Alysa Fairchild

Palliative Thoracic Radiotherapy for Lung Cancer: A Systematic Review

PURPOSE The optimal dose of radiotherapy (RT) to palliate symptomatic advanced lung cancer is unclear. We systematically reviewed randomized controlled trials (RCTs) of palliative thoracic RT. METHODS RCTs comparing two or more dose fractionation schedules were reviewed using the random-effects model of a freely available information management system. The relative risk and 95% CI for each outcome were presented in Forrest plots. Exploratory analysis comparing dose schedules after conversion to the time-adjusted biologically equivalent dose (BED) was performed to investigate for a dose-response relationship. RESULTS A total of 13 RCTs involving 3,473 randomly assigned patients were identified. Outcomes included symptom palliation, overall survival, toxicity, and reirradiation rate. For symptom control in assessable patients, lower-dose (LD) RT was comparable with higher-dose (HD), except for the total symptom score (TSS): 65.4% of LD and 77.1% of HD patients had improved TSS (P = .003). Greater likelihood of symptom improvement was seen with schedules of 35 Gy(10) versus lower BED. At 1 year after HD and LD RT, 26.5% versus 21.7% of patients were alive, respectively (P = .002). Sensitivity analysis suggests this survival improvement was seen with 35 Gy(10) BED schedules compared with LDs. Physician-assessed dysphagia was significantly greater in the HD arm (20.5% v 14.9%; P = .01), and the likelihood of reirradiation was 1.2-fold higher after LD RT. CONCLUSION No significant differences were observed for specific symptom-control end points, although improvement in survival favored HD RT. Consideration of palliative thoracic RT of at least 35 Gy(10) BED may therefore be warranted, but must be weighed against increased toxicity and greater time investment.

International Patterns of Practice in Palliative Radiotherapy for Painful Bone Metastases: Evidence-Based Practice?

PURPOSE Multiple randomized controlled trials have demonstrated the equivalence of multifraction and single-fraction (SF) radiotherapy for the palliation of painful bone metastases (BM). However, according to previous surveys, SF schedules remain underused. The objectives of this study were to determine the current patterns of practice internationally and to investigate the factors influencing this practice. METHODS AND MATERIALS The members of three global radiation oncology professional organizations (American Society for Radiology Oncology [ASTRO], Canadian Association of Radiation Oncology [CARO], Royal Australian and New Zealand College of Radiologists) completed an Internet-based survey. The respondents described what radiotherapy dose fractionation they would recommend for 5 hypothetical cases describing patients with single or multiple painful BMs from breast, lung, or prostate cancer. Radiation oncologists rated the importance of patient, tumor, institution, and treatment factors, and descriptive statistics were compiled. The chi-square test was used for categorical variables and the Student t test for continuous variables. Logistic regression analysis identified predictors of the use of SF radiotherapy. RESULTS A total of 962 respondents, three-quarters ASTRO members, described 101 different dose schedules in common use (range, 3 Gy/1 fraction to 60 Gy/20 fractions). The median dose overall was 30 Gy/10 fractions. SF schedules were used the least often by ASTRO members practicing in the United States and most often by CARO members. Case, membership affiliation, country of training, location of practice, and practice type were independently predictive of the use of SF. The principal factors considered when prescribing were prognosis, risk of spinal cord compression, and performance status. CONCLUSION Despite abundant evidence, most radiation oncologists continue to prescribe multifraction schedules for patients who fit the eligibility criteria of previous randomized controlled trials. Our results have confirmed a delay in the incorporation of evidence into practice for palliative radiotherapy for painful bone metastases.

Is Pain Intensity a Predictor of the Complexity of Cancer Pain Management

PURPOSE The lack of a standardized cancer pain (CP) classification system prompted the development of the Edmonton Classification System for Cancer Pain (ECS-CP). Its five features have demonstrated value in predicting pain management complexity. Pain intensity (PI) at initial assessment has been proposed as having additional predictive value. We hypothesized that patients with moderate to severe CP would take longer to achieve stable pain control, use higher opioid doses, and require more complicated analgesic regimens than would patients with mild CP at initial assessment. METHODS A secondary analysis of a multicenter ECS-CP validation study involving patients with advanced cancer was conducted (n = 591). Associations between PI and length of time to stable pain control (Cox regression), final opioid dose (Kruskal-Wallis one-way analysis of variance), and number of adjuvant modalities (chi(2)) were calculated. PI at initial assessment was defined using a numerical scale as mild (0 to 3), moderate (4 to 6), or severe (7 to 10). RESULTS Patients with moderate and severe pain required a significantly longer time to achieve stable pain control (P < .0001). PI was a significant predictor of length of time to stable pain control in the univariate regression analysis. The four significant predictors in the multivariate model were moderate and severe PI (P < .0001), age (P = .001), and neuropathic pain (P = .002). Patients with moderate to severe pain required significantly higher final opioid doses (P < .0001) and more adjuvant modalities (P = .015). CONCLUSION PI at initial assessment is a significant predictor of pain management complexity and length of time to stable pain control. Incorporation of this feature into the ECS-CP needs additional consideration.

Dexamethasone for the Prophylaxis of Radiation-induced Pain Flare after Palliative Radiotherapy for Symptomatic Bone Metastases: a Phase II Study

AIMS Pain flare occurs in over one-third of patients receiving palliative radiotherapy for bone metastases. A single dose of dexamethasone can decrease the incidence of pain flare during the first 2 days immediately after radiotherapy. We conducted a phase II prospective study to investigate the prophylactic role of prolonged dexamethasone. MATERIALS AND METHODS Patients with bone metastases treated with a single 8Gy were prescribed 8mg dexamethasone just before palliative radiotherapy and for 3 consecutive days after treatment. Worst pain score and analgesic consumption data were collected at baseline and daily for 10 days after treatment. Analgesic consumption was converted into a total daily oral morphine equivalent dose in the analysis. Pain flare was defined (a priori) as a two-point increase in worst pain on an 11-point numeric rating scale compared with baseline with no decrease in analgesic intake, or a 25% increase in analgesic intake with no decrease in worst pain score. To distinguish pain flare from progressive disease, we required that the worst pain score and analgesic intake returned to baseline levels after the increase/flare. RESULTS Forty-one patients were evaluable (32 men, nine women). Their median age was 67 years. The overall incidence of pain flare was 9/41 (22%) within 10 days after the completion of radiotherapy. Most (55%) of these pain flares occurred on day 5. Absence of pain flare was 34/41(83%) and 39/41 (95%) for days 1-5 and 6-10 after the completion of radiotherapy, respectively. CONCLUSION Dexamethasone is effective in the prophylaxis of radiotherapy-induced pain flare after palliative radiotherapy for bone metastases. Randomised studies are needed to confirm this finding.

Does quality of radiation therapy predict outcomes of multicenter cooperative group trials? A literature review

Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.

Multidisciplinary Team Contributions Within a Dedicated Outpatient Palliative Radiotherapy Clinic: A Prospective Descriptive Study

PURPOSE Patients with bone metastases may experience pain, fatigue, and decreased mobility. Multiple medications for analgesia are often required, each with attendant side effects. Although palliative-intent radiotherapy (RT) is effective in decreasing pain, additional supportive care interventions may be overlooked. Our objective was to describe the feasibility of multidisciplinary assessment of patients with symptomatic bone metastases attending a dedicated outpatient palliative RT clinic. METHODS AND MATERIALS Consecutive patients referred for RT for painful bone metastases were screened for symptoms and needs relevant to their medications, nutritional intake, activities of daily living, and psychosocial and spiritual concerns from January 1 to December 31, 2007. Consultations by appropriate team members and resulting recommendations were collected prospectively. Patients who received RT were contacted by telephone 4 weeks later to assess symptom outcomes. RESULTS A total of 106 clinic visits by 82 individual patients occurred. As determined by screening form responses, the clinical Pharmacist, Occupational Therapist, Registered Dietician and Social Worker were consulted to provide assessments and recommendations within the time constraints presented by 1-day palliative RT delivery. In addition to pain relief, significant improvements in tiredness, depression, anxiety, drowsiness and overall well-being were reported at 4 weeks. CONCLUSIONS Systematic screening of this population revealed previously unmet needs, addressed in the form of custom verbal and written recommendations. Multidisciplinary assessment is associated with a high number of recommendations and decreased symptom distress. Our findings lend strong support to the routine assessment by multiple supportive care professionals for patients with advanced cancer being considered for palliative RT.

Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial

BACKGROUND Pain flare occurs after palliative radiotherapy, and dexamethasone has shown potential for prevention of such flare. We aimed to compare the efficacy of dexamethasone with that of placebo in terms of reduction of incidence of pain flare. METHODS In this double-blind, randomised, placebo-controlled phase 3 trial, patients from 23 Canadian centres were randomly allocated (1:1) with a web-based system and minimisation algorithm to receive either two 4 mg dexamethasone tablets or two placebo tablets taken orally at least 1 h before the start of radiation treatment (a single 8 Gy dose to bone metastases; day 0) and then every day for 4 days after radiotherapy (days 1-4). Patients were eligible if they had a non-haematological malignancy and bone metastasis (or metastases) corresponding to the clinically painful area or areas. Patients reported their worst pain scores and opioid analgesic intake before treatment and daily for 10 days after radiation treatment. They completed the European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C15-PAL, the bone metastases module (EORTC QLQ-BM22), and the Dexamethasone Symptom Questionnaire at baseline, and at days 10 and 42 after radiation treatment. Pain flare was defined as at least a two-point increase on a scale of 0-10 in the worst pain score with no decrease in analgesic intake, or a 25% or greater increase in analgesic intake with no decrease in the worst pain score from days 0-10, followed by a return to baseline levels or below. Primary analysis of incidence of pain flare was by intention-to-treat (patients with missing primary data were classified as having pain flare). This study is registered with ClinicalTrials.gov, number NCT01248585, and is completed. FINDINGS Between May 30, 2011, and Dec 11, 2014, 298 patients were enrolled. 39 (26%) of 148 patients randomly allocated to the dexamethasone group and 53 (35%) of 150 patients in the placebo group had a pain flare (difference 8·9%, lower 95% confidence bound 0·0, one-sided p=0·05). Two grade 3 and one grade 4 biochemical hyperglycaemic events occurred in the dexamethasone group (without known clinical effects) compared with none in the placebo group. The most common adverse events were bone pain (61 [41%] of 147 vs 68 [48%] of 143), fatigue (58 [39%] of 147 vs 49 [34%] of 143), constipation (47 [32%] of 147 vs 37 [26%] of 143), and nausea (34 [23%] of 147 vs 34 [24%] of 143), most of which were mild grade 1 or 2. INTERPRETATION Dexamethasone reduces radiation-induced pain flare in the treatment of painful bone metastases. FUNDING The NCIC CTGs programmatic grant from the Canadian Cancer Society Research Institute.

International field testing of the reliability and validity of the EORTC QLQ‐BM22 module to assess health‐related quality of life in patients with bone metastases

The objective of this international field study was to test the reliability, validity, and responsiveness of the European Organization for Research and Treatment of Cancer (EORTC) QLQ‐BM22 module to assess health‐related quality of life (HRQOL) in patients with bone metastases.

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.

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.