Reevaluating Intensive Treatment Strategies for Breast Cancer-Related Lymphedema Following Aggressive Therapy: A Retrospective Study

Reevaluating Intensive Treatment Strategies for Breast Cancer-Related Lymphedema Following Aggressive Therapy: A Retrospective Study | 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 Reevaluating Intensive Treatment Strategies for Breast Cancer-Related Lymphedema Following Aggressive Therapy: A Retrospective Study Inah Kim, Joon Young Choi, Ji Young Lim, Gyoung Ho Nam, Ji Hye Hwang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8232253/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 Aggressive breast cancer treatment increases the risk of breast cancer-related lymphedema(BCRL). However, whether all high-risk patients require equally intensive long-term management remains unclear. This study aimed to characterize the long-term manifestations of the BCRL pattern in patients who received aggressive cancer therapies yet showed favorable lymphoscintigraphy findings. Methods This retrospective study included 104 patients with BCRL with a history of mastectomy with axillary lymph node dissection and locoregional radiation therapy between 2008 and 2022, all of whom showed favorable lymphoscintigraphy findings. The patients were stratified into four groups based on their initial percentage of excessive volume(PEV). Volume changes and individualized lymphedema treatment during the first 12 months were analyzed. From months 12 to 24, the treatment intensity, including the frequency of medical compression therapy, was adjusted based on expert assessment. Results Despite similar treatment histories and lymphoscintigraphy findings, the patients showed different volume change patterns based on the initial PEV, although the overall outcomes were favorable over two years in all groups. Patients with BCRL and a low initial PEV maintained stable reduced volumes after 6 months of minimal or no compression therapy. However, the high-initial PEV group required active surveillance and long-term management despite favorable lymphoscintigraphy results. Conclusion Initial PEV effectively predicted long-term outcomes and treatment needs in patients with BCRL with an aggressive cancer treatment history and favorable lymphoscintigraphy findings. Personalized treatment planning using initial PEV and lymphoscintigraphy may provide the appropriate intensity of therapy to patients for an optimal duration to reduce time and financial burdens. Lymphedema Breast neoplasms Lymphoscintigraphy Complex decongestive therapy Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Breast cancer-related lymphedema (BCRL) affects approximately 8.4%–21.4% of patients treated for breast cancer, significantly impairing their quality of life. 1 – 4 It typically arises from lymphatic disruption caused by surgery, radiation, or a combination of both. 5 Key risk factors for developing BCRL include axillary lymph node dissection (ALND), radiation to the regional lymph nodes, and cellulitis. 2 , 6 , 7 Nonetheless, not all patients receiving rigorous cancer treatment develop severe lymphedema (LE). Szuba et al. suggested that collateral circulation or lymphovenous compensation may preserve the drainage function, thereby potentially preventing severe LE. 8 Lymphoscintigraphy plays a crucial role in the diagnosis and prediction of BCRL prognosis. 9 – 11 This procedure helps identify lymphatic flow, location, and the number of lymph nodes, thereby providing reliable information for LE assessment. 12 A study by Kim et al. found that early lymphoscintigraphy following breast cancer surgery is useful in predicting the likelihood of LE. 13 Moreover, lymphoscintigraphy has been acknowledged for its utility in assessing and predicting treatment responses. Quantitative lymphoscintigraphy findings correlate with the response to LE therapy in patients with BCRL. 14 , 15 According to Hwang et al., although patient responses to complex physical therapy showed no significant differences in clinical variables, significant differences were observed in lymphoscintigraphic findings. 16 Specifically, the presence of main lymphatic vessels without collateral lymphatic vessels emerged as the strongest predictor of a positive therapeutic response, demonstrating a sensitivity of 91%, specificity of 100%, and accuracy of 95%. 16 Collectively, baseline lymphoscintigraphy is likely to be useful in predicting long-term responses to BCRL treatment. 14 – 16 To the best of our knowledge, no previous study has tracked the long-term manifestations of BCRL in patients with a history of aggressive cancer therapy in relation to the lymphoscintigraphic findings. Therefore, this study aimed to evaluate whether patients with favorable lymphoscintigraphy findings require long-term intensive LE treatment, despite a history of aggressive cancer therapy. Additionally, this study aimed to determine whether the initial percentage of excessive volume (PEV) can guide personalized treatment decisions, potentially sparing patients from unnecessary treatment burden through clinical prediction. Methods Study design and participants This retrospective study recruited 280 patients with unilateral BCRL who visited the Department of Rehabilitation Medicine at a tertiary hospital between January 2008 and December 2022 and met the eligibility criteria. The criteria included a history of mastectomy with ALND, locoregional radiation therapy, and favorable lymphoscintigraphy findings. The diagnosis of LE was based on the PEV and clinical assessment by a clinician 11 , 17 . Favorable lymphoscintigraphy findings were defined as uptake in the axillary lymph nodes or minimally visible main lymphatic vessels with collateral lymph node uptake (via the deltopectoral, supraclavicular, or forearm), with or without regional dermal backflows, while explicitly excluding cases with only dermal backflow and no nodal visualization. All patients were of Korean ethnicity. The exclusion criteria included comorbidities, such as current metastasis or recurrent cancer, vascular disease, cellulitis, history of trauma or surgery in the affected upper extremity, and insufficient medical records. Finally, 104 patients were included in the study ( Fig. 1 ). Procedure LE was clinically diagnosed by physical examination and optoelectronic volume analysis (Perometer, Pero-System, Wuppertal, Germany). The diagnosis was confirmed by a physiatrist specializing in cancer rehabilitation, who excluded generalized edema after chemotherapy and venous congestion. PEV was calculated using the flowing formula: % excess volume (mL) = [(Va – Vu)/Vu] x 100. Va, affected arm volume; Vu, unaffected arm volume; LE, PEV > 5%. The patients were divided into four groups according to their initial PEV: Group 1 (PEV < 5%, n = 19), Group 2 (5%≤PEV < 10%, n = 33), Group 3 (10%≤PEV < 20%, n = 33), and Group 4 (PEV ≥ 20%, n = 19). All groups received self-management education and compression garments and/or intensive LE treatment (e.g., complex decongestive therapy with elastic bandages), if necessary, during the first 12 months. From 12 to 24 months, stocking use was reduced based on expert judgment and PEV. The PEV was measured at the first visit and after 3, 6, 12, 18, and 24 months. Lymphoscintigraphy was performed using a dual-headed gamma camera (Bio-Rad; Trionix Research Laboratory, Hercules, CA, USA). The patients were placed in the supine position, and 0.2 mL of 99m Tc-phytate (100 nm filtered at 37 MBq) was injected subcutaneously into the second interdigital space of both hands. The patients were asked to grip and release their hands repeatedly to improve radiopharmaceutical transport. Anterior, posterior, and spot images of both upper extremities were captured 1 and 2 h after the injection. Patients with minimal LE (< 20% volume increase) were managed with patient education, commercially available compressive stockings, and/or self-bandaging. Complex decongestive therapy (CDT) was considered a treatment option for patients with a marked volume increase (≥ 20% volume increase). CDT was administered in two phases: decongestive and maintenance. CDT comprises manual lymphatic drainage, compression of the affected upper extremity with a low-stretch bandage, specific remedial exercises to enhance lymphatic drainage, skin care, and patient education. The patients underwent 30 min of CDT on five consecutive days per week for 2 weeks. The bandages were applied after manual lymphatic drainage and were left in place between successive daily treatments. The decongestive phase of CDT aims to achieve a substantial reduction in LE volume. During the maintenance phase, patients were educated to perform self-management, including daytime compression stockings, self-bandaging, self-massage, and self-skincare. Statistical analysis Distributions were evaluated using the Kolmogorov–Smirnov test. Pearson’s chi-square test, Fisher’s exact test, and the Kruskal–Wallis test were used to compare the clinical parameters and characteristics according to the initial PEV (four groups). Generalized estimating equation analysis was used to evaluate temporal changes in PEV over the follow-up period within each group. To compare the time interval from axillary surgery to the presentation of LE across groups, the Kruskal–Wallis test was employed because of the non-normal distribution of the data. Upon identifying a significant overall difference, post-hoc pairwise comparisons were conducted using Dunn’s test with Bonferroni correction to control for multiple comparisons. To compare the body mass index (BMI) among the groups, Welch’s ANOVA was applied, given the presence of unequal variance. All statistical analyses were performed using SPSS (version 20.0; IBM, Armonk, NY, USA) and R software version 4.3.0 (R Foundation for Statistical Computing, Vienna, Austria). Statistical significance was set at 5% (two-sided). Results A total of 104 patients were included in the study. The clinical characteristics of the patients are summarized in Table 1 . There were no significant differences in age, BMI, laterality, number of node dissections, chemotherapy, radiation therapy, or hormonal therapy among the four groups (Table 1 ). Table 1 General characteristics and cancer treatment history of each group of patients (n = 104). Variables Group 1 Group 2 Group 3 Group 4 P-value (n = 19) (n = 33) (n = 33) (n = 19) Age (years) 52 (45–67) 51 (40–73) 54 (42–75) 51 (33–71) 0.219 Body mass index (kg/m²) 22.06 ± 3.04 23.46 ± 4.54 24.35 ± 3.84 22.60 ± 3.11 0.0116 Laterality Right 6 (31.6) 14 (42.4) 20 (60.6) 9 (47.4) 0.208 Left 13 (68.4) 19 (57.6) 13 (39.4) 10 (52.6) Node dissection Number of dissected nodes 17.0 (11–29) 18 (9–37) 21 (8–30) 18 (12–51) 0.809 Number of positive nodes 3.0 (0–8) 3.0 (0–11) 3.0 (0–20) 4.0 (0–26) 0.429 Breast reconstruction surgery 3 (15.8) 5 (15.2) 2 (6.1) 2 (10.5) 0.662 Chemotherapy None 1 (5.3) 0 (0.0) 1 (3.0) 1 (5.3) 0.418 Neoadjuvant 7 (36.8) 9 (27.3) 4 (12.1) 5 (26.3) Adjuvant 11 (57.9) 23 (69.7) 26 (78.8) 12 (63.2) Neoadjuvant & Adjuvant 0 (0.0) 1 (3.0) 2 (6.1) 1 (5.3) Locoregional radiation therapy Fraction 25 (17–28) 25 (16–31) 25 (16–33) 25 (16–33) 0.663 Dose 5000 (4590–6050) 5000 (4200–6050) 5000 (4240–6050) 5040 (4240–6050) 0.219 Hormonal therapy 11 (57.9) 25 (75.8) 26 (78.8) 16 (84.2) 0.270 Values are presented as the number of patients (%) and median [IQR].Group 1 (Initial PEV < 5%, n = 19); Group 2 (5%≤Initial PEV < 10%, n = 33); Group 3 (10%≤Initial PEV < 20%, n = 33); Group 4 (Initial PEV ≥ 20%, n = 19) Favorable lymphoscintigraphy findings All participants showed favorable lymphoscintigraphy findings (Fig. 2 ). As shown in Fig. 2 a, one patient underwent ALND, with 17 lymph nodes removed, followed by adjuvant radiotherapy to the chest wall and supraclavicular lymph node area, receiving a total dose of 5000 cGy. Lymphoscintigraphy was performed approximately two years after the completion of radiotherapy (Fig. 2 a). As shown in Fig. 2 b, another patient underwent ALND involving 17 lymph nodes and received adjuvant radiotherapy to the breast and supraclavicular fossa at a total dose of 6050 cGy. Lymphoscintigraphy was conducted approximately two years after radiotherapy (Fig. 2 b). Initial PEV and lymphedema management Upon completion of the 24-month follow-up period, the severity of the initial LE, as indicated by higher PEV values, was associated with a greater proportion of patients requiring CDT (P < 0.001; Table 2 ). Specifically, 15.8% of patients in Group 1 (Initial PEV < 5%, n = 19) required intensive CDT, compared to 39.4% in Group 2 (5%≤Initial PEV < 10%), 54.5% in Group 3 (10%≤Initial PEV < 20%), and 78.9% in Group 4 (PEV ≥ 20%). Moreover, the larger the initial LE volume, the more restrictions on sports activities and daily life were observed; however, the difference was not statistically significant (Table 2 ). Table 2 Lymphedema management and daily functionality of each group of patients (n = 104). Variables Group 1 Group 2 Group 3 Group 4 P-value (n = 19) (n = 33) (n = 33) (n = 19) Intensive CDT No 16 (84.2) 20 (60.6) 15 (45.5) 4 (21.1) < 0.001* Yes 3 (15.8) 13 (39.4) 18 (54.5) 15 (78.9) Frequency of applying garment in daily activity Not used 7 (36.8) 6 (18.2) 6 (18.2) 1 (5.3) 0.120 Using compressive stocking sometimes 12 (63.2) 16 (48.5) 16 (48.5) 10 (52.6) Using compressive stocking everyday 0 (0.0) 5 (15.2) 5 (15.2) 4 (21.1) Using compressive stocking and bandaging 0 (0.0) 6 (18.2) 6 (18.2) 4 (21.1) Daily activity level Limitation 0 (0.0) 1 (3.0) 4 (12.1) 4 (21.1) 0.158 No limitation 2 (10.5) 6 (18.2) 8 (24.2) 4 (21.1) Possible sports activity 17 (89.5) 26 (78.8) 21 (63.6) 11 (57.9) Time from axillary surgery to lymphedema onset Months 8.00 [6.00, 21.50] 14.00 [7.00, 22.00] 16.00 [8.00, 46.00] 30.00 [11.00, 60.50] 0.014* < 1 year 13 (68.4) 14 (42.4) 11 (33.3) 5 (26.3) 1–2 years 1 (5.3) 11 (33.3) 7 (21.2) 3 (15.8) 2–3 years 2 (10.5) 3 ( 9.1) 4 (12.1) 3 (15.8) ≥ 3 years 3 (15.8) 5 (15.2) 11 (33.3) 8 (42.1) Values are presented as the number of patients (%) and median [IQR]. Abbreviations: PEV, percentage of excessive volume; Group 1 (Initial PEV < 5%, n = 19); Group 2 (5%≤Initial PEV < 10%, n = 33); Group 3 (10%≤Initial PEV < 20%, n = 33); Group 4 (Initial PEV ≥ 20%, n = 19) In addition, groups stratified by initial PEV levels demonstrated that higher initial PEV levels were associated with the need for more intensive LE treatment (P < 0.001, Fig. 3 ). A statistically significant difference was observed across the four groups (P = 0.014), and post-hoc analysis revealed a significant difference between Groups 1 and 4 (P = 0.035) (Table 2 ). Temporal changes in the PEV after lymphedema diagnosis In the generalized estimating equation analysis, the PEV values of all groups exhibited significant time-dependent changes (P < 0.05, Fig. 4 ). All groups showed a tendency of decreased PEV until the first 12 months, which was then well-maintained for up to 24 months. In Groups 1 and 2, there were significant decreases at 3 and 6 months compared with baseline (i.e., at the diagnosis of LE), after which the PEV values were maintained. In Group 3, significant decreases were observed at 3, 6, and 12 months compared to baseline. Thereafter, the PEV values increased, although the changes were not significant. In Group 4, there were significant decreases at 3, 6, 12, and 18 months compared with the baseline, and the PEV value at 24 months showed an increase, although this change was not significant. After 12 months, the group with a low initial PEV maintained a low PEV, with or without minimal medical compression. However, groups with high-initial PEV showed a tendency toward an increase in volume, although this was less than that of the initial PEV. Patients with low initial PEV received less intensive LE treatment and showed well-maintained volumetry for 24 months (Fig. 4 ). Discussion To the best of our knowledge, this is the first study to investigate the long-term manifestations of the BCRL pattern in patients who received aggressive cancer therapy yet exhibited good lymphatic function on lymphoscintigraphy. Previous studies have provided fragmented information on the risk and prognostic factors for BCRL. 1 , 13 , 18 – 23 While it is well established that aggressive cancer treatment increases the risk of developing LE and that favorable lymphatic function on lymphoscintigraphy is associated with better outcomes, little is known about cases in which both conditions co-exist. In particular, long-term patterns of BCRL in such cases have not been thoroughly investigated. Consequently, patients with a history of intensive cancer treatment tend to have an increased risk of excessive LE and heightened anxiety. The treatment of LE poses significant time and financial burdens. 18 , 24 – 26 Therefore, it is crucial to target the appropriate population and determine the appropriate treatment duration for intensive LE. ALND and regional lymph node radiation are independent risk factors for aggressive cancer treatment, and their combination has a synergistic effect on LE development. 27 , 28 For each additional lymph node removed, the risk of LE development increased by 3%. 1,4,29 Additionally, regional lymph node radiation alone is known to increase the risk by 1.7 times. 1 , 29 . When radiation therapy was combined with lymph node dissection, the incidence of LE increased to 18.2%, the highest observed risk. In comparison, the risk of LE development is not only strongly associated with nodal destruction but also with a patient's capacity to regenerate alternative lymphatics. 21 , 30 Thus, lymphoscintigraphy is frequently used as an effective adjunctive tool. Qualitative lymphoscintigraphy of the upper extremities has been identified as a valuable tool for functional assessment, offering high sensitivity (70.6% to 92%) and specificity of nearly 100%. 9,12,31,32 In addition, Kim et al. reported that the quantitative asymmetry index on lymphoscintigraphy reflected LE severity. 14 However, the lack of analysis of the long-term features of BCRL poses limitations in providing comprehensive treatment. The results of this study showed that despite aggressive cancer treatment, approximately half of the patients achieved favorable outcomes during the 24-month follow-up period without intensive treatment or significant activity restrictions. With the support of expert opinion, the removal of minimal medical compression after 12 months could be considered for patients with BCRL and a low initial PEV. Nevertheless, for most patients with a high-initial PEV, accounting for approximately 18% of the total cohort, intensive CDT with long-term surveillance is warranted, irrespective of the favorable lymphoscintigraphic findings. Therefore, a skilled physician is required to determine the tailored treatment duration and intensity for different patient groups. This finding suggests that patients with BCRL, similar aggressive cancer treatment histories, and favorable lymphoscintigraphic findings can be stratified based on early PEV values for personalized treatments. Clinicians should avoid instilling excessive fear and anxiety in patients or forcing extensive LE therapy in unsuitable populations, particularly when patients present with minimal initial PEV and favorable lymphoscintigraphic findings. Moreover, significant enhancements in both physical and emotional well-being can be realized by addressing the psychosocial needs of patients with upper extremity LE, which can be achieved by regulating the appropriate duration of therapy. 33 Favorable lymphoscintigraphy findings in all patients undergoing rigorous cancer treatment may be attributed to individual variations in anatomical and functional structures. Lymphatic drainage from the arm may be altered after ALND. In such cases, the tricipital pathway, also known as Caplan’s pathway, has been described as a potential compensatory route. 34 This pathway bypasses the axillary lymph node group and drains lymph fluid directly into the scapular lymph nodes. 34 , 35 In a cohort study by Friedman et al., the tricipital pathway was visualized in 90% of patients who had undergone ALND for unilateral breast cancer, with drainage observed in the posterior upper arm. 34 Furthermore, 63% of patients exhibited the long bundle variant of the tricipital pathway, while 27% showed the short bundle variant. 34 These anatomic variations in lymphatic drainage may help explain the observed discrepancies in the initial PEV despite similar treatment histories and lymphoscintigraphy findings. This study had some limitations. First, compliance with LE treatments, such as self-manual lymphatic drainage exercises, may differ among patients. To overcome these limitations, this study focused on serial changes in the volume of the same person. Second, selection bias cannot be completely ruled out because our data were retrospectively collected from a single center. However, consecutive enrollment according to uniform eligibility criteria and the hospital’s role as a tertiary referral center serving patients from diverse regions may partially mitigate this limitation. Third, the quality of 99m Tc tin-colloid lymphoscintigraphy imaging is often inferior to that achieved with nanocolloidal tracers such as 99m Tc-labeled human serum albumin, 99m Tc-labeled human immunoglobulin, and 99m Tc-labeled dextran. 36 – 42 Nevertheless, these tracers remain clinically inaccessible in many countries, including the study setting. Therefore, a more refined prospective study is required to overcome these limitations. Fourth, although there was an observable trend toward increased daily activity limitation in Groups 1–4, this difference was not statistically significant, potentially due to the limited power associated with small subgroup sizes (Table 2 ). Larger sample sizes are required to validate these findings. Lastly, differences in the initial PEV, despite similar cancer treatment history and comparable functional outcomes on lymphoscintigraphy, may also be attributed to variations in the timing of LE onset. A statistically significant difference in the time from axillary surgery to the presentation of LE was observed among the four groups. The inconsistent intervals between LE onset and the timing of clinical visits likely contributed to discrepancies in baseline measurements. Future studies with larger sample sizes are required to validate these findings. Determining how long intensive LE control therapy is necessary represents a perspective different from that of considering LE solely as a disease entity. It is essential to consider BCRL as a condition that requires lifelong management rather than aggressive treatment. At present, many patients with BCRL undergo excessive LE treatment, especially those with a history of vigorous cancer treatment, driven by fear and lack of evidence. In conclusion, this study demonstrates that initial PEV serves as a valuable predictor of long-term outcomes and treatment needs in patients with BCRL with an aggressive cancer treatment history and favorable lymphoscintigraphy findings. This stratified approach may help identify patients with low initial PEV, thereby avoiding unnecessary interventions. Concurrently, this ensures that patients with a higher initial PEV receive appropriate therapy in the context of prior aggressive cancer treatment even though when favorable lymphoscintigraphy findings are present. Therefore, active lymphoscintigraphy in patients with mild LE in the early phase is warranted for personalized treatment. Further studies are warranted to broaden the disease spectrum and extend the follow-up period to increase the generalizability of this study’s findings. Abbreviations BCRL, Breast cancer-related lymphedema; ALND, axillary lymph node dissection; LE, lymphedema; PEV, percentage of excessive volume; CDT, complex decongestive therapy; BMI, body mass index Declarations Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Author Contributions IK and JHH contributed to conception and design of the study. Formal analysis was performed by IK and JYL. The investigation was carried out by GHN. Material preparation and data acquisition were performed by JYC, JYL and GHN. The data were analyzed by IK, JYL and GHN. The first draft of the manuscript was written by IK and the manuscript was reviewed and edited by IK and JHH. Visualization was performed by IK. All authors read and approved the final manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Data Availability The data that support the findings of this study are not publicly available due to institutional restrictions but are available from the corresponding author on reasonable request. Ethics Approval The research was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The study was approved by the Institutional Review Board of the Samsung Medical Center (IRB No. 2023-02-149). Consent to Participate Informed consent was not required, as this study was retrospective in design and the researchers did not collect or record any personally identifiable information. Given this design, no direct interaction with human participants occurred, and the study was approved with a waiver of consent by the Institutional Review Board. Consent to Publish Consent for publication was not applicable, since the study does not involve any individual person’s data in any form, including identifiable details, images, or other personal information. Acknowledgement The authors thank the staff and management of the Samsung Medical Center’s Department of Physical and Rehabilitation Medicine for their support and access to the patient archives, which were indispensable for this retrospective analysis. The authors also thank their peer reviewers, whose insights helped refine this manuscript. References Gillespie TC, Sayegh HE, Brunelle CL et al (2018) Breast cancer-related lymphedema: risk factors, precautionary measures, and treatments. Gland Surg 7:379–403 https://doi.org/10.21037/gs.2017.11.04 Kim N, Kim H, Hwang JH et al (2021) Longitudinal impact of postmastectomy radiotherapy on arm lymphedema in patients with breast cancer: an analysis of serial changes in arm volume measured by infrared optoelectronic volumetry. 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Br J Surg 73:580–584 https://doi.org/10.1002/bjs.1800730723 Allam O, Park KE, Chandler L et al (2020) The impact of radiation on lymphedema: a review of the literature. Gland Surg 9:596–602 http://dx.doi.org/10.21037/gs.2020.03.20 Gross JP, Sachdev S, Helenowski IB et al (2018) Radiation therapy field design and lymphedema risk after regional nodal irradiation for breast cancer. Int J Radiat Oncol Biol Phys 102:71–78 https://doi.org/10.1016/j.ijrobp.2018.03.046 Razavi MS, Lei PJ, Amoozgar Z et al (2023) Regeneration of collecting lymphatic vessels following injury. Res Sq https://doi.org/10.21203/rs.3.rs-3025656/v1 Golueke PJ, Montgomery RA, Petronis JD et al (1989) Lymphoscintigraphy to confirm the clinical diagnosis of lymphedema. J Vasc Surg 10:306–312 Gloviczki P, Calcagno D, Schirger A et al (1989) Noninvasive evaluation of the swollen extremity: experiences with 190 lymphoscintigraphic examinations. J Vasc Surg 9:683–689 https://doi.org/10.1067/mva.1989.vs0090683 Noh S, Hwang JH, Yoon TH et al (2015) Limb differences in the therapeutic effects of complex decongestive therapy on edema, quality of life, and satisfaction in lymphedema patients. Ann Rehabil Med 39:347–359 https://doi.org/10.5535/arm.2015.39.3.347 Friedman R, Bustos VP, Pardo J et al (2023) Superficial and functional imaging of the tricipital lymphatic pathway: a modern reintroduction. Breast Cancer Res Treat 197:235–242 https://doi.org/10.1007/s10549-022-06777-z Fanning JE, Chung DKV, Reynolds HM et al (2024) Collateralization of the upper extremity lymphatic system after axillary lymph node dissection. J Surg Oncol https://doi.org/10.1002/jso.27827 Henze E, Schelbert HR, Collins JD et al (1982) Lymphoscintigraphy with Tc-99m labeled dextran. J Nucl Med 23:923–929 Henze E, Schelbert HR, Collins JD et al (1983) Lymphoscintigraphy with Tc-99m labeled dextran. J Nucl Med 24:370–371 Nawaz K, Hamad MM, Sadek S et al (1986) Dynamic lymph flow imaging in lymphedema: normal and abnormal patterns. Clin Nucl Med 11:653–658 https://doi.org/10.1097/00003072-198609000-00015 Svensson W, Glass DM, Bradley D et al (1999) Measurement of lymphatic function with technetium-99m-labelled polyclonal immunoglobulin. Eur J Nucl Med 26:504–510 Witte CL, Witte MH (1999) Diagnostic and interventional imaging of lymphatic disorders. Int Angiol 18:25–30 Szuba A, Shin WS, Strauss HW et al (2003) The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med 44:43–57 Pappalardo M, Cheng MH (2020) Lymphoscintigraphy for the diagnosis of extremity lymphedema: current controversies regarding protocol, interpretation, and clinical application. J Surg Oncol 121:37–47 https://doi.org/10.1002/jso.25526 Additional Declarations No competing interests reported. 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8232253","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":563717796,"identity":"ea0f6964-6472-4fd5-9388-de35b58cc378","order_by":0,"name":"Inah Kim","email":"","orcid":"","institution":"Hallym University Dongtan Sacred Heart Hospital","correspondingAuthor":false,"prefix":"","firstName":"Inah","middleName":"","lastName":"Kim","suffix":""},{"id":563717798,"identity":"987238b9-e24c-435e-8e3e-b8362a73dfe2","order_by":1,"name":"Joon Young Choi","email":"","orcid":"","institution":"Samsung Medical Center, Sungkyunkwan University 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1","display":"","copyAsset":false,"role":"figure","size":1117724,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the selection and grouping of patients. Abbreviations: BCRL, breast cancer-related lymphedema; PEV, percentage of excessive volume\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8232253/v1/746a205545000ef221410830.png"},{"id":99190495,"identity":"87a8118f-6bc8-4fcc-ad86-91ae2b8d17ac","added_by":"auto","created_at":"2025-12-30 00:51:38","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":6041375,"visible":true,"origin":"","legend":"\u003cp\u003eFavorable lymphoscintigraphy findings. Fig. 2a Initial imaging shows uptake in the main lymphatic vessel on the right side, along with uptake indicating a collateral lymphatic pathway. Delayed imaging reveals lymph node uptake in the right axilla region suggestive of deltopectoral nodal uptake. Dermal backflow is observed in the distal part of the right upper arm. Fig. 2b Delayed imaging reveals increased heterogeneous radiotracer uptake, likely indicative of dermal backflow, primarily in the left forearm. Additionally, there is marked reduction in radiotracer uptake in the left axillary lymph node, with localized increased uptake in the left deltopectoral area, likely representing a collateral lymph node\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8232253/v1/48ac7b5a5071f84744ee625c.png"},{"id":99190494,"identity":"7e483c1b-945a-43c7-a6e7-450c667ab92c","added_by":"auto","created_at":"2025-12-30 00:51:38","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":716881,"visible":true,"origin":"","legend":"\u003cp\u003eComposition of Lymphedema Treatments by Group. Abbreviations: CDT, Complex decongestive therapy. Group 1 (Initial PEV\u0026lt;5%, n=19), Group 2 (5%≤Initial PEV\u0026lt;10%, n=33), Group 3 (10%≤Initial PEV\u0026lt;20%, n=33) and Group 4 (Initial PEV≥20%, n=19)\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8232253/v1/3793d6f33fbc989c0f963d09.png"},{"id":99315951,"identity":"0026b45e-7e32-4415-ac62-2bf2a8fe29a5","added_by":"auto","created_at":"2025-12-31 16:27:30","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1082661,"visible":true,"origin":"","legend":"\u003cp\u003eTemporal changes in the percentage of excessive volume (PEV) % after lymphedema diagnosis. * Group 1 (Initial PEV\u0026lt;5%, n=19), Group 2 (5%≤Initial PEV\u0026lt;10%, n=33), Group 3 (10%≤Initial PEV\u0026lt;20%, n=33) and Group 4 (Initial PEV≥20%, n=19)\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8232253/v1/7196c3405edd08fe06730f8a.png"},{"id":109296529,"identity":"b6b01a22-107c-427c-afc8-583bf897c39d","added_by":"auto","created_at":"2026-05-15 08:47:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":8816974,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8232253/v1/21cc0c52-966b-4159-b08a-1a242dcd407f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Reevaluating Intensive Treatment Strategies for Breast Cancer-Related Lymphedema Following Aggressive Therapy: A Retrospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer-related lymphedema (BCRL) affects approximately 8.4%\u0026ndash;21.4% of patients treated for breast cancer, significantly impairing their quality of life.\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e It typically arises from lymphatic disruption caused by surgery, radiation, or a combination of both.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Key risk factors for developing BCRL include axillary lymph node dissection (ALND), radiation to the regional lymph nodes, and cellulitis.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Nonetheless, not all patients receiving rigorous cancer treatment develop severe lymphedema (LE). Szuba et al. suggested that collateral circulation or lymphovenous compensation may preserve the drainage function, thereby potentially preventing severe LE.\u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eLymphoscintigraphy plays a crucial role in the diagnosis and prediction of BCRL prognosis.\u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e This procedure helps identify lymphatic flow, location, and the number of lymph nodes, thereby providing reliable information for LE assessment.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e A study by Kim et al. found that early lymphoscintigraphy following breast cancer surgery is useful in predicting the likelihood of LE.\u003csup\u003e13\u003c/sup\u003e Moreover, lymphoscintigraphy has been acknowledged for its utility in assessing and predicting treatment responses. Quantitative lymphoscintigraphy findings correlate with the response to LE therapy in patients with BCRL.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e According to Hwang et al., although patient responses to complex physical therapy showed no significant differences in clinical variables, significant differences were observed in lymphoscintigraphic findings.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Specifically, the presence of main lymphatic vessels without collateral lymphatic vessels emerged as the strongest predictor of a positive therapeutic response, demonstrating a sensitivity of 91%, specificity of 100%, and accuracy of 95%.\u003csup\u003e16\u003c/sup\u003e Collectively, baseline lymphoscintigraphy is likely to be useful in predicting long-term responses to BCRL treatment.\u003csup\u003e\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTo the best of our knowledge, no previous study has tracked the long-term manifestations of BCRL in patients with a history of aggressive cancer therapy in relation to the lymphoscintigraphic findings. Therefore, this study aimed to evaluate whether patients with favorable lymphoscintigraphy findings require long-term intensive LE treatment, despite a history of aggressive cancer therapy. Additionally, this study aimed to determine whether the initial percentage of excessive volume (PEV) can guide personalized treatment decisions, potentially sparing patients from unnecessary treatment burden through clinical prediction.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eThis retrospective study recruited 280 patients with unilateral BCRL who visited the Department of Rehabilitation Medicine at a tertiary hospital between January 2008 and December 2022 and met the eligibility criteria. The criteria included a history of mastectomy with ALND, locoregional radiation therapy, and favorable lymphoscintigraphy findings. The diagnosis of LE was based on the PEV and clinical assessment by a clinician\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Favorable lymphoscintigraphy findings were defined as uptake in the axillary lymph nodes or minimally visible main lymphatic vessels with collateral lymph node uptake (via the deltopectoral, supraclavicular, or forearm), with or without regional dermal backflows, while explicitly excluding cases with only dermal backflow and no nodal visualization. All patients were of Korean ethnicity. The exclusion criteria included comorbidities, such as current metastasis or recurrent cancer, vascular disease, cellulitis, history of trauma or surgery in the affected upper extremity, and insufficient medical records. Finally, 104 patients were included in the study \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eProcedure\u003c/h3\u003e\n\u003cp\u003eLE was clinically diagnosed by physical examination and optoelectronic volume analysis (Perometer, Pero-System, Wuppertal, Germany). The diagnosis was confirmed by a physiatrist specializing in cancer rehabilitation, who excluded generalized edema after chemotherapy and venous congestion.\u003c/p\u003e \u003cp\u003ePEV was calculated using the flowing formula:\u003c/p\u003e \u003cp\u003e% excess volume (mL) = [(Va \u0026ndash; Vu)/Vu] x 100.\u003c/p\u003e \u003cp\u003eVa, affected arm volume; Vu, unaffected arm volume; LE, PEV\u0026thinsp;\u0026gt;\u0026thinsp;5%.\u003c/p\u003e \u003cp\u003eThe patients were divided into four groups according to their initial PEV: Group 1 (PEV\u0026thinsp;\u0026lt;\u0026thinsp;5%, n\u0026thinsp;=\u0026thinsp;19), Group 2 (5%\u0026le;PEV\u0026thinsp;\u0026lt;\u0026thinsp;10%, n\u0026thinsp;=\u0026thinsp;33), Group 3 (10%\u0026le;PEV\u0026thinsp;\u0026lt;\u0026thinsp;20%, n\u0026thinsp;=\u0026thinsp;33), and Group 4 (PEV\u0026thinsp;\u0026ge;\u0026thinsp;20%, n\u0026thinsp;=\u0026thinsp;19).\u003c/p\u003e \u003cp\u003eAll groups received self-management education and compression garments and/or intensive LE treatment (e.g., complex decongestive therapy with elastic bandages), if necessary, during the first 12 months. From 12 to 24 months, stocking use was reduced based on expert judgment and PEV. The PEV was measured at the first visit and after 3, 6, 12, 18, and 24 months.\u003c/p\u003e \u003cp\u003eLymphoscintigraphy was performed using a dual-headed gamma camera (Bio-Rad; Trionix Research Laboratory, Hercules, CA, USA). The patients were placed in the supine position, and 0.2 mL of \u003csup\u003e99m\u003c/sup\u003eTc-phytate (100 nm filtered at 37 MBq) was injected subcutaneously into the second interdigital space of both hands. The patients were asked to grip and release their hands repeatedly to improve radiopharmaceutical transport. Anterior, posterior, and spot images of both upper extremities were captured 1 and 2 h after the injection.\u003c/p\u003e \u003cp\u003ePatients with minimal LE (\u0026lt;\u0026thinsp;20% volume increase) were managed with patient education, commercially available compressive stockings, and/or self-bandaging. Complex decongestive therapy (CDT) was considered a treatment option for patients with a marked volume increase (\u0026ge;\u0026thinsp;20% volume increase). CDT was administered in two phases: decongestive and maintenance. CDT comprises manual lymphatic drainage, compression of the affected upper extremity with a low-stretch bandage, specific remedial exercises to enhance lymphatic drainage, skin care, and patient education. The patients underwent 30 min of CDT on five consecutive days per week for 2 weeks. The bandages were applied after manual lymphatic drainage and were left in place between successive daily treatments. The decongestive phase of CDT aims to achieve a substantial reduction in LE volume. During the maintenance phase, patients were educated to perform self-management, including daytime compression stockings, self-bandaging, self-massage, and self-skincare.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eDistributions were evaluated using the Kolmogorov\u0026ndash;Smirnov test. Pearson\u0026rsquo;s chi-square test, Fisher\u0026rsquo;s exact test, and the Kruskal\u0026ndash;Wallis test were used to compare the clinical parameters and characteristics according to the initial PEV (four groups). Generalized estimating equation analysis was used to evaluate temporal changes in PEV over the follow-up period within each group. To compare the time interval from axillary surgery to the presentation of LE across groups, the Kruskal\u0026ndash;Wallis test was employed because of the non-normal distribution of the data. Upon identifying a significant overall difference, post-hoc pairwise comparisons were conducted using Dunn\u0026rsquo;s test with Bonferroni correction to control for multiple comparisons. To compare the body mass index (BMI) among the groups, Welch\u0026rsquo;s ANOVA was applied, given the presence of unequal variance. All statistical analyses were performed using SPSS (version 20.0; IBM, Armonk, NY, USA) and R software version 4.3.0 (R Foundation for Statistical Computing, Vienna, Austria). Statistical significance was set at 5% (two-sided).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 104 patients were included in the study. The clinical characteristics of the patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There were no significant differences in age, BMI, laterality, number of node dissections, chemotherapy, radiation therapy, or hormonal therapy among the four groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\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\u003eGeneral characteristics and cancer treatment history of each group of patients (n\u0026thinsp;=\u0026thinsp;104).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup 3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGroup 4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (45\u0026ndash;67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (40\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54 (42\u0026ndash;75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51 (33\u0026ndash;71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBody mass index (kg/m\u0026sup2;)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.06\u0026thinsp;\u0026plusmn;\u0026thinsp;3.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.46\u0026thinsp;\u0026plusmn;\u0026thinsp;4.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.35\u0026thinsp;\u0026plusmn;\u0026thinsp;3.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.60\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0116\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLaterality\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (31.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (42.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (60.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9 (47.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.208\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (68.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (57.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNode dissection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of dissected nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.0 (11\u0026ndash;29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (9\u0026ndash;37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (8\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18 (12\u0026ndash;51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.809\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of positive nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.0 (0\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0 (0\u0026ndash;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.0 (0\u0026ndash;20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.0 (0\u0026ndash;26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.429\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBreast reconstruction surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.662\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChemotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.418\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (36.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (57.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (69.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (78.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 (63.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant \u0026amp; Adjuvant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLocoregional radiation therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFraction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (17\u0026ndash;28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (16\u0026ndash;31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (16\u0026ndash;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25 (16\u0026ndash;33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.663\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5000 (4590\u0026ndash;6050)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5000 (4200\u0026ndash;6050)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5000 (4240\u0026ndash;6050)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5040 (4240\u0026ndash;6050)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHormonal therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (57.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (75.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (78.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16 (84.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.270\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eValues are presented as the number of patients (%) and median [IQR].Group 1 (Initial PEV\u0026thinsp;\u0026lt;\u0026thinsp;5%, n\u0026thinsp;=\u0026thinsp;19); Group 2 (5%\u0026le;Initial PEV\u0026thinsp;\u0026lt;\u0026thinsp;10%, n\u0026thinsp;=\u0026thinsp;33); Group 3 (10%\u0026le;Initial PEV\u0026thinsp;\u0026lt;\u0026thinsp;20%, n\u0026thinsp;=\u0026thinsp;33); Group 4 (Initial PEV\u0026thinsp;\u0026ge;\u0026thinsp;20%, n\u0026thinsp;=\u0026thinsp;19)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eFavorable lymphoscintigraphy findings\u003c/h3\u003e\n\u003cp\u003eAll participants showed favorable lymphoscintigraphy findings (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea, one patient underwent ALND, with 17 lymph nodes removed, followed by adjuvant radiotherapy to the chest wall and supraclavicular lymph node area, receiving a total dose of 5000 cGy. Lymphoscintigraphy was performed approximately two years after the completion of radiotherapy (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb, another patient underwent ALND involving 17 lymph nodes and received adjuvant radiotherapy to the breast and supraclavicular fossa at a total dose of 6050 cGy. Lymphoscintigraphy was conducted approximately two years after radiotherapy (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eInitial PEV and lymphedema management\u003c/h2\u003e \u003cp\u003eUpon completion of the 24-month follow-up period, the severity of the initial LE, as indicated by higher PEV values, was associated with a greater proportion of patients requiring CDT (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Specifically, 15.8% of patients in Group 1 (Initial PEV\u0026thinsp;\u0026lt;\u0026thinsp;5%, n\u0026thinsp;=\u0026thinsp;19) required intensive CDT, compared to 39.4% in Group 2 (5%\u0026le;Initial PEV\u0026thinsp;\u0026lt;\u0026thinsp;10%), 54.5% in Group 3 (10%\u0026le;Initial PEV\u0026thinsp;\u0026lt;\u0026thinsp;20%), and 78.9% in Group 4 (PEV\u0026thinsp;\u0026ge;\u0026thinsp;20%). Moreover, the larger the initial LE volume, the more restrictions on sports activities and daily life were observed; however, the difference was not statistically significant (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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\u003eLymphedema management and daily functionality of each group of patients (n\u0026thinsp;=\u0026thinsp;104).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup 3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGroup 4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntensive CDT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (84.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20 (60.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15 (45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18 (54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e15 (78.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFrequency of applying garment in daily activity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot used\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (36.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUsing compressive stocking sometimes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (63.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16 (48.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16 (48.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUsing compressive stocking everyday\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUsing compressive stocking and bandaging\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDaily activity level\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLimitation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.158\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo limitation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8 (24.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePossible sports activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17 (89.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26 (78.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11 (57.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime from axillary surgery to lymphedema onset\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonths\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.00 [6.00, 21.50]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.00 [7.00, 22.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16.00 [8.00, 46.00]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e30.00 [11.00, 60.50]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.014*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt; 1 year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (68.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (42.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;2 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7 (21.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 ( 9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge; 3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8 (42.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eValues are presented as the number of patients (%) and median [IQR].\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: PEV, percentage of excessive volume; Group 1 (Initial PEV\u0026thinsp;\u0026lt;\u0026thinsp;5%, n\u0026thinsp;=\u0026thinsp;19); Group 2 (5%\u0026le;Initial PEV\u0026thinsp;\u0026lt;\u0026thinsp;10%, n\u0026thinsp;=\u0026thinsp;33); Group 3 (10%\u0026le;Initial PEV\u0026thinsp;\u0026lt;\u0026thinsp;20%, n\u0026thinsp;=\u0026thinsp;33); Group 4 (Initial PEV\u0026thinsp;\u0026ge;\u0026thinsp;20%, n\u0026thinsp;=\u0026thinsp;19)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn addition, groups stratified by initial PEV levels demonstrated that higher initial PEV levels were associated with the need for more intensive LE treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). A statistically significant difference was observed across the four groups (P\u0026thinsp;=\u0026thinsp;0.014), and post-hoc analysis revealed a significant difference between Groups 1 and 4 (P\u0026thinsp;=\u0026thinsp;0.035) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTemporal changes in the PEV after lymphedema diagnosis\u003c/h3\u003e\n\u003cp\u003eIn the generalized estimating equation analysis, the PEV values of all groups exhibited significant time-dependent changes (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). All groups showed a tendency of decreased PEV until the first 12 months, which was then well-maintained for up to 24 months. In Groups 1 and 2, there were significant decreases at 3 and 6 months compared with baseline (i.e., at the diagnosis of LE), after which the PEV values were maintained. In Group 3, significant decreases were observed at 3, 6, and 12 months compared to baseline. Thereafter, the PEV values increased, although the changes were not significant. In Group 4, there were significant decreases at 3, 6, 12, and 18 months compared with the baseline, and the PEV value at 24 months showed an increase, although this change was not significant. After 12 months, the group with a low initial PEV maintained a low PEV, with or without minimal medical compression. However, groups with high-initial PEV showed a tendency toward an increase in volume, although this was less than that of the initial PEV. Patients with low initial PEV received less intensive LE treatment and showed well-maintained volumetry for 24 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, this is the first study to investigate the long-term manifestations of the BCRL pattern in patients who received aggressive cancer therapy yet exhibited good lymphatic function on lymphoscintigraphy. Previous studies have provided fragmented information on the risk and prognostic factors for BCRL.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e While it is well established that aggressive cancer treatment increases the risk of developing LE and that favorable lymphatic function on lymphoscintigraphy is associated with better outcomes, little is known about cases in which both conditions co-exist. In particular, long-term patterns of BCRL in such cases have not been thoroughly investigated. Consequently, patients with a history of intensive cancer treatment tend to have an increased risk of excessive LE and heightened anxiety. The treatment of LE poses significant time and financial burdens.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e Therefore, it is crucial to target the appropriate population and determine the appropriate treatment duration for intensive LE.\u003c/p\u003e \u003cp\u003eALND and regional lymph node radiation are independent risk factors for aggressive cancer treatment, and their combination has a synergistic effect on LE development.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e For each additional lymph node removed, the risk of LE development increased by 3%.\u003csup\u003e1,4,29\u003c/sup\u003e Additionally, regional lymph node radiation alone is known to increase the risk by 1.7 times.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. When radiation therapy was combined with lymph node dissection, the incidence of LE increased to 18.2%, the highest observed risk.\u003c/p\u003e \u003cp\u003eIn comparison, the risk of LE development is not only strongly associated with nodal destruction but also with a patient's capacity to regenerate alternative lymphatics.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Thus, lymphoscintigraphy is frequently used as an effective adjunctive tool. Qualitative lymphoscintigraphy of the upper extremities has been identified as a valuable tool for functional assessment, offering high sensitivity (70.6% to 92%) and specificity of nearly 100%.\u003csup\u003e9,12,31,32\u003c/sup\u003e In addition, Kim et al. reported that the quantitative asymmetry index on lymphoscintigraphy reflected LE severity.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e However, the lack of analysis of the long-term features of BCRL poses limitations in providing comprehensive treatment.\u003c/p\u003e \u003cp\u003eThe results of this study showed that despite aggressive cancer treatment, approximately half of the patients achieved favorable outcomes during the 24-month follow-up period without intensive treatment or significant activity restrictions. With the support of expert opinion, the removal of minimal medical compression after 12 months could be considered for patients with BCRL and a low initial PEV. Nevertheless, for most patients with a high-initial PEV, accounting for approximately 18% of the total cohort, intensive CDT with long-term surveillance is warranted, irrespective of the favorable lymphoscintigraphic findings. Therefore, a skilled physician is required to determine the tailored treatment duration and intensity for different patient groups. This finding suggests that patients with BCRL, similar aggressive cancer treatment histories, and favorable lymphoscintigraphic findings can be stratified based on early PEV values for personalized treatments. Clinicians should avoid instilling excessive fear and anxiety in patients or forcing extensive LE therapy in unsuitable populations, particularly when patients present with minimal initial PEV and favorable lymphoscintigraphic findings. Moreover, significant enhancements in both physical and emotional well-being can be realized by addressing the psychosocial needs of patients with upper extremity LE, which can be achieved by regulating the appropriate duration of therapy.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eFavorable lymphoscintigraphy findings in all patients undergoing rigorous cancer treatment may be attributed to individual variations in anatomical and functional structures. Lymphatic drainage from the arm may be altered after ALND. In such cases, the tricipital pathway, also known as Caplan\u0026rsquo;s pathway, has been described as a potential compensatory route.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e This pathway bypasses the axillary lymph node group and drains lymph fluid directly into the scapular lymph nodes.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e In a cohort study by Friedman et al., the tricipital pathway was visualized in 90% of patients who had undergone ALND for unilateral breast cancer, with drainage observed in the posterior upper arm.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e Furthermore, 63% of patients exhibited the long bundle variant of the tricipital pathway, while 27% showed the short bundle variant.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e These anatomic variations in lymphatic drainage may help explain the observed discrepancies in the initial PEV despite similar treatment histories and lymphoscintigraphy findings.\u003c/p\u003e \u003cp\u003eThis study had some limitations. First, compliance with LE treatments, such as self-manual lymphatic drainage exercises, may differ among patients. To overcome these limitations, this study focused on serial changes in the volume of the same person. Second, selection bias cannot be completely ruled out because our data were retrospectively collected from a single center. However, consecutive enrollment according to uniform eligibility criteria and the hospital\u0026rsquo;s role as a tertiary referral center serving patients from diverse regions may partially mitigate this limitation. Third, the quality of \u003csup\u003e99m\u003c/sup\u003eTc tin-colloid lymphoscintigraphy imaging is often inferior to that achieved with nanocolloidal tracers such as \u003csup\u003e99m\u003c/sup\u003eTc-labeled human serum albumin, \u003csup\u003e99m\u003c/sup\u003eTc-labeled human immunoglobulin, and \u003csup\u003e99m\u003c/sup\u003eTc-labeled dextran.\u003csup\u003e\u003cspan additionalcitationids=\"CR37 CR38 CR39 CR40 CR41\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e Nevertheless, these tracers remain clinically inaccessible in many countries, including the study setting. Therefore, a more refined prospective study is required to overcome these limitations. Fourth, although there was an observable trend toward increased daily activity limitation in Groups 1\u0026ndash;4, this difference was not statistically significant, potentially due to the limited power associated with small subgroup sizes (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Larger sample sizes are required to validate these findings. Lastly, differences in the initial PEV, despite similar cancer treatment history and comparable functional outcomes on lymphoscintigraphy, may also be attributed to variations in the timing of LE onset. A statistically significant difference in the time from axillary surgery to the presentation of LE was observed among the four groups. The inconsistent intervals between LE onset and the timing of clinical visits likely contributed to discrepancies in baseline measurements. Future studies with larger sample sizes are required to validate these findings.\u003c/p\u003e \u003cp\u003eDetermining how long intensive LE control therapy is necessary represents a perspective different from that of considering LE solely as a disease entity. It is essential to consider BCRL as a condition that requires lifelong management rather than aggressive treatment. At present, many patients with BCRL undergo excessive LE treatment, especially those with a history of vigorous cancer treatment, driven by fear and lack of evidence.\u003c/p\u003e \u003cp\u003eIn conclusion, this study demonstrates that initial PEV serves as a valuable predictor of long-term outcomes and treatment needs in patients with BCRL with an aggressive cancer treatment history and favorable lymphoscintigraphy findings. This stratified approach may help identify patients with low initial PEV, thereby avoiding unnecessary interventions. Concurrently, this ensures that patients with a higher initial PEV receive appropriate therapy in the context of prior aggressive cancer treatment even though when favorable lymphoscintigraphy findings are present. Therefore, active lymphoscintigraphy in patients with mild LE in the early phase is warranted for personalized treatment. Further studies are warranted to broaden the disease spectrum and extend the follow-up period to increase the generalizability of this study\u0026rsquo;s findings.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBCRL, Breast cancer-related lymphedema; ALND, axillary lymph node dissection; \u0026nbsp;LE, lymphedema; \u0026nbsp;PEV, \u0026nbsp; percentage of excessive volume; \u0026nbsp; CDT, complex decongestive therapy; \u0026nbsp; BMI, body mass index\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\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\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIK and JHH contributed to conception and design of the study. Formal analysis was performed by IK and JYL. The investigation was carried out by GHN. Material preparation and data acquisition were performed by JYC, JYL and GHN. The data were analyzed by IK, JYL and GHN. The first draft of the manuscript was written by IK and the manuscript was reviewed and edited by IK and JHH. Visualization was performed by IK. All authors read and approved the final manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are not publicly available due to institutional restrictions but 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\u003eThe research was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The study was approved by the Institutional Review Board of the Samsung Medical Center (IRB No. 2023-02-149).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was not required, as this study was retrospective in design and the researchers did not collect or record any personally identifiable information. Given this design, no direct interaction with human participants occurred, and the study was approved with a waiver of consent by the Institutional Review Board.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent for publication was not applicable, since the study does not involve any individual person’s data in any form, including identifiable details, images, or other personal information.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThe authors thank the staff and management of the Samsung Medical Center’s Department of Physical and Rehabilitation Medicine for their support and access to the patient archives, which were indispensable for this retrospective analysis. The authors also thank their peer reviewers, whose insights helped refine this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGillespie TC, Sayegh HE, Brunelle CL et al (2018) Breast cancer-related lymphedema: risk factors, precautionary measures, and treatments. Gland Surg 7:379\u0026ndash;403 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.21037/gs.2017.11.04\u003c/span\u003e\u003cspan address=\"10.21037/gs.2017.11.04\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim N, Kim H, Hwang JH et al (2021) Longitudinal impact of postmastectomy radiotherapy on arm lymphedema in patients with breast cancer: an analysis of serial changes in arm volume measured by infrared optoelectronic volumetry. 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J Surg Oncol 121:37\u0026ndash;47 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/jso.25526\u003c/span\u003e\u003cspan address=\"10.1002/jso.25526\" targettype=\"DOI\" class=\"RefTarget\"\u003e\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":"Lymphedema, Breast neoplasms, Lymphoscintigraphy, Complex decongestive therapy","lastPublishedDoi":"10.21203/rs.3.rs-8232253/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8232253/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eAggressive breast cancer treatment increases the risk of breast cancer-related lymphedema(BCRL). However, whether all high-risk patients require equally intensive long-term management remains unclear. This study aimed to characterize the long-term manifestations of the BCRL pattern in patients who received aggressive cancer therapies yet showed favorable lymphoscintigraphy findings.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included 104 patients with BCRL with a history of mastectomy with axillary lymph node dissection and locoregional radiation therapy between 2008 and 2022, all of whom showed favorable lymphoscintigraphy findings. The patients were stratified into four groups based on their initial percentage of excessive volume(PEV). Volume changes and individualized lymphedema treatment during the first 12 months were analyzed. From months 12 to 24, the treatment intensity, including the frequency of medical compression therapy, was adjusted based on expert assessment.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eDespite similar treatment histories and lymphoscintigraphy findings, the patients showed different volume change patterns based on the initial PEV, although the overall outcomes were favorable over two years in all groups. Patients with BCRL and a low initial PEV maintained stable reduced volumes after 6 months of minimal or no compression therapy. However, the high-initial PEV group required active surveillance and long-term management despite favorable lymphoscintigraphy results.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eInitial PEV effectively predicted long-term outcomes and treatment needs in patients with BCRL with an aggressive cancer treatment history and favorable lymphoscintigraphy findings. Personalized treatment planning using initial PEV and lymphoscintigraphy may provide the appropriate intensity of therapy to patients for an optimal duration to reduce time and financial burdens.\u003c/p\u003e","manuscriptTitle":"Reevaluating Intensive Treatment Strategies for Breast Cancer-Related Lymphedema Following Aggressive Therapy: A Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-30 00:51:33","doi":"10.21203/rs.3.rs-8232253/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":"ee7c5522-4297-4aec-a5d7-1fce7c43d29e","owner":[],"postedDate":"December 30th, 2025","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-14T20:51:05+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T20:54:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-30 00:51:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8232253","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8232253","identity":"rs-8232253","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}