Effect of local radiotherapy for bone pain on urinary markers of osteoclast activity

doi:10.1016/S0140-6736(00)02144-9

The Lancet

Volume 355, Issue 9213, 22 April 2000, Pages 1428-1429

https://doi.org/10.1016/S0140-6736(00)02144-9 Get rights and content

Urinary markers of bone resorption, pyridinoline and deoxypyridinoline were measured before and at 4 weeks after radiotherapy for metastatic bone pain. An association was shown between relief of metastatic skeletal pain by radiotherapy and low marker concentrations before and after treatment, lending support to the hypothesis that relief of metastatic bone pain by radiotherapy relates to an effect on bone, rather than tumour physiology.

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Radiotherapy (RT) reduces pain in about 60% of patients with painful bone metastases, leaving many patients without clinical benefit. This study assesses predictors for RT effectiveness in patients with painful bone metastases.
We included adult patients receiving RT for painful bone metastases in a multicenter, multinational longitudinal observational study. Pain response within 8 weeks was defined as ≥2-point decrease on a 0−10 pain score scale, without increase in analgesics; or a decrease in analgesics of ≥25% without increase in pain score. Potential predictors were related to patient demographics, RT administration, pain characteristics, tumor characteristics, depression and inflammation (C-reactive protein [CRP]). Multivariate logistic regression analysis with multiple imputation of missing data were applied to identify predictors of RT response.
Of 513 eligible patients, 460 patients (90 %) were included in the regression model. 224 patients (44%, 95% confidence interval (CI) 39%−48%) responded to RT. Better Karnofsky performance status (Odds ratio (OR) 1.39, CI 1.15−1.68), breast cancer (OR 2.54, CI 1.12−5.73), prostate cancer (OR 2.83, CI 1.27−6.33) and soft tissue expansion (OR 2.00, CI 1.23−3.25) predicted RT response. Corticosteroids were a negative predictor (OR 0.57, CI 0.37−0.88). Single and multiple fraction RT had similar response. The discriminative ability of the model was moderate; C-statistic 0.69.
This study supports previous findings that better performance status and type of cancer diagnosis predicts analgesic RT response, and new data showing that soft tissue expansion predicts RT response and that corticosteroids is a negative predictor for RT response in patients with painful bone metastases.
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A systematic review examining clinical markers and biomarkers of analgesic response to radiotherapy for cancer-induced bone pain
2019, Critical Reviews in Oncology/Hematology
Citation Excerpt :
Hoskin et al. explored the effects of XRT on levels of pyridinoline (PYD) and deoxypyridinoline (DPD) in urine of 22 patients with breast or prostate cancer. ( Hoskin et al., 2000) The urine samples were collected before (baseline) and one month post-XRT (follow-up). Pain was assessed using a 4-point scale (none, mild, moderated and severe).
Cancer frequently spreads to bone, causing cancer-induced bone pain (CIBP) which affects quality of life. The best treatment is radiotherapy (XRT), but response is variable. The aim of this systematic review was to identify factors that predict analgesic response.
Using PRISMA guidelines, Medline (1946–2018), Embase Classic + Embase (1947–2018) and Cochrane (setup-2018) databases were searched. Eligible studies examined adult patients receiving external beam XRT for CIBP with clinical marker and/or biomarkers evaluated.
Twenty-one studies (n = 4490) were included: Urinary markers in three studies (n = 357), genomic biomarkers in one study (n = 107), imaging techniques in five studies (n = 231) and demographics and disease parameters in eight studies (n = 4572). Quantitative sensory testing (n = 23) and physical activity and/or gait (n = 42) have been examined in one study each, while two studies have evaluated grade of spinal instability (n = 276).
No predictors of analgesic response from XRT in CIBP were identified but several show promise.
Development and Internal Validation of a Clinical Risk Score to Predict Pain Response After Palliative Radiation Therapy in Patients With Bone Metastases
2017, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
To improve the discriminative ability of the prediction model and accurately guide treatment decision making, adding new predictive variables beyond known clinical predictors might improve the prediction model. In this context, recent studies have shown promising results using imaging features of positron emission tomography (30-32) or serum and urinary markers of osteoclast activity (33-36). The clinical relevance of these findings has not yet been validated.
To investigate the relationship between patient and tumor characteristics and pain response in patients with metastatic bone disease, and construct and internally validate a clinical prediction model for pain response to guide individualized treatment decision making.
A total of 965 patients with painful bone metastases undergoing palliative radiation therapy at a tertiary referral center between 1999 and 2007 were identified. Pain scores were measured at 1, 2, and 3 months after radiation therapy. Pain response was defined as at least a 2-point decrease on a pain score scale of 0-10, without increase in analgesics, or an analgesic decrease of at least 25% without an increase in pain score. Thirteen candidate predictors were identified from the literature and expert experience. After multiple imputation, final predictors were selected using stepwise regression and collapsed into a prediction model. Model performance was evaluated by calibration and discrimination and corrected for optimism.
Overall 462 patients (47.9%) showed a response. Primary tumor site, performance status, and baseline pain score were predictive for pain response, with a corrected c-statistic of 0.63. The predicted response rates after radiation therapy increased from 37.5% for patients with the highest risk score to 79.8% for patients with the lowest risk score and were in good agreement with the observed response rates.
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Useful radiotherapy of symptomatic bone metastases: Indications and technics
2017, Revue du Rhumatisme Monographies
Les métastases osseuses sont fréquentes au cours de l’évolution des cancers. Leur prise en charge doit être pluridisciplinaire. La radiothérapie garde une place privilégiée dans le traitement de la douleur, en cas de compression médullaire et en postopératoire. De nombreux essais randomisés ont prouvé l’efficacité des traitements monofractionnés (8 Gy/1 fraction) qui sont peu utilisés. Ces protocoles permettent d’indiquer ces traitements même en situation palliative. L’utilisation d’antalgique et de dexaméthasone permet d’améliorer le confort des patients lors de ces traitements. La radiothérapie stéréotaxique permet de délivrer avec précision des doses très élevées qui peuvent stériliser des tumeurs jusqu’à présent considérées comme radiorésistantes. Sa place peut être discutée en cas de compression médullaire ou en situation de réirradiation. Des essais en cours permettront de préciser la place de l’irradiation en situation d’oligométastase ou en situation d’évolution concomitante de la tumeur primitive et de métastase.
Bone metastases are common in the evolution of cancers. Their management should be multidisciplinary. Radiotherapy keeps a special place in the treatment of pain in cases of spinal cord compression and postoperatively. Many randomized trials have proved the effectiveness of single fraction (8 Gy/1 fraction) which are rarely used. These protocols allow to indicate these treatments even in palliative situation. The use of analgesic and dexamethasone improves patient comfort during these treatments. Stereotactic radiotherapy can deliver with precision very high doses that can sterilize tumors considered radioresistant. His place may be discussed in case of spinal cord compression or in situation of re-irradiation. Ongoing trials will determine the place of irradiation of oligometastases or in situation of concurrent evolution of the primary tumor and metastasis.

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Research LettersEffect of local radiotherapy for bone pain on urinary markers of osteoclast activity

Bone and Mineral

Radiother Oncol

Research Letters
Effect of local radiotherapy for bone pain on urinary markers of osteoclast activity