Increased numbers of small circulating endothelial cells in renal cell cancer patients treated with sunitinib

Mature circulating endothelial cell (CEC) as well as endothelial progenitor populations may reflect the activity of anti-angiogenic agents on tumor neovasculature or even constitute a target for anti-angiogenic therapy. We investigated the behavior of CECs in parallel with hematopoietic progenitor cells (HPCs) in the blood of renal cell cancer patients during sunitinib treatment. We analyzed the kinetics of a specific population of small VEGFR2-expressing CECs (CD45(neg)/CD34(bright)), HPCs (CD45(dim)/CD34(bright)), and monocytes in the blood of 24 renal cell cancer (RCC) patients receiving 50 mg/day of the multitargeted VEGF inhibitor sunitinib, on a 4-week-on/2-week-off schedule. Blood was taken before treatment (C1D1), on C1D14, C1D28, and on C2D1 before the start of cycle 2. Also plasma VEGF and erythropoietin (EPO) were determined. Remarkably, while CD34(bright) HPCs and monocytes decreased during treatment, CD34(bright) CECs increased from 69 cells/ml (C1D1) to 180 cells/ml (C1D14; P = 0.001) and remained high on C1D28. All cell populations recovered to near pre-treatment levels on C2D1. Plasma VEGF and EPO levels were increased on C1D14 and partly normalized to pre-treatment levels on C2D1. In conclusion, opposite kinetics of two circulating CD34(bright) cell populations, HPCs and small CECs, were observed in sunitinib-treated RCC patients. The increase in CECs is likely caused by sunitinib targeting of immature tumor vessel

The Prospective Dutch Colorectal Cancer (PLCRC) cohort: real-world data facilitating research and clinical care

Real-world data (RWD) sources are important to advance clinical oncology research and evaluate treatments in daily practice. Since 2013, the Prospective Dutch Colorectal Cancer (PLCRC) cohort, linked to the Netherlands Cancer Registry, serves as an infrastructure for scientific research collecting additional patient-reported outcomes (PRO) and biospecimens. Here we report on cohort developments and investigate to what extent PLCRC reflects the “real-world”. Clinical and demographic characteristics of PLCRC participants were compared with the general Dutch CRC population (n = 74,692, Dutch-ref). To study representativeness, standardized differences between PLCRC and Dutch-ref were calculated, and logistic regression models were evaluated on their ability to distinguish cohort participants from the Dutch-ref (AU-ROC 0.5 = preferred, implying participation independent of patient characteristics). Stratified analyses by stage and time-period (2013–2016 and 2017–Aug 2019) were performed to study the evolution towards RWD. In August 2019, 5744 patients were enrolled. Enrollment increased steeply, from 129 participants (1 hospital) in 2013 to 2136 (50 of 75 Dutch hospitals) in 2018. Low AU-ROC (0.65, 95% CI: 0.64–0.65) indicates limited ability to distinguish cohort participants from the Dutch-ref. Characteristics that remained imbalanced in the period 2017–Aug’19 compared with the Dutch-ref were age (65.0 years in PLCRC, 69.3 in the Dutch-ref) and tumor stage (40% stage-III in PLCRC, 30% in the Dutch-ref). PLCRC approaches to represent the Dutch CRC population and will ultimately meet the current demand for high-quality RWD. Efforts are ongoing to improve multidisciplinary recruitment which will further enhance PLCRC’s representativeness and its contribution to a learning healthcare system

Indicators for Enteral Nutrition Use and Prophylactic Percutaneous Endoscopic Gastrostomy Placement in Patients With Head and Neck Cancer Undergoing Chemoradiotherapy

BACKGROUND: Chemoradiotherapy (CRT) is a major risk factor for malnutrition and dehydration in patients with head and neck cancer. Enteral support is often needed, and a percutaneous endoscopic gastrostomy (PEG) is frequently placed. Specific indicators for PEG placement remain unclear. This study retrospectively determined which factors contributed to enteral nutrition (EN) use and PEG placement in a large patient group to gain insight on potential indicators for PEG placement protocol creation. METHODS: A retrospective chart review of 240 patients with head and neck cancer who underwent CRT in 2012-2015 was conducted. Lifestyle, oncological, treatment, and nutrition outcome characteristics were examined and compared between patients who used EN and those who did not, as well as between patients who received a PEG and those who did not. RESULTS: In total, 195 patients used EN (via PEG or nasogastric tube). Multivariate analysis showed that nodal disease presence ( P = .01) and bilateral neck irradiation ( P = .01) were significantly related to EN use while increased age ( P = .01), nodal disease presence ( P = .02), reconstruction extent other than primary closure ( P = .02), bilateral neck irradiation ( P < .01), and an adapted intake consistency prior to treatment ( P = .03) were significantly related to PEG placement. CONCLUSION: Important factors for EN usage and PEG placement consideration include nodal disease and planned bilateral neck irradiation. Results from this study in combination with existing literature can be taken into consideration in the design of a PEG placement protocol. A better understanding of predictive indicators to PEG placement should be explored in further prospective studies

Trajectories of health-related quality of life and psychological distress in patients with colorectal cancer: A population-based study

Background: The aim of this nationwide cohort study was to examine the course of symptoms and trajectories of health-related quality of life (HR-QoL) and psychological distress during follow-up and to identify vulnerable patients. Methods: Patients with pathological stage I–III colorectal cancer (CRC) between 2013 and 2018 were included. Baseline characteristics were collected from the Netherlands Cancer Registry, and patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30/CR29, Hospital Anxiety and Depression Scale and low anterior resection syndrome (LARS) questionnaires at the baseline and subsequently at 3, 6, 12, 18 and 24 months. Latent class growth and multinomial logistic regression analyses were performed to outline 24-month trajectories in HR-QoL and distress and to identify predictive factors. Results:: A total of 1535 patients with colon cancer or rectal cancer were included. Trajectory analysis of HR-QoL identified three patient classes: high HR-QoL (62.7%), improving HR-QoL (29.0%) and low HR-QoL (8.3%). The following patient groups were identified with having low distress (64.0%), moderate distress (26.9%) and high distress (9.1%). Around 13% of the total cohort had either persistent low HR-QoL or high psychological distress throughout follow-up. Patients belonging to this vulnerable group were significantly more likely to be female, to be younger aged, to have lower education, to have disease stage II–III or to have major LARS. Conclusions: Although most patients treated for stage I–III CRC fared well, a small but significant proportion of around 13% did not recover during follow-up and reported low HR-QoL and/or high psychological distress levels throughout. This study's findings should be taken into account when organising and selecting patients for tailored follow-up

Physical Activity Is Associated with Improved Overall Survival among Patients with Metastatic Colorectal Cancer

Regular physical activity (PA) is associated with improved overall survival (OS) in stage I-III colorectal cancer (CRC) patients. This association is less defined in patients with metastatic CRC (mCRC). We therefore conducted a study in mCRC patients participating in the Prospective Dutch Colorectal Cancer cohort. PA was assessed with the validated SQUASH questionnaire, filled-in within a maximum of 60 days after diagnosis of mCRC. PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week. American College of Sports and Medicine (ACSM) PA guideline adherence, tertiles of moderate to vigorous PA (MVPA), and sport and leisure time MVPA (MVPA-SL) were assessed as well. Vital status was obtained from the municipal population registry. Cox proportional-hazards models were used to study the association between PA determinants and all-cause mortality adjusted for prognostic patient and treatment-related factors. In total, 293 mCRC patients (mean age 62.9±10.6 years, 67% male) were included in the analysis. Compared to low levels, moderate and high levels of MET-hours were significantly associated with longer OS (fully adjusted hazard ratios: 0.491, (95% CI 0.299-0.807, p value=0.005) and 0.485 (95% CI 0.303-0.778, p value=0.003), respectively), as were high levels of MVPA (0.476 (95% CI 0.278-0.816, p value=0.007)) and MVPA-SL (0.389 (95% CI 0.224-0.677, p value<0.001)), and adherence to ACSM PA guidelines compared to non-adherence (0.629 (95% CI 0.412-0.961, p value=0.032)). The present study provides evidence that higher PA levels at diagnosis of mCRC are associated with longer OS

Physical Activity Is Associated with Improved Overall Survival among Patients with Metastatic Colorectal Cancer

SIMPLE SUMMARY: Physical activity is linked to longer survival among non-metastasized colorectal cancer patients. It is unclear if physical activity is also beneficial for survival among patients with metastatic colorectal cancer. We researched this question in our study of 293 patients with metastatic colorectal cancer. We found that participants who reported higher levels of physical activity at diagnosis lived longer compared to patients who reported low activity levels. Furthermore, adherence to the physical activity guidelines for cancer survivors was related to prolonged survival. Our findings suggest that patients with metastatic colorectal cancer also benefit from being physically active. Future studies are needed to investigate whether improving exercise levels after diagnosis of metastasis is also beneficial and what kind of exercise interventions are most optimal for possibly improving survival time of patients with metastatic colorectal cancer. ABSTRACT: Regular physical activity (PA) is associated with improved overall survival (OS) in stage I–III colorectal cancer (CRC) patients. This association is less defined in patients with metastatic CRC (mCRC). We therefore conducted a study in mCRC patients participating in the Prospective Dutch Colorectal Cancer cohort. PA was assessed with the validated SQUASH questionnaire, filled-in within a maximum of 60 days after diagnosis of mCRC. PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week. American College of Sports and Medicine (ACSM) PA guideline adherence, tertiles of moderate to vigorous PA (MVPA), and sport and leisure time MVPA (MVPA-SL) were assessed as well. Vital status was obtained from the municipal population registry. Cox proportional-hazards models were used to study the association between PA determinants and all-cause mortality adjusted for prognostic patient and treatment-related factors. In total, 293 mCRC patients (mean age 62.9 ± 10.6 years, 67% male) were included in the analysis. Compared to low levels, moderate and high levels of MET-hours were significantly associated with longer OS (fully adjusted hazard ratios: 0.491, (95% CI 0.299–0.807, p value = 0.005) and 0.485 (95% CI 0.303–0.778, p value = 0.003), respectively), as were high levels of MVPA (0.476 (95% CI 0.278–0.816, p value = 0.007)) and MVPA-SL (0.389 (95% CI 0.224–0.677, p value < 0.001)), and adherence to ACSM PA guidelines compared to non-adherence (0.629 (95% CI 0.412–0.961, p value = 0.032)). The present study provides evidence that higher PA levels at diagnosis of mCRC are associated with longer OS

Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): Study protocol for a trial within a cohort study

Background: Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recurrent disease. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces the risk of recurrence in these patients. Methods/design: MEDOCC-CrEATE follows the 'trial within cohorts' (TwiCs) design. Patients with colorectal cancer (CRC) are included in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) and give informed consent for collection of clinical data, tissue and blood samples, and consent for future randomization. MEDOCC-CrEATE is a subcohort within PLCRC consisting of 1320 stage II CC patients without indication for ACT according to current guidelines, who are randomized 1:1 into an experimental and a control arm. In the experimental arm, post-surgery blood samples and tissue are analyzed for tissue-informed detection of plasma ctDNA, using the PGDx elio™ platform. Patients with detectable ctDNA will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin while patients without detectable ctDNA and patients in the control group will standard follow-up according to guideline. The primary endpoint is the proportion of patients receiving ACT when ctDNA is detectable after resection. The main secondary outcome is 2-year recurrence rate (RR), but also includes 5-year RR, disease free survival, overall survival, time to recurrence, quality of life and cost-effectiveness. Data will be analyzed by intention to treat. Discussion: The MEDOCC-CrEATE trial will provide insight into the willingness of stage II CC patients to be treated with ACT guided by ctDNA biomarker testing and whether ACT will prevent recurrences in a high-risk population. Use of the TwiCs design provides the opportunity to randomize patients before ctDNA measurement, avoiding ethical dilemmas of ctDNA status disclosure in the control group. Trial registration: Netherlands Trial Register: NL6281/NTR6455. Registered 18 May 2017, https://www.trialregister.nl/trial/628

The Prospective Dutch Colorectal Cancer (PLCRC) cohort: real-world data facilitating research and clinical care

Real-world data (RWD) sources are important to advance clinical oncology research and evaluate treatments in daily practice. Since 2013, the Prospective Dutch Colorectal Cancer (PLCRC) cohort, linked to the Netherlands Cancer Registry, serves as an infrastructure for scientific research collecting additional patient-reported outcomes (PRO) and biospecimens. Here we report on cohort developments and investigate to what extent PLCRC reflects the “real-world”. Clinical and demographic characteristics of PLCRC participants were compared with the general Dutch CRC population (n = 74,692, Dutch-ref). To study representativeness, standardized differences between PLCRC and Dutch-ref were calculated, and logistic regression models were evaluated on their ability to distinguish cohort participants from the Dutch-ref (AU-ROC 0.5 = preferred, implying participation independent of patient characteristics). Stratified analyses by stage and time-period (2013–2016 and 2017–Aug 2019) were performed to study the evolution towards RWD. In August 2019, 5744 patients were enrolled. Enrollment increased steeply, from 129 participants (1 hospital) in 2013 to 2136 (50 of 75 Dutch hospitals) in 2018. Low AU-ROC (0.65, 95% CI: 0.64–0.65) indicates limited ability to distinguish cohort participants from the Dutch-ref. Characteristics that remained imbalanced in the period 2017–Aug’19 compared with the Dutch-ref were age (65.0 years in PLCRC, 69.3 in the Dutch-ref) and tumor stage (40% stage-III in PLCRC, 30% in the Dutch-ref). PLCRC approaches to represent the Dutch CRC population and will ultimately meet the current demand for high-quality RWD. Efforts are ongoing to improve multidisciplinary recruitment which will further enhance PLCRC’s representativeness and its contribution to a learning healthcare system