Σάββατο, 18 Φεβρουαρίου 2017

RT FOR BONE METASTASES

A single dose of radiation significantly reduces pain and improves quality of life (QOL) in the short and medium term in a significant proportion of patients with painful bone metastases from a variety of cancers, a secondary analysis of a Canadian study indicates.
"In the US, you see more multiple-fraction treatments being prescribed compared with a single-fraction treatment, but we found that a single treatment provides good pain relief and QOL improvements for many patients so the study provides an argument that you really only need one treatment to get good results," lead author, Rachel McDonald MD(C), a medical student at the Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, told Medscape Medical News.
"And we were also able to pick up these improvements by day 10 so this is one of the novel things about our study — we were able to identify good results at a really early time point," she added.
"Palliative care is very important throughout the disease trajectory, so treatment shouldn't just be working towards prolonging survival; it should also be working towards improving QOL no matter how long a patient has left," McDonald commented.
"And since radiation treatment clearly improves QOL, it can be offered at any point during the disease trajectory but especially when there are no other treatment options," she added.
The study was published online February 9 in JAMA Oncology.
In an accompanying editorial, Charles Thomas Jr, MD, Oregon Health Sciences University, Portland, suggested that the current study is a "step forward" from previous work because of the uniformity of the single 8-Gy dose that all patients received.
Two weeks after receiving that single dose of radiation, up to two fifths of patients may experience pain relief, which may portend improved QOL in patients, Dr Thomas notes.
"Early pain relief may be a surrogate de facto marker of future short-term improved QOL," he writes.
"In fact, the current trial may be immediately beneficial to patients with advanced disease and their respective caregivers and health care practitioners," he adds.
Secondary Analysis 
The new findings come from a secondary analysis of data collected during the National Cancer Institute of Canada (NCIC) Clinical Trials Group Symptom Control trial SC.23 (NCIC-CTG-SC.23). This trial was primarily designed to evaluate whether a single oral dose of dexamethasone (multiple brands) taken an hour before palliative radiotherapy followed by four additional doses over the next 4 days would decrease the risk for painful flares as well as the severity of those flares in patients with painful bone metastases.
As previously reported by Medscape Medical News, the 5-day course of dexamethasone, starting on the same day on which patients received a single dose of radiation, resulted in less frequent and less severe pain compared with placebo control.
In the current study, the authors evaluated the effect of a single 8-Gy radiation dose delivered to 298 patients with one or two bone metastases and a worst pain score of at least 2 on a scale of 0 to 10.
"Patients reported their worst pain score and daily opioid analgesic intake at baseline, days 1 to 10 after treatment, and day 42 after treatment," investigators report.
Several recent and highly validated tools were used to measure QOL, including the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 15 Palliative (QLQ-C15-PAL) and the EORTC Quality of Life Questionnaire Bone Metastases Module (QLQ-BM22).At day 10, almost 41% of the cohort had responded well to the single fraction of radiotherapy; 37 patients achieved a complete response (CR) and 85 others achieved a partial response (PR).
At day 42, almost 39% had responded to radiotherapy, with 61 patients achieving a CR and 55 others achieving a PR, the study authors report. (The group of patients who responded at day 10 were not necessarily the same patients who responded at day 42, although investigators expected that most of them were the same.)
Approximately three quarters of the cohort had complete QOL data at day 10, while about 63% had complete QOL data at day 42.
At day 42, 46% of the cohort with evaluable QOL data reported a worse pain score of 7 to 10. In this same cohort, 54.5% responded to the single 8-Gy dose of radiation with a noticeable reduction in pain.
Interestingly, QOL scores did not significantly differ between patients who responded to radiation at day 42 and those who did not, although patients with primary prostate cancer were considerably more likely than others to respond to radiotherapy, the researchers note.
Responders Had Less Pain, Better Function 
Among those who reported less pain at day 10 after the single dose of radiation, responders had better physical function, less pain, and an improvement in constipation compared with nonresponders.
Responders also reported fewer painful metastatic sites, better pain characteristics, and less interference with function compared with nonresponders, the investigators add.
"The greatest difference observed was in the pain item of the QLQ-C15-PAL, where responder-reported scores were a mean of 17.1 points lower than scores reported by nonresponders (P < .001)," the researchers observe.
Table. Changes in QOL Measures From Baseline to Day 10 in Responders vs Nonresponders 
VariableRespondersNonrespondersP Value
Mean reduction in pain (mean score)17.01.8.002
Mean reduction in pain characteristics12.81.1.002
Mean improvement in functional interference11.63.6.01
Mean change in psychosocial aspects1.2–2.2.04

Again at day 42, "[r]esponders reported better QOL scores in every item of the QLQ-C15-PAL except for dyspnea...and insomnia," the investigators continued. In addition, in all domains of the QLQ-C15-PAL (physical, emotional, and global), mean scores reported by responders "were at least 10 points greater than those reported by nonresponders, representing significant differences," they add.
As was true for responders vs nonresponders at day 10, the biggest differences at day 42 between those who responded to the 8-Gy dose of radiation was in pain scores, which were significantly higher (P < .001) for responders than nonresponders, as were all domains of the QLQ-BM22, with the exception of psychosocial aspects.
Responders also had significantly greater improvements in the physical, emotional, and global domains of the QLQ-C15-PAL compared with their nonresponding counterparts (P < .001 for all comparisons).
Reductions in both pain and fatigue and improvements in appetite and constipation on the QLQ-C15-PAL score again at day 42 were all significantly better in responders than nonresponders, as were improvements in painful metastatic sites, pain characteristics, psychosocial aspects, and less interference in function, the authors note.
The authors and Dr. Thomas have disclosed no relevant financial relationships.
JAMA Oncol. Published online February 9, 2017. AbstractEditorial

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