ESTRO 2021 Abstract Book

S190

ESTRO 2021

infiltrating lymphocytes were significantly lower in the more hypoxic than less hypoxic tumours (P < 0.0001), but differed considerably within the two tumour groups. The immune score was associated with PFS (Cox PH, P = 0.019), and to determine its effect on treatment outcome for patients with more and less hypoxic tumours separately, the score was dichotomized using the percentile giving the best association to PFS. For patients with a less hypoxic tumour, a low immune score was associated with poor PFS (50% vs 81%, HR = 3.8). However, there was no significant difference in PFS for patients with a more hypoxic tumour stratified based on the immune score. Moreover, patients with a less hypoxic tumour and low immune score had an outcome which was similar to those with a more hypoxic tumour. Conclusion Our results indicate that the tumour immunity is lower in more hypoxic than less hypoxic cervix tumours. Moreover, the immunity is a predictor of chemoradiotherapy outcome for patients with a less hypoxic tumour. Combined information of hypoxia and immunity are therefore important for assessing treatment resistance in locally advanced cervical cancer. OC-0281 Tumour reoxygenation by intratumoural hydrogen peroxide: a mechanism for enhanced radiosensitivity S. Nimalasena 1,2 , S. Anbalagan 1 , C. Box 1 , J.K. Boult 1 , N. Bush 1 , S.P. Robinson 1 , J. Yarnold 1 , N. Somaiah 1,3 1 The Institute of Cancer Research, Division of Radiotherapy and Imaging, London, United Kingdom; 2 The Royal Marsden Hospital NHS Foundation Trust, Clinical Oncology, London, United Kingdom; 3 The Royal Marsden NHS Foundation Trust, Clinical Oncology, London, United Kingdom Purpose or Objective Following a Phase I trial confirming safety, a multicentre Phase II trial is underway comparing the efficacy of radiotherapy (RT) vs. intratumoural (IT) H 2 O 2 + RT in breast cancer patients. The hypothesis under test is that H 2 O 2 leads to tumour reoxygenation, via breakdown into H 2 O and O 2 within tumours. This is evidenced by O 2 bubbles visible on ultrasound following IT injection. In vitro and in vivo studies were performed in a human colorectal tumour model to confirm the effect, and to investigate the reoxygenation hypothesis. Materials and Methods Subcutaneous HCT116 xenografts were established in Foxn1 nu mice (n=12). Dual hypoxia markers were used to measure the difference in tumour hypoxia pre- and post- IT injection of 0.05ml 0.5% H 2 O 2 + 1% sodium hyaluronate gel. IT injections were into the centre of the tumour under US guidance. A control cohort received no injection (n=3). CCI-103F was administered to provide a record of baseline tumour hypoxia, followed by pimonidazole (1 hour following IT injection). The experimental schema is shown in Fig.1A. A thresholding technique was used to quantify fluorescence on imaged tumour sections. In order to test the combined effect of H 2 O 2 + IR in a 3D in vitro model, HCT116 spheroids were treated with 0.6mM H 2 O 2 , 3Gy ionising radiation (IR), or a combination (0.6mM H 2 O 2 administered 30 min pre-IR) and compared with untreated controls. Spheroid diameter was measured at 3-day intervals (until day 23) using an automated cytometer (Celigo) to monitor growth kinetics. Results HCT116 xenografts injected with H 2 O 2 + sodium hyaluronate exhibited a reduction in hypoxia adduct formation (expressed as percentage of tumour area) from baseline (Fig.1B-C), in comparison to non-injected controls. A significant decrease (paired t-test) in hypoxia staining was demonstrated in H 2 O 2 -injected tumours (mean reduction 45%, range 25-61, p=0.02), compared to control tumours. Areas within the tumour showing abundant CCI-103F adducts were associated with less pimonidazole adducts following H 2 O 2 injection.

Growth inhibition was demonstrated in spheroids treated with the combination of H 2 O 2 H 2 O 2 or IR alone, at all time points, and reaching statistical significance on day 15 and 19 (p=0.01) (Fig. 2). + IR, compared with