: The aim of this study was to elucidate the usefulness of measuring the fucosylation index (FI) of alpha-fetoprotein (AFP) before the initiation of therapy as a new prognostic indicator for patients with hepatocellular carcinoma (HCC). METHODS: One hundred twelve patients with HCC who underwent transcatheter arterial embolization, chemoembolization, and/or percutaneous ethanol injection were examined in the current study. FI was determined by crossed immunoaffino-electrophoresis in the presence of Lens culinaris agglutinin. RESULTS: When the tentative discriminating value of FI was set at 18%, the mean survival rate for the group whose FI was higher than 18% was significantly lower than that for the group whose FI was equal to or less than 18%, according to the generalized Wilcoxon test (P = 0.0117) and the log rank test (P = 0.0183). The survival rate for HCC patients with AFP concentrations of more than 200 ng/mL was also significantly lower than that for patients with AFP in the range of 21-200 ng/mL, according to the generalized Wilcoxon test (P = 0.0017) and the log rank test (P = 0.0018). When FI was combined with AFP concentration, a highly significant difference was observed between the group with FI >18% and AFP >200 ng/mL and another group with FI < or =18% and AFP < or =200 ng/mL, as determined by the generalized Wilcoxon test (P < 0.0001) and the log rank test (P = 0.0003). An analysis of multiple covariates in the prognostic factors with the Cox proportional hazards model showed that FI was one of the independent prognostic factors. CONCLUSIONS: The current study indicates that measuring FI from sera before the initiation of treatment serves as a new prognostic factor and may improve prognostic estimates and appraisal of therapeutic outcomes for patients with HCC.

Analysis of Variance↗

Coexpression of cyclooxygenase-2 and thymidine phosphorylase as a prognostic indicator in patients with FIGO stage IIB squamous cell carcinoma of uterine cervix treated with radiotherapy and concurrent chemotherapy.

PURPOSE: To evaluate the prognostic significance of thymidine phosphorylase (TP) and coexpression of cyclooxygenase-2 (COX-2)/TP, and to investigate the relationship between COX-2 and TP expression in squamous cell carcinoma of the uterine cervix. METHODS AND MATERIALS: Cancer specimens from 75 patients with International Federation of Gynecology and Obstetrics Stage IIB squamous cell carcinoma of the uterine cervix who had undergone radiotherapy and concurrent chemotherapy were immunohistochemically stained with COX-2 and TP antibodies and scored. The prognostic significance of their expression status, and the relationship between COX-2 and TP was investigated. RESULTS: TP predominantly stained cytoplasm and the cell membrane of the tumor cells mainly in a diffuse and intense manner. TP was negative (<10% distribution) in 17%, 1+ (10-50%) in 25%, and 2+ (>50%) in 57% of patients. TP overexpression was related to a marginal prognostic significance of a poor 5-year overall survival (p = 0.082, log-rank test) and a high locoregional recurrence rate (p < 0.1, chi-square test). COX-2 and TP coexpression was observed in 24% of patients and was significantly related to poor 5-year disease-free and overall survival rates (p = 0.0083 and p = 0.025, respectively), a high pelvic lymph node involvement rate, a poor response to treatment, and a greater incidence of locoregional recurrence (p < 0.05). By multivariate analyses, only COX-2, TP, and coexpression of COX-2/TP were significant independent prognostic indicators of patient survival. All tumors showed 1+ or 2+ TP expression when COX-2 was positive, and no tumor expressed COX-2 when TP was negative (p = 0.03). In contrast, 77% of tumors expressed 1+ or 2+ TP without the synchronous expression of COX-2. CONCLUSIONS: Thymidine phosphorylase expression or COX-2/TP coexpression may be used as a molecular prognostic marker for squamous cell carcinoma of the uterine cervix. TP appears to be an important downstream molecule of COX-2 during angiogenesis and may be a new target for the treatment of uterine cervical cancer.

Carcinoma, Squamous Cell↗

Prognostic indicators for patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma.

BACKGROUND: This study evaluates clinical, radiological and histopathological prognostic indicators for survival of patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma (DMPM). METHODS: Sixty-two consecutive patients with DMPM underwent cytoreduction and perioperative intraperitoneal chemotherapy at the Washington Cancer Institute. Twenty-six clinical, radiological and histopathological parameters were analyzed in univariate and multivariate analyses using overall survival as an endpoint. RESULTS: The overall survival was 79 months (range 1-143 months), with 1-, 3- and 5-year survival rates of 84%, 58% and 50%, respectively. The following 14 prognostic variables were significant for survival in the univariate analysis: gender (P = .045), peritoneal cancer index (P = .038), completeness of cytoreduction score (P = .010), interpretive CT findings of the small bowel and mesentery (P = .001), mesothelioma cell type (P < .001), mesothelioma nuclear size (P < .001), nuclear/cytoplasmic ratio (P < .001), mitotic count (P < .001), atypical mitosis (P < .001), chromatin pattern (P < .001), cellular necrosis (P < .001), perineural invasion (P = .037), stroma pattern (P < .001) and depth of invasion (P = .014). In the multivariate analysis, the only factor that was independently associated with an improved survival after cytoreduction and perioperative intraperitoneal chemotherapy was mesothelioma nuclear size. CONCLUSIONS: Mesothelioma nuclear size was the dominant factor determining overall survival in patients with DMPM. A histopathological staging system based on measurement of the nuclear size was proposed.

Antineoplastic Combined Chemotherapy Protocols↗

Molecular prognostic indicators in breast cancer.

Here we review a panel of oncogene products, proteases and markers of proliferation that have shown potential as prognostic indicators in primary breast cancer. The relative merits of specific genetic mutations as well as alterations at the protein level are discussed. Finally an assessment is made of the transfer of knowledge from the laboratory to the bed-side.

Biomarkers, Tumor↗

Coagulation factor V levels as a prognostic indicator in fulminant hepatic failure.

Data reported by Bernuau et al. have strongly supported the measurement of coagulation factor V as the best prognostic indicator in fulminant hepatic failure (FHF) and as the test on which selection for urgent liver transplantation should be made. In this study, we have measured plasma factor V in 110 patients with FHF, in grades I-IV coma, in 88 of whom the etiology was acetaminophen overdose. On admission, patients who did not survive had significantly lower factor V levels (median, 5%; range, 1-27; n = 49), compared with those who did (median, 10%; range, 2-70; P < .001). In the 81 patients with acetaminophen-induced FHF who did not receive a transplant, there was no cutoff level of factor V that clearly separated the patients. On statistical analysis, a positive predictive value (the mortality in patients predicted to have a poor prognosis) of 0.49 was calculated for factor V <20% and 0.57 for factor V < 10%. If the prognostic criteria included deep coma (grades III and IV) as well as factor V <20%, a positive predictive value of 0.73 was calculated. This compared with a value of 0.92 for the well-established King's prognostic criteria based on pH, and a combination of international normalized ratio (INR), renal failure, and coma. In the 17 mixed, nonacetaminophen group of patients who did not receive a liver graft, the positive predictive value was 0.85 for a factor V level <20% and 1.00 for factor V <10%, compared with 0.93 for the King's criteria for that etiologic group. This study demonstrates that the predictive accuracy of plasma factor V level is much less effective than the well-validated King's criteria in the selection of patients with acetaminophen-induced FHF needing liver grafting, although it may be useful in patients with FHF due to other causes.

Acetaminophen↗

p16 and p53 Protein expression as prognostic indicators of survival and disease recurrence from head and neck cancer.

PURPOSE: Markers of somatic mutation such as p16 and p53 remain controversial prognostic indicators for patients with squamous cell carcinoma of the head and neck (SCCHN). The relationship between p53 protein expression and radiation therapy is also unclear. EXPERIMENTAL DESIGN: We made a prospective cohort study (n = 171) of incident cases receiving standardized therapy for SCCHN. RESULTS: Patients whose tumors showed increased p53 protein expression had over twice the risk of all-cause mortality after 550 days [hazard ratio (HR), 2.7; 95% confidence interval (CI), 1.07-6.66] and three times the risk of dying from cancer-specific causes after 550 days (HR, 3.09; 95% CI, 1.15-8.30) after adjustment for age, therapy, and stage. Tumors demonstrating alteration of both p16 and p53 did not confer any additional diagnostic information over p53 alone. Patients whose tumors expressed increased levels of p53 protein and received radiation were almost three times more likely to die as compared with those who received radiation but whose tumors did not express increased p53 protein after adjustment for age and stage (HR, 2.6; 95% CI, 1.03-6.50). CONCLUSIONS: p53 protein expression was found to violate the proportional hazards assumption for our cohort, which may explain the controversial prognostic ability of this protein in the literature. p53 protein expression, but not p16 protein expression, was related to poor survival in general for men and women. In addition, an interaction between p53 expression and radiation therapy was demonstrated. Additional studies are needed to confirm and extend our results.

Aged↗

Proliferating cell nuclear antigen in prostatic adenocarcinoma: correlation with established prognostic indicators.

OBJECTIVE: The utility of an antibody to proliferating cell nuclear antigen (PCNA), a growth-specific nuclear protein, was assessed as a prognostic variable for prostatic adenocarcinoma. Its expression was correlated with established prognostic indicators, including tumor grade, stage, prostatic-specific antigen (PSA), and percent of tumor in the gland at excision. METHODS: Forty archival needle biopsies containing a minimum of four hundred tumor cells were analyzed. Immunoperoxidase staining of paraffin sections was performed for PCNA (PC10) after pretreatment in antigen retrieval solution. A proliferative index (PI) for each case was derived using image analysis with measurement of at least four hundred twenty-five nuclei. RESULTS: PI values ranged from 2.4 to 31.3 percent. Mean PI values varied significantly (ANOVA, p = 0.005) among cases with dominant Gleason grade (DGG) of 3 (mean PI = 9.3%), 4 (mean PI = 13.7%), and 5 (mean PI = 18.8%). By t test, significant differences were noted for PI in cases with DGG 2 and 3 versus those with DGG 4 and 5 (p = 0.0065). PI for cases with DGG 3 versus 5 showed significant difference (p = 0.0017). Tumors of Gleason scores 5 to 7 differed significantly from those with scores 8 to 10 (p = 0.014). A statistical relationship for PI and PSA, clinical stage, and percent tumor at resection could not be established by linear regression. CONCLUSIONS: These findings suggest that additional study of the PI, as determined by PCNA immunohistochemistry and image analysis, may be warranted to determine its usefulness as an adjunctive parameter in prostate adenocarcinoma. This technique may be particularly useful in needle biopsies where limited tumor may render assessment of grade difficult.

Adenocarcinoma↗

Is the binding of mistletoe lectins I and III a useful prognostic indicator in colorectal carcinoma?

A retrospective study on 127 patients with colorectal carcinoma was performed to evaluate the use of mistletoe lectins I and III as possible prognostic indicators. Tissue sections were stained by a histochemical technique using these lectins and the staining results correlated with survival. No correlation between survival and the presence of lectin binding or non-binding was found. A lectin with the same monosaccharide specificity as ML-III, Helix pomatia agglutinin, which was of prognostic significance in the same patient cohort in another study showed on Western blot analysis a slightly different lectin binding pattern towards glycoproteins than the MLs. The results of this study indicate that even subtle differences in the carbohydrate composition of glycoconjugates which can be differentiated by lectins are of biological significance in terms of the metastatic spread of tumours.

Blotting, Western↗

3H-thymidine-labeling index as a prognostic indicator in node-positive breast cancer.

The prognostic relevance of 3H-thymidine-labeling index (3H-TdR-LI) was retrospectively evaluated in 523 women with resectable node-positive breast cancer given adjuvant combination chemotherapy consisting of cyclophosphamide, methotrexate, and fluorouracil (CMF) +/- Adriamycin (doxorubicin; Farmitalia, Carlo Ezba, Italy). The 5-year relapse-free survival (RFS) and overall survival (OS) rates were significantly higher for patients with slowly proliferating tumors (3H-TdR-LI less than or equal to 2.8%) compared with rapidly proliferating tumors (RFS, 66% v 50%, P = .0007; OS, 85% v 73%, P = .0012). In the analysis of RFS, 3H-TdR-LI provided prognostic information independent of axillary node involvement, tumor size, and estrogen receptor (ER) status, with an estimated lower hazard ratio compared with the degree of nodal involvement, but equivalent to that of the other indicators. Conversely, nodal involvement was found to interact with 3H-TdR-LI and receptors on survival. Present findings confirm that tumor cell kinetics represents a prognostic indicator also in an adjuvant situation. 3H-TdR-LI can substantially contribute to a more precise definition of high-risk patients within subsets having the traditionally favorable prognostic characteristics.

Analysis of Variance↗