The Use of SBRT in the Management of Oligometastatic Gynecological Cancer: Report of Promising Results in Terms of Tolerability and Clinical Outcomes

The Use of SBRT in the Management of Oligometastatic Gynecological Cancer: Report of Promising Results in Terms of Tolerability and Clinical Outcomes | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Use of SBRT in the Management of Oligometastatic Gynecological Cancer: Report of Promising Results in Terms of Tolerability and Clinical Outcomes Francesco Cuccia, Edoardo Pastorello, Claudio Vitale, Luca Nicosia, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-809076/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Background The use of stereotactic radiotherapy (SBRT) for oligometastases is supported by several literature studies, but in the setting of gynecological malignancies, this scenario remains quite unexplored. This study reports a preliminary assessment of clinical outcomes in a cohort of 40 patients with oligometastatic gynecological neoplasms. Methods Radiotherapy was delivered in 3-10 fractions with VMAT-IGRT technique. Toxicity was retrospectively collected according to CTCAE v4.0. Data were retrospectively collected and analyzed. Univariate and multivariate analysis were performed for assessing any potential predictive factor for clinical outcomes. Results A total of 63 oligometastases were treated from December 2014 to February 2021. Median age was 63 years (range, 30-89). Most frequent primary tumors were ovarian cancer in 42.5% and endometrium cancer in 42.5%. With a median follow-up of 27 months (range, 6-69), no local failures were observed, our progression-free survival rates were 43.6% and 23% at one and 2 years, respectively, while 1- and 2-years overall survival rates were both 70%. No acute or late G≥2 adverse events were observed. Conclusions In our experience, SBRT for oligometastatic gynecological malignancies resulted in promising results in terms of clinical outcomes, with excellent local control and no evidence of severe toxicity, highilighting the effectiveness of this therapeutic option. Prospective studies to further explore this approach in this setting are advocated. Cancer Biology Oncology stereotactic body radiotherapy gynecological malignancies oligometastases Figures Figure 1 Introduction Gynecological malignancies are highly represented in general population. Endometrial is the most common among them [ 1 ], with continuously rising incidence rates, also due to the increasing prevalence of obesity [ 2 ]; cervical cancer is one of the leading causes of death among women, while ovarian cancer is the seventh most common cancer worldwide and it is frequently diagnosed in advanced stage. [ 3 , 4 ] In the last years, improvements in diagnostic imaging techniques, such as 18F-FDG-positron-emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI), have led to a significant improvement in terms of tumor detection rate, increasing the number of patients characterized by a limited number of metastases. This brings to a newly-defined subgroup of patients, so called oligometastatic, represented by an intermediate stage of disease between locally-advanced and widely-disseminated. In this scenario, local control may help improving systemic control and the SABR COMET study has clearly demonstrated that stereotactic body radiotherapy (SBRT) in addition to standard of care can improve overall survival in oligometastatic patients. [ 5 ] Oligometastatic disease (usually considered between 3 and 5 lesions) can be divided into three main categories: oligorecurrence, oligoprogression, and oligopersistence. Nowadays the best therapeutic strategies for the different kinds of oligometastatic disease remain undefined. [ 6 ] The traditional and current management of patients with metastatic or recurrent cervical, endometrial and ovarian cancer is represented by systemic therapy, with addition of PARP inhibitors and bevacizumab to platinum-based chemotherapy. [ 7 – 9 ] Currently, SBRT in the setting of metastatic gynecological patients has been rarely investigated in the literature, mainly consisting of retrospective series. Macchia et al. [ 10 ] and Reschko et al. [ 11 ] described SBRT as a well-tolerated and efficient treatment in recurrent, persistent or oligometastatic gynecological cancers. Furthermore, also within a previously irradiated fiels, SBRT for isolated pelvic or intra-abdominal recurrences of gynecologic malignancies is feasible with an acceptable toxicity rate. [ 12 ] In the present study, we have retrospectively evaluated the outcomes of a cohort of 40 patients affected by gynecological malignancies who have received extracranial SBRT for oligometastatic cancer. Methods Written informed consent was obtained from all the patients. From December 2014 to February 2021, 40 patients with extracranial oligometastatic gynecological malignancies were treated at our Department, assuming as oligometastatic disease any presentation with up to five lesions amenable for a local treatment, with a maximum diameter ≤ 5 cm. Concurrent systemic therapy or previous pelvic radiotherapy were not exclusion criteria for the purpose of this study. SBRT was proposed to all patients with a Karnofsky Performance Status ≥ 70 and a life expectancy of ≥ 6 months. Treatment management was assessed basing on a multidisciplinary assessment. Table 1 collects patients’ characteristics. Table 1 Patients’ characteristics Characteristic Results Age 63 years (30–89) Primary Histology Endometrium = 42.5% (n = 17); Cervix = 10%(n = 4); Ovary = 42.5% (n = 17); Vagina = 5%(n = 2); RT site Lymph nodes = 55.5%(n = 35); liver = 8%(n = 5); lung = 30%(n = 19); bone = 3%(n = 2); other = 3%(n = 2) Concurrent CT 20% (n = 8) Type of Oligometastases Oligorecurrent = 55.5% (n = 35); oligoprogressive = 27%(n = 17); oligopersistent = 17.4% (n = 11) Number of metastases treated 1 lesion = 65%(n = 26); 2 = 22.5%(n = 9); ≥3 = 12.5%(n = 5); BED 72Gy 10 (range, 48–180 Gy 10 ). Radiotherapy Procedures A 1-2.5 mm slice thickness computed tomography (CT) was acquired for planning purposes. Immobilization for treatment simulation was performed either with an abdominal thermoplastic mask plus compression in the case of abdominal targets, or with 4-dimensional CT for thoracic targets. In the case of liver SBRT, contrast-enhanced CT-scans were acquired. In the case of pelvic targets, immobilization was performed in supine position by means of a knee-ankle device. Regarding the target volume delineation process, the gross tumor volume (GTV) consisted of the radiologically evident disease; when available, contouring was performed with co-registered diagnostic imaging (PET or MRI). Clinical target volume (CTV) was considered equal to the GTV. The planning target volume (PTV) was created by adding an isotropic margin ranging from 5 to 7 mm, depending on tumor site and critical structures proximity. The dosimetric goal for treatment planning was to guarantee at least 95% of the prescribed dose to the 95% of the PTV. Dose constraints for organs at risk were derived from peer-reviewed literature. [ 13 – 16 ] In all cases, SBRT was performed by means of image guided volumetric modulated arc therapy (IGRT-VMAT). Clinical Outcomes Assessment Follow-up visits were performed every 3 months after SBRT for the first year, and every 6 months starting from the second year. Treatment response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 and PET Response Evaluation Criteria in Solid Tumors (PERCIST) criteria v1.0 in the case of metabolic imaging. Toxicity was prospectively collected and assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Statistical Analysis Descriptive statistics were collected for baseline patients’ characteristics. Local control (LC), progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier method. Univariate and multivariate analyses were performed to assess any potential predictive factor for clinical outcomes. A p < 0.05 was assumed as statistically significant. All statistical analyses were carried out using Graphpad Prism v9.0.2 (Graphpad, San Diego, CA, USA) Results A total of 63 oligometastases treated in 40 oligometastatic gynecological patients were retrospectively analyzed for the purpose of this study. The median age of the cohort was 63 years (range, 30–89). The majority of the treated metastases were from ovarian cancer in 43% of cases (n = 27), endometrial cancer in 41% (n = 26), cervical cancer in 13% (n = 8), vaginal cancer in 3% (n = 2). SBRT to oligometastatic disease was delivered to lymph nodal metastases in 55.5% (n = 35); lung metastases in 30% (n = 19), liver metastases in 8% (n = 5), bone metastases in 3% (n = 2), paravaginal space in 3% (n = 2). 35 oligometastases out of 63 were oligo-recurrent lesions (55.5%), oligo-persistent in 17.4% (n = 11), oligo-progressive in the remaining 27% of cases (n = 17). In nine patients, SBRT was delivered to 2 sinchronous oligometastases, while five subjects received SBRT to more than 2 lesions. In the remaining cases (n = 26), SBRT was delivered to a single oligometastatic target. Concurrent systemic therapy was administered in 8 patients (20%), consisting of PARP-inhibitors in 5 cases, anti-VEGF antibody in 2 cases and trastuzumab in one patient. SBRT was delivered in 3–10 fractions for a median total dose of 42 Gy (range, 24–70), and a median biologically effective dose (BED) = 72Gy 10 (range, 48–180 Gy 10 ). Clinical outcomes The median follow-up was 27 months (range, 6–69); for the entire cohort, median local control (LC) was 19 months, leading to 2-years LC rates of 100%. (Fig. 1 ) One and two-years progression-free survival (PFS) rates for the entire population were respectively 43.6% and 23%. Neither univariate nor multivariate analysis found any significant correlation for this clinical outcome. (Tables 2 – 3 ) Table 2 Univariate analysis PFS OS BED ≥ 90 0.55 0.08 RT site 0.13 0.11 Primary Histology 0.31 0.12 Age 0.49 0.21 DFI 0.39 0.13 Concurrent CT 0.08 0.82 N° of metastases treated 0.78 0.82 Type of oligometastases 0.08 0.62 SOMD - 0.47 PFS - 0.05 Table 3 Multivariate Analysis PFS OS BED ≥ 90 - 0.96 RT site 0.7 0.28 Primary Histology - 0.92 Age 0.47 0.45 DFI - 0.92 Concurrent CT 0.26 - N° of metastases treated - - Type of oligometastases 0.11 - PFS - 0.97 Sixteen patients developed a sequential oligometastatic disease, for which a further SBRT course was proposed, with a second progression-free survival (PFS2) of 13 months (range, 2–27), although this did not lead to a survival advantage, when compared to patients who developed immediate polymetastatic spread (p = 0.47). In the remaining 24 patients, polymetastatic spread occurred in 47.5% of cases (n = 19), with five subjects with no evidence of disease until last follow-up. Two and 3-years overall survival rates were both 70%, with only one patient who died by other causes. (Fig. 2) At univariate analysis, progression-free survival was associated to worse OS rates (p = 0.05), although this was not confirmed on multivariate analysis. (Tables 2 – 3 ) Toxicity SBRT treatment was well tolerated and all patients completed the planned treatment without any interruption. No acute or late grade 2 or higher adverse events were observed. Discussion The role of SBRT in the management of oligometastatic cancer disease has been supported by several literature experiences, both as a potentially curative treatment option, and as a means to postpone the start of a new systemic therapy. [ 17 , 18 ] Nonetheless, in the specific setting of gynecological malignancies, it is hard to draw definitive conclusions, since this subpopulation is usually under-represented in these trials. [ 19 ] This is probably due to the natural history of gynecological cancer, such as ovarian or cervical cancer, in which the addition of systemic therapy takes place early, given the high propensity to metastatic spread. A recent review by Zhang et al. highlights the substantial feasibility of SBRT for oligometastatic gynecological cancer especially for lymph-nodal metastases, even in the case of previous pelvic irradiation. On the contrary, a major risk of G ≥ 3 adverse events is reported in the case of pelvic side wall or central pelvic recurrences treated with SBRT. [ 20 ] In the present series, we have recorded the outcomes of 63 lesions in 40 patients treated with SBRT for extracranial oligometastases from gynecological malignancies. No local failures were observed in our series, highlighting the effectiveness of the SBRT treatment. Unlike previous experiences, we have not recorded a survival advantage in those patients who developed a sequential oligometastatic progression, further treated with a second course of SBRT. [ 21 , 22 ] This evidence may raise the issue of the real role of focal treatments in this setting, suggesting a different natural history of gynecological malignancies when compared to other scenarios, as also highlighted by the sub-optimal PFS rates of most of the published studies concerning gynecological oligometastases. Nonetheless, in the last years, encouraging preliminary experiences report the outcomes of SBRT applied to this setting of patients. (Table 4 10,11,23−27 ) Table 4 Literature experiences of SBRT for gynecological malignancies Author Number of patients Number of metastases Follow-up (months) Primary Histology Toxicity Clinical Outcomes Iftode et al. 23 26 44 28.5 OC = 100% Late G2 = 11% 2yrLC = 92.9% 2yrPFS = 38% 2yrOS = 92.7% Macchia et al. 10 261 449 22 OC = 100% 2 year late G2 toxicity-free survival = 95.1% 2yrLC = 95.1% 2yrPFS = 15.4% 2yrOS = 73.6% Reshko et al. 11 86 209 20 OC = 30/86 CC = 20/86 EC = 27/86 Other = 9/86 Acute G ≥ 2 = 4.3% 3yrLC = 68% 3yrPFS= 3yrOS = 39% Reddy et al. 24 27 61 16.9 EC = 100% One case of late G2 pneumonitis 1yrLC = 80.3% 1yrPFS = 75.9% 1yrOS = 62% Ning et al. 25 38 41 35.2 CC = 100% Acute G2 = 39% 2yrLC= 2yrPFS = 48% 2yrOS = 74% Onal et al. 26 29 35 15.3 CC = 21/29 OC = 8/29 Acute G2 = 17% 2yrLC = 95.1% 2yrPFS = 18% 2yrOS = 73.6% Smile et al. 27 34 43 12 OC = 12/34 EC = 11/34 CC = 7/34 Other = 4/34 3 acute G2 events 2yrLC = 92.5% 1yrPFS = 60.2% 2yrOS = 70.2% Present experience 40 63 27 OC = 17/40 CC = 4/40 EC = 17/40 Other = 2/40 No acute or late G ≥ 2 events 2yrLC = 100% 2yrPFS = 23%; 2yrOS = 70% Abbreviations: CC=cervical cancer; EC=endometrial cancer; OC=ovarian cancer; LC=local control; PFS=progression-free survival; OS=overall survival Iftode et al. collected data concerning a series of 44 metastatic lesions arising from ovarian cancer who received SBRT, collecting satisfactory outcomes in terms of LC and PFS, with negligible toxicity. [ 23 ] Ning et al. in a previous report focused their attention on cervical cancer oligometastases, collecting promising results, in agreement with the abovementioned studies. Of note, this study included both SBRT and conventional fractionation treatments, making harder to draw definitive conclusions. [ 25 ] Reddy et al. documented excellent local control results in a series of 27 patients with oligometastatic uterine cancer, recording worse local control rates in the case of liver metastases. [ 24 ] The favorable toxicity profile of our series supports this therapeutic approach, also when combined with conventional systemic therapies that for gynecological malignancies still represent the standard of care. This is also confirmed by one of the largest series available in the literature, in which in a multicenter series published by Macchia et al., the authors collected a 2-years toxicity free survival rate of 95.1%. Interestingly, keeping in mind that this study refers to ovarian cancer oligometastases, a statistically significant correlation was found for higher LC rates, when a BED > 70 Gy radiotherapy schedule is applied. [ 10 ] Similarly to our experience, a recent study by Smile et al. included different primary gynecological cancers also highlighting excellent results in terms of both toxicity and clinical outcomes. [ 27 ] The present study has several limitations; first of all, we retrospectively collect data of a heterogeneous sample of patients including different primary histologies and both patients who received and received not systemic therapy. Nonetheless, we report one of the largest series with the longest follow-up currently available, and the results are promising and in agreement with other literature experiences supporting the role of SBRT, also in this relatively unexplored field of the oligometastatic disease. Conclusions This mono-institutional experience supports the use of SBRT in the management of the oligometastatic gynecological cancer, by collecting no relevant toxicity and promising results in terms of clinical outcomes. Prospective studies are needed to further evaluate this therapeutic option in this scenario. Declarations Authors’ Contribution: FC, CV and EP: manuscript drafting; LN, VF, MR, FR, CV, GA: data collection; FC, CV, FA: study design; FA, RM, NGL, RR: editing and revision; All author: final approval Competing interests: all authors declare no competing interests Fundings: not applicable Acknowledgments: none Ethics approval and consent to participate: not applicable Consent for publication: not applicable Availability of data and materials: not applicable References Cronin KA, Lake AJ, Scott S, et al. Annual report to the nation on the status of cancer, part I: national cancer statistics. Cancer 2018;124:2785–800 Passarello K, Kurian S, Villanueva V. 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Int J Gynecol Cancer. 2020 Jun;30(6):865-872. doi: 10.1136/ijgc-2019-001115. Smile TD, Reddy CA, Qiao-Guan G, Winter WI, Stephans KL, Woody NM, Balagamwala EH, Amarnath SR, Magnelli A, AlHilli MM, Michener CM, Mahdi H, DeBernardo RL, Rose PG, Cherian SS. Stereotactic body radiotherapy for the treatment of oligometastatic gynecological malignancy in the abdomen and pelvis: A single-institution experience. J Radiosurg SBRT. 2021;7(3):189-197 Figure Figure 2 is not available with this version. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 28 Aug, 2021 Reviewers invited by journal 13 Aug, 2021 Editor assigned by journal 13 Aug, 2021 First submitted to journal 12 Aug, 2021 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies 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-809076","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":45848751,"identity":"7573751c-22e8-4de4-9a9b-38bba6a156cc","order_by":0,"name":"Francesco Cuccia","email":"","orcid":"","institution":"Ospedale Sacro Cuore Don Calabria","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Francesco","middleName":"","lastName":"Cuccia","suffix":""},{"id":45848752,"identity":"7ab42d20-de97-4d2b-aa61-1c3d1d8a1e15","order_by":1,"name":"Edoardo Pastorello","email":"","orcid":"","institution":"Ospedale Sacro Cuore Don 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Calabria","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Claudio","middleName":"","lastName":"Vitale","suffix":""},{"id":45848754,"identity":"96634361-9a5f-4d70-bb3a-fdff852f5395","order_by":3,"name":"Luca Nicosia","email":"","orcid":"","institution":"Ospedale Sacro Cuore Don Calabria","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Luca","middleName":"","lastName":"Nicosia","suffix":""},{"id":45848755,"identity":"08bcf082-c8b0-438a-8b8a-53d19d68c7b7","order_by":4,"name":"Rosario Mazzola","email":"","orcid":"","institution":"Ospedale Sacro Cuore Don Calabria","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rosario","middleName":"","lastName":"Mazzola","suffix":""},{"id":45848756,"identity":"227a164a-84ea-4cb7-8a67-8c937c397636","order_by":5,"name":"Vanessa Figlia","email":"","orcid":"","institution":"Ospedale Sacro Cuore Don Calabria","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Vanessa","middleName":"","lastName":"Figlia","suffix":""},{"id":45848757,"identity":"977a77c8-d127-4023-a795-729c36bdc1cd","order_by":6,"name":"Niccolò Giaj-Levra","email":"","orcid":"","institution":"Ospedale Sacro Cuore Don Calabria","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Niccolò","middleName":"","lastName":"Giaj-Levra","suffix":""},{"id":45848758,"identity":"740ec643-8a71-4fbd-a346-fb491bf66c85","order_by":7,"name":"Francesco Ricchetti","email":"","orcid":"","institution":"Ospedale Sacro Cuore Don Calabria","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Francesco","middleName":"","lastName":"Ricchetti","suffix":""},{"id":45848759,"identity":"54bdfdd7-e783-40bb-8aad-b1242b134229","order_by":8,"name":"Michele Rigo","email":"","orcid":"","institution":"Ospedale Sacro Cuore Don Calabria","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Michele","middleName":"","lastName":"Rigo","suffix":""},{"id":45848760,"identity":"09d456f3-9528-4397-9a78-5fa9d83cffd7","order_by":9,"name":"Giorgio Attinà","email":"","orcid":"","institution":"Ospedale Sacro Cuore Don Calabria","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Giorgio","middleName":"","lastName":"Attinà","suffix":""},{"id":45848761,"identity":"f1cabd24-ed52-48a0-9f4b-c1f76682296c","order_by":10,"name":"Marcello Ceccaroni","email":"","orcid":"","institution":"Ospedale Sacro Cuore Don Calabria","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Marcello","middleName":"","lastName":"Ceccaroni","suffix":""},{"id":45848762,"identity":"aeb38549-b804-466b-93c1-ee090a2670a5","order_by":11,"name":"Ruggero Ruggieri","email":"","orcid":"","institution":"Ospedale Sacro Cuore Don Calabria","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ruggero","middleName":"","lastName":"Ruggieri","suffix":""},{"id":45848763,"identity":"3688e801-20dc-4809-853f-f4127bb3837a","order_by":12,"name":"Filippo Alongi","email":"","orcid":"","institution":"Ospedale Sacro Cuore Don Calabria","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Filippo","middleName":"","lastName":"Alongi","suffix":""}],"badges":[],"createdAt":"2021-08-13 07:35:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-809076/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-809076/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":12546381,"identity":"9dba84a4-969e-4cc8-a087-4f340d3319d9","added_by":"auto","created_at":"2021-08-18 14:50:34","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":115767,"visible":true,"origin":"","legend":"Kaplan-Meier curves for progression-free survival (PFS) and overall survival (OS)","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-809076/v1/3f1273b979decb68365c29b8.jpg"},{"id":13710204,"identity":"320f9e03-5ea6-4355-9b0d-625894c4c0e9","added_by":"auto","created_at":"2021-09-17 14:16:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":410205,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-809076/v1/6a07ff6c-0719-4733-ad84-8bb0c3d4ec62.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eThe Use of SBRT in the Management of Oligometastatic Gynecological Cancer: Report of Promising Results in Terms of Tolerability and Clinical Outcomes\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGynecological malignancies are highly represented in general population. Endometrial is the most common among them [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], with continuously rising incidence rates, also due to the increasing prevalence of obesity [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]; cervical cancer is one of the leading causes of death among women, while ovarian cancer is the seventh most common cancer worldwide and it is frequently diagnosed in advanced stage. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn the last years, improvements in diagnostic imaging techniques, such as 18F-FDG-positron-emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI), have led to a significant improvement in terms of tumor detection rate, increasing the number of patients characterized by a limited number of metastases.\u003c/p\u003e \u003cp\u003eThis brings to a newly-defined subgroup of patients, so called oligometastatic, represented by an intermediate stage of disease between locally-advanced and widely-disseminated. In this scenario, local control may help improving systemic control and the SABR COMET study has clearly demonstrated that stereotactic body radiotherapy (SBRT) in addition to standard of care can improve overall survival in oligometastatic patients. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOligometastatic disease (usually considered between 3 and 5 lesions) can be divided into three main categories: oligorecurrence, oligoprogression, and oligopersistence. Nowadays the best therapeutic strategies for the different kinds of oligometastatic disease remain undefined. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe traditional and current management of patients with metastatic or recurrent cervical, endometrial and ovarian cancer is represented by systemic therapy, with addition of PARP inhibitors and bevacizumab to platinum-based chemotherapy. [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eCurrently, SBRT in the setting of metastatic gynecological patients has been rarely investigated in the literature, mainly consisting of retrospective series. Macchia et al. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and Reschko et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] described SBRT as a well-tolerated and efficient treatment in recurrent, persistent or oligometastatic gynecological cancers. Furthermore, also within a previously irradiated fiels, SBRT for isolated pelvic or intra-abdominal recurrences of gynecologic malignancies is feasible with an acceptable toxicity rate. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn the present study, we have retrospectively evaluated the outcomes of a cohort of 40 patients affected by gynecological malignancies who have received extracranial SBRT for oligometastatic cancer.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWritten informed consent was obtained from all the patients. From December 2014 to February 2021, 40 patients with extracranial oligometastatic gynecological malignancies were treated at our Department, assuming as oligometastatic disease any presentation with up to five lesions amenable for a local treatment, with a maximum diameter\u0026thinsp;\u0026le;\u0026thinsp;5 cm. Concurrent systemic therapy or previous pelvic radiotherapy were not exclusion criteria for the purpose of this study.\u003c/p\u003e\n\u003cp\u003eSBRT was proposed to all patients with a Karnofsky Performance Status\u0026thinsp;\u0026ge;\u0026thinsp;70 and a life expectancy of \u0026ge;\u0026thinsp;6 months. Treatment management was assessed basing on a multidisciplinary assessment. Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e collects patients\u0026rsquo; characteristics.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ePatients\u0026rsquo; characteristics\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"2\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eResults\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63 years (30\u0026ndash;89)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary Histology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEndometrium\u0026thinsp;=\u0026thinsp;42.5% (n\u0026thinsp;=\u0026thinsp;17); Cervix\u0026thinsp;=\u0026thinsp;10%(n\u0026thinsp;=\u0026thinsp;4); Ovary\u0026thinsp;=\u0026thinsp;42.5% (n\u0026thinsp;=\u0026thinsp;17); Vagina\u0026thinsp;=\u0026thinsp;5%(n\u0026thinsp;=\u0026thinsp;2);\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRT site\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLymph nodes\u0026thinsp;=\u0026thinsp;55.5%(n\u0026thinsp;=\u0026thinsp;35); liver\u0026thinsp;=\u0026thinsp;8%(n\u0026thinsp;=\u0026thinsp;5); lung\u0026thinsp;=\u0026thinsp;30%(n\u0026thinsp;=\u0026thinsp;19); bone\u0026thinsp;=\u0026thinsp;3%(n\u0026thinsp;=\u0026thinsp;2); other\u0026thinsp;=\u0026thinsp;3%(n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConcurrent CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20% (n\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eType of Oligometastases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOligorecurrent\u0026thinsp;=\u0026thinsp;55.5% (n\u0026thinsp;=\u0026thinsp;35); oligoprogressive\u0026thinsp;=\u0026thinsp;27%(n\u0026thinsp;=\u0026thinsp;17); oligopersistent\u0026thinsp;=\u0026thinsp;17.4% (n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of metastases treated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 lesion\u0026thinsp;=\u0026thinsp;65%(n\u0026thinsp;=\u0026thinsp;26); 2\u0026thinsp;=\u0026thinsp;22.5%(n\u0026thinsp;=\u0026thinsp;9); \u0026ge;3\u0026thinsp;=\u0026thinsp;12.5%(n\u0026thinsp;=\u0026thinsp;5);\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBED\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72Gy\u003csub\u003e10\u003c/sub\u003e (range, 48\u0026ndash;180 Gy\u003csub\u003e10\u003c/sub\u003e).\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\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv class=\"Section2\" id=\"Sec6\"\u003e\n \u003ch2\u003eRadiotherapy Procedures\u003c/h2\u003e\n \u003cp\u003eA 1-2.5 mm slice thickness computed tomography (CT) was acquired for planning purposes. Immobilization for treatment simulation was performed either with an abdominal thermoplastic mask plus compression in the case of abdominal targets, or with 4-dimensional CT for thoracic targets. In the case of liver SBRT, contrast-enhanced CT-scans were acquired. In the case of pelvic targets, immobilization was performed in supine position by means of a knee-ankle device.\u003c/p\u003e\n \u003cp\u003eRegarding the target volume delineation process, the gross tumor volume (GTV) consisted of the radiologically evident disease; when available, contouring was performed with co-registered diagnostic imaging (PET or MRI). Clinical target volume (CTV) was considered equal to the GTV. The planning target volume (PTV) was created by adding an isotropic margin ranging from 5 to 7 mm, depending on tumor site and critical structures proximity. The dosimetric goal for treatment planning was to guarantee at least 95% of the prescribed dose to the 95% of the PTV. Dose constraints for organs at risk were derived from peer-reviewed literature. [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e\n \u003cp\u003eIn all cases, SBRT was performed by means of image guided volumetric modulated arc therapy (IGRT-VMAT).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec7\"\u003e\n \u003ch2\u003eClinical Outcomes Assessment\u003c/h2\u003e\n \u003cp\u003eFollow-up visits were performed every 3 months after SBRT for the first year, and every 6 months starting from the second year. Treatment response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 and PET Response Evaluation Criteria in Solid Tumors (PERCIST) criteria v1.0 in the case of metabolic imaging. Toxicity was prospectively collected and assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec8\"\u003e\n \u003ch2\u003eStatistical Analysis\u003c/h2\u003e\n \u003cp\u003eDescriptive statistics were collected for baseline patients\u0026rsquo; characteristics. Local control (LC), progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier method. Univariate and multivariate analyses were performed to assess any potential predictive factor for clinical outcomes. A p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was assumed as statistically significant. All statistical analyses were carried out using Graphpad Prism v9.0.2 (Graphpad, San Diego, CA, USA)\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 63 oligometastases treated in 40 oligometastatic gynecological patients were retrospectively analyzed for the purpose of this study. The median age of the cohort was 63 years (range, 30\u0026ndash;89). The majority of the treated metastases were from ovarian cancer in 43% of cases (n\u0026thinsp;=\u0026thinsp;27), endometrial cancer in 41% (n\u0026thinsp;=\u0026thinsp;26), cervical cancer in 13% (n\u0026thinsp;=\u0026thinsp;8), vaginal cancer in 3% (n\u0026thinsp;=\u0026thinsp;2). SBRT to oligometastatic disease was delivered to lymph nodal metastases in 55.5% (n\u0026thinsp;=\u0026thinsp;35); lung metastases in 30% (n\u0026thinsp;=\u0026thinsp;19), liver metastases in 8% (n\u0026thinsp;=\u0026thinsp;5), bone metastases in 3% (n\u0026thinsp;=\u0026thinsp;2), paravaginal space in 3% (n\u0026thinsp;=\u0026thinsp;2). 35 oligometastases out of 63 were oligo-recurrent lesions (55.5%), oligo-persistent in 17.4% (n\u0026thinsp;=\u0026thinsp;11), oligo-progressive in the remaining 27% of cases (n\u0026thinsp;=\u0026thinsp;17).\u003c/p\u003e\n\u003cp\u003eIn nine patients, SBRT was delivered to 2 sinchronous oligometastases, while five subjects received SBRT to more than 2 lesions. In the remaining cases (n\u0026thinsp;=\u0026thinsp;26), SBRT was delivered to a single oligometastatic target.\u003c/p\u003e\n\u003cp\u003eConcurrent systemic therapy was administered in 8 patients (20%), consisting of PARP-inhibitors in 5 cases, anti-VEGF antibody in 2 cases and trastuzumab in one patient.\u003c/p\u003e\n\u003cp\u003eSBRT was delivered in 3\u0026ndash;10 fractions for a median total dose of 42 Gy (range, 24\u0026ndash;70), and a median biologically effective dose (BED)\u0026thinsp;=\u0026thinsp;72Gy\u003csub\u003e10\u003c/sub\u003e (range, 48\u0026ndash;180 Gy\u003csub\u003e10\u003c/sub\u003e).\u003c/p\u003e\n\u003cdiv class=\"Section2\" id=\"Sec10\"\u003e\n \u003ch2\u003eClinical outcomes\u003c/h2\u003e\n \u003cp\u003eThe median follow-up was 27 months (range, 6\u0026ndash;69); for the entire cohort, median local control (LC) was 19 months, leading to 2-years LC rates of 100%. (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003eOne and two-years progression-free survival (PFS) rates for the entire population were respectively 43.6% and 23%. Neither univariate nor multivariate analysis found any significant correlation for this clinical outcome. (Tables \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eUnivariate analysis\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOS\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBED\u0026thinsp;\u0026ge;\u0026thinsp;90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRT site\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary Histology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDFI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConcurrent CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN\u0026deg; of metastases treated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eType of oligometastases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSOMD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003e0.05\u003c/span\u003e\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\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMultivariate Analysis\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOS\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBED\u0026thinsp;\u0026ge;\u0026thinsp;90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRT site\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary Histology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDFI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConcurrent CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN\u0026deg; of metastases treated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eType of oligometastases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePFS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.97\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\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eSixteen patients developed a sequential oligometastatic disease, for which a further SBRT course was proposed, with a second progression-free survival (PFS2) of 13 months (range, 2\u0026ndash;27), although this did not lead to a survival advantage, when compared to patients who developed immediate polymetastatic spread (p\u0026thinsp;=\u0026thinsp;0.47). In the remaining 24 patients, polymetastatic spread occurred in 47.5% of cases (n\u0026thinsp;=\u0026thinsp;19), with five subjects with no evidence of disease until last follow-up.\u003c/p\u003e\n \u003cp\u003eTwo and 3-years overall survival rates were both 70%, with only one patient who died by other causes. (Fig.\u0026nbsp;2)\u003c/p\u003e\n \u003cp\u003eAt univariate analysis, progression-free survival was associated to worse OS rates (p\u0026thinsp;=\u0026thinsp;0.05), although this was not confirmed on multivariate analysis. (Tables\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec11\"\u003e\n \u003ch2\u003eToxicity\u003c/h2\u003e\n \u003cp\u003eSBRT treatment was well tolerated and all patients completed the planned treatment without any interruption. No acute or late grade 2 or higher adverse events were observed.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe role of SBRT in the management of oligometastatic cancer disease has been supported by several literature experiences, both as a potentially curative treatment option, and as a means to postpone the start of a new systemic therapy. [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e\n\u003cp\u003eNonetheless, in the specific setting of gynecological malignancies, it is hard to draw definitive conclusions, since this subpopulation is usually under-represented in these trials. [\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e\n\u003cp\u003eThis is probably due to the natural history of gynecological cancer, such as ovarian or cervical cancer, in which the addition of systemic therapy takes place early, given the high propensity to metastatic spread. A recent review by Zhang et al. highlights the substantial feasibility of SBRT for oligometastatic gynecological cancer especially for lymph-nodal metastases, even in the case of previous pelvic irradiation. On the contrary, a major risk of G\u0026thinsp;\u0026ge;\u0026thinsp;3 adverse events is reported in the case of pelvic side wall or central pelvic recurrences treated with SBRT. [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e\n\u003cp\u003eIn the present series, we have recorded the outcomes of 63 lesions in 40 patients treated with SBRT for extracranial oligometastases from gynecological malignancies. No local failures were observed in our series, highlighting the effectiveness of the SBRT treatment. Unlike previous experiences, we have not recorded a survival advantage in those patients who developed a sequential oligometastatic progression, further treated with a second course of SBRT. [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e\n\u003cp\u003eThis evidence may raise the issue of the real role of focal treatments in this setting, suggesting a different natural history of gynecological malignancies when compared to other scenarios, as also highlighted by the sub-optimal PFS rates of most of the published studies concerning gynecological oligometastases.\u003c/p\u003e\n\u003cp\u003eNonetheless, in the last years, encouraging preliminary experiences report the outcomes of SBRT applied to this setting of patients. (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e \u003csup\u003e\u003cstrong\u003e10,11,23\u0026minus;27\u003c/strong\u003e\u003c/sup\u003e)\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab4\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eLiterature experiences of SBRT for gynecological malignancies\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAuthor\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNumber of patients\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNumber of metastases\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFollow-up (months)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePrimary Histology\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eToxicity\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eClinical Outcomes\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIftode et al.\u003csup\u003e23\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOC\u0026thinsp;=\u0026thinsp;100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLate G2\u0026thinsp;=\u0026thinsp;11%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2yrLC\u0026thinsp;=\u0026thinsp;92.9%\u003c/p\u003e\n \u003cp\u003e2yrPFS\u0026thinsp;=\u0026thinsp;38%\u003c/p\u003e\n \u003cp\u003e2yrOS\u0026thinsp;=\u0026thinsp;92.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMacchia et al.\u003csup\u003e10\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e261\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e449\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOC\u0026thinsp;=\u0026thinsp;100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u0026nbsp;year late G2 toxicity-free survival\u0026thinsp;=\u0026thinsp;95.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2yrLC\u0026thinsp;=\u0026thinsp;95.1%\u003c/p\u003e\n \u003cp\u003e2yrPFS\u0026thinsp;=\u0026thinsp;15.4%\u003c/p\u003e\n \u003cp\u003e2yrOS\u0026thinsp;=\u0026thinsp;73.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReshko et al.\u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOC\u0026thinsp;=\u0026thinsp;30/86\u003c/p\u003e\n \u003cp\u003eCC\u0026thinsp;=\u0026thinsp;20/86\u003c/p\u003e\n \u003cp\u003eEC\u0026thinsp;=\u0026thinsp;27/86\u003c/p\u003e\n \u003cp\u003eOther\u0026thinsp;=\u0026thinsp;9/86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAcute G\u0026thinsp;\u0026ge;\u0026thinsp;2\u0026thinsp;=\u0026thinsp;4.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3yrLC\u0026thinsp;=\u0026thinsp;68%\u003c/p\u003e\n \u003cp\u003e3yrPFS=\u003c/p\u003e\n \u003cp\u003e3yrOS\u0026thinsp;=\u0026thinsp;39%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReddy et al.\u003csup\u003e24\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEC\u0026thinsp;=\u0026thinsp;100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOne case of late G2 pneumonitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1yrLC\u0026thinsp;=\u0026thinsp;80.3%\u003c/p\u003e\n \u003cp\u003e1yrPFS\u0026thinsp;=\u0026thinsp;75.9%\u003c/p\u003e\n \u003cp\u003e1yrOS\u0026thinsp;=\u0026thinsp;62%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNing et al.\u003csup\u003e25\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCC\u0026thinsp;=\u0026thinsp;100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAcute G2\u0026thinsp;=\u0026thinsp;39%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2yrLC=\u003c/p\u003e\n \u003cp\u003e2yrPFS\u0026thinsp;=\u0026thinsp;48%\u003c/p\u003e\n \u003cp\u003e2yrOS\u0026thinsp;=\u0026thinsp;74%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOnal et al.\u003csup\u003e26\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCC\u0026thinsp;=\u0026thinsp;21/29\u003c/p\u003e\n \u003cp\u003eOC\u0026thinsp;=\u0026thinsp;8/29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAcute G2\u0026thinsp;=\u0026thinsp;17%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2yrLC\u0026thinsp;=\u0026thinsp;95.1%\u003c/p\u003e\n \u003cp\u003e2yrPFS\u0026thinsp;=\u0026thinsp;18%\u003c/p\u003e\n \u003cp\u003e2yrOS\u0026thinsp;=\u0026thinsp;73.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmile et al.\u003csup\u003e27\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOC\u0026thinsp;=\u0026thinsp;12/34\u003c/p\u003e\n \u003cp\u003eEC\u0026thinsp;=\u0026thinsp;11/34\u003c/p\u003e\n \u003cp\u003eCC\u0026thinsp;=\u0026thinsp;7/34\u003c/p\u003e\n \u003cp\u003eOther\u0026thinsp;=\u0026thinsp;4/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 acute G2 events\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2yrLC\u0026thinsp;=\u0026thinsp;92.5%\u003c/p\u003e\n \u003cp\u003e1yrPFS\u0026thinsp;=\u0026thinsp;60.2%\u003c/p\u003e\n \u003cp\u003e2yrOS\u0026thinsp;=\u0026thinsp;70.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePresent experience\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOC\u0026thinsp;=\u0026thinsp;17/40\u003c/p\u003e\n \u003cp\u003eCC\u0026thinsp;=\u0026thinsp;4/40\u003c/p\u003e\n \u003cp\u003eEC\u0026thinsp;=\u0026thinsp;17/40\u003c/p\u003e\n \u003cp\u003eOther\u0026thinsp;=\u0026thinsp;2/40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo acute or late G\u0026thinsp;\u0026ge;\u0026thinsp;2 events\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2yrLC\u0026thinsp;=\u0026thinsp;100%\u003c/p\u003e\n \u003cp\u003e2yrPFS\u0026thinsp;=\u0026thinsp;23%; 2yrOS\u0026thinsp;=\u0026thinsp;70%\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\u003e\u003cem\u003eAbbreviations: CC=cervical cancer; EC=endometrial cancer; OC=ovarian cancer; LC=local control; PFS=progression-free survival; OS=overall survival\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIftode et al. collected data concerning a series of 44 metastatic lesions arising from ovarian cancer who received SBRT, collecting satisfactory outcomes in terms of LC and PFS, with negligible toxicity. [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\n\u003cp\u003eNing et al. in a previous report focused their attention on cervical cancer oligometastases, collecting promising results, in agreement with the abovementioned studies. Of note, this study included both SBRT and conventional fractionation treatments, making harder to draw definitive conclusions. [\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e\n\u003cp\u003eReddy et al. documented excellent local control results in a series of 27 patients with oligometastatic uterine cancer, recording worse local control rates in the case of liver metastases. [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e\n\u003cp\u003eThe favorable toxicity profile of our series supports this therapeutic approach, also when combined with conventional systemic therapies that for gynecological malignancies still represent the standard of care. This is also confirmed by one of the largest series available in the literature, in which in a multicenter series published by Macchia et al., the authors collected a 2-years toxicity free survival rate of 95.1%. Interestingly, keeping in mind that this study refers to ovarian cancer oligometastases, a statistically significant correlation was found for higher LC rates, when a BED\u0026thinsp;\u0026gt;\u0026thinsp;70 Gy radiotherapy schedule is applied. [\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e\n\u003cp\u003eSimilarly to our experience, a recent study by Smile et al. included different primary gynecological cancers also highlighting excellent results in terms of both toxicity and clinical outcomes. [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e\n\u003cp\u003eThe present study has several limitations; first of all, we retrospectively collect data of a heterogeneous sample of patients including different primary histologies and both patients who received and received not systemic therapy. Nonetheless, we report one of the largest series with the longest follow-up currently available, and the results are promising and in agreement with other literature experiences supporting the role of SBRT, also in this relatively unexplored field of the oligometastatic disease.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis mono-institutional experience supports the use of SBRT in the management of the oligometastatic gynecological cancer, by collecting no relevant toxicity and promising results in terms of clinical outcomes. Prospective studies are needed to further evaluate this therapeutic option in this scenario.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contribution:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFC, CV and EP: manuscript drafting; LN, VF, MR, FR, CV, GA: data collection; FC, CV, FA: study design; FA, RM, NGL, RR: editing and revision; All author: final approval\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eall authors declare no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFundings:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003enot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eCronin KA, Lake AJ, Scott S, et al. 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Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol Off J Am Soc Clin Oncol 2015;33:2129\u0026ndash;35\u003c/li\u003e\n \u003cli\u003eLong 3rd HJ, Bundy BN, Grendys Jr EC, Benda JA, McMeekin DS, Sorosky J, et al. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol 2005;23:4626\u0026ndash;33\u003c/li\u003e\n \u003cli\u003eBuechel M, Herzog TJ, Westin SN et al. Treatment of patients with recurrent epithelial ovarian cancer for whom platinum is still an option. 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JAMA Oncol. 2021 Jan 1;7(1):92-106. doi: 10.1001/jamaoncol.2020.6146\u003c/li\u003e\n \u003cli\u003ePalma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, Mulroy L, Lock M, Rodrigues GB, Yaremko BP, Schellenberg D, Ahmad B, Senthi S, Swaminath A, Kopek N, Liu M, Moore K, Currie S, Schlijper R, Bauman GS, Laba J, Qu XM, Warner A, Senan S. Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. J Clin Oncol. 2020 Sep 1;38(25):2830-2838. doi: 10.1200/JCO.20.00818.\u003c/li\u003e\n \u003cli\u003eChalkidou A, Macmillan T, Grzeda MT, Peacock J, Summers J, Eddy S, Coker B, Patrick H, Powell H, Berry L, Webster G, Ostler P, Dickinson PD, Hatton MQ, Henry A, Keevil S, Hawkins MA, Slevin N, van As N. Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: a prospective, registry-based, single-arm, observational, evaluation study. Lancet Oncol. 2021 Jan;22(1):98-106. doi: 10.1016/S1470-2045(20)30537-4.\u003c/li\u003e\n \u003cli\u003eZhang TW, Palma D, D\u0026apos;Souza D, Velker V, Mendez LC. Stereotactic Ablative Radiotherapy for Recurrent or Metastatic Gynecological Cancer: Extending Lives? Curr Treat Options Oncol. 2020 Jun 12;21(7):58. doi: 10.1007/s11864-020-00748-6.\u003c/li\u003e\n \u003cli\u003eNicosia L, Cuccia F, Mazzola R, Ricchetti F, Figlia V, Giaj-Levra N, Rigo M, Tomasini D, Pasinetti N, Corradini S, Ruggieri R, Alongi F. Disease course of lung oligometastatic colorectal cancer treated with stereotactic body radiotherapy. Strahlenther Onkol. 2020 Sep;196(9):813-820. doi: 10.1007/s00066-020-01627-7.\u003c/li\u003e\n \u003cli\u003eNicosia L, Cuccia F, Mazzola R, Figlia V, Giaj-Levra N, Ricchetti F, Rigo M, Bon\u0026ugrave; M, Corradini S, Tolia M, Alongi F. Stereotactic body radiotherapy (SBRT) can delay polymetastatic conversion in patients affected by liver oligometastases. J Cancer Res Clin Oncol. 2020 Sep;146(9):2351-2358. doi: 10.1007/s00432-020-03223-9.\u003c/li\u003e\n \u003cli\u003eIftode C, DʼAgostino GR, Tozzi A, Comito T, Franzese C, De Rose F, Franceschini D, Di Brina L, Tomatis S, Scorsetti M. Stereotactic Body Radiation Therapy in Oligometastatic Ovarian Cancer: A Promising Therapeutic Approach. Int J Gynecol Cancer. 2018 Oct;28(8):1507-1513. doi: 10.1097/IGC.0000000000001324.\u003c/li\u003e\n \u003cli\u003eReddy AV, Mills MN, Reshko LB, Martin Richardson K, Kersh CR. Stereotactic Body Radiation Therapy in Oligometastatic Uterine Cancer: Clinical Outcomes and Toxicity. Cancer Invest. 2020 Sep;38(8-9):522-530. doi: 10.1080/07357907.2020.1817483.\u003c/li\u003e\n \u003cli\u003eNing MS, Ahobila V, Jhingran A, Stecklein SR, Frumovitz M, Schmeler KM, Eifel PJ, Klopp AH. Outcomes and patterns of relapse after definitive radiation therapy for oligometastatic cervical cancer. Gynecol Oncol. 2018 Jan;148(1):132-138. doi: 10.1016/j.ygyno.2017.10.017.\u003c/li\u003e\n \u003cli\u003eOnal C, Gultekin M, Oymak E, Guler OC, Yilmaz MT, Yuce Sari S, Akkus Yildirim B, Yildiz F. Stereotactic radiotherapy in patients with oligometastatic or oligoprogressive gynecological malignancies: a multi-institutional analysis. Int J Gynecol Cancer. 2020 Jun;30(6):865-872. doi: 10.1136/ijgc-2019-001115.\u003c/li\u003e\n \u003cli\u003eSmile TD, Reddy CA, Qiao-Guan G, Winter WI, Stephans KL, Woody NM, Balagamwala EH, Amarnath SR, Magnelli A, AlHilli MM, Michener CM, Mahdi H, DeBernardo RL, Rose PG, Cherian SS. Stereotactic body radiotherapy for the treatment of oligometastatic gynecological malignancy in the abdomen and pelvis: A single-institution experience. J Radiosurg SBRT. 2021;7(3):189-197\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Figure","content":"\u003cp\u003eFigure 2 is not available with this version.\u003c/p\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":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-cancer-research-and-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocr","sideBox":"Learn more about [Journal of Cancer Research and Clinical Oncology](https://www.springer.com/journal/432)","snPcode":"432","submissionUrl":"https://submission.nature.com/new-submission/432/3","title":"Journal of Cancer Research and Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"stereotactic body radiotherapy, gynecological malignancies, oligometastases","lastPublishedDoi":"10.21203/rs.3.rs-809076/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-809076/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\u003cp\u003eThe use of stereotactic radiotherapy (SBRT) for oligometastases is supported by several literature studies, but in the setting of gynecological malignancies, this scenario remains quite unexplored. This study reports a preliminary assessment of clinical outcomes in a cohort of 40 patients with oligometastatic gynecological neoplasms. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eRadiotherapy was delivered in 3-10 fractions with VMAT-IGRT technique. Toxicity was retrospectively collected according to CTCAE v4.0. Data were retrospectively collected and analyzed. Univariate and multivariate analysis were performed for assessing any potential predictive factor for clinical outcomes. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eA total of 63 oligometastases were treated from December 2014 to February 2021. Median age was 63 years (range, 30-89). Most frequent primary tumors were ovarian cancer in 42.5% and endometrium cancer in 42.5%. With a median follow-up of 27 months (range, 6-69), no local failures were observed, our progression-free survival rates were 43.6% and 23% at one and 2 years, respectively, while 1- and 2-years overall survival rates were both 70%. No acute or late G≥2 adverse events were observed.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eIn our experience, SBRT for oligometastatic gynecological malignancies resulted in promising results in terms of clinical outcomes, with excellent local control and no evidence of severe toxicity, highilighting the effectiveness of this therapeutic option. Prospective studies to further explore this approach in this setting are advocated.\u003c/p\u003e","manuscriptTitle":"The Use of SBRT in the Management of Oligometastatic Gynecological Cancer: Report of Promising Results in Terms of Tolerability and Clinical Outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-08-18 14:50:32","doi":"10.21203/rs.3.rs-809076/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2021-08-28T09:16:53+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-08-13T14:14:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-08-13T13:04:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cancer Research and Clinical Oncology","date":"2021-08-12T09:58:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cancer-research-and-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocr","sideBox":"Learn more about [Journal of Cancer Research and Clinical Oncology](https://www.springer.com/journal/432)","snPcode":"432","submissionUrl":"https://submission.nature.com/new-submission/432/3","title":"Journal of Cancer Research and Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5272f593-f78d-4cc7-86e0-4355c741250b","owner":[],"postedDate":"August 18th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":6518539,"name":"Cancer Biology"},{"id":6518540,"name":"Oncology"}],"tags":[],"updatedAt":"2021-09-12T14:58:16+00:00","versionOfRecord":[],"versionCreatedAt":"2021-08-18 14:50:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-809076","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-809076","identity":"rs-809076","version":["v1"]},"buildId":"omnImTCwR2MFx8CMYfrG7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}