Radiofrequency localization of nonpalpable breast cancer in a multicentre prospective cohort study: feasibility, clinical acceptability, and safety.

PURPOSE: In breast conserving surgery, accurate lesion localization is essential for obtaining adequate surgical margins. Preoperative wire localization (WL) and radioactive seed localization (RSL) are widely accepted methods to guide surgical excision of nonpalpable breast lesions but are limited by logistical challenges, migration issues, and legislative complexities. Radiofrequency identification (RFID) technology may offer a viable alternative. The purpose of this study was to evaluate the feasibility, clinical acceptability, and safety of RFID surgical guidance for localization of nonpalpable breast cancer. METHODS: In a prospective multicentre cohort study, the first 100 RFID localization procedures were included. The primary outcome was the percentage of clear resection margins and re-excision rate. Secondary outcomes included procedure details, user experience, learningcurve, and adverse events. RESULTS: Between April 2019 and May 2021, 100 women underwent RFID guided breast conserving surgery. Clear resection margins were obtained in 89 out of 96 included patients (92.7%), re-excision was indicated in three patients (3.1%). Radiologists reported difficulties with the placement of the RFID tag, partially related to the relatively large needle-applicator (12-gauge). This led to the premature termination of the study in the hospital using RSL as regular care. The radiologist experience was improved after a manufacturer modification of the needle-applicator. Surgical localization involved a low learning curve. Adverse events (n = 33) included dislocation of the marker during insertion (8%) and hematomas (9%). The majority of adverse events (85%) occurred using the first-generation needle-applicator. CONCLUSION: RFID technology is a potential alternative for non-radioactive and non-wire localization of nonpalpable breast lesions.

The Areola study: design and rationale of a cohort study on long-term health outcomes in women with implant-based breast reconstructions.

BACKGROUND: Implant-based breast reconstructions contribute considerably to the quality of life of breast cancer patients. A knowledge gap exists concerning the potential role of silicone breast implants in the development of so-called "breast implant illness" (BII) and autoimmune diseases in breast cancer survivors with implant-based reconstructions. BII is a constellation of non-specific symptoms reported by a small group of women with silicone breast implants. METHODS: The Areola study is a multicenter retrospective cohort study with prospective follow-up aiming to assess the risk of BII and autoimmune diseases in female breast cancer survivors with and without silicone breast implants. In this report, we set out the rationale, study design, and methodology of this cohort study. The cohort consists of breast cancer survivors who received surgical treatment with implant-based reconstruction in six major hospitals across the Netherlands in the period between 2000 and 2015. As a comparison group, a frequency-matched sample of breast cancer survivors without breast implants will be selected. An additional group of women who received breast augmentation surgery in the same years will be selected to compare their characteristics and health outcomes with those of breast cancer patients with implants. All women who are still alive will be invited to complete a web-based questionnaire covering health-related topics. The entire cohort including deceased women will be linked to population-based databases of Statistics Netherlands. These include a registry of hospital diagnostic codes, a medicines prescription registry, and a cause-of-death registry, through which diagnoses of autoimmune diseases will be identified. Outcomes of interest are the prevalence and incidence of BII and autoimmune diseases. In addition, risk factors for the development of BII and autoimmune disorders will be assessed among women with implants. DISCUSSION: The Areola study will contribute to the availability of reliable information on the risks of BII and autoimmune diseases in Dutch breast cancer survivors with silicone breast implants. This will inform breast cancer survivors and aid future breast cancer patients and their treating physicians to make informed decisions about reconstructive strategies after mastectomy. REGISTRATION: This study is registered at ClinicalTrials.gov on June 2, 2022 (NCT05400954).

Longitudinal Serum Protein Analysis of Women with a High Risk of Developing Breast Cancer Reveals Large Interpatient Versus Small Intrapatient Variations: First Results from the TESTBREAST Study.

The prospective, multicenter TESTBREAST study was initiated with the aim of identifying a novel panel of blood-based protein biomarkers to enable early breast cancer detection for moderate-to-high-risk women. Serum samples were collected every (half) year up until diagnosis. Protein levels were longitudinally measured to determine intrapatient and interpatient variabilities. To this end, protein cluster patterns were evaluated to form a conceptual basis for further clinical analyses. Using a mass spectrometry-based bottom-up proteomics strategy, the protein abundance of 30 samples was analyzed: five sequential serum samples from six high-risk women; three who developed a breast malignancy (cases) and three who did not (controls). Serum samples were chromatographically fractionated and an in-depth serum proteome was acquired. Cluster analyses were applied to indicate differences between and within protein levels in serum samples of individuals. Statistical analyses were performed using ANOVA to select proteins with a high level of clustering. Cluster analyses on 30 serum samples revealed unique patterns of protein clustering for each patient, indicating a greater interpatient than intrapatient variability in protein levels of the longitudinally acquired samples. Moreover, the most distinctive proteins in the cluster analysis were identified. Strong clustering patterns within longitudinal intrapatient samples have demonstrated the importance of identifying small changes in protein levels for individuals over time. This underlines the significance of longitudinal serum measurements, that patients can serve as their own controls, and the relevance of the current study set-up for early detection. The TESTBREAST study will continue its pursuit toward establishing a protein panel for early breast cancer detection.

A multicenter prospective cohort study to evaluate feasibility of radio-frequency identification surgical guidance for nonpalpable breast lesions: design and rationale of the RFID Localizer 1 Trial.

BACKGROUND: Breast cancer screening and improving imaging techniques have led to an increase in the detection rate of early, nonpalpable breast cancers. For early breast cancer, breast conserving surgery is an effective and safe treatment. Accurate intraoperative lesion localization during breast conserving surgery is essential for adequate surgical margins while sparing surrounding healthy tissue to achieve optimal cosmesis. Preoperative wire localization and radioactive seed localization are accepted standard methods to guide surgical excision of nonpalpable breast lesions. However, these techniques present significant limitations. Radiofrequency identification (RFID) technology offers a new, nonradioactive method for localizing nonpalpable breast lesions in patients undergoing breast conserving surgery. This study aims to evaluate the feasibility of RFID surgical guidance for nonpalpable breast lesions. METHODS: This multicenter prospective cohort study was approved by the Institutional Review Board of the University Medical Center Utrecht. Written informed consent is obtained from all participants. Women with nonpalpable, histologically proven in situ or invasive breast cancer, who can undergo breast conserving surgery with RFID localization are considered eligible for participation. An RFID tag is placed under ultrasound guidance, up to 30 days preoperatively. The surgeon localizes the RFID tag with a radiofrequency reader that provides audible and visual real-time surgical guidance. The primary study outcome is the percentage of irradical excisions and reexcision rate, which will be compared to standards of the National Breast Cancer Organisation Netherlands (NABON)(≤ 15% irradical excisions of invasive carcinomas). Secondary outcomes include user acceptability/experiences, learning curve, duration and ease of the placement- and surgical procedure and adverse events. DISCUSSION: This study evaluates the feasibility of RFID surgical guidance for nonpalpable breast lesions. Results may have implications for the future localization techniques in women with nonpalpable breast cancer undergoing breast conserving surgery. TRIAL REGISTRATION: Netherlands National Trial Register, NL8019 , registered on September 12th 2019.

Breast MRI in patients after breast conserving surgery with sentinel node procedure using a superparamagnetic tracer.

BACKGROUND: A procedure for sentinel lymph node biopsy (SLNB) using superparamagnetic iron-oxide (SPIO) nanoparticles and intraoperative sentinel lymph node (SLN) detection was developed to overcome drawbacks associated with the current standard-of-care SLNB. However, residual SPIO nanoparticles can result in void artefacts at follow-up magnetic resonance imaging (MRI) scans. We present a grading protocol to quantitatively assess the severity of these artefacts and offer an option to minimise the impact of SPIO nanoparticles on diagnostic imaging. METHODS: Follow-up mammography and MRI of two patient groups after a magnetic SLNB were included in the study. They received a 2-mL subareolar dose of SPIO (high-dose, HD) or a 0.1-mL intratumoural dose of SPIO (low-dose, LD). Follow-up mammography and MRI after magnetic SLNB were acquired within 4 years after breast conserving surgery (BCS). Two radiologists with over 10-year experience in breast imaging assessed the images and analysed the void artefacts and their impact on diagnostic follow-up. RESULTS: A total of 19 patients were included (HD, n = 13; LD, n = 6). In the HD group, 9/13 patients displayed an artefact on T1-weighted images up to 3.6 years after the procedure, while no impact of the SPIO remnants was observed in the LD group. CONCLUSIONS: SLNB using a 2-mL subareolar dose of magnetic tracer in patients undergoing BCS resulted in residual artefacts in the breast in the majority of patients, which may hamper follow-up MRI. This can be avoided by using a 0.1-mL intratumoural dose.

Phase II study of docetaxel, cisplatin and capecitabine as preoperative chemotherapy in resectable gastric cancer.

AIM: To investigate the feasibility of preoperative docetaxel, cisplatin and capecitabine (DCC) in patients with resectable gastric cancer. METHODS: Patients with resectable gastric cancer fulfilling the inclusion criteria, were treated with 4 cycles of docetaxel (60 mg/m2), cisplatin (60 mg/m2) and capecitabine (1.875 mg/m2 orally on day 1-14, two daily doses) repeated every three weeks, followed by surgery. Primary end point was the feasibility and toxicity/safety profile of DCC, secondary endpoints were pathological complete resection rate and pathological complete response (pCR) rate. RESULTS: All of the patients (51) were assessable for the feasibility and safety of the regimen. The entire preoperative regimen was completed by 68.6% of the patients. Grade III/IV febrile neutropenia occurred in 10% of all courses. Three patients died due to treatment related toxicity (5.9%), one of them (also) because of refusing further treatment for toxicity. Of the 45 patients who were evaluable for secondary endpoints, four developed metastatic disease and 76.5% received a curative resection. In 3 patients a pCR was seen (5.9%), two patients underwent a R1 resection (3.9%). CONCLUSION: Four courses of DCC as a preoperative regimen for patients with primarily resectable gastric cancer is highly demanding. The high occurrence of febrile neutropenia is of concern. To decrease the occurrence of febrile neutropenia the prophylactic use of granulocyte colony-stimulating factor (G-CSF) should be explored. A curative resection rate of 76.5% is acceptable. The use of DCC without G-CSF support as preoperative regimen in resectable gastric cancer is debatable.

Gastric cancer: decreasing incidence but stable survival in the Netherlands.

BACKGROUND: Gastric cardia and non-cardia cancer exhibit differences in biological and epidemiological features across the world. The aims of this study were to analyze trends in incidence, stage distribution, and survival over a 20-year period in the Netherlands, separately for both types of gastric cancer. METHODS: Data on all patients with a diagnosis of gastric cancer in the period 1989-2008 were obtained from the nationwide Netherlands Cancer Registry. Time trends in incidence [analyzed as European Standard Rate per 100 000 (ESR)] and relative survival were separately analyzed for cardia and non-cardia gastric cancer. RESULTS: A total of 47 295 patients were included. Incidence rates per 100 000 for cardia cancer declined from 5.7 to 4.3 for males and remained stable for females (1.2). For non-cardia cancer, the incidence in males declined from 25 to 14 and in females from 10 to 7. Proportional incidence in stage IV cardia and non-cardia cancer increased in 2004-2008 (cardia 32-42%, non-cardia 33-45%). Five-year survival rates for stage I-III and X (unknown) remained stable (cardia cancer: 20%, non-cardia gastric cancer: 31%). Five-year survival for stage IV disease was 1.9% and 1.0% for cardia and non-cardia gastric cancer. CONCLUSION: The incidence of gastric cancer in the Netherlands markedly decreased over the past decades, in particular of non-cardia cancer. Survival remained dismal. Improvement of survival remains a challenge for the multidisciplinary team involved in gastric cancer treatment.

The lymph node ratio as a prognostic factor for gastric cancer.

To predict prognosis of gastric cancer, an adequate assessment of the stage of gastric cancer is important. The UICC/AJCC TNM classification is the most commonly used classification system. For adequate N staging at least 15 lymph nodes should be retrieved. In some countries, this amount of lymph nodes is not met, which can lead to understaging. Therefore, the lymph node ratio (LNR) is proposed as an alternative N staging modality. The purpose of this study was to compare the different staging modalities. Patients and methods. We included all patients who underwent surgery for gastric cancer, newly diagnosed between 2000 and 2009 and staged patient by UICC/AJCC TNM 5th/6th or 7th and by LNR. We conducted crude survival analysis, univariate and multivariate analyses according to the different staging systems. Results. The five-year overall survival rates ranged from 58% for N0 disease to 18% in case of more than 15 metastatic lymph nodes. The distribution of overall five-year survival according to LNR was 58% for LNR0 and 10% for LNR3. Univariate analysis showed that all the UICC/AJCC TNM classification systems as well as the LNR were strong prognostic factors for overall survival. The LNR correlated less with the number of nodes examined. Conclusion. LNR is a good prognostic tool for overall survival, it is an independent prognostic factor with a more homogenous spread of hazard ratios and five-year survival rates than UICC/AJCC systems. Furthermore, the LNR has a lower correlation with the number of nodes examined, making it less vulnerable for stage migration.

Effect of hospital volume on postoperative mortality and survival after oesophageal and gastric cancer surgery in the Netherlands between 1989 and 2009.

BACKGROUND: High hospital volume is associated with better outcomes after oesophagectomy and gastrectomy. In the Netherlands, a minimal volume standard of 10 oesophagectomies per year was introduced in 2006. For gastrectomy, no minimal volume standard was set. Aims of this study were to describe changes in hospital volumes, mortality and survival and to explore if high hospital volume is associated with better outcomes after oesophagectomy and gastrectomy in the Netherlands. METHODS: From 1989 to 2009, 24,246 patients underwent oesophagectomy (N = 10,025) or gastrectomy (N = 14,221) in the Netherlands. Annual hospital volumes were defined as very low (1-5), low (6-10), medium (11-20), and high (≥ 21). Volume-outcome analyses were performed using Cox regression, adjusting for year of diagnosis, case-mix and the use of multi-modality treatment. RESULTS: From 1989 to 2009, the percentage of patients treated in high-volume hospitals increased for oesophagectomy (from 7% to 64%), but decreased for gastrectomy (from 8% to 5%). Six-month mortality (from 15% to 7%) and 3-year survival (from 41% to 52%) improved after oesophagectomy, and to a lesser extent after gastrectomy (6-month mortality: 15%-10%, three-year survival: 55-58%). High hospital volume was associated with lower 6-month mortality (hazard ratio (HR) 0.48, P<0.001) and longer 3-year survival (HR 0.77, P<0.001) after oesophagectomy, but not after gastrectomy. CONCLUSIONS: Oesophagectomy was effectively centralised in the Netherlands, improving mortality and survival. Gastrectomies were mainly performed in low volumes, and outcomes after gastrectomy improved to a lesser extent, indicating an urgent need for improvement in quality of surgery and perioperative care for gastric cancer in the Netherlands.