ESTRO 2023 - Abstract Book

S328

Sunday 14 May 2023

ESTRO 2023

Conclusion Prospective review of all outlines and plans in a multinational clinical trial is achievable and ensures that all patients receive high quality RT. This is particularly important in a rare tumour where some centres submit less than 1 case per year and have little familiarity with the protocol.

The QA process was robust, ensuring a high level of consistency of RT treatment in the ROAM study (EORTC 1308).

Proffered Papers: Tumour radiobiology

OC-0425 ATR inhibition as a novel radiosensitization strategy for glioblastoma B. Mukherjee 1 , S. Kanji 1 , N. Tomimatsu 1 , J. Floyd 1 , S. Burma 1 1 UT Health Science Center at San Antonio, Neurosurgery, San Antonio, USA

Purpose or Objective Glioblastomas (GBM) are lethal brain tumors for which surgical resection followed by treatment with ionizing radiation (IR) and concurrent administration of Temozolomide (TMZ) is the mainstay of therapy. These tumors are extremely radioresistant, and resistance to radiation is one of the primary causes of therapy failure. Therefore, there is an urgent need for rational radiosensitization approaches to improve GBM therapy. IR induces double strand breaks (DSBs) in the DNA, and these are extremely deleterious lesions that can be repaired either by error-prone non-homologous end joining (NHEJ) or the error-free homologous recombination (HR) pathway. Research in our and other laboratories has shown that the ATR kinase promotes the HR pathway. We therefore hypothesized that ATR inhibition would block DSB repair in rapidly- dividing GBM cells that are HR dependent but not in non-dividing normal brain cells that are dependent upon NHEJ for repair. Materials and Methods A panel of GBM cell lines and normal human astrocytes were treated with VX-803 and/or IR and assessed for multiple endpoints including HR, DSB repair, and cell survival. PDX mouse models of GBM were treated with VX-803 followed by XRT and monitored for tumor growth and survival of tumor bearing mice. In addition, the effect of the drug on tumor cells versus normal brain cells was assessed by immunostaining for DSB markers. Results We find that VX-803 blocks HR and DSB repair in a panel of GBM cell lines but does not significantly affect repair in non- dividing normal human astrocytes. Hence, treatment with VX-803 sensitizes GBM lines to IR in vitro as measured by the colony formation assay. In vivo, we find that the drug can cross the blood-brain barrier and, in conjunction with IR, block DNA repair in intracranial tumors, attenuate tumor growth, and consequently extend survival of tumor-bearing mice. Importantly, the drug does not significantly affect DSB repair in normal brain cells indicating that ATR inhibition might selectively block repair in GBM cells resulting in increased tumor control with minimal normal tissue toxicity. Conclusion Our results indicate that regulation of HR by ATR is critical for optimal DSB repair, especially in rapidly-dividing GBM cells, and that ATR inhibition could be used to improve GBM radiotherapy in the clinic. OC-0426 Immunomonitoring in prostate cancer patients treated with 3 different radiotherapy strategies M. Bottero 1 , A. Faiella 1 , B. Palermo 2 , I. Sperduti 3 , S. Masi 4 , M.L. Foddai 5 , I. Cordone 4 , P. Nisticò 2 , G. Sanguineti 1 1 IRCCS Regina Elena National Cancer Institute, Radiation Oncology, Rome, Italy; 2 IRCCS Regina Elena National Cancer Institute, Unit Tumor Immunology and Immunotherapy, Rome, Italy; 3 IRCCS Regina Elena National Cancer Institute, Biostatistical Unit, Rome, Italy; 4 IRCCS Regina Elena National Cancer Institute, Clinical Pathology and Cancer Biobank, Rome, Italy; 5 IRCCS Regina Elena National Cancer Institute, Transfusion Medicine, Rome, Italy

Purpose or Objective