ESTRO 2021 Abstract Book

S252

ESTRO 2021

Spain; 8 Hospital Plató, Radiation Oncology, Barcelona, Spain; 9 8Hospital Clinic, Radiation Oncology, Barcelona, Spain; 10 Institut Català d’Oncologia, Radiation Oncology, Barcelona, Spain; 11 Hospital Do Meixoeiro, Radiation Oncology, Vigo, Spain Purpose or Objective Recent data suggest that additional suppression of serum testosterone to <20 ng/dL could be a better target than <50 ng/dL in prostate cancer (PCa) treated with androgen deprivation therapy (ADT). We studied the effect of serum testosterone levels on clinical outcome in localized PCa treated with ADT and high-dose radiotherapy (HRT). Materials and Methods This phase III trial randomized 355 men with intermediate and high-risk PCa to 4 months of ADT plus HRT (STADT, N=178) or the same treatment followed by 24 months of ADT (LTADT, N=177). This study only included patients treated with LTADT who had at least 3 determinations of serum testosterone during ADT (N=154). Patients were stratified into 3 subgroups by serum testosterone level as follows: minimum, <20 ng/dL; median, 20-49 ng/dL; and maximum, ≥50 ng/dL. Biochemical disease-free survival (bDFS), metastasis free survival (MFS), overall survival (OS), and testosterone recovery were compared between the groups using Gray’s test in the unadjusted analyses and multivariable Fine & Gray regression in the adjusted analyses. Results The median testosterone nadir was 19 ng/dL (IQR: 10 - 27 ng/dL), with a median time to nadir of 10.2 months (IQR: 7.3 - 15.9 months). There were no statistically significant differences in 10-year bDFS, MFS, or OS between <20 ng/mL and 20-49 ng/dL subgroups. Multivariable Fine & Gray analysis showed that median testosterone ≥50 ng/dL was significantly associated with a decrease in bDFS (HR: 6.58, 95%CI 1.28- 33.76, p=0.03). Time to testosterone recovery after ADT did not correlate with bDFS, MFS, or OS and was not significantly associated with any of the testosterone subgroups. Conclusion Our results do not support the concept that additional serum testosterone suppression below 20 ng/dL is associated with better outcomes than 20-49 ng/dL. Time to testosterone recovery after ADT and HRT did not impact clinical failure.

Joint symposium: ESTRO-JASTRO - Current status of hyperthermia in radiation oncology

SP-0339 Introduction to hyperthermic radiation oncology J. Overgaard Denmark

Abstract not available

SP-0340 Biological rationale for combining heat and radiation J. Crezee 1 1 Amsterdam University Medical Centers, Radiation Oncology, Amsterdam, The Netherlands

Abstract Text Radiosensitivity varies for different tumors, and factors like tumor hypoxia are known to be associated with resistance to radiotherapy treatment. Moderate Hyperthermia (39-43°C) is a logical option for overcoming radiation resistance as it is a powerful, clinically proven radiosensitizer. The biological rationale for combining heat and radiation is that hyperthermia has pleiotropic effects which complement and synergize with the effect of radiotherapy on tumor tissue, also in radiotherapy-resistant tumors. Hyperthermia selectively eliminates radioresistant hypoxic tumor cells, thus complementing the effect of radiotherapy. This elimination of hypoxic cells is the result of both direct cell kill and by reoxygenation, rendering tumor cells more sensitive to radiotherapy. Hyperthermia causes tumor reperfusion and reoxygenation as blood vessels open up at 39-40°C and shut down for temperatures >44°C. The ensuing reoxygenation effect is reported to last for 24-48 hours, lasting long after perfusion levels have returned to normal after the end of hyperthermia. Radiotherapy relies on inducing lethal DNA damage in tumor cells. Hyperthermia enhances the effect of radiotherapy by inhibiting repair of sublethal DNA damage after radiotherapy by temporarily inactivating or degrading crucial proteins for DNA repair pathways. For DNA double strand break repair this includes BRCA1 and BRCA2 for the homologous recombination (HR) repair pathway and Ku, DNA-PK, KU70, KU80 and Ligase IV for non-homologous end joining (NHEJ). Inhibition of DNA repair requires temperatures >41°C and strongly depends on the temperature level, heat duration and time interval between hyperthermia and radiotherapy, with nearly simultaneous application of heat and radiation yielding the highest radiosensitization. Hyperthermia can also activate a tumor-specific immune response. Different immunogenic effects have been identified, including induction of specific heat shock proteins like HSP70, which leads to stimulation and proliferation of natural killers cells. Effective clinical exploitation of these immunogenic effects is subject of ongoing research. Thermotolerance is an effect relevant for the optimal frequency of hyperthermia treatment delivery. Hyperthermia can induce thermotolerance, a temporary resistance to subsequent HT treatments lasting 2-3 days after a hyperthermia treatment. Onset, duration and degree of thermotolerance depend on temperature and heating time. To prevent thermotolerance hyperthermia is not given daily, but less frequently, once or twice a week. Hyperthermia thus induces different relevant effects, partly directed against the hypoxic tumor fraction and thus intrinsically tumor selective. Identification of the clinical contribution and relevance of each of these hyperthermia effects will help to further optimize the effectiveness of combined radiotherapy- hyperthermia treatment delivery. Based on current knowledge efficacy of combined radiotherapy-