Chronic fatigue in childhood cancer survivors is associated with lifestyle and psychosocial factors; a DCCSS LATER study.

BACKGROUND: The purpose of this study was to determine factors associated with chronic fatigue (CF) in childhood cancer survivors (CCS). PATIENTS AND METHODS: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS (≥5 years after diagnosis) and siblings as controls. Fatigue severity was assessed with the 'fatigue severity subscale' of the Checklist Individual Strength ('CIS-fatigue'). CF was defined as scoring ≥35 on the 'CIS-fatigue' and having fatigue symptoms for ≥6 months. Twenty-four parameters were assessed, categorized into assumed fatigue triggering, maintaining and moderating factors. Multivariable logistic regression analyses were carried out to investigate the association of these factors with CF. RESULTS: A total of 1927 CCS participated in the study (40.7% of invited cohort), of whom 23.6% reported CF (compared with 15.6% in sibling controls, P < 0.001). The following factors were associated with CF: obesity [versus healthy weight, odds ratio (OR) 1.93; 95% confidence interval (CI) 1.30-2.87], moderate physical inactivity (versus physical active, OR 2.36; 95% CI 1.67-3.34), poor sleep (yes versus no, OR 2.03; 95% CI 1.54-2.68), (sub)clinical anxiety (yes versus no, OR 1.55; 95% CI 1.10-2.19), (sub)clinical depression (yes versus no, OR 2.07; 95% CI 1.20-3.59), pain (continuous, OR 1.49; 95% CI 1.33-1.66), self-esteem (continuous, OR 0.95; 95% CI 0.92-0.98), helplessness (continuous, OR 1.13; 95% CI 1.08-1.19), social functioning (continuous, OR 0.98; 95% CI 0.97-0.99) and female sex (versus male sex, OR 1.79; 95% CI 1.36-2.37). CONCLUSION: CF is a prevalent symptom in CCS that is associated with several assumed maintaining factors, with lifestyle and psychosocial factors being the most prominent. These are modifiable factors and may therefore be beneficial to prevent or reduce CF in CCS.

Selecting a PRO-CTCAE-based subset for patient-reported symptom monitoring in prostate cancer patients: a modified Delphi procedure.

BACKGROUND: Clinician-based reporting of adverse events leads to underreporting and underestimation of the impact of adverse events on prostate cancer patients. Therefore, interest has grown in capturing adverse events directly from patients using the Patient-Reported Outcomes (PROs) version of the Common Terminology Criteria for Adverse Events (CTCAE). We aimed to develop a standardized PRO-CTCAE subset tailored to adverse event monitoring in prostate cancer patients. MATERIALS AND METHODS: We used a mixed-method approach based on the 'phase I guideline for developing questionnaire modules' by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life group, including a literature review, and interviews with patients (n = 30) and health care providers (HCPs, n = 16). A modified Delphi procedure was carried out to reach consensus on the final subset selected from the complete PRO-CTCAE item library. RESULTS: Fourteen multidisciplinary HCPs and 12 patients participated in the Delphi rounds. Ninety percent agreed on the final subset, consisting of: 'ability to achieve and maintain erection', 'decreased libido', 'inability to reach orgasm', 'urinary frequency', 'urinary urgency', 'urinary incontinence', 'painful urination', 'fecal incontinence', 'fatigue', 'hot flashes', 'feeling discouraged', 'sadness', and 'concentration'. From 16 articles identified in the literature review, the following adverse events for which no PRO-CTCAE items are available, were included to the recommendation section: 'nocturia', 'blood and/or mucus in stool', 'hemorrhoids', 'hematuria', 'cystitis', 'neuropathy', and 'proctitis'. CONCLUSIONS: The obtained PRO-CTCAE-subset can be used for multidisciplinary adverse event monitoring in prostate cancer care. The described method may guide development of future PRO-CTCAE subsets.

The impact of image acquisition time on registration, delineation and image quality for magnetic resonance guided radiotherapy of prostate cancer patients.

BACKGROUND AND PURPOSE: Magnetic resonance (MR) guided radiotherapy utilizes MR images for (online) plan adaptation and image guidance. The aim of this study was to investigate the impact of variation in MR acquisition time and scan resolution on image quality, interobserver variation in contouring and interobserver variation in registration. MATERIALS AND METHODS: Nine patients with prostate cancer were included. Four T2-weighted 3D turbo spin echo (T2w 3D TSE) sequences were acquired with different acquisition times and resolutions. Two radiologists assessed image quality, conspicuity of the capsule, peripheral zone and central gland architecture and motion artefacts on a 5 point scale. Images were delineated by two radiation oncologists and interobserver variation was assessed by the 95% Hausdorff distance. Seven observers registered the MR images on the planning CT. Registrations were compared on systematic offset and interobserver variation. RESULTS: Acquisition times ranged between 1.3 and 6.3 min. Overall image quality and capsule definition were significantly worse for the MR sequence with an acquisition time of 1.3 min compared to the other sequences. Median 95% Hausdorff distance showed no significant differences in interobserver variation of contouring. Systematic offset and interobserver variation in registration were small (<1 mm) and of no clinical significance. CONCLUSIONS: Our results can be used to effectively shorten overall fraction time for online adaptive MR guided radiotherapy by optimising the imaging sequence used for registration. From the sequences studied, a sequence of 3.1 min with anisotropic voxels of 1.2 × 1.2 × 2.4 mm3 provided the shortest acquisition time without compromising image quality.

Management of meningeal solitary fibrous tumors/hemangiopericytoma; surgery alone or surgery plus postoperative radiotherapy?

INTRODUCTION: A meningeal solitary fibrous tumor (SFT), also called hemangiopericytoma, is a rare mesenchymal malignancy. Due to anatomic constrains, even after macroscopic complete surgery with curative intent, the local relapse risk is still relatively high, thus increasing the risk of dedifferentiation and metastatic spread. This study aims to better define the role of postoperative radiotherapy (RT) in meningeal SFTs. PATIENTS AND METHODS: A retrospective study was performed across seven sarcoma centers. Clinical information was retrieved from all adult patients with meningeal primary localized SFT treated between 1990 and 2018 with surgery alone (S) compared to those that also received postoperative RT (S + RT). Differences in treatment characteristics between subgroups were tested using independent samples t-test for continuous variables and chi-square tests for proportions. Local control (LC) and overall survival (OS) rates were calculated as time from start of treatment until progression or death from any cause. LC and OS in groups receiving S or S + RT were compared using Kaplan-Meier survival curves. RESULTS: Among a total of 48 patients, 7 (15%) underwent S and 41 (85%) underwent S + RT. Median FU was 65 months. LC was significantly associated with treatment. LC after S at 60 months was 60% versus 90% after S + RT (p = 0.052). Furthermore, R1 resection status was significantly associated with worse LC (HR 4.08, p = 0.038). OS was predominantly associated with the mitotic count (HR 3.10, p = 0.011). CONCLUSION: This retrospective study, investigating postoperative RT in primary localized meningeal SFT patients, suggests that combining RT to surgery in the management of this patient population may reduce the risk for local failures.

Adjuvant chemotherapy is superior to chemoradiation after D2 surgery for gastric cancer in the per-protocol analysis of the randomized CRITICS trial.

BACKGROUND: The Intergroup 0116 and the MAGIC trials changed clinical practice for resectable gastric cancer in the Western world. In these trials, overall survival improved with post-operative chemoradiotherapy (CRT) and perioperative chemotherapy (CT). Intention-to-treat analysis in the CRITICS trial of post-operative CT or post-operative CRT did not show a survival difference. The current study reports on the per-protocol (PP) analysis of the CRITICS trial. PATIENTS AND METHODS: The CRITICS trial was a randomized, controlled trial in which 788 patients with stage Ib-Iva resectable gastric or esophagogastric adenocarcinoma were included. Before start of preoperative CT, patients from the Netherlands, Sweden and Denmark were randomly assigned to receive post-operative CT or CRT. For the current analysis, only patients who started their allocated post-operative treatment were included. Since it is uncertain that the two treatment arms are balanced in such PP analysis, adjusted proportional hazards regression analysis and inverse probability weighted analysis were used to minimize the risk of selection bias and to estimate and compare overall and event-free survival. RESULTS: Of the 788 patients, 478 started post-operative treatment according to protocol, 233 (59%) patients in the CT group and 245 (62%) patients in the CRT group. Patient and tumor characteristics between the groups before start of the post-operative treatment were not different. After a median follow-up of 6.7 years since the start of post-operative treatment, the 5-year overall survival was 57.9% (95% confidence interval: 51.4% to 64.3%) in the CT group versus 45.5% (95% confidence interval: 39.2% to 51.8%) in the CRT group (adjusted hazard ratio CRT versus CT: 1.62 (1.24-2.12), P = 0.0004). Inverse probability weighted analysis resulted in similar hazard ratios. CONCLUSION: After adjustment for all known confounding factors, the PP analysis of patients who started the allocated post-operative treatment in the CRITICS trial showed that the CT group had a significantly better 5-year overall survival than the CRT group (NCT00407186).

Treatment Variation of Sequential versus Concurrent Chemoradiotherapy in Stage III Non-Small Cell Lung Cancer Patients in the Netherlands and Belgium.

AIMS: Concurrent chemoradiotherapy (CCRT) is considered the standard treatment regimen in non-surgical locally advanced non-small cell lung cancer (NSCLC) patients and sequential chemoradiotherapy (SCRT) is recommended in patients who are unfit to receive CCRT or when the treatment volume is considered too large. In this study, we investigated the proportion of CCRT/SCRT in the Netherlands and Belgium. Furthermore, patient and disease characteristics associated with SCRT were assessed. MATERIALS AND METHODS: An observational study was carried out with data from three independent national registries: the Belgian Cancer Registry (BCR), the Netherlands Cancer Registry (NCR) and the Dutch Lung Cancer Audit-Radiotherapy (DLCA-R). Differences in patient and disease characteristics between CCRT and SCRT were tested with unpaired t-tests (for continuous variables) and with chi-square tests (for categorical variables). A prognostic model was constructed to determine patient and disease parameters predictive for the choice of SCRT. RESULTS: This study included 350 patients from the BCR, 780 patients from the NCR and 428 patients from the DLCA-R. More than half of the stage III NSCLC patients in the Netherlands (55%) and in Belgium more than a third (35%) were treated with CCRT. In both the Dutch and Belgian population, higher age and more advanced N-stage were significantly associated with SCRT. Performance score, pulmonary function, comorbidities and tumour volume were not associated with SCRT. CONCLUSION: In this observational population-based study, a large treatment variation in non-surgical stage III NSCLC patients was observed between and within the Netherlands and Belgium. Higher age and N-stage were significantly associated with the choice for SCRT.

Effectiveness of insulin therapy in people with Type 2 diabetes in the Hoorn Diabetes Care System.

AIMS: To identify HbA1c trajectories after the start of insulin treatment and to identify clinically applicable predictors of the response to insulin therapy. METHODS: The study population comprised 1203 people with Type 2 diabetes included in the Hoorn Diabetes Care System (n = 9849). Inclusion criteria were: age ≥ 40 years; initiation of insulin during follow-up after failure to reach HbA1c levels ≤ 53 mmol/mol (7%) with oral glucose-lowering agents; and a follow up ≥ 2 years after initiating insulin. Latent class growth modelling was used to identify trajectories of HbA1c . Subjects considered to be 'off target' had HbA1c levels ≥ 53 mmol/mol (7.0%) during one-third or more of the follow-up time, and those considered to be 'on target' had HbA1c levels ≥ 53 mmol/mol (7.0%) during less than one-third of the follow-up time. RESULTS: Four HbA1c trajectories were identified. Most people (88.7%) were classified as having a stable HbA1c trajectory of ~57 mmol/mol (7.4%). Only 24.4% of the people were on target in response to insulin; this was associated with lower HbA1c levels and a higher age at the start of insulin treatment. CONCLUSIONS: Using latent class growth modelling, four HbA1c trajectories were identified. A quarter of the people starting insulin were on target. Low HbA1c levels and advanced age at the start of insulin therapy were associated with better response to insulin therapy. Initiating insulin earlier improves the likelihood of achieving and sustaining glycaemic control.

Fasting proinsulin levels are significantly associated with 20 year cancer mortality rates. The Hoorn Study.

AIMS/HYPOTHESIS: Proinsulin is possibly associated with cancer through activation of insulin receptor isoform A. We sought to investigate the associations between proinsulin and 20 year cancer mortality rates. METHODS: The study was performed within the Hoorn Study, a population-based study of glucose metabolism in individuals aged 50-75 years in the Dutch population. Fasting proinsulin levels were measured twice by a double-antibody radioimmunoassay. Participants were continuously followed to register mortality; causes of death were derived from medical records. Cox survival analyses were performed to assess the 20 year risk of death from cancer in relation to proinsulin. All analyses were adjusted for age and sex, with additional adjustments for traditional risk factors. The effect modification of glucose metabolism and sex was tested. RESULTS: Proinsulin levels were measured in 438 individuals (41% normal glucose tolerance, 35.7% impaired glucose metabolism, 23.3% type 2 diabetes). Of these participants, 53 died from cancer. After adjustment for age and sex, proinsulin >16.5 pmol/l (the upper tertile) was significantly associated with a twofold risk of cancer mortality (HR 2.01, 95% CI 1.16, 3.46) compared with individuals with lower proinsulin levels. Additional adjustment for glucose metabolism, BMI and smoking did not substantially change the results (HR 1.91, 95% CI 1.04, 3.52). No interaction with glucose metabolism or sex was observed. CONCLUSIONS/INTERPRETATION: Individuals with fasting proinsulin levels >16.5 pmol/l have a twofold risk of cancer mortality over a 20 year time span. These findings provide population-based evidence for the independent association between high proinsulin levels and cancer mortality rates.