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Results for “prognostic stratification”

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PubMed2001

Combined examination of p27(Kip1), p21(Waf1/Cip1) and p53 expression allows precise estimation of prognosis in patients with gastric carcinoma.

AIMS: In order to estimate the prognostic values of p27(Kip1), p21(Waf1/Cip1), and p53, alone and in combination, we investigated immunohistochemically the expression of p27(Kip1), p21(Waf1/Cip1), and p53 proteins in gastric carcinomas. METHODS AND RESULTS: The expression of p27(Kip1), p21(Waf1/Cip1), and p53 was immunohistochemically examined in 140 gastric carcinomas. Positive expression of p27(Kip1) and p21(Waf1/Cip1) correlated significantly with a favourable prognosis (P < 0.05), whereas, positive expression of p53 tended to correlate with poor prognosis. Multivariate survival analysis revealed that TNM stage of tumour (P < 0.001), lymph node state (P=0.005), and p27(Kip1) expression (P=0.006) were independent prognostic factors. A striking stratification of mortality rate was found when patients were divided into four groups according to the expression of p21(Waf1/Cip1) and p27(Kip1). The mortality rate was higher in patients with both p21(Waf1/Cip1)- and p27(Kip1)-negative gastric carcinoma than in patients with one or both positive carcinomas (P < 0.01). In addition, if the four p21(Waf1/Cip1)/p27(Kip1) groups were compared based on p53 status, p53+ cases tended to have a higher mortality rate than p53- cases. CONCLUSION: Our results suggest that low expression of both p27(Kip1) and p21(Waf1/Cip1), could be useful as markers of poorer prognosis, and the combined examination of p27(Kip1), p21(Waf1/Cip1) and p53 expression allows reliable estimation of prognosis for patients with gastric carcinoma.

Adult↗

PubMed2001

Interleukin-6 levels are inversely correlated with heart rate variability in patients with decompensated heart failure.

INTRODUCTION: Increased local and systemic elaboration of cytokines have an important role in the pathogenesis of congestive heart failure (CHF) through diverse mechanisms. Because cytokines are known to act at the neuronal level in both the peripheral and central nervous system, we sought to determine whether increased cytokine levels are associated with the autonomic dysfunction that characterizes CHF. METHODS AND RESULTS: We studied 64 patients admitted for decompensated CHF (mean age 59+/-12 years). Autonomic function was assessed using time- and frequency-domain heart rate variability (HRV) measures, obtained from 24-hour Holter recordings. In addition, norepinephrine, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured in all patients. TNF-alpha levels did not correlate with any of the HRV measures. IL-6 inversely correlated with the time-domain parameters of standard deviation of RR intervals (SDNN) (r = -0.36, P = 0.004) and standard deviation of all 5-minute mean RR intervals (SDANN) (r = -0.39, P = 0.001), and with the frequency-domain parameters of total power (TP) (r = -0.37, P = 0.003) and ultralow-frequency (ULF) power (r = -0.43, P = 0.001). No correlation was found between IL-6 and indices of parasympathetic modulation. Using multiple linear regression models, adjusting for clinical variables and drug therapies, the strong inverse relationship between IL-6 and SDNN (P = 0.006), SDANN (P = 0.001), TP (P = 0.04), and ULF power (P = 0.0007) persisted. CONCLUSION: Reduction of long-term HRV indices is associated with increased levels of IL-6 in patients with decompensated heart failure. The ability of long-term HRV parameters to better reflect activation of diverse hormonal systems may explain their greater prognostic power for risk stratification in patients with CHF.

Aged↗

PubMed2001

Activity of the neurohormonal system and its relationship to autonomic abnormalities in decompensated heart failure.

BACKGROUND: The syndrome of congestive heart failure (CHF) entails complex autonomic and hormonal responses. Profound abnormalities in autonomic function, characterized by sympathetic overactivity and parasympathetic withdrawal, exert direct deleterious effects on the heart and contribute to progressive circulatory failure. We investigated the relationship of heart rate variability (HRV) with levels of neurohormones in plasma. METHODS AND RESULTS: We studied 64 patients admitted to the hospital for treatment of decompensated CHF (mean age, 59 +/- 2 years; New York Heart Association class III [72%] and IV [28%]). Time- and frequency-domain HRV indices were obtained from 24-hour Holter recordings. Neurohormonal activation was assessed by measuring plasma renin activity and aldosterone and norepinephrine levels. In the time domain, norepinephrine correlated negatively with average NN interval (r = -.34; P =.007), SDNN (r = -.35; P =.005), and SDANN (r = -.36; P =.004). In the frequency domain, norepinephrine was negatively associated with the total power (r = -.39; P =.001) and ultralow power (r = -.43; P =.0005). No correlation was found between indices indicative of parasympathetic modulation, except for a borderline correlation with the high-frequency power (r = -.25; P =.048). CONCLUSIONS: Reduced HRV may be associated with increased norepinephrine levels in patients with severe CHF. The ability of long-term HRV parameters to reflect in part the activation of diverse hormonal systems may explain their greater prognostic power for risk stratification in patients with CHF.

Aged↗

PubMed2005

The prognostic value of a nomogram for exercise capacity in women.

BACKGROUND: Recent studies have demonstrated that exercise capacity is an independent predictor of mortality in women. Normative values of exercise capacity for age in women have not been well established. Our objectives were to construct a nomogram to permit determination of predicted exercise capacity for age in women and to assess the predictive value of the nomogram with respect to survival. METHODS: A total of 5721 asymptomatic women underwent a symptom-limited, maximal stress test. Exercise capacity was measured in metabolic equivalents (MET). Linear regression was used to estimate the mean MET achieved for age. A nomogram was established to allow the percentage of predicted exercise capacity to be estimated on the basis of age and the exercise capacity achieved. The nomogram was then used to determine the percentage of predicted exercise capacity for both the original cohort and a referral population of 4471 women with cardiovascular symptoms who underwent a symptom-limited stress test. Survival data were obtained for both cohorts, and Cox survival analysis was used to estimate the rates of death from any cause and from cardiac causes in each group. RESULTS: The linear regression equation for predicted exercise capacity (in MET) on the basis of age in the cohort of asymptomatic women was as follows: predicted MET = 14.7 - (0.13 x age). The risk of death among asymptomatic women whose exercise capacity was less than 85 percent of the predicted value for age was twice that among women whose exercise capacity was at least 85 percent of the age-predicted value (P<0.001). Results were similar in the cohort of symptomatic women. CONCLUSIONS: We have established a nomogram for predicted exercise capacity on the basis of age that is predictive of survival among both asymptomatic and symptomatic women. These findings could be incorporated into the interpretation of exercise stress tests, providing additional prognostic information for risk stratification.

Adult↗

PubMedDate not supplied

Transient myocardial ischemia is an independent predictor of adverse in-hospital outcomes in patients with acute coronary syndromes treated in the telemetry unit.

OBJECTIVE: The purpose of this study was to determine whether transient myocardial ischemia (TMI) is predictive of adverse in-hospital outcomes among patients admitted to a telemetry unit with acute coronary syndrome (ACS). DESIGN AND SETTING: The study was designed as a prospective clinical trial in a telemetry unit of a large, urban, university medical center. SAMPLE: The sample was comprised of adult patients admitted to the telemetry unit for treatment of acute myocardial infarction, unstable angina, or coronary artery disease warranting cardiac catheterization or percutaneous coronary intervention. METHODS: Continuous 12-lead electrocardiographic (ECG) ST-segment monitoring was initiated in patients admitted to the telemetry unit. TMI was defined as a change in ST amplitude of > or = 100 microV (elevation or depression) in > or = 1 ECG lead lasting > or = 60 seconds, comparing a baseline 12-lead ECG with an event ECG. Frequencies, measurements of central tendency, t test, chi(2) test, and logistic regression analysis were used for data analysis. A P value of <.05 was adopted as the critical value to determine statistical significance. RESULTS: In 237 telemetry unit patients, 39 patients (17%) had ischemia. Overall, 46% of the patients with ischemia had in-hospital complications compared with 10% of the group without ischemia (P <.001). After controlling for other predictors of adverse outcomes (eg, age, gender, Norris prognostic indicator), patients with TMI were 8.5 times more likely to have in-hospital complications (95% CI, 3.71 to 19.71). CONCLUSION: TMI is an independent predictor of in-hospital complications among patients with ACS treated in the telemetry unit setting. Continuous 12-lead ECG ST-segment monitoring provides prognostic information for risk stratification of patients admitted to the hospital for treatment of ACS.

Adult↗

PubMed2001

A systematic overview of chemotherapy effects in acute myeloid leukaemia.

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy in patients with acute myeloid leukaemia (AML) is based on 129 scientific articles: one meta-analysis, 51 randomised trials, 39 prospective and 18 retrospective studies, and 20 other articles. Altogether, 39,557 patients were included in these studies. The conclusions reached can be summarized into the following points: Standard induction therapy for patients with AML, consisting of daunorubicin and ara-C in conventional doses, results in a complete remission (CR) rate of 50-60% in an unselected population and a long-term survival of about 10-20%. The total doses of both ara-C and daunorubicin are of importance for remission duration and in some studies also for survival. High-dose ara-C in the induction therapy prolongs remission duration in randomised trials, but has not been proven to affect long-term survival. It also increases toxicity and is not generally recommended. Idarubicin, another anthracyclin, has been compared with daunorubicin in conjunction with ara-C, resulting in a higher CR rate, especially in younger patients. In a meta-analysis of the five-randomised trials performed, a slight survival advantage was also seen with idarubicin. Yet, there is inconclusive evidence to conclude that idarubicin is superior to daunorubicin, and further trials are needed. Mitoxantrone improves the outcome of induction therapy in comparison with daunorubicin in some randomised studies, but conclusive evidence is still lacking. The addition of etoposide to daunorubicin or mitoxantrone and ara-C has improved CR rates, but has not convincingly improved survival and secondary leukaemias may be induced. New induction treatment strategies are defined by identification of prognostic subgroups. A risk stratification of AML patients as to chromosomal aberrations might be of importance for the choice of therapy. Moreover, the speed and the morphological response to the first induction course are predictive for relapse. However, no prospective randomised studies are as yet published regarding risk-adapted induction therapy. Post-remission dose-intensive chemotherapy prolongs the duration of remission, seemingly most in patients < 60 years. However, the data in support of these conclusions are sparse. A convincing effect on survival has not been shown. Limited data indicate that post-remission maintenance therapy with long-term attenuated chemotherapy prolongs time to recurrence, without evidence for prolongation of survival. Allogeneic bone marrow transplantation is an established practice for consolidation in first remission for young patients with an HLA-matched sibling. It is however not known which patients will really benefit from transplantation as no truly randomised comparison of allogeneic vs autologous transplantation or conventionally-dosed chemotherapy has been performed. Patients with and without an HLA-identical sibling have been compared on the basis of intention-to-treat principles ('genetic randomisation'). The disease-free survival seems to be prolonged in the donor group, due to a lower relapse rate with allogeneic transplantation. A higher procedure-related mortality makes the effects on total survival uncertain. Randomised trials with autologous transplantation vs conventional consolidation show a lower relapse rate and a trend for an improved disease-free survival. In one study, in which an autograft was added to four courses of intensive therapy, there was also a late survival advantage. Thus, the role for intensified post-remission treatment in first complete remission with high-dose chemotherapy followed by allogeneic or autologous marrow or stem cell transplantation requires further studies. Moreover, studies with stratification of therapy according to predictors for prognosis in the individual patient are needed. Allogeneic stem cell transplantation after minimal or reduced myeloablative conditioning ('mini-transplantation' or non-myelo stem cell transplantation) induces a host-vs-graft tolerance and an immune graft-vs-leukaemia effect. This new concept of immunotherapy seems to have a low procedure-related mortality, but long-term effects are unknown and evaluation in controlled clinical studies is required. Patients with relapsed AML can only infrequently achieve long-term remissions with chemotherapy in conventional doses. trolled data indicate that allogeneic transplantation can be a curative treatment for these patients a

Acute Disease↗

PubMed1981

Axillary micro- and macrometastases in breast cancer: prognostic significance of tumor size.

Recurrence and survival data at 10 years were examined for 147 women with single axillary lymph node metastases found in a modified radical or standard radical mastectomy. The cases were identified through a review of all patients with primary operable breast cancer treated at Memorial Hospital from 1964 to 1970. The patients were stratified into groups according to size of the primary tumor and of the metastatic deposit (micro less than or equal to 2 mm; macro greater than 2 mm) as well as level of the positive node. In the entire series, there was a significantly poorer prognosis among those patients with single macrometastases (30/77 patients; 39% recurrence rate) when compared with those having micrometastases (17/70 patients: 24% recurrence rate). A major prognostic difference emerged after stratification by tumor size. Within the first six years of the follow-up period, T1 patients with negative nodes and those with single micrometastases had similar survival curves, significantly better than those with macrometastases. However, at 12 years, the survival rats of those patients with either a micro- or macrometastases was nearly identical, and significantly worse than for those patients with negative lymph nodes. On the other hand, among women with primary tumors 2.1-5.0 cm (T2), patients with negative lymph nodes or single micrometastases had survival curves that did not differ significantly throughout the course of the follow-up period. Both had an outcome significantly better than observed for patients with macrometastases. These findings have important implications for our understanding of the clinical behaviour of breast cancer and for the stratification of patients entered into randomized treatment trials.

Axilla↗

PubMed1996

Dispersion of the QT interval as a predictor of cardiac death in patients with coronary heart disease.

Abnormal dispersion of the QT interval (QTd), measured as interlead variability of QT, may reflect a regional variation in duration of ventricular action potential and, hence, of cardiac electrical instability. In this retrospective study, we analyzed the effect of QTd on survival and its relation to other known predictors of subsequent cardiac death (CD) and sudden cardiac death (SCD) in 162 patients with coronary heart disease (CHD). QTd was calculated as the difference between the highest and lowest values measured in each of the 12 ECG leads (Qtmax - QTmin). Seventeen CDs occurred, including nine SCDs, during a 25 +/- 11 month follow-up. There were significant differences in CD (P < 0.001 in log-rank test) and in SCD (P < 0.01). The 1- and 3-year survivals were 87.5% and 76.5% in patients with QTd > 0.060 seconds versus 98% and 93.5% in patients with QTd < 0.060 seconds, respectively. Additionally, a stepwise Cox regression analysis revealed that increased QTd was an independent risk factor of CD and SCD. A cut-off value of 60 ms for QTd had a 53% sensitivity and 79% specificity in discriminating patients who are at risk of CD. The positive and negative prognostic values were 23% and 93%, respectively. Our findings support the hypothesis that increased QTd has a prognostic value in the stratification of patients with CHD independent of other known risk factors.

Action Potentials↗

PubMed2002

Expression of components of the IGF signalling system in childhood acute lymphoblastic leukaemia.

BACKGROUND: Alterations in the insulin-like growth factor (IGF) system have been reported for different tumours. They are of particular interest in the search for new prognostic and therapeutic approaches in cancer. In childhood acute lymphoblastic leukaemia (ALL) the amount of "tumour mass" at diagnosis can exceed 1 kg. To understand the endocrine, paracrine, and autocrine potential of the malignant transformed progenitor cells, the ability of these cells to express components of the IGF system needs to be investigated. AIM: To characterise the expression pattern of genes of the IGF system in malignant lymphoblasts of children suffering from ALL. METHODS: Reverse transcription polymerase chain reaction of Ficoll separated mononuclear cells from 142 children with ALL, 127 cord blood samples, and 55 blood samples of age matched controls were studied. RESULTS: The expression of IGF-I, IGF-II, IGF binding protein 5 (IGFBP-5), and CTGF (IGFBP-rP2) was seen in a higher proportion of mononuclear cells of patients with ALL than in controls. Patients with ALL who were in continuous remission had a lower percentage of IGFBP-2 and IGFBP-3 expressing mononuclear cells at diagnosis than did those who developed a relapse. Only malignant lymphoblasts of B cell origin showed expression of CTGF (IGFBP-rP2). Malignant lymphoblasts of T cell origin more often expressed IGFBP-2 and IGFBP-5, whereas IGF-II and IGFBP-3 expression was seen more often in lymphoblasts of B cell origin. CONCLUSIONS: Malignant lymphoblasts of patients with ALL express components of the IGF system and therefore promote their own growth in an autocrine, paracrine, or endocrine manner. Whether these components will be useful as prognostic factors in the stratification of ALL treatment in children needs to be evaluated.

Biomarkers, Tumor↗

PubMed1994

Factors affecting outcome after recovery from myocardial infarction.

Patients surviving acute myocardial infarction are susceptible to heart failure, recurrence of angina, reinfarction, arrhythmias, and sudden cardiac death. Most deaths occur in the first six months after infarction. Advancing age is the most important nonmodifiable prognostic factor for long-term prognosis, whereas left ventricular function assessed clinically or measured as either ejection fraction or end-systolic volume is the most important modifiable factor. Other significant long-term prognostic factors include: postinfarction angina at rest, inducible ischemia during exercise testing with or without radioisotope imaging, severity and extent of coronary artery disease, patency of the infarct-related artery, late ventricular arrhythmias, decreased heart rate variability, cigarette smoking, hypercholesterolemia, and diabetes mellitus. Identification of these adverse prognostic factors permits risk stratification and enables physicians to determine the most appropriate and cost-effective treatment. Most patients should have a stress test for inducible ischemia and a non-invasive (echo or radionuclide) assessment of left ventricular function. For high-risk patients such as those with prior infarction, heart failure, early postinfarction angina, or frequent late ventricular arrhythmias, coronary angiography and ventriculography prior to discharge are recommended. Assessment of late potentials and heart rate variability will help identify a subgroup of patients at risk for ventricular arrhythmias and cardiac death. However, a more accurate prediction of reinfarction is not possible at present, and no reliable test for atherosclerotic plaque instability has been developed.

Age Factors↗

PubMed1999

Genome-wide allelotyping indicates increased loss of heterozygosity on 9p and 14q in early age of onset colorectal cancer.

Colorectal cancer remains a significant public health challenge, despite our increased understanding of the genetic mechanisms involved in the initiation and progression of this disorder. It has become clear that multiple mechanisms lead to the tumorigenic phenotype, with familial predisposition syndromes accounting for less than 15% of all colorectal cancers. A genome-wide scan for loss of heterozygosity (LOH) was carried out with 150 highly polymorphic markers in an effort to identify additional loci involved in colorectal tumorigenesis in DNA samples from 42 colorectal cancer patients. The results confirm earlier observations that tumor DNAs from patients with hereditary nonpolyposis colon cancer (HNPCC) either maintain heterozygosity or exhibit altered or additional alleles. DNAs from patients with early onset colorectal carcinomas (diagnosed prior to age 50) revealed a higher overall degree of LOH than DNAs from patients with sporadic colorectal cancers diagnosed later in life (after age 50). While regions on 1p, 10q and 14q are suggestive, statistical analysis of LOH at these regions failed to reach significance. However, LOH at 9p did reveal a statistically significant increase in the early onset patient group, compared to the greater than age 50 group. LOH on 9p may involve inactivation of p16/CDKN2 through aberrant DNA methylation on the remaining chromosome, resulting in a situation analogous to a homozygous deletion of p16 and providing a selective growth advantage to these cells. This marker may prove to be a useful prognostic indicator for patient stratification in the design of therapy for early onset colorectal cancer patients.

Age of Onset↗

PubMed1990

Prognostic factors in clinical stage I nonseminomatous germ cell tumors of the testis: multivariate analysis of a prospective multicenter study. Swedish-Norwegian Testicular Cancer Group.

Between 1981 and 1986, 279 consecutive patients with clinical stage I (CS1) nonseminomatous germ cell tumors (NSGCT) of the testis underwent pathological staging (PS) with retroperitoneal lymphadenectomy (RPLND). Patients with retroperitoneal metastases (PS2) received adjuvant chemotherapy. The median follow-up time after RPLND was 50 months (range, 30 to 90). Clinical and histopathologic features were registered prospectively and analyzed for association with risk of having PS2, relapse despite pathological stage 1 (PS1) or the combined risk of either event, metastatic disease (MET). Seventy-five (26.9%) of the patients had PS2 disease, and 30 (14.7%) of the 204 PS1 patients relapsed, indicating that at least 105 (37.6%) of this CS1 population had subclinical MET at the time of orchiectomy. Four (1.4%) of the 279 CS1 patients died of testicular cancer. Multivariate analyses showed several variables to be significantly associated with outcome for the CS1 patients; vascular invasion in primary tumor and normal preorchiectomy serum alpha-fetoprotein (Pre-AFP) level indicated PS2 disease. If Pre-AFP was excluded from the model, the absence of teratoma or yolk sac elements in the primary tumor became significant predictors of PS2. Vascular invasion, absence of teratoma, and a short interval between orchiectomy and RPLND indicated increased risk of relapse in PS1 patients. Vascular invasion, normal Pre-AFP, absence of teratoma elements, and a short orchiectomy to RPLND interval were predictive of MET. Our results indicate that prognostic factors useful for stratification of CS1 patients with NSGCT to different treatment options may be established.

Chorionic Gonadotropin↗

PubMed2005

Revisiting the role of hematopoietic stem cell transplantation in chronic lymphocytic leukemia.

Since the advent of hematopoietic stem cell transplantation more than 40 years ago, numerous methods of transplantation have been developed, modified and improved upon. Although hematopoietic stem cell transplantation has been used in a variety of malignant diseases since then, its use in the treatment of chronic lymphocytic leukemia has recently started to gain interest. Patients with chronic lymphocytic leukemia are generally elderly, and because of its relatively benign course, they were not considered suitable candidates for hematopoietic stem cell transplantation. Nonetheless, there have been marked improvements in transplantation techniques, including better conditioning regimens that have decreased treatment-related morbidity and mortality. In this article, the authors review the most recent data on hematopoietic stem cell transplantation in chronic lymphocytic leukemia as well as the change in risk stratification based on newer prognostic factors and its impact on treatment decisions in chronic lymphocytic leukemia.

Age Factors↗

PubMed2024

A comprehensive meta-analysis of tissue resident memory T cells and their roles in shaping immune microenvironment and patient prognosis in non-small cell lung cancer.

Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. In addition, TRM signatures are strongly associated with immune checkpoint and stimulatory genes and the prognosis of NSCLC patients. A TRM-based machine learning model to predict patient survival was validated and an 18-gene risk score was further developed to effectively stratify patients into low-risk and high-risk categories, wherein patients with high-risk scores had significantly lower overall survival than patients with low-risk. The prognostic value of the risk score was independently validated by the Cancer Genome Atlas Program (TCGA) dataset and multiple independent NSCLC patient datasets. Notably, low-risk NSCLC patients with higher TRM infiltration exhibited enhanced T-cell immunity, nature killer cell activation, and other TIME immune responses related pathways, indicating a more active immune profile benefitting from immunotherapy. However, the TRM signature revealed low TRM abundance and a lack of prognostic association among lung squamous cell carcinoma patients in contrast to adenocarcinoma, indicating that the two NSCLC subtypes are driven by distinct TIMEs. Altogether, this study provides valuable insights into the complex interactions between TRM and TIME and their impact on NSCLC patient prognosis. The development of a simplified 18-gene risk score provides a practical prognostic marker for risk stratification.

Humans↗

PubMed1999

[Treatment of adult acute lymphoblastic leukemia].

In patients with adult ALL, substantial progress has been made in the past 20 years. At present a cure rate of 30-40% can be achieved and varies in defined subgroups between 10-51%. ALL does not represent an uniform disease but is formed by biologic subentities, which differ in their natural history, clinical presentation and prognosis. A comprehensive diagnostic examination, including morphology, cytochemistry, immunology, cytogenetic and molecular genetic analysis is a precondition for prognostic assessment and therapeutic stratification. The basic principle of ALL treatment is a combination chemotherapy with sequential administration of induction, consolidation and maintenance therapy. Bone marrow transplantation has become an important part of the treatment strategy and is performed in patients with high risk. In the subgroup of T-ALL a significant progress has been made in the last years with survival rates of 40-50%. In B-ALL the results have been greatly improved to 48-51% by introduction of a specific treatment strategy. However, the results (about 30%) stagnate for the total group of B-lineage-ALL (common ALL, pre-B-ALL, pro-B-ALL). Patients with B-lineage-ALL can be subdivided in a high and low risk group according to the presence of risk factors (age, white blood cell count, time to achieve a complete remission, pro-B-ALL and the translocations t[4;11], t[9;22]). The outcome of the subgroup of adult pro-B-ALL has been substantially improved (50%). An increase of treatment results (20%) appears in outlines for patients above 50 years. The Ph/bcr-abl positive ALL has in spite of improved complete remission rates (60-70%) consistently unfavourable survival rates (10%).

Adult↗

PubMed1999

Evaluation of a simplified staging system for prognosis of hepatocellular carcinoma.

The current TNM (tumor, nodes, metastases) staging system for human hepatocellular carcinoma (HCC) has been challenged since a new T staging system was proposed to correlate the staging group with patient outcome after curative liver resection. The new T staging system proposed T1 as no vascular invasion, small size (< or = 5 cm), and solitary tumor. T2 was defined as the presence of one of the following factors: size greater than 5 cm, vascular invasion, or multiple tumors; T3 as the presence of two of the above three factors; and T4, the presence of all three factors. A total of 323 patients undergoing curative partial hepatectomy for HCC were studied. Kaplan-Meier survival analysis was used to evaluate the postoperative outcome. The new T staging showed good correlation between the staging group and patient outcome. The 1-year disease-free survival (DFS) rate and overall survival (OS) rate were 80.0% and 87.8% for stage 1 (n = 115), 67.6% and 81.6% for stage 2 (n = 136), 40.0% and 58.0% for stage 3 (n = 58), and 21.4% and 42.8% for stage 4 (n = 14), respectively. The 3-year DFS rate and OS rate were 61.0% and 64.5% for stage 1, 37.8% and 50.7% for stage 2, 21.4% and 29.8% for stage 3, and 21.4% and 34.3% for stage 4, respectively. When analyzed using the current International Union Against Cancer (UICC) pathologic (p) TNM staging system, the 1-year and 3-year DFS rates were 86.2% and 64.0% for stage 1 (n = 30), 73.9% and 50.0% for stage 2 (n = 182), and 46.8% and 22.3% for stage 3 (n = 111), respectively. Our results showed that, while both staging systems allow clear stratification of patients into prognostic groups, the modified TNM system is not superior to the UICCpTNM system in predicting survival of HCC patients after curative partial hepatectomy. A larger scale, multicenter study may be needed to test the revised TNM system.

Carcinoma, Hepatocellular↗

PubMed2003

[Radiation therapy of localized diffuse large B-cell lymphoma].

Diffuse large B-cell lymphoma is most frequently encountered non-Hodgkin's lymphoma in Japan, and about half of the cases present as Ann-Arbor stage I or II localized disease. Randomized clinical trials have revealed that chemotherapy combined with radiation therapy of the involved field yields superior outcome compared with chemotherapy alone. However, optimal chemotherapy cycles remain to be studied. Short-course chemotherapy, such as 3 cycles of CHOP, seems to be adequate for low bulk tumors, and full-course chemotherapy, such as 6-8 cycles of CHOP, seems to be required for larger tumors. Involved field radiation is a regional radiation that includes involved lymph nodes or extranodal sites, although the details vary between institutes. The precise definition of involved field radiation must be examined and clarified. The dose of involved field radiation after chemotherapy is also controversial. Most researchers apply at least 30 Gy to sites in complete remission, whereas a larger dose seems to be necessary for sites in partial remission. Stratification according to various prognostic factors is mandatory to tailor the management of localized diffuse large B-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Hyperthermia--its actual role in radiation oncology. Part II: Clinical fundamentals and results in superficial tumors.

This overview summarizes the most important clinical fundamentals to implement combined hyperthermia (HT) and radiotherapy (RT) in clinical trials and reviews clinical HT-RT data obtained in superficial and medium depth tumors treated with external heating devices. In the first part we discuss the following clinical fundamentals: selection of appropriate clinical sites for HT-RT studies, selection of suitable HT-devices, principle design of clinical HT-RT studies, requirements for treatment prescription, relevant treatment endpoints, definition and assessment of a thermal enhancement ratio (TER) and therapeutic gain factor (TGF), impact of prognostic parameters on treatment stratification and statistical evaluation. In the second part we review and discuss clinical results of thermoradiotherapy (HT-RT) for advanced breast carcinoma, recurrent breast cancer, advanced head and neck tumors, cervical neck node metastases, malignant melanomas and residual microscopic disease. In addition, clinical results of pilot studies are reviewed, which have applied a triple modality approach of thermo-radiochemotherapy (HRC) for various tumors. Finally, possible future perspectives of clinical HT-RT research are outlined.

Antineoplastic Combined Chemotherapy Protocols↗