What impact local failure after post-operative radiotherapy of resected brain metastases in breast cancer patients

What impact local failure after post-operative radiotherapy of resected brain metastases in breast cancer patients | 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 What impact local failure after post-operative radiotherapy of resected brain metastases in breast cancer patients Ory Haisraely, Zvi Symon, Thila Kaisman-elbaz, Anton Whol, Zvi Cohen, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3832058/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 Background Single brain metastasis surgical resection remains an effective treatment for brain metastases. However, surgery alone associate with a high rate of local failure. The current guidelines recommend radiation to surgical cavity. The recommended dose for brain cavity after surgery remain to be define as most guidelines gives a very general suggestion about the dose and fractionation. The aim of this study was to determine what variable influence local control in this specific population. Methods Retrospective analysis of 62 patients with breast cancer who undergo surgical resection to single brain metastases and who received post-operative radiotherapy between the years 2011–2022. All clinical and dosimetric variables were analyzed to evaluate their impact on local control. Results One year local control was 70.9%. HER-2 disease, size of initial tumor, time from initial surgery, total dose deliver, inclusion of corridor and type of lesion were all significant for local control. Patients with HER-2 positive disease had higher local control rate without any difference in other variables. Conclusion Brain metastases from breast cancer remain a life-threating condition. Surgery plays a critical role in the treatment of large symptomatic brain metastases for which Post-operative radiotherapy is essential. Choosing a regime with a dose of more then 40Gy (BED) seems important for achieving local control and without increase toxicity. Different biology and systemic therapy options can differentiate Breast cancer population after brain surgery for metastatic disease. A larger prospective trial is needed to addressed the question whether lower dosage can be use in HER-2 positive disease. Introduction Bain metastases are a major cause of mortality in breast cancer 1 . The brain is the first site of metastasis from breast cancer in 12 % of patients. Metastatic breast cancer (BC) is, after lung cancer, the second most common cancer associated with brain metastases. As cancer research breakthroughs considerably improved survival of patients with advanced stage BC in the last decades, the incidence of BMs is increasing accordingly 2 . It has been suggested that brain metastases from breast cancer (BMBC) occur more frequently among younger women, those with larger tumors or higher nuclear grade, in certain subtypes such as estrogen-receptor (ER)-negative and HER2 overexpressing tumors, and those with nodal metastases 3 . Single brain metastasis surgical resection remains an effective treatment for brain metastases, especially for larger lesions causing mass effect and consequentially serious neurological symptoms 4 . However, surgery alone associate with a very high rate of local failure that can be high up to 70% for 1 year. 5,6 In most patients who undergo surgery, focal radiation of the surgical cavity may be suggested to reduce the risk of local relapse. In this regard, a randomized clinical trial (RCT) evaluated stereotactic RT to the resection cavity after surgery of BMs. After a median follow-up of 11.1 months, 12-month freedom from local recurrence was 43% (95% CI, 31–59) in the observation group compared to 72% in the stereotactic RT group (hazard ratio, HR, 0.46, 95% CI: 0.24–0.88, p = 0.015). There were no adverse events or treatment-related deaths in either group . Another RCT compared stereotactic RT with whole-brain radiotherapy (WBRT), showing no differences in overall survival (OS), but more frequent decline in cognitive function after WBRT (median cognitive-deterioration-free survival: stereotactic RT, 3.7 months, 95% CI, 3.45–5.06; WBRT, 3 months, 95% CI, 2.86–3.25; HR: 0.47, 95% CI, 0.35–0.63, p < 0.0001) . On this basis, the International Stereotactic Radiosurgery Society recommends stereotactic RT as standard of care in post-resection eligible patients 7,8 The current guidelines of both Society of neuro-oncology and the international stereotactic radiosurgery recommend radiation to surgical cavity 9 . The recommended dose for brain cavity after surgery remain to be define as most guidelines gives a very general suggestion about the dose and fractionation. In addition, specific dose control relationship has never been published for breast cancer metastases. The unique radio-sensitivity and other biological aspect of this etiology need to be addressed. Here we perform a comprehensive analysis of dosimetry, biology and clinical variable and their influence on local control and on brain failure among breast cancer patients who been treated with surgery and post-operative fractionated stereotactic radiotherapy for a single brain metastasis. Methods Institutional review board approval for a retrospective review was obtained. Inclusion criteria were all patients treated between 2012-2022 with radiotherapy to the surgical cavity after craniotomy for a single brain metastases of breast cancer origin based upon pathology report. We excluded patients who had previously received either RT or WBRT or neo-adjuvant SRS for the resected lesion. Background demographics, pathologic and radiographic data, prior oncologic therapy, and detailed radiotherapy data was extracted from the electronic medical record and from institutional radiotherapy databases. Local failure was defined as tumor growth in the surgical cavity inside the Planning target volume as defined by other works 7 . Time to failure was calculated from the completion of radiotherapy. Toxicity was evaluated and graded by CTCAE v5.0 criteria. Statistical analysis Descriptive analyses were performed using mean and SD for parametric variables and median with range for non-parametric variables. X 2 test was used for categorical variables. Total dose (BED) and dose per fraction and planning target volumes were analyzed as both a continues and categorical variables at different thresholds. A binary regression model was applied to study variables shown to have an impact on local control Data was analyzed using statistical software SPSS V26 (version 26, IBM © , Armonk, NY, USA). Results A total of 62 patients with the diagnosis of brain metastatic breast cancer who had undergone surgery and post-operative radiation were treated at our institution from 2010-2022. The median age was 53.5 years. Breast cancer type was predominantly HER-2 positive (40.3%), among them 5 were ER/PR positive and 20 were ER/PR negative. Luminal A was the histology pattern in 8% and luminal B in 22.5%. Triple negative disease was in 29% of the cohort. Patient's presentation was variable. The most frequent complaint was loss of gross limb weakness with secondary headache, aphasia and imbalance. 30.4% of patients had widespread systemic metastatic disease while surgery. Six patients had solitary brain lesion with the rest of the cohort presented with oligometastatic disease. The most frequent location was frontal lobe (35.4%). Solid appearance was more prevalent than cystic (69.4% and 30.6% respectively). Radiation was initiated on average 33 days from surgery with a range of 16 up to 48 days. Patients' characteristics are presented in table 1. Radiation treatment A total of 40 radiation treatment were delivered using VMAT, 20 using IMRT and two with 3D planning. A BED calculated using α/β of 10 Using this approach, the median dose was 37.5Gy (28Gy to 59.5Gy (BED10) ). Clinical target volume (CTV) was defined as the surgical cavity. CTV to planning target volume (PTV) was expand 2-5mm. In 79% of cases the surgical corridor was included in the CTV. The avarge PTV was 67.1 cc(23.4-112.6). During this analysis we used the TG101 report constrains 8 . In all 62 treatment planning dose constrain were met. Radiotherapy parameters are shown in Table 2 Local control The one-year local control rate was 70.3%.. The total brain failure after 1 year was 41.6%. Among them 18 patients had only local failure 15 received salvage radiosurgery and 3 received systemic therapy. 6 had distant brain failure without local failure and all received radiosurgery for the new lesion. Clinical and survival outcomes are presented in table 3. Impact on local control One year local control was 70.9%. We compare different variables between patients who achieved local control and those who did not. The median planning target volume was significantly larger among those who had experienced local failure (83.7cc vs 56.2cc, P=0.042). Size of a initial tumor was also important in achieving local control. Size of tumor above 5cm was distributed differently between those with local control and local failure with 18.1% and 66.7% respectively (p<0.001). The total dose delivered was lower for those with local failure with a median of 37.5Gy for local failure and 42.5Gy for local control (p=0.008). In regards to the biology of breast cancer. We notice different distribution of HER-2 positive disease among those who had local control and those who did not (50% vs16.1%, P=0.015). Local control was associated with the inclusion of surgical corridor within the PTV(P=0.034) in addition shorter time to radiotherapy from initial surgery with a median of 26.9 days for those who achived local control versus 32.5 days for those who didn't (p=0.039). Cystic lesion were more prevalence in recurring lesion then in control lesions (55.5% and 20.4% respectively P<0.009). The location of the tumor was also significance for local control, there was higher rate of cerebral location for those were recurred than for the control lesions (27.7% vs 6.8%, P=0.039). Table 4 demonstrate all clinical variable between control lesion to reccuring lesion after 1 year and odds ratio for failure. There was no association between the age and the oncological setting and local control. Multivariable analysis was not available due to a small sample size. Discussion In this retrospective cohort we evaluate the variable impact local control among a specific group of metastatic breast cancer undergoing surgery and post-operative RT. We found that the tumor biology, size, and are all significant for local control in addition to time from initial surgery. Our local control rate is lower than previously studies that showed local control rate of 70-95% 4,7,11,12 . That can be partially explained by a high percentage of patients receiving a lower dose of our trial compare to the others. In our study 46% received a BED (10) lower then 40 (i.e 25 Gy in 5 fraction) which recently been shown by Minnti et al to decrease local control 12 . We demonstrated correlation between dose and local control. In our analysis we used an α/β ratio of 4Gy which is more realistic in breast cancer tumors 14 . We notice that Dose above 70Gy (BED4) had HR of 0.51 (CI 0.16-0.91) even when adjusting to other variables. Another explanation of the lower local rate results in our cohort is the timing from initial surgery until start of radiation. In a recent Meta-analysis of post-operative SRS showed a Lower local control when surgery-to-SRS delay longer than 3 weeks. The estimated 12-month control rates dropped from 87 to 61% if SRS was performed more than 3 weeks after resection 15 . In our study the median day for starting radiation was 33. We found that starting radiation more than 30 days from surgery has a HR of 1.46 (1.13-2.78) for local failure. In regards to other parameters. The average size of tumor in our cohort was similar to other studies 16,17 and reflects the current change in practice to operate only on symptomatic large lesions, with the remainder undergoing definitive radiosurgery. Tumor larger than 3.5 cm had significantly worsen local failure with HR of 1.61 (CI 1.11-1.31). The current guidelines recommend the inclusion of surgical tract with 1-5 mm margin 13 . In our cohort inclusion of surgical tract was seen in 64.7% of those who achieved local control and 55.5% at those who didn’t. However, this difference did not reach statistical significance. Different studies had shown contradictory results on the impact of cystic lesions and response to local treatment. 18 Studies have suggested that the causes of cystic masses may include the breakdown of the blood–brain barrier or the higher risk of developing cystic BM in patients with poor histological grade ,18,19 . In addition, the complications seen in operations on cystic lesion and the less than Gross tumor resection achieved can have an impact on overall survival and local control respectively 20 . in our study cystic had much higher risk of local failure with HR of 1.55 (1.13-2.34). Toxicity We found 8 cases of reported radiation necrosis on MRI. Two of whom were asymptomatic. The two symptomatic patients were treated successfully with dexamethasone. In the entire cohort 38% reported Grade 2 fatigue and 11% with Grade 2 headache. Breast cancer biology Different classical sub- types of breast cancer have different biology in regards of brain metastases prevalence, pathophysiology and response to treatment 18 . HER2-positive breast cancer has the inherent tendency of metastasis to the brain but because of variable systemic treatment options with good brain response and even longer survival among all breast cancer population with brain metastases 20 . Surprisingly, in our cohort patients the prevalence of HER-2 sub type was higher among those who achieved local control. Having HER-2 disease decrease the odds for local failure (OR=0.2). the population of paitents with HER-2 disease wasn't different in any of the other variables with the population oh HER-2 negative disease (table 5) The different in local control can be explained by the fact that most patients in our cohort had visceral metastatic disease at presentation and received systemic therapy after the course of radiation. HER-2 targeted therapy like transtuzumab, transtuzumab-emtansine, fam-transtuzumab-deruxtecan, lapatinib with capecitabine and tucatinib have all high response rate in the CNS 21,22 . In the TUDEXO-1 trial recently showed 83% intracranial response 23 . and can help reduced the risk of recurrence by effectively treating microscopic disease. This advantage is lacking in other sub-type populations. Our study has some limitations including the retrospective nature of the data and the fact that it is a single institution analysis. On the other hand, the advantageous of our study is the relative large homogenous cohort of only breast cancer patients with single brain metastases who had resection. Most of the Current literature of post-operative radiotherapy analyzed all sub types of cancer in the same manner without consideration of the different biology of each tumor type. Conclusions Brain metastases from breast cancer remain a life-threating condition. Surgery plays a critical role in the treatment of large symptomatic brain metastases for whom Post-operative radiotherapy is essential. Choosing a regime with a dose of more than 40Gy (BED) seem important for achieving local control and without increase toxicity. We have defined the clinical characteristics associated with local failure amongst brain metastases of breast cancer origin following surgical resection and post-operative irradiation. Higher radiation dose is associated with both higher rates of local control but also increased rates of radiation brain injury. Larger trails need in order to addressed individualization of the dosage in regards to all clinical variables. Abbreviations BC-Breast cancer, ER-Estrogen receptor, RCT-randomized clinical trial, OS- over all survival, LC-local control, WBRT-whole brain radiotherapy, CTV- clinical target volume, PTV-planning target volume. Declarations Author contribution OH- study conception and design, data collection, statistical analysis ZS, YL-data collection, analysis and interpretation of results TKE, OG- analysis and interpretation of results ZC,AW- data collection AT- draft manuscript preparation, analysis and interpretation of results Ethical Approval and Consent to participate - IRB approval number 0265-23-SMC Consent for publication - This article has not been published before. All authors read this manuscript and approved it submission Availability of supporting data - none Competing interests/Authors' contributions - none Funding - none References Yajie Wang et al, Breast cancer brain metastasis: insight into molecular mechanisms and therapeutic strategies, Br J Cancer, 2021 Oct;125(8):1056-106 C corti, Targeting brain metastases in breast cancer, Cancer Treatment Reviews, 2022-02-01, Volume 103 Sava A, Brain metastases originating in breast cancer: clinical-pathological analysis and immunohistochemical profile, Rom J Morphol Embryol. 2021 Apr-Jun; 62(2): 435–444. Chibawanye I. Ene et al, Surgical Management of Brain Metastasis: Challenges and Nuances, Front Oncol. 2022; 12: 847110. Patchell RA et al, Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial, JAMA,1998 Nov 4;280(17):1485-9.. Kocer M et al, Adjuvant Whole-Brain Radiotherapy Versus Observation After Radiosurgery or Surgical Resection of One to Three Cerebral Metastases: Results of the EORTC 22952-26001 Study, J Clin Oncol. 2011 Jan 10; 29(2): 134–141 A Mahajan et al, Prospective Randomized Trial of Post-operative Stereotactic Radiosurgery versus Observation for Completely Resected Brain Metastases, Lancet 2017 Aug Brown PD et al, Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial, lancet 2017 Aug. Stanley H Benedict et al, Stereotactic body radiation therapy: the report of AAPM Task Group 101, Med Phys 2010 Aug;37(8) Redmina KJ et al, Stereotactic Radiosurgery for Postoperative Metastatic Surgical Cavities: A Critical Review and International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines, Int J Radiat Oncol Biol Phys, 2021 Sep Kumar AMS et al Postoperative hypofractionated stereotactic brain radiation (HSRT) for resected brain metastases: improved local control with higher BED 10 . J Neurooncol. 2018;139:449–54 Gui C et al. Local recurrence patterns after postoperative stereotactic radiation surgery to resected brain metastases: a quantitative analysis to guide target delineation. Pract Radiat Oncol. 2018;8:388–96. Musunuru HB et al, Impact of adjuvant fractionated stereotactic radiotherapy dose on local control of brain metastases. J Neurooncol. 2019;145:385–90. Minnti G et al, Current status and recent advances in resection cavity irradiation of brain metastases, Radiation oncology, 15 Apr 2021 C. M. van Leeuwen et al, The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies, radiation oncology, 16 May 2018 D. Early et al, Gamma Knife stereotactic radiosurgery to the tumor bed of resected brain metastasis for improved local control. J Neurosurg. 2014;121(Suppl):69–74. Ahmed KA et al, Fractionated stereotactic radiotherapy to the post-operative cavity for radioresistant and radiosensitive brain metastases. J Neurooncol. 2014;118:179–186 Keller A et al, Hypofractionated stereotactic radiation therapy to the resection bed for intracranial metastases. Int J Radiat Oncol Biol Phys. 2017;99:1179–1189. Wang H et al, Cystic brain metastases had slower speed of tumor shrinkage but similar prognosis compared with solid tumors that underwent radiosurgery, treatment Cancer Management and Research, 2019, volume 11 Pages 1753—1763 Santai Song et al, Cystic brain metastasis is associated with poor prognosis in patients with advanced breast cancer, Oncotarget. 2016 Nov 8; 7(45): 74006–74014 Hongna Sun et al, Breast cancer brain metastasis: Current evidence and future directions, cancer medicine, 2023 ;12:1007–1024 E. Stavrou et al, How we treat HER2-positive brain metastases, ESMO Open. 2021 Oct; 6(5): 100256. Bartsch R, Berghoff A, Furtner J, et al. 280P - Intracranial activity of trastuzumab-deruxtecan (T-DXd) in HER2-positive breast cancer patients with active brain metastases: Results from the first stage of the phase II TUXEDO-1 trial. Annals of Oncology . 16 Sep 2021;32(S457-S515) Tables Table 1 Patients characteristics Variable Number of patients 62 Age (mean, range) 53 (23-78) Breast CA type Luminal A Luminal B HER-2 positive Triple negative 5 (8%) 14 (22.5%) 25 (40.3%) 18 (29%) GPA 0-1 1.5-2 2.5-3 3.5-4 0 (0%) 9 (14.5%) 23 (37%) 30 (48.3%) Size of metastases 0.5-1.99cm 2-3.99cm 4-4.99cm 5-6.99cm >7cm 3 (4.8%) 10 (16%) 28 (45.1%) 15 (24.1%) 5 (8%) Location Frontal Parietal Temporal Occipital Cerebellum 22 (35.4%) 13 (20.9%) 10 (16.1%) 8 (12.9%) 8 (12.9%) Type of lesion Solid Cystic 43 (69.3%) 19 (30.6%) Time from surgery to RT in Days (mean, range) 33(20-61) Clinical presentation Solitary brain lesion Oligometastatic disease (<5 mets) Metastatic disease 6 (9.6%) 37 (59.6%) 19 (30.6%) Table 2 –radiation parameters Variable PTV (median, range) 67.1 cc(23.4-112.6) Dose (BED α/β=10) (median, range) 37.5Gy (28-59.5) All dosage regiment Total dose (Gy), n of fraction (BED α/β=10) 24Gy,3 (43.2) 24Gy,4 (38.4) 20Gy,4 (30) 25Gy,5 (37.5) 27.5Gy,5 (42.6) 30Gy,5 (48) 32.5Gy,5 (53.3) 30Gy,6 (45) 35Gy,7 (59.5) 4 (6.4%) 1 (1.6%) 3 (4.8%) 32 (51.6%) 6 (9.6%) 11 (17.7%) 2 (3.2%) 2 (3.2%) 1 (1.6%) Dose>40Gy 38.8% Inclusion of corridor in PTV 79% Days from surgery to RT (median, range) 28.5 (16-44) >28 days from RT 50% BrainV25 (Brain-PTV) (median, range) 4.4cc(0-9.1cc) Table 3- outcome parameters follow up months (median, range) 28 (14-43) 1 year LC (%) 70.9% Radiation necrosis (%) Asymptomatic Symptomatic 12.9% 6 2 1 year brain failure (local + distant) (%) 41.9% 1 years distant only brain failure (%) 12.9% 1 year Overall survival (%) 80.6% Table 4 local control vs local failure after 1 year Variables Local control (n=44) Local progression(n=18) OR (CI95%) P Age 53Y 53.5Y 0.97 (0.74-2.1) 0.87 HER-2 positive (yes) 50% 16.7% 0.2(0.05-0.79) 0.015 Size of tumor (>5cm) 18.1% 66.7% 9 (2.5-31.2) 40Gy 52.5% 16.6% 0.18 (0.049-0.79) 0.015 Inclusion of surgical corridor (Yes) 13.6% 38.3% 4.03 (1.1-14.5) 0.034 Time from surgery to radiation (days median, range) 26.9days (18-42) 32.5days (16-44) 0.009 Time from surgery >28days 38.6% 77.8% 5.5 (1.56-19.7) 0.008 Type of metastases ( Cystic ) 20.4% 55.5% 4.8(1.4-15.8) 0.009 Location (cerebellum) 6.8% 27.7% 5.2(1.1-25.4) 0.039 Clinical presentation ( solitary brain lesion ) 9% 11.1% 1.25(0.2-7.5) 0.8 Table 5 Her -2 disease HER-2 positive (n=25) HER-2 negative (n=37) P Age 55y 52.2y 0.76 BED>40Gy 40% 37.8% 0.39 Days to RT >28days 56% 45.9% 0.93 Inclusion of corridor 76% 81% 0.62 Cystic lesion 32% 29.7% 0.84 Location at cerebellum 16% 10.8% 0.54 Size of tumor >5cm 28% 35.1% 0.6 Additional Declarations No competing interests reported. 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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-3832058","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":267559680,"identity":"6be7aa55-31d1-447d-ada9-b61dd4fd821c","order_by":0,"name":"Ory Haisraely","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABE0lEQVRIie3RsUrEMBjA8YRApx5dvxs0rxB3oa/SINx00LWD1BYhUx6ggniv0EO40WsJnEseoE4Kgi4O53aL4pe70ba33pD/mObXL2kJ8flOsIhbwUKRx/Ft9MHCLJfrRVmQXWYIr/rJtJojyUDWzzpgoTWyBtNQbQ0JoJ+IbpbgTkiEtQG9Uw0SXKFqjFw1bKKQdPOAfD84gkelajZMXtuC/SiI4yrdELnKb9ZcHyO0cFPoE+AUuWKHKWdj5KVE8gv0kX8huXck3eJLLkfu0h6mLCs3pXAEv+EYmVayMEhk7a6fbMz+YK22EA6RCGT5PlF5LLr0c5tcu1+pL952GZzzRdNvsP9P3Eo4uN/n8/l8R/sDW4xqFzVaRjAAAAAASUVORK5CYII=","orcid":"","institution":"Sheba Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Ory","middleName":"","lastName":"Haisraely","suffix":""},{"id":267559681,"identity":"710cdd06-baba-4425-8f7c-0a1f4be493ce","order_by":1,"name":"Zvi Symon","email":"","orcid":"","institution":"Sheba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Zvi","middleName":"","lastName":"Symon","suffix":""},{"id":267559682,"identity":"6ba866d7-cfa2-46d9-99bc-8ee12d988773","order_by":2,"name":"Thila Kaisman-elbaz","email":"","orcid":"","institution":"Sheba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Thila","middleName":"","lastName":"Kaisman-elbaz","suffix":""},{"id":267559683,"identity":"b3ee91eb-5e46-4aba-8f64-224de5e9da33","order_by":3,"name":"Anton Whol","email":"","orcid":"","institution":"Sheba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Anton","middleName":"","lastName":"Whol","suffix":""},{"id":267559684,"identity":"4828cf4b-e923-4a28-9da9-427a89cee44e","order_by":4,"name":"Zvi Cohen","email":"","orcid":"","institution":"Sheba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Zvi","middleName":"","lastName":"Cohen","suffix":""},{"id":267559685,"identity":"e8825392-8e7e-40a8-8f7f-b337cd6f7471","order_by":5,"name":"Alica Taliansky","email":"","orcid":"","institution":"Sheba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Alica","middleName":"","lastName":"Taliansky","suffix":""},{"id":267559686,"identity":"f988a7a7-8971-48b5-8280-718db120fbea","order_by":6,"name":"Yaacov Lawerence","email":"","orcid":"","institution":"Sheba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yaacov","middleName":"","lastName":"Lawerence","suffix":""}],"badges":[],"createdAt":"2024-01-03 14:29:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3832058/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3832058/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50822969,"identity":"2f0c7532-88d7-426c-9781-d722f3b4daa7","added_by":"auto","created_at":"2024-02-07 22:10:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":275471,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3832058/v1/efbe5038-5808-4862-a6ea-69ebee1a5c71.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"What impact local failure after post-operative radiotherapy of resected brain metastases in breast cancer patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBain metastases are a major cause of mortality in breast cancer\u003csup\u003e1\u003c/sup\u003e. The brain is the first site of metastasis from breast cancer in 12 % of patients.\u0026nbsp;Metastatic breast cancer (BC) is, after lung cancer, the second most common cancer associated with brain metastases. As cancer research breakthroughs considerably improved survival of patients with advanced stage BC in the last decades, the incidence of BMs is increasing accordingly\u003csup\u003e2\u003c/sup\u003e. It has been suggested that brain metastases from breast cancer (BMBC) occur more frequently among younger women, those with larger tumors or higher nuclear grade, in certain subtypes such as estrogen-receptor (ER)-negative and HER2 overexpressing tumors, and those with nodal metastases\u003csup\u003e3\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSingle brain metastasis surgical resection remains an effective treatment for brain metastases, especially for larger lesions causing mass effect and consequentially serious neurological symptoms\u003csup\u003e4\u003c/sup\u003e. However, surgery alone associate with a very high rate of local failure that can be high up to 70% for 1 year.\u003csup\u003e5,6\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIn most patients who undergo surgery, focal radiation of the surgical cavity may be suggested to reduce the risk of local relapse. In this regard, a randomized clinical trial (RCT) evaluated stereotactic RT to the resection cavity after surgery of BMs. After a median follow-up of 11.1\u0026nbsp;months, 12-month freedom from local recurrence was 43% (95% CI, 31\u0026ndash;59) in the observation group compared to 72% in the stereotactic RT group (hazard ratio, HR, 0.46, 95% CI: 0.24\u0026ndash;0.88, p\u0026nbsp;=\u0026nbsp;0.015). There were no adverse events or treatment-related deaths in either group\u0026nbsp;. Another RCT compared stereotactic RT with whole-brain radiotherapy (WBRT), showing no differences in overall survival (OS), but more frequent decline in cognitive function after WBRT (median cognitive-deterioration-free survival: stereotactic RT, 3.7\u0026nbsp;months, 95% CI, 3.45\u0026ndash;5.06; WBRT, 3\u0026nbsp;months, 95% CI, 2.86\u0026ndash;3.25; HR: 0.47, 95% CI, 0.35\u0026ndash;0.63, p\u0026nbsp;\u0026lt;\u0026nbsp;0.0001)\u0026nbsp;. On this basis, the International Stereotactic Radiosurgery Society recommends stereotactic RT as standard of care in post-resection eligible patients\u003csup\u003e7,8\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eThe current guidelines of both Society of neuro-oncology and the international stereotactic radiosurgery recommend radiation to surgical cavity\u003csup\u003e\u0026nbsp;9\u003c/sup\u003e. The recommended dose for brain cavity after surgery remain to be define as most guidelines gives a very general suggestion about the dose and fractionation. In addition, specific dose control relationship has never been published for breast cancer metastases. The unique radio-sensitivity and other biological aspect of this etiology need to be addressed. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHere we perform a comprehensive analysis of dosimetry, biology and clinical variable and their influence on local control and on brain failure among breast cancer patients who been treated with surgery and post-operative fractionated stereotactic radiotherapy for a single brain metastasis.\u003c/p\u003e"},{"header":"Methods ","content":"\u003cp\u003eInstitutional review board approval for a retrospective review was obtained. Inclusion criteria were all patients treated between 2012-2022 with radiotherapy to the surgical cavity after craniotomy for a single brain metastases of breast cancer origin based upon pathology report. We excluded patients who had previously received either RT or WBRT or neo-adjuvant SRS for the resected lesion.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBackground demographics, pathologic and radiographic data, prior oncologic therapy, and detailed radiotherapy data was extracted from the electronic medical record and from institutional radiotherapy databases.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLocal failure was defined as tumor growth in the surgical cavity inside the Planning target volume as defined by other works\u003csup\u003e7\u003c/sup\u003e. Time to failure was calculated from the completion of radiotherapy. \u0026nbsp; Toxicity was evaluated and graded by CTCAE v5.0 criteria.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDescriptive analyses were performed using mean and SD for parametric variables and median with range for non-parametric variables. X\u003csup\u003e2\u003c/sup\u003e test was used for categorical variables. Total dose (BED) and dose per fraction and planning target volumes \u0026nbsp;were analyzed as both a continues and categorical variables at different thresholds. \u0026nbsp;A binary regression model was applied to study variables shown to have an impact on local control Data was analyzed using statistical software SPSS V26 (version 26, IBM\u003csup\u003e\u0026copy;\u003c/sup\u003e, Armonk, NY, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 62 patients with the diagnosis of brain metastatic breast cancer who had undergone surgery and post-operative radiation were treated at our institution from 2010-2022. The median age was 53.5 years. Breast cancer type was predominantly HER-2 positive (40.3%), among them 5 were ER/PR positive and 20 were ER/PR negative. Luminal A was the histology pattern in 8% and luminal B in 22.5%. Triple negative disease was in 29% of the cohort.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatient\u0026apos;s presentation was variable. The most frequent complaint was loss of gross limb weakness with secondary headache, aphasia and imbalance. 30.4% of patients had widespread systemic metastatic disease while surgery. Six patients had solitary brain lesion with the rest of the cohort presented with oligometastatic disease.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe most frequent location was frontal lobe (35.4%). Solid appearance was more prevalent than cystic (69.4% and 30.6% respectively). Radiation was initiated on average 33 days from surgery with a range of 16 up to 48 days. Patients\u0026apos; characteristics are presented in table 1. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eRadiation treatment\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eA total of 40 radiation treatment were delivered using VMAT, 20 using IMRT and two with 3D planning. \u0026nbsp;A BED calculated using \u0026alpha;/\u0026beta; of 10 Using this approach, the median dose was 37.5Gy (28Gy\u003csub\u003e\u0026nbsp;\u003c/sub\u003eto 59.5Gy\u003csub\u003e(BED10)\u003c/sub\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eClinical target volume (CTV) was defined as the surgical cavity. CTV to planning target volume (PTV) was expand 2-5mm. In 79% of cases the surgical corridor was included in the CTV. The avarge PTV was 67.1 cc(23.4-112.6).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDuring this analysis we used the TG101 report constrains\u003csup\u003e8\u003c/sup\u003e. In all 62 treatment planning dose constrain were met. Radiotherapy parameters are shown in Table 2 \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eLocal control\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe one-year local control rate was 70.3%..\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The total brain failure after 1 year was 41.6%. Among them 18 patients \u0026nbsp;had only local failure 15 received salvage radiosurgery and 3 received systemic therapy. 6 had distant brain failure without local failure and all received radiosurgery for the new lesion.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eClinical and survival outcomes are presented in table 3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eImpact on local control\u0026nbsp;\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eOne year local control was 70.9%. We compare different variables between patients who achieved local control and those who did not. The median planning target volume was significantly larger among those who had experienced local failure (83.7cc vs 56.2cc, P=0.042). \u0026nbsp;Size of a initial tumor was also important in achieving local control. Size of tumor above 5cm was distributed differently between those with local control and local failure with 18.1% and 66.7% respectively (p\u0026lt;0.001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe total dose delivered was lower for those with local failure with a median of \u0026nbsp;37.5Gy for local failure and 42.5Gy for local control (p=0.008).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn regards to the biology of breast cancer. We notice different distribution of HER-2 positive disease among those who had local control and those who did not (50% vs16.1%, P=0.015).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLocal control was associated with the inclusion of surgical corridor within the PTV(P=0.034) in addition \u0026nbsp;shorter time to radiotherapy from initial surgery with a median of 26.9 \u0026nbsp;days for those who achived local control versus 32.5 days for those who didn\u0026apos;t (p=0.039). Cystic lesion were more prevalence in recurring lesion then in control lesions (55.5% and 20.4% respectively P\u0026lt;0.009). The location of the tumor was also significance for local control, there was higher rate of cerebral location for those were recurred than for the control lesions (27.7% vs 6.8%, P=0.039).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4 demonstrate all clinical variable between control lesion to reccuring lesion after 1 year and odds ratio for failure.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere was no association between the age and the oncological setting and local control.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMultivariable analysis was not available due to a small sample size.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this retrospective cohort we evaluate the variable impact local control among a specific group of metastatic breast cancer undergoing surgery and post-operative RT. We found that the tumor biology, size, and are all significant for local control in addition to time from initial surgery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur local control rate is lower than previously studies that showed local control rate of 70-95% \u003csup\u003e4,7,11,12\u003c/sup\u003e. That can be partially explained by a high percentage of patients receiving a lower dose of our trial compare to the others. In our study 46% received a BED\u003csub\u003e\u0026nbsp;(10)\u003c/sub\u003e lower then 40 (i.e 25 Gy in 5 fraction) which recently been shown by Minnti et al to decrease local control \u003csup\u003e12\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eWe demonstrated correlation between dose and local control. In our analysis we used an \u0026alpha;/\u0026beta; ratio of 4Gy which is more realistic in breast cancer tumors\u003csup\u003e14\u003c/sup\u003e. We notice that Dose above 70Gy\u003csub\u003e(BED4)\u003c/sub\u003e had HR of 0.51 (CI 0.16-0.91) even when adjusting to other variables.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAnother explanation of the lower local rate results in our cohort is the timing from initial surgery until start of radiation. In a recent Meta-analysis of post-operative SRS showed a Lower local control when surgery-to-SRS delay longer than 3 weeks. The estimated 12-month control rates dropped from 87 to 61% if SRS was performed more than 3 weeks after resection \u003csup\u003e15\u003c/sup\u003e. In our study the median day for starting radiation was 33. We found that starting radiation more than 30 days from surgery has a HR of 1.46 (1.13-2.78) for local failure. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn regards to other parameters. The average size of tumor in our cohort was similar to other studies\u003csup\u003e16,17\u0026nbsp;\u003c/sup\u003eand reflects the current change in practice to operate only on symptomatic large lesions, with the remainder undergoing definitive radiosurgery. Tumor larger than 3.5 cm had significantly worsen local failure with HR of 1.61 (CI 1.11-1.31).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe current guidelines recommend the inclusion of surgical tract with 1-5 mm margin\u003csup\u003e13\u003c/sup\u003e. In our cohort inclusion of surgical tract was seen in 64.7% of those who achieved local control and 55.5% at those who didn\u0026rsquo;t. However, this difference did not reach statistical significance.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDifferent studies had shown contradictory results on the impact of cystic lesions and response to local treatment. \u003csup\u003e18\u003c/sup\u003e Studies have suggested that the causes of cystic masses may include the breakdown of the blood\u0026ndash;brain barrier or the higher risk of developing cystic BM in patients with poor histological grade\u003csup\u003e,18,19\u003c/sup\u003e. In addition, the complications seen in operations on cystic lesion and the less than Gross tumor resection achieved can have an impact on overall survival and local control respectively\u003csup\u003e20\u003c/sup\u003e. in our study cystic had much higher risk of local failure with HR of 1.55 (1.13-2.34).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eToxicity\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe found 8 cases of reported radiation necrosis on MRI. Two of whom were asymptomatic. The two symptomatic patients were treated successfully with dexamethasone. In the entire cohort 38% reported Grade 2 fatigue and 11% with Grade 2 headache. \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eBreast cancer biology\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDifferent classical sub- types of breast cancer have different biology in regards of brain metastases prevalence, pathophysiology and response to treatment\u003csup\u003e18\u003c/sup\u003e. \u003csup\u003e\u0026nbsp;\u003c/sup\u003eHER2-positive breast cancer has the inherent tendency of metastasis to the brain but because of variable systemic treatment options with good brain response and even longer survival among all breast cancer population with brain metastases\u003csup\u003e20\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSurprisingly, in our cohort patients the prevalence of HER-2 sub type was higher among those who achieved local control. Having HER-2 disease decrease the odds for local failure (OR=0.2). the population of paitents with HER-2 disease wasn\u0026apos;t different in any of the other variables with the population oh HER-2 negative disease (table 5)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The different in local control can be explained by the fact that most patients in our cohort had visceral metastatic disease at presentation \u0026nbsp;and received systemic therapy after the course of radiation. HER-2 targeted therapy like transtuzumab, transtuzumab-emtansine, fam-transtuzumab-deruxtecan, \u0026nbsp;lapatinib with capecitabine and tucatinib have all high response rate in the \u0026nbsp;CNS\u003csup\u003e21,22\u003c/sup\u003e. In the TUDEXO-1 trial recently showed 83% intracranial response\u003csup\u003e23\u003c/sup\u003e. and can help reduced the risk of recurrence by effectively treating microscopic disease. This advantage is lacking in other sub-type populations.\u003c/p\u003e\n\u003cp\u003eOur study has some limitations including the retrospective nature of the data and the fact that it is a single institution analysis. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOn the other hand, the advantageous of our study is the relative large homogenous cohort of only breast cancer patients with single brain metastases who had resection. Most of the Current literature of post-operative radiotherapy analyzed all sub types of cancer in the same manner without consideration of the different biology of each tumor type.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eBrain metastases from breast cancer remain a life-threating condition. Surgery plays a critical role in the treatment of large symptomatic brain metastases for whom Post-operative radiotherapy is essential. Choosing a regime with a dose of more than 40Gy (BED) seem important for achieving local control and without increase toxicity.\u003c/p\u003e \u003cp\u003eWe have defined the clinical characteristics associated with local failure amongst brain metastases of breast cancer origin following surgical resection and post-operative irradiation. Higher radiation dose is associated with both higher rates of local control but also increased rates of radiation brain injury. Larger trails need in order to addressed individualization of the dosage in regards to all clinical variables.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBC-Breast cancer, ER-Estrogen receptor, RCT-randomized clinical trial, OS- over all survival, LC-local control, WBRT-whole brain radiotherapy, CTV- clinical target volume, PTV-planning target volume.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eAuthor contribution \u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eOH- study conception and design, data collection, statistical analysis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eZS, YL-data collection, analysis and interpretation of results\u003c/p\u003e\n\u003cp\u003eTKE, OG- analysis and interpretation of results\u003c/p\u003e\n\u003cp\u003eZC,AW- data collection\u003c/p\u003e\n\u003cp\u003eAT- draft manuscript preparation, analysis and interpretation of results\u003c/p\u003e\u003cp\u003e\u003cu\u003eEthical Approval and Consent to participate\u003c/u\u003e- IRB approval number 0265-23-SMC\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConsent for publication\u003c/u\u003e- This article has not been published before. All authors read this manuscript and approved it submission\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAvailability of supporting data\u003c/u\u003e- none\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCompeting interests/Authors\u0026apos; contributions\u003c/u\u003e- none\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eFunding\u003c/u\u003e- none\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eYajie Wang et al, Breast cancer brain metastasis: insight into molecular mechanisms and therapeutic strategies, Br J Cancer, 2021 Oct;125(8):1056-106\u003c/li\u003e\n\u003cli\u003eC corti, Targeting brain metastases in breast cancer, Cancer Treatment Reviews, 2022-02-01, Volume 103\u003c/li\u003e\n\u003cli\u003e Sava A, Brain metastases originating in breast cancer: clinical-pathological analysis and immunohistochemical profile, Rom J Morphol Embryol. 2021 Apr-Jun; 62(2): 435\u0026ndash;444.\u003c/li\u003e\n\u003cli\u003eChibawanye I. Ene et al, Surgical Management of Brain Metastasis: Challenges and Nuances, Front Oncol. 2022; 12: 847110.\u003c/li\u003e\n\u003cli\u003ePatchell RA et al, Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial, JAMA,1998 Nov 4;280(17):1485-9..\u003c/li\u003e\n\u003cli\u003eKocer M et al, Adjuvant Whole-Brain Radiotherapy Versus Observation After Radiosurgery or Surgical Resection of One to Three Cerebral Metastases: Results of the EORTC 22952-26001 Study, J Clin Oncol. 2011 Jan 10; 29(2): 134\u0026ndash;141\u003c/li\u003e\n\u003cli\u003eA Mahajan et al, Prospective Randomized Trial of Post-operative Stereotactic Radiosurgery versus Observation for Completely Resected Brain Metastases, Lancet 2017 Aug\u003c/li\u003e\n\u003cli\u003eBrown PD et al, Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC\u0026middot;3): a multicentre, randomised, controlled, phase 3 trial, lancet 2017 Aug.\u003c/li\u003e\n\u003cli\u003eStanley H Benedict et al, Stereotactic body radiation therapy: the report of AAPM Task Group 101, Med Phys 2010 Aug;37(8)\u003c/li\u003e\n\u003cli\u003eRedmina KJ et al, Stereotactic Radiosurgery for Postoperative Metastatic Surgical Cavities: A Critical Review and International Stereotactic Radiosurgery Society (ISRS) Practice Guidelines, Int J Radiat Oncol Biol Phys, 2021 Sep\u003c/li\u003e\n\u003cli\u003eKumar AMS et al Postoperative hypofractionated stereotactic brain radiation (HSRT) for resected brain metastases: improved local control with higher BED\u003csub\u003e10\u003c/sub\u003e. J Neurooncol. 2018;139:449\u0026ndash;54\u003c/li\u003e\n\u003cli\u003eGui C et al. Local recurrence patterns after postoperative stereotactic radiation surgery to resected brain metastases: a quantitative analysis to guide target delineation. Pract Radiat Oncol. 2018;8:388\u0026ndash;96.\u003c/li\u003e\n\u003cli\u003eMusunuru HB et al, Impact of adjuvant fractionated stereotactic radiotherapy dose on local control of brain metastases. J Neurooncol. 2019;145:385\u0026ndash;90.\u003c/li\u003e\n\u003cli\u003eMinnti G et al, Current status and recent advances in resection cavity irradiation of brain metastases, Radiation oncology, 15 Apr 2021\u003c/li\u003e\n\u003cli\u003eC. M. van Leeuwen et al, The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies, radiation oncology, 16 May 2018\u003c/li\u003e\n\u003cli\u003eD. Early et al, Gamma Knife stereotactic radiosurgery to the tumor bed of resected brain metastasis for improved local control. J Neurosurg. 2014;121(Suppl):69\u0026ndash;74.\u003c/li\u003e\n\u003cli\u003eAhmed KA et al, Fractionated stereotactic radiotherapy to the post-operative cavity for radioresistant and radiosensitive brain metastases. J Neurooncol. 2014;118:179\u0026ndash;186\u003c/li\u003e\n\u003cli\u003eKeller A et al, Hypofractionated stereotactic radiation therapy to the resection bed for intracranial metastases. Int J Radiat Oncol Biol Phys. 2017;99:1179\u0026ndash;1189.\u003c/li\u003e\n\u003cli\u003eWang H et al, Cystic brain metastases had slower speed of tumor shrinkage but similar prognosis compared with solid tumors that underwent radiosurgery, treatment Cancer Management and Research, 2019, volume 11 Pages 1753\u0026mdash;1763 \u003c/li\u003e\n\u003cli\u003eSantai Song et al, Cystic brain metastasis is associated with poor prognosis in patients with advanced breast cancer, Oncotarget. 2016 Nov 8; 7(45): 74006\u0026ndash;74014 \u003c/li\u003e\n\u003cli\u003eHongna Sun et al, Breast cancer brain metastasis: Current evidence and future directions, cancer medicine, \u003cspan dir=\"RTL\"\u003e2023\u003c/span\u003e;12:1007\u0026ndash;1024\u003c/li\u003e\n\u003cli\u003eE. Stavrou et al, How we treat HER2-positive brain metastases, ESMO Open. 2021 Oct; 6(5): 100256.\u003c/li\u003e\n\u003cli\u003eBartsch R, Berghoff A, Furtner J, et al. 280P - Intracranial activity of trastuzumab-deruxtecan (T-DXd) in HER2-positive breast cancer patients with active brain metastases: Results from the first stage of the phase II TUXEDO-1 trial. Annals of Oncology . 16 Sep 2021;32(S457-S515)\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003ePatients characteristics\u003cstrong\u003e\u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"left\" dir=\"ltr\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.61124121779859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eVariable\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.38875878220141%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.61124121779859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eNumber of patients\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.38875878220141%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.61124121779859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eAge (mean, range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.38875878220141%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e53 (23-78)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.61124121779859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eBreast CA type\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eLuminal A\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eLuminal B\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eHER-2 positive\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eTriple negative\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.38875878220141%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e5 (8%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e14 (22.5%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e25 (40.3%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e18 (29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.61124121779859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eGPA\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e0-1\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1.5-2\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e2.5-3\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e3.5-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.38875878220141%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e0 (0%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e9 (14.5%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e23 (37%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e30 (48.3%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.61124121779859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eSize of metastases\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e0.5-1.99cm\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e2-3.99cm\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e4-4.99cm\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e5-6.99cm\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026gt;7cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.38875878220141%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e3 (4.8%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e10 (16%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e28 (45.1%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e15 (24.1%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e5 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.61124121779859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eLocation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eFrontal\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eParietal\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eTemporal\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eOccipital\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eCerebellum\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.38875878220141%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e22 (35.4%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e13 (20.9%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e10 (16.1%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e8 (12.9%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e8 (12.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.61124121779859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eType of lesion\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eSolid\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eCystic\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.38875878220141%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e43 (69.3%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e19 (30.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.61124121779859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTime from surgery to RT in Days (mean, range)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.38875878220141%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e33(20-61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.61124121779859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eClinical presentation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eSolitary brain lesion\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eOligometastatic disease (\u0026lt;5 mets)\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eMetastatic disease\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.38875878220141%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e6 (9.6%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e37 (59.6%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e19 (30.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTable 2 \u0026ndash;radiation parameters\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"left\" dir=\"ltr\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eVariable\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003ePTV (median, range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e67.1 cc(23.4-112.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eDose (BED \u0026alpha;/\u0026beta;=10) (median, range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e37.5Gy (28-59.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eAll dosage regiment\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eTotal dose (Gy), n of fraction\u0026nbsp;(BED \u0026alpha;/\u0026beta;=10)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e24Gy,3 (43.2)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e24Gy,4 (38.4)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e20Gy,4 (30)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e25Gy,5 (37.5)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e27.5Gy,5 (42.6)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e30Gy,5 (48)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e32.5Gy,5 (53.3)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e30Gy,6 (45)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e35Gy,7 (59.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e4 (6.4%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1 (1.6%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e3 (4.8%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e32 (51.6%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e6 (9.6%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e11 (17.7%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e2 (3.2%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e2 (3.2%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e1 (1.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eDose\u0026gt;40Gy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e38.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eInclusion of corridor in PTV\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e79%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eDays from surgery to RT (median, range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e28.5 (16-44)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026gt;28 days from RT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e50%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eBrainV25 (Brain-PTV) \u0026nbsp;(median, range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e4.4cc(0-9.1cc)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTable 3- outcome parameters \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"left\" dir=\"ltr\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;follow up months (median, range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e28 (14-43)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e1 year LC (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e70.9%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eRadiation necrosis (%)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eAsymptomatic\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003eSymptomatic\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e12.9%\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e6\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e1 year brain failure (local + distant) (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e41.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e1 years distant only brain failure (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e12.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e1 year Overall survival (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e80.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTable 4 local control vs local failure after 1 year\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"left\" dir=\"ltr\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eVariables\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eLocal control (n=44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eLocal progression(n=18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eOR (CI95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e53Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e53.5Y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.97 (0.74-2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eHER-2 positive (yes)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e50%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e16.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.2(0.05-0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eSize of tumor\u0026nbsp;(\u0026gt;5cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e18.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e66.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e9 (2.5-31.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003ePTV (CC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e56.2CC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e83.7CC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.042\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eDose BED\u0026nbsp;(\u0026alpha;/\u0026beta;=10)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(median, range) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e42.5Gy (37.5-59.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e37.5Gy\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(30-48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eBED\u0026gt;40Gy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e52.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e16.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.18 (0.049-0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eInclusion of surgical corridor (Yes)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e13.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e38.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e4.03 (1.1-14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eTime from surgery to radiation (days median, range)\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e26.9days\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(18-42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e32.5days\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(16-44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eTime from surgery\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u0026gt;28days\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e38.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e77.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e5.5 (1.56-19.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eType of metastases (\u003cstrong\u003eCystic\u003c/strong\u003e)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e20.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e55.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e4.8(1.4-15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eLocation (cerebellum)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e6.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e27.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e5.2(1.1-25.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.270758122743683%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eClinical presentation\u0026nbsp;\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e(\u003cstrong\u003esolitary brain lesion\u003c/strong\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.342960288808664%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.133574007220215%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e11.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.63176895306859%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e1.25(0.2-7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.620938628158845%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTable 5\u003c/strong\u003e\u003c/p\u003e\n\u003cp dir=\"LTR\"\u003eHer -2 disease\u0026nbsp;\u003c/p\u003e\n\u003cdiv align=\"left\" dir=\"ltr\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.71353251318102%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.307557117750438%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eHER-2 positive (n=25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eHER-2 negative (n=37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.319859402460455%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.71353251318102%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.307557117750438%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e55y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e52.2y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.319859402460455%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.71353251318102%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eBED\u0026gt;40Gy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.307557117750438%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e40%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e37.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.319859402460455%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.71353251318102%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eDays to RT \u0026gt;28days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.307557117750438%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e56%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e45.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.319859402460455%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.71353251318102%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eInclusion of corridor\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.307557117750438%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e76%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e81%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.319859402460455%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.71353251318102%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eCystic lesion\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.307557117750438%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e32%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e29.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.319859402460455%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.71353251318102%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eLocation at cerebellum\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.307557117750438%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e16%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e10.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.319859402460455%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.71353251318102%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eSize of tumor \u0026gt;5cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.307557117750438%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e28%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.659050966608085%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e35.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.319859402460455%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\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":"","lastPublishedDoi":"10.21203/rs.3.rs-3832058/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3832058/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSingle brain metastasis surgical resection remains an effective treatment for brain metastases. However, surgery alone associate with a high rate of local failure. The current guidelines recommend radiation to surgical cavity. The recommended dose for brain cavity after surgery remain to be define as most guidelines gives a very general suggestion about the dose and fractionation. The aim of this study was to determine what variable influence local control in this specific population.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eRetrospective analysis of 62 patients with breast cancer who undergo surgical resection to single brain metastases and who received post-operative radiotherapy between the years 2011\u0026ndash;2022. All clinical and dosimetric variables were analyzed to evaluate their impact on local control.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOne year local control was 70.9%. HER-2 disease, size of initial tumor, time from initial surgery, total dose deliver, inclusion of corridor and type of lesion were all significant for local control. Patients with HER-2 positive disease had higher local control rate without any difference in other variables.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eBrain metastases from breast cancer remain a life-threating condition. Surgery plays a critical role in the treatment of large symptomatic brain metastases for which Post-operative radiotherapy is essential. Choosing a regime with a dose of more then 40Gy (BED) seems important for achieving local control and without increase toxicity. Different biology and systemic therapy options can differentiate Breast cancer population after brain surgery for metastatic disease. A larger prospective trial is needed to addressed the question whether lower dosage can be use in HER-2 positive disease.\u003c/p\u003e","manuscriptTitle":"What impact local failure after post-operative radiotherapy of resected brain metastases in breast cancer patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-18 10:08:57","doi":"10.21203/rs.3.rs-3832058/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":"de9cedf3-fe82-4a00-82ae-7619266a72eb","owner":[],"postedDate":"January 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-07T22:02:40+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-18 10:08:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3832058","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3832058","identity":"rs-3832058","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}