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PubMed1981

The efficacy of nutritional assessment and support in cancer surgery.

Malnutrition is common in cancer patients and may be an important determinant of operative morbidity and mortality. To determine whether preoperative nutritional assessment can be used to identify a group of high-risk patients, and whether preoperative TPN decreases morbidity and mortality in this group, retrospective, nonrandomized review of 159 patients who were subjected to major cancer surgery was performed. All patients underwent preoperative multiparameter assessment. A previously developed and validated nutritional assessment model (Prognostic Nutritional Index) was used to evaluate the probability of operative complications. Based on predicted outcome (PNI), patients were assigned to either a high-risk or low-risk group for statistical comparison with actual outcome. The effect of preoperative TPN was then analyzed in both risk groups for determination of efficacy of preoperative nutritional support. Substantial malnutrition was found to exist among patients undergoing major cancer surgery and was closely correlated with subsequent morbidity and mortality. This predictive nutritional assessment model accurately identifies a subset of cancer surgery patients at increased risk of operative morbidity and mortality. In this high risk group (PNI greater than or equal to 40%), preoperative nutritional support significantly reduces operative morbidity.

Aged↗

PubMed2001

Prognosis of Alzheimer's disease: the Rotterdam Study.

The aim of this study was to construct a prognostic model to predict the progression of Alzheimer's disease (AD). Prevalent and incident cases with AD came from the Rotterdam Study, a population-based prospective cohort study of persons aged 55 years and older, including those living in institutions. Rate of cognitive decline, as measured by the Mini Mental State Examination (MMSE score), was predicted by a random effects model. Risk of institutionalization and death were estimated with polytomous logistic regression analysis. At baseline, 306 subjects were diagnosed with prevalent AD and had complete data on living conditions and cognitive function. After a mean follow-up of 2.1 years, 95 subjects with incident AD had been diagnosed. Prevalent patients showed a slower decline in cognitive function than incident patients (p = 0.004). For prevalent and incident AD patients, high age and low cognitive performance were the strongest predictors for institutionalization and death. These prognostic risk functions can provide information on the decline of Alzheimer patients and might be used to better evaluate the effect of treatments for AD.

Activities of Daily Living↗

PubMed1999

Assessment of severity of community-acquired pneumonia.

Community-acquired pneumonia (CAP) is the most common serious infection encountered in medical practice, with 1% to 10% of patients requiring admission to a hospital. The mortality rate of patients admitted is considerable, ranging from 5% to 25%. Motivated by the results of the British Thoracic Society (BTS) study, different investigators have identified several risk factors associated with a high mortality rate. The assessment of the severity of CAP can be determined at three stages: (1) At home or during the general practitioner's (GP) consultation; (2) In the hospital outpatient clinic or emergency room; and (3) In the medical ward and/or intensive care unit (ICU). At stage 1, medical history, symptoms, and signs (respiratory rate!) seem to be relevant. However, it is not easy for GPs to diagnose pneumonia with any degree of certainty because of the limited diagnostic tools available. Once a patient is referred to a hospital (stage 2), factors such as clinical presentation, comorbidities, and laboratory and radiographic factors must be determined to identify those patients who are at risk. BTS criteria (respiratory rate > or =30/min, diastolic blood pressure < or = 60 mm Hg, blood urea nitrogen >7 mmol/L), but also other combinations of criteria, are associated with a multiple-fold increased risk of death. However, most of these prognostic models have low positive predictive value, suggesting that the risk of death is overestimated when these models are implemented in daily practice. In general, younger patients without comorbidities can be treated in an outpatient setting; sometimes brief inpatient observation is necessary. Elderly patients, especially those with comorbidities and severe illness need inpatient care, sometimes resulting in treatment from an ICU. Severe CAP (stage 3) is defined as pneumonia associated with respiratory failure and/or hemodynamic instability requiring treatment in an ICU, and has a death rate varying from 21% to 54%. Pneumonia- and non-pneumonia-related complications are often observed. Adverse prognostic factors that have been reported in several studies are: advanced age, the presence of comorbidities, development of septic shock, need for mechanical ventilation (including use of positive end-expiratory pressure and FiO2 >60%), development of adult respiratory distress syndrome, progression of radiographic abnormalities, bacteremia (especially when due to P aeruginosa), non-pneumonia-related complications, and inadequate antibiotic treatment. To reduce mortality, prospective studies focusing on adverse prognostic factors at the start of and during antibiotic treatment are urgently needed at all three stages.

Adult↗

PubMed2001

Towards a biological staging model for operable non-small cell lung cancer.

Non-small cell lung cancer is the most common cause of cancer-related death in North America and Europe. Despite improvements in the diagnosis and treatment of the disease the prognosis remains poor, the overall 5-year survival being 4-14%. An increased understanding of the molecular biology of the disease may identify novel targets for drug development. We evaluated epidermal growth factor receptor (EGFR), HER-2/neu, matrix metalloproteinase (MMP)-2, MMP-9, p53 and bcl-2 expression and microvessel density (MVD) in patients who underwent surgery with curative intent in our department between 1991 and 1996. Co-expression of EGFR/MMP-9, MVD and bcl-2 were found to be independent prognostic variables, which allowed prediction of patient outcome independent of surgical stage. Other prognostic factors identified in our series were gender, surgical stage, platelet count, extent of necrosis, the hypoxia marker carbonic anhydrase-9 and beta-catenin. In collaboration with groups in Oxford and Greece, we were also able to establish the angiogenic growth factors vascular endothelial growth factor and platelet-derived endothelial growth factor as prognostic variables. The inter-relationships between these factors are currently being examined in an expanded patient series. Through this work we hope to be able to construct an integrated biological prognostic model which can be tested in prospective studies. This work has identified several potential targets for novel therapeutic agents currently in development.

Adult↗

PubMed2002

Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population.

BACKGROUND: Median survival of patients with primary sclerosing cholangitis (PSC) has been estimated to be 12 years. Cholangiography is the gold standard for diagnosis but is rarely used in estimating prognosis. AIMS: To assess the natural history of Dutch PSC patients and to evaluate the prognostic value of a cholangiographic classification system. PATIENTS: A total of 174 patients with established PSC attending a university hospital and three teaching hospitals from 1970 to 1999. METHODS: Charts were reviewed for validity and time of diagnosis, concurrent inflammatory bowel disease, interventions, liver transplantation, occurrence of cholangiocarcinoma, and death. Follow up data were obtained from the charts and from the attending clinician or family physician. Median follow up was 76 months (range 1-300). The earliest available cholangiography was scored using a radiological classification system for the severity of sclerosis, developed in our institution. Survival curves were computed by the Kaplan-Meier method. Cholangiographic staging was used to construct a prognostic model, applying Cox proportional hazards analysis. RESULTS: The estimated median survival from time of diagnosis to death from liver disease or liver transplantation was 18 years. Cholangiocarcinoma was found in 18 (10%) patients. Fourteen patients (8%) underwent liver transplantation. Cholangiographic scoring was inversely correlated with survival. A combination of intrahepatic and extrahepatic scoring, together with age at endoscopic retrograde cholangiopancreatography, proved strongly predictive of survival. CONCLUSIONS: The observed survival was considerably better than reported in earlier series from Sweden, the UK, and the USA. Classification and staging of cholangiographic abnormalities has prognostic value.

Adult↗

PubMed1989

Prognostication including DNA analysis in osteosarcoma.

In a retrospective study of 83 osteosarcoma patients treated by surgery and adjuvant interferon from 1971 to 1986, the clinical course was related to different clinicopathologic features and tumor DNA content. DNA analysis was feasible in 60 cases. Four tumors were diploid and 56 hyperploid. The 7-year survival rate, estimated by life-table analysis, was 0.44 for the whole series. Multivariate analysis disclosed that male sex, proximal tumor location, and histologic Grade IV were independent risk factors--all approximately of equal strength. DNA analysis did not provide prognostic information, except for tumors with extreme abnormality of the DNA content, which was associated with a very poor prognosis. A prognostication model was created, based on the number of risk factors present. The 7-year survival rate for patients with none, one, two, or three risk factors was 0.80, 0.59, 0.42, and 0.13, respectively. The estimated 7-year rate of local recurrence was 0.29: 0.07 after ablative surgery and 0.54 after local surgery. Among patients who were free of metastasis 1 year after diagnosis, local recurrence reduced the 7-year survival rate from 0.86 to 0.48. In high-grade osteosarcoma, conventional clinicopathologic features and local tumor control remain the most important prognostic factors.

Adolescent↗

PubMed1998

Statistical models for predicting a beneficial response to interferon-alpha in patients with chronic hepatitis B.

Therapy with interferon-alpha has been reported to induce remissions in 35% of patients with chronic hepatitis B. The ability to identify patients likely to respond would be helpful in making recommendations for treatment. In this statistical analysis we included 82 patients with chronic hepatitis B who received interferon-alpha in clinical trials at the National Institutes of Health between 1984 and 1991. A response was defined as the loss of hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) within 1 year of therapy. Multiple clinical parameters measured at pretreatment (month 0) and after the first month (month 1) of therapy were selected by stepwise regression to support the development of the prognostic models: the two-stage logistic regression model and a neural network that utilized higher-order non-linear interactions between variables. Among the 82 patients, 24 (29%) were responders. The two-stage logistic model using pretreatment variables: sex, hepatic fibrosis and alanine aminotransferase (ALT) levels correctly identified 61% of responders and 76% of non-responders. When HBV DNA at month 1 along with sex, initial ALT and fibrosis was included, the resultant model correctly identified 69% of responders and 77% of non-responders. The neural network, by incorporating interactions between variables, correctly identified 77% and 86% of responders, and 87% and 92% of non-responders, using pretreatment factors alone and the combination of pretreatment and month 1 factors respectively. Hence, the neural network was more accurate than the simple logistic regression model in predicting a response to interferon-alpha in chronic hepatitis B. The universality of these models needs to be further verified.

Antiviral Agents↗

PubMed2004

Hematopoietic recovery following induction therapy of acute leukemias: prognostic implications and a new look at the definition of remission.

Adult patients with acute leukemia may expect relatively high initial response rates with chemotherapy, but most will ultimately relapse and die from their disease. Prognostic models based mostly on pretreatment factors have been established and attempt to identify good- and poor-prognosis patients to assign them to risk-adapted therapies. Although achievement of a complete response (CR) is still the most significant clinical endpoint for survival, criteria for CR are arbitrarily defined. Besides the questionable numerical cut-off points that characterize CR, remission is not an all-or-none phenomenon. The shorter the time to CR, the better is the long-term outcome in chemotherapy-treated patients. Response during therapy can thus supplement pretreatment prognostic information. Shorter time to platelet recovery in patients achieving CR has been demonstrated to be associated with longer overall and disease-free survival in patients with acute lymphoblastic leukemia (ALL), including Philadelphia chromosome-positive ALL. Focusing on hematpoietic recovery may reflect a multitude of biological processes that occur during response to therapy and provide important information about the host's ability to fight and contain residual leukemic cells. It may complement current approaches to measuring minimal residual disease by flow cytometry and polymerase chain reaction (PCR).

Blood Platelets↗

PubMed1997

International scoring system for evaluating prognosis in myelodysplastic syndromes.

Despite multiple disparate prognostic risk analysis systems for evaluating clinical outcome for patients with myelodysplastic syndrome (MDS), imprecision persists with such analyses. To attempt to improve on these systems, an International MDS Risk Analysis Workshop combined cytogenetic, morphological, and clinical data from seven large previously reported risk-based studies that had generated prognostic systems. A global analysis was performed on these patients, and critical prognostic variables were re-evaluated to generate a consensus prognostic system, particularly using a more refined bone marrow (BM) cytogenetic classification. Univariate analysis indicated that the major variables having an impact on disease outcome for evolution to acute myeloid leukemia were cytogenetic abnormalities, percentage of BM myeloblasts, and number of cytopenias; for survival, in addition to the above, variables also included age and gender. Cytogenetic subgroups of outcome were as follows: "good" outcomes were normal, -Y alone, del(5q) alone, del(20q) alone; "poor" outcomes were complex (ie, > or = 3 abnormalities) or chromosome 7 anomalies; and "intermediate" outcomes were other abnormalities. Multivariate analysis combined these cytogenetic subgroups with percentage of BM blasts and number of cytopenias to generate a prognostic model. Weighting these variables by their statistical power separated patients into distinctive subgroups of risk for 25% of patients to undergo evolution to acute myeloid leukemia, with: low (31% of patients), 9.4 years; intermediate-1 (INT-1; 39%), 3.3 years; INT-2 (22%), 1.1 years; and high (8%), 0.2 year. These features also separated patients into similar distinctive risk groups for median survival: low, 5.7 years; INT-1, 3.5 years; INT-2, 1.2 years; and high, 0.4 year. Stratification for age further improved analysis of survival. Compared with prior risk-based classifications, this International Prognostic Scoring System provides an improved method for evaluating prognosis in MDS. This classification system should prove useful for more precise design and analysis of therapeutic trials in this disease.

Acute Disease↗

PubMed2001

Prevalence and prognostic value of quantified electroencephalogram (EEG) alterations in cirrhotic patients.

BACKGROUND/AIMS: The electroencephalogram (EEG) is frequently altered in cirrhotic patients. We, therefore, performed a study to ascertain the features and the prognosis of cirrhotic patients without current overt hepatic encephalopathy (OHE) who have EEG alterations. METHODS: A series of 296 consecutive cirrhotic patients who had undergone quantified-EEG was studied. The median follow-up was 442 days, 128 patients had bouts of OHE and 78 patients died from liver-related causes. Another group of 124 cirrhotic patients with a median follow-up of 223 days was examined to validate the prognostic model. RESULTS: EEG alterations were detected in 38% of the patients. The prevalence of EEG alterations was associated with the severity of cirrhosis (class B: odds ratio (OR) = 2.3, 95% confidence interval (CI) = 1.2-4.7; class C: OR = 3.5, 95% CI = 1.6-7.7), but not with the aetiology (alcoholic vs. non-alcoholic: OR = 0.9; 95% CI = 0.5-1.5). The EEG predicted the occurrence of OHE (chi2 = 26; P < 0.001) and mortality (chi2 = 34; P < 0.001), also adjusting for Child-Pugh class by a multivariate analysis. In the patients with a Child-Pugh score of > or = 8, the EEG discriminated between those patients with a higher 1-year risk of OHE (hazard ratio (HR) = 3.3, 95% CI = 1.8-6.1) and death (HR = 3.1, 95% CI = 1.7-5.6). CONCLUSIONS: In conclusion, quantified-EEG had a prognostic value for the occurrence of bouts of OHE and mortality in cirrhotic patients.

Aged↗

PubMed2004

Laser myringotomy versus ventilation tubes in children with otitis media with effusion: a randomized trial.

OBJECTIVES: Insertion of ventilation tubes in children with otitis media with effusion (OME) is an accepted and common treatment procedure. The majority of patients require general anesthesia. Although laser myringotomy can be performed in local anesthesia, evidence is lacking that this treatment modality is an alternative for tubes, and outcome predictors for laser myringotomy are not available. STUDY DESIGN: Prospective randomized trial. METHODS: We screened 1,403 children with chronic OME that were indicated for placement of ventilation tubes. In the eligible patients, we performed laser myringotomy in one ear and placed a tube in the other ear, both within the same patient. Follow-up was scheduled each month for 6 months. Success was defined as absence of effusion or aural discharge. A logistic regression model was used with success of the therapy as binary outcome. This model was based on base-line variables, asked for in a parent's questionnaire. RESULTS: Two hundred eight children received the allocated intervention, and no complications occurred. The mean closure time of the laser perforation was 2.4 weeks, and the mean patency time of the ventilation tube was 4.0 months. The mean success rate was 40% for laser and 78% for tubes. Ten known variables were found to predict middle ear status after therapy. CONCLUSION: Laser myringotomy is a safe but less-effective procedure than insertion of a ventilation tube in the treatment of chronic OME. The prognostic model enables the otolaryngologist to choose the surgical treatment for the child that benefits most: laser myringotomy or ventilation tube.

Acoustic Impedance Tests↗

PubMed2004

The Association of Coloproctology of Great Britain and Ireland study of large bowel obstruction caused by colorectal cancer.

BACKGROUND: This study was designed to investigate the early outcomes after surgical treatment of malignant large bowel obstruction (MBO) and to identify risk factors affecting operative mortality. METHODS: Data were prospectively collected from 1046 patients with MBO by 294 surgeons in 148 UK hospitals during a 12-month period from April 1998. A predictive model of in-hospital mortality was developed using a 3-level Bayesian logistic regression analysis. RESULTS: The median age of patients was 73 years (interquartile range 64-80). Of the 989 patients having surgery, 91.7% underwent bowel resection with an overall mortality of 15.7%. The multilevel model used the following independent risk factors to predict mortality: age (odds ratio [OR] 1.85 per 10 year increase), American Society of Anesthesiologists grade (OR for American Society of Anesthesiologists grade I versus II,III,IV-V = 3.3,11.7,22.2), Dukes' staging (OR for Dukes' A versus B,C,D = 2.0, 2.1, 6.0), and mode of surgery (OR for scheduled versus urgent, emergency = 1.6, 2.3). A significant interhospital variability in operative mortality was evident with increasing age (variance = 0.004, SE = 0.001, P < 0.001). No detectable caseload effect was demonstrated between specialist colorectal and other general surgeons. CONCLUSIONS: Using prognostic models, it was possible to develop a risk-stratification index that accurately predicted survival in patients presenting with malignant large bowel obstruction. The methodology and model for risk adjusted survival can set the reference point for more accurate and reliable comparative analysis and be used as an adjunct to the process of informed consent.

Adult↗

PubMed2004

Targeting neuroprotection clinical trials to ischemic stroke patients with potential to benefit from therapy.

BACKGROUND AND PURPOSE: Clinical trials of neuroprotective drugs have had limited success. We investigated whether selecting patients according to prognostic features would improve the statistical power of a trial to identify an efficacious treatment. METHODS: Using placebo data from the Glycine Antagonist in Neuroprotection (GAIN) International and National Institute of Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator (rtPA) clinical trials, we developed and validated simple prognostic models for stroke trial end points: Barthel Index > or =95, modified Rankin Scale < or =1, National Institutes of Health Stroke Scale < or =1, and Glasgow Outcome Scale=1. Using these models, we simulated 1000 clinical trials and estimated, under several hypothetical treatment effect patterns of neuroprotection, the effect on statistical power of including only patients with moderate prognosis. We calculated the number of patients that would have to be enrolled to maintain the statistical power achieved in selecting the whole trial population. Reanalysis of actual data from the NINDS rtPA trials confirmed the results independently. RESULTS: Selecting patients with moderate prognosis (predicted probability of favorable outcome 0.2 to 0.8) enabled a sample size reduction, without loss of statistical power, of between 54.6% (51.3% to 57.6%) and 68.6% (66.0% to 71.1%), depending on the treatment effect pattern and outcome measure. These benefits were largely due to the exclusion of patients with poor prognosis. CONCLUSIONS: Targeting patients with potential to benefit enables a substantial sample size reduction without compromising statistical power or duration of recruitment. As part of a broader trial design strategy, informed use of prognostic data available acutely would help in identifying effective neuroprotective treatments.

Aged↗

PubMed1999

Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumours.

The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. 'Progressive disease' included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of 'conventional' platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0-99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23-38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a 'small' centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l(-1) or hCG >100 IU l(-1)) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37-56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60-88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated 'conventional' platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l(-1) and AFP < 100 kU l(-1)). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors.

Adolescent↗

PubMed2004

Factors associated with prognosis of lateral epicondylitis after 8 weeks of physical therapy.

OBJECTIVE: To identify key factors associated with outcomes of patients who underwent 8 weeks of physical therapy (PT) for lateral epicondylitis. DESIGN: Multicenter prospective design with inception cohort of lateral epicondylitis patients commencing PT. Baseline clinical examinations were conducted by 1 physical therapist; self-report outcome measures were completed at baseline and 8 weeks later. SETTING: Nine private sports medicine clinics and 2 hospital outpatient departments in Ontario, Canada. PARTICIPANTS: Eighty-three patients with unilateral lateral epicondylitis identified by the treating physical therapists. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The final scores of the Disability of the Arm, Shoulder and Hand (DASH) questionnaire and a vertical pain visual analog scale (VAS) were used as the dependent variables. RESULTS: The final prognostic model for the 8-week DASH scores included the baseline score (95% confidence interval [CI], 0.34-0.66), sex (female) (95% CI, 3.3-14.5), and self-reported nerve symptoms (95% CI, 0.8-13.8). The model for the 8-week VAS scores included the baseline score (95% CI, 0.01-0.37), sex (female) (95% CI, 0.4-18.2), and self-reported nerve symptoms (95% CI, 4.7-25.5). A subanalysis indicated that women were more likely than men to have work-related onsets, repetitive keyboarding jobs, and cervical joint signs. Among women, these factors were associated with higher final DASH and VAS scores. CONCLUSIONS: Women and patients who report nerve symptoms are more likely to experience a poorer short-term outcome after PT management of lateral epicondylitis. Work-related onsets, repetitive keyboarding jobs, and cervical joint signs have a prognostic influence on women.

Adult↗

PubMed1999

Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer.

BACKGROUND: Proper treatment of lymph node-negative breast cancer depends on an accurate prognosis. To improve prognostic models for this disease, we evaluated whether an immunohistochemical marker for proliferating cells, Ki-S2 (a monoclonal antibody that binds to a 100-kd nuclear protein expressed in S, G2, and M phases of the cell cycle), is an accurate indicator of prognosis. METHODS: We studied 371 Swedish women with lymph node-negative breast cancer; the median follow-up time was 95 months. The fraction of tumor cells in S phase was assessed by flow cytometry, and tumor cell proliferation was measured immunohistochemically with the monoclonal antibodies Ki-S2 and Ki-S5 (directed against the nuclear antigen Ki-67). A combined prognostic index was calculated on the basis of the S-phase fraction, progesterone receptor content, and tumor size. RESULTS: In multivariate analyses that did or did not (263 and 332 observations, respectively) include the S-phase fraction and the combined prognostic index, the Ki-S2 labeling index (percentage of antibody-stained tumor cell nuclei) emerged as the most statistically significant predictor of overall survival, disease-specific survival, and disease-free survival (all two-sided P<.0001). In the risk group defined by a Ki-S2 labeling index of 10% or less, life expectancy was not statistically significantly different from that of age-matched women without breast cancer, whereas the group with a high Ki-S2 labeling index had an increased risk of mortality of up to 20-fold. CONCLUSIONS: Cellular proliferation is a major determinant of the biologic behavior of breast cancer. Prognosis is apparently best indicated by the percentage of cells in S through M phases of the cell cycle. Measurement of the Ki-S2 labeling index of a tumor sample may improve a clinician's ability to make an accurate prognosis and to identify patients with a low risk of recurrence who may not need adjuvant therapy.

Adult↗

PubMed2026

Integrated Genomic and Tumor Microenvironment Subtyping Improved Risk Stratification in Primary Central Nervous System Lymphoma.

Current prognostic models fail to capture the biological complexity of primary central nervous system lymphoma (PCNSL). We integrated whole-genome sequencing and multiplex immunofluorescence in 68 treatment-naïve patients to define four genomic subtypes (C1, C2, C3, and C4) with divergent survival (C4 worst: median overall survival [OS], 26 months). In parallel, a novel tumor microenvironment (TME) classification based on CD8+T/M2 macrophage ratio stratified patients into High (> 1.5), Intermediate (0.8-1.5), and Low (< 0.8) groups. Unexpectedly, the Intermediate TME group showed the poorest outcomes (5-year OS: 10%). Integration revealed a lethal subgroup (C4 + Intermediate TME; 9.8% of cohort) with a median OS of 3.0 months (hazard ratio = 7.24, p = 0.006). Prognostic nomograms incorporating these subtypes showed promising discriminative performance in internal validation (C-index > 0.78), but external validation is needed. Together, these findings identify a high-risk biological subset and provide a hypothesis-generating framework for future biomarker-driven risk stratification and therapeutic discovery in PCNSL.

Humans↗

PubMed2000

Machine learning for survival analysis: a case study on recurrence of prostate cancer.

Machine learning techniques have recently received considerable attention, especially when used for the construction of prediction models from data. Despite their potential advantages over standard statistical methods, like their ability to model non-linear relationships and construct symbolic and interpretable models, their applications to survival analysis are at best rare, primarily because of the difficulty to appropriately handle censored data. In this paper we propose a schema that enables the use of classification methods--including machine learning classifiers--for survival analysis. To appropriately consider the follow-up time and censoring, we propose a technique that, for the patients for which the event did not occur and have short follow-up times, estimates their probability of event and assigns them a distribution of outcome accordingly. Since most machine learning techniques do not deal with outcome distributions, the schema is implemented using weighted examples. To show the utility of the proposed technique, we investigate a particular problem of building prognostic models for prostate cancer recurrence, where the sole prediction of the probability of event (and not its probability dependency on time) is of interest. A case study on preoperative and postoperative prostate cancer recurrence prediction shows that by incorporating this weighting technique the machine learning tools stand beside modern statistical methods and may, by inducing symbolic recurrence models, provide further insight to relationships within the modeled data.

Artificial Intelligence↗