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

Gabriella Macchia, Roberta Lazzari, Nicoletta Colombo, Concetta Laliscia, Giovanni Capelli, Giuseppe Roberto D'Agostino, Francesco Deodato, Ernesto Maranzano, Edy Ippolito, Sara Ronchi, Fabiola Paiar, Marta Scorsetti, Savino Cilla, Rossana Ingargiola, Alessandra Huscher, Anna Maria Cerrotta, Andrei Fodor, Lisa Vicenzi, Donatella Russo, Simona Borghesi, Elisabetta Perrucci, Sandro Pignata, Cynthia Aristei, Alessio Giuseppe Morganti, Giovanni Scambia, Vincenzo Valentini, Barbara Alicja Jereczek-Fossa, Gabriella Ferrandina, Gabriella Macchia, Roberta Lazzari, Nicoletta Colombo, Concetta Laliscia, Giovanni Capelli, Giuseppe Roberto D'Agostino, Francesco Deodato, Ernesto Maranzano, Edy Ippolito, Sara Ronchi, Fabiola Paiar, Marta Scorsetti, Savino Cilla, Rossana Ingargiola, Alessandra Huscher, Anna Maria Cerrotta, Andrei Fodor, Lisa Vicenzi, Donatella Russo, Simona Borghesi, Elisabetta Perrucci, Sandro Pignata, Cynthia Aristei, Alessio Giuseppe Morganti, Giovanni Scambia, Vincenzo Valentini, Barbara Alicja Jereczek-Fossa, Gabriella Ferrandina

Abstract

Background: Recent studies have reported improvement of outcomes (progression-free survival, overall survival, and prolongation of androgen deprivation treatment-free survival) with stereotactic body radiotherapy (SBRT) in non-small cell lung cancer and prostate cancer. The aim of this retrospective, multicenter study (MITO RT-01) was to define activity and safety of SBRT in a very large, real-world data set of patients with metastatic, persistent, and recurrent ovarian cancer (MPR-OC).

Materials and methods: The endpoints of the study were the rate of complete response (CR) to SBRT and the 24-month actuarial local control (LC) rate on "per-lesion" basis. The secondary endpoints were acute and late toxicities and the 24-month actuarial late toxicity-free survival. Objective response rate (ORR) included CR and partial response (PR). Clinical benefit (CB) included ORR and stable disease (SD). Toxicity was evaluated by the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) and Common Terminology Criteria for Adverse Events (CTCAE) scales, according to center policy. Logistic and Cox regression were used for the uni- and multivariate analysis of factors predicting clinical CR and actuarial outcomes.

Results: CR, PR, and SD were observed in 291 (65.2%), 106 (23.8%), and 33 (7.4%) lesions, giving a rate of CB of 96.4%. Patient aged ≤60 years, planning target volume (PTV) ≤18 cm3 , lymph node disease, and biologically effective dose α/β10 > 70 Gy were associated with higher chance of CR in the multivariate analysis. With a median follow-up of 22 months (range, 3-120), the 24-month actuarial LC rate was 81.9%. Achievement of CR and total dose >25 Gy were associated with better LC rate in the multivariate analysis. Mild toxicity was experienced in 54 (20.7%) patients; of 63 side effects, 48 were grade 1, and 15 were grade 2. The 24-month late toxicity-free survival rate was 95.1%.

Conclusions: This study confirms the activity and safety of SBRT in patients with MPR-OC and identifies clinical and treatment parameters able to predict CR and LC rate.

Implications for practice: This study aimed to define activity and safety of stereotactic body radiotherapy (SBRT) in a very large, real life data set of patients with metastatic, persistent, recurrent ovarian cancer (MPR-OC). Patient age <60 years, PTV <18 cm3 , lymph node disease, and biologically effective dose α/β10 >70 Gy were associated with higher chance of complete response (CR). Achievement of CR and total dose >25 Gy were associated with better local control (LC) rate. Mild toxicity was experienced in 20.7% of patients. In conclusion, this study confirms the activity and safety of SBRT in MPR-OC patients and identifies clinical and treatment parameters able to predict CR and LC rate.

Keywords: Oligometastasis; Oligorecurrences; Ovarian cancer; Personalized medicine; Stereotactic body radiotherapy; Stereotactic radiosurgery.

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

© AlphaMed Press 2019.

Figures

Figure 1
Figure 1
Summary of different radiotherapy schedules according to stereotactic body radiotherapy (A) and single fraction radiotherapy (B).

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:7–34.
    1. Wilson MK, Pujade‐Lauraine E, Aoki D et al; participants of the Fifth Ovarian Cancer Consensus Conference . Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: Recurrent disease. Ann Oncol 2017;28:727–732.
    1. Pignata S, Cecere S, DuBois A et al. Treatment of recurrent ovarian cancer. Ann Oncol 2017; 28(suppl 8):viii51–viii56.
    1. Buechel M, Herzog TJ, Westin SN et al. Treatment of patients with recurrent epithelial ovarian cancer for whom platinum is still an option. Ann Oncol 2019;30:721–732.
    1. Moore K, Colombo N, Scambia G et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018;379:2495–2505.
    1. Fields EC, McGuire WP, Lin L et al. Radiation treatment in women with ovarian cancer: Past, present, and future. Front Oncol 2017; 7:177.
    1. Rodríguez‐Ruiz ME, Vanpouille‐Box C, Melero I et al. Immunological mechanisms responsible for radiation‐induced abscopal effect. Trends Immunol 2018;39:644–655.
    1. Césaire M, Thariat J, Candéias SM et al. Combining PARP inhibition, radiation, and immunotherapy: A possible strategy to improve the treatment of cancer? Int J Mol Sci 2018;19.
    1. Alongi F, Arcangeli S, Filippi AR et al. Review and uses of stereotactic body radiation therapy for oligometastases. The Oncologist 2012;17:1100–1107.
    1. Rusthoven KE, Kavanagh BD, Burri SH et al. Multi‐institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. J Clin Oncol 2009;27:1579–1584.
    1. Rusthoven KE, Kavanagh BD, Cardenes H et al. Multi‐institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol 2009;27:1572–1578.
    1. Kunos CA, Brindle J, Waggoner S et al. Phase II clinical trial of robotic stereotactic body radiosurgery for metastatic gynecologic malignancies. Front Oncol 2012;2:181.
    1. Macchia G, Deodato F, Cilla S et al. Volumetric intensity modulated arc therapy for stereotactic body radiosurgery in oligometastatic breast and gynecological cancers: Feasibility and clinical results. Oncol Rep 2014;32:2237–2243.
    1. Macchia G, Deodato F, Cilla F et al. Volumetric modulated arc therapy for treatment of solid tumors: Current insights. Onco Targets Ther 2017;10:3755–3772.
    1. Palma DA, Olson R, Harrow S et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR‐COMET): A randomised, phase 2, open‐label trial. Lancet 2019;393:2051–2058.
    1. Deodato F, Macchia G, Cilla S et al. Dose escalation in extracranial stereotactic ablative radiotherapy (DESTROY‐1): A multiarm Phase I trial. Br J Radiol 2019;92:20180422.
    1. Milano MT, Kong FS, Movsas B. Stereotactic body radiotherapy as salvage treatment for recurrence of non‐small cell lung cancer after prior surgery or radiotherapy. Transl Lung Cancer Res. 2019;8:78–87.
    1. Gurka MK, Kim C, He AR et al. Stereotactic Body Radiation Therapy (SBRT) combined with chemotherapy for unresected pancreatic adenocarcinoma. Am J Clin Oncol 2017;40:152–157.
    1. Mazzola R, Fersino S, Ferrera G et al. Stereotactic body radiotherapy for lung oligometastases impacts on systemic treatment‐free survival: A cohort study. Med Oncol 2018;35:121.
    1. Triggiani L, Alongi F, Buglione M et al. Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: New evidence from a multicentric study. Br J Cancer 2017;116:1520–1525.
    1. Formenti SC, Rudqvist NP, Golden E et al. Radiotherapy induces responses of lung cancer to CTLA‐4 blockade. Nat Med 2018;24:1845–1851.
    1. Gomez DR, Blumenschein GR Jr, Lee JJ et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non‐small‐cell lung cancer without progression after first‐line systemic therapy: A multicentre, randomised, controlled, phase 2 study. Lancet Oncol 2016;17:1672–1682.
    1. Ost P, Reynders D, Decaestecker K et al. Surveillance or metastasis‐directed therapy for oligometastatic prostate cancer recurrence: A prospective, randomized, multicenter phase II trial. J Clin Oncol 2018;36:446–453.
    1. Iyengar P, Wardak Z, Gerber DE et al. Consolidative radiotherapy for limited metastatic non‐small‐cell lung cancer: A phase 2 randomized clinical trial. JAMA Oncol 2018;4:e173501.
    1. Laliscia C, Fabrini MG, Delishaj D et al. Clinical outcomes of stereotactic body radiotherapy in oligometastatic gynecological cancer. Int J Gynecol Cancer 2017;27:396–402.
    1. Trippa F, Casale M, Draghini L et al. Stereotactic body radiotherapy for lymph node relapse in Ovarian Cancer. Clin Oncol 2016;1:1038.
    1. Iftode C, DʼAgostino GR, Tozzi A et al. Stereotactic Body Radiation Therapy in oligometastatic ovarian cancer: A promising therapeutic approach. Int J Gynecol Cancer 2018;28:1507–1513.
    1. Lazzari R, Ronchi S, Gandini S et al. Stereotactic Body Radiation Therapy for oligometastatic ovarian cancer: A step toward a drug holiday. Int J Radiat Oncol Biol Phys 2018;101:650–660.
    1. Potters L, Steinberg M, Rose C et al. American Society for Therapeutic Radiology and Oncology and American College of Radiology practice guideline for the performance of stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys 2004;60:1026–1032.
    1. Guckenberger M, Andratschke N, Dieckmann K et al. ESTRO ACROP consensus guideline on implementation and practice of stereotactic body radiotherapy for peripherally located early stage non‐small cell lung cancer. Radiother Oncol 2017;124:11–17.
    1. Jabbari S, Gerszten PC, Ruschin M et al. Stereotactic Body Radiotherapy for spinal metastases: Practice guidelines, outcomes, and risks. Cancer J 2016;22:280–289.
    1. Ponti E, Lancia A, Ost P et al. Exploring all avenues for radiotherapy in oligorecurrent prostate cancer disease limited to lymph nodes: A systematic review of the role of stereotactic body radiotherapy. Eur Urol Focus 2017;3:538–544.
    1. Palma DA, Louie AV, Rodrigues GB. New strategies in stereotactic radiotherapy for oligometastases. Clin Cancer Res 2015;21:5198–5204.
    1. Shiue K, Cerra‐Franco A, Shapiro R et al. Histology, tumor volume, and radiation dose predict outcomes in NSCLC patients after stereotactic ablative radiotherapy. J Thorac Oncol 2018;13:1549–1559.
    1. Moraru IC, Tai A, Erickson B et al. Radiation dose responses for chemoradiation therapy of pancreatic cancer: An analysis of compiled clinical data using biophysical models. Pract Radiat Oncol 2014;4:13–19.
    1. Reynders K, Illidge T, Siva S et al. The abscopal effect of local radiotherapy: Using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev 2015;41:503–510.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa