The Feasibility of Sentinel Lymph Node Biopsy Omission After Integrate 18F-FDG Dedicated Lymph Node PET in Early Breast Cancer: A Prospective Phase II Trial

The Feasibility of Sentinel Lymph Node Biopsy Omission After Integrate 18F-FDG Dedicated Lymph Node PET in Early Breast Cancer: A Prospective Phase II Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Feasibility of Sentinel Lymph Node Biopsy Omission After Integrate 18 F-FDG Dedicated Lymph Node PET in Early Breast Cancer: A Prospective Phase II Trial Junjie Li, Jingyi Cheng, Guangyu Liu, Yifeng Hou, Genghong Di, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1139873/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Sentinel lymph node biopsy (SLNB) is currently the standard of care in clinically node-negative (cN0) breast cancer. The present study aimed to evaluate the negative predictive value (NPV) of 18 F-FDG dedicated lymph node positron emission tomography (LymphPET) in cN0 patients. Methods This is a prospective phase II trial divided into two stages (NCT04072653). In the first stage, cN0 patients underwent axillary LymphPET, followed by SLNB. In the second stage, SLNB was omitted in patients with a negative preoperative axillary assessment after integrating LymphPET. Here, we report the results of the first stage; the primary outcome was the NPV of LymphPET to detect macrometastases of lymph nodes. Results 189 invasive breast cancer patients underwent LymphPET, followed by surgery, with definitive pathological reports. Forty patients had lymph node macrometastasis (LN-macro), and 16 patients had only lymph node micrometastasis (LN-micro). Of the 131 patients who had a negative LymphPET, 16 patients had LN-macro, the NPV was 87.8%. After combining axillary imaging evaluation with ultrasound and LymphPET, 100 patients were found to be both LymphPET and ultrasound negative, 9 patients had LN-macro, the NPV was 91%. Conclusions LymphPET can be used to screen potential patients to avoid SLNB with an NPV >90%. The second stage of the SOAPET trial is ongoing to confirm the safe omission of SLNB according to preoperational axillary evaluation when integrating LymphPET. Nuclear Medicine & Medical Imaging Breast cancer sentinel lymph node biopsy 18F-fluorodeoxyglucose LymphPET the negative predictive value Figures Figure 1 Introduction Sentinel lymph node biopsy (SLNB) has replaced axillary dissection (AD) as the standard surgical procedure due to similar diagnostic accuracy and prognosis, and reduced surgical morbidity [ 1 – 3 ]. However, surgical morbidities still exit in patients with SLNB, with one-quarter occurring in the early postoperative period [ 4 ], and 4% occurring in the late period [ 5 ]. A recent review of seven trials involving 9426 participants found that the surgical complications of SLNB resulted in 4.8% cases of lymphedema, 4% of subjective arm movement impairment, 34% of paresthesia, 8.6% of pain, and 18.5% of numbness [ 6 ]. Due to the increased prevalence of screening mammography, early diagnose rate of breast cancer is increased [ 7 ], and about two-thirds of clinical node negative (cN0) patients were pathology node-negative after SLNB [ 3 ]. Therefore, it is of considerable interest to investigate the omission of SLNB in cN0 patients to avoid physical and emotional distress further. So far, the accuracy of physical examination combined with ultrasound, magnetic resonance imaging (MRI), and even 18F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) for preoperative axillary evaluation are not satisfactory (negative predictive value [NPV]90% in preoperative nodal staging is a key unmet need for clinicians when determining to omit SLNB. Based on our previous study, a novel high-resolution dedicated axillary lymph node Positron Emission Tomography (LymphPET) could be used to identify and recognize more indolent axillary lymph nodes of the breast cancer because of more sensitivity and much higher negative predictive value, with NPV reached 90% [ 10 ]. Hence, we launched a prospective phase II study to investigate the NPV of LymphPET and to verify whether SLNB can be omitted in cN0 patients (SOAPET, NCT04072653). Patients And Methods Study design and patients SOAPET (Sentinel node biopsy vs. Observation After axillary PET) is a prospective, open-label, phase II clinical trial conducted at Fudan University Shanghai Cancer Center and was divided into two stages. The study protocol is available in the DataSupplement (online only). In the first stage, cN0 patients were detected by clinical examination and underwent axillary imaging evaluation and LymphPET, followed by axillary surgery (SLNB or AD). In the second stage, SLNB was omitted for patients with the negative preoperative axillary assessment after integrating LymphPET. Here, we report the results of the first stage. The eligibility criteria were: females≥18 years old with newly diagnosed, histologically confirmed unilateral invasive breast cancer,with a negative axillary physical examination. The key exclusion criteria were: the presence of distant metastases; previous neoadjuvant therapy; previous axillary biopsy or axillary surgery 7 days before LymphPET; current pregnancy or lactating; and diabetes mellitus without bloodglucose management. The study protocol was approved by independent ethics committees at Fudan University Shanghai Cancer Centre, and the study was conducted in accordance with Good Clinical Practice and the Declaration of Helsinki. All patients provided written informed consent before study participation. Procedures Patients with a negative axillary physical examination underwent routine breast and axillary imaging evaluation, and core needle biopsy in breast lesion to diagnose invasive carcinoma. LymphPET system and examination The LymphPET (PEMTECHTM, Shanghai, China) device contains movable double-planar confronted detectors with an axillary view and an adjustable distance between the two detector plates from 8 to 37 cm. The size of the sensitive detection area is 208×208 mm. Patients were fasted at least 6 h prior to receiving a standardized injection of 4mCi 18F-FDG (injection in the contralateral arm to the breast lesion). Blood glucose levels were required to be lower than 10 mmol/L. After a resting period of 60 min to allow tracer distribution, LymphPET was performed and the acquisition duration was 3 minutes each region and both bilateral axillary regions were detected one by one. After acquisition, the images are reconstructed with a 3D standard maximum likelihood expectation maximization (MLEM 3D) algorithm, and be were checked immediately. LymphPET image analysis According to our previous study, LUV (LymphPET Uptake Value) has been used as a surrogate for SUV. The maximum single-voxel standardized LUV (maxLUV) was performed using commercial Medical Image Merge (version 6.5.4; MI M Software Inc, OH, USA), and two experienced nuclear medicine physicians were blinded to all study-related information (except breast cancer laterality) and analyzed the images separately. The maxLUV lymph node cut-off value was set at 0.27. 10 ALNs were considered positive under the following three conditions: (1) the positive focus was located in the axillary region but not in skin, muscle, or bone; (2) 18F-FDG uptake was higher than the reference background (fat tissue); and (3) the physiological lymphatic uptake was excluded, such as symmetrically bilateral positive focus, like two funicular ropes. Surgical procedure and pathological evaluation of lymph nodes SLNB was performed in cN0 patients. Patients with ultrasound-detected lymph nodes would undergo ultrasound-guided fine-needle aspiration (FNA), if FNA was negative, SLNB was routinely performed. The SLN was identified with blue dye and/or radio colloid. SLNs were defined as any blue-stained node, any node with blue-stained lymphatic channel directly leading to it, any node with radioactive counts ≥ 10%, or any pathologically palpable nodes. Touch imprint cytology was routinely applied on every SLN harvested. Also, slices were fixed formalin and paraffin-embedded for further evaluation. Serial sectioning with the HE staining was performed. The pathological results were classified as macrometastasis (>2 mm), micrometastasis (0.2–2.0 mm), and isolate tumor cells (<0.2 mm), according to the TMN staging system. For patients with no more than two lymph node macrometastases (LN-macro), the decision to perform further axillary dissection was dependent on the operative type (breast-conserving therapy or mastectomy) and individual pathological characteristics. Outcomes LymphPET accuracy was evaluated by comparing results separately with the final histology. The results were classified as true positive (TP), true negative (TN), false positive (FP), and false-negative (FN). The evaluation of the results was on the calculation of sensitivity (TP/[TP+FN]), specificity (TN/[TN+FP]), and NPV (TN/[TN+FN]). The primary outcome was the NPV of LymphPET to detect macrometastases of lymph nodes, defined as the proportion of non-macrometastases lymph nodes in patients with negative LymphPET results. Statistical analysis As we expected, the NPV for LymphPET to be 87.5%, with a two-sided type I error of 2.5% and a power of 80%, 196 patients were needed for the present study. Assuming that 3% of patients would be lost to follow up, a total of 202 patients were needed in the first stage. For categorical variables, χ 2 -test calculated the difference or Fisher’s exact test when necessary. Statistical analysis was performed with IBM SPSS version 20.0 software, and statistical significance was defined as two-sided P ≤ .05. Results Patients From September 9, 2019, to May 30, 2020, 224 patients were screened, and 189 patients with invasive breast cancer (180 invasive ductal carcinoma and 9 invasive lobular carcinomas) underwent LymphPET, followed by surgery, with definitive pathological reports. (Figure 1 ) The median age was 50 years, 36% underwent breast-conserving surgery. 53% o had T1-stage disease, 64% had grade I and II, and 58.7% had a ki67<30%. 63% were luminal type, 26% were HER2 positive, and 10% were triple negative. 40 patients had at least one LN-macro, and 16 only had lymph node micrometastasis (LN-micro). (Table 1 ) Table 1 Patient demographics and clinical characteristics Characteristics n (%) Age (years) 49.9 (28–75) <50 97 (51.3) ≥ 50 92 (48.7) Operation type Breast-conserving surgery 68 (36) Mastectomy 121 (64) Axillary evaluation SLNB 133 (70.4) SLNB, then AD 40 (21.2) AD 16 (8.4) Node stage N0 133 (70.3) N1mic 16 (8.5) N1 32 (17) N2 7 (3.7) N3 1 (0.5) T stage T1a 19 (10.1) T1b 11 (5.8) T1c 64 (33.9) T2 89 (47.1) Unknown 6 (3.1) Histology IDC 180 (95.2) ILC 9 (4.8) Grade I 25 (13.2) II 96 (50.8) III 68 (36) Subtype HR-positive &HER2 negative 120 (63.5) HR-positive & HER2 positive 23 (12.2) HR negative & HER2 positive 27 (14.3) HR negative &HER2 negative 19 (10) Ki67 ≥ 30%+ 78 (41.3) LVI positive 61 (32.3) AD, axillary dissection; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; LVI, lymphovascular invasion; SLNB, sentinel lymph node biopsy. Efficacy Outcomes According to the ultrasound reports, 124 patients had no lymph nodes detected (US-neg), 46 had lymph nodes detected (US-det), and 16 had suspected metastatic lymph nodes detected. Of the patients who had US-neg, 17 had LN-macro, and 12 had LN-micro. The NPV for US-neg was 86.3%. According to the LymphPET reports, 131 patients were LymphPET negative (maxLUV0.27), 24 had LN-macro, and five had LN-micro. When combined clinical axillary evaluation with ultrasound and LymphPET, 100 patients were found to be both LymphPET and ultrasound negative. Of these patients, nine had LN-macro, the NPV was 91% (Table 2 ). Table 2 Diagnostic performance of LymphPET and ultrasoundin axillary staging Axillary imaging assessment n Macrometastases Micrometastases non-metastases Sensitivity Specificity NPV Ultrasound‡ 40 16 US-neg 124 17 12 95 57.5 71.8 86.3 US-det 46 14 4 28 US-met 19 9 0 10 LymphPET† Negative 131 16 11 104 60 77.2 87.8 Positive 58 24 5 29 Combination* Negative 100 9 9 82 77.5 61.1 91 Positive 89 31 7 51 ‡ US-neg, no lymph nodes detected by ultrasound; US-met, suspected metastatic lymph nodes detected by ultrasound; US-det, lymph nodes detected by ultrasound. †maxLUV of LymphPET was set at 0.27 (negative <0.27, positive ≥ 0.27). *Negative, no lymph nodes detected by ultrasound and maxLUV in LymphPET<0.27; positive, lymph nodes detected by ultrasound and/or maxLUV in LymphPET ≥ 0.27. Sensitivity, specificity, and NVP were calculated according to lymph node macrometastases. The clinical characteristics of the nine patients with FN evaluation by ultrasound and LymphPET are listed in Table 3; seven patients had N1 disease, and two had N2 disease, one had invasive lobular carcinoma, and six had a lymphovascular invasion. Three patients were luminal A (patient ID: 83, 116, 129), three were luminal B (ID: 117, 128, 144), two were HER2 positive (ID: 57, 76), and one was triple-negative (ID: 147). Table 3. Clinical characteristics of patients with a false-negative axillary node evaluation by LymphPET and ultrasound Patient ID Age (years) Side Operation MG Location Size cm Histology Grade LV ER PR HER2 Ki67 SLN no. No. lymph node macrometastases AD 57 44 Right M Mass Center 1.5 IDC III + 80 60 + 15 4 1 0/19 76 67 Right BCS MC Outer upper 3.7 IDC II – 80 10 + 20 3 1 0/12 83 41 Right M MC Outer upper 1.5 IDC II + 80 80 – 15 5 2 0/15 116 67 Right M MC Outer upper 2.8 IDC II + 80 80 – 10 6 3 0/12 117 41 Right BCS Mass Outer upper 3 IDC II + 80 80 – 30 3 2 2/20 128 69 Right M Mass Inner upper 2 ILC II – 80 20 – 30 3 2 6/24 129 47 Left M Mass Outer 2.2 IDC II + 80 80 – 10 4 2 0/25 144 57 Left M Mass Outer lower 3.5 IDC II + 80 80 – 30 3 1 1/22 147 61 Right M Mass Outer upper 1.2 IDC II – 0 0 – 80 4 1 0/8 AD, axillary dissection; BCS, breast-conserving surgery; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; LV, lymphovascular invasion; M, mastectomy; MC, mass with calcification; MG, mammography. Efficacy Outcomes After a median follow-up 14 months, no side-effects related to LymphPET scan were reported. Discussion The SOAPET study is the first prospective trial to investigate the accuracy of LymphPET in evaluating axillary status in cN0 patients detected by clinical examination. Its primary endpoint of an NPV of 87.8% for LymphPET was met. According to our results, in patients with a negative axillary physical examination, approximately 21% will have LN-macro after SLNB, even when combined with preoperative ultrasound, 13.7% of patients with no lymph nodes detected by preoperative ultrasound, still had LN-macro. Importantly, after combining ultrasound and LymphPET, we were able to screen potential patients who may avoid axillary evaluation with an NPV >90%. Currently, in primary cN0 breast cancer, SLNB is the gold standard for regional axillary staging, with better physical function of the upper limb when compared with AD; however, it can also lead to specific axillary morbidity in both the early and late postoperative periods. In patients treated with SLNB alone, the rate of wound infections, axillary seromas, and paresthesia was 25% in Z0011 [ 11 ], and long-term postsurgical complications were recorded as 4% lymphoedema, 13% sensory neuropathy, and 13% motor neuropathy in IBCSG 23-01 [ 12 ]. Higher rates of lymphedema and an arm circumference increase of >10% were recorded after SLNB followed by axillary radiotherapy in AMAROS [ 13 ]. Therefore, screening cN0 patients to avoid surgical evaluation is an essential focus of current research. Several ongoing prospective randomized trials, such as SOUND trial and BOOG 2013-08 trial, are comparing SLNB with observation in cN0 patients treated with breast-conserving therapy [ 4 , 14 ]. The key technical indicators for such trials are the NPV of preoperative assessment, as a higher number of FN means LN-macro remain in the axillary, which may lead to a higher local failure rate. Initial data of the SOUND trial showed that 13.4% of patients in the SLNB group had LN-macro [ 15 ], the NPV of preoperative axillary assessment by physical examination and ultrasound was approximately 87%. It is still unclear whether 13% of FN with no lymph node surgical evaluation will influence outcomes. Our study had a similar finding, among patients with a negative axillary physical examination and no lymph nodes detected by preoperative ultrasound, 13.7% still had LN-macro. Therefore, it is essential to determine the omission of SLNB with increasing the NPV of preoperative axillary assessment. Several studies have investigated axillary ultrasound in patients with early breast cancer. Retrospective data of 577 axillary ultrasounds demonstrated that a negative axillary ultrasound generally excludes the presence of pN2–3 disease, whereas ultrasound cannot accurately differentiate between pN1 and pN2-3 disease [ 16 ]. FN is relatively high, as in 118 patients with no node detected by ultrasound, 21% were ultimately found to be node-positive [ 17 ]; although these FN results did not significantly impact adjuvant medical decision-making, as patients with FN had recurrence-free survival equivalent to patients with pathological N0 disease [ 18 ]. Other studies have further evaluated whether metabolic imaging technology may increase accuracy in evaluating axillary status in early breast cancer. In 349 T1 patients who were preoperatively examined using ultrasound, MRI, and 18 F-FDG PET/CT, the NVP was around 81.7–82.6%, suggesting that there are no definitive modalities for detecting node metastasis in T1 breast cancer to replace SLNB [ 8 ]. After combining 18 F-FDG PET/CT and ultrasound, in 138 ultrasound-negative and 18 F-FDG uptake-negative patients, 15% were found to have lymph node involvement [ 9 ]. Therefore, even with high specificity, 18 F-FDG PET/CT demonstrated poor sensitivity in the detection of axillary metastases [ 19 ]. A possible explanation for this is that, currently, the whole-body 18 F-FDG PET/CT system typically yields reconstructed images with a resolution of 5–15mm, depending on the injected dose, imaging time, post-reconstruction filtering, and intrinsic resolution of the scanner. This reduces the system’s ability to detect small lesions (<1 cm) and/or lesions with low tracer uptake [ 20 ]. According to our previous study, the spatial resolution of LymphPET is much higher than whole-body PET/CT, with 88% sensitivity and 79% specificity [ 10 ]. In the current study, we found that the diagnostic accuracy of LymphPET was nearly equal to ultrasound. The sensitivity, specificity, and NPV for LymphPET were 60%, 77.2%, and 87.8%, respectively, and those for US-neg were 57.5%, 71.8%, and 86.3%. When combined LymphPET in the preoperative assessment, in the physical exam-negative and ultrasound-negative patients, we were able to further screen 80% of patients (100/124) with a 91% NPV for axillary lymph node macrometastases, and providing technical support for future studies looking at the omission of axillary evaluation. Usually, FN rate of 10% for SLNB is acceptable. In Z0011, patients who underwent AD had 27% non-SLN positive, assuming patients with SLNB only still had around 30% with positive node remain in axillary, with the additional local treatment of radiotherapy, the local regional recurrence is less than 1% [ 11 ]. Similarly, in the AD group in AMAROS, 33% of patients had additional positive nodes; 5-year axillary lymph node recurrence was found to be 1.19% in SLNB group after axillary radiotherapy [ 13 ]. Therefore, we believe that LymphPET could be a reliable preoperative evaluation method, and axillary surgical evaluation can be omitted if both ultrasound and LymphPET are negative. Limitations Our study has several limitations. Firstly, isolated tumor cells (<0.2mm) and micrometastases (0.2–2 mm) were not calculated in the analysis. Currently, such small metastases are hard to detect by any imaging technique. Patients with micrometastatic tumor deposits, pN0(i+) or pN1mi, do not appear to have a worse 8-year disease-free survivalor overall survival compared with SLN-negative patients [ 21 ]. Whether treatment recommendations for systemic therapy should consider the presence of a single micrometastatic lymph node identified during complete serial sectioning of sentinel node(s) is still controversial [ 22 ].Axillary radiotherapy might reduce axillary lymph node recurrence, especially in patients following breast-conserving therapy with no axillary surgical intervention [ 23 ]. Secondly, in patients with FN detected by ultrasound and LymphPET, adjuvant systemic therapy may be inadequate without knowing the definitive node status. In our study, three patients who were HER2 positive and/or triple-negative would receive system adjuvant therapy in any case. For 5 patients with Luminal type N1 diseases, genomic signatures now represent an important progress in optimal selection of high risk patients that might benefit from the addition of chemotherapy to adjuvant endocrine therapy [ 24 , 25 ]. One patient with invasive lobular carcinoma N2 disease (ID 128) might receive inadequate adjuvant treatment if the axillary node status is unknown. Due to these limitations, in the second stage of the SOAPET, we will select patients ready for breast-conserving therapy who are both ultrasound and LymphPET negative, and genomic signatures will be recommended to patients with Luminal type, to assess the safety of omitting surgical axillary evaluation in such population. In conclusion, the results of our study indicate that LymphPET can be used to identify cN0 patients, reducing the FN rate by <10%. The second stage of the SOAPET trial is ongoing to confirm the safety of omitting SLNB according to preoperational axillary evaluation when integrating LymphPET. Declarations Acknowledgements We thank all the patients, their families involved in this study. Funding: This work was supported by: The Ministry of Education Innovation Team (grant number IRT1223) and the Shanghai Health System Joint Project of Key Disease (grant number 2013ZYJB0302). Competing Interests The authors have no relevant financial or non-financial interests to disclose Authors contribution Junjie Li: Conceptualization, Data curation, Methodology, Analysis, Investigation, Writing – original draft,Writing – review & editing; Jingyi Cheng: Data curation, Investigation, Methodology, Writing – review & editing; Guangyu Liu: Data curation, Methodology, Analysis, Investigation, Writing – review & editing; Yifeng Hou: Data curation, Investigation, Writing – review & editing; Genghong Di: Data curation, Investigation, Writing – review & editing; Benglong Yang: Investigation, Writing – review & editing; Yizhou Jiang: Investigation, Writing – review & editing; Liang Huang: Investigation, Writing – review & editing; Feilin Qu: Investigation, Writing – review & editing; Sheng Chen: Investigation, Writing – review & editing; Yan Wang: Investigation, Writing – review & editing; Keda Yu: Data curation, Investigation, Writing – review & editing; Zhimin Shao: Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Writing – review & editing; Data Availability The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request Ethics approval This study was performed in line with the principles of the Declaration of Helsinki. 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J Clin Oncol. 2009 Oct 1;27(28):4679-84. doi: 10.1200/JCO.2008.19.0686 . Epub 2009 Aug 31. Montagna E, Viale G, Rotmensz N, Maisonneuve P, Galimberti V, Luini A, Intra M, Veronesi P, Mazzarol G, Pruneri G, Renne G, Torrisi R, Cardillo A, Cancello G, Goldhirsch A, Colleoni M. Minimal axillary lymph node involvement in breast cancer has different prognostic implications according to the staging procedure. Breast Cancer Res Treat. 2009 Nov;118(2):385–94. doi: 10.1007/s10549-009-0446-6 . Epub 2009 Jun 27. Veronesi U, Orecchia R, Zurrida S, Galimberti V, Luini A, Veronesi P, Gatti G, D'Aiuto G, Cataliotti L, Paolucci R, Piccolo P, Massaioli N, Sismondi P, Rulli A, Lo Sardo F, Recalcati A, Terribile D, Acerbi A, Rotmensz N, Maisonneuve P. Avoiding axillary dissection in breast cancer surgery: a randomized trial to assess the role of axillary radiotherapy. Ann Oncol. 2005 Mar;16(3):383–8. Epub 2005 Jan 24. Gluz O, Nitz UA, Christgen M, Kates RE, Shak S, Clemens M, Kraemer S, Aktas B, Kuemmel S, Reimer T, Kusche M, Heyl V, Lorenz-Salehi F, Just M, Hofmann D, Degenhardt T, Liedtke C, Svedman C, Wuerstlein R, Kreipe HH, Harbeck N. West German Study Group Phase III PlanB Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment. J Clin Oncol. 2016 Jul 10;34(20):2341–9. doi: 10.1200/JCO.2015.63.5383 . Epub 2016 Feb 29. Cardoso F, van't Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S, Pierga JY, Brain E, Causeret S, DeLorenzi M, Glas AM, Golfinopoulos V, Goulioti T, Knox S, Matos E, Meulemans B, Neijenhuis PA, Nitz U, Passalacqua R, Ravdin P, Rubio IT, Saghatchian M, Smilde TJ, Sotiriou C, Stork L, Straehle C, Thomas G, Thompson AM, van der Hoeven JM, Vuylsteke P, Bernards R, Tryfonidis K, Rutgers E, Piccart M; MINDACT Investigators. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med. 2016 Aug 25;375(8):717–29. doi: 10.1056/NEJMoa1602253 . Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1139873","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":68697963,"identity":"cc678c7d-287f-4961-b8fe-f4948b55f8a8","order_by":0,"name":"Junjie Li","email":"","orcid":"https://orcid.org/0000-0002-0787-4240","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Junjie","middleName":"","lastName":"Li","suffix":""},{"id":68697964,"identity":"d569131f-6b66-401f-9bb5-5e14177188e1","order_by":1,"name":"Jingyi Cheng","email":"","orcid":"","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jingyi","middleName":"","lastName":"Cheng","suffix":""},{"id":68697965,"identity":"968b56b4-2dbd-4988-9ec5-bf55794c13e6","order_by":2,"name":"Guangyu Liu","email":"","orcid":"","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Guangyu","middleName":"","lastName":"Liu","suffix":""},{"id":68697966,"identity":"2c89fa2e-34f9-429b-856c-fa6cac981428","order_by":3,"name":"Yifeng Hou","email":"","orcid":"","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yifeng","middleName":"","lastName":"Hou","suffix":""},{"id":68697967,"identity":"0ab2866b-3563-4561-9bd8-d8738b401b35","order_by":4,"name":"Genghong Di","email":"","orcid":"","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Genghong","middleName":"","lastName":"Di","suffix":""},{"id":68697968,"identity":"2afae364-6420-4b20-9fc1-dac61183945f","order_by":5,"name":"Benglong Yang","email":"","orcid":"","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Benglong","middleName":"","lastName":"Yang","suffix":""},{"id":68697969,"identity":"4bfad37d-b45c-4d08-980b-8aeb56e669b9","order_by":6,"name":"Yizhou Jiang","email":"","orcid":"","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yizhou","middleName":"","lastName":"Jiang","suffix":""},{"id":68697970,"identity":"10fa4e93-a652-4894-9209-dafba2398f9c","order_by":7,"name":"Liang Huang","email":"","orcid":"","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Liang","middleName":"","lastName":"Huang","suffix":""},{"id":68697971,"identity":"61d48d2d-dbc7-44e3-ae02-c600d6b95bb6","order_by":8,"name":"Feilin Qu","email":"","orcid":"","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Feilin","middleName":"","lastName":"Qu","suffix":""},{"id":68697972,"identity":"25b0e86a-a3cb-46f2-bfc9-86657439b448","order_by":9,"name":"Sheng Chen","email":"","orcid":"","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sheng","middleName":"","lastName":"Chen","suffix":""},{"id":68697973,"identity":"5ad1037a-0587-4d58-bc36-a0d37572edc8","order_by":10,"name":"Yan Wang","email":"","orcid":"","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Wang","suffix":""},{"id":68697974,"identity":"f688c174-bf1d-45de-a13a-a01944d833f3","order_by":11,"name":"Keda Yu","email":"","orcid":"","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Keda","middleName":"","lastName":"Yu","suffix":""},{"id":68697975,"identity":"7a4d9a48-7e6b-41bb-8414-f6a393c5ec86","order_by":12,"name":"Zhimin Shao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIiWNgGAWjYDACCcYGhgQgbcDAwPgASCeQpIXZAKoFKIRXC5QGKmeTIEqL/Ozm1g0PdzDYm7MfPlbNU2GXxyDdfPwBPi2Mcw623Ug8w5C4syct7TbPmeRiBpljiXhtYZZIBGppY0gwOJBjdpu3jTmxQSLHEK8WNqgWe4Pzb8yKef/VA7Xkf8SrhQeqhXHDjRwzZt6GwyBb8HtfAqolccONZ8mSc44dT2yTSDOcgU+L/Iz0Zzd/gh2WfPDDm5rqxH6J5Acf8GmBgv9gkokH5DsilCMA4w+SlI+CUTAKRsFIAQBF0U5JsSp4SAAAAABJRU5ErkJggg==","orcid":"","institution":"Shanghai Cancer Hospital: Fudan University Shanghai Cancer Center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Zhimin","middleName":"","lastName":"Shao","suffix":""}],"badges":[],"createdAt":"2021-12-04 07:03:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1139873/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1139873/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":16320074,"identity":"ac15e9e7-f83a-4214-879c-c9a105e06a8b","added_by":"auto","created_at":"2021-12-09 16:18:48","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":79935,"visible":true,"origin":"","legend":"CONSORT diagram of patient disposition.\n*cN+: patients with a positive axillary physical examination","description":"","filename":"fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1139873/v1/a6532f247e90d162ae5c52fa.jpg"},{"id":16825951,"identity":"e97f88ff-b390-4020-a3c8-bc4f1a82db97","added_by":"auto","created_at":"2021-12-29 10:50:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":423208,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1139873/v1/d8c33d23-0f6f-4984-853d-4a137e6786c6.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eThe Feasibility of Sentinel Lymph Node Biopsy Omission After Integrate \u003csup\u003e18\u003c/sup\u003eF-FDG Dedicated Lymph Node PET in Early Breast Cancer: A Prospective Phase II Trial\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSentinel lymph node biopsy (SLNB) has replaced axillary dissection (AD) as the standard surgical procedure due to similar diagnostic accuracy and prognosis, and reduced surgical morbidity [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, surgical morbidities still exit in patients with SLNB, with one-quarter occurring in the early postoperative period [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and 4% occurring in the late period [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. A recent review of seven trials involving 9426 participants found that the surgical complications of SLNB resulted in 4.8% cases of lymphedema, 4% of subjective arm movement impairment, 34% of paresthesia, 8.6% of pain, and 18.5% of numbness [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDue to the increased prevalence of screening mammography, early diagnose rate of breast cancer is increased [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and about two-thirds of clinical node negative (cN0) patients were pathology node-negative after SLNB [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Therefore, it is of considerable interest to investigate the omission of SLNB in cN0 patients to avoid physical and emotional distress further. So far, the accuracy of physical examination combined with ultrasound, magnetic resonance imaging (MRI), and even 18F-fluorodeoxyglucose (\u003csup\u003e18\u003c/sup\u003eF-FDG) positron emission tomography (PET) for preoperative axillary evaluation are not satisfactory (negative predictive value [NPV]\u0026lt;85%) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. How to increase the NPV of axillary assessments to \u0026gt;90% in preoperative nodal staging is a key unmet need for clinicians when determining to omit SLNB.\u003c/p\u003e \u003cp\u003eBased on our previous study, a novel high-resolution dedicated axillary lymph node Positron Emission Tomography (LymphPET) could be used to identify and recognize more indolent axillary lymph nodes of the breast cancer because of more sensitivity and much higher negative predictive value, with NPV reached 90% [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Hence, we launched a prospective phase II study to investigate the NPV of LymphPET and to verify whether SLNB can be omitted in cN0 patients (SOAPET, NCT04072653).\u003c/p\u003e"},{"header":"Patients And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and patients\u003c/h2\u003e \u003cp\u003eSOAPET (Sentinel node biopsy vs. Observation After axillary PET) is a prospective, open-label, phase II clinical trial conducted at Fudan University Shanghai Cancer Center and was divided into two stages. The study protocol is available in the DataSupplement (online only). In the first stage, cN0 patients were detected by clinical examination and underwent axillary imaging evaluation and LymphPET, followed by axillary surgery (SLNB or AD). In the second stage, SLNB was omitted for patients with the negative preoperative axillary assessment after integrating LymphPET. Here, we report the results of the first stage.\u003c/p\u003e \u003cp\u003eThe eligibility criteria were: females\u0026ge;18 years old with newly diagnosed, histologically confirmed unilateral invasive breast cancer,with a negative axillary physical examination. The key exclusion criteria were: the presence of distant metastases; previous neoadjuvant therapy; previous axillary biopsy or axillary surgery 7 days before LymphPET; current pregnancy or lactating; and diabetes mellitus without bloodglucose management.\u003c/p\u003e \u003cp\u003e The study protocol was approved by independent ethics committees at Fudan University Shanghai Cancer Centre, and the study was conducted in accordance with Good Clinical Practice and the Declaration of Helsinki. All patients provided written informed consent before study participation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eProcedures\u003c/h2\u003e \u003cp\u003ePatients with a negative axillary physical examination underwent routine breast and axillary imaging evaluation, and core needle biopsy in breast lesion to diagnose invasive carcinoma.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003eLymphPET system and examination\u003c/h2\u003e \u003cp\u003eThe LymphPET (PEMTECHTM, Shanghai, China) device contains movable double-planar confronted detectors with an axillary view and an adjustable distance between the two detector plates from 8 to 37 cm. The size of the sensitive detection area is 208\u0026times;208 mm.\u003c/p\u003e \u003cp\u003ePatients were fasted at least 6 h prior to receiving a standardized injection of 4mCi 18F-FDG (injection in the contralateral arm to the breast lesion). Blood glucose levels were required to be lower than 10 mmol/L. After a resting period of 60 min to allow tracer distribution, LymphPET was performed and the acquisition duration was 3 minutes each region and both bilateral axillary regions were detected one by one. After acquisition, the images are reconstructed with a 3D standard maximum likelihood expectation maximization (MLEM 3D) algorithm, and be were checked immediately.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section4\"\u003e \u003ch2\u003eLymphPET image analysis\u003c/h2\u003e \u003cp\u003eAccording to our previous study, LUV (LymphPET Uptake Value) has been used as a surrogate for SUV. The maximum single-voxel standardized LUV (maxLUV) was performed using commercial Medical Image Merge (version 6.5.4; MI M Software Inc, OH, USA), and two experienced nuclear medicine physicians were blinded to all study-related information (except breast cancer laterality) and analyzed the images separately. The maxLUV lymph node cut-off value was set at 0.27.\u003csup\u003e10\u003c/sup\u003e ALNs were considered positive under the following three conditions: (1) the positive focus was located in the axillary region but not in skin, muscle, or bone; (2) 18F-FDG uptake was higher than the reference background (fat tissue); and (3) the physiological lymphatic uptake was excluded, such as symmetrically bilateral positive focus, like two funicular ropes.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eSurgical procedure and pathological evaluation of lymph nodes\u003c/h2\u003e \u003cp\u003eSLNB was performed in cN0 patients. Patients with ultrasound-detected lymph nodes would undergo ultrasound-guided fine-needle aspiration (FNA), if FNA was negative, SLNB was routinely performed.\u003c/p\u003e \u003cp\u003eThe SLN was identified with blue dye and/or radio colloid. SLNs were defined as any blue-stained node, any node with blue-stained lymphatic channel directly leading to it, any node with radioactive counts \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e10%, or any pathologically palpable nodes. Touch imprint cytology was routinely applied on every SLN harvested. Also, slices were fixed formalin and paraffin-embedded for further evaluation. Serial sectioning with the HE staining was performed. The pathological results were classified as macrometastasis (\u0026gt;2 mm), micrometastasis (0.2\u0026ndash;2.0 mm), and isolate tumor cells (\u0026lt;0.2 mm), according to the TMN staging system.\u003c/p\u003e \u003cp\u003eFor patients with no more than two lymph node macrometastases (LN-macro), the decision to perform further axillary dissection was dependent on the operative type (breast-conserving therapy or mastectomy) and individual pathological characteristics.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eLymphPET accuracy was evaluated by comparing results separately with the final histology. The results were classified as true positive (TP), true negative (TN), false positive (FP), and false-negative (FN). The evaluation of the results was on the calculation of sensitivity (TP/[TP+FN]), specificity (TN/[TN+FP]), and NPV (TN/[TN+FN]). The primary outcome was the NPV of LymphPET to detect macrometastases of lymph nodes, defined as the proportion of non-macrometastases lymph nodes in patients with negative LymphPET results.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAs we expected, the NPV for LymphPET to be 87.5%, with a two-sided type I error of 2.5% and a power of 80%, 196 patients were needed for the present study. Assuming that 3% of patients would be lost to follow up, a total of 202 patients were needed in the first stage. For categorical variables, χ\u003csup\u003e2\u003c/sup\u003e-test calculated the difference or Fisher\u0026rsquo;s exact test when necessary. Statistical analysis was performed with IBM SPSS version 20.0 software, and statistical significance was defined as two-sided \u003cem\u003eP\u003c/em\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026le;\u003c/span\u003e.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv class=\"Section2\" id=\"Sec11\"\u003e\n \u003ch2\u003ePatients\u003c/h2\u003e\n \u003cp\u003eFrom September 9, 2019, to May 30, 2020, 224 patients were screened, and 189 patients with invasive breast cancer (180 invasive ductal carcinoma and 9 invasive lobular carcinomas) underwent LymphPET, followed by surgery, with definitive pathological reports. (Figure \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) The median age was 50 years, 36% underwent breast-conserving surgery. 53% o had T1-stage disease, 64% had grade I and II, and 58.7% had a ki67\u0026lt;30%. 63% were luminal type, 26% were HER2 positive, and 10% were triple negative. 40 patients had at least one LN-macro, and 16 only had lymph node micrometastasis (LN-micro). (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u003ctable border=\"1\" id=\"Tab1\" style=\"margin-right: calc(15%); width: 85%;\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ePatient demographics and clinical characteristics\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"2\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e49.9 (28\u0026ndash;75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003e\u0026lt;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e97 (51.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003e\u003cspan class=\"Underline\" name=\"Emphasis\" type=\"Underline\"\u003e\u0026ge;\u003c/span\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e92 (48.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eOperation type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eBreast-conserving surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e68 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eMastectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e121 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eAxillary evaluation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eSLNB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e133 (70.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eSLNB, then AD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e40 (21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e16 (8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eNode stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eN0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e133 (70.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eN1mic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e16 (8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eN1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e32 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eN2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e7 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eN3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e1 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eT stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eT1a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e19 (10.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eT1b\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e11 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eT1c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e64 (33.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e89 (47.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e6 (3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e180 (95.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eILC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e9 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e25 (13.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e96 (50.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e68 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eSubtype\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eHR-positive \u0026amp;HER2 negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e120 (63.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eHR-positive \u0026amp; HER2 positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e23 (12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eHR negative \u0026amp; HER2 positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e27 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eHR negative \u0026amp;HER2 negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e19 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eKi67 \u003cspan class=\"Underline\" name=\"Emphasis\" type=\"Underline\"\u003e\u0026ge;\u003c/span\u003e30%+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e78 (41.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 51.3857%;\"\u003e\n \u003cp\u003eLVI positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 48.4988%;\"\u003e\n \u003cp\u003e61 (32.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003eAD, axillary dissection; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; LVI, lymphovascular invasion; SLNB, sentinel lymph node biopsy.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec12\"\u003e\n \u003ch2\u003eEfficacy Outcomes\u003c/h2\u003e\n \u003cp\u003eAccording to the ultrasound reports, 124 patients had no lymph nodes detected (US-neg), 46 had lymph nodes detected (US-det), and 16 had suspected metastatic lymph nodes detected. Of the patients who had US-neg, 17 had LN-macro, and 12 had LN-micro. The NPV for US-neg was 86.3%. According to the LymphPET reports, 131 patients were LymphPET negative (maxLUV\u0026lt;0.27). Of these patients, 16 had LN-macro, and 11 had LN-micro. The NPV of LymphPET was 87.8%. In 58 patients who LymphPET positive (maxLUV\u0026gt;0.27), 24 had LN-macro, and five had LN-micro. When combined clinical axillary evaluation with ultrasound and LymphPET, 100 patients were found to be both LymphPET and ultrasound negative. Of these patients, nine had LN-macro, the NPV was 91% (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDiagnostic performance of LymphPET and ultrasoundin axillary staging\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAxillary imaging assessment\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMacrometastases\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMicrometastases\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003enon-metastases\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSensitivity\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSpecificity\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNPV\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUltrasound\u0026Dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS-neg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS-det\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUS-met\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLymphPET\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e77.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCombination*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003e\u0026Dagger; US-neg, no lymph nodes detected by ultrasound; US-met, suspected metastatic lymph nodes detected by ultrasound; US-det, lymph nodes detected by ultrasound.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003e\u0026dagger;maxLUV of LymphPET was set at 0.27 (negative \u0026lt;0.27, positive\u003cspan class=\"Underline\" name=\"Emphasis\" type=\"Underline\"\u003e\u0026ge;\u003c/span\u003e0.27).\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003e*Negative, no lymph nodes detected by ultrasound and maxLUV in LymphPET\u0026lt;0.27; positive, lymph nodes detected by ultrasound and/or maxLUV in LymphPET\u003cspan class=\"Underline\" name=\"Emphasis\" type=\"Underline\"\u003e\u0026ge;\u003c/span\u003e0.27.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003eSensitivity, specificity, and NVP were calculated according to lymph node macrometastases.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eThe clinical characteristics of the nine patients with FN evaluation by ultrasound and LymphPET are listed in Table 3; seven patients had N1 disease, and two had N2 disease, one had invasive lobular carcinoma, and six had a lymphovascular invasion. Three patients were luminal A (patient ID: 83, 116, 129), three were luminal B (ID: 117, 128, 144), two were HER2 positive (ID: 57, 76), and one was triple-negative (ID: 147).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e Clinical characteristics of patients with a false-negative axillary node evaluation by LymphPET and ultrasound\u003c/p\u003e\n \u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003ePatient ID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.840163934426229%\"\u003e\n \u003cp\u003eSide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.19672131147541%\"\u003e\n \u003cp\u003eOperation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.532786885245901%\"\u003e\n \u003cp\u003eMG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.118852459016393%\"\u003e\n \u003cp\u003eLocation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.479508196721311%\"\u003e\n \u003cp\u003eSize cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.377049180327869%\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.122950819672131%\"\u003e\n \u003cp\u003eGrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.4836065573770494%\"\u003e\n \u003cp\u003eLV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3811475409836067%\"\u003e\n \u003cp\u003eER\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.278688524590164%\"\u003e\n \u003cp\u003ePR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.225409836065574%\"\u003e\n \u003cp\u003eHER2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.508196721311475%\"\u003e\n \u003cp\u003eKi67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.30327868852459%\"\u003e\n \u003cp\u003eSLN no.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.680327868852459%\"\u003e\n \u003cp\u003eNo. lymph node macrometastases\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.200819672131147%\"\u003e\n \u003cp\u003e\u0026nbsp;AD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.840163934426229%\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.19672131147541%\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.532786885245901%\"\u003e\n \u003cp\u003eMass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.118852459016393%\"\u003e\n \u003cp\u003eCenter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.479508196721311%\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.377049180327869%\"\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.122950819672131%\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.4836065573770494%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3811475409836067%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.278688524590164%\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.225409836065574%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.508196721311475%\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.30327868852459%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.680327868852459%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.200819672131147%\"\u003e\n \u003cp\u003e0/19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.840163934426229%\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.19672131147541%\"\u003e\n \u003cp\u003eBCS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.532786885245901%\"\u003e\n \u003cp\u003eMC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.118852459016393%\"\u003e\n \u003cp\u003eOuter upper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.479508196721311%\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.377049180327869%\"\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.122950819672131%\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.4836065573770494%\"\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3811475409836067%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.278688524590164%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.225409836065574%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.508196721311475%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.30327868852459%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.680327868852459%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.200819672131147%\"\u003e\n \u003cp\u003e0/12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.840163934426229%\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.19672131147541%\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.532786885245901%\"\u003e\n \u003cp\u003eMC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.118852459016393%\"\u003e\n \u003cp\u003eOuter upper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.479508196721311%\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.377049180327869%\"\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.122950819672131%\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.4836065573770494%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3811475409836067%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.278688524590164%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.225409836065574%\"\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.508196721311475%\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.30327868852459%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.680327868852459%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.200819672131147%\"\u003e\n \u003cp\u003e0/15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.840163934426229%\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.19672131147541%\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.532786885245901%\"\u003e\n \u003cp\u003eMC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.118852459016393%\"\u003e\n \u003cp\u003eOuter upper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.479508196721311%\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.377049180327869%\"\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.122950819672131%\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.4836065573770494%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3811475409836067%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.278688524590164%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.225409836065574%\"\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.508196721311475%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.30327868852459%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.680327868852459%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.200819672131147%\"\u003e\n \u003cp\u003e0/12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e117\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.840163934426229%\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.19672131147541%\"\u003e\n \u003cp\u003eBCS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.532786885245901%\"\u003e\n \u003cp\u003eMass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.118852459016393%\"\u003e\n \u003cp\u003eOuter upper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.479508196721311%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.377049180327869%\"\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.122950819672131%\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.4836065573770494%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3811475409836067%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.278688524590164%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.225409836065574%\"\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.508196721311475%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.30327868852459%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.680327868852459%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.200819672131147%\"\u003e\n \u003cp\u003e2/20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.840163934426229%\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.19672131147541%\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.532786885245901%\"\u003e\n \u003cp\u003eMass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.118852459016393%\"\u003e\n \u003cp\u003eInner upper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.479508196721311%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.377049180327869%\"\u003e\n \u003cp\u003eILC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.122950819672131%\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.4836065573770494%\"\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3811475409836067%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.278688524590164%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.225409836065574%\"\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.508196721311475%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.30327868852459%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.680327868852459%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.200819672131147%\"\u003e\n \u003cp\u003e6/24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.840163934426229%\"\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.19672131147541%\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.532786885245901%\"\u003e\n \u003cp\u003eMass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.118852459016393%\"\u003e\n \u003cp\u003eOuter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.479508196721311%\"\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.377049180327869%\"\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.122950819672131%\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.4836065573770494%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3811475409836067%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.278688524590164%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.225409836065574%\"\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.508196721311475%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.30327868852459%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.680327868852459%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.200819672131147%\"\u003e\n \u003cp\u003e0/25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.840163934426229%\"\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.19672131147541%\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.532786885245901%\"\u003e\n \u003cp\u003eMass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.118852459016393%\"\u003e\n \u003cp\u003eOuter lower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.479508196721311%\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.377049180327869%\"\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.122950819672131%\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.4836065573770494%\"\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3811475409836067%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.278688524590164%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.225409836065574%\"\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.508196721311475%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.30327868852459%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.680327868852459%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.200819672131147%\"\u003e\n \u003cp\u003e1/22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e147\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.635245901639344%\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.840163934426229%\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.19672131147541%\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.532786885245901%\"\u003e\n \u003cp\u003eMass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.118852459016393%\"\u003e\n \u003cp\u003eOuter upper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.479508196721311%\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.377049180327869%\"\u003e\n \u003cp\u003eIDC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.122950819672131%\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.4836065573770494%\"\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.3811475409836067%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"3.278688524590164%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.225409836065574%\"\u003e\n \u003cp\u003e\u0026ndash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.508196721311475%\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.30327868852459%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.680327868852459%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.200819672131147%\"\u003e\n \u003cp\u003e0/8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eAD, axillary dissection; BCS, breast-conserving surgery; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; LV, lymphovascular invasion; M, mastectomy; MC, mass with calcification; MG, mammography.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec13\"\u003e\n \u003ch2\u003eEfficacy Outcomes\u003c/h2\u003e\n \u003cp\u003eAfter a median follow-up 14 months, no side-effects related to LymphPET scan were reported.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe SOAPET study is the first prospective trial to investigate the accuracy of LymphPET in evaluating axillary status in cN0 patients detected by clinical examination. Its primary endpoint of an NPV of 87.8% for LymphPET was met. According to our results, in patients with a negative axillary physical examination, approximately 21% will have LN-macro after SLNB, even when combined with preoperative ultrasound, 13.7% of patients with no lymph nodes detected by preoperative ultrasound, still had LN-macro. Importantly, after combining ultrasound and LymphPET, we were able to screen potential patients who may avoid axillary evaluation with an NPV \u0026gt;90%.\u003c/p\u003e \u003cp\u003eCurrently, in primary cN0 breast cancer, SLNB is the gold standard for regional axillary staging, with better physical function of the upper limb when compared with AD; however, it can also lead to specific axillary morbidity in both the early and late postoperative periods. In patients treated with SLNB alone, the rate of wound infections, axillary seromas, and paresthesia was 25% in Z0011 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and long-term postsurgical complications were recorded as 4% lymphoedema, 13% sensory neuropathy, and 13% motor neuropathy in IBCSG 23-01 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Higher rates of lymphedema and an arm circumference increase of \u0026gt;10% were recorded after SLNB followed by axillary radiotherapy in AMAROS [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Therefore, screening cN0 patients to avoid surgical evaluation is an essential focus of current research. Several ongoing prospective randomized trials, such as SOUND trial and BOOG 2013-08 trial, are comparing SLNB with observation in cN0 patients treated with breast-conserving therapy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The key technical indicators for such trials are the NPV of preoperative assessment, as a higher number of FN means LN-macro remain in the axillary, which may lead to a higher local failure rate.\u003c/p\u003e \u003cp\u003eInitial data of the SOUND trial showed that 13.4% of patients in the SLNB group had LN-macro [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], the NPV of preoperative axillary assessment by physical examination and ultrasound was approximately 87%. It is still unclear whether 13% of FN with no lymph node surgical evaluation will influence outcomes. Our study had a similar finding, among patients with a negative axillary physical examination and no lymph nodes detected by preoperative ultrasound, 13.7% still had LN-macro. Therefore, it is essential to determine the omission of SLNB with increasing the NPV of preoperative axillary assessment.\u003c/p\u003e \u003cp\u003eSeveral studies have investigated axillary ultrasound in patients with early breast cancer. Retrospective data of 577 axillary ultrasounds demonstrated that a negative axillary ultrasound generally excludes the presence of pN2\u0026ndash;3 disease, whereas ultrasound cannot accurately differentiate between pN1 and pN2-3 disease [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. FN is relatively high, as in 118 patients with no node detected by ultrasound, 21% were ultimately found to be node-positive [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]; although these FN results did not significantly impact adjuvant medical decision-making, as patients with FN had recurrence-free survival equivalent to patients with pathological N0 disease [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOther studies have further evaluated whether metabolic imaging technology may increase accuracy in evaluating axillary status in early breast cancer. In 349 T1 patients who were preoperatively examined using ultrasound, MRI, and \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT, the NVP was around 81.7\u0026ndash;82.6%, suggesting that there are no definitive modalities for detecting node metastasis in T1 breast cancer to replace SLNB [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. After combining \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT and ultrasound, in 138 ultrasound-negative and \u003csup\u003e18\u003c/sup\u003eF-FDG uptake-negative patients, 15% were found to have lymph node involvement [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, even with high specificity, \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT demonstrated poor sensitivity in the detection of axillary metastases [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA possible explanation for this is that, currently, the whole-body \u003csup\u003e18\u003c/sup\u003eF-FDG PET/CT system typically yields reconstructed images with a resolution of 5\u0026ndash;15mm, depending on the injected dose, imaging time, post-reconstruction filtering, and intrinsic resolution of the scanner. This reduces the system\u0026rsquo;s ability to detect small lesions (\u0026lt;1 cm) and/or lesions with low tracer uptake [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. According to our previous study, the spatial resolution of LymphPET is much higher than whole-body PET/CT, with 88% sensitivity and 79% specificity [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the current study, we found that the diagnostic accuracy of LymphPET was nearly equal to ultrasound. The sensitivity, specificity, and NPV for LymphPET were 60%, 77.2%, and 87.8%, respectively, and those for US-neg were 57.5%, 71.8%, and 86.3%. When combined LymphPET in the preoperative assessment, in the physical exam-negative and ultrasound-negative patients, we were able to further screen 80% of patients (100/124) with a 91% NPV for axillary lymph node macrometastases, and providing technical support for future studies looking at the omission of axillary evaluation.\u003c/p\u003e \u003cp\u003eUsually, FN rate of 10% for SLNB is acceptable. In Z0011, patients who underwent AD had 27% non-SLN positive, assuming patients with SLNB only still had around 30% with positive node remain in axillary, with the additional local treatment of radiotherapy, the local regional recurrence is less than 1% [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Similarly, in the AD group in AMAROS, 33% of patients had additional positive nodes; 5-year axillary lymph node recurrence was found to be 1.19% in SLNB group after axillary radiotherapy [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Therefore, we believe that LymphPET could be a reliable preoperative evaluation method, and axillary surgical evaluation can be omitted if both ultrasound and LymphPET are negative.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eOur study has several limitations. Firstly, isolated tumor cells (\u0026lt;0.2mm) and micrometastases (0.2\u0026ndash;2 mm) were not calculated in the analysis. Currently, such small metastases are hard to detect by any imaging technique. Patients with micrometastatic tumor deposits, pN0(i+) or pN1mi, do not appear to have a worse 8-year disease-free survivalor overall survival compared with SLN-negative patients [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Whether treatment recommendations for systemic therapy should consider the presence of a single micrometastatic lymph node identified during complete serial sectioning of sentinel node(s) is still controversial [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].Axillary radiotherapy might reduce axillary lymph node recurrence, especially in patients following breast-conserving therapy with no axillary surgical intervention [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Secondly, in patients with FN detected by ultrasound and LymphPET, adjuvant systemic therapy may be inadequate without knowing the definitive node status. In our study, three patients who were HER2 positive and/or triple-negative would receive system adjuvant therapy in any case. For 5 patients with Luminal type N1 diseases, genomic signatures now represent an important progress in optimal selection of high risk patients that might benefit from the addition of chemotherapy to adjuvant endocrine therapy [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. One patient with invasive lobular carcinoma N2 disease (ID 128) might receive inadequate adjuvant treatment if the axillary node status is unknown. Due to these limitations, in the second stage of the SOAPET, we will select patients ready for breast-conserving therapy who are both ultrasound and LymphPET negative, and genomic signatures will be recommended to patients with Luminal type, to assess the safety of omitting surgical axillary evaluation in such population.\u003c/p\u003e \u003cp\u003eIn conclusion, the results of our study indicate that LymphPET can be used to identify cN0 patients, reducing the FN rate by \u0026lt;10%. The second stage of the SOAPET trial is ongoing to confirm the safety of omitting SLNB according to preoperational axillary evaluation when integrating LymphPET.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all the patients, their families involved in this study.\u003c/p\u003e\n\u003cp id=\"isPasted\"\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThis work was supported by:\u0026nbsp;\u003c/strong\u003eThe Ministry of Education Innovation Team (grant number IRT1223) and the Shanghai Health System Joint Project of Key Disease (grant number 2013ZYJB0302).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors contribution\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJunjie Li:\u0026nbsp;Conceptualization, Data curation, Methodology, Analysis, Investigation, Writing \u0026ndash; original draft,Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eJingyi Cheng: Data curation, Investigation, Methodology, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eGuangyu Liu: Data curation, Methodology, Analysis, Investigation, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eYifeng Hou: Data curation, Investigation, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eGenghong Di: Data curation, Investigation, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eBenglong Yang: Investigation, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eYizhou Jiang: Investigation, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eLiang Huang: Investigation, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eFeilin Qu: Investigation, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eSheng Chen: Investigation, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eYan Wang: Investigation, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eKeda Yu: Data curation, Investigation, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003eZhimin Shao: Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Writing \u0026ndash; review \u0026amp; editing;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of\u0026nbsp;\u003c/em\u003eFudan University Shanghai Cancer Centre (Aug 2019)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish:\u0026nbsp;\u003c/strong\u003eNA\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMuriel Brackstone; Fulvia G. Baldassarre; Francisco E. Perera, et al. Management of the Axilla in Early-Stage Breast Cancer: Ontario Health (Cancer Care Ontario) and ASCO Guideline. \u003cem\u003eJournal of Clinical Oncology\u003c/em\u003e. 2021 Jul 19;JCO2100934. 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Epub 2016 Feb 29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCardoso F, van't Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S, Pierga JY, Brain E, Causeret S, DeLorenzi M, Glas AM, Golfinopoulos V, Goulioti T, Knox S, Matos E, Meulemans B, Neijenhuis PA, Nitz U, Passalacqua R, Ravdin P, Rubio IT, Saghatchian M, Smilde TJ, Sotiriou C, Stork L, Straehle C, Thomas G, Thompson AM, van der Hoeven JM, Vuylsteke P, Bernards R, Tryfonidis K, Rutgers E, Piccart M; MINDACT Investigators. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. \u003cem\u003eN Engl J Med.\u003c/em\u003e 2016 Aug 25;375(8):717\u0026ndash;29. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1602253\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Breast cancer, sentinel lymph node biopsy, 18F-fluorodeoxyglucose, LymphPET, the negative predictive value","lastPublishedDoi":"10.21203/rs.3.rs-1139873/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1139873/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eSentinel lymph node biopsy (SLNB) is currently the standard of care in clinically node-negative (cN0) breast cancer. The present study aimed to evaluate the negative predictive value (NPV) of \u003csup\u003e18\u003c/sup\u003eF-FDG dedicated lymph node positron emission tomography (LymphPET) in cN0 patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis is a prospective phase II trial divided into two stages (NCT04072653). In the first stage, cN0 patients underwent axillary LymphPET, followed by SLNB. In the second stage, SLNB was omitted in patients with a negative preoperative axillary assessment after integrating LymphPET. Here, we report the results of the first stage; the primary outcome was the NPV of LymphPET to detect macrometastases of lymph nodes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e189 invasive breast cancer patients underwent LymphPET, followed by surgery, with definitive pathological reports. Forty patients had lymph node macrometastasis (LN-macro), and 16 patients had only lymph node micrometastasis (LN-micro). Of the 131 patients who had a negative LymphPET, 16 patients had LN-macro, the NPV was 87.8%. After combining axillary imaging evaluation with ultrasound and LymphPET, 100 patients were found to be both LymphPET and ultrasound negative, 9 patients had LN-macro, the NPV was 91%.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eLymphPET can be used to screen potential patients to avoid SLNB with an NPV \u0026gt;90%. The second stage of the SOAPET trial is ongoing to confirm the safe omission of SLNB according to preoperational axillary evaluation when integrating LymphPET.\u003c/p\u003e","manuscriptTitle":"The Feasibility of Sentinel Lymph Node Biopsy Omission After Integrate 18F-FDG Dedicated Lymph Node PET in Early Breast Cancer: A Prospective Phase II Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-12-09 16:18:47","doi":"10.21203/rs.3.rs-1139873/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5e10b837-a48c-4a13-8675-53491d4e6430","owner":[],"postedDate":"December 9th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":9044547,"name":"Nuclear Medicine \u0026 Medical Imaging"}],"tags":[],"updatedAt":"2021-12-29T10:50:34+00:00","versionOfRecord":[],"versionCreatedAt":"2021-12-09 16:18:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1139873","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1139873","identity":"rs-1139873","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}