MyHealth:specialist nurse-led follow-up in breast cancer. A randomized controlled trial - development and feasibility

Background: Traditionally, women treated for breast cancer (BC) have been followed up through regular oncologist-led visits in outpatient clinics, focusing on detection of recurrences, new primary BC, symptom management, and psychological support. However, this follow-up routine is expensive and its effectiveness has been questioned. Consequently, alternative follow-up programs have been tested. The Guided Self-Determination method (GSD), which facilitates partnership between health-care provider and patient, has been shown to improve self-management in patients with chronic conditions, including cancer. Patient-reported outcomes (PRO) is another increasingly used tool to improve patient–provider communication, symptom monitoring and control. In combination, GSD and PRO may have the potential to meet the objectives of BC follow-up. To test this, we developed the MyHealth study, a randomized controlled trial comparing a nurse-led follow-up program based on GSD, collection of PRO, and patient navigation with routine oncologist-led follow-up. Here we describe how we developed the intervention and are currently testing the feasibility of the MyHealth protocol in terms of recruitment, adherence to the intervention, collection of PRO, and patient navigation. Material and methods: We have invited the first 25 consecutively enrolled patients to test the MyHealth intervention. This consists of (1) 3–5 initial GSD appointments with a nurse, (2) collection of PRO, and (3) symptom management and patient navigation. The randomized trial was launched in January 2017 and is still recruiting. Results of the feasibility study: Of 32 patients invited, 25 accepted participation. At 18-month follow-up, two patients have withdrawn, 143 PRO questionnaires have been completed (mean 5.7/patient) resulting in 59 nurse contacts (mean 2.4 per patient) and 14 project physician contacts (mean 0.6 per patient). Conclusion: A high recruitment rate and response rate to PRO indicate that follow-up led by specialist nurses, based on collection of PRO is feasible and acceptable for patients treated for early stage BC. Trial registration:ClinicalTrials.gov identifier: NCT02949167.</p

Positron emission tomography/computed tomography and biomarkers for early treatment response evaluation in metastatic colon cancer

BACKGROUND. Treatment options for metastatic colon cancer (mCC) are widening. We prospectively evaluated serial 2-deoxy-2-[18F]fluoro-d-glucose positron-emission tomography/computed tomography (PET/CT) and measurements of tissue inhibitor of metalloproteinases-1 (TIMP-1), carcinoembryonic antigen (CEA), and liberated domain I of urokinase plasminogen activator receptor (uPAR(I)) for early assessment of treatment response in mCC patients. METHODS. Thirty-three mCC patients scheduled for first-line chemotherapy with capecitabine and oxaliplatin (CAPOX) and bevacizumab participated; 27 were evaluated by PET/CT before treatment, after one and four treatment series. Morphological and metabolic response was independently assessed according to Response Evaluation Criteria in Solid Tumors and European Organization for Research and Treatment of Cancer PET criteria. Plasma TIMP-1, plasma uPAR(I), and serum CEA were determined. RESULTS. Metabolic response after one treatment course predicted the ability of CAPOX and bevacizumab to induce morphological response after four treatment series with a sensitivity of 80%, specificity of 69%, and odds ratio of 13.9 (95% confidence interval [CI] 1.9; 182). Early metabolically stable or progressive disease was associated with shorter progression-free survival (hazard ratio [HR] = 3.2 [CI 1.3; 7.8]). Biomarker levels at early evaluation were associated with shorter OS (TIMP-1 per unit increase on a log-2-transformed ng/mL scale: HR = 2.6 [CI 1.4; 4.9]; uPAR(I) per 25 fmol/mL increase: HR = 1.5 [CI 1.1; 2.1]). CONCLUSION. This monocentric study demonstrated predictive value of early metabolic PET response and prognostic value of TIMP-1 and uPAR(I) levels in mCC treated with CAPOX and bevacizumab. Results support investigation of PET/CT, TIMP-1, and uPAR(I) guided early treatment adaptation in mCC

Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

<label>PURPOSE</label>We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.<label>PATIENTS AND METHODS</label>In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay.<label>RESULTS</label>Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22-5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months).<label>CONCLUSIONS</label>Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis

Tissue microRNAs as predictors of outcome in patients with metastatic colorectal cancer treated with first line Capecitabine and Oxaliplatin with or without Bevacizumab

PURPOSE: We tested the hypothesis that expression of microRNAs (miRNAs) in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX) in patients with metastatic colorectal cancer (mCRC). EXPERIMENTAL DESIGN: Patients with mCRC treated with first line CAPEOX and bevacizumab (CAPEOXBEV): screening (n = 212) and validation (n = 121) cohorts, or CAPEOX alone: control cohort (n = 127), were identified retrospectively and archival primary tumor samples were collected. Expression of 754 miRNAs was analyzed in the screening cohort using polymerase chain reaction (PCR) arrays and expression levels were related to time to disease progression (TTP) and overall survival (OS). Significant miRNAs from the screening study were analyzed in all three cohorts using custom PCR arrays. In situ hybridization (ISH) was done for selected miRNAs. RESULTS: In the screening study, 26 miRNAs were significantly correlated with outcome in multivariate analyses. Twenty-two miRNAs were selected for further study. Higher miR-664-3p expression and lower miR-455-5p expression were predictive of improved outcome in the CAPEOXBEV cohorts and showed a significant interaction with bevacizumab effectiveness. The effects were strongest for OS. Both miRNAs showed high expression in stromal cells. Higher expression of miR-196b-5p and miR-592 predicted improved outcome regardless of bevacizumab treatment, with similar effect estimates in all three cohorts. CONCLUSIONS: We have identified potentially predictive miRNAs for bevacizumab effectiveness and additional miRNAs that could be related to chemotherapy effectiveness or prognosis in patients with mCRC. Our findings need further validation in large cohorts, preferably from completed randomized trials

Kaplan-Meier survival curves showing the association between pre-treatment plasma YKL-40 (A), plasma IL-6 (B), and serum CA 19.9 (C) in patients with PC stage IIB and III.

<p>D shows the survival curves for 0–3 elevated biomarkers. The P-value refers to the log-rank test for equality of strata. Patients were dichotomized by the upper normal level for each biomarker.</p