Impact of Primary Tumor Location on Demographics, Resectability, Outcomes, and Quality of Life in Finnish Metastatic Colorectal Cancer Patients (Subgroup Analysis of the RAXO Study).

The primary tumor location (PTL) is associated with the phenotype, metastatic sites, mutations, and outcomes of metastatic colorectal cancer (mCRC) patients, but this has mostly been studied according to sidedness (right vs. left sided). We studied right colon vs. left colon vs. rectal PTL in a real-life study population (n = 1080). Health-related quality of life (HRQoL) was assessed multi-cross-sectionally with QLQ-C30, QLQ-CR29, EQ-5D, and 15D. A chi-square, Kaplan-Meier, and Cox regression were used to compare the groups. The PTL was in the right colon in 310 patients (29%), the left colon in 396 patients (37%), and the rectum in 375 patients (35%). The PTL was associated with distinct differences in metastatic sites during the disease trajectory. The resectability, conversion, and resection rates were lowest in the right colon, followed by the rectum, and were highest in the left colon. Overall survival was shortest for right colon compared with left colon or rectal PTL (median 21 vs. 35 vs. 36 months), with the same trends after metastasectomy or systemic therapy only. PTL also remained statistically significant in a multivariable model. The distribution of symptoms varied according to PTL, especially between the right colon (with general symptoms of metastases) and rectal PTL (with sexual- and bowel-related symptoms). mCRC, according to PTL, behaves differently regarding metastatic sites, resectability of the metastases, outcomes of treatment, and HRQoL.

Resectability, Resections, Survival Outcomes, and Quality of Life in Older Adult Patients with Metastatic Colorectal Cancer (the RAXO-Study).

Older adults are underrepresented in metastatic colorectal cancer (mCRC) studies and thus may not receive optimal treatment, especially not metastasectomies. The prospective Finnish real-life RAXO-study included 1086 any organ mCRC patients. We assessed repeated centralized resectability, overall survival (OS), and quality of life (QoL) using 15D and EORTC QLQ-C30/CR29. Older adults (>75 years; n = 181, 17%) had worse ECOG performance status than adults (<75 years, n = 905, 83%), and their metastases were less likely upfront resectable. The local hospitals underestimated resectability in 48% of older adults and in 34% of adults compared with the centralized multidisciplinary team (MDT) evaluation (p < 0.001). The older adults compared with adults were less likely to undergo curative-intent R0/1-resection (19% vs. 32%), but when resection was achieved, OS was not significantly different (HR 1.54 [CI 95% 0.9-2.6]; 5-year OS-rate 58% vs. 67%). 'Systemic therapy only' patients had no age-related survival differences. QoL was similar in older adults and adults during curative treatment phase (15D 0.882-0.959/0.872-0.907 [scale 0-1]; GHS 62-94/68-79 [scale 0-100], respectively). Complete curative-intent resection of mCRC leads to excellent survival and QoL even in older adults. Older adults with mCRC should be actively evaluated by a specialized MDT and offered surgical or local ablative treatment whenever possible.

Higher number of steps and breaks during sedentary behaviour are associated with better lipid profiles.

BACKGROUND: Physical activity (PA) is known to be associated with lipid profiles and the risk of both cardiovascular diseases and cancer. The aim of this study was to evaluate the association of objectively measured PA, sedentary behaviour (SB), amount of breaks during SB and number of daily steps with serum lipids in a healthy, Finnish, middle-aged, female population. METHODS: The participants (571) were recruited at mammography screening, target group was women aged 50-60 years. A measurement of PA was done with accelerometer, blood lipid profile was assessed, and questionnaires of participants characteristics were sent to participants. RESULTS: The participants with the highest number of daily breaks during SB (≥ 41) had the highest mean concentration of HDL-cholesterol (high density lipoprotein cholesterol, HDL-c) (1.9 mmol/l, standard deviation (SD) 0.4) and the lowest mean concentration of triglycerides (1.0 mmol/l, SD 0.5). HDL-c level was 0.16 mmol/l higher (p < 0.001) in the group with 28-40.9 breaks/day and 0.25 mmol/l higher (p < 0.001) among participants with ≥41 breaks/day than in the group with the fewest breaks during SB (< 28). Those with the most daily steps (≥ 9100) had the highest mean HDL-c level (1.9 mmol/l). HDL-c level was 0.16 mmol/l higher (p < 0.001) among the participants with 5600-9099 steps/day and 0.26 mmol/l higher (p < 0.001) among participants with ≥9100 steps/day than those with the fewest steps (< 5600). The number of daily steps was inversely associated with the triglyceride concentration. From wake-time, participants spent 60% in SB, 18% standing, 14% in light PA, and 9% in moderate-to-vigorous PA (MVPA). PA was associated with serum total cholesterol (TC), HDL-c and triglyceride levels. The mean HDL-c level was the highest in the lowest quartile of SB and in the highest quartile of MVPA. CONCLUSIONS: To our knowledge, this is the first study showing a high number of objectively measured breaks during SB is associated with a favourable effect on the level of serum lipids, which may later translate into cardiovascular health among middle-aged women. TRIAL REGISTRATION: This study was registered and approved by the Regional Ethics Committee of Tampere University Hospital in Finland (approval code R15137 ).

High baseline Tie1 level predicts poor survival in metastatic breast cancer.

BACKGROUND: Angiopoietin growth factors (Angs) regulate angiogenesis and lymphangiogenesis by binding to the endothelial Tie2 receptor. Ang2 expression is elevated in tissue hypoxia and inflammation, which also induce cleavage of the extracellular domain of the orphan Tie1 receptor. Here we have examined if the concentrations of Ang2 and the soluble extracellular domain of Tie1 in patient plasma are associated with the prognosis of patients with metastatic breast cancer. METHODS: Plasma Tie1 and Ang2 levels were measured in metastatic breast cancer patients treated in a phase II trial with a taxane-bevacizumab combination chemotherapy in the first-line treatment setting. They were analyzed before treatment, after 6 weeks and 6 months of treatment, and at the final study visit. Using the median concentrations as cutoffs, Tie1 and Ang2 data were dichotomized into low and high concentration groups. Additionally, we analyzed Tie1 concentrations in plasma from 10 healthy women participating in a breast cancer primary prevention study. RESULTS: Plasma samples were available from 58 (89%) of the 65 patients treated in the trial. The baseline Tie1 levels of the healthy controls were significantly lower than those of the metastatic patients (p < 0.001). The overall survival of the patients with a high baseline Tie1 level was significantly shorter (multivariate HR 3.07, 95% CI 1.39-6.79, p = 0.005). Additionally, the progression-free survival was shorter for patients with a high baseline Tie1 level (multivariate HR 3.78, 95% CI 1.57-9.09, p = 0.003). In contrast, the baseline Ang2 levels had no prognostic impact in a multivariate Cox proportional hazard regression analysis. The combined analysis of baseline Tie1 and Ang2 levels revealed that patients with both high Tie1 and high Ang2 baseline levels had a significantly shorter overall survival than the patients with low baseline levels of both markers (multivariate HR for overall survival 4.32, 95% CI 1.44-12.94, p = 0.009). CONCLUSIONS: This is the first study to demonstrate the prognostic value of baseline Tie1 plasma concentration in patients with metastatic breast cancer. Combined with the results of the Ang2 analyses, the patients with both high Tie1 and Ang2 levels before treatment had the poorest survival. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00979641, registration date 19-DEC-2008. The regional Ethics Committee: R08142M, registration date 18-NOV-2008.

Life with an unwelcome guest - caring in a context of protracted bodily pain.

Protracted bodily pain is a phenomenon that often affects a human being's whole life. Care of human beings with protracted pain is challenging because pain is not always measureable, and the experiences of pain are subjective, unique and shapeshifting. Therefore, the aim is to highlight what protracted bodily pain signifies for the human being, and human beings' experiences of what is caring in a context of protracted bodily pain. Four informants with protracted bodily pain took part in a focus group interview. The interview was analysed by using a qualitative content analysis with a hermeneutic approach. The findings show that protracted pain renders human beings speechless, limits and robs them of their lives. The pain is described as a domineering, unpleasant and unwelcome guest. The pain can change the human being's personality and creates feelings of guilt. Uncertainty about the origin of the pain as well as a nonchalant treatment or not being believed intensifies the pain. Human being experience mastering the pain, encounters with caregivers who can ease the burden, community with others and finding that little something extra in everyday life is experienced as caring. From a caring science perspective, the relation between protracted pain and suffering is obvious. Suffering emerges as illness suffering, as life suffering and as suffering caused by care. Professional as well as natural caring is important in a context of protracted bodily pain. The human being longs to encounter caregivers who are courageous enough to lay themselves on the line. Community with people who are prepared to share the burden eases the heavy burden that pain brings to life, it brings hope and relief.