Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from ...clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.
Breast cancer (BC) patients have an increased risk of developing cancer therapy-related cardiac dysfunction (CTRCD) and cardiovascular morbidity, which seems to have a substantial prognostic impact. ...Oncologists, in collaboration with dedicated cardiologists, have the opportunity to perform cardiovascular risk stratification. Despite guideline recommendations, strategies to detect cardiac damage at an early stage are not structurally implemented in clinical practice. The perspectives of oncology professionals regarding cardiac surveillance in BC patients have not been qualitatively evaluated. We aim to explore the perceptions of oncology professionals regarding cardiac surveillance in BC patients and, more specifically, the influencing factors of delivering cardiac surveillance. A qualitative study with semi-structured interviews was conducted and thematically analyzed. Twelve oncology professionals participated in this study. Four themes were selected to answer the study objectives: (1) sense of urgency, (2) multidisciplinary collaboration, (3) patient burden, and (4) practical tools for cardiac surveillance. Most professionals did not feel the need to deliver cardiac surveillance as they considered the incidence of CTRCD as rare. Multidisciplinary collaboration was also perceived as unnecessary, and cardiac surveillance was considered disproportionately burdensome with respect to its benefits. Nevertheless, professionals affirmed the need for practical tools to deliver cardiac surveillance. Most professionals are currently unaware of CTRCD incidence and cardiac surveillance benefits. Encouraging multidisciplinary collaboration and improving their knowledge of cardiotoxic effects of treatments and possibility of early detection can lead to structured cardiac surveillance for breast cancer patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The prognosis of multiple myeloma (MM) patients who become refractory to lenalidomide and bortezomib is very poor, indicating the need for new therapeutic strategies for these patients. Next to the ...development of new drugs, the strategy of combining agents with synergistic activity may also result in clinical benefit for patients with advanced myeloma. We have previously shown in a retrospective analysis that lenalidomide combined with continuous low-dose cyclophosphamide and prednisone (REP) had remarkable activity in heavily pretreated, lenalidomide-refractory MM patients. To evaluate this combination prospectively, we initiated a phase 1/2 study to determine the optimal dose and to assess its efficacy and safety in lenalidomide-refractory MM patients. The maximum tolerated dose (MTD) was defined as 25 mg lenalidomide (days 1-21/28 days), combined with continuous cyclophosphamide (50 mg/d) and prednisone (20 mg/d). At the MTD (n = 67 patients), the overall response rate was 67%, and at least minimal response was achieved in 83% of the patients. Median progression-free survival and overall survival were 12.1 and 29.0 months, respectively. Similar results were achieved in the subset of patients with lenalidomide- and bortezomib-refractory disease as well as in patients with high-risk cytogenetic abnormalities, defined as t(4;14), t(14;16), del(17p), and/or ampl(1q) as assessed by fluorescence in situ hybridization. Neutropenia (22%) and thrombocytopenia (22%) were the most common grade 3-4 hematologic adverse events. Infections (21%) were the most common grade 3-5 nonhematologic adverse events. In conclusion, the addition of continuous low-dose oral cyclophosphamide to lenalidomide and prednisone offers a new therapeutic perspective for multidrug refractory MM patients. This trial was registered at www.clinicaltrials.gov as #NCT01352338.
•REP is an active combination in MM patients refractory to lenalidomide.•REP is an all-oral and generally well-tolerated regimen.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Childhood, adolescent, and young adult (CAYA) cancer survivors, at risk for late effects, including cancer-related fatigue, cardiovascular issues, and psychosocial challenges, may benefit ...from interventions stimulating behaviour adjustments. Three nurse-led eHealth interventions (REVIVER) delivered via video calls and elaborating on person-centred care, cognitive behaviour therapy and/or motivational interviewing were developed. These interventions target: 1) fatigue management, 2) healthier lifestyle behaviours, and 3) self-efficacy and self-management. This study aimed to assess the feasibility and potential effectiveness of the REVIVER interventions for CAYA cancer survivors and healthcare professionals. Methods In a single-group mixed methods design, CAYA cancer survivors aged 16-54, more than five years post-treatment, were enrolled. Feasibility, assessed via Bowen's outcomes for feasibility studies, included acceptability, practicality, integration and implementation, demand and adherence. Qualitative data from semi-structured interviews and a focus group interview with survivors and healthcare professionals supplemented the evaluation. Paired sample t-tests assessed changes in self-reported quality of life, fatigue, lifestyle, self-management, and self-efficacy at baseline (T0), post-intervention (T1), and 6-month follow-up (T2). Results The interventions and video consults were generally acceptable, practical, and successfully integrated and implemented. Success factors included the nurse consultant (i.e., communication, approach, and attitude) and the personalised approach. Barriers included sustainability concerns, technical issues, and short intervention duration. Regarding demand, 71.4%, 65.4%, and 100% of eligible CAYA cancer survivors engaged in the fatigue (N = 15), lifestyle (N = 17) and empowerment (N = 3) intervention, respectively, with 5, 5 and 2 participants interviewed, correspondingly. Low interest (demand) in the empowerment intervention (N = 3) and dropout rates of one-third for both fatigue and empowerment interventions were noted (adherence). Improvements in quality of life, fatigue (fatigue intervention), lifestyle (lifestyle intervention), self-efficacy, and self-management were evident among survivors who completed the fatigue and lifestyle interventions, with medium and large effect sizes observed immediately after the intervention and six months post-intervention. Conclusions Our study demonstrates the feasibility of nurse-led video coaching (REVIVER interventions) despite lower demand for the empowerment intervention and lower adherence to the fatigue and empowerment interventions. The medium and high effect sizes found for those who completed the interventions hold potential clinical significance for future studies investigating the effectiveness of the REVIVER interventions. Keywords: eHealth, Interventions, Cognitive behaviour therapy, Motivational interviewing, Person-centred care, CAYA cancer survivors, Fatigue, Lifestyle, Empowerment
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim of this study was to investigate the potential of 18F-FDG PET, diffusion weighted imaging (DWI) and susceptibility-weighted (T2*) MRI to predict response to systemic treatment in patients with ...colorectal liver metastases. The predictive values of pretreatment measurements and of early changes one week after start of therapy, were evaluated.
Imaging was performed prior to and one week after start of first line chemotherapy in 39 patients with colorectal liver metastases. 18F-FDG PET scans were performed on a PET/CT scanner and DWI and T2* were performed on a 1.5T MR scanner. The maximum standardized uptake values (SUV), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC) and T2* value were assessed in the same lesions. Up to 5 liver metastases per patient were analyzed. Outcome measures were progression free survival (PFS), overall survival (OS) and size response.
Pretreatment, high SUVmax, high TLG, low ADC and high T2* were associated with a shorter OS. Low pretreatment ADC value was associated with shorter PFS. After 1 week a significant drop in SUVmax and rise in ADC were observed. The drop in SUV was correlated with the rise in ADC (r=-0.58, p=0.002). Neither change in ADC nor in SUV was predictive of PFS or OS. T2* did not significantly change after start of treatment.
Pretreatment SUVmax, TLG, ADC, and T2* values in colorectal liver metastases are predictive of patient outcome. Despite sensitivity of DWI and 18F-FDG PET for early treatment effects, change in these parameters was not predictive of long term outcome.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
In order to understand the multidimensional mechanism of fear of cancer recurrence (FCR) and to identify potential targets for interventions, it is important to empirically test the ...theoretical model of FCR. This study aims at assessing the validity of Lee-Jones et al.’s FCR model.
Methods
A total of 1205 breast cancer survivors were invited to participate in this study. Participants received a questionnaire booklet including questionnaires on demographics and psychosocial variables including FCR. Data analysis consisted of the estimation of direct and indirect effects in mediator models.
Results
A total of 460 women (38 %) participated in the study. Median age was 55.8 years (range 32–87). Indirect effects of external and internal cues via FCR were found for all mediation models with limited planning for the future (
R
2
= .28) and body checking (
R
2
= .11–.15) as behavioral response variables, with the largest effects for limited planning for the future. A direct relation was found between feeling sick and seeking professional advice, not mediated by FCR.
Conclusions
In the first tested models of FCR, all internal and external cues were associated with higher FCR. In the models with limited planning for the future and body checking as behavioral response, an indirect effect of cues via FCR was found supporting the theoretical model of Lee-Jones et al.
Implications for Cancer Survivors
An evidence-based model of FCR may facilitate the development of appropriate interventions to manage FCR in breast cancer survivors.
Background
The awareness of cancer therapy–related adverse cardiac effects is fueled by recent literature on cardiotoxicity incidence and detection strategies. Although this influences the sense of ...urgency, in current practice, cardiotoxicity monitoring and treatment is not structurally performed. With this study, we aimed to evaluate current perspectives on cardio-oncology and to assess needs, ultimately to determine an agenda for improvements in current practice.
Material and methods
A national multidisciplinary 36-question survey was conducted. The survey was developed by a multidisciplinary team, theoretically based on an implementation checklist and distributed by email, through cardiology and oncology societies as well as social media.
Results
One hundred ninety professionals completed the survey, of which 66 were cardiologists, 66 radiation oncologists, and 58 medical oncologists and hematologists. Many professionals were unaware of their specialisms’ cardio-oncology guidelines: 62.1% of cardiologists and 29.3% of the hematologists and medical oncologists respectively. Many cardiologists (
N
= 46; 69.7%), radiation oncologists (
N
= 45; 68.2%), and hematologists and medical oncologists (
N
= 38; 65.5%) expressed that they did not have sufficient knowledge to treat cardio-oncology patients and would either refer a patient or aspire to gain more knowledge on the topic.
Conclusion
The field of cardio-oncology is advancing rapidly, with progress in stratification and detection strategies leading to the development of new guidelines and consensus statements. However, the application of these guidelines in current practice appears to be lagging. Professionals express a need for additional training and a practical guideline including risk stratification, monitoring, and treatment strategies. Multidisciplinary discussion and consensus on cardio-oncology care is vital to improve implementation of cardio-oncology guidelines, ultimately to improve cardiac care for oncology patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Impairment of cognitive functioning has been reported in several studies in patients treated with chemotherapy. So far, no studies have been published on the effects of the vascular endothelial ...growth factor receptor (VEGFR) inhibitors on cognitive functioning. We investigated the objective and subjective cognitive function of patients during treatment with VEGFR tyrosine kinase inhibitors (VEGFR TKI).
Three groups of participants, matched on age, sex and education, were enrolled; 1. metastatic renal cell cancer (mRCC) or GIST patients treated with sunitinib or sorafenib (VEGFR TKI patients n = 30); 2. patients with mRCC not receiving systemic treatment (patient controls n = 20); 3. healthy controls (n = 30). Sixteen neuropsychological tests examining the main cognitive domains (intelligence, memory, attention and concentration, executive functions and abstract reasoning) were administered by a neuropsychologist. Four questionnaires were used to assess subjective cognitive complaints, mood, fatigue and psychological wellbeing.
No significant differences in mean age, sex distribution, education level or IQ were found between the three groups. Both patient groups performed significantly worse on the cognitive domains Learning & Memory and Executive Functions (Response Generation and Problem Solving) compared to healthy controls. However only the VEGFR TKI patients showed impairments on the Executive subdomain Response Generation. Effect sizes of cognitive dysfunction in patients using VEGFR TKI were larger on the domains Learning & Memory and Executive Functions, compared to patient controls. Both patients groups performed on the domain Attention & Concentration the same as the healthy controls. Longer duration of treatment on VEGFR TKI was associated with a worse score on Working Memory tasks.
Our data suggest that treatment with VEGFR TKI has a negative impact on cognitive functioning, specifically on Learning & Memory, and Executive Functioning. We propose that patients who are treated with VEGFR TKI are monitored and informed for possible signs or symptoms associated with cognitive impairment.
ClinicalTrials.gov Identifier: NCT01246843.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Survival rates determined at diagnosis are often too negative for cancer survivors. Conditional relative survival reflects actual prognosis during follow-up better. Data from all 54,015 patients ...newly diagnosed in the Netherlands with B-cell non-Hodgkin lymphoma during 1989-2008, aged 15-89 years (Netherlands Cancer Registry), were used. Five-year conditional relative survival was computed for every additional year of survival up to 16 years after diagnosis, according to entity, grade, gender, age, and Ann Arbor stage. The prognosis for survivors of indolent B-cell non-Hodgkin lymphoma improved slightly with each additional year survived up to 91%. For patients with aggressive non-Hodgkin lymphoma conditional relative survival improved strongly during the first year after diagnosis (from 48% to 68%) and gradually thereafter to 93% after 16 years. There were differences between morphological entities. Initial differences in conditional relative survival at diagnosis between groups with different disease stages became smaller with increasing number of years survived. Age remained a prognostic indicator, also after prolonged follow-up. These results help caregivers to plan optimal surveillance and inform patients about their actual prognosis during follow-up. Long-lasting excess mortality among patients with B-cell non-Hodgkin lymphoma indicates the need for additional care long after their diagnosis.
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