ESTRO 2021 Abstract Book

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ESTRO 2021

significant toxicity, the question has been raised whether axillary treatment can be de-escalated in specific cases. After primary surgery, the AMAROS trial showed that an ALND could safely be replaced by regional radiotherapy (RT) in case of a positive sentinel node biopsy (SNB) [Donker et al, 2014], and resulted in less lymph-edema. By analogy of this trial, it has been proposed also to replace an ALND by RT after PST, in case of (limited) residual axillary disease. Since selection of patients is essential when de-escalating treatment, axillary staging procedures after PST will be discussed first in this presentation. This will be followed by indications for regional RT in case of cN+, ypN+, and by an overview of the major current clinical trials on RT after an axillary non-pCR. Axillary staging after PST in cN+ patients Several studies have investigated whether imaging or a sentinel lymph node biopsy (SNB) after PST was sufficiently accurate to stage the axilla. These studies all showed however a relatively high false negative rate [Schipper et al, 2015]. Subsequent studies investigated whether Targeted Axillary Dissection (TAD), i.e. removal of a marked pathologic axillary node prior to PST, alone or in combination with an SNB would improve the accuracy of the staging procedure [Caudle et al, 2016]. These studies showed that the combination of SNB and TAD resulted in the highest negative predictive value, i.e. up to 93.6% [Simons et al, SABCS 2020]. Indication for regional RT in case of cN+, ypN+ In patients undergoing an ALND after PST, most guidelines recommend to apply locoregional RT in case of extensive nodal involvement, i.e. ≥ypN2 and / or ≥ 4 suspicious axillary nodes on imaging prior to PST. In case of limited nodal involvement, the indication for regional RT is less clear. Although the EBCTCG meta-analysis showed a survival benefit of regional RT in pN1 disease, preliminary results of the RAPCHEM study showed a 5 yr. locoregional recurrence rate of 1.1%, in 200 patients with cN+, ypN1(ALND) disease in whom regional RT was omitted [De Wild et al, ESTRO 2021]. This suggests that omission of regional RT is safe in patients with cN+, ypN1 disease, in whom an ALND has been performed. Recently, an increasing number of groups are replacing an ALND by RT, after a positive SNB and/or TAD [Noorda et al, 2018]. In this situation, often a discrimination is made between low and high axillary tumour load prior to PST using a PET-CT, where low axillary tumour load is defined as < 4 suspicious nodes, and high axillary tumour load is defined as ≥ 4 suspicious nodes. In case of low axillary tumour load prior to PST and a positive SNB/TAD after PST, the ALND is replaced by RT of level 1 -4; in case of an axillary high tumour load prior to PST, and a positive SNB/TAD after PST, an ALND is performed followed by RT of level 3 &4. Several clinical trials are currently ongoing to investigate the safety of replacing an ALND by regional RT in these situations. Current clinical trials in case of ypN+ Several trials are currently ongoing, or in preparation, to investigate whether axillary RT can replace an ALND, in case of a positive SNB/TAD after PST, e.g. the ALLIANCE 11202 trial [NCT01901094]. This trial started in 2014, and aims to include 1660 patients. In the Netherlands, a wide practice variation is currently present with respect to axillary treatment after PST. This is being evaluated in a prospective cohort study, i.e. the MiniMAX study [NCT04486495]. In this presentation, an overview will be given of the major ongoing clinical trials on this issue. SP-0354 Radiotherapy in case of complete pathological response after primary systemic therapy L. Bech Jellesmark Thorsen 1 1 Aarhus University Hospital, Department of Oncology, Aarhus, Denmark Abstract Text Primary systemic therapy (PST) in locally advanced breast cancer comes with a number of advantages to the patient. While PST does not affect survival compared to traditional adjuvant systemic treatment, it does increase the chance of breast-conserving surgery (BCS). Additionally, it allows adaptation of the type of systemic treatment in case of insufficient clinical tumor response during PST, and selection of patients for intensified adjuvant systemic treatment in case of a poor pathological response. Consequently, PST is increasingly used in the treatment of locally advanced breast cancer worldwide. While the concept of PST is attractive, it does at times make the life of the radiation oncologist more challenging. The evidence in favor of adjuvant post mastectomy radiation therapy (PMRT) and indeed regional nodal irradiation (RNI) after breast conserving surgery (BCS) is based on randomized trials and meta-analyses of such trials with thousands of patients included. The 2011 meta-analysis from the Early Breast Cancer Trialists’ Collaborative Group concluded that for every four recurrences prevented at year ten, one death was avoided at fifteen years. Rates of LRR have been very low in recent trials on RNI such as the NCIC-CTG MA.20 and the EORTC 22922-10925 trials, but still, RNI has prevented distant metastasis and deaths from breast cancer. Importantly, the proportionate risk reduction with PMRT/RNI seems constant across risk-groups. Unfortunately, the same high-quality evidence is not at hand for patients treated with PST. Especially in patients with a complete pathological nodal response (pCRN) after PST, prognosis is excellent. Current practice in this subset of patients’ ranges from the conservative option of offering PMRT/RNI based on the pre- PST nodal stage to refraining completely from PMRT in patients with otherwise favorable prognostics. Whether PMRT/RNI is necessary in all or some of patients with a pCRN after PST is the subject of the NSABP B- 51 trial, which randomizes women with cT1-3cN1 early breast cancer with pathologically confirmed nodal involvement and a pCRN to +/- PMRT/RNI. Until results from this and similar trials are mature, the radiation oncologist must rely on less firm evidence to select patients for PMRT/RNI in case of a pCRN. Early randomized trials on PST prohibited PMRT and thereby allowed the identification of risk factors for loco-regional recurrence (LRR). Observational and retrospective studies on the effect of PMRT, albeit with an inherent risk of bias, might also be of aid in selecting patients for radiotherapy. This lecture addresses current guidelines and the evidence presently at hand and for patient-selection for PMRT/RNI in case of a pCRN. Furthermore, it gives an overview of ongoing clinical trials on the subject.

SP-0355 SBRT as a strategy to delay systemic treatment in metastatic breast cancer