Oligometastatic Disease, Ovarian Neoplasms, Recurrent Ovarian Carcinoma
Conditions
Keywords
Oligometastasis, Stereotactic body radiotherapy, SBRT, SABR
Brief summary
This is a prospective, multicenter, Phase II study aimed at defining the activity and safety of SBRT in MPR-OC. Clinical and imaging data as well as SBRT parameters would be analyzed with the aim to identify potential predictors of response to treatment and clinical outcome.
Detailed description
Stereotactic Body Radiotherapy (SBRT) represents the cutting edge within high conformal and modulated radiotherapy techniques; it can provide high local control (LC) for curative-intent of low burden metastatic, persistent and metastatic lesions in face of minimal acute and late toxicities. SBRT is amenable even in patients who had already been managed by radiotherapy. In addition, SBRT has been shown to be active in chemoresistant disease, and potentially able to mount immune response through the release of tumor neoantigens after cell killing, thus allowing to synergize with immunotherapeutic approaches. SBRT has been widely adopted in the clinical setting of oligometastatic/persistent/recurrent (MPR) disease (up to \<5 lesions) in several malignancies including also ovarian cancer (OC); the recently published retrospective, multicenter Italian study (MITO-RT1) has confirmed the activity and safety of SBRT in MPR OC, thus providing a model able to predict the higher chance of complete response of tumor lesions to SBRT, and local control rate. The MITO-RT3/RAD trial is a prospective, Italian multicenter Phase II study aimed at evaluating the activity and safety of SBRT in MPR-OC patients. Clinical and imaging data, as well as SBRT technical parameters, would be analyzed with the aim to identify potential predictors of response to treatment and clinical outcome: in this context, additional insights into the tissue features of tumor lesions would be of clinical interest in the context of the personalized treatment, as testified by studies demonstrating that image-based quantitative features from pre-treatment imaging could predict clinical outcomes in several malignancies. Furthermore, given the crucial role played by the mutational status of BRCA 1/2 genes in this disease, the assessment of BRCA gene status was considered mandatory, thus representing inclusion criteria. The study will include patients with oligo-metastatic/persistent/recurrent lesions (MPR) from OC patients for which salvage surgery or other local therapies resulted not feasible, as per relative contraindication to further systemic therapy because of serious comorbidities, as per previous severe toxicity, unavailability of potentially active chemotherapy, or patient refusal of systemic therapy
Interventions
RADIATIONStereotactic body radiotherapy
All patients accrued will be treated with SBRT to all sites of active metastatic disease as per CT scan or PET/CT and/or MRI. A range of schedules and doses are provided, it is advised that the maximum dose that can be achieved whilst meeting the organs at risk planning constraints is prescribed.
Sponsors
Fondazione Policlinico Universitario A. Gemelli, IRCCS
Gemelli Molise Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* diagnosis of ovarian cancer * age \>18 yrs, * ECOG performance status 0-3, * expected life expectancy \>6 months, * 1-5 synchronous lesions * any site of disease, * compulsory assessment of mutational status of BRCA1/2 genes (either germline or somatic), * salvage surgery or other local therapies not feasible, * relative contraindication to further systemic therapy because of serious comorbidities, * previous severe systemic therapy toxicity * unavailability of potentially active systemic therapy, * patient refusal of systemic therapy, * Re-treatment of lesions already treated with conventional external beam radiotherapy is allowed\*
Exclusion criteria
* mucinous OC, * borderline ovarian tumors, * non-epithelial OC, * previous radiotherapy severe toxicity * co-morbidities and functional impairment considered clinically precluding the safe use of SBRT, * pregnancy * any psychological, sociological, or geographical issue potentially hampering compliance with the study, * lesion diameter larger than 5 centimeters
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical complete response to SBRT by imaging | Assessment of Clinical complete response at six months | Radiologic response will be evaluated by morphological (contrast-enhanced CT scan and/or MRI) or functional imaging modalities (18F-fluorodeoxyglucose-PET) and classified according to the RECIST (version 1.1) or PERCIST criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2-yr actuarial LC rate | 2 years | progression of disease inside SBRT field on a per lesion basis |
| 2-yr progression-free survival | 2 years | progression of disease out of SBRT field |
| 2-yr overall survival | 2 years | patient survival |
| rate of toxicity | 2 years | SBRT acute and late toxicity rate |
| 2-yr actuarial late toxicity free survival | 2 years | actuarial evaluation of late toxicity |
| treatment free interval | 2 years | time without any new treatment start after SBRT |
Other
| Measure | Time frame | Description |
|---|---|---|
| Breast cancer genes 1/2 (BRCA genes) characterization | 2 years | Investigation of the mutational status of BRCA 1/2 genes in this disease |
| Radiomic clusters analysis | 2 years | Investigation of radiomic features for clustering analysis to predict response according to other histological and clinical parameters |
Countries
Italy
Outcome results
None listed