Inflammatory breast cancer (IBC) is a rare and rapidly progressive form of invasive breast cancer. The aim of this study was to explore the clinical evolution, stromal tumour-infiltrating lymphocytes ...(sTIL) infiltration and programmed death-ligand 1 (PD-L1) expression in a large IBC cohort.
Data were collected prospectively from patients with IBC as part of an international collaborative effort since 1996. In total, 143 patients with IBC starting treatment between June 1996 and December 2016 were included. Clinicopathological variables were collected, and sTIL were scored by two pathologists on standard H&E stained sections. PD-L1 expression was assessed using a validated PD-L1 (SP142) assay. A validation cohort of 64 patients with IBC was used to test our findings.
Survival outcomes of IBC remained poor with a 5-year overall survival (OS) of 45.6%. OS was significantly better in patients with primary non-metastatic disease who received taxane-containing (neo)adjuvant therapy (P = 0.01), had a hormone receptor-positive tumour (P = 0.001) and had lower cN stage at diagnosis (P = 0.001). PD-L1 positivity on immune cells (42.9%) was higher in IBC than in non-IBC in both our patient samples and the validation cohort. Furthermore, PD-L1 expression predicted pCR (P = 0.002) and correlated with sTIL infiltration (P < 0.001). sTIL infiltration of more than 10% of the stroma was a significant predictor of improved OS (HR 0.47, 95% CI 0.27-0.81, P = 0.006) in a multivariate model.
IBC is characterised by poor survival and high PD-L1 immunoreactivity on sTIL. This suggests a role for PD1/PD-L1 inhibitors in the treatment of IBC. Furthermore, we showed that PD-L1 expression predicts response to neo-adjuvant therapy and that sTIL have prognostic significance in IBC.
Summary
Background
The correlation between vedolizumab trough levels during induction therapy and mucosal healing remains unknown.
Aim
To compare early vedolizumab trough levels in patients with and ...without mucosal healing within the first year after treatment initiation.
Methods
We prospectively collected vedolizumab trough levels in all inflammatory bowel disease patients at weeks 2, 6 and 14 of vedolizumab treatment in three French referral centres between 1 June 2014 and 31 March 2017. Results of every patient that underwent mucosal assessment by magnetic resonance imaging and/or endoscopy in the first year after treatment initiation were analysed.
Results
Median vedolizumab trough levels in the overall population (n = 82) were 27 μg/mL (interquartile range, IQR 21.2‐33.8 μg/mL) at week 2, 23 μg/mL (IQR 15‐34.5 μg/mL) at week 6 and 10.7 μg/mL (IQR 4.6‐20.4 μg/mL) at week 14. Only median vedolizumab trough levels at week 6 differed between patients with and without mucosal healing within the first year after treatment initiation (26.8 vs 15.1 μg/mL, P = 0.035). A cut‐off trough level of 18 μg/mL at week 6 predicted mucosal healing within the first year after the start of vedolizumab with an area under the receiver operating curve of 0.735 (95% confidence interval 0.531‐0.939). A vedolizumab trough level above 18 μg/mL at week 6 was the only independent variable associated with mucosal healing within the first year of treatment (odds ratio 15.7, 95% confidence interval 2.4‐173.0, P = 0.01).
Conclusion
Early therapeutic drug monitoring might improve timely detection of vedolizumab‐treated patients in need for an intensified dosing regimen.
Linked ContentThis article is linked to Fragaki and Karmiris and Marabotto papers. To view these articles visit https://doi.org/10.1111/apt.14588 and https://doi.org/10.1111/apt.14800.
Current treatment modalities in IBD allow us to render normal quality of life to most patients. Ideally, structured digital care pathways can be harmonised in order to measure (semi-) automatically ...key outcome quality indicators and compare between institutions.
Key quality criteria were selected through a consensus process and aligned with the ICHOM quality criteria in IBD, including clinical parameters, PROMs, quality of life, health care utilisation and productivity.
Measurements of the 11 selected key quality criteria were integrated in the structured care pathways of three IBD units. All patients received (at least) twice a year three questionnaires (PRO2 or SCCAI, ICHOM criteria and IBD Disk) through the electronic application to collect necessary information ahead of their planned outpatient clinic. In addition, interpretation of biomarkers was automated, and more difficult outcome indicators were manually added by the caregiver during the visit in anticipation of adaptations to or improvements of the electronic record. All information was collected centrally electronically in a structured way allowing benchmarking between the three centres, and stored for future retrospective research.
A (partially) automated benchmarking for measuring quality of care is feasible. It provides an objective assessment of IBD care, enables benchmarking between centres and facilitates quality improvements projects.
Linked Content
This article is linked to Goncalves et al papers. To view these articles visit https://doi.org/10.1111/apt.14808 and https://doi.org/10.1111/apt.14860.
The enumeration of circulating tumour cells (CTCs) with the EpCAM-based CellSearch system has prognostic significance in patients with metastatic breast cancer (MBC). The aim of this study was to ...explore potential differences in the detection and prognostic significance of CTCs in MBC according to immunohistochemical subtypes of breast cancer.
CellSearch CTC counts were obtained from 154 MBC patients before first-line systemic treatment between November 2007 and August 2012. Patients were categorised in five subgroups according to immunohistochemical surrogate definitions of intrinsic subtypes in breast cancer based on hormone receptor status, HER2/neu status and histological grade. Differences in progression-free (PFS) and overall survival (OS) were assessed relative to the cut-off value of ≥5 CTCs per 7.5 ml blood.
No significant differences were observed in the absolute CTC counts (P=0.120) or in CTC positivity rates according to ≥1 and ≥5 CTCs per 7.5 ml blood detection thresholds (P=0.165 and P=0.651, respectively) between immunohistochemical subtypes. However, very high CTC counts, defined as ≥80 CTCs per 7.5 ml, were observed more frequently in patients with Luminal A and triple negative (TN) breast cancer (P=0.024). In the total study population, the presence of ≥5 CTCs was the single most significant prognostic factor for both PFS and OS in multivariate analysis (P<0.001). A more limited prognostic impact, not reaching statistical significance, was observed in patients with HER2-positive disease as opposed to patients with Luminal A, Luminal B-HER2-negative and TN disease.
The detection of EpCAM+CTCs was not clearly associated with any of the immunohistochemical subtypes of breast cancer in patients with MBC before first-line treatment. Potentially clinically relevant differences were however observed at very high CTC counts. Furthermore, our data suggest a lower prognostic significance of CTC evaluation in HER2-positive patients with MBC.
Abstract
Background
IBD requires tight monitoring of disease activity. E-health applications are associated with improved clinical outcomes and have a positive impact on healthcare costs. INTERACTION ...(telemedIciNe as parT of an intEgRAted IBD Care paThway @Imelda bONheiden) is a pilot project exploring the feasibility of implementation of teleconsultation in an existing tight monitoring care pathway and potential (dis)advantages for patients, health-care workers and quality-of-care.
Methods
INTERACTION is an ongoing, single-centre feasibility project including patients with moderate-to-severe IBD (UC/CD) treated with immunomodulators, subcutaneous biotherapy or oral small molecules since February 2022. Eligibility criteria include (i) stable treatment and remission, based on physician global assessment, patient-reported outcomes (UC: SCCAI<3; CD: PRO-2 ≤11), and faecal calprotectin (<250 µg/g) or endoscopy (UC: MES ≤1; CD: SES-CD ≤5), and (ii) digital access.. Participants agreed to embark in an adapted care pathway implementing video consultations with the treating physician alternating with in-person consultations. PRO’s and biomarkers were collected on dedicated time points (Figure 1). Patients’ expectations were questioned at the start of the pathway. Outcomes included patients’ experiences (assessed with the adapted Telehealth Usability Questionnaire), socio-economic impact, and clinical evolution (IBD-related flares or hospitalizations).
Results
At the moment of interim analysis (Oct 24th 2022), 37/44 (84%) invited patients wanted to participate. The majority expected that teleconsultations could be equal to in-person consultations (86%) and lead to an increased access to healthcare (92%) and time gain (97%). Seven patients refused participation for various reasons (Table 1). Four patients were screen failures due to lack of remission. Ultimately, 33 patients (baseline characteristics: Table 2) underwent a total of 67 consultations. The majority (92%) experienced the video consultations as (strongly) satisfactory (Figure 2). Patients’ time savings with video consultation compared to an in-person consultation varied between 0-30’ (16%); 30-60’ (36%), 60-120’ (36%) and more than 120’ (12%). The majority (92%) avoided a round trip to the hospital of at least 10 km. Forty percent averted absenteeism. One patient experienced an IBD flare without the need for hospitalisation during the median follow-up of 3 (IQR 3-5.5) months .
Conclusion
Implementing video consultations in the IBD care pathway of the ongoing INTERACTION project seems feasible, well-received and safe in patients with IBD in stable remission. In a second phase, video consultations led by an advanced IBD-nurse warrant further exploration.
Abstract
Background
Subcutaneous (SC) formulations were recently approved for CT-P13 and vedolizumab (VED). No insights in the willingness of patients with Inflammatory Bowel Disease (IBD) to switch ...from intravenous (IV) to SC maintenance therapy with CT-P13 and VED are available. The aims of this study were (1) to evaluate the percentage of patients with IBD in favour of switching to SC formulations, (2) to define the factors influencing this decision, and (3) to explore the role of the IBD nurse in the process of switching.
Methods
This was a monocentric study in patients with IBD on maintenance IV CT-P13 or VED. All patients attending the infusion unit were invited to complete a survey exploring the willingness to switch to SC formulations. Prior to completing the survey, patients were informed on the new SC formulations and the accompanying care pathway. The survey was performed prior to the market introduction of SC CT-P13 and VED. Demographics, patient reported outcomes, willingness to switch and reason for IV vs. SC preferences were captured.
Results
In total, 183 (91%) patients completed the survey (m/f: 84/99; CD/UC/IBD-U: 120/57/6; median age 45 IQR 34–59; remission CD/UC: 67%/75%). The majority of patients preferred switching to SC (56% yes, 12% no, 32% doubt). The main driver to switch was an anticipated decrease in hospital visits (90%); the main reason to continue IV was fear of change (61%). Patients doubting to switch had a lower stool frequency compared with patients making a definite decision (p=0.012). Factors significantly associated with the willingness to switch in the univariate analysis were younger age (p<0.0001), experience with SC therapy (p=0.03), full time work occupancy (p=0.001), younger age at start IV therapy (p=0.001), shorter disease duration (p=0.012), and compliance level (p<0.0001). Multivariate analysis retained younger age as the only independent factor. For patients doubting to switch, an electronic alert (71%), an information brochure (69%), and a personal teaching moment (60%) were recognised as valuable support. An information package should cover patient-focused efficacy and safety data of SC therapy, therapeutic options in case of disease worsening, and practical concerns including information about administrative issues and travelling.
Conclusion
This is the first study exploring the willingness to switch from IV to SC maintenance therapy with CT-P13 and VED in patients with IBD. The majority prefers to switch to a SC formulation, with willingness to switch being most likely in younger patients. Further studies are required to investigate the impact of nurse led interventions on the willingness to switch, patient satisfaction, and treatment compliance.
Abstract
Background
The α4β7 integrin monoclonal antibody vedolizumab (VDZ) has been shown to be efficacious for patients with moderate-to-severe Crohn’s disease (CD). This study aimed to analyse the ...added value of budesonide in combination with VDZ as an induction treatment for this indication.
Methods
A multicentre, retrospective chart review study was conducted in Belgium, Israel, and Switzerland. Adult patients with moderately to severely active CD (defined as an abdominal pain AP score of ≥2 and/or a mean daily loose stool frequency LSF score of ≥4 for the previous 7 days) who initiated induction therapy with either VDZ monotherapy (mono) or a combination therapy (combo) of VDZ with budesonide (index date) between 1 January 2015 and 31 January 2019 were included. Patients who received VDZ by IV infusion at weeks 0, 2, 6, 10 (only some patients received VDZ during week 10), and 8 weeks thereafter were assessed for time to patient-reported outcome (PRO) clinical remission (Kaplan-Meier curves), defined as an average daily composite score of AP ≤1 and LSF ≤31 within 14 weeks. Regression models were used to assess differences and associations.
Results
Overall, 123 patients were included (mono, n=73; combo, n=50). Patients initiating combo presented with more severe disease at index date than patients initiating mono. PRO clinical remission rates were estimated at 71.4% (50/70) in the mono and 68.0% (34/50) in the combo groups, with a similar median time to PRO remission of 91 days (95% CI: 70–98) and 95 days (95% CI: 70–98), respectively (Figure 1). Figure 2 shows the mean % change in AP and LSF from baseline to week 14, which was comparable for mono and combo. The variables associated with mean % change were moderate and severe AP scores for AP and being a current smoker for LSF. One patient in each group discontinued VDZ before week 14 (due to lack of effectiveness mono and adverse event AE; combo); 68.0% of patients in the combo group discontinued budesonide by the end of the follow up period. The reasons for discontinuation were routine treatment regimen (8 weeks 9 mg/day+subsequent tapering-off) in 85.3% of the patients, lack of effectiveness in 5.9% and AEs in 2.9% (5.8% other reasons). Safety event rates were similar among the groups for overall AEs (mono, 23.3%; combo, 26.0%), with the majority designated as mild to moderate in severity, and 83.3% resolved within the follow-up period.
Conclusion
Comparable effectiveness and safety outcomes were observed with mono and combo therapy in patients with CD; however, disease state among patients receiving combo was more refractory/severe at baseline. Further evidence is needed to corroborate these findings.
Reference
Abstract
Background
Treating beyond endoscopic remission, aiming for histological remission, has shown to reduce relapse and hospitalization rates in patients with ulcerative colitis (UC). However, ...very little is known on how histological remission associates with patient reported outcomes (PROMs).
Methods
PROMs (Simple clinical colitis activity index SCCAI, IBD disk and Visual Analogue Scales VAS) were prospectively collected through a digital questionnaire in all patients with UC undergoing colonoscopy between July 21st 2020-Jan 21st 2021. Mayo endoscopic sub score and UCEIS were determined, as well as the Nancy histologic index (NHI) of the most affected area. Endoscopic remission was defined as Mayo endoscopic sub score 0 and UCEIS 0; histologic remission as NHI 0, absence of active inflammation as NHI ≤ 1. PRO2 remission was defined as stool frequency ≤ 1 (absolute stool frequency ≤ 3 OR 1–2 stools more than usual) and rectal bleeding score of 0.
Results
Fifty-six paired assessments were collected in 48 unique patients (Table 1), with a histologic, endoscopic and PRO-2 remission rate of 23.2%, 28.6% and 38.2% respectively. Patients with histologic remission or absence of histologic inflammation had a significantly lower overall IBD disability (p=0.007, p=0.003) and disease activity score (p=0.003, p<0.001), as compared to patients without. In line, NHI correlated with the overall IBD disk (r=0.40, p=0.002) and SCCAI score (r=0.50, p<0.001). Many individual components of both scores (abdominal pain, arthralgia, impact on education and work/interpersonal interactions/sexual function, regulation of defecation, blood loss, general wellbeing, joint pain, numbers of stools during night/day, urgency) differed significantly between patients with and without histologic remission. VAS scores assessing general wellbeing (r=0.33, p=0.01), impact on daily activities (r=0.41, p=0.002), UC-related symptoms (r=0.42, p=0.001) and worries (r=0.40, p=0.002) correlated with histology. Quartile analysis of the overall IBD disk and SCCAI scores confirmed the highest likelihood for histologic remission in patients with the lowest scores (Q1-Q2 vs Q3-Q4 39.3% vs 7.1%, p=0.01; 40.0% vs 9.7%, p=0.01) (Figure 1). Nevertheless, the overall accuracy of the IBD disk (0.75) or SCCAI score (0.76) for histologic remission is lower (p<0.05) than the accuracy of the Mayo endoscopic (0.90) or UCEIS (0.90) score.
Table 1: Baseline features
Abstract OP09 – Figure 1: Quartile analysis
Conclusion
In patients with UC, PROMs for disability and clinical disease activity reflect histologic disease activity and should therefore be further explored in (trial) endpoint discussions. However, they cannot fully replace endoscopic and histologic findings, and should be considered complementary.
Abstract
Background
Quality of care in inflammatory bowel disease (IBD) depends on multiple factors and is assessed through structure, process and outcome indicators. Structure and process indicators ...are more static and can easily be measured by an audit. Patient-oriented outcome indicators that impact on the quality of life are more difficult to assess.
The aim of the project was to build a platform that automatically captures key outcome quality indicators and provide benchmarking output to improve quality of care in IBD centres.
Methods
Literature was reviewed for relevant quality indicators in IBD. After two non-anonymized Delphi like review and consensus meetings, twelve quality indicators were selected for implementation. The definitions of the outcomes were aligned in consensus with the available International Consortium for Health Outcomes Measurement (ICHOM). A web-based interface was built in three large volume IBD centres in Belgium to collect data on multiple ways: (i) Patients complete patient-reported outcome questionnaires and disease specific questions when attending the outpatient clinic and/or day clinic; (ii) The software automatically extracts data from the electronic medical files including biochemical and endoscopic reports; (iii) The medical baseline characteristics and outcome indicators for each patient are completed by the healthcare professional at inclusion and after this on a yearly basis.
Results
In total 265 patients were included in the participating IBD centres. Three indicators could be directly extracted from the patient-reported outcome questionnaires (clinical remission, fatigue, work productivity). Two items could be retrieved by use of the bot that automatically extracts biochemical and endoscopic reports from the medical files (anaemia, deep remission). The other items were collected throughout yearly confirmation by a health care professional (colorectal cancer, steroid use systemic/topical, severe infections, hospital admission, IBD surgery perianal/abdominal). All items are benchmarked in an anonymous way on a benchmarking dashboard. Each centre can only see his own position in the benchmarking diagram. Additionally, the case mix per centre (type IBD, severity, demographic data) was added to the benchmarking output to provide a balanced evaluation of the outcome indicators.
Conclusion
This is the first partially automated benchmarking initiative for quality of care in IBD. The data collection is feasible and provides an objective assessment and comparison of the IBD related quality of care in different centres. Further prospective evaluation needs to confirm that implementation of benchmarking improves the performance and quality of IBD management.
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