Efficacy and Safety of SBRT in Oligo-metastatic/Persistent/Recurrent Ovarian Cancer

Ovarian Neoplasms

Ovarian Neoplasms — a type of gynecological cancer.

Treatment of Oligometastatic Parenchymal Lesions in Ovarian Cancer With Stereotactic Ablative Radiation Therapy: A Multicenter Prospective Phase 2 Trial (MITO RT3/RAD)

The results of stereotactic body radiation therapy (SBRT) for parenchymal lesions in the setting of oligometastatic ovarian cancer are reported in the context of the prospective multicenter phase 2 MITO-RT3/RAD trial (NCT04593381). The primary endpoint was the complete response (CR) rate, secondary endpoints included local control (LC), progression-free survival, overall survival, treatment-free interval, and toxicity rates. Sample size was based on a previous study reporting an average 40.0% CR with SBRT. The study was powered to detect an improvement in the CR rate from 40.0% to 55.0%, with an α error of 0.05 (one-side) and a β error of 0.1. The study met its primary endpoint of a statistically significant improvement of CR. A total of 88 patients with 127 lesions were enrolled across 15 institutions from May 2019 to November 2023. CRs were observed in 71 lesions (55.9%), partial response in 37 (29.1%), stable disease in 14 (11.0%), and progressive disease in 5 lesions (4.0%). The objective response rate was 85.0%, with an overall clinical benefit rate of 96.0%. The overall 12-month LC was 81.6%, with CR lesions exhibiting a significantly higher rate than partial or not responding lesions (12-month LC: 96.3% vs 61.4%, P < .001). The 12-month actuarial rates for progression-free survival and for overall survival were 34.9% and 91.5%, respectively. The median actuarial treatment-free interval was 9 months (range, 2.5-15.4 months), whereas the 12-month actuarial rate was 44.1%. No grade 3 or higher toxicity was reported. In particular, 15 (20.5%) patients experienced mild acute toxicity (≤grade 2). There were 12 grade 1 events and 6 grade 2 events, the latter mostly represented by pain flare (N = 2). Late toxicity was reported in 4 patients (4.5%) accounting for 4 events, mostly grade 1, except for one case of moderate asthenia (grade 2). Parenchymal oligometastatic lesions showed a high rate of CR and encouraging long-term outcomes for patients achieving CR, including a substantial period of systemic therapy-free survival after radiation therapy. The observed toxicity was minimal, strengthening the safety of ablative SBRT as a noninvasive alternative to surgical resection for parenchymal metastases in high-risk areas.

Efficacy and safety of stereotactic body radiotherapy (SBRT) in oligometastatic/persistent/recurrent ovarian cancer: a prospective, multicenter phase II study (MITO-RT3/RAD)

Stereotactic body radiotherapy (SBRT) has shown promising results in the clinical setting of oligometastatic, persistent, or recurrent disease in several malignancies including ovarian cancer. The MITO-RT3/RAD trial is a prospective, multicenter phase II study aimed at identifying potential predictors of response and clinical outcome after SBRT treatment. Radiotherapy delivered by pre-defined SBRT treatment schedules and shared constraints could improve the rate of complete response. All patients accrued will be treated with a radiotherapy dose in the range of 30-50 Gy by 1, 3, or 5 SBRT daily fractions to all sites of active metastatic disease according to diagnostic imaging. Schedules of treatment and dose prescription have been established before considering target sites and healthy organ dose constraints. Follow-up and monitoring of side effects will be carried out every 3 months for the first year with imaging and clinical evalutation, and every 4 months within the second year; thereafter, surveillance will be carried out every 6 months. The best response on a per lesion basis will be evaluated by computed tomographic (CT) scan, positron emission tomography/CT, or magnetic resonance imaging in case of brain lesions, every 3 months. The study includes patients with oligometastatic, persistent, or recurrent ovarian cancer for which salvage surgery or other local therapies are not feasible due to any relative contra-indication to further systemic therapy because of serious co-morbidities, previous severe toxicity, unavailability of potentially active systemic therapy, or patient refusal. The primary endpoint of the study is the clinical complete response rate to SBRT by imaging on a per lesion basis. Approximately 205 lesions will be treated (90 lymph nodes and 115 parenchyma lesions). Fifty-two centers have expressed their intention to participate. Enrollment should be completed by March 2023 and analysis will be completed in September 2023. NCT04593381.

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

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 &amp;gt; 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 &amp;gt;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.

Donato Pezzulla

Gabriella Macchia

Radioterapista Oncologo Dirigente medico Responsabile dell’ Unità Operativa Semplice di Radioterapia per Fasci Esterni del Gemelli Molise Hospital-Campobasso. Vicedirettore Scientifico del Gemelli Molise Hospital con funzione di coordinamento e gestione dei dati clinici, scientifici e laboratoristici per finalità di ricerca (2019-2024). Responsabile della Ricerca Clinica dell’Unità Operativa Complessa di Radioterapia Oncologica e referente per le neoplasie ginecologiche, mammarie e dell’apparato gastroenterico. Abilitazione scientifica nazionale alle funzioni di Professore Universitario di prima e seconda fascia Docente di radioterapia c/o Corso di Laurea in Tecniche di Radiologia medica per immagini e Radioterapia, Facoltà di Medicina e Chirurgia dell’Università Cattolica del S. Cuore, Campobasso e Potenza Coordinatore del gruppo di Ginecologia dell’Associazione Italiana di Radioterapia Oncologica (AIRO) Coordinatore del gruppo di Radioterapia del Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) Autore di 730 pubblicazioni su riviste scientifiche nazionali ed internazionali (Cineca/Miur), di cui: • Articolo in rivista: 274 • Abstract in rivista: 324 • Contributo in volume/atti di Convegni:132 Parametri bibliometrici da Scopus al 18/4/2023: • h-index: 29 • Citations index: 3201 • ORCID: 0000-0002-0529-201X