ESTRO 2021 Abstract Book

S6

ESTRO 2021

Abstract Text Tumor cell metabolism plays a key role in the cellular respons to radiation therapy. In the classic approach tumor cell metabolism is glycolytic. As such, a lot of glucose is used without oxygen consumption. This is the basis of the application of [18F]FDG PET scans for treatment selection and more importantly, treatment monitoring. In NSCLC, for instance, [18F]FDG PET scans are routinely applied in the phase of tumor screening but has also been shown to be a strong prognostic tool for prediction of treatment outcome. Changes in FDG uptake as early as twee weeks after start of treatment can predict tumor control. Interestingly, more recently it was described that oxidative phosphorylation (OXPHOS) remains active in many cancers and it is a potential therapeutic target. Therefore, the use of OXPHOS inhibitors has gained interest. Smaller studies already showed strong evidence that OXPHOS inhibition can be used to modify the metabolic status of a tumor, from OXPHOS to glycolysis. This metabolic programming results in a reduction of the use of oxygen. The reduction in hypoxia results in the theoretical improvement of radiation therapy efficacy. To select patients for treatment and to evaluate the anti-hypoxic effects of these OXPHOS inhibitors, functional hypoxia imaging is a useful tool. Several aspects of metabolism or the consequences of aberrant active metabolism can be monitored with PET imaging. Tumor cell metabolism can be quantified and monitored by [18F]FDG PET. For the oxygenation status the most commonly applied are redox-sensitive probes, such as [18F]HX4-PET, [18F]FAZA-PET and [18F]FMISO- PET. Another approach is by targeting endogenous hypoxia related markers by which only tumor cells are visualized that have adapted to the harsh hypoxic microenvironment. In this perspective carbonicanhydrase IX (CAIX) is a promising marker and is currently under preclinical investigation as an imaging target. In a recently published study on NSCLC, the change in metabolism by means of mitochondrial complex inhibition (atovaquone) could be detected as a reduction in hypoxia assessed by [18F]FMISO PET imaging. Careful selection of the metabolic imaging modality is of utmost important. The use of the appropriate imaging tool, i.e. visualizing the target under investigation, can prevent unnecessary rejection of new treatment modalities.

SP-0018 Radiation-driven tumour metabolic reprogramming T. Burns USA

Abstract not available

SP-0019 Targeting tumour metabolism for enhancing radiotherapy response L. Kuntz-Schugart

Abstract not available

Symposium: New endpoints for early breast cancer - Less is more?

SP-0020 Health-related quality of life - Primary or surrogate endpoint? I. Meattini 1 1 University of Florence, Department of Experimental and Clinical Biomedical Sciences "M. Serio", Florence, Italy Abstract Text Breast cancer (BC) becomes a largely curable disease, with more than 70% of women surviving at 10 years after diagnosis mainly thanks to early detection and treatments improvement. Health-related quality of life (HRQoL) and cancer has become an important aspect of the patient management that may be inadequately addressed with current standards of research. BC survivors differ widely in the burden of symptoms they experience revealing an unmet need for tailored treatment approaches. Several practice changing trials in BC did not show significant impact in classical primary endpoints outcomes, such as overall-, BC specific- survival, and distant metastases free- survival. Especially in potentially frail populations, such as older adults or patients affected by multiple comorbidities, HRQoL might represent a key- point in our treatment decision making process. De-escalation treatments for very-low risk patients after breast-conserving surgery is a matter of debate for some decades now; although radiation therapy was shown to benefit these patients concerning local disease control, the absolute benefit was small and potentially negligible. Frailty represents a risk factor for mortality and the knowledge of pre-existing frailty is a crucial factor in the treatment decision of patients. Moreover, it is marked in patients with multiple comorbidities or at least one geriatric syndrome. Frail patients constitute a unique population with regards to prognosis and potential comorbidities, thus minimizing treatment to maintain HRQoL without compromising survival is extremely important. In the decision-making process for all available adjuvant therapies, estimates of the patient's risk of benefit and/or harm with treatment should be performed together with an assessment of baseline comorbidities, life expectancy, and care preferences. Unfortunately, for decades both frail patient populations and patient reported outcome measures (PROMs) were not adequately integrated in main trials. HRQoL is not included among endpoints in a relevant proportion of recently published studies in solid tumors; moreover, PROMs protocol content is frequently inadequate, and nonreporting of PROMs findings is widespread, meaning patient important information may not be available to benefit patients, clinicians, and regulators. Thanks to the efforts of international multidisciplinary-based initiatives, nowadays several tools are structured and well-validated and should be used as reliable endpoints in large series. Robust data will probably improve precision medicine aimed to identify an optimized and cost-effective treatment approach focused on the patient. Therefore, time has probably come for future research attempting to measure patients’ HRQoL