VHL synthetic lethality screens uncover CBF-ß as a negative regulator of STING.

Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer and is typified by biallelic inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene. Here, we undertake genome-wide CRISPR/Cas9 screening to reveal synthetic lethal interactors of VHL, and uncover that loss of Core Binding Factor ß (CBF-ß) causes cell death in VHL-null ccRCC cell lines and impairs tumour establishment and growth in vivo. This synthetic relationship is independent of the elevated activity of hypoxia inducible factors (HIFs) in VHL-null cells, but does involve the RUNX transcription factors that are known binding partners of CBF-ß. Mechanistically, CBF-ß loss leads to upregulation of type I interferon signalling, and we uncover a direct inhibitory role for CBF-ß at the STING locus controlling Interferon Stimulated Gene expression. Targeting CBF-ß in kidney cancer both selectively induces tumour cell lethality and promotes activation of type I interferon signalling.

Hypoxia drives HIF2-dependent reversible macrophage cell cycle entry.

Low-oxygen conditions (hypoxia) have been associated primarily with cell-cycle arrest in dividing cells. Macrophages are typically quiescent in G0 but can proliferate in response to tissue signals. Here we show that hypoxia (1% oxygen tension) results in reversible entry into the cell cycle in macrophages. Cell cycle progression is largely limited to G0-G1/S phase transition with little progression to G2/M. This cell cycle transitioning is triggered by an HIF2α-directed transcriptional program. The response is accompanied by increased expression of cell-cycle-associated proteins, including CDK1, which is known to phosphorylate SAMHD1 at T592 and thereby regulate antiviral activity. Prolyl hydroxylase (PHD) inhibitors are able to recapitulate HIF2α-dependent cell cycle entry in macrophages. Finally, tumor-associated macrophages (TAMs) in lung cancers exhibit transcriptomic profiles representing responses to low oxygen and cell cycle progression at the single-cell level. These findings have implications for inflammation and tumor progression/metastasis where low-oxygen environments are common.

Effectiveness of a guided online primary care intervention for fear of cancer recurrence: A randomised controlled trial.

OBJECTIVE: Fear of Cancer Recurrence (FCR) is highly prevalent among cancer survivors and leads to decreased quality of life and increased healthcare costs. We assessed the effectiveness of a guided online primary care intervention for FCR, compared to waiting list. METHODS: In this RCT, participants were recruited online and randomised 1:1. All adults who finished successful curative cancer treatment between 3 months and 10 years ago, wanted support for FCR, and had sufficient Dutch skills were eligible. The intervention consisted of a 10-week online programme and three to five video calling sessions with a trained mental health worker. After 6 months, the control group received the same intervention. The primary outcome was the difference between the groups in the change in FCR severity from baseline (T0) to 6 months (T2), measured online with the short form of the Fear of Cancer Recurrence Inventory. RESULTS: One hundred and seventy-three participants were enroled and randomised to the intervention (n = 86) or control group (n = 87). FCR severity dropped 2.1 points more in the intervention group than in the control group (2.7 points (SD = 3.9) versus 0.6 points (SD = 3.6), t(154) = 3.4, p = 0.0007). General mental well-being also improved significantly in the intervention group and remained stable in the control group. These improvements remained at 10 months follow up. CONCLUSIONS: This easily accessible and relatively inexpensive intervention effectively reduces FCR and has potential to replace or precede existing more intensive psychological treatments, improving patients' access to care. TRIAL REGISTRATION: The trial was prospectively registered in the Netherlands Trial Register on 25-02-2019 with number NL7573.

A HIF independent oxygen-sensitive pathway for controlling cholesterol synthesis.

Cholesterol biosynthesis is a highly regulated, oxygen-dependent pathway, vital for cell membrane integrity and growth. In fungi, the dependency on oxygen for sterol production has resulted in a shared transcriptional response, resembling prolyl hydroxylation of Hypoxia Inducible Factors (HIFs) in metazoans. Whether an analogous metazoan pathway exists is unknown. Here, we identify Sterol Regulatory Element Binding Protein 2 (SREBP2), the key transcription factor driving sterol production in mammals, as an oxygen-sensitive regulator of cholesterol synthesis. SREBP2 degradation in hypoxia overrides the normal sterol-sensing response, and is HIF independent. We identify MARCHF6, through its NADPH-mediated activation in hypoxia, as the main ubiquitin ligase controlling SREBP2 stability. Hypoxia-mediated degradation of SREBP2 protects cells from statin-induced cell death by forcing cells to rely on exogenous cholesterol uptake, explaining why many solid organ tumours become auxotrophic for cholesterol. Our findings therefore uncover an oxygen-sensitive pathway for governing cholesterol synthesis through regulated SREBP2-dependent protein degradation.

Patients' views on the decision to investigate cancer symptoms in older adults: a qualitative interview study in primary care.

BACKGROUND: Cancer is predominantly a disease of older adults. To date there has been little research on the experiences of older adults or their views on the diagnostic pathway. AIM: To gain an improved understanding of the views and experiences of older adults on all aspects of cancer investigation. DESIGN AND SETTING: This was a qualitative study using semi-structured interviews with patients aged ≥70 years. Patients were recruited from primary care in West Yorkshire, UK. METHOD: Data were analysed using a thematic framework analysis. RESULTS: The themes identified in participants' accounts included the patients' process of decision making, the value of having a diagnosis, the patients' experience of cancer investigations, and the impact of the COVID-19 pandemic on the diagnostic pathway. Older adults in this study indicated a clear preference for having clarity on the cause of symptoms and the diagnosis, even in the face of unpleasant investigations. Patients suggested they wanted to be involved in the decision process. CONCLUSION: Older adults who present to primary care with symptoms suggestive of cancer may accept diagnostic testing solely for the benefit of knowing the diagnosis. There was a clear patient preference that referrals and investigations for cancer symptoms should not be deferred or delayed based on age or subjective assessments of frailty. Shared decision making and being involved in the decision-making process are important to patients, regardless of age.

A histone deacetylase 3 and mitochondrial complex I axis regulates toxic formaldehyde production.

Cells produce considerable genotoxic formaldehyde from an unknown source. We carry out a genome-wide CRISPR-Cas9 genetic screen in metabolically engineered HAP1 cells that are auxotrophic for formaldehyde to find this cellular source. We identify histone deacetylase 3 (HDAC3) as a regulator of cellular formaldehyde production. HDAC3 regulation requires deacetylase activity, and a secondary genetic screen identifies several components of mitochondrial complex I as mediators of this regulation. Metabolic profiling indicates that this unexpected mitochondrial requirement for formaldehyde detoxification is separate from energy generation. HDAC3 and complex I therefore control the abundance of a ubiquitous genotoxic metabolite.

Impact of the COVID-19 Outbreak-Delayed Referral of Colorectal and Lung Cancer in Primary Care: A National Retrospective Cohort Study.

The Coronavirus disease 2019 (COVID-19) outbreak impacted health care. We investigated its impact on the time to referral and diagnosis for symptomatic cancer patients in The Netherlands. We performed a national retrospective cohort study utilizing primary care records linked to The Netherlands Cancer Registry. For patients with symptomatic colorectal, lung, breast, or melanoma cancer, we manually explored free and coded texts to determine the durations of the primary care (IPC) and secondary care (ISC) diagnostic intervals during the first COVID-19 wave and pre-COVID-19. We found that the median IPC duration increased for colorectal cancer from 5 days (Interquartile Range (IQR) 1-29 days) pre-COVID-19 to 44 days (IQR 6-230, p < 0.01) during the first COVID-19 wave, and for lung cancer, the duration increased from 15 days (IQR) 3-47) to 41 days (IQR 7-102, p < 0.01). For breast cancer and melanoma, the change in IPC duration was negligible. The median ISC duration only increased for breast cancer, from 3 (IQR 2-7) to 6 days (IQR 3-9, p < 0.01). For colorectal cancer, lung cancer, and melanoma, the median ISC durations were 17.5 (IQR (9-52), 18 (IQR 7-40), and 9 (IQR 3-44) days, respectively, similar to pre-COVID-19 results. In conclusion, for colorectal and lung cancer, the time to primary care referral was substantially prolonged during the first COVID-19 wave. In such crises, targeted primary care support is needed to maintain effective cancer diagnosis.

Patient-reported needs for coping with worry or fear about cancer recurrence and the extent to which they are being met: a survey study.

PURPOSE: Many cancer patients and survivors experience fear or worry about cancer recurrence (FCR). Evidence suggests support for FCR is their largest unmet need. We aimed to assess which types of support are needed, which providers are preferred and to what extent patients' needs are being met. METHODS: Together with the Dutch Federation of Cancer Patient Organisations (NFK), a purpose-designed questionnaire was distributed online via e-mail, newsletters and social media. All questions were multiple choice or Likert scales, except for an open-ended question about the preferred provider of care. RESULTS: Out of 5323 respondents, 4511 had experienced FCR and were included. Among them, 94% indicated a need for support. The required types of support that were reported the most were talking about FCR (69%), enjoyable activities for distraction (56%) and psychological help or coaching (40%). On average, younger respondents and women wanted more support than older respondents and men. Eighty-five percent of respondents received at least one type of support they wanted. Practical tips about FCR and additional medical check-ups were most often missed. Social contacts provided an important part of support, especially with talking and distracting activities. For other types of support, respondents usually preferred professionals. CONCLUSIONS: Almost all patients who experience FCR have a need for support. Even though most receive some support, several gaps remain. IMPLICATIONS FOR CANCER SURVIVORS: Many report an unmet need for psychological help or practical tips about FCR. We recommend for healthcare providers to discuss FCR with patients and inform them about the support available.

The Impact of the COVID Pandemic on the Incidence of Presentations with Cancer-Related Symptoms in Primary Care.

Introduction: In the Netherlands, the onset of the coronavirus pandemic saw shifts in primary health service provision away from physical consultations, cancer-screening programs were temporarily halted, and government messaging focused on remaining at home. In March and April 2020, weekly cancer diagnoses decreased to 73% of their pre-COVID levels, and 39% for skin cancer. This study aims to explore the effect of the COVID pandemic on patient presentations for cancer-related symptoms in primary care in The Netherlands. Methods: Retrospective cohort study using routine clinical primary care data. Monthly incidences of patient presentations for cancer-related symptoms in five clinical databases in The Netherlands were analysed from March 2018 to February 2021. Results: Data demonstrated reductions in the incidence of cancer-related symptom presentations to primary care during the first COVID wave (March-June 2020) of -34% (95% CI: -43 to -23%) for all symptoms combined. In the second wave (October 2020-February 2021) there was no change in incidence observed (-8%, 95% CI -20% to 6%). Alarm-symptoms demonstrated decreases in incidence in the first wave with subsequent incidences that continued to rise in the second wave, such as: first wave: breast lump -17% (95% CI: -27 to -6%) and haematuria -15% (95% CI -24% to -6%); and second wave: rectal bleeding +14% (95% CI: 0 to 30%) and breast lump +14% (95% CI: 2 to 27%). Presentations of common non-alarm symptom such as tiredness and naevus demonstrated decreased in-cidences in the first wave of 45% (95% CI: -55% to -33%) and 37% (95% CI -47% to -25%). In the second wave, tiredness incidence was reduced by 20% (95% CI: -33% to -3%). Subgroup analy-sis did not demonstrate difference in incidence according to sex, age groups, comorbidity status, or previous history of cancer. Conclusions: These data describe large-scale primary care avoidance that did not increase until the end of the first COVID year for many cancer-related symptoms, suggestive that substantial numbers of patients delayed presenting to primary care. For those patients who had underlying cancer, this may have had impacted the cancer stage at diagnosis, treatment, and mortality.

Mental Health Morbidities and Time to Cancer Diagnosis Among Adults With Colon Cancer in England.

Importance: Mental health morbidity (MHM) in patients presenting with possible cancer symptoms may be associated with prediagnostic care and time to cancer diagnosis. Objective: To compare the length of intervals to cancer diagnosis by preexisting MHM status in patients who presented with symptoms of as-yet-undiagnosed colon cancer and evaluate their risk of emergency cancer diagnosis. Design, Setting, and Participants: This cohort study was conducted using linked primary care data obtained from the population-based Clinical Practice Research Datalink, which includes primary care practices in England, linked to cancer registry and hospital data. Included participants were 3766 patients diagnosed with colon cancer between 2011 and 2015 presenting with cancer-relevant symptoms up to 24 months before their diagnosis. Data analysis was performed in January 2021 to April 2022. Exposures: Mental health conditions recorded in primary care before cancer diagnosis, including anxiety, depression, schizophrenia, bipolar disorder, alcohol addiction, anorexia, and bulimia. Main Outcomes and Measures: Fast-track (also termed 2-week wait) specialist referral for investigations, time to colonoscopy and cancer diagnosis, and risk of emergency cancer diagnosis. Results: Among 3766 patients with colon cancer (median [IQR] age, 75 [65-82] years; 1911 [50.7%] women ), 623 patients [16.5%] had preexisting MHM recorded in primary care the year before cancer diagnosis, including 562 patients (14.9%) with preexisting anxiety or depression (accounting for 90.2% of patients with preexisting MHM) and 61 patients (1.6%) with other MHM; 3143 patients (83.5%) did not have MHM. Patients with MHM had records of red-flag symptoms or signs (ie, rectal bleeding, change in bowel habit, or anemia) in the 24 months before cancer diagnosis in a smaller proportion compared with patients without MHM (308 patients [49.4%] vs 1807 patients [57.5%]; P < .001). Even when red-flag symptoms were recorded, patients with MHM had lower odds of fast-track specialist referral (adjusted odds ratio [OR] = 0.72; 95% CI, 0.55-0.94; P = .01). Among 2115 patients with red-flag symptoms or signs, 308 patients with MHM experienced a more than 2-fold longer median (IQR) time to cancer diagnosis (326 [75-552] days vs 133 [47-422] days) and higher odds of emergency diagnosis (90 patients [29.2%] vs 327 patients [18.1%]; adjusted OR = 1.63; 95% CI, 1.23-2.24; P < .001) compared with 1807 patients without MHM. Conclusions and Relevance: This study found that patients with MHM experienced large and prognostically consequential disparities in diagnostic care before a colon cancer diagnosis. These findings suggest that appropriate pathways and follow-up strategies after symptomatic presentation are needed for earlier cancer diagnoses and improved health outcomes in this large patient group.

Who are the patients being offered the faecal immunochemical test in routine English general practice, and for what symptoms? A prospective descriptive study.

OBJECTIVES: The faecal immunochemical test (FIT) was introduced to triage patients with lower-risk symptoms of colorectal cancer (CRC) in English primary care in 2018. While there is growing evidence on its utility to triage patients in this setting, evidence is still limited on how official FIT guidance is being used, for which patients and for what symptoms. We aimed to investigate the use of FIT in primary care practice for lower-risk patients who did not immediately meet criteria for urgent referral. DESIGN: A prospective, descriptive study of symptomatic patients offered a FIT in primary care between January and June 2020. SETTING: East of England general practices. PARTICIPANTS: Consenting patients (aged ≥40 years) who were seen by their general practitioners (GPs) with symptoms of possible CRC for whom a FIT was requested. We excluded patients receiving a FIT for asymptomatic screening purposes, or patients deemed by GPs as lacking capacity for informed consent. Data were obtained via patient questionnaire, medical and laboratory records. PRIMARY AND SECONDARY OUTCOME MEASURES: FIT results (10 µg Hb/g faeces defined a positive result); patient sociodemographic and clinical characteristics; patient-reported and GP-recorded symptoms, symptom severity and symptom agreement between patient and GP (% and kappa statistics). RESULTS: Complete data were available for 310 patients, median age 70 (IQR 61-77) years, 53% female and 23% FIT positive. Patients most commonly reported change in bowel habit (69%) and fatigue (57%), while GPs most commonly recorded abdominal pain (25%) and change in bowel habit (24%). Symptom agreement ranged from 44% (fatigue) to 80% (unexplained weight loss). Kappa agreement was universally low across symptoms. CONCLUSION: Almost a quarter of this primary care cohort of symptomatic patients with FIT testing were found to be positive. However, there was low agreement between patient-reported and GP-recorded symptoms. This may impact cancer risk assessment and optimal patient management in primary care.

The evolution and co-evolution of a primary care cancer research network: From academic social connection to research collaboration.

Academic networks are expected to enhance scientific collaboration and thereby increase research outputs. However, little is known about whether and how the initial steps of getting to know other researchers translates into effective collaborations. In this paper, we investigate the evolution and co-evolution of an academic social network and a collaborative research network (using co-authorship as a proxy measure of the latter), and simultaneously examine the effect of individual researcher characteristics (e.g. gender, seniority or workplace) on their evolving relationships. We used longitudinal data from an international network in primary care cancer research: the CanTest Collaborative (CanTest). Surveys were distributed amongst CanTest researchers to map who knows who (the 'academic social network'). Co-authorship relations were derived from Scopus (the 'collaborative network'). Stochastic actor-oriented models were employed to investigate the evolution and co-evolution of both networks. Visualizing the development of the CanTest network revealed that researchers within CanTest get to know each other quickly and also start collaborating over time (evolution of the academic social network and collaborative network respectively). Results point to a stable and solid academic social network that is particularly encouraging towards more junior researchers; yet differing for male and female researchers (the effect of individual researcher characteristics). Moreover, although the academic social network and the research collaborations do not grow at the same pace, the benefit of creating academic social relationships to stimulate effective research collaboration is clearly demonstrated (co-evolution of both networks).

Pre-diagnostic clinical features and blood tests in patients with colorectal cancer: a retrospective linked-data study.

BACKGROUND: The majority of colorectal cancer is diagnosed in patients following symptomatic presentation in the UK. AIM: To identify windows of opportunity for timely investigations or referrals in patients presenting with colon and rectal cancer-relevant symptoms or abnormal blood tests. DESIGN AND SETTING: A retrospective cohort study was undertaken using linked primary care and cancer registry data for patients with colorectal cancer diagnosed in England between 2012 and 2015. METHOD: Monthly consultation rates for relevant clinical features (change in bowel habit, rectal bleeding, abdominal pain, abdominal mass, constitutional symptoms, and other bowel symptoms) and abnormal blood test results (low haemoglobin, high platelets, and high inflammatory markers) up to 24 months pre-diagnosis were calculated. Poisson regression adjusted for age, sex, and relevant comorbidities was used to estimate the most likely month when consultation rates increased above baseline. RESULTS: In total, 5033 patients with colon cancer and 2516 with rectal cancer were included. Consultations for all examined clinical features and abnormal blood tests increased in the year pre-diagnosis. Rectal bleeding was the earliest clinical feature to increase from the baseline rate: at 10 months (95% confidence interval [CI] = 8.3 to 11.7) pre-diagnosis for colon cancer and at 8 months (95% CI = 6.1 to 9.9) pre-diagnosis for rectal cancer. Low haemoglobin, high platelets, and high inflammatory markers increased from as early as 9 months pre-diagnosis. CONCLUSION: This study found evidence for an early increase in rates of consultation for relevant clinical features and abnormal blood tests in patients with colorectal cancer, suggesting that earlier instigation of cancer-specific investigations or referrals may be warranted in some patients who were symptomatic.

What is the prevalence of fear of cancer recurrence in cancer survivors and patients? A systematic review and individual participant data meta-analysis.

OBJECTIVE: Care for fear of cancer recurrence (FCR) is considered the most common unmet need among cancer survivors. Yet the prevalence of FCR and predisposing factors remain inconclusive. To support targeted care, we provide a comprehensive overview of the prevalence and severity of FCR among cancer survivors and patients, as measured using the short form of the validated Fear of Cancer Recurrence Inventory (FCRI-SF). We also report on associations between FCR and clinical and demographic characteristics. METHODS: This is a systematic review and individual participant data (IPD) meta-analysis on the prevalence of FCR. In the review, we included all studies that used the FCRI-SF with adult (≥18 years) cancer survivors and patients. Date of search: 7 February 2020. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool. RESULTS: IPD were requested from 87 unique studies and provided for 46 studies comprising 11,226 participants from 13 countries. 9311 respondents were included for the main analyses. On the FCRI-SF (range 0-36), 58.8% of respondents scored ≥13, 45.1% scored ≥16 and 19.2% scored ≥22. FCR decreased with age and women reported more FCR than men. FCR was found across cancer types and continents and for all time periods since cancer diagnosis. CONCLUSIONS: FCR affects a considerable number of cancer survivors and patients. It is therefore important that healthcare providers discuss this issue with their patients and provide treatment when needed. Further research is needed to investigate how best to prevent and treat FCR and to identify other factors associated with FCR. The protocol was prospectively registered (PROSPERO CRD42020142185).

Factors determining development of researchers within a research network on cancer diagnosis in primary care (CanTest): an interview study.

OBJECTIVES: Developing connections with other researchers in a network, learning informally through these connections and using them to reach goals, is expected to increase research capacity and strengthen performance. So far, this has not been empirically demonstrated. We assessed what and how network collaboration adds to development of researchers. DESIGN: Exploratory qualitative study using semistructured online interviews, analysed by inductive and deductive methods. For the deductive analysis, an existing value creation framework to study informal learning in networks was used and adjusted to our context. SETTING: The CanTest Collaborative-an international team of primary care cancer researchers working on early detection and diagnosis of cancer. PARTICIPANTS: Sixteen primary care cancer researchers. RESULTS: Connections with other researchers in an international network created diverse value cycles, where most outcomes were in the potential value cycle, acquiring knowledge, skills, social capital, resources and ideas. Not all potential value will be applied but many interviewees described realised as well as transformational value. In our context, the transformational value from the framework appeared to be related to other perspectives on the research process. Advancement of the network depends on opportunities, timing, role models and connections between different perspectives. CONCLUSIONS: Focus on the factors that are relevant for network advancement will support researchers in early detection and diagnosis of cancer research patients who participate in an international network and bring sustainable change in this domain. When, subsequently, researchers in the CanTest network bring about more realised and transformational learning outcomes, this will contribute to capacity development.

Factors affecting the decision to investigate older adults with potential cancer symptoms: a systematic review.

BACKGROUND: Older age and frailty increase the risk of morbidity and mortality from cancer surgery and intolerance of chemotherapy and radiotherapy. The effect of old age on diagnostic intervals is unknown; however, older adults need a balanced approach to the diagnosis and management of cancer symptoms, considering the benefits of early diagnosis, patient preferences, and the likely prognosis of a cancer. AIM: To examine the association between older age and diagnostic processes for cancer, and the specific factors that affect diagnosis. DESIGN AND SETTING: A systematic literature review. METHOD: Electronic databases were searched for studies of patients aged >65 years presenting with cancer symptoms to primary care considering diagnostic decisions. Studies were analysed using thematic synthesis and according to the Synthesis Without Meta-analysis guidelines. RESULTS: Data from 54 studies with 230 729 participants were included. The majority of studies suggested an association between increasing age and prolonged diagnostic interval or deferral of a decision to investigate cancer symptoms. Thematic synthesis highlighted three important factors that resulted in uncertainty in decisions involving older adults: presence of frailty, comorbidities, and cognitive impairment. Data suggested patients wished to be involved in decision making, but the presence of cognitive impairment and the need for additional time within a consultation were significant barriers. CONCLUSION: This systematic review has highlighted uncertainty in the management of older adults with cancer symptoms. Patients and their family wished to be involved in these decisions. Given the uncertainty regarding optimum management of this group of patients, a shared decision-making approach is important.

Dealing with Discontinuity in Cancer Care Trajectories: Patients' Solutions.

INTRODUCTION: Patients with cancer require specialized care from different care providers, challenging continuity of care in terms of information, relationships, and/or management. The recognition of discontinuity of care has led to different initiatives by the healthcare system over the years. Yet, making use of the theory on boundary objects and brokers, this research explores the active role of patients themselves in resolving discontinuity along their care trajectories. METHODS: Semi-structured interviews were conducted with 33 patients to unravel the discontinuities that they experience and their attempts to resolve these. Interview data were analyzed using directed-content analysis informed by concepts from boundary crossing literature (i.e., data were searched for potential boundary objects and brokers). RESULTS: To re-establish continuity of care, patients actively use the objects and people provided by the healthcare system when these meet their needs. Patients also introduce own objects and people into the care trajectory. As such, information and management discontinuity can typically be resolved. Relational continuity appears to be more difficult to resolve, in some cases leaving patients to take drastic measures, such as changing care providers. DISCUSSION: The use of boundary crossing theory in improving care from a patient perspective is relatively novel. When patients and providers together address the objects and people that support establishing continuity of care, a continuous care process may be encouraged. We advocate an integrated approach, rather than provider or healthcare system initiatives exclusively, to patient care and continuity.

Cancer detection during the COVID-19 pandemic-Experiences in primary care and recommendations for the future.

Background: To describe general practitioners (GPs) experiences with the impact COVID-19 on the duration of cancer detection. Methods: Cross-sectional survey study among Dutch GPs. Results: Fifty-eight GPs participated. During the first wave, COVID-19-related delays were experienced by 88%, 52%, and 67% of GPs in the contact-seeking, primary care, and referral phases, respectively. GPs reported delays due to telehealth consultations, longer waiting times and patient's concerns of COVID infections and overburdening GPs. Conclusions: The majority of GPs experienced delays in cancer diagnostic processes during the beginning of the COVID pandemic, which was most prominent in the timeliness in which patients sought GP care.

Shared decision making in cancer treatment: A Dutch national survey on patients' preferences and perceptions.

OBJECTIVE: Shared decision making (SDM) for cancer treatment yields positive results. However, it appears that discussing essential topics for SDM is not fully integrated into treatment decision making yet. Therefore, we aim to explore to what extent discussion of therapy options, treatment consequences, and personal priorities is preferred and perceived by (former) cancer patients. METHODS: An online questionnaire was distributed by the Dutch Federation of Cancer Patient Organisations among (former) cancer patients in 2018. RESULTS: Among 3785 (former) cancer patients, 3254 patients (86%) had discussed treatments with their health care provider (HCP) and were included for analysis. Mean age was 62.1 ± 11.5; 55% were female. Discussing the option to choose no (further) treatment was rated by 2751 (84.5%) as very important (median score 9/10-IQR 8-10). Its occurrence was perceived by 28% (N = 899), and short- and long-term treatment consequences were discussed in 81% (N = 2626) and 53% (N = 1727), respectively. An unmet wish to discuss short- and long-term consequences was reported by 22% and 26%, respectively. Less than half of the (former) cancer patients perceived that personal priorities (44%) and future plans (34%) were discussed. CONCLUSION: In the perception of (former) cancer patients, several essential elements for effective SDM are insufficiently discussed during cancer treatment decision making.

Do presenting symptoms, use of pre-diagnostic endoscopy and risk of emergency cancer diagnosis vary by comorbidity burden and type in patients with colorectal cancer?

BACKGROUND: Cancer patients often have pre-existing comorbidities, which can influence timeliness of cancer diagnosis. We examined symptoms, investigations and emergency presentation (EP) risk among colorectal cancer (CRC) patients by comorbidity status. METHODS: Using linked cancer registration, primary care and hospital records of 4836 CRC patients (2011-2015), and multivariate quantile and logistic regression, we examined variations in specialist investigations, diagnostic intervals and EP risk. RESULTS: Among colon cancer patients, 46% had at least one pre-existing hospital-recorded comorbidity, most frequently cardiovascular disease (CVD, 18%). Comorbid versus non-comorbid cancer patients more frequently had records of anaemia (43% vs 38%), less frequently rectal bleeding/change in bowel habit (20% vs 27%), and longer intervals from symptom-to-first relevant test (median 136 vs 74 days). Comorbid patients were less likely investigated with colonoscopy/sigmoidoscopy, independently of symptoms (adjusted OR = 0.7[0.6, 0.9] for Charlson comorbidity score 1-2 and OR = 0.5 [0.4-0.7] for score 3+ versus 0. EP risk increased with comorbidity score 0, 1, 2, 3+: 23%, 35%, 33%, 47%; adjusted OR = 1.8 [1.4, 2.2]; 1.7 [1.3, 2.3]; 3.0 [2.3, 4.0]) and for patients with CVD (adjusted OR = 2.0 [1.5, 2.5]). CONCLUSIONS: Comorbid individuals with as-yet-undiagnosed CRC often present with general rather than localising symptoms and are less likely promptly investigated with colonoscopy/sigmoidoscopy. Comorbidity is a risk factor for diagnostic delay and has potential, additionally to symptoms, as risk-stratifier for prioritising patients needing prompt assessment to reduce EP.