Lori Holden

Quality of life in surgical treatment of metastatic spine disease

Study Design. Overall quality of life after surgical management of metastatic disease of the spine was prospectively assessed using a validated global health status quality-of-life instrument—the Edmonton Symptom Assessment Scale. Objectives. To prospectively evaluate the efficacy of surgery in patients with metastatic spinal disease with respect to quality of life. Summary of Background Data. Management of spinal metastases is palliative and is aimed at improving quality of life at an acceptable risk. Although previous studies have evaluated physical outcomes, improvements in pain, and neurologic function after surgery, a multidimensional assessment of quality of life is more relevant in the palliative patient. Methods. Twenty-five consecutive patients undergoing surgery for spinal metastases were prospectively evaluated. Pre- and postoperative assessments were performed using the Edmonton Symptom Assessment Scale. The surgical procedure consisted of decompression and instrumented stabilization. Results. After surgery, the largest improvement was noted in the domain of pain (P < 0.00001). There were also significant improvements noted in the domains of tiredness (P = 0.004), nausea (P = 0.01), anxiety (P = 0.006), drowsiness (P = 0.044), appetite (P = 0.02), and well-being (P = 0.004). Conclusions. The current study demonstrates that in the appropriate patient, surgical management brings about a positive effect on the overall quality of life in patients with spinal metastases. The greatest benefit occurred in the reduction of a patient’s level of pain.

Phase I/II Study of a Five-fraction Hypofractionated Accelerated Radiotherapy Treatment for Low-risk Localised Prostate Cancer: Early Results of pHART3

AIMS Most men with low-risk localised prostate cancer prefer treatments with high control rates and minimal disruption to their lives. Hypofractionating external radiation treatments can theoretically maintain high bioequivalent tumour doses, decrease treatment visits and decrease acute and late toxicities. The aim of this study was to assess the toxicity and feasibility of a hypofractionated accelerated regimen for these patients. MATERIALS AND METHODS The present study was a phase I/II study in which patients with T1-2b, Gleason < or = 6 and prostate-specific antigen (PSA) < or = 10 ng/ml prostate cancer received 35Gy in five fractions, once a week over 29 days. Treatment was delivered with intensity-modulated radiotherapy on standard linear accelerators, with daily image guidance using gold seed fiducials, and a 4mm clinical target volume to planning target volume margin. RESULTS As of January 2008, the target accrual of 30 patients had been reached and all had completed treatment and at least 6 months of follow-up. Dose-volume histogram objectives were achievable in all patients. Treatment was very well tolerated with no grade 3 or 4 genitourinary toxicity, gastrointestinal toxicity nor fatigue observed (95% confidence interval 0-12%). As a group, compared with baseline, the following additional grade 2 toxicities were observed: 13% genitourinary, 7% gastrointestinal and 10% fatigue. At 6 months all scores had returned to or improved over baseline. The median PSA before treatment was 6.0 ng/ml. At 6 months, the median PSA was 1.8 ng/ml and 75% had a PSA < or = 3.0 ng/ml. CONCLUSIONS This novel technique using standard linear accelerators seems feasible and is well tolerated. Further follow-up will be carried out to document late toxicity and efficacy.

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

AIMS To 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. MATERIALS AND METHODS Patients 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. RESULTS One 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. CONCLUSION Conventional 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.

EORTC QLQ-C15-PAL quality of life scores in patients with advanced cancer referred for palliative radiotherapy

PurposeSymptom control and improved quality of life (QOL) are primary goals of treatment in palliative oncology. The present study assessed and compared patient demographics, baseline Karnofsky Performance Status (KPS) and QOL using the QLQ-C15-PAL questionnaire prior to palliative radiotherapy (RT) for bone, brain, or lung disease. Few studies have used this questionnaire, an abbreviated version that was developed by the European Organization for Research and Treatment of Cancer specifically for patients with advanced cancer to decrease the burden of completing the longer, more time-consuming QLQ-C30.MethodsPatients referred to an outpatient palliative RT clinic completed QLQ-C15-PAL questionnaires prior to palliative RT for bone, brain, or lung cancer sites. The associations between baseline QLQ-C15-PAL functional/symptom scales, patient demographics, and clinical variables including KPS were explored.ResultsWhen data from all 369 patients were analyzed, higher KPS scores correlated significantly with better overall QOL and higher physical and emotional functioning. The QLQ-C15-PAL provided more detailed information regarding how symptom burden varied depending on disease site. Patients with bone metastases had worse QLQ-C15-PAL scores for pain, while those with brain and lung disease had worse scores for fatigue. Other health-related QOL scores measured by the QLQ-C15-PAL varied as a function of age and gender.ConclusionAs the QLQ-C15-PAL provides detailed and often critical information regarding symptom burden, it may eventually be recognized as a universal core questionnaire to assess QOL in this patient population with advanced cancer while relieving the survey burden.

Prospective patient-based assessment of effectiveness of palliative radiotherapy for bone metastases.

PURPOSE The primary objective of this report is to prospectively evaluate pain control provided by palliative radiotherapy for all irradiated patients with bone metastases by using their own assessments. MATERIALS AND METHODS A prospective database was set up for all patients referred for palliative radiotherapy for bone metastases. Patients were asked to rate their pain intensity using an 11 categorical point scale (0=lack of pain, 10=worst pain imaginable). Analgesic consumption during the preceding 24 h was recorded and converted into equivalent total daily dose of oral morphine. For those who received radiotherapy, follow-up was conducted via telephone interviews at week 1, 2, 4, 8 and 12 post treatment using the same pain scale and analgesic diary. Radiotherapy outcome was initially assessed by pain score alone. Complete response (CR) was defined as a pain score of 0. Partial response (PR) was defined as a reduction of score > or =2 or a> or =50% reduction of the pre-treatment pain score. We further analyzed outcomes using integrated pain and analgesic scores. Response was defined as either a reduction of pain score > or =2 with at least no increase in analgesics or at least stable pain score with a > or =50% reduction in analgesic intake. RESULTS One hundred and five patients were treated with palliative radiotherapy. When response evaluation was by pain score alone, the PR rates at 2, 4, 8 and 12 weeks were 44, 42, 30 and 38%, respectively; while the CR rates were 24, 32, 31 and 29%, respectively. The overall response rate at 12 weeks was 67%. When assessed by the integrated pain and analgesic scores, the response rates were 50, 46, 43 and 43%, respectively. CONCLUSION The response rate in our patient population is comparable with those reported in clinical trials. This is important when counselling our patients on the expected effectiveness of radiotherapy outside of clinical trials. Our observations confirm the generalizability of the trials conducted to date. While randomized trials still remain the gold standard of research, observational studies can serve as useful adjuncts to randomized trials to confirm the efficacy and guide the design of new controlled trials.

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

PURPOSE The 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. METHODS AND MATERIALS Patients 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. RESULTS Among 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. CONCLUSION After 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.

Prospective Assessment of Symptom Palliation for Patients Attending a Rapid Response Radiotherapy Program: Feasibility of Telephone Follow-Up

Clinical trials generally include motivated patients with relatively good performance status. This can result in an overestimation of the effectiveness of an intervention. Clinic follow-up protocols for outcome assessment after palliative treatments suffer from high attrition rates. In this study, the feasibility of telephone follow-up for the assessment of symptom palliation in patients receiving outpatient palliative radiotherapy as a tool to evaluate outcome was examined. Patients referred for palliative radiotherapy were asked to rate their symptom distress using the modified Edmonton Symptom Assessment System (ESAS) at initial consultation. Patient demographics and analgesic consumption were collected. For those who received radiotherapy, follow-up was conducted through telephone interviews at week 1, 2, 4, 8, and 12 post-treatment using the same modified ESAS and analgesic diary. One hundred ninety patients received radiotherapy to 256 sites from January to August 1999. Seventy-eight patients (41%) died during the 12-week follow-up period. The percentage of surviving patients responding to the telephone interview ranged from 63% to 68% during the 12-week study. Telephone follow-up is a feasible tool for the prospective outcome assessment of symptom palliation in this population. It compares well to clinic visits or mailed questionnaires. However, to improve the follow-up rates, other modalities may also need to be implemented.

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.

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

AIMS To determine the efficacy of radiotherapy for the palliation of pain from bone metastases among patients in their last 3 months of life. MATERIALS AND METHODS Mutually 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. RESULTS From 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. CONCLUSIONS Despite 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.

Intra-fraction motion during extreme hypofractionated radiotherapy of the prostate using pre- and post-treatment imaging.

AIMS To determine intra-fraction displacement of the prostate during extreme hypofractionated radiotherapy using pre- and post-treatment orthogonal images with three implanted gold seed fiducial markers. MATERIALS AND METHODS In total, 265 image pairs were obtained from 53 patients who underwent extreme hypofractionated radiotherapy to a dose of 35 Gy in five fractions on standard linear accelerators. Position verification was obtained with orthogonal X-rays before and after treatment and were used to determine intra-fraction prostate displacement. RESULTS The mean intra-fraction prostate displacements were -0.03 ± 0.61 mm (one standard deviation), 0.21 ± 1.50 mm and -0.86 ± 1.73 mm in the left-right, superior-inferior and anterior-posterior directions, respectively. The mean intra-fraction displacement during the first two fractions was moderately correlated with the displacement in the remaining three fractions, with correlation coefficients of 0.63 (95% confidence interval 0.43-0.77) and 0.47 (95% confidence interval 0.22-0.65) in the superior-inferior and anterior-posterior directions, respectively. There was no significant correlation in the left-right direction with a coefficient of -0.04 (95% confidence interval -0.31-0.23). CONCLUSIONS The mean intra-fraction prostate displacement during a course of extreme hypofractionated radiotherapy is small. A strategy using the first two fractions to predict future displacements >5 mm warrants further validation.