Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries

PURPOSE: To compare the risk for fatal myocardial infarction (MI) after adjuvant radiotherapy (RT) for left-sided breast cancer with the risk for MI after adjuvant RT for right-sided breast cancer. METHODS: We studied women with local- and regional-stage breast cancer diagnosed from 1973 to 1992 from the Surveillance, Epidemiology, and End-Results (SEER) cancer registries. We performed life-table analysis, the log-rank test, and Cox proportional hazards regression to compare the time to fatal MI from diagnosis between left-sided and right-sided cases, censoring deaths from other causes. RESULTS: Among irradiated patients, the relative risk (RR) for fatal MI in women with left-sided breast cancer was 1.17 (95% confidence interval [CI], 1.01 to 1.36), controlling for age, compared with those with right-sided breast cancer. The RR for fatal MI among left-sided cases was increased for those under the age of 60 years (RR = 1.98; 95% CI, 1.31 to 2.97) compared with right-sided cases, but not at age 60 years or older. Among women with irradiated regional-stage cancer who were younger than 60 years of age, the risk was significantly increased (RR = 2.24; 95% CI, 1.38 to 3.64) for those with left-sided compared with right-sided breast cancer, but not among patients aged 60 years or older. Among irradiated local-stage cases, the risk for those with left-sided breast cancer was not significantly elevated in either age category. Analysis of 5-year conditional survival cohorts showed an increased risk for irradiated left-sided cases among women younger than 60 years of age in the 10- to 15-year conditional survival cohort (RR = 5.28; 95% CI, 1.82 to 15.3). CONCLUSION: Adjuvant RT for left-sided breast cancer diagnosed in women younger than 60 years of age is associated with a higher risk for fatal MI 10 to 15 years later compared with adjuvant RT for right-sided cases.     

Social support and survival among women with breast cancer

BACKGROUND: Two recently reported randomized trials, one among patients with advanced breast cancer and the other among patients with early stage melanoma, suggested that social support may affect survival favorably. This study assesses relationships of social support indicators with 7-year survival among women diagnosed with localized or regional stage breast cancer. METHODS: All newly diagnosed patients with surgically treated localized or regional disease in seven Quebec City hospitals in 1984 were considered for this analysis. Among 235 eligible patients, 224 (95%) participated in a home interview 3 months after surgery. This interview provided information on the use of confidants in the 3 months after surgery. Data on disease and treatment characteristics were abstracted from patients' medical records. RESULTS: Compared with women who used no confidant in the 3 months after surgery, the hazard ratio for the 7-year period was 0.61 (95% confidence interval [CI], 0.33-1.12) among those who had used at least one confidant, 0.54 (95% CI, 0.28-1.06) in women who used two or more types of confidant, and 0.51 (95% CI, 0.22-1.18) among those whose confidants included either physician or nurse. These results were adjusted for age, presence of invaded axillary lymph nodes, adjuvant radiotherapy, and adjuvant systemic therapy (hormone or chemotherapy). CONCLUSION: These results support the view that social support may be associated with longer survival among women with localized or regional stage breast cancer.     

A randomized trial of long term adjuvant tamoxifen plus postoperative radiation therapy versus radiation therapy alone for patients with early stage breast carcinoma treated with breast-conserving surgery. Stockholm Breast Cancer Study Group

BACKGROUND: The use of adjuvant tamoxifen to treat postmenopausal breast carcinoma patients as an adjunct to primary surgery is well established. The current study reports the long term results for a low risk stratum in a randomized trial of adjuvant tamoxifen. The main focus of this analysis was to determine whether tamoxifen would result in a reduced local failure rate for lymph node negative, postmenopausal patients treated with breast-conserving surgery and postoperative radiotherapy. METHODS: The study population included 432 lymph node negative, postmenopausal patients with invasive breast carcinoma (classified as T1-T2) who underwent breast-conserving surgery followed by radiotherapy in Stockholm during the period 1976-1990. The patients constituted a separate stratum of the Stockholm Adjuvant Tamoxifen Trial, which included a total of 2729 patients. Of 432 patients, 213 received 40 mg of tamoxifen daily for either 2 or 5 years. The median follow-up time was 8 years (range, 5-19 years). RESULTS: At 10 years, the overall survival was 90% for the tamoxifen group and 88% for the control group. The event free survival at 10 years was 80% for the tamoxifen group and 70% for the control group (P=0.03). Tamoxifen reduced the overall rate of ipsilateral (hazard ratio=0.4, 95% confidence interval [CI]=0.2-0.9, P=0.02) and contralateral breast tumor recurrences (hazard ratio=0.4, 95% CI=0.1-1.1, P=0.06). Trends toward a reduced number of distant metastases (hazard ratio=0.6, 95% CI=0.3-1.2, P=0.1) and deaths due to breast carcinoma (hazard ratio=0.5, 95% CI=0.2-1.2, P=0.1) also were observed. CONCLUSIONS. The addition of tamoxifen to radiotherapy for postmenopausal, lymph node negative breast carcinoma patients treated with breast-conserving surgery resulted in a reduced rate of ipsilateral and contralateral breast tumor recurrences. The avoidance of salvage mastectomies, reexcisions, and new contralateral malignancies justifies the use of tamoxifen even in the treatment of patients with a 10-year survival rate of 90%.     

Poorer survival of nulliparous women with endometrial carcinoma

BACKGROUND: Several epidemiologic studies have shown an inverse relationship between parity and the incidence of endometrial carcinoma. A prognostic influence of reproductive factors has been reported for carcinomas of the breast and uterine cervix; but no such independent influence has been reported for endometrial carcinoma, to the authors' knowledge. Therefore, the authors investigated the prognostic importance of parity in an unselected group of patients. METHODS: Clinical and histopathologic data on all 316 patients treated for endometrial carcinoma during the period 1981-1990 in Hordaland County, Norway, were related to cause specific death in univariate (Kaplan-Meier) and multivariate (Cox proportional hazards regression model) analyses. The median follow-up for the survivors was 9 years (range, 4-16 years). No patients were lost due to insufficient follow-up information. RESULTS: Nulliparous women had a poorer 5-year survival rate compared with patients who had had 1 or more deliveries (57% vs. 81%, P = 0.0001), and they were significantly older and had more advanced disease at the time of primary surgery than the parous women. After adjustment for traditional risk factors, a hazard ratio of 2.81 (95% confidence interval, 1.55-5.06) was found for nulliparous versus parous women. International Federation of Gynecology and Obstetrics stage, curative treatment, and tumor differentiation grade were also identified as independent prognostic factors, whereas age and menopausal status had prognostic significance in the univariate analysis only. CONCLUSIONS: The decreased survival among nulliparous women reported herein may reflect biologic differences between parous and nulliparous endometrial carcinoma patients. It may also be due in part to a greater delay in diagnosing the women in the nulliparous group.     

Angiogenesis as a predictor of long-term survival for patients with node-negative breast cancer

BACKGROUND: Angiogenesis (the formation of new blood vessels) is necessary for tumor growth and metastasis. PURPOSE: We investigated whether angiogenesis as measured by microvessel count (MVC) predicts clinical outcome in a series of patients with axillary lymph node-negative breast cancer who received no adjuvant therapy and who were followed for a long period of time. Our long-term goal is to identify those patients who may or may not need adjuvant chemotherapy. METHODS: Pathologic archival material and clinical information were analyzed for 167 patients treated with mastectomy from 1941 through 1987; none received adjuvant treatment. The median follow-up time among living patients was 15.4 years (range, 2.6-35.8 years). Ninety-six (58%) patients had a tumor size of 2 cm or less, 52 (31%) had tumors of 2.1-3 cm, and 19 (11%) had tumors of larger than 3 cm. Paraffin-embedded tissue sections were stained for expression of CD34 antigen on microvessel-associated endothelial cells by use of a monoclonal anti-CD34 antibody. Vascularity was defined as the number of microvessels (average of the three highest counts) per high-power microscopic field (400 x magnification) in the area of highest vascular density. A high vascular count was defined as 15 or more microvessels per field. Actuarial survival curves were calculated according to the Kaplan-Meier method and comparisons were made with the logrank test. The Cox proportional hazards model was used for multivariate analysis. All P values were based on two-sided testing. RESULTS: The 20-year disease-free survival (DFS) for the 167 node-negative patients treated with mastectomy and no adjuvant therapy was 74.8% (95% confidence interval [CI] = 64.7%-82.0%). The 20-year DFS was 93.1% (95% CI = 79.9%-97.7%) if the MVC was low versus 68.9% (95% CI = 56.8%-78.0%) if the MVC was high (P = .018). This difference was maintained irrespective of tumor size: for tumor size of 2 cm or less (93.3% [95% CI = 75.3%-98.3%] versus versus 67.8% [95% CI = 50.1%-80.3%]) and for tumor size of larger than 2 cm (92.3% [95% CI = 56.6%-98.9%] versus 70.9% [95% CI = 54.6%-81.6%]). However, the likelihood of a high MVC was greater with large tumors (P = .05). The proportions of tumors with low and high MVC were 33% and 67%, respectively, if the tumor size was 2 cm or less, and 20% and 80%, respectively, if tumor size was larger than 2 cm. There was no significant difference in the 20-year DFS as a function of tumor grade (P = .2). After combining patients with tumors of nuclear grades 2 and 3 compared with those of nuclear grade 1, the 20-year DFS was 93.9% (95% CI = 77.2%-98.4%) for low MVC versus 66.9% (95% CI = 52.2%-78.0%) for high MVC (P = .02). In a multivariate analysis that included the variables tumor size, age, nuclear grade, estrogen receptor status, and MVC, only MVC appeared to be an independent prognostic indicator (P = .04). CONCLUSIONS: Angiogenesis as measured by MVC is a reliable independent prognostic marker of long-term survival in patients with node-negative breast cancer. The prognostic usefulness of this marker is maintained after more than 15 years of follow-up. A low MVC identifies a subgroup of patients with DFS of 92% or more, independent of tumor size or grade.     

病例对照Meta分析显示男性乳腺癌与女性乳腺癌预后相同

Objective: Male breast cancer (MBC) is a rare disease, and studies to compare the prognosis between the MBC and female breast cancer (FBC) available now were case-control studies and population-based studies, however, with controversial outcomes. To further investigate whether sex affects the prognosis of breast cancer, we performed a meta-analysis based on all the peered papers. Methods: The PubMed database was screened. Subsequently, the hazard ratios (HRs) for overall survival (OS) and disease special survival (DSS), were pooled using the Review Manager 5.0 package. Results: This study comprised of 254 MBC and 733 FBC patients enrolled in six case-control studies. There was no statistically significant heterogeneity among the trials for either outcome variable. The pooled HR showed that there was no significant difference in 5-year or 10-year DSS (HR: 1.25, 95% CI: 0.76-2.08; HR: 1.04, 95% CI: 0.66-1.59) and 5-year or 10-year OS (HR: 0.76, 95%CI: 0.51-1.14; HR: 0.74, 95% CI: 0.54-1.02) between MBCs and FBCs. Conclusion: MBC and FBC with similar prognosis are found in this meta-analysis based on only case-control studies which matched main potential prognostic factors such as age, clinical stage, and time at diagnosis.     

Clinical significance of cyclin D1 expression in patients with node-positive breast carcinoma treated with adjuvant therapy

BACKGROUND: Experimental and clinical studies suggest that cyclin D1 is involved in transformation and tumour progression. However, there is little and contradictory data on the clinical significance of cyclin D1 in human invasive breast carcinoma. PATIENTS AND METHODS: We investigated whether the determination of cyclin D1 has prognostic value in a series of 180 patients with node-positive breast carcinoma and treated with adjuvant therapy with a median follow-up exceeding 6 years. We assessed cyclin D1 expression using the CDS-6 monoclonal antibody and a highly sensitive immunohistochemical technique. RESULTS: We found that most of the evaluable tumours (117 of 167; 70.1%) presented nuclear cyclin D1 staining and that its expression was significantly associated with both the hormone receptors (P = 0.009 and P = 0.005 for ER and PgR, respectively). Furthermore, 29 (17%) of 167 tumours had a weak (15 cases) or strong (9 cases) cytoplasmic cyclin D1 staining. In a subgroup of cases we also studied the amplification of the cyclin D1 gene and a moderate agreement between cyclin D1 nuclear overexpression assessed immunohistochemically and the gene amplification was found. In univariate analysis, cyclin D1 nuclear positivity was significantly associated with improved 6-year relapse-free survival (RFS) (P = 0.004), but not with overall survival (OS) (P = 0.12). The results of the Cox multivariate analysis (final model) indicate that cyclin D1 expression (P = 0.0049) as well as the number of involved nodes (P < 0.001) and tumour size (P = 0.036) are significant prognostic indicators for RFS. Only the number of involved nodes retained significance (P < 0.001) for OS in our series. The joint assessment of the variables considered in the final model of the multivariate analyses had a moderate prognostic capability as determined using the Harrell c statistic (c = 0.66 and 0.64 for RFS and OS, respectively). CONCLUSIONS: The patients with node-positive breast cancer who have a higher likelihood of gaining benefit from adjuvant therapy are those with tumours with cyclin D1 nuclear expression, small size and less than 3 metastatic nodes. Further studies are needed to verify the prognostic value of cyclin D1 in relation to different adjuvant treatments and to deepen the biological pathways that regulate its activation/ suppression in human breast carcinoma.     

Sensitization of olfactory guanylyl cyclase to a specific imprinted odorant in coho salmon

PURPOSE: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. METHODS AND MATERIALS: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. RESULTS: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). CONCLUSION: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and may improve overall survival in certain subgroups. As salvage rates after developing local recurrence are poor adjuvant vulvar radiation should be considered for patients at risk after primary surgery.     

A theory of 4-stage therapy in psychiatric acute care--from the scene of hard emergency care

In a retrospective cohort study of 262 premenopausal breast cancer patients treated at the Mayo Clinic between 1965 and 1985, we investigated whether survival was associated with the timing of tumor removal during the menstrual cycle. Participants were women < or = 50 years old who had not used exogenous hormones, been pregnant, been lactating, or given birth within 6 months of diagnosis. The menstrual cycle day at surgery was used to assign women to group 1 (cycle days 0-7), group 2 (cycle days 8-15), or group 3 (after cycle day 15). Cox proportional hazards analysis adjusting for age at diagnosis, stage, tumor size, grade, and node involvement showed a nonsignificantly worse survival for group 2 than for group 3 [hazard ratio (HR), 1.41; 95% confidence interval (CI), 0.89-2.23]. Stratification revealed that the association between survival and timing of tumor removal during the menstrual cycle was slightly stronger among patients with stage II disease (adjusted HR, 1.56; 95% CI, 0.92-2.63). The association was the same among patients with stage II disease and node involvement (adjusted HR, 1.57; 95% CI, 0.82-3.03). Prospective studies using hormone measurements to define menstrual cycle status more accurately than the reported day of the menstrual cycle could provide further insight about the postulated association.     

Results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with standard dose doxorubicin-containing chemotherapy: a reference

BACKGROUND: The authors report results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with doxorubicin-containing combination chemotherapy at a single institution; this report is meant to serve as a reliable reference for single-arm studies of newer therapies in this patient population. METHODS: Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast carcinoma were evaluated. RESULTS: The response rate was 65.0% (95% confidence interval [CI]: 62.5-67.3%), complete response (CR) rate was 16.6% (95% CI: 14.8-18.6%), and partial response (PR) rate was 48.5% (95% CI: 46.0-50.9%). Median progression free survival (PFS) was 11.5 months (95% CI: 10.9-12.3 months) and median overall survival (OS) was 21.3 months (95% CI: 20.3-22.7 months). Survival correlated with response to therapy; median PFS and OS were 22.4 and 41.8 months, respectively, for the patients who achieved CR (n=263) and 14 and 24.6 months, respectively, for PR patients (n=766). The median OS of patients who had progressive disease during chemotherapy was 3.8 months. The response rate, PFS and OS correlated with number of organs involved and especially with tumor burden. Patients with hormone receptor-positive tumors had a similar response rate to that of patients with hormone receptor negative tumors but had significantly longer PFS (medians of 14.3 and 8.7 months, respectively) and OS (medians of 28.6 and 18.1 months, respectively). CONCLUSIONS: In patients with metastatic breast carcinoma, doxorubicin-containing chemotherapy had a response rate of 65% and a CR rate of 16.6%. PFS and OS were 11.5 months and 21.3 months, respectively, for all responders and 22.4 months and 41.8 months, respectively, for those who had CR.     

Pathogenesis of Babesia caballi infection in experimental horses

OBJECTIVE: The spread of nosocomial multiresistant microorganisms is affected by compliance with infection control measures and antibiotic use. We hypothesized that "colonization pressure" (ie, the proportion of other patients colonized) also is an important variable. We studied the effect of colonization pressure, compliance with infection control measures, antibiotic use, and other previously identified risk factors on acquisition of colonization with vancomycin-resistant enterococci (VRE). METHODS: Rectal colonization was studied daily for 19 weeks in 181 consecutive patients who were admitted to a single medical intensive care unit. A statistical model was created using a Cox proportional hazards regression model including length of stay in the medical intensive care unit until acquisition of VRE, colonization pressure, personnel compliance with infection control measures (hand washing and glove use), APACHE (Acute Physiology and Chronic Health Evaluation) 11 scores, and the proportion of days that a patient received vancomycin or third-generation cephalosporins, sucralfate, and enteral feeding. RESULTS: With survival until colonization with VRE as the end point, colonization pressure was the most important variable affecting acquisition of VRE (hazard ratio [HR], 1.032; 95% confidence interval [C1], 1.012-1.052; P=.002). In addition, enteral feeding was associated with acquisition of VRE (HR, 1.009; 95% CI, 1.000-1.017; P=.05), and there was a trend toward association of third-generation cephalosporin use with acquisition (HR, 1.007; 95% CI, 0.999-1.015; P=.11). The effects of enteral feeding and third-generation cephalosporin use were more important when colonization pressure was less than 50%. Once colonization pressure was 50% or higher, these other variables hardly affected acquisition of VRE. CONCLUSIONS: Acquisition of VRE was affected by colonization pressure, the use of antibiotics, and the use of enteral feeding. However, once colonization pressure was high, it became the major variable affecting acquisition of VRE.     

Treatment-related leukemia in breast cancer patients treated with fluorouracil-doxorubicin-cyclophosphamide combination adjuvant chemotherapy: the University of Texas M.D. Anderson Cancer Center experience

PURPOSE: Adjuvant chemotherapy for breast cancer has been the routine practice in the past decade. A number of studies have observed an increased incidence of treatment-related leukemias following chemotherapy with alkylating agents and/or topoisomerase II inhibitors. We evaluated the incidence of treatment-related leukemias in breast cancer patients treated in four adjuvant and two neoadjuvant chemotherapy trials at The University of Texas M.D. Anderson Cancer Center. PATIENTS AND METHODS: Between 1974 and 1989, 1,474 patients with stage II or III breast cancer were treated in six prospective trials of adjuvant (n = 4) or neoadjuvant (n = 2) chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (CTX) (FAC) with or without other drugs. The median observation time was 97 months. In 1,107 patients, FAC chemotherapy was given postoperatively; 367 patients received induction chemotherapy, as well as postoperative chemotherapy. Eight hundred ten patients had surgery followed by radiotherapy and chemotherapy; 664 patients had surgery and chemotherapy only. Patients in two adjuvant and one neoadjuvant study received higher cumulative doses of CTX compared with those in the other studies. RESULTS: Fourteen cases of leukemia were observed. Twelve of these patients had received radiotherapy and chemotherapy, and two had received chemotherapy only. Six of the reported patients with leukemia were treated with a cumulative CTX dose of greater than 6 g/ m2. Five of these patients had received both radiotherapy and chemotherapy. The median latency period in the 14 patients was 66 months (range, 22 to 113). Six of 10 patients with adequate cytogenetic analyses had abnormalities that involved chromosomes 5 and/or 7. The rest of the patients had nonspecific cytogenetic abnormalities or lacked cytogenetic information. The 10-year estimated leukemia rate was 1.5% (95% confidence interval [CI], 0.7% to 2.9%) for all patients treated, 2.5% (95% CI, 1.0% to 5.1%) for the radiotherapy-plus-chemotherapy group, and 0.5% (95% CI, 0.1% to 2.4%) for the chemotherapy-only group; this difference was statistically significant (P = .01). The 10-year estimated leukemia risk for the higher-dose (> 6 g/m2) CTX group was 2% (95% CI, 0.5% to 5.0%) compared with 1.3% (95% CI, 0.4% to 3.0%) for the lower-dose group, a difference that was not statistically significant (P = .53). CONCLUSION: These data illustrate that patients treated with adjuvant FAC chemotherapy plus radiotherapy have a slightly increased risk of leukemia. This information needs to be considered in the treatment plans for patients with breast cancer. However, for most patients, the benefits of adjuvant therapy exceed the risk of treatment-related leukemia.     

High risk of breast carcinoma after irradiation of young women with Hodgkin's disease

BACKGROUND: Treatment-associated second neoplasms have emerged as a major threat to the continued survival of patients cured of Hodgkin's disease. In this study, the authors investigated the risk of breast carcinoma in an irradiated Hodgkin's disease population. METHODS: One hundred and eleven women younger than 60 years presenting between 1964 and 1984 with Stage I and II Hodgkin's disease who received mantle irradiation were retrospectively analyzed and compared with an age specific population. Median follow-up was 18 years (range, 10-30 years), and the median age at initiation of therapy was 24 years. Kaplan-Meier actuarial risks, relative risks (RRs) (the ratio of the observed to the expected cases) with 95% confidence intervals (CIs), and the log rank test for trends were calculated. RESULTS: Fourteen women developed breast carcinoma: 8 of 33 patients younger than 20 years at the time of irradiation, 5 of 48 patients age 20 to 29 years, and 1 of 30 patients age 30 years or older. Actuarial calculation predicted a 34.0% (CI, 14.2-53.8) risk of breast carcinoma at 25 years after therapy for the youngest group, 22.3% (CI, 4.1-40.5) for the group of intermediate age, and 3.5% (CI, 0-10.1) for the oldest group. The RR of breast carcinoma was 56 (CI, 23.3-107) for those 19 years or younger at the time of treatment, 7.0 (CI, 2.3-16.4) for those age 20-29 years, and 0.9 (CI, 0-5.3) for those 30 years and older. Excluding 1 patient who was age 38 years at the time of irradiation, the remaining 13 breast carcinomas were tightly clustered in women irradiated between the ages of 14 through 25, and were detected in years 11 through 25 after treatment, with 7 occurring in years 15 through 18. CONCLUSIONS: Women younger than 30 years, particularly those younger than 20 years, who have received mantle irradiation for Hodgkin's disease require meticulous follow-up for breast carcinoma. The high incidence of breast carcinoma in this patient population should be considered when making treatment decisions in young women with early stage Hodgkin's disease.     

Egg components and hatchling lipid reserves: parental investment in kinosternid turtles from the southeastern United States

PURPOSE: Identification of prognostic factors in patients with malignant pleural mesothelioma based on prospectively collected international data. PATIENTS AND METHODS: From October 1984 to October 1993, 204 eligible adult patients with malignant pleural mesothelioma were entered into five consecutive prospective European Organization for Research and Treatment of Cancer (EORTC) phase II clinical trials designed to assess the efficacy of various anticancer drugs (mitoxantrone, epidoxorubicin, etoposide, and paclitaxel). The Cox model was used to assess 13 factors related to biology and disease history with respect to survival. RESULTS: The median survival duration was 12.6 months from diagnosis and 8.4 months from trial entry. In the multivariate analysis, poor prognosis was associated with a poor performance status, a high WBC count, a probable/possible histologic diagnosis of mesothelioma, male gender, and having sarcomatous tissue as the histologic subtype. Taking these five factors into consideration, patients were classified into two groups: a good-prognosis group (1-year survival rate, 40%; 95% confidence interval [CI], 30% to 50%) and a poor-prognosis group (1-year survival, 12%; 95% CI, 4% to 20%). CONCLUSION: These results may help to design new clinical trials in pleural mesothelioma by selecting more homogenous groups of patients.     

Expression of c-met is a strong independent prognostic factor in breast carcinoma

BACKGROUND: The c-met protooncogene encodes the met protein, the receptor for scatter factor/hepatocyte growth factor, a growth factor that modulates the motility and stable interaction of the epithelial cells. This study assesses the expression of met receptor in breast carcinoma and its prognostic value with respect to survival. METHODS: Immunofluorescence was used to evaluate 91 archival breast carcinoma specimens using a polyclonal antibody to the cytoplasmic domain of the receptor. Cases were scored by two pathologists on a percentage basis and then converted to binary scores (positive or negative) on the basis of a bimodal distribution. RESULTS: Strong expression of met was found in 20 invasive ductal breast tumor specimens (22%). The 5-year survival of patients whose tumors showed decreased met expression was 89%, in contrast to a 52% 5-year survival rate in patients whose tumors expressed met (P = 0.008). This trend also was observed in patients without lymph node metastases at presentation, in whom met negative patients had a 95% 5-year survival compared with only 62% for met positive patients (P = 0.006) Multivariate analysis using the Cox proportional hazards model showed met expression to be an independent predictor of survival, with a predictive value nearly equivalent to that associated with lymph node status. CONCLUSIONS: The authors conclude that expression of met in patients with invasive ductal carcinoma of the breast is a strong, independent predictor of decreased survival and may be a useful prognostic marker with which to identify a subset of patients with more aggressive disease.     

Influence of socioeconomic and cultural factors on racial differences in late-stage presentation of breast cancer

CONTEXT: Breast cancer mortality is higher among African American women than among white women in the United States, but the reasons for the racial difference are not known. OBJECTIVE: To evaluate the influence of socioeconomic and cultural factors on the racial difference in breast cancer stage at diagnosis. DESIGN: Case-control study of patients diagnosed as having breast cancer at the University Medical Center of Eastern Carolina from 1985 through 1992. SETTING: The major health care facility for 2 rural counties in eastern North Carolina. SUBJECTS: Five hundred forty of 743 patients with newly diagnosed breast cancer and 414 control women from the community matched by age, race, and area of residence. MAIN OUTCOME MEASURES: Breast cancer stage at diagnosis. RESULTS: Of the 540 patients, 94 (17.4%) presented with TNM stage III or IV disease. The following demographic and socioeconomic factors were significant predictors of advanced stage: being African American (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.9-4.7); having low income (OR, 3.7; 95% CI, 2.1-6.5); never having been married (OR, 2.9; 95% CI, 1.4-5.9); having no private health insurance (OR, 2.5; 95% CI, 1.6-4.0); delaying seeing a physician because of money (OR, 1.6; 95% CI, 1.1-2.5); or lacking transportation (OR, 2.0; 95% CI, 1.2-3.6). Univariate analysis also revealed a large number of cultural beliefs to be significant predictors. Examples include the following beliefs: air causes a cancer to spread (OR, 2.8; 95% CI, 1.8-4.3); the devil can cause a person to get cancer (OR, 2.1; 95% CI, 1.2-3.5); women who have breast surgery are no longer attractive to men (OR, 1.9; 95% CI, 1.1-3.5); and chiropractic is an effective treatment for breast cancer (OR, 2.4; 95% CI, 1.4-4.4). When the demographic and socioeconomic variables were included in a multivariate logistic regression model, the OR for late stage among African Americans decreased to 1.8 (95% CI, 1.1 -3.2) compared with 3.0 (95% CI, 1.9-4.7) for race alone. However, when the belief measures were included with the demographic and socioeconomic variables, the OR for late stage among African Americans decreased further to 1.2 (95% CI, 0.6-2.5). CONCLUSIONS: Socioeconomic factors alone were not sufficient to explain the dramatic effect of race on breast cancer stage; however, socioeconomic variables in conjunction with cultural beliefs and attitudes could largely account for the observed effect.     

Long term prognosis after hepatectomy for hepatocellular carcinoma: a survival analysis of 204 consecutive patients

BACKGROUND: Intrahepatic recurrence continues to be the main cause of late death among hepatocellular carcinoma patients after hepatic resection. The aims of the current study were to identify the prognostic factors affecting long term survival and to evaluate the clinical value of pTNM classification as a prognostic factor for these patients. The identification of significant prognostic factors plays an important role in the selection of patients for postoperative adjuvant therapy and counseling. METHODS: From January 1989 to August 1995, 204 consecutive patients underwent hepatectomy for hepatocellular carcinoma. The overall cumulative and disease free survival rates for these patients were analyzed. Univariate and multivariate analyses of 16 clinicopathologic factors, including factors associated with pTNM classification, were performed to determine the significant prognostic factors. RESULTS: The median periods of overall cumulative survival and disease free survival were 35 months and 12.4 months, respectively. By univariate analysis, all factors associated with tumor (T) classification, namely, tumor size, vascular invasion, the number of tumor nodules, and tumor localization, were correlated with survival. By Cox regression analysis, preoperative indocyanine green retention value at 15 minutes, tumor size, and number of tumor nodules were independent prognostic factors of long term survival, whereas the number of tumor nodules, tumor size, and venous permeation were the most powerful predictors of tumor recurrence. The cumulative 5-year survival rates for patients with Stages I, II, III, and IVA tumors were 72%, 55%, 34%, and 8%, respectively. Significant differences in cumulative survival curves were observed among the categories of pTNM classification. CONCLUSIONS: The results of this study showed that pTNM classification correlated well with postoperative survival. Preoperative evaluation of hepatic functional reserve with an indocyanine green clearance test plays an important role in determining the long term prognoses of patients with hepatocellular carcinoma.     

A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group

BACKGROUND: Interferon alfa is a conservative and widely used alternative to bone marrow transplantation in treatment of patients with early chronic myeloid leukemia (CML). A meta-analysis was conducted to develop a reliable prognostic scoring system for estimation of survival of patients with CML treated with interferon alfa. METHODS: Patients treated in prospective studies, including major randomized trials, were separated into learning and validation samples. Cox regression analysis and the minimum P-value approach were used to identify prognostic factors for patient survival and to discover groups in the learning sample with the greatest differences in survival. These findings were then validated by applying the new scoring system to patients in the validation sample. RESULTS: We collected data on 1573 patients who were participants in 14 studies involving 12 institutions; 1303 patients (learning sample, n = 981; validation sample, n = 322) were eligible for inclusion in this analysis, and their median survival time was 69 months (range, 1-117 months). Because two previously described prognostic scoring systems failed to discriminate risk groups satisfactorily, we developed a new scoring system that utilizes the following covariates: age, spleen size, blast count, platelet count, eosinophil count, and basophil count. Among 908 patients with complete data in the learning sample, three distinct risk groups were identified (median survival times of 98 months [n = 369; 40.6%], 65 months [n = 406; 44.7%], or 42 months [n = 133;14.6%]; two-sided logrank test, P< or =.0001). The ability of the new scoring system to discriminate these risk groups was confirmed by analysis of 285 patients with complete data in the validation sample (two-sided logrank test, P = .0002). CONCLUSIONS: A new prognostic scoring system for estimating survival of patients with CML treated with interferon alfa has been developed and validated through use of a large dataset.     

Prognostic features and treatment outcome in locoregionally advanced nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy

PURPOSE: Concurrent chemotherapy and radiotherapy (CCRT) are effective in treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the prognostic factors after CCRT have not been evaluated. We therefore attempt to evaluate factors that influence treatment outcomes following CCRT. METHODS AND MATERIALS: Seventy-four (5 in stage III and 69 in stage IV) patients with locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5-fluorouracil. Cox proportional-hazards model was used to analyze the prognostic factors which included age, gender, pathologic type, T, N, lactate dehydrogenase (LDH), and infiltration of the clivus. RESULTS: The primary tumor control rate at 3 years was 96.7% (95% confidence interval [CI]: 92.5-100), distant metastasis-free survival 81.1% (95% CI: 70.6-91.6), disease-free survival 77.0% (95% CI: 65.3-88.7), and overall survival 79.8% (95% CI: 69.2-90.4) with a median follow-up interval of 29 months (range 15-74 months). Cox proportional-hazards model revealed that infiltration of the clivus and serum level of LDH before treatment were the most two important factors that predict distant metastases. Infiltration of the clivus and the serum LDH level greater than 410 U/L were strongly associated with distant metastasis-free survival (p = 0.0004 and p = 0.0002, respectively). When these two risk factors were considered together, no distant metastasis was observed in 40 patients with both intact clivus and LDH < or = 410 U/L. On the contrary, 13 of the remaining 34 patients with at least one risk factor developed distant metastasis (p = 0.0001). CONCLUSION: Our study demonstrates that CCRT can improve the primary tumor control of 96.7% and disease-free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the major cause of failure. Infiltration of the clivus by the tumor and LDH greater than 410 U/L are the two independent and useful prognostic factors in patients with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk patients can be distinguished by virtue of their having both conditions.     

Relationship between cleaved L-selectin levels and the outcome of acute myeloid leukemia

High plasma levels of the shed form of L-selectin (sL-selectin) are frequently detectable in acute myeloid leukemia (AML). sL-selectin can inhibit blast cell adhesion to vascular endothelium and may thereby influence the phenotype of AML. In this study, we have investigated the relationship between sL-selectin levels and clinical presentation or disease outcome in 100 patients with AML. Fifty-eight patients were found to have sL-selectin levels >/=3.12 microgram/mL (>/=3 SD above the mean of healthy controls: "increased"). Patients with extramedullary disease such as lymphadenopathies, splenomegaly, hepatomegaly, and/or muco-cutaneous infiltration had significantly increased sL-selectin levels (P < .001). sL-selectin levels were significantly heterogeneous in the French-American-British subtypes (P = .0003). Patients with "normal" sL-selectin levels had higher probability of achieving complete remission (CR) than with "increased" levels: 81% versus 64%, respectively (P = .06). When adjusting for clinically relevant covariates predictive for CR (sex, age, Auer rods), "normal" sL-selectin levels were significantly associated with CR (odds ratio, 3.08; 95% confidence interval [CI], 1.10 to 8.58; P = .03). Moreover, patients with "increased" sL-selectin levels (>/=3.12 microgram/mL) had shorter event-free survival (EFS) (median 7.3 v 12 months, P = .008) and overall survival (median 1 v 2.05 years, P = .03) than patients with sL-selectin <3.12 microgram/mL. Multivariate statistical analysis (adjusted for age and presence of Auer rods) indicated that sL-selectin was an independent prognostic factor for EFS (hazard ratio [HR], 1.96; 95% CI, 1.21 to 3.17, P = .006) and overall survival (HR, 1.80; 95% CI, 1.09 to 2.98; P = .02). Thus, plasma sL-selectin may be a useful prognostic marker in the evaluation of AML at diagnosis.