About this trial
Stereotactic body radiotherapy (SBRT) is a modern radiotherapy technique, through which extremely high doses of irradiation are delivered in a very precise manner, within a few fractions. SBRT is increasingly used into clinical practice because it can provide excellent local control, comparable to surgery, in many tumor locations, such as lung, liver or bone. Efforts to develop it for BC treatment are promising, as it is safe, convenient, and effective. To date, SBRT for BC has been developed as an alternative method of partial-breast irradiation (PBI) in the pre- or post-operative setting. Therefore, the doses tested are comparable to the conventional doses used with surgery although its potential as sole local treatment for BC remains unknown. Higher SBRT doses are expected to permit obtaining an ablative effect on tumor and be suitable as an alternative to surgery, but this hypothesis has yet to be tested.
The aim of the present study is to prove the feasibility of SBRT as an ablative treatment in early breast cancer (BC). The primary objective is to find the maximum tolerated dose of SBRT that can be safely administered in inoperable patients with BC, the majority of whom are elderly or oldest old.
The overall objective is to determine whether high precision, dose- and fractionation- adapted SBRT is feasible and safe in inoperable patients with BC. The dose and fractionation-adapted SBRT regimen permits to test feasibility in different tumor sizes.
The primary objective of this study is to establish the maximum tolerated dose (MTD) that can be delivered with a single or few (up to 5) fractions of SBRT in inoperable patients with BC.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age over 70 years
Histologically confirmed diagnosis of BC, any time before study enrollment.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.
Patient considered inoperable in multidisciplinary board decision or refusing surgery. Main criteria determining inoperability are inability to receive general anesthesia after anesthetics and/or surgical evaluation. Criteria described in the statement of American Society of Anesthesiologists (ASA) {, #4699} and American College of Surgeons Surgical risk calculators {, #4695} are usually addressed in the multidisciplinary discussion (Appendix ).
Disqualifiers
Prior surgery for the current diagnosis.
Prior whole or partial breast irradiation to the involved breast.
Absolute contraindication to RT, such as Li-Fraumeni syndrome.
Current participation and receipt of study therapy or previous participation in a study of an investigational agent and receipt of study therapy or used an investigation device within 4 weeks of the first day of treatment.
Trial design
Parallel
Treatments tested in this trial
SBRT
RadiationAdapted to tumor volume BC SBRT
Treatment groups
Trial outcomes
Primary outcomes
Maximum Tolerated Dose (MTD)
Dose before the dose-level at which one or more dose-limiting toxicity (DLT) (any treatment-related toxicity equal or superior to Grade 3, according to CTCAE v5) occurs within 4 weeks after end of study treatment (EOT).
Secondary outcomes
Early and late toxicities
• Early (up to 3 months after treatment start) and late (over 3 months and up to 2 years after treatment start) rates of toxicities, as graded by CTCAE v5, other than a dose-limiting toxicity (DLT), possibly, probably or definitely related to delivered treatment.
Differential safety profile between arms
Toxicity rates, as graded by CTCAE v5, will be compared between the fractionation regimens.
Explorative: clinically relevant technical parameters of SBRT
Technical parameters of treatment planning/ dose delivery and dose-volume histogram (DVH) parameters will be associated to toxicity in order to identify potential associations and constraints' thresholds.
Efficacy o SBRT on local control
Non progression, described as: stable local disease (SD), shrinkage of treated tumor (partial response (PR)) in imaging, as classified by RECIST v1.1 criteria, will be considered as response to treatment. Imaging should be consistent within study for a given patient. Progressive disease (PD) by RECIST v1.1 will be considered as disease progression, therefore non-response.
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