1.5 T MR-guided and daily adapted SBRT for prostate cancer: feasibility, preliminary clinical tolerability, quality of life and patient-reported outcomes during treatment

In the case of localized prostate cancer (PC), active surveillance, surgery and radiotherapy represent viable therapeutic options due to similar long-term oncologic outcomes [1]. According to the treatment received, genitourinary side effects are more pronounced after surgery, whereas rectal toxicity represents the most common adverse event after radical radiotherapy (RT). Finally, the active monitoring can be affected by a higher incidence of distant metastases compared to active therapies, although lower rates of patient-reported harms are described [2]. Furthermore, the effects on quality of life among prostatectomy, 3-dimensional conformal RT and active monitoring were reported by the Protect Trial [1]. 3-dimensional conformal RT has resulted in a limited negative impact on patient reported outcomes (PROMs) of urinary continence, whereas late bowel function has been worse compared to the other Protect Trial arms [3].

Clinical experiences in PC RT by means of intensity-modulated and image-guided techniques (IMRT-IGRT) have demonstrated a lower probability of RT-related adverse events [4‐6]. These RT-technological and technical advances have allowed clinicians to deliver higher radiation doses to the target with similarly limited toxicities. To date, moderate PC hypofractionation represents the standard of care [7, 8]. Moreover, since 2014, the National Comprehensive Cancer Network (NCCN) Guidelines [9] have stated that, in centers with appropriate technology and expertise, extreme hypofractionated treatment could be considered as a potential option to offer for selected localized PC. Since then, more robust evidence and new technological platforms are consolidating the role of extreme hypofractionation (also known as stereotactic body radiotherapy - SBRT) for localized PC [10‐12].

Elekta (Stockolm, Sweden) Unity is a unique magnetic resonance (MR)-linac that conjugates a 1.5 Tesla MR unit with a 7 MV flattening filter free accelerator mounted on a rotating gantry system, enabling the daily verification of real-time patient anatomy, and allowing daily treatment planning.

A prospective observational study for the clinical use of Elekta Unity is currently ongoing in our department. Herein, we present our preliminary report on the feasibility, quality of life and patient-reported outcomes measures (PROMs) for localized PC treated with stereotactic body radiotherapy (SBRT).

The present study depicts the PC subgroup of the ongoing prospective observational study, which had received approval from the local Ethical Committee on April 2019 (MRI/LINAC n°23,748).

The inclusion criteria of the present study were: age > 18 years, Karnofsky index > 70% (Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2), PSA < 20 ng/ml, histologically proven prostate adenocarcinoma, cT1-T2 stage, no pathological lymph nodes on computed tomography (CT) and magnetic resonance imaging (MRI), no distant metastases, no previous prostate surgery other than transurethral resection of the prostate (at least a 6-week interval before the initiation of RT), no malignant tumors in the last 5 years, International Prostate Symptom Score (IPSS) 0–15, combined androgen deprivation therapy (ADT) according to risk category.

The exclusion criteria were: prostate size greater than 80 cc, clinically positive nodes or a lymph node involvement risk > 15%, previous transurethral resection of the prostate (TURP) less than 6 months before RT, previous prostate surgery other than TURP, previous pelvic irradiation, MRI contraindications (electronic devices such as pacemakers, defibrillators, deep brain stimulators, cochlear implants or foreign metal bodies or aneurysm clips or severe claustrophobia), the inability to obtain written informed consent. For each patient, specific informed consent was collected.

Between October 2019 and January 2020, 25 consecutive patients affected by low or intermediate-risk PC were treated at the Advanced Radiation Oncology Department of the IRCCS Sacro Cuore Don Calabria Hospital in Negrar, Verona, by means of 1.5 T MR-guided adaptive SBRT.

Four patients (16%) were affected by low risk PC, with the remaining 21 (84%) by favourable intermediate (11) and unfavourable intermediate (10) risk PC.

Six-months of androgen deprivation therapy was concomitantly administered in 9 (36%) unfavourable intermediate risk PC cases. One patient affected by unfavourable intermediate risk refused androgen deprivation therapy. No treatment interruption occurred.

In Table 1, the baseline patients and treatment characteristics are reported.

For all patients analyzed herein, clinician-reported outcome measurements and PROMs were collected at the end of treatment.

In the management of localized PC, the use of SBRT as primary treatment is steadily increasing. Crucial components to improve this therapeutic approach in daily clinical practice are the proper selection of patients in terms of pre-RT genitourinary functioning, adequate technological equipment, and dedicated radiation oncologists [17].

In the context of SBRT for PC, a five session schedule has been extensively investigated by several authors [17]. Few differences exist in QoL among the RT modalities, with SBRT using 35–40 Gy/5 fractions and resulting in lesser bowel QoL impact, whereas brachytherapy has a greater impact on urinary obstruction [17].

Elekta Unity is an innovative system for RT that conjugates 1.5 Tesla MRI with 7 MV FFF linac. After the installation phase in our Advanced Radiation Oncology Department, the first patient affected by localized PC was treated in October 2019. Herein, we report preliminary data in terms of clinician-reported outcome measurements and PROMs in a series of 25 localized PC patients treated by means of 1.5 T MRI-Guided adaptive SBRT using ATS workflow. Briefly, ATS (daily recontouring of structures of interest and daily adapted replanning) allows clinicians to reshape the dose based on daily changes in the shape, size and position of target volume and OARs, enabling daily accurate dose delivery with real-time visualization of the patient’s anatomy [13, 18]. Early assessment of clinician-reported outcome measurements and PROMs does not permit drawing definitive conclusions. Despite being preliminary, these data may be of great interest to the scientific community. First of all, Elekta Unity represents a new system for the oncologic community with limited worldwide diffusion, and implies new challenges for both users and patients. It is known that MRI-scanning could increase claustrophobia and anxiety in oncologic patients, affecting their quality of life [19]. Furthermore, treatment compliance and acceptance among patients could be negatively influenced by the overall fraction time. In fact, the session time is longer using adaptive MRI-guided RT compared to other devices adopted in PC RT. In our experience, the median fraction time was 56 min (range, 34–86 min). As previously reported, the ATS workflow is longer than the ATP strategy, resulting in more advanced plan adaptations that meet the clinical dose criteria [13].

To the best of our knowledge, this is the first report evaluating QoL and PROMs during 1.5 T MR-guided SBRT for prostate cancer. Similarly, Bruynzeel et al. [20] recently published an early toxicity report using a different MRI-guided SBRT (0.35 T MR, MRIdian system - ViewRay Inc.) in a large prostate cancer sample size. Regarding the PROMs, Bruynzeel et al. [20] recorded a significant worsening of the role-functioning domain.

Concerning the preliminary findings reported here, the EORTC QLQ-C30 questionnaire showed no difference from baseline to the end of treatment. More specifically, the functional scales, including emotional and role-functioning domains, were not affected by the patient’s anxiety potentially related to such complex radiation treatment procedures. Conversely, a slight impairment of the physical functioning item was noted. This domain decreased by approximately 3.1% from baseline to the end of treatment. This functional decline for prostate cancer patients is not new in active therapy. In fact, a prospective longitudinal cohort study [21] documented that, for men with newly diagnosed localised PC, physical distress was significantly more common following surgery and radiotherapy than active surveillance.

Bruynzeel et al. [20] observed low incidence of early GI and GU toxicities using 0.35 T MRI-guided SBRT for prostate cancer, both in clinician- and patient-reported outcome measurements. Specifically, the maximum cumulative grade ≥ 2 early GU and GI toxicity was 23.8 and 5.0%, respectively. In our study population, the grade ≤ 2 GU and GI toxicities were 12 and 4%, respectively. No grade 3 or higher acute toxicity was observed.

Moreover, IIEF-5 and ICIQ-SF questionnaires showed no statistically significant worsening of erectile function and urinary incontinence at the end of radiation treatment. In regard to prostate SBRT, a previous study showed promising results about erectile function without significant difference from other radiotherapy techniques, evaluated by the sexual items of the EPIC-26 instrument [22].

To the best of our knowledge, this is the first investigation reporting clinician-reported outcome measurements and PROMs for 1.5 T MR-guided adaptive SBRT for localized PC. The preliminary data collected here report optimal safety and tolerability, as also confirmed by PROMs questionnaires. Long-term data are warranted.