ESTRO 2024 - Abstract Book

S5211

Radiobiology - Microenvironment

ESTRO 2024

[4] Cancer Genome Atlas Research Network; Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013 Oct;45(10):1113-20. doi: 10.1038/ng.2764. PMID: 24071849; PMCID: PMC3919969.

[5] Chander, A. et al. PO-2213 The impact of the tumour microenvironment on head and neck SCC cell viability and radiosensitivity. Radiotherapy and Oncology 182, S1991–S1992 (2023).

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Digital Poster

ANTI-TUMOR AND ACUTE TOXICITY OF FRACTIONATED STEREOTACTIC RADIOTHERAPY COMBINED WITH HYPERTHERMIA

Folefac C Asonganyi 1 , Priyanshu M Sinha 1 , Niels Bassler 2 , Michael R Horsman 1

1 Aarhus University Hospital, Experimental Clinical Oncology-Dept. Oncology, Aarhus, Denmark. 2 Aarhus University Hospital, Danish Center for Particle Therapy, Aarhus, Denmark

Purpose/Objective:

Combining hyperthermia temperature with stereotactic body radiotherapy (SBRT) suggests a potential treatment that can offer significant benefits to various cancer patients. SBRT in addition to it superior cancer cell killing also induces hypoxia via vascular damage in tumor. Non-toxic hyperthermia treatment can kill radiation resistance hypoxic cancer cells, radiosensitize cancer cells and inhibit their DNA repair after damage. Obtaining optimal results also depends on various treatment conditions between the application of these two modalities. An ongoing experiment with tumor studies using 3x15Gy fractionated SBRT doses and heat treatment (40.5°-42.5°C for 1 hour) at various time intervals (30-180 minutes) have shown significant results in terms of tumor delay growth and tumor control. Translating these preclinical results into clinical settings will depend if these same treatment conditions on tumor are tolerable on healthy tissues.

Material/Methods:

C3H mammary carcinomas were implanted in the rear legs of CDF1 mice and treated over one week when tumor reached about 200mm³. This treatment involved three sessions of 15 Gy irradiation, using either photons or protons. Additional animals received the same radiation doses along with a single hyperthermia treatment at temperatures of 40.5°C, 41.5°C, or 42.5°C for one hour, with intervals of 30, 90, or 180 minutes after the last radiation session. For acute toxicity assessment, animals will be treated with same treatment as above but, with radiation doses ranging between 5-17 Gy per fraction. Tumor study experiments concluded when the tumors reached three times their initial treatment volume (TGT3) or showed tumor control at 90 days post-treatment. Various treatment groups for tumor studies were compared using Student t-test, with significance set at P<0.05. Acute toxicity will be evaluated by assessing moist desquamation (MD) on the animals' legs over 30 days post treatment, assigning arbitrary scored from 0 to 3.5. Non-linear regression curves will be used to determine the radiation dose that elicited a response in 50% of mice (MD50) based on given scores. This MD50 radiation dose value represents the maximum allowable radiation dose for each treatment condition, determined based on the tolerable acute skin score. Statistics analyses for acute toxicity will be perform using software and employing Student's t-test to compare treatment groups.

Results: