ESTRO 36 Abstract Book

S250 ESTRO 36 2017 _______________________________________________________________________________________________

mastectomy. The 18-gene classifier was found to be an independent predictor of LRR in multivariate analysis regardless of ER status and nodal stage. The performance of the classifier has been tested in 87 patients treated with BCT, but the index is not yet validated and holds no predictive information in terms of postmastectomy radiotherapy (PMRT). The DBCG-RT profile has, however, been found to hold both prognostic information in terms of LRR and predictive impact in regard to PMRT. The gene profile was derived from a training set 191 high-risk breast cancer patients treated with mastectomy and randomized to PMRT or not, and independently validated in another 112 patients. Among non-irradiated patients in the training set, the profile attained prognostic impact by identifying two groups with a significant 6-fold difference in LRR risk. Furthermore, the DBCG-RT profile showed a predictive impact, since PMRT could be seen to reduce the risk of LRR in the “High LRR risk” patients, whereas the “Low LRR risk” patients experienced no additional benefit from PMRT. More recently, a radiation sensitivity signature has been derived from breast cancer cell lines, and has been found to accurately identify patients with LRR among 185 breast cancer patients. The latter two signatures have been found to be independent of the intrinsic subtypes. Finally, exploring the heterogeneity of the tumormicroenvironment may lead to targets that can affect radiosensitivity or reverse radioresistance. Hypoxic areas may leave possibilities for potential therapeutic targets, and a more profound understanding of the interaction between the immune system and RT (including different treatment schemes) may lead to an increased understanding of non-targeted effects. The progress towards integrating molecular profiling into precision radiation oncology is currently in its infancy, but 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