Ex vivo fluorescence-guided resection margin assessment in breast cancer surgery using a topically applied, cathepsin-activatable imaging agent.

Up to 40 % of breast cancer patients have a tumor-positive resection margin (TPRM) - defined as cancer cells at the surface of the resected specimen - after breast-conserving surgery (BCS), necessitating re-resection or boost radiation. To prevent these additional treatments, intraoperative near-infrared (NIR) fluorescence imaging with the topically applied, cathepsin-activatable imaging agent AKRO-6qcICG might be used to detect TPRMs and guide additional resection. Here, to validate its performance, the agent is topically applied to all surfaces of freshly resected breast cancer specimens (n = 11 patients) and to 3-5 mm thick tissue slices of the specimens (n = 26 patients). NIR fluorescence images of the resection surfaces and tissue slices are acquired and correlated to final histopathology. AKRO-6qcICG detects TPRMs with a sensitivity, specificity, PVV, and NPV of 100 %, 67 %, 10 %, and 100 %, respectively. On the tissue slices, the fluorescence signal has a median tumor-to-background ratio of 1.8. These findings indicate that topically applied AKRO-6qcICG can visualize TPRMs ex vivo with a high sensitivity and NPV, with sufficient contrast to adjacent healthy breast tissue.

Physical Function and Physical Activity in Older Breast Cancer Survivors: 5-Year Follow-Up from the Climb Every Mountain Study.

BACKGROUND: A decline in physical activity and the ability to perform activities of daily living (ADL) and instrumental activities of daily living (IADL) could interfere with independent living and quality of life in older patients, but may be prevented with tailored interventions. The aim of the current study was to assess changes in physical activity and ADL/IADL in the first 5 years after breast cancer diagnosis in a real-world cohort of older patients and to identify factors associated with physical decline. METHODS: Patients aged ≥70 years with in situ or stages I-III breast cancer were included in the prospective Climb Every Mountain cohort study. Linear mixed models were used to assess physical activity (according to Metabolic Equivalent of Task (MET) hours per week) and ADL/IADL (according to the Groningen Activity Restriction Scale (GARS)) over time. Secondly, the association with geriatric characteristics, treatment, quality of life, depression, apathy, and loneliness was analyzed. RESULTS: A total of 239 patients were included. Physical activity and ADL/IADL changed in the first 5 years after diagnosis (mean change from baseline -11.6 and +4.2, respectively). Geriatric characteristics at baseline were strongly associated with longitudinal change in physical activity and ADL/IADL, whereas breast cancer treatment was not. A better quality of life was associated with better physical activity and preservation of ADL/IADL, while depression and loneliness were negatively associated with these outcomes. DISCUSSION: Geriatric characteristics, loneliness, and depressive symptoms were associated with physical decline in older patients with breast cancer, while breast cancer treatment was not.

Perfectionism, intolerance of uncertainty and coping in relation to fear of cancer recurrence in breast cancer patients.

OBJECTIVE: Improved medical treatment has led to an increased cohort of cancer survivors. The prevalence of emotional problems in this group is high, with fear of cancer recurrence (FCR) being among the most prevalent and distressing conditions. In order to gain more insight in the psychological mechanisms playing a role in levels of FCR, this study examined the relationship between perfectionism and FCR in breast cancer patients, as well as the mediating role of intolerance of uncertainty (IU) and coping in this relationship. In order to contribute to a more comprehensive understanding of the mechanisms related to the experience of FCR in breast cancer patients, the purpose of the present study is to investigate the relationship between perfectionism and FCR, with IU and coping strategies as possible mediating factors. METHODS: Validated Dutch versions of the FCR Inventory, the Multidimensional Perfectionism Scale, the Intolerance of Uncertainty Scale and the Utrechtse Coping List were filled out by 146 breast cancer patients, at least one year after (finishing) medical treatment. Correlation analyses were conducted to administer the associations between FCR, perfectionism, IU, coping and demographic/medical variables. PROCESS was used to examine mediation mechanisms. RESULTS: A significant correlation was found between perfectionism and FCR (r = 0.19, p = 0.024). IU was found to mediate the relationship between perfectionism and FCR. In contrast, coping style did not emerge as a significant mediating factor. CONCLUSIONS: This study shows that intolerance of uncertainty mediates the relationship between perfectionism and FCR. Psychological interventions targeting FCR may benefit from incorporating specific modules on dealing with uncertainty. Future research is necessary to further increase understanding of the mechanisms that play a role in FCR, in order to optimize and personalize psychological treatment for cancer patients with this type of emotional distress.

Discontinuation of adjuvant endocrine therapy and impact on quality of life and functional status in older patients with breast cancer.

PURPOSE: Side effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation of adjuvant endocrine therapy within the first 2 years after initiation, and to study the association between early discontinuation and functional status and quality of life (QoL). METHODS: Patients aged ≥ 70 years with stage I-III breast cancer who received adjuvant endocrine therapy were included. The primary endpoint was discontinuation of endocrine therapy within 2 years. Risk factors for discontinuation were assessed using univariate logistic regression models. Linear mixed models were used to assess QoL and functional status over time. RESULTS: Overall, 258 patients were included, of whom 36% discontinued therapy within 2 years after initiation. No geriatric predictive factors for treatment discontinuation were found. Tumour stage was inversely associated with early discontinuation. Patients who discontinued had a worse breast cancer-specific QoL (b = - 4.37; 95% CI - 7.96 to - 0.78; p = 0.017) over the first 2 years, in particular on the future perspective subscale (b = - 11.10; 95% CI - 18.80 to - 3.40; p = 0.005), which did not recover after discontinuation. Treatment discontinuation was not associated with functional improvement. CONCLUSION: A large proportion of older patients discontinue adjuvant endocrine treatment within 2 years after initiation, but geriatric characteristics are not predictive of early discontinuation of treatment. Discontinuation of adjuvant endocrine therapy did not positively affect QoL and functional status, which implies that the observed poorer QoL in this group is probably not caused by adverse effects of endocrine therapy.

Perspectives on cancer screening participation in a highly urbanized region: a Q-methodology study in The Hague, the Netherlands.

BACKGROUND: The Netherlands hosts, as many other European countries, three population-based cancer screening programmes (CSPs). The overall uptake among these CSPs is high, but has decreased over recent years. Especially in highly urbanized regions the uptake rates tend to fall below the minimal effective rate of 70% set by the World Health Organization. Understanding the reasons underlying the decision of citizens to partake in a CPS are essential in order to optimize the current screening participation rates. The aim of this study was to explore the various perspectives concerning cancer screening among inhabitants of The Hague, a highly urbanized region of the Netherlands. METHODS: A Q-methodology study was conducted to provide insight in the prevailing perspectives on partaking in CSPs. All respondents were inhabitants of the city of The Hague, the Netherlands. In an online application they ranked a set of 31 statements, based on the current available literature and clustered by the Integrated Change model, into a 9-column forced ranking grid according to level of agreement, followed by a short survey. Respondents were asked to participate in a subsequent interview to explain their ranking. By-person factor analysis was used to identify distinct perspectives, which were interpreted using data from the rankings and interviews. RESULTS: Three distinct perspectives were identified: 1). "Positive about participation", 2). "Thoughtful about participation", and 3). "Fear drives participation". These perspectives provide insight into how potential respondents, living in an urbanized region in the Netherlands, decide upon partaking in CSPs. CONCLUSIONS: Since CSPs will only be effective when participation rates are sufficiently high, it is essential to have insight into the different perspectives among potential respondents concerning partaking in a CSP. This study adds new insights concerning these perspectives and suggests several ideas for future optimization of the CSPs.

Psychological distress and quality of life following positive fecal occult blood testing in colorectal cancer screening.

OBJECTIVE: This study aimed to assess psychological functioning, quality of life, and regret about screening after a positive fecal immunochemical test (FIT) and subsequent colonoscopy, and to evaluate changes over time. METHODS: This is a prospective cohort study. Individuals aged 55 to 75 with a positive FIT that were referred for colonoscopy between July 2017 and November 2018, were invited to complete questionnaires related to psychological distress and health-related quality of life at three predefined time points: before colonoscopy, after histopathology result notification, and after 6 months. Four questionnaires were used: the Psychological Consequences Questionnaire (PCQ), the six-item Cancer Worry Scale (CWS), the Decision Regret Scale (DRS), and the 36-item Short-Form (SF-36). RESULTS: A total of 1066 participants out of 2151 eligible individuals were included. Patients with cancer showed a significant increase in psychological dysfunction (P = .01) and cancer worry (P = .008) after colonoscopy result notification, and a decline to pre-colonoscopy measurements after 6 months. In the no-cancer groups, psychological dysfunction and cancer worry significantly decreased over time (P < .05) but there was no ongoing decline. After 6 months, 17% of participants with no cancer experienced high level of cancer worry (CWS ≥ 10). Yet, only 5% reported high level of regret about screening participation (DRS > 25). A good global quality of life was reported in participants with no cancer. CONCLUSION: Some psychological distress remains up to 6 months after colonoscopy in participants who tested false-positive in the Dutch bowel cancer screening program.

Do Outcomes in Elective Colon and Rectal Cancer Surgery Differ by Weekday? An Observational Study Using Data From the Dutch ColoRectal Audit.

BACKGROUND: Previous studies showing higher mortality after elective surgery performed on a Friday were based on administrative data, known for insufficient case-mix adjustment. The goal of this study was to investigate the risk of adverse events for patients with colon and rectal cancer by day of elective surgery using clinical data from the Dutch ColoRectal Audit. PATIENTS AND METHODS: Prospectively collected data from the 2012-2015 Dutch ColoRectal Audit (n=36,616) were used to examine differences in mortality, severe complications, and failure to rescue by day of elective surgery (Monday through Friday). Monday was used as a reference, analyses were stratified for colon and rectal cancer, and case-mix adjustments were made for previously identified variables. RESULTS: For both colon and rectal cancer, crude mortality, severe complications, and failure-to-rescue rates varied by day of elective surgery. After case-mix adjustment, lower severe complication risk was found for rectal cancer surgery performed on a Friday (odds ratio, 0.84; 95% CI, 0.72-0.97) versus Monday. No significant differences were found for colon cancer surgery performed on different weekdays. CONCLUSIONS: No weekday effect was found for elective colon and rectal cancer surgery in the Netherlands. Lower severe complication risk for elective rectal cancer surgery performed on a Friday may be caused by patient selection.

Weekend Effect in Emergency Colon and Rectal Cancer Surgery: A Prospective Study Using Data From the Dutch ColoRectal Audit.

Background: It is unclear whether emergency weekend colon and rectal cancer surgery are associated with worse outcomes (ie, weekend effect) because previous studies mostly used administrative data, which may insufficiently adjust for case-mix. Materials and Methods: Prospectively collected data from the 2012-2015 Dutch ColoRectal Audit (n=5,224) was used to examine differences in 30-day mortality and severe complication and failure-to-rescue rates for emergency weekend (Saturday and Sunday) versus Monday surgery, stratified for colon and rectal cancer. Analyses were adjusted for age, sex, body mass index, Charlson comorbidity index, American Society of Anesthesiologists classification score, tumor stage, presence of metastasis, preoperative complication, additional resection for metastasis or locally advanced tumor, location primary colon tumor, type of rectal surgery (lower anterior resection or abdominal perineal resection), and type of neoadjuvant therapy (short-course radiotherapy or chemoradiotherapy). Results: A total of 5,052 patients undergoing colon cancer surgery and 172 undergoing rectal cancer surgery were included. Patients undergoing colon or rectal cancer surgery during weekends had significantly more preoperative tumor complications compared with those undergoing surgery on a weekday. Additionally, differences in year of surgery and location of primary tumor were found for colon cancer surgery. Emergency colon cancer surgery during the weekend was associated with increased 30-day mortality (odds ratio [OR], 1.66; 95% CI, 1.10-2.50) and severe complications (OR, 1.29; 95% CI, 1.03-1.63) compared with surgery on Monday. Estimates for emergency weekend rectal cancer surgery were similar but not statistically significant, likely explained by small numbers. Conclusions: Weekend emergency colon cancer surgery was associated with higher mortality and severe complication rates. More research is needed to understand which factors explain and contribute to these differences.

Impact of comorbidity on outcome of older breast cancer patients: a FOCUS cohort study.

Older breast cancer patients often suffer from comorbid diseases, which may influence life expectancy. The aim of this study was to assess the impact of specific comorbidities on overall survival and distant recurrence free period (DRFP) of older breast cancer patients. Patients were included from the population-based FOCUS cohort which contains 3,672 breast cancer patients aged 65 years or older. The impact of comorbidity on overall survival and DRFP was analyzed using multivariable Cox proportional hazard models and Poisson regression models. Median follow-up time was 6.8 years (range 0-14.0). Irrespective of age; the number of comorbid diseases was significantly associated with worse overall survival [hazard ratio (HR) per increasing number of comorbid diseases: 1.20, 95 % confidence interval (CI) 1.13-1.27 and HR 1.09, 95 % CI 1.05-1.13 for age <75 and age ≥ 75, respectively]. Median follow-up time for DRFP was 5.7 years (range 0-14.0). An increasing number of comorbid diseases was associated with a decreasing risk of metastases among patients aged ≥ 75 (HR 0.94, 95 % CI 0.87-1.02), whereas an increasing risk was shown for patients aged <75 (HR 1.09, 95 % CI 1.01-1.19). This study shows that in older breast cancer, patients overall survival and DRFP are influenced by comorbidity. This reiterates that patient outcome is not only influenced by breast cancer, and non-cancer-related factors should be taken into account.

Perceptions and beliefs of general practitioners on their role in the cancer screening programmes in the Netherlands: a mixed-methods study.

BACKGROUND: In the Netherlands, population-based cancer screening programmes (CSPs) are organized aiming at cervical, breast and colorectal cancer. For a CSP to be effective, high participation rates are essential; however, there is an alarming downward trend, including wide regional variation in screening uptake. General practitioner (GP) involvement can have a stimulating effect on screening participation. Current GP involvement is however, limited, varies between the programmes and has changed over time. Unexplored is what GPs think of their role(s) in the CSPs. The aim of this study was therefore to map the perceptions and beliefs of GPs regarding their current and future role in the Dutch CSPs. METHODS: A mixed-methods sequential explanatory study was conducted in the Leiden/The Hague area of the Netherlands, between the end of 2021 and 2022. A questionnaire was developed and distributed among 110 GPs. The aggregated results obtained from the questionnaires served as starting points for conducting semi-structured interviews, with purposefully selected GPs. With this sequential approach we aimed to further enhance the understanding of the questionnaire data, and delved into the topics that emerged from the questionnaire responses. RESULTS: In total, 46 GPs completed the online questionnaire (response rate 42%). Subsequent five semi-structured comprehensive interviews were conducted. GPs indicated that they frequently encounter the CSP in their daily practice and consider it important. They also emphasised it is important that GPs remain closely involved with the CSPs in the future. Nevertheless, GPs also repeatedly mentioned that they are not eager to take on more logistical/organizational tasks. They are however willing to empower CSPs in a positive manner. CONCLUSION: GPs were generally positive about the CSPs and their current role within these programmes. Nevertheless, several options have been proposed to improve the CSPs, especially to increase screening uptake for populations in a socioeconomically disadvantaged position. Since it is of utmost importance to screen those who are most at risk of developing the screening-specific tumours, efforts should be made to achieve this goal.

Attendance characteristics of the breast and colorectal cancer screening programmes in a highly urbanised region of the Netherlands: a retrospective observational study.

OBJECTIVES: Throughout Europe, many countries offer population-based cancer screening programmes (CSPs). In the Netherlands, two implemented CSPs are targeting people of 50 years and older, aiming at breast cancer (BC) and colorectal cancer (CRC). In order for a CSP to be (cost-)effective, high participation rates and outreach to the populations at risk are essential. People living in highly urbanised areas and big cities are known to participate less in CSPs. The aim of this study was to gain further insight into the participation patterns of a screening-eligible population of 50 years and over, living in a highly urbanised region, over a longer time period. DESIGN: A retrospective observational study. SETTING: Participation data of the regional screening organisation, linked to the cancer incidence data derived from the Netherlands Cancer Registry, concerning the city of The Hague, between 2005 and 2019. Attendance groups were defined as attenders (attending >50% of the invitations) and non-attenders (attending ≤50% of the invitations), and were mutually compared. RESULTS: The databases contained 106 377 unique individuals on the BC screening programme (SP) and 73 669 on the CRC-SP. Non-attendance at both CSPs was associated with living in a lower socioeconomic status (SES) neighbourhood and as a counter effect, also associated with a more unfavourable, relatively late-stage, tumour diagnosis. When combining the results of the two CSPs, our results imply high screening adherence over time. Women who did not participate in both CSPs were older, and more often lived in neighbourhoods with a lower SES score. CONCLUSIONS: Since low screening uptake is one of the factors that contribute to increasing inequalities in cancer survival, future outreach strategies should be focused on engaging specific non-attending subgroups.

Association between endocrine therapy and cognitive decline in older women with early breast cancer: Findings from the prospective CLIMB study.

INTRODUCTION: Studies investigating the long-term effects of breast cancer treatment on cognition in older women with breast cancer are lacking, even though preserving cognition is highly valued by the older population. Specifically, concerns have been raised regarding the detrimental effects of endocrine therapy (ET) on cognition. Therefore, we investigated cognitive functioning over time and predictors for cognitive decline in older women treated for early breast cancer. METHODS: We prospectively enrolled Dutch women aged ≥70 years with stage I-III breast cancer in the observational CLIMB study. The Mini-Mental State Examination (MMSE) was performed before ET initiation and after 9, 15 and 27 months. Longitudinal MMSE scores were analysed and stratified for ET. Linear mixed models were used to identify possible predictors of cognitive decline. RESULTS: Among the 273 participants, the mean age was 76 years (standard deviation 5), and 48% received ET. The mean baseline MMSE score was 28.2 (standard deviation 1.9). Cognition did not decline to clinically meaningful differences, irrespective of ET. MMSE scores of women with pre-treatment cognitive impairments slightly improved over time (significant interaction terms) in the entire cohort and in women receiving ET. High age, low educational level and impaired mobility were independently associated with declining MMSE scores over time, although the declines were not clinically meaningful. CONCLUSION: Cognition of older women with early breast cancer did not decline in the first two years after treatment initiation, irrespective of ET. Our findings suggest that the fear of declining cognition does not justify the de-escalation of breast cancer treatment in older women.

Mental health outcomes in older breast cancer survivors: Five-year follow-up from the CLIMB study.

BACKGROUND: There is a lack of information on mental health outcomes for the increasing older population. Therefore, the aim of the current study is to assess depressive symptoms, loneliness, and apathy in older patients with breast cancer within the first 5 years after diagnosis. METHODS: Women aged ≥70 years with early-stage breast cancer were included. Multivariate linear mixed models were used to assess longitudinal changes in symptoms of depression (according to the 15-item Geriatric Depression Scale), loneliness (according to the De Jong Gierveld Loneliness Scale) and apathy (according to the Starkstein Apathy Scale) over time at 3, 9, 15, 27 and 60 months follow-up. RESULTS: In total, 299 patients were included (mean [standard deviation (SD)] age: 75.8 [5.2] years). At 3 months follow-up, shortly after the acute treatment, 10% of patients had significant depressive symptoms, while loneliness and apathy were present in 31% and 41% of all patients, respectively. Depression, loneliness and apathy scores showed no clinically relevant changes over time in the whole cohort. Patients who received adjuvant systemic therapies (i.e. endocrine therapy and/or chemotherapy and/or targeted therapy (trastuzumab)) had similar mental health outcomes as those who did not. However, frail patients had more symptoms (p < 0.001) and were more prone to develop depressive symptoms over time than non-frail patients (p = 0.002). DISCUSSION: Depression, loneliness and apathy were frequently observed in older women with breast cancer and did not change over time. Patients who received adjuvant systemic therapies had similar mental health outcomes as those who did not. However, frail patients were at higher risk to experience these symptoms.

[Atypical presentation of male breast cancer]. / Atypische presentatie van borstkanker bij een man.

BACKGROUND: Approximately 1% of all breast cancers occur in men. With an annual incidence of 130 cases in the Netherlands, the occurrence of male breast cancer is rare. CASE DESCRIPTION: We report the case of a 72-year-old male who was referred to a breast outpatient clinic for the evaluation of a multinodular skin lesion of the nipple. The nipple lesion was found to be an invasive carcinoma of the breast with neuroendocrine differentiation. Retrospectively, a breast abnormality could be detected on radiologic imaging 2 years prior to cancer diagnosis. CONCLUSION: Breast cancer in men is associated with an increased diagnostic delay compared to women and is subsequently diagnosed at a later stage. Studies on the survival of breast cancer report worse survival in men compared to women. Health care professionals should be alerted to the presence of a malignancy when dealing with abnormalities of the male breast.

Differences in treatment and survival of older patients with operable breast cancer between the United Kingdom and the Netherlands - A comparison of two national prospective longitudinal multi-centre cohort studies.

BACKGROUND: Previous studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has been hypothesised that these differences in survival outcomes could be related to treatment variation. OBJECTIVES: We aimed to compare patient and tumour characteristics, treatment selection and survival outcomes between two large prospective cohorts of older patients with operable breast cancer from the United Kingdom (UK) and The Netherlands. METHODS: Women diagnosed with operable breast cancer aged ≥70 years were included. A baseline comprehensive geriatric assessment was performed in both cohorts, with data collected on age, comorbidities, cognition, nutritional and functional status. Baseline tumour characteristics and treatment type were collected. Univariable and multivariable Cox regression models were used to compare overall survival between the cohorts. RESULTS: 3262 patients from the UK Age Gap cohort and 618 patients from the Dutch Climb cohort were included, with median ages of 77.0 (IQR: 72.0-81.0) and 75.0 (IQR: 72.0-81.0) years, respectively. The cohorts were generally comparable, with slight differences in rates of comorbidity and frailty. Median follow-up for overall survival was 4.1 years (IQR 2.9-5.4) in Age Gap and 4.3 years (IQR 2.9-5.5) in Climb. In Age Gap, both the rates of primary endocrine therapy and adjuvant hormonal therapy after surgery were approximately twice those in Climb (16.6% versus 7.3%, p < 0.001 for primary endocrine therapy, and 62.2% versus 38.8%, p < 0.001 for adjuvant hormonal therapy). There was no evidence of a difference in overall survival between the cohorts (adjusted HR 0.94, 95% CI 0.74-1.17, p = 0.568). CONCLUSIONS: In contrast to previous studies, this comparison of two large national prospective longitudinal multi-centre cohort studies demonstrated comparable survival outcomes between older patients with breast cancer treated in the UK and The Netherlands, despite differences in treatment allocation.

Determinants of (non-)attendance at the Dutch cancer screening programmes: A systematic review.

OBJECTIVE: The Netherlands host three population-based cancer screening programmes: for cervical, breast, and colorectal cancer. For screening programmes to be effective, high participation rates are essential, but participation in the Netherlands' programmes is starting to fall below the minimal effective rate. We aimed to produce a systematic overview of the current known determinants of (non-)attendance at the Dutch cancer screening programmes. METHODS: A literature search was conducted in the electronic databases Academic Search Premier, Cochrane Library, Embase, EMCare, PubMed, PsycINFO, Web of Science, and also in grey literature, including all articles published before February 2018. The I-Change model was used to categorize the identified determinants of cancer screening attendance. RESULTS: In total, 19/1232 identified studies and 6 grey literature reports were included. Fifteen studies reported on predisposing factors. Characteristics such as social economic status, country of birth, and residency were most often reported, and correlate with cancer screening attendance. Thirteen studies addressed information factors. Factors on awareness, motivation, ability, and barriers were less often studied. CONCLUSION: Current studies tend to describe the general characteristics of (non-)attendance and (non-)attenders, but rarely provide in depth information on other factors of (non-)participation. The I-Change model proved to be a useful tool in mapping current knowledge on cancer screening attendance and revealed knowledge gaps regarding determinants of (non-)participation in the screening programmes. More research is needed to fully understand determinants of participation, in order to influence and optimize attendance rates over the long term.

Spontaneous rupture of a non-parasitic splenic cyst.

Rupture of a non-parasitic splenic cyst is a rare but possibly dangerous complication with 21 cases described so far. We present a 46-year-old woman who presented with acute abdominal pain and was diagnosed with a spontaneous ruptured splenic cyst that was successfully treated by laparoscopic splenectomy. Histological examination showed characteristics corresponding with a non-parasitic congenital cyst that had lost its epithelial lining. Several treatment options can be considered for splenic cysts, depending on size and location. In case of rupture, the clinical condition of the patient should be taken into account.

The first steps in the evaluation of a "black-box" decision support tool: a protocol and feasibility study for the evaluation of Watson for Oncology.

BACKGROUND AND AIM: Medical specialists aim to provide evidence-based care based on the most recent scientific insights, but with the ongoing expansion of medical literature it seems unfeasible to remain updated. "Black-box" decision support tools such as Watson for Oncology (Watson) are gaining attention as they offer a promising opportunity to conquer this challenging issue, but it is not known if the advice given is congruent with guidelines or clinically valid in other settings. We present a protocol for the content evaluation of black-box decision support tools and a feasibility study to test the content and usability of Watson using this protocol. METHODS: The protocol consists of developing synthetic patient cases based on Dutch guidelines and expert opinion, entering the synthetic cases into Watson and Oncoguide, noting the response of each system and evaluating the result using a cross-tabulation scoring system resulting in a score range of -12 to +12. Treatment options that were not recommended according to the Dutch guideline were labeled with a "red flag" if Watson recommended it, and an "orange flag" if Watson suggested it for consideration. To test the feasibility of applying the protocol, we developed synthetic patient cases for the adjuvant treatment of stage I to stage III colon cancer based on relevant patient, clinical and tumor characteristics and followed our protocol. Additionally, for the feasibility study we also compared the recommendations from the NCCN guideline with Watson's advice, and evaluated usability by a cognitive walkthrough method. RESULTS: In total, we developed 190 synthetic patient cases (stage I: n=8; stage II: n=110; and stage III: n=72). Overall concordance scores per case for Watson versus Oncoguide ranged from a minimum score of -4 (n=6) to a maximum score of+12 (n=17) and from -4 (n=9) to +12 (n=24) for Watson versus the NCCN guidelines). In total, 69 cases (36%) were labeled with red flags, 96 cases (51%) with orange flags and 25 cases (13%) without flags. For the comparison of Watson with the NCCN guidelines, no red or orange flags were identified. CONCLUSIONS: We developed a research protocol for the evaluation of a black-box decision support tool, which proved useful and usable in testing the content and usability of Watson. Overall concordance scores ranged considerably between synthetic cases for both comparisons between Watson versus Oncoguide and Watson versus NCCN. Non-concordance is partially attributable to guideline differences between the United States and The Netherlands. This implies that further adjustments and localization are required before implementation of Watson outside the United States. RELEVANCE FOR PATIENTS: This study describes the first steps of content evaluation of a decision support tool before implementation in daily oncological patient care. The ultimate goal of the incorporation of decision support tools in daily practice is to improve personalized medicine and quality of care.

Importance of patient reported outcome measures versus clinical outcomes for breast cancer patients evaluation on quality of care.

INTRODUCTION: Given increasing numbers of breast cancer survivors, there is an increased focus on quality of life and quality of care. This study aims to investigate whether clinical or patient reported outcomes are most important for perceived quality of care by breast cancer patients. METHODS: Overall, 606 patients aged 18 years or older, who underwent breast cancer surgery 9-18 months ago in five hospitals in the Netherlands, were invited to complete an internet-based questionnaire. Patients were asked to judge a random selection of 24 patient profiles and choose which of 2 presented patients had received the best quality of care, using conjoint analysis. The individual relative importance (RI) for each outcome was estimated using Hierarchical Bayes Estimation, and averaged over all patients to assess which outcomes were most important. RESULTS: Complete data were available for 350 patients (58%). Avoiding severe breast symptoms was most important for good quality of care according to patients (RI 23.22 [95% Confidence Interval (95% CI) 22.32-24.12]), followed by a 2 year longer disease free survival (18.30 [17.38-19.22]). However, the importance differed by age: younger patients (<50 years) assigned higher importance to longer disease free survival (21.99 [19.52-24.46]) than older patients (65 + years) (15.03 [13.88-16.18]). CONCLUSION: Avoiding severe breast symptoms rather than 2 year longer disease free survival is considered most important in our population of breast cancer patients for evaluation of quality of care. These data should thus be included in both information provision prior to treatment choices and post treatment quality of care evaluation.