De-escalation of axillary treatment in the event of a positive sentinel lymph node biopsy in cT1-2 N0 breast cancer treated with mastectomy: nationwide registry study (BOOG 2013-07).

BACKGROUND: Trials have demonstrated the safety of omitting completion axillary lymph node dissection in patients with cT1-2 N0 breast cancer operated with breast-conserving surgery who have limited metastatic burden in the sentinel lymph node. The aim of this registry study was to provide insight into the oncological safety of omitting completion axillary treatment in patients operated with mastectomy who have limited-volume sentinel lymph node metastasis. METHODS: Women diagnosed in 2013-2014 with unilateral cT1-2 N0 breast cancer treated with mastectomy, with one to three sentinel lymph node metastases (pN1mi-pN1a), were identified from the Netherlands Cancer Registry, and classified by axillary treatment: no completion axillary treatment, completion axillary lymph node dissection, regional radiotherapy, or completion axillary lymph node dissection followed by regional radiotherapy. The primary endpoint was 5-year regional recurrence rate. Secondary endpoints included recurrence-free interval and overall survival, among others. RESULTS: In total, 1090 patients were included (no completion axillary treatment, 219 (20.1%); completion axillary lymph node dissection, 437 (40.1%); regional radiotherapy, 327 (30.0%); completion axillary lymph node dissection and regional radiotherapy, 107 (9.8%)). Patients in the group without completion axillary treatment had more favourable tumour characteristics and were older. The overall 5-year regional recurrence rate was 1.3%, and did not differ significantly between the groups. The recurrence-free interval was also comparable among groups. The group of patients who did not undergo completion axillary treatment had statistically significantly worse 5-year overall survival, owing to a higher percentage of non-cancer deaths. CONCLUSION: In this registry study of patients with cT1-2 N0 breast cancer treated with mastectomy, with low-volume sentinel lymph node metastasis, the 5-year regional recurrence rate was low and comparable between patients with and without completion axillary treatment.

Extracapsular extension in the positive sentinel lymph node: a marker of poor prognosis in cT1-2N0 breast cancer patients?

OBJECTIVE: This study aims to evaluate whether extracapsular extension (ECE) in the sentinel lymph node (SLN) is associated with involvement of ≥ 4 lymph node metastases at completion axillary lymph node dissection (ALND) and the effect on 5-year disease-free survival (DFS) and 10-year overall survival (OS). ECE in a SLN is usually a contraindication for omitting completion ALND in cT1-2N0 breast cancer patients treated with breast-conserving therapy and 1-2 positive SLN(s). METHODS: All cT1-2N0 breast cancer patients with 1-3 positive SLN(s) who underwent ALND between 2005 and 2008 were selected from the Netherlands Cancer Registry. Logistic regression analysis was used to determine the association between ECE and ≥ 4 lymph node metastases. Five-year DFS and 10-year OS were analyzed using Kaplan-Meier survival analysis. Cox regression analysis was performed to correct for other prognostic factors. RESULTS: A total of 3502 patients were included. Information on ECE was available for 2111 (60.3%) patients, consisting of 741 (35.1%) patients with and 1370 (64.9%) without ECE. The incidence of ≥ 4 lymph node metastases was 116 (15.7%) in the ECE group vs. 80 (5.8%) in the group without ECE (p < 0.001). Five-year DFS rate was 86.4% in the ECE group compared to 88.8% in the group without ECE (p = 0.085). 10-year OS rate was 78.6% compared to 83.0% (p = 0.018), respectively. Cox regression analysis showed that ECE was not an independent prognostic factor for both DFS and OS. CONCLUSIONS: ECE was significantly associated with involvement of ≥ 4 lymph node metastases in the completion ALND group. ECE was not an independent prognostic factor for both DFS and OS.

Risk of regional recurrence in triple-negative breast cancer patients: a Dutch cohort study.

Triple-negative breast cancer is associated with early recurrence and low survival rates. Several trials investigate the safety of a more conservative approach of axillary treatment in clinically T1-2N0 breast cancer. Triple-negative breast cancer comprises only 15 % of newly diagnosed breast cancers, which might result in insufficient power for representative results for this subgroup. We aimed to provide a nationwide overview on the occurrence of (regional) recurrences in triple-negative breast cancer patients with a clinically T1-2N0 status. For this cohort study, 2548 women diagnosed between 2005 and 2008 with clinically T1-2N0 triple-negative breast cancer were selected from the Netherlands Cancer Registry. Follow-up data until 2014 were analyzed using Kaplan-Meier. Sentinel lymph node biopsy was performed in 2486 patients, and (completion) axillary lymph node dissection in 562 patients. Final pathologic nodal status was pN0 in 78.5 %, pN1mi in 4.5 %, pN1 in 12.3 %, pN2-3 in 3.6 %, and pNx in 1.1 %. During a follow-up of 5 years, regional recurrence occurred in 2.9 %, local recurrence in 4.2 % and distant recurrence in 12.2 %. Five-year disease-free survival was 78.7 %, distant disease-free survival 80.5 %, and 5-year overall survival 82.3 %. Triple-negative clinically T1-2N0 breast cancer patients rarely develop a regional recurrence. Their disease-free survival is more threatened by distant recurrence, affecting their overall survival. Consequently, it seems justified to include triple-negative breast cancer patients in randomized controlled trials investigating the safety of minimizing axillary staging and treatment.

Three-Dimensional Breast Radiotherapy and the Elective Radiation Dose at the Sentinel Lymph Node Site in Breast Cancer.

BACKGROUND: Several trials are presently randomizing clinically node-negative breast cancer patients treated with breast-conserving therapy (BCT) to sentinel lymph node biopsy (SLNB) or watchful waiting. We aimed to investigate the elective radiation dose at the sentinel lymph node (SLN) site while evaluating two techniques for SLN localization, in breast cancer patients treated with lumpectomy and three-dimensional (3D) whole-breast radiotherapy. METHODS: The SLN site of consecutive Tis-2N0 breast cancer patients undergoing lumpectomy and forward intensity-modulated whole-breast radiotherapy was determined by the location of the hotspot on preoperative single-photon emission computed tomography (SPECT)/computed tomography (CT) and by a surgical clip placed at the removed SLN(s) during SLNB. The radiation dose at the SLN site was subsequently determined on the postoperative radiotherapy planning CT. An elective radiation dose to the SLN site was defined as at least 95 % of the breast dose. RESULTS: Of the 42 included patients, the mean percentage of the breast dose on the SLN site was 90 % (standard deviation 26, range 7-132, median 99), with a non-significant difference between the two techniques (surgical clip or SPECT/CT) (p = 0.608). In 32/42 patients (76 %) the SLN site received an elective radiation dose. CONCLUSIONS: A surgical clip placed at the removed SLN(s) during SLNB proved to be an adequate method of determining the radiation dose at the SLN site when compared with using SPECT/CT. With the use of 3D radiotherapy, the site of the SLN is treated with an elective radiation dose in the majority of patients who are treated with BCT.

The use of intravenous indocyanine green in minimally invasive segmental lung resections: a systematic review.

Background: To identify intersegmental planes (ISPs) in video/robot-assisted thoracoscopic segmentectomies, indocyanine green (ICG) is commonly used. The aim of this systematic review is to evaluate the efficacy of intravenous ICG in the identification of ISP. Methods: A systematic search was performed. Studies evaluating patients who underwent a video/robot-assisted thoracoscopic segmentectomy using intravenous ICG were included. The primary outcome measure was the frequency and percentage of patients in whom the ISP was adequately visualized. Secondary outcomes encompassed the ICG dose, time to visualization, time to maximum ICG visualization, time to disappearance of ICG effect and adverse reactions to ICG. Results: Eighteen studies were included for systematic review, enrolling a total of 1,090 patients. Irrespective of the injected dose, intravenous ICG identified the ISP in 94% of the cases (range, 30-100%). Overall, there was a considerable amount of heterogeneity regarding the injected dose of ICG (range, 5-25 mg or 0.05-0.5 mg/kg). The mean time before first effect of ICG was visible ranged from 10 to 40 seconds. The mean total time of ICG visibility ranged from 90 to 140 seconds after a bolus injection and was 170 seconds after continuous infusion. No adverse reactions were reported. Conclusions: After administration of intravenous ICG, visualization of the ISP is successful in up to 94% of cases, even after administration of a low dose (0.05 mg/kg) of ICG. The use of intravenous ICG is safe with no reported adverse effects in the immediate peri-operative period.

Intercostal nerve cryoablation versus thoracic epidural analgesia for minimal invasive Nuss repair of pectus excavatum: a protocol for a randomised clinical trial (ICE trial).

INTRODUCTION: Epidural analgesia is currently considered the gold standard in postoperative pain management for the minimally invasive Nuss procedure for pectus excavatum. Alternative analgesic strategies (eg, patient-controlled analgesia and paravertebral nerve block) fail in accomplishing adequate prolonged pain management. Furthermore, the continuous use of opioids, often prescribed in addition to all pain management strategies, comes with side effects. Intercostal nerve cryoablation seems a promising novel technique. Hence, the primary objective of this study is to determine the impact of intercostal nerve cryoablation on postoperative length of hospital stay compared with standard pain management of young pectus excavatum patients treated with the minimally invasive Nuss procedure. METHODS AND ANALYSIS: This study protocol is designed for a single centre, prospective, unblinded, randomised clinical trial. Intercostal nerve cryoablation will be compared with thoracic epidural analgesia in 50 young pectus excavatum patients (ie, 12-24 years of age) treated with the minimally invasive Nuss procedure. Block randomisation, including stratification based on age (12-16 years and 17-24 years) and sex, with an allocation ratio of 1:1 will be performed.Postoperative length of hospital stay will be recorded as the primary outcome. Secondary outcomes include (1) pain intensity, (2) operative time, (3) opioid usage, (4) complications, including neuropathic pain, (5) creatine kinase activity, (6) intensive care unit admissions, (7) readmissions, (8) postoperative mobility, (9) health-related quality of life, (10) days to return to work/school, (11) number of postoperative outpatient visits and (12) hospital costs. ETHICS AND DISSEMINATION: This protocol has been approved by the local Medical Ethics Review Committee, METC Zuyderland and Zuyd University of Applied Sciences. Participation in this study will be voluntary and informed consent will be obtained. Regardless of the outcome, the results will be disseminated through a peer-reviewed international medical journal. TRIAL REGISTRATION NUMBER: NCT05731973.

Management of soft tissue sarcomas of the chest wall: a comprehensive overview.

Sarcomas of the chest wall are rare and their current treatment regimen is diverse and complex due to the heterogeneity of these tumors as well as the variations in tumor location and extent. They only account for 0.04% of newly diagnosed cancers of whom about 45% comprise soft tissue sarcomas. Larger cohort studies are scarce and often focus on one specific treatment item. We therefore aim to provide helicopter view for clinicians treating patients with sarcomas of the chest wall, focusing mainly on soft tissue sarcomas. This overview includes the value of neoadjuvant systemic or radiotherapy, surgical resection, approaches for thoracic wall reconstruction, and the need for follow-up. Provided the heterogeneity and relative rarity, we recommend that treatment decisions in soft tissue sarcoma of the chest wall are discussed in a multidisciplinary tumor board at a reference sarcoma center or within sarcoma networks to ensure personalized, rational decision making. A surgical oncologist specialized in sarcoma surgery is crucial, and for extensive resections involving the thoracic cavity we recommend involvement of a thoracic surgeon. In addition, a specialized medical- and radiation oncologist as well as a plastic surgeon is required to ensure the best multimodality treatment plan to optimize patient outcome.

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 non-palpable 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.

VATS-assisted surgical stabilization of rib fractures in flail chest: 1-year follow-up of 105 cases.

OBJECTIVES: Early surgical stabilization of flail chest has been shown to improve chest wall stability and diminish respiratory complications. The addition of video­assisted thoracoscopic surgery (VATS) can diagnose and manage intrathoracic injuries and evacuate hemothorax. This study analyzed the outcome of our 7-year experience with VATS-assisted surgical stabilization of rib fractures (SSRF) for flail chest. METHODS: From January 2013 to December 2019, all trauma patients undergoing VATS-assisted SSRF for flail chest were included. Patient characteristics and complications during 1-year follow-up were reported. RESULTS: VATS­assisted SSRF for flail chest was performed in 105 patients. Median age was 65 years (range 21-92). Median injury severity score was 16 (range 9-49). Hemothorax was evacuated with VATS in 80 patients (median volume 200 ml, range 25-2500). In 3 patients entrapped lung was freed from the fracture site and in 2 patients a diaphragm rupture was repaired. Median postoperative ICU admission was 2 days (range 1-41). Thirty-two patients (30%) had a post­operative complication during admission and six patients (6%) a complication within 1 year. In-hospital mortality rate was 1%. Six patients (6%) died after discharge, due to causes unrelated to the original injury. CONCLUSIONS: Addition of VATS to SSRF for flail chest seems helpful to diagnose and manage intrathoracic injuries and adequately evacuate hemothorax. The majority of complications are low grade and occur during admission. Further prospective research needs to be conducted to identify potential risk factors for complications and better selection for addition of VATS to improve care in the future.

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) and adult (>24 years old). The primary end point was the occurrence of perioperative or postoperative complications, subdivided into major (Clavien-Dindo class IIIa or higher) and minor (less severe than Clavien-Dindo class III). Between-group differences were analyzed using the Mann-Whitney U and the χ2 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.

Conditional regional recurrence risk: The effect of event-free years in different subtypes of breast cancer.

BACKGROUND: Regional recurrence (RR), also known as lymph node recurrence, is an endpoint in several trials concerning reducing axillary treatment in cT1-2N0 breast cancer patients. The risk of RR may decrease with each subsequent event-free year, affecting the yield and consequently usefulness of long (er) follow-up. The aim of this study is to determine the risk of RR as a first event within five years after diagnosis in subtypes of breast cancer, conditional to being event-free for one, two, three and four years. METHODS: From the Netherlands Cancer Registry, cT1-2N0 breast cancer patients diagnosed from 2005 to 2008 were analyzed. Subgroup analysis was performed for pT1-2N+(sn) patients. RR risk was calculated with Kaplan-Meier analysis. Conditional RR (assuming x event-free years) was determined by selecting patients without an event at x years, and calculating the remaining risk for RR within five years after diagnosis. RESULTS: A total of 18,009 cT1-2N0 (all pN stages) breast cancer patients were included. RR occurred in 1.3% of cT1-2N0 and 1.5% of pT1-2N+(sn) patients. The risk of RR varied between subtypes; it was highest for triple negative tumors and lowest for ER + PR + Her2-and ER + Her2+ tumors. After event-free years, the risk of RR decreased subsequently in both groups and in all subtypes. After two event-free years, the risk of RR was 0.8%. CONCLUSION: The absolute yield of follow-up to detect RR beyond two years is low; for every 125 event-free patients, one RR can be expected until five years. This suggests that follow-up longer than two years is of limited value for detecting RR in both clinical and research setting.

Surgical treatment of bronchial rupture in blunt chest trauma: a review of literature.

Bronchial rupture by blunt chest trauma is rare. We present a case of bronchial injury after blunt chest trauma that was repaired surgically by primary reconstruction. We performed a review of literature to verify if primary reconstruction is suitable for the treatment of adult patients with blunt bronchial injury. A systematic search was conducted to identify cohort studies of bronchial rupture after blunt chest trauma in adult patients between 1985 and 2016 (n=215 articles). Studies were included concerning four or more patients and in case patient data could be extracted. This resulted in 19 articles for final review, consisting of 155 patients. Mean age of 155 patients was 28 (range, 18-60) years. The main bronchus was mostly injured (81%), in 5% including an injury of the trachea and in 14% lobar bronchi injury. Surgical repair was performed in 95% of patients: primary anastomosis in 72%, pneumonectomy in 15%, lobectomy or sleeve resection in 12% and other in 1%. Perioperative mortality rate was 10%. Other complications occurred in 17% (empyema, rebleeding, stenosis and fistula, among others). Data concerning the occurrence of long-term complications or long-term follow-up was not found. Statistical evaluation could not be performed due to lack of consistent patient data. No strong recommendations regarding type and timing of surgery can be made based on the available literature. Based on our multidisciplinary opinion we would advocate primary anastomosis in case of stable vital signs with the goal to preserve healthy lung parenchyma. Moreover, it may be considered transferring these rare cases to an experienced thoracic and trauma surgery center.

Maastricht Delphi consensus on event definitions for classification of recurrence in breast cancer research.

BACKGROUND: In breast cancer studies, many different endpoints are used. Definitions are often not provided or vary between studies. For instance, "local recurrence" may include different components in similar studies. This limits transparency and comparability of results. This project aimed to reach consensus on the definitions of local event, second primary breast cancer, regional and distant event for breast cancer studies. METHODS: The RAND-UCLA Appropriateness method (modified Delphi method) was used. A Consensus Group of international breast cancer experts was formed, including representatives of all involved clinical disciplines. Consensus was reached in two rounds of online questionnaires and one meeting. RESULTS: Twenty-four international breast cancer experts participated. Consensus was reached on 134 items in four categories. Local event is defined as any epithelial breast cancer or ductal carcinoma in situ (DCIS) in the ipsilateral breast, or skin and subcutaneous tissue on the ipsilateral thoracic wall. Second primary breast cancer is defined as epithelial breast cancer in the contralateral breast. Regional events are breast cancer in ipsilateral lymph nodes. A distant event is breast cancer in any other location. Therefore, this includes metastasis in contralateral lymph nodes and breast cancer involving the sternal bone. If feasible, tissue sampling of a first, solitary, lesion suspected for metastasis is highly recommended. CONCLUSION: This project resulted in consensus-based event definitions for classification of recurrence in breast cancer research. Future breast cancer research projects should adopt these definitions to increase transparency. This should facilitate comparison of results and conducting reviews as well as meta-analysis.

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.