Elizabeth Barnes

Determining the Incidence of Pain Flare Following Palliative Radiotherapy for Symptomatic Bone Metastases: Results From Three Canadian Cancer Centers

PURPOSEnTo determine the incidence of pain flare following radiotherapy (RT) for painful bone metastases.nnnMATERIALS AND METHODSnPatients with bone metastases treated with RT were eligible. Worst pain scores and analgesic consumption were collected before, daily during, and for 10 days after treatment. Pain flare was defined as a 2-point increase in the worst pain score (0-10) compared to baseline with no decrease in analgesic intake, or a 25% increase in analgesic intake with no decrease in worst pain score. Pain flare was distinguished from progression of pain by requiring the worst pain score and analgesic intake return to baseline levels after the increase/flare (within the 10-day follow-up period).nnnRESULTSnA total of 111 patients from three cancer centers were evaluable. There were 50 male and 61 female patients with a median age of 62 years (range, 40-89 years). The primary cancers were mainly breast, lung, and prostate. Most patients received a single 8 Gy (64%) or 20 Gy in five fractions (25%). The overall pain flare incidence was 44/111 (40%) during RT and within 10 days following the completion of RT. Patients treated with a single 8 Gy reported a pain flare incidence of 39% (27/70) and, with multiple fractions, 41% (17/41).nnnCONCLUSIONnMore than one third of the enrolled patients experienced a pain flare. Identifying at-risk individuals and managing potential pain flares is crucial to achieve an optimal level of care.

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

AIMSnPain 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.nnnMATERIALS AND METHODSnPatients 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.nnnRESULTSnForty-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.nnnCONCLUSIONnDexamethasone is effective in the prophylaxis of radiotherapy-induced pain flare after palliative radiotherapy for bone metastases. Randomised studies are needed to confirm this finding.

Palliative Response and Functional Interference Outcomes Using the Brief Pain Inventory for Spinal Bony Metastases Treated with Conventional Radiotherapy

AIMSnTo report pain and functional interference responses in patients radiated for painful spinal metastases, and to determine if location within the vertebral column or dose fractionation are associated with response.nnnMATERIALS AND METHODSnPatients treated with palliative radiotherapy for symptomatic spinal metastases from May 2003 to June 2005 were analysed. All patients completed the Brief Pain Inventory (BPI) assessment tool at 1, 2 and 3 months after radiotherapy. The pain response was determined using the International Bone Metastases Consensus response definitions. Given seven BPI functional interference items, a Bonferroni adjusted P value of less than 0.007 was considered significant.nnnRESULTSnOne hundred and nine treated patients were assessed. About 50% of patients were treated with a single fraction of 8Gy. All pain scores and functional interference scores significantly decreased over time after radiotherapy. At 3 months, 64% of patients achieved a response. Mood was significantly improved for responders (P=0.003) and a trend in improvement was observed for general activity (P=0.01) and normal work (P=0.04). Breast and prostate primaries were more likely to achieve an early response as compared with a lung primary. Neither location within the vertebral column or radiotherapy dose fractionation independently predicted for pain or functional interference responses.nnnCONCLUSIONnConventional radiotherapy with 8Gy in a single fraction for spine metastases resulted in effective palliation of pain at 3 months and had a positive effect on a patients mood. Location within the spine was not a predictive factor.

Symptoms and Quality of Life in Cancer Patients With Brain Metastases Following Palliative Radiotherapy

PURPOSEnTo examine prospectively patient self-rated symptoms and quality of life (QOL) indicators in patients with brain metastases following whole brain radiotherapy (WBRT).nnnMETHODS AND MATERIALSnConsecutive patients with brain metastases referred for WBRT were approached for this study. Patients were asked to rate their symptoms and QOL using the Spitzer Quality of Life Index questionnaire. Follow-up was at 1, 2, and 3 months following WBRT. Linear regression analysis was used to determine the change in symptom severity over time.nnnRESULTSnBetween August 2005 to October 2007, 129 patients with brain metastases were enrolled. The majority of patients (88%) received 20 Gy in five fractions. Median age was 64 years, and median Karnofsky Performance Status at baseline was 70. The most commonly experienced symptoms at baseline were headaches, weakness, balance problems, and fatigue. Thirty-five percent of patients rated neurological functional (NF) status as 1, indicating moderate neurological symptoms and need for assistance. Forty-three percent of patients had stable or decreased fatigue, and 47% had a stable or improved NF status over time (p = 0.0040). Although certain QOL domains improved over time, all other QOL domains and symptom items did not change significantly following WBRT.nnnCONCLUSIONnWBRT may have contributed to symptom stabilization in our study. An alternative goal of WBRT may be the prevention of symptom progression and QOL deterioration. Further research is required to select the most appropriate group of patients with brain metastases who would benefit most from WBRT.

Quality of Life in Patients With Brain Metastases Using the EORTC QLQ-BN20+2 and QLQ-C15-PAL

PURPOSEnThe 20-item European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Brain Neoplasm (QLQ-BN20) is a validated quality-of-life (QOL) questionnaire for patients with primary brain tumors. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15 Palliative (QLQ-C15-PAL) core palliative questionnaire is a 15-item version of the core 30-item QLQ-C30 and was developed to decrease the burden on patients with advanced cancer. The combination of the QLQ-BN20 and QLQ-C30 to assess QOL may be too burdensome for patients. The primary aim of this study was to assess QOL in patients before and after treatment for brain metastases using the QLQ-BN20+2 and QLQ-C15-PAL, a version of the QLQ-BN20 questionnaire with 2 additional questions assessing cognitive functioning that were not addressed in the QLQ-C15-PAL.nnnMETHODS AND MATERIALSnPatients with brain metastases completed the QLQ-C15-PAL and QLQ-BN20+2 questionnaires to assess QOL before and 1 month after radiation. Linear regression analysis was used to assess changes in QOL scores over time, as well as to explore associations between the QLQ-BN20+2 and QLQ-C15-PAL scales, patient demographics, and clinical variables. Spearman correlation assessed associations between the QLQ-BN20+2 and QLQ-C15-PAL scales.nnnRESULTSnAmong 108 patients, the majority (55%) received whole-brain radiotherapy only, with 65% of patients completing follow-up at 1 month after treatment. The most prominent symptoms at baseline were future uncertainty (QLQ-BN20+2) and fatigue (QLQ-C15-PAL). After treatment, significant improvement was seen for the QLQ-C15-PAL insomnia scale, as well as the QLQ-BN20+2 scales of future uncertainty, visual disorder, and concentration difficulty. Baseline Karnofsky Performance Status was negatively correlated to QLQ-BN20+2 motor dysfunction but positively related to QLQ-C15-PAL physical functioning and QLQ-BN20+2 cognitive functioning at baseline and follow-up. QLQ-BN20+2 scales of future uncertainty and motor dysfunction correlated with the most QLQ-C15-PAL scales, including overall QOL (negative association) at baseline and follow-up.nnnCONCLUSIONnAfter radiation, the questionnaires showed maintenance of QOL and improvement of QOL scores such as future uncertainty, which featured prominently in this patient population. It is proposed that the 37-item QLQ-BN20+2 and QLQ-C15-PAL, as opposed to the 50-item QLQ-BN20 and QLQ-C30, may be used together as a universal QOL assessment tool in this setting.

Retrospective Assessment of Cancer Pain Management in an Outpatient Palliative Radiotherapy Clinic Using the Pain Management Index

CONTEXTnThe Pain Management Index (PMI) is a simple index linking the usual severity of cancer pain with the category of medication prescribed to treat it. Medication categories are derived from the World Health Organizations analgesic ladder approach to cancer pain, and the PMI is an indicator of the extent to which the medication prescribed corresponds to the recommended categories for mild, moderate, and severe pain.nnnOBJECTIVESnThe aim of this study was to assess prevalence of inadequate pain management in an outpatient palliative radiotherapy clinic using the PMI.nnnMETHODSnAll patients with bone metastases referred for palliative radiotherapy from 1999 to 2006 were retrospectively analyzed for patient-rated pain scores (0-10 scale) and analgesic consumption. Pain scores were assigned 0, 1, 2, and 3 when patients reported no pain (0), mild (1-4), moderate (5-6), or severe pain (7-10), respectively. Analgesic scores of 0, 1, 2, and 3 were assigned when patients were prescribed no pain medication, nonopioids, weak opioids, and strong opioids, respectively. The PMI score was calculated by subtracting the pain score from the analgesic score. A negative PMI score was considered an indicator of potentially inadequate pain management by the prescriber. Descriptive statistics, Pearsons r correlation, and univariate and multivariate logistic regression analysis were used to determine the relationship of PMI over time, and the relationship with predictive factors.nnnRESULTSnOne thousand patients were included from January 1999 to December 2006. A negative PMI was calculated for 25.8% of patients at initial consultation. Prevalence of negative PMI significantly increased over years (P<0.0001). Higher Karnofsky Performance Status (P<0.0001) and breast primary cancer site (P<0.0001) were significantly associated with negative PMI after adjusting for year variable.nnnCONCLUSIONnDespite publication of numerous cancer pain management guidelines, undermedication appears to be a persistent problem for patients with painful bone metastases referred for radiotherapy.

Has Pain Management in Cancer Patients with Bone Metastases Improved? A Seven-Year Review at An Outpatient Palliative Radiotherapy Clinic

The primary objective of this study was to determine the prevalence of underdosage of analgesics for pain associated with bone metastases in outpatients referred to the Rapid Response Radiotherapy Program at the Odette Cancer Centre from 1999 to 2006. A prospective database containing data for all patients with bone metastases who were referred to the Rapid Response Radiotherapy Program for palliative radiotherapy from 1999 to 2006 was analyzed. The database included patient demographic information, including age at referral for radiation to the bone, gender, primary cancer site, and Karnofsky Performance Status; information on treatment-related factors, such as worst pain ratings and analgesic consumption in the past 24 hours (recorded as oral morphine equivalent doses); pain intensity ratings (none [rating=0], mild [rating=1-4], moderate [rating=5-6] or severe [rating=7-10]; and analgesic consumption (rated as none, nonopioids, weak opioids [e.g., codeine] and strong opioids [e.g., morphine and hydromorphone]). Patients who experienced moderate or severe pain and were prescribed no pain medication, nonopioids, or weak opioids were considered to be undermedicated. Between January 1999 and December 2006, 1,038 patients were included in the study database. Approximately 56% of patients were male and 44% were female. The median age was 68 years (range 28-95) and the median Karnofsky Performance Status was 70 (range 10-100). The percentages of undermedicated patients were 40% in 1999, 34% in 2000, 29% in 2001, 37% in 2003, 39% in 2004, 36% in 2005, and 48% in 2006. No appreciable decline was noted in the proportion of patients with moderate-to-severe pain who received no pain medication, nonopioids, or weak opioids during the study period. Despite the publication of pain management guidelines and the dissemination of data regarding the proportion of patients with bone metastases who are being prescribed inadequate analgesics, our findings suggest that a significant proportion of patients continue to be undermedicated.

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

CONTEXTnLongitudinal 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.nnnOBJECTIVESnThe 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).nnnMETHODSnBetween 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.nnnRESULTSnA 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.nnnCONCLUSIONnMCIDs 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.

Palliative radiotherapy for bone metastases in the last 3 months of life: worthwhile or futile?

AIMSnTo determine the efficacy of radiotherapy for the palliation of pain from bone metastases among patients in their last 3 months of life.nnnMATERIALS AND METHODSnMutually exclusive, prospectively gathered Edmonton Symptom Assessment System and Brief Pain Inventory databases compiled from patients with bone metastases receiving palliative radiotherapy were reviewed. Demographic information and response rates from patients dying within 3 months of beginning radiotherapy were analysed.nnnRESULTSnFrom a total of 918 patients, 232 dying within 3 months of beginning treatment were identified. There were 148 men and 84 women. Their median age was 69 years and their median Karnofsky Performance Status was 60. The three most common primary cancers were lung (34%), prostate (18%) and gastrointestinal (14%). Fifty-eight percent of patients received single fraction treatment. A pain response was evaluable for the 109 (47%) patients with available follow-up information. The overall response rates were 70% at 1 month and 63% at 2 months, which included complete and partial responses in accordance with the International Bone Metastases Consensus definitions.nnnCONCLUSIONSnDespite their limited lifespan, patients reported pain relief after palliative radiotherapy. Patients suffering from painful bone metastases with an estimated survival of 3 months should still be considered for palliative radiotherapy.

First report on the patient database for the identification of the genetic pathways involved in patients over-reacting to radiotherapy: GENEPI-II

BACKGROUNDnIdentifying the most radiosensitive patient group would have huge clinical implications.nnnMETHODSnA tissue bank containing skin fibroblasts, whole blood, lymphocytes, plasma and lymphoblastoid cell lines from clinically radiation hypersensitive patients was established from patients in Europe and Canada. Over-reacting individuals had CTCAE3.0 severe acute side effects grade 2 or more occurring at very low radiation doses where these side effects are unexpected or grade 3-4 lasting more than 4 weeks after the end of radiotherapy and/or requiring surgical intervention at any time or severe late side effects grade 3-4.nnnRESULTSnEleven patients have been identified with a mean age of 61.6±8.5 years (range 49-74). Two patients were male, 9 female. One patient had non-small cell lung cancer, 6 breast cancer, 2 head and neck cancer, one lymphoma and one meningioma. The mean follow-up time after radiotherapy was 1658±1048 days (range 84-3752).nnnCONCLUSIONSnThe establishment of an international tissue bank of the rare group of patients with extreme hypersensitivity to radiotherapy was proven to be feasible and should enable in-depth molecular studies.