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Biomedical subjects

A Norman

Publications and source records attributed to A Norman.

At least 37 records · Page 2Linked to original sources

Baseline quality of life predicts survival in patients with advanced colorectal cancer.

The aim of this study was to investigate the influence of baseline quality of life (QoL) on survival in patients with advanced colorectal cancer. From 1992 to 1998, four randomised clinical trials in advanced colorectal cancer were conducted at this institution. The European Organization for Research and Treatment of Cancer-Quality of Life Core 30 (EORTC-QLQ-C30) questionnaire was completed prior to the commencement of chemotherapy. Analyses were performed on median-dichotomised baseline Quality of Life (QoL) and clinical prognostic factors. Baseline QoL questionnaires were completed by 501 patients. One-year survival was 38.3 and 72.5% (P<0.0001) for patients with global QoL scores below and above the median (67), respectively. Other than cognitive functioning, fatigue, appetite, constipation, diarrhoea and financial domains, all QoL scales were significant independent predictors of survival (P<0.035). In the final model, the global QoL score remained highly significant as an independent predictor of survival (P<0.0001). Baseline QoL is a strong independent predictor of survival in patients with advanced colorectal cancer. Measurements should be routinely recorded in clinical trials to stratify cohorts and aid in trial comparison.

Adult↗

Total physical activity in relation to age, body mass, health and other factors in a cohort of Swedish men.

BACKGROUND: Despite a large public health interest in physical activity and its role in obesity and other chronic diseases, only a few reports to date have addressed total levels of physical activity in relation to age, body mass, health and other lifestyle factors. OBJECTIVE: To investigate whether levels of total physical activity among men are associated with age, body mass, self-rated health and other lifestyle factors in a cross-sectional setting. METHODS: In a population-based cohort of 33 466 men aged 45-79 y in central Sweden, we collected information about physical activity through a self-administered questionnaire. Level of total physical activity was assessed quantitatively based on six questions on different activities: work/occupation, housework, walking/bicycling, exercise, inactive leisure time and sleeping. The physical activity levels were measured as metabolic equivalents, MET-h/day. The relation between age, body mass index, smoking, education, marital status and self-rated health, and total physical activity was studied in a cross-sectional analysis, using multivariate regression. RESULTS: Total daily physical activity was decreasing systematically between age 45 and 79 (-4.1%, 95% CI -4.6, -3.6). Obese men reported -2.6% (95% CI -3.0, -2.1) lower physical activity than normal weight men. Those with high education had -7.0% (95%CI -7.3, -6.7) lower total physical activity than those with elementary school. Men with self-rated poor health had -11.3% (95%CI -12.1, -10.6) lower physical activity than those reporting very good health. The cross-sectionally observed decrease with age was greatest among obese men (-8.7%), current smokers (-7.9%), low-educated men (-5.6%) and those with poor health (-9.8%); the subgroups with very good health reported almost the same level of total physical activity (-0.6%) for age 74-79 as for age 45-49. CONCLUSIONS: The observed decreasing levels of total physical activity with age to large degree depend on health status and other factors. The characterization of subjects with low total physical activity levels is of importance for understanding observed worldwide trends in increasing prevalence of obesity. The better understanding of these phenomena might also facilitate a better planning of public health interventions with messages specifically adjusted for subgroups of population with lower physical activity.

Aged↗

A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer.

BACKGROUND: This randomised study compared protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin C (MMC) in patients with advanced oesophago-gastric cancer. PATIENTS AND METHODS: Two hundred and fifty-four patients with adenocarcinoma, squamous cell carcinoma or undifferentiated carcinoma involving the oesophagus, oesophago-gastric junction or the stomach were randomised. The major end points were tumour response, survival, toxicity and quality of life. RESULTS: The median age of patients treated was 72 years and the two arms were well-balanced for baseline demographic factors. The overall response rate was 16.1% [95% confidence interval (CI) 9.5% to 22.7%] in patients treated with PVI 5-FU alone compared with 19.1% (95% CI 12.0% to 26.0%) for those treated with PVI 5-FU plus MMC (P = 0.555). Median time to treatment failure was 3.9 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC (P = 0.195). Median survival was 6.3 months for PVI 5-FU and 5.3 months for PVI 5-FU plus MMC (P = 1.0). Toxicity was mild for both treatments. Symptomatic benefit measured by improvement in pain control, weight loss, dysphagia and oesophageal reflux was observed in over 64% of patients in each arm. Quality of life scores were comparable in each arm. CONCLUSIONS: PVI 5-FU is a safe, effective form of palliation for patients with advanced oesophago-gastric cancer although the addition of MMC adds little extra benefit.

Aged↗

A multicentre phase II trial of primary chemotherapy with cisplatin and protracted venous infusion 5-fluorouracil followed by chemoradiation in patients with carcinoma of the oesophagus.

BACKGROUND: We undertook a multicentre phase II trial to evaluate the safety and efficacy of primary chemotherapy followed by chemoradiation for localised adenocarcinoma or squamous carcinoma of the oesophagus. PATIENTS AND METHODS: Chemotherapy comprised five 3-weekly cycles of cisplatin and protracted continuous infusion 5-fluorouracil, with conformally planned radiotherapy commencing at the start of the fifth cycle. RESULTS: The planned treatment programme was completed by 39 of 72 patients (54%), and a further 13% completed chemotherapy and proceeded to surgical oesophagectomy. Response rates to chemotherapy and to the entire treatment programme were 47% [95% confidence interval (CI) 34% to 60%] and 56% (CI 43% to 68%). The dysphagia score improved in 54% of patients. The median survival duration was 14.6 months with 1- and 2-year survival rates of 58.7% and 44.1%, respectively. Grade III/IV chemotherapy-related toxicity occurred in 38% of patients, and there were no treatment-related deaths. CONCLUSIONS: This is a feasible and active treatment regimen providing palliative benefits for patients with poor-prognosis localised oesophageal cancer.

Adenocarcinoma↗

Accuracy of set-up of thoracic radiotherapy: prospective analysis of 24 patients treated with radiotherapy for lung cancer.

In thoracic radiotherapy, a number of factors hinder the use of portal films and electronic portal imaging devices for measuring field placement errors (FPEs). The aim of this study was to assess the accuracy of treatment set-up using simulator check films (SCFs) in radiotherapy for lung cancer. Prospective evaluation was performed on 24 patients. During their radiotherapy, patients returned to the simulator weekly for a minimum of four SCFs, for which the parameters from the original simulator planning film were set, positioning being achieved without fluoroscopy. A total of 96 SCFs were taken. FPEs in left-right (L-R) and superior-inferior (S-I) direction, as well as coronal rotational errors, were measured. The mean absolute FPE was 0.35 cm in the L-R axis and 0.43 cm in the S-I axis. Statistically, the FPEs in the S-I direction were greater than those in the L-R direction (p<0.001). A margin of 0.93 cm between the clinical target volume and the planning target volume would cover 95% of FPEs in the L-R direction, whilst a margin of 1.13 cm is needed for this degree of certainty in the S-I direction. Mean coronal rotational error was 1.6 degrees. Systematic errors were greater than random errors. This study demonstrated that the FPEs were within clinical tolerance (< or = 0.7 cm) in 84.9% of the measurements. The planning margins used in our clinical practice compare favourably with the FPEs in this study.

Adult↗

The prevalence of avascular necrosis in patients treated with chemotherapy for testicular tumours.

To study the prevalence of avascular necrosis in patients receiving chemotherapy for testicular cancer we invited 103 consecutive patients treated by chemotherapy to attend for MRI scan of the hips. Four of 47 (9% (CI 2-20%)) patients scanned and 4/103 (3.8% (CI 1-10%)) of patients invited to participate in the study had evidence of avascular necrosis. As not all patients in the study had completed the at risk period this equates to a 3-year actuarial risk of 6.3% (95% confidence limits (CI) 2.4-16.1). These data suggest that avascular necrosis is an uncommon but significant complication of chemotherapy including steroids as anti-emetics.

Adolescent↗

Oxaliplatin and protracted venous infusion of 5-fluorouracil in patients with advanced or relapsed 5-fluorouracil pretreated colorectal cancer.

The purpose of this study was to evaluate the activity and safety of oxaliplatin and protracted venous infusion of 5-fluorouracil (PVI 5-FU) in patients with advanced or relapsed 5-FU pretreated colorectal cancer. 38 patients with advanced or metastatic colorectal carcinoma with documented progression on or within 6 months following 5-FU or thymidylate synthase inhibitor containing chemotherapy were recruited between June 1997 and September 2000. Oxaliplatin (100 mg x m(-2)) was given every 2 weeks and PVI 5-FU (300 mg x m(-2) x day(-1)) was administered. Median age of patients was 61 years. 17 patients had >2 sites of disease involvement. 10 had received 5-FU based adjuvant chemotherapy. 16 received oxaliplatin and PVI 5-FU as second-line chemotherapy for advanced disease and 22 as third or subsequent lines. Median follow up was 6.1 months. The best achieved objective tumour response rate was 29% (11 partial responses 95% confidence interval [CI] = 15-46%). 20 patients (52.6%) had stable disease. The median duration of response was 3.9 months. Even for patients who had previously received both 5-FU and irinotecan (n = 22), 27.3% had partial response with oxaliplatin and PVI 5-FU. 37 patients had symptoms on entry into the study. 25 patients had pain, 10 had anorexia and 28 had lethargy. 64%, 70% and 17.9% had symptomatic improvement after treatment respectively. Grade 3-4 toxicities were anaemia 10.6%, neutropenia 2.6%, thrombocytopenia 5.2%, diarrhoea 18.9%, nausea and vomiting 2.7%, infection 5.4% and lethargy 37.8%. The median survival was 9.1 months. Probability of overall survival at 6 months was 58.4% (95% CI = 38.7-73.7%). The median failure-free survival was 4 months. Oxaliplatin and PVI 5FU is an active and well tolerated regimen in patients with heavily pre-treated advanced colorectal cancer.

Adult↗

Validity and reproducibility of self-reported total physical activity--differences by relative weight.

OBJECTIVE: Physical activity is hypothesized to reduce the risk of obesity and several other chronic diseases and enhance longevity. However, most of the questionnaires used measure only part of total physical activity, occupational and/or leisure-time activity, which might lead to misclassification of total physical activity level and to dilution of risk estimates. We evaluated the validity and reproducibility of a short self-administered physical activity questionnaire, intended to measure long-term total daily 24 h physical activity. METHOD: The questionnaire included questions on level of physical activity at work, hours per day of walking/bicycling, home/household work, leisure-time activity/inactivity and sleeping and was sent twice during one year (winter/spring and late summer). Two 7-day activity records, performed 6 months apart, were used as the reference method. One-hundred and eleven men, aged 44-78, completed the questionnaire and one or two activity records. The physical activity levels were measured as metabolic equivalents (MET)xh/day. RESULTS: Spearman correlation coefficient between total daily activity score estimated from the first questionnaire and the records (validity) was 0.56 (deattenuated) and between the first and the second questionnaire (reproducibility) 0.65. Significantly higher validity correlations were observed in men with self-reported body mass index below 26 kg/m(2) than in heavier men (r=0.73 vs r=0.39). CONCLUSIONS: This study indicates that the average total daily physical activity scores can be estimated satisfactorily in men using this simple self-administered questionnaire.

Adult↗

An oxaliplatin-based chemotherapy in patients with relapsed or refractory intermediate and high-grade non-Hodgkin's lymphoma.

This study was designed to assess the efficacy and safety of substituting cisplatin with oxaliplatin in the DHAP (dexamethasone, cytarabine and cisplatin) regimen for patients with relapsed or refractory non-Hodgkin's lymphoma. Twenty-four evaluable patients with intermediate or high-grade non-Hodgkin's lymphoma were treated at 3-weekly intervals with oxaliplatin (130 mg/m2, d 1), cytarabine (2 g/m2 for two doses, d 2) and dexamethasone (40 mg, d 1-4). The median age of the patients was 58 (range 18-70). Histological subtypes were diffuse large B cell, 20; mantle cell, two; anaplastic large cell, one; and peripheral T cell, one. The overall objective response rate (RR) was 50% [95% confidence interval (CI) = 29-71%] including four complete responses and eight partial responses. RR for those patients treated at first relapse was higher than those treated at second and subsequent relapse (77% versus 29%). Grade 3 and 4 toxicity was mainly haematological: anaemia 17%, neutropenia 75% and thrombocytopenia 75%. No grade 4 non-haematological toxicity was reported. No significant renal and neurotoxicity was demonstrated. Median survival was 10.6 months. Probabilities of 1-year progression-free survival and overall survival were 47% (95% CI = 26-66%) and 50% (95% CI = 23-72%) respectively. In conclusion, dexamethasone, cytarabine and oxaliplatin (DHAX) is a novel combination in salvage therapy for relapsed or refractory non-Hodgkin's lymphoma. It has clinically significant activity with an acceptable toxicity profile. Lack of renal toxicity makes DHAX an attractive cytoreductive regimen before high-dose chemotherapy.

Adolescent↗

Accelerated chemotherapy in the treatment of urothelial cancer.

To evaluate an alternative treatment for advanced or metastatic urothelial cancers, a dose-intensive combination chemotherapy regimen using carboplatin, methotrexate, vincristine and cisplatin was given to 60 patients over a 3-year period (1990 to 1993). There were 26 patients with locally advanced disease and 34 with metastatic disease; 49 patients were evaluable for response. A complete response was noted in four patients (8%) and a partial response in 15 (31%), for an overall response rate of 39%. The median survival was 12 months. Two- and 5-year survival rates were 25.5% (95% confidence interval CI) 15.2-37.0) and 7.3% (95% CI 2.2-16.4) respectively. Failure-free survival was 15.3% (95% CI 7.5-25.6) at 2 years and 5.9% (95% CI 1.6-14.4) at 5 years, with a median of 8 months. For the responders, the median duration of response was 14 months, with a range of 2-59+ months. Toxicity included myelosuppression (28% grade 4/5 neutropenia, 19% grade 4 thrombocytopenia), peripheral neuropathy (54% grade 1 and 23% grade 2/3) and ototoxicity (21% grade 1, 19% grade 2). This schedule of dose-intensified platinum-based chemotherapy for bladder cancer resulted in significant neurotoxicity without evidence of enhanced response rates or survival. Regimens such as methotrexate, vinblastine, doxorubicin and cisplatin should remain standard. Accelerated regimens may be useful in situations were it is necessary to administer chemotherapy over a short time (e.g. as part of combined modality treatment).

Antineoplastic Combined Chemotherapy Protocols↗

Using intact nerve to bridge peripheral nerve defects: an alternative to the use of nerve grafts.

This preliminary study was conducted to determine whether a regenerating peripheral nerve in a rat model can use the epineurium of an intact nerve to bridge a nerve gap defect. To create the intact nerve bridge a 1-cm segment of the peroneal nerve is resected leaving a gap defect. The proximal and distal peroneal nerve stumps are sutured 1-cm apart, in an end-to-side fashion, to the epineurium of the intact tibial nerve. The following experimental groups were used (n = 12): group A, immediate primary repair of resected segment; group B, intact nerve bridge technique; group C, nerve autograft; and group D, gap in situ control. Evaluation 12 weeks after surgery included measurement of the tibialis anterior muscle contraction force, axonal counting, wet weight of the tibialis anterior muscle, and histologic examination. The results of this animal study support 3 main conclusions: regenerating axons can use the epineurium of an intact nerve to bridge a gap in nerve continuity; when using functional recovery to assess regeneration, there is no significant difference between standard nerve autografts and the intact nerve bridge technique; and based on histologic examination, the intact nerve bridge technique does not injure the intact tibial nerve used to bridge the gap defect. Taken together, the results of this preliminary animal study suggest that the intact nerve bridge technique may be a potential alternative to standard nerve autografts in appropriate circumstances. Further investigation in a higher animal model is warranted before considering clinical application of the intact nerve bridge technique.

Analysis of Variance↗

Meta-analysis of increases in micronuclei in peripheral blood lymphocytes after angiography or excretory urography.

Norman, A., Cochran, S. T. and Sayre, J. W. Meta-analysis of Increases in Micronuclei in Peripheral Blood Lymphocytes after Angiography or Excretory Urography. Radiat. Res. 155, 740-743 (2001). Meta-analysis of 10 studies confirms a significant increase in the frequency of micronuclei in peripheral blood lymphocytes after angiography or excretory urography; the weighted average increase is 4.2 (95% confidence interval 2.8-5.6) per 1000 binucleate lymphocytes, about the same increase in micronuclei as that produced in vitro by a diagnostic X-ray dose of 4 cGy. The analysis failed to reveal a significant effect of the specific contrast medium used in the X-ray examinations on the increased frequency of micronuclei. These results are consistent with the hypothesis that the effect of the contrast media is limited to the enhancement, by the photoelectric effect, of the X-ray dose absorbed by the lymphocytes irradiated while suspended in the contrast medium. Therefore, an estimate of increased cancer risk based on elevated frequencies of micronuclei or chromosome aberrations in peripheral blood lymphocytes may be greatly exaggerated whenever the radiation damage is largely confined to the cells circulating in the blood, as it is in people who have recently had X-ray examinations that use intravenous injections of contrast medium. Such examinations include angiography, excretory urography and CT scans, which are received annually by millions of people.

Angiography↗

Family physicians and cancer care. Palliative care patients' perspectives.

OBJECTIVE: To explore factors that affect the integrity of palliative cancer patients' relationships with family physicians and to ascertain their perceptions of their FPs' roles in their care. DESIGN: Qualitative study using grounded-theory methods, taped semistructured interviews, and chart reviews. SETTING: Two palliative care hospital wards in Winnipeg, Man. PARTICIPANTS: A purposeful sample of 11 men and 14 women. METHOD: Qualitative content analysis of interview transcripts. MAIN FINDINGS: Cancer care is organized in a sequential, parallel, or shared manner between FPs and cancer specialists, with sequential care a common outcome if patients' relationships with their FPs wane. Cancer patients can lose contact with FPs because of patient or physician relocation, distrust over delays in diagnosis, failure to perceive a need for FPs, poor communication between FPs and specialists, and a lack of FP involvement in the hospital. People with cancer value FPs for being accessible through prompt appointments and telephone contact; for providing emotional and family support; and for referral, triage, and general medical care. CONCLUSION: Family physicians can enhance care of cancer patients. Contact with FPs can be maintained by ensuring good communication between specialists and FPs, defining a clear role for FPs, addressing concerns about delays in diagnosis, and referring patients back to FPs, particularly after hospitalization.

Adult↗

ECF in gastric cancer.

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Antineoplastic Combined Chemotherapy Protocols↗

A randomized study of the use of a customized immobilization system in the treatment of prostate cancer with conformal radiotherapy.

PURPOSE: To evaluate the impact of a customized immobilisation system on field placement accuracy, simulation and treatment delivery time, radiographer convenience and patient acceptability. PATIENTS AND METHODS: Thirty men receiving radical radiotherapy for prostate cancer were randomised using a cross over trial design to have radiotherapy planning and treatment given either in a conventional treatment position (CTP) or using an immobilisation system (IMS). The randomisation was to have either the CTP or IMS for the initial 3 weeks of radiotherapy after which patients were replanned and changed to the alternative treatment set-up. Treatment accuracy was measured using an electronic portal imaging device. Radiographers and patients completed weekly questionnaires. RESULTS: Median simulation time was 22.5 min (range 20-30 min) in the CTP and 25 min (range 15-40 min) for the IMS (P < 0.001). Median treatment time was 9 min for CTP (range 8-10 min), and 10 min (range 8.5-13.5 min) for IMS (P < 0.001). Median isocentre displacement for anterior fields was 1.7 mm from the simulated isocentre for the CTP compared to 2.0 mm for IMS (P = 0.07). For left lateral fields values were 1.8 and 1.8 mm (P = 0.98), and for right lateral fields 2.1 and 1.7 mm (P = 0.06), respectively. No clinically significant reduction in either systematic or random field placement errors was demonstrated. Radiographers reported that patients found the IMS more comfortable than CTP (P < 0.001), but when using the IMS, they noticed greater difficulty in patient positioning (P < 0.001), and alignment to skin tattoos (P < 0.001). CONCLUSIONS: Although IMS may have been more comfortable, treatment accuracy was not improved compared to the CTP in our department. In addition, treatment took longer and patient set-up was more difficult.

Aged↗

A clinical nomogram for predicting long-term survival in advanced colorectal cancer.

From our prospectively accrued database of patients with gastrointestinal cancer, 1057 patients with advanced colorectal cancer were identified with the aim of determining predictive factors for survival of greater than 2 years and to use this information to develop a predictive nomogram. Patient's baseline characteristics, type and number of chemotherapy regimens received, and response to chemotherapy were assessed by univariate and multivariate logistic regression comparing those who survived greater than or less than 2 years. A total of 161 (15.2%) patients survived more than 2 years, so-called long survivors (LS). In multivariate analysis, positive predictive factors for LS were: good performance status (PS), normal serum carcinoembryonic antigen (CEA), rectal primary, Dukes' stage A-B, well or moderate differentiation, two or less disease sites, response to chemotherapy and treatment used protracted venous infusion (PVI) 5-fluorouracil (5-FU) in first-line chemotherapy, and the increasing number of chemotherapy treatments received. From these PS, CEA, number of sites and response to first-line chemotherapy were used to develop a nomogram capable of predicting the probability of survival beyond 2 years for an individual patient. This large study confirmed the relevance of known prognostic factors in metastatic colorectal cancer and demonstrated the importance of response to chemotherapy as an independent factor to predict LS. By combining these, we developed a nomogram which provides information which is likely to prove useful in the management of patients with advanced colorectal cancer.

Adolescent↗

Are 18fluorodeoxyglucose positron emission tomography and magnetic resonance imaging useful in the prediction of relapse in lymphoma residual masses?

Treatment of both Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) frequently results in a residual mass visible radiologically. Such patients may receive radiotherapy unnecessarily because the residual mass may represent benign fibrotic tissue rather than residual active lymphoma. Radiotherapy has been shown to have significant short and more worrying long-term toxicity. Refining the criteria for its use would be a major advance. A number of clinical investigations have been evaluated to more accurately determine the nature of such lesions, including erythrocyte sedimentation rate (ESR), magnetic resonance imaging (MRI) and high-dose gallium-67 scanning (HDGS) but none has proven utility. 18[F]-fluorodeoxyglucose positron emission tomography (FDG-PET) is an imaging technique that has been shown to be useful in distinguishing fibrosis from residual active disease in solid tumours. The aim of this study was to compare FDG PET and MRI in the assessment of residual masses following treatment for lymphoma. Patients with NHL/HD who had a residual mass following chemotherapy were eligible for this study. Patients had a combination of MRI and/or PET. All scans were completed within 5 months of the end of treatment. Patients were followed-up for relapse. 56 patients had an MRI scan, 24 had a PET scan and 22 patients had both investigations. Overall sensitivity and specificity, respectively, were for MRI 45% and 74%, PET 50% and 69%, and PET/MRI concurring 50% and 67%. There was a trend for improved relapse-free survival (RFS) with a negative result of both MRI and PET, but this was not statistically significant. The predictive value for both tests failed to reach statistical significance. Subgroup analysis suggests that PET may be better at predicting relapse in patients with NHL, especially those with masses above the diaphragm. There is no convincing evidence that either MRI or PET or the combination can reliably predict relapse within residual masses after treatment for lymphoma. A negative PET scan however appears to be more informative than a positive result and may well aid clinical decision making. There are a number of factors that may produce false-positive results, including post-treatment inflammatory changes, the sensitivity of the test in the setting of minimal residual disease and the heterogeneity of the histological subtypes studied. A negative PET (or MRI) result in lymphoma residual masses following therapy may negate the necessity for further therapy such as chemotherapy or radiotherapy and their concomitant toxicities.

Adolescent↗