Clinical Outcomes Observation in Stage IIB–III Cervical Cancer Treated by Adjuvant Surgery Following Concurrent Chemoradiotherapy

Clinical Outcomes Observation in Stage IIB–III Cervical Cancer Treated by Adjuvant Surgery Following Concurrent Chemoradiotherapy | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Clinical Outcomes Observation in Stage IIB–III Cervical Cancer Treated by Adjuvant Surgery Following Concurrent Chemoradiotherapy Yong Li, Zhiying Chen, Xiang Wang, Xiumei Li, Jie Zhou, Yongchun Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-53507/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 Objective : To explore the feasibility of adjuvant surgery following concurrent chemoradiation therapy (CCRT) in stage ⅡB–Ⅲ cervical cancer. And analyze risk factors of recurrence after surgery. Methods : Forty-nine patients diagnosed with stage ⅡB–Ⅲ cervical cancer were reviewed retrospectively. Investigated the risk factors of recurrence after surgery using Chi-squared Test and further analyzed multiple factors affecting postoperative recurrence using the multi-factor logistic regression. Furthermore, the correlation of surgery outcomes (including operation time, bleeding, and hospitalization date and surgery complications) with the time which carried out between CCRT and completion surgery was analyzed. Results : Tumor histology and residual tumor in the cervix were significantly associated with postoperative recurrence (P = 0.014 and P = 0.040, respectively). Logistic regression analysis demonstrated that the independent risk factors of postoperative recurrence were age and residual tumor in the cervix (P = 0.017 and P = 0.030, respectively). Compared with completion surgery was carried out ≤ 6 weeks after CCRT, the operation time, bleeding, hospitalization date and surgery complications were more than > 6 weeks group. Moreover, bleeding and surgery complications were statistically significant (P = 0.019 and P = 0.044, respectively). Conclusion : CCRT combined surgery for stage ⅡB–Ⅲ cervical cancer was feasible, reduced the rate of postoperative recurrence and surgery complications were tolerated. CCRT combined surgery might improve the local control of lesion. Oncology Cervical cancer concurrent chemoradiation surgery recurrence Introduction Cervical cancer is a worldwide major public health issue. It is the second most common malignancy in women and represents the third-leading cancer in women worldwide [ 1 ]. Approximately 500,000 new cases and 237,500 deaths of cervical cancer occur annually. Advanced cervical cancer is not easy to control and has poor prognosis because of the lymph node metastasis or distant metastasis. Cisplatin- based concurrent chemoradiotherapy is the standard treatment for advanced cervical cancer, but the local recurrence rate after chemoradiotherapy is high and 5-year survival rate is only 50 to 65 percent [ 2 ]. In order to further improve the local control rate of cervical cancer and improve the 5-year survival rate, many scholars have explored the efficacy and safety of concurrent radiotherapy and chemotherapy combined with surgery in the treatment of advanced cervical cancer [ 3 ]. Some studies have reported that CCRT combined surgery can improve local lesion control and overall survival, but the role of adjuvant surgery is still controversial, because these studies differ in disease stage, surgical scope, and form of CCRT (radiotherapy dose, internal irradiation or not, and type of chemotherapy) [ 4 ]. The purpose of this paper is to explore the feasibility of CCRT joint surgery in cervical cancer patients with ⅡB–Ⅲ period and retrospectively analyze the related factors of postoperative recurrence. Materials And Methods Patients This study includes 49 patients with biopsy proven cervical cancer between June 2006 and October 2012 was treated in department of Radiotherapy Center and Gynecology of the Affiliated Hospital of Qingdao University. The Institutional Review Board approved this study and informed consent was obtained. Inclusion criteria: a) Eastern Cooperative Oncology Group (ECOG) status was less than or equal to 1; b) International Federation of Gynecology and Obstetrics (FIGO) stages ⅡB–Ⅲ cervical cancer through gynecological examination by two veteran gynecologic oncologists; c) All patients underwent a medical history, gynecological examination; punch biopsy, chest X-ray, pelvic magnetic resonance imaging (MRI) and transvaginal ultrasound (TVS). Exclusion criteria: a) Patients with serious heart, lung, liver or hematologic system disease; b) Patients with other cancer; c) Treatment was interrupted or radiotherapy did not reach the radical dose; d) Lost to follow-up or death from other causes. CCRT All patients completed the radical radiotherapy in department of Radiotherapy Center. Patients were immobilized with a body net in the supine position and underwent a computed tomography (CT) simulation scan (General Electric, Milwaukee WI, USA) with intravenous contrast, using 5 mm slice thickness. Simulation images extended from L1 to 5 cm below the ischial tuberosities. The gross tumor volume (GTV), clinical target volume (CTV) and planning target volume (PTV) were defined according to Radiation Therapy Oncology Group (RTOG) guidelines. The CTV-high risk included the GTV, parametrium, the upper part of the vagina to 3 cm below the tumor invasion, and metastasis lymph node. The CTV-low risk included the CTV-high risk and regional lymph nodes (common, external, internal iliac lymph nodes, obturator and presacral lymph nodes). The treatment planning was designed and computed using the Plato system version 2.7.5 (Varian, USA). The external radiation dose was 40-50 Gy in 20-25 fractions with 2 Gy per fraction using a linear accelerator (Trilogy, Varian, USA). And followed by high-dose-rate brachytherapy to 90% of the high-risk CTV was delivered with 30-40 Gy using an intracavity applicator (microSelectron-HDR Ir-192 set; Nucletron, Veenendaal, Netherlands). All patients received concomitant chemotherapy of cis-platinum (40mg/m 2 ) alone every week starting with external radiotherapy (4-5 circles). Adjacent surgery After reevaluated the relationship between cervix, bladder, rectum and parauterine tissue through gynecological examination and pelvic MRI, all patients underwent extrafascial hysterectomy with adnexectomy followed by CCRT. According to postoperative pathology, nine patients with invading ½ of the cervical stroma recived 4 circles chemotherapy consisted of the association of cis-platinum (100mg/ m 2 ) in combination with paclitaxel (135mg/ m 2 ). Follow-up Patient follow-up was designed to be conducted every 3 months during the first two years and every 6 months over the next three years after surgery. The follow-up included gynecological examination, TVS, vaginal apical cytology, abdominal plevic and chest CT. Statistical analysis All data were performed using SPSS 20.0 (Chicago IL, USA). Quantitative data are expressed as the mean ± standard deviation (S.D.).  2 test or Fisher exact test was used to evaluate categorical variable. Groups were compared using Student’s t -test. . Multivariate analysis of prognostic factors was performed with Cox proportional hazards regression. A p < 0.05 was regarded as statistically significant. Results After the combination of CCRT and surgery, recurrence of disease was observed in 12 (22.4%) patients, which were distributed as follows: 9 local recurrences and 3 distant metastases (1 lung metastasis and 2 bone metastases). Median follow-up from the date of surgery was 76 months (range 29–129 months),and 5 patients died during follow-up. The 3-year OS and 5-year OS were 95.9% and 89.8%, respectively. The correlations of major clinical/pathological factors and recurrence after CCRT and adjacent surgery in LACC were summarized in Table 1 . Median age of 49 patients was 49 years (range 29–66) and there was statistically significant difference between age and recurrence of disease (P = 0.023). Table 1 Correlations of major clinical/pathological factors and recurrence after CCRT and adjacent surgery in stage ⅡB–Ⅲ cervical cancer Factors Number (%) Recurrence χ 2 p No Yes Age HPV infection Tumor diameters Pathological differentiation Pathologic subtypes FIGO stage Microscopic residual ༜50 ≥ 50 No Yes ≤ 4 cm ༞4 cm High Moderatly Low Adenocarcinoma/mixed subtypes SCC IIB IIIA IIIB No Disease invading less than 50% of the myometrium Disease invading more than 50% of the myometrium 28(57.1) 21(42.9) 31(63.3) 18(36.7) 20(40.8) 29(59.2) 7(14.3) 33(67.3) 9(18.4) 7(14.3) 42(85.7) 41(83.7) 1(2.0) 7(14.3) 27(55.1) 13(26.5) 9(18.4) 50 13 25 13 14 24 5 25 8 4 34 32 1 5 20 13 5 3 8 6 5 6 5 2 8 1 3 8 9 0 2 7 0 4 5.168 0.464 1.107 0.979 1.954 0.657 8.920 0.023* 0.496 0.293 0.613 0.162 0.720 0.012* CCRT, concurrent chemoradiotherapy; HPV, human papillomavirus; FIGO, International Federation of Gynecology and Obstetrics; SCC, squamous cell carcinoma; *P༜0.05 After adjacent surgery, 27 patients (55.1%) showed a complete response to CCRT treatment, and 22 cases (44.9%) showed a microscopic residual disease (9 cases with disease invading more than 50% of the myometrium and 13 cases with disease invading less than 50% of the myometrium). There was statistically significant difference between recurrence of disease and microscopic residual (P = 0.012). On multivariate analysis showed both age and microscopic residual were highly correlated with recurrence of disease (Table 2 ) (P = 0.017 and P = 0.030, respectively).Although there was not statistically significant difference between tumor diameters and recurrence of disease, tumor diameters was highly correlated with microscopic residual on further analysis (Table 3 ). Table 2 Multivariate analysis of recurrence after CCRT and adjacent surgery in stage ⅡB–Ⅲ cervical cancer Parameters βi S.E Walds P Exp ( B ) 95% CI Age HPV infection Tumor diameters Pathological differentiation Pathologic subtype FIGO stage Residual cancer Constant 3.222 1.290 -0.336 1.153 -1.586 -2.521 -3.274 1.176 1.351 1.173 1.125 1.659 1.660 2.201 1.506 2.907 5.691 1.211 0.089 0.483 0.913 1.312 4.723 0.369 0.017* 0.271 0.765 0.487 0.339 0.252 0.030* 0.544 25.086(1.777 ~ 354.179) 3.633(0.365 ~ 36.167) 0.715(0.079 ~ 6.476) 3.168(0.123 ~ 81.769) 0.205(0.008 ~ 5.296) 0.080(0.001 ~ 6.008) 0.038(0.002 ~ 0.725) CCRT, concurrent chemoradiotherapy; *P༜0.05 Table 3 The relationship between macroscopic residual and clinical/pathological factors clinical/pathological factors Macroscopic residual χ 2 p No Yes Tumor diameters Pathological differentiation Pathologic subtype ≤ 4 cm ༞4 cm High Moderately Low Adenocarcinoma/mixed subtypes SCC 18 9 4 18 5 3 24 2 20 3 5 4 4 18 14.337 0.017 0.086 ༜0.001* 0.992 0.769 SCC, squamous cell carcinoma; *P༜0.05 In early postoperative period (≤ 30 days), 2 incomplete intestinal obstruction and 3 deep venous thrombosis were found. As far as long-term postoperative period (> 30 days), 3 complications were observed: 2 patients developed colorectal fistula and 1 patient showed pelvic pain. The average of operation time was 2.0 ± 0.4 h (range 1.2–3.1 h) and blood loss during the surgery was 133.5 ± 66.7 mL (range 50–400 mL). The average hospital stay was 9.4 ± 2.1 days (range 6–15 days). The relationship between the time to start operation after CCRT and blood loss during the surgery, hospital stay and postoperative complication were analyzed furthermore (Table 4 ). Although blood loss during the surgery, hospital stay and postoperative complication in > 6 weeks group were less than that in ≤ 6 weeks group, only blood loss during surgery and postoperative complication were closely related with the time to start operation after CCRT (F = 5.866,P = 0.019;F = 4.056༌P = 0.044). Table 4 The evaluation of operation time Groups Operation time (h) p Bleeding (mL) p Hospital stay (day) p Complications p No Yes ≤ 6 weeks ༞6 weeks 1.812 ± 0.376 1.944 ± 0.368 0.942 147.41 ± 78.377 115.70 ± 43.425 0.019* 9.740 ± 2.141 9.050 ± 2.081 0.225 20 21 7 1 0.044* *P༜0.05 Disscussion Local and distant recurrence is the main reason for the failure of treatment of locally advanced cervical cancer. Studies have reported that CCRT can improve the local control of lesions, progression-free survival and total survival in patients with locally advanced cervical cancer. Some researchers [ 5 , 6 ] believe that the control of local lesions can improve the surgical resection rate. At present, there are few studies on adjuvant surgery, which is controversial for further reducing recurrence rate and improving prognosis. In this study, a total of 49 patients with locally advanced cervical cancer were included. The lesions all shrank to different degrees after CCRT treatment, among which 18 patients showed significant improvement in paratactic infiltration. About 3–9 weeks after CCRT treatment, all patients underwent extrafascial hysterectomy and bilateral adnexectomy, and the incidence of postoperative complications was 16.3%, similar to 19.8% in the previous study [ 7 ]. 9 cases of patients were proved to be local recurrence with pathologically, and distant metastasis was observed in 3 patients. The recurrence rate (22.4%) was little higher compared with the previous work, which 192 ⅡB–ⅣA stage cervical cancer patients was included. The recurrence rate in our study is slightly higher than CCRT joint surgery (16.7%), however, there was a decrease compared to CCRT alone (31.7%). Maybe it was the small sample size that led to such different results. This study showed that pathological cancer residue was closely related to recurrence, and multivariate analysis of variance showed that cancer residue was an independent risk factor for postoperative recurrence, which was consistent with previous research results [ 7 , 8 ]. Further study found that residual carcinoma associated with preoperative lesions in diameter, suggesting that patients with tumor lesions of large diameter were more likely to relapse. The higher recurrence rate may be associated with the lack of oxygen in the center of tumors, which leading to a decrease in the sensitivity of tumor cells to radiation and weakens the efficacy of radiotherapy [ 9 ]. In this study, postoperative pathological types were significantly correlated with postoperative recurrence. The recurrence rate of patients with simple squamous cell carcinoma was lower than other pathological types. This may because squamous cell carcinoma has higher radiosensitivity than other pathological types [ 10 ]. In this study, multivariate analysis of variance showed that age was also an independent risk factor for postoperative recurrence, which may be related to difference in hormone and immune levels in different age groups. However, it is still controversial whether age is related to recurrence and prognosis. Other previous studies [ 11 ] have pointed out that the degree of tumor differentiation can affect the sensitivity of tumor cells to radiation. However, this study did not suggest that the degree of differentiation of cervical cancer is related to local recurrence. This may be related to the small number of included cases and the uneven proportion of the degree of differentiation and a large sample study is needed for further validation. In this study, the incidence of postoperative complications was 16.3%, mainly due to mild myelosuppression and gastrointestinal reactions. The 2 cases of postoperative incomplete intestinal obstruction and intestinal fistula recovered after conservative treatment. By contrast to the previous studies (12.8–19.8%), the complication rate was within an acceptable range in our study [ 12 , 13 ]. In addition, in this study, the time between the CCRT and surgery was compared in different group. By comparing the operative time, bleeding volume and postoperative complications, the interval > 6weeks group was better than the group with interval ≤ 6weeks and the result was statistically different. By analyzing the reason, the tissue was still in a state of hyperemia and edema after chemoradiotherapy, so the risk of bleeding and infection after operation in short-interval increased. Therefore, appropriately extending the time between CCRT and surgery can reduce intraoperative bleeding and facilitate postoperative recovery. This study retrospectively analyzed the cervical cancer patients with ⅡB–Ⅲ stage who accepted extra-fascial hysterectomy and bilateral adnexectomy hysterectomy surgery after CCRT. The postoperative recurrence rate decreased than pure CCRT treatment and there was no obvious increase in postoperative complications. The joint is expected to improve the local control rate of locally advanced cervical cancer patients and improve the long-term curative effect. Declarations Acknowledgements Not applicable. Authors' contributions Yongchun Zhang, conception; Yong Li and Yongchun Zhang, design of the work; Xiumei Li and Jie Zhou, the acquisition, analysis; Yong Li, drafted the work; Zhiying Chen and Xiang Wang, interpretation of data. Competing interests The authors declare that they have no competing interests. Funding Not applicable. Availability of data and materials All data generated or analyzed during this study are included in this published article. Ethics approval and consent to participate This study was approved by the Affiliated Hospital of Qingdao University (the Institutional Review Board). Consent for publication Not applicable. References Wei LC, Wang N, Shi M, Liu JY, Li JP, Zhang Y, Huang YH, Li X, Chen Y: Clinical outcome observation of preoperative concurrent chemoradiotherapy/radiotherapy alone in 174 Chinese patients with local advanced cervical carcinoma. Onco Targets Ther 2013, 6:67-74. Chereau E, C DLH, Ballester M, Monnier L, Rouzier R, Touboul E, Darai E: The role of completion surgery after concurrent radiochemotherapy in locally advanced stages IB2-IIB cervical cancer. Anticancer Res 2013, 33:1661-1666. Houvenaeghel G, Lelievre L, Gonzague-Casabianca L, Buttarelli M, Moutardier V, Goncalves A, Resbeut M: Long-term survival after concomitant chemoradiotherapy prior to surgery in advanced cervical carcinoma. Gynecol Oncol 2006, 100:338-343. Malzoni M, Spina V, Perniola G, Aleandri V, Mossa B, Iuele T, Imperato F: Laparoscopic surgery in treatment of stage IIb cervical cancer after neoadjuvant chemotherapy. A case report and review of the literature. Eur J Gynaecol Oncol 2003, 24:393-397. Ota T, Takeshima N, Tabata T, Hasumi K, Takizawa K: Adjuvant hysterectomy for treatment of residual disease in patients with cervical cancer treated with radiation therapy. Br J Cancer 2008, 99:1216-1220. Classe JM, Rauch P, Rodier JF, Morice P, Stoeckle E, Lasry S, Houvenaeghel G, Groupe des Chirurgiens de Centre de Lutte Contre le C: Surgery after concurrent chemoradiotherapy and brachytherapy for the treatment of advanced cervical cancer: morbidity and outcome: results of a multicenter study of the GCCLCC (Groupe des Chirurgiens de Centre de Lutte Contre le Cancer). Gynecol Oncol 2006, 102:523-529. Sun L, Sheng X, Jiang J, Li X, Liu N, Liu Y, Zhang T, Li D, Zhang X, Wei P: Surgical morbidity and oncologic results after concurrent chemoradiation therapy for advanced cervical cancer. Int J Gynaecol Obstet 2014, 125:111-115. Hirakawa M, Nagai Y, Toita T, Kudaka W, Inamine M, Ogawa K, Murayama S, Aoki Y: High-risk group for locoregional recurrence in patients with stage IB-IIB squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy. Anticancer Res 2011, 31:1437-1441. Gray LH, Conger AD, Ebert M, Hornsey S, Scott OC: The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 1953, 26:638-648. Ferrandina G, Margariti PA, Smaniotto D, Petrillo M, Salerno MG, Fagotti A, Macchia G, Morganti AG, Cellini N, Scambia G: Long-term analysis of clinical outcome and complications in locally advanced cervical cancer patients administered concomitant chemoradiation followed by radical surgery. Gynecol Oncol 2010, 119:404-410. Kim YH, Chung WK, Jeong JU, Cho IJ, Yoon MS, Song JY, Nam TK, Ahn SJ, Lee DH, Yoon TM, et al: Evaluation of Prognostic Factors for the Parotid Cancer Treated With Surgery and Postoperative Radiotherapy. Clin Exp Otorhinolaryngol 2019. Mariagrazia D, Anna F, Gabriella F, Francesco F, Daniela S, Giuseppe D, Alessio M, Giovanni S: Preoperative chemoradiotherapy in locally advanced cervical cancer: long-term outcome and complications. Gynecol Oncol 2005, 99:S166-170. Trimbos JB, Franchi M, Zanaboni F, Velden J, Vergote I: 'State of the art' of radical hysterectomy; current practice in European oncology centres. Eur J Cancer 2004, 40:375-378. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About 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-53507","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":1361446,"identity":"c3104b0c-bf33-4eea-9df4-268f113cecdf","order_by":0,"name":"Yong Li","email":"","orcid":"","institution":"the affiliated hospital of qingdao university","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yong","middleName":"","lastName":"Li","suffix":""},{"id":1361447,"identity":"1d472924-e1d6-4909-810c-469ab867fae3","order_by":1,"name":"Zhiying Chen","email":"","orcid":"","institution":"the Affiliated Hospital of Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhiying","middleName":"","lastName":"Chen","suffix":""},{"id":1361448,"identity":"7f6e6f21-b068-44d8-abef-90af9ede6186","order_by":2,"name":"Xiang Wang","email":"","orcid":"","institution":"the Affiliated Hospital of Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiang","middleName":"","lastName":"Wang","suffix":""},{"id":1361449,"identity":"1ec23d4e-dd41-4290-bbf4-91896a029276","order_by":3,"name":"Xiumei Li","email":"","orcid":"","institution":"the Affiliated Hospital of Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiumei","middleName":"","lastName":"Li","suffix":""},{"id":1361450,"identity":"5ebddc55-264a-4f95-9afe-93dd97637151","order_by":4,"name":"Jie Zhou","email":"","orcid":"","institution":"the Affiliated Hospital of Qingdao University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Zhou","suffix":""},{"id":1361451,"identity":"2e24b7dd-6e13-4cdb-96a2-b12134b56d85","order_by":5,"name":"Yongchun Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYFCD442NDz6QpuXM4WbDGaRpuZHeJs1BjEL5GdmpGz7u2SbHd/NhgzQDg52cbgMBLQY3crfdnPHstrHk7cQG4wKGZGOzA4S0SORuu81z4HbiBqCW5BkMBxK3EdIiPwOo5c+B2/Ubbh5sOMxDjBYGoMNuMxy4nWBwg7GxmSgtBmfebrvZc+C24cwzic2MMwyI8It8e+62Gz8O3JbnO378+Y8PFXZyBLWgW0qa8lEwCkbBKBgFOAAACvFQA2t6MQ0AAAAASUVORK5CYII=","orcid":"","institution":"the Affiliated Hospital of Qingdao University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Yongchun","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2020-08-04 11:39:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-53507/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-53507/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":13572972,"identity":"35cca74f-3526-404c-99d1-b749633fb077","added_by":"auto","created_at":"2021-09-17 03:53:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":296588,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-53507/v1/0dd153f4-5cab-4b56-bf6b-a2727b38772e.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eClinical Outcomes Observation in Stage IIB–III Cervical Cancer Treated by Adjuvant Surgery Following Concurrent Chemoradiotherapy\u003c/p\u003e","fulltext":[{"header":"Introduction","content":" \u003cp\u003eCervical cancer is a worldwide major public health issue. It is the second most common malignancy in women and represents the third-leading cancer in women worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Approximately 500,000 new cases and 237,500 deaths of cervical cancer occur annually. Advanced cervical cancer is not easy to control and has poor prognosis because of the lymph node metastasis or distant metastasis. Cisplatin- based concurrent chemoradiotherapy is the standard treatment for advanced cervical cancer, but the local recurrence rate after chemoradiotherapy is high and 5-year survival rate is only 50 to 65 percent [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In order to further improve the local control rate of cervical cancer and improve the 5-year survival rate, many scholars have explored the efficacy and safety of concurrent radiotherapy and chemotherapy combined with surgery in the treatment of advanced cervical cancer [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Some studies have reported that CCRT combined surgery can improve local lesion control and overall survival, but the role of adjuvant surgery is still controversial, because these studies differ in disease stage, surgical scope, and form of CCRT (radiotherapy dose, internal irradiation or not, and type of chemotherapy) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The purpose of this paper is to explore the feasibility of CCRT joint surgery in cervical cancer patients with ⅡB\u0026ndash;Ⅲ period and retrospectively analyze the related factors of postoperative recurrence.\u003c/p\u003e "},{"header":"Materials And Methods","content":"\u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study includes 49 patients with biopsy proven cervical cancer between June 2006 and October 2012 was treated in department of Radiotherapy Center and Gynecology of the Affiliated Hospital of Qingdao University. The Institutional Review Board approved this study and informed consent was obtained. Inclusion criteria: a) Eastern Cooperative Oncology Group (ECOG) status was less than or equal to 1; b) International Federation of Gynecology and Obstetrics (FIGO) stages ⅡB\u0026ndash;Ⅲ cervical cancer through gynecological examination by two veteran gynecologic oncologists; c) All patients underwent a medical history, gynecological examination; punch biopsy, chest X-ray, pelvic magnetic resonance imaging (MRI) and transvaginal ultrasound (TVS). Exclusion criteria: a) Patients with serious heart, lung, liver or hematologic system disease; b) Patients with other cancer; c) Treatment was interrupted or radiotherapy did not reach the radical dose; d) Lost to follow-up or death from other causes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCCRT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll patients completed the radical radiotherapy in department of Radiotherapy Center. Patients were immobilized with a body net in the supine position and underwent a computed tomography (CT) simulation scan (General Electric, Milwaukee WI, USA) with intravenous contrast, using 5 mm slice thickness. Simulation images extended from L1 to 5 cm below the ischial tuberosities. The gross tumor volume (GTV), clinical target volume (CTV) and planning target volume (PTV) were defined according to Radiation Therapy Oncology Group (RTOG) guidelines. The CTV-high risk included the GTV, parametrium, the upper part of the vagina to 3 cm below the tumor invasion, and metastasis lymph node. The CTV-low risk included the CTV-high risk and regional lymph nodes (common, external, internal iliac lymph nodes, obturator and presacral lymph nodes). The treatment planning was designed and computed using the Plato system version 2.7.5 (Varian, USA). The external radiation dose was 40-50 Gy in 20-25 fractions with 2 Gy per fraction using a linear accelerator (Trilogy, Varian, USA). And followed by high-dose-rate brachytherapy to 90% of the high-risk CTV was delivered with 30-40 Gy using an intracavity applicator (microSelectron-HDR Ir-192 set; Nucletron, Veenendaal, Netherlands). All patients received concomitant chemotherapy of cis-platinum (40mg/m\u003csup\u003e2\u003c/sup\u003e) alone every week starting with external radiotherapy (4-5 circles).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdjacent surgery\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter reevaluated the relationship between cervix, bladder, rectum and parauterine tissue through gynecological examination and pelvic MRI, all patients underwent extrafascial hysterectomy with adnexectomy followed by CCRT. According to postoperative pathology, nine patients with invading \u0026frac12; of the cervical stroma recived 4 circles chemotherapy consisted of the association of cis-platinum (100mg/ m\u003csup\u003e2\u003c/sup\u003e) in combination with paclitaxel (135mg/ m\u003csup\u003e2\u003c/sup\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFollow-up\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient follow-up was designed to be conducted every 3 months during the first two years and every 6 months over the next three years after surgery. The follow-up included gynecological examination, TVS, vaginal apical cytology, abdominal plevic and chest CT.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data were performed using SPSS 20.0 (Chicago IL, USA). Quantitative data are expressed as the mean \u0026plusmn; standard deviation (S.D.). \u003csup\u003e2\u003c/sup\u003e test or \u003cem\u003eFisher\u003c/em\u003e exact test was used to evaluate categorical variable. Groups were compared using Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test. . Multivariate analysis of prognostic factors was performed with Cox proportional hazards regression. A \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05 was regarded as statistically significant.\u003c/p\u003e"},{"header":"Results","content":" \u003cp\u003eAfter the combination of CCRT and surgery, recurrence of disease was observed in 12 (22.4%) patients, which were distributed as follows: 9 local recurrences and 3 distant metastases (1 lung metastasis and 2 bone metastases). Median follow-up from the date of surgery was 76\u0026nbsp;months (range 29\u0026ndash;129\u0026nbsp;months),and 5 patients died during follow-up. The 3-year OS and 5-year OS were 95.9% and 89.8%, respectively.\u003c/p\u003e \u003cp\u003eThe correlations of major clinical/pathological factors and recurrence after CCRT and adjacent surgery in LACC were summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Median age of 49 patients was 49\u0026nbsp;years (range 29\u0026ndash;66) and there was statistically significant difference between age and recurrence of disease (P\u0026thinsp;=\u0026thinsp;0.023).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelations of major clinical/pathological factors and recurrence after CCRT and adjacent surgery in stage ⅡB\u0026ndash;Ⅲ cervical cancer\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFactors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNumber (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eRecurrence\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003cp\u003eHPV infection\u003c/p\u003e \u003cp\u003eTumor diameters\u003c/p\u003e \u003cp\u003ePathological differentiation\u003c/p\u003e \u003cp\u003ePathologic subtypes\u003c/p\u003e \u003cp\u003eFIGO stage\u003c/p\u003e \u003cp\u003eMicroscopic residual\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e༜50\u003c/p\u003e \u003cp\u003e\u0026ge;\u0026thinsp;50\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003e\u0026le;\u0026thinsp;4\u0026nbsp;cm\u003c/p\u003e \u003cp\u003e༞4\u0026nbsp;cm\u003c/p\u003e \u003cp\u003eHigh\u003c/p\u003e \u003cp\u003eModeratly\u003c/p\u003e \u003cp\u003eLow\u003c/p\u003e \u003cp\u003eAdenocarcinoma/mixed subtypes\u003c/p\u003e \u003cp\u003eSCC\u003c/p\u003e \u003cp\u003eIIB\u003c/p\u003e \u003cp\u003eIIIA\u003c/p\u003e \u003cp\u003eIIIB\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eDisease invading less than 50% of the myometrium\u003c/p\u003e \u003cp\u003eDisease invading more than 50% of the myometrium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28(57.1)\u003c/p\u003e \u003cp\u003e21(42.9)\u003c/p\u003e \u003cp\u003e31(63.3)\u003c/p\u003e \u003cp\u003e18(36.7)\u003c/p\u003e \u003cp\u003e20(40.8)\u003c/p\u003e \u003cp\u003e29(59.2)\u003c/p\u003e \u003cp\u003e7(14.3)\u003c/p\u003e \u003cp\u003e33(67.3)\u003c/p\u003e \u003cp\u003e9(18.4)\u003c/p\u003e \u003cp\u003e7(14.3)\u003c/p\u003e \u003cp\u003e42(85.7)\u003c/p\u003e \u003cp\u003e41(83.7)\u003c/p\u003e \u003cp\u003e1(2.0)\u003c/p\u003e \u003cp\u003e7(14.3)\u003c/p\u003e \u003cp\u003e27(55.1)\u003c/p\u003e \u003cp\u003e13(26.5)\u003c/p\u003e \u003cp\u003e9(18.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003cp\u003e13\u003c/p\u003e \u003cp\u003e25\u003c/p\u003e \u003cp\u003e13\u003c/p\u003e \u003cp\u003e14\u003c/p\u003e \u003cp\u003e24\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e25\u003c/p\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e34\u003c/p\u003e \u003cp\u003e32\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e20\u003c/p\u003e \u003cp\u003e13\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.168\u003c/p\u003e \u003cp\u003e0.464\u003c/p\u003e \u003cp\u003e1.107\u003c/p\u003e \u003cp\u003e0.979\u003c/p\u003e \u003cp\u003e1.954\u003c/p\u003e \u003cp\u003e0.657\u003c/p\u003e \u003cp\u003e8.920\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.023*\u003c/p\u003e \u003cp\u003e0.496\u003c/p\u003e \u003cp\u003e0.293\u003c/p\u003e \u003cp\u003e0.613\u003c/p\u003e \u003cp\u003e0.162\u003c/p\u003e \u003cp\u003e0.720\u003c/p\u003e \u003cp\u003e0.012*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eCCRT, concurrent chemoradiotherapy; HPV, human papillomavirus; FIGO, International Federation of Gynecology and Obstetrics; SCC, squamous cell carcinoma; *P༜0.05\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAfter adjacent surgery, 27 patients (55.1%) showed a complete response to CCRT treatment, and 22 cases (44.9%) showed a microscopic residual disease (9 cases with disease invading more than 50% of the myometrium and 13 cases with disease invading less than 50% of the myometrium). There was statistically significant difference between recurrence of disease and microscopic residual (P\u0026thinsp;=\u0026thinsp;0.012). On multivariate analysis showed both age and microscopic residual were highly correlated with recurrence of disease (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) (P\u0026thinsp;=\u0026thinsp;0.017 and P\u0026thinsp;=\u0026thinsp;0.030, respectively).Although there was not statistically significant difference between tumor diameters and recurrence of disease, tumor diameters was highly correlated with microscopic residual on further analysis (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate analysis of recurrence after CCRT and adjacent surgery in stage ⅡB\u0026ndash;Ⅲ cervical cancer\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eβi\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS.E\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWalds\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eExp (\u003cem\u003eB\u003c/em\u003e) 95% \u003cem\u003eCI\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003cp\u003eHPV infection\u003c/p\u003e \u003cp\u003eTumor diameters\u003c/p\u003e \u003cp\u003ePathological differentiation\u003c/p\u003e \u003cp\u003ePathologic subtype\u003c/p\u003e \u003cp\u003eFIGO stage\u003c/p\u003e \u003cp\u003eResidual cancer\u003c/p\u003e \u003cp\u003eConstant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.222\u003c/p\u003e \u003cp\u003e1.290\u003c/p\u003e \u003cp\u003e-0.336\u003c/p\u003e \u003cp\u003e1.153\u003c/p\u003e \u003cp\u003e-1.586\u003c/p\u003e \u003cp\u003e-2.521\u003c/p\u003e \u003cp\u003e-3.274\u003c/p\u003e \u003cp\u003e1.176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.351\u003c/p\u003e \u003cp\u003e1.173\u003c/p\u003e \u003cp\u003e1.125\u003c/p\u003e \u003cp\u003e1.659\u003c/p\u003e \u003cp\u003e1.660\u003c/p\u003e \u003cp\u003e2.201\u003c/p\u003e \u003cp\u003e1.506\u003c/p\u003e \u003cp\u003e2.907\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.691\u003c/p\u003e \u003cp\u003e1.211\u003c/p\u003e \u003cp\u003e0.089\u003c/p\u003e \u003cp\u003e0.483\u003c/p\u003e \u003cp\u003e0.913\u003c/p\u003e \u003cp\u003e1.312\u003c/p\u003e \u003cp\u003e4.723\u003c/p\u003e \u003cp\u003e0.369\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.017*\u003c/p\u003e \u003cp\u003e0.271\u003c/p\u003e \u003cp\u003e0.765\u003c/p\u003e \u003cp\u003e0.487\u003c/p\u003e \u003cp\u003e0.339\u003c/p\u003e \u003cp\u003e0.252\u003c/p\u003e \u003cp\u003e0.030*\u003c/p\u003e \u003cp\u003e0.544\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25.086(1.777\u0026thinsp;~\u0026thinsp;354.179)\u003c/p\u003e \u003cp\u003e3.633(0.365\u0026thinsp;~\u0026thinsp;36.167)\u003c/p\u003e \u003cp\u003e0.715(0.079\u0026thinsp;~\u0026thinsp;6.476)\u003c/p\u003e \u003cp\u003e3.168(0.123\u0026thinsp;~\u0026thinsp;81.769)\u003c/p\u003e \u003cp\u003e0.205(0.008\u0026thinsp;~\u0026thinsp;5.296)\u003c/p\u003e \u003cp\u003e0.080(0.001\u0026thinsp;~\u0026thinsp;6.008)\u003c/p\u003e \u003cp\u003e0.038(0.002\u0026thinsp;~\u0026thinsp;0.725)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eCCRT, concurrent chemoradiotherapy; *P༜0.05\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe relationship between macroscopic residual and clinical/pathological factors\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eclinical/pathological factors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eMacroscopic residual\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor diameters\u003c/p\u003e \u003cp\u003ePathological differentiation\u003c/p\u003e \u003cp\u003ePathologic subtype\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;4\u0026nbsp;cm\u003c/p\u003e \u003cp\u003e༞4\u0026nbsp;cm\u003c/p\u003e \u003cp\u003eHigh\u003c/p\u003e \u003cp\u003eModerately\u003c/p\u003e \u003cp\u003eLow\u003c/p\u003e \u003cp\u003eAdenocarcinoma/mixed subtypes\u003c/p\u003e \u003cp\u003eSCC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e18\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e20\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.337\u003c/p\u003e \u003cp\u003e0.017\u003c/p\u003e \u003cp\u003e0.086\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e༜0.001*\u003c/p\u003e \u003cp\u003e0.992\u003c/p\u003e \u003cp\u003e0.769\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eSCC, squamous cell carcinoma; *P༜0.05\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn early postoperative period (\u0026le;\u0026thinsp;30 days), 2 incomplete intestinal obstruction and 3 deep venous thrombosis were found. As far as long-term postoperative period (\u0026gt;\u0026thinsp;30 days), 3 complications were observed: 2 patients developed colorectal fistula and 1 patient showed pelvic pain.\u003c/p\u003e \u003cp\u003eThe average of operation time was 2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u0026nbsp;h (range 1.2\u0026ndash;3.1\u0026nbsp;h) and blood loss during the surgery was 133.5\u0026thinsp;\u0026plusmn;\u0026thinsp;66.7\u0026nbsp;mL (range 50\u0026ndash;400\u0026nbsp;mL). The average hospital stay was 9.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 days (range 6\u0026ndash;15 days). The relationship between the time to start operation after CCRT and blood loss during the surgery, hospital stay and postoperative complication were analyzed furthermore (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Although blood loss during the surgery, hospital stay and postoperative complication in \u0026gt;\u0026thinsp;6 weeks group were less than that in \u0026le;\u0026thinsp;6 weeks group, only blood loss during surgery and postoperative complication were closely related with the time to start operation after CCRT (F\u0026thinsp;=\u0026thinsp;5.866,P\u0026thinsp;=\u0026thinsp;0.019;F\u0026thinsp;=\u0026thinsp;4.056༌P\u0026thinsp;=\u0026thinsp;0.044).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe evaluation of operation time\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOperation time\u003c/p\u003e \u003cp\u003e(h)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBleeding\u003c/p\u003e \u003cp\u003e(mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHospital stay\u003c/p\u003e \u003cp\u003e(day)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eComplications\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;6 weeks\u003c/p\u003e \u003cp\u003e༞6 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.812\u0026thinsp;\u0026plusmn;\u0026thinsp;0.376\u003c/p\u003e \u003cp\u003e1.944\u0026thinsp;\u0026plusmn;\u0026thinsp;0.368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.942\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e147.41\u0026thinsp;\u0026plusmn;\u0026thinsp;78.377\u003c/p\u003e \u003cp\u003e115.70\u0026thinsp;\u0026plusmn;\u0026thinsp;43.425\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.019*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.740\u0026thinsp;\u0026plusmn;\u0026thinsp;2.141\u003c/p\u003e \u003cp\u003e9.050\u0026thinsp;\u0026plusmn;\u0026thinsp;2.081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.225\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e20\u003c/p\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.044*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e*P༜0.05\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e "},{"header":"Disscussion","content":" \u003cp\u003eLocal and distant recurrence is the main reason for the failure of treatment of locally advanced cervical cancer. Studies have reported that CCRT can improve the local control of lesions, progression-free survival and total survival in patients with locally advanced cervical cancer. Some researchers [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] believe that the control of local lesions can improve the surgical resection rate. At present, there are few studies on adjuvant surgery, which is controversial for further reducing recurrence rate and improving prognosis. In this study, a total of 49 patients with locally advanced cervical cancer were included. The lesions all shrank to different degrees after CCRT treatment, among which 18 patients showed significant improvement in paratactic infiltration. About 3\u0026ndash;9 weeks after CCRT treatment, all patients underwent extrafascial hysterectomy and bilateral adnexectomy, and the incidence of postoperative complications was 16.3%, similar to 19.8% in the previous study [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. 9 cases of patients were proved to be local recurrence with pathologically, and distant metastasis was observed in 3 patients. The recurrence rate (22.4%) was little higher compared with the previous work, which 192 ⅡB\u0026ndash;ⅣA stage cervical cancer patients was included. The recurrence rate in our study is slightly higher than CCRT joint surgery (16.7%), however, there was a decrease compared to CCRT alone (31.7%). Maybe it was the small sample size that led to such different results.\u003c/p\u003e \u003cp\u003eThis study showed that pathological cancer residue was closely related to recurrence, and multivariate analysis of variance showed that cancer residue was an independent risk factor for postoperative recurrence, which was consistent with previous research results [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Further study found that residual carcinoma associated with preoperative lesions in diameter, suggesting that patients with tumor lesions of large diameter were more likely to relapse. The higher recurrence rate may be associated with the lack of oxygen in the center of tumors, which leading to a decrease in the sensitivity of tumor cells to radiation and weakens the efficacy of radiotherapy [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In this study, postoperative pathological types were significantly correlated with postoperative recurrence. The recurrence rate of patients with simple squamous cell carcinoma was lower than other pathological types. This may because squamous cell carcinoma has higher radiosensitivity than other pathological types [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In this study, multivariate analysis of variance showed that age was also an independent risk factor for postoperative recurrence, which may be related to difference in hormone and immune levels in different age groups. However, it is still controversial whether age is related to recurrence and prognosis. Other previous studies [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] have pointed out that the degree of tumor differentiation can affect the sensitivity of tumor cells to radiation. However, this study did not suggest that the degree of differentiation of cervical cancer is related to local recurrence. This may be related to the small number of included cases and the uneven proportion of the degree of differentiation and a large sample study is needed for further validation. In this study, the incidence of postoperative complications was 16.3%, mainly due to mild myelosuppression and gastrointestinal reactions. The 2 cases of postoperative incomplete intestinal obstruction and intestinal fistula recovered after conservative treatment. By contrast to the previous studies (12.8\u0026ndash;19.8%), the complication rate was within an acceptable range in our study [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In addition, in this study, the time between the CCRT and surgery was compared in different group. By comparing the operative time, bleeding volume and postoperative complications, the interval\u0026thinsp;\u0026gt;\u0026thinsp;6weeks group was better than the group with interval\u0026thinsp;\u0026le;\u0026thinsp;6weeks and the result was statistically different. By analyzing the reason, the tissue was still in a state of hyperemia and edema after chemoradiotherapy, so the risk of bleeding and infection after operation in short-interval increased. Therefore, appropriately extending the time between CCRT and surgery can reduce intraoperative bleeding and facilitate postoperative recovery.\u003c/p\u003e \u003cp\u003eThis study retrospectively analyzed the cervical cancer patients with ⅡB\u0026ndash;Ⅲ stage who accepted extra-fascial hysterectomy and bilateral adnexectomy hysterectomy surgery after CCRT. The postoperative recurrence rate decreased than pure CCRT treatment and there was no obvious increase in postoperative complications. The joint is expected to improve the local control rate of locally advanced cervical cancer patients and improve the long-term curative effect.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYongchun Zhang, conception; Yong Li and Yongchun Zhang, design of the work; Xiumei Li and Jie Zhou, the acquisition, analysis; Yong Li, drafted the work; Zhiying Chen and Xiang Wang, interpretation of data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\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\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Affiliated Hospital of Qingdao University (the Institutional Review Board).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWei LC, Wang N, Shi M, Liu JY, Li JP, Zhang Y, Huang YH, Li X, Chen Y: Clinical outcome observation of preoperative concurrent chemoradiotherapy/radiotherapy alone in 174 Chinese patients with local advanced cervical carcinoma. Onco Targets Ther 2013, 6:67-74.\u003c/li\u003e\n\u003cli\u003eChereau E, C DLH, Ballester M, Monnier L, Rouzier R, Touboul E, Darai E: The role of completion surgery after concurrent radiochemotherapy in locally advanced stages IB2-IIB cervical cancer. Anticancer Res 2013, 33:1661-1666.\u003c/li\u003e\n\u003cli\u003eHouvenaeghel G, Lelievre L, Gonzague-Casabianca L, Buttarelli M, Moutardier V, Goncalves A, Resbeut M: Long-term survival after concomitant chemoradiotherapy prior to surgery in advanced cervical carcinoma. Gynecol Oncol 2006, 100:338-343.\u003c/li\u003e\n\u003cli\u003eMalzoni M, Spina V, Perniola G, Aleandri V, Mossa B, Iuele T, Imperato F: Laparoscopic surgery in treatment of stage IIb cervical cancer after neoadjuvant chemotherapy. A case report and review of the literature. Eur J Gynaecol Oncol 2003, 24:393-397.\u003c/li\u003e\n\u003cli\u003eOta T, Takeshima N, Tabata T, Hasumi K, Takizawa K: Adjuvant hysterectomy for treatment of residual disease in patients with cervical cancer treated with radiation therapy. Br J Cancer 2008, 99:1216-1220.\u003c/li\u003e\n\u003cli\u003eClasse JM, Rauch P, Rodier JF, Morice P, Stoeckle E, Lasry S, Houvenaeghel G, Groupe des Chirurgiens de Centre de Lutte Contre le C: Surgery after concurrent chemoradiotherapy and brachytherapy for the treatment of advanced cervical cancer: morbidity and outcome: results of a multicenter study of the GCCLCC (Groupe des Chirurgiens de Centre de Lutte Contre le Cancer). Gynecol Oncol 2006, 102:523-529.\u003c/li\u003e\n\u003cli\u003eSun L, Sheng X, Jiang J, Li X, Liu N, Liu Y, Zhang T, Li D, Zhang X, Wei P: Surgical morbidity and oncologic results after concurrent chemoradiation therapy for advanced cervical cancer. Int J Gynaecol Obstet 2014, 125:111-115.\u003c/li\u003e\n\u003cli\u003eHirakawa M, Nagai Y, Toita T, Kudaka W, Inamine M, Ogawa K, Murayama S, Aoki Y: High-risk group for locoregional recurrence in patients with stage IB-IIB squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy. Anticancer Res 2011, 31:1437-1441.\u003c/li\u003e\n\u003cli\u003eGray LH, Conger AD, Ebert M, Hornsey S, Scott OC: The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 1953, 26:638-648.\u003c/li\u003e\n\u003cli\u003eFerrandina G, Margariti PA, Smaniotto D, Petrillo M, Salerno MG, Fagotti A, Macchia G, Morganti AG, Cellini N, Scambia G: Long-term analysis of clinical outcome and complications in locally advanced cervical cancer patients administered concomitant chemoradiation followed by radical surgery. Gynecol Oncol 2010, 119:404-410.\u003c/li\u003e\n\u003cli\u003eKim YH, Chung WK, Jeong JU, Cho IJ, Yoon MS, Song JY, Nam TK, Ahn SJ, Lee DH, Yoon TM, et al: Evaluation of Prognostic Factors for the Parotid Cancer Treated With Surgery and Postoperative Radiotherapy. Clin Exp Otorhinolaryngol 2019.\u003c/li\u003e\n\u003cli\u003eMariagrazia D, Anna F, Gabriella F, Francesco F, Daniela S, Giuseppe D, Alessio M, Giovanni S: Preoperative chemoradiotherapy in locally advanced cervical cancer: long-term outcome and complications. Gynecol Oncol 2005, 99:S166-170.\u003c/li\u003e\n\u003cli\u003eTrimbos JB, Franchi M, Zanaboni F, Velden J, Vergote I: 'State of the art' of radical hysterectomy; current practice in European oncology centres. Eur J Cancer 2004, 40:375-378.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cervical cancer, concurrent chemoradiation, surgery, recurrence","lastPublishedDoi":"10.21203/rs.3.rs-53507/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-53507/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: To explore the feasibility of adjuvant surgery following concurrent chemoradiation therapy (CCRT) in stage ⅡB–Ⅲ cervical cancer. And analyze risk factors of recurrence after surgery. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: Forty-nine patients diagnosed with stage ⅡB–Ⅲ cervical cancer were reviewed retrospectively. Investigated the risk factors of recurrence after surgery using Chi-squared Test and further analyzed multiple factors affecting postoperative recurrence using the multi-factor logistic regression. Furthermore, the correlation of surgery outcomes (including operation time, bleeding, and hospitalization date and surgery complications) with the time which carried out between CCRT and completion surgery was analyzed. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Tumor histology and residual tumor in the cervix were significantly associated with postoperative recurrence (P = 0.014 and P = 0.040, respectively). Logistic regression analysis demonstrated that the independent risk factors of postoperative recurrence were age and residual tumor in the cervix (P = 0.017 and P = 0.030, respectively). Compared with completion surgery was carried out ≤ 6 weeks after CCRT, the operation time, bleeding, hospitalization date and surgery complications were more than \u0026gt; 6 weeks group. Moreover, bleeding and surgery complications were statistically significant (P = 0.019 and P = 0.044, respectively).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: CCRT combined surgery for stage ⅡB–Ⅲ cervical cancer was feasible, reduced the rate of postoperative recurrence and surgery complications were tolerated. CCRT combined surgery might improve the local control of lesion.\u003c/p\u003e","manuscriptTitle":"Clinical Outcomes Observation in Stage IIB–III Cervical Cancer Treated by Adjuvant Surgery Following Concurrent Chemoradiotherapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-08-12 16:05:41","doi":"10.21203/rs.3.rs-53507/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":"f4dc7c8a-9643-4ce8-adbc-fdfd0a9c6e7d","owner":[],"postedDate":"August 12th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":280828,"name":"Oncology"}],"tags":[],"updatedAt":"2020-09-10T13:01:07+00:00","versionOfRecord":[],"versionCreatedAt":"2020-08-12 16:05:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-53507","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-53507","identity":"rs-53507","version":["v1"]},"buildId":"iFTdqyg4nuje_uAy1AHro","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}