HELSENORGE
PRC Research Projects

PRC Projects

The PRC is involved in a variety of national and international multicentre studies.

Below you can browse all of them, and find contact information to PI's and study coordinators.

Several of the studies are recruiting centres. If your centre is interested in joining, please contact the person stated in the project information site.

The Brain Metastases Study - Hjernemetastasestudien

Ongoing study.
Patient inclusion closed March 2021, closure of follow-up by the end of 2022.

Background and study rationale.
The overall BrainMet (BM) study comprises several subprojects, the prospective study presented below, supplemented with one large retrospective study of previous BM patients treated at Oslo University Hospital, one translational study on biomarkers and molecular similarities/dissimilarities of BMs and primary tumor tissue, and one qualitative study on patients' and caregivers' perception of how a BM diagnosis influences daily life and functioning from diagnosis and onwards. In Oct 2021, we also embarked on a follow-up study of long-term survivors of BM, consisting of thorough clinical and imaging examinations, self-reported QoL and physical and cognitive functioning and neurocognitive testing.

Patients diagnosed with brain metastases (BM) comprise a very heterogeneous group, with different cancer diagnoses, diverse symptoms and problems, treatment options and outcomes. The treatment offered varies across regions, and no systematic prospective follow-up has been conducted in Norway hitherto. The aim of this prospective BM-study, representing a Norwegian population-based cohort, is to follow patients from initial BM diagnosis during the disease and treatment trajectory with clinical data and patient-reported outcome measures.

Outcomes.
Primary outcome is overall survival, treatment patterns and progression and QoL. Secondary outcomes are patient reported outcomes.

Methods.
The BrainMet study is a multicenter, population-based prospective cohort study in cancer patients with newly diagnosed first BM. Patients are approached when admitted with a verified BM. Clinical data are registered every 3 months for 2 years, and consenting patients receive a set of PROMs by postal mail every month for at least 1 year or until death.

Results.
Preliminary data show that more than 900 patients have been included. The median overall survival is approximately 6 months. Many patients die <3months after BM diagnosis, but >20% live >12 months. Almost 50% of patients treated with whole brain radiotherapy die < 3 months after diagnosis.

Clinical and research implications.
The short life expectancy after the BM diagnosis emphasizes the importance of selecting the right treatment to the right patients, i.e. those who are most likely to benefit with the least impairments of QoL and functioning. Our findings so far suggest that a more restrictive use of whole brain radiotherapy should be considered. A closer follow-up of long-term survivors, i.e. patients living >1 year after diagnosis is necessary.

Publications.
Winther RR et al. Surgery for brain metastases - real-world prognostic factors' association with survival. Acta Oncol 2021; https://doi.org/10.1080/0284186x.2021.1930150 

Karlsson AT et al. Overall survival after initial radiotherapy for brain metastases; a population based study of 2140 patients with non-small cell lung cancer. Acta Oncol 2021; DOI: https://doi.org/10.1080/0284186x.2021.1924399

Gullhaug A et al. Use of radiotherapy in breast cancer patients with brain metastases– a retrospective 11-year single center study. J Med Imaging Radiat Sci 2021; DOI: https://doi.org/10.1016/j.jmir.2021.01.002

Main responsible person: Olav E. Yri, e-mail: olavy@ous-hf.no

Eir – Computerized assessment of patient reported outcomes in cancer clinical care

Ongoing project.
The Eir development and implementation project was initiated about a decade ago, with the first computerized solution (PAT-C) developed by our group in Trondheim together with NTNU Technology Transfer AS (ntnutto.no). With EirV3, our work aims at widespread clinical use nationally and internationally in the next few years.

Background and study rationale.
Several publications have addressed substantial shortcomings in systematic assessment and use of patient reported outcomes (PROMs) in cancer care. This is despite robust evidence of improved symptom management, QoL, and satisfaction with care, even prolonged survival. Eliciting the patient voice is instrumental in patient centered care; a major PRC research objective.

EirV3 is a user-friendly electronic solution that combines PROMs and treatment decision support, for use before and during the consultations, as well as remotely by patients and health care providers. Eir has been used in a clinical trial; COMBAT, at the cancer outpatient clinic at Trondheim University Hospital, and is currently part of the Norwegian cluster-RCT PALLiON. Usability results have shown that patients and health care providers found Eir intuitive, easy to use and relevant.

Outcomes.
Primary project goals are to revise EirV3, extend the decision support section and to establish the necessary technical solutions compliant to all confidentiality and security regulations for implementation at OUH. Secondary goal is to promote widespread use in Norwegian cancer clinics as part of the medical health record systems. The long-term goal is to implement EirV3 as the standard symptom assessment tool in our international PRC-studies.

Methods. EirV3 has two modules: Eir-Patient for PROMs registration on tablets, and Eir-Doctor for presentation of PROMs in a user-friendly interface on computers. Eir-Patient starts with Level 0; screening of 19 common cancer symptoms. The endorsed symptoms are subject to scoring of intensity at Level 1, followed by symptom characterizations and in-depth questions at Level 2. The idea is to perform a systematic hierarchical symptom assessment from the patient's perspective. The pain section includes a body map for pain location and intensity. Questions about physical functioning, wellbeing are standard questions for all as are those on appetite and food intake for prediction of nutritional risk.

The patient's responses are immediately available wirelessly in Eir-Doctor and presented with a graphical overview of symptom development over time and the current symptom intensity scores. Symptoms with intensity scores >3 (0-10 scale) are marked in red, with brighter colors with higher intensities, supplemented with graphs displaying. At present, algorithms combining clinical information and PROMs provide decision support according to internationally acknowledged treatment guidelines for a few symptoms. 

Clinical and research implications.
The immediate implications is to perform a slight update of the content based on its use in PALLiON, and to establish the necessary technical solutions that allow widespread use in Norwegian Hospitals, according to all confidentiality and security regulations. A close collaboration with Imatis/DNV; a leading provider of ICT tools in health care, has been established to implement Eir at OUS to begin with. As EirV3 is one of the bearing elements of our recently submitted EU Horizon 2022 grant proposal, expansion is a long-term goal.   

Publications.

  • Krogstad H et al. Computer-based symptom assessment is feasible in patients with advanced cancer: results from an international multicenter study, the EPCRC-CSA. J Pain Sympt Manage 2012; https://doi.org/10.1016/j.jpainsymman.2011.10.025
  • Krogstad H et al. Development of EirV3: A Computer-Based Tool for Patient-Reported Outcome Measures in Cancer. JCO Clin Cancer Inform 2017; https://doi.org/10.1200/cci.17.00051
  • Krogstad H et al. The paper on usability perceptions among end-users. Usability testing of EirV3-a computer-based tool for patient-reported outcome measures in cancer. Supp Care Cancer 2019; https://doi.org/10.1007/s00520-018-4435-3
  • Raj SX et al. The COMBAT paper using Eir for pain assessment in an outpatient setting. COMBAT study - Computer based assessment and treatment - A clinical trial evaluating impact of a computerized clinical decision support tool on pain in cancer patients. Scand J Pain 2017; https://doi.org/10.1016/j.sjpain.2017.07.016

Main responsible persons. Stein Kaasa; e-mail: stein.kaasa@medisin.uio.no, Marianne Jensen Hjermstad: e-mail: mariajhj@medisin.uio.no

MENAC (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia) trial

Background and study rationale.
Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support alone. Cachexia has a high prevalence in cancer and a major impact on patient physical function, morbidity and mortality. Despite the consequences of cachexia, there is no licensed treatment for cachexia and no accepted standard of care. It has been argued that the multifactorial genesis of cachexia lends itself to therapeutic targeting through a multimodal treatment approach. Following a successful phase II trial, a phase III randomized controlled trial was initiated. The MENAC intervention is based on evidence to date and consists of non-steroidal anti-inflammatory drugs and eicosapentaenoic acid to reduce inflammation, a physical exercise program using resistance and aerobic training to increase anabolism, combined with dietary counselling and oral nutritional supplements to promote energy and protein balance.

Outcomes.
Study objective is to establish whether a multimodal intervention is effective in treating cachexia. The primary outcome is difference in body weight (Kg) at six weeks across groups. Secondary outcomes are difference in muscle mass (CT at L3) and physical activity (ActivPAL).

Methods.
The MENAC trial is a multicenter randomized controlled trial of a multimodal therapy (ONS plus ibuprofen plus exercise) versus standard care. Following randomization, patients will be allocated to either the intervention or the control arm and key endpoints will be assessed after 6 weeks. Patients with NSCLC or pancreatic cancer starting palliative chemotherapy are eligible.

Clinical and research implications.
At present, there are no established treatments for cachexia, and the condition is often neglected. Moreover, there is increasing evidence that current intensive oncological treatments are both exacerbating cachexia and are being curtailed by increased toxicity due to cachexia. There is consensus that cachexia is a multidimensional problem and that a multimodal approach to treatment is necessary. The intervention in the MENAC trial aims to establish a practical rehabilitation program that hopefully provide the first evidence-based method to reverse this currently intractable syndrome, that affects >50% of patients with advanced cancer and reduces their quality of life and life expectancy. Successful management of cachexia could have major impact on supportive oncology, but could in addition also improve the tolerance and probability of completing chemotherapy and radiotherapy treatment. This trial that includes patients from multiple countries, will hopefully help to improve the standardization of nutritional and metabolic care of patients undergoing anticancer therapy

Publications.
Solheim, TS et al. Cancer cachexia: Rationale for the MENAC (Multimodal - Exercise, Nutrition and Anti-inflammatory medication for Cachexia) trial. BMJ Supportive & Palliative Care, 2018. DOI: https://doi.org/10.1136/bmjspcare-2017-001440

Solheim, TS et al. A randomized phase II trial of a multimodal intervention for the treatment of cachexia in lung and pancreatic cancer. J Cachexia Sarcopenia Muscle 2017. DOI: 10.1002/jcsm.12201

Responsible persons. Marie Fallon: Marie.Fallon@ed.ac.uk, Stein Kaasa: stein.kaasa@medisin.uio.no

The Orkdal Model: Development, implementation, and evaluation of collaboration between specialist and community care within palliative cancer care

Closed project.
Data collection started Nov. 2014 and closed Dec 31, 2019. A spin-off project in Møre og Romsdal Hospital Trust is ongoing and will close the data collection March 31, 2022.

Background and study rationale.
Early access to palliative care for cancer patients is recommended. Descriptions of structures and processes of outpatient palliative care clinics operated within smaller hospitals are scarce. The overall aim of the project was to improve the provision of palliative care for cancer patients and their families in the Orkdal region (Orkdal Hospital and 13 surrounding municipalities) by the implementation of a standardized care pathway integrating cancer and palliative care.

Outcomes.
Primary outcomes are the proportion of patient's time spent at home (in days) during the last three months of life, and caregiver health-related quality of life after the patient is dead, assessed with the RAND-Short Form-36.

Secondary outcomes are number of home deaths, use of tumor-directed treatment (radiotherapy and chemotherapy) in the last three months of life and change over time in health care providers' knowledge and skills assessed with prospective questionnaires.

Methods.
The study has a prospective controlled non-randomized intervention design comparing two similar regions in Mid-Norway. Romsdal region with Molde Hospital and 9 surrounding municipalities were control group. A standardized care pathway (SCP) integrating cancer and palliative care across care levels was developed and implemented in the intervention region. The intervention and the implementation strategy were evaluated using a mixed methods approach. Cancer patients 18 years or older who received treatment with non-curative intent, their caregivers, and healthcare professionals were included.

Results.
Two-hundred and five patients were included, 129 in the intervention region and 76 in the control region. Of these, 165 died before end of follow-up, 106 in the intervention group and 59 in the control group. One-hundred carers were included, 64 in the intervention region and 36 in the control region. In addition, 411 and 115 healthcare professionals were recruited for evaluation of quantitative measurements. The intervention was developed and implemented as planned. Due to slower inclusion rate and longer survival time of the patients than estimated, inclusion and follow-up were extended with one and two years, respectively. Process evaluation revealed that despite an extensive implementation process, there was limited use of the SCP in clinical practice. Healthcare professionals reported improved quality of cancer care following the implementation process. Evaluation of clinical outcomes will be published later.

Clinical and research implications. Future research must address what are the most important elements for useful and successful implementation of a care pathway for palliative cancer patients in clinical practice.

Publications.
Brenne AT et al. Implementing a Standardized Care Pathway Integrating Oncology, Palliative Care and Community Care in a Rural Region of Mid-Norway. Oncol Ther. 2021 . DOI: 10.1007/s40487-021-00176-y

Brenne AT et al. Fully Integrated Oncology and Palliative Care Services at a Local Hospital in Mid-Norway: Development and Operation of an Innovative Care Delivery Model. Pain Ther. 2020. DOI: 10.1007/s40122-020-00163-7

Main responsible person. Anne-Tove Brenne, e-mail: anne.tove.brenne@ntnu.no

PALLiON: PALLiative care Integrated in Oncology

Ongoing study.
Patient inclusion closed October 2021, closure of follow-up by the end of 2022.

Background and study rationale.
Several publications have addressed the need for a systematic integration of oncological care focusing on the tumor and palliative care (PC) focusing on the patient with cancer. Internationally, there is now a persuasive argument that introducing PC early during anticancer treatment in patients with advanced disease has beneficial effects on symptoms, psychological distress, quality of life and survival.

The exponential increase in anticancer treatments adds to the complexity of anticancer care. The treatment effect is hard to predict, and might be of little benefit to patients in the last stages of disease. Thus, this cluster-RCT investigates effects of early, systematic integration of oncology and specialized PC in patients with advanced cancer on use of anticancer treatment at the end of life.

Outcomes. The primary outcome is use of chemotherapy in the last 3 months before death, number of patients, initiation, discontinuation and number of cycles. Secondary outcomes are administration of other medical interventions in the last month of life, symptom burden, quality of life (QoL), satisfaction with information and follow-up, and caregiver health, QoL, and satisfaction with care.

Methods.
This national cluster-RCT is conducted in 12 Norwegian hospitals. Hospitals are stratified on the size of local catchment areas before randomization. In the intervention hospitals, a three-tiered complex intervention is implemented. The backbone of intervention in the 6 intervention sites is the implementation of patient-centered care pathways that contain early, compulsory referral to PC and regular and systematic registrations of symptoms. Oncologists and palliative care physicians completed an educational program before patient inclusion started. Control sites follow common procedures for symptom assessment and referral to palliative care.

Results.
660 patients were included by closure of inclusion at the end of October 2021, some patients are still being followed. Analyses are ongoing.

Clinical and research implications.
Regardless of study results, we will pursue the implementation of patient centered care pathways with systematic symptom assessment, preferably electronic, as part of routine cancer care.  

Publications.
Hjermstad et al. PALLiON – PALLiative care Integrated in ONcology: study protocol for a Norwegian national cluster-randomized control trial with a complex intervention of early integration of palliative care. Trials 2020; https://doi.org/10.1186/s13063-020-4224-4

Lundeby et al. Challenges and Learning Needs for Providers of Advanced Cancer Care: Focus Group Interviews with Physicians and Nurses. Palliative Medicine Reports 2020; https://doi.org/10.1089/pmr.2020.0059

Hjermstad et al. Using Process Indicators to Monitor Documentation of Patient-Centred Variables in an Integrated Oncology and Palliative Care Pathway-Results from a Cluster Randomized Trial  
https://doi.org/10.3390/cancers13092194

Main responsible person. Marianne Jensen Hjermstad, e-mail: mariajhj@medisin.uio.no

Read more about PALLiON (in Norwegian)

Paracetamol with Strong Opioids (ParaStop)

A randomized, double-blind, parallel-group non-inferiority phase III withdrawal trial of paracetamol versus placebo in conjunction with opioids for moderate to severe cancer-related pain.

Ongoing study.
Patient inclusion, first patient included in October 2021

Background and study rationale.
The World Health Organization's (WHO) three step analgesic ladder has been the standard approach for treating cancer-related pain for more than 30 years. However, this therapy is partly based on tradition and opinion and not on evidence from randomized trials.

Systematic reviews, including the Cochrane Review “Oral paracetamol (acetaminophen) for cancer pain" by Wiffen et al (2017), point out the lack of evidence of paracetamol's analgesic efficacy. Despite this, the prescribing of paracetamol in conjunction with strong opioids for patients with cancer pain is common practice in most countries worldwide and still recommended by the WHO.

There is a need to establish high quality evidence on whether paracetamol provides additional analgesic effect in cancer pain patients receiving strong opioids. Therefore, a definitive withdrawal study of paracetamol in patients using strong opioids for cancer pain will be an important contribution to provide evidence based care for patients with advanced cancer and reduce patients' burden from possible futile and inefficient treatment practices.

The primary study objective is to establish whether the analgesic efficacy of strong opioids is non-inferior after withdrawal of paracetamol compared to the analgesic efficacy of strong opioids and paracetamol for cancer-related pain.

Outcomes.
The primary outcome is average pain intensity at day 8 measured by “Average pain past 24 hours" (numeric rating scale, NRS, 0-10). Secondary outcomes are changes in opioid requirements, opioid related side effects, and patient self-reported rating of overall improvement of pain.

Methods.
This is a prospective international multi-center parallel group, randomized, placebo-controlled, double-blinded non-inferiority withdrawal trial of placebo versus paracetamol in patients using strong opioids for cancer pain. The study will be conducted at 11 sites in Norway, UK and Italy. The inclusion period is estimated to about 24 months with last patient last visit in Q4 2023. A total number of 204 patients will be included.

Eligible patients have metastatic cancer with a life expectancy of more than 2 months; using both strong opioids and 1 gram of paracetamol 3-4 times daily. When entering the trial at baseline, Day 1, they will be randomized to receive either paracetamol or placebo for seven days in addition to their usual opioid doses. The study team will provide paracetamol or placebo tablets from day 1 of study. After a week, the participants will come to the last study visit (day 8). A follow-up phone call will be conducted 3-7 days after the day 8 visit.

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Results. First results are anticipated early 2024.

Main responsible person: Ørnulf Paulsen, Telemark Hospital Trust / University of Oslo, e-mail: paor@sthf.no

PRAIS – The Palliative Radiotherapy and Inflammation Study

Closed study.
Inclusion ended in December 2017, follow-up was completed in December 2018.

Background and study rationale.
More than one third of patients with bone metastases experience pain, and cancer-induced bone pain account for at least 70% of cancer related pain. Because life expectancy in patients with bone metastases 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, and radiotherapy is well-established treatment option for these patients, with about 40-60 percent having a meaningful pain response after treatment.

About 200 patients receive palliative radiotherapy for bone metastases in the Department of radiology at St. Olavs hospital, Trondheim University Hospital due to skeletal. This number is expected to increase in the years to come, as more patients live longer with metastatic disease. The identification of subgroups of patients with a high likelihood of successful analgesia from palliative radiotherapy by use of robust predictors are important from a clinical, patient-centered and societal point of view. The identification of responders reduces both over- and under-treatment.

Outcomes. The primary study outcome is the main research question being; “Which are the clinical predictors and biomarkers of pain response in patients with painful bone metastases?

Secondary study outcomes are the identification of;

  • Which clinical variables and biomarkers predict the development of cachexia in patients with metastatic cancer disease? 
  • Which clinical variables and biomarkers predict the development of depression in patients with metastatic cancer disease? 
  • Which inflammatory substances are associated with cancer pain, cancer cachexia and depression respectively 

Methods.
PRAIS is a multicenter, longitudinal observational study of patients commencing palliative radiotherapy for bone cancer pain. 574 patients admitted to palliative radiotherapy for bone cancer pain were included. Demographic data, clinical variables, blood samples and patient reported outcome measures (pain, quality of life etc.) were obtained before the start of radiotherapy and during follow-up at 3, 8, 16, 32 weeks and one year. 

Results.
We found that better performance status, breast or prostate cancer and presence of soft tissue expansion outside bone predicted RT response in patients with painful bone metastases. Inflammation measured with CRP was not a predictor for RT response, but patients using corticosteroids had significantly lower response rates.  

The explorative research questions are still under investigation and results from these analyses are expected to be published within the next year.

Clinical and research implications.
Results from the PRAIS study may be helpful in selecting patients with a higher likelihood of response to radiotherapy due to painful bone metastases and could be of interest for oncologists caring for patients with cancer pain.

Publications.
Habberstad R et al. Clinical Predictors for Analgesic Response to Radiotherapy in Patients with Painful Bone Metastases. J Pain Sympt Man 2021. DOI: https://doi.org/10.1016/j.jpainsymman.2021.03.022

Habberstad R et al. The Palliative Radiotherapy and Inflammation Study (PRAIS) - protocol for a longitudinal observational multicenter study on patients with cancer induced bone pain. BMC Palliat Care 2018. DOI: https://doi.org/10.1186/s12904-018-0362-9

Main responsible person. Pål Klepstad, e-mail: pal.klepstad@ntnu.no