...treatment decisions have been derived from small phase 2 studies,1 or from results of phase 3 randomised studies that included patients with adenocarcinoma histology or a mix of both ...histologies.2,3 In those trials, patients with squamous cell carcinoma consistently had inferior survival outcomes compared with those with adenocarcinoma.4 The randomised KEYNOTE-181 and ATTRACTION-3, trials have led to important changes in the treatment landscape with the introduction of PD-1 inhibitors. In the KEYNOTE-181 trial, although second-line treatment with pembrolizumab did not show improvement of survival in the whole population—including both squamous and adenocarcinomas—when compared with chemotherapy, a significant benefit was found in patients whose tumour had a PD-L1 combined positive score of ten or higher, and this difference was mainly due to squamous cell carcinomas.5 ATTRACTION-3 reported a significant survival benefit in second-line treatment with nivolumab compared with chemotherapy in patients with squamous cell carcinoma who were mainly from Asia.6 The ESCORT study7 adds to this body of evidence, showing that camrelizumab improves survival in patients (in China) with squamous cell carcinoma compared with the investigator's choice of chemotherapy, irrespective of PDL-L1 expression on tumour cells. Unfortunately, microsatellite instability and Epstein-Barr-virus positivity—two of the most consistent predictors for response to checkpoint inhibition in oesophagogastric cancer—are almost absent in patients with squamous cell carcinomas.9 In fact, in addition to novel biomarkers reflecting tumour biology, biomarkers that characterise the tumour host, such as patients' gut microbiome composition, might be as relevant to explore.
A diagnosis of advanced cancer can be described as an unexpected disruption of someone’s life story, an experience of contingency.1 To address an experience of contingency, a new sense of direction ...and coherence in life needs to be found. One’s story of life needs to be rewritten, which requires creative thinking. This process may be supported by a specific art-perception method: Art-Based Learning. Art-Based Learning is a step-wise process of observing an artwork, creating a new narrative related to this artwork, and connecting this narrative to the personal situation.2 Art-Based Learning is designed to stimulate creative thinking through four steps: 1. Formulation of a personal question. 2. Observation of details of an artwork. 3. Imagination of a story based on the artwork. 4. Sharing the art-perception experience and reflection on the link with the personal question with a fellow participant. We aimed to explore how persons with advanced cancer could benefit from Art-Based Learning to deal with contingency experiences and stimulate meaning-making.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundance of stroma. Multiple molecular classification efforts have identified a mesenchymal tumor subtype that is consistently ...characterized by high‐grade growth and poor clinical outcome. The relation between PDAC stroma and tumor subtypes is still unclear. Here, we aimed to identify how PDAC cells instruct the main cellular component of stroma, the pancreatic stellate cells (PSCs). We found in primary tissue that high‐grade PDAC had reduced collagen deposition compared to low‐grade PDAC. Xenografts and organotypic co‐cultures established from mesenchymal‐like PDAC cells featured reduced collagen and activated PSC content. Medium transfer experiments using a large set of PDAC cell lines revealed that mesenchymal‐like PDAC cells consistently downregulated ACTA2 and COL1A1 expression in PSCs and reduced proliferation. We identified colony‐stimulating factor 1 as the mesenchymal PDAC‐derived ligand that deactivates PSCs, and inhibition of its receptor CSF1R was able to counteract this effect. In conclusion, high‐grade PDAC features stroma that is low in collagen and activated PSC content, and targeting CSF1R offers direct options to maintain a tumor‐restricting microenvironment.
Synopsis
This study reveals that PDAC cells counteract mechanical restrictions of tumor stroma by secreting CSF‐1, which could be a potential therapeutic target.
Poorly differentiated, high‐grade pancreatic cancers, corresponding with the mesenchymal subtype, feature stroma that is low in collagen and activated pancreatic stellate cell content.
These mesenchymal subtype cancer cells secrete high amounts of CSF‐1.
CSF‐1 downregulates stromal activation markers and reduces proliferation via STAT3 in PSCs.
Depletion of CSF‐1 in high‐grade PDAC abolishes PSC deactivation.
High‐grade CSF‐1‐positive PDAC patient samples exhibit deactivated stroma.
This study reveals that PDAC cells counteract mechanical restrictions of tumor stroma by secreting CSF‐1, which could be a potential therapeutic target.
Background
Digital self-management support tools (DSMSTs)—electronic devices or monitoring systems to monitor or improve health status—have become increasingly important in cancer care.
Objective
The ...aim of this review is to analyze published randomized clinical trials to assess the effectiveness of DSMSTs on physical and psychosocial symptoms or other supportive care needs in adult patients with cancer.
Methods
Five databases were searched from January 2013 to January 2020. English or Dutch language randomized controlled trials comparing DSMSTs with no intervention, usual care, alternative interventions, or a combination and including patients aged ≥18 years with pathologically proven cancer in the active treatment or survivorship phases were included. The results were summarized qualitatively.
Results
A total of 19 publications describing 3 types of DSMSTs were included. Although the content, duration, and frequency of interventions varied considerably across studies, the commonly used elements included an assessment component, tailored symptom self-management support, an information section, a communication section, and a diary. Significant positive effects were observed on quality of life in 6 (out of 10) studies, on anxiety in 1 (out of 5) study and depression in 2 (out of 8) studies, on symptom distress in 5 (out of 7) studies, on physical activity in 4 (out of 6) studies, on dietary behavior in 1 (out of 4) study, and on fatigue in 2 (out of 5) studies. Moreover, significant negative effects were observed on anxiety in 1 (out of 5) study and depression in 1 (out of 8) study. Most interventions were web-based interventions; 2 studies used mobile apps, and 1 study used a game as a DSMST. The overall quality of the studies was found to be good, with 13 out of 19 studies classified as high quality.
Conclusions
This review suggests that DSMSTs have a beneficial effect on the quality of life. For effects on other patient outcomes (eg, anxiety and depression, symptom distress, physical activity, dietary behavior, and fatigue), the evidence is inconsistent and limited or no effect is suggested. Future research should focus on specific tumor types, study different types of interventions separately, and assess the effects of specific interventions at different stages of disease progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Many patients with cancer, including older patients (aged ≥65 years), consult the Web to prepare for their doctor's visit. In particular, older patients have varying needs regarding the mode in which ...information is presented (eg, via textual, visual, or audiovisual modes) owing to age-related sensory (eg, impaired vision and hearing) and cognitive decline (eg, reduced processing speed). Therefore, Web-based information targeted at older patient populations is likely to be used and processed more effectively, and evaluated more positively, when tailored to age-related capabilities and preferences. This, in turn, may benefit patient outcomes.
This randomized controlled trial tested the effects of a Web-based tailored educational intervention among newly diagnosed younger (<65 years) and older (≥65 years) patients with cancer. We compared the intervention group who viewed a mode-tailored website (ie, enabling patients to tailor information using textual, visual, and audiovisual modes) with 3 control groups view a nontailored website (ie, text only, text with images, and text with videos). We examined website experience outcomes (ie, website satisfaction, website involvement, knowledge, anxiety, and communication self-efficacy) and consultation experience outcomes (ie, question asking during consultation, anxiety, and information recall).
Patients from a multidisciplinary outpatient clinic (N=232) viewed a mode-tailored or nontailored website as preparation before their hospital consultations to discuss diagnosis and treatment. Data were collected before (T1), during (T2), and after (T3) visitation. Website experience outcomes were assessed with questionnaires (T1). Patients' question asking was coded from videotaped consultations, and anxiety was assessed through a questionnaire (T2). Telephone interviews were conducted to assess knowledge acquired from the website before (T1) and after consultation (T3), and information recall from the consultation (T3).
The preparatory website was well used across all conditions (mean 34 min). Younger patients viewing the mode-tailored website were more satisfied before consultation (P=.02) and reported lower anxiety after consultation (P=.046; vs text only). This pattern was not found in older patients. Mode tailoring yielded no other significant differences in patient outcomes. Regression analyses showed that website involvement (beta=.15; P=.03) and, to a lesser extent, website satisfaction (beta=.15; P=.05) positively associated with knowledge before consultation (T1). In turn, higher knowledge before consultation (beta=.39; P<.001), together with time on the website (beta=.21; P=.002; T1), predicted information recall from consultations (T3). Patients with higher knowledge before consultation (T1) also reported higher knowledge from the website afterward (T3; beta=.22; P=.003).
Offering preparatory online information before consultations benefits information processing and patient outcomes of both younger and older newly diagnosed patients with cancer. Younger patients benefit even more when information is offered in a mode-tailored manner. We discuss the theoretical, methodological, and practical implications for patient-provider communication research in an electronic health era.
Netherlands Trial Register NTR5904; https://www.trialregister.nl/trial/5750.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background:
Muslims are the largest religious minority in Europe. When confronted with life-threatening illness, they turn to their local imams for religious guidance.
Aim:
To gain knowledge about ...how imams shape their roles in decision-making in palliative care.
Design:
Direct Content Analysis through a typology of imam roles. To explore motives, this was complemented by Narrative Analysis.
Setting/Participants:
Ten Turkish imams working in the Netherlands, with experience in guiding congregants in palliative care.
Results:
The roles of Jurist, Exegete, Missionary, Advisor and Ritual Guide were identified. Three narratives emerged: Hope can work miracles, Responsibility needs to be shared, and Mask your grief. Participants urged patients not to consent to withholding or terminating treatment but to search for a cure, since this might be rewarded with miraculous healing. When giving consent seemed unavoidable, the fear of being held responsible by God for wrongful death was often managed by requesting fatwa from committees of religious experts. Relatives were urged to hide their grief from dying patients so they would not lose hope in God.
Conclusion:
Imams urge patients’ relatives to show faith in God by seeking maximum treatment. This attitude is motivated by the fear that all Muslims involved will be held accountable by God for questioning His omnipotence to heal. Therefore, doctors may be urged to offer treatment that contradicts medical standards for good palliative care. To bridge this gap, tailor-made palliative care should be developed in collaboration with imams. Future research might include imams of other Muslim organizations.
IntroductionHigh-grade chondrosarcoma, high-grade glioma and intrahepatic cholangiocarcinoma are aggressive types of cancer with a dismal outcome. This is due to the lack of effective treatment ...options, emphasising the need for novel therapies. Mutations in the genes IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2) occur in 60% of chondrosarcoma, 80% of WHO grade II–IV glioma and 20% of intrahepatic cholangiocarcinoma. IDH1/2-mutated cancer cells produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are metabolically vulnerable to treatment with the oral antidiabetic metformin and the oral antimalarial drug chloroquine.Methods and analysisWe describe a dose-finding phase Ib/II clinical trial, in which patients with IDH1/2-mutated chondrosarcoma, glioma and intrahepatic cholangiocarcinoma are treated with a combination of metformin and chloroquine. Dose escalation is performed according to a 3+3 dose-escalation scheme. The primary objective is to determine the maximum tolerated dose to establish the recommended dose for a phase II clinical trial. Secondary objectives of the study include (1) determination of pharmacokinetics and toxic effects of the study therapy, for which metformin and chloroquine serum levels will be determined over time; (2) investigation of tumour responses to metformin plus chloroquine in IDH1/2-mutated cancers using CT/MRI scans; and (3) whether tumour responses can be measured by non-invasive D-2HG measurements (mass spectrometry and magnetic resonance spectroscopy) of tumour tissue, serum, urine, and/or bile or next-generation sequencing of circulating tumour DNA (liquid biopsies). This study may open a novel treatment avenue for IDH1/2-mutated high-grade chondrosarcoma, glioma and intrahepatic cholangiocarcinoma by repurposing the combination of two inexpensive drugs that are already approved for other indications.Ethics and disseminationThis study has been approved by the medical-ethical review committee of the Academic Medical Center, Amsterdam, The Netherlands. The report will be submitted to a peer-reviewed journal.Trial registration numberThis article was registered at ClinicalTrials.gov identifier (NCT02496741): Pre-results.
Background:
The COVID-19 pandemic impacted cancer diagnosis and treatment. However, little is known about end-of-life cancer care during the pandemic.
Aim:
To investigate potentially inappropriate ...end-of-life hospital care for cancer patients before and during the COVID-19 pandemic.
Design:
Retrospective population-based cohort study using data from the Netherlands Cancer Registry and the Dutch National Hospital Care Registration. Potentially inappropriate care in the last month of life (chemotherapy administration, >1 emergency room contact, >1 hospitalization, hospitalization >14 days, intensive care unit admission or hospital death) was compared between four COVID-19 periods and corresponding periods in 2018/2019.
Participants:
A total of 112,919 cancer patients (⩾18 years) who died between January 2018 and May 2021 were included.
Results:
Fewer patients received potentially inappropriate end-of-life care during the COVID-19 pandemic compared to previous years, especially during the first COVID-19 peak (22.4% vs 26.0%). Regression analysis showed lower odds of potentially inappropriate end-of-life care during all COVID-19 periods (between OR 0.81; 95% CI 0.74–0.88 and OR 0.92; 95% CI 0.87–0.97) after adjustment for age, sex and cancer type. For the individual indicators, fewer patients experienced multiple or long hospitalizations, intensive care unit admission or hospital death during the pandemic.
Conclusions:
Cancer patients received less potentially inappropriate end-of-life care during the COVID-19 pandemic. Because several factors may have contributed, it is unclear whether this reflects better quality care. However, these findings raise important questions about what pandemic-induced changes in care practices can help provide appropriate end-of-life care for future patients in the context of increasing patient numbers and limited resources.
PDF
