The Palliative Radiotherapy and Inflammation Study (PRAIS) - protocol for a longitudinal observational multicenter study on patients with cancer induced bone pain

Ragnhild Habberstad, Trude Camilla Salvesen Frøseth, Nina Aass, Tatiana Abramova, Theo Baas, Siri Tessem Mørkeset, Augusto Caraceni, Barry Laird, Jason W Boland, Romina Rossi, Elena Garcia-Alonso, Hanne Stensheim, Jon Håvard Loge, Marianne Jensen Hjermstad, Ellen Bjerkeset, Asta Bye, Jo-Åsmund Lund, Tora Skeidsvoll Solheim, Ola Magne Vagnildhaug, Cinzia Brunelli, Jan Kristian Damås, Tom Eirik Mollnes, Stein Kaasa, Pål Klepstad, Ragnhild Habberstad, Trude Camilla Salvesen Frøseth, Nina Aass, Tatiana Abramova, Theo Baas, Siri Tessem Mørkeset, Augusto Caraceni, Barry Laird, Jason W Boland, Romina Rossi, Elena Garcia-Alonso, Hanne Stensheim, Jon Håvard Loge, Marianne Jensen Hjermstad, Ellen Bjerkeset, Asta Bye, Jo-Åsmund Lund, Tora Skeidsvoll Solheim, Ola Magne Vagnildhaug, Cinzia Brunelli, Jan Kristian Damås, Tom Eirik Mollnes, Stein Kaasa, Pål Klepstad

Abstract

Background: Radiation therapy (RT) results in pain relief for about 6 of 10 patients with cancer induced bone pain (CIBP) caused by bone metastases. The high number of non-responders, the long median time from RT to pain response and the risk of adverse effects, makes it important to determine predictors of treatment response. Clinical features such as cancer type, performance status and pain intensity, and biomarkers for osteoclast activity are proposed as predictors of response to RT. However, results are inconsistent and there is a need for better predictors of RT response. A similar argument can be stated for the development of cachexia; there are currently no predictors that can identify patients who will develop cachexia later in the cancer disease trajectory. Experimental and preclinical studies show that pain, depression and cachexia are related to inflammation. However, it is not known if inflammatory biomarkers can predict CIBP, depression or development of cachexia.

Methods: This multicenter, multinational longitudinal observational study will include 600 adult patients receiving RT for CIBP. Demographic data, clinical variables, osteoclast and inflammatory biomarkers will be assessed before start of RT, and 3, 8, 16, 24 and 52 weeks after last course of RT. The primary aim of the study is to identify potential predictors for pain relief from RT. Secondary aims are to explore potential predictors for development of cachexia, the longitudinal relationship between pain intensity and depression, and if inflammatory biomarkers are associated with changes in pain intensity, cachexia and depression during one-year follow up.

Discussion: The immediate clinical implication of the PRAIS study is to identify potential predictive factors for a RT response on CIBP, and thereby reduce non-efficacious RT. Patient benefits are fewer hospital visits, reduced risk of adverse effects and more individualized pain treatment. The long-term clinical implication of the PRAIS study is to improve the knowledge about inflammation in relation to CIBP, cachexia and depression and potentially identify associations and mechanisms that can be targeted for treatment.

Trial registration: ClinicalTrials.gov NCT02107664 , date of registration April 8, 2014 (retrospectively registered).

Trial sponsor: The European Palliative Care Research Centre (PRC), Department of Clinical and Molecular Medicine, NTNU, Faculty of medicine and Health Sciences, Trondheim, N-7491, Norway.

Keywords: Bone metastases; Cachexia; Cancer; Depression; Inflammation; Pain; Palliative; Radiation therapy.

Conflict of interest statement

Ethics approval and consent to participate

A signed consent will be obtained from all participants by an investigator at each site. The study is approved by The Regional Committee for Medical and Health Research Ethics, REC central Norway, (2013/1126/REK midt) and by the regulatory authorities at each trial site.

Consent for publication

Not applicable. The manuscript does not contain any individual person’s data.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study objectives with Research Questions (RQ)

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