ESTRO 38 Abstract book

S73 ESTRO 38

be associated with higher pathological complete response (pCR) after neoadjuvant anthracycline-based chemotherapy+- anti-HER2 agents, but very little is known regarding TILs and exclusive radiotherapy (RT) treatment in breast cancer (BC). Our series of exclusive preoperative RT is a unique opportunity to address such question. The objective of this study is to evaluate the impact of exclusive preoperative RT on immune infiltrate in BC. Material and Methods TILs were estimated in a retrospective series of 187 BC patients with a median age of 49 years (43-60) with T2-T4 or N2 tumours treated between 1970 and 1984 with exclusive preoperative RT with a median follow-up of 32 years. Patients received a moderately hypofractionated RT (45-55 Gy in18 fractions of 2.5 Gy over 34 days) to the whole breast and nodes, followed by a modified radical mastectomy plus axillary dissection. The percentage of stromal TILs was centrally evaluated for each patient on her diagnostic biopsy and her mastectomy specimen following the address International TILS working group recommendations. Results Complete pathological response (pCR) was achieved in 18 (9.6%) of the 187 patients: six (8.4%) in Luminal A subtype, one (2.9%) in Luminal B, one (3.4%) in HER2 positive (3.4%) and eight (20%) in triple negative breast cancer (TNBC). The distribution of TILS in biopsies and mastectomy samples within subtypes is shown in figure 1. Overall, median TILs in biopsies was: <10% in 30.7%, between 10 - 40% in 64.5% and ≥50% in 4.8%. In the mastectomies TILs was <10% in 48.1%, between 10 - 40% in 50.3% and ≥50% in 1.6%. The subtypes with higher TILS levels were HER2 positive and TNBC (20% for both in biopsies and 15% and 20% for HER2 and TNBC in surgical samples) compared to Luminal A and B (10% in biopsies and 5% in surgical samples for both). Paired TILS measurements before and after radiotherapy were obtained in 122 (65.2%) patients. There was a slight decrease in TILS level with a mean change value of -3.0 (p=0.001) in the whole population. The decrease was stronger in Luminal B subtype and HER2 positive, as shown in table 1.

2 Kyoto University, Institute for Integrated Radiation and Nuclear Science, Osaka, Japan ; 3 German Cancer Research Center, German Cancer Consortium- Partner site Freiburg, Heidelberg, Germany Purpose or Objective Indoleamine-2,3-dioxygenease (IDO) is an enzyme that degrades the essential amino acid tryptophan to the immunosuppressive metabolite kynurenine. IDO- expressing immune cells play critical roles in peripheral immune tolerance and anergy. A recent phase 3 trial evaluating an IDO inhibitor/anti-PD1 antibody (aPD1) combination in metastatic melanoma patients missed its primary endpoint of improving progression-free survival compared to aPD1 monotherapy. However, IDO is induced by IFN-g, and hypofractionated radiotherapy (hRT) alone or in combination with immune checkpoint blockade can induce IFN-g-secreting, tumor-specific T cells. We therefore decided to study, in syngeneic mouse tumor models, whether the triple combination of hRT, aPD1, and an IDO inhibitor (IDOi) is superior to the respective double combinations. Material and Methods We compared the triple treatment of hRT (12 Gy × 2) + aPD1 + IDOi with the double combinations of hRT + aPD1, hRT + IDOi, and aPD1 + IDOi, and with the respective monotherapies in mice bearing relatively large (300 ‒ 500 mm 3 ), aggressively growing B16 melanoma or 4T1 breast adenocarcinoma tumors. Tumor growth and survival of the mice were determined. The dependence of the therapeutic effects on CD8+ T cells and NK cells was studied by additional injection of depleting antibodies. Frequencies and functionality of tumor-specific CD8+ T cells in tumor and secondary lymphoid organs were determined flow cytometrically by using MHC tetramers and various types of antibodies. Results In our models with relatively large tumors, the tumors did not regress following treatment with hRT + aPD1. The aPD1/IDOi double combination was not effective at all. In contrast, the triple treatment induced marked tumor regressions in both tumor models. The survival benefits were highly significant compared to hRT + aPD1 (B16 melanoma model p = 0.002; 4T1 model p = 0.0001). CD8+ T cell depletion strongly, and NK cell depletion partly, abrogated tumor control and survival benefits. Flow- cytometric analyses showed significant increases in tumor- specific CD8+ T cells for the triple combination group compared to the other groups. In addition, a significant increase in NK cell function was found. Conclusion Our data in two aggressive tumor models show that the triple therapy with hRT, aPD1, and an IDOi can induce much stronger tumor regression than double combinations or monotherapy with the individual components. Our findings may serve as a rationale for the clinical evaluation of this triple combination therapy in patients with high- risk locally advanced tumors. OC-0153 Immune infiltrate modulation induced by preoperative radiotherapy in breast cancer patients A. Matias Perez 1 , A. Bardet 2 , M. Lacroix-Triki 3 , F. Riet 4 , M.C. Mathieu 3 , E. Deutsch 1 , S. Michiels 2 , S. Rivera 1 1 Institut Gustave Roussy, Département de Radiothérapie, Villejuif, France; 2 Institut Gustave Roussy, Service de Biostatistique et d’Epidémiologie, Villejuif, France; 3 Institut Gustave Roussy, Département de Biologie et Pathologie Médicales, Villejuif, France ; 4 Hôpital Pitié- Salpêtrière, Département de Radiothérapie, Paris, France Purpose or Objective There is increasing evidence showing that tumor- infiltrating lymphocytes (TILs) are a marker for adaptive immune response. High level of TILs has been shown to

Conclusion Our preoperative RT series showed higher levels of TILS in HER2 positive and TNBC than in other subtypes before and after RT. In the paired samples, a slight decrease in TILS