{"paper_id":"2dbfa520-2093-4b27-9f06-63cd037002af","body_text":"Radiotherapy for benign conditions: management of persistent lymphorrea | 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 Radiotherapy for benign conditions: management of persistent lymphorrea Verónica Cañón, Javier Anchuelo, Claudia Laborda, Ana Galán, Ana Laura Rivero, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7077827/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Dec, 2025 Read the published version in Radiation Oncology → Version 1 posted 7 You are reading this latest preprint version Abstract Background: Lymphorrhea is a complication that can arise after vascular, abdominal or pelvic interventions and is associated with significant morbidity. While conservative management is typically effective, some cases remain refractory. Methods: This retrospective cross-sectional study analyzed 43 patients with persistent inguinal lymphorrhea treated at a tertiary hospital between 2008 and 2018. All patients received external beam radiotherapy (EBRT) using 3D conformal techniques with photons (6–18 MV). The delivered dose was 7.5 Gy in five 1,5 Gy/fractions. Results: Complete closure of the lymphatic fistula was achieved in all patients. Three required reirradiation with the same schedule to reach complete resolution. No acute or late toxicity was observed in any case. Conclusions: Low-dose EBRT is a safe and effective treatment option for persistent lymphorrhea refractory to conservative measures. Its anti-inflammatory and fibrosing effects support its therapeutic use in benign lymphatic complications. Trial Registration Not applicable. Lymphorrhea Lymphatic fistula Low-dose radiotherapy Benign pathology External beam radiation therapy Figures Figure 1 Figure 2 Background Lymphoceles are fluid-filled cavities that arise following surgical procedures, particularly those involving lymphatic disruption ( 1 ). Lymphorrhea refers to the external leakage of lymphatic fluid through persistent lymphocutaneous fistulas (LCFs). However, the definition of LCF is inconsistently described in the literature. Giovannacci et al. ( 2 ) defined an LCF as persistent lymphatic drainage of ≥ 30 mL/day for more than three days postoperatively, or any continuous drainage beyond postoperative day five. In some cases, LCFs have been reported as late as four years after surgery, with drainage volumes up to 50 mL/day ( 3 ). Primary congenital lymphatic fistulas are rare. Most LCFs are secondary and result from invasive procedures, particularly vascular, abdominal, pelvic, or cardiac surgeries. Persistent LCFs are associated with a high risk of wound complications, including infection, delayed healing, prolonged hospitalization, delayed rehabilitation, and increased healthcare costs. The incidence of lymphoceles and LCFs (Fig. 1 ) varies across published series, but is generally estimated to occur in 2–8% of all vascular, abdominal, or pelvic interventions ( 4 , 5 ). The risk appears to be higher in patients with pre-existing comorbidities. Management of LCFs should be individualized. First-line conservative treatment includes limb immobilization, elevation, and compression, where applicable. If these measures fail, percutaneous instillation of sclerosing agents such as ethanol, tetracycline, iodine solution, or bleomycin may be considered, as well as radiopharmaceuticals like yttrium-90 or rhenium-186 ( 6 – 8 ). Reported success rates for conservative management vary. Twine et al. ( 9 ) reported control rates between 80% and 100%, while others describe an 82% resolution rate after three weeks of conservative therapy ( 10 ). Nonetheless, some authors advocate for early surgical reintervention, particularly in cases with high output drainage, wound infection, or the presence of foreign material. However, surgical reintervention is not without risks. Radiotherapy (RT) for benign conditions is typically administered at significantly lower doses than those used for malignant disease ( 11 ). RT has been employed in a variety of benign indications, including chronic degenerative joint disease ( 12 ), soft tissue disorders such as Dupuytren’s and Peyronie’s disease ( 13 ), keloid scars, Graves’ orbitopathy ( 14 ), and persistent lymphoceles or LCFs ( 15 ). In complex or refractory LCFs, RT may be considered as a therapeutic option. RT is thought to exert anti-inflammatory effects at low doses. These include reduced secretion of pro-inflammatory cytokines by immune cells, alterations in endothelial permeability, and increased lymphatic reabsorption. Moreover, radiation induces fibroblast differentiation into fibrocytes, promoting localized fibrosis, increasing nitric oxide production, and reducing lymphatic flow in the irradiated area ( 16 ). Doses of 1–2 Gy per fraction are known to induce aseptic endotheliitis and obliteration of lymphatic vessels. Emerging evidence suggests that even lower doses (0.3–0.5 Gy per fraction) may be sufficient for therapeutic effect in the context of LCFs. The aim of this study is to evaluate the efficacy and safety of low-dose radiotherapy in the treatment of persistent lymphocutaneous fistulas, and to report the rate of secondary complications. Methods Study Design and Setting This was a retrospective, single-center, observational study conducted at a tertiary hospital in northern Spain. The study included patients with persistent inguinal lymphocutaneous fistulas (LCFs) who were treated with external beam radiotherapy (EBRT) between January 2008 and December 2018. Eligibility Criteria Patients were eligible if they met all of the following criteria: Presence of a persistent lymphocutaneous fistula unresponsive to conservative management. Absence of active malignancy in the irradiated region. Adequate general condition to undergo outpatient radiotherapy. Capacity to remain immobilized during simulation and treatment. Patients were excluded if they had received prior radiotherapy to the same anatomical region, had a poor performance status preventing EBRT, or presented with non-inguinal lymphorrhea. Radiotherapy Planning and Delivery All patients underwent CT-based simulation for treatment planning. The clinical target volume (CTV) was defined as the subcutaneous lymphatic vessels surrounding the surgical site and/or the persistent fistulous tract. A planning target volume (PTV) was generated by applying a 0.5–1.0 cm isotropic margin to the CTV to account for setup uncertainties. Three-dimensional conformal radiotherapy (3D-CRT) was used in all cases, with photon beams of 6 or 18 MV (Fig. 2 ). The most frequently used dose schedule was 7.5 Gy in 5 daily fractions (n = 39). Alternative regimens included 5.5 Gy in 3 fractions (n = 1), 8 Gy in 2 fractions (n = 2), and 15 Gy in 5 fractions (n = 1). Image guidance was performed using electronic portal imaging (EPID) or cone-beam CT, according to local protocols. Outcome Measures The primary endpoint was clinical resolution of the lymphorrhea, defined as complete cessation of lymphatic discharge at the treated site. Secondary outcomes included the need for reirradiation and the incidence of acute or late treatment-related toxicities. Toxicity Assessment Toxicities were prospectively assessed during treatment and follow-up visits using the Radiation Therapy Oncology Group (RTOG) grading system. Both acute (within 90 days post-treatment) and late (after 90 days) effects were recorded. Statistical Analysis Descriptive statistical analyses were performed using IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA). Quantitative variables were summarized using median and interquartile ranges (IQR), while categorical variables were presented as frequencies and percentages. Due to the descriptive nature of the study and the lack of a comparison group, no inferential statistical tests were conducted. Results A total of 43 patients with persistent inguinal lymphocutaneous fistulas were treated with external beam radiotherapy (EBRT) during the study period. The median age was 69 years (range: 48–84 years), and 88.4% (n = 38) were male. The most frequently prescribed radiotherapy schedule was 7.5 Gy delivered in 5 daily fractions, used in 90.7% of patients (n = 39). Alternative dose-fractionation regimens included 5.5 Gy in 3 fractions (n = 1), 8 Gy in 2 fractions (n = 2), and 15 Gy in 5 fractions (n = 1). All patients achieved complete clinical resolution of the lymphatic fistula. Three patients (7.0%) required reirradiation with the same schedule (7.5 Gy in 5 fractions) after an initial incomplete response. In all three cases, complete closure was subsequently achieved. No acute or late toxicities related to radiotherapy were observed. Specifically, no patients developed skin reactions, infections, or delayed wound healing attributable to the radiation treatment. All procedures were well tolerated and completed as scheduled. Discussion This retrospective series demonstrates that low-dose external beam radiotherapy (EBRT) is an effective and well-tolerated treatment for persistent lymphocutaneous fistulas (LCFs) unresponsive to conservative measures. All 43 patients included in this study achieved complete closure of the fistula, and no radiation-related toxicities were observed. These findings support the integration of radiotherapy into the therapeutic algorithm for benign lymphatic complications in selected patients. Our results are consistent with previous reports suggesting that low-dose radiotherapy promotes lymphatic closure through multiple mechanisms, including endothelial apoptosis, reduced inflammatory cytokine production, enhanced lymphatic reabsorption, and stimulation of fibroblast differentiation ( 11 ). Mayer et al. was among the first to report successful outcomes with radiotherapy in the management of lymphatic fistulas, although the evidence remains scarce and limited to small series or case reports ( 17 ). Several recent publications have provided more robust data supporting the use of radiotherapy for LCFs. Habermehl et al. described the effectiveness of radiotherapy as a non-invasive yet underutilized option for managing lymphatic fistulas, advocating its broader adoption. They support the efficacy of very low-dose RT (0.3–0.5 Gy per fraction) in controlling lymphatic leakage with no reported acute toxicity and a negligible risk of carcinogenesis. Importantly, the authors recommend discontinuing treatment immediately after resolution of lymphorrhea, reinforcing the safety and clinical utility of RT as a minimally invasive alternative in complex settings ( 18 ). Hautmann et al. ( 19 ) conducted a large retrospective analysis involving 206 lymphatic fistulas in 191 patients following vascular surgery in the groin region. Their findings showed that radiotherapy significantly reduced lymphatic secretion volumes (from a median of 150 mL/day to 60 mL/day) and enabled early drain removal in most cases, with 75% of patients avoiding further surgical interventions. Interestingly, the timing of radiotherapy (before or after postoperative day 10) did not influence outcomes, supporting its flexibility in clinical practice. More recently, Jazmati et al. ( 20 ) reported excellent results using extremely low-dose fractionated radiotherapy (0.3–0.4 Gy per fraction, median total dose 1.2 Gy) in 12 patients with persistent lymphatic fistulas after groin vascular surgery. Complete resolution was achieved in all cases, without adverse events. The authors emphasized the importance of initiating RT early—ideally within 72 hours of diagnosis—and highlighted the benefit of modern planning techniques such as intensity-modulated arc therapy (VMAT) using high-energy photons (6–15 MV). While the optimal dose and fractionation scheme have not been standardized, regimens delivering total doses between 3 and 12 Gy appear effective. In our cohort, the most frequently prescribed scheme was 7.5 Gy in 5 daily fractions, which proved sufficient in the majority of cases. Notably, three patients (7.0%) required reirradiation with the same regimen, after which complete closure was achieved. These cases suggest that a second low-dose course may be safely administered if the initial response is suboptimal. The absence of both acute and late toxicity in our study confirms the safety profile of low-dose RT in this setting. Importantly, treatment was delivered on an outpatient basis and completed without interruptions, making it a feasible and cost-effective option for patients who may not be candidates for surgery or in whom further invasive procedures are undesirable. This study has several limitations, including its retrospective nature, lack of a control group, and absence of long-term functional or quality-of-life assessments. Nonetheless, it represents one of the largest series published to date focusing specifically on radiotherapy for inguinal lymphorrhea. Future prospective studies are warranted to confirm these findings, establish standardized dose and fractionation protocols, and explore the role of radiotherapy earlier in the treatment algorithm for persistent lymphatic fistulas. Conclusions Low-dose external beam radiotherapy is a safe, effective, and non-invasive treatment option for persistent inguinal lymphocutaneous fistulas refractory to conservative management. In this retrospective series, complete clinical resolution was achieved in all patients, including those requiring reirradiation, with no acute or late toxicities observed. These findings, together with growing evidence from recent studies, reinforce the therapeutic potential of radiotherapy in the management of benign lymphatic complications. Given its excellent tolerability, low cost, and feasibility in the outpatient setting, radiotherapy should be considered early in the treatment algorithm for selected patients with refractory lymphorrhea. Prospective studies are needed to further define the optimal dose and fractionation, assess long-term outcomes, and establish standardized treatment protocols. Abbreviations VC: Verónica Cañón JA: Javier Anchuelo CL: Claudia Laborda AGa: Ana Galán ALR: Ana Laura Rivero FP: Frandeína Pinto MG: Mara García PN: Paola Navarrete PG: Piedad Galdós AAli: Ana Aliaga AAye: Arantxa Ayete CG: Cristina García GL: Gemma Liria MC: Maria Cerrolaza RF: Rosa Fabregat PJPr: Pedro José Prada Declarations Ethics approval and consent to participate The study was conducted in accordance with institutional ethical standards and the principles of the Declaration of Helsinki. Ethical approval was obtained from the local ethics committee of the participating center. Written informed consent for radiotherapy treatment was obtained from all patients at the time of treatment. Consent for publication Not applicable. This study does not contain identifiable personal data from any individual participant. Competing interests The authors declare that they have no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contribution VC, JA, and PJPr conceived the study and supervised the clinical coordination.CL, AGa, ALR, FP, MG, PN, PG, AAli, AAye, CG, GL, MC, and RF participated in patient data collection and treatment delivery.JA and CL performed the data analysis and interpretation.JA drafted the manuscript.All authors critically reviewed the content, contributed to revisions, and approved the final version of the manuscript.Abbreviations:•VC: Verónica Cañón•JA: Javier Anchuelo•CL: Claudia Laborda•AGa: Ana Galán•ALR: Ana Laura Rivero•FP: Frandeína Pinto•MG: Mara García•PN: Paola Navarrete•PG: Piedad Galdós•AAli: Ana Aliaga•AAye: Arantxa Ayete Acknowledgements The authors would like to thank the staff of the Radiation Oncology Department for their support in patient care and treatment delivery. No professional medical writing assistance was used in the preparation of this manuscript. Availability of data and materials All data generated or analyzed during this study are included in this published article. Additional anonymized data may be available from the corresponding author upon reasonable request. References Ranghino A, Segoloni GP, Lasaponara F, et al. Lymphatic disorders after renal transplantation: new insights for an old complication. ClinKidney J. 2015;8:615–22. Giovannacci L, Eugster T, Stierli P, et al. Does fibrin glue reduce complications after femoral artery surgery? A randomised trial. Eur J VascEndovascSurg. 2002;24:196–201. Dietl B, Pfister K, Aufschlager C, et al. Radiotherapy of inguinal lymphorrhea after vascular surgery. A retrospective analysis. StrahlentherOnkol. 2005;181:396–400. Ramasastry SS, Liang MD, Hurwitz DJ. Surgical management of difficult wounds of the groin. SurgGynecol Obstet. 1989;169:418–22. Tyndall SH, Shepard AD, Wilczewski JM, et al. 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Lymphatic fistulas: obliteration by low-dose radiotherapy. Strahlenther Onkol. 2005;181(10):660–4. Habermehl D, Habl G, Eckstein HH, Meisner F, Combs SE. Radiotherapeutic management of lymphatic fistulas: An effective but disregarded therapy option. Chirurg. 2017;88(4):311–6. Hautmann MG, Dietl B, Wagner L, et al. Radiation Therapy of lymphatic fistulae after vascular surgery in the groin. Int J Radiat Oncol Biol Phys. 2021;15(4):949–58. Jazmati D, Tamaskovics B, Hoff NP, et al. Percutaneous fractionated radiotherapy of the groin to eliminate lymphatic fistulas after vascular surgery. Eur J Med Res. 2023;9(1):70. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 20 Dec, 2025 Read the published version in Radiation Oncology → Version 1 posted Editorial decision: Revision requested 11 Aug, 2025 Reviews received at journal 28 Jul, 2025 Reviewers agreed at journal 18 Jul, 2025 Reviewers invited by journal 14 Jul, 2025 Editor assigned by journal 10 Jul, 2025 Submission checks completed at journal 09 Jul, 2025 First submitted to journal 08 Jul, 2025 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-7077827\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":485566461,\"identity\":\"6f2171c8-56bd-46d6-a583-ac1bed902e6a\",\"order_by\":0,\"name\":\"Verónica Cañón\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Hospital de Cruces\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Verónica\",\"middleName\":\"\",\"lastName\":\"Cañón\",\"suffix\":\"\"},{\"id\":485566463,\"identity\":\"5c40aa0f-592a-4298-8402-ae0d6139c747\",\"order_by\":1,\"name\":\"Javier 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lymphorrea.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage1.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7077827/v1/04f254925a4c096c67a31d22.jpeg\"},{\"id\":87036350,\"identity\":\"348f42b7-5f35-41d5-a34f-bd31eaaba334\",\"added_by\":\"auto\",\"created_at\":\"2025-07-18 13:20:35\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":413077,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eExtern \\u0026nbsp;al Beam Radiotherapy. Dosimetry.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7077827/v1/03e187e530099ab23aff0b28.png\"},{\"id\":98815071,\"identity\":\"9a42dd46-3388-4f75-a819-814bd3079480\",\"added_by\":\"auto\",\"created_at\":\"2025-12-22 16:13:26\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1364613,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7077827/v1/10f13fb8-7127-48a5-92dd-681315faafeb.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Radiotherapy for benign conditions: management of persistent lymphorrea\",\"fulltext\":[{\"header\":\"Background\",\"content\":\"\\u003cp\\u003eLymphoceles are fluid-filled cavities that arise following surgical procedures, particularly those involving lymphatic disruption (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). Lymphorrhea refers to the external leakage of lymphatic fluid through persistent lymphocutaneous fistulas (LCFs). However, the definition of LCF is inconsistently described in the literature. Giovannacci et al. (\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e) defined an LCF as persistent lymphatic drainage of ≥ 30 mL/day for more than three days postoperatively, or any continuous drainage beyond postoperative day five. In some cases, LCFs have been reported as late as four years after surgery, with drainage volumes up to 50 mL/day (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003ePrimary congenital lymphatic fistulas are rare. Most LCFs are secondary and result from invasive procedures, particularly vascular, abdominal, pelvic, or cardiac surgeries. Persistent LCFs are associated with a high risk of wound complications, including infection, delayed healing, prolonged hospitalization, delayed rehabilitation, and increased healthcare costs.\\u003c/p\\u003e\\u003cp\\u003eThe incidence of lymphoceles and LCFs (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e) varies across published series, but is generally estimated to occur in 2–8% of all vascular, abdominal, or pelvic interventions (\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e). The risk appears to be higher in patients with pre-existing comorbidities.\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cp\\u003eManagement of LCFs should be individualized. First-line conservative treatment includes limb immobilization, elevation, and compression, where applicable. If these measures fail, percutaneous instillation of sclerosing agents such as ethanol, tetracycline, iodine solution, or bleomycin may be considered, as well as radiopharmaceuticals like yttrium-90 or rhenium-186 (\\u003cspan additionalcitationids=\\\"CR7\\\" citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e–\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e). Reported success rates for conservative management vary. Twine et al. (\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e) reported control rates between 80% and 100%, while others describe an 82% resolution rate after three weeks of conservative therapy (\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e). Nonetheless, some authors advocate for early surgical reintervention, particularly in cases with high output drainage, wound infection, or the presence of foreign material. However, surgical reintervention is not without risks.\\u003c/p\\u003e\\u003cp\\u003eRadiotherapy (RT) for benign conditions is typically administered at significantly lower doses than those used for malignant disease (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e). RT has been employed in a variety of benign indications, including chronic degenerative joint disease (\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e), soft tissue disorders such as Dupuytren’s and Peyronie’s disease (\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e), keloid scars, Graves’ orbitopathy (\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e), and persistent lymphoceles or LCFs (\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e). In complex or refractory LCFs, RT may be considered as a therapeutic option.\\u003c/p\\u003e\\u003cp\\u003eRT is thought to exert anti-inflammatory effects at low doses. These include reduced secretion of pro-inflammatory cytokines by immune cells, alterations in endothelial permeability, and increased lymphatic reabsorption. Moreover, radiation induces fibroblast differentiation into fibrocytes, promoting localized fibrosis, increasing nitric oxide production, and reducing lymphatic flow in the irradiated area (\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eDoses of 1–2 Gy per fraction are known to induce aseptic endotheliitis and obliteration of lymphatic vessels. Emerging evidence suggests that even lower doses (0.3–0.5 Gy per fraction) may be sufficient for therapeutic effect in the context of LCFs.\\u003c/p\\u003e\\u003cp\\u003eThe aim of this study is to evaluate the efficacy and safety of low-dose radiotherapy in the treatment of persistent lymphocutaneous fistulas, and to report the rate of secondary complications.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003e\\u003cb\\u003eStudy Design and Setting\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eThis was a retrospective, single-center, observational study conducted at a tertiary hospital in northern Spain. The study included patients with persistent inguinal lymphocutaneous fistulas (LCFs) who were treated with external beam radiotherapy (EBRT) between January 2008 and December 2018.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eEligibility Criteria\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003ePatients were eligible if they met all of the following criteria:\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cul\\u003e\\u003cli\\u003e\\u003cp\\u003ePresence of a persistent lymphocutaneous fistula unresponsive to conservative management.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003eAbsence of active malignancy in the irradiated region.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003eAdequate general condition to undergo outpatient radiotherapy.\\u003c/p\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cp\\u003eCapacity to remain immobilized during simulation and treatment.\\u003c/p\\u003e\\u003c/li\\u003e\\u003c/ul\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cp\\u003ePatients were excluded if they had received prior radiotherapy to the same anatomical region, had a poor performance status preventing EBRT, or presented with non-inguinal lymphorrhea.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eRadiotherapy Planning and Delivery\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eAll patients underwent CT-based simulation for treatment planning. The clinical target volume (CTV) was defined as the subcutaneous lymphatic vessels surrounding the surgical site and/or the persistent fistulous tract. A planning target volume (PTV) was generated by applying a 0.5–1.0 cm isotropic margin to the CTV to account for setup uncertainties.\\u003c/p\\u003e\\u003cp\\u003eThree-dimensional conformal radiotherapy (3D-CRT) was used in all cases, with photon beams of 6 or 18 MV (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). The most frequently used dose schedule was 7.5 Gy in 5 daily fractions (n = 39). Alternative regimens included 5.5 Gy in 3 fractions (n = 1), 8 Gy in 2 fractions (n = 2), and 15 Gy in 5 fractions (n = 1). Image guidance was performed using electronic portal imaging (EPID) or cone-beam CT, according to local protocols.\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eOutcome Measures\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eThe primary endpoint was clinical resolution of the lymphorrhea, defined as complete cessation of lymphatic discharge at the treated site. Secondary outcomes included the need for reirradiation and the incidence of acute or late treatment-related toxicities.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eToxicity Assessment\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eToxicities were prospectively assessed during treatment and follow-up visits using the Radiation Therapy Oncology Group (RTOG) grading system. Both acute (within 90 days post-treatment) and late (after 90 days) effects were recorded.\\u003c/p\\u003e\\u003ch2\\u003eStatistical Analysis\\u003c/h2\\u003e\\u003cp\\u003eDescriptive statistical analyses were performed using IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA). Quantitative variables were summarized using median and interquartile ranges (IQR), while categorical variables were presented as frequencies and percentages. Due to the descriptive nature of the study and the lack of a comparison group, no inferential statistical tests were conducted.\\u003c/p\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eA total of 43 patients with persistent inguinal lymphocutaneous fistulas were treated with external beam radiotherapy (EBRT) during the study period. The median age was 69 years (range: 48\\u0026ndash;84 years), and 88.4% (n\\u0026thinsp;=\\u0026thinsp;38) were male.\\u003c/p\\u003e\\u003cp\\u003eThe most frequently prescribed radiotherapy schedule was 7.5 Gy delivered in 5 daily fractions, used in 90.7% of patients (n\\u0026thinsp;=\\u0026thinsp;39). Alternative dose-fractionation regimens included 5.5 Gy in 3 fractions (n\\u0026thinsp;=\\u0026thinsp;1), 8 Gy in 2 fractions (n\\u0026thinsp;=\\u0026thinsp;2), and 15 Gy in 5 fractions (n\\u0026thinsp;=\\u0026thinsp;1).\\u003c/p\\u003e\\u003cp\\u003eAll patients achieved complete clinical resolution of the lymphatic fistula. Three patients (7.0%) required reirradiation with the same schedule (7.5 Gy in 5 fractions) after an initial incomplete response. In all three cases, complete closure was subsequently achieved.\\u003c/p\\u003e\\u003cp\\u003eNo acute or late toxicities related to radiotherapy were observed. Specifically, no patients developed skin reactions, infections, or delayed wound healing attributable to the radiation treatment. All procedures were well tolerated and completed as scheduled.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThis retrospective series demonstrates that low-dose external beam radiotherapy (EBRT) is an effective and well-tolerated treatment for persistent lymphocutaneous fistulas (LCFs) unresponsive to conservative measures. All 43 patients included in this study achieved complete closure of the fistula, and no radiation-related toxicities were observed. These findings support the integration of radiotherapy into the therapeutic algorithm for benign lymphatic complications in selected patients.\\u003c/p\\u003e\\u003cp\\u003eOur results are consistent with previous reports suggesting that low-dose radiotherapy promotes lymphatic closure through multiple mechanisms, including endothelial apoptosis, reduced inflammatory cytokine production, enhanced lymphatic reabsorption, and stimulation of fibroblast differentiation (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e). Mayer et al. was among the first to report successful outcomes with radiotherapy in the management of lymphatic fistulas, although the evidence remains scarce and limited to small series or case reports (\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eSeveral recent publications have provided more robust data supporting the use of radiotherapy for LCFs. Habermehl et al. described the effectiveness of radiotherapy as a non-invasive yet underutilized option for managing lymphatic fistulas, advocating its broader adoption. They support the efficacy of very low-dose RT (0.3\\u0026ndash;0.5 Gy per fraction) in controlling lymphatic leakage with no reported acute toxicity and a negligible risk of carcinogenesis. Importantly, the authors recommend discontinuing treatment immediately after resolution of lymphorrhea, reinforcing the safety and clinical utility of RT as a minimally invasive alternative in complex settings (\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eHautmann et al. (\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e) conducted a large retrospective analysis involving 206 lymphatic fistulas in 191 patients following vascular surgery in the groin region. Their findings showed that radiotherapy significantly reduced lymphatic secretion volumes (from a median of 150 mL/day to 60 mL/day) and enabled early drain removal in most cases, with 75% of patients avoiding further surgical interventions. Interestingly, the timing of radiotherapy (before or after postoperative day 10) did not influence outcomes, supporting its flexibility in clinical practice.\\u003c/p\\u003e\\u003cp\\u003eMore recently, Jazmati et al. (\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e) reported excellent results using extremely low-dose fractionated radiotherapy (0.3\\u0026ndash;0.4 Gy per fraction, median total dose 1.2 Gy) in 12 patients with persistent lymphatic fistulas after groin vascular surgery. Complete resolution was achieved in all cases, without adverse events. The authors emphasized the importance of initiating RT early\\u0026mdash;ideally within 72 hours of diagnosis\\u0026mdash;and highlighted the benefit of modern planning techniques such as intensity-modulated arc therapy (VMAT) using high-energy photons (6\\u0026ndash;15 MV).\\u003c/p\\u003e\\u003cp\\u003eWhile the optimal dose and fractionation scheme have not been standardized, regimens delivering total doses between 3 and 12 Gy appear effective. In our cohort, the most frequently prescribed scheme was 7.5 Gy in 5 daily fractions, which proved sufficient in the majority of cases. Notably, three patients (7.0%) required reirradiation with the same regimen, after which complete closure was achieved. These cases suggest that a second low-dose course may be safely administered if the initial response is suboptimal.\\u003c/p\\u003e\\u003cp\\u003eThe absence of both acute and late toxicity in our study confirms the safety profile of low-dose RT in this setting. Importantly, treatment was delivered on an outpatient basis and completed without interruptions, making it a feasible and cost-effective option for patients who may not be candidates for surgery or in whom further invasive procedures are undesirable.\\u003c/p\\u003e\\u003cp\\u003eThis study has several limitations, including its retrospective nature, lack of a control group, and absence of long-term functional or quality-of-life assessments. Nonetheless, it represents one of the largest series published to date focusing specifically on radiotherapy for inguinal lymphorrhea.\\u003c/p\\u003e\\u003cp\\u003eFuture prospective studies are warranted to confirm these findings, establish standardized dose and fractionation protocols, and explore the role of radiotherapy earlier in the treatment algorithm for persistent lymphatic fistulas.\\u003c/p\\u003e\"},{\"header\":\"Conclusions\",\"content\":\"\\u003cp\\u003eLow-dose external beam radiotherapy is a safe, effective, and non-invasive treatment option for persistent inguinal lymphocutaneous fistulas refractory to conservative management. In this retrospective series, complete clinical resolution was achieved in all patients, including those requiring reirradiation, with no acute or late toxicities observed.\\u003c/p\\u003e\\u003cp\\u003eThese findings, together with growing evidence from recent studies, reinforce the therapeutic potential of radiotherapy in the management of benign lymphatic complications. Given its excellent tolerability, low cost, and feasibility in the outpatient setting, radiotherapy should be considered early in the treatment algorithm for selected patients with refractory lymphorrhea.\\u003c/p\\u003e\\u003cp\\u003eProspective studies are needed to further define the optimal dose and fractionation, assess long-term outcomes, and establish standardized treatment protocols.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cul type=\\\"disc\\\"\\u003e\\n \\u003cli\\u003eVC: Ver\\u0026oacute;nica Ca\\u0026ntilde;\\u0026oacute;n\\u003c/li\\u003e\\n \\u003cli\\u003eJA: Javier Anchuelo\\u003c/li\\u003e\\n \\u003cli\\u003eCL: Claudia Laborda\\u003c/li\\u003e\\n \\u003cli\\u003eAGa: Ana Gal\\u0026aacute;n\\u003c/li\\u003e\\n \\u003cli\\u003eALR: Ana Laura Rivero\\u003c/li\\u003e\\n \\u003cli\\u003eFP: Frande\\u0026iacute;na Pinto\\u003c/li\\u003e\\n \\u003cli\\u003eMG: Mara Garc\\u0026iacute;a\\u003c/li\\u003e\\n \\u003cli\\u003ePN: Paola Navarrete\\u003c/li\\u003e\\n \\u003cli\\u003ePG: Piedad Gald\\u0026oacute;s\\u003c/li\\u003e\\n \\u003cli\\u003eAAli: Ana Aliaga\\u003c/li\\u003e\\n \\u003cli\\u003eAAye: Arantxa Ayete\\u003c/li\\u003e\\n \\u003cli\\u003eCG: Cristina Garc\\u0026iacute;a\\u003c/li\\u003e\\n \\u003cli\\u003eGL: Gemma Liria\\u003c/li\\u003e\\n \\u003cli\\u003eMC: Maria Cerrolaza\\u003c/li\\u003e\\n \\u003cli\\u003eRF: Rosa Fabregat\\u003c/li\\u003e\\n \\u003cli\\u003ePJPr: Pedro Jos\\u0026eacute; Prada\\u003c/li\\u003e\\n\\u003c/ul\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate\\u003c/strong\\u003e\\u003cp\\u003e The study was conducted in accordance with institutional ethical standards and the principles of the Declaration of Helsinki. Ethical approval was obtained from the local ethics committee of the participating center. Written informed consent for radiotherapy treatment was obtained from all patients at the time of treatment.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003cp\\u003eNot applicable. This study does not contain identifiable personal data from any individual participant.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003ch2\\u003eCompeting interests\\u003c/h2\\u003e\\u003cp\\u003eThe authors declare that they have no competing interests.\\u003c/p\\u003e\\u003c/p\\u003e\\u003ch2\\u003eFunding\\u003c/h2\\u003e\\u003cp\\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\\u003c/p\\u003e\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\u003cp\\u003eVC, JA, and PJPr conceived the study and supervised the clinical coordination.CL, AGa, ALR, FP, MG, PN, PG, AAli, AAye, CG, GL, MC, and RF participated in patient data collection and treatment delivery.JA and CL performed the data analysis and interpretation.JA drafted the manuscript.All authors critically reviewed the content, contributed to revisions, and approved the final version of the manuscript.Abbreviations:\\u0026bull;VC: Ver\\u0026oacute;nica Ca\\u0026ntilde;\\u0026oacute;n\\u0026bull;JA: Javier Anchuelo\\u0026bull;CL: Claudia Laborda\\u0026bull;AGa: Ana Gal\\u0026aacute;n\\u0026bull;ALR: Ana Laura Rivero\\u0026bull;FP: Frande\\u0026iacute;na Pinto\\u0026bull;MG: Mara Garc\\u0026iacute;a\\u0026bull;PN: Paola Navarrete\\u0026bull;PG: Piedad Gald\\u0026oacute;s\\u0026bull;AAli: Ana Aliaga\\u0026bull;AAye: Arantxa Ayete\\u003c/p\\u003e\\u003ch2\\u003eAcknowledgements\\u003c/h2\\u003e\\u003cp\\u003eThe authors would like to thank the staff of the Radiation Oncology Department for their support in patient care and treatment delivery. No professional medical writing assistance was used in the preparation of this manuscript.\\u003c/p\\u003e\\u003ch2\\u003eAvailability of data and materials\\u003c/h2\\u003e\\u003cp\\u003eAll data generated or analyzed during this study are included in this published article. Additional anonymized data may be available from the corresponding author upon reasonable request.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eRanghino A, Segoloni GP, Lasaponara F, et al. Lymphatic disorders after renal transplantation: new insights for an old complication. ClinKidney J. 2015;8:615\\u0026ndash;22.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eGiovannacci L, Eugster T, Stierli P, et al. Does fibrin glue reduce complications after femoral artery surgery? A randomised trial. Eur J VascEndovascSurg. 2002;24:196\\u0026ndash;201.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eDietl B, Pfister K, Aufschlager C, et al. Radiotherapy of inguinal lymphorrhea after vascular surgery. A retrospective analysis. StrahlentherOnkol. 2005;181:396\\u0026ndash;400.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eRamasastry SS, Liang MD, Hurwitz DJ. Surgical management of difficult wounds of the groin. SurgGynecol Obstet. 1989;169:418\\u0026ndash;22.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eTyndall SH, Shepard AD, Wilczewski JM, et al. Groin lymphatic complications after arterial reconstruction. J VascSurg. 1994;9:858\\u0026ndash;63.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eHackert T, Werner J, Loos M, et al. Successful doxycycline treatment of lymphatic fistulas: report of five cases and review of the literature. Langenbecks Arch Surg. 2006;391:435\\u0026ndash;8.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eKhorramO, Stern JL. Bleomycinsclerotherapy of an intractable inguinal lymphocyst. GynecolOncol. 1993;50:244\\u0026ndash;6.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eSun GH, Fu YT, Wu CJ, et al. Povidone-iodine instillation for management of pelvic lymphocele after pelvic lymphadenectomy for staging prostate cancer. ArchAndrol. 2003;49:463\\u0026ndash;6.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eTwine CP, Lane IF, Williams IM. Management of lymphatic fistulas after arterial reconstruction in the groin. Ann Vasc Surg. 2013;27:1207\\u0026ndash;15.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eVan Den Brande P, Von Kemp K, Aerden D, et al. Treatment of lymphocutaneous fistulas after vascular procedures of thelowerlimb: accuratewoundreclosure and 3 weeks of consistent and continuingdrainage. Ann Vasc Surg. 2012;26:833\\u0026ndash;8.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eSeegenschmiedt MH, Katalinic A, Makoski HB, et al. Radiotherapy of benign disease: a patterns of care study in Germany. Strahlenther Onkol. 1999;175:541\\u0026ndash;7.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eMucke R, Schonekaes K, Micke O, et al. Low-dose radiotherapy for painful heel spur. Retrospective study of 117 patients. Strahlenther Onkol. 2003;179:774\\u0026ndash;8.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eMeineke V, Uebler C, Kohn FM, et al. Radiotherapy in benign diseases: Morbus Peyronie. Strahlenther Onkol. 2003;179:181\\u0026ndash;6.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eHeyd R, Seegenschmiedt MH, Strassmann G, et al. German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD). Radiotherapy for Graves\\u0026rsquo; orbitopathy: results of a national survey. Strahlenther Onkol. 2003;179:372\\u0026ndash;6.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eNeu B, Gauss G, Haase W, et al. Radiotherapy of lymphatic fistula and lymphocele. Strahlenther Onkol. 2000;176:9\\u0026ndash;15.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eLara PC, Russel NS, Smolders IJ, Bartelink H, Begg AC, Coco-Martin JM. Radiation-induced differentiation of human skin fibroblasts: Relationship with cell survival and collagen production. Int J Radiat Biol. 1996;70:683\\u0026ndash;92.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eMayer R, Sminia P, McBride WH, et al. Lymphatic fistulas: obliteration by low-dose radiotherapy. Strahlenther Onkol. 2005;181(10):660\\u0026ndash;4.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eHabermehl D, Habl G, Eckstein HH, Meisner F, Combs SE. Radiotherapeutic management of lymphatic fistulas: An effective but disregarded therapy option. Chirurg. 2017;88(4):311\\u0026ndash;6.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eHautmann MG, Dietl B, Wagner L, et al. Radiation Therapy of lymphatic fistulae after vascular surgery in the groin. Int J Radiat Oncol Biol Phys. 2021;15(4):949\\u0026ndash;58.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eJazmati D, Tamaskovics B, Hoff NP, et al. Percutaneous fractionated radiotherapy of the groin to eliminate lymphatic fistulas after vascular surgery. Eur J Med Res. 2023;9(1):70.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"radiation-oncology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"raon\",\"sideBox\":\"Learn more about [Radiation Oncology](http://ro-journal.biomedcentral.com/)\",\"snPcode\":\"13014\",\"submissionUrl\":\"https://submission.nature.com/new-submission/13014/3\",\"title\":\"Radiation Oncology\",\"twitterHandle\":\"@OncoBioMed\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC/SO AJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Lymphorrhea, Lymphatic fistula, Low-dose radiotherapy, Benign pathology, External beam radiation therapy\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-7077827/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-7077827/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eLymphorrhea is a complication that can arise after vascular, abdominal or pelvic interventions and is associated with significant morbidity. While conservative management is typically effective, some cases remain refractory.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis retrospective cross-sectional study analyzed 43 patients with persistent inguinal lymphorrhea treated at a tertiary hospital between 2008 and 2018. All patients received external beam radiotherapy (EBRT) using 3D conformal techniques with photons (6–18 MV). The delivered dose was 7.5 Gy in five 1,5 Gy/fractions.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eComplete closure of the lymphatic fistula was achieved in all patients. Three required reirradiation with the same schedule to reach complete resolution. No acute or late toxicity was observed in any case.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusions:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eLow-dose EBRT is a safe and effective treatment option for persistent lymphorrhea refractory to conservative measures. Its anti-inflammatory and fibrosing effects support its therapeutic use in benign lymphatic complications.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTrial Registration\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Radiotherapy for benign conditions: management of persistent lymphorrea\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-07-18 13:20:30\",\"doi\":\"10.21203/rs.3.rs-7077827/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2025-08-11T09:33:40+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2025-07-28T22:33:59+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"146038866801744508942905337746073627033\",\"date\":\"2025-07-18T08:06:03+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2025-07-14T11:26:26+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2025-07-10T05:24:36+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2025-07-09T04:29:48+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Radiation Oncology\",\"date\":\"2025-07-08T19:52:32+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"radiation-oncology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"raon\",\"sideBox\":\"Learn more about [Radiation Oncology](http://ro-journal.biomedcentral.com/)\",\"snPcode\":\"13014\",\"submissionUrl\":\"https://submission.nature.com/new-submission/13014/3\",\"title\":\"Radiation Oncology\",\"twitterHandle\":\"@OncoBioMed\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC/SO AJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"cb0511e2-d16d-4721-9519-2ef508139321\",\"owner\":[],\"postedDate\":\"July 18th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-12-22T16:08:25+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-7077827\",\"link\":\"https://doi.org/10.1186/s13014-025-02746-0\",\"journal\":{\"identity\":\"radiation-oncology\",\"isVorOnly\":false,\"title\":\"Radiation Oncology\"},\"publishedOn\":\"2025-12-20 15:57:49\",\"publishedOnDateReadable\":\"December 20th, 2025\"},\"versionCreatedAt\":\"2025-07-18 13:20:30\",\"video\":\"\",\"vorDoi\":\"10.1186/s13014-025-02746-0\",\"vorDoiUrl\":\"https://doi.org/10.1186/s13014-025-02746-0\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-7077827\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-7077827\",\"identity\":\"rs-7077827\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}