Comparison of outcomes following surgical resection, percutaneous ablation or stereotactic body radiation therapy in early-stage, solitary and small (≤3 cm) treatment-naïve hepatocellular carcinoma.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is associated with high local control rates in hepatocellular carcinoma (HCC). This study reports the outcomes of SBRT compared to surgical resection (SR) and percutaneous ablation (PA) for treatment-naïve, solitary HCCs ≤3 cm. METHODS: This was a retrospective study of patients with BCLC stage 0/A HCC with a single ≤3 cm lesion, treated with curative intent between 2016 and 2020. SBRT was used for patients considered unsuitable for SR or PA. The co-primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were treatment-related clinical toxicity rates and local control (LC) rates. RESULTS: There were 112 patients included in this study. SBRT was delivered in 36 patients (32.1%), 51 had PA (45.5%) and 25 underwent SR (22.3%). Median follow-up was 23 months (range, 3-60 months) from diagnosis. The 3-year PFS and OS were 67% and 69% following SBRT, 55% and 80% following PA, and 85% and 100% following SR, respectively. Patients in the SR cohort had significantly better 3-year PFS and OS compared to SBRT and PA groups (p = 0.03 and p = 0.04, respectively). There was no significant difference in PFS (p = 0.15) or OS (p = 0.23) between SBRT and PA treated patients. The 3-year LC rate for the entire cohort was 98%. CONCLUSIONS: In patients with treatment-naïve, early-stage solitary HCCs ≤3 cm, SBRT was associated with comparable PFS, OS and LC outcomes to PA. SBRT should be considered as a curative intent therapy to avoid treatment stage migration in this favourable prognostic cohort of patients.

Definitive Stereotactic Body Radiation Therapy in Early-Stage Solitary Hepatocellular Carcinoma: An Australian Multi-Institutional Review of Outcomes.

AIMS: Standard curative options for early-stage, solitary hepatocellular carcinoma (HCC) are often unsuitable due to liver dysfunction, comorbidities and/or tumour location. Stereotactic body radiation therapy (SBRT) has shown high rates of local control in HCC; however, limited data exist in the treatment-naïve, curative-intent setting. We report the outcomes of patients with solitary early-stage HCC treated with SBRT as first-line curative-intent therapy. MATERIALS AND METHODS: A multi-institutional retrospective study of treatment-naïve patients with Barcelona Clinic Liver Cancer stage 0/A, solitary ≤5 cm HCC, Child-Pugh score (CPS) A liver function who underwent SBRT between 2010 and 2019 as definitive therapy. The primary end point was freedom from local progression. Secondary end points were progression-free survival, overall survival, rate of treatment-related clinical toxicities and change in CPS >1. RESULTS: In total, 68 patients were evaluated, with a median follow-up of 20 months (range 3-58). The median age was 68 years (range 50-86); 54 (79%) were men, 62 (91%) had cirrhosis and 50 (74%) were Eastern Cooperative Oncology Group 0. The median HCC diameter was 2.5 cm (range 1.3-5) and the median prescription biologically effective dose with a tumour a/b ratio of 10 Gy (BED10) was 93 Gy (interquartile range 72-100 Gy). Two-year freedom from local progression, progression-free survival and overall survival were 94.3% (95% confidence interval 86.6-100%), 59.5% (95% confidence interval 46.3-76.4%) and 88% (95% confidence interval 79.2-97.6%), respectively. Nine patients (13.2%) experienced grade ≥2 treatment-related clinical toxicities. A rise >1 in CPS was observed in six cirrhotic patients (9.6%). CONCLUSION: SBRT is an effective and well-tolerated option to consider in patients with solitary, early-stage HCC. Prospective, randomised comparative studies are warranted to further refine its role as a first-line curative-intent therapy.

Efficacy and Toxicity of Stereotactic Body Radiotherapy for Early to Advanced Stage Hepatocellular Carcinoma - Initial Experience From an Australian Liver Cancer Service.

AIMS: Intrahepatic progression remains the predominant mode of cancer-related death in hepatocellular carcinoma (HCC) underscoring the need for effective local therapies. We report our initial experience with liver stereotactic body radiotherapy (SBRT) in the management of early to advanced stage HCC at an Australian tertiary liver cancer service. MATERIALS AND METHODS: Patients with liver-confined HCC unsuitable for surgical resection or thermal ablation treated with SBRT between October 2013 and December 2018 were retrospectively evaluated. The primary end point was freedom from local progression. Secondary end points were progression-free survival, disease-specific survival, overall survival and toxicity. RESULTS: Ninety-six patients were treated for 112 lesions (median size 3.8 cm, range 1.5-17 cm). The median follow-up was 13 months (range 3-65). Forty-six patients had received prior local therapies (median 1, range 1-5), 83 (86%) patients had cirrhosis with baseline Child-Pugh scores of A (88%) and B7-8 (12%). Fifty-nine (61%) patients had Barcelona Clinic Liver Cancer (BCLC) stage 0/A disease and 37 (39%) had stage B/C. Macrovascular invasion was present in 20 (21%). The median biologically effective dose (BED10) was 86 and 60 Gy for the BCLC 0/A and B/C cohorts, respectively. Freedom from local progression at 18 months was 94% for BCLC 0/A and 74% for BCLC B/C. Progression-free survival and overall survival at 12 months were 80 and 95% for BCLC 0/A and 40 and 71% for BCLC B/C, respectively. Five patients (7%) with cirrhosis and without disease progression had an increase in Child-Pugh score >1 within 3 months of SBRT, four of whom had intercurrent infections. Clinical toxicities grade ≥2 were reported in 20% of patients. CONCLUSION: SBRT is an effective ablative modality for early stage HCC with low rates of significant toxicity. Lower dose SBRT can provide durable local control for advanced stage HCC. However, out-of-field relapse remains common, providing a rationale to investigate SBRT in combination with other therapies.

The clinical efficacy of PSMA PET/MRI in biochemically recurrent prostate cancer compared with standard of care imaging modalities and confirmatory histopathology: results of a single-centre, prospective clinical trial.

Prospective evidence for the clinical role and efficacy of prostate specific membrane antigen (PSMA) positron emission tomography (PET)/magnetic resonance imaging (MRI) combining MRI characterization and localization of lesions with PET avidity in comparison to conventional imaging is limited. In a prospective clinical trial, we aimed to evaluate the diagnostic yield and therapeutic impact of PSMA PET/MRI in men with biochemical recurrence (BCR) following curative therapy. A single-centre, prospective clinical trial at the Princess Alexandra Hospital recruited 30 patients with BCR. Patients underwent PSMA PET/MRI and concurrent conventional CT chest, abdomen, pelvis and whole-body bone scan. Biopsy was performed when safety possible for histological correlation of identified lesions. Clinical efficacy and impact of PSMA PET findings were evaluated. 30 patients with BCR were recruited (median PSA 0.69 ng/ml). PSMA avid lesions were present in 21 patients (70%). 23 patients were previously treated with definitive surgery, 6 patients received external beam radiotherapy and 1 patient had low dose rate brachytherapy. A total of 8 of 9 lesions biopsied were positive (88.9% histological correlation). PSMA PET/MRI detected local recurrence (p = 0.005) and pelvic lesions (p = 0.06) more accurately than conventional imaging. PSMA PET/MRI may be useful in staging men with biochemical recurrence, especially when PSA is low. Our data demonstrates a high detection rate, especially for locally recurrent disease, and highlights the role of this modality when PSA is low. This modality has the potential to significantly improve prostate cancer detection and may have implications for earlier salvage treatment, avoidance of futile local therapy and change patient management to lead to improved outcomes.

Patterns of Failure Following Dose-escalated Chemoradiotherapy for Fluorodeoxyglucose Positron Emission Tomography Staged Squamous Cell Carcinoma of the Oesophagus.

AIMS: To analyse outcomes and patterns of failure following dose-escalated definitive chemoradiotherapy (CRT) for oesophageal squamous cell carcinoma using fluorodeoxyglucose positron emission tomography for staging and treatment planning. MATERIALS AND METHODS: A retrospective review of patients with oesophageal squamous cell carcinoma receiving definitive CRT to a dose of ≥56 Gy was conducted. Patient and tumour characteristics, treatment received and first sites of relapse were analysed. RESULTS: Between 2003 and 2014, 72 patients were treated with CRT to a median dose of 60 Gy (range 56-66 Gy). The median age was 63 years; most (61%) were stage III/IVa. The median follow-up was 57 months. Three year in-field control, relapse-free survival and overall survival was 64% (95% confidence interval 50-75%), 38% (95% confidence interval 27-50%) and 42% (95% confidence interval 30-53%), respectively. Of the 41 failures prior to death or at last follow-up date, isolated locoregional relapse occurred in 16 patients (22%) with isolated in-field recurrence in 11 patients (15%). Distant failure as first site of relapse was present in 25 patients (35%). No in-field failures occurred in the 11 patients with cT1-2, N0-1 tumours. The median survival for cT4 tumours was 8 months, with five of eight patients developing local progression within the first 6 months. CONCLUSIONS: Dose-escalated radiotherapy was associated with promising rates of in-field local control, with the exception of cT4 tumours. Distant failure remains a significant competing risk. Our data supports the need for current trials re-examining the role of dose escalation in the modern era.

Engaging Future Clinical Oncology Researchers: An Initiative to Integrate Teaching of Biostatistics and Research Methodology into Specialty Training.

AIMS: To evaluate the learner's perspectives on a novel workshop programme designed to improve skills in biostatistics, research methodology and critical appraisal in oncology. MATERIALS AND METHODS: Trainees were surveyed anonymously at the completion of each annual workshop from 2012 to 2015. In total, 103 trainees in years 2-4 of training in radiation oncology responded, giving a 94% survey response rate. A 1 day workshop, designed by biostatisticians and radiation oncologist facilitators, is the central component of a programme teaching skills in biostatistics, research methods and critical appraisal. This links short didactic lectures about statistical concepts to interactive trainee discussions around discipline-related publications. RESULTS: The workshop was run in conjunction with the major radiation oncology clinical trials group meeting with alternating programmes (A and B). Most of the participants (44-47/47 for A and 48-55/56 for B), reported that their understanding of one or more individual topics improved as a result of teaching. Refinement of the workshop over time led to a more favourable perception of the 'optimal' balance between didactic/interactive teaching: nine of 27 (33%) 'optimal' responses seen in 2013 compared with 23 of 29 (79%) in 2015 (P < 0.001). Commonly reported themes were: clinician facilitators and access to biostatisticians helped contextualise learning and small group, structured discussions provided an environment conducive to learning. CONCLUSIONS: Overall, radiation oncology trainees reported positive perceptions of the educational value of this programme, with feedback identifying areas where this resource might be improved. This model could readily be adapted to suit other medical disciplines and/or other training environments, using specialty-specific research to illuminate key statistical concepts.

Data for cardiovascular modeling.

Data are required for a meaningful approach to quality and cost-conscious cardiovascular care. How to identify the types of data available and their sources, advantages and limitations to their use, issues involved in combining data from different sources for decision modeling and some possible solutions are discussed in this summary of the Working Group on Data for Cardiovascular Modeling.

Estimated contribution of coronary artery bypass graft surgery to the decline in coronary heart disease mortality: the Minnesota Heart Survey.

OBJECTIVES: This study assessed the possible contribution of coronary artery bypass graft surgery to the decline in coronary heart disease mortality in the Minneapolis-St. Paul metropolitan area population between 1970 and 1984. BACKGROUND: Coronary artery bypass graft surgery is a major contemporary therapeutic approach for coronary heart disease. Its use has increased over the past two decades because it provides relief of symptoms and, in certain circumstances, prolongs life. During the period that age-adjusted coronary heart disease mortality has decreased, the use of coronary artery bypass graft surgery has increased dramatically, suggesting a relation. METHODS: All 30- to 74-year old Minneapolis-St. Paul area residents undergoing coronary artery bypass graft surgery between 1970 and 1984 (9,548 patients) were registered; their medical records were abstracted; and their survival was ascertained. These data were used in a medical survival probability model using a multivariate analytical approach developed from registries of patients treated medically. The model assumed that coronary artery bypass graft surgery was not available. Two annual mortality rates were compared: the observed Minneapolis-St. Paul annual coronary heart disease mortality rate and the modeled annual coronary heart disease mortality rate. The difference between these rates was the estimated contribution of coronary artery bypass graft surgery to the decline in coronary heart disease mortality rates. RESULTS: Between 1970 and 1984, the estimated surgical contribution increased from 0.2% (increased mortality) to +6.6% of the annual decrease in Minneapolis-St. Paul coronary heart disease mortality. CONCLUSIONS: Between 1970 and 1984, the contribution of coronary artery bypass graft surgery to the decline in coronary heart disease mortality, although small, gradually increased. This change appeared to be related to an increased frequency of coronary artery bypass graft surgery, improved operative mortality and changes in the clinical mix of surgical patients.

Clinical judgment and therapeutic decision making.

Clinical decision making is under increased scrutiny due to concerns about the cost and quality of medical care. Variability in physician decision making is common, in part because of deficiencies in the knowledge base, but also due to the difference in physicians' approaches to clinical problem solving. Evaluation of patient prognosis is a critical factor in the selection of therapy, and careful attention to methodology is essential to provide reliable information. Randomized controlled clinical trials provide the most solid basis for the establishment of broad therapeutic principles. Because randomized studies cannot be performed to address every question, observational studies will continue to play a complementary role in the evaluation of therapy. Randomized studies in progress, meta analyses of existing data, and increased use of administrative and collaborative clinical data bases will improve the knowledge base for decision making in the future.

Comparison of predictions based on observational data with the results of randomized controlled clinical trials of coronary artery bypass surgery.

Clinical decisions are most secure when based on findings from several large randomized clinical trials, but relevant randomized trial data are often unavailable. Analyses using clinical data bases might provide useful information if statistical methods can adequately correct for the lack of randomization. To test this approach, the findings of the three major randomized trials of coronary bypass surgery were compared with predictions of multivariable statistical models derived from observations in the Duke Cardiovascular Disease Databank. Clinical characteristics of patients at Duke University Medical Center who met eligibility requirements for each major randomized trial were used in the models to predict 5 year survival rates expected for medical and surgical therapy in each randomized trial. Model predictions agreed well with randomized trial results and were within the 95% confidence limits of the observed survival rates in 24 (92%) of 26 clinical subgroups. The overall correlation between predicted and observed survival rates was good (Spearman coefficient 0.73, p less than 0.0001). These results suggest that carefully performed analyses of observational data can complement the results of randomized trials.

Importance of clinical measures of ischemia in the prognosis of patients with documented coronary artery disease.

To examine the value of clinical measures of ischemia for stratifying prognosis, 5,886 consecutive patients who had symptomatic significant (greater than or equal to 75% stenosis) coronary artery disease were studied. Using the Cox regression model in a randomly selected half of the patients, the prognostically independent clinical variables were weighted and arranged into a simple angina score: angina score = angina course X (1 + daily angina frequency) + ST-T changes, where angina course was equal to 3 if unstable or variant angina was present, 2 if the patient's angina was progressive with nocturnal episodes, 1 if it was progressive without nocturnal symptoms and 0 if it was stable; 6 points were added for the presence of "ischemic" ST-T changes. This angina score was then validated in an independent patient sample. The score was a more powerful predictor of prognosis than was any individual anginal descriptor. Furthermore, the angina score added significant independent prognostic information to the patient's age, sex, coronary anatomy and left ventricular function. Patients with three vessel disease and a normal ventricle (n = 1,233) had a 2 year infarction-free survival rate of 90% with an angina score of 0 and a 68% survival rate with an angina score greater than or equal to 9. With an ejection fraction less than 50% and three vessel disease (n = 1,116), the corresponding infarction-free survival figures were 76 and 56%.(ABSTRACT TRUNCATED AT 250 WORDS)

Feasibility and cost-saving potential of outpatient cardiac catheterization.

To determine the feasibility and cost-saving potential of substituting outpatient for inpatient cardiac catheterization, 986 consecutive procedures were studied at a large referral hospital. Patients were classified prospectively as to their eligibility for outpatient cardiac catheterization according to published guidelines. Resource consumption was recorded, and cost savings were then calculated by analyzing the specific supply and personnel costs that could change as a result of inpatient versus outpatient status. Of the total of 986 patients who underwent diagnostic catheterization, 240 (24%) were outpatients, 279 (28%) were inpatients but had no exclusion criteria for outpatient catheterization and 467 (47%) were inpatients who had one or more exclusions for outpatient catheterization. The most common reasons for exclusion from outpatient catheterization were congestive heart failure (22%), unstable angina (15%), noncoronary heart disease (14%), recent myocardial infarction (11%) and severe noncardiac disease (9%). Inpatients with no exclusions for the outpatient procedure tended to be sicker than outpatients because they were older (p = 0.002), had a lower ejection fraction (p = 0.009) and had more triple vessel coronary artery disease (p less than 0.0001). The cost of the catheterization procedure itself was not different between inpatients and outpatients. Laboratory testing was more frequent among inpatients, however, and "room and board" costs were significantly higher. Although the difference in hospital charges for inpatients and outpatients was $580, a rigorous analysis indicated that the potential cost savings was only 38% of this amount, or $218 per eligible patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration of thrombolytic therapy in the community hospital: established principles and unresolved issues.

In patients with acute myocardial infarction presenting to community hospitals, thrombolytic therapy should be initiated as rapidly as possible under the supervision of a physician. Paramedic or nurse-initiated pre-hospital therapy is currently investigational. Each hospital must have a detailed evaluation and treatment protocol for acute myocardial infarction that specifies the timetable for patient evaluation, who should or should not receive thrombolytic therapy and the proper dose and mode of administration of the agent or agents to be used. Monitoring after the administration of thrombolytic therapy should focus on arrhythmias, hemodynamic problems, recurrent ischemia and bleeding. The role of early cardiac catheterization to detect patients who have unsuccessful thrombolysis or who require mechanical revascularization procedures is under active investigation. The design of the Thrombolysis and Angioplasty in Acute Myocardial Infarction (TAMI) 5 study, which addresses the role of acute interventional catheterization in the treatment of patients with acute myocardial infarction, is described.

Cardiac rupture, mortality and the timing of thrombolytic therapy: a meta-analysis.

This study examined the relation between the risk of cardiac rupture and the timing of thrombolytic therapy for acute myocardial infarction. To test the hypothesis that cardiac rupture is prevented by early thrombolytic therapy but is promoted by late treatment, randomized controlled trials of thrombolytic agents for myocardial infarction were pooled. A logistic regression model including 58 cases of cardiac rupture among 1,638 patients from four trials showed that the odds ratio (treated/control) of cardiac rupture was directly correlated with time to treatment (p = 0.01); at 7 h, the odds ratio was 0.4 (95% confidence limits 0.17 to 0.93); at 11 h, it was 0.93 (0.53 to 1.60) and at 17 h, it was 3.21 (1.10 to 10.1). Analysis of data from the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) trial independently confirmed the relation between time to thrombolytic therapy and risk of cardiac rupture (p = 0.03). Analysis of 4,692 deaths in 44,346 patients demonstrated that the odds ratio of death was also directly correlated with time to treatment (p = 0.006); at 3 h, the odds ratio for death was 0.72 (0.67 to 0.77); at 14 h, it was 0.88 (0.77 to 1.00) and at 21 h, it was 1 (0.82 to 1.37). Thrombolytic therapy early after acute myocardial infarction improves survival and decreases the risk of cardiac rupture. Late administration of thrombolytic therapy also appears to improve survival but may increase the risk of cardiac rupture.

Comparison of survival of amiodarone-treated patients with coronary artery disease and malignant ventricular arrhythmias with that of a control group with coronary artery disease.

Although amiodarone is effective in the treatment of ventricular arrhythmias, it is associated with serious toxic effects. In addition, the prognosis of patients with malignant ventricular arrhythmias and coronary artery disease treated with amiodarone remains poor. The survival of 54 consecutive patients with angiographically documented coronary artery disease and symptomatic ventricular tachycardia or ventricular fibrillation treated with amiodarone was compared with that of 5,125 medically treated patients with coronary artery disease. The amiodarone group was older, with worse left ventricular function and more peripheral and cerebrovascular disease. The 1 year survival probability was 0.73 for the amiodarone group and 0.94 for the control coronary artery disease group. At 2 years of follow-up, the survival probabilities were 0.60 and 0.90 for the amiodarone and the control group, respectively. When the survival curves were adjusted for group differences in baseline prognostic characteristics (integrated as a previously published hazard score), there was no difference in the prognosis of the two groups. These findings suggest that treatment with amiodarone of malignant ventricular arrhythmias associated with coronary artery disease maintains patients on an underlying survival curve determined by the degree of myocardial dysfunction, clinical characteristics and coronary anatomy, and that amiodarone does not have a deleterious effect on survival.

Prognosis in cardiogenic shock after acute myocardial infarction in the interventional era.

OBJECTIVES: The purpose of this study is to describe the outcome in cardiogenic shock treated with aggressive reperfusion therapy and to identify factors predictive of in-hospital and long-term mortality. BACKGROUND: Cardiogenic shock is the most common cause of death in patients admitted to the coronary care unit. Although studies have reported lower mortality rates in shock treated with angioplasty, few studies have described a cohort of patients with shock who were not selected because they were most likely to benefit from reperfusion therapy. METHODS: A consecutive series of 200 patients admitted with acute myocardial infarction complicated by cardiogenic shock were studied. RESULTS: The in-hospital mortality rate was 53%. Variables with significant univariable association with in-hospital death included patency of the infarct-related artery, patient age, lowest cardiac index, highest arteriovenous oxygen difference and left main coronary artery disease. The most important independent predictors of in-hospital death were patency of the infarct-related artery, cardiac index and peak creatine kinase, MB fraction. The mortality rate in patients with patent infarct-related arteries was 33% versus 75% in those with closed arteries and 84% in those in whom arterial patency was unknown. Patients who survived to hospital discharge were followed up for a median of 2 years, with a mortality rate of 18% after 1 year. The best descriptors of the relation between these variables and postdischarge mortality included age, peak creatine kinase, ejection fraction and patency of the infarct-related artery. CONCLUSIONS: In a large consecutive series of patients with cardiogenic shock with complete follow-up, patency of the infarct-related artery was most strongly associated with in-hospital and long-term mortality. This finding supports an aggressive interventional strategy in patients with cardiogenic shock.

Ergonovine maleate testing during cardiac catheterization: a 10-year perspective in 3,447 patients without significant coronary artery disease or Prinzmetal's variant angina.

The utility of ergonovine testing for coronary artery spasm was assessed in 3,447 patients with angiographically insignificant (less than 50% diameter stenosis) or no coronary artery disease. No patients clinically had Prinzmetal's variant angina. Overall, 4% had a positive ergonovine test result, defined by spasm causing greater than or equal to 75% focal stenosis. Complications related to ergonovine use occurred in 11 patients (0.03%). In a training sample of 1,136 patients (studied between 1980 and 1984), two independent predictors of spasm were found by using multivariate analysis: the amount of visible coronary artery disease on the coronary angiogram (p less than 0.0001) and a smoking history (p = 0.001). A model to predict spasm based on these variables was validated in a test group of 2,311 patients who received ergonovine from 1985 to 1989. This model allowed the identification of a subset of 400 patients in the validation sample who had a 10% positive test rate compared with a 2% positive test rate in the remaining patients. These results should permit clinicians who use provocative testing in the catheterization laboratory to reserve testing for the subset of this group of patients most likely to have abnormal findings.

Painless exercise ST deviation on the treadmill: long-term prognosis.

To evaluate the clinical correlates and long-term prognostic significance of silent ischemia during exercise, 1,698 consecutive symptomatic patients with coronary artery disease who had both treadmill testing and cardiac catheterization were studied. These patients were classified into three groups: Group 1 = patients with no exercise ST deviation (n = 856), Group 2 = patients with painless exercise ST deviation (n = 242) and Group 3 = patients with both angina and ST segment deviation during exercise (n = 600). Patients with exercise angina had a history of a longer and more aggressive anginal course (with a greater frequency of angina, with nocturnal episodes and/or progressive symptom pattern) and more severe coronary artery disease (almost two-thirds had three vessel disease). The 5 year survival rate among the patients with painless ST deviation was similar to that of patients without ST deviation (86% and 88%, respectively) and was significantly better than that of patients with both symptoms and ST deviation (5 year survival rate 73% in patients with exercise-limiting angina). Similar trends were obtained in subgroups defined by the amount of coronary artery disease present. In the total study group of 1,698 patients, silent ischemia on the treadmill was not a benign finding (average annual mortality rate 2.8%) but, compared with symptomatic ischemia, did indicate a subgroup of patients with coronary artery disease who had a less aggressive anginal course, less coronary artery disease and a better prognosis. Thus, silent ischemia during exercise testing in patients with symptomatic coronary artery disease represents an intermediate risk response in the spectrum of exercise-induced ischemia.