Abstract

PAOLO BONOME¹, GABRIELLA MACCHIA², MILENA FERRO¹, SAVINO CILLA³, CARMELA ROMANO⁴, ALESSIA RE¹, VINCENZO PICARDI¹, MARICA FERRO¹, MARIANGELA BOCCARDI¹, DONATO PEZZULLA¹, SILVIA CAMMELLI^5,6, MILLY BUWENGE^5,6, LUCA TAGLIAFERRI^7,8, ALESSIO G. MORGANTI⁵, ALESSIO MORGANTI⁶, VINCENZO VALENTINI^7,9, FRANCESCO DEODATO^7,1

¹Università Cattolica del Sacro Cuore, Gemelli Molise Hospital, Radiation Oncology Unit, Campobasso, Italy; ²Università Cattolica del Sacro Cuore, Gemelli Molise Hospital, Radiation Oncology Unit, Campobasso , Italy; ³Università Cattolica del Sacro Cuore, Gemelli Molise Hospital, Medical Physics Unit, Campobasso, Italy; ⁴Università Cattolica del Sacro Cuore, Gemelli Molise Hospital, Medical Physics Unit, Campobasso, Italy; ⁵Alma Mater Studiorum Bologna University, Department of Experimental, Diagnostic and Speciality Medicine - DIMES, Bologna, Italy; ⁶IRCCS Azienda Ospedaliera - Università di Bologna, Radiation Oncology, Bologna, Italy; ⁷Università Cattolica del Sacro Cuore, Istituto di Radiologia, Roma, Italy; ⁸Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC di Radioterapia, Dipartimento di Scienze Radiologiche, Radioterapiche ed Ematologiche Roma, Italy, Roma, Italy; ⁹Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC di Radioterapia, Dipartimento di Scienze Radiologiche, Radioterapiche ed Ematologiche Roma, Italy Roma, Italy, Roma, Italy

To evaluate the safety and feasibility of stereotactic ablative radiotherapy  (SABR) on prostate cancer patients treated with escalating doses to the dominant intraprostatic lesion (DIL).

A Phase I clinical trial was performed in patients with low and intermediate – risk prostate carcinoma (NCCN risk classes), and American Urological Association (AUA) score ≤ 15. Rectal voiding, bladder filling and gold fiducials were mandatory for patients’ set-up. A Volumetric Modulated Arc with simultaneous integrated boost (VMAT-SIB) technique was used with progressively increased total dose to the DIL defined by magnetic resonance imaging (MRI). The prescribed dose to the prostate plus 3-mm margin (PTV2) was 35 Gy (7 Gy per fraction) and remained unchanged. The MRI enhancing lesion with 3-mm margin (PTV1) received the dose escalation in five fractions (planned dose levels: 40, 42.5, 45, 47.5, 50 Gy) (Figure 1). Dose-limiting toxicity (DLT) was defined as any grade ≥ 3 gastrointestinal (GI) or genitourinary (GU) toxicity by Common Terminology Criteria of Adverse Events. Rectal sigmoidoscopy was performed in all patients 12 months after SABR. The Vienna Rectoscopy Score (VRS) was used to grade the 1 year-late rectal toxicity outcome, such as telangiectasia, congested mucosa and ulcers.

Thirteen patients (median age: 73 years, range: 58-78) were enrolled between May 2014 and December 2020. All patients had T2a-c N0 M0 clinical stage and/or a Gleason score of ≤ 7; patients were treated as follows: 8 patients (40 Gy), 5 patients (42.5 Gy). Prostate volumes ranged from 28.9 to 97.7 cc, with a median DIL volumes of 4.6 cc (range 1.4-14.3). With a median follow-up of 28 months (range 2-72), no patients experienced dose-limiting toxicity (Table 1). Rectal bleeding (2 patients) and pollachiuria (4 patients) were mainly reported as late toxicity, none higher than grade 2. One-year VRS score was available in 12 of 13 patients and grade 0, 1, 2, 3 were recorded in 3 (25%), 4 (33.3%), 3 (25%) and 2 (16.7%) patients, respectively. Ten of 13 patients (76.9%) underwent short course androgen deprivation therapy (from 3 months before to 3 months after SABR). The median PSA value decreased from 5.4 ng/ml (range 4.2–9.6 ng/ml) (values at diagnosis) to 0.21 ng/ml (range 0.05–2.28 ng/ml) (values at the last follow-up). According to Phoenix definition, one biochemical failure was registered at the first dose level. One year-actuarial local control (defined as irradiated site progression-free) was 100%.

A SABR schedule of 35 Gy with a boost dose to the DIL up to 42.5 Gy in 5 fractions resulted to be safe and feasible in low and intermediate-risk prostate cancer. The maximum tolerable dose has not yet been reached and the study is actually ongoing.