Gillian Bedard

Quality of Life After Palliative Radiation Therapy for Patients With Painful Bone Metastases: Results of an International Study Validating the EORTC QLQ-BM22

PURPOSE Radiation therapy (RT) is an effective method of palliating painful bone metastases and can improve function and reduce analgesic requirements. In advanced cancer patients, quality of life (QOL) is the primary outcome of interest over traditional endpoints such as survival. The purpose of our study was to compare bone metastasis-specific QOL scores among patients who responded differently to palliative RT. METHODS AND MATERIALS Patients receiving RT for bone metastases across 6 countries were prospectively enrolled from March 2010-January 2011 in a trial validating the QLQ-BM22 and completed the QLQ-BM22 and the core measure (QLQ-C30) at baseline and after 1 month. Pain scores and analgesic intake were recorded, and response to RT was determined according to the latest published guidelines. The Kruskal-Wallis nonparametric and Wilcoxon rank sum tests compared changes in QOL among response groups. A Bonferroni-adjusted P<.003 indicated statistical significance. RESULTS Of 79 patients who received palliative RT, 59 were assessable. Partial response, pain progression, and indeterminate response were observed in 22, 8, and 29 patients, respectively; there were no patients with a complete response. Patients across all groups had similar baseline QOL scores apart from physical functioning (patients who progressed had better initial functioning). One month after RT, patients who responded had significant improvements in 3 of 4 QLQ-BM22 domains (painful site, P<.0001; painful characteristic, P<.0001; and functional interference, P<.0001) and 3 QLQ-C30 domains (physical functioning, P=.0006; role functioning, P=.0026; and pain, P<.0001). Patients with progression in pain had significantly worse functional interference (P=.0007) and pain (P=.0019). CONCLUSIONS Patients who report pain relief after palliative RT also have better QOL with respect to bone metastasis-specific issues. The QLQ-BM22 and QLQ-C30 are able to discriminate among patients with varying responses and are recommended for use in future bone metastasis clinical trials.

Re-irradiation for painful bone metastases - a systematic review.

The purpose of this review was to determine the efficacy of re-irradiation in patients with bone metastases. A literature search was conducted in Ovid Medline, OldMedline, Embase, Embase Classic, and Cochrane Central Register of Controlled Trials using relevant subject headings and keywords such as bone metastases, radiotherapy and palliative care. The resulting articles were sorted for inclusion for palliative external beam radiation retreatment response rate data. The literature search produced 2164 references and 15 articles were included in the final selection. Complete, partial and overall response rates were calculated to be 20%, 50% and 68%, respectively. Information on treatment toxicities was scarce. The efficacy of re-irradiation is comparable to initial radiation treatment. However, aspects of re-irradiation treatment including dose fractionation, related adverse events and toxicities require further corroboration.

Predictive factors for overall quality of life in patients with advanced cancer

ObjectiveThis study examined which domains/symptoms from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 15 Palliative (QLQ-C15-PAL), an abbreviated version of the health-related EORTC QLQ-C30 questionnaire designed for palliative cancer patients, were predictive of overall quality of life (QOL) in advanced cancer patients.MethodsPatients with advanced cancer from six countries completed the QLQ-C15-PAL at consultation and at one follow-up point. Univariate and multivariate regression analyses were conducted to determine the predictive value of the EORTC QLQ-C15-PAL functional/symptom scores for global QOL (question 15).ResultsThree hundred forty-nine patients completed the EORTC QLQ-C15-PAL at baseline. In the total patient sample, worse emotional functioning, pain, and appetite loss were the most significant predictive factors for worse QOL. In the subgroup of patients with bone metastases (n = 240), the domains mentioned above were also the most significant predictors, whereas in patients with brain metastases (n = 109), worse physical and emotional functioning most significantly predicted worse QOL. One-month follow-up in 267 patients revealed that the significant predictors changed somewhat over time. For example, in the total patient sample, physical functioning, fatigue, and appetite loss were significant predictors at the follow-up point. A sub-analysis of predictive factors affecting QOL by primary cancer (lung, breast, and prostate) was also conducted for the total patient sample.ConclusionDeterioration of certain EORTC QLQ-C15-PAL functional/symptom scores significantly contributes to worse overall QOL. Special attention should be directed to managing factors most influential on overall QOL to ensure optimal management of advanced cancer patients.

Minimal Clinically Important Differences in the Edmonton Symptom Assessment System in Patients With Advanced Cancer

CONTEXT Longitudinal symptom monitoring is important in the setting of patients with advanced cancer. Scores over time may naturally fluctuate, although a patient may feel the same. OBJECTIVES The purpose of this study was to determine the minimal levels of change required to be clinically relevant (minimal clinically important difference [MCID]) using the Edmonton Symptom Assessment System (ESAS). METHODS Between 1999 and 2009, patients completed the ESAS before palliative radiotherapy and at follow-up. MCIDs were calculated using both the anchor- and distribution-based methods for improvement and deterioration; 95% confidence intervals for the differences in mean change scores between adjacent categories also were calculated. RESULTS A total of 276 patients completed the ESAS at baseline and during at least one follow-up visit. At the four-week follow-up, decrease of 1.2 and 1.1 units in pain and depression scales, respectively, constituted clinically relevant improvement, whereas increase of at least 1.4, 1.8, 1.1, 1.1, and 1.4 units, respectively, in pain, tiredness, depression, anxiety, and appetite loss items were required for deterioration. At the subsequent follow-ups, these values were similar. Overall, the MCID for improvement tended to be smaller than that for deterioration. The distribution-based method estimates tended to be larger than the 0.3 SD estimates, but closer to the 0.5 SD estimates. CONCLUSION MCIDs allow health care professionals to determine the success of treatment in improving the patients quality of life. MCIDs may prompt health care professionals to intervene with new treatment. Future studies should confirm our findings with a variety of anchors.

Quality of life after palliative radiotherapy in bone metastases: A literature review.

Objective To investigate the quality of life (QOL) following palliative radiotherapy for painful bone metastases. Methods A literature search was conducted in OvidSP Medline (1946–Jan Week 4 2014), Embase (1947–Week 5 2014), and the Cochrane Central Register of Controlled Trials (Dec 2013) databases. The search was limited to English. Subject headings and keywords included ‘palliative radiation’, ‘cancer palliative therapy’, ‘bone metastases’, ‘quality of life’, and ‘pain’. All studies (prospective or retrospective) reporting change in QOL before and after palliative radiotherapy for painful bone metastases were included. Results Eighteen articles were selected from a total of 1730. The most commonly used tool to evaluate QOL was the Brief Pain Inventory. Seventeen studies collected data prospectively. An improvement in symptoms and functional interference scores following radiotherapy was observed in all studies. The difference in changes in QOL between responders and non responders was inconsistently reported. Conclusion QOL improves in patients who respond to palliative radiotherapy for painful bone metastases.

Determinants of quality of life in advanced cancer patients with bone metastases undergoing palliative radiation treatment.

PurposeAssessment of health-related quality of life (HRQOL) is critical to effective delivery of palliative care in patients with advanced cancer. The current study analyzes relationships between baseline social determinants of health and medical factors, and self-reported HRQOL in patients with bone metastases receiving palliative radiotherapy.Methods and materialsAdvanced cancer patients referred for radiotherapy treatment of bone metastases completed the EORTC QLQ-C30 questionnaire in multiple outpatient clinics internationally. Demographics and social determinants were collected as baseline information. Univariate and Bonferroni-adjusted multivariate linear regression analyses were used to detect significant correlations between baseline determinants and different HRQOL domains.ResultsKarnofsky Performance Status (KPS) was correlated with better physical (p = 0.0002), role (p < 0.0001), emotional (p < 0.0001), and social (p < 0.0001) functioning, and global health scores (p = 0.0015) and predicted lower symptom scores for fatigue (p < 0.0001), pain (p < 0.0001), appetite loss (p < 0.0001), and constipation (p < 0.0001). Increased age was predictive of better social functioning (p < 0.0001) and less insomnia (p = 0.0036), higher education correlated with better global health status (p = 0.0043), and patients who were employed or retired had improved physical functioning (p = 0.0004 and p = 0.0030, respectively) and less financial challenges compared to patients who were unemployed (p = 0.0005).ConclusionsBaseline KPS had the greatest influence on EORTC QLQ-C30 domain scores. Age, education level, and employment status had significant impacts, although on fewer domains. Further studies that investigate baseline determinants are worthwhile to clarify relationships in order to care for patients more effectively at the end of life.

Review of international patterns of practice for the treatment of painful bone metastases with palliative radiotherapy from 1993 to 2013

BACKGROUND AND PURPOSE Numerous randomized controlled trials and meta-analyses have affirmed that single and multiple fractions of radiotherapy provide equally efficacious outcomes in the palliation of painful, uncomplicated bone metastases (UBM). We aim to determine geographic, temporal and ancillary factors that influence the global patterns of practice in this setting. MATERIALS AND METHODS A literature search was conducted on Ovid MEDLINE and EMBASE. Studies were included if they disclosed prescription patterns of single fraction radiotherapy, either through hypothetical cases or actual patient data. Weighted analysis of variance was conducted for binary predictors while weighted linear regression analysis was performed for continuous parameters. RESULTS Nine hypothetical case studies and thirteen actual patterns of practice articles were included from 301 search results. Radiation oncologists prescribed dose fractionations ranging from 3Gy×1 to 2Gy×30, with a median of 3Gy×10, for the palliation of UBM. Actual data demonstrated a weak, non-significant, negative linear relationship between the use of single fraction radiotherapy and the year of treatment. Geographical location of treatment was a key predictor of prescription patterns. CONCLUSION In the last twenty years, there was an overall global reluctance to practice evidence-based medicine by employing single fractions for UBM.

Continued success in providing timely palliative radiation therapy at the Rapid Response Radiotherapy Program: a review of 2008-2012.

OBJECTIVE We set out to review the Rapid Response Radiotherapy Program (rrrp). METHODS We retrospectively reviewed a prospective database of patients referred to the rrrp between August 1, 2008, and June 30, 2012, extracting patient demographics, case dispositions, and wait times in days from referral to consultation and from consultation to treatment. RESULTS Of 2742 patients referred to the rrrp, 1458 (53%) were men, and 1284 (47%) were women. Median age was 64 years. The most prevalent primary cancer sites were lung (33%), breast (21%), and prostate (17%). The most common reasons for referral were bone metastases (53%) and brain metastases (21%). Palliative radiation therapy was given to 1890 patients. The median wait time from referral to consultation was 3 days. Among treated patients, 60% were treated on the day of their consultation, and 33%, within 1-6 days. CONCLUSIONS The rrrp continues to deliver timely palliative radiation therapy to patients, comparable to earlier reviews. The continued success of the rrrp will remain a model for future rapid-access palliative radiation therapy clinics.

Minimal important differences in the EORTC QLQ-C30 in patients with advanced cancer

Quality of life (QOL) is important in patients with advanced cancer. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ‐C30 is a general QOL tool used in cancer patients. Often, with a large enough sample, statistical significance of changecan be reached, however the clinical significance is often unknown. This study aimed to determine the magnitude of change that is meaningful to advanced cancer patients in the EORTC QLQ‐C30.

Minimal clinically important differences in the brief pain inventory in patients with bone metastases

PurposeThe brief pain inventory (BPI) is often used to assess pain and functional interference as a result of pain in cancer patients. Minor improvements or deteriorations in BPI may be statistically significant due to large sample sizes but may not necessarily be clinically relevant. The purpose of this study was to determine the minimal clinically important differences (MCID) in the functional BPI in patients with pain due to bone metastases.MethodsBPI scores were collected from patients with painful bone metastases who visited the Rapid Response Radiotherapy Program for palliative radiotherapy. Pain and functional interferences scores were also collected monthly for three months. Patients were categorized into “complete or partial response,” “pain progression,” and “indeterminate response” based on their pain scores as recommended by the latest consensus definitions. Anchor-based determination of MCIDs of functional interference scores was calculated by determining the difference between the mean follow-up scores and the mean baseline scores for patients from each of the three response groups. Distribution-based estimates were obtained utilizing 0.2, 0.3, and 0.5 standard deviation (SD) effect sizes and the standard error of measurement. The anchor-based method results were compared with the distribution-based method results.ResultsStatistically significant MCIDs were determined for all of the functional interference items of BPI for patients with “complete or partial response”; whereas, no statistically significant MCIDs in BPI scores could be determined for patients with “pain progression.” Some of the functional interference items of BPI had statistically significant MCIDs for patients with “indeterminate response,” although these were generally smaller than patients with complete or partial response. Using the distribution-based approach, an effect size of 0.5 SD was the closest estimate for determining the MCID for both patients with complete or partial response and those with indeterminate response.ConclusionsThe MCIDs determined for pain improvement were rather large, where as statistically significant MCIDs could not be detected for pain deterioration. Knowledge of MCIDs utilizing the BPI will allow physicians to evaluate the impact of treatment (or no treatment) on a patient’s functional abilities. Knowledge of MCIDs may allow for sample size determination in future clinical trials.