Linac-based versus MR-guided SBRT for localized prostate cancer: a comparative evaluation of acute tolerability.

AIM: This study aims to compare acute toxicity of prostate cancer (PCa) stereotactic body radiotherapy (SBRT) delivered by MR-guided radiotherapy (MRgRT) with 1.5-T MR-linac or by volumetric modulated arc (VMAT) with conventional linac. METHODS: Patients with low-to-favorable intermediate risk class PCa were treated with exclusive SBRT (35 Gy in five fractions). Patients treated with MRgRT were enrolled in an Ethical Committee (EC) approved trial (Prot. n° 23,748), while patients treated with conventional linac were enrolled in an EC approved phase II trial (n° SBRT PROG112CESC). The primary end-point was the acute toxicity. Patients were included in the analysis if they had at least 6 months of follow-up for the primary end-point evaluation. Toxicity assessment was performed according to CTCAE v5.0 scale. International Prostatic Symptoms Score (IPSS) was also performed. RESULTS: A total of 135 patients were included in the analysis. Seventy-two (53.3%) were treated with MR-linac and 63 (46.7%) with conventional linac. The median initial PSA before RT was 6.1 ng/ml (range 0.49-19). Globally, acute G1, G2, and G3 toxicity occurred in 39 (28.8%), 20 (14.5%), and 5 (3.7%) patients. At the univariate analysis, acute G1 toxicity did not differ between MR-linac and conventional linac (26.4% versus 31.8%), as well as G2 toxicity (12.5% versus 17.5%; p = 0.52). Acute G2 gastrointestinal (GI) toxicity occurred in 7% and 12.5% of cases in MR-linac and conventional linac group, respectively (p = 0.06), while acute G2 genitourinary toxicity occurred in 11% and 12.8% in MR-linac and conventional linac, respectively (p = 0.82). The median IPSS before and after SBRT was 3 (1-16) and 5 (1-18). Acute G3 toxicity occurred in two cases in the MR-linac and three cases in the conventional linac group (p = n.s.). CONCLUSION: Prostate SBRT with 1.5-T MR-linac is feasible and safe. Compared to conventional linac, MRgRT might to potentially reduce the overall G1 acute toxicity at 6 months, and seems to show a trend toward a lower incidence of grade 2 GI toxicity. A longer follow-up is necessary to assess the late efficacy and toxicity.

Stereotactic Body Radiotherapy for a Rare Case of Sinonasal Metastasis Arising from Renal Cell Cancer.

BACKGROUND/AIM: Sinonasal metastases arising from renal cell cancer are rare and usually managed with surgery. Few studies describe the use of radiotherapy in this specific setting, while the use of stereotactic body radiotherapy (SBRT) has been rarely reported as well. CASE REPORT: We present the case of a solitary left sinonasal metastasis in a 65-year-old man with clear cell renal cancer who also received bilateral nephrectomy and subsequent kidney transplantation. The patient received subtotal surgery and subsequently he was candidate to SBRT to avoid systemic treatment, due to renal comorbidities. CONCLUSION: The patient was treated with SBRT for a total dose of 35 Gy in 5 fractions and after 24 months of follow-up there is no evidence of local relapse. No major side-effects were reported. Our experience supports SBRT as a safe and feasible treatment option in the case of sinonasal metastases from RCC.

1.5T MR-Guided Daily-Adaptive SBRT for Prostate Cancer: Preliminary Report of Toxicity and Quality of Life of the First 100 Patients.

Purpose: The present study reports the preliminary outcomes in terms of adverse events and quality of life in the first 100 patients treated with 1.5T MR-guided daily-adaptive stereotactic body radiotherapy for prostate cancer. Methods: From October 2019 to December 2020, 100 patients, enrolled in a prospective study, received MR-guided SBRT for prostate cancer. Rectal spacer insertion was optional and administered in 37 patients. In total, 32 patients received androgen deprivation therapy in accordance with international guidelines. A prospective collection of data regarding toxicity and quality of life was performed. Results: The median age was 71 years (range, 52-84). The median total dose delivered was 35 Gy (35-36.25 Gy) in five sessions, either on alternate days (n = 25) or consecutive days (n = 75). For acute toxicity, we recorded: seven cases of acute G2 urinary pain and four cases of G2 gastrointestinal events. The median follow-up was 12 months (3-20), recording three late G2 urinary events and one G3 case, consisting of a patient who required a TURP 8 months after the treatment. For gastrointestinal toxicity, we observed 3 G ≥ 2 GI events, including one patient who received argon laser therapy for radiation-induced proctitis. Up to the last follow-up, all patients are alive and with no evidence of biochemical relapse, except for an M1 low-volume patient in distant progression two months after radiotherapy. QoL evaluation reported a substantial resolution of any discomfort within the second follow-up after radiotherapy, with the only exception being sexual items. Notably, after one year, global health items were improved compared to the baseline assessment. Conclusions: This study reports very promising outcomes in terms of adverse events and QoL, supporting the role of 1.5T MR-guided SBRT for prostate cancer. To date, this series is one of the first and largest available in the literature. Long-term results are warranted.

Hypofractionated Postoperative Radiotherapy in Prostate Cancer with Ialuril Soft Gels®: Toxicity and Efficacy Analysis on a Retrospective Series of 305 Patients.

Aim: To evaluate the impact of Ialuril soft Gels® (HA) in reducing acute genito-urinary (GU) toxicity in patients treated with adjuvant or salvage radiotherapy for a prostate cancer relapse. Material and Methods: The data of 305 patients were retrospectively collected. One hundred and five patients underwent adjuvant radiotherapy (aRT), while 200 a salvage treatment (sRT). GU toxicity was evaluated according to CTCAE v5.0. Every patient received RT combined with HA. Results: Grade 1-2 GU toxicity during RT was represented by: urgency (36%), dysuria (23%), increased urinary frequency (12.1%), and urinary retention (11.8%). Nevertheless, the majority of symptoms were present at the baseline. Grade 3 severe toxicity was represented by 10 (3.2%) cases of incontinence and 3 (1%) cases of urgency. The incidence of any-grade RT-related GU toxicity was significantly higher in the aRT group than the salvage group (esRT + sRT) (83.8% versus 64.5%). When comparing the incidence of any-grade RT-related GU toxicity in the aRT, esRT, and sRT groups we observed a significant correlation favoring sRT, over esRT, and aRT. Conclusion: Postoperative hypofractionated radiotherapy is safe and not correlated with increase of unexpected toxicity when administered with oral hyaluronic acid. A prospective study is necessary to confirm these results.

Stereotactic body radiotherapy for pulmonary oligometastases: a monoinstitutional analysis of clinical outcomes and potential prognostic factors.

PURPOSE: We report the retrospective data of a cohort of patients who received stereotactic body radiotherapy for pulmonary oligometastases, aiming to assess the clinical factors potentially affecting clinical outcomes. METHODS: The present series reports the outcomes of a cohort of 71 patients with pulmonary oligometastases with no extrapulmonary disease. All patients were treated with stereotactic body radiotherapy (SBRT) performed with volumetric modulated arc therapy-image guided radiotherapy (VMAT-IGRT) to up to five secondary lesions. Survival estimates were performed using the Kaplan-Meier method. RESULTS: A total of 98 lesions in 71 patients were treated from February 2014 to August 2020. The most frequent histologies were colorectal in 37.7%, lung cancer in 44.8%, head and neck cancer in 8.1%, and other in 9.4%. Median age was 71 years (range 32-93 years). Concurrent systemic therapy was administered in 32.3%. SBRT was delivered to a median total dose of 60 Gy (range 55-70 Gy) in 3-10 fractions for a median BED10 = 105 Gy (range 96-180 Gy). Median follow-up was 29.5 months (range 6-81), with no acute or late G > 2 adverse event. Our LC rates at 2 and 4 years were 92.4 and 89.8%, respectively. DPFS rates at 2 and 4 years were 45.3 and 27.2%, respectively. A second SBRT course was proposed in 21 patients (29.5%) who developed an oligoprogression, resulting in median time to second progression of 9 months (range 2-44) and 2­year PFS2 rate of 42.4%. At univariate analysis, patients with sequential oligometastases reported better OS rates (p = 0.002), which was also confirmed at multivariate analysis, where distant progression was also related to worse OS (p = 0.022). Higher local control rates relate to better PFS (p = 0.04). The 2­ and 4­year OS rates were 61 and 39.7% CONCLUSION: SBRT is feasible for pulmonary oligometastases with favorable outcomes and toxicity. At multivariate analysis, patients with sequential oligometastatic progression maintain a survival advantage. Also, local control was found to be related to improved PFS rates.

Postoperative moderately hypofractionated radiotherapy in prostate cancer: a mono-institutional propensity-score-matching analysis between adjuvant and early-salvage radiotherapy.

AIM: To evaluate the impact of moderately hypofractionated postoperative radiotherapy (RT) in prostate cancer (PCa). MATERIALS AND METHODS: The data of 304 surgically resected PCa patients were analyzed. One hundred and five patients underwent adjuvant RT (aRT), 77 early-savage RT (esRT), and 123 salvage RT (sRT). Biochemical relapse-free survival (BRFS), progression-free survival (PFS) and toxicity were analyzed. A propensity score matching (PSM) was performed to account for potential confounders between aRT and esRT groups. RESULTS: The median follow-up was 33 months. Three-year BRFS and PFS were 82 and 85.2%, respectively, in the overall population. At the multivariate analysis, Gleason score and hormone therapy were factors independently correlated with BRFS and PFS. After PSM, there was no difference in BRFS and PFS between aRT and esRT patients. Severe toxicity was represented by grade 3 urinary incontinence (3.5%) and urgency (1%), and aRT correlated with increased any-grade acute toxicity. Severe grade 3 gastrointestinal late toxicity occurred in 1.3% of cases. CONCLUSION: Postoperative moderately hypofractionated RT achieved acceptable disease control rate and demonstrated no increased or unexpected toxicity. Future prospective studies should evaluate the role of postoperative RT in patients with unfavorable disease characteristics.

Reduction of inter-observer differences in the delineation of the target in spinal metastases SBRT using an automatic contouring dedicated system.

BACKGROUND: Approximately one third of cancer patients will develop spinal metastases, that can be associated with back pain, neurological symptoms and deterioration in performance status. Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) have been offered in clinical practice mainly for the management of oligometastatic and oligoprogressive patients, allowing the prescription of high total dose delivered in one or few sessions to small target volumes, minimizing the dose exposure of normal tissues. Due to the high delivered doses and the proximity of critical organs at risk (OAR) such as the spinal cord, the correct definition of the treatment volume becomes even more important in SBRT treatment, thus making it necessary to standardize the method of target definition and contouring, through the adoption of specific guidelines and specific automatic contouring tools. An automatic target contouring system for spine SBRT is useful to reduce inter-observer differences in target definition. In this study, an automatic contouring tool was evaluated. METHODS: Simulation CT scans and MRI data of 20 patients with spinal metastases were evaluated. To evaluate the advantage of the automatic target contouring tool (Elements SmartBrush Spine), which uses the identification of different densities within the target vertebra, we evaluated the agreement of the contours of 20 spinal target (2 cervical, 9 dorsal and 9 lumbar column), outlined by three independent observers using the automatic tool compared to the contours obtained manually, and measured by DICE similarity coefficient. RESULTS: The agreement of GTV contours outlined by independent operators was superior with the use of the automatic contour tool compared to manually outlined contours (mean DICE coefficient 0.75 vs 0.57, p = 0.048). CONCLUSIONS: The dedicated contouring tool allows greater precision and reduction of inter-observer differences in the delineation of the target in SBRT spines. Thus, the evaluated system could be useful in the setting of spinal SBRT to reduce uncertainties of contouring increasing the level of precision on target delivered doses.

SBRT for elderly oligometastatic patients as a feasible, safe and effective treatment opportunity.

The constantly increasing life expectancy is raising the issue of treating oncological older patients, who were traditionally candidates to best supportive care or palliative treatments. Several literature data support SBRT in the treatment of the oligometastatic patient as a potentially curable therapeutic option. However, data on older patients are lacking. This study presents the outcomes of a cohort of 61 oligometastatic patients over the age of 80 years who received SBRT, that was proposed to all patients with a minimum Karnofsky Performance Status ≥ 70 and a life expectancy of at least 6 months, with up to five oligometastatic lesions. Radiotherapy was delivered in 3-10 fractions with VMAT-IGRT technique. Toxicity was retrospectively collected according to CTCAE v4.0. Data were retrospectively collected and analyzed. Univariate and multivariate analysis were performed for assessing any potential predictive factor for clinical outcomes. A total of 90 oligometastases were treated in 61 patients with median age 82 years (range, 80-90). The most frequent histology was colorectal cancer (27% of cases). Median follow-up was 20 months (range, 2-63). Local control rates at 1- and 2-years were 98.8% and 88.2%, with colorectal histology being associated with worse LC rates (p = 0.014) at univariate analysis. Progression-free survival rates at 1- and 2-years were 48.6% and 30.5%. Oligorecurrent lesions and single oligometastases were associated with better PFS rates (respectively, p = 0.04 and p = 0.011). Overall survival rates were 75% and 60.5%, polymetastatic spread being predictive of worse survival outcomes at multivariate analysis (p = 0.012). No G2 or higher adverse events were recorded. Our study supports the role of SBRT for the treatment of elderly oligometastatic patients, highlighting the possibility to further explore this therapeutic option in the management of older oncological patients.

The use of SBRT in the management of oligometastatic gynecological cancer: report of promising results in terms of tolerability and clinical outcomes.

BACKGROUND: The use of stereotactic radiotherapy (SBRT) for oligometastases is supported by several literature studies, but in the setting of gynecological malignancies, this scenario remains quite unexplored. This study reports a preliminary assessment of clinical outcomes in a cohort of 40 patients with oligometastatic gynecological neoplasms. METHODS: Radiotherapy was delivered in 3-10 fractions with VMAT-IGRT technique. Toxicity was retrospectively collected according to CTCAE v4.0. Data were retrospectively collected and analyzed. Univariate and multivariate analyses were performed for assessing any potential predictive factor for clinical outcomes. RESULTS: A total of 63 oligometastases were treated from December 2014 to February 2021. Median age was 63 years (range 30-89). Most frequent primary tumors were ovarian cancer in 42.5% and endometrium cancer in 42.5%. With a median follow-up of 27 months (range 6-69), no local failures were observed, our progression-free survival rates were 43.6% and 23% at one and 2 years, respectively, while 1 and 2-year overall survival rates were both 70%. No acute or late G ≥ 2 adverse events were observed. CONCLUSIONS: In our experience, SBRT for oligometastatic gynecological malignancies resulted in promising results in terms of clinical outcomes, with excellent local control and no evidence of severe toxicity, highlighting the effectiveness of this therapeutic option. Prospective studies to further explore this approach in this setting are advocated.

Impact of hydrogel peri-rectal spacer insertion on seminal vesicles intrafraction motion during 1.5 T-MRI-guided adaptive stereotactic body radiotherapy for localized prostate cancer.

OBJECTIVES: MR-guided daily-adaptive radiotherapy is improving the accuracy in the planning and delivery phases of the treatment. Rectal hydrogel-spacer may help in mitigating organ motion, but few data are currently available. METHODS: We aimed to assess any potential impact of the device on seminal vesicles motion by measuring translational and rotational shifts between the pre- and post-treatment MRI scans of a total of 50 fractions in the first 10 patients who underwent MR-guided prostate SBRT (35 Gy/5 fx). Of them, five patients received the hydrogel-spacer. The comparative analysis was performed using the Mann-Whitney U-test. RESULTS: Median rotational shifts were: in anteroposterior 0° (range, 0.097°/0.112°; SD = 0.05°) vs 0° (-0.162/0.04°; SD = 0.07°) in the no-spacer subgroup (p = 0.36); lateral shifts were 0° (-0.1°/0.54°; SD = 0.28°) vs -0.85° in the no-spacer cohort (-1.56°/0.124°; SD = 0.054°; p = 0.22). Cranio-caudal shifts were 0° (-0.121°/0.029°; SD = 0.06°) in the spacer-cohort vs 0° (-0.066°/0.087°; SD = 0.69°; p = 0.53). Median translational shifts were: in anteroposterior 0.9 mm (-0.014 mm/0.031 mm; SD = 0.036 mm) in the spacer-group vs 0.030 mm (-0.14 mm/0.03 mm; SD = 0.032 mm; p = 0.8); latero-lateral shifts were -0.042 mm (-0.047 mm/0.07 mm; SD = 0.054 mm), vs -0.023 mm (-0.027 mm/-0.01 mm; SD = 0.023 mm) in the no-spacer group (p = 0.94). In cranio-caudal, statistically significant shifts were reported: 0.082 mm (0.06 mm/0.15 mm; SD = 0.04 mm) vs 0.06 mm (-0.06/0.08 mm; SD = 0.09 mm) in the no-spacer cohort (p = 0.031). CONCLUSIONS: A favorable impact of the hydrogel-spacer on seminal vesicles motion was observed only in cranio-caudal translational shifts, although being not clinically significant. Further studies are required to fully investigate the potential contribution of this device on vesicles motion. ADVANCES IN KNOWLEDGE: MR-guided daily adaptive radiotherapy may represent a game changer for prostate stereotactic body radiotherapy, given the possibility to better visualize soft-tissues anatomy and to daily recalculate the treatment plan based on real-time conditions. The use of devices like rectal ballon or rectal gel spacers has gained interest in the last years for the possibility to better spare the rectum during prostate radiotherapy. This is one of the first experiences exploring the role of rectal spacer on seminal vesicles intrafraction motion during MR-guided SBRT for prostate cancer.

Stereotactic body radiotherapy for oligometastatic castration sensitive prostate cancer using 1.5 T MRI-Linac: preliminary data on feasibility and acute patient-reported outcomes.

OBJECTIVES: To report preliminary data on feasibility and patient-reported outcomes following PSMA-PET/CT guided SBRT by means of 1.5 T MRI-Linac. METHODS AND MATERIALS: Between October 2019 and April 2020, twenty consecutive castration sensitive oligorecurrent prostate cancer patients were enrolled in an ethical committee approved prospective observational study (Protocol n. XXXX) and treated with PSMA-PET/CT guided SBRT by means of 1.5 T MRI-Linac (Unity, Elekta AB, Stockholm, Sweden). The mean delivered dose was 35 Gy in 5 fractions. Clinicians reported toxicity was prospectively collected according to Common Terminology Criteria for Adverse Events v5.0. Quality of life (QoL) assessment was performed using EORTC-QLQ C30 questionnaires administered at baseline, end of treatment and at first follow-up. RESULTS: Twenty-five lesions in 20 castration sensitive oligorecurrent patients were treated: the most commonly treated anatomic sites were nodal (n = 16) and pelvic bone (n = 9). Median PSA-value preMRI guided SBRT was 1.16 ng/mL (range, 0.27-8.9), whereas median PSA value at first follow-up after SBRT was 0.44 ng/mL (range, 0.06-8.15). At first follow-up, for 16 patients showing detectable PSA, PSMA-PET/CT was performed detecting, respectively, in 6 cases partial response and in 10 cases complete response. In the remaining cases, PSA-value was undetectable after SBRT. Radiotherapy treatment was safe and well tolerated according to the PROMs. No acute G2 or higher toxicities were recorded. CONCLUSIONS: The current series represent the largest one exploring the feasibility and patient-reported outcomes following PSMA-PET/CT guided SBRT by means of 1.5 T MRI-Linac. The preliminary findings here reported are encouraging in terms of effectiveness and tolerability.

Daily dosimetric variation between image-guided volumetric modulated arc radiotherapy and MR-guided daily adaptive radiotherapy for prostate cancer stereotactic body radiotherapy.

AIM: To evaluate differences between MR-guided daily-adaptive RT (MRgRT) and image-guided RT (IGRT) with or without fiducial markers in prostate cancer (PCa) stereotactic body radiotherapy (SBRT) in terms of dose distribution on critical structures. MATERIAL AND METHODS: Two hundred treatment sessions in 40 patients affected by low and intermediate PCa were evaluated. The prescribed dose was 35 Gy in 5 fractions delivered on alternate days. MRgRT patients (10) were daily recontoured, re-planned, and treated with IMRT technique. IGRT patients without (20) and with (10) fiducials were matched on soft tissues or fiducials and treated with VMAT technique. Respective CBCTs were retrospectively delineated and the prescribed plan was overlaid for dosimetric analysis. The daily dose for rectum, bladder, and prostate was registered. RESULTS: MRgRT resulted in a significantly lower rate of constraints violation as compared to IGRT without fiducials, especially for rectum V28Gy, rectum V32Gy, rectum V35Gy, rectum Dmax, and bladder Dmax. IGRT with fiducials reported high accuracy levels, comparable to MRgRT. MRgRT and IGRT with fiducials reported no significant prostate CTV underdosage, while IGRT without fiducials was associated with occasional cases of prostate CTV under dosage. CONCLUSION: MR-guided daily-adaptive SBRT seems a feasible and accurate strategy for treating prostate cancer with ablative doses. IGRT with the use of fiducials provides a comparable level of accuracy and acceptable real-dose distribution over treatment fractions. Future study will provide additional data regarding the tolerability and the clinical outcome of this new technological approach.

Rectal spacer hydrogel in 1.5T MR-guided and daily adapted SBRT for prostate cancer: dosimetric analysis and preliminary patient-reported outcomes.

OBJECTIVE: The main aim of the current analysis was to explore the hypothetical advantages using rectal spacer during 1.5T MR-guided and daily adapted prostate cancer stereotactic body radiotherapy (SBRT) compared to a no-rectal spacer hydrogel cohort of patients. METHODS: The SBRT-protocol consisted of a 35 Gy schedule delivered in 5 fractions. Herein, we present a dosimetric analysis between spacer and no-spacer patients. Furthermore, treatment tolerability and feasibility were preliminarily assessed according to clinicians-reported outcomes at the end of treatment and patient-reported outcomes measures (PROMs) in both arms. Toxicity and quality of life were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v. 5.0, International Prostatic Symptoms Score, ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires. RESULTS: 120 plans (pre- and daily adaptive SBRT planning) were analyzed in 20 patients (10 patients in spacer group and 10 patients in no-spacer group) treated using 1.5T MR-guided adaptive SBRT. Statistically significant dosimetric advantages were observed in favor of the spacer insertion, improving the planning target volume coverage in terms of V33.2Gy >95% and planning target volume 37.5 Gy <2% mainly during daily-adapted SBRT. Also, rectum V32, V28 and V18Gy and bladder V35Gy <1 cc were significantly reduced in the spacer cohort. Concerning the PROMS, all questionnaires showed no difference between the pre- and post-SBRT evaluation in both arms, excepting the physical functioning item of EORTC QLQ-C30 questionnaire that was declined in the no-spacer group. CONCLUSION: These preliminary results strongly suggest the adoption of perirectal spacer due to dosimetric advantages not only for rectal sparing but also for target coverage. Longer follow-up is required to validate the clinical impact in terms of clinicians-reported toxicity and PROMs. ADVANCES IN KNOWLEDGE: This the first experience reporting preliminary data concerning the potential dosimetric impact of rectal hydrogel spacer on MR-guided SBRT for prostate cancer.

Adaptive SBRT by 1.5 T MR-linac for prostate cancer: On the accuracy of dose delivery in view of the prolonged session time.

PURPOSE: Adaptive Stereotactic Body Radiotherapy (SBRT) of prostate cancer (PC) by online 1.5 T MRi-guidance prolongs session-time, due to contouring and planning tasks, thus increasing the risk of prostate motion. Hence, the interest to verify the adequacy of the delivered dose. MATERIAL AND METHODS: For twenty PC patients treated by 35 Gy (Dp) in five fractions, daily pre- and post- delivery MRi scans were respectively used for adapt-to-shape (ATS) optimization, and re-computation of the delivered irradiation (Drec). Two expansion recipes, from Clinical (CTV) to Planning target volume (PTV), which slightly differed in the posterior margin were used for groups I and II, of ten patients each. Plans had to assure D95% ≥ 95%Dp to PTV, and D1cc ≤ Dp to rectum, bladder, penile bulb, and urethral planning-risk-volume (urethral-PRV). The adequacy of the delivered dose was estimated by inter-fraction average (ifa) of dose-volume metrics computed from Drec. A cumulative dose (Dsum) was calculated from the five daily Drec deformed onto the simulation MRi. RESULTS: For each patient, CTV coverage resulted in D95% > 95%Dp when estimated as ifa by Drec. No significant difference for D95% and D99% metrics to CTV resulted between groups I and II. D1cc was < Dp for rectum, urethral-PRV, and penile bulb, whereas < 103.5%Dp for the bladder. Significant correlations resulted between metrics computed by Dsum and as ifa by Drec, by both linear-correlation analysis, and Receiver-Operating-Characteristic curve analysis. CONCLUSIONS: Our results for PC-SBRT confirm the adequacy of the delivered dose by ATS with 1.5 T MR-linac, and the consistency between dose-volume metrics computed by Drec and Dsum.

Prostate re-irradiation: current concerns and future perspectives.

INTRODUCTION: To date, the optimal management of locally relapsed prostate cancer patients after an initial course of radiotherapy remains a matter of debate. In recent years, local approaches have been proposed as a therapeutic option, which may potentially delay the initiation of hormone therapy. In the case of external beam radiotherapy (EBRT), re-irradiation has been supported by growing evidence in the literature, mostly represented by extreme hypofractionated schedules delivered with stereotactic body radiotherapy (SBRT). AREAS COVERED: We performed a systematic review of the literature using the PICO methodology to explore the available evidence regarding the use of EBRT in the setting of locally relapsed prostate cancer, both in terms of safety, tolerability and preliminary clinical outcomes. EXPERT OPINION: Current literature data report the use of EBRT and particularly of SBRT for the safe and feasible re-treatment of locally recurrent prostate cancer after an initial treatment course of radiotherapy. When extreme hypofractionation is adopted, only occasional grade ≥3 late adverse events are reported. Despite the current lack of high-level evidence and the short follow-up, preliminary clinical outcomes are promising and allow clinicians to hypothesize further prospective studies to evaluate SBRT as an alternative to the early initiation of androgen-deprivation therapy.

Impact of hydrogel peri-rectal spacer insertion on prostate gland intra-fraction motion during 1.5 T MR-guided stereotactic body radiotherapy.

BACKGROUND: The assessment of organ motion is a crucial feature for prostate stereotactic body radiotherapy (SBRT). Rectal spacer may represent a helpful device in order to outdistance rectal wall from clinical target, but its impact on organ motion is still a matter of debate. MRI-Linac is a new frontier in radiation oncology as it allows a superior visualization of the real-time anatomy of the patient and the current highest level of adaptive radiotherapy. METHODS: We present data regarding a total of 100 fractions in 20 patients who underwent MRI-guided prostate SBRT for low-to-intermediate risk prostate cancer with or without spacer. Translational and rotational shifts were computed on the pre- and post-treatment MRI acquisitions referring to the delivery position for antero-posterior, latero-lateral and cranio-caudal direction, and assessed using the Mann-Whitney U-Test. RESULTS: All patients were treated with a five sessions schedule (35 Gy/5fx) using MRI-Linac for a median fraction treatment time of 50 min (range, 46-65). In the entire study sample, median rotational displacement was 0.1° in cranio-caudal, - 0.002° in latero-lateral and 0.01° in antero-posterior direction; median translational shift was 0.11 mm in cranio-caudal, - 0.24 mm in latero-lateral and - 0.22 mm in antero-posterior. A significant difference between spacer and no-spacer patients in terms of rotational shifts in the antero-posterior direction (p = 0.033) was observed; also for translational shifts a positive trend was detected in antero-posterior direction (p = 0.07), although with no statistical significance. We observed statistically significant differences in the pre-treatment planning phase in favor of the spacer cohort for several rectum dose constraints: rectum V32Gy < 5% (p = 0.001), V28 Gy < 10% (p = 0.001) and V18Gy < 35% (p = 0.039). Also for bladder V35 Gy < 1 cc, the use of spacer provided a dosimetric advantage compared to the no-spacer subpopulation (p = 0.04). Furthermore, PTV V33.2Gy > 95% was higher in the spacer cohort compared to the no-spacer one (p = 0.036). CONCLUSION: In our experience, the application of rectal hydrogel spacer for prostate SBRT resulted in a significant impact on rotational antero-posterior shifts contributing to limit prostate intra-fraction motion. Further studies with larger sample size and longer follow-up are required to confirm this ideally favorable effect and to assess any potential impact on clinical outcomes.

Feasibility and safety of 1.5 T MR-guided and daily adapted abdominal-pelvic SBRT for elderly cancer patients: geriatric assessment tools and preliminary patient-reported outcomes.

BACKGROUND: We present preliminary data of the first older cancer patients treated with Hybrid Linac for stereotactic body radiotherapy (SBRT) consisting of 1.5 T MRI-guided and daily-adapted treatment. The aim was to assess feasibility, safety and the role of G8 and Charlson Comorbidity Index (CCI) questionnaires in predicting patients' QoL, evaluated by patient-reported outcome measures (PROMs). METHODS: Two groups of patients with localized prostate cancer or abdominal-pelvic oligometastases were analyzed. SBRT schedule consisted of 35 Gy delivered in 5 fractions. The primary endpoint was to measure the impact of G8 and CCI on PROMs. Both G8 and the CCI were performed at baseline, while the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) for PROMs assessment was prospectively performed at baseline and after SBRT. RESULTS: Forty older patients were analyzed. The median age was 73 years (range 65-85). For the entire population, the median G8 score was 15 (10-17) and the median CCI score was 6 (4-11). Concerning the PROMS, the EORTC-QLQ C30 questionnaire reported no difference between the pre- and post-SBRT evaluation in all patients, except for the fatigue item that declined after SBRT, especially in the group of patients with a G8 score < 15 and with age < 75 years (p = 0.049). No grade 3 or higher acute toxicity occurred. CONCLUSION: This is the first report documenting for older cancer patients that 1.5 T MRI-guided daily-adapted SBRT is feasible, safe and does not impact on the QoL at the end of treatment. Longer follow-up is advocated to report long-term outcomes. TRIAL REGISTRATION: Date of approval April 2019 and numbered MRI/LINAC no. 23748.

Linac-based SBRT as a feasible salvage option for local recurrences in previously irradiated prostate cancer.

BACKGROUND AND OBJECTIVE: The optimal management of prostate cancer (PC) recurrences after definitive or postoperative radiotherapy (RT) is still controversial. The aim of the present retrospective study was to report the preliminary clinical results and toxicity of a mono-institutional series of patients re-irradiated with linac-based SBRT in recurrent prostate cancer. METHODS: Inclusion criteria were previous definitive or adjuvant/salvage RT, evidence of biochemical recurrence and radiological detection of local relapse (Magnetic Resonance Imaging or PSMA/choline-Positron Emission Tomography), and IPSS <10. Toxicity was assessed according to Common Terminology Criteria for Adverse Events v4.0. RESULTS: Between 12/2014 and 12/2019, 24 patients with median age 75 years (65-89) underwent re-RT for PC recurrence. Median follow-up was 21 months (2-68). The recurrences occurred in 13 cases within the prostate and in 11 cases within the prostate bed. All patients were treated with SBRT to a median total dose of 30 Gy (25-36 Gy) in 5-6 fractions, and simultaneous androgen deprivation therapy was administered in 4 patients. Acute toxicity was G1 in 8.3% and G2 in 12.5% for genitourinary (GU), no acute gastrointestinal (GI) toxicity occurred. Concerning late side effects, 19.7% of patients were found to have ≥G2 GU toxicity, including one G3 urethral stenosis. Only one case of G1 late GI toxicity occurred and no ≥G2. The 2­year overall survival was 95%. The 1­ and 2­year biochemical relapse-free survival (BRFS) and progression-free survival (PFS) rates were 80 and 54.9%, respectively. CONCLUSION: Despite of the heterogeneity of the sample, linac-based SBRT as a salvage treatment in previously irradiated locally recurrent PC patients seems to be a safe and feasible treatment option. Long-term data are pending.

Neck emphysema in a HNSCC cancer patient undergoing concurrent radiotherapy and cetuximab.

BACKGROUND: Lung toxicity in patients undergoing cetuximab and radiotherapy (Cetux-RT) for head and neck squamous cell carcinoma (HNSCC) has been reported in literature and represents a serious side effect of concurrent therapies. METHODS: We report a case of a HNSCC patient that developed neck emphysema during the course of Cetux-RT. The patient was an old male (80 years old) in a good performance status, with an oropharyngeal cancer (T4aN3a). RESULTS: During RT, cone-beam computed tomography (CBCT) showed bilateral neck emphysema that was confirmed at restaging CT. We decided to stop the treatment and to treat the neck emphysema with conservative strategies. After one week CT was repeated and the neck emphysema had improved, so we decided to complete the RT treatment. CONCLUSIONS: Patients undergoing Cetux-RT must be properly selected, whereas IGRT imaging must be viewed carefully in order to permit an early diagnosis and careful management of the patients.