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PubMed2006

Development and validation of a prognostic index for 4-year mortality in older adults.

CONTEXT: Both comorbid conditions and functional measures predict mortality in older adults, but few prognostic indexes combine both classes of predictors. Combining easily obtained measures into an accurate predictive model could be useful to clinicians advising patients, as well as policy makers and epidemiologists interested in risk adjustment. OBJECTIVE: To develop and validate a prognostic index for 4-year mortality using information that can be obtained from patient report. DESIGN, SETTING, AND PARTICIPANTS: Using the 1998 wave of the Health and Retirement Study (HRS), a population-based study of community-dwelling US adults older than 50 years, we developed the prognostic index from 11,701 individuals and validated the index with 8009. Individuals were asked about their demographic characteristics, whether they had specific diseases, and whether they had difficulty with a series of functional measures. We identified variables independently associated with mortality and weighted the variables to create a risk index. MAIN OUTCOME MEASURE: Death by December 31, 2002. RESULTS: The overall response rate was 81%. During the 4-year follow-up, there were 1361 deaths (12%) in the development cohort and 1072 deaths (13%) in the validation cohort. Twelve independent predictors of mortality were identified: 2 demographic variables (age: 60-64 years, 1 point; 65-69 years, 2 points; 70-74 years, 3 points; 75-79 years, 4 points; 80-84 years, 5 points, >85 years, 7 points and male sex, 2 points), 6 comorbid conditions (diabetes, 1 point; cancer, 2 points; lung disease, 2 points; heart failure, 2 points; current tobacco use, 2 points; and body mass index <25, 1 point), and difficulty with 4 functional variables (bathing, 2 points; walking several blocks, 2 points; managing money, 2 points, and pushing large objects, 1 point. Scores on the risk index were strongly associated with 4-year mortality in the validation cohort, with 0 to 5 points predicting a less than 4% risk, 6 to 9 points predicting a 15% risk, 10 to 13 points predicting a 42% risk, and 14 or more points predicting a 64% risk. The risk index showed excellent discrimination with a cstatistic of 0.84 in the development cohort and 0.82 in the validation cohort. CONCLUSION: This prognostic index, incorporating age, sex, self-reported comorbid conditions, and functional measures, accurately stratifies community-dwelling older adults into groups at varying risk of mortality.

Aged↗

PubMed1996

Prognostic factors in angiosarcoma: a multivariate analysis of 55 cases.

Data for prognostic factors in angiosarcoma (AS) are limited, prompting a large-scale study of AS with multivariate analysis. To analyze prognostic factors in angiosarcoma (AS), clinical and histologic findings in 55 patients collected from hospitals in Japan were reviewed. Prognostic factors were evaluated by univariate and multivariate Cox's proportional hazards models. The study involved 32 males and 23 females, ages 18-93 (median, 69) years. The primary sites of tumors included head and neck (32 cases), trunk (10), extremities (3), spleen (3), breast (3), and other (4). The overall 2-year survival rate was 21%. Univariate analysis of clinical factors including age, sex, size and depth of tumor, tumor-related symptoms, interval between onset of symptoms and admission, surgical procedures, adjuvant chemotherapy, and adjuvant radiotherapy showed that age, tumor size, and mode of treatment were significant for survival. Histologic factors analyzed were mitotic counts, cellularity, cellular pleomorphism, extent of necrosis, vascular differentiation, and nonspecific diagnosis. Only mitotic counts were significant for prognosis. Multivariate analysis on these four factors revealed that tumor size, mode of treatment, and mitotic counts were independent prognostic factors.

Adolescent↗

PubMed1997

Prognostic value of MIB-1 in advanced ovarian carcinoma as determined using automated immunohistochemistry and quantitative image analysis.

BACKGROUND AND OBJECTIVES: The monoclonal antibody MIB-1 is an immunohistochemical marker reacting most strongly with cells in late S phase, G2, and M portions of the cell cycle. This antibody, reactive in formalin-fixed, paraffin-embedded tissue, allows the quantitation of a proliferation index (PI) in both current clinical cases and archival material using a computerized image analyzer (CIA). METHODS: Since many laboratories make use of automated immunohistochemistry (AIH), this study was performed to explore the technical feasibility of using AIH (Ventana ES 320) in combination with CIA (CAS 200) to evaluate MIB-1 PI as a prognostic marker as assessed by overall survival in 50 archival (formalin-fixed, paraffin-embedded), advanced stage primary ovarian carcinomas. RESULTS: Exploratory methods confirmed that 15% was a cutpoint that could dichotomize these 50 patients into two prognostic groups based on overall survival. The median survival of patients whose carcinoma had a high MIB-1 expression (> or = 15%) was 16 months compared with 30 months in the patients whose tumors demonstrated low MIB-1 expression (< 15%, P = 0.01). After adjustment for age, MIB-1 retained its prognostic significance (P = 0.02). Patients 60 years and older had shorter survival than younger patients (P = 0.06), but these two groups did not differ with respect to PI (P = 0.76). Those patients with a negative second look laparotomy had a longer median survival of 70 months compared with 18.5 months in patients with a positive second look (P < 0.001); the median PIs were 17% and 27%, respectively (P = 0.36). There were no significant relationships between clinical stage, nuclear grade, DNA ploidy, p53, and either survival or PI. CONCLUSIONS: In this study, we concluded that the combination of AIH and CIA yielded a reliable quantitation of MIB-1 proliferative index and that this proliferative marker had prognostic significance in late stage ovarian carcinoma. Further studies in a larger group of patients are needed to confirm the relationship between proliferation index and other known clinicopathologic and genetic variables.

Antibodies, Monoclonal↗

PubMed1998

Diagnostic and prognostic value of incidence of K-ras codon 12 mutations in resected distal bile duct carcinoma.

BACKGROUND AND OBJECTIVES: The K-ras gene is one of the most extensively investigated oncogenes in a wide variety of human tumors, but has rarely been studied in distal bile duct carcinoma (DBDC). We sought to investigate the diagnostic and prognostic value of K-ras codon 12 mutations in this type of tumor. METHODS: Forty-seven patients who had undergone resection for DBDC were analyzed to reveal the incidence of K-ras codon 12 mutations, the locus most frequently involved. A rapid and simple two-step, semi-nested polymerase chain reaction (PCR) technique was used to detect mutations in paraffin-embedded tumor samples. RESULTS: The PCR mismatch amplification technique demonstrated that 35 (75%) of the 47 tumors harbored a point mutation in codon 12 of the K-ras oncogene. Patients with mutated tumors had no statistically different survival time compared to those patients without a mutation in the tumor. In contrast, negative microscopic margins proved to be a significant prognosticator. CONCLUSIONS: K-ras codon 12 mutations are common in DBDC and may be useful in the diagnosis and early detection of these tumors. However, no prognostic value of these mutations could be identified in this analysis. The results of this study also suggest that negative surgical margins remain the mainstay of prognostication in resectable DBDC. However, due to the small number of patients included in this study, the results obtained should be interpreted with care.

Adenocarcinoma↗

PubMed1999

Liver fatty acid-binding protein is a new prognostic factor for hepatic resection of colorectal cancer metastases.

BACKGROUND AND OBJECTIVES: Liver fatty acid-binding protein (L-FABP) is reported as a biological marker for enterocytic differentiation. We evaluated the prognostic value of L-FABP expression for patients undergoing hepatic resection of colorectal cancer metastases. METHODS: The study group comprised 68 patients who underwent hepatic resection for colorectal cancer metastases between 1982 and 1996 at Niigata University Medical Hospital, Niigata, Japan. L-FABP expression was immunohistochemically studied in metastatic liver tumors and their primary colorectal cancers. The relationship between L-FABP expression and patient prognoses was statistically analyzed. RESULTS: L-FABP was positively stained in 56% (38/68) of liver metastases from colorectal cancers and in 56% (38/68) of their primary tumors. Of 68 cases, 54 (79%) showed similar immunohistochemical findings between primary and metastatic tumors. Patients with L-FABP-positive liver metastases showed better prognosis than patients with L-FABP-negative metastases (P = 0.046). L-FABP expression in primary colorectal cancers more significantly (P = 0.009) affected long-term survival after hepatic surgery. Multivariate analysis revealed that the prognostic effect of L-FABP expression in primary colorectal cancers was exerted independently and that its impact was larger than conventional pathological prognosticators. CONCLUSIONS: L-FABP expression is suitable for use as a new presurgical prognostic factor for patients undergoing hepatic surgery for colorectal cancer metastases.

Adult↗

PubMed1997

Long-term survival data and prognostic factors of a complete response to chemotherapy in patients with head and neck cancer treated with platinum-based induction chemotherapy: a Hellenic Co-operative oncology Group study.

A group of 154 patients with locally advanced head and neck cancer, treated with platinum-based induction chemotherapy, were followed up for 5 years and several pretreatment characteristics were analyzed for possible correlation to a complete response (CR) to chemotherapy, time to progression (TTP) and overall survival (OS). Clinical stage (p = 0.0024) and a history of smoking (p = 0.0125) were selected as important prognostic factors for CR by step wise logistic regression. We also identified response to chemotherapy (p = 0.0120), age (p = 0.0066), clinical stage (p = 0.0363), N stage (p = 0.0028), and tumor grade (p = 0.0101) as significant prognostic variables for TTP. Response to chemotherapy (p < 0.0001) and age (p = 0.0017) were found also significant for OS. These long-term prognostic factors which retain their prognostic significance after several years of follow-up could be helpful in the design of future trials in this patient population.

Adolescent↗

PubMed1999

Evaluation of prognostic factors in a tumor volume-adapted treatment strategy for localized Ewing sarcoma of bone: the CESS 86 experience. Cooperative Ewing Sarcoma Study.

BACKGROUND: The Cooperative Ewing Sarcoma Study (CESS 86), conducted by the German Society of Pediatric Oncology and Hematology (GPOH), was planned on the basis of the results of the preceding CESS 81 study. The prognostic significance of tumor volume in localized Ewing sarcoma of bone was well documented in the CESS 81 trial. As a consequence, the treatment intensity was adapted to volume in the follow-up CESS 86 trial: the four-drug combination used in CESS 81 was amended for patients with large tumor volume (> or = 100 ml), where ifosfamide was substituted for cyclophosphamide. PROCEDURE: From January 1986 to June 1991, 177 protocol patients with localized Ewing sarcoma of bone were registered in CESS 86. The prognostic implication of tumor volume and several covariates was evaluated using Kaplan-Meier life table analysis and Cox's proportional hazard model. RESULTS: The estimated 5- and 8-year event-free survival (EFS) rates were both 59%. Age, gender, tumor site, and a tumor volume of 100 ml did not distinguish groups of patients with different prognosis. However, the prognosis of patients with tumors >200 ml (8-year EFS rate: 42%) was significantly inferior compared to patients with tumors both of 100 to 200 ml (70%) and of <100 ml (63%). In contrast to CESS 81, the histological response to chemotherapy was no longer a significant prognostic factor (EFS: 64% for good and 50% for poor responders, respectively). CONCLUSIONS: Despite risk-adapted treatment intensity, tumor volume retained its prognostic significance; the cut point, however, was shifted toward larger volumes.

Adolescent↗

PubMed1998

Argyrophilia and chromogranin A and B immunostaining in patients with sporadic medullary thyroid carcinoma. A critical appraisal of their prognostic utility.

The purpose of the present study was to evaluate the prognostic utility of tumour argyrophilia and chromogranin A (CgA) and B (CgB) immunocytochemical expression in patients with sporadic medullary thyroid carcinoma. To this end, the histo-immunocytochemical data on a consecutive series of 99 such tumours were submitted to statistical analysis. In univariate analysis, a significantly increased risk of disease progression and death was present in patients with CgA-poor and CgB-poor tumours, respectively. Multivariate analyses were performed by adding the histo-immunocytochemical variables to the final (reference) models obtained in earlier work on the same case series, in which 18 clinicopathological variables had been taken into account. This addition did not change the prognostic impact of the variables considered in the two reference models; it did, however, increase the prognostic information for overall survival, since the adjunctive contribution of CgB immunocytochemical expression (as assessed by the likelihood ratio test) was statistically significant. It is concluded that the chromogranin B immunostaining pattern of the primary tumour allows the distinction of patients with an increased risk of death. Argyrophilia and expression of chromogranin A seem instead to be of no prognostic value in patients with sporadic medullary thyroid carcinoma.

Adolescent↗

PubMed1998

Rapid and prognostically valid quantification of immunohistochemical reactions by immunohistometry of the most positive tumour focus. A prospective follow-up study on breast cancer using antibodies against MIB-1, PCNA, ER, and PR.

The prognostic significance of immunohistochemical markers for cell proliferation [MIB-1, proliferating cell nuclear antigen (PCNA)] and hormone receptor analysis [oestrogen receptor (ER), progesterone receptor (PR)] was tested by means of immunohistometry in a series of 103 breast cancer patients in comparison with the lymph node status N, the tumour size T, histomorphological grading, and the biochemical ER and PR status. Immunohistochemical reactions were performed on 2 microns sections from paraffin-embedded tissue, using an indirect peroxidase method. The proportion of immunostained tumour cell nuclei was determined using a TV-image analysis system. Measurements were performed using a 20 x objective on 40 viewing fields (1.94 mm2, MIB-1 and PCNA) or 20 viewing fields (0.97 mm2, ER and PR). The mean immunopositivity of all viewing fields and the value of the most immunopositive viewing field (MIB-1max, PCNAmax, PRmax, ERmax) were calculated. The mean values and the maximal values were highly correlated (r = 0.903, P < 0.001). After 1:2:1 quantilization, 84.2 per cent of the 412 single measurements revealed mean and maximal values in the same category (P < 0.0001). For each of the four immunohistochemical markers, the prognostic significance of the maximal values was higher than that of the mean values. The highest prognostic significance was found for MIC-1max (P = 0.0002), followed by PRmax (P = 0.0046), ERmax (P = 0.0154), and PCNAmax (P = 0.0161). From the results of a Cox model, a 'prognostic index (PI)' was developed, ranging from -1 to 8: PI = 2 x N + T + MIB-1max-PRmax. The four groups of patients with PI values of < 2, 2-3, 4-5, and > 5 revealed significantly different 7.5-year survival probabilities (P < 0.0001). The simplicity of the PI makes it a clinically useful, routinely applicable, and understandable parameter in the surgical pathology of breast carcinoma.

Adult↗

PubMed1996

Prognostic significance of Ki-67 labeling indices obtained using MIB-1 monoclonal antibody in patients with supratentorial astrocytomas.

BACKGROUND: Identification of the prognosis of patients with gliomas is important for selecting and evaluating the effectiveness of treatment. The aim of this study was to evaluate the Ki-67 labeling index (LI) using the newly generated MIB-1 monoclonal antibody (MoAb) as a prognostic indicator for patients with astrocytomas. METHODS: Ki-67 immunohistochemistry was performed on paraffin sections to estimate the growth potential of 72 supratentorial astrocytomas using the MIB-1 MoAb after hydrated autoclaving treatment. Multivariate analysis using the Cox proportional hazard stepwise model was used to evaluate the influence of Ki-67 LI, as well as other prognostic factors, on the duration of survival of patients with supratentorial astrocytomas. RESULTS: The mean Ki-67 LI was 3.8% (+/- 2.7%; standard deviation [SD]) in Grade 2 gliomas (n = 19), 18.4% (+/- 9.7% SD) in Grade 3 gliomas (n = 25), and 31.6% (+/- 12.9% SD) in Grade 4 gliomas (n = 28). Multivariate survival analysis showed that histologic grade, Ki-67 LI, and Karnofsky performance status (KPS) score before and after treatment were independent, statistically significant prognostic factors for patients with all grades of astrocytomas. In high grade lesions, Ki-67 LI, tumor location (superficial vs. deep), and KPS score after treatment were significant prognostic variables, whereas histologic grade did not meet the significance level for entry into the stepwise model. CONCLUSIONS: These results indicate that the Ki-67 LI obtained using MIB-1 MoAb is an important and practical tool for estimating biologic behavior of gliomas, as well as for predicting survival.

Adolescent↗

PubMed1996

Metastatic neuroblastoma in children older than one year: prognostic significance of the initial metaiodobenzylguanidine scan and proposal for a scoring system.

BACKGROUND: Metaiodobenzylguanidine (mIBG) is a guanethidine analog that has demonstrated a high sensitivity and specificity in detecting bone metastases in about 90% of metastatic neuroblastomas. However, the predictive value of initial mIBG scan in neuroblastoma patients older than 1 year of age regarding response to initial chemotherapy has yet to be ascertained. Therefore, a scoring system for grading the positivity of mIBG scans was devised and applied in a retrospective study in an attempt to determine whether this score had a prognostic value in neuroblastoma patients older than 1 year of age at diagnosis. METHODS: Eighty-six children, older than 1 year of age, with metastatic neuroblastomas were homogeneously treated and had a mIBG scan performed at diagnosis and following the induction regimen to assess bone metastases. Each mIBG scan was assigned a reproducible score and the predictive value of the initial mIBG score was assessed in order to evaluate response to induction regimen. RESULTS: The relative risk of failing to achieve complete remission after four courses of induction therapy was 6.9 times higher in patients who had more than four mIBG spots at diagnosis. A multivariate analysis including the established prognostic factors revealed that the initial mIBG score was the only significant factor (P < 0.001). CONCLUSIONS: The initial mIBG scan is of prognostic significance to predict response to chemotherapy for metastatic neuroblastoma in children older than 1 year of age. A prospective study comparing this initial mIBG score with other recently established prognostic factors is warranted.

3-Iodobenzylguanidine↗

PubMed1996

New prognostic factors in nasopharyngeal carcinoma. Tumor angiogenesis and C-erbB2 expression.

BACKGROUND: This study was conducted to determine the prognostic significance of tumor angiogenesis, c-erbB2, epidermal growth factor receptor, Ki-67, and p53 for patients with nasopharyngeal carcinoma. METHODS: In this retrospective study, the authors retrieved clinical data and made immunohistochemical preparations on archival tissue specimens from 30 patients with nasopharyngeal carcinoma treated with radiation therapy at the University of California at San Francisco between 1956 and 1990. The pretreatment clinical and immunohistochemical data were correlated with cervical lymph node metastasis at diagnosis, and endpoints including development of locoregional failure, distant metastasis, disease free survival, and overall survival. RESULTS: Intense tumor angiogenesis, defined as microvessel counts for 60 or more microvessels per 200 x field correlated with the development of distant metastasis (P = 0.03), shorter overall survival (P = 0.02), and disease free survival (P = 0.05). Strong c-erbB2 expression correlated with a shorter overall survival (P = 0.02) and disease free survival (P = 0.02). Stage IV disease (P = 0.04) and the presence of cervical lymph node metastasis (P = 0.05) correlated with a shorter overall survival. A duration of symptoms of fewer than 6 months correlated with a shorter disease free survival (P = 0.05). No association was observed between any of the biologic prognostic factors and lymph node involvement or locoregional failure. CONCLUSIONS: The results of this study show that the tumor angiogenesis and c-erbB2 expression are significant prognostic indicators for patients with nasopharyngeal carcinoma. The presence of cervical lymph node metastasis, Stage IV disease, and a duration of symptoms fewer than 6 months also indicate a poor prognosis. The authors did not find any prognostic significance for epidermal growth factor receptor, Ki-67, or p53. These results suggest that tumor microvessel counts and c-erbB2 may be useful in identifying patients who may benefit from systemic chemotherapy or other novel treatment strategies.

Adolescent↗

PubMed1996

Prostate specific antigen density as a prognostic factor for patients with prostate carcinoma treated with radiotherapy.

BACKGROUND: The pretreatment serum prostate specific antigen level (PSAL) is the most significant predictor of biochemical and local failure in patients treated with definitive radiotherapy. The role of prostate specific antigen (PSA) density (PSAD) relative to PSAL for such patients is controversial. In this article, we describe a comparative analysis of the prognostic value of PSAL and PSAD. METHODS: The study was comprised of 365 patients who were treated with external beam radiotherapy for regionally localized (T1-T4, Nx, M0) adenocarcinoma of the prostate between 1987-1993 and in whom PSAL and pretreatment prostate volume by transrectal ultrasound were available. The mean and median doses were 66.8 Gy and 66 Gy. Median follow-up for those patients living was 27 months. The mean PSAL was 12.7 ng/mL with a median of 9.1 ng/mL. PSAD was calculated by dividing the PSAL by the pretreatment prostate transectal ultrasound volume (in cc). The mean PSAD was 0.44 and the median was 0.31. Biochemical failure was defined as two consecutive increases in follow-up PSAs, one increase by a factor of greater than 1.5 of an absolute increase of greater than 1 ng/mL. RESULTS: The distributions of PSAD and PSAL were similar and were positively skewed. When log-transformed, the distributions of both parameters were normalized and linear regression revealed a high correlation (P < 0.0001). PSAD was significantly associated with several potential prognostic factors, including stage, Gleason score, PSAL, and pretreatment prostatic acid phosphatase. Univariate analyses of PSAD and PSAL revealed that these were the most significant correlates of local and biochemical control. By contrast, stage and Gleason score were the only factors predictive of freedom from distant metastasis. Multivariate analyses using Cox proportional hazards models were then performed to determine if PSAD provided prognostic information independent of PSAL. The manner in which PSAD and PSAL were categorized (four, three, of two groups) dramatically influenced the significance of these covariates. Optimization of these groups for significance showed grouped PSAD to be the stronger predictor of the local control and grouped PSAL to be the stronger predictor of biochemical control. However, when PSAD and PSAL were used as continuous variables, PSAL was the only independently significant prognostic factor for local or biochemical control. CONCLUSIONS: PSAD was highly correlated with actuarial patient outcome in the univariate analyses and appeared to provide independent information when PSAL was between 4 and 20 ng/mL. However, the differences based on PSAD were relatively small and, therefore, not clinically useful.

Adenocarcinoma↗

PubMed1996

Intensive treatment of patients age 60 years and older with de novo acute myeloid leukemia: analysis of prognostic factors.

BACKGROUND: This study aimed to define pre-treatment parameters with prognostic significance in elderly patients with de novo acute myeloid leukemia (AML) who were treated with aggressive regimens. METHODS: We analyzed, retrospectively, the clinical and laboratory features of 159 consecutive patients age >60 years with AML. Ninety-two patients presenting as de novo AML were considered suitable for aggressive chemotherapy according to inclusion criteria not different from those commonly used for younger adults. They belonged to all of the French-American-British classification types except M3, and their median age was 67 years (range: 60-79). Antileukemic treatment consisted of 1 of 3 sequential protocols adopted at the S. Eugenio University Hospital of Rome between 1987 and 1993. The three therapeutic groups were similar in number and presenting characteristics. In addition to arabinosylcytosine, induction schedules included mitoxantrone (Groups I and II) or daunorubicin (Group III), and etoposide (Groups I and III). Once in complete remission (CR), patients were consolidated with two other courses of chemotherapy using reduced dosages of the same drugs given during induction. RESULTS: Induction treatment achieved a 52.2% CR rate, with median remission duration and event free survival (EFS) of 35 and 27 weeks, respectively. Because no significant differences between the results of the three therapeutic groups were observed, all cases were pooled to evaluate the prognostic factors. In univariate analysis, the only presenting characteristic significantly associated with failure of induction treatment was age >67 years (P=0.007). Factors associated with an increased likelihood of shorter remission duration were CD7 expression on leukemic cells (P=0.007) and an abnormal karyotype (P=0.010; those predicting shorter EFS were a chromosomal status other than normal (P=0.002) and detection of CD14 antigen (P=0.008). Logistic regression results identified age and CD14 expression as the variables with independent prognostic impact on CR achievement. In a stepwise proportional hazards general linear model, CD7 and karyotype retained their predictive value regarding remission duration, whereas the karyotypic pattern at diagnosis and CD14 antigen expression were the most important determinants of EFS, with age showing a borderline statistical value. A simple "risk factor score" was developed that would allow for stratification of patients into prognostic groups. CONCLUSIONS: Cytogenetic analysis and immunophenotyping might help to select elderly patients with AML who have little benefit from current therapeutic strategies and with whom new approaches might be experimented.

Acute Disease↗

PubMed1996

The proliferation index of MIB-1 as a prognostic factor for patients with transitional cell carcinoma of the upper urinary tract.

BACKGROUND: Recently, several reports have shown that immunohistochemical analysis using MIB-1 antibody, which recognizes Ki-67 (a human nuclear antigen expressed of proliferating cells), is a useful method for determining the proliferative activity of various cancers. In this study, the authors evaluated the prognostic usefulness of the proliferation index using MIB-1 antibody in transitional cell carcinoma of the upper urinary tract. METHODS: Proliferation activity was investigated immunohistochemically using monoclonal antibody MIB-1 in formalin fixed, paraffin embedded tissues obtained from 67 specimens of renal pelvic and ureteral cancer. The MIB-1 proliferation index values were calculated from each sample as the percentage of positive nuclei expressed in tumor cells and the clinicopathologic correlation evaluated. RESULTS: The MIB-1 proliferation index values were correlated with prognostic parameters such as pathologic stage ( < or = pT1 vs. > or = pT2, P < 0.0005), histologic grade (G1 vs. G2, P < 0.01; G1 vs. G3, P < 0.0001; G2 vs. G3, P < 0.001), and prognosis (P < 0.0001). When patients were subgrouped using index values, patients with higher indices ( > or = 24%) had significantly poorer survival (P < 0.0001). This was especially observed in the G2 group, in which 9 of 10 patients in the higher indices subgroup had a high incidence of recurrence and died. In contrast, only 2 of 29 patients in the lower indices subgroup died. The higher indices subgroup had significantly worse cause specific survival (P < 0.0001). Furthermore, with regard to the muscle invasive tumors ( > or = pT2), the higher indices subgroup also had significantly worse cause specific survival (P < 0.0001). CONCLUSIONS: The results of the evaluation of prognostic parameters indicate that the MIB-1 proliferation index is a useful prognostic factor and may enhance the accuracy of conventional morphologic grading and pathologic staging systems.

Adult↗

PubMed1996

Independent prognostic importance of vascular invasion in nodular melanomas.

BACKGROUND: The role of vascular invasion as an independent predictor of outcome in cutaneous melanoma is controversial, mostly because of a close relationship with tumor thickness. Therefore, the prevalence of vascular involvement and its prognostic impact has been studied in a series of patients with aggressive cutaneous melanoma. METHODS: One hundred and two patients with nodular malignant melanoma diagnosed between 1981 and 1989 were studied retrospectively. The vessels were stained with factor VIII antibody, and vascular invasion as well as other features of the primary tumor and essential clinical variables were related to time to recurrence and death due to melanoma using univariate survival analysis (product-limit method) and the multivariate Cox regression method. RESULTS: Definite vascular invasion was present in 15 cases (15%), and it was significantly associated with tumor thickness, histologic diameter, ulceration, and presence of lymph node metastases and distant spread at the time of diagnosis. In univariate analysis, vascular invasion was a significant predictor of patient survival (P = 0.006), and this variable also showed an independent prognostic impact in multivariate analysis (P = 0.02). Furthermore, anatomic site (P = 0.03), histologic diameter (P = 0.004), and Clark's level of invasion (P = 0.006) were independently associated with decreased patient survival. In the multivariate analysis of time to recurrence, anatomic site (P = 0.003), tumor thickness (P = 0.002), and histologic diameter (P = 0.003) were independent risk factors. CONCLUSIONS: Although vascular invasion was significantly associated with tumor thickness and histologic diameter of the primary tumor, it provided an independent prognostic information by multivariate analysis of patient survival, in addition to anatomic site and indicators of tumor size (histologic diameter and level of invasion). Our findings further indicate that the prognostic importance of vascular invasion is associated with both lymphatic and hematogeneous spread, although the latter is probably more important.

Blood Vessels↗

PubMed1998

Treatment of patients with acute lymphoblastic leukemia with bulky extramedullary disease and T-cell phenotype or other poor prognostic features: randomized controlled trial from the Children's Cancer Group.

BACKGROUND: Children with acute lymphoblastic leukemia with multiple poor prognostic factors and who have a lymphomatous mass at diagnosis, whether of T- or non-T-immunophenotype, are at increased risk of short term remission and extramedullary recurrence, and are in need of better therapies. METHODS: Six hundred and ninety-four eligible patients ranging in age from 1-20 years were entered on the study. Sixty-five percent of the patients had T-cell immunophenotype. Of these, 678 were randomized to one of four regimens: Regimen A: Berlin-Frankfurt-Munster (BFM) 76/79; Regimen B: LSA2-L2 with cranial irradiation; Regimen C: LSA2-L2 without cranial irradiation; and Regimen D: the New York (NY) regimen. RESULTS: Complete remission was induced in 97% of patients. The overall event free survival (EFS) +/- the standard deviation was 60 +/- 4% 6 years after diagnosis, in contrast to 36 +/- 6% in a comparable historic group. The EFS of the 371 T-cell patients was 62 +/- 7%. EFS was best on the NY (67 +/- 7%) and the BFM (67 +/- 6%) arms. These were significantly better than the EFS on the 2 LSA-L2 regimens, with an EFS of 53 +/- 8% (Regimen B) and 42 +/- 11% (Regimen C) (P = 0.03 and 0.0003 for NY vs. Regimen B and NY vs. Regimen C; P = 0.01 and 0.0001 for BFM vs. Regimen B and BFM vs. Regimen C). Regimen C had a 3-fold greater central nervous system (CNS) recurrence rate than the identical chemotherapy Regimen B (16 +/- 5% vs. 6 +/- 4%; P = 0.02), although the difference in overall EFS did not reach the required level for significance. Testicular recurrence varied from 2-8% in comparison with 20% in the historic group. EFS was not influenced by age, gender, CNS disease at diagnosis, morphology, or immunophenotype. In addition to treatment regimen and early response rate, initial leukocyte count, hemoglobin level, liver, spleen, and lymph node enlargement, and the presence of a mediastinal mass had univariate prognostic influence on EFS. In multivariate analysis, only the kinetics of response, leukocyte count (unfavorably, P < 0.0001), and mediastinal mass status (favorably, P = 0.01) were prognostic. CONCLUSIONS: The adverse prognostic implications of lymphomatous ALL can be minimized by the NY and BFM regimens. Cranial irradiation resulted in better CNS disease control when added to the LSA2-L2 regimen, but did not improve the overall disease free survival. With improved systemic chemotherapy, there was no excess of lymph node, testicular, or other local recurrence without prophylactic irradiation to sites of initial bulk disease or to the testes.

Adolescent↗

PubMed1998

Application of the international prognostic index in a study of Chinese patients with non-Hodgkin's lymphoma and a high incidence of primary extranodal lymphoma.

BACKGROUND: Chemotherapy containing anthracycline is the standard initial treatment for aggressive non-Hodgkin's lymphoma (NHL), and the International Prognostic Index (IPI) is widely accepted as the standard tool for determining the prognosis of patients with this disease. However, the data on which the IPI was based primarily came from studies conducted in Western countries. It may not be directly applicable to Asian populations, in which the incidence of primary extranodal lymphoma (PENL) is known to be high. METHODS: The authors conducted a retrospective study of 218 patients with aggressive NHL who were treated with chemotherapy. They analyzed the distribution of stage and pathology, prognostic factors, toxicity, and treatment outcome. The IPI was then applied and its ability to identify distinct prognostic groups tested. RESULTS: Eighty-six patients (39.4%) had lymph node lymphoma (LNL) and 132 (60.6%) had primary extranodal lymphoma (defined as non-Hodgkin's lymphoma with primary presentation, bulk of disease, and histologic confirmation at an extranodal site). The most common primary extranodal sites were the stomach (22%) and Waldeyer's tonsillar ring (18.9%). The complete response rate of PENL patients to chemotherapy containing anthracycline was 52%, as compared with 64% of the LNL group. The 5-year survival rates for patients with LNL and PENL were 57.4% and 52.1%, respectively. The toxicity in the two patient groups was similar. Four of the prognostic factors in the IPI-age, serum LDH, performance status, and disease stage-predicted significantly different survival for PENL and LNL patients. However, the number of extranodal sites involved was not a significant predictive variable in PENL. CONCLUSIONS: The IPI was applicable to this Chinese population in which the incidence of PENL was high, although the number of extranodal sites did not achieve statistical significance as a risk factor. A proposal for modification was made. Chemotherapy containing anthracycline was an effective treatment for both PENL and LNL patients.

Adolescent↗