ESTRO 37 Abstract book

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ESTRO 37

progression free survival (PFS) were evaluated with Kaplan Maier curves and correlated with prognostic factors with log-rank test. Quality-adjusted survival (QAS) was evaluated according to the Murray model with the NNS scheme (Int J Radiat Oncol Biol Phys. 1995 Feb 1;31(3):453-9.) Results From 2010 to 2015, 31 pts were enrolled in 6 Radiotherapy Centers: 17 pts in the CHT group and 14 pts in the RT one. Four pts were excluded from analysis: 2 pts withdrew informed consent and 2 had clinical deterioration before the beginning of treatment and had supportive therapy only. Median age was 69 years (55-82 years). Two pts had IMRT with daily IGRT, the others had 3D conformal radiotherapy. CHT was interrupted after an average of 2 cycles (range 1-6) for clinical deterioration and disease progression. Median OS and PFS was 7,6 and 3,8 months respectively. Age> 70 years (p=0,048) and RPA VI (p=0,03) worsened OS significantly. Biopsy instead of extended surgery (p=0,038), RPA class VI (p=0,001) and chemotherapy (p=0,007 – Figure 1a) are related to a worse PFS. In the RTT arm, mild headache (grade I) was recorded in 90% of pts; in the CHT one, 3/17 pts had to reduce the dose of chemotherapy for grade I-II thrombocytopenia. In the two arms the initial NNS score was overlapping: 12.23 in CHT group and 12.3 in RT group. Figure 2 shows how NNS score progressively decreased in both groups but became significantly worse after 6 months in CHT group (p = 0.005- Anova test). Median QAS was 3,4 months (range 1-15,4 months); QAS was significantly better in RTT group (p=0,001 – Figure 1b).

tissue effects prior to clinical studies. We hypothesize that Notch inhibition has a protective effect in cells exposed to radiotherapy and may represents a potential target for intervention to modulate normal tissue toxicity. Material and Methods We established and characterized primary lung organoids and air liquid interface system (ALI), pseudo-stratified cultures derived from primary human bronchial epithelial cells (PBECs) from 6 different donors. In these cultures, basal cells proliferate and differentiate into ciliated and mucous/secretory cell types resembling the human bronchus. We irradiated lung epithelium with 2 and 4 Gy and early and late response to radiotherapy were evaluated. We investigated the consequences of blocking Notch signaling pathway using the pan-notch γ-secretase inhibitor DBZ (1uM) alone and when combined with irradiation (2, 4 Gy). Results Using immunofluorescence, western blot and q PCR we found that basal cells (p63 + , CK5 + ) cease proliferation (Ki67, EdU) at day 21 and mucous cell differentiation (Muc1/5ac + ) precedes ciliary differentiation (Ac-Tub + ) and both complete at day 28. Proliferation decreases overtime but inhibiting Notch in undifferentiated progenitors and in differentiated cells at day 21 increases p63 proliferation alone and even more in combination with radiotherapy. In all the 6 donors Notch inhibition increases p63+basal progenitors and ciliated cells and decreases mucous cells alone and in combination with radiation. In irradiated cultures we observed increased pATM and pCHK2 12h and 24h post-irradiation when Notch signaling was inhibited. γH2AX staining shows reduced DNA breaks 24h post-irradiation when Notch was inhibited. Conclusion These data support the use of normal patient tissue for predictive toxicity, screening of combination treatments and disclose important novel interactions between Notch inhibition and radiotherapy. OC-0587 Hypofractionated radiotherapy vs temozolomide in glioblastoma RPA V-VI: a randomized phase II trial S. Pedretti 1 , L. Masini 2 , E. Turco 3 , L. Triggiani 1 , M.Krengli 2 , B. Meduri 3 , L. Pirtoli 4 , M. Faedi 5 , R. Gatta 1 , S. Scoccianti 6 , U. Ricardi 7 , R. Santoni 8 , S. Magrini 1 , M. Buglione 1 1 Spedali Civili di Brescia and Brescia University, Radiation Oncology, Brescia, Italy 2 AOU Maggiore della Carità, Radiation Oncology, Novara, Italy 3 AOU Modena, Radiiation Oncology, Modena, Italy 4 AOU Senese, Radiation Oncology, Siena, Italy 5 IRST IRCCS, Radiation Oncology, Meldola, Italy 6 AOU Careggi, Radiation Oncology, Firenze, Italy 7 University of Turin, Radiation Oncology, Torino, Italy 8 University of Rome - Tor Vergata, Radiation Oncology, Rome, Italy Purpose or Objective To compare hypofractionated radiotherapy and temozolomide chemotherapy in terms of survival and quality of life in patients affected by poor prognosis glioblastoma. Material and Methods Patients (pts) with histologic diagnosis of glioblastoma (RPA V-VI) were randomized to hypofractionated radiotherapy (RT -30 Gy in 6 fractions on alternate days) and exclusive chemotherapy (CHT - temozolomide 5 days/28 days - 200mg/m 2 /day). Overall (OS) and Proffered Papers: CL 11: CNS

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Conclusion The data obtained from this multicentre randomized phase II clinical trial are limited by the poor accrual. Both treatments were well tolerated by patients without evidence of severe toxicities. Patients treated with hypofractionated radiotherapy have a better PFS and QAS, compared to patients in the CHT group, without incident on OS. In our case the deterioration of the NNS score would seem caused by disease progression rather than by the toxicity of the treatment. On behalf of Brain Study Group of the Italian Association of Radiation Oncology (AIRO).