S253
ESTRO 36
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recent discoveries have been promising. The identification
and validation of prognostic and predictive genes and gene
profiles needs, however, to take into account the various
treatment regimes as the prognostic information may
potentially not be applicable in all treatment settings.
SP-0477 Where should we place radiotherapy: before
or after surgery?
L.J. Boersma
1
, S. Lightowlers
2
, B.V. Offersen
3
, A.N.
Scholten
4
, N. Somaiah
5
, C. Coles
6
1
MAASTRO Clinic, Dept. Radiation Oncology, Maastricht,
The Netherlands
2
Cambridge University NHS Foundation Trust, Oncology
Centre, Cambridge, United Kingdom
3
Aarhus University Hospital, Oncology, Aarhus, Denmark
4
Antoni van Leeuwenhoek Hospital, Dept. Radiation
Oncology, Amsterdam, The Netherlands
5
The Institute of Cancer Research and The Royal
Marsden, Clinical Oncology, Sutton, United Kingdom
6
Cambridge University NHS Foundation Trust, Clinical
Oncology, Cambridge, United Kingdom
Introduction
Traditionally, radiotherapy (RT) for breast cancer has
been largely delivered after surgery. Pre-operative (pre-
op RT) with or without chemotherapy has usually been
limited to patients with inoperable locally advanced
breast cancer. More recently, pre-op RT is being
investigated in early stage breast cancer for both whole
and partial breast irradiation.
Clinical data on pre-operative radiotherapy
The clinical data on pre-operative RT are sparse. There
are some older series of pre-op RT in locally advanced
disease showing varying response rates. The older studies
also suggest an increased post-operative complication rate
and increased acute toxicity, possibly due to older
techniques. More recently, data are emerging on pre-
operative partial breast irradiation with promising results
both on local control (although follow-up is still short),
toxicity and on post-operative complication rate. Several
fractionation schedules are being used, which mirrors
partial breast irradiation in the post-operative setting.
Pros and cons of post-operative radiotherapy
The advantage of post-operative RT (post-op RT) is the
availability of post-operative pathology characteristics, in
combination with a huge amount of follow-up data,
supporting the indication for RT. However, since patients
are increasingly treated with primary systemic treatment,
the value of post-operative pathology to decide on post-
op RT has become less clear. Another problem with post-
op RT in breast conserving treatment is that the target
volume of the tumor bed is extremely difficult to
determine, as is clear from the inter-observer-variation
when delineating the tumor bed. In addition, when the RT
indication is clear prior to mastectomy, some oncoplastic
surgeons prefer to delay breast reconstruction until after
the post-mastectomy RT.
Potential pros and cons of pre-operative radiotherapy
The obvious disadvantages of pre-op RT are loss of post-
operative pathologic characteristics to guide treatment
and the lack of strong and long term clinical follow-up
data, similar to our experiences with primary systemic
treatment. However, the advantages of pre-op RT are also
likely to be similar to primary systemic treatment: it
allows evaluation of the effect of RT with or without
additional agents, directly on the tumor. In addition, it
may downstage the tumor and thereby facilitate surgery:
in case of inoperable locally advanced disease, the tumor
may become resectable; patients with large tumors likely
to require mastectomy, may become eligible for breast
conserving treatment after pre-op RT, especially those
patients who have luminal A type tumors not responding
to primary chemotherapy. Another advantage is the
possibility of using tumor response as a surrogate endpoint
for local control, although, as with primary systemic
therapy, pathological response may be highly dependent
on tumor type. Time for regression following RT may also
be an important factor determining pathological response
rates, especially for strongly estrogen receptor positive
tumors. If pathological response following RT proves to be
a valid surrogate endpoint, then this is very attractive for
future trial designs; for example, fewer patients will be
needed, the primary outcome will be sooner and there is
huge potential for developing translational radiobiology
research. Due to the better visibility of the target volume,
a reduction in inter observer variation has been shown
when delineating the tumor for breast conserving therapy,
resulting in smaller irradiated (boost) volumes. Finally, it
may facilitate routine immediate breast reconstruction,
sparing the patient not only a second operation, but also
sparing the patient an awkward time without a breast.
Future developments
As is clear from the above mentioned pros and cons, pre-
op RT potentially has several advantages above post-op
RT. To investigate whether these potential advantages can
be exploited in clinical practice, several trials are
currently ongoing. In the presentation an overview of
ongoing trials will be given.
SP-0478 Radiation therapy after complete response
after primary systemic therapy. Is it needed?
P. Poortmans
1
1
UMC St Radboud Nijmegen, Department of Radiation
Oncology, Nijmegen, The Netherlands
Radiation therapy (RT) improves disease-free and overall
survival in the framework of breast conserving therapy
(BCT) and when regional lymph nodes are involved.
Outcomes improved a lot following progress in diagnosis
and in loco-regional and systemic therapies. This has lead,
among others, to the introduction of primary systemic
therapy (PST) to reduce the delay in initiation of systemic
therapy in high-risk patients as well as to improve an
unfavourable tumour/breast size ratio for BCT purposes.
The outcome in terms of disease-free and overall survival
is, however, similar irrespective of the timing of systemic
therapy.
Current guidelines recommend that RT should be
prescribed based on risk factors at diagnosis, irrespective
of the administration of adjuvant or PST. Nevertheless, a
wide variation in the indication and extent for both RT and
surgery following PST is seen. Whilst a pathologically
complete response following PST may lead to a better
prognosis on an individual patient basis, the question
remains whether this allows for de-escalation of loco-
regional treatment. One of the cases of controversy is
nodal treatment when patients with node-positive disease
at diagnosis have a pathologically node-negative axilla
after PST. A progressively more popular approach after
PST is to remove only the sentinel and/or initially marked
lymph node(s), followed by completion axillary surgery in
case where there is residual macroscopical involvement
and RT in all other cases.
Research should further elaborate on the complex
interaction between risk factors of the primary tumour,
the effectiveness of adjuvant systemic therapy and the
influence of loco-regional treatments on outcome. The
results of recent trials rather suggest that those patients
treated with effective systemic therapy may benefit even
more from loco-regional treatments compared to patients
who respond poorly, as the latter are more likely to bear
unsuccessfully treated subclinical metastatic disease.
Several studies are exploring the contribution of loco-
regional treatments after PST, especially in the case of a
good tumour response.