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. NCT01362816). 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.

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.

Relief of Neuropathic Pain Through Epidermal Growth Factor Receptor Inhibition: A Randomized Proof-of-Concept Trial.

OBJECTIVE: Case reports and a case series have described relief of neuropathic pain (NP) after treatment with epidermal growth factor receptor inhibitors (EGFR-Is). These observations are supported by preclinical findings. The aim of this trial was to explore a potential clinical signal supporting the therapeutic efficacy of EGFR-Is in NP. METHODS: In a proof-of-concept trial using a randomized, double-blind, placebo-controlled design, 14 patients with severe, chronic, therapy-resistant NP due to compressed peripheral nerves or complex regional pain syndrome were randomized to receive a single infusion of the EGFR-I cetuximab and placebo in crossover design, followed by a single open-label cetuximab infusion. RESULTS: The mean reduction in daily average pain scores three to seven days after single-blinded cetuximab infusion was 1.73 points (90% confidence interval [CI] = 0.80 to 2.66), conferring a 1.22-point greater reduction than placebo (90% CI = -0.10 to 2.54). Exploratory analyses suggested that pain reduction might be greater in the 14 days after treatment with blinded cetuximab than after placebo. The proportion of patients who reported ≥50% reduction in average pain three to seven days after cetuximab was 36% (14% after placebo), and comparison of overall pain reduction suggests a trend in favor of cetuximab. Skin rash (grade 1-2) was the most frequent side effect (12/14, 86%). CONCLUSIONS: This small proof-of-concept evaluation of an EGFR-I against NP did not provide statistical evidence of efficacy. However, substantial reductions in pain were reported, and confidence intervals do not rule out a clinically meaningful treatment effect. Evaluation of EGFR-I against NP therefore warrants further investigation.

Lifestyle changes in cancer patients undergoing curative or palliative chemotherapy: is it feasible?

INTRODUCTION: This study aimed to explore the feasibility of an individualized comprehensive lifestyle intervention in cancer patients undergoing curative or palliative chemotherapy. MATERIAL AND METHODS: At one cancer center, serving a population of 180,000, 100 consecutive of 161 eligible newly diagnosed cancer patients starting curative or palliative chemotherapy entered a 12-month comprehensive, individualized lifestyle intervention. Participants received a grouped startup course and monthly counseling, based on self-reported and electronically evaluated lifestyle behaviors. Patients with completed baseline and end of study measurements are included in the final analyses. Patients who did not complete end of study measurements are defined as dropouts. RESULTS: More completers (n = 61) vs. dropouts (n = 39) were married or living together (87 vs. 69%, p = .031), and significantly higher baseline physical activity levels (960 vs. 489 min.wk-1, p = .010), more healthy dietary choices (14 vs 11 points, p = .038) and fewer smokers (8 vs. 23%, p = .036) were observed among completers vs. dropouts. Logistic regression revealed younger (odds ratios (OR): 0.95, 95% confidence interval (CI): 0.91, 0.99) and more patients diagnosed with breast cancer vs. more severe cancer types (OR: 0.16, 95% CI: 0.04, 0.56) among completers vs. dropouts. Improvements were observed in completers healthy (37%, p < 0.001) and unhealthy dietary habits (23%, p = .002), and distress (94%, p < .001). No significant reductions were observed in physical activity levels. Patients treated with palliative intent did not reduce their physical activity levels while healthy dietary habits (38%, p = 0.021) and distress (104%, p = 0.012) was improved. DISCUSSION: Favorable and possibly clinical relevant lifestyle changes were observed in cancer patients undergoing curative or palliative chemotherapy after a 12-month comprehensive and individualized lifestyle intervention. Palliative patients were able to participate and to improve their lifestyle behaviors.

Cancer patients participating in a lifestyle intervention during chemotherapy greatly over-report their physical activity level: a validation study.

BACKGROUND: The short form of the International Physical Activity Questionnaire (IPAQ-sf) is a validated questionnaire used to assess physical activity (PA) in healthy adults and commonly used in both apparently healthy adults and cancer patients. However, the IPAQ-sf has not been previously validated in cancer patients undergoing oncologic treatment. The objective of the present study was to compare IPAQ-sf with objective measures of physical activity (PA) in cancer patients undergoing chemotherapy. METHODS: The present study was part of a 12-month prospective individualized lifestyle intervention focusing on diet, PA, stress management and smoking cessation in 100 cancer patients undergoing chemotherapy. During the first two months of the lifestyle intervention, participants were wearing an activity monitor (SenseWear™ Armband (SWA)) for five consecutive days while receiving chemotherapy before completing the IPAQ-sf. From SWA, Moderate-to-Vigorous intensity PA (MVPA) in bouts ≥10 min was compared with self-reported MVPA from the IPAQ-sf. Analyses both included and excluded walking in MVPA from the IPAQ-sf. Results were extrapolated to a wearing time of seven days. RESULTS: Sixty-six patients completed IPAQ-sf and wore the SWA over five days. Mean difference and limit of agreement between the IPAQ-sf and SWA including walking was 662 (±1719) min(.)wk(-1). When analyzing time spent in the different intensity levels separately, IPAQ-sf reported significantly higher levels of moderate (602 min(.)wk(-1), p = 0.001) and vigorous (60 min(.)wk(-1), p = 0.001) PA compared to SWA. CONCLUSIONS: Cancer patients participating in a lifestyle intervention during chemotherapy reported 366 % higher MVPA level from the past seven days using IPAQ-sf compared to objective measures. The IPAQ-sf appears insufficient when assessing PA level in cancer patients undergoing oncologic treatment. Activity monitors or other objective tools should alternatively be considered, when assessing PA in this population.

Individualized Comprehensive Lifestyle Intervention in Patients Undergoing Chemotherapy with Curative or Palliative Intent: Who Participates?

OBJECTIVE: Knowledge about determinants of participation in lifestyle interventions in cancer patients undergoing chemotherapy, particularly with palliative intent, remains poor. The objective of the present study was to identify determinants of participating in a 12 month individualized, comprehensive lifestyle intervention, focusing on diet, physical activity, mental stress and smoking cessation, in cancer patients receiving chemotherapy with curative or palliative intent. The secondary objective was to identify participation determinants 4 months into the study. METHODS: Newly diagnosed cancer patients starting chemotherapy at the cancer center in Kristiansand/Norway (during a 16 month inclusion period) were screened. Demographic and medical data (age, sex, body mass index, education level, marital status, smoking status, Eastern Cooperative Oncology Group performance status (ECOG), diagnosis, tumor stage and treatment intention) was analyzed for screened patients. RESULTS: 100 of 161 invited patients participated. There were more females (69 vs. 48%; P = 0.004), breast cancer patients (46 vs. 25%; P = 0.007), non-smokers (87 vs. 74%; P = 0.041), younger (mean age 60 vs. 67 yrs; P < 0.001) and fitter (82 vs. 64% with EGOC 0; P = 0.036) participants vs. non-participants included. In multivariate logistic regression analyses, age (Odds Ratio 0.94, 95% Confidence Interval 0.91, 0.97) and smoking (0.42, 0.18, 0.99) were negatively associated with participation. After 4 months, 63 participants were still participating. Cancer type, smoking and age increased the probability of dropping out. Multivariate logistic regression revealed that age was the only significant determinant of 4 month participation (0.95, 0.91, 0.99). Patients aged >70 years were less likely to participate at baseline and 4 months. CONCLUSION: Individualized lifestyle interventions in cancer patients undergoing chemotherapy appear to facilitate a high participation rate that declines with increasing age; both during the enrollment process and completing the intervention. Neither oncologic nor socioeconomic variables deterred participation.

Does in-house availability of multidisciplinary teams increase survival in upper gastrointestinal-cancer?

AIM: To investigate the effect of the establishment of in-house multidisciplinary team (MDT) availability (iMDTa) on survival in upper gastrointestinal cancer (UGI) patients. METHODS: In 2001, a cancer centre with irradiation and chemotherapy facilities was established in the Norwegian county of West Agder with a change of iMDTa (WA/MDT-Change). "iMDTa"-status was defined according to the availability of the necessary specialists within one institution on one campus, serving the population of one county. We compared survival rates during 2000-2008 for UGI patients living in counties with (MDT-Yes), without (MDT-No), with a mix (MDT-Mix) and WA/MDT-Change. Survival was calculated with Kaplan-Meier method. Cox model was used to uncover differences between counties with different MDT status when adjusted for age, sex and stage. RESULTS: We analyzed 395 patients from WA/MDT-Change and compared their survival to 12 135 UGI patients from four other Norwegian regions. Median overall survival for UGI patients in WA/MDT-Change increased from 129 to 300 d from 2000-2008, P = 0.001. The regions with the highest level of iMDTa achieved the largest decrease in risk of death for UGI cancers (compared to the county with MDT-Mix: MDT-Yes 11%, P < 0.05 and WA/MDT-Change 15%, P < 0.05). Analyzing the different tumour entities separately, patients living in the WA/MDT-Change county reached a statistically significant reduction in the risk of death [hazard ratios (HR)] compared to patients in the county with MDT-Mix for oesophageal and gastric, but not for pancreatic cancer. HR for the study period 2000-2004 are given first and then for the period 2005-2008: The HR for oesophageal cancers was reduced from [HR = 1.12; 95%CI: 0.75-1.68 to HR = 0.60, 95%CI: 0.38-0.95] and for gastric cancers from [HR = 0.87, 95%CI: 0.66-1.15 to HR = 0.63, 95%CI: 0.43-0.93], but not for pancreatic cancer [HR = 1.04-, 95%CI: 0.83-1.3 for 2000-2004 and HR = 1.01, 95%CI: 0.78-1.3 for 2005-2008]. UGI patients treated during the second study period in the county of WA/MDT-Change had a higher probability of receiving chemotherapy. In the first study period, only one out of 43 patients (2.4%, 95%CI: 0-6.9) received chemotherapy, compared to 18 of 42 patients diagnosed during 2005-2008 (42.9%, 95%CI: 28.0-57.8). CONCLUSION: Introduction of iMDTa led to a two-fold increase of UGI patients, whereas no increase in survival was found in the MDT-No or MDT-Mix counties.

Epithelial growth factor receptor (EGFR)-inhibition for relief of neuropathic pain-A case series.

Background Neuropathic pain remains a significant challenge with unsatisfactory therapeutic options. Its pathogenesis may involve the neuropathic triad of neuronal, glial and immune cells. Communication between these cells is possibly perpetuated by mitogen-activated protein kinase (MAPK)-signaling. For several years, we successfully treated a rectal cancer patient with the epithelial growth factor receptor (EGFR)-inhibitor cetuximab, for debilitating neuropathic pain due to progressive malignant invasion of the sacral plexus. Here, we report the effect of treatment with various EGFR-inhibitors in five additional patients with severe and long-standing, therapy-resistant neuropathic pain. Methods All patients had well-documented neuropathic pain syndromes with the following etiologies: inflammatory polyneuropathy, complex regional pain syndrome type 1, radiculopathy after failed back surgery, malignant invasion of the sacral plexus by bladder cancer, and phantom limb pain. All patients were given intravenous (extracellular) EGFR-inhibitors (cetuximab, panitumumab) initially, and switched to oral (intracellular) agents (gefitinib, erlotinib) after an analgesic effect was obtained. Results Four of the five patients responded, all within 24h of intravenous administration, with a mean decrease in worst pain from 9 to 1 on a 10-point scale. All four EGFR-inhibitors were effective. The clinical courses, including patient-reported pain relief, are prospectively documented with 78-219 days follow-up for those who responded to treatment. Toxicities were transient and manageable. Conclusions/implications EGFR-inhibition resulted in dramatic relief of neuropathic pain. A plausible biological explanation involves the interruption of MAPK-signaling. The role of EGFR-inhibition as a target for the treatment of neuropathic pain appears promising and warrants investigation.