ESTRO 36 Abstract Book

S253 ESTRO 36 _______________________________________________________________________________________________

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.