Effectiveness of low-dose radiation therapy on symptoms in patients with knee osteoarthritis: a randomised, double-blinded, sham-controlled trial.

OBJECTIVES: Low-dose radiation therapy (LDRT) for benign disorders such as knee osteoarthritis (OA) is widely used in some parts of the world, despite absence of controlled studies. We evaluated the effect of LDRT on symptoms and inflammation in patients with knee OA. METHODS: In this randomised, double-blinded, sham-controlled clinical trial (RCT), we recruited patients with knee OA (clinical ACR criteria) in the Netherlands, aged ≥50 years, pain score ≥5/10 and non-responding to analgesics and exercise therapy. Patients were randomised 1:1 to receive LDRT (1 Gray per fraction) or sham intervention six times in 2 weeks, stratified by pain (<8 versus ≥8/10). Primary outcome was the proportion of OMERACT-OARSI responders, 3 months postintervention. Secondary outcomes included pain, function and inflammatory signs assessed by ultrasound, MRI and serum inflammatory markers. RESULTS: We randomly assigned 55 patients: 27 (49%) to LDRT and 28 (51%) to sham. At 3 months postintervention, 12/27 patients (44%; 95% CI 26% to 63%) in the LDRT vs 12/28 patients (43%; 95% CI 25% to 61%) in the sham group responded; difference 2% (95% CI 25% to 28%), OR adjusted for the stratifying variable was 1.1 (95% CI 0.4 to 3.2). Also, for clinical and any of the inflammatory signs, no differences were observed. CONCLUSIONS: We found no substantial beneficial effect on symptoms and inflammatory signs of LDRT in patients knee OA, compared with sham treatment. Therefore, based on this RCT and the absence of other high-quality evidence, we advise against the use of LDRT as treatment for knee OA. TRIAL REGISTRATION NUMBER: NTR4574.

Effectiveness and toxicity of conventional radiotherapy treatment for painful spinal metastases: a detailed course of side effects after opposing fields versus a single posterior field technique.

BACKGROUND: Conventional radiotherapy for painful spinal metastases can be delivered with a single posterior-anterior (PA) or two opposed anterior-posterior (APPA) fields. We studied the effectiveness and toxicity of both techniques and studied whether treatment technique was predictive for abdominal and skin toxicity. PATIENTS AND METHODS: Within the Dutch Bone Metastasis Study, 343 patients received 8 Gray in a single fraction or 24 Gray in six fractions for painful spinal metastases. Treatment technique was not randomized. At baseline and weekly during follow-up, patients reported pain and other physical complaints. Any complaint increasing within 4 weeks after treatment was noted as a side effect. Pain response was calculated according to international standards, taking into account changes in pain score and medication. Repeated measurement analyses and multivariate logistic analyses were performed. RESULTS: Patients were mainly treated on the thoracic (34%) and lumbar (53%) spine and 73% received a PA field. Pain response was similar between both techniques (74%). In patients treated at the thoraco-lumbar and lumbar spine, with multiple fractions, significantly more abdominal complaints were noticed. In multivariate analysis, radiotherapy technique did not predict for side effects. CONCLUSION: Conventional radiotherapy of painful spinal metastases provides limited toxicity. Radiotherapy technique is not an independent predictor of abdominal and skin toxicity of irradiation.

Screening for psychological distress before radiotherapy for painful bone metastases may be useful to identify patients with high levels of distress.

BACKGROUND: Psychological distress (PD) has a major impact on quality of life. We studied the incidence of PD before and after radiotherapy for painful bone metastases. Furthermore, we aimed to identify factors predictive for PD. METHODS: Between 1996 and 1998, the Dutch Bone Metastasis Study included 1157 patients with painful bone metastases. Patients were randomized between two fractionation schedules. The study showed a pain response of 74% in both groups. Patients filled out weekly questionnaires for 13 weeks, then monthly for two years. The questionnaires included a subscale for PD on the Rotterdam Symptom Checklist. We used generalized estimating equations and multivariable logistic regression analyses. RESULTS: At baseline, 290 patients (27%) had a high level of PD. For the entire group, the level of PD remained constant over time. The majority of patients with a low level of PD at baseline remained at a low level during follow-up. In patients with a high level of PD at baseline, the mean level of PD decreased after treatment and stabilized around the cutoff level. Female patients, higher age, worse performance, lower pain score and worse self-reported QoL were associated with an increased chance of PD, although the model showed moderate discriminative power. CONCLUSIONS: A substantial proportion of patients had a high level of PD before and after radiotherapy for painful bone metastases. Most patients who reported high levels of PD when referred for palliative radiotherapy remained at high levels thereafter. Therefore, screening of PD prior to treatment seems appropriate, in order to select patients requiring intervention.

Course of Quality of Life After Radiation Therapy for Painful Bone Metastases: A Detailed Analysis From the Dutch Bone Metastasis Study.

PURPOSE: To study the course of quality of life (QoL) after radiation therapy for painful bone metastases. PATIENTS AND METHODS: The Dutch Bone Metastasis Study randomized 1157 patients with painful bone metastases between a single fraction of 8 Gy and 6 fractions of 4 Gy between 1996 and 1998. The study showed a comparable pain response of 74%. Patients filled out weekly questionnaires for 13 weeks, then monthly for 2 years. In these analyses, physical, psychosocial, and functional QoL domain scores and a score of general health were studied. Mixed modeling was used to model the course of QoL and to study the influence of several characteristics. RESULTS: In general, QoL stabilized after 1 month. Psychosocial QoL improved after treatment. The level of QoL remained stable, steeply deteriorating at the end of life. For most QoL domains, a high pain score and intake of opioids were associated with worse QoL, with small effect sizes (-0.11 to -0.27). A poor performance score was associated with worse functional QoL, with a medium effect size (0.41). There is no difference in QoL between patients receiving a single fraction of 8 Gy and 6 fractions of 4 Gy, except for a temporary worsening of physical QoL after 6 fractions. CONCLUSION: Although radiation therapy for painful bone metastases leads to a meaningful pain response, most domains of QoL do not improve after treatment. Only psychosocial QoL improves slightly after treatment. The level of QoL is related to the actual survival, with a rather stable course of QoL for most of the remaining survival time and afterward a sharp decrease, starting only a few weeks before the end of life. Six fractions of 4 Gy lead to a temporary worse physical QoL compared with a single fraction of 8 Gy.

Does a decision aid for prostate cancer affect different aspects of decisional regret, assessed with new regret scales? A randomized, controlled trial.

OBJECTIVE: To develop and validate new regret scales and examine whether a decision aid affects different aspects of regret in the treatment choice for prostate cancer. METHODS: This was a multicentre trial (three sites) with imbalanced randomization (1 : 2). From 2008 to 2011, patients with localized prostate cancer were randomized 1 : 2 to usual care (N = 77) or usual care plus a decision aid presenting risks and benefits of different treatments (N = 163). The treatments were surgery and (external or interstitial) radiotherapy. Regret was assessed before, and 6 and 12 months after treatment, using the Decisional regret scale by Brehaut et al. (Medical Decision Making, 23, 2003, 281), and three new scales focusing on process, option and outcome regret. The relation between decision aid and regret was analysed by anova. RESULTS: The concurrent validity of the new regret scales was confirmed by correlations between regret and anxiety, depression, decision evaluation scales and health-related quality of life. With a decision aid, patient participation was increased (P = 0.002), but regret was not. If anything, in patients with serious morbidity the decision aid resulted in a trend to less option regret and less Brehaut regret (P = 0.075 and P = 0.061, with effect sizes of 0.35 and 0.38, respectively). Exploratory analyses suggest that high-risk patients benefitted most from the decision aid. CONCLUSION: The new regret scales may be of value in distinguishing separate aspects of regret. In general, regret was not affected by the decision aid. In patients with serious morbidity, a trend to lower option regret with a decision aid was observed.

Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases.

PURPOSE: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. PATIENTS AND METHODS: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within the Dutch Bone Metastasis Study were used. These patients, irradiated for painful bone metastases, rated pain, QoL, and overall health at baseline and weekly afterward for 12 weeks. Using generalized estimating equations analysis, the course of QoL was studied, adjusted for primary tumor. To identify predictive variables, proportional hazard analyses were performed, taking into account death as a competing risk, and C-statistics were calculated for discriminative value. RESULTS: In total, 722 patients (76%) responded to radiation therapy. During follow-up, responders had a better QoL in all domains compared with nonresponders. Patients with breast or prostate cancer had a better QoL than patients with lung cancer. In multivariate analysis, baseline predictors for a pain response were breast or prostate cancer as primary tumor, younger age, good performance status, absence of visceral metastases, and using opioids. The discriminative ability of the model was low (C-statistic: 0.56). CONCLUSIONS: Responding patients show a better QoL after radiation therapy for painful bone metastases than nonresponders. Our model did not have enough discriminative power to predict which patients are likely to respond to radiation therapy. Therefore, radiation therapy should be offered to all patients with painful bone metastases, aiming to decrease pain and improve QoL.

Humoral and cellular immune responses after influenza vaccination in patients with postcancer fatigue.

The aim of this study was to compare humoral and cellular immune responses to influenza vaccination in cancer survivors with and without severe symptoms of fatigue. Severely fatigued (n = 15) and non-fatigued (n = 12) disease-free cancer survivors were vaccinated against seasonal influenza. Humoral immunity was evaluated at baseline and post-vaccination by a hemagglutination inhibition assay. Cellular immunity was evaluated at baseline and post-vaccination by lymphocyte proliferation and activation assays. Regulatory T cells were measured at baseline by flow cytometry and heat-shock protein 90 alpha levels by ELISA. Comparable humoral immune responses were observed in fatigued and non-fatigued patients, both pre- and post-vaccination. At baseline, fatigued patients showed a significantly diminished cellular proliferation upon virus stimulation with strain H3N2 (1414 ± 1201 counts), and a trend in a similar direction with strain H1N1 (3025 ± 2339 counts), compared to non-fatigued patients (3099 ± 2401 and 5877 ± 4604 counts, respectively). The percentage of regulatory T lymphocytes was significantly increased (4.4 ± 2.1% versus 2.4 ± 0.8%) and significantly lower amounts of interleukin 2 were detected prior to vaccination in fatigued compared to non-fatigued patients (36.3 ± 44.3 pg/ml vs. 94.0 ± 45.4 pg/ml with strain H3N2 and 28.4 ± 44.0 pg/ml versus 74.5 ± 56.1 pg/ml with strain H1N1). Pre-vaccination heat-shock protein 90 alpha concentrations, post-vaccination cellular proliferation, and post-vaccination cytokine concentrations did not differ between both groups. In conclusion, influenza vaccination is favorable for severely fatigued cancer survivors and should be recommended when indicated. However, compared to non-fatigued cancer survivors, fatigued cancer survivors showed several significant differences in immunological reactivity at baseline, which warrants further investigation.

The role of central and peripheral muscle fatigue in postcancer fatigue: a randomized controlled trial.

CONTEXT: Postcancer fatigue is a frequently occurring problem, impairing quality of life. Little is known about (neuro)physiological factors determining postcancer fatigue. It may be hypothesized that postcancer fatigue is characterized by low peripheral muscle fatigue and high central muscle fatigue. OBJECTIVES: The aims of this study were to examine whether central and peripheral muscle fatigue differ between fatigued and non-fatigued cancer survivors and to examine the effect of cognitive behavioral therapy (CBT) on peripheral and central muscle fatigue of fatigued cancer survivors in a randomized controlled trial. METHODS: Sixteen fatigued patients in the intervention group (CBT) and eight fatigued patients in the waiting list group were successfully assessed at baseline and six months later. Baseline measurements of 20 fatigued patients were compared with 20 non-fatigued patients. A twitch interpolation technique and surface electromyography were applied, respectively, during sustained contraction of the biceps brachii muscle. RESULTS: Muscle fiber conduction velocity (MFCV) and central activation failure (CAF) were not significantly different between fatigued and non-fatigued patients. Change scores of MFCV and CAF were not significantly different between patients in the CBT and waiting list groups. Patients in the CBT group reported a significantly larger decrease in fatigue scores than patients in the waiting list group. CONCLUSION: Postcancer fatigue is neither characterized by abnormally high central muscle fatigue nor by low peripheral muscle fatigue. These findings suggest a difference in the underlying physiological mechanism of postcancer fatigue vs. other fatigue syndromes.

An easy tool to predict survival in patients receiving radiation therapy for painful bone metastases.

PURPOSE: Patients with bone metastases have a widely varying survival. A reliable estimation of survival is needed for appropriate treatment strategies. Our goal was to assess the value of simple prognostic factors, namely, patient and tumor characteristics, Karnofsky performance status (KPS), and patient-reported scores of pain and quality of life, to predict survival in patients with painful bone metastases. METHODS AND MATERIALS: In the Dutch Bone Metastasis Study, 1157 patients were treated with radiation therapy for painful bone metastases. At randomization, physicians determined the KPS; patients rated general health on a visual analogue scale (VAS-gh), valuation of life on a verbal rating scale (VRS-vl) and pain intensity. To assess the predictive value of the variables, we used multivariate Cox proportional hazard analyses and C-statistics for discriminative value. Of the final model, calibration was assessed. External validation was performed on a dataset of 934 patients who were treated with radiation therapy for vertebral metastases. RESULTS: Patients had mainly breast (39%), prostate (23%), or lung cancer (25%). After a maximum of 142 weeks' follow-up, 74% of patients had died. The best predictive model included sex, primary tumor, visceral metastases, KPS, VAS-gh, and VRS-vl (C-statistic = 0.72, 95% CI = 0.70-0.74). A reduced model, with only KPS and primary tumor, showed comparable discriminative capacity (C-statistic = 0.71, 95% CI = 0.69-0.72). External validation showed a C-statistic of 0.72 (95% CI = 0.70-0.73). Calibration of the derivation and the validation dataset showed underestimation of survival. CONCLUSION: In predicting survival in patients with painful bone metastases, KPS combined with primary tumor was comparable to a more complex model. Considering the amount of variables in complex models and the additional burden on patients, the simple model is preferred for daily use. In addition, a risk table for survival is provided.

Effect of age on response to palliative radiotherapy and quality of life in patients with painful bone metastases.

BACKGROUND: Multimorbidity and declining performance in elderly cancer patients may result in less treatment benefit. We investigated whether age is a predictor for pain response and quality of life (QoL) after radiotherapy in patients with painful bone metastases. METHODS: The database of the Dutch Bone Metastasis Study was used (1996-1999). 1157 patients, irradiated for painful bone metastases, rated their pain, QoL-domains and overall health at baseline and during follow-up. Response was calculated taking into account changes in pain score and medication. Patients were grouped into three age cohorts: A: <65 (n=520), B: 65-74 (n=410) and C: ⩾75years (n=227). RESULTS: No significant difference existed in pain response between cohorts: 78% in cohort A, 74% in B and 67% in C. When assessing baseline QoL, a significant difference in activity level was noticed, with more impairment in elderly compared to younger patients (C versus B (p=0.01), C versus A (p<0.001)). Other QoL-domains were similar at baseline and during follow-up among cohorts. A pain response was significantly associated with improvement of health-related QoL (OR 3.74, 95% CI 2.66-5.25). CONCLUSION: The majority of elderly patients with painful bone metastases responded to radiotherapy and showed comparable overall QoL compared to their younger counterparts. Age is not a predictor for pain response or QoL.

Magnetic resonance spectroscopic imaging and volumetric measurements of the brain in patients with postcancer fatigue: a randomized controlled trial.

BACKGROUND: Postcancer fatigue is a frequently occurring problem, impairing quality of life. Until now, little is known about (neuro) physiological factors determining postcancer fatigue. For non-cancer patients with chronic fatigue syndrome, certain characteristics of brain morphology and metabolism have been identified in previous studies. We investigated whether these volumetric and metabolic traits are a reflection of fatigue in general and thus also of importance for postcancer fatigue. METHODS: Fatigued patients were randomly assigned to either the intervention condition (cognitive behavior therapy) or the waiting list condition. Twenty-five patients in the intervention condition and fourteen patients in the waiting list condition were assessed twice, at baseline and six months later. Baseline measurements of 20 fatigued patients were compared with 20 matched non-fatigued controls. All participants had completed treatment of a malignant, solid tumor minimal one year earlier. Global brain volumes, subcortical brain volumes, metabolite tissue concentrations, and metabolite ratios were primary outcome measures. RESULTS: Volumetric and metabolic parameters were not significantly different between fatigued and non-fatigued patients. Change scores of volumetric and metabolic parameters from baseline to follow-up were not significantly different between patients in the therapy and the waiting list group. Patients in the therapy group reported a significant larger decrease in fatigue scores than patients in the waiting list group. CONCLUSIONS: No relation was found between postcancer fatigue and the studied volumetric and metabolic markers. This may suggest that, although postcancer fatigue and chronic fatigue syndrome show strong resemblances as a clinical syndrome, the underlying physiology is different. TRIAL REGISTRATION: ClinicalTrials.gov NCT01096641.

The updated ESTRO core curricula 2011 for clinicians, medical physicists and RTTs in radiotherapy/radiation oncology.

INTRODUCTION: In 2007 ESTRO proposed a revision and harmonisation of the core curricula for radiation oncologists, medical physicists and RTTs to encourage harmonised education programmes for the professional disciplines, to facilitate mobility between EU member states, to reflect the rapid development of the professions and to secure the best evidence-based education across Europe. MATERIAL AND METHODS: Working parties for each core curriculum were established and included a broad representation with geographic spread and different experience with education from the ESTRO Educational Committee, local representatives appointed by the National Societies and support from ESTRO staff. RESULTS: The revised curricula have been presented for the ESTRO community and endorsement is ongoing. All three curricula have been changed to competency based education and training, teaching methodology and assessment and include the recent introduction of the new dose planning and delivery techniques and the integration of drugs and radiation. The curricula can be downloaded at http://www.estro-education.org/europeantraining/Pages/EuropeanCurricula.aspx. CONCLUSION: The main objective of the ESTRO core curricula is to update and harmonise training of the radiation oncologists, medical physicists and RTTs in Europe. It is recommended that the authorities in charge of the respective training programmes throughout Europe harmonise their own curricula according to the common framework.

Cancer patients use hospital-based care until death: a further analysis of the Dutch Bone Metastasis Study.

PURPOSE: To describe health care utilization (HCU) at the end of life in cancer patients. These data are relevant to plan palliative care services, and to develop training programs for involved health care professionals. METHODS: The Dutch Bone Metastasis Study (DBMS) was a nationwide study proving equal effectiveness of single fraction palliative radiotherapy compared with multiple fractions for painful bone metastases in 1157 patients. The 860 (74%) patients who died during follow-up were included in the current analysis. The main outcome was the frequency of hospital-based (outpatient contact or admission) and/or general practitioner (GP) contact during the last 12 weeks of life. Changes in HCU towards death were related to data on quality of life and pain intensity using a multilevel regression model. RESULTS: Hospital-based HCU was reported in 1801 (63%) returned questionnaires, whereas GP contact was stated in 1246 (43%). In 573 (20%) questionnaires, both types of HCU were reported. In multilevel regression analyses, the frequency of outpatient contacts remained constant during the weeks towards death, whereas the frequency of GP contacts increased. Lower valuation of quality of life was related to both GP- and hospital-based HCU. CONCLUSIONS: There was a high consumption of hospital-based HCU in the last 12 weeks of life of cancer patients with bone metastases. Hospital-based HCU did not decrease during the weeks towards death, despite an increase in GP contacts. Future planning of palliative care and training programs should encompass close collaboration between medical specialists and GPs to optimize end-of-life care.

Efficacy of radiotherapy for painful bone metastases during the last 12 weeks of life: results from the Dutch Bone Metastasis Study.

BACKGROUND: Radiotherapy is an effective treatment for painful bone metastases. Whether this applies also in patients with limited survival remains to be investigated. This study analyzed the effect of radiotherapy for painful bone metastases in patients with a survival < or =12 weeks. METHODS: In the Dutch Bone Metastasis Study, 1157 patients with painful bone metastases were randomized to single fraction (1 x 8 grays [Gy]) or multiple fraction (6 x 4 Gy) radiotherapy. Patients who died within 12 weeks after randomization were included in this analysis. Patients were classified as responders or nonresponders, based on their pain response to radiotherapy. This response was calculated considering changes in pain intensity (measured with an 11-point numeric rating scale) and analgesic usage. Cox proportional hazards models were used to analyze pain response and survival. RESULTS: Two hundred seventy-4 patients were included in this analysis. At randomization, the mean pain intensity score (+/-standard deviation) was 7 (+/-2). The proportion showing a pain response did not differ between the single fraction and multiple fraction groups. Toward death, pain intensity score decreased to 5 (+/-3) in responders (45%), whereas in nonresponders (55%) no change was observed. Despite the benefit in responders, in 60% of all patients pain intensity remained 5 after randomization. CONCLUSIONS: Pain responded in about half of the patients who survived < or =12 weeks after randomization into the Dutch Bone Metastasis Study. When considering radiotherapy, single fraction should be preferred. Additional palliative measures remain essential for adequate pain control.

Local recurrences after different treatment strategies for ductal carcinoma in situ of the breast: a population-based study in the East Netherlands.

PURPOSE: Outcomes after different treatment strategies for ductal carcinoma in situ (DCIS) of the breast were analyzed for a geographically defined population in the East Netherlands. METHODS AND MATERIALS: A total of 798 patients with a first diagnosis of DCIS between January 1989 and December 2003 were included and their medical records were reviewed. Survival rates for ipsilateral recurrences were calculated by the Kaplan-Meier method and a multivariate Cox proportional hazards regression model was used to evaluate the prognostic significance of different variables. RESULTS: The 5-year recurrence-free survival was 75% for breast conserving surgery (BCS) alone (237 patients) compared with 91% for BCS followed by radiation therapy (RT; 153 patients) and 99% for mastectomy (408 patients, p < 0.01). Independent risk factors for local recurrences were treatment strategy, symptomatically detected DCIS, and presence of comedo necrosis. Margin status reached statistical significance only for patients treated by BCS (hazard ratio, 2.0; 95% confidence interval, 1.1-4.0) whereas significance of other prognostic variables did not change. CONCLUSIONS: In a defined population outside a trial setting, RT after BCS for DCIS lowered recurrence rates. Besides the use of RT, a microscopically complete excision of DCIS is essential. This is especially true for patients with symptomatically detected DCIS and with tumors that contain comedo necrosis, as these groups are at particular high risk for recurrent disease.

Monitoring and blunting in palliative and curative radiotherapy consultations.

OBJECTIVE: The present research paper investigates how cancer patients' monitoring and blunting coping styles are reflected in their communications during their initial radiotherapy consultations and in their evaluations of the consultation. Additionally, it is explored how a patient's disease status (curative versus palliative) influences the effects of his or her cognitive styles. METHODS: The study included 116 oncology patients receiving treatment from eight radiation oncologists. For 56 patients treatment intent was palliative and for the remaining 60 curative. The patients' communicative behaviors were assessed using the Roter Interaction Analysis System (RIAS). Within three days the patients completed a monitoring and blunting inventory and after another six weeks they evaluated the treatment decision and treatment information by postal questionnaire. RESULTS: Monitoring was positively and blunting negatively related to the patient's expression of questions, emotions and decision-making issues. After six weeks 'high monitors' as opposed to 'low monitors' reported having more doubts about the treatment decision and being less satisfied with the information received while 'high blunters' expressed fewer doubts and more satisfaction than 'low blunters' did. Significant associations were all attributable to the palliative treatment group. CONCLUSION: Cancer patients' communicative behaviors vis-à-vis their oncologist hinge on their cognitive styles and an unfavorable disease status enhances the effects.

Cost-utility analysis of short- versus long-course palliative radiotherapy in patients with non-small-cell lung cancer.

BACKGROUND: Radiotherapy can effectively palliate the symptoms of poor-prognosis patients with non-small-cell lung cancer. However, controversy remains about whether short-course or more protracted radiotherapy schedules provide better value for the money. We conducted a societal cost-utility analysis of a Dutch multicenter randomized trial with 1-year follow-up that compared the efficacy of radiotherapy schedules consisting of 10 fractions of 3 Gy (10 x 3 Gy) versus two fractions of 8 Gy (2 x 8 Gy) in 297 patients with inoperable stage IIIA/B or stage IV non-small-cell lung cancer. this trial found that the 10 x 3-Gy group had better survival than the 2 x 8-Gy group. METHODS: Lifetime quality-adjusted life-years (QALYs) were estimated using the EuroQol questionnaire. Lifetime societal costs were estimated using a model estimated based on data from cost questionnaires filled out by a subset of patients (n = 56). Differences were analyzed statistically using two-sided nonparametric bootstrapping. RESULTS: Compared with the 2 x 8-Gy group, the 10 x 3-Gy group accrued statistically significantly more QALYs (20.0 versus 13.2 weeks; difference = 6.8 weeks, 95% confidence interval [CI] = 0.1 to 13.5 weeks, P = .05), which was mainly due to the statistically significantly better survival (38.1 versus 27.4 weeks; difference = 10.7 weeks, 95% CI = 0.9 to 20.6 weeks, P = .03) without a statistically significant difference with respect to the average valuation of health (P = .27). Total radiotherapy and radiotherapy-related costs were estimated at 5236 dollars for the 10 x 3-Gy group and 2512 dollars for the 2 x 8-Gy group (difference = 2724 dollars, 95% CI = 2501 dollars to 2947 dollars, P<.001). The 39% increase in life expectancy in the 10 x 3-Gy group as compared with the 2 x 8-Gy group was associated with a 30% increase in survival-related nonradiotherapy costs (11,254 dollars versus 8651 dollars, difference 2602 dollars, 95% CI = -357 dollars to 5562 dollars, P = .09). The cost-utility ratio for the 10 x 3-Gy schedule versus the 2 x 8-Gy schedule was estimated at 40,900 dollars per QALY (95% CI = 19,400 dollars to 1,100,000 dollars per QALY). CONCLUSIONS: In these poor-prognosis non-small-cell lung cancer patients, the estimated cost-utility ratio for the palliative 10 x 3-Gy schedule was acceptable according to current economic standards. However, the additional costs for the protracted schedule were justified not by improved quality of life but by longer survival.