Inconsistent selection and definition of local and regional endpoints in breast cancer research

BACKGROUND: Results in breast cancer research are reported using study endpoints. Most are composite endpoints (such as locoregional recurrence), consisting of several components (for example local recurrence) that are in turn composed of specific events (such as skin recurrence). Inconsistent endpoint selection and definition might lead to unjustified conclusions when comparing study outcomes. This study aimed to determine which locoregional endpoints are used in breast cancer studies, and how these endpoints and their components are defined. METHODS: PubMed was searched for breast cancer studies published in nine leading journals in 2011. Articles using endpoints with a local or regional component were included and definitions were compared. RESULTS: Twenty-three different endpoints with a local or regional component were extracted from 44 articles. Most frequently used were disease-free survival (25 articles), recurrence-free survival (7), local control (4), locoregional recurrence-free survival (3) and event-free survival (3). Different endpoints were used for similar outcomes. Of 23 endpoints, five were not defined and 18 were defined only partially. Of these, 16 contained a local and 13 a regional component. Included events were not specified in 33 of 57 (local) and 27 of 50 (regional) cases. Definitions of local components inconsistently included carcinoma in situ and skin and chest wall recurrences. Regional components inconsistently included specific nodal sites and skin and chest wall recurrences. CONCLUSION: Breast cancer studies use many different endpoints with a locoregional component. Definitions of endpoints and events are either not provided or vary between trials. To improve transparency, facilitate trial comparison and avoid unjustified conclusions, authors should report detailed definitions of all endpoints

The changing role of axillary treatment in breast cancer: Who will remain at risk for developing arm morbidity in the future?

Primary aim is to give an overview of changes in axillary staging and treatment of breast cancer patients. Secondly, we aim to identify patients with a high arm/shoulder morbidity risk, and describe a strategy to improve early detection and treatment. Recent and initiated studies on axillary staging and treatment were evaluated and clustered for clinically node negative and clinically node positive breast cancer patients, together with studies on pathology, detection and (surgical) prevention and treatment of lymphedema. For clinically node negative patients, the indication for axillary lymph node dissection in sentinel node positive patients is fading. On the contrary, clinically node positive patients are routinely subjected to an axillary lymph node dissection, in combination with other therapies associated with an increased lymphedema risk, such as mastectomy, adjuvant radiation- and (taxane-based) chemotherapy. Techniques for prevention, early detection and (surgical) treatment of lymphedema are being developed. Axillary staging and treatment in breast cancer patients with a clinically node negative status will become less invasive, thereby reducing the incidence of morbidity. Nevertheless, in patients with a clinically node positive status, aggressive treatment will still be required for oncologic control. For these patients, a surveillance program should be implemented in order to apply (curative) surgical treatment for lymphedema

The value of completion axillary treatment in sentinel node positive breast cancer patients undergoing a mastectomy: a Dutch randomized controlled multicentre trial (BOOG 2013-07)

Contains fulltext : 154270.pdf (publisher's version ) (Open Access)BACKGROUND: Trials failed to demonstrate additional value of completion axillary lymph node dissection in case of limited sentinel lymph node metastases in breast cancer patients undergoing breast conserving therapy. It has been suggested that the low regional recurrence rates in these trials might partially be ascribed to accidental irradiation of part of the axilla by whole breast radiation therapy, which precludes extrapolation of results to mastectomy patients. The aim of the randomized controlled BOOG 2013-07 trial is therefore to investigate whether completion axillary treatment can be safely omitted in sentinel lymph node positive breast cancer patients treated with mastectomy. DESIGN: This study is designed as a non-inferiority randomized controlled multicentre trial. Women aged 18 years or older diagnosed with unilateral invasive clinically T1-2 N0 breast cancer who are treated with mastectomy, and who have a maximum of three axillary sentinel lymph nodes containing micro- and/or macrometastases, will be randomized for completion axillary treatment versus no completion axillary treatment. Completion axillary treatment can consist of completion axillary lymph node dissection or axillary radiation therapy. Primary endpoint is regional recurrence rate at 5 years. Based on a 5-year regional recurrence free survival rate of 98 % among controls and 96 % for study subjects, the sample size amounts 439 per arm (including 10 % lost to follow-up), to be able to reject the null hypothesis that the rate for study and control subjects is inferior by at least 5 % with a probability of 0.8. Results will be reported after 5 and 10 years of follow-up. DISCUSSION: We hypothesize that completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing mastectomy. If confirmed, this study will significantly decrease the number of breast cancer patients receiving extensive treatment of the axilla, thereby diminishing the risk of morbidity and improving quality of life, while maintaining excellent regional control and without affecting survival. TRIAL REGISTRATION: The BOOG 2013-07 study is registered in the register of ClinicalTrials.gov since April 10, 2014, Identifier: NCT02112682

Nuss Procedure for Pectus Excavatum: A Comparison of Complications Between Young and Adult Patients

Background. The Nuss procedure is the gold standard surgical treatment for pectus excavatum in young patients. Its use in adults has also been described, although it may be associated with increased postoperative morbidity resulting from higher chest wall rigidity. This study aimed to examine the risk of complications after the Nuss procedure in adult patients compared with young patients with pectus excavatum.Methods. This single-center retrospective cohort study evaluated all patients who underwent the Nuss procedure between 2006 and 2018. Patients were stratified by age as young (24 years old). The primary end point was the occurrence of perioperative or postoperative complications, subdivided into major (Clavien-Dindo class Ill a or higher) and minor (less severe than Clavien-Dindo class III). Between-group differences were analyzed using the Mann-Whitney U and the chi(2) test with post hoc analysis.Results. A total of 327 participants were included, 272 in the young group (median age, 16 years; interquartile range [IQR], 15 to 18 years; range, 11 to 24 years) and 55 in the adult group (median age, 32 years; IQR, 27 to 38 years; range, 25 to 47 years). The median Haller index was similar between groups (young, 3.7; IQR, 3.2 to 4.4 vs adult,3.6; IQR, 3.0 to 4.3; P = .44). The median follow-up was 34 and 36 months, respectively. The incidence of major complications was comparable between young and adult participants (P = .43). Minor complications occurred more often among adults (young, 4% vs adult, 11%; P = .002). Chronic postoperative pain was the only minor complication with a significant difference in incidence (young, 1% vs adult, 7%; P = .008).Conclusions. The Nuss procedure is a safe surgical treatment for pectus excavatum in both young and adult patients. The risk of major complications is comparable. However, adults more often have chronic pain. (C) 2021 by The Society of Thoracic Surgeon

Combined use of magnetic seed and tracer in breast conserving surgery with sentinel lymph node biopsy for non-palpable breast lesions: A pilot study describing pitfalls and solutions

Backgrounds: Traditionally, breast conserving surgery for non-palpable breast cancer is guided by wire or radioactive seed and radioactive tracer for sentinel lymph node biopsy (SLNB). Alternatively, a stain-less magnetic seed and superparamagnetic iron oxide tracer (SPIO) can be combined as a radioactive-free technique. The aim of this study was to define the pitfalls we encountered during implementation of this combined technique and provide solutions resulting in an instruction manual for a radio-active free procedure. Methods: Between January and March 2021, seventeen consecutive patients with cN0 non-palpable breast cancer were included. The magnetic seed was placed to localize the lesion and SPIO was used to identify the sentinel lymph node (SLN). A lymphoscintigraphy with Technetium-99m nano colloid was performed concomitantly in all patients as a control procedure for SPIO. Surgical outcomes are reported, including problems with placing and retrieval of the seed and SPIO and corresponding solutions. Results: Surgical excision was successful with invasive tumor-free margins in all patients. SLN detection was successful in 82% patients when compared to Technetium-99m. The most challenging issue was an overlapping magnetic signal of the seed and SPIO. Solutions are provided in detail. Conclusions: Combined use of magnetic seed and SPIO for wide local excision and SLNB patients with nonpalpable breast lesions appeared challenging due to overlapping magnetic signals. After multiple adaptations, the protocol proved to be feasible with an added advantage of eliminating the use of radioisotopes. We described the pitfalls and solutions resulting in an instruction manual for a totally radioactive-free procedure

Noninvasive nodal staging in patients with breast cancer using gadofosveset-enhanced magnetic resonance imaging: a feasibility study

OBJECTIVES: The objectives of this study were to evaluate whether the axillary lymph nodes show enhancement on magnetic resonance imaging (MRI) after gadofosveset administration, to assess the time to peak enhancement, and to determine the diagnostic performance of gadofosveset-enhanced MRI for axillary nodal staging. MATERIALS AND METHODS: Ten women whose conditions had been diagnosed with invasive breast cancer (>2 cm) underwent both nonenhanced and gadofosveset-enhanced 3-dimensional T1-weighted axillary MRI. Signal intensity of the axillary lymph nodes and different adjacent tissues was measured, and relative signal intensity (rSI) was calculated. A Wilcoxon signed rank test was used to compare results of rSI between different time intervals. A radiologist evaluated all lymph nodes with regard to size, morphologic features, and gadofosveset uptake. All MRI-depicted lymph nodes were matched with the lymph nodes that were removed during surgery. Nodal status was investigated by a pathologist. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of gadofosveset-enhanced MRI for axillary lymph node staging were calculated. RESULTS: After contrast administration, a significant signal increase was observed in the lymph nodes (P < 0.05). When compared with muscle or fat, rSI of the lymph nodes demonstrated a significant postcontrast peak enhancement between 11 minutes and 30 seconds and 20 minutes and 50 seconds (P < 0.05). A total of 152 lymph nodes were harvested during sentinel lymph node biopsy or axillary lymph node dissection, of which 116 were matched with the lymph nodes that were depicted on MRI. Histopathological examination resulted in 21 macrometastases and 8 micrometastases. Using contrast-enhanced MRI, 20 lymph nodes were rated as true positive; 83 as true negative; 4 as false positive; and 9 as false negative. This resulted in an overall node-by-node sensitivity, specificity, PPV, and NPV of 69%, 95%, 83%, and 90%, respectively. If the micrometastases were excluded from the analysis, MRI showed a sensitivity of 86% and a specificity of 94%. Calculated PPV and NPV were 75% and 97%, respectively. CONCLUSIONS: The axillary lymph nodes show enhancement on MRI after gadofosveset administration, with a peak enhancement between 11 minutes and 30 seconds and 20 minutes and 50 seconds. Diagnostic performance of gadofosveset-enhanced axillary lymph node imaging in patients with breast cancer is promising, but further studies need to confirm these results