NcXHF

ABLATIVE THERAPY FOR OLIGOMETASTATIC BREAST CANCER
or more metastases, there is also a phase I dose de-escalation
study (NRG BR001: NCT02206334) being conducted in
which patients with breast, lung, and prostate cancer with
two metastases in close proximity (less than 5 cm) or those
with three to four metastases will receive radiation to all
known sites of disease. Each metastasis will be assigned to
one of seven regions (neck and mediastinum, lung central,
lung peripheral, spinal, osseous, abdominopelvic, and hepatic)
based on the potential for normal tissue toxicity. Doses
for each region were selected based on all available data and
expert consensus. Doses will be de-escalated to each region
should toxicity be seen. An alternative approach, currently
used in the SABR COMET study (NCT01446744) is a dosestratifıed
method. 51 Careful analysis of adverse events combined
will help to truly understand the tolerances of normal
tissues to this type of ablative radiation.
Recent investigations have suggested potential biologic
markers of the oligometastatic state. Analyses of resected
pulmonary metastases, and the combination of primary and
metastatic tumors have identifıed a microRNA signature
that, when present, identifıes patients whose disease is unlikely
to progress rapidly or in a widespread manner. In
particular, increased expression of microRNA 200c was
found to be associated with a polymetastatic phenotype in
vivo as well as in clinically selected patients with oligometastatic
disease. 52 When restricted to patients with lung
metastases only, microRNA signatures can classify patients
as oligometastatic compared with polymetastatic,
and also differentiate those patients with a low recurrence
probability following surgical resection. 53 Further validation
is needed in prospective series to validate this as a
potential patient selection tool.
Currently, there are no validated biomarkers for response
evaluation after ablative radiotherapy for patients with oligometastatic
disease. PET scans utilizing fludeoxyglucose as an
imaging biomarker have shown potential for response evaluation
after ablative therapy. Only 10% of patients with a PR
on fırst postradiotherapy PET, and 29% of those with a complete
response progressed during follow-up. 54 Additionally,
PET was able to detect responses in those with nonmeasureable
lesions by standard RECIST, particularly useful in patients
with breast cancer who often present with osseousonly
metastases. Another potential biomarker to evaluate
response to ablative therapy is via enumeration of circulating
tumor cells (CTCs). Already established as a prognostic tool
for patients with MBC as well as a predictive tool evaluating
response to systemic therapy, 55 the presence of less than fıve
CTCs per 7.5 mL whole blood at baseline may also serve as a
way to identify those patients with truly oligometastatic disease
from the cohort of patients with few clinically apparent
metastases. Furthermore, the ability of surgery or ablative radiotherapy
to reduce the number of CTCs to less than fıve
may predict good responses to therapy. Furthermore, the
eradication of previously detectable CTCs after metastasectomy
or ablative radiation may indicate that the primary
sources of CTCs were the known and treated metastases and
not from the occult sites reseeding after ablative therapy preventing
durable long-term control.
In conclusion, from available data many if not most patients
with MBC present with a limited number of metastases,
which portents improved outcomes. Ablation of
imaging-detected metastases, with either surgery or radiation,
has been associated with long disease-free intervals for
patients with breast cancer. Although ablative therapies are
gaining in popularity, only now are prospective trials open to
identify the role of ablative therapy in oligometastatic breast
cancer. Patients should be enrolled in these studies to identify
the true effect of ablative therapy. Although early data are
beginning to elucidate the biologic underpinnings of patients
with oligometastatic disease, more work is needed, and biomarkers
need to be validated in this patient population to
better identify responses to treatment. All of this work is
needed to truly determine if there is potentially a subset of
patients with MBC that can achieve long-term survival. With
better identifıcation of which patients belong in this subset
and what the utility is of the ablative therapy options, a new
treatment paradigm may become the cure for a subset of patients
with MBC.
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: None. Stock or Other Ownership Interests: None. Honoraria: None. Consulting or Advisory Role: None.
Speakers’ Bureau: None. Research Funding: Joseph K. Salama, Merk (I), BMS (I), GSK (I), Abbvie. Patents, Royalties, or Other Intellectual Property:
None. Expert Testimony: None. Travel, Accommodations, Expenses: None. Other Relationships: None.
References
1. Macdermed DM, Weichselbaum RR, Salama JK. A rationale for the targeted
treatment of oligometastases with radiotherapy. J Surg Oncol.
2008;98:202-206.
2. Pockaj BA, Wasif N, Dueck AC, et al. Metastasectomy and surgical resection
of the primary tumor in patients with stage IV breast cancer: time for a
second look? Ann Surg Oncol. 2010;17:2419-2426.
3. Halstead W. The results of radical operations for the cure of carcinoma
of the breast. Ann Surg. 1907;46:1-19.
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