Prognosis of patients with breast cancer who underwent breast-conserving surgery using a 3D-printed surgical guide after neoadjuvant chemotherapy

Prognosis of patients with breast cancer who underwent breast-conserving surgery using a 3D-printed surgical guide after neoadjuvant chemotherapy | 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 Article Prognosis of patients with breast cancer who underwent breast-conserving surgery using a 3D-printed surgical guide after neoadjuvant chemotherapy Ah Yoon Kim, Sae Byul Lee, Tae Kyung Yoo, Ji Sun Kim, Il Yong Chung, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4792541/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted 12 You are reading this latest preprint version Abstract In breast-conserving surgery (BCS), clear resection margins are crucial to prevent recurrence. Accurate imaging is vital for precise BCS, with MRI being the most accurate. However, MRI has limitations in identifying the exact extent of breast cancer in patients who have undergone neoadjuvant chemotherapy (NACT). A 3D-Printed Breast Surgical Guide (3DP-BSG) can address this issue by effectively pinpointing cancer extent in NACT patients, thus enhancing surgical accuracy. This retrospective single-institution cohort study focused on female patients diagnosed with invasive breast cancer who underwent NACT. Between November 2015 and October 2021, patients received BCS with the aid of a 3DP-BSG. Personalized 3DP-BSG targeted tumors by tracking changes in breast and tumor anatomy on MRI before and after NACT. 203 patients with invasive breast cancer were enrolled in the study. According to exclusion criteria, 197 patients were analyzed. The median follow-up period was 35.3 months (range: 2.2–96.8 months). 3 patients (1.5%) had positive resection margins. During the follow-up period, 17 patients (8.6%) experienced recurrence, with one patient (0.5%) confirmed local recurrences. The application of MRI-based 3DP-BSG is effective in achieving low positive margins and local recurrence in patients undergoing BCS after NACT, offering a promising approach for improving surgical outcomes. Health sciences/Medical research Health sciences/Oncology Breast cancer 3D-Printed Breast Surgical Guide 3DP-BSG breast-conserving surgery neoadjuvant chemotherapy MRI Figures Figure 1 Figure 2 Introduction Breast-conserving surgery (BCS), also known as lumpectomy, aims to remove the tumor while preserving as much healthy breast tissue as possible. Neoadjuvant chemotherapy (NACT) can significantly decrease tumor size, allowing BCS to be a viable option for larger tumors that might otherwise have necessitated mastectomy. 1,2 Magnetic resonance imaging (MRI) is often used to assess tumor size and location after NACT, but its accuracy can be compromised due to the reduced contrast of the tumor caused by diminished angiogenesis, posing a challenge to surgeons during BCS. 3,4 Achieving clear resection margins—removing the tumor with a tumor-free zone around the excised tissue—is a critical goal during BCS. Positive resection margins are associated with higher rates of local recurrence. 5 Preoperative imaging modalities such as mammography, ultrasound, and MRI can assist in tumor localization, with MRI in particular recognized for its accuracy in predicting tumor extent. 6 Despite the advantages of MRI, it faces limitations, particularly in marking the extent of the tumor on breast imaging, especially when NACT is performed when treatment can alter the appearance of the tumor. 7–9 Efforts such as projection and 3D scanning have been made to map MRI areas directly onto the breast, but these techniques have seen limited adoption owing to various constraints. 10,11 The development of 3D-printed breast surgical guides (3DP-BSG) aims to overcome the limitations associated with MRI. 12 This study analyzes the surgical results and prognosis of patients who underwent BCS using 3DP-BSG after NACT. Results Patients An overview of the patient characteristics can be seen in Table 1 . From November 2015 to October 2021, 203 patients with invasive cancer were enrolled in the study. After excluding patients with Stage IV cancer or those who had undergone NASSM, the study focused on 197 patients. The median follow-up period was 35.3 months (range 2.2–96.8 months).The median age of the patients was 49.6 years (range 26–76 years), with 103 patients (52.3%) aged over 50 years. The average BMI of the patients was 25.1; 79 (40.1%) patients were classified as normal weight, 99 (50.3%) as overweight, and 19 (9.6%) as mildly obese. All patients underwent axillary surgery, with sentinel lymph node biopsy performed in 194 patients (97%). Table 1 Patient characteristics Variables N (%) Age (years) Median 49.6 range 26–76 ≥50 103 (52.3) 30) 19 (9.6) Overweight (24–29.9) 99 (50.3) Normal (< 24) 79 (40.1) Axillary surgery SNB 115 (58.4) SNB + ALND 78 (39.6) ALND 4 ( 2 ) ** SNB : sentinel lymph node biopsy, ALND : axillary lymph node dissection PATHOLOGY Table 2 summarizes the pathology results of the patients. In 194 cases (98.5%), pathology revealed invasive ductal carcinoma (IDC), while the remaining 3 cases were diagnosed with invasive lobular carcinoma (ILC). Most histologic grades were (95.5%) 2 or higher. In terms of clinical stage, 1 patient was classified as Stage I (0.5%), 152 as Stage II (77.2%), and 44 as Stage III (22.3%). For the pathologic stage, 67 patients (34.0%) were classified as Stage 0, 63 as Stage I (31.5%), 51 as Stage II (25.9%), and 16 as Stage III (8.0%). Complete remission was confirmed in 67 patients (34.0%) based on the permanent pathology results. Pathologic complete remission refers to no residual invasive cancer in the tissue after surgery. The four molecular subtypes were evenly distributed, with a similar pattern observed in the Ki-67 index. Table 2 Pathological results Variables N (%) Pathology IDC 194 (98.5) ILC 3 (1.5) Histologic grade I 1 (0.5) II 92 (46.7) III 104 (52.8) Clinical stage Stage 0 0 (0.0) Stage I 1 (0.5) Stage II 152 (77.2) Stage III 44 (22.3) Pathologic stage Stage 0 67 (34.0) Stage I 63 (31.5) Stage II 51 (25.9) Stage III 16 (8.6) Subtype HR + Her2+ 32 (16.2) HR + Her2- 61 (31.0) HR- Her2+ 44 (22.3) HR- Her2- 60 (30.5) Ki-67 index 0–19% 95 (48.2) 20–49% 43 (21.8) >50% 59 (30.0) Recurrence Local 1 (0.5) Regional 5 (2.5) Distant 11 (5.6) Total 17 (8.6) ** IDC : invasive ductal carcinoma, ILC : invasive lobular carcinoma, HR : hormone receptor *** Stratified according to the American Joint Committee in Cancer(AJCC) 8th stage The average specimen weight was 31.5g (range: 2.5–215g). Three patients (1.5%) were found to have positive resection margins, and re-excision was performed in these cases. During the follow-up period, 17 patients experienced recurrence, including one case of local recurrence. Regional recurrence occurred in 5 patients in the ipsilateral axillary lymph node. The most common site of recurrence was lung metastasis, followed by liver metastasis. The use of 3D-printed surgical guides enhanced the precision of BCS, resulting in favorable outcomes. Discussion Neoadjuvant therapy in patients with breast cancer offers several advantages, including the early initiation of systemic treatment, the ability to assess treatment response, and the potential shift from mastectomy to BCS by reducing the size of the tumor. 1 In some cases, NACT renders previously inoperable tumors operable or shrinks tumors sufficiently to increase breast preservation rates from 7–12%. 1 A meta-analysis of 10 randomized trials found that the BCS rate in patients who received NACT was 65% compared with 49% in the adjuvant chemotherapy group. 2 Achieving optimal cosmetic results during BCS requires preserving as much normal tissue as possible while ensuring complete tumor resection. Positive margin status is associated with higher local recurrence rates, distant metastasis, and lower overall survival. 5 Accurately predicting tumor extent before surgery is crucial for achieving clear margins in BCS. Imaging modalities such as MMG, USG, and MRI are commonly used for this purpose, with MRI known for its high accuracy. 6 However, MRI has limitations, including difficulties in marking the tumor area on the breast due to differences in the traditional prone position of MRI scans and the supine position during surgery. 8,9 Several attempts have been made to map MRI regions onto the breast. For instance, using projection and reproduction techniques in surgical-position breast MRI in 24 patients with DCIS resulted in smaller pathologic specimen volumes and a lower positive margin rate compared with conventional BCS. 10 Kutomi et al. conducted a study analyzing the surgical results of 1,150 patients who underwent supine MRI before BCS. They concluded that supine MRI is an effective method for determining the extent of resection, with a positive margin rate of 18.8%. 8 However, after NACT, tumor shrinkage and decreased contrast intensity can obscure the area of the remaining cancer. Additionally, because MRI cannot confirm tumor cell level, it may be challenging to determine the original tumor area before treatment. 3,4 A meta-analysis of 10 randomized trials tracking the prognosis of 4,756 patients with breast reported a 15-year local recurrence rate of 21.4% in the NACT group, higher than 15.9% in the adjuvant group. The authors concluded that NACT should prioritize careful tumor localization, through detailed pathological assessment, and appropriate radiotherapy. 2 Before NACT, various methods were explored for marking tumors, including the use of metallic markers or 125I-radioactive seeds (RSL) around the tumor, as well as the classic method of tattooing the skin. A review of 15 studies examining tumor marking before NACT reported a 13.9% negative margin in surgical outcomes, including complete pathological response, leading to improvements in margins and survival outcomes. 13 The use of multiple markers to obtain more detailed information about the tumor area was also considered. Comparing resection margins in BCS using single or double radiopaque markers revealed no difference in additional resection rate after frozen biopsy or re-excision rate, and no difference in local recurrence-free survival. 14 3DP-BSG was developed and clinically used to quantitatively mark the tumor area on the breast based on MRI and track tumor changes after NACT. 12,15,16 A study analyzing 39 patients who underwent BCS using 3DP-BSG after NACT found that frozen sections showed positive margins of 10.3%, indicating a high clear margin rate. Additionally, it was reported that 3DP-BSG targeting was painless for patients, did not involve radiation, and did not increase the procedure time. 16 While the use of markers in BCS is expected to improve the local recurrence rate, reports on prognosis remain limited. A study involving 373 patients reported that the 5-year rate of local control was 98.6% in patients with radiopaque clips, compared with 91.7% in patients without tumor marker clips. The insertion of clips was beneficial for local control. 17 In this study, the median follow-up period was 38.5 months, which is relatively short, yet demonstrated a low local recurrence rate of 1.0%. Previous reports showed local recurrence rates in patients who underwent NACT and BCS ranging from 9.2 to 21.4%. 2,18 The use of 3DP-BSG during BCS in this study may have contributed to the lower local recurrence rate compared with previous studies, but there are limitations. This study was a retrospective analysis of surgeries performed at a single institution, which could limit the evaluation of recurrence rates. Although the follow-up period is relatively short, it remains meaningful as recurrence rates often peak 2–3 years after surgery. Additionally, the absence of a control group in this single-group study using 3DP-BSG is a limitation, and a multicenter prospective randomized study is needed for further evaluation. Methods PATIENTS This retrospective single-center cohort study analyzed patients diagnosed with invasive breast cancer who underwent BCS using 3DP-BSG after NACT between November 2015 and October 2021. Patients with Stage IV or those who received NASSM (nipple areolar complex skin sparing mastectomy) were excluded from the analysis. Patient outcomes after surgery were assessed through the review of medical records. Cases involving other cancers before the occurrence of local recurrence were also excluded. This study was approved by the Institutional Review Board of Asan Medical Center (2021 − 1198). Research had been performed in accordance with the Declaration of Helsinki. Patients provided informed consent and agreed to the inclusion of a supine series in the standard baseline MRI protocol. 3DP-BSG DESIGN Breast imaging was performed using a 3.0T MRI system with a breast coil. Additional images were obtained in the same supine position as the surgical position. Breast tissue and tumors were segmented and 3D-modeled in prone/supine MRI/CT scans using Mimics Medical v17 (Materialise Inc., Belgium) (Fig. 1 A, B). The changed tumor area was tracked and segmented based on the enhanced tumor visible in the post-NACT MRI and the tumor/surrounding tissue pattern observed in the pre-operation MRI (Fig. 1 C). In accordance with the final 3D modeled breast and tumor, a hybrid 3DP-BSG was designed and printed, which had a groove for marking the breast skin and a pillar for dye injection, targeting the tumor inside the breast (Fig. 1 D). SURGERY AND MARGIN EVALUATION The surgical position was performed with the patient in the supine position with the affected arm spread at a 90-degree angle. The 3DP-BSG was applied after general anesthesia. Designed to fit the shape of the breast, the guide was positioned precisely by aligning it with the nipple on the affected side, the suprasternal notch, and a guideline extending toward the opposite nipple (Fig. 2 ). The tumor area was marked on the skin along the groove of the 3DP-BSG, and a dye was injected around the tumor inside the breast using a syringe along the column. The tumor was excised based on these markings, and the surrounding margins were assessed for the presence of tumors using frozen sections. If a tumor was observed at the margin, additional resection was performed. Margins that could not be confirmed using frozen sections were evaluated using permanent pathology results to determine whether reoperation was necessary. Sentinel lymph node biopsy (SLNB) was performed, and the decision to proceed with axillary lymph node dissection (ALND) was made based on the results. CONCLUSION The use of MRI-based 3D-BSG during BCS following NACT enables precise targeting of the original tumor area. This innovative approach holds promise as a next-generation breast targeting method, providing significant benefits to both patients and surgeons through low rates of positive margins and local recurrence. Declarations All data generated or analysed during this study are included in this published article. Competing Interests BeomSeok Ko and Namkug Kim have a patent on the 3DP BSG and are the founding members of the Anymedi company, Byung Ho Son has a patent on the 3DP BSG. Funding This research was supported by the Asan Medical Center, funded by the Asan Foundation (Grant number: 2021IF0020). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author Contribution BSK and NKK planned overall research.SBL, TKY, JSK, IYC, HJK, JWL, BHS, JHJ and HJL collected the data.AYK and BSK analyed the data.AYK and BSK wrote the main manuscript text, figure and table. All authors reviewed the manuscrip. Acknowledgement 3DP BSG was produced and applied to patients with the help of Sangwook Lee, Joo Yun Won and Guk Bae Kim of Anymedi Inc. Data Availability The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. References Wang H, Mao X. Evaluation of the efficacy of neoadjuvant chemotherapy for breast cancer. Drug design, development and therapy . 2020:2423-2433. Asselain B, Barlow W, Bartlett J, et al. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. The Lancet Oncology . 2018;19(1):27-39. Xiao J, Rahbar H, Hippe DS, et al. Dynamic contrast-enhanced breast MRI features correlate with invasive breast cancer angiogenesis. NPJ breast cancer . 2021;7(1):42. Gezer NS, Orbay Ö, Balcı P, Durak MG, Demirkan B, Saydam S. Evaluation of neoadjuvant chemotherapy response with dynamic contrast enhanced breast magnetic resonance imaging in locally advanced invasive breast cancer. The journal of breast health . 2014;10(2):111. Bundred JR, Michael S, Stuart B, et al. Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis. bmj . 2022;378 Azhdeh S, Kaviani A, Sadighi N, Rahmani M. Accurate estimation of breast tumor size: a comparison between ultrasonography, mammography, magnetic resonance imaging, and associated contributing factors. European Journal of Breast Health . 2021;17(1):53. Kwon M-r, Chu J, Kook SH, Kim EY. Factors associated with radiologic-pathologic discordance in magnetic resonance imaging after neoadjuvant chemotherapy for breast cancer. Clinical Imaging . 2022;89:1-9. Kutomi G, Shima H, Kyuno D, et al. Positional advantages of supine MRI for diagnosis prior to breast‑conserving surgery. Molecular and Clinical Oncology . 2023;18(5):1-4. Wang C-B, Lee S, Kim T, et al. Breast tumor movements analysis using MRI scans in prone and supine positions. Scientific Reports . 2020;10(1):4858. Sakakibara M, Nagashima T, Sangai T, et al. Breast-conserving surgery using projection and reproduction techniques of surgical-position breast MRI in patients with ductal carcinoma in situ of the breast. Journal of the American College of Surgeons . 2008;207(1):62-68. Pallone MJ, Poplack SP, Avutu HBR, Paulsen KD, Barth RJ. Supine breast MRI and 3D optical scanning: a novel approach to improve tumor localization for breast conserving surgery. Annals of surgical oncology . 2014;21:2203-2208. Ko BS, Kim N, Lee JW, et al. MRI-based 3D-printed surgical guides for breast cancer patients who received neoadjuvant chemotherapy. Scientific reports . 2019;9(1):11991. Jha CK, Johri G, Singh PK, Yadav SK, Sinha U. Does Tumor Marking Before Neoadjuvant Chemotherapy Helps Achieve Better Outcomes in Patients Undergoing Breast Conservative Surgery? A Systematic Review. Indian Journal of Surgical Oncology . 2021;12(3):624-631. Cha C, Lee J, Kim D, et al. Comparison of resection margin status after single or double radiopaque marker insertion for tumor localization in breast cancer patients receiving neoadjuvant chemotherapy. Breast Cancer Research and Treatment . 2020;184:797-803. Ock J, Lee S, Kim T, et al. Accuracy evaluation of a 3D printing surgical guide for breast-conserving surgery using a realistic breast phantom. Computers in Biology and Medicine . 2021;137:104784. Lee HS, Kim HJ, Chung IY, et al. Usefulness of 3D-surgical guides in breast conserving surgery after neoadjuvant treatment. Scientific Reports . 2021;11(1):3376. Oh JL, Nguyen G, Whitman GJ, et al. Placement of radiopaque clips for tumor localization in patients undergoing neoadjuvant chemotherapy and breast conservation therapy. Cancer: Interdisciplinary International Journal of the American Cancer Society . 2007;110(11):2420-2427. Zhou X, Li Y. Local recurrence after breast-conserving surgery and mastectomy following neoadjuvant chemotherapy for locally advanced breast cancer-a meta-analysis. Breast care . 2016;11(5):345-351. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 02 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 07 Nov, 2024 Reviews received at journal 04 Nov, 2024 Reviews received at journal 31 Oct, 2024 Reviewers agreed at journal 22 Oct, 2024 Reviewers agreed at journal 20 Oct, 2024 Reviewers agreed at journal 28 Aug, 2024 Reviewers agreed at journal 25 Aug, 2024 Reviewers invited by journal 05 Aug, 2024 Editor assigned by journal 31 Jul, 2024 Editor invited by journal 28 Jul, 2024 Submission checks completed at journal 24 Jul, 2024 First submitted to journal 24 Jul, 2024 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-4792541","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":342513818,"identity":"83b92d73-89a5-4085-8447-109799317a3a","order_by":0,"name":"Ah Yoon Kim","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ah","middleName":"Yoon","lastName":"Kim","suffix":""},{"id":342513819,"identity":"b2d9ff59-7a19-470d-8a1b-ed0fcb3aa92d","order_by":1,"name":"Sae Byul Lee","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Sae","middleName":"Byul","lastName":"Lee","suffix":""},{"id":342513820,"identity":"fcffc8bc-8c11-4d32-9117-c7dfae0b1a6a","order_by":2,"name":"Tae Kyung Yoo","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Tae","middleName":"Kyung","lastName":"Yoo","suffix":""},{"id":342513821,"identity":"06769103-60ab-409d-b1e2-7bd4ef6993d3","order_by":3,"name":"Ji Sun Kim","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ji","middleName":"Sun","lastName":"Kim","suffix":""},{"id":342513822,"identity":"4cab4696-660b-444e-b3cf-89d30a4b8c2b","order_by":4,"name":"Il Yong Chung","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Il","middleName":"Yong","lastName":"Chung","suffix":""},{"id":342513823,"identity":"baaa671c-3801-497d-bab9-a963026ead70","order_by":5,"name":"Hee Joung Kim","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Hee","middleName":"Joung","lastName":"Kim","suffix":""},{"id":342513824,"identity":"b897e6ef-a685-4439-ba07-6227ef50e5fa","order_by":6,"name":"Jong Won Lee","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Jong","middleName":"Won","lastName":"Lee","suffix":""},{"id":342513825,"identity":"e37c9203-3245-4218-b32f-d9ae6d24ad79","order_by":7,"name":"Byung Ho Son","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Byung","middleName":"Ho","lastName":"Son","suffix":""},{"id":342513826,"identity":"4706e106-d141-414b-9e77-91678f2051c6","order_by":8,"name":"Jae Ho Jeong","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Jae","middleName":"Ho","lastName":"Jeong","suffix":""},{"id":342513827,"identity":"9748bb75-8d10-4141-8975-b68857e2dbd1","order_by":9,"name":"Hee Jin Lee","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Hee","middleName":"Jin","lastName":"Lee","suffix":""},{"id":342513828,"identity":"2022e431-0456-445c-9567-58347f37c6c5","order_by":10,"name":"Nam kug Kim","email":"","orcid":"","institution":"Asan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Nam","middleName":"kug","lastName":"Kim","suffix":""},{"id":342513831,"identity":"95044060-6d93-4a67-906d-77e036fe13e1","order_by":11,"name":"BeomSeok Ko","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYHACAzApwcB8AETJEKklAaSFLQGkhYcULTxg6whrkZ/dvPHBzx82+ZLtPZ9f3aix4GFgP3x0A14r7hwrNuxJSLOczXN2m3XOMaDDeNLSbuDVIpFjJs2QcNhATiJ3m3EOG1CLBI8ZXi3yM+Bacp4Z5/wjQgvDDagWaYkc5se5bURogfglLc1AsueYGXNunwQPGyG/gEPsh42NgcTx5sefc77VyfGzHz6G32ESCCYbmM2GVzmaFuYPBFWPglEwCkbBiAQAguNClQhVC7QAAAAASUVORK5CYII=","orcid":"","institution":"Asan Medical Center","correspondingAuthor":true,"prefix":"","firstName":"BeomSeok","middleName":"","lastName":"Ko","suffix":""}],"badges":[],"createdAt":"2024-07-24 05:33:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4792541/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4792541/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-82968-6","type":"published","date":"2025-01-02T15:56:52+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":63313094,"identity":"cb56c330-3484-4e79-9746-55b7663921a5","added_by":"auto","created_at":"2024-08-26 20:49:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":852468,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA. Prone MRI (Pre)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTumor segmentation in prone MRI before NACT\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB. Supine CT (Pre)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTumor segmentation in supine CT before NACT\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eC. Supine MRI (Post)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSegmentation of tumors shrunk by NACT on MRI\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eD. 3DP-BSG modeling\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e3DP-BSG modeling to target tumors shrunk with NACT\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4792541/v1/01bcdc604a125994ceafca75.png"},{"id":63313091,"identity":"a5574955-19eb-4418-ab3a-a8b48790192d","added_by":"auto","created_at":"2024-08-26 20:49:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":556443,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePositioning of 3DP-BSG\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePosition the 3DP-BSG by placing the ipsilateral nipple in its hole and aligning it using two guide lines: one pointing towards the suprasternal notch and another towards the contralateral nipple.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4792541/v1/dc604bdbf1dcd6084282e342.png"},{"id":73093105,"identity":"4a5d29a4-dd17-4fdd-8e31-75172faa2e65","added_by":"auto","created_at":"2025-01-06 16:03:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1891433,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4792541/v1/bb74b661-2704-4c2c-bf61-2d48b4fbced4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognosis of patients with breast cancer who underwent breast-conserving surgery using a 3D-printed surgical guide after neoadjuvant chemotherapy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast-conserving surgery (BCS), also known as lumpectomy, aims to remove the tumor while preserving as much healthy breast tissue as possible. Neoadjuvant chemotherapy (NACT) can significantly decrease tumor size, allowing BCS to be a viable option for larger tumors that might otherwise have necessitated mastectomy.\u003csup\u003e1,2\u003c/sup\u003e Magnetic resonance imaging (MRI) is often used to assess tumor size and location after NACT, but its accuracy can be compromised due to the reduced contrast of the tumor caused by diminished angiogenesis, posing a challenge to surgeons during BCS.\u003csup\u003e3,4\u003c/sup\u003e Achieving clear resection margins\u0026mdash;removing the tumor with a tumor-free zone around the excised tissue\u0026mdash;is a critical goal during BCS. Positive resection margins are associated with higher rates of local recurrence.\u003csup\u003e5\u003c/sup\u003e Preoperative imaging modalities such as mammography, ultrasound, and MRI can assist in tumor localization, with MRI in particular recognized for its accuracy in predicting tumor extent.\u003csup\u003e6\u003c/sup\u003e Despite the advantages of MRI, it faces limitations, particularly in marking the extent of the tumor on breast imaging, especially when NACT is performed when treatment can alter the appearance of the tumor.\u003csup\u003e7\u0026ndash;9\u003c/sup\u003e Efforts such as projection and 3D scanning have been made to map MRI areas directly onto the breast, but these techniques have seen limited adoption owing to various constraints.\u003csup\u003e10,11\u003c/sup\u003e The development of 3D-printed breast surgical guides (3DP-BSG) aims to overcome the limitations associated with MRI.\u003csup\u003e12\u003c/sup\u003e This study analyzes the surgical results and prognosis of patients who underwent BCS using 3DP-BSG after NACT.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePatients\u003c/p\u003e \u003cp\u003eAn overview of the patient characteristics can be seen in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. From November 2015 to October 2021, 203 patients with invasive cancer were enrolled in the study. After excluding patients with Stage IV cancer or those who had undergone NASSM, the study focused on 197 patients. The median follow-up period was 35.3 months (range 2.2\u0026ndash;96.8 months).The median age of the patients was 49.6 years (range 26\u0026ndash;76 years), with 103 patients (52.3%) aged over 50 years. The average BMI of the patients was 25.1; 79 (40.1%) patients were classified as normal weight, 99 (50.3%) as overweight, and 19 (9.6%) as mildly obese. All patients underwent axillary surgery, with sentinel lymph node biopsy performed in 194 patients (97%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u0026ndash;76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103 (52.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94 (47.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI (kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erange\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.8\u0026ndash;36.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObese (\u0026gt;\u0026thinsp;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (9.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverweight (24\u0026ndash;29.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99 (50.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal (\u0026lt;\u0026thinsp;24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79 (40.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAxillary surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSNB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115 (58.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSNB\u0026thinsp;+\u0026thinsp;ALND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78 (39.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e** SNB : sentinel lymph node biopsy, ALND : axillary lymph node dissection\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePATHOLOGY\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the pathology results of the patients. In 194 cases (98.5%), pathology revealed invasive ductal carcinoma (IDC), while the remaining 3 cases were diagnosed with invasive lobular carcinoma (ILC). Most histologic grades were (95.5%) 2 or higher. In terms of clinical stage, 1 patient was classified as Stage I (0.5%), 152 as Stage II (77.2%), and 44 as Stage III (22.3%). For the pathologic stage, 67 patients (34.0%) were classified as Stage 0, 63 as Stage I (31.5%), 51 as Stage II (25.9%), and 16 as Stage III (8.0%). Complete remission was confirmed in 67 patients (34.0%) based on the permanent pathology results. Pathologic complete remission refers to no residual invasive cancer in the tissue after surgery. The four molecular subtypes were evenly distributed, with a similar pattern observed in the Ki-67 index.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePathological results\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIDC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e194 (98.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eILC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (1.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistologic grade\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (46.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104 (52.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical stage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e152 (77.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (22.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathologic stage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (34.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63 (31.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (25.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (8.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSubtype\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR\u0026thinsp;+\u0026thinsp;Her2+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (16.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR\u0026thinsp;+\u0026thinsp;Her2-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (31.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR- Her2+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (22.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR- Her2-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (30.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKi-67 index\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;19%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95 (48.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u0026ndash;49%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (21.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (30.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRecurrence\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (5.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (8.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e** IDC : invasive ductal carcinoma, ILC : invasive lobular carcinoma, HR : hormone receptor\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e*** Stratified according to the American Joint Committee in Cancer(AJCC) 8th stage\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe average specimen weight was 31.5g (range: 2.5\u0026ndash;215g). Three patients (1.5%) were found to have positive resection margins, and re-excision was performed in these cases. During the follow-up period, 17 patients experienced recurrence, including one case of local recurrence. Regional recurrence occurred in 5 patients in the ipsilateral axillary lymph node. The most common site of recurrence was lung metastasis, followed by liver metastasis.\u003c/p\u003e \u003cp\u003eThe use of 3D-printed surgical guides enhanced the precision of BCS, resulting in favorable outcomes.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eNeoadjuvant therapy in patients with breast cancer offers several advantages, including the early initiation of systemic treatment, the ability to assess treatment response, and the potential shift from mastectomy to BCS by reducing the size of the tumor.\u003csup\u003e1\u003c/sup\u003e In some cases, NACT renders previously inoperable tumors operable or shrinks tumors sufficiently to increase breast preservation rates from 7\u0026ndash;12%.\u003csup\u003e1\u003c/sup\u003e A meta-analysis of 10 randomized trials found that the BCS rate in patients who received NACT was 65% compared with 49% in the adjuvant chemotherapy group.\u003csup\u003e2\u003c/sup\u003e Achieving optimal cosmetic results during BCS requires preserving as much normal tissue as possible while ensuring complete tumor resection. Positive margin status is associated with higher local recurrence rates, distant metastasis, and lower overall survival.\u003csup\u003e5\u003c/sup\u003e Accurately predicting tumor extent before surgery is crucial for achieving clear margins in BCS. Imaging modalities such as MMG, USG, and MRI are commonly used for this purpose, with MRI known for its high accuracy.\u003csup\u003e6\u003c/sup\u003e However, MRI has limitations, including difficulties in marking the tumor area on the breast due to differences in the traditional prone position of MRI scans and the supine position during surgery. \u003csup\u003e8,9\u003c/sup\u003e Several attempts have been made to map MRI regions onto the breast. For instance, using projection and reproduction techniques in surgical-position breast MRI in 24 patients with DCIS resulted in smaller pathologic specimen volumes and a lower positive margin rate compared with conventional BCS.\u003csup\u003e10\u003c/sup\u003e Kutomi et al. conducted a study analyzing the surgical results of 1,150 patients who underwent supine MRI before BCS. They concluded that supine MRI is an effective method for determining the extent of resection, with a positive margin rate of 18.8%.\u003csup\u003e8\u003c/sup\u003e However, after NACT, tumor shrinkage and decreased contrast intensity can obscure the area of the remaining cancer. Additionally, because MRI cannot confirm tumor cell level, it may be challenging to determine the original tumor area before treatment.\u003csup\u003e3,4\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eA meta-analysis of 10 randomized trials tracking the prognosis of 4,756 patients with breast reported a 15-year local recurrence rate of 21.4% in the NACT group, higher than 15.9% in the adjuvant group. The authors concluded that NACT should prioritize careful tumor localization, through detailed pathological assessment, and appropriate radiotherapy.\u003csup\u003e2\u003c/sup\u003e Before NACT, various methods were explored for marking tumors, including the use of metallic markers or 125I-radioactive seeds (RSL) around the tumor, as well as the classic method of tattooing the skin. A review of 15 studies examining tumor marking before NACT reported a 13.9% negative margin in surgical outcomes, including complete pathological response, leading to improvements in margins and survival outcomes.\u003csup\u003e13\u003c/sup\u003e The use of multiple markers to obtain more detailed information about the tumor area was also considered. Comparing resection margins in BCS using single or double radiopaque markers revealed no difference in additional resection rate after frozen biopsy or re-excision rate, and no difference in local recurrence-free survival.\u003csup\u003e14\u003c/sup\u003e 3DP-BSG was developed and clinically used to quantitatively mark the tumor area on the breast based on MRI and track tumor changes after NACT.\u003csup\u003e12,15,16\u003c/sup\u003e A study analyzing 39 patients who underwent BCS using 3DP-BSG after NACT found that frozen sections showed positive margins of 10.3%, indicating a high clear margin rate. Additionally, it was reported that 3DP-BSG targeting was painless for patients, did not involve radiation, and did not increase the procedure time. \u003csup\u003e16\u003c/sup\u003e While the use of markers in BCS is expected to improve the local recurrence rate, reports on prognosis remain limited. A study involving 373 patients reported that the 5-year rate of local control was 98.6% in patients with radiopaque clips, compared with 91.7% in patients without tumor marker clips. The insertion of clips was beneficial for local control.\u003csup\u003e17\u003c/sup\u003e In this study, the median follow-up period was 38.5 months, which is relatively short, yet demonstrated a low local recurrence rate of 1.0%. Previous reports showed local recurrence rates in patients who underwent NACT and BCS ranging from 9.2 to 21.4%.\u003csup\u003e2,18\u003c/sup\u003e The use of 3DP-BSG during BCS in this study may have contributed to the lower local recurrence rate compared with previous studies, but there are limitations. This study was a retrospective analysis of surgeries performed at a single institution, which could limit the evaluation of recurrence rates. Although the follow-up period is relatively short, it remains meaningful as recurrence rates often peak 2\u0026ndash;3 years after surgery. Additionally, the absence of a control group in this single-group study using 3DP-BSG is a limitation, and a multicenter prospective randomized study is needed for further evaluation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePATIENTS\u003c/h2\u003e \u003cp\u003eThis retrospective single-center cohort study analyzed patients diagnosed with invasive breast cancer who underwent BCS using 3DP-BSG after NACT between November 2015 and October 2021. Patients with Stage IV or those who received NASSM (nipple areolar complex skin sparing mastectomy) were excluded from the analysis. Patient outcomes after surgery were assessed through the review of medical records. Cases involving other cancers before the occurrence of local recurrence were also excluded. This study was approved by the Institutional Review Board of Asan Medical Center (2021\u0026thinsp;\u0026minus;\u0026thinsp;1198). Research had been performed in accordance with the Declaration of Helsinki. Patients provided informed consent and agreed to the inclusion of a supine series in the standard baseline MRI protocol.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3DP-BSG DESIGN\u003c/h2\u003e \u003cp\u003eBreast imaging was performed using a 3.0T MRI system with a breast coil. Additional images were obtained in the same supine position as the surgical position. Breast tissue and tumors were segmented and 3D-modeled in prone/supine MRI/CT scans using Mimics Medical v17 (Materialise Inc., Belgium) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e1\u003c/span\u003eA, B). The changed tumor area was tracked and segmented based on the enhanced tumor visible in the post-NACT MRI and the tumor/surrounding tissue pattern observed in the pre-operation MRI (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). In accordance with the final 3D modeled breast and tumor, a hybrid 3DP-BSG was designed and printed, which had a groove for marking the breast skin and a pillar for dye injection, targeting the tumor inside the breast (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e1\u003c/span\u003eD).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSURGERY AND MARGIN EVALUATION\u003c/h2\u003e \u003cp\u003eThe surgical position was performed with the patient in the supine position with the affected arm spread at a 90-degree angle. The 3DP-BSG was applied after general anesthesia. Designed to fit the shape of the breast, the guide was positioned precisely by aligning it with the nipple on the affected side, the suprasternal notch, and a guideline extending toward the opposite nipple (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The tumor area was marked on the skin along the groove of the 3DP-BSG, and a dye was injected around the tumor inside the breast using a syringe along the column. The tumor was excised based on these markings, and the surrounding margins were assessed for the presence of tumors using frozen sections. If a tumor was observed at the margin, additional resection was performed. Margins that could not be confirmed using frozen sections were evaluated using permanent pathology results to determine whether reoperation was necessary. Sentinel lymph node biopsy (SLNB) was performed, and the decision to proceed with axillary lymph node dissection (ALND) was made based on the results.\u003c/p\u003e \u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe use of MRI-based 3D-BSG during BCS following NACT enables precise targeting of the original tumor area. This innovative approach holds promise as a next-generation breast targeting method, providing significant benefits to both patients and surgeons through low rates of positive margins and local recurrence.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eBeomSeok Ko and Namkug Kim have a patent on the 3DP BSG and are the founding members of the Anymedi company, Byung Ho Son has a patent on the 3DP BSG.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research was supported by the Asan Medical Center, funded by the Asan Foundation (Grant number: 2021IF0020). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eBSK and NKK planned overall research.SBL, TKY, JSK, IYC, HJK, JWL, BHS, JHJ and HJL collected the data.AYK and BSK analyed the data.AYK and BSK wrote the main manuscript text, figure and table. All authors reviewed the manuscrip.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003e3DP BSG was produced and applied to patients with the help of Sangwook Lee, Joo Yun Won and Guk Bae Kim of Anymedi Inc.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWang H, Mao X. Evaluation of the efficacy of neoadjuvant chemotherapy for breast cancer. \u003cem\u003eDrug design, development and therapy\u003c/em\u003e. 2020:2423-2433. \u003c/li\u003e\n\u003cli\u003eAsselain B, Barlow W, Bartlett J, et al. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. \u003cem\u003eThe Lancet Oncology\u003c/em\u003e. 2018;19(1):27-39. \u003c/li\u003e\n\u003cli\u003eXiao J, Rahbar H, Hippe DS, et al. Dynamic contrast-enhanced breast MRI features correlate with invasive breast cancer angiogenesis. \u003cem\u003eNPJ breast cancer\u003c/em\u003e. 2021;7(1):42. \u003c/li\u003e\n\u003cli\u003eGezer NS, Orbay \u0026Ouml;, Balcı P, Durak MG, Demirkan B, Saydam S. Evaluation of neoadjuvant chemotherapy response with dynamic contrast enhanced breast magnetic resonance imaging in locally advanced invasive breast cancer. \u003cem\u003eThe journal of breast health\u003c/em\u003e. 2014;10(2):111. \u003c/li\u003e\n\u003cli\u003eBundred JR, Michael S, Stuart B, et al. Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis. \u003cem\u003ebmj\u003c/em\u003e. 2022;378\u003c/li\u003e\n\u003cli\u003eAzhdeh S, Kaviani A, Sadighi N, Rahmani M. Accurate estimation of breast tumor size: a comparison between ultrasonography, mammography, magnetic resonance imaging, and associated contributing factors. \u003cem\u003eEuropean Journal of Breast Health\u003c/em\u003e. 2021;17(1):53. \u003c/li\u003e\n\u003cli\u003eKwon M-r, Chu J, Kook SH, Kim EY. Factors associated with radiologic-pathologic discordance in magnetic resonance imaging after neoadjuvant chemotherapy for breast cancer. \u003cem\u003eClinical Imaging\u003c/em\u003e. 2022;89:1-9. \u003c/li\u003e\n\u003cli\u003eKutomi G, Shima H, Kyuno D, et al. Positional advantages of supine MRI for diagnosis prior to breast‑conserving surgery. \u003cem\u003eMolecular and Clinical Oncology\u003c/em\u003e. 2023;18(5):1-4. \u003c/li\u003e\n\u003cli\u003eWang C-B, Lee S, Kim T, et al. Breast tumor movements analysis using MRI scans in prone and supine positions. \u003cem\u003eScientific Reports\u003c/em\u003e. 2020;10(1):4858. \u003c/li\u003e\n\u003cli\u003eSakakibara M, Nagashima T, Sangai T, et al. Breast-conserving surgery using projection and reproduction techniques of surgical-position breast MRI in patients with ductal carcinoma in situ of the breast. \u003cem\u003eJournal of the American College of Surgeons\u003c/em\u003e. 2008;207(1):62-68. \u003c/li\u003e\n\u003cli\u003ePallone MJ, Poplack SP, Avutu HBR, Paulsen KD, Barth RJ. Supine breast MRI and 3D optical scanning: a novel approach to improve tumor localization for breast conserving surgery. \u003cem\u003eAnnals of surgical oncology\u003c/em\u003e. 2014;21:2203-2208. \u003c/li\u003e\n\u003cli\u003eKo BS, Kim N, Lee JW, et al. MRI-based 3D-printed surgical guides for breast cancer patients who received neoadjuvant chemotherapy. \u003cem\u003eScientific reports\u003c/em\u003e. 2019;9(1):11991. \u003c/li\u003e\n\u003cli\u003eJha CK, Johri G, Singh PK, Yadav SK, Sinha U. Does Tumor Marking Before Neoadjuvant Chemotherapy Helps Achieve Better Outcomes in Patients Undergoing Breast Conservative Surgery? A Systematic Review. \u003cem\u003eIndian Journal of Surgical Oncology\u003c/em\u003e. 2021;12(3):624-631. \u003c/li\u003e\n\u003cli\u003eCha C, Lee J, Kim D, et al. Comparison of resection margin status after single or double radiopaque marker insertion for tumor localization in breast cancer patients receiving neoadjuvant chemotherapy. \u003cem\u003eBreast Cancer Research and Treatment\u003c/em\u003e. 2020;184:797-803. \u003c/li\u003e\n\u003cli\u003eOck J, Lee S, Kim T, et al. Accuracy evaluation of a 3D printing surgical guide for breast-conserving surgery using a realistic breast phantom. \u003cem\u003eComputers in Biology and Medicine\u003c/em\u003e. 2021;137:104784. \u003c/li\u003e\n\u003cli\u003eLee HS, Kim HJ, Chung IY, et al. Usefulness of 3D-surgical guides in breast conserving surgery after neoadjuvant treatment. \u003cem\u003eScientific Reports\u003c/em\u003e. 2021;11(1):3376. \u003c/li\u003e\n\u003cli\u003eOh JL, Nguyen G, Whitman GJ, et al. Placement of radiopaque clips for tumor localization in patients undergoing neoadjuvant chemotherapy and breast conservation therapy. \u003cem\u003eCancer: Interdisciplinary International Journal of the American Cancer Society\u003c/em\u003e. 2007;110(11):2420-2427. \u003c/li\u003e\n\u003cli\u003eZhou X, Li Y. Local recurrence after breast-conserving surgery and mastectomy following neoadjuvant chemotherapy for locally advanced breast cancer-a meta-analysis. \u003cem\u003eBreast care\u003c/em\u003e. 2016;11(5):345-351. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Breast cancer, 3D-Printed Breast Surgical Guide, 3DP-BSG, breast-conserving surgery, neoadjuvant chemotherapy, MRI","lastPublishedDoi":"10.21203/rs.3.rs-4792541/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4792541/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn breast-conserving surgery (BCS), clear resection margins are crucial to prevent recurrence. Accurate imaging is vital for precise BCS, with MRI being the most accurate. However, MRI has limitations in identifying the exact extent of breast cancer in patients who have undergone neoadjuvant chemotherapy (NACT). A 3D-Printed Breast Surgical Guide (3DP-BSG) can address this issue by effectively pinpointing cancer extent in NACT patients, thus enhancing surgical accuracy.\u003c/p\u003e \u003cp\u003eThis retrospective single-institution cohort study focused on female patients diagnosed with invasive breast cancer who underwent NACT. Between November 2015 and October 2021, patients received BCS with the aid of a 3DP-BSG. Personalized 3DP-BSG targeted tumors by tracking changes in breast and tumor anatomy on MRI before and after NACT.\u003c/p\u003e \u003cp\u003e203 patients with invasive breast cancer were enrolled in the study. According to exclusion criteria, 197 patients were analyzed. The median follow-up period was 35.3 months (range: 2.2\u0026ndash;96.8 months). 3 patients (1.5%) had positive resection margins. During the follow-up period, 17 patients (8.6%) experienced recurrence, with one patient (0.5%) confirmed local recurrences.\u003c/p\u003e \u003cp\u003eThe application of MRI-based 3DP-BSG is effective in achieving low positive margins and local recurrence in patients undergoing BCS after NACT, offering a promising approach for improving surgical outcomes.\u003c/p\u003e","manuscriptTitle":"Prognosis of patients with breast cancer who underwent breast-conserving surgery using a 3D-printed surgical guide after neoadjuvant chemotherapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-26 20:48:56","doi":"10.21203/rs.3.rs-4792541/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-07T06:54:54+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-04T11:39:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-31T06:08:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"2670508728598194525999733950841973128","date":"2024-10-22T21:01:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"21555089427936691780545438461148096387","date":"2024-10-20T22:04:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"31829417398832762874162624646006794370","date":"2024-08-28T19:07:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"285334569592081416408372959747327664811","date":"2024-08-25T15:17:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-05T06:16:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-31T20:03:25+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-28T16:49:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-25T03:12:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-07-24T05:30:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c280ed25-93e6-4399-a8e1-e0cace98128e","owner":[],"postedDate":"August 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":36284693,"name":"Health sciences/Medical research"},{"id":36284694,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2025-01-06T15:58:09+00:00","versionOfRecord":{"articleIdentity":"rs-4792541","link":"https://doi.org/10.1038/s41598-024-82968-6","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-01-02 15:56:52","publishedOnDateReadable":"January 2nd, 2025"},"versionCreatedAt":"2024-08-26 20:48:56","video":"","vorDoi":"10.1038/s41598-024-82968-6","vorDoiUrl":"https://doi.org/10.1038/s41598-024-82968-6","workflowStages":[]},"version":"v1","identity":"rs-4792541","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4792541","identity":"rs-4792541","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}