Interim Results of a Prospective Prostate-Specific Membrane Antigen-Directed Focal Stereotactic Reirradiation Trial for Locally Recurrent Prostate Cancer.

To report the feasibility, toxicity, and preliminary outcomes (metabolic and biochemical) of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-directed focal prostate reirradiation using linear accelerator (LINAC)-based stereotactic body radiation treatment (SBRT). From March 2016 to March 2019, 25 patients were enrolled in a prospective single institution trial (ACTRN12617000035325). Eligibility criteria included patients with biopsy proven isolated prostate recurrence after definitive irradiation, with concordant multiparametric MRI and 68Ga-PSMA PET/CT findings, and a prostate-specific antigen of less than 15 ng/mL at the time of recurrence. The study included a sequential dose escalation component with the first 18 patients receiving 36 Gy in 6 fractions on alternate days with subsequent patients receiving 38 Gy in 6 fractions assuming acceptable toxicity. Median age was 72 years (range, 62-83) with a median time between first radiation treatment and salvage SBRT of 8.3 years (range, 4.5- 13.6). Median prostate-specific antigen at reirradiation was 4.1 (range, 1.1-16.6). The median follow-up was 25 months (range, 13-46). Acute grade 1 and 2 genitourinary (GU) toxicity occurred in 6 (24%) and 1 (4%) men, respectively. Acute grade 1 gastrointestinal (GI) toxicity occurred in 8% with one acute grade 3 GI toxicity (4%) due to a rectal ulcer overlying the hydrogel. Late grade 1 and 2 GU toxicity occurred in 28% and 4%. Late grade 1 GI toxicity occurred in 8% with no grade 2 or greater toxicity. Twenty-four patients have undergone per-protocol 12-month 68Ga-PSMA PET/CT, of which 23 (92%) demonstrated a complete metabolic response. Biochemical freedom from failure was 80% at 2 years with 3 out of 4 of the biochemical failures exhibiting recurrent local disease. PSMA-directed salvage focal reirradiation to the prostate using linear accelerator-based SBRT is feasible and safe. Toxicity was low, with very favorable short term local and biochemical control in a carefully selected cohort of patients.

Bergamin S ，Eade T ，Kneebone A ，Booth J ，Hsiao E ，Schembri GP ，Szymura K ，Le A ，Kwong C ，Brown C ，Hunter J ，Hruby G ... -  《-》

Hyaluronic acid spacer in focal prostate reirradiation: A single centre experience.

The optimal management of locally recurrent prostate cancer after curative radiotherapy is still unknown. In this study, we evaluated the preliminary results of reirradiation using stereotactic body radiotherapy for locally recurrent prostate cancer after initial definitive local radiotherapy. Between April 2016 and February 2019, 11 patients with recurrent disease at the previously irradiated prostate were treated. Local recurrence was detected by radiological with or without functional imaging modalities including prostate multiparametric/pelvic MRI or positron-emission tomography-computerised tomography with (68Ga)-labelled prostate-specific membrane antigen performed after rising prostate specific antigen serum level during follow-up. All patients received stereotactic body radiotherapy to the recurrent nodule to a total dose of 30Gy in five fractions. Hyaluronic acid spacer was injected between prostate and rectum in seven patients to decrease the rectal dose. Acute toxicity was evaluated by using Common Terminology Criteria for Adverse Events version 4.0, and late toxicity was evaluated by using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring schema. At the diagnosis, the median age was 64 years, and the mean prostate specific antigen serum concentration was 17.7ng/mL. The median interval time between local recurrence and initial definitive radiotherapy was 63 months. Mean prostate specific antigen concentration nadir value during follow-up was 0.43ng/mL. With a median follow up of 19 months, three patients developed either local or distant relapse. One patient had grade 3 acute rectal toxicity, and one patient had grade 2 late urinary toxicity. We did not observe any acute or late toxicity due to hyaluronic acid spacer injection. Reirradiation after local recurrence following initial definitive radiotherapy together with hyaluronic acid spacer use seems to be effective and safe.

Ozyigit G ，Hurmuz P ，Akinci D ，Esen SCB ，Yilmaz MT ，Akdogan B ，Akyol FH ... -  《-》

Salvage re-irradiation using stereotactic body radiation therapy for locally recurrent prostate cancer: the impact of castration sensitivity on treatment outcomes.

Lewin R ，Amit U ，Laufer M ，Berger R ，Dotan Z ，Domachevsky L ，Davidson T ，Portnoy O ，Tsvang L ，Ben-Ayun M ，Weiss I ，Symon Z ... -  《Radiation Oncology》

Retreatment for Local Recurrence of Prostatic Carcinoma After Prior Therapeutic Irradiation: Efficacy and Toxicity of HDR-Like SBRT.

We evaluated the use of high dose-rate-like stereotactic body radiation therapy (SBRT) retreatment for biopsy-proven local persistence in prostate postradiation therapy, evaluating efficacy and toxicity. From 2009 to 2018, 50 patients with biopsy-proven recurrent prostate cancer >2 years after prior treatment were retreated with a high dose-rate-like dose of 3400 cGy over 5 fractions. Previous radiation therapy dose measured 75.6 Gy (64.8-81.0) and median salvage interval was 8.1 years (32-241 mo.). Eighty-three percent of patients had Gleason score 7 or higher disease at retreatment. Those with preexisting toxicity >grade 1 from their prior course were excluded. The planning target volume was comprised of the clinical target volume (prostate + any contiguous extension only) with no additional expansion. Toxicity assessment used CTCAE v.3.0 criteria. Median follow-up was 44 months (3-110). Median pre-SBRT salvage baseline prostate specific antigen (PSA) of 3.97 ng/mL decreased to 0.6 ng/mL and 0.16 ng/mL at 1 and 5 years in nonrelapsed patients, respectively. Actuarial 5-year biochemical disease-free survival (DFS) measured 60%, with corresponding 5-year actuarial local, distant, and salvage androgen deprivation therapy free rates of 94%, 89%, and 69%, respectively. Actuarial 5-year biochemical DFS measured 78% if PSA at salvage was <6.92 ng/mL versus 12% with ≥6.92 ng/mL (P = .0001). Toxicity was primarily in the GU domain, with an 8% 5-year actuarial rate of grade 3+, 3% when limited to salvage of "conventional external beam only" local relapse. No gastrointestinal (GI) toxicity >grade 1 occurred. Of the 30% sexually potent at the time of salvage, 82% subsequently lost potency. SBRT salvage of local prostate recurrence in previously irradiated patients appears clinically feasible in this challenging group. It demonstrates favorable PSA and DFS response, typically deferring the need for salvage androgen deprivation therapy or other treatment by over 5 years, with low GU and GI toxicity.

Fuller D ，Wurzer J ，Shirazi R ，Bridge S ，Law J ，Crabtree T ，Mardirossian G ... -  《-》

Reirradiation of Locally Recurrent Prostate Cancer With Volumetric Modulated Arc Therapy.

This study explores the efficacy and safety of reirradiation with modern radiation therapy techniques in patients previously irradiated for prostate cancer and affected by local relapse of disease. Patients affected by previously irradiated prostate cancer were enrolled in this reirradiation study if they had a biochemical relapse and a 11C-choline positron emission tomography scan revealing the presence of a local recurrence of disease. Reirradiation consisted of a stereotactic treatment delivered by image guided radiation therapy-volumetric modulated arc therapy with flattening filter-free technology in 5 daily fractions. Twenty-three patients underwent reirradiation to the prostate, prostatic bed, or prostate and local recurrence. Re-treatment consisted of a median total dose of 25 Gy in 5 fractions. A biochemical response was observed in all cases. Acute toxicity was mainly genitourinary (GU) grade 1 to 2 (n = 13; 56.5%). One patient (4.3%) had grade 3 hematuria. A grade 1 GU late toxicity was registered in 4 patients (17.4%) and grade 3 in 1 patient (4.3%, urethral obstruction). Gastrointestinal toxicity was negligible. Regression analysis showed that only a short elapsed time in months from primary radiation therapy was significantly correlated with acute GU toxicity. After a median follow-up of 33 months (range, 5-58 months), the median biochemical recurrence-free survival was 19 months, and the 2-year biochemical recurrence-free survival (BRFS) was 41.7%. Median local control was 30 months; the 2-year local control rate was 58.1%. Reirradiation of patients with prostate cancer who underwent previous radiation therapy is a valuable option that can be safely considered to delay the beginning of hormonal treatment.

D'Agostino GR ，Di Brina L ，Mancosu P ，Franzese C ，Iftode C ，Franceschini D ，Clerici E ，Tozzi A ，Navarria P ，Scorsetti M ... -  《-》