Predictive model for survival in patients having repeat radiation treatment for painful bone metastases.
*Models; Aged; Bone metastases; Bone Neoplasms/*mortality/*radiotherapy/secondary; Dose Fractionation; Female; Humans; Male; Middle Aged; Predictive model; Predictive Value of Tests; Proportional Hazards Models; Radiation; Randomized Controlled Trials as Topic/methods; Re-irradiation; Statistical; Survival; Survival Analysis; Survival Rate
PURPOSE: To establish a survival prediction model in the setting of a randomized trial of re-irradiation for painful bone metastases. METHODS: Data were randomly divided into training and testing sets with an approximately 3:2 ratio. Baseline factors of gender, primary cancer site, KPS, worst-pain score and age were included with backward variable selection to derive a model using the training set. A partial score was assigned by dividing the value of each statistically significant regression coefficient by the smallest statistically significant regression coefficient. The survival prediction score (SPS) was obtained by adding together partial scores for the variables that were statistically significant. Three risk groups were modelled. RESULTS: The training set included 460 patients and the testing set 351 patients. Only KPS and primary cancer site reached the 5%-significance level. Summing up the partial scores assigned to KPS (90-100, 0; 70-80, 1; 50-60, 2) and primary cancer site (breast, 0; prostate, 1.3; other, 2.6; lung, 3) totalled the SPS. The 1/3 and 2/3 percentiles of the SPS were 2 and 3.6. For the testing set, the median survival of the 3 groups was not reached, 11.3 (95% C.I. 8.5 - not reached) and 5.2 months (95% C.I. 3.7-6.5). The 3, 6 and 12 month survival rates for the worst group were 64.4% (95% C.I. 55.3-72.1%), 43.0% (95% C.I. 34.0-51.8%) and 19.7% (95% C.I. 12.4-28.1%) respectively, similar to that in the training set. CONCLUSION: This survival prediction model will assist in choosing dose fractionation. We recommend a single 8 Gy in the worst group identified.
Chow Edward; Ding Keyue; Parulekar Wendy R; Wong Rebecca K S; van der Linden Yvette M; Roos Daniel; Hartsell William F; Hoskin Peter; Wu Jackson S Y; Nabid Abdenour; Leer Jan Willem; Vonk Ernest; Babington Scott; Demas William F; Wilson Carolyn F; Brundage Michael; Zhu Liting; Meyer Ralph M
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
2016
2016-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.radonc.2015.10.018" target="_blank" rel="noreferrer noopener">10.1016/j.radonc.2015.10.018</a>
Revisiting classification of pain from bone metastases as mild, moderate, or severe based on correlation with function and quality of life.
*Quality of Life; *Severity of Illness Index; 80 and over; 80 and Over; Adolescence; Adolescent; Adult; Aged; Bone metastases; Bone Neoplasms; Bone Neoplasms – Complications; Bone Neoplasms/*complications/secondary; Brief Pain Inventory; Female; Functional interference; Funding Source; Human; Humans; Male; Middle Age; Middle Aged; Pain – Classification; Pain – Etiology; Pain Measurement – Methods; Pain Measurement/*methods; Pain severity; Pain/*classification/etiology; Quality of life; Quality of Life; Questionnaires; Re-irradiation; Severity of Illness Indices; Survival; Young Adult
PURPOSE: The objective of our study was to determine the optimal cut points for classification of pain scores as mild, moderate, and severe based on interference with function and quality of life (QOL). METHODS: We evaluated 822 patients who completed the Brief Pain Inventory (BPI) and/or the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 30 (QLQ-C30) prior to receiving repeat radiation therapy for previously irradiated painful bone metastases. Optimal cut points for mild, moderate, and severe pain were determined by the MANOVA that yielded the largest F ratio for the between category effect on the seven interference items of BPI and the six functional domains of QOL (physical, role, emotional, cognitive, social functioning, and global QOL) as indicated by Pillai's Trace, Wilk's lambda, and Hostelling's Trace F statistics. RESULTS: For BPI and for QOL domains separately, the two largest F ratios for Wilk's lambda, Pillai's Trace, and Hotelling's Trace F statistics were from the cut points 4, 8 and 6, 8. When combining both, the optimal cut points were 4, 8 with 1-4 (mild), 5-8 (moderate), and 9-10 (severe). With this classification, the mean scores of all the seven interference items in BPI and the six functional domains were all highly statistically different. Patients with severe pain survived significantly shorter than those with mild and moderate pain (p \textless 0.0001). CONCLUSION: Our analysis supports the classification of pain scores as follows: 1-4 as mild pain, 5-8 as moderate pain, and 9-10 as severe pain. This may facilitate conduct of future clinical trials.
Chow Edward; Ding Keyue; Parulekar Wendy R; Wong Rebecca K S; van der Linden Yvette M; Roos Daniel; Hartsell William F; Hoskin Peter; Wu Jackson S Y; Nabid Abdenour; Ong Francisca; van Tienhoven Geertjan; Babington Scott; Demas William F; Wilson Carolyn F; Brundage Michael; Zhu Liting; Meyer Ralph M
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
2016
2016-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00520-015-2957-5" target="_blank" rel="noreferrer noopener">10.1007/s00520-015-2957-5</a>
Impact of reirradiation of painful osseous metastases on quality of life and function: a secondary analysis of the NCIC CTG SC.20 randomized trial.
*Quality of Life; 80 and over; Adult; Aged; Bone Neoplasms/complications/psychology/*radiotherapy/*secondary; Dose Fractionation; Emotions; Female; Health Status; Humans; Male; Mental Health; Middle Aged; Pain Measurement; Pain/diagnosis/etiology/*prevention & control/psychology; Radiation; Retreatment; Surveys and Questionnaires; Time Factors; Treatment Outcome; Young Adult
PURPOSE: We previously demonstrated that 48% of patients with pain at sites of previously irradiated bone metastases benefit from reirradiation. It is unknown whether alleviating pain also improves patient perception of quality of life (QOL). PATIENTS AND METHODS: We used the database of a randomized trial comparing radiation treatment dose fractionation schedules to evaluate whether response, determined using the International Consensus Endpoint (ICE) and Brief Pain Inventory pain score (BPI-PS), is associated with patient perception of benefit, as measured using the European Organisation for Resesarch and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and functional interference scale of the BPI (BPI-FI). Evaluable patients completed baseline and
Chow Edward; Meyer Ralph M; Chen Bingshu E; van der Linden Yvette M; Roos Daniel; Hartsell William F; Hoskin Peter; Wu Jackson S Y; Nabid Abdenour; Tissing-Tan Caroline J A; Oei Bing; Babington Scott; Demas William F; Wilson Carolyn F; Wong Rebecca K S; Brundage Michael
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
2014
2014-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1200/JCO.2014.57.6264" target="_blank" rel="noreferrer noopener">10.1200/JCO.2014.57.6264</a>
Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial.
*Dose Fractionation; *Radiotherapy; Aged; Analgesics – Therapeutic Use; Analgesics/therapeutic use; Australia; Bone Neoplasms; Bone Neoplasms – Complications; Bone Neoplasms – Radiotherapy; Bone Neoplasms/complications/*radiotherapy/*secondary; Brief Pain Inventory; Canada; Cauda Equina; Chi Square Test; Chi-Square Distribution; Clinical Assessment Tools; Clinical Trials; Computer-Assisted; Computer-Assisted – Adverse Effects; Computer-Assisted/adverse effects; Europe; Female; Fractures; Funding Source; Human; Humans; Intention to Treat Analysis; Israel; Logistic Models; Logistic Regression; Male; Middle Age; Middle Aged; New Zealand; Odds Ratio; Pain – Diagnosis; Pain – Drug Therapy; Pain – Etiology; Pain – Radiotherapy; Pain Measurement; Pain/diagnosis/drug therapy/*etiology/*radiotherapy; Questionnaires; Radiation; Radiation Dosage; Radiotherapy; Radiotherapy Planning; Risk Factors; Scales; Spinal Cord Compression – Etiology; Spinal Cord Compression/etiology; Spontaneous – Etiology; Spontaneous/etiology; Surveys and Questionnaires; Time Factors; Treatment Outcome; Treatment Outcomes
BACKGROUND: Although repeat radiation treatment has been shown to palliate pain in patients with bone metastases from multiple primary origin sites, data for the best possible dose fractionation schedules are lacking. We aimed to assess two dose fractionation schedules in patients with painful bone metastases needing repeat radiation therapy. METHODS: We did a multicentre, non-blinded, randomised, controlled trial in nine countries worldwide. We enrolled patients 18 years or older who had radiologically confirmed, painful (ie, pain measured as \textgreater/=2 points using the Brief Pain Inventory) bone metastases, had received previous radiation therapy, and were taking a stable dose and schedule of pain-relieving drugs (if prescribed). Patients were randomly assigned (1:1) to receive either 8 Gy in a single fraction or 20 Gy in multiple fractions by a central computer-generated allocation sequence using dynamic minimisation to conceal assignment, stratified by previous radiation fraction schedule, response to initial radiation, and treatment centre. Patients, caregivers, and investigators were not masked to treatment allocation. The primary endpoint was overall pain response at 2 months, which was defined as the sum of complete and partial pain responses to treatment, assessed using both Brief Pain Inventory scores and changes in analgesic consumption. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00080912. FINDINGS: Between Jan 7, 2004, and May 24, 2012, we randomly assigned 425 patients to each treatment group. 19 (4%) patients in the 8 Gy group and 12 (3%) in the 20 Gy group were found to be ineligible after randomisation, and 140 (33%) and 132 (31%) patients, respectively, were not assessable at 2 months and were counted as missing data in the intention-to-treat analysis. In the intention-to-treat population, 118 (28%) patients allocated to 8 Gy treatment and 135 (32%) allocated to 20 Gy treatment had an overall pain response to treatment (p=0.21; response difference of 4.00% [upper limit of the 95% CI 9.2, less than the prespecified non-inferiority margin of 10%]). In the per-protocol population, 116 (45%) of 258 patients and 134 (51%) of 263 patients, respectively, had an overall pain response to treatment (p=0.17; response difference 6.00% [upper limit of the 95% CI 13.2, greater than the prespecified non-inferiority margin of 10%]). The most frequently reported acute radiation-related toxicities at 14 days were lack of appetite (201 [56%] of 358 assessable patients who received 8 Gy vs 229 [66%] of 349 assessable patients who received 20 Gy; p=0.011) and diarrhoea (81 [23%] of 357 vs 108 [31%] of 349; p=0.018). Pathological fractures occurred in 30 (7%) of 425 patients assigned to 8 Gy and 20 (5%) of 425 assigned to 20 Gy (odds ratio [OR] 1.54, 95% CI 0.85-2.75; p=0.15), and spinal cord or cauda equina compressions were reported in seven (2%) of 425 versus two (\textless1%) of 425, respectively (OR 3.54, 95% CI 0.73-17.15; p=0.094). INTERPRETATION: In patients with painful bone metastases requiring repeat radiation therapy, treatment with 8 Gy in a single fraction seems to be non-inferior and less toxic than 20 Gy in multiple fractions; however, as findings were not robust in a per-protocol analysis, trade-offs between efficacy and toxicity might exist. FUNDING: Canadian Cancer Society Research Institute, US National Cancer Institute, Cancer Council Australia, Royal Adelaide Hospital, Dutch Cancer Society, and Assistance Publique-Hopitaux de Paris.
Chow Edward; van der Linden Yvette M; Roos Daniel; Hartsell William F; Hoskin Peter; Wu Jackson S Y; Brundage Michael D; Nabid Abdenour; Tissing-Tan Caroline J A; Oei Bing; Babington Scott; Demas William F; Wilson Carolyn F; Meyer Ralph M; Chen Bingshu E; Wong Rebecca K S
The Lancet. Oncology
2014
2014-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/S1470-2045(13)70556-4" target="_blank" rel="noreferrer noopener">10.1016/S1470-2045(13)70556-4</a>
Gender and age make no difference in the re-irradiation of painful bone metastases: A secondary analysis of the NCIC CTG SC.20 randomized trial.
*Age; *Bone metastases; *Gender; *Pain response; *Quality of life; *Radiotherapy; *Re-irradiation; Age Factors; Aged; Bone Neoplasms/physiopathology/*radiotherapy/*secondary; Cancer Pain/etiology/*radiotherapy; Female; Humans; Male; Middle Aged; Pain Measurement; Palliative Care/methods/statistics & numerical data; Patient Reported Outcome Measures; Physicians'/*statistics & numerical data; Practice Patterns; Quality of Life; Re-Irradiation; Sex Factors
BACKGROUND AND PURPOSE: Patient's gender and age may influence physicians in prescribing palliative radiotherapy. The purpose of this secondary analysis of the National Cancer Institute of Canada Clinical Trials Group Symptom Control Trial SC.20 was to explore the gender and age differences in pain and patient reported outcomes in cancer patients with bone metastases undergoing re-irradiation. MATERIALS AND METHODS: Response to radiation was evaluated using the International Bone Metastases Consensus Endpoint Definitions. Patients completed the Brief Pain Inventory (BPI) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (C30) before and 2months after re-irradiation. RESULTS: A total of 847 patients were analyzed. At baseline, men had more dyspnea, and mild pain. Older patients consumed less analgesic. More women reported clinically significant improvement in mood and enjoyment of life in the BPI after radiation. Similarly, younger patients reported better improvement in enjoyment of life. There were no significant gender or age differences in overall survival, response to radiation, or in C30 scores at 2months. CONCLUSION: Similar benefit in terms of pain relief was observed across all patient groups. Cancer patients with bone metastases should be offered palliative re-irradiation irrespective of gender or age. TRIAL REGISTRATION: NCT00080912; https://clinicaltrials.gov/ct2/show/NCT00080912.
Chow Ronald; Ding Keyue; Ganesh Vithusha; Meyer Ralph M; van der Linden Yvette M; Roos Daniel; Hartsell William F; Hoskin Peter; Wu Jackson S Y; Nabid Abdenour; van Acht Manouk; Wanders Rinus; Babington Scott; Demas William F; Wilson Carolyn F; Wong Rebecca K S; Brundage Michael; Zhu Liting; Chow Edward
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
2018
2018-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.radonc.2017.10.006" target="_blank" rel="noreferrer noopener">10.1016/j.radonc.2017.10.006</a>
Minimal clinically important differences in the EORTC QLQ-C30 and brief pain inventory in patients undergoing re-irradiation for painful bone metastases.
*Bone metastases; *Brief pain inventory; *EORTC QLQ-C30; *Minimal Clinically Important Difference; *Minimal clinically important differences; *Radiation; 80 and over; 80 and Over; Adolescence; Adolescent; Adult; Aged; Bone Metastases – Radiotherapy; BONE metastasis; BONE metastasis – Treatment; Bone Neoplasms/*complications/radiotherapy/secondary; Brief Pain Inventory; BRIEF Pain Inventory; Cancer Patients; CANCER patients; CANCER radiotherapy; Clinical Assessment Tools; Female; Funding Source; Human; Humans; Instrument Scaling; LONGITUDINAL method; Male; Middle Age; Middle Aged; Pain Management; PAIN management; Pain/*diagnosis; Prospective Studies; Quality of Life/*psychology; Questionnaires; QUESTIONNAIRES; RANDOMIZED controlled trials; Re-Irradiation/*adverse effects; REOPERATION; Repeat Procedures; RESEARCH funding; SCALING (Social sciences); Secondary Analysis; SECONDARY analysis; Surveys and Questionnaires; Young Adult
PURPOSE: The EORTC QLQ-C30 and the Brief Pain Inventory (BPI) are validated tools for measuring quality of life (QOL) and the impact of pain in patients with advanced cancer. Interpretation of these instrument scores can be challenging and it is difficult to know what numerical changes translate to clinically significant impact in patients' lives. To address this issue, our study sought to establish the minimal clinically important differences (MCID) for these two instruments in a prospective cohort of patients with advanced cancer and painful bone metastases. METHODS: Both anchor-based and distribution-based methods were used to estimate the MCID scores from patients enrolled in a randomized phase III trial evaluating two different re-irradiation treatment schedules. For the anchor-based method, the global QOL item from the QLQ-C30 was chosen as the anchor. Spearman correlation coefficients were calculated for all items and only those items with moderate or better correlation (\textbarr\textbar \textgreater/= 0.30) with the anchor were used for subsequent analysis. A 10-point difference in the global QOL score was used to classify improvement and deterioration, and the MCID scores were calculated for each of these categories. These results were compared with scores obtained by the distribution-method, which estimates the MCID purely from the statistical characteristics of the sample population. RESULTS: A total of 375 patients were included in this study with documented pain responses and completed QOL questionnaires at 2 months. 9/14 items in the QLQ-C30 and 6/10 items in the BPI were found to have moderate or better correlation with the anchor. For deterioration, statistically significant MCID scores were found in all items of the QLQ-C30 and BPI. For improvement, statistically significant MCID scores were found in 7/9 items of the QLQ-C30 and 2/6 items of the BPI. The MCID scores for deterioration were uniformly higher than the MCIDs for improvement. Using the distribution-based method, there was good agreement between the 0.5 standard deviation (SD) values and anchor-based scores for deterioration. For improvement, there was less agreement and the anchor-based scores were lower than the 0.5 SD values obtained from the distribution-based method. CONCLUSION: We present MCID scores for the QLQ-C30 and BPI instruments obtained from a large cohort of patients with advanced cancer undergoing re-irradiation for painful bone metastases. The results from this study were compared to other similar studies which showed larger MCID scores for improvement compared to deterioration. We hypothesize that disease trajectory and patient expectations are important factors in understanding the contrasting results. The results of this study can guide clinicians and researchers in the interpretation of these instruments.
Raman Srinivas; Ding Keyue; Chow Edward; Meyer Ralph M; van der Linden Yvette M; Roos Daniel; Hartsell William F; Hoskin Peter; Wu Jackson S Y; Nabid Abdenour; Haas Rick; Wiggenraad Ruud; Babington Scott; Demas William F; Wilson Carolyn F; Wong Rebecca K S; Zhu Liting; Brundage Michael
Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation
2018
2018-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s11136-017-1745-8" target="_blank" rel="noreferrer noopener">10.1007/s11136-017-1745-8</a>