Prospective Multicenter Study Research Articles

Impact of clinical and treatment characteristics on HR-QoL in patients with prolactinoma - cross-sectional analysis of a dutch multicenter prospective cohort study

Impact of clinical and treatment characteristics on HR-QoL in patients with prolactinoma - cross-sectional analysis of a dutch multicenter prospective cohort study

FASTOCH: Feasibility of Electronic Patient-Reported Outcomes in Older Patients With Cancer-A Multicenter Prospective Study.

Multiple studies have demonstrated that electronic patient-reported outcomes (ePROs) improve overall survival and quality of life in cancer care. However, there are no specific prospective data on remote ePRO monitoring in the older population, although they represent a significant proportion of patients with cancer. From February 2021 to April 2022, patients age 75 years and older under active anticancer treatment were consecutively recruited in six institutions. Remote ePRO feasibility was determined in intention-to-test (ITT) on the basis of the number of active users in the overall population. Primary failure applied to patients who had no Internet access or declined to test ePROs, while the other patients were assigned to the ITT population. Feasibility was also determined per-protocol on the basis of the number of active patients in the ITT population. Of the 473 patients included, primary failure applied to 288 patients (233 of whom had no Internet access). Among the 185 patients in ITT, 122 used ePROs, leading to a 26% feasibility in ITT and a 66% feasibility per protocol. In a multivariate analysis, the intent to test population was from a higher socioprofessional category (P = .009) and felt in better general condition in the Geriatric 8-score evaluation (P = .002). Active patients significantly differed from the inactive on their self-assessment of a better general condition (P < .001) only. Our multicenter study showed a limited feasibility rate (26%) of remote ePROs monitoring for older patients with cancer, mainly because of technology barriers. Yet, among the patients who did have Internet access, most of them indeed used ePROs (66%). Given the expected benefit of ePROs, the technology barriers therefore need to be lifted to improve cancer care in older patients.

Lipoprotein subclasses are associated with Hepatic steatosis: insights from the prospective multicenter imaging study for the evaluation of chest pain (PROMISE) clinical trial

ObjectivesTo determine the relationship between lipoprotein particle size/number with hepatic steatosis (HS), given its association with traditional lipoproteins and coronary atherosclerosis. MethodsIndividuals with available CT data and blood samples enrolled in the PROMISE trial were studied. HS was defined based on CT attenuation. Lipoprotein particle size/number were measured by nuclear magnetic resonance spectroscopy. Principal components analysis (PCA) was used for dimensionality reduction. The association of PCA factors and individual lipoprotein particle size/number with HS were assessed in multivariable regression models. Associations were validated in an independent cohort of 59 individuals with histopathology defined HS. ResultsIndividuals with HS (n=410/1,509) vs those without (n=1,099/1,509), were younger (59±8 vs 61±8 years) and less often females (47.6 % vs 55.9 %). All PCA factors were associated with HS: factor 1 (OR:1.36, 95 %CI:1.21–1.53), factor 3 (OR:1.75, 95 %CI:1.53–2.02) and factor 4 (OR:1.49; 95 %CI:1.32–1.68) were weighted heavily with small low density lipoprotein (LDL) and triglyceride-rich (TRL) particles, while factor 2 (OR:0.86, 95 %CI:0.77–0.97) and factor 5 (OR:0.74, 95 %CI:0.65–0.84) were heavily loaded with high density lipoprotein (HDL) and larger LDL particles. These observations were confirmed with the analysis of individual lipoprotein particles in PROMISE. In the validation cohort, association between HS and large TRL (OR: 8.16, 95 %CI:1.82–61.98), and mean sizes of TRL- (OR: 2.82, 95 %CI:1.14–9.29) and HDL (OR:0.35, 95 %CI:0.13–0.72) were confirmed. ConclusionsLarge TRL, mean sizes of TRL-, and HDL were associated with radiographic and histopathologic HS. The use of lipoprotein particle size/number could improve cardiovascular risk assessment in HS.

Efficacy of Tegoprazan in Patients With Functional Dyspepsia: A Prospective, Multicenter, Single-arm Study.

Acid-suppressive drugs, such as proton pump inhibitors (PPIs), are treatment options for functional dyspepsia (FD). However, the efficacy of potassium-competitive acid blockers (P-CABs) in treating FD has not yet been established. This prospective multicenter clinical trial-based study aimed to assess the efficacy and safety of tegoprazan as a P-CAB treatment in patients with FD. FD was diagnosed using the Rome IV criteria. All patients received tegoprazan 50 mg once daily for 8 weeks. Dyspeptic symptoms were assessed using a dyspepsia symptom questionnaire (5-point Likert scale, Nepean Dyspepsia Index-Korean (NDI-K), and gastroesophageal reflux disease-health-related quality of life (GERD-HRQL). The main outcome was satisfactory symptom relief rates at 8 weeks. In this study, from the initial screening of 209 patients, 173 were included in the per-protocol set analysis. Satisfactory symptom relief rates at 8 and 4 weeks were 86.7% and 74.6%, respectively. In addition, the NDI-K and GERD-HRQL scores significantly improved at 8 and 4 weeks compared with the baseline scores. The efficacy of tegoprazan was not influenced by the FD subtype or Helicobacter pylori status. In patients with overlapping FD and GERD, there was a greater improvement in the NDI-K and GERD-HRQL scores than in patients with FD symptoms only. No serious drug-related adverse events occurred during this study. Tegoprazan (50 mg) administered once daily provided satisfactory symptom relief for FD.

Prospective observational study comparing the perioperative outcomes of laparoscopic colectomy with or without epidural anesthesia: the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC) 1806.

There have been no adequate comparisons of the efficacy, safety, and efficiency of analgesia after laparoscopic colorectal resection (LAC), with and without epidural anesthesia (EDA). This was a multicenter prospective observational study of patients undergoing LAC. The primary end point was the mean visual analog scale (VAS) score on postoperative days (PODs) 1-7. The secondary end points were the highest VAS, complication rate, days to first ambulation and fatigue, length of hospital stay, and time to commencement of surgery. We compared an EDA group (Group E, n = 48) and a no-EDA group (Group O, n = 48) after matching. The mean VAS was not significantly different between the groups (28.7 vs. 30.1, p = 0.288). On assessing the secondary end points, the highest VAS was not significantly different between the groups. In fact, the VAS was lower in Group E only on POD 2. There was no difference in the incidence of complications, the time to first postoperative evacuation was shorter in Group E, and postoperative hospitalization was similar. The time to surgery was shorter in Group O. These results suggest that LAC without EDA is a feasible option, but with the early and regular use of adjunctive measures to provide more stable analgesia.

Ultrafast intraoperative parathyroid hormone monitoring system: prospective, multicentre, clinical validity study.

Intraoperative parathyroid hormone (PTH) monitoring is a proven and reliable adjunct to parathyroid surgery, able to improve the outcomes and efficiency of the diagnostic and therapeutic pathway for patients with primary hyperparathyroidism. This study evaluated the innovative, compact, fully automated NBCL CONNECT Analyzer, which can measure whole-blood PTH in 5 min. A prospective multicentre study was conducted in stages: results reviews, recommendations, and implementation of improvements to the mechanical design, components of cartridges, calibration, and sampling protocols. Patients undergoing parathyroidectomy had PTH levels measured on the Analyzer and main laboratory platforms, either Roche or Abbott. The Miami criterion of a 50% drop in PTH concentration was used to define biochemical cure during surgery, and normal postoperative calcium level as cure of primary hyperparathyroidism. Measurements on the Analyzer were done by laboratory staff in London and nurses in Stuttgart. The Pearson coefficient (R) and Wilcoxon test were used for statistical analysis. Some 234 patients (55 male, 179 female) with a median age of 58.5 (age full range 15-88) years underwent parathyroidectomy (195 minimally invasive, 38 bilateral neck exploration, 1 thoracoscopic; 12 conversions) for primary hyperparathyroidism between November 2021 and July 2022. Primary hyperparathyroidism was cured in 225 patients (96.2%). The sensitivity, specificity, and overall accuracy of the Analyzer assay in predicting biochemical cure were 83.9, 100, and 84.8% in phase 1; 91.2, 100, and 91.3% in phase 2; and 98.6, 100, and 98.6% in phase 3. There were no false-positive results (positive predictive value 100%). Correlations between Analyzer measurements and those obtained using the Roche device were very strong (R = 0.98, P < 0.001 in phase 1; R = 0.92, P < 0.001 in phase 2; R = 0.94, P < 0.001 in phase 3), and correlations for Analyzer readings versus those from the Abbott platform were strong (R = 0.82, P < 0.001; R = 0.89, P < 0.001; R = 0.91, P < 0.001). The Analyzer showed continued good mechanical performance, with stable and repeatable operations (calibrations, quality controls). Introducing a stricter sampling protocol and improvements in the clot-detecting system led to a decrease in the number of clotted samples and false-negative results. Outcomes were not affected by measurements performed either by nurses or laboratory staff. Intraoperative PTH monitoring during parathyroid surgery can be done accurately, simply, and quickly in whole blood using the Analyzer.

Bronchiectasis in Türkiye: Data from a Multicenter Registry (Turkish Adult Bronchiectasis Database).

Bronchiectasis is a chronic lung disease characterized by permanent bronchial wall dilatation. Although it has been known as an orphan disease, it has recently gained attention because of registry-based studies and drug research. We aimed to use a multicenter database to analyze and compare data regarding the etiology, associated comorbidities, microbiological characteristics, and preventive strategies of bronchiectasis in Türkiye to those of other countries. A multicenter prospective cohort study. The multicenter, prospective cohort study was conducted between March 2019 and January 2022 using the Turkish Adult Bronchiectasis Database, in which 25 centers in Türkiye participated. Patients aged > 18 years who presented with respiratory symptoms such as cough, sputum, and dyspnea and were diagnosed with non-cystic fibrosis bronchiectasis using computed tomography were included in the study. Demographic information, etiologies, comorbidities, pulmonary functions, and microbiological, radiological, and clinical data were collected from the patients. Of the 1,035 study participants, 518 (50%) were females. The mean age of the patients was 56.1 ± 16.1 years. The underlying etiology was detected in 565 (54.6%) patients. While postinfectious origin was the most common cause of bronchiectasis (39.5%), tuberculosis was identified in 11.3% of the patients. An additional comorbidity was detected in 688 (66.5%) patients. The most common comorbidity was cardiovascular disease, and chronic obstructive pulmonary disease (COPD) and bronchiectasis was identified in 19.5% of the patients. The most commonly detected microbiological agent was Pseudomonas aeruginosa (29.4%). Inhaled corticosteroids (ICS) were used in 70.1% of the patients, and the frequency of exacerbations in the last year was significantly higher in patients using ICS than in nonusers (p < 0.0001). Age [odds ratio (OR): 1.028; 95% confidence interval (CI): 1.005-1.051], cachexia (OR: 4.774; 95% CI: 2,054-11,097), high modified medical research council dyspnea scale score (OR: 1,952; 95% CI: 1,459-2,611), presence of chronic renal failure (OR: 4,172; 95% CI: 1,249-13,938) and use of inhaled steroids (OR: 2,587; 95% CI: 1,098-6,098) were significant risk factors for mortality. Mortality rates were higher in patients with COPD than in those with no COPD (21.7-9.1%, p = 0.016). Patients with bronchiectasis and COPD exhibited more frequent exacerbations, exacerbation-related hospitalizations, and hospitalization in the intensive care unit in the previous year than patients without COPD. This is the first multicenter study of bronchiectasis in Türkiye. The study results will provide important data that can guide the development of health policies in Türkiye on issues such as infection control, vaccination, and the unnecessary use of antibiotics and steroids.

Telemedicine in Nail Psoriasis: Validation of a New Tool to Monitor (In-Person, In-Picture, and In-Video) Nail Psoriasis Severity in Patients with Concurrent Onychophagia and Onychotillomania.

Since during the COVID-19 pandemic nail psoriasis was evaluated exclusively with teledermatology, dermatologists started to face the difficulty in rating it concurrent with other onycopathies (i.e., onychotillomania and onychophagy). Thus, we aimed to improve the existing severity scores and verify the value in different clinical settings (i.e., in person vs. teledermatology (video or picture)). This multicenter prospective observational study evaluated patients with nail psoriasis and screened them for onychophagy or onychotillomania in telemedicine from May2020 to January 2021. For therapeutic purposes patients with nail psoriasis were followed and rated with the Nijmegen-Nail psoriasis Activity Index tooL (N-NAIL) for 9months; at the same time, N-NAIL and a new dedicated index that monitor also the changes in nail dimension (Galeazzi-(G) N-NAIL) were tested for accuracy. We assessed inter- and intraobserver agreement for the three different settings (in person, video, and pictures). In our cohort of 382 patients with nail psoriasis after a clinical and dermatoscopic assessment we found 20 (5.24%) patients with onychophagy and 17 (4.45%) patients with onychotillomania. Analysis of the impact of nail psoriasis on patients revealed that onycholysis and crumbing, followed by subungual hyperkeratosis, were the clinical signs that prevalently bothered patients. N-NAIL score displayed moderate intra- and interobserver agreement. Over the 9months follow-up, N-NAIL vs. GN-NAIL displayed a solid correlation at all the examined time points, i.e., baseline and after 3, 6, and 9months. We created a new tool, the GN-NAIL capable of efficiently scoring nail psoriasis severity in complex cases, such as patients with onychotillomania and onychophagy, and monitor response to treatment during the COVID-19 pandemic.

Estimates and Predictors of Mortality, Stroke Recurrence, and Functional Dependency 1-Year after Ischemic Stroke: A Prospective Multicenter Longitudinal Cohort Study in Central Norway

Background. Stroke incidence and mortality have drastically decreased in high-income countries in the past twenty years. In this study, we provide updated estimates on mortality, recurrent stroke, and functional dependency among patients with first-ever ischemic stroke and assess predictors associated with poor outcomes with a focus on age, vascular factors, stroke severity, function, and comorbidity burden. Methods. MIDNOR STROKE is a multicenter prospective longitudinal study including patients with first-ever ischemic stroke admitted to stroke units in Central Norway during 2015-2017. Data on survival, stroke recurrence, and functional dependency were collected during hospital stay and follow-up. Multivariable Cox proportional hazard models and logistic regression models were used to analyze predictors of mortality, stroke recurrence, and functional dependency. Results. A total of 794 participants were included in the study. After a year, 7.6% of the participants had died, 5.8% had a recurrent stroke, and 13.6% experienced functional deterioration to dependency. Multivariable analysis revealed that age (HR: 1.07, 96% CI: 1.03, 1.10), stroke severity (HR: 1.10, 95% CI: 1.07, 1.13), comorbidity burden (low: HR: 4.05, 95% CI: 1.48, 11.10; moderate: HR: 5.44, 95% CI: 2.06, 14.40; and high: 7.72, 95% CI: 2.85, 21.00), and coronary artery disease (HR: 2.40, 95% CI: 1.32, 4.38) predicted all-cause death. Statin therapy predicted improved survival (HR: 0.39, 95% CI: 0.21, 0.75). High age (HR: 1.09, 95% CI: 1.05, 1.14) and increased stroke severity (OR: 1.26, 95% CI: 1.17, 1.38) predicted elevated risk of functional dependency at one year. Conclusions. In this study, we have demonstrated that 1-year survival following first-ever ischemic stroke was high compared to previous reports and that statin therapy predicted improved survival. The risk of recurrent stroke after one year was found to be low compared to previous studies. Approximately 14% of stroke survivors who were initially functionally independent experienced deterioration to functional dependency. In addition to older age and stroke severity, increased comorbidity burden and a history of coronary artery disease predicted poor stroke prognosis. Interventions aimed at reducing stroke severity may improve patient outcomes. Furthermore, prevention efforts targeting conditions such as CAD and reducing overall comorbidity burden in stroke patients may favorably improve survival. This trial is registered with NCT03962127.

Nerve transfer for upper extremity reanimation in people with spinal cord injury: A 2-year follow-up case series

Objective To describe the 2-year functional outcomes of nerve transfer (NT) for upper extremity reanimation. Study Design A prospective case series. Setting A highly specialized rehabilitation hospital for spinal cord injury (SCI) in Italy. Intervention Upper limb nerve transfer (32 NTs, 15 upper limbs). Participants Twelve male individuals with traumatic SCI (AIS A or B, neurological level from C4 to C7) were enrolled; 24-month follow-up data were available for 11. Outcome measures We evaluated the strength recovery of recipient muscles through the Medical Research Council (MRC) Scale for Muscle Strength. Upper limb function and independence were assessed with the Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP) test version 1 and the Spinal Cord Independent Measure III (SCIM III). Patient satisfaction was also evaluated. Results After 24 months, median MRC scores (range) were: triceps 2 (1–2); extensor digitorum communis 3 (1–4); extensor pollicis longus 2.5 (1–4); flexor digitorum profundus 2 (0–4); flexor pollicis longus 2 (0–4). No complication occurred. GRASSP prehension ability and prehension performance total scores significantly improved at 24 months from 1 (0–4) to 2 (0–7) and from 1 (0–8) to 5 (0–-22), respectively. The SCIM III self-care sub-scale score improved at 24-month follow-up (p = 0.009). This study has important limitations, including a limited generalizability of the results and a small sample size that does not allow definitive conclusions to be drawn. A large multicenter prospective study is needed to confirm our findings. Conclusions NT represents a functional surgery option with few complications for the resuscitation of upper limbs in persons with tetraplegia.

Abstract PO4-11-04: Early Discontinuation of Adjuvant Chemotherapy in Older Adults with Early Breast Cancer: Results from the Prospective Multicenter HOPE Study

Abstract Background: Older adults with early breast cancer (EBC) treated with adjuvant chemotherapy frequently experience severe toxicities. As a result of such toxicities, many older adults do not complete all planned chemotherapy cycles (i.e., discontinue chemotherapy early). Early discontinuation may increase the risk of recurrence and decrease survival. However, aging is heterogeneous and identifying which older adult is at risk of early discontinuation before starting chemotherapy remains a key knowledge gap. To fill this gap, we examined the incidence, reasons, and risk factors for early discontinuation of adjuvant chemotherapy in older adults with EBC. Methods: This is a post-hoc analysis of 501 older adults (age&amp;gt;65) with EBC enrolled in the Hurria Older PatiEnts (HOPE) with Breast Cancer Study (NCT01472094, R01AG037037), a prospective multicenter study. All participants were treated with neo/adjuvant chemotherapy. Prior to initiating chemotherapy, participants completed survey measures on sociodemographic, clinical, and geriatric assessment characteristics. The primary outcome was early discontinuation (yes/no; yes, defined as failure to complete all planned chemotherapy cycles). Multivariable logistic regression with stepwise selection was used to evaluate the association between baseline variables (demographic, clinical, geriatric assessment) and early discontinuation. Results: A total of 501 participants (median [range] age, 70 [65-86] years and mean [SD] physician-rated KPS 93 [9.3]) were included. One hundred and thirteen (23%) had early discontinuation. Among participants with early discontinuation, 69% discontinued treatment within the last 3 cycles. In bivariate analysis, early discontinuation was associated with older age (continuous), higher stage (II/III), use of non-TC regimens (anthracycline-based or trastuzumab-based), lower albumin level (continuous), a history of diabetes, ≥1 fall in the last 6 months, and lower activities of daily living (ADL) score (&amp;lt; 85). Multivariable stepwise logistic regression analysis identified that ≥1 fall in the last 6 months, ADL score &amp;lt; 85, and regimen were associated with early discontinuation at p &amp;lt; 0.05. In the final model, after accounting for clinically meaningful variables including age, stage, and regimen, the results for falls (odds ratio [OR] = 2.04, 95% CI: 1.10-3.78, p=0.02) and ADL (OR=2.10, 95% CI: 1.32-3.34, p=0.002) remained highly significant. Compared to participants with no falls and ADL scores &amp;gt;85, participants with who reported both falls and an ADL score &amp;lt; 85 prior to initiation of chemotherapy had more than 4-fold increased odds of early discontinuation (Table). Conclusion: In this cohort of older adults with EBC, nearly 1 in 4 older patients initiated neo/adjuvant chemotherapy but did not complete all planned chemotherapy cycles. Older patients at risk for early discontinuation should be identified and targeted upfront before initiating chemotherapy. Table. Multivariable associations between falls, ADL score, and early discontinuation. *Adjusted for age (continuous), stage (I vs. II/III), and regimen (anthracycline based + no trastuzumab vs. non-anthracycline based + no trastuzumab vs. anthracycline based + trastuzumab vs. platinum/CMF + trastuzumab vs. taxol only + trastuzumab vs. other). ** Five patients missing fall information. Two patients missing ADL score. Citation Format: Jingran Ji, Canlan Sun, Rachel Freedman, Harvey Cohen, Heidi Klepin, William Tew, Beverly Moy, Andrew Chapman, Tanya Wildes, Efrat Dotan, Allison Magnuson, Tracey O'Connor, Mary Anne Fenton, Heeyoung Kim, Vani Katheria, Cary Gross, Hyman Muss, Mina Sedrak. Early Discontinuation of Adjuvant Chemotherapy in Older Adults with Early Breast Cancer: Results from the Prospective Multicenter HOPE Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-11-04.

Abstract PO4-07-08: Impact of an MRI/US fusion imaging for preoperative planning using non-wire localization technique in breast conserving surgery in patients with non-mass enhancement on MRI. A prospective multicenter study

Abstract [Background] Preoperative breast MRI is used to evaluate for additional and extent disease for newly diagnosed breast cancer patients with dense breasts. The potential benefit of preoperative MRI is still being controversial. However, when breast conserving surgery (BCS) is considered for non-mass enhancement (NME) on MRI, the precise image-guided localization is required. Although breast ultrasound (US) plays an adjunctive role in evaluation of MRI findings in preoperative planning for BCS, NME is less likely than a mass or focus to have a US correlate. Furthermore, the presence of NME increases the re-operation rate in BCS because of the difficulty in evaluating the tumor margin. An MRI/US fusion imaging has recently been developed that uses either real-time virtual sonography TM (RVS) or volume navigation TM (Vnav), and can overlay an US with the MRI image of the same site in real time by using magnetic position tracking system. The purpose of this prospective multicenter study was to evaluate the effect of MRI/US fusion imaging for preoperative planning using non-wire localization technique in BCS in patients with NME. [Methods] In 3 Japanese hospital, 13 patients who had lesions with NME that exceeded the US hypoechoic area were enrolled in this study from 2019 to 2022. Written informed consent was acquired, and then an additional supine MRI using a body surface coil was performed. During preoperative planning before BCS, RVS/Vnav was used to determine the NME enhancing area and to mark the area on the skin. Tissue markers were inserted under US at a location assessed by RVS/Vnav as the edge of extent of NME. We analyzed both the surgical margin positivity rate and the reoperation rate. [Results] The preoperative diagnosis by core needle biopsy were 6 DCIS and 7 invasive ductal carcinoma. NME distribution types were 7 segmental, 3 focal, 2 linear 4 and 1 regional. The median diameters of the NME and hypo-echoic lesions were 31 mm (range: 18–39 mm) and 16 mm (range: 9–32 mm), respectively (p = 0.0005). After confirming the localization of the tissue marker with intraoperative US, 12 lumpectomy and 1 quadrantectomy were conducted. The median specimen weight was 63g (range: 54-105g). In the final pathologic diagnosis of excised specimens were 5 DCIS and 8 IDC. In 8 cases (62%), the pathologic diameter was larger than the US diameter. All surgical margins were negative. None of the patients required additional resection. [Conclusions] The findings of study suggest that preoperative planning using non-wire localization technique under MRI/US fusion imaging for BCS in patients with NME could improve both a surgical margin positive rate and a reoperation rate. Citation Format: Shogo Nakano, Manabu Futamura, Keitaro Kamei, Takayoshi Uematsu, Miwa Yoshida, Sadako Akashi-Tanaka, Junta Sakakibara, Ichiro Isomoto, Hiroko Satake, Maiko Takahashi, Minami Hatono, Junko Araki. Impact of an MRI/US fusion imaging for preoperative planning using non-wire localization technique in breast conserving surgery in patients with non-mass enhancement on MRI. A prospective multicenter study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-08.

Abstract PO4-15-01: A multi-center prospective cohort study to evaluate the presence of circulating tumor cells using the Epic Sciences platform among women with metastatic breast cancer

Abstract Background: The presence of tumor cells (or their components) in the blood of women with a history of early breast cancer has the potential to herald the development of metastatic recurrence at its earliest stages. Such early detection could potentially lead to novel prevention strategies, but it requires a sensitive assay. Objective: To use the Epic Sciences platform to detect and enumerate CTCs in blood samples from patients with an established diagnosis of metastatic breast cancer (MBC), prior to initiation of 1st line systemic therapy in the metastatic setting. Methods: We conducted a multi-center prospective cohort study to evaluate the presence of CTCs using the Epic Sciences platform among patients with a new diagnosis of MBC. Men or women age 18 to 85 were included, irrespective of breast cancer subtype. Patients with a prior or concurrent malignancy whose natural history or treatment had the potential to interfere with the detection of MBC in a liquid biopsy were excluded. A one-time blood draw was performed before patients received any local or systemic therapy in the metastatic setting. In addition, those with recurrent disease must have been off any systemic adjuvant therapy for ≥3 weeks prior to blood collection. Two 5 mL blood samples were obtained for CTC identification and enumeration. CTC identification was based on immunofluorescence analysis using Epic Sciences platform as previously described (Ueno et al 2017). The presence of CTCs was correlated with clinical and pathological features, which were abstracted from medical records and pathology reports. The association between the presence of CTCs and clinical/pathologic characteristics was tested using Fisher’s exact test for categorical variables and t-test or Wilcoxon rank sum tests for numerical variables. All analyses were performed using the R software package. Results: 100 patients were recruited between February 2021 and January 2023 at five academic oncology centres in Ontario and Quebec, Canada. 95 patients had evaluable blood for analysis and 5 did not due to blood age and/or insufficient blood volume. Six patients were excluded after providing a blood sample because tissue biopsy ultimately revealed a 2nd primary tumor (n=4) or benign tissue (n=2). Hence, 89 patients with a clinical diagnosis of MBC and with evaluable blood for CTC analyses were ultimately included in our cohort. The average age of patients was 61 years. Most patients (n=49, 55%) had a prior history of early breast cancer, 38 (43%) had de-novo metastatic disease and prior breast cancer history was unknown for 2 patients. 50 (66%) of patients had visceral metastatic disease. The most common sites of metastases included bone (62%), lung (30%), liver (29%) and lymph nodes (17%). 63 of 89 patients (71%) had detectable CTCs at baseline, prior to any local or systemic treatment in the metastatic setting. The median number of detectable CTCs per 5mL sample was 2 (IQR 8.5) and the range was 0 – 12,798. Twenty nine of 89 (33%) patients had 5 or more CTCs detected per 5ml blood. The proportion of patients with detectable CTCs was numerically highest (n=39/51, 76%) among patients with hormone receptor (HR)+/HER2-ve breast cancer, followed by HER2+ (n=16/22, 73%) and triple negative (n=8/13, 62%) disease. Associations between CTC detection with prior history of early breast cancer, sites of metastatic disease and disease burden will also be presented. Conclusions: Approximately 3 in 4 women with newly diagnosed metastatic breast cancer have detectable CTCs using the Epic Sciences platform prior to initiation of first line systemic therapy. CTCs may be a promising tool for the monitoring of breast cancer recurrence and will be investigated in an ongoing Canadian prospective observational study that aims to elucidate biomarkers of late breast cancer recurrence. Citation Format: Katarzyna Jerzak, Pamela Goodwin, Marguerite Ennis, Christine Brezden-Masley, Nathaniel Bouganim, Mark Basik, Arushi Jain, Giuseppe Di Caro, Rick Wenstrup, Nadine Hartmann, Megan Slade, Ana Elisa Lohmann. A multi-center prospective cohort study to evaluate the presence of circulating tumor cells using the Epic Sciences platform among women with metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-15-01.

Abstract PO4-19-04: AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) alone are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study was initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with axillary lymph node metastasis scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without confirmation using a minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ-BR 23, Lymph ICF and SOC-13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: 4336 patients from 284 study sites and 26 countries were enrolled in the study between June 2020 and June 2023. Among 3722 patients with a defined surgical concept 1631 women were scheduled for TAD, 1483 for ALND, 469 for SLNB, 25 for TLNB and 109 for other procedures. A target lymph node was marked in 2309 patients, most frequently using clips/coils (1850, 80.1%), followed by magnetic seeds (219, 9.5%), carbon ink (171, 7.4%), radar marker (80, 3.5%), radioactive seeds (4, 0.2%) and other techniques (24, 1.0%). Funding: AGO-B, GBG, Claudia-von Schilling Foundation, Ehmann Foundation, Eugen und Irmgard Hahn Foundation, AWOgyn, Merit Medical, Endomagnetics, Mammotome Contact information: Prof. Dr. Thorsten Kühn Department of Gynecology and Obstetrics University of Ulm, Germany Baumreute 37 D-73730 Esslingen Germany E-Mail: kuehn.thorsten@t-online.de Citation Format: Thorsten Kühn, Steffi Hartmann, Elmar Stickeler, Jana de Boniface, Oreste Davide Gentilini, Sarah Fröhlich, Franziska Ruf, Marc Thill, Michael Hauptmann, Guldeniz Karadeniz Cakmak, Isabel Rubio, Maria Luisa Gasparri, Michalis Kontos, Eduard-Alexandru Bonci, Laura Niinikoski, Bilge Aktas Sezen, Rosa Di Micco, Dawid Murawa, Geeta Kadayaprath, David Pinto, Florentia Peintinger, Matilda Appelgren, Janine M. Simons, Marjolein Smidt, Ellen Schlichting, Lukas Dostalek, Elisabeth Thiemann, Markus Hahn, Michael Schrauder, Semra Gunay, Gunay Gurleyik, Nina Helidon, Hagigat Valiyeva, Ashutosh Kothari, Marian Vanhoeij, Andraz Perhavec, Tsvetomir Ivanov, Dov Zippel, Lia Rebaza, Sarun Thongvitokomarn, Sibylle Loibl, Maggie Banys-Paluchowski. AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-04.

Abstract PO2-23-02: Results of a prospective randomised multicentre study comparing indocyanine green (ICG) fluorescence combined with a standard tracer versus ICG alone for sentinel lymph node biopsy in early breast cancer: The INFLUENCE Trial

Abstract Background: Use of fluorescence mapping for visualization of lymphatic and nodal tissue for sentinel lymph node biopsy (SNB) reveals high rates of identification (&amp;gt;98%). Studies combining ICG with either blue dye or radioisotope (RI) have shown high levels of concordance (&amp;gt;90%) and comparable performance parameters between ICG and standard tracers for SNB localization. ICG combines many advantages of blue dye and RI without the disadvantages of allergic reactions, staining of skin and surgical tissues along with handling and disposal of radioactivity materials. Moreover, magnetic tracers pose challenges of interference relating to surgical instrumentation and magnetic resonance imaging (MRI). The combination of ICG with a conventional tracer may represent a transition phase and this randomized study evaluates ICG as a sole tracer agent for SNB in early-stage breast cancer. Methods: In a prospective randomized study, 100 patients with unilateral clinically node negative tumours scheduled to undergo routine SNB for core-biopsy proven invasive breast cancer (≤5cm) were identified at multidisciplinary meetings [non-invasive tumours excluded]. All patients had pre-operative axillary ultrasound and breast conserving surgery or mastectomy. Patients were recruited in two cohorts (n=50); cohort 1 was assigned to either ICG [2ml 0.5%] alone (n=25) or combined with RI [Technetium99 nanocolloid, 20MBq] (n=25). Cohort 2 received ICG alone (n=25) or combined with blue dye for SNB localization. The number of nodes whether blue, radioactive, fluorescent or a combination thereof were recorded. Lymphatic and nodal tissue was visualized with a fluorescent camera/detection system. Sensitivity of ICG alone and/or in combination with one or another standard tracer was calculated. The main objective was to assess the performance of ICG alone compared with a standard tracer combination in terms of rates of SNB identification along with procedural node positivity rates. Statistical analysis employed Chi-Square test, Fisher’s Exact test, and logistic regression to determine differences between groups. Results: A total of 100 patients were randomized between March and December 2022 with 3 patients excluded from analysis (non-receipt of treatment allocation). Amongst evaluable patients (n=97), the overall SNB identification rate was 96.9% and by tracer category as follows: ICG alone = 97.9% (46/47); ICG + RI = 100% (25/25); ICG + blue dye = 92% (23/25). For cohort 1, the procedural node positivity rates were 17% for ICG alone and 18% for ICG + RI with corresponding figures of 12% for ICG alone and 20% for ICG + blue dye for cohort 2. Mean procedural node retrieval per case was 2.5 in ICG alone Vs ICG + Blue Dye and 2.3 in ICG alone Vs ICG/RI cohorts. There were no significant differences (p&amp;gt;0.05) in performance of ICG alone or combined with a standard tracer, with ICG alone being non-inferior in terms of procedural and nodal detection rates. Similar conclusions were reached from a secondary analysis adjusting for BMI, age and mode of detection (screening/symptomatic). Conclusion: ICG fluorescence imaging permits real-time visualisation of lymphatics and gives an additional dimension to SNB that appears safe versus the competitive alternatives. These results confirm high sensitivity for fluorescence localisation alone for SNB with comparable performance to combined methods with blue dye or RI. The fluorochrome ICG is reliable as a sole tracer and avoids potential drawbacks of blue dye and RI including staining, allergic reactions, availability and costs. Citation Format: Vassilis Pitsinis, Rahul Kanitkar, Alessio Vinci, Emad Elseedawy, Laura Canna, John R Benson. Results of a prospective randomised multicentre study comparing indocyanine green (ICG) fluorescence combined with a standard tracer versus ICG alone for sentinel lymph node biopsy in early breast cancer: The INFLUENCE Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-02.

Abstract PO3-19-04: The CROWN STUDY: A multicenter prospective cohort study of cardiovascular outcomes in premenopausal women with hormone receptor positive breast cancer treated with ovarian suppression and an aromatase inhibitor

Abstract Background: Treatment for premenopausal women with high or intermediate risk hormone receptor (HR)+ breast cancer (BC) includes the concurrent use of ovarian function suppression (OFS) and an aromatase inhibitor (AI) to induce near complete estrogen deprivation (NCED). The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in non-cancer populations is associated with CV disease. The CROWN study (CaRdiac Outcomes With Near complete estrogen deprivation) will use sophisticated imaging assessments of cardiac dysfunction to understand the evolution of CV injury, as well as biomarker and demographic correlates, with the goal of developing tools to assess and mitigate CV risk. Methods: This is a NIH funded prospective cohort study conducted at 3 regional NCI-supported Cancer Centers (Atrium Health Wake Forest Baptist, Virginia Commonwealth and Duke) that will include premenopausal women, age ≤ 55, with Stage I-III BC following completion of planned chemotherapy, surgery and radiation with an ECOG 0-1. HR+ BC patients will receive an AI and OFS. Women with HR- BC are included as comparators. CV imaging and biomarkers will be obtained at baseline, 1 year and 2 years (Table 1). These assessments will include serial cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) imaging as well as laboratory measurements, including exploratory biomarkers. The primary objective is to determine the 24-month difference in stress myocardial blood flow as measured by adenosine CMR imaging in both groups. We will correlate CMR imaging with CCTA to provide complementary detail of coronary plaque changes. The study will also assess the relevance of pre-existing risk factors on study outcomes, including an emphasis on racial disparities, and dynamic change in modifiable and treatment related risk factors. We plan to enroll 90 women, 67 in the NCED group and 23 in the HR-group, allowing for a 10% drop out rate. There are two primary types of statistical analyses. The first includes testing hypotheses between group (NCED vs HR-) and within group (longitudinal changes within the NCED group). The second analyses, involve developing predictive equations utilizing a stepwise linear regression approach to determine if patient demographics, clinical parameters and serum biomarkers are associated with cardiovascular changes over time. A total of 17 patients are enrolled as of 07/2023. NCT05309655 Study Procedures XX- XX Citation Format: Susan Dent, Emily Douglas, Sarah Hatcher, Katherine Ansley, Carolyn Park, Nathaniel O'Connell, Mary Hackney, Ralph D'Agostino, Rani Bansal, Renee Avecilla, Monica Brown, Kacey Clayton-Stiglbauer, Igor Klem, Jennifer Jordan, Alexandra Thomas. The CROWN STUDY: A multicenter prospective cohort study of cardiovascular outcomes in premenopausal women with hormone receptor positive breast cancer treated with ovarian suppression and an aromatase inhibitor [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-19-04.

Abstract PO2-22-12: Patient-reported outcomes 3 and 18 months after prepectoral implant-based breast reconstruction: Results from the UK Pre-BRA multicentre prospective cohort study

Abstract Background: Prepectoral implant-based reconstruction (PPBR) with and without mesh is becoming the standard of care for prosthetic reconstruction in the UK. In addition to being easier and quicker to perform, the procedure is perceived to be associated with better patient-centred outcomes including decreased post-operative pain, avoidance of animation deformity and improved cosmesis. Evidence to support these benefits, however, is lacking. The UK PreBRA prospective multicentre cohort study (ISRCTN11898000) aimed to assess patient-reported outcomes (PROs) before and 3 and 18 months following PPBR to provide much needed evidence to support the effectiveness of the technique. Methods: Women aged 18 or over undergoing mastectomy for breast cancer or risk-reduction who opted to have PPBR between July 2019 and December 2020 were eligible to participate in the study. Demographic, operative, oncology and three-month complication data were collected. Participants were asked to complete the validated BREAST-Q questionnaire at before surgery and at 3 and 18 months following the procedure. Questionnaires were scored according to the developers’ instructions and scores compared over time. Exploratory analysis of covariance, adjusting for baseline scores was performed to explore factors impacting PROs following PPBR. Results: 347 women underwent PPBR at 40 centres across the UK. Of these, 334 (96.3%) completed PROMs at baseline with 237 (68.3%) completing at least two of the three main BREAST-Q scales at both 3 and 18 months. The median age of the cohort was 49 (range 23-74). Most women (n=291, 87.1%) had mastectomy for malignancy with a quarter (n=82, 24.6%) undergoing bilateral surgery. Approximately a fifth (n=68, 20.4%) had a body mass index &amp;gt;30 and 12% (n=40) were active smokers at the time of surgery. At 3 months, 68 (20.4%) had experienced a complication requiring readmission and/or re-operation and 27 (8.1%) experienced an implant loss. In the cohort overall, women undergoing PPBR reported slight increases in their ‘Satisfaction with Breasts’ scores from baseline to 3 months after surgery but by 18 months, their scores had fallen below baseline values (Table 1). ‘Physical well-being’ scores decreased from baseline to 3 months but then remained stable. No changes were seen in ‘Psychosocial well-being’ scores across the three timepoints. At 18 months, after adjusting for baseline BREAST Q scores, women having surgery for risk-reduction reported scores that were 10-16 points lower than those having surgery for malignancy across all four main domains for the BREAST-Q. This exceeded the minimum clinically meaningful difference and was highly statistically significant. Women with high mastectomy weights ( &amp;gt;600g) reported lower scores for ‘Physical’, ‘Psychosocial’ and ‘Sexual’ well-being but not ‘Satisfaction with Breasts’. Smoking adversely impacted ‘Psychosocial well-being’ and ‘Satisfaction with Breasts’ and women with BMI &amp;gt;30 reported lower ‘Physical well-being’ scores at 18 months. Having a major complication requiring readmission/re-operation did not affect BREAST-Q scores, but when considered separately, implant loss dramatically impacted all BREAST-Q domains Conclusions: Women having PPBR report short-term improvements in ‘Satisfaction with Breasts’ scores but these are not maintained over time and decrease to below baseline 18 months after surgery. ‘Physical well-being’ also decreased after PPBR despite no disruption to the pectoralis muscle. Women having surgery for risk-reduction reported the worse PROs. Further work is needed to establish the long-term patient-reported outcomes of PPBR and factors impacting these. Citation Format: Leigh Johnson, Kate Harvey, Parisa Sinai, Nicola Mills, Paul White, Chris Holcombe, Shelley Potter. Patient-reported outcomes 3 and 18 months after prepectoral implant-based breast reconstruction: Results from the UK Pre-BRA multicentre prospective cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-22-12.

Abstract PO3-23-06: Short-term clinical and patient-reported outcomes of oncoplastic breast conserving surgery and mastectomy with and without immediate breast reconstruction: The UK ANTHEM multicentre prospective cohort study

Abstract Background: Oncoplastic breast conserving surgery (OPBCS) may allow women with early breast cancer to avoid mastectomy leading to fewer complications and better quality of life. High quality comparative evidence, however, is lacking. The UK ANTHEM study (ISRCTN18238549) aimed to explore the feasibility of undertaking a large-scale multicentre study comparing the clinical and patient reported outcomes (PROs) of OPBCS as an alternative to mastectomy +/- immediate breast reconstruction (IBR) in women offered both options. Methods: Women aged 18 and over with invasive breast cancer or DCIS not suitable for standard breast conserving surgery, who were offered OPBCS as an alternative to mastectomy +/- IBR were eligible to participate in the study. Demographic, operative, oncological data were collected and the numbers of women experiencing complications at 3 months following surgery compared by procedure type. Participants completed the validated BREAST-Q at baseline and 3 months post-operatively. Questionnaires were scored according to the developers’ instructions and scores compared across timepoints by procedure group. Analysis of covariance, adjusting for baseline scores was used to explore factors influencing patient-reported outcomes after surgery. Results: 361 women from 32 UK centres participated in the study. When offered both options, the majority (n=284, 78.7%) elected to undergo OPBCS with either a therapeutic mammaplasty (TM) (n=207, 57.3%) or a chest wall perforator flap (CWPF) (n=77, 21.3%). The remaining 77 (21.3%) women chose mastectomy with (n=40, 11.1%) or without IBR (n=37, 10.3%). Women having mastectomy + IBR were significantly younger than those choosing other procedure types (p=0.002) and those choosing TM had higher BMIs (P=0.008), but there were no other differences between the groups. By 3 months post-operatively, 23.0% (n=83) women had experienced at least one complication, but there were no differences between the groups (p=0.50). The BREAST-Q was completed by 329 (91.1%) and 282 (78.1%) women at baseline and 3 months respectively. Although their scores were initially the lowest, women undergoing TMs reported clinically meaningful and statistically significant increases in ‘Satisfaction with Breasts’ (baseline 53.7 [95% confidence interval [CI] 50.4-57.0] to 3 months 68.9 [95% CI 65.5-72.2], p&amp;lt; 0.001) and ‘Psychosocial Well-being’ scores (baseline 62.1 [95% CI 59.2-65.0] to 3 months 70.4 [95% CI 66.9-73.8] p&amp;lt; 0.001) from baseline to 3 months. Women having CWPF and mastectomy +/- IBR did not report any significant changes in either ‘Satisfaction with Breasts’ or ‘Psychosocial Well-being’ scores over time. ‘Physical Well-being’ scores significantly decreased from baseline to three months in all treatment groups (p&amp;lt; 0.001) but were lowest after mastectomy only (56.5 [95% CI 47.4-65.5]) and highest in the TM group (68.6 [95% CI 65.9-71.3], p&amp;lt; 0.001). ‘Sexual Well-being’ decreased in all groups except for women having mastectomy + IBR. Adjusting for baseline, women undergoing OPBCS with TM (13.2, 95% CI 4.2-22.2, p&amp;lt; 0.001) or CWPF (11.4, 1.6-21.2, p=0.02) reported significantly higher ‘Satisfaction with Breasts’ scores at 3 months than those undergoing mastectomy. Receipt of IBR did not appear to lead to significantly higher scores compared with mastectomy alone (6.47, 95% CI -6.19 to 19.12, p=0.32). Women undergoing TM reported significantly higher ‘Psychosocial’ and ‘Physical well-being’ at 3 months compared with those having other procedure types. Experiencing a post-operative complication resulted in significant decreases in all BREAST-Q domains. Conclusions: When offered OPBCS as an alternative to mastectomy, most women choose breast conservation. This option is safe and appears to be associated with improved short-term PROs, particularly in the TM group. Further work is needed to establish the long-term outcomes of these techniques to support informed decision-making. Citation Format: Charlotte Davies, Leigh Johnson, Carmel Conefrey, Nicola Mills, Patricia Fairbrother, Chris Holcombe, Lisa Whisker, William Hollingworth, Joanna Skillman, Paul White, Douglas MacMillan, Charles Comins, Shelley Potter. Short-term clinical and patient-reported outcomes of oncoplastic breast conserving surgery and mastectomy with and without immediate breast reconstruction: The UK ANTHEM multicentre prospective cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-23-06.

CXCL13 as a biomarker in the diagnostics of European lyme Neuroborreliosis - A prospective multicentre study in Austria.

'Definite Neuroborreliosis (NB)' is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated Borrelia Burgdorferi antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy. Nevertheless, due to lacking prospective data, a definite CXCL13 cut-off for the diagnosis of NB is still pending. Definition of a CSF CXCL13 cut-off for the diagnosis of acute and untreated NB in a prospective study setting. This multicentre prospective study involved 6 neurological departments treating patients in the Lower Austria district (1.7 million inhabitants). The controls were patients scheduled for a spinal tap but not clinically diagnosed with NB. Demographic data, clinical characteristics and blood counts, as well as inflammatory CSF values and CSF CXCL13-concentration were analysed. We recruited 440 adult patients, of whom 42 have been diagnosed as having an acute and untreated 'definite NB'. Three hundred ninety-eight patients were assigned to the control group. The median intrathecal CXCL13 concentration was 2384 pg/ml for patients with NB and 0 pg/ml for controls. The difference was highly statistically significant (P ≤ .001). A CSF CXCL13 cut-off of 271 pg/ml resulted in a sensitivity of 95.2% and a specificity of 97.2% for the confirmation or exclusion of NB. Based on our results, we propose a CSF CXCL13 cut-off of 271 pg/ml with Euroimmun-Elisa for the diagnosis of acute and untreated NB. Due to its high sensitivity and specificity, CXCL13 is a strong candidate biomarker for routine NB assessment, especially in clinically unclear cases.

Abstract PO4-18-12: MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET, NCT 05559411)

Abstract Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins and re-operations are limited. In the majority of studies, the patient’s perspective with regard to discomfort and pain level has not been evaluated. The aim of MELODY (MEthods for LOcalization of Different types of breast lesions) is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://melody.eubreast.com). MELODY is a prospective intergroup cohort study which enrolls female and male pts. requiring breast-conserving surgery and imaging-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal, independent of margin status on final histopathology, and 2) Negative resection margin rates at first surgery. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, comparison of patient-reported outcomes, rates of “lost markers” and diagnostician/radiologist’s and surgeon’s satisfaction as well as the health economic evaluation of the different techniques. Target accrual: 7,416 patients. Enrollment started in January 2023. The study will be conducted in 30 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B and SENATURK. Financial support will be provided by Endomag, Merit Medical, Sirius Medical and Hologic. Citation Format: Maggie Banys-Paluchowski, Thorsten Kühn, Yazan Masannat, Nina Ditsch, Antonio Esgueva, Neslihan Cabıoğlu, Dawid Murawa, Nuh Zafer Canturk, Isabel Rubio, Jana de Boniface, Andreas Karakatsanis, Rajiv Dave, Shelley Potter, Ashutosh Kothari, Oreste Davide Gentilini, Walter Weber, Natalia Krawczyk, Steffi Hartmann, Guldeniz Karadeniz Cakmak, Markus Hahn, Michael P. Lux, Tove Tvedskov, Lina Pankratjevaite, Michalis Kontos, Florentia Peintinger, Aoife Lowery, Marjolein Smidt, Lia Rebaza, Maria Vasconcelos, Bahadir M. Gulluoglu, Bilge Aktas Sezen, Rosa Di Micco, Sarah Nietz, Francois Malherbe, Maria Luisa Gasparri, Séverine Alran, SVS Deo, Mah Muneer Khan, James Harvey. MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET, NCT 05559411) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-12.