PALLiative care in ONcology (PALLiON): A cluster-randomised trial investigating the effect of palliative care on the use of anticancer treatment at the end of life.

BACKGROUND: Effects on anticancer therapy following the integration of palliative care and oncology are rarely investigated. Thus, its potential effect is unknown. AIM: To investigate the effects of the complex intervention PALLiON versus usual care on end-of-life anticancer therapy. DESIGN: Cluster-randomised controlled trial (RCT), registered at ClinicalTrials.gov (No. NCT03088202). The complex intervention consisted of a physician education program enhancing theoretical, clinical and communication skills, a patient-centred care pathway and patient symptom reporting prior to all consultations. Primary outcome was overall use, start and cessation of anticancer therapy in the last 3 months before death. Secondary outcomes were patient-reported outcomes. Mixed effects logistic regression models and Cox proportional hazard were used. SETTING: A total of 12 Norwegian hospitals (03/2017-02/2021). PARTICIPANTS: Patients ⩾18 years, advanced stage solid tumour, starting last line of anticancer therapy, estimated life expectancy ⩽12 months. RESULTS: A total of 616 (93%) patients were included (intervention: 309/control:307); 63% males, median age 69, 77% had gastrointestinal cancers. Median survival time from inclusion was 8 (IQR 3-14) and 7 months (IQR 3-12), and days between anticancer therapy start and death were 204 (90-378) and 168 (69-351) (intervention/control). Overall, 78 patients (13%) received anticancer therapy in the last month (intervention: 33 [11%]/control: 45 [15%]). No differences were found in patient-reported outcomes. CONCLUSION: We found no significant differences in the probability of receiving end-of-life anticancer therapy. The intervention did not have the desired effect. It was probably too general and too focussed on communication skills to exert a substantial influence on conventional clinical practice.

Palliative appropriateness criteria: external validation of a new method to evaluate the suitability of palliative radiotherapy fractionation.

BACKGROUND: Recently, the palliative appropriateness criteria (PAC) score, a novel metric to aid clinical decision-making between different palliative radiotherapy fractionation regimens, has been developed. It includes baseline parameters including but not limited to performance status. The researchers behind the PAC score analyzed the percent of remaining life (PRL) on treatment. The latter was accomplished by calculating the time between start and finish of palliative radiotherapy (minimum 1 day in case of a single-fraction regimen) and dividing it by overall survival in days from start of radiotherapy. The purpose of the present study was to validate this novel metric. PATIENTS AND METHODS: The retrospective validation study included 219 patients (287 courses of palliative radiotherapy). The methods were identical to those employed in the score development study. The score was calculated by assigning 1 point each to several factors identified in the original study and using the online calculator provided by the PAC developers. RESULTS: Median survival was 6 months and death within 30 days from start of radiotherapy was recorded in 13% of courses. PRL on treatment ranged from 1 to 23%, median 8%. Significant associations were confirmed between online-calculated PAC score, observed survival, and risk of death within 30 days from the start of radiotherapy. Patients with score 0 had distinctly better survival than all other groups. The score-predicted median risk of death within 30 days from start of radiotherapy was 22% in our cohort. A statistically significant correlation was found between predicted and observed risk (p < 0.001). The original and present study were not perfectly concordant regarding number and type of baseline parameters that should be included when calculating the PAC score. CONCLUSION: This study supports the dual strategy of PRL and risk of early death calculation, with results stratified for fractionation regimen, in line with the original PAC score study. When considering multifraction regimens, the PAC score identifies patients who may benefit from shorter courses. Additional work is needed to answer open questions surrounding the underlying components of the score, because the original and validation study were only partially aligned.

Palliative non-small cell lung cancer treatment and end-of-life care stratified by sex and childlessness: an important interplay in unmarried patients?

PURPOSE: To analyze the interplay of sex and presence of children in unmarried patients with non-small cell lung cancer, because previous studies suggested sex-related disparities. Adult children may participate in treatment decisions and provision of social support or home care. METHODS: Retrospective single-institution analysis of 186 unmarried deceased patients, managed according to national guidelines outside of clinical trials. Due to the absence of other oncology care providers in the region and the availability of electronic health records, all aspects of longitudinal care were captured. RESULTS: Eighty-eight female and 98 male patients were included, the majority of whom had children. Comparable proportions in all four strata did not receive active therapy. Involvement of the palliative care team was similar, too. Patients without children were more likely to receive systemic therapy (39% utilization in women with children, 67% in women without children, 41% in men with children, 52% in men without children; p = 0.05). During the last 3 months of life, female patients spent significantly more days in hospital than their male counterparts. Place of death was not significantly different. Home death was equally uncommon in each group. In the multivariate analysis, survival was associated with age and cancer stage, in contrast to sex and presence of children. CONCLUSION: In contrast to studies from other healthcare systems, unmarried male patients were managed in a largely similar fashion to their female counterparts and with similar survival outcome. Unexpectedly, patients without children more often received systemic anti-cancer treatment.

Return to Work After Breast Cancer Treatment: An Electronic Health Record-based Study in North Norway.

BACKGROUND/AIM: Breast cancer treatment may interfere with work ability. Previous return-to-work studies have often focused on participants who were invited to participate after treatment completion. Participation varied, resulting in potential selection bias. This is a health-record-based study evaluating data completeness, both at baseline and one year after diagnosis. Correlations between baseline variables and return to work were also analyzed. PATIENTS AND METHODS: This is a retrospective review of 150 relapse-free survivors treated in Nordland county between 2019 and 2022 (all-comers managed with different types of systemic treatment and surgery). Work status was assessed in the regional electronic patient record (EPR). A 65-years age cut-off was employed to define two subgroups. RESULTS: At diagnosis, occupational status was assessable in all 150 patients. Almost all patients older than 65 years of age were retired (79%) or on disability pension for previously diagnosed conditions (19%). Data completeness one year after diagnosis was imperfect, because the EPR did not contain required information in 19 survivors. The majority of those ≤65 years of age at diagnosis returned to work. Only 14 of 88 patients (16%) did not return to work. Postoperative nodal stage was the only significant predictive factor. Those with pN1-3 had a lower return rate (68%) than their counterparts with lower nodal stage. CONCLUSION: This pilot study highlights the utility and limitations of EPR-based research in a rural Norwegian setting, emphasizing the need for comprehensive, individualized interventions to support breast cancer survivors in returning to work. The findings underscore the importance of considering diverse sociodemographic and clinical factors, as well as the potential benefits of long-term, population-based studies to address these complex challenges.

Palliative Radiation Treatment in Patients Managed With Advanced/Interventional Pain Therapy such as Pump-delivered Continuous Opioids.

BACKGROUND/AIM: The study aim was to analyze the feasibility and efficacy of palliative radiotherapy in patients receiving advanced/interventional pain therapy, such as epidural or spinal anesthesia or subcutaneous pump delivery of opioids. Endpoints such as pain relief, treatment in the last month of life and survival were evaluated. PATIENTS AND METHODS: Different baseline parameters including but not limited to age and Eastern Cooperative Oncology Group performance status (ECOG PS) were assessed. Outcomes were abstracted from electronic health records. The Edmonton Symptom Assessment System (ESAS) was utilized to score pain intensity. RESULTS: The study included 48 patients, 44 of whom completed radiotherapy as prescribed. Device malfunction was not observed. Overall, 31 patients (65%) had journal notes available allowing for evaluation of pain relief. Twenty-six of 31 experienced pain relief (54% in the intention-to-treat population of 48 study patients). Twelve patients (25%) stopped interventional pain therapy and were converted to transdermal or oral drugs. Median survival was 1.6 months. Forty-four percent had received radiotherapy during the last month of life. Sixty-four percent of patients with ECOG PS 3-4 had received radiotherapy during the last month of life, compared to 22% of those with ECOG PS <3, p=0.004. CONCLUSION: Palliative radiotherapy was feasible in this setting, but given the short median survival and high likelihood of treatment during the last month of life, patient selection and choice of fractionation regimen should be optimized. The record review identified several patients who experienced worthwhile pain relief, sometimes leading to conversion of pain therapy back to non-invasive oral or transdermal application.

Independent Validation of a Risk Stratification Model Predicting Survival in Elderly Patients Irradiated for Bone Metastases.

BACKGROUND/AIM: Many patients with bone metastases receive palliative radiotherapy. However, treatment personalization tools are needed, due to heterogeneous survival. The aim of this study was to analyze the validity of the prognostic survival model, originally developed by Rades et al., because international variations in clinical practice and survival outcomes may impact on the performance of predictive tools. PATIENTS AND METHODS: Data from a single institution were retrospectively analyzed. The study included 305 patients managed with palliative radiotherapy for bone metastases. The Rades et al. score was assigned and the resulting 3 prognostic strata were compared. RESULTS: The median overall survival for the 3 strata was 48, 248, and 1065 days, respectively (p<0.001). However, the original break-down (17 points versus 18-25 points versus >25 points) was not in accordance with the overlapping survival curves in some of the subgroups, leading us to propose slight adjustments. The modified model also performed satisfactorily in older patients (age ≥80 years; median survival 26, 192 and 489 days, respectively, p<0.001). CONCLUSION: The original Rades et al. survival score was a valid prognostic model in our Norwegian validation database. However, inclusion of patients with 18 points into the poor prognosis group is suggested as a modification to enhance the score's performance.

The LabPS score: Inexpensive, Fast, and Site-agnostic Survival Prediction.

OBJECTIVES: To provide a widely applicable, blood-biomarker-based and performance-status-based prognostic model, which predicts the survival of patients undergoing palliative non-brain radiotherapy. This model has already been examined in a cohort of patients treated for brain metastases and performed well. METHODS: This was a retrospective single-institution analysis of 375 patients, managed with non-ablative radiotherapy to extracranial targets, such as bone, lung, or lymph nodes. Survival was stratified by LabPS score, a model including serum hemoglobin, platelets, albumin, C-reactive protein, lactate dehydrogenase, and performance status. Zero, 0.5, or 1 point was assigned and the final point sum calculated. A higher point sum indicates shorter survival. RESULTS: The LabPS score predicted overall survival very well (median 0.6 to 26.5 mo, 3-month rate 0% to 100%, 1-year rate 0% to 89%), P =0.0001. However, the group with the poorest prognosis (4.5 points) was very small. Most patients with comparably short survival or radiotherapy administered in the last month of life had a lower point sum. Additional prognostic factors, such as liver metastases, opioid analgesic use, and/or corticosteroid medication, were identified. CONCLUSIONS: If busy clinicians prefer a general prognostic model rather than a panel of separate diagnosis-specific/target-specific scores, they may consider validating the LabPS score in their own practice. In resource-constrained settings, inexpensive standard blood tests may be preferable over imaging-derived prognostic information. Just like other available scores, the LabPS cannot identify all patients with very short survival.

Early death after palliative radiation treatment: 30-, 35- and 40-day mortality data and statistically robust predictors.

BACKGROUND: This study analyzed mortality after radiotherapy for bone metastases (287 courses). Endpoints such as treatment in the last month of life and death within 30, 35 and 40 days from start of radiotherapy were evaluated. METHODS: Different baseline parameters including but not limited to blood test results and patterns of metastases were assessed for association with early death. After univariate analyses, multi-nominal logistic regression was employed. RESULTS: Of 287 treatment courses, 42 (15%) took place in the last month of life. Mortality from start of radiotherapy was 13% (30-day), 15% (35-day) and 18% (40-day), respectively. We identified three significant predictors of 30-day mortality (performance status (≤ 50, 60-70, 80-100), weight loss of at least 10% within 6 months (yes/no), pleural effusion (present/absent)) and employed these to construct a predictive model with 5 strata and mortality rates of 0-75%. All predictors of 30-day mortality were also associated with both, 35- and 40-day mortality. CONCLUSION: Early death was not limited to the first 30 days after start of radiotherapy. For different cut-off points, similar predictive factors emerged. A model based on three robust predictors was developed.

Independent Validation of a Unifying Prognostic Model for Intracranial and Extracranial Metastasis-directed Radiotherapy.

BACKGROUND/AIM: The aim of this study was to analyze the validity of a unifying prognostic model, originally developed by Kowalchuk et al., because relevant variations in clinical practice and observed survival may impact on the performance of predictive tools. PATIENTS AND METHODS: Retrospectively, data from a single institution were analyzed. The study included 253 patients managed with radiotherapy for spine and/or brain metastases. The Kowalchuk et al. score [3 parameters including performance status, number of organ systems involved with disease outside of the organ system of the treatment target, and treatment of intracranial target(s)] was assigned and the resulting prognostic strata compared. RESULTS: The decision tool developed by Kowalchuk et al. performed well, e.g., in terms of 2-year survival. Complementary information could be obtained by analyses of blood test results such as hemoglobin, albumin, and C-reactive protein. CONCLUSION: The new unifying score emerged as a valid prognostic model in our external validation database.

Implementation of Locoregional Adjuvant Radiotherapy for Breast Cancer in a Rural Healthcare Region: Toxicity Outcomes in the Initial Cohort.

BACKGROUND/AIM: The aim of this study was to analyze the toxicity of locoregional adjuvant breast cancer radiotherapy after implementation of this service in a rural healthcare region with long travel distance. PATIENTS AND METHODS: This was a retrospective single-institution analysis of 87 consecutive female patients (the initial cohort), managed with conventionally fractionated 3-D conformal radiotherapy with or without boost, including both post mastectomy and breast conservation scenarios. Treatment was administered in line with comprehensive national guidelines. Intensity-modulated techniques were not utilized. RESULTS: The median follow-up time was 4 years. None of the patients developed any grade IV side-effects. According to Radiation Therapy Oncology Group criteria, acute grade 2b or 3 skin toxicity was observed in 16%. In addition, 35% developed acute grade 2a skin reactions. A trend was observed regarding grade 2-3 skin toxicities and administration of a boost (p=0.058). There was a significant association between the clinical target volume of the breast and grade 2-3 skin reactions in women who had breast-conserving surgery (p=0.016). Five patients (6%) developed grade 1 pneumonitis, unrelated to dosimetric or other baseline parameters. CONCLUSION: The toxicity profile after a median follow-up of 4 years was in accordance with published data. Recently, intensity-modulated techniques have been implemented at the study center, which may reduce radiotherapy toxicity in patients with large clinical target volume due to better dose homogeneity.

Survival and Early Death Within Three Months from the Start of Immune Checkpoint Inhibitors in Patients With Different Types of Cancer.

BACKGROUND/AIM: Implementation of new anticancer treatments in rural healthcare might not always result in identical survival outcomes as those seen in the randomized trials leading to approval. Therefore, the survival of patients treated with immune checkpoint inhibitors (ICI) in Nordland county was analyzed. PATIENTS AND METHODS: Retrospective analysis of 199 patients, mainly treated in adjuvant or palliative settings, e.g, for non-small cell lung cancer (NSCLC) or malignant melanoma (from 2018 to 2021). Overall survival and death within 3 months from start of ICI were evaluated. RESULTS: All patients who received (neo)adjuvant treatment were alive at the time of this analysis. Median survival was not reached for patients treated with consolidation durvalumab for NSCLC. Twenty-five patients died within 3 months [none after (neo)adjuvant or consolidation ICI]. Among these 25 patients, none had performance status (PS) 0 and only 7 had PS 1. Among 13 patients aged ≥80 years, 5 (38%) died within 3 months. Four of five patients treated on an individual basis outside of generally accepted indications died within 3 months. CONCLUSION: The overall survival outcomes observed after limited follow-up appear satisfactory. Death within 3 months was typically caused by cancer progression and mostly related to reduced PS (≥2) and/or advanced age (≥80 years).

Shortened Palliative Radiotherapy Results in a Lower Rate of Treatment During the Last Month of Life.

Introduction Palliative radiotherapy (PRT) during the last month of life (PRT30) should be avoided because relevant clinical benefits are unlikely to occur. While traditional short-course fractionation regimens are suitable for most patients, a minority may derive gains from higher doses of PRT. Compared to older regimens such as 13 fractions of 3 Gy, more hypofractionated, non-ablative concepts with reduced overall treatment time are not well studied. Methods Retrospective analysis (2017-2020) of 107 patients treated to metastatic lesions (one or two target volumes per patient) with traditional >2 weeks regimens or newer ≤2 weeks regimens, e.g. seven fractions of 5 Gy or five fractions of 6 Gy. Results Failure to complete radiotherapy was registered in 8% of patients (traditional fractionation) and 1%, respectively (p=0.12). Moderate rates of PRT30 were observed (11% and 6%, respectively, p=0.44). PRT30 was more likely in patients irradiated for brain or lymph node metastases. Utilization of newer ≤2 weeks regimens was highest in 2020, presumably as a result of the coronavirus disease 2019 (COVID-19) pandemic. Conclusion The implementation of newer fractionation regimens for selected patients has resulted in acceptable rates of non-completion and PRT30. Optimal selection criteria remain to be determined. Established, guideline-endorsed short-course regimens such as five fractions of 4 Gy and 8-Gy single fractions continue to represent important PRT approaches.

Palliative Radiotherapy During the Last Month of Life: Have COVID-19 Recommendations Led to Reduced Utilization?

BACKGROUND/AIM: The study aimed to evaluate practice changes in the time period of the early wave of the COVID-19 pandemic. PATIENTS AND METHODS: This was a retrospective single institution study. We defined palliative radiotherapy (PRT) initiated before Saturday, March 14th as pre-COVID and PRT initiated later as during-COVID (through June 30th). RESULTS: National COVID-19 recommendations led to a significant decrease in PRT with 10 or more fractions, while re-irradiation and radiotherapy during the final 30 days of life were equally common before and after these recommendations had been issued in March 2020. CONCLUSION: Rapid adoption of modified PRT regimens was feasible. However, the challenge of overtreatment in the final phase of the disease, due to inaccurate survival prediction, persisted.

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.

BACKGROUND: Several publications have addressed the need for a systematic integration of oncological care focused on the tumor and palliative care (PC) focused on the patient with cancer. The exponential increase in anticancer treatments and the high number of patients living longer with advanced disease have accentuated this. 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, and survival. METHODS: This is a national cluster-randomized trial (C-RCT) in 12 Norwegian hospitals. The trial investigates effects of early, systematic integration of oncology and specialized PC in patients with advanced cancer in six intervention hospitals compared with conventional care in six. Hospitals are stratified on the size of local catchment areas before randomization. In the intervention hospitals, a three-part complex intervention will be implemented. The backbone of the intervention is the development and implementation of patient-centered care pathways that contain early, compulsory referral to PC and regular and systematic registrations of symptoms. An educational program must be completed before patient inclusion. A total of 680 patients with advanced cancer and one caregiver per patient are included when patients come for start of last line of chemotherapy, defined according to national treatment guidelines. Data registration, clinical variables, and patient- and caregiver-reported outcomes take place every 2 months for 1 year or until death. The primary outcome is use of chemotherapy in the last 3 months of life by comparing the proportion of patients who receive this in the intervention and control groups. Primary outcome is use of chemotherapy in the last 3 months before death, i.e. number of patients. Secondary outcomes are initiation, discontinuation and number of cycles, last 3 months of life, 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. DISCUSSION: Results from this C-RCT will be used to raise the awareness about the positive outcomes of early provision of specialized palliative care using pathways for patients with advanced cancer receiving medical anticancer treatment. The long-term clinical objective is to integrate these patient-centered pathways in Norwegian cancer care. The specific focus on the patient and family and the organization of a predictable care trajectory is consistent with current Norwegian strategies for cancer care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03088202. Registered on 23 March 2017.

Development of EirV3: A Computer-Based Tool for Patient-Reported Outcome Measures in Cancer.

PURPOSE: Immediate transfer of patient-reported outcome measures (PROMs) for use in medical consultations is facilitated by electronic assessments. We aimed to describe the rationale and development of Eir version 3 (EirV3), a computer-based symptom assessment tool for cancer, with emphasis on content and user-friendliness. METHODS: EirV3's specifications and content were developed through multiprofessional, stepwise, and iterative processes (from 2013 to 2016), with literature reviews on traditional and electronic assessment and classification methods, formative iterative usability tests with end-users, and assessment of patient preferences for paper versus electronic assessments. RESULTS: EirV3 has the following 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 19 common cancer symptoms followed by specific, in-depth questions for endorsed symptoms. The pain section includes a body map for pain location and intensity, whereas physical functioning, nutritional intake, and well-being are standard questions for all. Data are wirelessly transferred to Eir-Doctor. Symptoms with intensity scores ≥ 3 (on a 0 to 10 scale) are marked in red, with brighter colors corresponding to higher intensity, and supplemented with graphs displaying symptom development over time. Usability results showed that patients and health care providers found EirV3 to be intuitive, easy to use, and relevant. When comparing PROM assessments on paper versus tablets (n = 114), 19% of patients preferred paper, 41% preferred tablets, and 40% had no preference. Median intraclass correlation coefficient between paper and tablets (0.815) was excellent. CONCLUSION: Iterative test rounds followed by continuous improvements led to a user-friendly, applicable symptom assessment tool, EirV3, developed for and by end-users. EirV3 is undergoing international testing of clinical and cross-cultural adaptability.