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[The correlation between prognostic factors and outcome of second look laparotomy in ovarian cancer].

OBJECTIVES: The objective of this study was to verify the correlation between prognostic factors, positive or negative second look laparotomy (SLL) and 5-year survival in patients with ovarian cancer. MATERIAL: Between 1984 and 1993, 178 patients after primary surgery and first-line chemotherapy with complete clinical response underwent second look laparotomy. The correlation between clinical stage and grade of cancers, residual disease, age of patients in two group of patients: with positive and negative second look laparotomy were evaluated. RESULTS: 95 patients (53%) had positive SLL. The 5-years survival in this group was only 20%. Adverse prognostic factors were: advanced primary stage (IV-0% of 5-years survival), low grade of differentiation (9.1% of 5-years survival) and residual disease > 2cm (9.4% of 5-years survival). The 5-year survival in group with negative SLL was 78.3%. The analysed prognostic factors in this group were insignificant in predicting 5-year survival. CONCLUSIONS: This study confirms that the SLL can provide an important prognostic evaluation in patients without evidence of disease and allows surgical cytoreduction in group with positive SLL (more than 50% of patients). The analyzed prognostic factors in group with negative SLL were insignificant in predicting 5-year survival. The multicenter research for new prognostic factors in this group are required.

Female↗

Prognostic factors and survival of stage IB-IIA cervical cancer.

OBJECTIVE: This study investigated the prognostic significance of age at diagnosis, stage, tumor subtype, pelvic lymph node metastasis (PLNM), lymph-vascular space involvement (LVSI), presence or absence of deep cervical stromal invasion (DCSI) in stage IB-IIA cervical cancer patients. It also investigated the inter-relationship among these factors. METHODS: 152 patients treated with radical hysterectomy plus pelvic lymphadenectomy were followed up for a median of 49 months and were evaluated retrospectively. RESULTS: The 5-year overall survival rate was 84.8%. The distribution of age at diagnosis is of bimodal shape, peaking at 42 and 68 years, respectively. Tumor subtype, PLNM, DCSI, and LVSI were found to be significant prognostic factors individually. After multivariate analysis, only tumor subtype and PLNM were found to be independent, significant prognostic factors for survival. The prognostic importance of LVSI appeared to be eclipsed by the presence of PLNM. DCSI was statistically related with FIGO stage, LVSI and PLNM. CONCLUSION: Tumor subtype and PLNM are the two most important independent prognostic factors for stages IB-IIA cervical cancer. Some prognostic factors are inter-related and may reflect different facets of tumor progression.

Adolescent↗

Comparative long-term prognostic value of quantitative HER-2/neu protein expression, DNA ploidy, and morphometric and clinical features in paraffin-embedded invasive breast cancer.

Data regarding the prognostic value of HER-2/neu protein expression in breast cancer are conflicting, perhaps because of short follow-up and technical difficulties in the determination (the admixture of benign elements with the biochemical method and the subjectivity of the immunohistochemical assessment). Therefore, using digital image processing, we compared the correlation between and the prognostic value of (a) quantitative immunohistochemical HER-2/neu protein expression and (b) clinical, morphometric, and flow-cytometric DNA ploidy features; histologic grade; and biochemically assessed estrogen receptor content. Paraffin-embedded invasive breast Pancers of 82 patients with long-term follow-up were used. None of the patients had received adjuvant systemic therapy. HER-2/neu protein expression was significantly correlated with DNA index, lymph node status, and tumor size and, in the diploid tumors, was weakly correlated with the percentage of S-phase cells. Strong HER-2/neu protein expression was associated with a worse prognosis (although not significantly, p = 0.07). No differences were detected between cancers with or without axillary lymph node metastases. In survival analysis, the Multivariate Prognostic Index and the morphometric features were much stronger prognosticators than HER-2/neu protein overexpression, which, however, had additional prognostic value to that of many of the features analyzed, especially when more than 35% HER-2/neu protein levels (relative to the high expression SKBR3 cell line) were present. Combined diploidy and HER-2/neu protein content greater than 35% occurred in a small group of patients (n = 3), all of whom died. Likewise, in tetraploid cancers a combination of S-phase cells greater than or equal to 7% and HER-2/neu protein content greater than 35% was an ominous sign. In multivariate analysis, strong HER-2/neu protein overexpression was prognostically over-shadowed by the morphometric features. Nevertheless, it is important to further analyze the intriguing possibility of identifying a subgroup of breast cancer patients with a very poor outcome merely using cytometric analysis of paraffin-embedded material of the primary tumor.

Biomarkers, Tumor↗

[Prognostic factors of hepatocellular carcinoma after liver transplantation].

BACKGROUND & OBJECTIVE: Liver transplantation (LT) is the best treatment for hepatocellular carcinoma (HCC), however, prognostic factors and selection of patients with HCC for LT are controversial. This study was to summarize our experience of LT for HCC, and identify prognostic factors. METHODS: The clinical and follow-up data of 98 patients who underwent LT for HCC between Feb. 1999 and Dec. 2004 in our center were analyzed retrospectively. Their survival rates were calculated by Kaplan-Meier method. Log-rank test and Cox proportional hazards regression model were performed to analyze prognostic factors of HCC after LT. All statistical evaluations were performed using SPSS10.0 statistical software. RESULTS: The follow-up time ranged from 1 to 78 months (median, 37.6 months). The mortality was 31.6%. The recurrence rate was 52.0%. The 1-, 3-, and 5-year survival rates were 84.9%, 49.3%, and 33.2%, respectively. Univariate analysis showed that portal vein tumor thrombus (PVTT), tumor size, serum alpha-fetoprotein (AFP) level, pTNM stage, and histological differentiation were prognostic factors of HCC after LT. Multivariate Cox regression analysis showed that the tumor size and PVTT were independent prognostic factors of HCC after LT. CONCLUSIONS: Tumor size and PVTT are major prognostic factors of HCC after LT.

Adult↗

International prognostic index (IPI)--a critical comparison with five multiple myeloma staging systems in the group of 270 patients treated by conventional chemotherapy.

In the group of 270 patients with multiple myeloma (MM) treated during 1991-2004 by conventional chemotherapy, the prognostic value and practical utility of IPI (International Prognostic Index) was assessed and compared with five other actual staging systems. Prognostic significance was assessed using the curves of overall survival (OS) according to Kaplan-Meier and log rank test (p<0.05). Good practical utility and prognostic significance of Durie-Salmon (D-S) system was confirmed (p<0.001). Good overall prognostic significance was observed in simple staging systems based on the measurement of beta2-microglobulin and albumin serum levels according to Bataille (p<0.001), SWOG (South West Oncology Group, p<0.001) and IPI (p<0.001). Regardless of a short 5-year duration of the study, the scoring system according to San Miguel enclosing apart from other parameters also propidium iodide proliferation index (PC-PI) of myeloma plasmocytes seems to be promising with very different characteristics of curves of overall survival (p<0.001). Very good prognostic value and easy practical utility were examined in Olomouc staging system (OSS) based on the measurement of beta2-microglobulin and thymidinekinase serum levels (p<0.001). With regard to detection of patients of stage 1, i. e. "low risk", not requiring an immediate initiation of conventional chemotherapy ("wait and see" approach), the most suitable was the system according to D-S, SWOG and IPI (median OS 77, 76 and 77 months). To select a cohort of "high risk" patients, i.e. stage 3, with very unfavourable disease prognosis, the most advantageous was the system OSS and San Miguel (median OS was 5 and 6 months) and/or SWOG system selecting patients of stage 4, i.e. "worst prognosis", with median OS 8 months. It was found that IPI did not meet expectations for effective identification of "high risk" patients (median OS of stage 3 was 20 months) nor for the distinction of different prognosis of patients during initial 25 months of MM course at stage 2 vs. 3. The study indicates that under conditions of common clinical practice and conventional chemotherapy, the staging system according to D-S is still useful, while practical application of SWOG and IPI as simpler alternative to the assessment of clinical stage should be verified by further comparative studies. In harmony with the progress in cytogenetics and molecular biology as well as a prospective requirement of individual target therapy, a future suitable stratification system should be based on parameters of internal biological properties of myeloma tissue and microenvironment of bone marrow, allowing in addition a continuous evaluation of the disease course and the effect of therapy.

Adult↗

The limited prognostic value of measuring and grading small invasive breast carcinomas: the whole sick lobe versus the details within it.

Although tumor size and grade are well-established prognostic parameters in unselected series or in advanced cases of invasive breast carcinoma, studying their prognostic value in small invasive carcinomas has generated variable results. The significance of these parameters was recently questioned in three large studies on invasive carcinomas less than 15 mm in size, in which neither grade nor size were found to be independent prognostic parameters. Two of these studies were carried out on material of our institution and evidenced the outstanding prognostic significance of a radiological parameter (presence of casting type microcalcifications) in these tumors, challenging the traditional approach in breast pathology in which conventional morphologic prognostic parameters are clearly insufficient to explain these results. In the present article we discuss the practical difficulties in measuring and grading invasive breast carcinomas to point out the disturbing lack of wide international consensus considering the optimal assessment of these parameters, contributing to discordant results in the reviewed studies. We also present the unifying concept of the theory of the sick lobe which, by shifting the focus from the debated details of measuring and grading towards the judgement of the pattern of tumoral growth, offers alternative morphologic prognostic parameters which fulfill the needs of a modern interdisciplinary approach to diagnosing small breast carcinomas.

Breast Neoplasms↗

Early proximal tibial valgus osteotomy as a very important prognostic factor in Thai children with infantile tibia vara.

OBJECTIVES: To find the effectiveness of the early surgery (2-3 years of age)as a very important prognostic factor affecting the outcomes in Thai children with infantile tibia vara and all the prognostic factors including the usefulness of arthrographic study in correcting the deformity. MATERIAL AND METHOD: From 1994 to 2004, sixteen children aged average 3.61 years old (2.08-7.0) were treated in Siriraj Hospital and diagnosed as infantile tibia vara by Langenskiold radiographic staging were included in the present study and retrospectively reviewed with an average of 6.4 years follow up (range 6 month - 11.1 years). All cases were initially treated by surgery because of low compliance for brace or brace failure. They consisted of 3 boys and 13 girls. There were 24 legs including the bilateral involvement in 8 cases (2 boy and 6 girls). After arihrography, the midshaft fibular osteotomy was performed then the proximal tibial dome-shaped valgus osteotomy was done and fixed with 2 pins. The desired position was 12 degree knee valgus . The patients were divided in two groups, 1)group A,the successful group with the knee becoming normal without any deformity after single osteotomy, 2)group B,the recurrent group with recurrence of the varus deformity required further corrective osteotomies to make normal axis of the knee. All variables were analyzed and compared between group A and group B. The general characteristics and radiographic findings were recorded in 1)age, 2)sex, 3)side, 4)weight in kilogram and in percentage of normal or overweight(obesity) compared with the standard Thai weight chart, 5)tibiofemoral angle (TFA) pre and postoperative treatment, 6) metaphyseal diaphyseal angle (MDA), 7)the medial physeal slope angle (MPS, 8)The preoperative arthrographic articulo-diaphyseal angle (ADA), 9.arthrographic articulo-medial physeal angle (AMPA). RESULTS: There were 14 legs in group A and the remaining 10 legs were in group B (average 2.4 operations). All cases healed in good alignment of the legs without major complication. All patients who were operated on early before 3 years old were 100% cured by single osteotomy in group A(11 legs). Arthrography was useful in evaluating the knee joint and drawing the angle. Considering the prognostic factors affecting the outcomes after surgery, there were 6 prognostic factors . First, the age less than 3 years old (P<0.001). Second, the normal weight (P<0.047). Third, the Langenskiold stage 1-2 (P=0.002). Fourth, the MPS angle equal or less than 59 degree (P < 0.001). Fifth, the ADA preperative angle equal or less than 18 degrees (P<0.001). Sixth and the last factor, the TFA angle postoperative treatment, equal or more than 10 degrees valgus (mean 13 degrees valgus) (P=0.009).In multivariate analysis with stepwise logistic regression of these 6 prosnostic factors, the MPS angle had the most important significance. The proximal tibial valgus osteotomy was a very important factor(P < 0.001). CONCLUSION: The 6 prognostic factors and usefulness of arthrography were identified. The authors suggest that surgery should be performed early in Thai children who have met these criterias 1)age of the patients more than 2 years old, 2)Langenskiold roentgenographic characteristics of infantile tibia vara stage 2 or more at the time of diagnosis, 3)Low compliance for brace treatment.or brace failure but not more than 3 years old. The surgery should not be delayed more than 3 years of age by waiting for effectiveness of brace treatment in Thai children with infantile tibia vara. The early proximal valgus dome- shaped osteotomy was a very important controllable prognostic factor by surgeon decision.

Arthrography↗

[Prognostic analysis of 220 colorectal cancer patients with synchronous liver metastases].

BACKGROUND & OBJECTIVE: Colorectal cancer is one of the most common malignant tumors in China. Synchronous liver metastases occur in 10%-25% colorectal cancer patients. This study was to elucidate the prognostic factors and treatment choices for colorectal cancer patients with synchronous liver metastases. METHODS: Records of 220 colorectal cancer patients with synchronous liver metastases initially treated at Cancer Center of Sun Yat-sen University from Dec. 1995 to Dec. 2002 were reviewed. Prognostic factors were analyzed by Kaplan-Meier method and Cox regression model with SPSS12.0 software. RESULTS: The 5-year overall survival rate was 5.52%, the median survival time of the patients was 12.93 months. Univariate analysis of clinical characteristics revealed that the number, size and distribution of liver metastases, extrahepatic disease, serum CEA level at diagnosis, N status, and histology were prognostic factors. Univariate analysis of clinical treatment factors showed that treatment modality, primary site resection, and chemotherapy regimen were prognostic factors. Multivariate analysis showed that the number and size of liver metastases, extrahepatic disease, serum CEA value at diagnosis, treatment modality, primary tumor resection, and chemotherapy regimen were independent prognostic factors of colorectal cancer patients with synchronous liver metastases. CONCLUSIONS: Liver metastases larger than 5 cm in diameter, bilobar liver metastases, extrahepatic invasion or metastases, and CEA level more than 200 microg/L at diagnosis are adverse prognostic factors. Primary tumor resection and liver resection should be considered for all suitable patients with colorectal metastases to the liver alone. Liver-target intervention and/or systemic chemotherapy might be a good choice for inoperable patients. If possible, systemic chemotherapy containing oxaliplatin is preferred.

Adenocarcinoma↗

Survival from operable breast cancer: prognostic factors in Yogyakarta, Indonesia.

OBJECTIVE: The aim of this study was to determine most significant prognostic factor for overall survival of invasive duct operable breast cancer from clinical stage, pathological stage, epidemiological, anatomic and cellular and molecular genetic factors. MATERIALS AND METHODS: Research design was prospective cohort. Duct invasive operable breast cancer patients who were diagnosed and treated with standard protocol since 1993, followed prospectively until November 2003 by clinical stage, pathological stage, age, tumor size, lymph node status, histological grade, mitotic index, ER,PR, c-erbB2, p53 and MIB-1, until revealed outcome (death). Prognostic factor was analyzed univariately for overall survival with Kaplan Meier method. Difference between two survival group was analyzed with log- rank test. Independent prognostic factor was analyzed multivariately using proportional hazard (Cox) regression. RESULTS: With univariate analysis, significant prognostic factors for overall survival were clinical stage (p<0.001), pathological stage (p<0.001), tumor size (p<0.001), lymph node status (p<0.001) and adjuvant chemotherapy (p<0.005). Multivariately, most significant prognostic factors for survival were lymph node status (p=0.001; Exp beta=7.775; 95% CI: 2.276-26.56) and clinical stage (p=0.029; Exp beta=2.142; 95% CI: 1.081-4.244). CONCLUSION: Independent prognostic factors for survival are lymph node status and clinical stage.

Breast Neoplasms↗

Tumor HGF lacks prognostic significance in Mexican breast cancer patients.

Hepatocyte growth factor-scatter factor (HGF-SF) is a pleiotropic protein implicated in tumor formation and metastasis. Since increased levels of HGF-SF were first identified in breast cancer tissue or patient serum, some evidence has suggested that tumor or serum HGF-SF concentration could be one of the most accurate prognostic factors for this disease. However, other recent investigations have not been able to corroborate this finding. The study aims to establish the prognostic significance of HGF-SF in Mexican breast cancer women. Surgical specimens were obtained from 67 incident breast cancer patients at the Mexican National Cancer Institute between 1994 and 1995. Primary breast cancer tissue HGF-SF was measured by quantitative sandwich enzyme immunoassay. Relapse-free and overall survival curves were generated using Kaplan-Meier method. Significance of survival differences was calculated by log-rank test. chi2 was used for the association analysis between prognostic variables. Disease-free survival and overall survival were similar between the high tumor HGF group of patients and the low HGF patients (p = 0.7 and p = 0.36 respectively). No association was found between HGF and other clinicopathological variables (age, menopause status, clinical tumor size, clinical node involvement, metastasis, tumor grade, Estrogen Receptor and Progesterone Receptor). We found no prognostic significance for HGF, nor did we find a clear association between HGF and other known prognostic factors. A firm conclusion cannot be established regarding the role of HGF as a prognostic tool in breast cancer patients.

Adult↗

[An overview of new prognostic factors for ovarian cancer].

One of the most characteristic features of epithelial ovarian cancer is its inherent heterogeneity with respect to biological behavior ranging from the relatively indolent nature of borderline tumors to highly aggressive malignant diseases. This can be reflected in a wide variety of prognostic factors, among which the stage of disease is by far the most important, followed by histologic subtype, histologic grade, volume of residual disease, age at diagnosis, and performance status (PS). Within a given stage, histologic grade is the most powerful prognostic factor in stage I disease, followed by dense adherence and large volume of ascites. On the other hand, the main prognostic factor in more advanced stage disease (II-IV) includes an effect of chemotherapy and a volume of residuum, and PS. However, these factors alone cannot always predict patients' survival correctly. A number of new and potentially valuable prognostic factors have emerged as a result of the recent technical advances in molecular genetics, flow cytometric analysis, development of monoclonal antibody, immunohistochemical study, and steroid hormone receptor analysis. This article reviews some of these newly developed "investigational" prognostic variables, as well as the "widely accepted" clinicopathological prognostic factors.

Cell Division↗

Definitive radiation therapy in the treatment of carcinoma of the uterine cervix. Treatment results and prognostic factors.

219 patients suffering from cervix carcinoma received definitive radiation therapy using moderate doses of external beam therapy and high dose-rate afterloading brachytherapy from 1979 to 1986. At five years, the actuarial survival (AS) for stage Ib patients was 81%, for stage IIa 53%, for stage IIb 56%, for stage IIIa 25%, for stage IIIb 33% and for stages IVa and IVb 0%. Significant prognostic factors for actuarial survival were FIGO stage, histological type, grading and, marginally, age of the patient at the time of diagnosis. The survival data censored for death caused by intercurrent disease (tumor related survival, TUS) at five years were: 90% (Ib), 66% (IIa), 63% (IIb), 50% (IIIa), 41% (IIIb) and 0% (IVa and IVb). The prognostic factors were stage and grading. Age and histology failed to be a significant prognostic factor. The disease-free survival (DFS) according to FIGO stage at five years were: Ib 84%, IIa 64%, IIb 59%, IIIa 50%, IIIb 38%, IVa and IVb 0%. Prognostic factors for disease-free survival were limited to FIGO stage and grading. The five-year local control results (LC) according to stage were 90% (Ib), 64% (IIa), 67% (IIb), 43% (IIIb) and 0% (IVa and IVb) with stage as prognostic factor. High dose-rate afterloading therapy for cervix carcinoma yields good results for local control and survival with a low ratio of severe side effects (6%). Radiation therapy eliminates the prognostic influence of histological type and grading of the tumor on local control. External beam and afterloading doses, however, are relevant factors for prognosis, if the patients are stratified by FIGO stage.

Adenocarcinoma↗

[Medulloblastoma: towards new prognostic factors].

Current therapeutic protocols for medulloblastoma combining, with surgery, radiation therapy and chemotherapy allow 5-year survival rates of over 50%. However these therapies induce mainly in children long-term adverse effects, which produce a therapeutic dilemma emphasizing the need for reliable prognostic factors in order to adapt the treatment modalities to the degree of the tumor's aggressiveness. Contradictory results have been reported concerning the conventional clinical and histological prognostic factors in medulloblastoma. Recent development and simplification of cell biology technologies could now help in the resolution of this issue. The aim of this review is to present some new prognostic factors available from these advances, and to discuss their potential usefulness in the field of medulloblastoma: The measurement of the proliferative potential of tumors using thymidine analogues such as bromodeoxyuridine (BUdR), or the monoclonal antibody Ki-67 is promising. The flow cytometric determination of D.N.A. content in medulloblastomas appears to show a correlation of diploidy with a worse prognosis than aneuploidy. Modern cytogenetic and molecular biology techniques are permitting the current assessment of amplification and overexpression of oncogenes, or the presence of deletions, as prognostic factors in medulloblastoma. The study of the cellular phenotype and particularly the search for differentiation markers has not yet led to clear-cut results from a prognostic viewpoint, but further advances are to be expected in this field, thanks to the development of more specific monoclonal antibodies. The investigation of the tumoral stroma and metabolism is very promising too. These novel approaches to prognostic factors in medulloblastoma should allow a better classification and management of these tumors in the near future.

Antibodies, Monoclonal↗

An improved prognostic index of axillary node involvement in breast cancer incorporating DNA ploidy and tumour size.

A multivariate prognostic index based on clinical data and the results of flow cytometry for the grading of breast cancer was evaluated in 117 patients whose disease had been detected and treated by mastectomy with axillary clearance between 1974 and 1976. Survival analysis with Cox's regression model pointed to three important prognostic factors: lymph node involvement (p less than 0.001), DNA ploidy (p less than 0.01) and tumour size (p less than 0.01). These factors were incorporated into a prognostic index, in which the lymph node involvement, DNA ploidy, and tumour size contributed to the index in that order. Logistic discriminant analysis with five year follow-up as the fixed end point (70 alive, 47 dead) gave the same result; lymph node involvement, tumour size, and DNA ploidy were the best prognostic indicators of survival. The result showed that our multivariate prognostic index was more powerful than lymph node involvement alone. The use of this prognostic index is recommended for selecting patients for different treatments.

Adult↗

Toward comprehensive management tailored to prognostic factors of patients with clinical stages I and II in Hodgkin's disease. The EORTC Lymphoma Group controlled clinical trials: 1964-1987.

From 1964 to 1987, the EORTC Lymphoma Group conducted four consecutive controlled clinical trials on clinical stages I and II Hodgkin's disease in which 1,579 patients were entered. From the onset the main aim of these trials was to identify the subsets of patients who could be treated safely by regional radiotherapy (RT). Therefore, several prognostic indicators were prospectively registered and progressively used in the trial protocols for the delineation of the favorable and unfavorable subgroups as soon as they were recognized of high predictive value. In the H2 trial (1972 to 1976), the histologic subtype was the only variable taken into account for the therapeutic strategy and the staging laparotomy findings were found to be of prognostic value only in patients with favorable prognostic indicators. In the H5 trial (1977 to 1982), patients were subdivided into two subgroups according to six prognostic indicators. Patients with favorable features were submitted to a staging laparotomy (lap); lap negative patients were randomized between mantle field RT and mantle field plus paraaortic RT. Disease free survival (DFS) and total survival (S) were similar in the two arms. Among patients with unfavorable features, DFS and S were significantly higher in the arm treated by combination of mechlorethamine, vincristine, procarbazine, prednisone (MOPP) chemotherapy (CT) and RT than in the arm treated by total nodal irradiation. Nevertheless, in patients below the age of 40, the overall survival rates were equivalent in the two arms. In the H6 trial, the delineation of the favorable subgroup was based on (a) absence of systemic symptoms and elevated ESR, (b) no more than one or two lymph node areas involved. The aim of the study was to assess the impact on survival of a therapeutic strategy including staging laparotomy. At a 4-year follow-up, no difference in survival was evidenced. In patients with unfavorable prognostic indicators, 3 MOPP-RT-3 MOPP were compared with 3 ABVD-RT-3 ABVD. From H1 to H5 trials, the proportion of patients having received CT during the course of the disease gradually decreased; the data suggest that a further reduction in the proportion of patients aggressively treated is conceptually possible. On the basis of the prognostic factors identified, one can delineate three subsets of patients and modulate toxic cost of the initial treatment according to the characteristics of these subsets. In the most favorable subgroup, RT alone produces high survival and CT is not justified.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Prognostic factors in breast cancer.

A variety of tumor characteristics can provide prognostic information useful in managing the patient with primary breast cancer. Some of these characteristics are firmly established, whereas others are observer dependent or require prospective validation. No single characteristic, however, is likely to fully define which patient with primary breast cancer is destined to relapse. This clinical dilemma--recognition of the high-risk patient--is particularly important in the management of women with node-negative breast cancer. Because most women with this early stage of disease will be cured by surgery alone, the use of adjuvant chemotherapy must be limited to high-risk subsets. Tumor size and ER status are established prognostic factors. Histologic and nuclear grade may be important, but problems of interobserver variability remain. Some studies have shown that aneuploidy or a high S-phase fraction may be independent, high-risk characteristics. Flow cytometric DNA content analysis must be applied with caution, however, because the calculation of S-phase fraction has not been standardized and because the prognostic utility of this approach has not been prospectively confirmed. For now, a prudent approach might be to gather as much prognostic information about each patient's tumor as possible. Those with several of the high-risk characteristics listed in Table 2 should receive strongest consideration for adjuvant treatment. Some of these same prognostic factors, along with several others, can be used to characterize the high-risk node-positive patient. The number of involved axillary nodes is the most important established predictor. Progesterone-receptor status is associated with both disease-free and overall survival, whereas ER status is independently related only to overall survival. Histologic grade, DNA ploidy, and S-phase fraction can also be used to help define the high-risk patient. Finally, tumors that amplify or overexpress the HER-2 gene may have a higher risk of relapse, although this finding has been questioned. Management of patients with breast cancer requires an individualized approach that is based on a careful weighing of a variety of prognostic considerations. The relative importance of these factors will require further large-scale, prospective, multiparameter studies. Although results from such studies are awaited, an understanding of the clinical heterogeneity of breast cancer must be based on a multiplicity of observations, each of which characterizes, in a limited way, the biology of this disease.

Axilla↗

Prognosis of aggressive lymphomas: a study of five prognostic models with patients included in the LNH-84 regimen.

Four prognostic models described for aggressive malignant lymphomas and the classical Ann Arbor staging system were used to compare the survival of 737 patients treated with the LNH-84 regimen. The aim of the study was to determine the optimal prognostic system at the time of diagnosis. Three institutions have described these models after multivariate analyses: the Dana Farber Cancer Institute (DFCI1 and DFCI2), the MD Anderson Hospital (MDAH), and the Memorial Sloan-Kettering Cancer Center (MSKCC). The models were constructed with the following variables: performance status, LDH level, and tumor extension. The latter is the most difficult to assess: it was considered as the number of extranodal sites and the diameter of the largest mass in DFCI1, stage and the diameter of the largest mass in DFCI2, the number of extranodal and extensive nodal sites in MDAH, and the number of nodal sites and their localization in MSKCC. Univariate studies with LNH-84 regimen patients showed all these variables to have major prognostic significance (logrank tests: P less than 10(-4)). All five prognostic systems divided patients into three subgroups: good, intermediate, and poor prognosis. Logrank analyses of survival showed highly significant differences (X2 greater than 90 and P less than 10(-6)) between the subgroups. No gross difference was found between the models, and none was better than the others. A new, internationally accepted prognostic system for the expression and comparison of treatment results in aggressive malignant lymphomas should include major univariate prognostic parameters and must be reliable and easy to use in clinical practice. Until such time, stage or LDH level are the best alternatives.

Antineoplastic Combined Chemotherapy Protocols↗

A multivariate analysis of prognostic factors in adult Hodgkin's disease.

A multivariate analysis of the prognostic factors was carried out with a Cox model on 167 patients with Stage I-IV Hodgkin's disease. The following indicators were prospectively registered: Sex, age, clinical stage, systemic symptoms, histological type, number of involved areas, nodal size, mediastinal thoracic ratio (MTR), localization of mediastinal involvement according to the aortic arcus, hilar involvement, extent of radiotherapy, and extent and mode of chemotherapy. A linear logistic analysis showed that most of the indicators were interrelated. This emphasizes the necessity of a multivariate analysis in order to assess the independent influence of each of them. The three main prognostic indicators for complete remission achievement were age, clinical stage and involvement of lung hili. The three main prognostic indicators for disease-free survival were sex, size of mediastinal involvement (MTR) and use of alternating chemotherapy COPP/ABVD in the initial treatment strategy. The most important prognostic factor for survival was clinical stage followed by hilar involvement, age, and nodal size. The coefficients estimated by Cox regression analysis can be used to combine the important prognostic factors into a single index for each patient at presentation. The prognostic index for each patient would allow the identification of cases with poor prognosis who might benefit from additional initial treatment.

Antineoplastic Combined Chemotherapy Protocols↗