Prognostic factors in patients with recurrent ovarian cancer treated with radiation therapy

Objectives: Radiation therapy (RT) for recurrent ovarian cancer may be considered not only for palliation of symptoms, but also to prolong survival in selected patients. Herein, we investigated the efficacy of RT and associated prognostic factors. Methods: The relationship between clinicopathological factors including age, PS, FIGO stage at initial diagnosis, histological type, number of relapsed lesions (solitary or multiple), aim of RT (curative or palliative intent), and treatment-free interval (TFI) and progression-free survival (PFS) and overall survival (OS) was investigated in 17 patients with recurrent ovarian cancer treated with RT. Results: The median age was 58.5 years. Eight patients (three with solitary and five with multiple relapsed lesions) were treated with curative-intent RT, and nine patients (all with multiple relapsed lesions) were treated with palliative RT. Response to RT was as follows: CR: 3 patients, PR: 5 patients, SD: 3 patients, and PD: 6 patients. The response rate (CR + PR) and disease control rate (CR + PR + SD) were 47.1% and 64.7%, respectively; neither were associated with TFI. The 2-year PFS and OS rates after RT were 11.8% and 29.4%, respectively. In univariate analysis, solitary relapsed lesions and curative-intent RT were judged as favorable prognostic factors for PFS and OS. However, in multivariate analysis, only curative-intent RT was identified as an independent favorable prognostic factor for OS (hazard ratio: 3.65, 95% confidence interval: 1.03–12.00, P = 0.045). Conclusions: This retrospective study indicated that curative-intent RT may be an effective treatment method for patients when clinically indicated, regardless of whether recurrent tumors are sensitive to chemotherapy.

Recurrent ovarian cancer; Radiation therapy; Curative-intent RT; Palliative RT; Prognostic factors

[1] NCCN Guideline Version 3. Ovarian Cancer. 2019. Available at: https://www.nccn.org/professionals/physician_gls/default.a spx (Accessed: 12 January 2020).

[2] Cmelak AJ, Kapp DS. Long-term survival with whole abdominopelvic irradiation in platinum-refractory persistent or recurrent ovarian cancer. Gynecologic Oncology. 1997; 65: 453– 460.

[3] Corn BW, Lanciano RM, Boente M, Hunter WM, Ladazack J, Ozols RF. Recurrent ovarian cancer. Effective radiotherapeutic palliation after chemotherapy failure. Cancer. 1994; 74: 2979– 2983.

[4] Tinger A, Waldron T, Peluso N, Katin MJ, Dosoretz DE, Blitzer PH, et al. Effective palliative radiation therapy in advanced and recurrent ovarian carcinoma. International Journal of Radiation Oncology, Biology, Physics. 2001; 51: 1256–1263.

[5] Smart A, Chen Y, Cheng T, King M, Lee L. Salvage radiation therapy for localized recurrent ovarian cancer. International Journal of Gynecologic Cancer. 2019; 29: 916–921.

[6] Komura N, Mabuchi S, Isohashi F, Yokoi E, Shimura K, Matsumoto Y, et al. Radiotherapy for isolated recurrent epithelial ovarian cancer: a single institutional experience. Journal of Obstetrics and Gynaecology Research. 2019; 45: 1173–1182.

[7] Albuquerque K, Patel M, Liotta M, Harkenrider M, Guo R, Small W, et al. Long-term benefit of tumor volume-directed involved field radiation therapy in the management of recurrent ovarian cancer. International Journal of Gynecological Cancer. 2016; 26: 655–660.

[8] Yahara K, Ohguri T, Imada H, Yamaguchi S, Kawagoe T, Matsuura Y, et al. Epithelial ovarian cancer: definitive radiotherapy for limited recurrence after complete remission had been achieved with aggressive front-line therapy. Journal of Radiation Research. 2013; 54: 322–329.

[9] Firat S, Erickson B. Selective irradiation for the treatment of recurrent ovarian carcinoma involving the vagina or rectum. Gynecologic Oncology. 2001; 80: 213–220.

[10] Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. The Lancet Oncology. 2014; 15: 852–861.

[11] Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European Journal of Cancer. 2009; 45: 228–247.

[12] Ozols RF. Systemic therapy for ovarian cancer: current status and new treatments. Seminars in Oncology. 2006; 33: S3–S11.

[13] Colombo N, Sessa C, Bois AD, Ledermann J, McCluggage W, McNeish I, et al. ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. International Journal of Gynecologic Cancer. 2019; 29: 728–760.

[14] Harter P, du Bois A, Hahmann M, Hasenburg A, Burges A, Loibl S, et al. Surgery in recurrent ovarian cancer: the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR trial. Annals of Surgical Oncology. 2006; 13: 1702–1710.

[15] Harter P, Sehouli J, Reuss A, Hasenburg A, Scambia G, Cibula D, et al. Prospective validation study of a predictive score for operability of recurrent ovarian cancer: the Multicenter Intergroup Study DESKTOP II. A project of the AGO Kommission OVAR, AGO Study Group, NOGGO, AGO-Austria, and MITO. International Journal of Gynecological Cancer. 2011; 21: 289–295.

[16] Coleman RL, Enserro D, Spirtos N, Herzog TJ, Sabbatini P, Armstrong DK, et al. A phase III randomized controlled trial of secondary surgical cytoreduction (SSC) followed by platinumbased combination chemotherapy (PBC), with or without be- vacizumab (B) in platinum-sensitive, recurrent ovarian cancer (PSOC): a NRG Oncology/Gynecologic Oncology Group (GOG) study. Journal of Clinical Oncology. 2018; 36: 5501.

[17] Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, et al. OCEANS: a randomized, double-blind, placebocontrolled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. Journal of Clinical Oncology. 2012; 30: 2039–2045.

[18] Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA openlabel randomized phase III trial. Journal of Clinical Oncology. 2014; 32: 1302–1308.

[19] Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. The Lancet Oncology. 2017; 18: 1274–1284.

[20] Choi N, Chang JH, Kim S, Kim HJ. Radiation for persistent or recurrent epithelial ovarian cancer: a need for reassessment. Radiation Oncology Journal. 2019; 35: 144–152.

[21] Lee S, Park S, Kim Y, Kim Y, Choi E, Kim D, et al. Radiation therapy is a treatment to be considered for recurrent epithelial ovarian cancer after chemotherapy. Tumori. 2011; 97: 590–595.

[22] Kim N, Chang JS, Kim SW, Kim GM, Lee JY, Kim YB. Involvedfield radiation therapy for selected cases of recurrent ovarian cancer. Journal of Gynecologic Oncology. 2019; 30: e67.

[23] Brown AP, Jhingran A, Klopp AH, Schmeler KM, Ramirez PT, Eifel PJ. Involved-field radiation therapy for locoregionally recurrent ovarian cancer. Gynecologic Oncology. 2013; 130: 300–305.

[24] Jiang G, Balboni T, Taylor A, Liu J, Lee LJ. Palliative radiation therapy for recurrent ovarian cancer: efficacy and predictors of clinical response. International Journal of Gynecological Cancer. 2018; 28: 43–50.

[25] Eifel PJ. Role of radiation therapy. Best Practice & Research: Clinical Obstetrics & Gynaecology. 2017; 41: 118–125.

[26] Chundury A, Apicelli A, DeWees T, Powell M, Mutch D, Thaker P, et al. Intensity modulated radiation therapy for recurrent ovarian cancer refractory to chemotherapy. Gynecologic Oncology. 2016; 141: 134–139.

[27] Chang JS, Kim SW, Kim Y, Kim J, Park S, Kim JH, et al. Involved- field radiation therapy for recurrent ovarian cancer: results of a multi-institutional prospective phase II trial. Gynecologic Oncology. 2018; 151: 39–45.

[28] Macchia G, Lazzari R, Colombo N, Laliscia C, Capelli G, D’Agostino GR, et al. A large, multicenter, retrospective study on efficacy and safety of stereotactic body radiotherapy (SBRT) in oligometastatic ovarian cancer (MITO RT1 Study): a collaboration of MITO, AIRO GYN, and MaNGO groups. The Oncologist. 2020; 25: e311–e320.