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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.