Franzese Milano 2024 AIRO.pptx

Ciro Franzese, Associate Professor Humanitas University Humanitas Research Hospital IRCCS & San Pio X Mlano, Italy  RT in evolution RT fractionation new RT indication treatments integration  Hypofractionation in PC RT Multicenter, non-inferiority, rand...

Ciro Franzese, Associate Professor Humanitas University Humanitas Research Hospital IRCCS & San Pio X Mlano, Italy  RT in evolution RT fractionation new RT indication treatments integration  Hypofractionation in PC RT Multicenter, non-inferiority, randomized phase 3 trial with acute toxicity as the primary endpoint, comparing: 56 Gy in 4 weeks (16x3.5 Gy, 4 days/week, Arm A) 67 Gy in 5 weeks (25x2.68 Gy, 5 days/week, Arm B) 170 patients in Arm A and 172 patients in Arm B Median follow-up time for all patients was 42 months Fonteyne et al., Rad Oncol 2024  Hypofractionation in PC RT Acute grade ≥ 2 gastrointestinal toxicity was reported by 24 % of patients in both groups Acute grade 2 and 3 urinary toxicity was observed in 52 % and 9 % of patients in Arm A and 53 % and 7 % in Arm B Fonteyne et al., Rad Oncol 2024  Hypofractionation in PC RT Late grade 2 and grade ≥ 3 gastrointestinal toxicity occurred in 19 % and 4 % of patients in Arm A compared with 15 % and 4 % in Arm B Late grade 2 and grade ≥ 3 urinary toxicity was observed in 37 % and 10 % of patients in Arm A and 36 % and 6 % in Arm B Fonteyne et al., Rad Oncol 2024  Hypofractionation in High Risk PC 329 high-risk PCa patients were randomized to receive either SF or HF RT Standard fractionation RT consisted of 76 Gy in 2 Gy per fraction to the prostate, where 46 Gy was delivered to the pelvic lymph nodes Hypofractionated RT included concomitant dose escalation of 68 Gy in 2.72 Gy per fraction to the prostate and 45 Gy in 1.8 Gy per fraction to the pelvic lymph nodes. All patients received neoadjuvant, concurrent, and long-term adjuvant androgen deprivation therapy Niazi et al., IJROBP 2024  Hypofractionation in High Risk PC First study of moderate HF dose-escalated RT in exclusively high-risk patients with prostate cancer treated with long-term androgen deprivation therapy and pelvic RT. Results demonstrate that moderately HF RT is well-tolerated, similar to SF RT at 2 years Niazi et al., IJROBP 2024  Treatment personalization in High Risk PC 3604 patients from 10 trials treated with RT and lt-ADT for HRPC defined by any of the following three risk factors: Gleason score >=8 cT3–4 PSA >20 ng/ml cN1 disease Ravi et al., Eur Urol 2024  Treatment personalization in High Risk PC HR-PC patients with 2 to 3 RFs or cN1 disease had the poorest outcomes on RT and lt-ADT. This will help in counseling patients treated in routine practice and in guiding adjuvant trials in HRLPC Ravi et al., Eur Urol 2024  Extreme hypofractionation in PC 45 patients recruited in 5 centers between 2017 and 2022, 43 received the single fraction of 19 Gy was delivered to the prostate, with 17 Gy dose-reduction to the urethra The worst GU toxicity was observed at day-5 after SBRT (42.5 % and 20 % with grade 1 and 2, respectively), returning to baseline at week-12 and month-6 Zilli et al., Rad Oncol 2024  Extreme hypofractionation in PC Grade-3 proctitis was observed in one patient at month 12, with < 3 % grade 2 toxicity at month 18 Mean GU and GI bother scores showed a decline at day 5, a complete recovery at month 6, and a flare between month 12 and 18 Mean PSA dropped from 6.2 ng/ml to 1.2 ng/ml at month 18 and 0.7 ng/ml at month 24 Zilli et al., Rad Oncol 2024  SBRT for re-irradiation 38 patients with biopsy-proven locally recurrent PCa >2 - years after previous treatment and absence of grade 2-3 toxicity from the first course of radiation were included The treatment was 35 Gy in five fractions to the MRI-based target volume and 6 months of androgen-deprivation therapy starting 3 months before radiation Ekanger et al., J Clin Oncol 2024 SBRT for re-irradiation Ekanger et al., J Clin Oncol 2024 SBRT for re-irradiation Ekanger et al., J Clin Oncol 2024  Salvage Radiotherapy 5-yr outcomes from OLIGOPELVIS (GETUG-P07), an open-label phase 2 trial assessing long- term outcomes and patterns of relapse after 67 enrolled patients treated with 6-mo ADT and ENRT in men with pelvic nodal oligorecurrence Grade 2+ toxicities at 3, 4, and 5 yr were 15%, 9%, and 4% for GU, and 2%, 3%, and 4% for GI 5-yr progression-free, biochemical relapse–free, and ADT-free survival rates were 39%, 31%, and 64%, respectively. The major site of relapse was the para-aortic lymph nodes Vaugier et al., Eur Urol 2024  Post-operative SBRT Post-Prostatectomy Ablative Radiation Therapy trial, investigating possible predictors of toxicities and patient-reported outcomes Patients with PSA levels between 0.1–2.0 ng/mL after radical prostatectomy received Linac-based SBRT to the prostate bed in five fractions every other day for a total dose of 32.5 Gy (EQD21.5 = 74.3 Gy) 50 pts were enrolled and treated with a median follow-up was 12.2 months Ferrario et al., CTRO 2024  Post-operative SBRT No late ≥ G2 GI or GU toxicity was registered Late G1 urinary and rectal toxicities occurred in 46% and 4% of patients, respectively. Among 47 patients completing all EPIC-CP domains, 4 (9%) showed worsened QoL, and 11 (26 %) developed erectile dysfunction correlating with PTV D2% (P = 0.032) Ferrario et al., CTRO 2024  Salvage Radiotherapy: 6mo vs no-ADT 1480 patients were randomly assigned to receive short-course ADT (737) or no ADT (743) in addition to postoperative radiotherapy With a median follow-up of 9 years, 268 metastasis-free survival events were reported overall (126 in the short-course ADT group and 142 in the no-ADT group; HR 0.886; p=0.35) 10-year MFS was 80.4% in the short-course and 79.2% in the no- ADT group Parker et al., Lancet 2024  Salvage Radiotherapy: 6 vs 24mo 1523 patients were randomly assigned to receive short-course ADT (761) or long-course ADT (762) in addition to postoperative radiotherapy With a median follow-up of 8.9 years, 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0.773; p=0·029) 10-year MFS was 71.9% in the short-course and 78.1% in the long-course ADT group. Parker et al., Lancet 2024 New hormonal agents  Relugolix: mechanism of action A non-peptide antagonist of the GnRH receptor that competitively binds to GnRH receptors in the anterior pituitary gland. GnRH blockade prevents native GnRH from binding and signaling the secretion of LH and FSH, leading to reduced testosterone production from the testes. The HERO trial  The HERO trial: study design A randomized, phase III, open-label, two-arm clinical trial, conducted in 155 countries across North and South America, Europe, and Asia-Pacific Objectives To evaluate the efficacy and safety of relugolix vs. leuprolide in men with advanced prostate cancer Treatment Relugolix 120 mg PO OD vs. leuprolide 22.5 mg every 3 months Primary Endpoint Sustained castration rate, defined as the cumulative probability of testosterone suppression to less than 50 ng per deciliter during the experimental treatment from day 29 to 48 weeks Shore ND et al., N Engl J Med 2020 The HERO trial population Shore ND et al., N Engl J Med 2020  Primary end-point: efficacy Sustained suppression of testosterone below castration levels (