ESTRO 36 Abstract Book

S539 ESTRO 36 _______________________________________________________________________________________________

isolated from blood drawns harvested before the administration of the first fractioned dose of RT and 24 h later. 4. Statistical analysis: Anova test is performed to analyse the differential expression across IRS classes and a Spearman analysis is performed to assess correlation between expression and IRS index. Results The expression of DDB2, GADD45A, CDKN1A, and ATM genes following irradiation 2,3 has been correlated with the in vitro IRS evaluated by the G2-chromosomal assay; at present, a positive correlation between ATM expression and IRS could be inferred despite the unavoidable inter- individual variability. The analyses on other DDR genes are The innovation of this study is the use of a molecular biology approach to assess patient radiosensitivity before RT, in the frame of an integrated approach between clinicians and biologists. References 1. Pantelias GE. & Terzoudi G. I. Radiother. Oncol. 101 (2011). 2. Mognato M. & Celotti L. Mutat. Res. Mol. Mech. Mutagen. 578 (2005). 3. Girardi C. et al. PLoS One 7 (2012). in progress. Conclusion PO-0975 Clinical utilization of the radiation-hypoxia- induced abscopal/bystander effect in lung cancer S. Tubin 1,2 , S. Gupta 3 , A.M. Mansoor 4 1 KABEG Klinikum Klagenfurt, Radioonkologie, Klagenfurt, Austria 2 Sylvester Comprehensive Cancer Center- University of Miami Leonard Miller School of Medicine, Department of Radiation Oncology, Miami, USA 3 Georgia Cancer Center- Augusta University- Augusta- GA- USA, Health Sciences, Augusta, USA 4 National Cancer Institute- National Institutes of Health, Radiotherapy Development Branch- Radiation Research Program- Division of Cancer Treatment and Diagnosis, Rockville, USA Purpose or Objective To report on initial results in a small series of consecutive patients treated with high-dose hypofractioneted radiotherapy (1-3 fractions) in the treatment of oligometastatic patients with large tumor masses focusing on application of results previously obtained by in vitro studies on radiation-induced abscopal/bystander effect. Our previous study (unpublished data) focused on targeting tumor hypoxia that induced a strong abscopal/bystander effect. We provide data that support the contention that high-dose radiation to the part of a large gross tumor volume (GTV) has the potency to induce a robust bystander effect, as well as abscopal (distant) effects. Material and Methods In the in vitro studies conditioned medium-transfer experiments with A-549, H-460 lung cancer cells, as well as their hypoxic clones (A-549HR, H-460HR), were performed. All the cells were irradiated in normoxic or hypoxic conditions with 10Gy single dose and cell growth and survival were monitored by real time cell electronic sensing (RTCES) System and colony forming assay, respectively. In the clinical study, 5 consecutive oligometastatic patients with large hypoxic cancers of lung (3), neck (1) and mediastinum (1) were treated with high dose radiotherapy using high-energy photons. All lesions were irradiated partially by targeting the central hypoxic region (Figure 1), which corresponded to 30% of total GTV (Mean GTV volume 181 cc, mean diameter 6, 8 Poster: Radiobiology track: Radiobiology of lung cancer

cm) with 10Gy single fraction prescribed to the 70% isodose line (Dmax 14 Gy). No patient got chemotherapy/immune therapy.

Results 10Gy- in vitro induced abscopal effect in hypoxic conditions was very effective in inducing growth delay of both, unirradiated normoxic and hypoxic lung cancer cells (Table 1), so we moved forward with clinical application of bystander/abscopal effect. In all the treated patients, a significant bystander effect after mean time of 3 weeks and in 1 of the patients significant abscopal effect was also observed (Figure 2). Overall response rates for symptom relief and mass response were 100% (1 complete and 4 good partial response).No patient experienced acute or late toxicity of any grade.

Conclusion Considering the clinical benefit/toxicity ratio, the clinical exploitation of biological properties of bystander/abscopal effect induced by partial irradiation of large tumor masses, and almost any dose distribution to the normal tissue outside the irradiated tumor, could make bystander/abscopal effect at least more effective than conventional radiation therapy for treatment of advanced cancers and the perfect treatment option for symptomatic patient. Further, by inducing the distal responses, like in the case of one of the patients,