Job Kievit

THE EFFECT OF A SINGLE FRACTION COMPARED TO MULTIPLE FRACTIONS ON PAINFUL BONE METASTASES : A GLOBAL ANALYSIS OF THE DUTCH BONE METASTASIS STUDY

PURPOSE To answer the question whether a single fraction of radiotherapy that is considered more convenient to the patient is as effective as a dose of multiple fractions for palliation of painful bone metastases. PATIENTS 1171 patients were randomised to receive either 8 Gy x 1 (n = 585) or 4 Gy x 6 (n = 586). The primary tumour was in the breast in 39% of the patients, in the prostate in 23%, in the lung in 25% and in other locations in 13%. Bone metastases were located in the spine (30%), pelvis (36%), femur (10%), ribs (8%), humerus (6%) and other sites (10%). METHOD Questionnaires were mailed to collect information on pain, analgesics consumption, quality of life and side effects during treatment. The main endpoint was pain measured on a pain scale from 0 (no pain at all) to 10 (worst imaginable pain). Costs per treatment schedule were estimated. RESULTS On average, patients participated in the study for 4 months. Median survival was 7 months. Response was defined as a decrease of at least two points as compared to the initial pain score. The difference in response between the two treatment groups proved not significant and stayed well within the margin of 10%. Overall, 71% experienced a response at some time during the first year. An analysis of repeated measures confirmed that the two treatment schedules were equivalent in terms of palliation. With regard to pain medication, quality of life and side effects no differences between the two treatment groups were found. The total number of retreatments was 188 (16%). This number was 147 (25%) in the 8 Gy x 1 irradiation group and 41 (7%) in the 4 Gy x 6 group. It was shown that the level of pain was an important reason to retreat. There were also indications that doctors were more willing to retreat patients in the single fraction group because time to retreatment was substantially shorter in this group and the preceding pain score was lower. Unexpectedly, more pathological fractures were observed in the single fraction group, but the absolute percentage was low. In a cost-analysis, the costs of the 4 Gy x 6 and the 8 Gy x 1 treatment schedules were calculated at 2305 and 1734 Euro respectively. Including the costs of retreatment reduced this 25% cost difference to only 8%. The saving of radiotherapy capacity, however, was considered the major economic advantage of the single dose schedule. CONCLUSION The global analysis of the Dutch study indicates the equality of a single fraction as compared to a 6 fraction treatment in patients with painful bone metastases provided that 4 times more retreatments are accepted in the single dose group. This equality is also shown in long term survivors. A more detailed analysis of the study is in progress.

Follow-up of patients with colorectal cancer. A meta-analysis.

ObjectiveThe authors sought to determine whether intensive follow-up improves 5-year survival rates in patients with colorectal cancer who were operated on for cure. Summary Background DataIntensive follow-up of patients with colorectal cancer is still controversial. The present uncertainty in regard to the value of intensive follow-up could be the result of the absence of prospective randomized studies comparing patients with and without follow-up.Methods Studies comparing two follow-up programs of different intensities were identified in the medical literature and were aggregated in a meta-analysis using the “random effects method.” even nonrandomized studies describing 3283 patients were analyzed. ResultsPatients with intensive follow-up did have 9% better 5-year survival rates than did those with minimal or no follow-up, only when intensive follow-up included carcinoembryonic antigen (CEA) assays. In addition, more asymptomatic recurrences were detected and more recurrences were resected in patients with intensive follow-up. ConclusionsThis meta-analysis indicated that intensive follow-up using CEA assays can identify treatable recurrences at a relatively early stage. Treatment of these recurrences appears to be associated with improved 5-year survival rates. However, not all intensive follow-up strategies will be equally effective. Follow-up may yield the best results if diagnostic tests are used only to detect those recurrences that can be operated on with curative intent and when follow-up is “individualized,” according to patient characteristics.

Follow-up of patients with colorectal cancer: numbers needed to test and treat

Follow-up after curative treatment of patients with colorectal cancer has as its main aims the quality assessment of the treatment given, patient support, and improved outcome by the early detection and treatment of cancer recurrence. How often, and to what extent, the final aim, improved survival, is indeed realised is so far unclear. A literature search was performed to provide quantitative estimates for the main determinants of the effectiveness of the follow-up. Data were extracted from a total of 267 articles and databases, and were aggregated using modern meta-analytic methods. In order to provide one more colorectal cancer patient with long-term survival through follow-up, 360 positive follow-up tests and 11 operations for colorectal cancer recurrence are needed. In the remaining 359 tests and 10 operations, either no gains are achieved or harm is done. As the third aim of colorectal cancer follow-up, improved survival, is realised in only few patients, follow-up should focus less on diagnosis and treatment of recurrences. It should be of limited intensity and duration (3 years), and the search for preclinical cancer recurrence should primarily be performed by carcino-embryonic antigen (CEA) testing and ultrasound (US). The focus of colorectal cancer follow-up should shift from the early detection of recurrence towards quality assessment and patient support. As support that is as good or even better can be provided by a patients general practitioner (GP) or by specialised nursing personnel, there is no need for routine follow-up to be performed by the surgeon.

Carotid Recurrent Stenosis and Risk of Ipsilateral Stroke A Systematic Review of the Literature

BACKGROUND The main goal of follow-up after carotid endarterectomy is to prevent new strokes caused by recurrent stenosis. To determine the most cost-effective follow-up schedule, it is necessary to know the incidence of recurrent stenosis and the risk of stroke it carries. METHODS A systematic review of the literature was performed using standard meta-analytical techniques. RESULTS Incidence of recurrent stenosis: The data were very heterogeneous. The risk of recurrent stenosis was 10% in the first year, 3% in the second, and 2% in the third. Long-term risk of recurrent stenosis is about 1% per year. Risk of stroke: The reported relative risks of stroke in patients with recurrent stenosis compared with patients without recurrent stenosis showed extreme heterogeneity and ranged from 10 to 0.10. The random effects summary estimator of relative risk was 1.88. CONCLUSIONS The data were very heterogeneous, and much better data are needed to arrive at truly reliable estimates of these important parameters of follow-up. It is clear, though, that the risk of recurrent stenosis is highest in the first few years after carotid endarterectomy and very low in later years. By use of general decision-analytic arguments, it can be argued that, given the test characteristics of carotid ultrasound, a small number of tests can be done in the first few years and that testing for restenosis should not be done after 4 years.

Complications of thyroid surgery

AbstractBackground: The morbidity of thyroid surgery is low. Despite this, some authors advocate a subtotal thyroidectomy instead of a total thyroidectomy, to avoid the higher morbidity associated with a total thyroidectomy. Methods: We retrospectively evaluated the complications of thyroid surgery in Leiden between January 1, 1982 and October 1, 1990. Three hundred forty-one patients—261 women and 80 men—had 356 operations; 15 patients were operated on twice; there were 152 total hemithyroidectomies, 3 subtotal hemithyroidectomies, 33 total thyroidectomies, 122 bilateral subtotal hemithyroidectomies, 12 combinations of total and subtotal hemithyroidectomies, and 34 other operations. Results: Calculated for the nerves at risk (n=489), the percentage of permanent recurrent nerve lesions was 3.1 (in the 5 most recent years it was 1.2%). There was no significant difference between total or subtotal (hemi)thyroidectomies. Initial symptomatic hypocalcemia necessitating supplementation was encountered 42 times (12.5%). The occurrence of permanent symptomatic hypocalcemia (6%) was not significantly different between total and subtotal (hemi)thyroidectomies (p=0.06). The duration of surgery was 137.8 min for bilateral subtotal thyroidectomies and 182.9 min for bilateral total thyroidectomies (p<0.0001). There was no difference in blood loss between total and subtotal (hemi)thyroidectomies. Conclusions: Because total thyroidectomy carries a risk of complications similar to that for subtotal thyroidectomy, it is not logical to avoid total resections. If the number of total resections were increased, it is anticipated that fewer reoperations, which involve a relatively high morbidity rate, would have to be performed.

Utility assessment in cancer patients : adjustment of time tradeoff scores for the utility of life years and comparison with standard gamble scores

The standard gamble (SG) and the time tradeoff (TTO), two frequently used methods of utility assessment, have often been found to lead to different utilities for the same health state. The authors investigated whether adjustment of TTO scores for the utility of life years (risk attitude) eliminated this difference. In addition, the association between risk attitude and sociodemographic and medical variables was studied. In 30 disease-free testicular cancer patients, SG and TTO were used to assess the utilities of four health profiles relevant to testicular cancer. Utility of life years was estimated from certainty equivalents (CEs). SG scores were significantly higher than unadjusted TTO scores for all profiles. As the majority of patients (85%) were risk-averse, CE-adjusted TTO scores were higher than unadjusted scores, and were not significantly different from those obtained from the SG for three of the four profiles. However, adjusted scores were still slightly but consistently lower than SG scores. Possible explanations for this discrepancy are discussed. An association was found between risk aversion and medical treatment: patients who had received chemotherapy for their cancers were more risk-averse than were patients who had been in a surveillance protocol only. As risk aversion can have an impact on treatment decisions, it is important to assess the risk posture of the patient to whom the decision pertains. Key words: utility assessment; QALY; risk aversion; oncology; treatment preferences. (Med Decis Making 1994;14:82-90)

Diagnostic value of serum thyroglobulin measurements in the follow‐up of differentiated thyroid carcinoma, a structured meta‐analysis

objective  To investigate to what extent thyroid remnant ablation and withdrawal from thyroxine are required to achieve sufficient accuracy of serum thyroglobulin (Tg) measurements as an indicator of tumour recurrence in the follow‐up of patients with differentiated thyroid carcinoma.

Internet-Based Self-management Plus Education Compared With Usual Care in Asthma: A Randomized Trial

Context Patient self-management is an essential component of asthma care, and the Internet is a medium to potentially support patients in self-management. Contribution This randomized trial compared Internet-based asthma self-management with usual care and found modest improvements in asthma control and lung function with the Internet intervention, but found no reduction in exacerbations and changes in asthma-related quality of life that were less than clinically significant at 12 months. Implication Although Internet-based self management can improve some asthma outcomes, the improvements were small and the program did not reduce the number of exacerbations. The Editors Asthma is a chronic disorder of the airways that is characterized by recurring respiratory symptoms, variable airflow obstruction, airway hyperresponsiveness, and underlying inflammation (1, 2). Recent clinical guidelines for the management of asthma distinguish 4 essential components of asthma care: assessment and monitoring, patient education, control of environmental and comorbid factors that affect asthma, and drug treatment. With appropriate medical care, well-informed and empowered patients can control their asthma and live full, active lives (1, 2). However, despite the availability of monitoring tools and effective therapy, asthma control is suboptimal in many patients worldwide, and long-term management falls far short of the goals set in the guidelines (3). Self-monitoring, education, and specific medical care are important aspects in improving the lives of patients with asthma (1, 2). However, many patients with mild or moderate persistent asthma do not attend checkups regularly or visit their physician with symptoms of the disease (4). In addition, in practice, both patients and their health care providers are reluctant to use written self-management plans (5). Internet technology is increasingly seen as an appealing tool to support self-management for patients with chronic disease in remote and underserved populations (68). However, to date, studies on Internet-based asthma self-management show only short-term improvements in asthma control, lung function, and quality of life (911). Long-term studies on the effect of Internet-based self-management, including all its essential features, are not available. Therefore, we developed a guided self-management tool for adult patients with asthma that included Internet-based home monitoring and treatment advice (action plan), online education, and remote Web communication with a specialized asthma nurse. The goal of our study was to assess the long-term clinical effectiveness of Internet-based self-management education compared with usual physician-provided care alone. Methods Design Overview We conducted a 12-month, multicenter, nonblinded, randomized, controlled trial. We randomly assigned patients to Internet-based self-management (Internet group) as an adjunct to usual care or to usual physician-provided care alone (usual care group). The Internet-based self-management program included weekly asthma control monitoring and treatment advice, online and group education, and remote Web communications with a specialized asthma nurse. The intervention continued for 12 months after enrollment. The Medical Ethics Committee of the Leiden University Medical Center, Leiden, the Netherlands, approved the study. Setting and Participants We recruited patients from 37 general practices (69 general practitioners) in the Leiden and The Hague area and the Outpatient Clinic of the Department of Pulmonology at the Leiden University Medical Center from September 2005 to September 2006. Inclusion criteria were physician-diagnosed asthma coded according to the International Classification of Primary Care in the electronic medical record (12), age 18 to 50 years, prescription of inhaled corticosteroids for at least 3 months in the previous year, no serious comorbid conditions that interfered with asthma treatment, access to the Internet at home, and mastery of the Dutch language. We excluded patients who were receiving maintenance oral glucocorticosteroid treatment. On the basis of diagnosis, age, prescribed asthma medication, and comorbid conditions, we sent eligible patients an invitation letter followed by 1 reminder letter after 2 to 4 weeks if they did not respond to the first. We continued this process until a total of 200 patients had entered the study (September 2006). All participants gave written consent. Randomization and Intervention In a 2-week baseline period before randomization, we collected data on patient demographic characteristics, asthma-related quality of life, symptom control, lung function, and medication level. We provided basic education about core information on asthma, action of medications, and inhaler technique instructions to all patients. We trained all participants to measure FEV1 daily with a hand-held electronic spirometer (PiKo-1, Ferraris Respiratory, Hertford, United Kingdom) and to report the highest value of 3 measurements in the morning before taking medication (2, 13). They were shown how to report these values on a personal page on a secure Web application by using a login password (or how to report by mobile telephone text message). Patients were also asked to report their nighttime and daytime asthma symptom scores on this Internet page or by text message. We asked all participants to complete the Asthma Control Questionnaire on their personal Internet page each week (14). We did not give any patients feedback about lung function or asthma control. After the 2-week baseline period, we randomly assigned participants to either the Internet group or the usual care group. We stratified according to care provider (primary vs. subspecialty care) and asthma control at baseline (15). We randomly assigned patients to the 2 groups (1:1 ratio) by using a computer-generated, permuted-block scheme. Allocation took place by computer after collection of the baseline data, ensuring concealment of allocation. The Internet-based self-management program consisted of the 4 principal components of asthma self-management and was accessed through the specially designed Web site, which allowed monitoring through the Web site (or text message on a mobile telephone), use of an Internet-based treatment plan, online education, and Web communications with a specialized asthma nurse (16). Patients monitored their asthma weekly by completing an electronic version of the Asthma Control Questionnaire on the Web site and instantly received feedback on the current state of their asthma control along with advice on how to adjust their treatment according to a predefined algorithm and treatment plan (Table 1 and Appendix Figures 1, 2, 3, 4, and 5). Depending on the scores submitted, patients received 4 types of self-treatment advice. When 4 consecutive Asthma Control Questionnaire scores were 0.5 or less, patients were advised to decrease treatment according to treatment plan. When 2 consecutive scores were greater than 0.5 but less than 1.0, patients were advised to increase treatment according to treatment plan. When 1 score was 1.0 or more but less than 1.5, patients were advised to immediately increase treatment according to treatment plan. Finally, when 1 score was 1.5 or more, patients were advised to immediately increase treatment and contact the asthma nurse. Table 1. Treatment Plan Appendix Figure 1. Algorithm based on consecutive ACQ scores to adjust medical treatment. * ACQ = Asthma Control Questionnaire. At entry of the algorithm, the evaluation period is bypassed. The evaluation period starts after treatment was stepped up. The optimal control period starts after 1 ACQ score 0.5 and ends after 1 ACQ score >0.5. Appendix Figure 2. Screen shot of daily lung function and symptom monitoring. Appendix Figure 3. Screen shot of feedback on daily lung function and symptom monitoring. Appendix Figure 4. Screen shot of weekly Asthma Control Questionnaire monitoring. Appendix Figure 5. Screen shot of feedback on Asthma Control Questionnaire, treatment advice according to personalized treatment plan, and results of past 6 months. We advised no medication changes during the 4 weeks after treatment was stepped up (evaluation period). In addition to weekly assessments, patients could optionally report daily symptoms and lung function and were able to contact our asthma nurse though the Web or by telephone. Thus, any acute deterioration warranting a visit to the general practitioner or hospital could be detected (Appendix Figures 2 and 3). We aimed to empower patients to use the Internet-based self-management tool and to develop a patientprovider partnership in asthma care (2). Self-management education consisted of both Web-based and face-to-face, group-based education. Web-based education included asthma information, news, frequently asked questions, and interactive communication with a respiratory nurse specialist. We scheduled 2 group-based education sessions, which lasted 45 to 60 minutes, for patients in the Internet-based self-management group within 6 weeks after entering the trial. Both sessions included exploration of a patients interests and previous knowledge (negotiating an agenda and patient-centered education), personalized feedback, and empowerment of self-management (self-efficacy and implementing a plan for change) (2, 17). The first educational session also included pathophysiology of asthma, information on the Web-based action plan, and information and review of inhalation technique. The second educational session gave information about the mechanisms and side effects of medication and explained trigger avoidance. Patients in the usual care group received asthma care according to the Dutch general practice guidelines on asthma management in adults, which recommend a medical review and treatment adjustment every 2 to 4 weeks in unstable asthma and medical review once or twice yearly

Patient's needs and preferences in routine follow-up after treatment for breast cancer

The purpose of the study was to analyse the needs of women who participated in a routine follow-up programme after treatment for primary breast cancer. A cross-sectional survey was conducted using a postal questionnaire among women without any sign of relapse during the routine follow-up period. The questionnaire was sent 2–4 years after primary surgical treatment. Most important to patients was information on long-term effects of treatment and prognosis, discussion of prevention of breast cancer and hereditary factors and changes in the untreated breast. Patients preferred additional investigations (such as X-ray and blood tests) to be part of routine follow-up visits. Less satisfaction with interpersonal aspects and higher scores on the Hospital Anxiety and Depression Scale (HADS) scale were related to stronger preferences for additional investigation. Receiving adjuvant hormonal or radiotherapy was related to a preference for a more intensive follow-up schedule. There were no significant differences between patients treated with mastectomy compared to treated with breast-conserving therapy. During routine follow-up after a diagnosis of breast cancer, not all patients needed all types of information. When introducing alternative follow-up schedules, individual patients’ information needs and preferences should be identified early and incorporated into the follow-up routine care, to target resources and maximise the likelihood that positive patient outcomes will result.

Long-term results of total adrenalectomy for Cushing's disease.

The objective of this study was to present the long-term results of total adrenalectomy for Cushings disease. Forty-four patients undergoing total adrenalectomy for Cushings disease between 1953 and 1989 at Leiden University Medical Center, The Netherlands, were studied retrospectively. Remission was achieved in 42 patients (95%), with a mean duration of 19 years. Adrenal remnants were observed in 12 patients (27%), and were without clinical consequence in the majority of patients, but caused early recurrent disease in 2 patients. Nine patients (20%) experienced Addisonian crises up to 30 years following treatment. Nelsons syndrome developed in 10 patients (23%) 7–24 years following total adrenalectomy. Prior pituitary irradiation was a protective factor against Nelsons syndrome as it delayed its onset (p= 0.025). On the other hand, subnormal dose or noncontinuous glucocorticoid replacement therapy was associated with increased risk of development of Nelsons syndrome (p= 0.047). The incidence of Nelsons syndrome increased with prolonged follow-up, and female patients seemed to be at increased risk. Quality-of-life assessment showed less favorable scores on mental health and health perception scales, for which no explanation can be found except the long-lasting metabolic effects of Cushings disease, even when successfully treated. In conclusion, total adrenalectomy remains the final treatment for Cushings disease. The presence of adrenal remnants which can cause recurrent disease and the development of Nelsons syndrome during prolonged follow-up enhance the need for continued regular follow-up. Pituitary irradiation prior to total adrenalectomy delays the onset of Nelsons syndrome.