Home » Latest ECRF Blog Articles » High C-Reactive Protein (CRP) as a Predictor of Specialist Palliative Care Needs

High C-Reactive Protein (CRP) as a Predictor of Specialist Palliative Care Needs

Author: Dr Cliona Lorton, Our Lady’s Hospice & Care Services.

Keywords: Lung cancer, Inflammation, C-reactive protein, Body composition, Quality of life, Symptoms, Specialist Palliative Care, Referral


Early specialist palliative care in cancer is associated with better patient outcomes. “Red flags” to identify people with specialist palliative care needs who are at risk of high symptom burden and poor quality of life could prompt a comprehensive assessment and early referral. Inflammation may be one such “red flag”. Inflammation is the body’s response to many challenges, including infection and illness. Although we know that inflammation is often seen in cancer, this link is still not well understood. Recent studies suggest that inflammation may be related to increased symptoms and poor quality of life (Laird 2013). It is also thought that inflammation can affect muscle in the body. Early research has shown that people with high levels of inflammation may have less muscle than people with little inflammation. It also appears that the muscle may have more fat inside than usual.

C-reactive protein is the most commonly used blood test to measure inflammation (Ryan 2015). Abnormal skeletal muscle can be measured using a Computerised Tomography scan. Blood tests and Computerised Tomography imaging are a standard part of the cancer diagnostic process. Thus, information on inflammation and skeletal muscle change could be easily accessed, without any additional burden to the patient. In the future, if a high C-reactive protein and abnormal skeletal muscle were shown to predict symptoms and quality of life in cancer patients, they could potentially be used as a prompt for detailed holistic assessment and specialist palliative care referral. The healthcare team could act early to treat or perhaps even prevent problems with symptoms and poor quality of life.

Researchers would like to determine if this is possible. To answer this question, a large study of people with advanced cancer would be needed. When a new study is being designed, it is often advisable to do a feasibility study first. A feasibility study provides information out how best to design a bigger study, gives information about likely challenges, the numbers of patients who would be needed in a bigger study and, importantly, whether a bigger study is even possible.

This feasibility study set out to recruit at least 30 people with inoperable lung cancer, prior to treatment. Previous studies of people with advanced illness have found that many study participants do not complete the whole study, especially where there are follow-up assessments – called study attrition. While the research was designed using the recommended ways to overcome attrition (short duration of study, simple methodology and assessments at times convenient to participants) it was still a significant problem with almost one quarter of participants not completing the study.

Symptom burden, quality of life and performance status were assessed with validated tools (The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core Questionnaire (EORTC QLQ-C30)). Research participants were asked to complete a questionnaire about their symptoms and quality of life at the time of recruitment. 6-8 weeks later, the participants were asked the same questions. Follow-up questionnaires were completed in person or over the telephone, depending on participants’ preferences. The research team analysed participants most recent C-reactive protein blood test and Computerised Tomography scan results to see if there was a link between people with high levels of C-reactive protein or skeletal muscle changes in the body and increased symptom burden and poor quality of life.

This research project proved challenging. After the first 8 weeks of the study the research team reviewed the methodological approach and recruitment processes and made changes as necessary to achieve maximum participant engagement. Researchers made major changes to the recruitment process twice before they successfully recruited participants. The inclusion criteria was amended to make it less restrictive, the timing at which the study was proposed to potential participants was amended to reduce patient distress and an appropriate time to introduce the study to potential participants was identified (during a hospital visit for a Bronchoscopy examination). In the end, over a period of 8 months (February to October 2018), 100 people with suspected lung cancer were recruited for this study; of these 35 had inoperable lung cancer. See Figure 1. for a breakdown of research participants.

The rest of this report concentrates on the 35 people with inoperable lung cancer, since this group was the focus of the study conducted for this fellowship. Despite alterations to the research approach a number of problems were identified that would mean this study would be unlikely to work on a larger scale. Firstly, in order to recruit enough people with inoperable cancer, lots of people with operable lung cancer and who did not have lung cancer were also included. While this led to the researchers being able to conduct another study of CRP and skeletal muscle in these other people, it would not be a very efficient way to carry out a bigger study of people with possible palliative care needs. Secondly, the research design resulted in a very diverse group of participants. Although all 35 participants had inoperable disease, some had more advanced disease than others. There was a mix of different types of lung cancer within the people studied. Some people went on to have chemotherapy, some radiotherapy, some had best supportive care. This variety means it can be difficult to know if any differences in symptoms and quality of life are really related to inflammation, or are just because of differences between cancer types, stages and treatments.

This was a feasibility study – its main aim was to see if a similar study could be run on a larger scale. However, it is worth noting that no significant association between C-reactive protein and skeletal muscle and change in quality of life or increased symptom burden/function score was found. There was a wide range of C-reactive protein level, muscle change and changes in symptoms / quality of life among participants. This makes it very hard to see if there is any pattern worth investigating in a larger study.

This study has provided some useful information. Ultimately, this research demonstrates the value of a feasibility study in palliative care research. It highlights which issues can be addressed and which remain, as well as giving an indication of likely recruitment rates in an eventual full-scale trial. This helps to ensure scarce resources and patient time are used efficiently. Hagen et al (Hagen 2011) advocate for the use of a kinaesthetic learning model in feasibility studies. Essentially, this means learning through doing so that the research design evolves during the study as the research team learn what works and make changes to the design accordingly. This research project used an iterative or cyclical process to identify and address barriers to the successful conduct of the study. One cycle of this research project fed into the next cycle based on the emerging experience. This process was key to the conduct of this study.

A strength of this study was the development and maintenance of a good working relationship with the clinical teams; this may be key to recruitment. Moreover, in this research, discussion of the recruitment challenges with the clinical team informed the changes in study design that finally led to successful recruitment. The full research report is available to read at the following link: Research Report.

Figure 1: Breakdown of Recruited Patients


Thank you to everyone who supported and participated within this research. I give particular thanks to the patients of St James’s Hospital, Dublin; staff at St James’s Hospital especially Dr Barry O’Connell, Dr Parthiban Nadarajan, Finola Fitzsimons, Rosemary Kennedy; staff in Endoscopy, Dr Sinead Cuffe, Dr Norma O’Leary, Dr Lucy Balding; Professor Declan Walsh; the Education and Research team in Our Lady’s Hospice & Care Services, Dr Joanne Lysaght, Dr Noel Donlon, the Department of Surgery team in Trinity Translational Medicine Institute, Dr Brenda O’Connor and All Ireland Institute of Hospice and Palliative Care.


  1. Laird BJ, McMillan DC, Fayers P, Fearon K, Kaasa S, Fallon MT, Klepstad P.The systemic inflammatory response and its relationship to pain and other symptoms in advanced cancer. Oncologist 2013;18(9):1050-5. doi: 10.1634/theoncologist.2013-0120. Epub 2013 Aug 21.
  2. Ryan AM, Cushen S, Ni Bhuachalla E, Dwyer F, Power DG. The Role of Inflammatory Biomarkers in the Assessment of Nutritional Status and Disease States. Topics in Clinical Nutrition. 2015;30(1):3-15.
  3. Neil A. Hagen, Patricia D. Biondo, PhDa, Penny M.A. Brasher, PhDc, Carla R. Stiles, BNa. Formal Feasibility Studies in Palliative Care: Why They Are Important and How to Conduct Them. JPSM August 2011 Volume 42, Issue 2, Pages 278–289.