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Therapy of small breast cancer: a prospective study on 1036 patients with special emphasis on prognostic factors.

In 1983, The German Breast Cancer Study Group, sponsored by the Federal Ministry of Research and Technology, started a prospective multicenter trial on the treatment of early breast cancer pT1 pN0 M0. Treatment consisted of initial tumorectomy with microscopically free margins and lower axillary dissection. After conformation of a pT1 pN0-stage, additional treatment was either mastectomy or adjuvant radiotherapy (50 Gy in 25 fractions to the entire breast plus 12 Gy electron boost). In medially located tumors, the parasternal and supraclavicular area was also irradiated with 50 Gy. A randomization between both treatment modalities was initially planned but was not feasible and abandoned. Nearly all patients were treated according to their own choice. From November 1983 through December 1989, 1119 patients were recruited. Eighty-three were excluded from the protocol. Out of the remaining 1036 patients, 733 (71%) underwent breast preservation and 303 (29%) mastectomy. A detailed pathohistological examination of all tumorectomy specimens was performed in a pathologic reference center. Oncogen overexpression was evaluated by immunohistological detection of the transmembrane protein p-185 (corresponding to c-erb-B2) in 425 cases. After a median follow-up of 48 months, the frequency of local recurrences (4.7%), regional recurrences (1%), and distant metastases (5.4%) was the same in the breast preservation group and the mastectomy group. The 3-year disease-free survival was 90% after breast preservation and 88% after mastectomy (p = 0.21). In the breast preserving group, 24 patients with microscopically involved margins had a poorer disease-free survival than the study group (75% vs 90% after 3 years). The width of the margins had no impact on prognosis. Other prognostic factors in an univariate and multivariate analysis were tumor size and tumor grade. Age, menopausal status, hormone receptor status, histological tumor type, and treatment (mastectomy vs breast preservation) were not significant. P-185-expression was dependent on tumor grade and was the strongest prognostic factor in an univariate and multivariate analysis (p less than 0.001). The results emphasize the central role of tumor grade for prognosis and suggest the independent prognostic significance of the c-erb-B2 oncogen (corresponding to p-185) in pN0-patients.

Adenocarcinoma

The Second Medical Research Council study of prognostic factors in nonseminomatous germ cell tumors. Medical Research Council Testicular Tumour Working Party.

PURPOSE: To assess prognostic factors in a large population of patients with metastatic nonseminomatous germ cell tumors (NSGCT) arising in gonadal or extragonadal sites. PATIENTS AND METHODS: Data from 795 patients treated with chemotherapy between 1982 and 1986 in 13 centers were analyzed. Particular emphasis was placed on exact tumor measurements (eg, size of nodal masses, number of lung metastases), and the diagnostic pathology was also reviewed. Cox regression analysis was performed on these data. The patients were treated with a variety of cisplatin-containing chemotherapy regimens, 86% of which included etoposide. RESULTS: With median follow-up of 45 months, overall 3-year survival is 85%. The independently adverse features proved to be (1) the presence of liver, bone, or brain metastases; (2) raised marker levels (alpha-fetoprotein [AFP] level greater than 1,000 kU/L or beta subunit of human chorionic gonadotropin [HCG] greater than 10,000 IU/L [corrected]); (3) the presence of a mediastinal mass greater than 5 cm in diameter; (4) the presence of 20 or more lung metastases; (5) increasing age; and (6) absence of undifferentiated teratoma (embryonal carcinoma) or fibrous tissue from the primary tumor. CONCLUSIONS: The first four factors were used to define a simple prognostic classification. A good-prognosis group having none of these features comprised 67% of our patient population and had a 3-year survival of 93%. The remaining 33% of patients having at least one of these features had a 3-year survival rate of 68%. These patient groups are currently the subjects of international randomized clinical trials.

Adult

[Human mammary carcinoma. A model for the relationship between tumor proliferation, tumor-associate macrophages, and prognostic factors].

As compared with the lymphatic system, the mononuclear phagocyte system (MPS) represents the older defense system in the course of evolution. Organisms with defective or with no lymphocytic function are able to live for a certain time while metazoa cannot develop and exist without cells capable of phagocytosis. It is known that up to 80% of the mass of malignant experimental tumors may consist of macrophages. The biological relevance of these tumor-associated macrophages (TAM), however, is contested to date. Besides well-known tasks in specific and non-specific defense, the cells of the MPS possess nutritive functions. The different functions of TAM have been essentially examined in animal experiments in vivo and in vitro up to now. These studies have shown, e.g., that TAM of different phenotypes to some extent are assigned to different functions and that each tumor or tumor cell line has a specific TAM pattern. The available number of monoclonal antibodies (MAB) able to recognize different groups of human macrophages has only increased in the recent past. This also provided evidence of the phenotypic heterogeneity of macrophages in the human system. On the other hand, there is little knowledge to date of the possible biological cause of the presence of numerous macrophages also in the stroma of malignant tumors in man and on the functional relevance of particular macrophage phenotypes. In the present studies, the phenotypic pattern of tumor-associated cells was examined by immunohistochemistry in the model of human mammary carcinoma, using 18 monoclonal antibodies (Ki-M1-8, Leu-M1-3, Leu-M5, EBM11, CD1, anti-transferrin receptor [TFR], anti-MHC I, anti-MHC II or anti HLA-DR) and one polyclonal antibody (anti protein-S100). The first part of the study contains a semiquantitative evaluation of 216 cases of mammary carcinoma. The analytical results are correlated with established prognostic factors available in the case of malignant tumors in general and in that of mammary carcinomas in particular (age, menopausal status of patients, axillary lymph node and estrogen/progesterone receptor status, size of tumor, tumor type according to WHO, degree of malignancy according to histopathological and nuclear grading). As tumor parameters of absolute biological relevance, proliferating activity (Ki67) and MHC phenotype of tumor cells and amount or types of tumor-associated lymphocytes (TAL) are examined in order to analyze their correlation with prognostic factors and their importance in the tumor-macrophage system.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibody-Dependent Cell Cytotoxicity

Established and emerging prognostic factors in mycosis fungoides and Sézary syndrome.

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL), characterized by heterogeneous clinical behavior and variable prognosis. Accurate prognostication is essential for risk-adapted management. This review synthesizes emerging evidence on prognostic factors in MF and SS, with a focus on recent genomic advances. Traditional prognostic frameworks are outlined, highlighting the prognostic impact of demographics, stage, clinical features, and histologic findings. More advanced prognostics are then outlined, including genomic alterations and impact of the tumor microenvironment. We highlight realms in which integration of traditional and more biological prognostic frameworks can support more individualized treatment strategies.

Sézary syndrome

Prognostic factors in choroidal and ciliary body melanomas.

We reviewed 293 cases of choroidal and ciliary body melanoma with a followup period of five years or more. Nine factors influenced significantly the prognosis: Age of the patient at the time of enucleation, location of the tumor and of its anterior border, largest tumor diameter in contact with the sclera, height of the tumor, integrity of the Bruch membrane, cell type, pigmentation, and scleral infiltration by tumor cells. Some of these factors can be evaluated clinically before the enucleation. Seven sets of three factors each were determined in order to have better prognostic values based on the clinical data and the cell type. The largest tumor diameter is the single most important clinical and pathological prognostic factor. The prognosis is relatively good when this diameter is 10 mm or less and becomes poor when it exceeds 10mm.

Adolescent

Papillary thyroid carcinoma: a multivariate analysis of prognostic factors including an evaluation of the p-TNM staging system.

OBJECTIVE: To analyse the prognostic factors in papillary thyroid carcinoma, and in particular to evaluate the accuracy of the pathological tumour, nodes, metastases (p-TNM) staging. DESIGN: Retrospective univariate and multivariate analysis. SETTING: University hospital in Norway. SUBJECTS: 167 patients who were operated on for papillary thyroid carcinoma between 1971 and 1985. Main outcome measures--Death of papillary thyroid carcinoma, and length of recurrence free survival. RESULTS: Male sex, increasing age, larger tumours, and spread of growth beyond the thyroid all independently increased the risk of dying of papillary thyroid carcinoma, whereas the period of recurrence free survival was influenced only by the presence of regional metastases and the patient's age. The age related p-TNM staging is suitable for predicting the likelihood of death, but is less accurate in the prediction of recurrence free survival. The age of 45 years is too low to be useful in predicting survival, especially in women. CONCLUSION: The identification of sex in the multivariate analysis as a strong independent predictor of death of papillary thyroid cancer suggests that the prognostic value of the age related p-TNM staging system could be improved if sex was adjusted for, and if a different age was used for men and women.

Adult

Tuberculous meningitis in children: a retrospective study of 79 patients, with an analysis of prognostic factors.

A study of 79 cases of tuberculous meningitis in children, with an emphasis on prognostic factors, was conducted by means of a review of hospital records and completion of a follow-up questionnaire. The survival rate was 62%. Stage 3 disease (with severe changes in the sensorium and often severe neurologic abnormalities) at the time of admission, age 3 years or less, associated miliary tuberculosis and delay in the initiation of therapy correlated significantly with poor outcome. Severe neurologic complications in the acute phase were also related to poor outcome and severe sequelae. General recommendations pertaining to treatment are made.

Age Factors

Prognostic factors in Hodgkin's disease.

The clinical records and treatment results of 163 patients with Hodgkin's disease, who were seen at Ellis Fischel State Cancer Hospital (EFSCH) between 1940 and 1971, were reviewed and analyzed. More than 200 clinical and histological variables were recorded for each case of Hodgkin's disease, including details of radiotherapy and chemotherapy. Statistical studies were carried out in order to evaluate the independent prognosis significance of each of these factors. All of the lesions were reclassified according to the Lukes proposal which was modified and recommended at the 1965 Rye classification (except for hepatomegaly which was included in Stage IV). This is a retrospective study, and the modern techniques of staging were rarely used in pretreatment studies (since 1965, only ten patients have had an abdominal exploration). The basic work-up consisted of a complete blood count, urinalysis, blood type, chest X ray, and EKG. Lymphangiogram and radioisotope liver scans were used on less than 10% of the patients. About 30% of the patients had gastrointestinal X rays and 70% had IVP. Bone marrow biopsies -- the majority of which were done by needle aspiration -- were obtained for approximatley 50% of the patients. Clinical stage, histological type, and presence of absence of systemic symptoms appeared to be themost significant prognostic factors. The classification of systemic symptoms according to the criteria of either the Rye or Ann Arbor conferences showed no particular difference in determining the survival rate. Among the systemic symptoms, fever appeared to be the most important for survival rate. Survival rates were higher in nonanemic and nonlymphocytopenic patients. Eosinophilia, blood group, and Rh factor had no prognostic significance. The relapse-free interval was an important indicator of long-term prognosis. The unfavorable influence of relapse in ultimate prognosis was clearly seen; however, the extent of the relapse site was shown to have no significant influence on survival.

Adolescent

Prognostic factors in the initial response to therapy by patients with advanced breast cancer.

Identification of important prognostic factors with respect to the patient's initial response to therapy was made from a set of 25 covariates available on 281 patients with advanced breast cancer. Since the patients studied were all participants in a randomized clinical trial that involved three different treatment regimens (repeated weekly treatment of a combination of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone; intermittent treatment of the same preceding five drugs given in 5-day courses every 4 weeks; or treatment every 3 weeks with adriamycin as a single agent), the effect of these treatments on the selection of important covariates was assessed. Although some evidence indicated that the set of important covariates differed by treatment, the differences were not strong enough to be of practical importance. Non-Caucasian patients did poorly on all regimens with a response rate of only 31% compared to 62% for Caucasian patients. The covariates of major prognostic importance for Caucasians were: disease-free interval, liver involvement, and performance status. Ambulatory patients with long disease-free intervals and no liver involvement had the best prognosis. After adjustments were made for these three covariates, the remaining covariates (such as menopausal status, bone involvement, number of metastatic sites, and duration of metastatic disease) were not significantly related to response. As reported earlier, the treatment effect was significant, even after adjustments were made for the important covariates.

Adult

[Long-term survival and prognostic factors in stage II-III multiple myeloma treated with conventional chemotherapy].

In this retrospective study, survival and prognostic factors were analysed in 65 patients with stage II-III multiple myeloma with osteolytic lesions. Multiple myeloma was diagnosed from 1976 to 1984, and patients were treated with conventional chemotherapy. The response rate to initial chemotherapy was 46%. The median survival time was 31 months. The 10-year survival rate was 10%. Four variables were individually prognostic: response to initial chemotherapy, bone marrow plasma cell percentage, the Durie and Salmon staging system, a biological staging system derived from Durie and Salmon's biological criteria regardless of bone lesions. In the multivariate analysis, only two prognostic variables were retained, namely the response to chemotherapy and the biological staging system. No prognostic value was observed for the extent of osteolytic lesions. This study suggests that, in conventionally treated multiple myeloma, long-term survival has improved compared with the previous decade. It also indicates that the extent of osteolytic lesions has little value for the definition of high-risk myeloma.

Adult

Prognostic factors in patients surviving for more than 1 or 5 years after removal of metastatic brain tumors.

Favorable and unfavorable prognostic factors were identified in 28 patients surviving for more than 1 year after surgery for metastatic brain tumor and 18 patients surviving for more than 5 years. A high incidence of favorable factors, including neurological grade and location of the brain lesion, indicated significance in the prognosis. A low incidence of favorable factors, including tumor-free interval and presence or absence of extracranial tumor, indicated little significance to the prognosis.

Adult

[Non-Hodgkin's lymphomas. II. Analysis of the prognostic factors in a series of 307 patients].

PURPOSE: To analyse different clinico-biologic data in order to assess their prognostic value in non-Hodgkin's lymphoma (NHL) patients. MATERIAL AND METHODS: The series comprises 307 patients with NHL diagnosed and treated between 1975 and 1988. The histopathologic diagnosis was revised in accordance with the working formulation system, three prognostic groups being thus considered: low-grade (LGL), intermediate-grade (IGL) and high-grade (HGL) lymphomas. Age, sex, clinical course prior to diagnosis, presence of B symptoms, histologic type, number of lymph-node areas involved, bulky disease, anaemia, thrombocytopenia, LDH, stage and response to therapy were all evaluated for the study. Survival curves were drawn with the Kaplan-Meier method, and the log-rank test was used for comparison of median survival. Whenever the univariate analysis achieved statistical significance, a multivariate analysis was performed by means of a multiple correlation and regression study in accordance with the Cox's model, in which the variables were expressed in a binary model. RESULTS: The following 8 values were found significant in the univariate study of low-grade lymphomas: age, number of involved areas, bulky disease anaemia, thrombocytopenia, LDH, stage, and initial response to treatment. In intermediate-grade lymphomas, the significant findings were age, number of affected areas, bulky disease, thrombocytopenia, LDH, stage, and initial response. For high-grade lymphomas, number of affected areas, thrombocytopenia, LDH, stage and initial response were found statistically significant. Although no significant differences were found for survival within each of the three grades, such differences were significant between them. In the multivariate analysis, age was significant only in the LGL (p < 0.0001) in IGL, age (p < 0.07) and initial response to therapy (p < 0.0001) achieved significant value, and in HGL, stage (p < 0.02) and initial response to treatment (p < 0.0001) attained significance. CONCLUSIONS: The univariate analysis provides various prognostic factors of statistically significance, as reported in the literature, but these after the multivariate analysis was applied, were reduced to age, stage and initial response to treatment.

Adolescent

Clinical Outcome and Prognostic Factors in Childhood Acute Lymphoblastic Leukemia-A Retrospective Cohort Study of Patients from Southern Mexico.

Background/Objectives: B-cell acute lymphoblastic leukemia (B-ALL) remains the most common pediatric malignancy. This study aimed to evaluate clinical outcomes in pediatric B-ALL in Southern Mexico and determine how socioeconomic vulnerabilities-specifically indigenous status and treatment non-adherence-independently drive relapse and compromise survival in a resource-limited setting. Methods: A retrospective cohort study was conducted, including 146 patients (0-17 years) treated between 2010 and 2024 using modified Total XIII and XV protocols. Survival was estimated via Kaplan-Meier. Independent prognostic factors for overall survival (OS) and relapse were identified using multivariable Cox proportional hazards models. Results: The 5-year OS was 50%, and event-free survival (EFS) was 37.6%. Survival varied significantly by clinical risk: 88% for low-risk, 77% for standard-risk, and 31% for high-risk patients. Relapse occurred in 45.8% of patients. Beyond established biological predictors like hyperleukocytosis and high-risk cytogenetics, socioeconomic vulnerabilities profoundly impacted outcomes. Documented treatment non-adherence significantly reduced 5-year OS (23.4% vs. 56.1%, p = 0.001) and disproportionately affected indigenous patients (55.5% vs. 10.1% in non-indigenous). Multivariable analysis identified indigenous status as an independent predictor of increased relapse hazard (HR = 1.89, p = 0.049), alongside male sex and high leukocyte count. Conclusions: Survival outcomes in this cohort are markedly lower than in high-income countries. The high incidence of relapse is deeply intertwined with local structural inequities. Improving survival requires complementing biological risk stratification with targeted strategies to overcome socioeconomic barriers and prevent treatment non-adherence.

Kaplan&#x2013;Meier

Prognostic factors in 227 patients with malignant fibrous histiocytoma.

Malignant fibrous histiocytoma, the major subset of soft tissue sarcomas, was examined for prognostic factors that could influence clinical management and research. Two hundred twenty-seven patients with localized disease, having surgery as the principal modality, were reviewed retrospectively to identify clinical outcomes. The mean age of the patients was 54 years. Extremities were the primary tumor site in 157 patients (62.2%). Overall survival rate was 50%, including 38 patients who died of other causes. Distant metastases were most common to the lung (90%). Local recurrence alone occurred in 37 patients (16%), distant metastases alone in 52 (23%), and distant metastases with local recurrence in 25 (11%). The primary tumor size indicated the 5-year survival rate: tumors smaller than 5 cm had a survival rate of 82%; 5 to 10 cm, 68%; and larger than 10 cm, 51%. Intermediate-grade tumors yielded a 5-year survival rate of 80%, and the 5-year survival rate for high-grade tumors was 60%. Survival rates for both grades were affected by size: tumors of high grade and smaller than 5 cm in diameter had a survival rate of 79%; 5 to 10 cm, 63%; and more than 10 cm, 41%. Grade and size emerge as significant prognostic indicators. These variables will prove helpful in treatment decisions and design of clinical studies.

Adolescent

Relationship between pathologic prognostic factors and abnormal levels of des-gamma-carboxy prothrombin and alpha-fetoprotein in hepatocellular carcinoma.

The relationship between pathologic prognostic factors and abnormal levels of des-gamma-carboxy prothrombin and alpha-fetoprotein was investigated in 42 patients with resectable hepatocellular carcinoma. The frequencies of macroscopic massive type, intrahepatic metastasis, and portal vein tumor thrombus were significantly higher in patients with positive des-gamma-carboxy prothrombin (p less than 0.05) but not with alpha-fetoprotein. Other histologic factors in tumorous and nontumorous tissues were not significantly different irrespective of the positivity of these markers. In patients with tumors not more than 6 cm in diameter, the frequency of intrahepatic metastasis was positively correlated with the positivity of des-gamma-carboxy prothrombin (p less than 0.05) and inversely with that of alpha-fetoprotein (p less than 0.05). Furthermore, intrahepatic metastasis was most frequently observed in patients with positive des-gamma-carboxy prothrombin and negative alpha-fetoprotein (eight of nine) and least frequently in cases with negative des-gamma-carboxy prothrombin and positive alpha-fetoprotein (one of eight). These findings indicated that both des-gamma-carboxy prothrombin and alpha-fetoprotein might be useful markers for the prediction of intrahepatic spread of hepatocellular carcinoma.

Biomarkers

Proliferating cell nuclear antigen (PCNA) as a prognostic factor in non-Hodgkin's lymphoma.

The prognostic value of immunoperoxidase staining for proliferating cell nuclear antigen (PCNA) was studied in a series of 140 non-Hodgkin's lymphomas with median follow-up of 9 years. Lymphomas where > 50% of cells showed positive staining for PCNA had inferior 5-year survival as compared with those with less than 50% of positive cells (57% vs 41%, P = 0.008). The presence of > 50% of positively staining cells for PCNA was strongly associated with a larger than the median size of the SPF (median, 8.3%), and high histological grade of malignancy (P < 0.0001 for both). Lymphomas with both a large percentage (> 50%) of PCNA positive cells and a larger than the median SPF had inferior outcome as compared with lymphomas where either one or both of these factors were small. Although PCNA staining was not an independent prognostic factor in a multivariate analysis, it appears to be supplementary to the SPF even if determined from old paraffin-embedded tissue material.

Adolescent