Official Title
Stereotactic Body Radiation Therapy (SBRT) for the Treatment of OligoMetastasis in Breast Cancer Patients (STOMP): A Prospective Feasibility Trial
Summary:
The purpose of this study is to evaluate feasibility to treat metachronous multi-site breast
cancer oligometastasis with stereotactic body radiation therapy (SBRT) in patients on systemic
therapy.
Trial Description
Primary Outcome:
- Technical feasibility of planning SBRT to multiple sites
Secondary Outcome:
- Toxicity: Incidence of treatment-emergent adverse events [safety and tolerability] as assessed by CTCAE 4.0
- Feasibility of patient accrual: Successful accrual of 30 patients to study
- Local Control: CT scan or MRI as assessed by RECIST criteria 1.1
- Progression Free Survival (PFS)
- Overall Survival (OS)
- Quality of Life defined by EORTC Quality of Life Questionnaire core-30
Patients who present with or develop metastatic breast cancer after initial therapy are
typically considered incurable. Treatments offered are to relieve symptoms and are palliative
in intent, including chemotherapy, hormonal therapy, biologics (e.g. trastuzumab for Her2
positive disease), bisphosphonates (for bone protection), palliative radiation therapy for symptom
relief, and supportive care. Prognosis is guarded, with median OS estimated at 2-3 years, and
progression free survival (PFS) approximately 9-12 months.
Based on research observing the natural history of breast cancer, it was discovered that some
cancers have a predilection for spread to a limited number of sites and remain in these sites
for a number of months before acquiring widespread malignant potential. This is defined as
the oligometastatic state, and patients with up to five sites of disease are said to have
oligometastatic (OM) cancer. A number of studies of systemic therapy in metastatic breast
cancer have reported that patients with OM disease have a better prognosis compared to other
patients with more widespread disease, and in particular in patients with bone-only
metastastic breast cancer, outcomes may be better.
In the setting of OM disease in particular, local therapies could be considered. For example,
metastatectomies have been adopted into clinical practice in patients with colorectal cancer
liver metastases and sarcoma lung metastases with encouraging long-term outcomes. In the case
of metastatic breast cancer, there is less data to support a local therapy approach. Breast
cancer patients in particular commonly present with metastatic bone, lung and liver disease.
Some of these sites, for example bony or spinal disease, are not as easily amenable to
surgical resection, and surgery itself can cause significant morbidity. In such patients, it
would be desirable to consider a locally ablative therapy that is non-invasive, versatile
(can treat multiple sites simultaneously); generalizable to patients of various performance
statuses; have low rates of toxicity; and be proven to eradicate disease in treated areas.
Standard conformal radiation therapy (RT) is traditionally used for the treatment of metastatic
breast cancer. The main indication for RT has been with palliative intent, and relatively low
doses are used with the goal of symptom control. Higher RT doses given in 5-6 weeks (50-60
Gy/25-30 fractions) may improve local control (LC); however they are inconvenient and may be
associated with increased acute toxicity. Over the past 10 years, due to technical advances
in RT planning and delivery, the ability to precisely and safely deliver larger daily doses
over shorter periods of time has developed, known as stereotactic body radiation therapy (SBRT).
This technique is defined by the Canadian Association of Radiation Oncology as: "The precise
delivery of highly conformal and image-guided hypo-fractionated external beam radiation therapy,
delivered in a single or few fraction(s), to an extra-cranial body target with doses at least
biologically equivalent to a radical course when given over a conventionally fractionated
(1.8-3.0 Gy/fraction) schedule". SBRT is a non-invasive method involving delivery of multiple
small radiation beams from many angles with sub-millimetre precision, targeted to eradicate
intracranial lesions. The goal is to use large ablative doses to achieve permanent tumour
control with 1-6 fractions of 5-20 Gy per fraction. Ultimately this represents a
philosophical shift in treating a metastatic site with locally "ablative" doses of radiation
in a safe, effective, and convenient fashion.
There is growing evidence to support the safety and efficacy of SBRT to many single organ
sites, and literature reviews demonstrate LC of 70-90% in OM sites at 1-2 years. A recent
systematic review of the literature of ablative therapies in metastatic breast cancer
(including SBRT) revealed significant heterogeneity in observed studies, and no clearly
definable subgroups that may benefit, with the exception of patients who had complete
ablation of their residual disease. The conclusion from this study was that further clinical
trials were necessary to demonstrate benefit of ablative therapies as compared to standard
treatment in breast OM.
Therefore, while SBRT has been used safely and effectively to treat OM evidence suggests
there is still a need in better characterizing the role of SBRT with respect to local
control, freedom from distant progression and potentially survival. The investigators believe
that patients with metastatic breast cancer are likely to benefit from SBRT for a number of
reasons: 1) a significant portion of patients develop OM disease; 2) the most common breast
OM sites including bone, liver and lung are amenable to SBRT; 3) with improvements in
systemic therapy, there is a high probability that microscopic (non-clinically evident)
metastatic disease will be controlled, so that additional local therapy may be synergistic
and improve local control and symptom development in the future. Notwithstanding these
factors, SBRT to bony and other sites is rarely used in metastatic breast cancer patients in
Canada for several reasons: there is a gap in knowledge regarding the potential role of SBRT
in these patients, a current pattern of referrals and triage for more traditional palliative
treatments, and lack of standardized protocols to treat, assess response and follow these
patients. The investigators propose a feasibility study, which addresses these issues in
patients with OM breast cancer to bony and visceral sites, which may provide the background
foundation for future research and patient care. The study aims to address not only
feasibility, but local control, survival, toxicity, and quality of life.
View this trial on ClinicalTrials.gov
