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A prognostic-factor risk index in advanced non-small-cell lung cancer treated with cisplatin-containing combination chemotherapy.

Prognostic factors for response and survival were retrospectively evaluated in 192 previously untreated patients with advanced non-small-cell lung cancer (NSCLC) who had received either vindesine plus cisplatin or mitomycin plus vindesine plus cisplatin as initial treatment. Univariate analysis demonstrated that squamous-cell histology, early stage, and a small number of metastatic sites were favorable prognostic factors for response to chemotherapy. Multivariate analysis using Cox's proportional hazard model indicated that the number of metastatic sites was the only significant pretreatment factor for response (P = 0.0005). Multivariate regression analysis revealed that the number of metastatic sites (P = 0.0002), sex (P = 0.0009), serum albumen levels (P = 0.0018), performance status (P = 0.0026) and lactic dehydrogenase values (P = 0.0026) contributed independently to survival. On the basis of these five prognostic factors, a prognostic index for survival was used to define three prognostic groupings (good, intermediate, and poor) for survival (median survival, 16.5 vs 9.4 vs 4.6 months; P = 0.0001). This particular regression model should aid in the design and analysis of new treatment strategies and may be useful for indirect comparisons of different studies carried out in similar patient populations.

Adenocarcinoma↗

VAB-5 combination chemotherapy in prognostically poor risk patients with germ cell tumors.

Forty-four patients with nonseminomatous germ cell tumors with "poor prognostic features" were entered on the VAB-5 regimen and 38 are evaluable. VAB-5 represents an intensified version of the VAB-4 protocol. Poor prognostic features were considered to be bulky metastases ( greater than 5 cm in diameter), palpable retroperitoneal disease, liver metastases, brain metastases, involvement of two or more parenchymal organs, pure choriocarcinoma, alpha fetoprotein or human chorionic gonadotropin serum levels over 1000 ng/ml, lactic acid dehydrogenase serum levels over 400 mg/dl, and failure to prior chemotherapy. Eighteen of 38 evaluable patients became free of neoplasm, 11 with chemotherapy alone, and seven with combined chemotherapy and surgery. Fourteen of 18 complete responders remain alive and free of disease with a median follow-up of 50 months. Complete remission with testis tumor occurred in 13/15 without and 5/15 with prior chemotherapy and in none of eight patients with primary extragonadal germ cell tumors. Thirty-one patients received antibiotics when they developed fever during myelosuppression. Ten patients developed transient serum creatinine levels over 2 mg/dl after cis-platinum and one required hemodialysis with subsequent recovery. All patients had severe mucositis after induction. An apparent improvement of results over prior VAB protocols in patients with poor prognostic features was compromised by significant increases in toxicity and such patients require special study to improve cure rates.

Antineoplastic Agents↗

[Characteristics of hospitalized geriatric patients--a comparison of two cohorts using the screening of the Arbeitsgemeinschaft Geriatrisches Basisassessment (AGAST)].

The geriatric screening according to AGAST (Arbeitsgruppe Geriatrisches Basisassessment) contains functional and diagnosis related items, and risk indicators of prognostic relevance, particularly in hospitalized patients. In a retrospective, cohort study, we compared the screening results in 250 consecutive patients of geriatric in-hospital acute care, and 250 consecutive patients of geriatric in-hospital rehabilitation, as well as demographic characteristics, diagnoses, and functional status as measured by the Barthel index. There was a trend indicating the total number of positive screening findings being higher with older age. Positive correlations with age were found for hearing, leg function, and cognitive function in female patients. There were also associations between the frequencies of certain screening findings with diagnostic categories. Apart from the different official manner of admission to geriatric acute care or geriatric rehabilitation, there were differences between the cohorts in age, living place before hospitalization, discharge location, spectrum of diagnoses, and the degree of functional impairment. The screening results indicated that prognostic risk factors were not equally distributed among the study cohorts. These were, in particular, urinary incontinence, poor nutritional status, impaired cognitive function, and depressive mood. There were associations between risk frequency as indicated by the screening and complicated hospital stay, functional outcome, and death. Combined with additional data, the screening according to AGAST appears to be suitable for meaningful comparisons of different groups of geriatric patients.

Age Factors↗

Risk and prognostic factors in trophoblastic neoplasia.

Three hundred and seventeen patients with gestational trophoblastic tumors were investigated and treated between 1957-1973. The risk of trophoblastic tumor was influenced by the outcome of the antecedent pregnancy (hydatidiform mole, non-mole abortion, term delivery) and the ABO blood groups of the mating couple; it was also influenced by the patient's age. The response to treatment with chemotherapy and , where appropriate, with surgery and radiotherapy, was influenced prfoundly by several factors. These included 1) the outcome of the antecedent pregnancy, 2) the total body burden of tumor at the time treatment stated as reflected by the urinary output of human chorionic gonadotrophin (CG), 3) the interval between the antecedent pregnancy and the start of chemotherapy, 4) the ABO groups of the mating couple, 5) the extent of mononuclear cell infiltration in the tumor, 6) the immunological status of the patient at the start of treatment, 7) the size of tumor masses, 8) the site of metastases and particularly the presence of intracranial metastases, and possibly by 9) the age and 10) the parity of the patient. A detailed study of the HLA antigens of the patient, her husband, and antecedent child has shown no positive effect on risk or prognosis. These data provide a basis for a scoring system that allows the prognosis to be defined at the time of diagnosis and facilitates tisk of drug resistance. Applied retrospectively to the cases from which the scoring system was generated, prognostic groups with survival rates ranging from 0-100% can be defined. Unfavorable prognostic factors combine so as to increase the probability of drug resistance.

ABO Blood-Group System↗

[Incidence, risk and prognostic factors of pneumonia acquired at intensive care units].

OBJECTIVE: To estimate the incidence of pneumonia acquired in the intensive care unit, and to define risk factors for developing such an event. METHOD: A total of 158 patients were retrospectively analyzed and 108 of them acquied pneumonia at ICU of Zhongshan Hospital (surgical ICU and respiratory ICU) and Huashan Hospital (general ICU) from January 1996 to November 1997. Statistical analysis was made using SPSS, odds ratios and stepwise logistic regression analysis were used to determine the interrelationships between multiple variables. Statistical significance was predetermined to include p values of < 0.05. RESULT: The following five factors were significantly (P < 0.05) associated with HAP: cancer [OR = 6.73, 95% CI = 1.58 to 28.59], treatment with H2-blockers (OR = 5.5742, CI = 1.94 to 15.99), decreased consciousness (OR = 3.30, CI = 1.52 to 7.18), use of urethral catheters (OR = 1.07, CI = 1.01 to 1.13), and mechanical ventilation (OR = 1.05, CI = 1.00 to 1.01). The risk facors for HAP were different among different ICU. The risk of developing pneumonia increased when depressed level of consciousness and mechanical ventilation were present at general ICU. Factors significantly predisposing to HAP were underlying COPD, using H2-blockers and mechanical ventilation at respiratory ICU, and previously lower respiratory tract infection was the risk factor for HAP in surgical ICU. The following factors were associated with a significantly higher fatality rate in HAP patients: depressed level of consciousness (P = 0.02), previously lower respiratory tract infection (P = 0.001), and long-time mechanical ventilation (P = 0.03). CONCLUSION: The risk factors for HAP were different among different ICU, which may be related to the difference of patients with an ultimately or a rapidly fatal underlying illness admitted to these units.

Cross Infection↗

Risk and prognostic factors for Japanese patients with chronic graft-versus-host disease after bone marrow transplantation.

The incidence and prognostic factors for chronic graft-versus-host disease (cGVHD) were evaluated for 255 Japanese patients who survived more than 100 days after bone marrow transplantation, and of whom 119 (47%) developed cGVHD. Prior acute GVHD (grade 2-4) and use of an unrelated donor were significantly associated with the onset of cGVHD. Presence of cGVHD did not have an impact on mortality (hazard ratio (HR) = 0.89; 95% confidence interval (CI), 0.59-1.3). Three factors at diagnosis were associated with cGVHD-specific survival: presence of infection (HR = 4.1; 95% CI, 1.6-10.3), continuing use of corticosteroids at the onset of cGVHD (HR = 3.9; 95% CI, 1.7-9.1), and a Karnofsky performance score <80 (HR = 4.7; 95% CI, 2.0-11.3). The probability of cGVHD-specific survival at 4 years was 79% (95% CI, 70-86%). The severity and death rate of Japanese patients with cGVHD was lower than those for populations in Western countries, which might be the result of greater genetic homogeneity of Japanese ethnics. Our patients could not be accurately classified when the proposed prognostic models from Western countries were used, thus indicating the need for a different model to identify high-risk patients.

Adolescent↗

Thrombocytopenia in sepsis: a predictor of mortality in the intensive care unit.

Disseminated intravascular coagulation (DIC) and thrombocytopenia are well-known complications of sepsis, but the relationship between these coagulation abnormalities and outcome have not been well documented. We studied the incidence of thrombocytopenia and DIC in our Medical Intensive Care Unit, and evaluated their usefulness as prognostic risk factors for mortality. Platelet count was not found to be an independent risk factor associated with overall mortality in the 107 patients studied. In the sub-group of 53 patients with sepsis, 22 (42%) developed DIC, 31 (58%) developed thrombocytopenia (< 150,000 x 10(9)/L) and 27 (51%) died. Thrombocytopenia was associated with presence of DIC (p = 0.003), but not with the type of infecting organism. The platelet count in non-survivors (mean +/- sem, 97 +/- 18 x 10(9)/L) was significantly lower than survivors (194 +/- 27 x 10(9)/L, p < 0.005). Multiple regression analysis showed that thrombocytopenia was a risk factor for mortality, independent of the APACHE II score. The presence of DIC surprisingly was not an independent risk factor. We conclude that DIC and thrombocytopenia are common in our adult Medical Intensive Care patients with sepsis, but only the latter is a prognostic factor in addition to the APACHE II score. The incidence of DIC in our patients (mainly Chinese) seems to be more than that of 10 to 20% reported in other series of Caucasian patients. We would, therefore, like to emphasise the importance of platelet count as an prognostic risk factor in sepsis.

Adolescent↗

A population-based study of 518 very preterm neonates from high-risk pregnancies: prognostic value of umbilical and cerebral artery Doppler velocimetry for mortality before discharge and severe neurological morbidity.

OBJECTIVE: To evaluate in everyday practice the predictiveness of fetal umbilical artery and cerebral artery Doppler examination for mortality before discharge and for severe neurological morbidity among very preterm neonates from high-risk pregnancies. METHODS: Data came from a population-based study (EPIPAGE) of all births before 33 weeks' gestation during 1 year in nine French regions. We examined the prognostic value of Doppler findings among the liveborn singletons delivered after pregnancies with maternal hypertension or antenatal suspicion of small-for-gestational-age status. RESULTS: This study included 518 fetuses. Predischarge mortality for infants with abnormal umbilical artery Doppler findings was not significantly higher than for those with normal findings. Mortality for infants with abnormal cerebral artery Doppler findings was significantly higher in the bivariate analysis (crude OR: 3.5 (1.6-7.4)). After adjustment, the association between mortality and abnormal cerebral artery Doppler findings remained significant in the subgroup with an abnormal umbilical artery Doppler assessment (OR: 5.1 (1.1-23)). There was no significant association between neurological morbidity and Doppler findings. CONCLUSION: The prognostic value of Doppler examinations appears lower in this study than in previous hospital series. This suggests the need for quality control and improvements in these examinations.

Adult↗

Equivalent racial outcome after conformal radiotherapy for prostate cancer: a single departmental experience.

PURPOSE: African-American (AA) men with prostate cancer present with advanced disease, relative to white (W) men. This report summarizes our clinical and biochemical control (bNED) rates after conformal radiotherapy (RT). In particular, we aim to characterize any race-based outcome differences seen after comparable treatment. PATIENTS AND METHODS: We reviewed 893 patients (418 AA and 475 W) with clinically localized prostate cancer treated between 1988 and 1997. Neoadjuvant hormonal blockade was used in 22.5% of cases, and all patients received conformal RT to a median dose of 68 Gy (range, 60 to 74.8 Gy). Biochemical failure was defined according to the American Society of Therapeutic Radiology and Oncology consensus definition. Median follow-up was 24 months (range, 1 to 114 months). RESULTS: The 5-year actuarial survival, disease-free survival, and bNED rates for the entire population were 80.5%, 70.0%, and 57.6%, respectively. When classified by prognostic risk category, the 5-year actuarial bNED rates were 78.7% for favorable, 57.7% for intermediate, and 39.8% for unfavorable category patients. AA men presented at younger ages and with more advanced disease. Controlled for prognostic risk category, AA and W men had similar 5-year actuarial bNED rates in favorable (78% v 79%, P: = .91), intermediate (52% v 62%, P: =.44), and unfavorable categories (36% v 45%, P: = .09). Race was not an independent prognostic factor (P: = .36). CONCLUSION: Conformal RT is equally effective for AA and W patients. More research is needed in order to understand and correct the advanced presentations in AA men. These data suggest a need for early screening in AA populations.

Actuarial Analysis↗

A variable risk clinical prognostic compartmental model.

A model for predicting the occurrence of disease endpoints from a knowledge of baseline variables and intermediate events is described and illustrated with numerical examples. Maximum likelihood equations are developed and maximum likelihood estimates of coefficients in risk functions of variables included in a stepwise upward procedure are applied to a small set of data for illustrative purposes.

Adult↗

Risk factor adapted treatment of Hodgkin's lymphoma: strategies and perspectives.

In a national multicenter trial in the Federal Republic of Germany, patients with Hodgkin's lymphoma in stages I, II and IIIA presenting with large mediastinal tumor (MT), extranodal (E), or massive spleen (S) involvement received a combined modality treatment with 2x (COPP + ABVD) followed by 20 or 40 Gy EF radiation (HD1 protocol). By October 1987, 89 patients aged 15-60 years had finished therapy and were evaluable for response. Of these 74 (83%) achieved complete remission (CR). After 3 years freedom from treatment failure (FFTF) is 80% (+/- 8%, 95% confidence interval) and survival (SV) 92% (+/- 6%, 95% confidence interval). In a univariate and multivariate analysis using FFTF as endpoint we could not identify any particularly prominent prognostic risk factor among the following examined: stage, constitutional symptoms, MT, E stage, S involvement, age, sex, histology, laparotomy, erythrocyte sedimentation rate (ESR), leukocytes, lymphocytes, and alkaline phosphatase (AP). These data suggest that the inclusion criteria have selected a fairly homogeneous group of patients with respect to prognosis. In a separate trial (HD3 protocol) patients in stages IIIB/IV received induction chemotherapy with 3x (COPP + ABVD). Patients in complete remission (CR) received consolidation therapy by either radiotherapy (20 Gy IF) or further chemotherapy (COPP + ABVD). Patients not in CR received salvage therapy (40Gy in the case of persisting nodal disease, or else 4x CEVD chemotherapy). By October 1987, 137 patients had finished therapy and were evaluable for response. Of these 86 (63%) achieved CR after induction chemotherapy. Including salvage therapy a total of 104 patients (76%) achieved CR. After 3 years FFTF is 56% (+/- 10%, 95% confidence interval) and SV 84% (+/- 8%, 95% confidence interval). Univariate and multivariate prognostic risk factor analyses were performed using FFTF as endpoint. Sex, age, stage, splenectomy, bone marrow, and liver and bone involvement had no prognostic impact. In contrast, a pretreatment erythrocyte sedimentation rate (ESR) above 80 mm/h and a serum alkaline phosphatase (AP) above 230 IU/ml each appeared as significant prognostic factors (P less than 0.01; relative risk, 2.3). The two parameters can be combined to separate two groups (A: ESR and AP both low; B: ESR and/or AP high) which differ significantly for FFTF (P less than 0.001) and survival (P less than 0.04). The decision for risk-adapted treatment requires identification of groups of patients in the frame of specified diagnostic and therapeutic strategies.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer.

PURPOSE: We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized prostate cancer. MATERIALS AND METHODS: Between October 1988 and December 1998, 1,100 patients with clinical stages T1c-T3 prostate cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months. RESULTS: At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] +/- 4), 58% (95% CI +/- 6) and 38% (95% CI +/- 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI +/- 8) compared to 90% (95% CI +/- 8) for those treated with 75.6 to 86.4 Gy. (p = 0.04) [corrected]. The corresponding rates were 50% (95% CI +/- 8) versus 70% (95% CI +/- 6) in intermediate risk cases (p = 0.001), and 21% (95% CI +/- 8) versus 47% (95% CI +/- 6) in unfavorable risk cases (p = 0.008) [corrected]. Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI +/- 2) compared with 5% (95% CI +/- 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI +/- 2) compared with 14% (95% CI +/- 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity. CONCLUSIONS: Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio.

Adenocarcinoma↗

The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults.

The objective of this study was to refine the APACHE (Acute Physiology, Age, Chronic Health Evaluation) methodology in order to more accurately predict hospital mortality risk for critically ill hospitalized adults. We prospectively collected data on 17,440 unselected adult medical/surgical intensive care unit (ICU) admissions at 40 US hospitals (14 volunteer tertiary-care institutions and 26 hospitals randomly chosen to represent intensive care services nationwide). We analyzed the relationship between the patient's likelihood of surviving to hospital discharge and the following predictive variables: major medical and surgical disease categories, acute physiologic abnormalities, age, preexisting functional limitations, major comorbidities, and treatment location immediately prior to ICU admission. The APACHE III prognostic system consists of two options: (1) an APACHE III score, which can provide initial risk stratification for severely ill hospitalized patients within independently defined patient groups; and (2) an APACHE III predictive equation, which uses APACHE III score and reference data on major disease categories and treatment location immediately prior to ICU admission to provide risk estimates for hospital mortality for individual ICU patients. A five-point increase in APACHE III score (range, 0 to 299) is independently associated with a statistically significant increase in the relative risk of hospital death (odds ratio, 1.10 to 1.78) within each of 78 major medical and surgical disease categories. The overall predictive accuracy of the first-day APACHE III equation was such that, within 24 h of ICU admission, 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed (r2 = 0.41; receiver operating characteristic = 0.90). Recording changes in the APACHE III score on each subsequent day of ICU therapy provided daily updates in these risk estimates. When applied across the individual ICUs, the first-day APACHE III equation accounted for the majority of variation in observed death rates (r2 = 0.90, p less than 0.0001).

Age Factors↗