Point-of-care measurements reveal release of purines into venous blood of stroke patients.

Stroke is a leading cause of death and disability. Here, we examine whether point-of-care measurement of the purines, adenosine, inosine and hypoxanthine, which are downstream metabolites of ATP, has potential to assist the diagnosis of stroke. In a prospective observational study, patients who were suspected of having had a stroke, within 4.5 h of symptom onset and still displaying focal neurological symptoms at admission, were recruited. Clinical research staff in the Emergency Departments of two hospitals used a prototype biosensor array, SMARTCap, to measure the purines in the venous blood of stroke patients and healthy controls. In controls, the baseline purines were 7.1 ± (SD) 4.2 µM (n = 52), while in stroke patients, they were 11.6 ± 8.9 µM (n = 76). Using the National Institutes for Stoke Scale (NIHSS) to band the severity of stroke, we found that minor, moderate and severe strokes all gave significant elevation of blood purines above the controls. The purine levels fall over 24 h. This was most marked for patients with haemorrhagic strokes (5.1 ± 3.6 µM, n = 9 after 24 h). The purine levels measured on admission show a significant correlation with the volume of affected brain tissue determined by medical imaging in patients who had not received thrombolysis or mechanical thrombectomy. ClinicalTrials.gov Identifier: NCT02308605.

Quality of life, morbidity, and mortality results of a prospective phase II study of intermittent androgen suppression for men with evidence of prostate-specific antigen relapse after radiation therapy for locally advanced prostate cancer.

BACKGROUND: Observations of quality of life (QOL), morbidity, and mortality were obtained from the results of a prospective phase II study of intermittent androgen suppression for recurrent prostate cancer after radiation therapy. PATIENTS AND METHODS: Patients with histologically confirmed adenocarcinoma of the prostate and a rising serum prostate-specific antigen level after external-beam radiation of the prostate were treated intermittently with a 36-week course of cyproterone and leuprolide. At predetermined intervals, QOL was assessed using the Southwest Oncology Group 9346 QOL and the American Urological Association symptom score questionnaires. Progression-free and overall survival rates were estimated using the Kaplan-Meier method. Parameters related to progression were explored with univariate and multivariate analyses. RESULTS: The incidence of adverse events was higher when patients were on treatment. Fatigue, dyspnea, and hematuria were the most common symptoms and signs recorded (50.5%, 24.8%, and 17.4%, respectively). Less frequent were myocardial infarction (7.3%), cerebrovascular accident (6.4%), and deep vein thrombosis (5.5%). Quality of life improved when off treatment, as indicated by a shift toward baseline levels in the scales depicting physical and work functions, hot flashes, impotence, sexual performance, urgency, and nocturia. Biochemical recurrence-free survival at 5 years was 70%, with a median > 6 years. The overall 5-year survival was 80%, similar to that of an age-matched population of normal men. CONCLUSION: Intermittent androgen suppression is a potentially useful treatment for locally recurrent prostate cancer after radiation therapy with QOL benefits in the off-treatment interval and no apparent deleterious effects on short- to medium-term survival.

Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial.

BACKGROUND: The British Columbia randomized radiation trial was designed to determine the survival impact of locoregional radiation therapy in premenopausal patients with lymph node-positive breast cancer treated by modified radical mastectomy and adjuvant chemotherapy. Three hundred eighteen patients were assigned to receive no further therapy or radiation therapy (37.5 Gy in 16 fractions). Previous analysis at the 15-year follow-up showed that radiation therapy was associated with a statistically significant improvement in breast cancer survival but that improvement in overall survival was of only borderline statistical significance. We report the analysis of data from the 20-year follow-up. METHODS: Survival was analyzed by the Kaplan-Meier method. Relative risk estimates were calculated by the Wald test from the proportional hazards regression model. All statistical tests were two-sided. RESULTS: At the 20 year follow up (median follow up for live patients: 249 months) chemotherapy and radiation therapy, compared with chemotherapy alone, were associated with a statistically significant improvement in all end points analyzed, including survival free of isolated locoregional recurrences (74% versus 90%, respectively; relative risk [RR] = 0.36, 95% confidence interval [CI] = 0.18 to 0.71; P = .002), systemic relapse-free survival (31% versus 48%; RR = 0.66, 95% CI = 0.49 to 0.88; P = .004), breast cancer-free survival (48% versus 30%; RR = 0.63, 95% CI = 0.47 to 0.83; P = .001), event-free survival (35% versus 25%; RR = 0.70, 95% CI = 0.54 to 0.92; P = .009), breast cancer-specific survival (53% versus 38%; RR = 0.67, 95% CI = 0.49 to 0.90; P = .008), and, in contrast to the 15-year follow-up results, overall survival (47% versus 37%; RR = 0.73, 95% CI = 0.55 to 0.98; P = .03). Long-term toxicities, including cardiac deaths (1.8% versus 0.6%), were minimal for both arms. CONCLUSION: For patients with high-risk breast cancer treated with modified radical mastectomy, treatment with radiation therapy (schedule of 16 fractions) and adjuvant chemotherapy leads to better survival outcomes than chemotherapy alone, and it is well tolerated, with acceptable long-term toxicity.

Trends in prostate cancer incidence and mortality: an analysis of mortality change by screening intensity.

BACKGROUND: The rate of death from prostate cancer has recently declined in many areas of the world. Over the past 15 years prostate-specific antigen (PSA) screening has increased in popularity, which has resulted in increases in the incidence of prostate cancer. Over the same period there have been changes in the management of the disease and, in particular, the use of androgen ablation. We set out to examine the relation between changes in prostate cancer incidence (a surrogate for PSA screening) and subsequent changes in mortality in regions using common treatment recommendations. METHODS: We used data from prostate cancer cases and deaths reported to the British Columbia Cancer Registry during 1985-1999 to examine trends in incidence and mortality in 88 small health areas (SHAs) among men aged 50-74 years. We conducted 2 analyses. In the first we classified the SHAs by intensity of PSA screening (low, medium or high) according to their ranked age-standardized incidence rate of prostate cancer in 1990-1994 and examined subsequent trends in prostate cancer mortality. In the second analysis we examined the SHA-specific relative change in prostate cancer incidence between 1985-1989 and 1990-1994 and correlated it with the relative change in mortality for cases diagnosed after 1990. RESULTS: Between 1985-1989 and 1990-1994 the incidence of prostate cancer increased by 53.2% and 14.6% among men aged 50-74 and those 75 and over respectively. Between 1985-1989 and 1995-1999 prostate cancer mortality declined by 17.6% and 7.9% in the 2 age groups respectively. Among men aged 50-74 years SHAs with low, middle and high levels of screening had respective increases in prostate cancer incidence of 5.4%, 53.6% and 70.5% between 1985-1989 and 1990-1994. Corresponding decreases in mortality between 1985-1989 and 1995-1999 were 28.9%, 18.0% and 13.5%. Mortality declines were greatest in SHAs with low screening levels (p = 0.032). Before 1990 prostate cancer mortality was similar in the 3 screening groups (p = 0.72). Regions with the smallest increases in incidence had the largest declines in mortality. INTERPRETATION: We found no association between the intensity of PSA screening and subsequent decreases in prostate cancer mortality.

Estimating cancer prevalence using mixture models for cancer survival.

Knowledge of cancer prevalence is useful for estimating the ongoing level of resources utilized in the treatment of disease and is of some public health interest. Cancer prevalence is estimated first as the proportion of persons previously diagnosed (PD) with cancer that are still alive; and second as the proportion of individuals in the population who were previously diagnosed with cancer and who have not been cured (NC). The proportion of cases that are cured is estimated by assuming that the cured and uncured cases have distinct survival patterns. The hazard for cured cases is assumed to be a multiple of the hazard from causes other than cancer in the general population. The hazard for uncured cases is assumed to have two independent components: one corresponding to the disease-specific hazard, and the other a multiple of the population hazard from 'other causes'. Future prevalence estimates are obtained by projecting the survival of current prevalent cases as well as the survival of future incident cases.