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.

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.

Intensity-modulated radiotherapy and hypofractionated volumetric modulated arc therapy for elderly patients with breast cancer: comparison of acute and late toxicities.

PURPOSE: To evaluate the differences between conventional fractionated intensity-modulated radiotherapy (IMRT) and hypofractionated (HypoRT) volumetric modulated arc therapy (VMAT) in elderly women affected by early-stage breast cancer (BC) in terms of RT-related acute/late side effect. MATERIALS AND METHODS: Between October 2011 and July 2015, 80 consecutive elderly BC patients were treated with IMRT for 5 weeks (40 patients) or HypoRT-VMAT for 3 weeks (40 patients). Inclusion criteria were: age ≥ 70 years, early BC (pT1-2 pN0-1), no prior neoadjuvant chemotherapy and non-metastatic disease. For patients receiving IMRT or HypoRT-VMAT, a total dose of 50 Gy (25 fractions) or 40.5 Gy (15 fractions) was prescribed to the whole ipsilateral breast, respectively. All patients received a simultaneously integrated boost up to a total dose of 60 Gy for IMRT and 48 Gy for HypoRT-VMAT. Acute and late side effects were evaluated using the RTOG/EORTC radiation morbidity scoring system. RESULTS: With a median follow-up of 45 months, acute skin toxicity was overall very low, with grade 1 in 25 cases (62.5%) of the IMRT group and 21 cases (52.5%) of the HypoRT-VMAT group, while grade 2 toxicity was reported in 10 IMRT patients (25%) and 1 HypoRT-VMAT patient (2.5%) (p = 0.001). Regarding late adverse events, only grade 1 skin toxicity was recorded. CONCLUSION: The present study showed that whole breast IMRT and HypoRT-VMAT are feasible and well tolerated in early-stage BC elderly patients and that HypoRT-VMAT is affected by lower risk of acute and late RT-related side effects.

Synchronous bilateral breast cancer irradiation: clinical and dosimetrical issues using volumetric modulated arc therapy and simultaneous integrated boost.

OBJECTIVES: The aim of the present retrospective analysis was to evaluate dosimetric parameters, feasibility and outcome for Synchronous Bilateral Breast Cancer (SBBC) patients treated with adjuvant radiotherapy (RT) by Volumetric Modulated Arc Therapy (VMAT). METHODS: From September 2011 to April 2016, 1100 Breast Cancer (BC) patients were referred to our institution to receive adjuvant breast RT, and those with SBBC were selected for the present analysis. A total of 16 patients were identified. A total dose of 50 Gy in 25 fractions was prescribed to the Planning Target Volume of the whole bilateral breast (PTVBN) with or without the supraclavicular and infraclavicular nodes, while a total dose of 60 Gy in 25 fractions was prescribed to the surgical bed (PTVboost). Several V xGy and Dx% parameters were analyzed for the PTVs, together with Conformity and Homogeneity indexes (CI, HI), and for the critical Organs at risk (OARs), lungs and heart first. RESULTS: With a median follow-up of 24 months, no acute or late side effects more than grade 2 were observed. All patients are alive without any sign of disease. For target dose coverage, our observed inter-patients averages (±1 sd) were V 95% Dp = 96.7 ± 1.6% (96.3 ± 1.8%) to the left (right) PTVBN, V 95% Dp = 98.6 ± 2.7% (99.4 ± 0.9%) to the left (right) PTVboost, and D 2% = 64.4 ± 1.8 Gy (65.0 ± 2.0 Gy) to the left (right) PTVboost, respectively. With regard to the heart, the inter-patient average of D mean was 8.3 ± 3.3 Gy. For the lungs, the inter-patient average of D mean, V 5 Gy and V 20 Gy were 11.8 ± 2.3 Gy, 78.9 ± 15.3% and 15.7 ± 5%, respectively. CONCLUSIONS: The present retrospective analysis showed the feasibility, tolerability and safety of VMAT in the treatment of SBBC patients. Further studies are necessary to confirm these preliminary data.

Three-dimensional conformal versus intensity modulated radiotherapy in breast cancer treatment: is necessary a medical reversal?

OBJECTIVES: Aim of the present study is to compare three-dimensional conformal RT (3D-CRT) and 4-fields intensity modulated radiation therapy (4f-IMRT) treatment plans, in terms of target dose coverage, integral dose and dose to Organs at risk (OARs) in early breast cancer (BC). METHODS: Twenty consecutive BC patients, after lumpectomy, were selected for the present analysis. A total dose of 50 Gy and a simultaneous dose of 60 Gy in 25 fractions was prescribed to Planning Target Volume of the whole breast (PTVbreast) and of the surgical bed, respectively. For each patient, a 3D-CRT plan and a sliding-window 4f-IMRT plan were generated. Conformity and homogeneity indexes (CI, HI) and various organ specific VxGy values were analyzed for PTVs, OARs and normal tissue (NT), respectively. RESULTS: In terms of HI, 4f-IMRT was superior to 3D-CRT for the PTVbreast (p < 0.0001), and a significant difference for CI was observed in favor of 4f-IMRT (p < 0.0001).In terms of dose to OARs, a superiority of 4f-IMRT was shown. For NT, all parameters are in favor of IMRT, except the V 5Gy for which the difference was not statistically significant. The average NT-Dmean was 2.7 ± 0.7 for 3D-CRT and 1.8 ± 0.5 for 4f-IMRT (p < 0.0001). CONCLUSIONS: 4f-IMRT technique significantly reduced the dose to OARs and NT, with a better target coverage compared to 3D-CRT.

Whole brain radiotherapy with hippocampal avoidance and simultaneous integrated boost for brain metastases: a dosimetric volumetric-modulated arc therapy study.

OBJECTIVE: To develop a feasible volumetric modulated arc therapy (VMAT) treatment in whole brain radiotherapy (WBRT) with a simultaneous integrated boost (SIB) and hippocampal (HP) sparing in 1-5 brain metastases (BMs). METHODS AND MATERIALS: Ten patients with 20 BMs received a WBRT prescription of 20 Gy, SIB dose on BMs of 40 Gy/5 fractions. PTVWBRT was generated from brain minus BMs-PTVs (PTVSIB) and planning organ at risk volume to HP. All plans were evaluated in: homogeneity index (HI), target coverage (TC), maximum dose to prescription dose ratio (MDPD), prescription isodose to target volume ratio (PITV) and paddick conformity index (CI). We also evaluate D100%, mean and maximum doses to HP. Planning objectives were for PTVWBRT, D2% = 25 Gy with acceptable deviation of 26.7 Gy and D98% ≥ 16.7 Gy; for PTVSIB D95% ≥ 38 Gy; for HP, D100% = 6 Gy with acceptable deviation of 6.7 Gy, Dmax = 10.7 Gy with acceptable deviation of 11.3 Gy, a mean dose of 8 Gy. RESULTS: Mean number of BMs was 2 (range 1-5). Mean values for BMs were volume of PTVSIB = 5.1 ± 4.9 cc, dose to 95% of PTVSIB 39.3 ± 0.9 Gy, HI 0.083 ± 0.03, TC 0.96 ± 0.24, CI 0.78 ± 0.17. Mean MDPD was 1.06 ± 0.02 and PITV 0.96 ± 0.24. For WBRT, mean target volume was (13.46 ± 2)*10(2) cc, mean dose to 90% of PTVWBRT 19.8 ± 0.2 Gy, mean HI 0.42 ± 0.12 and TC 0.78 ± 0.11. Mean and maximum HP doses were 7.7 ± 0.3 Gy and 10.5 ± 0.5 Gy. Mean dose to 100% of HP volume (D100%) was 6.7 ± 0.3 Gy. CONCLUSIONS: WBRT plus SIB with HP avoidance with VMAT was feasible. All dosimetric parameters were satisfied for PTVWBRT and PTVSIB.

1.5T MR-Guided Daily Adaptive Stereotactic Body Radiotherapy for Prostate Re-Irradiation: A Preliminary Report of Toxicity and Clinical Outcomes.

Background: Prostate re-irradiation is an attractive treatment option in the case of local relapse after previous radiotherapy, either in the definitive or in the post-operative setting. In this scenario, the introduction of MR-linacs may represent a helpful tool to improve the accuracy and precision of the treatment. Methods: This study reports the preliminary data of a cohort of 22 patients treated with 1.5T MR-Linacs for prostate or prostate bed re-irradiation. Toxicity was prospectively assessed and collected according to CTCAE v5.0. Survival endpoints were measured using Kaplan-Meier method. Results: From October 2019 to October 2021, 22 patients received 1.5T MR-guided stereotactic body radiotherapy for prostate or prostate-bed re-irradiation. In 12 cases SBRT was delivered to the prostate, in 10 to the prostate bed. The median time to re-RT was 72 months (range, 12-1460). SBRT was delivered concurrently with ADT in 4 cases. Acute toxicity was: for GU G1 in 11/22 and G2 in 4/22; for GI G1 in 7/22, G2 in 4/22. With a median follow-up of 8 months (3-21), late G1 and G2 GU events were respectively 11/22 and 4/22. Regarding GI toxicity, G1 were 6/22, while G2 3/22. No acute/late G≥3 GI/GU events occurred. All patients are alive. The median PSA-nadir was 0.49 ng/ml (0.08-5.26 ng/ml), for 1-year BRFS and DPFS rates of 85.9%. Twenty patients remained free from ADT with 1-year ADT-free survival rates of 91.3%. Conclusions: Our experience supports the use of MR-linacs for prostate or prostate bed re-irradiation as a feasible and safe treatment option with minimal toxicity and encouraging results in terms of clinical outcomes.

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.

Automated Planning for Prostate Stereotactic Body Radiation Therapy on the 1.5 T MR-Linac.

PURPOSE: Adaptive stereotactic body radiation therapy (SBRT) for prostate cancer (PC) by the 1.5 T MR-linac currently requires online planning by an expert user. A fully automated and user-independent solution to adaptive planning (mCycle) of PC-SBRT was compared with user's plans for the 1.5 T MR-linac. METHODS AND MATERIALS: Fifty adapted plans on daily magnetic resonance imaging scans for 10 patients with PC treated by 35 Gy (prescription dose [Dp]) in 5 fractions were reoptimized offline from scratch, both by an expert planner (manual) and by mCycle. Manual plans consisted of multicriterial optimization (MCO) of the fluence map plus manual tweaking in segmentation, whereas in mCycle plans, the objectives were sequentially optimized by MCO according to an a-priori assigned priority list. The main criteria for planning approval were a dose ≥95% of the Dp to at least 95% of the planning target volume (PTV), V33.2 (PTV) ≥ 95%, a dose less than the Dp to the hottest cubic centimeter (V35 ≤ 1 cm3) of rectum, bladder, penile bulb, and urethral planning risk volume (ie, urethra plus 3 mm isotropically), and V32 ≤ 5%, V28 ≤ 10%, and V18 ≤ 35% to the rectum. Such dose-volume metrics, plus some efficiency and deliverability metrics, were used for the comparison of mCycle versus manual plans. RESULTS: mCycle plans improved target dose coverage, with V33.2 (PTV) passing on average (±1 SD) from 95.7% (±1.0%) for manual plans to 97.5% (±1.3%) for mCycle plans (P < .001), and rectal dose sparing, with significantly reduced V32, V28, and V18 (P ≤ .004). Although at an equivalent number of segments, mCycle plans consumed moderately more monitor units (+17%) and delivery time (+9%) (P < .001), whereas they were generally faster (-19%) in terms of optimization times (P < .019). No significant differences were found for the passing rates of locally normalized γ (3 mm, 3%) (P = .059) and γ (2 mm, 2%) (P = .432) deliverability metrics. CONCLUSIONS: In the offline setting, mCycle proved to be a trustable solution for automated planning of PC-SBRT on the 1.5 T MR-linac. mCycle integration in the online workflow will free the user from the challenging online-optimization task.

Mitigation on bowel loops daily variations by 1.5-T MR-guided daily-adaptive SBRT for abdomino-pelvic lymph-nodal oligometastases.

PURPOSE: We report preliminary dosimetric data concerning the use of 1.5-T MR-guided daily-adaptive radiotherapy for abdomino-pelvic lymph-nodal oligometastases. We aimed to assess the impact of this technology on mitigating daily variations for both target coverage and organs-at-risk (OARs) sparing. METHODS: A total of 150 sessions for 30 oligometastases in 23 patients were analyzed. All patients were treated with MR-guided stereotactic body radiotherapy (SBRT) for a total dose of 35 Gy in five fractions. For each fraction, a quantitative analysis was performed for PTV volume, V35Gy and Dmean. Similarly, for OARs, we assessed daily variations of volume, Dmean, Dmax. Any potential statistically significant change between baseline planning and daily-adaptive sessions was assessed using the Wilcoxon signed-rank test, assuming a p value < 0.05 as significant. RESULTS: Average baseline PTV, bowel, bladder, and single intestinal loop volumes were respectively 8.9 cc (range 0.7-41.2 cc), 1176 cc (119-3654 cc), 95 cc (39.7-202.9 cc), 18.3 cc (9.1-37.7 cc). No significant volume variations were detected for PTV (p = 0.21) bowel (p = 0.36), bladder (p = 0.47), except for single intestinal loops, which resulted smaller (p = 0.026). Average baseline V35Gy and Dmean for PTV were respectively 85.6% (72-98.8%) and 35.6 Gy (34.6-36.1 Gy). We recorded a slightly positive trend in favor of daily-adaptive strategy vs baseline planning for improved target coverage, although not reaching statistical significance (p = 0.11 and p = 0.18 for PTV-V35Gy and PTV-Dmean). Concerning OARs, a significant difference was observed in favor of daily-adapted treatments in terms of single intestinal loop Dmax [23.05 Gy (13.2-26.9 Gy) at baseline vs 20.5 Gy (12.1-24 Gy); p value = 0.0377] and Dmean [14.4 Gy (6.5-18 Gy) at baseline vs 13.0 Gy (6.7-17.6 Gy); p value = 0.0003]. Specifically for bladder, the average Dmax was 18.6 Gy (0.4-34.3 Gy) at baseline vs 18.3 Gy (0.7-34.3 Gy) for a p value = 0.28; the average Dmean was 7.0 Gy (0.2-16.6 Gy) at baseline vs 6.98 Gy (0.2-16.4 Gy) for a p value = 0.66. Concerning the bowel, no differences in terms of Dmean [4.78 Gy (1.3-10.9 Gy) vs 5.6 Gy (1.4-10.5 Gy); p value = 0.23] were observed between after daily-adapted sessions. A statistically significant difference was observed for bowel Dmax [26.4 Gy (7.7-34 Gy) vs 25.8 Gy (7.8-33.1 Gy); p value = 0.0086]. CONCLUSIONS: Daily-adaptive MR-guided SBRT reported a significantly improved single intestinal loop sparing for lymph-nodal oligometastases. Also, bowel Dmax was significantly reduced with daily-adaptive strategy. A minor advantage was also reported in terms of PTV coverage, although not statistically significant.

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.

Mammary Chain Irradiation in Left-Sided Breast Cancer: Can We Reduce the Risk of Secondary Cancer and Ischaemic Heart Disease with Modern Intensity-Modulated Radiotherapy Techniques?

INTRODUCTION: The aim of the present study was to estimate the impact of the addition of internal mammary chain (IMC) irradiation in node-positive left-sided breast cancer (BC) patients undergoing regional nodal irradiation (RNI) and comparatively evaluate excess relative and absolute risks of radiation-induced lung cancer/BC and ischaemic heart disease for intensity-modulated radiotherapy (IMRT) versus 3D conformal radiotherapy (3D-CRT). METHODS: Four treatment plans were created (3D-CRT and IMRT -/+ IMC) for each of the 10 evaluated patients, and estimates of excess relative risk (ERR) and 10-year excess absolute risk (EAR) were calculated for radiation-induced lung cancer/BC and coronary events using linear, linear-exponential and plateau models. RESULTS: The addition of IMC irradiation to RNI significantly increased the dose exposure of the heart, lung and contralateral breast using both techniques, increasing ERR for secondary lung cancer (58 vs. 44%, p = 0.002), contralateral BC (49 vs. 31%, p = 0.002) and ischaemic heart disease (41 vs. 27%, p = 0.002, IMRT plans). IMRT significantly reduced the mean cardiac dose and mean lung dose as compared to 3D-CRT, decreasing ERR for major coronary events (64% 3D-CRT vs. 41% IMRT, p = 0.002) and ERR for secondary lung cancer (75 vs. 58%, p = 0.004) in IMC irradiation, without a significant impact on secondary contralateral BC risks. CONCLUSION: Although IMC irradiation has been shown to increase survival rates in node-positive BC patients, it increased dose exposure of organs at risk in left-sided BC, resulting in significantly increased risks for secondary lung cancer/contralateral BC and ischaemic heart disease. In this setting, the adoption of IMRT seems advantageous when compared to 3D-CRT.

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.

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.

Severe hypofractionation: non-homogeneous tumour dose delivery can counteract tumour hypoxia.

BACKGROUND: The current rationale for severely hypofractionated schedules (3-5 fractions) used in stereotactic-body-radiotherapy (SBRT) of non-small-cell lung cancer (NSCLC) is the small size of the irradiated volumes. Being the dose prescribed to the 60-80% isodose line enclosing the PTV, a non-homogeneous tumour-dose-delivery results which might impact on tumour hypoxia. A comparison between homogeneous and SBRT-like non-homogeneous tumour-dose-delivery is then proposed here, using severe hypofractionation on large tumour volumes where both dose prescription strategies are applicable. MATERIALS AND METHODS: For iso-NTCP hypofractionated schedules (1f/d*5d/w) with respect to standard fractionation (d=2Gy), computed from the individual DVHs for lungs, oesophagus, heart and spinal cord (Lyman-Kutcher-Burman NTCP-model), TCP values were calculated (α-averaged Poissonian-LQ model) for homogeneous and SBRT-like non-homogeneous plans both with and without tumour hypoxia. Two different estimates of the oxygen-enhancement-ratio (OER) in combination with two distinct assumptions on the kinetics of reoxygenation were considered. Homogeneous and SBRT-like non-homogeneous plans were finally compared in terms of therapeutic ratio (TR), as the product of TCP and the four (1-NTCP(i)) values. RESULTS: For severe hypofractionation (3-5 fractions) and for any of the hypotheses on the kinetics of reoxygenation and the OER, there was a significant difference between the computed TRs with or without inclusion of tumour hypoxia (anova, p=0.01) for homogeneous tumour-dose-delivery, but no significant difference for the SBRT-like non-homogeneous one. Further, a significantly increased mean TR for the group of SBRT-like non-homogeneous plans resulted (t-test, p=0.05) with respect to the group with homogeneous target-dose-coverage. CONCLUSIONS: SBRT-like dose-boosting seems to counterbalance the loss of reoxygenation within a few fractions. For SBRT it then seems that, in addition to the high level of dose-sparing to the adjacent normal tissues, when severe hypofractionation is adopted it is probably the intrinsic ability of stereotactic techniques to perform intra-tumour simultaneous dose-boosting which yields the reported high clinical efficacy.

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.

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.

BACKGROUND: Unity Elekta is a unique magnetic resonance (MR)-linac that conjugates a 1.5 Tesla MR unit with a 7 MV flattening filter free accelerator.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 prostate cancer (PC) treated with stereotactic body radiotherapy (SBRT). METHODS: The SBRT protocol consisted of a 35 Gy schedule delivered in 5 fractions within 2 weeks. Toxicity and quality of life (QoL) were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v5.0, International Prostatic Symptoms Score (IPSS), ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires. RESULTS: Between October 2019 and January 2020, 25 patients with localized PC were recruited. The median age was 68 years (range, 54-82); 4 were low risk, 11 favorable intermediate risk (IR) and 10 unfavorable IR. Median iPSA was 6.8 ng/ml (range, 1-19), and 9 of these patients (36%) received concurrent androgen deprivation therapy. Median prostate volume was 36 cc (range, 20-61); median baseline IPSS was 5 (range, 0-10). Median time for fraction was 53 min (range, 34-86); adaptive strategy with daily critical structure and target re-contouring and daily replanning (adapt to shape) was performed in all cases. No grade ≥ 3 adverse event was observed, three patients (12%) reported grade 2 acute genitourinary toxicity (urinary frequency, urinary tract pain and urinary retention), while only one patient reported mild rectal pain. No relevant deteriorations were reported in PROMs. CONCLUSION: To the best of our knowledge, this is the first experience reporting feasibility, clinician-reported outcome measurements, and PROMs for 1.5 T MR-guided adaptive SBRT for localized prostate cancer. The preliminary data collected here report optimal safety and excellent tolerability, as also confirmed by PROMs questionnaires. Moreover, the data on technical feasibility and timing of online daily adapted planning and delivery are promising. More mature data are warranted. TRIAL REGISTRATION: Date of approval April 2019 and numbered MRI/LINAC n°23,748.

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.

Linac-based radiosurgery for multiple brain metastases: Comparison between two mono-isocenter techniques with multiple non-coplanar arcs.

BACKGROUND AND PURPOSE: Three mono-isocenter techniques with multiple non-coplanar arcs are nowadays clinically available for linac-based stereotactic radiosurgery (SRS) of multiple brain metastases (BM): HyperArc (HA), Multiple Brain Mets (MBM), and Monaco-HDRS. Two of them, HA and MBM, are here compared in terms of plan-quality, and dosimetric consistency between planning and delivering. MATERIALS AND METHODS: For 20 patients with multiple BM (2-10), treated by mono-isocenter volumetric modulated arc therapy (VMAT) HA plans, mono-isocenter MBM dynamic conformal arc plans were generated. Prescription dose (Dp) was 18-25 Gy, for single-fraction, and 21-27 Gy, for three-fractions. Mean overall Planning Target Volume (PTV), expanded by 2 mm from each lesion, was 9.6 cm3 (0.5-27.9 cm3). Dose normalization of 100%Dp at 98%PTV was adopted. Plan-quality was compared by the Paddick conformity (CI) and gradient (GI) index, for the target, mean dose and V12 volume, for the healthy brain, and number of monitor units (MU). Further, verification dosimetry by radiochromic films was performed for each plan, thus comparing also, by γ-analysis, the consistency between in-phantom computed and measured dose distributions. RESULTS: CI significantly improved for HA plans, changing on average from 0.75 (MBM) to 0.94 (HA) (p < .001). No significant differences between HA and MBM plans were computed for GI (p = .216), and for mean dose (p = .436) and V12 (p = .062) to the healthy brain; although V12 increased on average from 23.7 cm3 (HA) to 37.3 cm3 (MBM). No significant difference resulted for MU (p = .107), whereas γ (1 mm, 3%) and γ (2 mm, 2%) passing-rates significantly improved for HA plans (p = .006; p = .023). CONCLUSIONS: HA plans assured a higher CI, while no significant difference resulted for any of the other planning metrics. Although on average slightly higher for HA plans, the dosimetric consistency between planned and delivered was satisfactory from both techniques. Hence, our judgement of near equal plan-quality from HA and MBM SRS-techniques.

Linac-based VMAT radiosurgery for multiple brain lesions: comparison between a conventional multi-isocenter approach and a new dedicated mono-isocenter technique.

BACKGROUND: Linac-based stereotactic radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) of multiple brain lesions using volumetric modulated arc therapy (VMAT) is typically performed by a multiple-isocenter approach, i.e. one isocenter per lesion, which is time-demanding for the need of independent setup verifications of each isocenter. Here, we present our initial experience with a new dedicated mono-isocenter technique with multiple non-coplanar arcs (HyperArc™, Varian Inc.) in terms of a plan comparison with a multiple-isocenter VMAT approach. METHODS: From August 2017 to October 2017, 20 patients with multiple brain metastases (mean 5, range 2-10) have been treated by HyperArc in 1-3 fractions. The prescribed doses (Dp) were 18-25 Gy in single-fraction, and 21-27 Gy in three-fractions. Planning Target Volume (PTV), defined by a 2 mm isotropic margin from each lesion, had mean dimension of 9.6 cm3 (range 0.5-27.9 cm3). Mono-isocenter HyperArc VMAT plans (HA) with 5 non-coplanar 180°-arcs (couch at 0°, ±45°, ±90°) were generated and compared to multiple-isocenter VMAT plans (RA) with 2 coplanar 360°-arcs per isocenter. A dose normalization of 100%Dp at 98%PTV was adopted, while D2%(PTV) < 150%Dp was accepted. All plans had to respect the constraints on maximum dose to the brainstem (D0.5cm3 < 18 Gy) as well as to the optical nerves/chiasm, eyes and lenses (D0.5cm3 < 15 Gy). HA and RA plans were compared in terms of dose-volume metrics, by Paddick conformity (CI) and gradient (GI) index and by V12 and mean dose to the brain-minus-PTV, and in terms of MU and overall treatment time (OTT) per fraction. OTT was measured for HA treatments, whereas for RA plans OTT was estimated by assuming 3 min. For initial patient setup plus 5 min. For each CBCT-guided setup correction per isocenter. RESULTS: Significant variations in favour of HA plans were computed for both target dose indexes, CI (p < .01) and GI (p < .01). The lower GI in HA plans was the likely cause of the significant reduction in V12 to the brain-minus-PTV (p = .023). Although at low doses, below 2-5 Gy, the sparing of the brain-minus-PTV was in favour of RA plans, no significant difference in terms of mean doses to the brain-minus-PTV was observed between the two groups (p = .31). Finally, both MU (p < .01) and OTT (p < .01) were significantly reduced by HyperArc plans. CONCLUSIONS: For linac-based SRS/FSRT of multiple brain lesions, HyperArc plans assured a higher CI and a lower GI than standard multiple-isocenter VMAT plans. This is consistent with the computed reduction in V12 to the brain-minus-PTV. Finally, HyperArc treatments were completed within a typical 20 min. time slot, with a significant time reduction with respect to the expected duration of multiple-isocenters VMAT.