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.

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.

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.

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.

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.

Results of the Dutch National study of the palliative effect of irradiation using two different treatment schemes for non-small-cell lung cancer.

PURPOSE: A national multicenter randomized study compared the efficacy of 2 x 8 Gy versus our standard 10 x 3 Gy in patients with inoperable stage IIIA/B (with an Eastern Cooperative Oncology Group score of 3 to 4 and/or substantial weight loss) and stage IV non-small-cell lung cancer. PATIENTS AND METHODS: Between January 1999 and June 2002, 297 patients were eligible and randomized to receive either 10 x 3 Gy or 2 x 8 Gy by external-beam irradiation. The primary end point was a patient-assessed score of treatment effect on seven thoracic symptoms using an adapted Rotterdam Symptom Checklist. Study sample size was determined based on an average total symptom score difference of more than one point over the initial 39 weeks post-treatment. The time course of symptom scores were also evaluated, and other secondary end points were toxicity and survival. RESULTS: Both treatment arms were equally effective, as the average total symptom score over the initial 39 weeks did not differ. However, the pattern in time of these scores differed significantly (P < .001). Palliation in the 10 x 3-Gy arm was more prolonged (until week 22) with less worsening symptoms than in 2 x 8-Gy. Survival in the 10 x 3-Gy arm was significantly (P = .03) better than in the 2 x 8-Gy arm with 1-year survival of 19.6% (95%CI, 14.1% to 27.3%) v 10.9% (95%CI, 6.9% to 17.3%). CONCLUSION: The 10 x 3-Gy radiotherapy schedule is preferred over the 2 x 8-Gy schedule for palliative treatment, as it improves survival and results in a longer duration of the palliative response.

Impact of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: report of a multicenter randomized trial.

BACKGROUND: Few prospective studies have been performed about the impact of preoperative radiotherapy (PRT) or total mesorectal excision (TME) on health-related quality of life (HRQL) and sexual functioning in patients with resectable rectal cancer. This report describes the HRQL and sexual functioning of 990 patients who underwent TME and were randomly assigned to short-term PRT (5 x 5 Gy). PATIENTS AND METHODS: The Rotterdam Symptom Check List supplemented with additional items was used with questionnaires before treatment and at 3, 6, 12, 18, and 24 months after surgery. Patients without a recurrence the first 2 years were analyzed (n = 990). RESULTS: Few differences were found in HRQL between patients treated with or without PRT. Daily activities were significantly less for PRT patients 3 months postoperatively. Irradiated patients recovered slower from defecation problems than TME-only patients (P = .006). PRT had a negative effect on sexual functioning in males (P = .004) and females (P < .001). Irradiated males had more ejaculation disorders (P = .002), and erectile functioning deteriorated over time (P < .001). PRT had similar effects in patients who underwent a low anterior resection (LAR) versus an abdominoperineal resection (APR). Patients with an APR scored better on the physical (P = .004) and psychologic dimension (P = .007) than LAR patients, but worse on voiding (P = .0007). CONCLUSION: Short-term PRT leads to more sexual dysfunction, slower recovery of bowel function, and impaired daily activity postoperatively. However, this does not seriously affect HRQL. The comparison between LAR and APR patients demonstrates that the existence of a permanent stoma is not the only determinant of HRQL.

Patients with a favourable prognosis are equally palliated with single and multiple fraction radiotherapy: results on survival in the Dutch Bone Metastasis Study.

BACKGROUND AND PURPOSE: In the prospectively, randomized Dutch Bone Metastasis Study on the effect of a single fraction of 8 Gy versus 24 Gy in six fractions on painful bone metastases, 28% of the patients survived for more than 1 year. Purpose of the present study was to analyze the palliative effect of radiotherapy in long-term surviving patients, and to identify prognostic factors for survival. MATERIAL AND METHODS: Response rates were compared in all patients surviving>52 weeks. The Cox proportional hazards model stratified by primary tumour was used for multivariate (MV) analyses of prognostic factors for survival. RESULTS: In 320 patients surviving>52 weeks, responses were 87% after 8 Gy and 85% after 24 Gy (P=0.54). Duration of response and progression rates were similar. For all primary tumours, prognostic factors for survival were a good Karnofsky Performance Score, no visceral metastases, and non-opioid analgesics intake (all factors, MV P<0.001). CONCLUSIONS: Single fraction radiotherapy should be the standard dose schedule for all patients with painful bone metastases, including patients with an expected favourable survival. General prognosticators as the Karnofsky Performance Score and metastatic tumour load are useful in predicting survival.

Enhancing patient participation by training radiation oncologists.

OBJECTIVE: Several studies have shown that patients' active participation to their medical interaction is beneficial for their information processing and their quality of life. Unfortunately, cancer patients often act rather passively in contact with their oncologists. We investigated whether cancer patients' participation in radiation therapy consultations could be enhanced by specific communicative behaviours of the radiation oncologists (ROs). METHODS: Eight ROs and 160 patients participated; 80 patients in the pre training group and 80 patients in the post training group. The ROs were trained to use specific communicative behaviours that are supposed to encourage patient participation. In the training special attention was paid to communicative requirements in the first minutes of the consultation. The communicative behaviours of the ROs and the cancer patients were measured by the Roter Interaction Analysis System, and compared before and after the RO training. RESULTS: From the start throughout the entire consultation, patients in the post training group participated more in interactions than patients in the pre training group: they discussed more psychosocial issues, expressed more concerns and contributed more to decision-making. CONCLUSION: Cancer patients' participation in the initial radiation oncology consultations can be increased by training of ROs. PRACTICE IMPLICATIONS: The results suggest that doctors working with cancer patients should receive communication training and feedback on a regular base.

Single- versus multiple-fraction radiotherapy in patients with painful bone metastases: cost-utility analysis based on a randomized trial.

BACKGROUND: Radiotherapy is an effective palliative treatment for cancer patients with painful bone metastases. Although single- and multiple-fraction radiotherapy are thought to provide equal palliation, which treatment schedule provides better value for the money is unknown. We compared quality-adjusted life expectancy (the overall valuation of the health of the patients) and societal costs for patients receiving either single- or multiple-fraction radiotherapy. METHODS: A societal cost-utility analysis was performed on a Dutch randomized, controlled trial of 1157 patients with painful bone metastases that compared pain responses and quality of life from a single-fraction treatment schedule of 8 Gy with a treatment schedule of six fractions of 4 Gy each. The societal values of life expectancies were assessed with the EuroQol classification system (EQ-5D) questionnaire. A subset of 166 patients also answered additional questionnaires to estimate nonradiotherapy and nonmedical costs. Statistical tests were two-sided. RESULTS: Comparing the single- and multiple-fraction radiotherapy schedules, no differences were found in life expectancy (43.0 versus 40.4 weeks, P =.20) or quality-adjusted life expectancy (17.7 versus 16.0 weeks, P =.21). The estimated cost of radiotherapy, including retreatments and nonmedical costs, was statistically significantly lower for the single-fraction schedule than for the multiple-fraction schedule ($2438 versus $3311, difference = $873, 95% confidence interval [CI] on the difference = $449 to $1297; P<.001). The estimated difference in total societal costs was larger, also in favor of the single-fraction schedule, but it was not statistically significant ($4700 versus $6453, difference = $1753, 95% CI on the difference = -$99 to $3604; P =.06). For willingness-to-pay between $5000 and $40 000 per quality-adjusted life year, the single-fraction schedule was statistically significantly more cost-effective than the multiple-fraction schedule (P< or =.05). CONCLUSIONS: Compared with multiple-fraction radiotherapy, single-fraction radiotherapy provides equal palliation and quality of life and has lower medical and societal costs, at least in The Netherlands. Therefore, single-fraction radiotherapy should be considered as the palliative treatment of choice for cancer patients with painful bone metastases.

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.

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.

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.

Investigation of the added value of high-energy electrons in intensity-modulated radiotherapy: four clinical cases.

PURPOSE: Intensity-modulated radiotherapy (IMRT) with photon beams is currently pursued in many clinics. Theoretically, inclusion of intensity- and energy-modulated high-energy electron beams (15-50 MeV) offers additional possibilities to improve radiotherapy treatments of deep-seated tumors. In this study the added value of high-energy electron beams in IMRT treatments was investigated. METHODS AND MATERIALS: In a comparative treatment planning study, conventional treatment plans and various types of IMRT plans were constructed for four clinical cases (cancer of the bladder, pancreas, chordoma of the sacrum, and breast). The conventional plans were used for the actual treatment of the patients. The IMRT plans were optimized using the Orbit optimization code (Löf et al., 2000) with a radiobiologic objective function. The IMRT plans were either photon or combined electron and photon beam plans, with or without dose homogeneity constraints assuming standard or increased radiosensitivities of organs at risk. RESULTS: Large improvements in expected treatment outcome are found using IMRT plans compared to conventional plans, but differences in tumor control probability (TCP) and normal tissue complication probabilities (NTCP) values between IMRT plans with and without electrons are small. However, the use of electrons improves the dose-volume histograms for organs at risk, especially at lower dose levels (e.g., 0-40 Gy). CONCLUSIONS: This preliminary study indicates that addition of higher energy electrons to IMRT can only marginally improve treatment outcome for the selected cases. The dose-volume histograms of organs at risk show improvements for IMRT with higher energy electrons, which may reduce tumor induction but does not substantially reduce NTCP.

Hypofractionated external beam radiotherapy as retreatment for symptomatic non-small-cell lung carcinoma: an effective treatment?

PURPOSE: To evaluate prospectively the efficacy, toxicity, and duration of the palliative effect of retreatment with external beam radiotherapy in symptomatic patients with recurrent non-small-cell lung cancer. METHODS AND MATERIALS: Twenty-eight symptomatic patients with local recurrence of non-small-cell lung cancer underwent repeated treatment after previous radiotherapy (equivalent dose, 46-60 Gy). Reirradiation consisted of two fractions of 8 Gy on Days 1 and 8 with two opposed beams using 6-18-MV photon beams at the site of pulmonary recurrence. The physician scored symptom resolution. RESULTS: Relief of hemoptysis and superior vena cava syndrome could be obtained in all assessable cases (100%). Treatment was less effective for coughing (67%) and dyspnea (35%). The overall median duration of this palliative effect was 4 months. Palliation in almost all patients lasted more than one-half of their remaining life span. The Karnofsky performance score improved in 45% of assessable cases. One patient had Grade 2 esophagitis. Complications consisted of tumor-related fatal hemoptysis in 5 patients (17%) and 1 death from bronchoesophageal fistula (4%). CONCLUSION: External beam hypofractionated reirradiation can be effective as a palliative treatment for local complaints in non-small-cell lung cancer. The complication rate of reirradiation was acceptably low.

Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment.

PURPOSE: The Dutch Bone Metastasis Study on the effect on painful bone metastases of 8 Gy single fraction (SF) vs. 24 Gy in multiple fractions (MF) showed 24% retreatment after SF vs. 6% after MF (p < 0.001). The purpose of the present study was to evaluate factors influencing retreatment and its effect on response. METHODS AND MATERIALS: The database on all randomized patients was reanalyzed with separately calculated responses to initial treatment and retreatment. RESULTS: Response to initial treatment was 71% after SF vs. 73% after MF (p = 0.84). Retreatment raised response to 75% for SF; MF remained unaltered (p = 0.54). The response status after initial treatment did not predict occurrence of retreatment: 35% SF vs. 8% MF nonresponders and 22% SF vs. 10% MF patients with progressive pain were retreated. Logistic regression analyses showed the randomization arm and the pain score before retreatment to significantly predict retreatment (p < 0.001). Retreatment for nonresponders was successful in 66% SF vs. 33% MF patients (p = 0.13). Retreatment for progression was successful in 70% SF vs. 57% MF patients (p = 0.24). CONCLUSIONS: With or without the effect of retreatment, SF and MF radiotherapy provided equal palliation for painful bone metastases. Irrespective of response to initial treatment, physicians were more willing to retreat after a single fraction. Overall, retreatment was effective in 63% of retreated patients.

Simple radiographic parameter predicts fracturing in metastatic femoral bone lesions: results from a randomised trial.

BACKGROUND AND PURPOSE: In the randomised Dutch Bone Metastasis Study on the palliative effect of a single fraction (SF) of 8 Gy versus six fractions of 4 Gy on painful bone metastases, 14 fractures occurred in 102 patients with femoral metastases. Purpose of the present study was to identify lesional risk factors for fracturing and to evaluate the influence of the treatment schedule. MATERIAL AND METHODS: Pretreatment radiographs of femoral metastases were collected. Three observers separately measured the lesions and scored radiographic characteristics. RESULTS: Ten fractures occurred after median 7 weeks in 44 SF patients (23%) and four after median 20 weeks in 58 multiple fraction patients (7%) (UV, P=0.02). In 110 femoral metastases, an axial cortical involvement >30 mm significantly predicted fracturing (MV, P=0.02). Twelve out of 14 fractured lesions and 40 out of 96 non-fractured metastases had an axial cortical involvement >30 mm (negative predictive value, 97%). When correcting for the axial cortical involvement, the treatment schedule was not predictive anymore (MV, P=0.07). CONCLUSIONS: Fracturing of the femur mostly depended on the amount of axial cortical involvement of the metastasis. We recommend to treat femoral metastases with an axial cortical involvement < or =30 mm with an SF of 8 Gy for relief of pain. If the axial cortical involvement is >30 mm, prophylactic surgery should be performed to minimize the risk of pathological fracturing or, if the patient's condition is limited, irradiation to a higher total dose.

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.