Need for better documentation and definition of pain flare following external beam radiotherapy in the treatment of bone metastases.
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Publications and source records attributed to Edward Chow.
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INTRODUCTION: Since the 1980s, randomized clinical trials showed that single fraction radiotherapy (RT) provided equal pain relief as multiple fractions of RT in the treatment of bone metastases. MATERIALS AND METHODS: Using Medline, a literature search was conducted on patterns of practice among radiation oncologists and patients' preferences of dose fractionations for the treatment of bone metastases. RESULTS AND DISCUSSION: Fifteen studies on international patterns of practice published between 1966 and May 2006 were identified. Surveys of Canadian radiation oncologists indicated approximately 85% preferred multiple fractions, most often as 20 Gray in five fractions (20 Gy/5). Surveys in the United States indicated that 30 Gy/10 was most commonly used, and 90-100% of these oncologists preferred multiple over single fraction RT. Multiple fractions were most commonly used in the United Kingdom, Western Europe, Australia and New Zealand, and India; however, more radiation oncologists in these countries would prescribe a single fraction than in North America. Three studies investigated patients' preferences of dose fractionations. In the Australian study, most patients favored single fraction RT as long as long-term outcomes were not compromised. Durability of pain relief was considered more important than short-term convenience factors. In the Singapore study, 85% of patients would choose extended courses of RT (24 Gy/6) compared to a single 8 Gy. In the Canadian study, most patients (76%) would choose a single 8 Gy over 20 Gy/5 of palliative RT due to greater convenience. CONCLUSION: Despite strong evidence supporting the use of single fraction RT, current practices and preferences favor multiple fractions for the treatment of bone metastases. This has significant implications for the overall quality of life, RT department workload, costs to healthcare systems, and patient convenience.
PURPOSE: The Dutch Bone Metastases Study Group developed a survival prediction model in patients with symptomatic spinal bone metastases to guide the treating physician. The objective of this study was to validate the Dutch model and compare with our previously developed survival model at the Rapid Response Radiotherapy Program (RRRP model). METHODS AND MATERIALS: The following prognostic factors were extracted from a prospective database in an outpatient palliative radiotherapy clinic: Karnofsky Performance Scores (KPS), primary cancer site, and visceral involvement for the Dutch model; primary cancer site, site of metastases, KPS, fatigue, appetite, and shortness of breath scores in the Edmonton Symptom Assessment Scale for the RRRP model. Patients were assigned scores according to each model. The survival probabilities were generated and calibration was performed for each model. RESULTS: A total of 231 patients with spinal bone metastases from 1999 and 2002 were included in the analysis. The survival probabilities were similar to those in the original models. The calibration comparing actual survival with predicted survival from the Dutch and RRRP models gave R2 values of 0.90 and 0.86, respectively. CONCLUSION: The two models were successfully validated. The Dutch model using three clinical prognostic factors was easier to administer.
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PURPOSE: To examine how patients categorize their pain with the two commonly employed scales. METHODS AND MATERIALS: Patients with bone metastases referred to an outpatient palliative radiotherapy clinic were asked to rate their current pain on a numerical scale of 0-10 (0 = no pain, 10 = worst pain possible) and a categorized scale: none, mild, moderate and severe. RESULTS: Two hundred and seventeen patients were enrolled in the study. The median age was 66 years and median Karnofsky Performance Score was 70. The most common primary cancer sites were lung, prostate and breast. Based on patient-evaluated symptoms, 60% of patients who categorized pain as mild assigned it a 3 (24%) or 4 (36%), 63% who categorized pain as moderate assigned it a 5 (16.9%), 6 (19.1%) or 7 (27%) and 80% who categorized pain as severe assigned it an 8 (28.2%), 9 (12.6%) or 10 (39.8%). CONCLUSION: Our patients scored pain as mild if pain was < or =4, moderate if pain was 5-7 and severe if pain was > or =8.
PURPOSE: Percutaneous vertebroplasty (PVP) is a minimally invasive outpatient procedure whereby vertebral compression fractures are stabilized by the injection of bone cement, or polymethyl methacrylate (PMMA). Rapid partial or complete pain relief can usually be achieved through this procedure. We prospectively evaluate the efficacy of PVP in the relief of pain and improvement in quality of life of patients with intractable pain from osteoporotic and metastatic fractures. MATERIALS AND METHODS: Patients with intractable pain from vertebral metastases (many resistant to palliative radiation therapy) and patients with intractable painful osteoporotic fractures were treated with parapedicular or transpedicular injection of PMMA. Plane X-rays, computed tomography (CT) scan, and magnetic resonance imaging (MRI) scan were performed on all patients. With a reflex hammer, percussion pain was correlated to the imaging abnormalities. The preplanning CT scan was used to calculate the exact entry point and angle of the bone-biopsy needle. All patients were assessed before and after the procedure for quality of life and amount of pain. The following measures were used: 1) the Edmonton Symptom Assessment System (ESAS), for global pain, nausea, tiredness, depression, anxiety, drowsiness, appetite, sense of well-being, and shortness of breath; 2) a site-specific pain score (SSPS); 3) the amount of analgesic intake in morphine equivalents in the last 24 hours; and 4) the Townsend Functional Assessment Scale (TFAS), ascertaining mobility. A postprocedural CT scan was performed the same day on all patients. Follow-up assessment consisted of a phone call at Days 1, 2, and 4 and Weeks 1, 2, 4, 8, and 12. Patients with recurrent back pain or complications were followed in the bone metastases clinic. RESULTS: Thirty patients (19 women, 11 men) were evaluated. Their median age was 68 years (range 31 to 87 years). Thirty procedures (n = 30) at 45 vertebral levels were performed; 13 were for pathologic fractures, and 17 were for osteoporotic fractures. SSPS showed a decrease of 2 or more levels in 88.5% of patients at 12-week follow-up. The mean SSPS with movement was 8.7 preprocedure and 1.8 postprocedure (P < 0.0001). Also, there was significant improvement in all 9 ESAS domains (P < 0.0004). The ingestion of analgesics in morphine equivalents showed a trend toward reduction post-PVP (P < 0.0599). When the patients with pathologic fractures were separated out, the reduction in ingestion of analgesics was significant (P < 0.0008). The TFAS demonstrated significant improvement in patient mobility and function. Extravertebral extravasation of cement was noted in 55.6% of the levels. We used a general linear mixed-model repeated-measures analysis of variance to analyze the data. CONCLUSIONS: PVP in osteoporotic and metastatic fractures significantly improved many patients' global quality-of-life scores and function by markedly decreasing their back pain and reducing their intake of pain medications. The procedure is safe, with no serious complications noted in our study.
BACKGROUND: Renal cell carcinoma (RCC) has previously been described as being less responsive to radiotherapy (RT) than other tumor types. The authors conducted a prospective study to assess the effect of RT on symptoms and quality of life (QOL) in patients with metastatic RCC. METHODS: Between 1996 and 2002, patients with symptomatic metastatic RCC were entered into a prospective study in two cancer centers. Symptomatic sites of disease were treated with 30 grays (Gy) in 10 fractions. Patients reported pain, analgesic use, symptoms, and QOL using validated questionnaires before RT, 1 month and 3 months after treatment, and every 3 months to 1 year thereafter. RESULTS: Thirty-one patients (19 males and 12 females) were entered into the trial. The median age of the patients was 61 years (range, 35-81 yrs). The most common indication for RT was bone pain (n = 24). The median duration of follow-up was 4.3 months (range, 1-15 mos). Of 23 evaluable patients treated for pain, 83% (n = 19) experienced site-specific pain relief after RT, and 48% (n = 11) did not have an associated increase in analgesic medication use. The median duration of site-specific pain response was 3 months (range, 1-15 mos). The global pain response rate was only 15% (n = 3) because many patients developed other painful metastases. Global QOL was found to improve in 33% (n = 8) of the evaluable patients. CONCLUSIONS: A palliative radiotherapy dose of 30 Gy in 10 fractions can result in a significant response rate and the relief of local symptoms in patients with bone metastases from RCC. Improvements in global pain and QOL appear to be limited by the effects of progressive systemic disease.
PURPOSE: To determine the proportion of patients undergoing palliative radiotherapy (RT) for bone pain who would like to participate in the decision-making process, and to determine their choice of palliative RT regimen (2000 cGy in five fractions vs. 800 cGy in one fraction) for painful bone metastases. METHODS AND MATERIALS: Eligible patients were approached and all patients agreeing to participate provided written informed consent. Patients' decisional preferences were studied using a five-statement preference instrument. A decision board was used to help patients decide their preferred palliative RT regimen. Factors influencing patients' choices were studied using a visual analog scale. RESULTS: A total of 101 patients were enrolled in the study (55 women and 46 men). The preferences for decision-making were as follows: 30 active, 47 collaborative, and 24 passive. Most (55 [76%] of 72) patients favored one fraction of palliative RT (95% confidence interval, 65-86%). Patients were more likely to select the 800 cGy in one fraction because of the convenience of the treatment plan (odds ratio, 1.024; 95% confidence interval, 1.004-1044) but were less likely to choose it because of the chance of bone fracture (odds ratio, 0.973; 95% confidence interval, 0.947-1.000) compared with 2000 cGy in five fractions. CONCLUSION: Most participating patients preferred to decide either by themselves or with the radiation oncologists which treatment option they preferred. An 800-cGy-in-one-fraction regimen was favored, independent of the treated site. The convenience of the treatment plan and the likelihood of bone fracture were the most important factors influencing patients' choice.
BACKGROUND AND PURPOSE: To examine the incidence of pain flare following external beam radiotherapy and to determine what constitutes a meaningful change in pain scores in the treatment of bone metastases. PATIENTS AND METHODS: Patients with bone metastases treated with external beam radiotherapy were asked to score their pain on a scale of 0-10 before the treatment (baseline), daily during the treatment and for 10 days after completion of external beam radiation. Pain flare was defined as a two-point increase from baseline pain in the pain scale of 0-10 with no decrease in analgesic intake or a 25% increase in analgesic intake employing daily oral morphine equivalent with no decrease in pain score. To distinguish pain flare from progression of pain, we required the pain score and analgesic intake to return back to baseline levels after the increase/flare. They were also asked to indicate if their pain changed during that time compared to pre-treatment level. The change in pain score was compared with patient perception. RESULTS: Eighty-eight patients were evaluated in this study. There were 49 male and 39 female patients with the median age of 70 years. Twelve of 88 patients (14%) had pain flare on day 1. The overall incidence of pain flare during the study period ranged from 2 to 16%. A total of 797 pain scorings were obtained. Patients perceived an improvement in pain when their self-reported pain score decreased by at least two points. CONCLUSIONS: Our study confirms the occurrence of pain flare following the external beam radiotherapy in the treatment of bone metastases. Further studies are required to predict who are at risk for flare. Appropriate measures can be taken to alleviate the pain flare. The finding in the meaningful change in pain scores supports the investigator-defined partial response used in some clinical trials.
PURPOSE: To examine the accuracy of survival prediction by palliative radiation oncologists. METHODS AND MATERIALS: After consultation of cancer patients with metastatic disease for referral of palliative radiotherapy, radiation oncologists estimated the survival of the patients. These were compared with the actual dates of death obtained from the Cancer Death Registry. The time to death from all causes was the outcome. The survival times were measured from the date of the first consultation at the palliative radiotherapy clinics. RESULTS: Six radiation oncologists provided estimates for 739 patients. Of the 739 patients, 396 were men and 343 were women (median age, 69 years). The median survival of all patients was 15.9 weeks. The mean difference between the actual survival (AS) and the clinician predicted survival (i.e., actual survival minus clinician predicted survival) was -12.3 weeks (95% confidence interval, -15.0 to -9.5) for the entire population. The mean difference was -21.9 weeks when the actual survival was < or =12 weeks, -19.2 weeks when the AS was 13-26 weeks, -9.7 weeks when the AS was 27-52 weeks, and +23.0 weeks when the AS was >52 weeks. CONCLUSION: In this study, the prediction of survival by radiation oncologists was inaccurate and tended to be overly optimistic.
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BACKGROUND: The management of brain metastases is a significant health care problem. An estimated 20-40% of cancer patients will develop metastatic cancer to the brain during the course of their illness. METHODS: A systematic review of randomized trials on adult cancer patients with single or multiple brain metastases from cancer of any histology was conducted. Eligible studies investigated external beam radiotherapy or radiosurgery in one of the study arms. Outcomes of interest included survival, intracranial progression-free duration, response of brain metastases to therapy, quality of life, symptom control, neurological function, and toxicity. RESULTS: Twenty-seven trials were included in this systematic review of the evidence. Pooled results from three randomized trials of surgical excision combined with whole brain radiotherapy (WBRT) showed no improvement in overall survival as compared to WBRT alone in patients with single brain metastasis. One randomized study of postoperative WBRT following excision of a single brain metastasis versus surgery alone detected a significant reduction in intracranial tumour recurrence rates but no corresponding difference in overall survival. Nine trials of altered dose-fractionation schedules compared to a standard control fractionation schedule (3000 cGy in 10 fractions) of WBRT showed no difference in probability of survival at 6 months. The addition of radiosensitizers, as assessed in five trials, did not confer additional benefit to WBRT in terms of overall survival or the frequency of brain metastases response. Three trials examined the use of WBRT and radiosurgery boost versus WBRT alone in selected patients with brain metastases. Overall survival did not improve for patients with multiple brain metastases. However, one trial reported an improvement in survival for patients with single brain metastasis treated with WBRT and radiosurgery boost. One older randomized trial examined the use of WBRT versus supportive care alone (using oral prednisone). Results were not conclusive. CONCLUSION: For patients with a single brain metastasis, good performance status, and minimal or no evidence of extracranial disease, surgical excision and postoperative WBRT improves survival (as compared to WBRT alone). There may be a small survival advantage associated with the use of radiosurgery boost and WBRT as compared to WBRT alone in selected patients with a single brain metastasis. There is no difference in overall survival or in neurologic function improvement with the use of altered whole brain dose-fractionation schedules as compared to standard fractionation schedules (3000 cGy in 10 fractions or 2000 cGy in 5 fractions). There is no survival benefit associated with the use of radiosurgery boost and WBRT versus WBRT alone in patients with multiple brain metastases. Currently, neither chemotherapy nor radiosensitizers show a clear benefit in the objective parameters of survival and progression-free survival. For patients with poor performance status and active extracranial disease, steroids and supportive care are an option.
To prospectively assess patient-rated symptoms in patients with brain metastases treated with whole brain radiotherapy, these patients were asked to rate their symptoms on the Edmonton Symptom Assessment Scale (ESAS) before, and 1, 2, 4, 8, and 12 weeks following the radiation treatment. ESAS evaluates pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, sense of well-being, and shortness of breath on a scale of 0-10 (0=absence of symptom and 10=worst possible symptom). Patients with a language barrier or significant cognitive impairment were excluded. The mean difference of ESAS symptoms at each follow up were compared with baseline and P < 0.01 was considered statistically significant. One hundred seventy patients (102 female and 68 male) were included between January 1999 and January 2002. Their median age was 66 years (range 33-84) and the median Karnofsky performance score (KPS) at baseline was 60 (range 20-90). The most common primary cancer sites were lung (99; 58%), breast (32; 19%), gastrointestinal (16; 9%), unknown (14; 8%) and others (9; 6%). One-third had significant weight loss (> or =10% over the last 6 months). All patients were prescribed dexamethasone at varying doses during radiotherapy. The dose fractionations were 20 Gy in 5 fractions, 138 (81%); 30 Gy in 10 fractions, 7 (4%); and others, 25 (15%). The baseline mean +/- SD for ESAS scores were: pain 2.4 +/- 2.8, fatigue 5.3 +/- 2.8, nausea 1.3 +/- 2.2, depression 2.8 +/- 2.7, anxiety 3.6 +/- 3.0, drowsiness 3.5 +/- 2.9, appetite 3.0 +/- 3.2, sense of well-being 3.8 +/- 2.7, and shortness of breath 2.3 +/- 2.5. For the entire cohort, after the delivery of palliative radiotherapy for brain metastases, there were statistically significant deteriorations in the mean differences from the baseline for the following ESAS domains: fatigue 1.0 to 1.8; drowsiness 1.2 to 1.8; and appetite 2.2 to 2.4. The data demonstrate that certain parameters of quality of life worsen after whole brain radiotherapy.
Patients with advanced cancer are often polysymptomatic. Different symptoms occur with varying frequency, intensity, and impact. Despite the high prevalence of symptoms in this population, reports of symptomatology in palliative outpatients have been limited. We report the symptom distress in metastatic cancer patients attending an outpatient palliative radiotherapy clinic. Patients referred for palliative radiotherapy for symptom control to the Rapid Response Radiotherapy Program (RRRP) were asked to rate symptom distress using the Edmonton Symptom Assessment Scale (ESAS) at the time of initial consultation. Patient demographics, cancer history, disease status, and analgesic consumption during the previous 24 hours were recorded. Between January 1999 and January 2002, 1,296 patients were seen at the RRRP and consented to participate in the study. Mean symptom distress rates ranged from 1.41 to 5.04. Fatigue, poor sense of well-being, pain, and poor appetite were the highest scored symptoms consecutively. Patients with poorer performance status (KPS < or = 60) had significantly higher symptom distress scores for all nine symptoms (P < 0.001). We conclude that the symptoms of metastatic cancer, including pain, fatigue, depression, anxiety, drowsiness, poor appetite, and sense of well-being, are common among patients attending outpatient palliative clinics. Symptom assessment tools, such as the ESAS, allow for the identification of symptoms and their severity. The appropriate regimen for management of pain and symptoms in metastatic cancer patients can then be planned.
Radiation is an effective modality to aid in symptom management of patients with metastatic disease. The type and duration of treatment depends on the Karnofsky performance status (KPS) of the patient and type and status of the cancer. Abbreviated treatment regimens may be favored in this patient population. They provide quick palliation without the patient and family spending significant time traveling back and forth to the treatment center. Hypofractionated regimens have been found effective in relieving pain from metastatic bone disease, relieving obstruction from locally advanced lung cancer, bleeding from gynecologic cancers, and hematuria from advanced bladder cancer. More aggressive regimens such as whole-brain radiation therapy (WBRT) and stereotactic radiosurgery may be appropriate for select patients with a good KPS. Radiation has also been found to be effective in palliating recurrent cancer that has already received definitive radiation.
PURPOSE: To review the feasibility of telephone follow-up following a 3-year experience from 1999 to 2001 at the Rapid Response Radiotherapy Program as a prospective radiotherapy outcome assessment of symptom palliation. METHODS AND MATERIALS: Patients referred for palliative radiotherapy for symptom control from 1999 to 2001 were asked to rate symptom distress using the Edmonton Symptom Assessment System (ESAS) at initial consultation. Patient demographics and analgesic consumption were recorded. Telephone follow-up interviews were conducted with all patients who received radiotherapy during weeks 1, 2, 4, 8, and 12 after radiotherapy using the ESAS and an analgesic diary. Clinic follow-up visits were conducted only if necessary. RESULTS: Between January 1999 and December 2001, 830 patients received palliative radiotherapy. Of these patients, 260 (31.3%) died during the 12-week follow-up period. The percentage of surviving patients responding to the telephone interview ranged from 48.2% (week 12) to 56.6% (week 4) during the 12-week study. CONCLUSION: Telephone follow-up is a feasible tool for prospective outcome assessment of symptom palliation in metastatic cancer patients. Telephone follow-up is recommended for outcome assessment of symptom relief when it can achieve the same purpose as clinic follow-up. Data collection remains a challenge in the palliative patient population. Further studies are required to determine how well other methods of maximizing data collection, such as through the use of caregivers, can provide reliable and accurate information.
PURPOSE: Radiation oncologists and hospice professionals both provide end-of-life care for oncology patients, and little has been written about the interface between these two groups of specialists. Hospice professionals were surveyed to assess the perceived need for palliative radiotherapy in the hospice setting, to investigate factors that limit the access of hospice patients to radiotherapy, and to suggest areas of future collaboration on education, research, and patient advocacy. PATIENTS AND METHODS: Members of the National Hospice and Palliative Care Organization (NHPCO) and American Society for Therapeutic Radiology and Oncology jointly authored a questionnaire to investigate the beliefs of hospice professionals toward the use of radiotherapy for oncology patients in hospice. The questionnaire was distributed to all NHPCO member institutions, and the results were compiled and statistically analyzed. RESULTS: Four hundred eighty of more than 1,800 surveyed facilities responded to the questionnaire. The findings suggest that the majority of hospice professionals feel that radiotherapy is important in palliative oncology and that radiotherapy is widely available in the United States. Yet less than 3% on average of hospice patients served by hospices responding to the survey actually received radiotherapy in 2002. The most common barriers to radiotherapy in hospice care include radiotherapy expense, transportation difficulties, short life expectancy, and educational deficiencies between the specialties. CONCLUSION: Multiple barriers act to limit the use of palliative radiotherapy in hospice care. Finding ways to surmount these obstacles will provide opportunity for improvement in the end-of-life care of cancer patients.
PURPOSE: Recent studies have reported improved survival with concurrent chemoradiotherapy (ChRT) for inoperable non-small-cell lung cancer (NSCLC). ChRT includes the delivery of low-dose chemotherapy given daily during radiotherapy (RT) or higher doses administered weekly. It remains unknown whether a difference in efficacy or toxicity exists between these approaches. A systematic review was performed to compare the efficacy and toxicity of weekly vs. daily ChRT. METHODS AND MATERIALS: The results from randomized studies comparing ChRT to RT for NSCLC were pooled using meta-analyses. The relative risk (RR) of death at 1, 2, and 3 years and of acute esophagitis, pneumonitis, or neutropenia (World Health Organization Grade 3 or greater) were determined. RESULTS: Ten studies involving 1802 patients were included. No significant difference in mortality or toxicity was observed between the weekly and daily regimens: RR of death at 2 years-weekly 0.93, 95% confidence interval [CI] 0.87-0.99; daily 0.92, 95% CI 0.85-1.00; RR of death at 3 years-weekly 0.93, 95% CI 0.89-0.98; daily 0.90, 95% CI 0.81-1.01; RR of esophagitis-weekly 2.07, 95% CI 0.96-4.46; daily 1.70, 95% CI 1.17-2.48; RR of pneumonitis-weekly 1.52, 95% CI 0.93-2.48; daily 1.17, 95% CI 0.65-2.09; and RR of neutropenia-weekly 8.57, 95% CI 3.75-19.58; daily 11.93, 95% CI 1.55-92.12. CONCLUSION: No statistically significant difference in efficacy or acute toxicity was observed to suggest the superiority of daily vs. weekly ChRT regimens for NSCLC.