PALLiative care in ONcology (PALLiON): A cluster-randomised trial investigating the effect of palliative care on the use of anticancer treatment at the end of life.

BACKGROUND: Effects on anticancer therapy following the integration of palliative care and oncology are rarely investigated. Thus, its potential effect is unknown. AIM: To investigate the effects of the complex intervention PALLiON versus usual care on end-of-life anticancer therapy. DESIGN: Cluster-randomised controlled trial (RCT), registered at ClinicalTrials.gov (No. NCT01362816). The complex intervention consisted of a physician education program enhancing theoretical, clinical and communication skills, a patient-centred care pathway and patient symptom reporting prior to all consultations. Primary outcome was overall use, start and cessation of anticancer therapy in the last 3 months before death. Secondary outcomes were patient-reported outcomes. Mixed effects logistic regression models and Cox proportional hazard were used. SETTING: A total of 12 Norwegian hospitals (03/2017-02/2021). PARTICIPANTS: Patients ⩾18 years, advanced stage solid tumour, starting last line of anticancer therapy, estimated life expectancy ⩽12 months. RESULTS: A total of 616 (93%) patients were included (intervention: 309/control:307); 63% males, median age 69, 77% had gastrointestinal cancers. Median survival time from inclusion was 8 (IQR 3-14) and 7 months (IQR 3-12), and days between anticancer therapy start and death were 204 (90-378) and 168 (69-351) (intervention/control). Overall, 78 patients (13%) received anticancer therapy in the last month (intervention: 33 [11%]/control: 45 [15%]). No differences were found in patient-reported outcomes. CONCLUSION: We found no significant differences in the probability of receiving end-of-life anticancer therapy. The intervention did not have the desired effect. It was probably too general and too focussed on communication skills to exert a substantial influence on conventional clinical practice.

Surgery for brain metastases-impact of the extent of resection.

BACKGROUND: Surgical resection of brain metastases improves symptoms and survival in selected patients. The benefit of gross total resection is disputed, as most patients are believed to succumb from their non-CNS tumor burden. We investigated the association between overall survival and residual tumor after surgery for single brain metastases. METHODS: We reviewed adults who underwent surgery for a single brain metastasis at a regional referral center (2011-2018). Gross total resection was defined as no visible residual tumor on cerebral MRI 12-48 h postoperatively. RESULTS: We included 373 patients. The most common primary tumors were lung cancer (36%) and melanoma (24%). We identified gross total resection in 238 patients (64%). Median overall survival was 11.0 months, 8.0 (6.2-9.8) months for patients with subtotal resection and 13.0 (9.7-16.3) months for patients with gross total resection. In a multivariate regression analysis including preoperative prognostic factors, gross total resection was associated with longer overall survival (HR: 0.66, p = 0.003). Postoperative radiotherapy administered within 6 weeks did not significantly alter the hazard ratio estimates for grade of resection. CONCLUSIONS: Our study suggests improved survival with gross total resection compared to subtotal resection. The importance of extent of resection in surgery for brain metastases should not be discarded.

Overall survival after initial radiotherapy for brain metastases; a population based study of 2140 patients with non-small cell lung cancer.

BACKGROUND: Brain metastases (BM) occur in about 30% of all patients with non-small cell lung cancer (NSCLC). BM treatment guidelines recommend more frequent use of stereotactic radiotherapy (SRT). Overall, studies report no difference in overall survival (OS) comparing SRT to whole-brain radiotherapy (WBRT). We examined survival after radiotherapy for BM in a population-based sample from the South-Eastern Norway Regional Health Authority treated 2006-2018. METHODS: We reviewed electronic medical records of 2140 NSCLC patients treated with SRT or WBRT for BM from 2006-2018. Overall survival (OS) was compared to predicted survival according to the prognostic systems DS-GPA and Lung-molGPA. RESULTS: Use of SRT increased during the period, from 19% (2006-2014) to 45% (2015-2018). Median OS for all patients was 3.0 months, increasing from 2.0 (2006) to 4.0 (2018). Median OS after SRT was 7.0 months (n = 435) and 3.0 months after WBRT (n = 1705). Twenty-seven percent of SRT patients and 50% of WBRT patients died within 90 days after start of RT. Age ≥70, male sex, KPS ≤70, non-adenocarcinoma histology, ECM present, multiple BM, and WBRT were associated with shorter survival (p < .001). Actual mOS corresponded best with predicted mOS by DS-GPA and Lung-molGPA for the SRT group. CONCLUSION: Overall survival after radiotherapy (RT) for BM improved during the study period, but only for patients treated with SRT. Survival after WBRT remains poor; its use should be questioned. DS-GPA and Lung-molGPA seem most useful in predicting prognosis considered for SRT.

Surgery for brain metastases - real-world prognostic factors' association with survival.

BACKGROUND: Surgical resection of brain metastases (BM) improves overall survival (OS) in selected patients. Selecting those patients likely to benefit from surgery is challenging. The Graded Prognostic Assessment (GPA) and the diagnosis-specific Graded Prognostic Assessment (ds-GPA) were developed to predict survival in patients with BM, but not specifically to guide patient selection for surgery. Our aim was to evaluate the feasibility of preoperative GPA/ds-GPA scores and assess variables associated with OS. METHODS: We retrospectively reviewed first-time surgical resection of BM from solid tumors at a Norwegian regional referral center from 2011 to 2018. RESULTS: Of 590 patients, 51% were female and median age was 63 years. Median OS was 10.3 months and 74 patients (13%) died within three months after surgery. Preoperatively tumor origin was unknown in 20% of patients. A GPA score could be calculated for 92% of the patients preoperatively, but could not correctly predict survival. A ds-GPA score could be calculated for 46% of patients. Multivariable regression analysis revealed shorter OS in patients with higher age, worse functioning status, colorectal primary cancer compared to lung cancer, presence of extracranial metastases, and more than four BM. Patients with preoperative progressive extracranial disease or synchronous BM had shorter OS compared to patients with stable extracranial disease. CONCLUSION: Ds-GPA could be calculated in less than half of patients preoperatively and GPA poorly identified patients which had minimal benefit of surgery. Including status of extracranial disease improve prognostication and therefore selection to surgery for brain metastases.

The short-term impact of methylprednisolone on patient-reported sleep in patients with advanced cancer in a randomized, placebo-controlled, double-blind trial.

PURPOSE: Although corticosteroids are frequently used in patients with advanced cancer, few studies have examined the impact of these drugs on patient-reported sleep. We aimed to examine the short-term impact of methylprednisolone on patient-reported sleep in patients with advanced cancer. METHODS: Patient-reported sleep was a predefined secondary outcome in a prospective, randomized, placebo-controlled, double-blind trial that evaluated the analgesic efficacy of corticosteroids in advanced cancer patients (18+), using opioids, and having pain ≥ 4 past 24 h (NRS 0-10). Patients were randomized to the methylprednisolone group with methylprednisolone 16 mg × 2/day or placebo for 7 days. The EORTC QLQ-C30 (0-100) and the Pittsburgh Sleep Quality Index questionnaire (PSQI) (0-21) were used to assess the impact of corticosteroids on sleep at baseline and at day 7. RESULTS: Fifty patients were randomized of which 25 were analyzed in the intervention group and 22 in the control group. Mean age was 64 years, mean Karnofsky performance status was 67 (SD 13.3), 51% were female, and the mean oral daily morphine equivalent dose was 223 mg (SD 222.77). Mean QLQ-C30 sleep score at baseline was 29.0 (SD 36.7) in the methylprednisolone group and 24.2 (SD 27.6) in the placebo group. At day 7, there was no difference between the groups on QLQ-C30 sleep score (methylprednisolone 20.3 (SD 32.9); placebo 28.8 (SD 33.0), p = 0.173). PSQI showed similar results. CONCLUSIONS: Methylprednisolone 16 mg twice daily for 7 days had no impact on patient-reported sleep in this cohort of patients with advanced cancer. TRIAL REGISTRATION: Clinical trial information NCT00676936 (13.05.2008).

Patients with advanced cancer and depression report a significantly higher symptom burden than non-depressed patients.

OBJECTIVE: Clinical observations indicate that patients with advanced cancer and depression report higher symptom burden than nondepressed patients. This is rarely examined empirically. Study aim was to investigate the association between self-reported depression disorder (DD) and symptoms in patients with advanced cancer controlled for prognostic factors. METHOD: The sample included 935 patients, mean age 62, 52% males, from an international multicentre observational study (European Palliative Care Research Collaborative - Computerised Symptom Assessment and Classification of Pain, Depression and Physical Function). DD was assessed by the Patient Health Questionnaire-9 and scored with Diagnostic and Statistical Manual of Mental Disorder-5 algorithm for major depressive disorder, excluding somatic symptoms. Symptom burden was assessed by summing scores on somatic Edmonton Symptom Assessment Scale (ESAS) symptoms, excluding depression, anxiety, and well-being. Item-by-item scores and symptom burden of those with and without DD were compared using nonparametric Mann-Whitney U tests. The relative importance of sociodemographic, medical, and prognostic factors and DD in predicting symptom burden was assessed by hierarchical, multiple regression analyses. RESULT: Patients with DD reported significantly higher scores on ESAS items and a twofold higher symptom burden compared with those without. Factors associated with higher symptom burden were as follows. Diagnosis: lung (ß = 0.15, p < 0.001) or breast cancer (ß = 0.08, p < 0.05); poorer prognosis: high C-reactive protein (ß = 0.08, p < 0.05), lower Karnofsky Performance Status (ß = -0.14, p < 0.001), and greater weight loss (ß = -0.15, p < 0.001); taking opioids (ß = 0.11, p < 0.01); and having DD (ß = 0.23, p < 0.001). The full model explained 18% of the variance in symptom burden. DD explained 4.4% over and above that explained by all the other variables. SIGNIFICANCE OF RESULTS: Depression in patients with advanced cancer is associated with higher symptom burden. These results encourage improved routines for identifying and treating those suffering from depression.

Norwegian reference values for the Short-Form Health Survey 36: development over time.

PURPOSE: Reference values for patient-reported outcome measures are useful for interpretation of results from clinical trials. The study aims were to collect Norwegian SF-36 reference values and compare with data from 1996 to 2002. METHODS: In 2015, SF-36 was sent by mail to a representative sample of the population (N = 6165). Time trends and associations between background variables and SF-36 scale scores were compared by linear regression models. RESULTS: The 2015 response rate was 36% (N = 2118) versus 67% (N = 2323) in 1996 and 56% (N = 5241) in 2002. Only 5% of the youngest (18-29 years) and 27% of the oldest (>70 years) responded in 2015. Age and educational level were significantly higher in 2015 relative to 1996/2002 (p < .001). The oldest age group in 2015 reported better scores on five of eight scales (p < 0.01), the exceptions being bodily pain, vitality, and mental health compared to 1996/2002 (NS). Overall, the SF-36 scores were relatively stable across surveys, controlled for background variables. In general, the most pronounced changes in 2015 were better scores on the role limitations emotional scale (7.4 points, p < .001) and lower scores on the bodily pain scale (4.6 points, p < .001) than in the 1996/2002 survey. CONCLUSIONS: The low response rate in 2015 suggests that the results, especially among the youngest, should be interpreted with caution. The high response rate among the oldest indicates good representativity for those >70 years. Despite societal changes in Norway the past two decades, HRQoL has remained relatively stable.

Correction to: Norwegian reference values for the Short-Form Health Survey 36: development over time.

In the original publication of the article, the right number of participants included in the analysis should be 2107 and not 2118 as written in the paper. The flow-chart and corrected SF-36 scores for the 2015 data set for this article should have appeared as follows: Fig. 1 and Table 3. These changes did not influence the results. The authors would like to apologize for any inconvenience caused.

The Palliative Radiotherapy and Inflammation Study (PRAIS) - protocol for a longitudinal observational multicenter study on patients with cancer induced bone pain.

BACKGROUND: Radiation therapy (RT) results in pain relief for about 6 of 10 patients with cancer induced bone pain (CIBP) caused by bone metastases. The high number of non-responders, the long median time from RT to pain response and the risk of adverse effects, makes it important to determine predictors of treatment response. Clinical features such as cancer type, performance status and pain intensity, and biomarkers for osteoclast activity are proposed as predictors of response to RT. However, results are inconsistent and there is a need for better predictors of RT response. A similar argument can be stated for the development of cachexia; there are currently no predictors that can identify patients who will develop cachexia later in the cancer disease trajectory. Experimental and preclinical studies show that pain, depression and cachexia are related to inflammation. However, it is not known if inflammatory biomarkers can predict CIBP, depression or development of cachexia. METHODS: This multicenter, multinational longitudinal observational study will include 600 adult patients receiving RT for CIBP. Demographic data, clinical variables, osteoclast and inflammatory biomarkers will be assessed before start of RT, and 3, 8, 16, 24 and 52 weeks after last course of RT. The primary aim of the study is to identify potential predictors for pain relief from RT. Secondary aims are to explore potential predictors for development of cachexia, the longitudinal relationship between pain intensity and depression, and if inflammatory biomarkers are associated with changes in pain intensity, cachexia and depression during one-year follow up. DISCUSSION: The immediate clinical implication of the PRAIS study is to identify potential predictive factors for a RT response on CIBP, and thereby reduce non-efficacious RT. Patient benefits are fewer hospital visits, reduced risk of adverse effects and more individualized pain treatment. The long-term clinical implication of the PRAIS study is to improve the knowledge about inflammation in relation to CIBP, cachexia and depression and potentially identify associations and mechanisms that can be targeted for treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02107664 , date of registration April 8, 2014 (retrospectively registered). TRIAL SPONSOR: The European Palliative Care Research Centre (PRC), Department of Clinical and Molecular Medicine, NTNU, Faculty of medicine and Health Sciences, Trondheim, N-7491, Norway.

Overall Survival after Radiotherapy for Brain Metastases According to ECOG Status-A Prospective Study of 294 NSCLC Patients.

Up to 40% of non-smallcell lung cancer (NSCLC) patients develop brain metastases (BMs). The potential benefits of radiotherapy (RT) in patients with poor performance status (PS) are questionable, with considerable risk for futile treatment. We analyzed overall survival after initial radiotherapy in NSCLC patients with BMs, focusing on the relationship between PS and survival after RT. This study reports a prospective observational study including consecutive 294 NSCLC patients with first-time BMs. Overall survival (OS) was calculated from the start of RT to death or last follow-up (1 June 2023). Overall, in the 294 included patients (median age 69 years), the median OS was 4.6 months; 2.5 months after WBRT (n = 141), and 7.5 months after SRT (n = 153). After WBRT, mOS was equally poor for patients with ECOG 2 (1.9 months) and ECOG 3-4 (1.2 months). After SRT, mOS for patients with ECOG 2 was 4.1 months; for ECOG 3 patients, mOS was 4 1.6 months. For NSCLC patients with ECOG 2 diagnosed with BMs who are not candidates for surgery or SRT, WBRT should be questioned due to short survival.

Nutrition impact symptom monitoring and weight loss outcomes: a longitudinal radiotherapy study.

OBJECTIVES: Nutrition impact symptoms (NIS) are associated with weight loss (WL), and decreased energy intake in cross-sectional studies. We aimed to ascertain associations between changes in NIS burden, energy intake and WL over time in patients with advanced cancer. METHODS: Adult patients from an observational radiotherapy study for painful bone metastases self-reported NIS and WL using the Patient-Generated Subjective Global Assessment tool (PG-SGA) at baseline and week eight (W8). NIS burden, the sum of NIS per patient, categorised as 0, 1-2 and ≥3 with changes defined as 2-point differences from baseline to W8 were used. Energy intake was assessed by 24-hour recall interviews. RESULTS: 111 patients (72.1%) were analysed and grouped by NIS burden; 0 NIS (44.1%), 1-2 NIS (30.6%) and ≥3 NIS (25.2%). Patients with NIS burden of ≥3 reported higher baseline WL compared with those with 1-2 or 0 NIS (46.4% vs 18.2% vs 10.2%, respectively, p=0.002). At W8, 21 patients (19%) reported improved NIS burden, accompanied by a lower proportion of severe (≥5%) new-onset WL (19% vs 42.1%) and higher energy intake (median 29.6 vs 21.2 kcal/kg) than those with worsened NIS burden (17.1%). CONCLUSIONS: NIS management may improve energy intake and prevent WL, emphasising the importance of systematic follow-up and interventions. CLINICALTRIALSGOV REGISTRATION: NCT02107664.

Antidepressants to cancer patients during the last year of life--a population-based study.

OBJECTIVE: Although depression is common among incurable cancer patients, the prescription prevalence of antidepressants (ADs) to these patients is largely unknown. Aims were to examine the prescription prevalence of ADs in the last year of life in a 2-year national cancer death cohort and to examine its associations with sociodemographic and medical variables. METHODS: Nationwide, 20,627 cancer deaths in adults were identified by combining the Norwegian Central Population and Cancer Registries. Individual prescriptions of ADs in the 12 months prior to death were identified in the Norwegian Prescription Database. The study population consisted of 17,753 patients who died from cancer in 2005 and 2006, after excluding patients assumed to be hospitalized whose prescriptions were not registered in the Norwegian Prescription Database. RESULTS: Twenty-two percent (N = 3836) had at least one prescription of ADs in their last year of life (men 19%/women 25%), compared with 6% in the general population (men 4%/women 8%). Patients who died within 1 year from diagnosis had lower prescription prevalence (20%) than patients with longer disease duration (23%) (p < 0.001). Prescription prevalence increased toward death for both genders, but the prevalence of first-time prescriptions in the last 6 months of life was similar across genders. About 10% of ADs were prescribed for the first time 30 days or less before death. CONCLUSION: The prescription prevalence among cancer patients in the last year of life was almost four times higher than in the general population. One of 10 patients was prescribed with ADs so close to death that the clinical effects can be questioned.

Neuropathic cancer pain: prevalence, severity, analgesics and impact from the European Palliative Care Research Collaborative-Computerised Symptom Assessment study.

BACKGROUND: Neuropathic pain causes greater pain intensity and worse quality of life than nociceptive pain. There are no published data that confirm this in the cancer population. AIM: We hypothesised that patients with neuropathic cancer pain had more intense pain, experienced greater suffering and were treated with more analgesics than those with nociceptive cancer pain, and a neuropathic pain screening tool, painDETECT, would perform as well in those with cancer pain as is reported in those with non-cancer pain. DESIGN: The data were obtained from an international cross-sectional observational study. SETTING/PARTICIPANTS: A total of 1051 patients from inpatients and outpatients, with incurable cancer completed a computerised assessment on symptoms, function and quality of life. In all, 17 centres within eight countries participated. Medical data were recorded by physicians. Pain type was a clinical diagnosis recorded on the Edmonton Classification System for Cancer Pain. RESULTS: Of the patients, 670 had pain: 534 with nociceptive pain, 113 with neuropathic pain and 23 were unclassified. Patients with neuropathic cancer pain were significantly more likely to be receiving oncological treatment, strong opioids and adjuvant analgesia and have a reduced performance status. They reported worse physical, cognitive and social function. Sensitivity and specificity of painDETECT for identifying neuropathic cancer pain was less accurate than when used in non-cancer populations. CONCLUSIONS: Neuropathic cancer pain is associated with a negative impact on daily living and greater analgesic requirements than nociceptive cancer pain. Validated assessment methods are needed to enable early identification of neuropathic cancer pain, leading to more appropriate treatment and reduced burden on patients.

A complex communication skills training program for physicians providing advanced cancer care - content development and barriers and solutions for implementation.

Background: Early integration of oncology and patient-centered palliative care is the recommended clinical practice model for patients with advanced cancer. General and specific communication skills are necessary to achieve integrated patient-centered care, but require organized training to be adequately mastered. Challenges and barriers on several levels, i.e. organizational, professional and individual may, however, hamper implementation. The development, implementation, and evaluation of such an educational program focusing on communication skills contain many steps, considerations and lessons learned, which are described in this article.Methods: A multi-professional faculty developed, implemented, and evaluated an educational program through a 5-step approach. The program was part of a Norwegian cluster-randomized controlled trial aiming to test the effect of early integration of oncology and palliative care for patients with advanced cancer.Results: The result is the PALLiON educational program; a multi-faceted, evidence-based, and learner-centered program with a specific focus on physicians' communication skills. Four modules were developed: lectures, discussion groups, skills training, and coaching. These were implemented at the six intervention hospitals using different teaching strategies. Evaluation in a subgroup of participants showed a positive appraisal of the group discussions and skills training.Conclusion:We present our experiences and reflections regarding implementation and lessons learned, which should be considered in future developments and implementations; (1) Include experienced faculty with various backgrounds, (2) Be both evidence-based and learner-centered, (3) Choose teaching strategies wisely, (4) Expect resistance and skepticism, (5) Team up with management and gatekeepers, (6) Expect time to fly, and (7) Plan thorough assessment of the evaluation and effect.Trial registration: ClinicalTrials.gov identifier: NCT03088202.

Interviews with patients with advanced cancer--another step towards an international cancer pain classification system.

PURPOSE: Patients' involvement in the development of assessment tools is recommended, and the European Palliative Care Research Collaborative has adhered to this when developing a shared language for cancer pain, an international assessment and classification system. Study objectives were to investigate how patients ranked the relevance of several previously identified pain domains, to investigate patients' perception of the pain experience and to disclose additional, relevant pain domains for cancer pain classification to those identified in the literature. METHODS: Semistructured interviews with advanced cancer patients treated with opioids were performed and analysed verbatim. Patients scored the relevance of predefined pain domains on an 11-point Numerical Rating Scale. RESULTS: Thirty-three Norwegian and Austrian patients were included (16 females and 17 males); the mean age was 63 years, and the mean Karnofsky performance score was 65. The ranking of domains was as follows etiology (mean Numerical Rating Scale score, 8.5), duration (8.0), intensity (7.4), coping (7.1), physical (5.9) and psychological functioning (5.8). Sleep was identified as a new candidate domain to include in the system. The patients emphasised consequences of having pain, for example, poor physical functioning and psychological distress. CONCLUSIONS: Previously identified pain domains were confirmed to be relevant to the patients; however, the ranking differed from the experts' ranking. Sleep disturbances may be added as a domain in a future classification system.

Integration of palliative care in oncology-the intersection of cultures and perspectives of oncology and palliative care.

Palliative care complements anti-cancer treatment, and may actually improve the therapeutic effect by optimising performance status, functioning, symptom management and quality of life, thus improving compliance to treatment. A series of randomised controlled trials investigating early integration of palliative care and oncology document clear benefits in patient-centred outcomes. Still, palliative care is often introduced late in the disease trajectory, if at all. One reason may be that that palliative care is perceived as end-of-life care only, a too common perception among healthcare providers, patients and the public alike. Another, and maybe the most important, reason is the cultural differences between the two disciplines, oncology and palliative care. While the predominant focus in oncology is treatment and cure of the disease, i.e., a tumour-centred focus, the focus in palliative care is the patient with the disease, i.e., the patient-centred approach. Integration of oncology and palliative care implies that these two cultures approach each other, collaborate and recognise that this is not an either or, but time to collaborate with the best interest of the patients. To accomplish this, an organisational model to provide optimal patient-centred palliative care is necessary at all levels. Such a model must structure the collaborations between different professions, across different levels and the patient flow between the silos in healthcare, and should describe the content of care. Using models like this is not common, and requires changes in systems and cultures on organisational, administrative, educational and individual levels. To successfully achieve profound changes is challenging. For example, it may be hampered by professional autonomy in the different disciplines and hinder collaboration and the achievement of a shared mental model. The use of standardised care pathways may be one way to integrate the tumour-centred and patient-centred approaches, reduce cultural barriers and improve patient care.

Inflammatory Markers and Radiotherapy Response in Patients With Painful Bone Metastases.

CONTEXT: Inflammation is proposed to influence tumor response in radiotherapy (RT). Clinical studies to investigate the relationship between inflammatory markers and RT response is warranted to understand the variable RT efficacy in patients with painful bone metastases. OBJECTIVES: To evaluate the association between inflammatory markers and analgesic response to RT in patients with painful bone metastases. METHODS: Adult patients from 7 European study sites undergoing RT for painful bone metastases were included in this prospective and longitudinal analysis. The association between RT response and 17 inflammatory markers at baseline, as well as the association between RT response and the changes observed in inflammatory markers between baseline and three and eight weeks after RT, was analyzed with univariate regression analyses. Baseline analyses were adjusted for potential clinical predictors of RT response. RESULTS: None of the inflammatory markers were significantly associated with an upcoming RT response in the analysis of 448 patients with complete baseline data. In patients available for follow-up, the three-week change in TNF (P 0.017), IL-8 (P 0.028), IP-10 (P 0.032), eotaxin (P 0.043), G-CSF (P 0.033) and MCP-1 (P 0.002) were positively associated with RT response, while the three-week change in CRP (P 0.006) was negatively associated. CONCLUSION: Results from this study show an association between RT response and change in pro-inflammatory mediators and indicate that inflammation may be important to achieve an analgesic RT response in patients with painful bone metastases. None of the investigated inflammatory markers were found to be pre-treatment predictors of RT response.