To Örebro University

Purpose: Radiation therapy (RT) causes tissue damage and inflammation. Because cytokines play a key role in such processes, their expression levels can be an indicator of cell and tissue toxicity. This critical review aims to explore whether levels of circulating inflammatory biomarkers in peripheral blood are associated with proton-or photon-based therapy in the pelvic area and how these levels vary over time. Further, we investigated whether these levels can be linked to radiation dose, the incidence of toxicity, and changes in toxicity over time.

Methods and Materials: A literature search was conducted in PubMed to find studies involving comparative cohorts of pelvic irradiated patients with cancer. Studies reporting on the association of markers in peripheral blood with inflammatory processes and/ or toxicity were included.

Results: We found evidence of associations between changes in inflammatory cytokine levels and the total cumulative dose-volume together with RT-induced toxicity in patients with cancer treated with pelvic RT. Common patient-reported outcomes demonstrate an association between radiation toxicity (eg, genitourinary toxicity) and circulating inflammatory biomarker levels.

Conclusions: This review highlights that the total cumulative dose and irradiated tissue volume are the primary drivers of RT-induced biomarker expression, influencing both early and late toxicity outcomes. The diversity in RT techniques, total dose, and number of treatment sessions across studies likely contributes to the variation in observed results. Circulating cytokine and biomarker levels in the blood can provide valuable monitoring and predictive insights for patients undergoing proton-or photon-based RT of the pelvis. Biomarker analysis in the context of RT offers clinical value by enabling personalized treatment by helping predict which patients are higher risk for certain toxicities, guiding clinicians in tailoring treatment, optimizing supportive care, and adjusting RT plans. This approach could improve patient outcomes and quality of life by reducing long-term complications from radiation exposure.

INTRODUCTION: In radiotherapy for head and neck cancer, a mask is used to immobilise the head and shoulders. An open mask that does not cover the face is expected to cause less anxiety, but there is need to further investigate the patients' experience of open versus closed masks. Therefore, the aim of this study is to evaluate patient preferences for open or closed masks and whether an open mask can reduce discomfort and anxiety for patients.

METHODS: Twenty participants were treated in alternating weeks using open and closed masks. Their distress was evaluated through semi-structured interviews and patient-reported outcome measures.

RESULTS: When using the open mask, it took longer to position the patient correctly. The closed mask felt more confining and could induce a sense of claustrophobia. Participants employed both internal and external strategies to cope with the stressful situation. The Hospital Anxiety and Depression Scale (HADS) showed a significant reduction in anxiety over time during the treatment period, but no significant difference between the masks. When participants chose which mask to use for the final treatments, 12 chose the open mask, while 8 chose the closed mask. In addition to the 20 analysed participants, two participants withdrew from the study because they could only tolerate the open mask, one due to anxiety and the other due to swelling.

CONCLUSIONS: The open mask seems to provide a less confined experience but may lead to greater difficulties in achieving the correct treatment position. While both masks can be viable options for most patients, some cannot tolerate closed masks but do tolerate open masks.

BACKGROUND: Fatigue may significantly effect everyday- and working life for radiotherapy patients. Some studies indicate a correlation between radiation dose and irradiated volume of the brain and the presence of fatigue. Our hypothesis was that patient reported outcome measures (PROMs) can improve our understanding of the patients' symptoms following proton beam therapy (PBT) and optimize PBT for future patients.

METHODS: This study included 167 adult patients (>18 years) who received PBT for malignant brain tumours. Data on dose metrics to intra-cranial structures was obtained from PBT treatment plans. To explore fatigue and health related quality of life (HRQoL); Multidimensional Fatigue Inventory (MFI-20) and EORTC QLQ-C30 was used at 6-, 12-24- and 36 months post PBT. The correlation between fatigue and dosimetry was explored using Spearman's signed rank test.

RESULTS: No severe fatigue was recorded during the 36 months follow-up. Correlations between higher radiation dose and worsened fatigue scores were generally weak (rho < 0.3). At 12 months post PBT, higher mean dose to the brain, brainstem, hippocampi and pituitary was correlated to worsened MFI Physical Fatigue. Further, Reduced Motivation according to MFI was correlated to higher radiation dose to the brainstem and the pituitary gland. At 36 months follow-up post-PBT, both Reduced Activity and Reduced motivation according to MFI were correlated to higher radiation dose to the brain, brainstem and hippocampi.

CONCLUSION: Proton beam therapy are well tolerated, with similar degree of fatigue pre- and post PBT. Achieving further reduction in mean brain dose appears beneficial.

BACKGROUND: This study assessed the cost-effectiveness of proton beam therapy (PBT) compared to conventional radiotherapy (CRT) for treating patients with brain tumors in Sweden.

METHODS: Data from a longitudinal non-randomized study performed between 2015 and 2020 was used, and included adult patients with brain tumors, followed during treatment and through a one-year follow-up. Clinical and demographic data were sourced from the longitudinal study and linked to Swedish national registers to get information on healthcare resource use. A cost-utility framework was used to evaluate the cost-effectiveness of PBT vs. CRT. Patients in PBT group (n = 310) were matched with patients in CRT group (n = 40) on relevant observables using propensity score matching with replacement. Costs were estimated from a healthcare perspective and included costs related to inpatient and specialized outpatient care, and prescribed medications. The health outcome was quality-adjusted life-years (QALYs), derived from the EORTC-QLQ-C30. Generalized linear models (GLM) and two-part models were used to estimate differences in costs and QALYs.

RESULTS: PBT yielded higher total costs, 14,639 US$, than CRT, 13,308 US$, with a difference of 1,372 US$ (95% CI, -4,914-7,659) over a 58 weeks' time horizon. Further, PBT resulted in non-significantly lower QALYs, 0.746 compared to CRT, 0.774, with a difference of -0.049 (95% CI, -0.195-0.097). The probability of PBT being cost-effective was < 30% at any willingness to pay.

CONCLUSIONS: These results suggest that PBT cannot be considered a cost-effective treatment for brain tumours, compared to CRT.

BACKGROUND AND PURPOSE: Since patients with primary brain tumor are expected to become long-term survivors, the prevention of long-term treatment-induced side effects is particularly important. This study aimed to explore whether symptom experience and symptom distress change over five years in adults with primary brain tumors treated with proton therapy. An additional aim was to explore whether symptom experience and symptom distress correlate.

MATERIALS AND METHODS: The study had a longitudinal observational design. Adult (≥18 years) patients (n = 170) with primary brain tumors treated with proton therapy were followed over five years. Symptom experience and symptom distress were evaluated using the patient-reported Radiotherapy-Related Symptom Assessment Scale. Data from baseline, 1, 12, and 60 months were analyzed using non-parametric tests.

RESULTS: Of the 170 patients, the levels of symptoms and symptom distress were low. Fatigue increased at 1 (p=0.005) and 12 months (p=0.025) and was the most frequent symptom from baseline to 60 months' follow-up. Cognitive impairment increased at 12 (p=0.027) and 60 months (p<0.001) and was the most distressing symptom at 60 months' follow-up. There were significant, moderate to strong, correlations at all time points between symptom experience and symptom distress of fatigue, insomnia, pain, dyspnea, cognitive impairment, worry, anxiety, nausea, sadness, constipation, and skin reactions.

CONCLUSION: Symptom experience and symptom distress changed in intensity over time with cognitive impairment as the most distressing symptom at 60 months. Future research should focus on identifying effective interventions aimed at alleviating these symptoms and reducing symptom distress for this vulnerable group of patients.

BACKGROUND: Informal caregivers (ICs) of patients with cancer provide essential and mainly uncompensated care. A self-perceived preparedness to care for the patient is associated with a lower caregiver burden, described as the extent to which caregiving is perceived as having adverse effects on IC functioning and well-being. ICs' well-being is associated with patient-perceived quality of care, suggesting that interventions to optimize ICs' health are essential in order to improve patient care. Head and neck cancer (HNC) is the seventh most common malignant disease in the world. The disease and its treatment have a significant negative impact on the patient's health and quality of life. Symptoms usually interfere with swallowing, food and fluid intake, breathing, speaking, and communication. ICs frequently manage patients' symptoms and side effects, especially problems related to nutrition and oral pain, without being properly prepared. Carer eSupport is an Internet-administered intervention, based on focus group discussions with ICs, developed in collaboration with ICs and healthcare professionals, tested for feasibility, and deemed feasible. This study protocol outlines the methods of investigating the effects of Carer eSupport plus support as usual (SAU) on self-reported preparedness for caregiving, caregiver burden, and well-being in the ICs of patients with HNC, compared with ICs receiving SAU only.

METHODS AND ANALYSIS: In this randomized controlled trial, 110 ICs of patients with HNC, undergoing radiotherapy combined with surgery and/or medical oncological treatment, will be randomized (1:1) to Carer eSupport plus SAU or SAU only. Data will be collected at baseline (before randomization), post-intervention (after 18 weeks), and 3 months after post-intervention. The primary outcome is self-reported preparedness for caregiving. Secondary outcomes are self-reported caregiver burden, anxiety, depression, and health-related quality of life. The effect of Carer eSupport plus SAU on preparedness for caregiving and secondary outcomes, compared with SAU only, will be evaluated by intention to treat analyses using linear regression models, mixed-model regression, or analysis of covariance.

DISCUSSION: If proven effective, Carer eSupport has the potential to significantly improve ICs' preparedness for caregiving and their wellbeing, thereby improving patient-perceived quality of care and patient wellbeing.

TRIAL REGISTRATION: ClinicalTrials.gov; NCT06307418, registered 12.03.2024 (https://clinicaltrials.gov/search? term=NCT06307418).

PURPOSE: The aim of this study was to explore patients' experience of participation in the treatment decision of proton beam therapy versus conventional radiotherapy.

BACKGROUND: Proton beam therapy (PBT) has become a treatment option for some cancer patients receiving radiotherapy. The decision to give PBT instead of conventional radiotherapy (CRT) needs to be carefully planned together with the patient to ensure that the degree of participation is based on individuals' preferences. There is a knowledge gap of successful approaches to support patients' participation in the decision-making process, which is particularly important when it comes to the situation of having to choose between two treatment options such as PBT and CRT, with similar expected outcomes.

METHOD: We conducted a secondary analysis of qualitative data collected from interviews with patients who received PBT for their brain tumor. Transcribed verbatims from interviews with 22 patients were analyzed regarding experiences of participation in the decision-making process leading to PBT.

FINDINGS: Participants experienced their participation in the decision-making process to a varying degree, and with individual preferences. Four themes emerged from data: to be a voice that matters, to get control over what will happen, being in the hand of doctors' choice, and feeling selected for treatment.

CONCLUSION: A decision for treatment with PBT can be experienced as a privilege but can also cause stress as it might entail practical issues affecting everyday life in a considerable way. For the patient to have confidence in the decision-making process, patients' preferences, expectations, and experiences must be included by the healthcare team. Including the patient in the healthcare team as an equal partner by confirming the person enables and facilitates for patients' voice to be heard and reckoned with. Person-centered care building on a partnership between patients and healthcare professionals should provide the right basis for the decision-making process.

BACKGROUND: Assessment of Rehabilitation Needs Checklist (ARNC), has been developed to assess rehabilitation need in cancer patients and is recommended by the Confederation of Regional Cancer Centres in Sweden, known as Hälsoskattningen. The aim of the study was to test the reliability and validity of the ARNC, mainly by comparing it with the Distress thermometer and EORTC QLQ-C30.

METHODOLOGY: A sample of 993 persons identified in the Swedish cancer register. The study participants were diagnosed with cancer in 2021 in the Mid Sweden region. The psychometric methods tested reliability and validity including factor analysis.

RESULTS: The response rate was 38%. The test-retest analysis showed that ICC was 0.80 or higher for 12 of the ARNC items. A strong or modarete correlation between ARNC and the other instruments was found in all functional scales and for most items. CFA of the 13-item two-factor model showed a RMSEA value of 0.04, CFI and TLI values of 0.97 and 0.96, and a SRMR value of 0.05, indicating a satisfactory model fit.

CONCLUSION: The evaluation of the ARNC suggests that it is an acceptable and reliable screening instrument for detecting symptoms and signs indicating a possible need of rehabilitation. The medium to strong correlations between ARNC items and the EORTC QLQ- C30 items and scales suggest that ARNC could be an alternative also for research purposes when a shorter and less comprehensive instrument is needed. The simple design could be an advantage as it lowers the burden on cancer patients.

BACKGROUND: The ProtonCare Study Group (PCSG) was formed with the purpose to develop and implement a framework for evaluation of proton beam therapy (PBT) and the related care at a novel clinic (Skandionkliniken), based on patient reported data.

METHOD: A logic model framework was used to describe the process of development and implementation of a structured plan for evaluation of PBT for all diagnoses based on patient reported data. After the mission for the project was determined, meetings with networks and stakeholders were facilitated by PCSG to identify assumptions, resources, challenges, activities, outputs, outcomes, and outcome indicators.

RESULT: This paper presents the challenges and accomplishments PCSG made so far. We describe required resources, activities, and accomplished results. The long-term outcomes that were outlined as a result of the process are two; 1) Improved knowledge about health outcomes of patients that are considered for PBT and 2) The findings will serve as a base for clinical decisions when patients are referred for PBT.

CONCLUSION: Using the logical model framework proved useful in planning and managing the ProtonCare project. As a result, the work of PCSG has so far resulted in long-lasting outcomes that creates a base for future evaluation of patients' perspective in radiotherapy treatment in general and in PBT especially. Our experiences can be useful for other research groups facing similar challenges. Continuing research on patients´ perspective is a central part in ongoing and future research. Collaboration, cooperation, and coordination between research groups/networks from different disciplines are a significant part of the work aiming to determine the more precise role of PBT in future treatment options.