Conditions: Bone Neoplasm,Malignant Vertebral Column Thoracic Secondary
Keywords: Bone metastasis,Thoracic secondary, Cancer Pain,
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 69
Healthy volunteers: no

Brief summary:
AIM OF THE WORK To evaluate the effectiveness and safety of Pulsed and Thermal Radiofrequency lesion of the dorsal root ganglion (RF-DRG) on a consecutive group of patients presenting with chronic thoracic pain due to vertebral bone metastasis.

Detailed description:
STUDY DESIGN This is a Prospective Randomized Controlled trial that will be conducted at the National Cancer Institute. All patients who are eligible for the study will be included and randomized into 3 equal groups.

PATIENTS AND METHODS After approval from the Ethics Committee at the National Cancer Institute, Cairo University, and obtaining written informed consent, eighty-one patients with thoracic segmental pain due to metastasis, unresponsive to conventional therapy and meeting the inclusion criteria will be randomly assigned to either one of the two types of treatment, PRF or TRF lesioning of the DRG or the control group. Patients will be carefully evaluated for neurologic deficits and side effects. Assessment of pain will be done at baseline then at 1, 3, 6 months after the procedure. Randomization will be done using randomized permuted block design. Randomization list will be generated through random.org online site.

Patients will be randomly assigned and divided into 3 equal comparable groups. Before the procedure, laboratory investigations, Dorsal X-ray, CT and MRI will be done. All Patients will be interviewed and examined by physicians trained in interventional pain management. Patients will be carefully assessed on physical exam for sensory, motor, or reflex deficit and carefully documented. Patients will be informed about the technique of the blocks, and written informed consents will be obtained.

The types of measures used to assess pain relief will include single rating scales; VAS, and multiple-dimension composite measures; Oswestry Low Back Pain Disability Questionnaire (ODI), The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-BM22.

Arms:
arm 1: Patients will receive Pulsed Radiofrequency (PRF) on Dorsal root ganglion(DRG) of the selected metastatic painful dorsal vertebrae, with temperature 42°C for 480 sec.,2 active cycles per second of 20 milliseconds each , with a voltage output 40 to 60-V range, impedance ranges between 150 and 400 Ohms at all levels using Fluroscopic guidance (FG). arm 2: Patients will receive Thermal Radiofrequency (TRF) on Dorsal root ganglion(DRG) of the selected metastatic painful dorsal vertebrae, with temperature 80°C for 90 sec.,2 cycles, using Fluoroscopic guidance (FG) . arm 3: The control group will have identical needle placement and preparation like the 2 previous groups without the RF lesion, but with the injection of particulate Betamethasone steroids and local anesthetic on DRG of the selected metastatic painful dorsal vertebrae, using Fluoroscopic guidance (FG).

Interventions: intervention 1: PRF on DRG intervention 2: TRF on DRG intervention 3: Corticosteroid injection
Intervention descriptions: intervention 1: RF will be performed with the patient in a prone position with mild flexion of the spine. Fluoroscopy beam positioned in an antero-posterior direction. A 10 cm RF needle 20 G with a 10 mm active tip.The needle is inserted in a slightly medial-cephalad direction under the transverse processes, and using lateral fluoroscopic imaging, incrementally walking into the thoracic intervertebral foramen. So the location of the needle tip confirmed by sensory stimulation at 50 Hz. The point of maximum stimulation is at 0.5 V intensity and this is designated to be the location of the DRG. Slight redirection can be done to optimize the stimulation; injection of contrast reveals epidural uptake. After establishing the site for the RF, 1 ml 2% lidocaine should be injected through the needle. intervention 2: Similar to the group of " PRF on DRG", but the types of the waves will be different as previously described intervention 3: Similar to the previous groups, but without applying any type of Radio-frequency but just injecting steroids and local anesthetics as previously described

Protocol document:
Prot_SAP_000.pdf: 
1 
 
Comparison between Dorsal Root Ganglion Thermal 
Radiofrequency versus Pulsed Radiofrequency for the 
Management of Intractable Metastatic Pain in Thoracic 
Vertebral Body 
 
Trial registration on Clinical Trial.gov: Clinical Trials 
NCT03204942 on the 2nd of July 2017 
Protocol date approval by National Cancer Institute (NCI) 
Anaesthesia and Pain Management Department: 11 September 
2016 
NCI Cairo Ethics Committee approval: 14th of February 2017 
Recruitment started: 30 July 2017 
Recruitment Completed: 30 July 2018 
Document Date (the date on which the uploaded document was 
most recently updated): 31 March 2019 
 
 
 
 
 
 
 
 
 


2 
 
 
 
 
 
 
 
 
 
 
 
 
INTRODUCTION 
Metastatic disease to the bone has been a crippling devastating complication of various 
cancers, with unbearable pain 1. Knowledge surrounding the pathophysiology of painful 
osseous metastases is rapidly changing 2. Metastatic bone pain is characteristic of cancer pain 
and is a form of refractory cancer pain, as the pain includes not only nociceptive but also 
neuropathic pain that induces a peripheral and central sensitization. 
The development of medication dose-limiting side effects, limits analgesic efficacy in nearly 
42% of cancer pain patients 3. 
In recent years the use of pulsed radiofrequency (PRF) to treat chronic pain conditions has 
generated intense interest in the pain community 4. PRF is a minimally invasive, target-
selective technique that has reported benefit at reducing post-amputation stump pain, chronic 
radicular/ganglion pain , neuropathic pain , and arthropathic pain 5,6.  
In 2008, Zeldin and Ioscovich published 3 cases of  patients who suffered from uncontrolled 
vertebral/paravertebral metastatic pain and were successfully treated by fluoroscopically 


3 
 
guided selective dorsal root ganglion ( DRG)  PRF (PMG-230 Baylis Medical com. Inc. 
Canada) 7. They concluded that that PRF on selective DRG bilaterally under fluoroscopic 
guidance in patients with pain secondary to metastasis in the Thoracic vertebral body and 
who were unsuccessfully treated with opioids, may offer new opportunities for metastatic 
pain treatment and encourage future studies. 
 Another case series which was conducted by Young-Chang P. Arai et al., in 2015 has 
concluded that DRG pulsed RF procedure provided sound pain relief for patients with 
intractable vertebral metastatic pain. PRF on DRG procedure provided sound pain relief for 
patients with intractable vertebral metastatic pain 8.Studies using animal models have 
clarified the anti-nociceptive effects of  PRF on the DRG, it induces inhibition of excitatory 
c-fiber responses and a global reduction of evoked synaptic activity 9,10. Several authors have 
reported that the anti-nociceptive actions induced by PRF would be due to the enhancement 
of noradrenergic and serotonergic descending pain inhibitory pathways and the inhibition of 
excitatory c-fibers 11. It was found that the application of PRF to a DRG elicits the 
expression of c-fos in the dorsal horn 12. The importance of this finding for the clinical effect 
of PRF is still a subject of discussion. C-fos is a specific marker indicating cellular activity13.  
The alternative of modulation is clearly ablation, and in the vacuum that had persisted this 
possibility came up. The clinical effect of continuous radiofrequency treatment may 
therefore reflect a balance between analgesia produced by deafferentation-induced reduction 
in nociceptive input to the central nervous system and stimulation of pro-inflammatory,  
pro-nociceptive glial activation in the central nervous system as a consequence of 
deafferentation. Clinical experience indicates that analgesia is more commonly the result; 
however, central immune-mediated inflammation may predominate in patients who 
experience an increase in pain following the procedure 14. Thermal Radiofrequency (TRF) of 
the DRG was suggested as an alternative to ganglionectomy to destroy the primary afferents’ 
soma. There is robust literature surrounding RF strategies to treat chronic pain, including 
treatment of the DRG. TRF uses high frequency electrical current, creating ionic oscillation 
of the tissue and frictional dissipation of the ionic current, producing heat 15.  


4 
 
Three prospective controlled trials have examined TRF-DRG for treating neuropathic pain 
stemming from cervical DRG. Van Kleef et al., 1996,  Slappendel et al. , 1997 and 
Haspeslagh et al. , 2006. Van Kleef et al. performed a randomized, sham controlled, double 
blind study with cervicobrachialgia unresponsive to conventional therapy of 12 months 
duration and response to diagnostic selective nerve root blocks. In a double-blinded fashion, 
subjects were randomization to the RF group with conventional lesioning of the DRG at 
670C for 60 seconds versus no lesioning in the control group. At 8 weeks post operation, 
eight out of nine RF patients reported success, while two of 11 in the control group, defined 
as greater than 2- point reduction on the visual analog scale (VAS). This suggested short-
term success where dysthesia and hypoesthesia side effects were short lived (lasting <3 
months). 
There have been no prospective controlled trials on TRF of the thoracic DRG. Stolker et al. 
(Stolker et al., 1994) conducted a prospective uncontrolled trial using TRF of the thoracic 
DRG at 67 ºC to treat 45 patients afflicted with thoracic segmental pain. They reported that 
91% patients obtained > 50% pain relief at 2 months and that 78% continued to experience 
pain relief for 13 to 46 months. A smaller number of patients (13.3%) reported a transient 
burning pain in the corresponding dermatome that subsided within 3 weeks. In Neuropathic 
Pain their review, Malik and Benzon (Malik & Benzon, 2008) concluded that larger-scale, 
longer term, controlled clinical trials are required to clearly establish the efficacy of TRF-
DRG for different types of neuropathic pain, particularly pain originating from thoracic 
DRG16.  Although prospective observational and retrospective studies have yielded 
consistent support for DRG treatment in the cervical, thoracic, lumbar, and sacral regions , 
controlled studies are less compelling, complicated by the challenge of the lurking 
deafferentated pain potential. Further, patient selection appears to be vague in predicting 
treatment outcomes. Larger, sham-controlled, prospective studies are required to elucidate 
the place of  TRF treatment of the DRG for treatment of chronic pain.  
AIM OF THE WORK 


5 
 
To evaluate the effectiveness and safety of Pulsed and Thermal Radiofrequency lesion of the 
dorsal root ganglion (RF-DRG) on a consecutive group of patients presenting with chronic 
thoracic pain due to vertebral bone metastasis.  
 
 
 
STUDY DESIGN  
This is a Prospective Randomized Controlled trial that will be conducted at the National 
Cancer Institute. All patients who are eligible for the study will be included and randomized 
into 3 equal groups.  
 
 
 
 
 
 
 
 
PATIENTS AND METHODS 
After approval from the Ethics Committee at the National Cancer Institute, Cairo University, 
and obtaining written informed consent, eighty-one patients with thoracic segmental pain due 
to metastasis, unresponsive to conventional therapy and meeting the inclusion criteria will be 
randomly assigned to either one of the two types of treatment, PRF or TRF lesioning of the 
DRG or the control group. Patients will be carefully evaluated for neurologic deficits and 
side effects. Assessment of pain will be done at baseline then at 1, 3, 6 months after the 
procedure. Randomization will be done using randomized permuted block design. 
Randomization list will be generated through random.org online site.  
INCLUSION CRITERIA: 
1. A greater than 6-month history of segmental pain of thoracic vertebral body metastasis 
origin. 


6 
 
2. Unsatisfactory pain control with oral pharmacotherapy including strong opioid with  
VAS >5 . 
3. Absence of a chronic or progressive motor deficit. 
4. Absence of significant sensory deficit. 
5. No indication for percutaneous or open surgical intervention. 
6. Magnetic resonance imaging and Computed Tomogrophy evidence of thoracic 
involvement. 
7. ASA status of  II to III . 
8. Age > 18 . 
9. Body mass index (BMI) :less than forty and more than twenty . 
10. Informed consent 
 
 
 
 
 
EXCLUSION CRITERIA: 
1. Known sensitivity or contraindication to injected materials: local anesthetics. 
2. History of psychological disorders. 
3. Evidence of significant neurological deficit. 
4. Inability to lie prone. 
5. Local contraindication to procedure e.g. local sepsis at the site of intervention, 
coagulopathy. 
6.  Patient refusal. 
Patients will be randomly assigned and divided into 3 equal comparable groups. Before the 
procedure, laboratory investigations, Dorsal   X-ray, CT and MRI will be done. All Patients 
will be interviewed and examined by physicians trained in interventional pain management. 
Patients will be carefully assessed on physical exam for sensory, motor, or reflex deficit and 


7 
 
carefully documented. Patients will be informed about the technique of the blocks, and 
written informed consents will be obtained. 
The types of measures used to assess pain relief will include single rating scales; VAS, and 
multiple-dimension composite measures; Oswestry Low Back Pain Disability Questionnaire 
(ODI), The European Organisation for Research and Treatment of Cancer (EORTC) 
 QLQ-C30 and QLQ-BM22.  
VAS ; is commonly used to rate various subjective experiences a VAS is usually a horizontal 
line, 100 mm in length, anchored by word descriptors at each end such as "no pain" on the 
left and "severe pain" on the right, as illustrated in Fig. 1. The patient marks on the line three 
pain ratings, corresponding to current, best and worst intensity of pain experienced over the 
past 24 hours.The average of the 3 ratings will be used to represent the patient’s level of pain 
over the previous 24 hours.. The VAS score is determined by measuring in millimeters from 
the left hand end of the line to the point that the patient marks. 
 
Fig.(1) VAS, used in patients diary for guide in self-score pain. 
The VAS has consistently demonstrated sensitivity to changes in cancer pain associated with 
treatment or time ) and usually shows strong associations with other pain intensity ratings, it 
appears  adequately valid and reliable as measures of pain intensity among the many 
different samples of persons with cancer 17. 
ODI is a self-administered questionnaire divided into ten sections, each with six items 
designed to assess limitations of various activities of daily living. Each section is scored on a 
0 to 5 scale, with 5 representing the greatest disability. The index is calculated by dividing 


8 
 
the summed score by the total possible score, which is then multiplied by 100 and expressed 
as a percentage. Thus, for every question not answered, the denominator is reduced by 5. If a 
patient marked more than one statement for a question, the highest scoring statement is 
recorded as the true indication of disability. It takes 3.5 to 5 minutes to complete the 
questionnaire and approximately 1 minute to score. The scores are assessed from 0% to 20% 
to indicate minimal disability, 20% to 40%, to indicate moderate disability, 40% to 60% to 
indicate severe disability, 60% to 80% to indicate crippled, and 80% to 100% to indicate bed 
bound or exaggerating their symptoms 18.The ODI is the most commonly used disease 
specific patient reported outcome tool to measure functional disability related to back pain 19. 
When using only QOL tools as outcome measurement, the majority of cancer studies 
recommended CP ( Cut point) 1–5 as mild pain, 6 as moderate pain, and 7–10 as severe 
pain20. CPs is defined as the upper bound of a pain intensity category21 as shown in Fig. (2). 
 
Fig. (2). Cut points for Cancer Patients. 
 
EORTC has developed one of the most commonly used measurements for this purpose: the 
QLQ-C30 which is designed to capture QOL outcomes in a brief internationally recognized 
and validated tool 22. EORTC QLQ-C30 (version 3) ,contains 15 relevant items to palliative 
care from the QLQ-C30, including multi-item physical and emotional function scales, multi-
item symptom scales (fatigue and pain), single-item symptom scales (nausea/vomiting, 
appetite, dyspnea, insomnia, and constipation), and one scale pertaining to perceived overall 


9 
 
QOL. The EORTC QLQ-BM22 is a sub-module of the QLQ-C30 and is an internationally 
recognized and validated scale used to measure QOL in bone metastases patients 23. The 
QLQ-BM22, includes four subscales: painful sites, pain characteristics, functional 
interference, and psychosocial aspects. Both questionnaires use a 4-point Likert scale 
ranging from1 (not at all) to 4 (very much) to rate each item, except for the final 2 question 
of the QLQ-C30 pertaining to overall QOL which is scored from 1 (very poor) to 7 
(excellent). Each subscale is then linearly converted to a score from 0 to 100. For the QLQ-
BM22, a higher score indicates worse symptom burden for painful sites and pain 
characteristics, and better functioning for functional interference and psychosocial aspects. 
For the QLQ-30, higher scores in the emotional, physical, and QOL scales indicate 
greater functioning and better 21. 
 
VAS, ODI, QLQ-C30 and QLQ-BM22 will be used to evaluate pain, quality of life, and 
performance status before the procedure and at 3 days and 1, 3, 6 months after the 
procedure24. 
In the holding area, midazolam 0.02 mg/kg IV will be given after fixation of a 20 G cannula.  
All RF procedures will be performed in the hospital outpatient ambulatory care setting using 
local anesthesia and conscious sedation as necessary, with fluoroscopic guidance to facilitate 
needle placement. The segmental spinal levels treated will be selected based on the patients’ 
pain referral pattern as determined by history and physical examination findings. After sterile 
skin preparation, RF will be performed with the patient in the prone position with mild 
flexion of the spine and the fluoroscopy beam positioned in an antero-posterior (AP) 
direction. A 10 cm RF needle 20 G with a 10 mm active tip.  The image intensifier will be 
rotated in a cephalo-caudad direction until the endplates of the adjacent thoracic 
intervertebral discs is lined up and the transverse processes became discernable from the ribs. 
The needle is then inserted in a slightly medial-cephalad direction under the transverse 
processes, and using lateral fluoroscopic imaging, incrementally walking into the thoracic 
intervertebral foramen . The correct position of the needle's tip should be exactly in line with 
the facet joint spaces on the anteroposterior projection of the image intensifier, and in the 
posterior part of the foramen on the lateral projection. Once correct needle position is 


10 
 
confirmed by image and since neural tissue cannot be seen on plain radiographs and the 
DRG may vary with respect to its spatial relationship with the intervertebral foramen, so the 
location of the needle tip will confirmed not only by image but also by sensory stimulation at 
50 Hz. The point of maximum stimulation is where sensory response in the painful 
dermatome can be elicited with stimuli below 0.5 V  intensity and this is designated to be the 
location of the DRG. Slight  redirection can be done to optimize the stimulation; injection of 
contrast reveals  epidural uptake. After establishing the site for the RF, 1 ml 2% lidocaine 
should be injected through the needle. The needle is then connected to a RF generator 
(Baylis Medical com. Inc. Canada).   
 
 
Group 1: Patients will receive PRF with temperature 42°C for 480 sec.,2 active cycles per 
second of 20 milliseconds each , with a voltage output 40 to 60-V range, impedance ranges 
between 150 and 400 Ohms at all levels using Fluroscopic guidance (FG). The block will be 
done as that described by Young-Chang P. et al 8.  
Group 2: Patients will receive TRF with temperature 80°C for 90 sec.,2 cycles, using FG . 
The block will be done as that described by Ken-ichiro U 16. 
Group 3: The control group having  identical needle placement and preparation without the 
RF lesioning (only local anesthetic). 
  
OUTCOME AND ASSESSMENT 
Primary outcome measure: 
It will include:- 
-VAS, ODI, QLQ-C30 and QLQ-BM22 to evaluate pain, quality of life, and performance 
status at 1, 3, 6 months after the procedure. 
Secondary outcome measures: 


11 
 
It will include :-  
-Neurological defects .  
- Dysthesia and hypoesthesia. 
- Change in physical activities, and analgesic use. 
-Any other complication from either the technique as pneumothorax or local anesthetic, 
anesthesia dolorosa and burning pain. 
-Patients' satisfaction with analgesia through a phone call a week after procedure on 5-level 
likert scale, (not satisfied at all, only slightly satisfied, somewhat or partly satisfied, very 
satisfied, perfectly satisfied ) 
STATISTICS 
1 - Sample size estimation: 
 According to studies (13, 15,16) , to see a significant reduction in VAS defined as at 
least 50% reduction, ODI, QLQ-C30 and QLQ-BM22 score (P < 0.01) with a background 
standard deviation of 1.0, significance level of 0.05 and power of a test of 80%, minimum 
number of patients needed would be 25 per group. Because difference in VAS , ODI, QLQ-
C30 and QLQ-BM22 score will be more evidenced with control group, the number needed 
would be much smaller , so the total number needed in the present study  would be 69 
patients that will be randomized into 3 equal groups. For non-parametric correction, we 
increased the number to 27 patients for each group. 
2- Statistical analysis plan: 
   Data will be analyzed using SPSS version 18.0.  Numerical data will be presented as mean, 
standard deviation or median and range as appropriate. Categorical data will be presented as 
numbers and proportions. Mixed models ANOVA will be used to show effect of time on 
pain score and also to evaluate group interaction. Non-parametric tests ; Friedman's test will 
be used if data did not show normal distribution. Significance level will be considered at 
0.05.   


12 
 
 
 
 
 
 
 
 
 
REFERENCES 
 
1. Smith HS. and  Barkin RL, Painful boney metastases, American Journal of 
Therapeutics , 2014 ;21(2):106-130. 
2. Patrick W., Bone Cancer Pain: From Mechanism to Therapy,  Current opinion in 
supportive and palliative care 2014 ; 8(2): 83–90. 
3. Lauren M., Tally M. ,Todd W. , Use of Animal Models in Understanding Cancer-
induced Bone Pain,  Cancer Growth and Metastasis 2015;8(S1). 
4. Bhatia A. , Questions Regarding "Pulsed Radiofrequency for Chronic Intractable 
Lumbosacral Radicular Pain: A Six-Month Cohort Study", Pain Medicine 2016; 
17(5):989. 
5. Fujiwara S., Komasawa N., Hyoda A., Kuwamura A., Kido H., Minami T., 
Ultrasound-guided Sciatic Nerve Block (Pulsed Radiofrequency) for Intractable 
Cancer Pain Caused by Sacral Bone Metastasis, Masui. 2015 ;64(6):663-665. 
6. R. Carter W. Jones III,  Neuroinflammatory effects of Radiofrequency, European 
Journal of  Pain 2014; 18 :149-150. 
7. Zeldin A.  and Ioscovich A., Pulsed Radiofrequency for Metastatic Pain Treatment,  
Pain Physician 2008; 11:921-922 . 


13 
 
8. Young-Chang P. Arai, Makoto N., Yoshihiro Y., Maki A., Miki K., Chiharu S., 
Akiko K., Kazuyo K., and Tatsunori I., Dorsal Root Ganglion Pulsed 
Radiofrequency for the Management of Intractable Vertebral Metastatic Pain: A Case 
Series, Pain Medicine 2015; 16:1007 – 1012. 
9. Sluijter M. E. and Imani F. , Evolution and mode of action of Pulsed 
Radiofrequency, Anesthesiology and Pain Medicine 2013;2 (4):139-141.  
10. Liem, L., Van D., Eric H., Frank J. , Staats P., Kramer J., The Dorsal Root 
Ganglion as a Therapeutic Target for Chronic Pain,  Regional Anesthesia and Pain 
Medicine 2016; 41 (4):511 -519. 
11. Carter W. J., Neuroinflammatory effects of Radiofrequency, European  Journal of  
Pain 2014; 18 : 149–150. 
12. Guha D. and  Shamji MF., The Dorsal Root Ganglion in the Pathogenesis of 
Chronic Neuropathic Pain, Neurosurgery 2016 ; 63 (1):118-126. 
13. Jason E. Pope , Timothy R. Deer , Jeffery Kramer , A Systematic Review: Current 
and Future Directions of  Dorsal Root Ganglion Therapeutics to Treat Chronic Pain, 
Pain Medicine 2013; 14: 1477–1496. 
14. Stone J., and Matchett G., Combined Ultrasound and Fluoroscopic Guidance for 
Radiofrequency Ablation of the Obturator Nerve for Intractable Cancer-Associated 
Hip Pain, Pain Physician 2014; 17:E83-E87. 
15. Bale R., Ganglionic blockade , Radiologist 2015; 55(10): 886- 895. 
16. Ken-ichiro U., Cyprian C. (Ed.), Radiofrequency Treatments for Neuropathic Pain: 
Review and New Approaches, Neuropathic Pain 2012, ISBN: 978-953-51-0452-0,140 
pages. 
17. Jensen M., Wang W., Potts S., Gould E., Original Research Article Reliability and 
Validity of Individual and Composite Recall Pain Measures in Patients with Cancer, 
Pain Medicine 2012; 13: 1284–1291.  
18. Brodke DS, Goz V, Lawrence BD, Spiker WR, Neese A, Hung M., Oswestry 
disability index: a psychometric analysis with 1610 patients, Spine J. 2016; S1529-
9430(16): 30998-6. 


14 
 
19. Teles A., Khoshhal K., ABOSb , Falavigna A., Why and how should we measure 
outcomes in spine surgery, Journal of Taibah University Medical Sciences 2016); 
11(2),: 91-97. 
20. McDonald R., Ding K., Chow E., Meyer R., Nabid A., Chabot P., Coulombe G., 
Ahmed S., Kuk J., Dar R., Mahmud A., Fairchild A., Wilson  C., Wu J., Dennis 
K., DeAngelis C., Wong  R., Zhu L., Brundage M., Classification of painful bone 
metastases as mild, moderate, or severe using both EORTC QLQ-C15-PAL and 
EORTC QLQ-BM22, Support Care Cancer 2016 ; DOI 10.1007/s00520-016-
3341-9@Springer-Verlag Berlin Heidelberg 2016. 
 
 
21. Woo A., Lechner B., Fu T., Wong c., Chiu N., Lam H., Pulenzas N., Soliman H., 
DeAngelis C., Chow E., Cut points for mild, moderate, and severe pain among 
cancer and non-cancer patients: a literature review , Ann Palliat Med 2015;4(4):176-
183. 
 
22. Alsaleh K., Routine administration of standardized questionnaires that assess aspects 
of patients’ quality of life inmedical oncology clinics: A systematic review, Journal of 
the Egyptian National Cancer Institute 2013; 25: 63–70. 
 
23. Raman S, Ding K, Chow E, Meyer RM, Nabid A, Chabot P, Coulombe 
G, Ahmed S, Kuk J, Dar AR, Mahmud A, Fairchild AM, Wilson CF, Wu 
JS, Dennis K, de Angelis C, Wong R, Zhu L, Brundage M, A Prospective Study 
Validating the EORTC QLQ-BM22 Bone Metastases Module in Patients With 
Painful Bone Metastases, Int J Radiat Oncol Biol Phys 2016;96(2S):E514. 
24. McDonald R., Chow E., Rowbottom L., Bedard G., Lam H.,Wong E., Popovic 
M., Pulenzas N., Tsao M., Quality of life after palliative radiotherapy in bone 
metastases:A literature review, Journal of Bone Oncology 2015; 4:24–31. 
 
 


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