ESTRO 36 Abstract Book

S4 ESTRO 36 2017 _______________________________________________________________________________________________

were obtained for immune monitoring. Patients were evaluated for abscopal responses with baseline and post- treatment (day 88) PET/CTs. Metastases outside the RT field were measured on axial CTs in 2 perpendicular dimensions. The products of the measurements (l x w) in all abscopal lesions were summed. Baseline and post- treatment measurements of abscopal lesions were compared. Abscopal responses were reported as: CR – complete resolution, PR – decrease in size ≥30%, PD – increase in size ≥20%, or SD – insufficient shrinkage or growth to qualify for PR/CR or PD. Toxicities were reported according to the common terminology criteria for adverse events version 4.0. Thirty-nine patients accrued. Based on intent to treat abscopal response rate was 18%. Seven of the 21 patients who completed the 4 cycles of Ipilimumab had an abscopal response (33%). At median follow up of 16 months the achievement of an initial abscopal response to the regimen remains associated with better survival (HR=9.174, log-rank test p=0.061) (Figure). Expression of PD-L1 >10% in pre-treatment tumor biopsies was observed among patients who achieved complete and partial abscopal responses, suggesting that T cells activated by RT and CTLA-4 blockade can reject PDL-1 positive tumors. Finally, marked changes in peripheral blood T cell clonality 3 weeks after combined treatment was demonstrated in the patients who developed abscopal responses but not in non responders. In a patient with complete response and sufficient tumor material for TCR Vbeta deep sequencing a T cell clone found in the tumor at low levels before treatment appeared in the blood at 3 weeks and persisted after completion of treatment. In conclusion, objective abscopal responses were common in NSCLC patients treated with local RT and ipilimumab, independently from initial PD-L1 expression. Immunologic characterization of tumor infiltrating lymphocytes and tumor antigen-specific T- and B-cell responses in treated patients is ongoing [clinicaltrials.gov NCT02221739].

because protons have unique depth-dose characteristics that can potentially significantly reduce normal tissue doses proximal and distal to the target volume and allow escalation of tumor doses. Lung cancer is one of the many cancer types that could benefit from proton therapy. Treatment planning and plan evaluation of PSPT and IMPT demonstrated significant reduction of mean lung dose and mean heart dose. Results from retrospective studies from our institution and others were promising. However, the results of the first adaptive randomization trial comparing passively scattered proton therapy (PSPT) with intensity- modulated (photon) radiotherapy (IMRT), both with concurrent chemotherapy, for patients with inoperable lung cancer showed no statistically significant differences in the primary endpoint (radiation pneumonitis or local failure) were found between IMRT vs. PSPT. Higher-than- expected RP in the PSPT arm may have reflected larger high-dose volumes and a steeper learning curve for practitioners treating with protons. The results also suggest that the dose constraints used to guide IMRT may not be applicable for protons. The most current evidence and challenges in using protons for lung cancer will be reviewed in this symposium. SP-0014 In situ Cancer Vaccines: Tumor destruction and immune stimulation for local and systemic tumor control. G. Adema 1,2 , M. Den Brok 1,2 , R. Van den Bijgaart 1,2 , M. Wassink 1,2 , M. Hoogenboom 2 , J. Bussink 1,2 , J. Futterer 2 1 Radiotherapy & OncoImmunology lab, Dept. of Radiation Oncology, Nijmegen, The Netherlands 2 RadboudUMC, Nijmegen, The Netherlands In situ Cancer Vaccines: Tumor destruction and immune stimulation for local and systemic tumor control. T umor ablation techniques are successfully applied for the treatment of cancer. These techniques use e.g. radiation, heat or cold to locally destruct often inoperable tumor masses. After ablation tumor antigens become instantly available for antigen presenting cells, and the procedure itself creates an inflammatory environment that will effect the immune system and hence anti-tumor immunity. Despite the reported enhanced presence of key immunological correlates, strong immune responses (abscopal effect) have only rarely been observed after tumor ablation as monotherapy. As a result, patients often succumb to tumor micro-metastases being already present prior to treatment. Therefore, there is a strong need for systemic adjuvant therapy, like immunotherapy, targeting these residual tumor cells. To obtain robust immunity we showed in murine models that ablation should be combined with immune modulation using adjuvants or immune checkpoint blockade mAbs. Moreover, we showed the involvement of mature lymph node dendritic cells, actively scavenging and cross-presenting antigens from the tumor. This yielded long-lasting memory immune responses and protection against a tumor rechallenge and even pre-existing metastasis. It is currently not fully understood how immune responses following radiotherapy can be optimally initiated and regulated. More importantly, the most effective immune stimulating compounds for Immuno-radiotherapy are not known. We will discuss our ongoing research program to uncover the potency of RT in combination with immune based strategies to eliminate tumor cells and their microenvironment for both local and systemic tumor control. Symposium with Proffered Papers: Radiotherapy plus immunotherapy combination: rationale and results so far

SP-0013 The use of novel technologies (e.g. protons) in NSCLC Z. Liao 1 1 UT MD Anderson Cancer Center Radiation Physics, Houston- TX, USA Technological innovations during the last 2 decades has revolutionized photon radiotherapy and resulted in improved clinical outcomes of lung cancer patients in terms of reduced radiation toxicity and increased tumor control and survival. These innovations include intensity modulated radiation, volumetric modulated arc therapy, image guided radiation therapy. Proton therapy can offer substantial clinical advantage over the photon therapy