MENAC: The Multimodal Exercise/Nutrition/Anti-inflammatory treatment for Cachexia trial. MENAC is a large-scale open randomised phase III multimodal intervention trial.
To establish whether a multimodal intervention is effective in treating cachexia. This will be assessed after 2 cycles of chemotherapy (study endpoint -between 6 -9 weeks) by measuring weight. Importantly, benefits of trial will set a foundation for future nutritional and physical intervention for patients undergoing chemotherapy, an area that today is regularly neglected.
To examine the effect of a multimodal intervention for cancer cachexia on muscle mass (CT at L3) and physical activity (ActivPAL).
Diagnosis of lung cancer, pancreatic cancer or cholangiocarcinoma
Due to commence anti-cancer therapy
Patients and recruitment
A total of 240 patients will be recruited from out-patient oncology clinics at multiple sites in Europe, Canada and Australia. The trial is open for inclusion at 12 centers in Norway, UK, Canada, Germany and Switzerland. By May 2018, 80 patients are enrolled in the trial.
PIs: Professor Stein Kaasa, NTNU/Oslo University Hospital and Professor Marie Fallon, University of Edinburgh.
For more information, or if your centre is interested in recruiting patients, please contact trial coordinator Inger Storaker (firstname.lastname@example.org).
The Palliative Radiotherapy and Inflammation Study. A large international study planning to include 1000 patients from eight countries. The inclusion started in December 2013, at Trondheim University Hospital. By December 2015, over 230 patients are included
Primary research question
Which are the clinical predictors and biomarkers predictor of pain reduction response to palliative RT for bone cancer pain?
Explorative research questions
- Which clinical variables and biomarkers are predictors of development of cachexia in patients with metastatic cancer disease?
- Which clinical variables and biomarkers are predictors of development of depression in patients with metastatic cancer disease?
- Which inflammatory substances are associated with cancer pain?
- Which inflammatory substances are associated with cancer cachexia?
- Which inflammatory substances are associated with depression in cancer?
More than one third of patients with bone metastasis experience pain, and cancer-induced bone pain count for at least 70% of cancer related pain. Cancer-induced bone pain is often described as a combination of constant pain with episodic pain exacerbations or "breakthrough pain". Episodic pain may be spontaneous or provoked by movement or weight bearing.
Because life expectancy in patients with bone metastasis can be long, it is essential to optimize treatment to receive good symptom control and quality of life. Treatment of Cancer-induced bone pain is multimodal. Treatment options are pharmacological pain treatment, bone-modifying agents such as bifosfonates and denosumab, conventional anti cancer treatment like chemotherapy or hormonal treatment, surgical management of pathological fractures, radioisotope treatment or external beam radiation therapy.
Not all patients experience pain relief from radiotherapy. Complete pain response is reported in about one quarter of the patients, partial pain response in 40-60 percent. There are no established predictors that can be used to select patients that will respond to radiotherapy, or characteristics of patients where radiotherapy has no effect and should be abandoned.
In the radiology department in St. Olavs hospital, Trondheim University Hospital 184 patients received palliative radiotherapy due to skeletal metastasis in 2011. This number is expected to increase the next years because of a larger cancer population that is expected to live longer with metastatic disease. Identifying subgroups of patients that have increased likelihood of successful analgesia from palliative RT would make it possible to select responders for RT, and not give unneeded RT to non-responders.
A multicenter, longitudinal observational study of patients commencing on palliative radiotherapy for bone cancer pain.
All patients admitted to palliative radiotherapy for bone cancer pain will be screened for participation in the PRAIS study. The aim was to include 1000 patients.
Demographic data, clinical variables and blood samples will be obtained before the patient start radio therapy and during follow-up after 3, 8, 16, 32 weeks and one year.
The trial opened for recruitment at the Department of radiotherapy at St Olavs University Hospital, Trondheim Unviersity Hospital in December 2013. By November 2017, the study is open for recruitment at seven centres in Norway, Italy, Spain and UK, and so far 550 patients are included in PRAIS.
The study will allow for more centres to be included, each centre contributing with a minimum of 100 patients into the study.
For more information, or if your centre is interested in recruiting patients, please contact the principal investigator, Professor Pål Klepstad, Trondheim University Hospital,
email@example.com or study coordinator Trude Camilla S. Frøseth,
Eir. A computerised platform for communication and decision-support
The PRC is currently developing a computerised platform for symptom management, decision-support and communication support called Eir. Eir is developed for implementation in routine clinical practice.
How Eir works, is illustrated in this video:
The project is led by PRC with professor Stein Kaasa as PI. Other collaborators are the
NTNU Technology Transfer, the Cancer Clinic at St. Olavs Hospital, and the Faculty of Medicine and Health Sciences at NTNU.
Eir is based on a computer based decision support system which is tested in a clinical trial at the cancer outpatient clinic at Trondheim University Hospital, the COMBAT study. COMBAT is a prospective cohort study at present conducted at the outpatient clinic at the Cancer Clinic at St. Olavs Hospital. 149 patients have tested the software in this study.
In both COMBAT and Eir, the patients complete a series of questions focusing on patient reported outcomes (PROs) such as pain, depression, medication and other health related issues by use of an iPad. The questionnaires are outlined in a dynamic order by applying screening questions. If a patient provides a response above a predefined threshold value on a particular screening question, the patient is automatically presented to additional questions exploring the particular symptom/complaint in detail.
This information is immediately available on the physician's computer or tablet, even before the patient consultation. Hence, the physician is provided an overview of the symptoms and complaints of the patient prior to consultation and enabled to focus on the patient's concerns. Eir also contains decision support for the physician.
The software processes the information provided by the patients and physician in order to generate decision support for physician. The decision support is based on internationally acknowledged treatment guidelines; hence this computerized system is also a method of incorporating clinical guidelines into clinical practice.
Eir consists of different modules, for patients and health care providers.
The module for patients: The patient fills in responses to questions on an iPad. The main part of this module is the symptom registration. This part consists of three levels:
Level 0: Symptom screening, Level 1: Intensity and Level 2: Symptom characterizations. In Level 0, an initial screening section defines about which symptoms the patient will be asked further questions.
In Level 1, symptom intensity are measured by a numerical rating scale (NRS) from 0 to 10 were 0 = "No symptom X" and 10 = "Worst possible symptom X". If the patient scores over a certain threshold level in Level 1, he gets follow up questions at Level 2 regarding this symptom.
In a separate section of Eir, the patient gets questions regarding symptoms related to nutrition, and also about their height, weight and weight loss.
The module for health care personnel: The patient's data are immediately available for the health care provider, on a computer or a tablet – or whatever device he/she prefers. Read more about the development of Eir in
JCO Clinical Cancer Informatics (requires subscription)
Eir has been regularly tested by patients and physicians during the entire development process. Results from these tests have been presented at the
EAPC WRC in Dublin 2016 and at the PRC/EAPC RN seminar in Oslo 2017.
Pain assessment and classification
Projects regarding pain assessment and classification
1. Assessment of neuropathic pain in patient with cancer
This project aims at reaching consensus on the adaptation/operationalization of the International Association for the Study of Pain (IASP) NeuPSIG criteria for NP diagnosis to be applied in cancer patients and on the relevance of patient reported verbal descriptors for NP to be used with screening purpose.
The diagnosis of neuropathic pain (NP) in patients with cancer has been debated since sometime. Neuropathic pain definition is in fact broad, including a spectrum of different diseases and mechanisms. The value of recognizing clinical conditions in cancer pain that can be classified as neuropathic is to be found in the following clinical observations: NP due to cancer is associated with a worse analgesic treatment response, it seems to respond to higher doses of opioids, and it can be improved by specific adjuvant drugs to improve the efficacy of opioid analgesia. No evidence based algorithm for assessment, diagnosis and treatment recommendation algorithm for NP exists.
An international group of 42 experts was invited to participate in a consensus process through a modified 2-round Internet-based Delphi survey. Relevant topics investigated were: peculiarities of NP in patients with cancer, IASP NeuPSIG diagnostic criteria adaptation and assessment, and standardized PRO assessment for NP screening. Median consensus scores (MED) and interquartile ranges (IQR) were calculated to measure expert consensus after both rounds.
Twenty-nine experts answered, and good agreement was found on the statement "the pathophysiology of NP due to cancer can be different from non-cancer NP" (MED=9, IQR=2). Satisfactory consensus was reached for the first 3 NeuPSIG criteria (pain distribution, history, and sensory findings; MEDs⩾8, IQRs⩽3), but not for the fourth one (diagnostic test/imaging; MED=6, IQR=3). Agreement was also reached on clinical examination by soft brush or pin stimulation (MEDs⩾7 and IQRs⩽3) and on the use of PRO descriptors for NP screening (MED=8, IQR=3). Based on the study results, a clinical algorithm for NP diagnostic criteria in cancer patients with pain was proposed. Clinical research on PRO in the screening phase and on the application of the algorithm will be needed to examine their effectiveness in classifying NP in cancer patients.
This study was published in Pain in December 2014.
2. Assessment of breakthrough pain in patients with cancer
The aim of this project is to reach a higher degree of international consensus on assessment and classification of transient cancer pain
The registered prevalence of transient cancer pain exacerbations ranges from less than 20% to more than 90%. Although breakthrough pain is the most commonly used term for this condition, differences in definitions, terminology, and applications contribute to the heterogeneity in the literature. Methods A Delphi survey was performed to explore and if possibly enhance the level of agreement among international researchers on transient cancer pain exacerbation, including terminology, definitions and assessment. In order to achieve applicable and relevant results through a sound process a careful definition of problems, justified selection of experts, well-founded reasoning for number of rounds and rigorous analyses of results according to predefined rules are necessary.
The experts selected were the authors that had published the most on the subject over the past 10 years, identified by in PubMed.
Results from this study was published in Journal of Pain and Symptom Management in 2016.
Symptom prevalence in selected patients cohorts
The prevalence of adverse symptoms among patients with an advanced cancer disease and chronic heart and lung diseases seem to stay relative high, despite interventions conducted to reduce the patients' suffering and increase their quality of life.
To quantify the symptom burden experienced by several patient groups. The results will identify areas where medical efforts should be improved, and may identify important differences between patient groups.
This was a cross-sectional, questionnaire based study assessing pain, cachexia, fatigue, anxiety and depression among in- and outpatients with cancer, COPD or heart failure
The patient groups include cancer patients at three different hospitals, in-patients with COPD, out-patients with heart failure, and patients with different chronic diseases at a community based nursing home.
In total, 554 patients from St. Olavs Hospital, Trondheim University Hospital; Øya Community Hospital; and Ålesund Hospital were included (in August 2013 and in February 2014).
Preliminary results show that the symptom burden in cancer patients is still high, and so is the symptom burden in patients with non-malignant diseases pointing to the need for palliative care in Norway to expand so patient with other diagnosis get the same symptom management as patients with cancer, and the need for paying more attention to symptom control in nursing homes.
The Orkdal model
Palliative care early in the cancer disease trajectory improves health related quality of life (HRQOL) for patients and family members. Collaboration between community and specialist care and professions is paramount to achieve optimal cancer care.
The overall aim of the study is to improve care for cancer patients with metastatic and/or loco-regional disease in need of palliative care and their families in 13 municipalities belonging to a local hospital (Orkdal) addressing, among others, the following research questions: to what extent will the implementation of an integrated palliative care programme contribute to an increase in the time patients spend at home, and to an improvement of family members' self-reported HRQOL?
The intervention consists of three main parts: 1. A standardised care pathway for the palliative care cancer patient, 2. an educational program for health care personnel involved with care of cancer palliative patients in specialist and community care, and 3. information about cancer and palliative care to patients, family members, general public and health care providers.
The Orkdal Model will be evaluated as a prospective controlled pre-post study with the following outcomes: Primary: Patients' time spent at home, family members' HRQOL. Secondary: Number of home deaths, use of tumor- directed treatment the last three months of life and improvement of HCPs' knowledge and skills. Tertiary: Patient reported HRQOL, did the patients die where they preferred to die, extent of implementation of the care pathway, distribution of health care services use between specialist and community care, total cost per patient and share of costs between specialist and community. Comparisons: between data in the pre and post intervention phase from the region of Orkdal, and with data from a local hospital where the intervention is not implemented.
Status by September 2017
A standardised care pathway for all cancer palliative care patients has been developed and is revised every year. The pathway is bridging specialist and community care. The care pathway focuses on the availability of palliative care services, exchange of information between health care providers and symptom assessment.
The educational program consists of two parts: one to inform about the project and the care pathway, and one to increase knowledge and skills in cancer and palliative care. Information to the public, patients, and family carers regarding anti-cancer treatment, assessment and available treatment of symptoms, end-of-life care and available resources locally will be offered in written materials, electronically, during consultations and at public meetings.
A patient pre-study was completed in 2014 (n=119).
Three qualitative studies have been conducted within the frame of the Orkdal Model Study:
Marte Nilssen Neverdal and Kristina Rystad: “The establishment of a standardized care pathway across specialist and primary care”. Master Thesis in Strategic Change Management, Department of Industrial Economics and Technology Management, Faculty of Social Sciences and Technology Management, NTNU, 2014.
- Tone Inga Braseth: “Patient held record and individual plan: do they support care for patients receiving palliative care?” Master thesis in Clinical Health Science, Department of Circulation and Medical Imaging, Medical Faculty, NTNU, 2016.
- Marianne Johnsen: “Implementation of a standardized care pathway in palliative cancer care- health care professionals’ experiences”. Master thesis in Clinical Health Science, Department of Circulation and Medical Imaging, Medical Faculty, NTNU, 2016.
By November 2017, about 200 patients, 90 family members and 500 health care providers are included in the main study. Inclusion will be closed in December 2017, and follow-up will be closed in December 2019.
A longitudinal study of colorectal cancer patients with metastatic disease in Middle-Norway
In Norway, colorectal cancer is the second most diagnosed cancer for both sexes. For the vast majority of patients with metastatic disease cure is not possible. Many patients will receive cancer treatment (chemotherapy or radiotherapy) where the aim is life prolongation, symptom relief or symptom prevention. The evidence for this treatment is based on clinical trials with strict eligibility criteria. It is uncertain whether treatment is equally effective and tolerable in patients not fulfilling these criteria.
The main objective is to provide original research results that may change clinical practice related to metastatic colorectal cancer.
The study will evaluate treatment and patient care at different stages of the disease trajectory and the use of health care for this large group of patients. We will be able to compare the effectiveness of chemotherapy, radiotherapy and symptomatic treatment given to "real life" patients with the efficacy reported in randomised clinical trials. By using longitudinal information on imaging, biomarkers, clinical staging and place of care it will be possible to improve patient classification at various stages of the disease. Based on this, we may be able to recommend a more appropriate, individualized treatment for colorectal cancer during the phases of the disease trajectory.
This study is a prospective longitudinal observational study of patients with metastatic colorectal cancer in the health region of Central Norway. Patients with colorectal cancer will be recruited when they enter treatment due to metastases and followed until death. Eligible patients from the seven hospitals in Central Norway will be consecutively recruited for three years with a subsequent open ended follow-up with regularly repeated assessments.
All patients with metastatic colorectal cancer from the Central Norway Regional Health Authority are eligible. Patients will be consecutively recruited for three years with a subsequent open ended follow-up with regularly repeated assessments. The follow-up will continue after the three-year period of this project. The longitudinal study will include approximately 500 patients. The trial is open for recruitment until February 2018.
All hospitals in the Central Norway are open for inclusion. By November 2017, seven centres take part in the trial (i.e. the hospitals in Trondheim, Molde, Levanger, Namsos, Volda, Ålesund and Kristiansund), and a total of 288 patients are included.
EAPC Basic Dataset
Pilot-testing of the EAPC Basic Dataset
The EAPC Basic Dataset is a result of a Delphi process aiming at reaching consensus on a basic set of variables to describe a palliativ care population (Sigurdardottir et al 2014). PRC encourage palliative care services across Europe to try out the basic dataset and invite them to take part in the pilot-testing.
The EAPC basic dataset contains 31 variables, divided between a ‘patient form' – date of birth, gender, living situation, education, ethnicity and 12 symptoms – and a ‘health-care personnel form' – patient's date of birth, principal diagnosis, date of the principal diagnosis, stage of the cancer disease, site of metastases, present anticancer treatment, main additional diagnoses, stage of the additional diagnoses, medication, weight loss, performance status, cognitive impairment, place of care and provision of care.
The pilot-testing will be conducted at several centres internationally.
One forward translation from English into the target language. The translator should have medical background and the target language as his/her native language. Items from the ESAS-r should be taken from an authorized translation.
Testing the dataset
Each centre will contribute a minimum of 20 patients to the study. Patients and health care personnel will be asked to complete the EAPC basic dataset, followed by debriefing in a standard structured interview to assess any concerns the measure might have raised. The time for completion and need for assistance will be recorded. Specific questions will be asked to explore whether participants experienced any items as difficult to answer, annoying, confusing, or upsetting.
Centres in UK, Italy, France and Norway have included patients and health care personnel in the pilot study during 2015. Centres in Germany and Ireland will join in 2016.
For more information, or if your centre is interested in participating, please contact the PRC or the study coordinator Katrin Sigurdardottir.
EAPC pain guidelines
Guidelines development has been one action of the EAPC research network since its beginning. The European Association for Palliative Care (EAPC) Research Network published its first guidelines on the use of morphine and alternative opioids in cancer pain in 1996 and published an update in 2001. Subsequently, further work was performed to strengthen the scope of the EAPC recommendations by the application of rigorous, evidence-based methodology. This involved a number of collaborating groups who were assigned different topics which were identified by consensus as relevant and published as 12 systematic reviews in one monographic issue of Palliative Medicine. These results were summarized in the EAPC opioid evidence-based recommendations published in 2012 in Lancet Oncology. Since then the pain guidelines development group coordinated by Augusto Caraceni, Marie Fallon and Stein Kaasa undertook the commitment of revising and updating the 2012 guidelines and enlarging their scope from opioids to cancer pain management in general. Literature reviews on previously published topics have been updated, and reviews on new topics were performed.
The updated guidelines will be published 2017/2018.
EAPC PAIN GUIDELINES LIST OF TOPICS
- PAIN ASSESSMENT AND CLASSIFICATION
- OPIOID OF FIRST CHOICE
- ALTERNATIVE ROUTES
- EQUIANALGESIC RATIOS
- TRANSDERMAL OPIOIDS (FENTANYL AND BUPRENORPHINE)
- INCIDENT PAIN
- DRUGS IN NEUROPATHIC PAIN
- NSAIDS/PARACETAMOL + WHO STEP III OPIOIDS
- WHO STEP I DRUGS
- WHO STEP II DRUGS
- WHO STEP II VS WHO STEP III
- GASTROINTESTINAL SIDE EFFECTS MANAGEMENT (nausea and vomiting)
- GASTROINTESTINAL SIDE EFFECTS MANAGEMENT (constipation)
- CENTRAL SIDE EFFECTS MANAGEMENT
- LIVER FAILURE
- RENAL FAILURE
- SPINAL OPIOIDS
- INVASIVE ANALGESIC INTERVENTION
- DRUG INTERACTIONS
Palliative Care Integrated in Oncology (PALLiON)
Complexity of treatment is a big challenge in cancer care. The treatment effect is hard to predict, and might cause late side effects. For physicians it can be hard to estimate when it is time to stop active treatment.
Previous research has shown that systematic palliative care focusing on symptom control and quality of life for patients and their families, is often introduced too late in the disease trajectory. Early integration of palliative care services can improve quality of life, and in some cases improved survival.
PALLiON is a Norwegian cluster-randomised study testing the effect of complex intervention that integrates oncology and palliative care services for cancer patients with a life-expectancy <12 months who receive chemotherapy. The intervention in PALLiON includes three specific elements:
Implementation of standardized care pathways, systematic electronic assessment of symptoms, and an educational program for oncologists and palliative care physicians.
PALLiON is managed by a consortium that consists of an Advisory Board, with national/international stakeholders in oncology and palliative care, a Scientific Management Group and Work Package leaders. The PI is Jon Håvard Loge, University of Oslo/Oslo University Hospital.
The advisory board
- Thomas Smith, The Harry J. Duffey Family Professor of Pall. Med., Director of Palliative Medicine, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, USA)
- David Currow, Professor in Pall. and Support Services, CEO Cancer Institute NSW, Australia
- Marie Fallon, St Columba’s Hospice Chair of Palliative Medicine, Edinburgh Cancer Research Centre, UK
- Tone Nordøy, Chair, Department of Oncology, University Hospital of North Norway
- Sigbjørn Smeland, Chair, Advisory Board,Division of Cancer Medicine, Surgery and Transplantation Oslo University Hospital
- Augusto Caraceni, NTNU/ Fondazione IRCCS Istituto Nazionale Tumori, Milan
- A representative from the Norwegian Cancer Society.
The project received funding from the Norwegian regional health authorities funds for cross regional health research projects in 2015.
Read more about PALLiON on pallion.no (Norwegian)
Treatment of insomnia in palliative care
Pharmacological treatment of insomnia in palliative care
A randomized, double-blind, placebo controlled trial on sleep quality in patients with advanced cancer who use opioids
Sleep is important for all as it is vital for good health and well-being. Insomnia is the most prevalent sleep disorder in the general population and among cancer patients. A variety of sleep medications have been recommended for insomnia, but their efficacy and safety in adults with advanced cancer are not established.
The primary objective is to study the short time effectiveness of zopiclone on patient reported sleep quality in patients with advanced cancer who use opioids and report insomnia. The secondary objective is to study the effectiveness of zopiclone on self-reported total sleep time and sleep onset latency. The explorative objectives are to study the effectiveness of zopiclone on objectively measured (actigraphy) sleep variables and daytime sleepiness. The primary endpoint is patient-reported sleep quality during the final study night (night six) assessed on a numerical rating scale (NRS) 0-10. 0= Best sleep, 10=Worst possible sleep.
This is a randomized, double-blind, placebo-controlled, multicenter, phase IV study. Patients with advanced cancer who use opioids and who report insomnia are randomized to either a hypnotic; zopiclone (Arm A) or placebo (Arm B) for six nights. Total number of patients: 100
Figure 1. Overall study design. Basic structure of the trial
The initial dose is zopiclone/placebo 3.75 mg/day, which will be increased if needed every second night in the study period.
Assessment and data collection
General sleep quality is assessed by the Pittsburgh Sleep Quality Index (PSQI). Sleep quality during the treatment period will be assessed on the 0-10 (NRS). Cancer related symptoms and health related quality of life will be assessed by validated self-report questionnaires at baseline, during the treatment period (six nights) and at the end of treatment (Day 8).
Objective measurement of sleep will be assessed by actigraphy, a small wristwatch-like device that provides estimates of total sleep time and latency to sleep by monitoring periods of activity and rest. The actigraphy will be attached on baseline and sleep will be measured in one night without study treatment and then the actigraphy will monitor sleep continuously during the treatment period (night 1-6). Start of inclusion is in October 2016.
Sponsor: St. Olavs Hospital. Trondheim University Hospital.
Study personnel at the European Palliative Care Research Centre (PRC), NTNU will perform data management.
Figure 2. In total, 100 patients will be recruited from five participating hospitals in Norway in a clinical trial on the pharmacological treatment of insomnia in patients with advanced cancer.