ESTRO 2023 - Abstract Book

S719

Monday 15 May 2023

ESTRO 2023

S. Supiot 1 , L. Ah-Thiane 2 , L. Campion 3 , N. Allouache 4 , E. Meyer 4 , P. Pommier 5 , C. Carrie 5 , N. Mesgouez-Nebout 6 , G. Créhange 7 , V. Guimas 2 , E. Rio 2 , P. Sargos 8 , C. MAHIER AIT OUKHATAR 9 1 Nantes Université, Radiation Oncology, NANTES, France; 2 Institut de Cancérologie de l'Ouest, Radiation Oncology, NANTES, France; 3 Institut de Cancérologie de l'Ouest, Biostatistics, NANTES, France; 4 Centre François Baclesse, Radiation Oncology, Caen, France; 5 Centre Léon Bérard, Radiation Oncology, Lyon, France; 6 Institut de Cancérologie de l'Ouest, Radiation Oncology, Angers, France; 7 Centre GF Leclerc, Radiation Oncology, Dijon, France; 8 Institut Bergonié, Radiation Oncology, Bordeaux, France; 9 Unicancer, Research, Paris, France Purpose or Objective Following prostatectomy the treatment of biochemically-relapsing prostate cancer patients consists in salvage prostate bed radiotherapy combined with hormone therapy. Following local salvage treatment, most relapses are metastatic. At the metastatic stage novel androgen-receptor targeting agents such as abiraterone acetate are now routinely used. To further reduce the metastatic risk, we conducted an open-label, multicenter, single-arm, phase II trial (NCT01780220) to evaluate the efficacy and safety of the addition of abiraterone acetate to salvage prostate bed radiotherapy combined with goserelin in biochemically-relapsing prostate cancer patients and determined if the presence of circulating tumor cells could predict for the risk of relapse following treatment. Materials and Methods We hypothesized that combined abiraterone, goserelin and prostate bed radiotherapy would increase biochemical-relapse free survival above 70% at 3 years. We recruited men who had an history of adenocarcinoma of the prostate treated by surgery, and who had a rising of their serum PSA above or equal to 0.2 ng/mL, at least 6 months after radical prostatectomy. All patients were treated by prostate bed salvage radiotherapy (66 Gy in 33 f) and by abiraterone acetate plus prednisone plus LH-RH agonist for 6 months in total. Primary outcome consisted in biochemical recurrence-free survival (bRFS), in which recurrence was defined by a re-elevation of serum PSA ≥ 0.5 ng/ml. Secondary outcomes consisted in alternative biochemical recurrence-free survival (alt-bRFS) using an alternative PSA cut-off defined as ≥ 0.2 ng/ml, metastasis-free survival and overall survival. Circulating tumor cells (CTC) were detected using the CellsearchTM system (cut-off for positivity ≥ 5 CTC) prior to treatment. Results We enrolled 46 patients, of which 78% were considered at high-risk according to EAU guidelines for stratification. The median follow-up was 47 months. The experimental regimen showed good outcomes with 3-year rates of bRFS and alt-bRFS rate at 97.8% and 84.8%, respectively. Severe acute or late toxicities related to radiotherapy were scarce as expected. Rate of hepatic cytolysis of all grades, was surprisingly high with abiraterone acetate treatment (50% of patients), including cases of grades 3-4 (18% of patients). CTC were detected in 5 (11%) patients, which was not associated to baseline characteristics, such as PSA doubling time (p =0.892), PSA level (p =0.975), or ISUP group (p =0.991). Detecting circulating tumor cells at baseline was significantly associated to poorer bRFS (p =0.008) and alt-bRFS (p =0.04). Conclusion The addition of abiraterone acetate to salvage radiotherapy and LHRH agonist resulted in high rates of biochemical relapse free survival. Adverse effects were manageable, but a close surveillance of liver toxicity is advised. CTC detection at baseline could represent a promising prognostic factor of oncological outcomes following salvage treatment. MO-0873 Rapid increase in ctDNA at commencement of curative-intent radiotherapy for NSCLC M. MacManus 1 , B. Blyth 1 , O. Martin 2 , N. Plumridge 1 , M. Shaw 1 , F. Hegi-Johnson 1 , S. Siva 1 , O. Banks 3 , L. Kirby 3 , D. Ball 1 , S. Wong 4 1 Peter MacCallum Cancer Centre, Radiation Oncology, Melbourne, Australia; 2 University of Bern, Topographic and clinical Anatomy, Bern, Switzerland; 3 Peter MacCallum Cancer Centre, Translational Research, Melbourne, Australia; 4 Peter MacCallum Cancer Centre, Cancer Genomics Translational Research Centre, Melbourne, Australia Purpose or Objective A prospective, observational clinical trial was initiated to sequentially monitor a range of circulating biomarkers, including circulating tumour DNA (ctDNA) in patients with non-small cell lung cancer (NSCLC), treated with curative intent radiotherapy or chemoradiotherapy. It was hypothesised that a rapid increase in ctDNA may be observed after the first fraction of radiotherapy as a result of radiotherapy-induced tumour destruction. Preliminary ctDNA results are presented here. Materials and Methods Patients receiving curative intent for radiotherapy, with or without concurrent chemotherapy, for any stage of lung cancer were recruited. Blood was collected at predefined intervals before, during (including 24 hours after the first fraction of radiotherapy or chemoradiation) and after radiotherapy/chemoradiotherapy. Patients had baseline and post treatment FDG-PET scans and were followed up for clinical outcomes, including progression-free survival. Tumour specific mutations were identified through routine molecular diagnostic testing, with mutation specific droplet digital PCR assays used to track ctDNA levels throughout treatment. Results Seventy four of a planned 100 patients have so far been recruited to this ongoing study. Sequential ctDNA results are currently available for 7 patients, with follow-up of 81 to 552 days (median 266 days). Known tumour-based mutations including in EGFR, KRAS and TP53 that were assayed. Treatments delivered were fractionated radiotherapy (n=6) or SABR (n=1). An increase in ctDNA was observed after the first fraction of radiotherapy in 4 of 5 patients treated with fractionated radiotherapy with a complete set of results, including in 2 cases where ctDNA was initially undetectable prior to treatment (representative case of ctDNA “spike” shown in upper figure). The patient treated with SABR had small volume stage I disease and ctDNA was undetectable before or soon after radiotherapy but became detectable at the time of distant metastasis 552 days post treatment. In other cases, the ctDNA levels mirrored the clinical course. One patient who had a