Stage IV Colorectal Cancer Patients with High Risk Mutation Profiles Survived 16 Months Longer with Individualized Therapies.

Personalized treatment vs. standard of care is much debated, especially in clinical practice. Here we investigated whether overall survival differences in metastatic colorectal cancer patients are explained by tumor mutation profiles or by treatment differences in real clinical practice. Our retrospective study of metastatic colorectal cancer patients of confirmed European ancestry comprised 54 Americans and 54 gender-matched Germans. The Americans received standard of care, and on treatment failure, 35 patients received individualized treatments. The German patients received standard of care only. Tumor mutations, tumor mutation burden and microsatellite status were identified by using the FoundationOne assay or the IDT Pan-Cancer assay. High-risk patients were identified according to the mutational classification by Schell and colleagues. Results: Kaplan-Meier estimates show the high-risk patients to survive 16 months longer under individualized treatments than those under only standard of care, in the median (p < 0.001). Tumor mutation profiles stratify patients by risk groups but not by country. Conclusions: High-risk patients appear to survive significantly longer (p < 0.001) if they receive individualized treatments after the exhaustion of standard of care treatments. Secondly, the tumor mutation landscape in Americans and Germans is congruent and thus warrants the transatlantic exchange of successful treatment protocols and the harmonization of guidelines

Postdiagnostic physical activity, sleep duration, and TV watching and all-cause mortality among long-term colorectal cancer survivors: a prospective cohort study

Background: Lifestyle recommendations for cancer survivors are warranted to improve survival. In this study, we aimed to examine the association of total physical activity, different types of physical activity, hours of sleeping at day and night, and hours spent watching television (TV) with all-cause mortality in long-term colorectal cancer (CRC) survivors. Methods: We assessed physical activity in 1376 CRC survivors (44% women; median age, 69 years) at median 6 years after CRC diagnosis using a validated questionnaire. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) for all-cause mortality according to categories of physical activities, sleep duration, and TV watching. Results: During a median follow-up time of 7 years, 200 participants had died. Higher total physical activity was significantly associated with lower all-cause mortality (HR: 0.53; 95% CI: 0.36–0.80, 4th vs. 1st quartile). Specifically, sports, walking, and gardening showed a significant inverse association with all-cause mortality (HR: 0.34; 95% CI: 0.20–0.59, HR: 0.65; 95% CI: 0.43–1.00, and HR: 0.62; 95% CI: 0.42–0.91, respectively for highest versus lowest category). Individuals with ≥2 h of sleep during the day had a significantly increased risk of all-cause mortality compared to individuals with no sleep at day (HR: 2.22; 95% CI: 1.43–3.44). TV viewing of ≥4 h per day displayed a significant 45% (95% CI: 1.02–2.06) higher risk of dying compared to ≤2 h per day of watching TV. Conclusions: Physical activity was inversely related to all-cause mortality; specific activity types might be primarily responsible for this association. More hours of sleep during the day and a higher amount of TV viewing were each associated with higher all-cause mortality. Based on available evidence, it is reasonable to recommend CRC survivors to engage in regular physical activity. Electronic supplementary material The online version of this article (10.1186/s12885-017-3697-3) contains supplementary material, which is available to authorized users

Efficacy and Safety of an Everolimus- vs. a Mycophenolate Mofetil-Based Regimen in Pediatric Renal Transplant Recipients

<div><p>Introduction</p><p>Data on the efficacy and safety of everolimus in pediatric renal transplantation compared to other immunosuppressive regimens are scarce.</p><p>Patients/Methods</p><p>We therefore performed a multicenter, observational, matched cohort study over 4 years post-transplant in 35 patients on everolimus plus low-dose cyclosporine, who were matched (1:2) with a control group of 70 children receiving a standard-dose calcineurin-inhibitor- and mycophenolate mofetil-based regimen.</p><p>Results</p><p>Corticosteroids were withdrawn in 83% in the everolimus vs. 39% in the control group (p<0.001). Patient and graft survival were comparable. The rate of biopsy-proven acute rejection episodes Banff score ≥ IA during the first year post-transplant was 6% in the everolimus vs. 13% in the control group (p = 0.23). The rate of de novo donor-specific HLA antibodies (11% in everolimus, 18% in controls) was comparable (p = 0.55). At 4 years post-transplant, mean eGFR in the everolimus group was 56±33 ml/min per 1.73 m² vs. 63±22 ml/min per 1.73 m² in the control group (p = 0.14). Everolimus therapy was associated with less BK polyomavirus replication (3% vs. 17% in controls; p = 0.04), but with a higher percentage of arterial hypertension and more hyperlipidemia (p<0.001).</p><p>Conclusion</p><p>In pediatric renal transplantation, an everolimus-based regimen with low-dose cyclosporine yields comparable four year results as a standard regimen, but with a different side effect profile.</p></div

Patient characteristics at baseline.

<p>CMV, cytomegalovirus; HLA, human leukocyte antigen; RTx, renal transplantation: D, Donor; R, Recipient</p><p>(p calculated by t-test, Wilcoxon-test, chi-square-test or Fisher’s exact test).</p><p>*two sample t-test,</p><p>^#chi-square test,</p><p>^°Wilcoxon test,</p><p>^§Fisher’s exact test.</p><p>Patient characteristics at baseline.</p

Estimated glomerular filtration rate (eGFR) over the observation period of 4 years in the everolimus (EVR) group (n = 35 until year 2; n = 33 at year 3 and 4) and the control group (n = 70).

<p>Data are mean ± SD. BSA, body surface area.</p

Course of immunosuppressive therapy in the EVR group (a).

<p>CsA, cyclosporine; DSA, Donor Specific Antibodies; EVR, everolimus; BSA, body surface area;* Tx, transplantation; Pred, Prednisolone; TAC, tacrolimus; MMF, mycophenolate mofetil, PTLD, post transplant lymphoproliferative disease; CAMR, chronic antibody mediated rejection.</p

Results of indication biopsies during the first year post-transplant.

<p>CNI, calcineurin inhibitor; MPGN, membranoproliferative glomerulonephritis.</p><p>p values calculated by Fischer’s exact test. The respective numbers refer to number of patients. Acute Rejection Episodes (ARE) were defined as follows: (i) Biopsy-proven acute rejection episodes (BPAR) BANFF score ≥ IA on indication biopsy (11); (ii) BPAR including borderline findings on indication biopsy, which triggered anti-rejection therapy; (iii) over-all treated ARE (BPAR plus ARE, where a graft biopsy was either logistically not possible or medically contraindicated).</p><p>Results of indication biopsies during the first year post-transplant.</p

Immunosuppressive therapy (mean doses per day and corresponding trough levels).

<p>C₀, trough level; CsA, cyclosporine; EVR, everolimus; MMF, mycophenolate mofetil; TAC, tacrolimus</p><p>Immunosuppressive therapy (mean doses per day and corresponding trough levels).</p