NcXHF

ABLATIVE THERAPY FOR OLIGOMETASTATIC BREAST CANCER
months, and 5-year survivals have ranged from 27% to
80%. 2,25 To date, all of the reported studies have been retrospective,
and, therefore, although hypothesis generating,
they are not conclusive of the benefıts of these therapies. In
one of the largest retrospective analyses of patients with
breast cancer undergoing pulmonary metastasectomy pooling
data from more than 460 women from multiple international
institutions with specialty in pulmonary resection for
metastases, approximately 60% of the patients had a single
pulmonary metastasis and approximately 10% had three or
more metastases. The median survival for this cohort was 35
months. The cumulative 5-year survival rate was 35%, the 10-
year survival rate was 20%, and the 15-year survival rate was
18%. Patients with longer disease-free intervals, complete resections,
and fewer metastases had improved OS. In women
with a single metastasis completely resected and a diseasefree
interval longer than 36 months, the 5-year OS was 50%
compared with 13% in those with multiple metastases and a
disease-free interval less than 36 months. 25
Similar results are seen in large retrospective analyses of
patients with MBC undergoing hepatic metastasectomy; although,
in general, the number of patients reported in these
series are smaller than those reported for pulmonary metastasectomy.
In one of the largest series of 86 patients, with primarily
solitary (62%) and small (85% less than 5 cm)
metastases with a median follow-up of 62 months, the median
OS was 57 months. 26 Although the complication rate
was 21%, most (72%) required no intervention, and there
were no postoperative deaths. Ninety percent were able to
undergo complete resection (R0) and only one patient had
macroscopically positive resection margins (R2). Patients
with a partial response (PR) to chemotherapy before hepatic
resection had a median survival of 79.4 months compared
with 22.9 months in those progressing before hepatic surgery
(p 0.001). Additionally, patients with ER/progesterone receptor
(PR)-positive primary tumors had a median survival
of 76.8 months after hepatic resection compared with 28.3
months in ER/PR-negative primary tumors (p 0.001). Similar
to those undergoing a pulmonary metastasectomy, a longer
disease-free interval, longer than 24 months, was
associated with longer OS (100.7 vs. 47.5 months; p 0.001).
The importance of surgical removal or radiotherapy to all radiographically
or metabolically detected metastases is becoming
ever more important as systemic therapies are increasingly effective.
Although systemic therapies have improved control of
subclinical breast cancer metastases and prolonged of
progression-free intervals in patients with MBC, 27 most longterm
survivors following systemic therapy had aggressive treatment
to all known metastases. 11 This is likely because of the fact
that in patients with oligometastatic disease, from breast 28,29 as
well as other primary tumors, 30 sites of progression are most
likely in known metastases, and not in new metastatic locations.
Therefore, ablative therapy to all known metastases has the potential
to maximize the therapeutic benefıt for these patients.
The importance of achieving an R0, complete resection in
patients undergoing metastasectomy is clear from both pulmonary
and hepatic metastasectomy data. From the largest
analysis of patients undergoing pulmonary metastasectomy,
those undergoing a complete resection had 5-year survival of
38%, 10-year survival of 22% and 15-year survival of 20%,
and a median survival of 37 months compared with a 5-year
survival of 18% and a median survival of 25 months in those
who underwent incomplete resection (p 0.0009). 25 Additionally,
in patients undergoing a hepatic metastasectomy,
those undergoing a complete resection had a median OS of
57 months compared with 33.6 months in patients undergoing
R1/R2 resections (p 0.17).
From these data clinical characteristics of preferred patients
for surgical resection begin to emerge. Patients selected
for surgery should have longer disease-free intervals. The exact
disease-free interval is not known, but for both patients
undergoing both pulmonary and hepatic resection has been
reported at longer than 2 years. 26 Patients should also be able
to undergo a complete resection, have fewer metastases, and
have ER/PR or HER2-positive tumors. 2
RADIOTHERAPY FOR BREAST CANCER METASTASES
Advances in the planning, targeting, and delivery of radiotherapy
have recently added a new tool against oligometastases.
Many patients with MBC are not candidates for surgery
because of medical comorbidity, personal preference to
avoid surgery in the setting of metastasis, or invasion of metastases
into unresectable organs. In these situations, radiotherapy
is ideally suited for the treatment of limited
metastases. Newer radiation techniques, commonly termed
stereotactic body radiotherapy (SBRT) or stereotactic ablative
radiotherapy (SABR), but perhaps most accurately described
as hypofractionated image-guided radiotherapy
(HIGRT), precisely deliver single or few radiation treatments
at doses 2 to 10 times that of conventional radiation treatments.
31 Derived from intracranial stereotactic radiosurgery,
these treatments deliver radiation doses wrapped tightly
around targeted metastases, while sparing surrounding normal
tissues. These higher radiation doses are thought to engage
additional tumoricidal mechanisms beyond DNA
damage, including endothelial-mediated 32,33 and immunemediated.
34,35 Although doses of at least 54 Gy have been
shown necessary when using three radiation doses to target
tumors in the lung and liver, 36 other more protracted dosing
schemes have been shown effective as well. 22 These techniques
have been shown to be effective even when targeting
larger metastases 37 with treated metastasis control ranging
from 70% to 90%. 31
Perhaps the best data for the treatment of MBC with ablative
radiotherapy comes from the University of Rochester. 29
A pooled analysis of 40 women with limited breast cancer
metastases treated on two sequential protocols using radiotherapy
for limited metastatic disease reported promising
outcomes. The median time to enrollment was 12 months
after diagnosis of metastases and 56 months after initial
breast cancer diagnosis, and 90% had been pretreated with
systemic therapy. The 2-year and 4-year PFS was 44% and
38%, respectively. At 4 years, the treated metastasis control
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